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Higher
HUMAN
BIOLOGY
for CfE
Writing Team:
James Torrance
James Fullarton
Clare Marsh
James Simms
Caroline Stevenson
Diagrams by James Torrance
for Exc
um e
ul
C
fE
ic
lle
Curr
nce
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Contents
Unit 1 Human Cells 19 Communication and social behaviour 278
1 Dif ferentiation and stem cells 2 20 Ef fect of exper ience and group behaviour 289
2 DNA and its replication 16
Unit 4 Immunology and Public Health

3 RNA, transcr iption and translation 33
4 Proteins, mutations and genetic disorders 45 21 Immune system 308
5 Human genomics 63 22 Specif ic cellular defences 313
6 Metabolism and enzymes 78 23 Infectious diseases and epidemiology 328
7 Cellular respiration 97 24 Herd immunity and antigenic variation 336
Unit 2 Physiology and Health Appendix 1

The genetic code 351
8 Reproductive organs and hormonal control 124
Appendix 2
9 Biology of fer tility control 131
10 Ante- and postnatal screening 140

Box plots 352
11 Structure of the cardiovascular system 157 Appendix 3
12 The cardiovascular system in action 166
Statistical concepts 354
13 Cardiovascular disease, diabetes and obesity 174
Appendix 4
Unit 3 Neurobiology and False positives and negatives 357
Communication
Index 358
14 Ner vous system 202
Answers 362
15 Perception 220
16 Memor y 235
17 Ner ve cells and neural pathways 248
18 Neurotransmitters, mood and behaviour 265
Preface
This book has been written to act as a valuable resource Applying Your Knowledge and Skills
for students studying Higher Grade Human Biology. It A variety of questions at the end of each unit designed
provides a core text which adheres closely to the SQA to give students practice in exam questions and foster
syllabus for Higher Human Biology introduced in 2012. the development of Skills of Scientific Experimentation,
Each section of the book matches a unit of the revised Investigation and Enquiry (i.e. selection of relevant
syllabus; each chapter corresponds to a content area. In information, presentation of information, processing
addition to the core text, the book contains a variety of of information, planning experimental procedure,
special features: evaluating, drawing valid conclusions and making
predictions and generalisations). These questions are
Learning Activities especially useful as extensions to class work and as
Within each chapter, an appropriate selection of homework.
learning activities in the form of Case Studies, Case
Histories, Related Topics, Research Topics, Related Updates and syllabus changes: impor tant
Information, Related Activities and Investigations, as laid note to teachers and students from the
down in the new syllabus.
publisher
This book covers all course arrangements for Revised
Practical Activity and Repor t
Higher and CfE Higher, but does not attempt to give
An assignment designed to match the required
advice on any ‘added value assessments’ or ‘open
performance criteria and provide students with the
assignments’ that may form part of a final grade in the
opportunity to write a Scientific Report, which includes
CfE version of Higher Human Biology (2015 onwards).
description of procedure, recording of results, drawing
of conclusions and evaluation of procedure. This report Please remember that syllabus arrangements change
satisfies the requirements of a mandatory part of SQA from time to time. We make every effort to update our
assessment. textbooks as soon as possible when this happens, but –
especially if you are using an old copy of this book – it
Testing Your Knowledge is always advisable to check whether there have been
Key questions incorporated into the text of every any alterations to the arrangements since this book
chapter and designed to continuously assess Knowledge was printed. You can check the latest arrangements
and Understanding. These are especially useful as at the SQA website (www.sqa.org.uk), and you can
homework and as instruments of diagnostic assessment also check for any specific updates to this book at
to check that full understanding of course content has www.hoddereducation.co.uk/HigherScience.
been achieved.
We make every effort to ensure accuracy of content, but
What You Should Know if you discover any mistakes please let us know as soon
Summaries of key facts and concepts as ‘Cloze’ Tests as possible – see our contact details on the back cover.
accompanied by appropriate word banks. These feature
at regular intervals throughout the book and provide an
excellent source of material for consolidation and
revision prior to the SQA examination.
iv
Human
Unit
1 Cells
Human Cells Unit 1
1 Differentiation and stem cells

A multicellular organism such as a human being
consists of a large number of cells. Rather than each
fertilised egg
cell carrying out every function for the maintenance of (zygote)
life, a division of labour occurs and most of the cells
become differentiated. Differentiation is the process repeated mitosis
by which an unspecialised cell becomes altered and and cell division
adapted to perform a specialised function as part of a
permanent tissue. early embryo
(blastocyst)
Differentiation in human cells unspecialised

cells
A human being begins life as a fertilised egg (zygote), as
shown in Figure 1.1. The zygote divides repeatedly by
mitosis and cell division to form an embryo. Like the growth and
cells in an adult, each embryonic cell possesses all the differentiation
genes for constructing the whole organism. However,
unlike those in adult cells, all the genes in cells at this
early stage are switched on or have the potential to fully grown
adult
become switched on.
As embryological development proceeds, the

unspecialised cells of the early embryo undergo
differentiation and become specialised in structure
and biochemical properties, making them perfectly
adapted for carrying out a particular function. For
example, a motor neuron (see Figure 1.1) is a type of
nerve cell that possesses an axon (a long, insulated
cytoplasmic extension). This structure is ideally suited
to the transmission of nerve impulses. Similarly the cells spinal cord close-up windpipe close-up
of the epithelial lining of the windpipe are perfectly
suited to their job of sweeping dirty mucus up and away motor ciliated
epithelial cell
from the lungs. neuron
Selective gene expression motor fibre

mucus goblet
(axon)
Once a cell becomes differentiated, it only expresses cell
the genes that code (see chapter 3) for the proteins

differentiated
specific to the workings of that particular type of cell. cells
For example, in a nerve cell, genes that code for the
formation of neurotransmitter substances are switched
on and continue to operate but those for mucus are Figure 1.1 Dif ferentiation
switched off. The reverse is true of the genes in a goblet
cell in the lining of the windpipe. Only a fraction of the
2 genes in a specialised cell are expressed (e.g. 3–5% in a
typical human cell).
Differentiation and stem cells
Stem cells
Stem cells are unspecialised cells that can:
● reproduce themselves by repeated mitosis and cell

division while remaining undifferentiated
● differentiate into specialised cells when required to
do so by the multicellular organism that possesses
them.
Embr yonic stem cells

A human blastocyst is an early embryo consisting of a
ball of embryonic stem cells (see Figures 1.2 and 1.3).
All of the genes in an embryonic cell have the potential
Figure 1.3 Embr yonic stem cells
zygote
to be switched on, so the cell is capable of differentiating
repeated mitosis
into all of the cell types (more than 200) found in the
and cell division human body.
early embryo
(blastocyst composed
of unspecialised cells)
Tissue (adult) stem cells
embryonic
Tissue (adult) stem cells are found in locations such
stem cells as skin and red bone marrow (see Figure 1.2). They
have a much narrower differentiation potential than
embryonic stem cells because many of their genes are
differentiation and
growth to adulthood already switched off. However, they are able to replenish
continuously the supply of certain differentiated cells
multicellular adult needed by the organism such as skin, intestinal lining
(composed of structures and blood.
containing specialised
cells, e.g. heart, brain,
gut etc.) Tissue (adult) stem cells can only give rise to a limited
range of cell types closely related to the tissue in which
they are normally located. Those found in red bone
tissue (adult) marrow, for example, give rise to red blood cells,
stem cells in
bone marrow
white blood cells (various forms of phagocytes and
lymphocytes) and platelets. (See also the Related Topic
below.)
3
Figure 1.2 Two types of stem cell
Human Cells Unit 1
Related Topic
Origin of blood cells

The pool of tissue (adult) stem cells in red bone marrow
Tissue (adult) stem cells in red bone undergoes continuous mitosis and cell division
marrow (see Figure 1.4) give r ise to red

blood cells, platelets and specialised Within some of these cells, certain genes become
white blood cells including phagocytes, switched off leading to the formation of:
natural killer cells and B and T

lymphocytes – the cells of the immune relatively undifferentiated cells capable of making blood cells only.
system.
Within these cells further unnecessary genes become switched off. The genes affected differ from one
cell to another depending on the particular course of differentiation taken by the cell.
As differentiation continues, the genes that will influence the characteristic features of the blood cell
remain switched on or now become switched on to produce proteins characteristic of that cell type.
For example:
genes for genes for genes for enzymes that genes for genes for genes for cell-killing
haemoglobin healing- digest microorganisms formation antibodies proteins and cytokines
needed for associated following phagocytosis of anti- made in (see page 311)
oxygen growth (see page 310) coagulant response
transport factors chemicals to antigens
(see page 323)
red blood platelets eosinophil neutrophil monocyte basophil B lymphocyte T lymphocyte natural
cells killer cell
‘phagocytes’ ‘lymphocytes’
white blood cells (after staining)
Figure 1.4 Origin of blood cells
Differentiation in somatic cells oesophagus
All differentiated cells (except reproductive cells)

derived from stem cells are called somatic cells. Somatic
cells form several different types of body tissue. epithelial
lining
Epithelium lining of cells

Epithelial tissue is composed of cells that unite to form which are worn
membranes. These can be made of a single layer of cells away during
peristalsis and
or a number of layers. Epithelium provides the body constantly enlarge
surface with a protective, multilayered covering – the renewed
skin. Epithelium also lines body cavities and tubular
structures such as the oesophagus (see Figure 1.5) and
the blood vessels. Materials such as food and respiratory
gases are able to move easily through the thin layer of
epithelial cells that lines blood vessels.
4
Figure 1.5 Epithelium lining the oesophagus
Connective tissue Cartilage

Bone, cartilage and blood are all examples of There are several forms of cartilage. They differ in the
connective tissues. Connective tissue is characterised composition of their extracellular material. It might, for
by the large quantity of extracellular material present example, be solid and smooth, as in the type of cartilage
in the spaces between its cells. This matrix may be solid on the ends of long bones at joints, or it might consist
(e.g. in bone), fibrous or gelatinous (e.g. in different of dense fibres embedded in a solid background, as in
types of cartilage) or liquid (e.g. as plasma in blood). the slightly flexible type of cartilage found at the knee
joint (see Figure 1.8).
Bone
Bone consists of concentric layers of calcified material
laid down around blood vessels. Live bone cells deep
smooth,
within the calcified material receive oxygen and inflexible cartilage
essential nutrients via tiny canals in contact with blood cartilage on cell
end of long femur
hard
vessels (see Figures 1.6 and 1.7). bone enlarge
background
tibia material
kneecap
flexible
fibre
one of two pads of

slightly flexible
cartilage at
knee joint
Figure 1.8 Car tilage
Blood
Blood is classified as a connective tissue because
its extracellular space (about half of its volume) is
composed of plasma (see page 160).
Muscle tissue
Muscle tissue consists of cells capable of contraction.
The three types of muscle tissue are skeletal, smooth
Figure 1.6 Bone cell and cardiac. In skeletal muscle (see Figure 1.9) the cells
flexible fibres live bone cell

cartilage
containing living
bone cells
bone microscopic
canal
marrow cavity
enlarge canal
blood vessels
blood vessel calcified

small portion in canal background
of bone
material
enlarged
5
Figure 1.7 Structure of bone
Human Cells Unit 1
nucleus
biceps
triceps
close-up muscle
fibre
Figure 1.11 Cardiac muscle cells
flexor of fingers
Nervous tissue
This tissue is composed of a network of nerve cells
flexor of thumb called neurons, which receive and transmit nerve
impulses, and glial cells, which support and maintain
the neurons (see chapter 17).
Increasing levels of complexity

Somatic cells make up the different tissues in the
human body. A group of tissues makes up each of
the body’s organs. The skin, for example, is an organ
composed of a variety of tissues including epithelium,
Figure 1.9 Skeletal muscles of lef t arm blood, muscle and nerves. A collection of tissues and
organs make up a system. For example, the circulatory
take the form of striped fibres. In smooth (involuntary) system is composed of blood, heart and blood vessels.
muscle, the cells are spindle-shaped (see Figure 1.10) All the systems make up the whole, integrated human
and arranged in sheets, which form part of the walls organism.
of large blood vessels and of the wall of the alimentary
canal. In cardiac muscle (see Figure 1.11) each cell has
one or more branches in contact with adjacent cells. Maintenance of chromosome number
Certain somatic cells divide during growth and tissue
repair. In humans, each somatic cell contains 46
chromosomes and is diploid (i.e. contains 23 pairs of
homologous chromosomes). Prior to nuclear division
(mitosis), the genetic material undergoes replication
and becomes doubled in quantity for a brief time.
Nuclear division quickly follows and the genetic
material is divided equally between two daughter
nuclei. Therefore each somatic cell formed receives
an identical copy of the full set of 46 chromosomes
and the diploid chromosome number is maintained.
This process ensures that each somatic cell receives a
complete set of the genetic information.
6
Figure 1.10 Smooth muscle cells
Differentiation in germline cells between haploid and diploid cells as summarised in

Figure 1.12.
A germline cell is one that eventually leads to the
formation of sex cells (gametes). Germline cells are set
aside from somatic cells early in the course of human
Mutation in germline and somatic
development. A germline cell, like a somatic cell, is cells
diploid. Its nucleus contains 23 pairs of homologous If a mutation occurs in a germline cell, it is passed on to
chromosomes and it is able to undergo mitosis and offspring (see Figure 1.13). For example, a certain gene
form more germline cells. on chromosome 7 may mutate to the recessive form that
results in the formation of abnormally thick and sticky
Meiosis mucus. This mutant allele is passed on during meiosis
These germline cells are then able to undergo a second to gametes and then to offspring in the next generation.
form of nuclear division called meiosis. During this If a gamete with this recessive allele fuses with a gamete
process the genetic material is doubled by replication carrying a copy of the same allele (perhaps the result of
as before. However, this time, during nuclear division, a mutation in a germline cell many generations ago),
it is divided between four nuclei. Each receives a single the zygote formed will develop into a sufferer of cystic
set of 23 chromosomes, resulting in the formation of fibrosis (see page 58).
four haploid gametes. The human life cycle alternates
diploid zygote diploid zygote

mitosis mitosis
mitosis mitosis
repeated mitosis and differentiation to repeated mitosis and differentiation

form adult male composed of many to form adult female composed of
diploid somatic cells and a few diploid many diploid somatic cells and
germline cells a few diploid germline cells
diploid germline diploid

cell in testis germline cell in ovary
mitosis diploid mitosis

germline
cell
meiosis meiosis
haploid haploid
sperm cell egg cell
fertilisation
male female
diploid
zygote Key diploid cell (2n = 46 chromosomes)
haploid cell (n = 23 chromosomes)
7
Figure 1.12 Human life cycle
Human Cells Unit 1
hair
mole diploid germline
skin cell in testis
mitosis
gene in germline cell suffers a
mutation (e.g. becomes allele
causing cystic fibrosis)
meiosis
mutation normal
haploid
gene in somatic cell passed on haploid
sperm cell
suffers a mutation to gametes egg cell
(e.g. gene in skin cell
becomes allele that
leads to formation of
a mole) but mutation
is not passed on
to offspring
fertilisation
mutation has
zygote passed on
to offspring
Figure 1.13 Transmission of mutation in germline cell
A mutation can occur in a somatic cell. It might However, this type of somatic cell mutation is not
even lead to a localised change in phenotype such as passed on to the next generation.
the development of a mole from a mutated skin cell.
Testing Your Knowledge 1
1 a) Def ine the term differentiation. (2) 3 a) Name THREE dif ferent types of dif ferentiated tissue
b) In what way is a ciliated epithelial cell a good der ived from somatic cells in addition to connective
example of a specialised cell? (1) tissue. (3)
c) A goblet cell in the lining of the windpipe produces b) Arrange the following terms into order of increasing
mucus but not insulin. Explain br iefly how this complexity: body, cell, organ, system, tissue. (1)
specialisation is brought about with reference to c) Briefly descr ibe how chromosome number is
genes. (2) maintained in a somatic cell at cell division. (2)
2 a) Give T WO character istics of stem cells. (2) 4 a) What is the dif ference between the terms haploid
b) i) Name T WO types of stem cell found in and diploid? (2)
humans. b) What is a germline cell? (1)
ii) For each type, identify ONE location where these c) i) Br iefly describe how a diploid germline cell
cells could be found. (4) produces haploid gametes.
c) Which type of stem cell is capable of dif ferentiating ii) In which type of cell (somatic or germline) is a
into all the types of cell that make up the organism mutation not passed on to the members of the
to which it belongs? (1) next generation? (3)
8
Research value of stem cells as model organisms for humans since they possess
many genes equivalent to the genes in humans that are
Much of the research to date has been carried out using
responsible for certain inherited diseases. Research work
stem cells from mice and humans. Human stem cells
on the models helps to provide an understanding of the
can be grown in optimal culture conditions provided
malfunctioning of these genes and may lead the way to
that certain growth factors are present. In the absence of
the development of new treatments.
these growth factors, the stem cells differentiate rapidly.
Similarly stem cells, which are genetically identical to
By investigating why stem cells continue to multiply
differentiated somatic cells, can be used in research as
in the presence of a certain chemical yet undergo
model cells to investigate:
differentiation in its absence, scientists are attempting
to obtain a fuller understanding of cell processes such as ● the means by which certain diseases and disorders
develop
growth and differentiation. It is hoped that this will lead
● the responses of cells to new pharmaceutical drugs.
in turn to a better understanding of gene regulation
(including the molecular biology of cancer).
Therapeutic value of stem cells
Models In recent times the therapeutic value of stem cells has
A model organsim is one that is suitable for laboratory been appreciated and they have been successfully put
research because its biological characteristics are similar to use in bone marrow transplantation, skin grafts for
to those of a group of related (but often unavailable) burns and repair of damaged corneas. (Also see Case
organisms. For example, mice are used in research Study below.)
Case Study Therapeutic use of stem cells
Bone marrow transplantation Although umbilical cord blood is rich in HSCs,

Leukaemia the volume of blood obtained is relatively small.
Cancers of the blood such as leukaemia and Therefore its use in transplantation tends to be
lymphoma result from the uncontrolled proliferation restricted to very small adults and children.
of white blood cells. Treatment involves the
Figure 1.14 shows a simplified version of the
destruction of the patient’s own cancerous bone
procedure carried out during bone marrow
marrow cells by radiation or chemotherapy and their
transplantation.
replacement with a ‘bone marrow’ transplant of
normal, blood-forming stem cells. Skin graft
HSCs In a traditional skin graft, a relatively large section of
Haematopoietic stem cells (HSCs) are tissue stem skin is removed from a region of the person’s body
cells that can multiply and differentiate into a variety and grafted to the site of injury. This means that
of specialised blood cells. HSCs are present in bone the person has two bodily areas that need careful
marrow, peripheral (circulating) blood and umbilical treatment and time to heal.
cord blood. A skin graft using stem cells only requires a small
In the past, the most common source of HSCs was sample of skin to be taken to obtain stem cells.
bone marrow which was drawn from the donor using Therefore the site needs much less healing time and
a syringe. Most transplants now use HSCs obtained suffers minimum scarring. The sample is normally
by harvesting them from the donor’s peripheral taken from an area close to and similar in structure
blood. A few days before the harvest, the donor is to the site of injury. Enzymes are used to isolate and
injected with a chemical that coaxes additional HSCs loosen the stem cells, which are then cultured. Once
to migrate from the marrow to the bloodstream. a suspension of new stem cells has developed, they
As a result, up to 20% of the white cells collected are sprayed over the damaged area to bring about
in the sample are HSCs. This is at least double the regeneration of missing skin.
number present in a bone marrow sample and its use 9
normally leads to a speedier recovery by the patient. ➜
Human Cells Unit 1
Collection Processing
stem cells collected bone marrow or

from donor’s bone peripheral blood
marrow or peripheral processed to
blood concentrate stem cells
donor with a
tissue type that
matches that of
recipient Freezing
bone marrow or blood

frozen to preserve stem
cells until patient has
completed chemotherapy
Infusion Chemotherapy
thawed stem cells patient given high dose
infused into patient to of chemotherapy and/or
engraft in bone marrow radiation to destroy
and make normal cancerous cells in bone
blood cells marrow
recipient
Figure 1.14 Bone marrow transplantation
Cornea repair source of temporary skin while the patient is waiting

In recent years scientists have shown that corneal for grafts of their own skin to develop.
damage by chemical burning can be successfully
Embryonic stem cells are able to differentiate into any
treated using stem cell tissue. This can be grown from
type of cell in the body. Therefore they are believed
the patient’s own stem cells located at the edge of
to have the potential to provide treatments in the
the cornea. In many cases the person’s eyesight can
future for a wide range of disorders and degenerative
be restored following grafting of the stem cell tissue
conditions, such as diabetes, Parkinson’s disease
from the healthy eye to the surface of the damaged
and Alzheimer’s disease, that traditional medicine
eye. Since the skin graft and cornea repair techniques
has been unable to cure. Already scientists have
use the affected individual’s own cells, there is no
managed to generate nerve cells from embryonic
risk of the transplanted tissue being rejected.
stem cells in culture. It is hoped that this work will
Future therapeutic potential of stem cells eventually be translated into effective therapies
Recently human embryonic stem cells grown on to treat neurological disorders such as multiple
synthetic scaffolds have been successfully used to sclerosis. However, the use of embryonic stem cells
treat burn victims. The stem cell tissue provides a raises questions of ethics.
10
Ethical issues strongly that this practice is unethical (see Case Study –
Embryonic stem cell debate).
Ethics refers to the moral values and rules that ought
to govern human conduct. The use of stem cells raises Ethical issues are also raised by the use of induced
several ethical issues. For example the extraction of pluripotent stem cells (see Case Study – Sources of
human embryonic stem cells to create a stem cell line (a stem cells) and by the use of nuclear transfer technique
continuous culture) for research purposes results in the (see Case Study – Nuclear transfer technique).
destruction of the human embryo. Many people believe
Case Study Embryonic stem cell debate

At present the creation of a human embryonic The people who are in favour of stem cell research
stem cell line using cells from a human embryo (of using human embryos often support their case with
no more than 14 days) results in the destruction the following arguments:
of the embryo. The ethical debate about the use of
● An embryo is not a person although it has the
embryonic stem cells most commonly rests on the
potential to develop into a person.
controversial question: ‘Is a human embryo of less
● At 14 days or less an embryo is not sentient
than 2 weeks a human person?’
(i.e. it does not have a brain, a nervous system,
People on one side of the debate believe that the consciousness or powers of sensation).
embryo is definitely a human person and argue ● The death of a very young embryo is not of serious
that fatally extracting stem cells from it constitutes moral concern when it has the potential to benefit
murder. People on the other side of the debate feel humanity (particularly people whose daily lives are
certain that the embryo is not yet a person and compromised by debilitating medical conditions).
believe that removing stem cells from it is morally ● Abortion is legal in many countries including the
acceptable. UK. Destroying a 14-day-old embryo is far less
objectionable to most people than terminating a
The people who are against stem cell research using
fetus at 20 weeks.
human embryos often support their case with the
● Stem cell research uses embryos that were
following claims:
generated for IV fertilisation but were not used and
● A human life begins when a sperm cell fuses with would be destroyed as a matter of course.
an egg cell and it is inviolable (i.e. it is sacred and
Possible solutions to the problem
must not be harmed).
In the future the ethical issues raised by the use
● A unique version of human DNA is created at
of embryonic stem cells may become less heated
conception.
if advances in induced pluripotent stem cell
● A fertilised egg is a human being with a soul.
technology (see page 12) and increased use of stem
● Stem cell research violates the sanctity of life.
cells from amniotic fluid (see page 12) reduce the
need for their use.
11
Human Cells Unit 1
Case Study Sources of stem cells
Donated embryos
At present patients undergoing infertility treatment amniotic fluid containing stem cells
may agree to donate any extra embryos that are not
required for their treatment to medical science. These
very early embryos provide an immediate source of
embryonic stem cells for research. In addition long-
term cultures originally set up using cells isolated
from donated embryos and continued for many
years provide a further source of embryonic stem
fetus
cells. However, the number of human embryonic
cells available for research remains limited and this
restricts the ability of scientists to carry out research
uterus
work in this important area.
Amniotic fluid
Scientists continue to search for new sources of
stem cells. One of these is amniotic fluid. The stem Figure 1.15 Stem cells in amniotic fluid
cells that it contains can be harvested from the fluid
removed from pregnant women for amniocentesis Induced pluripotent stem cells are, strictly speaking,
tests (see Figure 1.15). The stem cells obtained not true stem cells. They are differentiated cells
are capable of differentiating into many types of (e.g. from human skin) that have been genetically
specialised cell such as bone, muscle, nerve and liver. reprogrammed using transcription factors (see
One advantage of using stem cells from amniotic chapter 3) to switch some of their turned-off genes
fluid is that it does not involve the destruction of a back on again. As a result they act as stem cells and
human embryo. can be used for research. However, the viruses used
Induced pluripotent stem cells as vectors to deliver the transcription factors have
A totipotent stem cell is one that is able to been shown to cause cancers in mouse models.
differentiate into any cell type and is capable of Therefore a significant amount of research is
giving rise to the complete organism. A pluripotent essential in this area before induced pluripotent cells
stem cell is a descendent of a totipotent stem cell and can be considered for use as part of a routine medical
is capable of differentiating into many different types procedure.
of cell.
Case Study Nuclear transfer technique

This technique involves removing the nucleus from they are not 100% human and must not be used for
an egg (see Figure 1.16) and then replacing it with a therapeutic procedures.
nucleus from a donor cell. Some cells constructed in
Some people feel that it is unethical to mix materials
this way divide normally, producing undifferentiated
from human cells with those of another species
stem cells.
even if the hybrid cells formed are used strictly for
Using this technique, a nucleus from a human cell research purposes only. Other people support the
(e.g. skin) can be introduced into an enucleated production of cytoplasmic hybrid cells because it
animal cell (e.g. an egg cell from a cow), as shown in helps to relieve the shortage of human embryonic
Figure 1.17. The cell formed is called a cytoplasmic stem cells available for research. In addition, they
hybrid cell. Once it begins to divide, stem cells can be point out that the practice allows the nucleus from a
12 extracted after 5 days and used for research. However, diseased human cell (e.g. from a patient suffering a
egg cell from

animal (e.g. cow)
nucleus
removed
enucleated cell
nucleus from human

cell (e.g. skin) inserted
cytoplasmic
Figure 1.16 Removing the nucleus from an egg hybrid cell
stimulation of cell division

degenerative disease or cancer) to be introduced into
the enucleated animal egg. This may allow scientists
to study the gene expression in these cells, observe
how the disease develops and eventually develop new further cell division
treatments that disrupt the disease process.
early embryo
hybrid
embryonic
stem cell
hybrid embryonic
stem cells extracted
to produce stem cell
line for research
Figure 1.17 Nuclear transfer technique
Regulation involving stem cells may be carried out (see Case Study
– Regulation of stem cell research).
In the UK, the use of stem cells in research is carefully
regulated by laws such as the Human Fertilisation and The aim of this strict regulation is to ensure that the
Embryology Act and the Human Reproductive Cloning quality of the stem cells used and the safety of the
Act. A licence from the Human Fertilisation and procedures carried out are of the highest order and that
Embryology Authority must be obtained before research abuses of the system are prevented.
13
Human Cells Unit 1
Case Study Regulation of stem cell research
The Human Fertilisation and Embryology Authority only Inter-species ban
grants a licence if it is satisfied that: It is illegal to place a human embryo in an animal
such as a cow or to place an animal’s embryo inside
● the use of human embryos is necessary and that
a human. Similarly it is against the law to allow a
the research work could not be carried out in
blastocyst from a cytoplasmic hybrid cell to develop
another way
within a human or an animal’s body to enable it to
● the purpose of the work is to increase knowledge
grow.
about serious disease
● the knowledge obtained will be applied in the Safeguards
development of treatments for the serious disease. A recent European directive entitled Tissues and Cells
ensures that the following further safeguards apply to
Time limit
the use of stem cells now and in the future:
An embryo may be used up to 14 days after
conception. Similarly a cytoplasmic hybrid cell ● Safety and quality of stem cells is ensured.
resulting from nuclear transfer (see page 12) may ● Donors are selected carefully.
be grown in the laboratory for up to 14 days. During ● Transfer of stem cells from donor to recipient is
this time stem cells may be removed for research tracked.
purposes. ● Adverse effects (e.g. illness) following stem cell
transplants are reported.
Use of embryos beyond 14 days is against the law.
● Sources of all materials used are able to be traced.
They must be destroyed. Experts have chosen this
time limit because it is the stage by which the embryo
(as a blastocyst) normally becomes implanted in the
uterus and begins to develop a nervous system.
Cancer cells
A cancer is an uncontrolled growth of cells. Cell
division in normal healthy cells is controlled by factors
such as cell cycle regulators and external chemical
signals. Cancerous cells do not respond to these
regulatory signals.
Tumours
Cancer cells divide uncontrollably to produce a mass of
abnormal cells called a tumour. A tumour is described
as benign if it remains as a discrete group of abnormal Figure 1.18 War t
cells in one place within an otherwise normal tissue.
Most benign tumours (e.g. warts – see Figure 1.18) do Genetic errors
not cause problems and can be successfully removed. Most cancers originate from a cell that has undergone
A tumour is said to be malignant if some of its cells a succession of mutations to the genes involved in
lose the surface molecules that keep them attached to the control of cell division. As these genetic errors
the original cell group, enter the circulatory system and accumulate, a point is reached where control of cell
spread through the body. This enables them to invade division is lost. The cell can now divide excessively,
other tissues and do harm by ‘seeding’ new tumours in unhindered by any regulatory signal or control
other parts of the body (see Figure 1.19). mechanism.
14
Normally it takes a very long time for a cell to
malignant tumour
from a single cancer cell
invasion of neighbouring
tissue by cancer cells
lymph vessel
(drains into Figure 1.20 Skin cancer
circulatory system)
cancer cells
1 a) i) Name ONE medical condition that is routinely

treated using tissue stem cells.
ii) From where in the human body are these cells
cancer cells spread through lymph
and blood circulatory systems

obtained? (2)
b) Give an example of a medical condition that might
be treated in the future using stem cells. (1)
c) Why can the stem cells used to treat the medical
to other parts of body condition you gave as your answer to a) not be
used to treat patients suf fer ing the condition you
gave as your answer to b)? (2)
new cancerous growth 2 a) One def inition of the word ethical is ‘in accordance
with pr inciples that are morally correct’. Briefly
explain why stem cell research using human
embr yos raises ethical issues. (2)
b) Why is it important that stem cell research is
Figure 1.19 Breast cancer carefully regulated? (2)
3 Identify T WO character istics of cancer cells. (2)
accumulate, and be affected by, several different

mutations. It is for this reason that the risk of cancer
increases with age. However, the risk is also increased
by exposure to agents that cause genetic damage such
as smoking, pollution and excessive exposure of skin
to ultraviolet radiation (see Figure 1.20). Cancer is
particularly common in skin, lung and bowel tissue
because the mutation rate is higher than normal in
these cells that have a high frequency of division.
15
Human Cells Unit 1
2 DNA and its replication

DNA (deoxyribonucleic acid) is a complex molecule Figure 2.3 shows how the deoxyribose molecule in a
present in all living cells. It is the molecule of nucleotide has a base attached to its carbon 1 and a
inheritance and it stores genetic information in its phosphate attached to its carbon 5. Since there are four
sequence of bases. This sequence determines the types of base, there are four types of nucleotide.
organism’s genotype and the structure of its proteins.
Sugar–phosphate backbone
A strong chemical bond forms between the phosphate
Structure of DNA group of one nucleotide and the carbon 3 of the
A molecule of DNA consists of two strands each deoxyribose on another nucleotide (see Figure 2.4). By
composed of repeating units called nucleotides. Each this means neighbouring nucleotides become joined
DNA nucleotide consists of a molecule of deoxyribose together into a long, permanent strand in which sugar
sugar joined to a phosphate group and an organic base. molecules alternate with phosphate groups, forming the
Figure 2.1 shows the carbon skeleton of a molecule of DNA molecule’s sugar–phosphate backbone.
deoxyribose. Figure 2.2 shows the four types of base
present in DNA. Base-pairing
Two of these strands of nucleotides become joined
together by weak hydrogen bonds forming between
note
3C = 3’ carbon atom their bases (see Figure 2.5). However, the hydrogen
5C
5C = 5’ carbon atom
bonds can be broken when it becomes necessary for the
two strands to separate.
4C 1C
Each base can only join up with one other type of
base: adenine (A) always bonds with thymine (T) and
3C 2C
guanine (G) always bonds with cytosine (C). A–T and
G–C are called base pairs.
Figure 2.1 Deoxyr ibose
Antiparallel strands
A DNA strand’s 3′ end on deoxyribose is distinct from
its 5′ end at a phosphate group. The chain is only able to
grow by adding nucleotides to its 3′ end. In Figure 2.6
the DNA strand on the left has its 3′ growing end at the
adenine (A) thymine (T) guanine (G) cytosine (C)
bottom of the diagram and its 5′ end at the top. The
reverse is true of its complementary strand on the right.
Figure 2.2 Four types of organic base
This arrangement of the two strands with their sugar–
phosphate backbones running in opposite directions is
5C P
phosphate
simplification
S B
deoxyribose
sugar one of four
3C organic bases P = phosphate
S = sugar
B = base
16
Figure 2.3 Structure of a DNA molecule
DNA and its replication
5’ end (at phosphate group) 3’ end (on deoxyribose)
A
sugar
A
T
phosphate
C G
C
chemical
bond
T A
T
G G
C
G
C C
sugar–phosphate
backbone 3’ end (on deoxyribose) 5’ end (at phosphate group)
Figure 2.4 Sugar–phosphate backbone Figure 2.6 Antiparallel strands
weak hydrogen bond

A T
C G
A T
T A C G
simplification
T A
G C
C G
G C
C G
17
Figure 2.5 Base-pair ing
Human Cells Unit 1
described as antiparallel. (For the sake of simplicity the twisted coil called a double helix (see Figure 2.7) with
letters in a diagram are normally all written the same the sugar–phosphate backbones on the outside and the
way up.) base pairs on the inside. As a result, a DNA molecule
is like a spiral ladder in which the sugar–phosphate
Double helix backbones form the uprights and the base pairs form
the rungs.
In order for the base pairs to align with each other,
the two strands in a DNA molecule take the form of a
A T
sugar–
phosphate
backbone
C G
two strands twisted

T A pairs of bases
into a coil (double helix)
linking strands
G C
C G
Figure 2.7 Double helix
Case Study Identity of genetic material
Proteins or DNA? and expression of all the traits inherited by every

During the early part of the twentieth century, genes species.
were known to be located on chromosomes and
chromosomes to be composed of protein and DNA. Bacterial transformation
However, scientists did not know for certain which of In 1928 a scientist called Griffith was working with
these two classes of molecule made up the genetic two strains of the bacterium Streptococcus pneumoniae.
material. Strain S caused pneumonia in mammals; strain R
was harmless. Griffith used these two strains in the
Proteins vary greatly in structure and therefore it
experiment shown in Figure 2.8.
was widely believed at the time that they were the
hereditary material. DNA on the other hand seemed From this experiment Griffith concluded that some
to lack diversity. Therefore it was thought unlikely chemical component had passed from dead S
that DNA would be able to carry the vast quantity cells to live R cells. These live R cells had become
of genetic information needed for the transmission transformed into live S cells. He called the chemical
18
live R and
live S cells live R cells dead S cells dead S cells
some live S
cells present
blood
sample
mouse dies mouse unaffected mouse unaffected mouse dies
Figure 2.8 Bacter ial transformation exper iment
substance the transforming principle but he did not

know which constituent of the bacterial cell was
protein coat
responsible.
Positive identification
DNA
The R cell/S cell line of enquiry was pursued by
a team of scientists led by Avery. They repeated
Griffith’s experiment and systematically isolated
each constituent of the disease-causing strain of the
bacterium. Over a period of 14 years they tested each hollow tail
substance for its ability to transform R cells to S cells.
In 1944 they were able to report that without doubt fibre
only DNA fragments (and not proteins) were able

to bring about this transformation. However, many
scientists remained sceptical.
Figure 2.9 Bacter iophage virus
Compelling evidence
Background
Phage experiments
A bacteriophage (phage for short) is a type of virus
In 1952 Hershey and Chase devised experiments to
that attacks a bacterium and multiplies inside
investigate whether the information needed to alter
it. Figure 2.9 shows a bacteriophage that attacks
the host cell’s biochemical machinery and make new
Escherichia coli bacteria. The virus’s DNA strand is
viral particles resided in the original virus’s DNA or in
contained inside a protein coat from which a tail
its protein coat.
projects. The virus launches an attack by injecting its
DNA into the bacterial host cell, which then becomes Sulphur is found in protein but not in DNA. Therefore
a virus-producing ‘factory’ (see Figure 2.10). they labelled the protein coats of a group 19
➜
Human Cells Unit 1
viral protein coat
left attached to
bacterial cell outside of host cell
viral DNA
injected into
host cell
host cell’s biochemical

machinery altered to
make it produce copies
of viral DNA and
viral protein coats
new copies of virus

become assembled
host cell bursts open

releasing many copies
of original virus
Figure 2.10 Multiplication of bacteriophage virus

of phage particles by growing them in E. coli cells cultured in the presence of 32P (a radioactive isotope
cultured in the presence of 35S (a radioactive isotope of phosphorus).
of sulphur).
Their experiments are shown in Figure 2.11. From
Phosphorus is found in DNA but not in protein. these results it was concluded that the viral protein
They labelled the DNA strands of a different group (labelled with 35S) did not enter the E. coli cells but
20
of phage particles by growing them in E. coli cells that the viral DNA (labelled with 32P) did enter the
Experiment 1 Experiment 2
one of many viral particles 35S in viral one of many viral particles 32P in viral
host cell of E. coli protein host cell of E. coli DNA
coat
virus allowed to virus allowed to

multiply inside host cell multiply inside host cell
host cells agitated (to separate original host cells agitated (to separate original
viral protein coats from outside of host viral protein coats from outside of host
cells) and then centrifuged cells) and then centrifuged
only original only original

viral protein viral protein
coats found 35S detected in coats found no 32P detected in
centrifuge centrifuge
here this region of here this region of
tube tube
tube only tube
only host cells full only host cells full

of new viral particles no 35S detected of new viral particles 32P detected
found here in this region found here in this region of
tube only
host cells returned to culture host cells returned to culture

medium until they burst open medium until they burst open
new viral new viral

particles found particles found
to lack 35S to contain 32P
21
Figure 2.11 Phage exper iments of Hershey and Chase ➜
Human Cells Unit 1
cells. Since the viral DNA was responsible for causing When the scatter pattern of X-rays is recorded using
the host cell to produce new copies of the virus, this a photographic plate, a diffraction pattern of spots is
experiment provided compelling evidence to support produced (see Figure 2.13). This reveals information
the theory that DNA (and not protein) is the genetic that can be used to build up a three-dimensional
material responsible for passing on hereditary picture of the molecules in the crystal. Wilkins and
information. Franklin found that the X-ray diffraction patterns
of DNA from different species (e.g. bull, trout and
Establishing the structure of DNA bacteria) were identical.
Once DNA was known for certain to be the genetic
material, scientists became keen to establish the
details of the molecule’s three-dimensional structure.
Chemical analysis
In the late 1940s, Chargaff analysed the base
composition of DNA extracted from a number of
different species. He found that the quantities of the
four bases were not all equal but that they always
occurred in a characteristic ratio regardless of the
source of the DNA. These findings, called Chargaff’s
rules, are summarised as follows:
● The number of adenine bases = the number of

thymine bases (i.e. A:T = 1:1).
● The number of guanine bases = the number of
cytosine bases (i.e. G:C = 1:1).
However, Chargaff’s rules remained unexplained until

the double helix was discovered.
X-ray cr ystallography Figure 2.13 X-ray dif fraction pattern of DNA

At around the time that Chargaff was carrying out
chemical analysis of DNA, Wilkins and Franklin
were employing X-ray crystallography. When X-rays Formation of an evidence-based conclusion
are passed through a crystal of DNA, they become From the X-ray diffraction patterns of DNA (produced
deflected (diffracted) into a scatter pattern, which is by Wilkins and Franklin) Watson and Crick figured
determined by the arrangement of the atoms in the out that the DNA must be a long, thin molecule of
DNA molecule (see Figure 2.12). constant diameter coiled in the form of a helix. In
addition, the density of the arrangement of the atoms
indicated to them that the DNA must be composed of
photographic plate two strands.
From Chargaff’s rules they deduced that base A must

be paired with T and base G with C. They figured
that this could only be possible if DNA consisted
X-ray source DNA sample of two strands held together by specific pairing
of bases. Taking into account further information
about distances between atoms and angles of bonds,
Watson and Crick set about building a wire model
of DNA and in 1953 were first to establish the three-
dimensional double helix structure of DNA.
22
Figure 2.12 X-ray cr ystallography
Arrangement of DNA in chromosomes bundle of protein

A strand of DNA is several thousand times longer than
the length of the cell to which it belongs. Therefore it
is essential that DNA molecules are organised in such DNA
a way that a chaotic tangle of strands in the nucleus is
prevented. This is achieved by the molecules of DNA
becoming tightly coiled and packaged around bundles
of protein like beads on a string (see Figure 2.14). They
are able to unwind again when required to do so.
Figure 2.14 Structure of a chromosome
1 a) i) How many dif ferent types of base molecule are i) Redraw the strand and then draw the
found in DNA? complementar y strand alongside it.
ii) Name each type. (3) ii) Label the 3′ end and the 5′ end on each
b) Which type of bond forms between the bases of strand. (2)
adjacent strands of a DNA molecule? (1) b) DNA consists of two strands whose backbones run in
c) Descr ibe the base-pair ing rule. (1) opposite directions. What term is used to describe
2 a) Figure 2.15 shows par t of one strand of a DNA this arrangement? (1)
molecule. 3 a) What name is given to the twisted coil arrangement
typical of a DNA molecule? (1)
C
A b) If DNA is like a spiral ladder, which par t of it
T corresponds to the ladder’s:
DNA strand G
C i) rungs
C
A ii) upr ights? (2)
T
G
T
A
G
3’ end
Figure 2.15
23
Human Cells Unit 1
Replication of DNA
DNA is a unique molecule because it is able to direct
its own replication and reproduce itself exactly.
The replication process is shown in a simple way in
Figure 2.16.
AT
CG DNA parental alignment of individual nucleotides
TA molecule composed of with nucleotides on templates
GC two complementary (according to base-pair ruling)
CG strands
AT
AT AT
CG CG
separation of two strands TA TA
GC GC
C G
A G C T
T
A
A T
C G each parental strand
T A acts as a template
formation of sugar–phosphate
G C
backbones in new strands
C G
A T
new strand
T
C C AT AT
A A pool of individual parental strand
C G CG CG
T T nucleotides
TA TA
A G
G GC GC each DNA molecule
CG CG composed of one parental
AT AT and one new strand
two DNA molecules genetically

identical to original parental molecule
Figure 2.16 DNA replication
Case Study Establishing which theory of DNA replication is correct

Watson and Crick accompanied their model of Testing the hypotheses
DNA with a theory for the way in which it could
Background
replicate. They predicted that the two strands
When E. coli bacteria are cultured, they take up
would unwind and each act as a template for the
nitrogen from the surrounding medium and build
new complementary strand. This would produce
it into DNA. They can be cultured for several
two identical DNA molecules each containing
generations in medium containing the common
one ‘parental’ strand and one newly synthesised
isotope of nitrogen (14N) or the heavy isotope (15N) as
strand. This so-called semi-conservative replication
their only source of nitrogen. When DNA is extracted
remained a theory until put to the test by Meselson
from each type of culture and centrifuged, the results
and Stahl.
shown in Figure 2.18 are obtained.
Hypotheses
Figure 2.17 shows three different hypotheses, each of
which could explain DNA replication.
24
hypothesis 1: hypothesis 2: hypothesis 3:

replication is conservative replication is semi-conservative replication is dispersive
parental
DNA
result of
first
replication
1 parental DNA: 1 new DNA all hybrid DNA all hybrid DNA
result of
second
replication
1 parental DNA: 3 new DNA 1 hybrid DNA: 1 new DNA all hybrid DNA
Figure 2.17 DNA replication hypotheses
Putting the hypotheses to the test replicate DNA once). Figure 2.19 predicts the outcome
Meselson and Stahl began with E. coli that had been of the experiment for each of the three hypotheses.
grown for many generations in medium containing Figure 2.20 shows the actual results of the
15N. They then cultured these bacteria in medium experiment. From these results it is concluded that
containing 14N and sampled the culture after hypothesis 2 is supported and that the replication of
20 minutes (the time needed by the bacteria to DNA is semi-conservative.
25
➜
Human Cells Unit 1
marker band of
DNA containing
14N
centrifugation
of DNA
E. coli cultured
in medium
containing 14N
centrifugation
of DNA
marker band of
‘heavy’ DNA
E. coli cultured
containing 15N
in medium
containing 15N
Figure 2.18 Labelling DNA with 14N or 15N
26
Figure 2.19 Predictions
predicted result if hypothesis supported
conservative replication semi-conservative replication dispersive replication
15N in molecule 14N in molecule

DNA
containing
14
N
after one DNA DNA
replication containing containing
14N and15N 14N and15N
DNA
containing
15N
1 parental DNA: 1 new DNA all hybrid DNA all hybrid DNA
DNA DNA
containing containing
14N 14N
DNA
after two containing
replications 14
N and15N
DNA
containing
15N DNA
containing
1 parental DNA: 3 new DNA 14 1 hybrid DNA: 1 new DNA
N and15N all hybrid DNA
➜
27
Human Cells Unit 1
centrifugation
of DNA
E. coli cultured band of

in 15N DNA containing 15N
after 20 minutes in 14N
centrifugation band of DNA

containing 14N and 15N
of DNA
E. coli in 14N
after a further
20 minutes in 14N
band of DNA
containing 14N
centrifugation band of DNA

containing 14N and 15N
of DNA
E. coli in 14N
Figure 2.20 Meselson and Stahl’s experiment
28
5’ end 3’ end
CG CG CG
CG CG CG
AT AT AT
GC GC GC
CG CG
DNA (drawn CG
TA TA TA
unwound GC GC GC
for sake of AT AT
AT
replication AT
simplicity) AT
CG fork AT
CG
GC GC C G
CG G C
CG DNA polymerase
AT
CG G
AT A T T
CG CG CG G
GC GC GC C
CG CG CG G
AT AT A T T
TA TA TA A
AT A T T
AT
CG CG
CG G
Enzyme control of DNA replication
C
enzymes. It begins when a starting point on DNA is
GC GC
GC
Figure 2.21 Formation of leading strand of replicated DNA

AT template A T
leading T
AT
DNA replication is a complex process involving many
CG strand of G
CG CG strand AT T
AT AT AT replicated DNA T
AT AT GC C
GC replication GC TA A
TA TA C G G
fork C
CG C G DNA polymerase GC
GC A T T
G C joins individual TA A
AT A T
nucleotides into T A
tion
TA T A A
A backbone G C C
ica
TA TA CG G
C
pl
GC GC A T T
template G
CG G
f re
CG (lagging strand C
T C
AT strand AT
C CG
no
GC formed on this GG
starting point GC G CG
CG A side as shown T
T
ctio
on parental C G CG G
CG T
CG in Figure 2.22) G
strand of DNA replication AT
dire
AT CG start of G
GC C
fork C
CG G
C G GC complementary G AT T
G C CG AT T
G 3’end of AT strand of T
C T T A A
A T primer AT replicated DNA CG G
T A
A TA
G G C C
TA A CG TA primer has been A
T G C
CG GC
A
CG replaced by DNA G
GC C TA primer
TA A CG G
CG C G 3’ end 5’ end
A G
3’end of individual
DNA strand nucleotides
primer
recognised. The DNA molecule unwinds and weak
hydrogen bonds between base pairs break, allowing
the two strands to separate (‘unzip’). These template
29
Human Cells Unit 1
strands become stabilised and expose their bases at a Formation of sugar–phosphate bonding between the
Y-shaped replication fork (see Figure 2.21). primer and an individual nucleotide and between the
individual nucleotides themselves is brought about
Formation of the leading DNA strand by DNA polymerase. Replication of the parental DNA
The enzyme that controls the sugar–phosphate bonding strand that has the 3′ end is continuous and forms the
of individual nucleotides into the new DNA strand is leading strand of the replicated DNA.
called DNA polymerase. This enzyme can only add
nucleotides to a pre-existing chain. For it to begin to Formation of the lagging DNA strand
function, a primer must be present. This is a short DNA polymerase is only able to add nucleotides to the
sequence of nucleotides formed at the 3′ end of the free 3′ end of a growing strand. Therefore the DNA
parental DNA strand about to be replicated, as shown parental template strand that has the 5′ end has to be
in Figure 2.21. replicated in fragments, each starting at the 3′ end of a
primer, as shown in Figure 2.22.
Once individual nucleotides have become aligned
with their complementary partners on the template Each fragment must be primed as before to enable
strand (by their bases following the base-pairing rules), the DNA polymerase to bind individual nucleotides
they become bound to the 3′ end of the primer and together. Once replication of a fragment is complete,
formation of the complementary DNA strand begins. its primer is replaced by DNA. Finally an enzyme called
5’ end 3’ end
CG
CG
AT parental DNA molecule
GC
CG
TA
GC
AT replication
AT fork
C G
G GC
C CG primer
A AT
C CG
G GC
C CG
A AT DNA polymerase bonds
T A
A T T nucleotides into backbone
C 3’ end G
A C
G of primer T
A C A G
C C
A G AT
A AT
G GC fragment of
T TA replicated DNA
C CG forming
dir
G C
G T
ect
A
A
ion
T A
A
T
T C primer has
of
G
CG been replaced
rep
C
A T AT by DNA
lica
G (leading DNA GC
G CG
tio
C
C
strand formed on CG
nw
A this side as shown AT ligase bonds

in Figure 2.21) CG
ith
C fragments of
G GC
in f
C CG replicated DNA
AT
rag
A into lagging
AT
A strand
me
T TA
CG
nts
C
G C
G
T TA
C CG
3’ end of parental 5’ end of parental

DNA molecule DNA molecule
30
Figure 2.22 Formation of lagging strand of replicated DNA
ligase joins the fragments together. The strand formed Requirements for DNA replication
is called the lagging strand of replicated DNA and its For DNA replication to occur, the nucleus must contain:
formation is described as discontinuous.
● DNA (to act as a template)
Many replication forks ● primers
When a long chromosome (e.g. one from a mammalian ● a supply of the four types of DNA nucleotide
cell) is being replicated, many replication forks operate ● the appropriate enzymes (e.g. DNA polymerase and
simultaneously to ensure speedy copying of the lengthy ligase)
DNA molecule (see Figure 2.23). ● a supply of ATP (for energy – see page 97).
part of lengthy
DNA molecule
Impor tance of DNA
DNA is the molecule of inheritance and it encodes the
replication fork hereditary information in a chemical language. This
takes the form of a sequence of organic bases, unique
to each species, which makes up its genotype. DNA
replication ensures that an exact copy of a species’
starting points
(origins of replication) genetic information is passed on from cell to cell
during growth and from generation to generation
during reproduction. Therefore DNA is essential for the
replication fork
continuation of life.
replication ‘bubble’
Figure 2.23 Replication forks
1 Decide whether each of the following statements is 2 Figure 2.24 shows part of a DNA molecule undergoing
true or false and then use T or F to indicate your choice. replication. Match numbers 1–6 with the following
Where a statement is false, give the word that should statements. (5)
have been used in place of the word in bold print. (5) a) DNA polymerase promotes formation of a fragment
a) Dur ing DNA replication, each DNA parental strand of the lagging strand of replicating DNA.
acts as a template. b) The parental double helix unwinds.
b) A guanine base can only pair up with a thymine c) DNA polymerase bonds nucleotide to pr imer.
base. d) Ligase joins fragments onto the lagging strand of
c) An adenine base can only pair with a cytosine base. replicating DNA.
d) Complementar y base pairs are held together by weak e) DNA polymerase promotes formation of the leading
antiparallel bonds. strand of replicating DNA.
e) Each new DNA molecule formed by replication f) The DNA molecule becomes stabilised as two
contains one parental and one new strand. template strands.
3 a) Name FOUR substances that must be present in a
nucleus for DNA replication to occur. (4)
b) Br iefly explain why DNA replication is impor tant. (2)
➜ 31
Human Cells Unit 1
Figure 2.24
32
RNA, transcription and translation
3 RNA, transcription and translation

A cell’s genotype (its genetic constitution) is
determined by the sequence of the DNA bases in
its genes (the genetic code). A cell’s phenotype (its
physical and chemical state) is determined by the
proteins that are synthesised when the genes are
adenine (A)
expressed. Gene expression involves the processes U
of transcription and translation (discussed in this C
chapter). It is affected by environmental factors acting
A
inside and outside the cell. Only a fraction of the genes
guanine (G) A
in a cell are expressed.
G
Structure of RNA U
uracil (U) C
The second type of nucleic acid is called RNA
G
(ribonucleic acid). Each nucleotide in an RNA molecule
is composed of a molecule of ribose sugar, an organic A
base and a phosphate group (see Figure 3.1). In RNA, G
the base uracil (U) replaces thymine found in DNA. cytosine (C)
C
Characteristic RNA DNA

Number of nucleotide One Two
strands present in one
molecule
Figure 3.2 Structure of RNA
Complementar y base Uracil Thymine
par tner of adenine
Unlike DNA, which consists of two strands, a molecule
Sugar present in a Ribose Deoxyr ibose of RNA is a single strand, as shown in Figure 3.2. The
nucleotide differences between RNA and DNA are summarised in
Table 3.1 Dif ferences between RNA and DNA Table 3.1.
note
5C
phosphate
simplification
ribose
sugar
organic base
3C
33
Figure 3.1 Structure of an RNA molecule
Human Cells Unit 1
Control of inherited types of base. Proteins contain 20 different types of
amino acid. If the bases are taken in groups of three
characteristics then this gives 64 (43) different combinations (see
The sequence of bases along the DNA strands contains Appendix 1). It is now known that each amino acid is
the genetic instructions that control an organism’s coded for by one or more of these 64 triplets of bases.
inherited characteristics. These characteristics are the Thus an individual’s genetic information is encoded
result of many biochemical processes controlled by in its DNA with each strand bearing a series of base
enzymes, which are made of protein. Each protein triplets arranged in a specific order for coding the
is made of one or more polypeptide chains. Each particular proteins needed by that individual.
polypeptide is composed of a large number of subunits
called amino acids. A protein’s exact molecular Gene expression through protein
structure, shape and ability to carry out its function
all depend on the sequence of its amino acids. This
synthesis
critical order is determined by the order of the bases in The genetic information for a particular polypeptide is
the organism’s DNA. By this means DNA controls the carried on a section of DNA in the nucleus. However,
structure of enzymes and, in doing so, determines the assembly of amino acids into a genetically determined
organism’s inherited characteristics. sequence takes place in the cell’s cytoplasm in tiny
structures called ribosomes. Figure 3.3 gives an
overview of gene expression through protein synthesis.
Genetic code A molecule of mRNA (messenger RNA) is formed
The information present in DNA takes the form of (transcribed) from the appropriate section of the DNA
a molecular language called the genetic code. The strand and carries that information to ribosomes. There
sequence of bases along a DNA strand represents a the mRNA meets tRNA (transfer RNA) and the genetic
sequence of ‘codewords’. DNA possesses four different information is translated into protein.
cell nuclear membrane
triplet
detail
A G A GG T T G A C G A A T A
T C T C C A A C T G C T T A T
DNA
transcription
mRNA
detail U C U C C A A C U G C U U A U
codon
translation at
ribosome
detail ser pro thr ala tyr

protein
amino acid
34
Figure 3.3 Over view of gene expression
Transcription transcription is initiated, as shown in Figure 3.4 (where

the DNA strand has been drawn uncoiled for the sake of
Transcription is the synthesis of mRNA from a section
simplicity).
of DNA. A promoter is a region of DNA in a gene where
polymerase
released
RNA
3’
5’
3’
5’
terminator
completed
transcript
of mRNA
released
primary
(see Figure
3.5)
3’
3’
5’
5’
transcript
of mRNA
forming
primary
3’
5’
DNA strand
mRNA
template
3’
5’
polymerase
RNA
3’
5’
5’
3’
DNA terminator
region (several
distant from
nucleotides
transcribed
promoter)
thousand
promoter
DNA of
of DNA
region
to be
gene
35
Figure 3.4 Transcr iption of mRNA
Human Cells Unit 1
RNA polymerase is the enzyme responsible for nucleotides are needed to code for an average-sized
transcription. As it moves along the gene from the polypeptide chain. This is explained by the fact that
promoter, unwinding and opening up the DNA strand, long stretches of DNA that exist within a gene do not
it brings about the synthesis of an mRNA molecule. play a part in the coding of the polypeptide. These non-
As a result of the base-pairing rule, the mRNA gets coding regions, called introns, are interspersed between
a nucleotide sequence complementary to one of the the coding regions, called exons. Therefore the region in
two DNA strands (the template strand), as shown in the primary transcript of mRNA responsible for coding
Figure 3.5. the polypeptide is fragmented.
RNA polymerase can only add nucleotides to the 3′
end of the growing mRNA molecule. The molecule
Splicing
Figure 3.6 shows how the introns are cut out and
elongates until a terminator sequence of nucleotides
removed from the primary transcript of mRNA and
is reached on the DNA strand. The resultant mRNA
the exons are spliced together to form mRNA with a
strand that becomes separated from its DNA template is
continuous sequence of nucleotides. This modified
called a primary transcript of mRNA.
mRNA passes out of the nucleus into the cytoplasm (see
Figure 3.7) and moves on to the next stage of protein
Modif ication of pr imar y transcr ipt
synthesis where it becomes translated into a sequence of
Normally the region of DNA transcribed to mRNA
amino acids.
is about 8000 nucleotides long yet only about 1200
T A
C G
C G
T A
RNA polymerase
template strand
of DNA C G RNA nucleotide
A T
G C C
A
G C
G RNA nucleotide
C G about to be joined
A U T to chain at 3’ end
3’
A U T
sugar–phosphate
G C C bond between
T adjacent nucleotides
A U
A U T hydrogen bonds
G C C between complementary
T A A bases
newly made
U
5’ to 3’ primary C
transcript of mRNA C
G
U T A
A C G
C G
G C
5’
Figure 3.5 Detail of transcr iption
36
DNA in a gene
intron exon transcription

primary transcript
of mRNA
5’ 3’
cutting out of introns
5’ 3’
splicing together of exons
mRNA ready excised

for translation introns
5’ 3’
Figure 3.6 Modif ication of primar y mRNA transcr ipt
1 State THREE ways in which RNA and DNA dif fer in

structure and chemical composition. (3)
2 a) In what way does the DNA of one species dif fer
from that of another, making each species
unique? (1)
b) How many bases in the genetic code correspond to
one amino acid? (1)
3 a) Draw a diagram of the mRNA strand that would be
transcr ibed from section X of the DNA molecule
shown in Figure 3.8. (2)
Figure 3.7 ‘Better luck next time, guys!’ section X
A T G G C A T A C
T A C C G T A T G
Figure 3.8
b) Name the enzyme that would direct this

process. (1)
4 a) What is the dif ference between an exon and an
intron? (1)
b) Which of these must be removed from the pr imar y
transcr ipt of mRNA? (1) 37
c) By what process are they removed? (1)
Human Cells Unit 1
Translation an anticodon. It is complementary to an mRNA codon
and corresponds to a specific amino acid carried by that
Translation is the synthesis of protein as a polypeptide
tRNA at its attachment site.
chain under the direction of mRNA. The genetic
message carried by a molecule of mRNA is made up Table 3.2 shows the relationship between mRNA’s
of a series of base triplets called codons. The codon codons, tRNA’s anticodons and the amino acids
is the basic unit of the genetic code. Each codon is coded. Many different types of tRNA are present in a
complementary to a triplet of bases on the original cell – one or more for each type of amino acid. Each
template DNA strand. tRNA picks up its appropriate amino acid molecule
from the cytoplasm’s amino acid pool at its site of
Transfer RNA attachment. The amino acid is then carried by the
A further type of RNA is found in the cell’s cytoplasm. tRNA to a ribosome and added to the growing end of a
This is called tRNA (transfer RNA) and it is composed polypeptide chain.
of a single strand of nucleotides. However, a molecule
The mRNA codon AUG (complementary to tRNA
of tRNA has a three-dimensional structure because it is
anticodon UAC) is unusual in that it codes for
folded back on itself in such a way that hydrogen bonds
methionine (met) and acts as the start codon. mRNA
form between many of its nucleotide bases, as shown
codons UAA, UAG and UGA do not code for amino
in Figure 3.9. Each molecule of tRNA has only one
acids but instead act as stop codons.
particular triplet of bases exposed. This triplet is called
site of attachment
5’ end for amino acid molecule
3’ end
hydrogen bond
simplification
site of attachment
for amino acid molecule
G U U
U
U anticodon anticodon
G
Figure 3.9 Structure of transfer RNA (tRNA)
38
Anticodon
Anticodon
Anticodon
Anticodon
(mRNA)
(mRNA)
(mRNA)
(mRNA)
(tRNA)
(tRNA)
(tRNA)
(tRNA)
Amino
Amino
Amino
Amino
Codon
Codon
Codon
Codon
acid
acid
acid
acid
UUU AAA phe UCU AGA ser UAU AUA tyr UGU ACA cys
UUC AAG phe UCC AGG ser UAC AUG tyr UGC ACG cys
UUA AAU leu UCA AGU ser UAA AUU STOP UGA ACU STOP
UUG AAC leu UCG AGC ser UAG AUC STOP UGG ACC trp
CUU GAA leu CCU GGA pro CAU GUA his CGU GCA arg
CUC GAG leu CCC GGG pro CAC GUG his CGC GCG arg
CUA GAU leu CCA GGU pro CAA GUU gln CGA GCU arg
CUG GAC leu CCG GGC pro CAG GUC gln CGG GCC arg
AUU UAA ile ACU UGA thr AAU UUA asn AGU UCA ser
AUC UAG ile ACC UGG thr AAC UUG asn AGC UCG ser
AUA UAU ile ACA UGU thr AAA UUU lys AGA UCU arg
AUG UAC met or ACG UGC thr AAG UUC lys AGG UCC arg
START
GUU CAA val GCU CGA ala GAU CUA asp GGU CCA gly
GUC CAG val GCC CGG ala GAC CUG asp GGC CCG gly
GUA CAU val GCA CGU ala GAA CUU glu GGA CCU gly
GUG CAC val GCG CGC ala GAG CUC glu GGG CCC gly
Table 3.2 mRNA codons, tRNA anticodons and the amino acids coded
(See Appendix 1 for full names of amino acids.)
Ribosomes
tRNA binding sites
Ribosomes are small, roughly spherical structures found ribosome
in all cells. They contain enzymes essential for protein
synthesis. Many ribosomes are present in growing cells
which need to produce large quantities of protein.
Binding sites
site site site
A ribosome’s function is to bring tRNA molecules E P A
(bearing amino acids) into contact with mRNA. A
ribosome has one binding site for mRNA and three
binding sites for tRNA, as shown in Figure 3.10.
Of the tRNA binding sites: mRNA binding site

● site P holds the tRNA carrying the growing 39
polypeptide chain Figure 3.10 Binding sites on a ribosome
Human Cells Unit 1
ribosome amino acid
leu
site P thr ser cys
pro
met
tRNA
hydrogen bonds A
U A G
form between G G C A
anticodon and A ant A G C
G G ico
start codon A codon don
U A C
A U G C C U A C U U C U U G C C U G U C C U U C A G A
5’ end of mRNA
template
peptide bond
leu
ser cys
site A thr
met pro
A G
site E A C A C
U G G
G A
A
U A C G G A
newly formed
start of polypeptide chain peptide bond ser
cys leu
met ser
pro thr
A G A G
C A G
tRNA discharged A G C
C G
from site E A
A
U G G A U G A
growing polypeptide chain
me newly formed peptide bond

t
pro
thr ph
ser cys e
leu ser
A A
C
G A A A G
G
A
G U C G G
G A C A G G
U
A A
40
Figure 3.11 Translation of mRNA into polypeptide

● site A holds the tRNA carrying the next amino acid Polyribosome
to be joined to the growing chain by a peptide bond A single molecule of mRNA is normally used to
● site E discharges a tRNA from the ribosome once its make many copies of the polypeptide. This multiple
amino acid has become part of the polypeptide chain.
translation is achieved by several ribosomes becoming
attached to the mRNA and translating its message
Start and stop codons in action at the same time. Such a string of ribosomes on the
Before translation can begin, a ribosome must bind to same mRNA molecule is called a polyribosome (see
the 5′ end of the mRNA template so that the mRNA’s Figure 3.12).
start codon (AUG) is in position at binding site P.
Next a molecule of tRNA carrying its amino acid
(methionine) becomes attached at site P by hydrogen
One gene, many proteins
bonds between its anticodon (UAC) and the start codon Alternative RNA splicing
(see Figure 3.11). Figure 3.6 on page 37 shows a primary transcript of
mRNA being cut up and its exons being spliced together
The mRNA codon at site A recognises and then forms
to form a molecule of mRNA ready for translation.
hydrogen bonds with the complementary anticodon on
This molecule of mRNA is not the only one that can
an appropriate tRNA molecule bearing its amino acid.
be produced from that primary transcript. Depending
When the first two amino acid molecules are adjacent to
on circumstances, alternative segments of RNA may
one another, they become joined by a peptide bond.
be treated as the exons and introns. Therefore the same
As the ribosome moves along one codon, the tRNA primary transcript has the potential to produce several
that was at site P is moved to site E and discharges from mRNA molecules each with a different sequence of base
the ribosome to be reused. At the same time the tRNA triplets and each coding for a different polypeptide. In
that was at site A is moved to site P. The vacated site A other words, one gene can code for several different
becomes occupied by the next tRNA bearing its amino proteins and a limited number of genes can give rise to
acid, which becomes bonded to the growing peptide a wide variety of proteins.
chain. The process is repeated many times allowing the
mRNA to be translated into a complete polypeptide One gene, two antibodies – an example of
chain. alternative splicing
An antibody is a Y-shaped protein molecule. The two
Eventually a stop codon (see Table 3.2) on the mRNA is
antibody molecules (P and Q) shown in Figure 3.13
reached. At this point, site A on the ribosome becomes
are coded for by the same gene yet they are different
occupied by a release factor, which frees the polypeptide
in structure. P possesses a membrane-anchoring unit
from the ribosome. The whole process needs energy
coded for by an exon present in its mRNA. However,
from ATP (see chapter 7).
this membrane-anchoring unit is absent from Q
because its mRNA lacks the necessary exon (discarded
completed polypeptide
growing polypeptide
antibody Q
antibody P
ribosome
membrane of white
membrane-anchoring unit blood cell
5’ end 3’ end
start end of mRNA direction of translation
inside cell
41
Figure 3.12 Polyribosome Figure 3.13 Products of alternative RNA splicing
Human Cells Unit 1
as an intron at the splicing stage). As a result, antibody
P functions as a membrane-bound protein on the
outer surface of a white blood cell whereas antibody Q
single polypeptide chain
operates freely in the bloodstream.
Post-translational modif ications

Once translation is complete, further modification (in
addition to the folding and coiling described on page
45) may be required to enable a protein to perform its
specific function.
molecular folding and
sulphur bridge formation
Cleavage
A single polypeptide chain may need to be cut (cleaved)
by enzymes to become active. The protein insulin,
for example, begins as a single polypeptide chain but sulphur bridges
requires its central section to be cut out by protease
enzymes. This results in the formation of an active
protein consisting of two polypeptide chains held
activity of protease
together by sulphur bridges, as shown in Figure 3.14. enzymes
Molecular addition
A protein’s structure can be modified by adding a
carbohydrate component or a phosphate group to
it. Mucus, for example, is a glycoprotein consisting enzyme
of protein to which carbohydrate has been added. action
Regulator y proteins often require the addition of
cleavage of central
a phosphate group to make them functional. p53, enzyme section of molecule
for example, is a regulatory protein that is normally action
inactive. However, in situations where a cell’s DNA

polypeptide A
has become damaged, phosphate is added to p53.
This process of phosphorylation (see page 99) makes active
insulin
inactive p53 change in structure and become active molecule
p53 tumour-suppressor protein. It then brings about
an appropriate outcome such as repair of DNA or, in
polypeptide B redundant
extreme cases, programmed cell death.
central
section
Figure 3.14 Post-translational modif ication by cleavage
42
1 a) How many anticodons in a molecule of tRNA are 4 Choose the correct answer from the underlined choice
exposed? (1) for each of the following statements. (6)
b) Each molecule of tRNA has a site of attachment at a) The basic units of the genetic code present on mRNA
one end. What becomes attached to this site? (1) are called anticodons/codons.
2 a) What is a ribosome? (1) b) The synthesis of mRNA from DNA is called
b) i) How many tRNA binding sites are present on a transcr iption/translation.
r ibosome? c) A non-coding region of mRNA is called an intron/
ii) To what does a tRNA’s anticodon become bound exon.
at one of these sites? (2) d) Protein synthesis occurs in a cell’s nucleus/
c) What type of bond forms between adjacent amino cytoplasm.
acids attached to tRNA molecules? (1) e) Cleavage of the insulin polypeptide is an example of
d) What is the fate of a tRNA molecule once its amino pre-/post-translational modif ication.
acid has been joined to the polypeptide chain? (2) f) To become functional, some molecules of regulator y
3 Copy and complete Table 3.3. (2) proteins need the addition of phosphate/r ibose
groups.
Stage of synthesis Site in cell
Formation of pr imar y transcr ipt of mRNA
Modif ication of pr imar y transcr ipt of mRNA
Collection of amino acid by tRNA
Formation of codon–anticodon links
Table 3.3
What You Should Know Chapters 1–3
1 Stem cells are ______ cells that can reproduce

adenine fragments research themselves and can ______ into specialised cells.
anticodons genetic r ibose 2 ______ stem cells are able to dif ferentiate into all the
antiparallel guanine r ibosomes cell types that make up the human body. ______ (adult)
backbone helix RNA polymerase stem cells are only able to regenerate a limited range of
cell types.
bonds introns splicing
character istic ligase star ting 3 A dif ferentiated cell only expresses the genes for the
proteins ______ of that cell type.
codons modif ication therapy
complementar y nucleotides thymine 4 Stem cells are used in ______ to gain a better
understanding of cell growth and gene regulation.
cytosine polypeptide tissue
In the future, several debilitating conditions may be
deoxyr ibose pr imar y transcr iption treated successfully using stem cell ______.
dif ferentiate pr imer translation
5 Cancerous cells fail to respond to cell cycle ______ and
DNA polymerase protein tumour divide excessively to form a ______.
embr yonic regulators unspecialised
6 DNA consists of two strands twisted into a double
exons replication uracil ______. Each strand is composed of ______. Each
nucleotide consists of ______ sugar, phosphate and one
Table 3.4 Word bank for chapters 1–3 of four types of base (______, thymine, ______ and
cytosine). 43
➜
Human Cells Unit 1
7 Adenine always pairs with ______; guanine always pairs 12 DNA contains an individual’s ______ information as a
with ______. coded language determined by the sequence of its bases
arranged in tr iplets called ______. Expression of this
8 Within each DNA strand neighbour ing nucleotides are
information through ______ synthesis occurs in two
joined by chemical ______ into a sugar–phosphate
stages when a gene is switched on.
______. The backbones of complementar y strands are
______ because they run in opposite directions. 13 The f irst stage, ______, begins when the enzyme
______ becomes attached to, and moves along,
9 DNA is unique because it can direct its own ______.
the DNA, br inging about the synthesis of a ______
This begins by DNA unwinding and its two strands
transcr ipt of mRNA from individual RNA nucleotides.
separating at a ______ point. A ______ forms beside
Pr imar y RNA is cut and spliced to remove non-coding
the DNA strand with the 3’ end. Individual nucleotides
regions called ______ and to bind together coding
aligned with ______ nucleotides on the DNA strand
regions called ______.
become joined into a new DNA strand by the enzyme
______. 14 The second stage, ______, occurs at ______ where
codons on the mRNA strand match up with the ______
10 The DNA strand with the 5’ end is replicated in ______
on tRNA molecules carr ying amino acids. These become
that are joined together by the enzyme ______.
joined together by peptide bonds to form a ______
11 RNA dif fers from DNA in that it is single-stranded, chain whose amino acid sequence reflects the code on
contains ______ (not deoxyr ibose) and the base the mRNA.
______ in place of thymine.
15 Alternative ______ of pr imar y mRNA and post
translational ______ of protein structure enable a gene
to be expressed as several proteins.
44
Proteins, mutations and genetic disorders
4 Proteins, mutations and genetic disorders
Structure of proteins cross-connections occur between amino acids in the

same polypeptide chain and those on adjacent chains.
All proteins contain the chemical elements carbon (C), They are important because they cause the molecule
hydrogen (H), oxygen (O) and nitrogen (N). Often they to adopt the final three-dimensional structure that it
contain sulphur (S). Each protein is built up from a needs to carry out its specific function.
large number of subunits called amino acids of which
there are 20 different types. The length of a protein Some types of protein molecule are formed by several
molecule varies from many thousands of amino acids to spiral-shaped polypeptide molecules becoming linked
just a few. Insulin, for example, contains only 51. together in parallel when bonds form between them.
This gives the protein molecule a rope-like structure
Polypeptides (see Figure 4.1). Other types of protein molecule consist
of one or more polypeptide chains folded together into
Amino acids become joined together into chains by
a roughly spherical shape like a tangled ball of string
chemical links called peptide bonds. Each chain is called
(see Figure 4.1). The exact form that the folding takes
a polypeptide and it normally consists of hundreds
depends on the types of further linkage that form
of amino acid molecules linked together. During the
between amino acids on the same and adjacent chains.
process of protein synthesis (see page 34), amino
acids are joined together in a specific order, which is A computer-generated representation of a protein
determined by the sequence of bases on a portion of molecule’s three-dimensional structure is shown in
DNA. This sequence of amino acids determines the Figure 4.2.
protein’s ultimate structure and function.
Hydrogen bonds
Chemical links known as hydrogen bonds form
between certain amino acids in a polypeptide chain,
causing the chain to become coiled or folded as shown
in Figure 4.1 on page 46.
Further linkages
During the folding process, different regions of the
chain(s) come into contact with one another. This
allows interaction between individual amino acids
in one or more chains. It results in the formation of
various types of cross-connection including bridges
between sulphur atoms, attraction between positive and
negative charges and further hydrogen bonding. These Figure 4.2 Protein molecule as visualised by RasMol sof tware
45
Human Cells Unit 1
amino acids
amino acids become joined together by peptide

bonds in a particular genetically-determined sequence
peptide bond
etc. etc.
hydrogen bonds form between certain amino acids

etc.
etc.
hydrogen bond hydrogen bond
or
polypeptide
chain folded
polypeptide
chain coiled
etc.
etc.
polypeptide chains become
polypeptide chains become

polypeptide chains
folded together into spherical
arranged in long
become folded together
shape which incorporates another
parallel strands
into spherical shape
chemical
sulphur non-protein part

polypeptide
bridge
chain 1
polypeptide
chain 2
hydrogen
bond
46
Figure 4.1 Structure of proteins
Related Activity
Separation of fish proteins by agarose Identif ication of f ish proteins

gel electrophoresis Protein Molecular weight (kDa)
Gel electrophoresis is a technique used to separate
a 210
electr ically charged molecules by subjecting them to an
electr ic current, which forces them to move through a b 107
sheet of gel. c 90
Eliminating two variable factors d 42
The behaviour of a protein molecule dur ing gel
e 35
electrophoresis is af fected by three variable factors:
its shape, its size and its net electr ic charge. In this f 30
exper iment variation in shape of the protein molecule g 5
and var iation in electr ic charge (e.g. positive or negative)
are eliminated by subjecting each protein sample to a Table 4.1 Proteins in standard sample
negatively charged detergent, a session of heat treatment
Figure 4.4 shows a gel with f ive lanes resulting from the
and a reducing agent. These processes give the molecule
electrophoresis process. The standard sample is known
a uniformly negative charge and disrupt its hydrogen
to contain the seven f ish proteins listed in Table 4.1. The
bonding and sulphur br idges. All the protein molecules
band nearest to the well in lane 1 represents the largest
become conver ted to one or more negatively charged
protein molecule, which has moved the shor test distance
linear polypeptides and therefore only var y in size
(i.e. protein a). Similarly, band b represents the next
(molecular weight).
largest and so on to band g, which has moved the fur thest
How the process works distance and must be the smallest. Compar ison of each
When negatively charged molecules of protein are placed of lanes 2–5 with the standard reveals the identity of the
at one end of a sheet of gel and subjected to an electr ic proteins present in the extract from a par ticular species
current, they move towards the opposite, positively of f ish.
charged end of the gel. However, the molecules do not all
move through the gel at the same rate. Smaller molecules standard extract of proteins from:
move at a faster rate and are therefore found to have sample fish W fish X fish Y fish Z
moved further than larger molecules in a given per iod of well
time. a
The technique illustrated in Figure 4.3 on page 48 is used

to separate the proteins present in extracts from four
species of f ish (W, X, Y and Z) and those in a standard
sample of known proteins. b
c
protein
d
e
lane 1 lane 2 lane 3 lane 4 lane 5
Figure 4.4 Banding results of gel electrophoresis

47
➜
Human Cells Unit 1
1
molten agarose is poured
into gel casting tray comb inserted into mould
to make wells while
gel is solidifying
2 comb removed
leaving wells in gel
gel casting tray
solidified gel
3
buffer solution
added sheet of gel transferred to
well
horizontal electrophoresis chamber
electrophoresis-
chamber
electrode –
different micro-
4 pipette used to
load each well
with a different fish
electrode + protein sample
standard W X Y Z
fish protein extracts

standard of –
5
known fish proteins
extract from fish chamber connected
W XY Z
proteins in the to power supply
sample become +
separated as
they move
through blue stain
the gel 6
staining tray added
sheet of gel transferred
to staining tray
POWER
SUPPLY
7 destaining solution added
gel rinsed with

gel turns
distilled water blue
blue background
of gel lightens
distinct blue banding

pattern revealed
48 Figure 4.3 Separation of f ish proteins by gel electrophoresis

Functions of proteins Antibodies

A vast variety of structures and shapes exists among Antibodies are also made of protein. They have a
proteins and as a result they are able to perform a wider characteristic Y-shape (see Figure 4.5). They are
range of functions than any other type of molecule produced by white blood cells to defend the body
in the body. Some are found in bone and muscle, against antigens (see chapter 22).
where their strong fibres provide support and allow
movement. Others are vital components of all living
cells and play a variety of roles, as follows.
Enzymes
Each molecule of enzyme is made of protein and is
folded in a particular way to expose an active surface
that readily combines with a specific substrate (see
chapter 6). Since intracellular enzymes speed up the
rate of biochemical processes such as respiration and
protein synthesis, they are essential for the maintenance
of life.
Structural proteins
Protein is one of two main components that make up
Figure 4.5 Antibody molecule
the membrane surrounding a living cell. Similarly it
forms an essential part of all membranes possessed by
a cell’s organelles. Therefore this type of protein plays a Associations with other chemicals
vital structural role in every living cell. Some types of protein molecule are associated with
non-protein chemicals (see Figure 4.1). A glycoprotein
Hormones is composed of protein and carbohydrate. An example
These are chemical messengers transported in an is mucus, the slimy viscous substance secreted
animal’s blood to ‘target’ tissues where they exert a by epithelial cells for protection and lubrication.
specific effect. Some hormones are made of protein and Haemoglobin is the oxygen-transporting pigment in
exert a regulatory effect on the animal’s growth and blood. It consists of protein associated with non-protein
metabolism. A few examples are given in Table 4.2. structures containing iron.
Hormone Secretor y gland Role of hormone

Insulin Pancreas Regulates concentration of glucose in blood
Anti-diuretic hormone Pituitar y Controls water balance of human body
Human growth hormone Pituitar y Promotes growth of long bones
Table 4.2 Hormones composed of protein
49
Human Cells Unit 1
1 a) How many dif ferent types of amino acid are known to a) Amino acid molecules become linked by hydrogen
occur in proteins? (1) bonds to form polypeptide chains.
b) What name is given to the chain formed when several b) A chemical element always present in protein but
amino acids become linked together? (1) absent from carbohydrates is sulphur.
c) What determines the order in which amino acids are c) Folding of polypeptide chains to form a three-
joined together into a chain? (1) dimensional protein molecule results from hydrogen
d) Descr ibe T WO ways in which chains of amino acids bonding.
can become arranged to form a protein. (2) d) Insulin is a hormone that regulates blood sugar
2 Decide whether each of the following statements is concentration.
true or false and then use T or F to indicate your choice. e) A glycoprotein such as mucus is composed of protein
Where a statement is false, give the word that should and haemoglobin.
have been used in place of the word in bold pr int. (5)
Mutation rarely. The mutation rate of a gene is expressed as the

number of mutations that occur at that gene site per
A mutation is a change in the structure or composition
million gametes. Mutation rate varies from gene to gene
of an organism’s genome. It varies in form from a
and species to species.
tiny change in the DNA structure of a gene to a large-
scale alteration in chromosome structure or number.
When such a change in genotype produces a change in Mutagenic agents
phenotype, the individual affected is called a mutant. Mutation rate can be artificially increased by mutagenic
agents. These include certain chemicals (e.g. mustard
Frequency of mutation gas) and various types of radiation (e.g. gamma rays,
X-rays and UV light). The resultant mutations are
In the absence of outside influences, gene mutations
described as induced.
arise spontaneously and at random but only occur
Related Activity
Investigating the effect of UV radiation Investigating the effect of UV radiation

on UV-sensitive yeast cells on ‘protected’ UV-sensitive yeast
Normal yeast cells have genes that code for enzymes The above exper iment is repeated and extended to
that repair damage done to their DNA by UV radiation. include two fur ther Petr i dishes, V and W, wrapped in
UV-sensitive yeast is a strain that has had these genes Clingf ilm. Their top sur faces are smeared each with a
‘knocked out’ by genetic engineer ing. Therefore it is dif ferent sun barr ier cream (e.g. protection factors 6 and
unable to repair damaged DNA resulting from exposure to 20) and then exposed to the UV light source as before.
UV radiation. If more yeast colonies grow on the plate with the higher
protection factor then this result suggests that the higher
The exper iment is carr ied out as shown in Figure 4.6.
factor has given them more protection from the harmful
Af ter 2 days of incubation, plate X is found to lack yeast
UV rays than the lower factor.
colonies whereas plate Y, the control, has many colonies.
Therefore it is concluded that exposure to UV radiation
has had a lethal ef fect on UV-sensitive yeast.
50
sterile yeast
sterile extract dextrose
inoculating (YED agar)
loop
culture of UV- loop used to inoculate
sensitive yeast
plate with yeast
multiple streaking carried out

UV-sensitive
yeast
plate wrapped in metal

foil and incubated
at 30 °C for 2 days
single colony transferred using a sterile loop

1 ml transferred after mixing, every time
A B C D E
sample of yeast
tube containing suspension added
10 ml of sterile to plates X and Y
water at start and spread
evenly over agar
tubes containing 9 ml of sterile water at the start

tube A B C D E
dilution factor 0 10 102 103 104
X Y sterile YED
agar in each
plate
sterile glass
spreader
plate exposed to UV light, plate wrapped in metal foil

wrapped in metal foil and and incubated at 30 °C
incubated at 30 °C for 2 days for 2 days
no yeast many
colonies yeast
colonies
Figure 4.6 Ef fect of UV radiation on UV-sensitive yeast 51

Human Cells Unit 1
Genetic disorder Most proteins are indispensible to the organism.
For example, an enzyme that controls a key step
A condition or disease that can be shown to be directly
in a metabolic pathway is essential for the normal
related to an individual’s genotype is called a genetic
functioning of the body. Therefore the presence of
disorder. For a protein to function properly it must
an altered version of the protein (or its total absence)
possess the correct sequence of amino acids determined
may result in disruption of the pathway and result in a
by the order of the nucleotide bases on a particular
genetic disorder. Many genetic disorders are disabling
region of DNA in a gene. A change to the gene (or
and some are lethal.
chromosome) caused by a mutation may result in the
gene expressing a version of the protein that does not Single-gene mutation
function correctly. The mutated gene may even fail to
This type of mutation involves an alteration of a
express the protein at all.
nucleotide sequence in the gene’s DNA.
(a) substitution of a nucleotide and its effect
nucleotide with base A has
replaced nucleotide with base T
normal mutant
DNA strand
T
A G A G T C T T C A G A G A C T T C
U C U C A G A A G U C U C U G A A G
mRNA coded
part of protein serine glutamine lysine serine leucine lysine

expressed
only this one amino
acid is altered
(b) insertion of a nucleotide and its effect

extra nucleotide with
base G inserted
normal mutant
DNA strand
A G A G T C T T C A G A G G T C T T
U C U C A G A A G U C U C C A G A A
mRNA coded
part of protein serine glutamine lysine serine proline glutamic

expressed acid
all amino acids after this

one are also altered
because of frameshift
(c) deletion of a nucleotide and its effect
nucleotide with
base T deleted
normal mutant T
DNA strand
A G A G T C T T C A G A G C T T C G
U C U C A G A A G U C U C G A A G C
mRNA coded
part of protein
serine glutamine lysine serine arginine serine
expressed
all amino acids after this
one are also altered
because of frameshift
52
Figure 4.7 Types of point mutation
Point mutation on page 37). Splicing is controlled by specific nucleotide

sequences at splice sites on those parts of introns
A point mutation involves a change in one nucleotide
that flank exons. If a mutation occurs at one of these
in the DNA sequence of a single gene. Three types
splice sites, the codon for an intron–exon splice may be
of point mutation are shown in Figure 4.7. A single
affected and an intron may be retained in error by the
nucleotide is either substituted, inserted or deleted. In
modified mRNA (see Figure 4.8).
each case this results in one or more codons for one or
more amino acids becoming altered.
Nucleotide sequence repeat
Splice-site mutation expansion
Before mRNA leaves the nucleus, introns (non-coding A gene mutation can also be the result of a
regions) are removed and exons (coding regions) are trinucleotide (triplet) repeat expansion. Figure 4.9
joined together. This process of post-transcriptional shows a simplified version of this process. In reality, it
processing of mRNA is called splicing (see Figure 3.6 normally involves the insertion of a large number of
mutation at splice
intron exon site on intron
primary transcript of mRNA
cutting out of introns

intron remains
attached to exon
splicing together of exons

intron retained by
modified mRNA
modified mRNA ready for translation

excised introns
Figure 4.8 Ef fect of splice-site mutation
mutation causes repeats

of GTC triplet
normal mutant
DNA strand
A G A G T C T T C A G A G T C G T C G T C T T C
U C U C A G A A G U C U C A G C A G C A G A A G
mRNA coded
part of protein
expressed serine glutamine lysine serine glutamine glutamine glutamine lysine
extra copies of an amino acid

present in protein
53
Figure 4.9 Tr inucleotide repeat expansion mutation
Human Cells Unit 1
copies of the nucleotide sequence (e.g. several hundred synthesis to be halted prematurely (see Figure 4.10) and
repeats) that makes the protein, if expressed, defective. results in the formation of a polypeptide chain that is
shorter than the normal one and unable to function.
Impact on protein structure This change in genome is called a nonsense mutation.
(See the Case Study on Duchenne muscular dystrophy.)
Missense
Following a substitution, the altered codon codes for Splice-site mutation
an amino acid that still makes sense but not the original If one or more introns have been retained by modified
sense (see Figure 4.10). This change in genome is called mRNA, they may in turn be translated into an altered
a missense mutation. (See the Case Studies on sickle- protein that does not function properly. (See the Case
cell disease and phenylketonuria.) Study on beta (β) thalassemia.)
Nonsense Frameshif t
As a result of a substitution, a codon that used to code mRNA is read as a series of triplets (codons) during
for an amino acid is exchanged for one that acts as a translation. Therefore, if one base pair is inserted or
stop codon (UAG, UAA or UGA). It causes protein deleted (see Figure 4.7) this affects the reading frame
part of normal gene

DNA strand
G T T T T T A A A
C A A A A A U U U
mRNA coded
part of protein
expressed
glutamine lysine phenylalanine missense mutation
T
G T T C T T A A A
C A A G A A U U U
Substitution of nucleotide glutamine glutamic phenylalanine

with base T for one with acid
base C. Altered amino acid (different chemical
makes protein function properties to lysine)
in a different way.
nonsense mutation
T
G T T A T T A A A
Substitution of nucleotide
with base T for one with base A. C A A U A A U U U
Altered codon’s STOP message
brings translation to a halt.
STOP
glutamine
54
Figure 4.10 Possible ef fects of a base-pair substitution on sequence of amino acids
(triplet grouping) of the genetic code. It becomes nucleotide sequence repeat may occur to such an extent
shifted in a way that alters every subsequent codon and that the gene is silenced and fails to express any protein
amino acid coded all along the remaining length of the at all. (See the Case Studies on fragile X syndrome and
gene. The protein formed is almost certain to be non Huntington’s disease.)
functional. This change in genome is called a frameshift
mutation. (See the Case Studies on Tay-Sachs syndrome Ef fect on suf ferer
and cystic fibrosis.) The effects of single gene mutations on the sufferers of
the resultant genetic disorders are exemplified in the
Nucleotide sequence repeat expansion accompanying case studies. Almost without exception, a
This can result in the production of a defective protein genetic disorder has an adverse effect on the individual
possessing a string of extra copies of one particular affected.
amino acid. On the other hand, expansion of a
Case Study Sickle-cell disease

When one of the genes on chromosome 11 that type and tend to stick together and interfere with
codes for haemoglobin undergoes a substitution blood circulation. The result of these problems is
(see Figure 4.11), it becomes expressed as an unusual severe shortage of oxygen followed by damage to vital
form of haemoglobin called haemoglobin S. This is organs and, in many cases, death. This potentially
an example of missense. Although haemoglobin S lethal genetic disorder is called sickle-cell anaemia.
differs from normal haemoglobin by only one amino
acid, that one tiny alteration leads to profound normal red sickle-shaped
blood cells red blood cells
changes in the folding and ultimate shape of the
haemoglobin S molecule, making it a very inefficient
carrier of oxygen.
People who are homozygous for the mutant allele

suffer drastic consequences. In addition to all of
their haemoglobin being type S, which fails to
perform the normal function properly, sufferers also
possess distorted, sickle-shaped red blood cells (see
Figure 4.12). These are less flexible than the normal
Figure 4.12 Two types of red blood cell
nucleotide with base A has

normal mutant replaced nucleotide with base T
DNA strand
G G C C T C C T C G G C C A C C T C
C C G G A G G A G C C G G U G G A G
mRNA coded
part of protein glutamic glutamic glutamic

expressed proline acid acid proline valine
acid
normal haemoglobin haemoglobin S
This mutation (involving a change

in only one amino acid) also results in
the formation of sickle-shaped red blood
cells. The homozygous mutants suffer
from sickle-cell anaemia.
55
Figure 4.11 Mutation causing sickle-cell disease ➜
Human Cells Unit 1
Sickle-cell trait Resistance to malar ia
People who are heterozygous for the mutant The sickle-cell mutant allele is rare in most
allele do not suffer sickle-cell anaemia. Instead populations. However, in some parts of Africa up
they are found to have a milder condition called to 40% of the population have the heterozygous
sickle-cell trait. Their red blood cells contain both genotype. This is because sickle-cell trait sufferers
forms of haemoglobin but do not show ‘sickling’. are resistant to malaria. The parasite cannot make
The slight anaemia that they tend to suffer does not use of the red blood cells containing haemoglobin S.
prevent moderate activity. This situation, where a genetic disorder confers an
advantage on its sufferers, is very unusual.
Case Study Phenylketonuria (PKU)
Phenylalanine and tyrosine are two amino acids of this inborn error of metabolism, phenylalanine
that human beings obtain from protein in their diet. is no longer converted to tyrosine. Instead it
During normal metabolism, excess phenylalanine accumulates and some of it is converted to toxins.
is acted on by an enzyme (enzyme 1 in the pathway
These poisonous metabolites inhibit one or more
shown in Figure 4.13).
of the enzymes that control biochemical pathways
Phenylketonuria is a genetic disorder caused by a in brain cells. The brain fails to develop properly,
mutation to a gene on chromosome 12 that normally resulting in the person having severe learning
codes for enzyme 1 in the pathway. Most commonly, difficulties. In Britain, newborn babies are screened
the mutated gene has undergone a substitution of a for PKU and sufferers are put on a diet containing
nucleotide and missense occurs. The altered form of minimum phenylalanine. By this means, the worst
the protein expressed contains a copy of tryptophan effects of PKU are reduced to a minimum.
in place of arginine and is non-functional. As a result
enzyme
intermediate 3 melanin
enzyme metabolite (skin pigment)
2
enzyme
phenylalanine 1 tyrosine
(an amino acid) (an amino acid)
other other metabolites,

enzymes e.g. thyroxine (hormone)
Figure 4.13 Normal fate of phenylalanine
56
Case Study Duchenne muscular dystrophy (DMD)
Duchenne muscular dystrophy (DMD) is caused by Duchenne muscular dystrophy is the most
any one of several types of mutation to a particular common form of muscular dystrophy (muscle
gene on chromosome X, such as a deletion or a wasting disease). In the absence of dystrophin,
nonsense mutation. The affected gene fails to code skeletal muscles become weak and lose their
for a protein called dystrophin, which is essential normal structure. This condition is accompanied
for the normal functioning of muscles. In skeletal by progressive loss of coordination. Sufferers are
and cardiac muscle, for example, dystrophin is part severely disabled from an early age and normally die
of a group of proteins that strengthen muscle fibres young without passing the mutant allele on to the
and protect them from injury during contraction and next generation. DMD is sex-linked and is almost
relaxation. entirely restricted to males, being passed on by
carrier mothers to their sons.
Case Study Beta (β) thalassemia
A molecule of haemoglobin is composed of two There are several forms of β-thalassemia, some
alpha-globin and two beta-globin polypeptide chains. more severe than others. One type, for example, is
These polypeptides are encoded by genes. characterised by the complete lack of production of
beta-globin; another by the production of an altered
Beta (β) thalassemia is a genetic disorder caused by
version of the protein. In either case, the sufferer has
any one of several types of mutation that affect a
a relative excess of alpha-globin in their bloodstream,
gene on chromosome 11 that codes for beta-globin.
which tends to bind to, and damage, red blood cells.
One of the most common of these mutations is a
Patients with severe β-thalassemia require medical
substitution that occurs at a splice site on an intron
treatment such as blood transfusions.
and causes base G to be replaced by base A.
Case Study Tay-Sachs disease
Tay-Sachs disease is a genetic disorder resulting in the frameshift effect. The protein expressed is
from a mutation to a gene on chromosome 15. Under so different from the normal one that it is non
normal circumstances the gene is responsible for functional. As a result, the enzyme’s unprocessed
encoding an enzyme that controls an essential substrate accumulates in brain cells. This leads to
biochemical reaction in nerve cells. neurological degeneration, generalised paralysis and
death at about 4 years of age. (See page 252.)
Changes to the gene take the form of point mutations
such as insertions and deletions, which result
57
Human Cells Unit 1
Case Study Cystic fibrosis
Cystic fibrosis is a genetic disorder caused by a three-

base-pair deletion to a gene on chromosome 7. This
type of mutation removes a codon for phenylalanine
and causes the coded message to be seriously
altered by the frameshift effect and produce a non
functional protein.
The normal allele for the gene codes for a membrane

protein that assists in the transport of chloride ions
into and out of cells. In the absence of this protein an
abnormally high concentration of chloride gathers
outside cells. Those regions of the body that coat
their cells with mucus become affected because
the high concentration of chloride causes mucus
to become thicker and stickier. Organs such as
the lungs, pancreas and alimentary canal become Figure 4.14 Easing symptoms of cystic f ibrosis
congested and blocked. Regular pounding on the
chest to clear thick mucus (see Figure 4.14) and daily
use of antibiotics can extend a sufferer’s life into their
thirties and beyond. Untreated, the sufferer normally
dies at age 4–5 years.
Case Study Fragile X syndrome
Fragile X syndrome is a leading cause of a wide normally active in brain synapses and involved in
spectrum of inherited mental disabilities. It is the control of synaptic plasticity (see page 262). Lack
characterised by a variety of physical features and of this essential protein results in retarded neural
mental limitations, such as a very elongated face, low development.
muscle tone, nervous speech, poor memory and a
Whereas the gene of an unaffected individual
very short attention span.
contains 6–53 repeats of the CGG triplet, a sufferer
This genetic disorder is caused by a nucleotide of fragile X syndrome may have as many as 4000
sequence repeat expansion of CGG coded from a repeats. Such expansion of the trinucleotide repeat
region of the X chromosome. This mutation results brings about silencing of the affected gene. There is
in the failure of a gene to encode a protein that is no treatment available for this condition.
58
Case Study Huntington’s disease
Huntington’s disease is caused by a gene on Unlike all of the other genetic disorders described
chromosome 4 that has been affected by a nucleotide above, the mutant allele for Huntington’s disease
sequence repeat expansion. This type of mutation is dominant and therefore affects people with a
results in the codon CAG being repeated more than heterozygous genotype. In addition, the symptoms
35 times. The affected gene no longer encodes a of this genetic disorder often do not appear until
certain protein essential for the normal functioning the person reaches early middle age. Death usually
of the nervous system. Instead it codes for a defective follows 10–20 years later. Prior to the onset of the
form of the protein bearing a long chain composed disease, each potential sufferer runs a 50% chance of
of repeats of glutamine (the amino acid encoded by passing the lethal allele on to each of their offspring
CAG). Lack of the correct protein leads to: before they themselves know if they are affected or
not. The condition is incurable.
● premature death of neurons in regions of the brain
● decreased production of neurotransmitters
● progressive degeneration of the central nervous
system.
Chromosome structure mutations (see Figures 4.15 and 4.16). The two ends then join
up giving a shorter chromosome, which lacks certain
This type of mutation involves the breakage of one or
genes. As a result, deletion normally has a drastic effect
more chromosomes. A broken end of a chromosome is
on the organism involved. (See the Case Study on Cri
‘sticky’ and it can join to another broken end. Three of
du-chat syndrome.)
the different ways in which this can occur are discussed
below. Each brings about a change in the number or
Duplication
sequence of the genes in a chromosome.
A chromosome undergoes duplication when a segment
of genes (e.g. deleted genes from its matching partner)
Deletion becomes attached to one end of the first chromosome
A deletion occurs when a chromosome breaks in two
or becomes inserted somewhere along its length, as
places and the segment in between becomes detached
shown in Figure 4.17. This results in a set of genes
genes
original
normal A B C D E F G H
chromosome
break break
A B C G H
D
E
F
join
deleted
G H genes
A B C D
E
F
59
Figure 4.15 Deletion Figure 4.16 ‘Look! Nessie’s had a deletion!’
Human Cells Unit 1
being repeated. Some duplications of genes may have Translocation
a detrimental effect on the organism. For example the Translocation involves a section of one chromosome
duplication of certain genes is a common cause of breaking off and becoming attached to another
cancer. chromosome that is not its matching partner.
Figure 4.18 shows two ways in which this can occur.
Translocation is the most common type of mutation
A B C D E F G H associated with cancer. (See the Case Study on chronic
break
myeloid leukaemia.) A translocation can bring about
a major change in an individual’s phenotype. (See the
Case Study on familial Down’s syndrome.)
A B C D E F G H Lethal ef fect
A mutation to a chromosome often involves such a
genes from substantial change to the chromosome’s structure (e.g.
D E F matching
chromosome loss of several functional genes) that the mutation is
lethal.
join join
A B C D E F D E F G H
duplicated genes
Figure 4.17 Duplication
(a) Non-reciprocal translocation (b) Reciprocal translocation

chromosome 1 chromosome 2 chromosome 1 chromosome 2
A B C D E F G H S T U V W X Y A B C D E F G H S T U V W X Y
break break break
A B C D E F G H S T U V W X Y A B C D E F G H S T U V W X Y
join join join
A B C D E F G H S T U V W X Y A B C D E S T F G H U V W X Y
translocated genes translocated genes
Figure 4.18 Translocation
60
Case Study Cri-du-chat syndrome

Cri-du-chat syndrome is caused by a deletion of part and widely spaced eyes. The condition is so-called
of chromosome 5. Children born with this genetic because the infant sufferer’s crying resembles that of
disorder suffer severe learning difficulties. They a distressed cat. Affected individuals usually die early
develop a small head with unusual facial features in childhood.
Case Study Chronic myeloid leukaemia (CML)
Chronic myeloid leukaemia is a form of cancer CML is treated by using drugs that inhibit the effect
that affects some of the stem cells that give rise to of tyrosine kinase and reduce the number of white
white blood cells. These stem cells are affected by a blood cells produced in the bone marrow. CML
reciprocal translocation involving genetic material occurs most commonly in middle-aged and elderly
on chromosomes 9 and 22, as shown in Figure 4.19. people. Its incidence is increased by exposure to
This translocation results in the formation of an ionising radiation. The atomic bombing of Hiroshima
oncogene. An oncogene encodes a protein that and Nagasaki in Japan at the end of World War 2
promotes uncontrolled cell growth (i.e. cancer). In resulted in greatly increased rates of CML among the
CML the encoded protein is called tyrosine kinase. population. The condition is lethal if left untreated.
chromosome 9
chromosome 22
reciprocal
translocation
break this combination forms

break join join a cancer-causing oncogene
one of many one of many

normal functional normal functional
genes on genes on
chromosome 9 chromosome 22
Figure 4.19 Mutation causing chronic myeloid leukaemia 61

Human Cells Unit 1
Case Study Familial Down’s syndrome
The vast majority of cases of Down’s syndrome are

the result of a mutant gamete (n = 24), containing an chromosome 14
extra copy of chromosome 21, fusing with a normal
gamete (n = 23) at fertilisation to form an abnormal
zygote (2n = 47). An individual affected in this way
suffers Down’s syndrome, which is characterised by
severe learning difficulties and distinctive physical
features.
About 5% of cases of Down’s syndrome result from break join join

break
a type of chromosome mutation that does not alter
the overall number of chromosomes present in reciprocal
the person’s genotype. These individuals are said translocation
two fragments
to suffer familial Down’s syndrome. A reciprocal join up
translocation between chromosomes 14 and 21, as
shown in Figure 4.20, affects the genotype of one
of the sufferer’s parents. This individual is a carrier chromosome 21 long arms of
of the mutated chromosome but is phenotypically chromosomes
14 and 21 join up
unaffected because he/she has two copies of all
essential genetic material.
Figure 4.20 Mutation causing familial Down’s syndrome
However, at gamete formation, some of the carrier
parent’s sex cells receive a copy of the mutated of every chromosome including chromosome 21,
chromosome ‘14 + 21’ and a copy of the normal the zygote produced contains three copies of the
chromosome 21. If one of these abnormal gametes long arm of chromosome 21. This abnormal zygote
meets a normal gamete containing a single copy develops into a sufferer of familial Down’s syndrome.
1 Distinguish between the terms mutation and mutant. (2) 4 Rewr ite the following sentences using only the correct
2 a) Name THREE types of point mutation that involve a answer from each choice. (5)
change in one nucleotide in the DNA sequence of a a) A mutation to a splice site on a gene may alter pre-/
gene. (3) post-transcr iptional processing of mRNA.
b) Which of your answers to a) could result in: b) An alteration in a chromosome’s structure that
i) a frameshif t mutation? involves a segment of genes being lost is called
ii) a missense mutation? (2) deletion/translocation.
c) When a section of one chromosome breaks of f and
3 a) Identify T WO possible ef fects that a nucleotide
joins onto another non-matching chromosome, this
sequence repeat expansion mutation can have on
type of mutation is called duplication/translocation.
the protein expressed. (2)
d) The type of chromosomal change involving a
b) Suggest why this type of mutation normally leads to
segment of genes from one chromosome becoming
a genetic disorder. (1)
inser ted somewhere along the length of its matching
par tner is called deletion/duplication.
e) A substantial change to a chromosome’s structure
most of ten has an adverse/benef icial ef fect on the
individual involved.
62
Human genomics
5 Human genomics
Sequencing DNA sequencing) and then relating this genetic information

about genes to their functions. Progress in this area
Human genomics is the study of the human genome. has been accelerated by bioinformatics (see page 66),
It involves determining the sequence of the nucleotide making genomics one of the major scientific advances
base molecules all the way along the DNA (genomic of recent years.
Case Study Human genome project (HGP)

A milestone in human history was reached in 2003 by their fluorescent dyes) is then read for the
when the DNA sequence of the human genome was complementary DNA using this separation. From this
completed. It is based on the combined genome of information the sequence of the bases in the original
a small number of donors and is regarded as the DNA can be deduced.
reference genome. This remarkable achievement
This process has been automated and links the
was accomplished by adopting several procedures,
detection of the four fluorescent dyes to a computer.
including the following one.
As these are monitored, the computer, working as
Sequencing DNA an automated sequence analyser, processes the
A portion of DNA with an unknown base sequence is information and rapidly displays the sequence of
chosen to be sequenced. Many copies of one of this bases in the DNA sample as a series of peaks (see
DNA’s strands (the template) are synthesised. Then, in Figure 5.2).
order to make DNA strands that are complementary
to these template strands, all the ingredients needed
for synthesis are added to the preparation. These
include DNA polymerase, primer and the four types
of DNA nucleotide, as shown in Figure 5.1 on page 64.
In addition the preparation receives a supply of
modified nucleotides (ddA, ddT, ddG and ddC), each
tagged with a different fluorescent dye.
Every so often during the synthesis process, a

molecule of modified nucleotide just happens to be T T A C T G G T T G A A C T A A T A G T A T T C
taken up instead of a normal one. However, when
a modified nucleotide is incorporated into the new Figure 5.2 Printout from a DNA sequence analyser
DNA strand, it brings the synthesis of that strand to
Results
a halt because a modified nucleotide does not allow
After 13 years of work (principally by biologists
any subsequent nucleotide to become bonded to it.
in the USA and the UK) the sequence of the three
Provided that the process is carried out on a large
billion nucleotide bases that make up the human
enough scale, the synthesis of a complementary
genome was finally unravelled. However, this was
strand will have been stopped at every possible
by no means the end of the story. Having unravelled
nucleotide position along the DNA template.
the molecular message, the challenge becomes
The resultant mixture of DNA fragments of various understanding what the message means. One of the
lengths (each with its modified nucleotide and many goals of the HGP was to identify the molecular
its unique fluorescent tag) are separated using cause of diseases such as cancer in the hope that
electrophoresis. In this process the smallest this knowledge would enable scientists to generate
(shortest) fragments travel the furthest distance. The effective treatments. Some progress has already been
identity and sequence of nucleotides (as indicated made in this area. 63
➜
Human Cells Unit 1

5’
+ supply of normal DNA nucleotides
A T
?
? C G
? region with
one of many ? unknown
copies of a ? sequence + supply of primer
single strand of bases
?
of DNA
(the template) ? + supply of modified nucleotides
? with fluorescent labels
ddC
region that ddA ddT
matches
ddC ddG ddT has halted
primer
synthesis of
3’ complementary
ddG
DNA at this point
DNA polymerase added

and preparation incubated
to allow synthesis of DNA
ddC
ddA has halted

e-u p synthesis of
clos complementary
DNA at this point
ddA
ddG has halted

synthesis of
complementary
ddT
DNA at this point
separation by
electrophoresis
(normal nucleotides
lacking fluorescent
labels not named)
large
molecule T A
base sequence of base sequence of
C G
complementary DNA original template
G C
C G
strand is read DNA strand is
A T
deduced
T A
small
G C
molecule
A T
Figure 5.1 Sequencing DNA
It is now known that more than 300 disease-causing accurately relate variation in genomic structure to
genes exist and that over 4000 genes each express variation in phenotypic expression and then to find
several different forms of the protein that they cures for the genes that cause disorders.
encode. However, much work remains to be done to
64
Human genomics
Case Study Comparison of individual genomes
Differences in genome located near the group of SNPs. If scientists know

A variation in DNA sequence that affects a single the exact location of these SNPs, then they can
base pair in a DNA chain is called a single nucleotide analyse nearby genes in the hope of finding the one
polymorphism (SNP). SNPs are one of the ways responsible for the disease.
in which genomes are found to differ from one
Single nucleotide polymorphisms are regarded as
individual to another. For example, the DNA of two
a valuable tool in biomedical research and may aid
people might differ by the SNP shown in Figure 5.3.
the development of future treatments for genetic
This difference has arisen as a result of a point
disorders.
mutation where one base pair has been substituted
for another. Two out of every three SNPs involve the Likelihood of Alzheimer’s disease
replacement of cytosine (C) with thymine (T). SNPs Some SNPs may indicate the likelihood of a person
can occur in coding and non-coding regions of the developing a particular illness. One of the genes
genome. associated with Alzheimer’s disease is called ApoE
(which codes for apolipoprotein E) and it illustrates
region of person 1’s genome how SNPs may be connected with the development
of a disorder. The gene is affected by two SNPs and
different combinations of these produce three alleles
G G C C G T A C G A A (ApoE2, ApoE3 and ApoE4). Each allele differs from
C C G G C A T G C T T
the others by one or two bases and the protein
expressed by each differs from the others by one or
SNP site two amino acids, as shown in Table 5.1.
Amino acid
G G C C A T A C G A A
C C G G T A T G C T T
Allele of ApoE Position of amino acid on
gene expressed protein chain
112 158
region of person 2’s genome
ApoE2 cysteine cysteine
Figure 5.3 Single nucleotide polymorphism (SNP) ApoE3 cysteine arginine

ApoE4 arginine arginine
The use of bioinformatics (see page 66) has enabled
Table 5.1 Three alleles of ApoE gene
scientists to catalogue more than a million SNPs,
specify their exact locations in the human genome Research shows that an individual who inherits
and use them as DNA markers. They believe that this at least one ApoE4 allele has an increased chance
SNP map will help them to identify and understand of developing Alzheimer’s disease. The change
the workings of genes associated with diseases. of one amino acid in the ApoE4 protein alters its
Imagine, for example, that people affected by a structure and function sufficiently to make disease
certain disease always inherit a particular group of development more likely. On the other hand,
SNPs and that unaffected people do not. This would inheriting the ApoE2 allele makes the person less
suggest that the gene responsible for the disease is likely to develop the condition.
65
Human Cells Unit 1
Bioinformatics Bioinformatics is the name given to the fusion of
molecular biology, statistical analysis and computer
The sequencing of the bases in DNA and the amino technology (see Figure 5.4). It is an ever-advancing area
acids in proteins generates an enormous quantity of that enables scientists to carry out rapid mapping and
data. This information is analysed using computers and analysis of DNA sequences on a huge scale and then
the results shared among the members of the molecular compare them. Individual gene sequences (and their
biology community over the internet. roles) can be identified by searching the complete DNA
sequence of the target genome for:
● protein-coding sequences the same as, or very
similar to, those present in known genes
molecular biology ● start sequences (because there is a good chance that
(e.g. genomic statistical each of these will be followed by a coding sequence)
sequencing) analysis
● long sequences that lack stop codons (because a
BIOINFORMATICS protein-coding sequence is normally a very long
chain of base triplets containing no stop codons
except the one at its end).
Similarly, a search for the identity (and role) of a base
sequence can be mounted to see if it matches a specific
amino acid sequence already known to be typical of a
computer
technology certain protein.
Information about genetic sequences that used to take
years to unravel is now obtained in days or even hours.
Bioinformatics can be used to investigate evolutionary
Figure 5.4 Bioinformatics biology, inheritance and personalised medicine.
Case Study Bioinformatics over the internet

Although many of the software packages on the
internet are commercial, some offer scientists the use DNA strand
from individual 1
of open sources of data and analysis free of charge.
The European Molecular Biology Open Software Suite A G C T T A C G A
(EMBOSS), for example, is a free software package
developed for the needs of molecular biologists. It A C T T A T G A
DNA strand
contains hundreds of programs useful to scientists from individual 2
who want to make use of bioinformatics. These
include:
● a comprehensive set of sequence analysis

alignment and
programs and tools analysis by computer
● an extensive library of programs for nucleotide
analysis tasks
● a database that mounts searches based on
sequence patterns
● programs that compare sequence alignments of A G C T T A C G A
chains of nucleotides (and amino acids). A – C T T A T G A
position of base 1 2 3 4 5 6 7 8 9
Sequence alignments
Analysing differences at nucleotide (and amino acid)
66 level between two sequences (e.g. from two different Figure 5.5 Nucleotide base alignment
Human genomics
individuals) begins with an alignment of the two a researcher to compare new sequences (‘queries’)
sequences by a computer. Then an interpretation of with those held in a database and identify known
the alignment is made. It would be concluded from sequences that match the ones being investigated.
the alignment shown in Figure 5.5, for example, that
an insertion or deletion has occurred at the second Openness
position, a substitution has occurred at the seventh EMBOSS and other suppliers of free software hope
position and that the other nucleotide bases have not to encourage scientists to analyse their data and
undergone any change. release the results online in a spirit of openness and
universal availability. However, many scientists prefer
BLAST (Basic Local Alignment Search Tool) is a further
to keep the results of their research projects under
bioinformatics instrument that enables biologists to
wraps in preparation for presentation at a conference
align new sequences with established ones. It allows
and/or publication in a scientific journal.
Systematics do exist between different human populations shows

that the greatest variation occurs among populations
Systematics can be defined as the study of a group of in Africa rather than those on other continents.
living things with respect to their diversity, relatedness Furthermore, genetic evidence indicates that all human
and classification. Data obtained by comparing human populations outside Africa possess only a small part
genome sequences are used in systematics to study the of the total genetic diversity found among African
origins of modern humans and their evolutionary populations.
relationships. Unlike other primates such as orang-
utans, whose DNA differs among the members of the These findings support the ‘out-of-Africa’ theory.
species by around 5%, the mean difference in genomic This proposes that humans originated in Africa and
sequence among the members of the human race is only underwent early evolutionary divergence in that
about 0.3%. This high degree of similarity indicates that continent over a very long period of time (e.g. millions
all humans are more closely related to one another than of years) to form a variety of genetically different
are other types of primate. populations. Then small groups migrated out of Africa
relatively recently (e.g. 100 000 years ago) and gave rise
Careful examination of the genetic differences that to all other human populations (see Figure 5.6).
15 000
4 500
25 000
40 000
12 000
100 000 70 000
30 000
200 000
50 000
1 500
67
Figure 5.6 Early human migration (f igures indicate ‘years ago’)
Human Cells Unit 1
Related Topic
Mitochondrial DNA universally, human genome sequence data show that Afr ica
has def initely played a major role in the or igins of human
Men and women both have DNA inside their mitochondria
beings.
(see Figure 5.7) that is inher ited from their mother
and not mixed with other DNA. Men have DNA in their Y
chromosome that does not mix with other DNA during Similarities in genome
gamete formation. Therefore both of these types of DNA In addition to displaying signif icant dif ferences, a
retain an accurate record of mutations that have occurred close comparison of genomes of ten reveals impor tant
over the generations in the individual’s ancestral line. For similar ities. For example they may show a high level of
example, those found in mitochondr ial DNA can be traced conser vation. This means that the same or ver y similar DNA
back to a female common ancestor (‘Mitochondr ial Eve’) sequences are present in the genomes. Highly conser ved
who lived in Afr ica about 150 000 years ago. DNA sequences can be used in compar isons of genomes of
two dif ferent groups to f ind out how close or distant their
mitochondrial DNA (mDNA) relationship is. The greater the number of conser ved DNA
sequences that their genomes have in common, the more
closely related the two groups that possess them.
Chimpanzees
The genomes of human beings and chimpanzees are
ver y similar. Analysis of the base sequence of the two
genomes reveals that the two groups have 98.5% of their
DNA in common. This makes the chimpanzee our closest
living relative. Fossil evidence shows that humans and
chimpanzees diverged from a common ancestor about six
million years ago.
mitochondrion Scientists have used a combination of genome sequence

data and fossil evidence to work out the sequence in
which many key events in evolution have taken place. The
Figure 5.7 Mitochondr ial DNA evidence strongly suppor ts the theor y that living things
have undergone a ser ies of modifications from the f irst
Sequence data from both mitochondr ial DNA and Y
emergence of life on Earth through to the present day,
chromosomes from a var iety of people native to dif ferent
gradually becoming more and more complex as evolution
par ts of the world are consistent with the ‘out-of-Afr ica’
has progressed.
theor y. Although this theor y is not (yet) accepted
Personalised medicine an individual’s DNA for medical reasons will soon

become a real possibility. In years to come, a person’s
Personal genome sequence entire genome may be sequenced early in life and stored
A complete sequencing of a person’s DNA bases is called as an electronic medical record available for future
a personal genome sequence. The branch of genomics consultation by doctors when required.
involved in sequencing the genomes of individuals
and analysing them using bioinformatics tools is Harmful and neutral mutations
called personal genomics. As a result of advances in Having located the mutant variants present in the
68
computer technology, the process of sequencing DNA genome, it is important to distinguish between those
is rapidly becoming faster and cheaper. Sequencing altered genetic sequences that are genuinely harmful
Human genomics
(e.g. fail to code for an essential protein) and those that an individual’s exact metabolic requirements. The
are neutral (i.e. have no negative effect). most suitable drug and the correct dosage would be
prescribed as indicated by personal genomic sequencing
Genetic disorders (and not as shown in Figure 5.8!). Ideally this advance
A genetic disorder or disease is the result of a variation would increase drug efficacy while reducing side effects
in genomic DNA sequence. The challenge for scientists and the ‘one-size-fits-all’ approach would be consigned
is to establish a causal link between a particular mutant to history.
variant in a genomic sequence and a specific genetic
disease or disorder.
Promise me
The causal genetic sequence has been identified, at least that this new
in part, for around 2200 genetic disorders and diseases personalised
in humans. However, this does not mean that it is a medicine
simple matter to produce treatments for these disorders. really works.
The nature of disease is highly complex. Most medical
disorders depend on both genetic and environmental
factors for their expression, though the specific effects
of these are not fully understood.
Pharmacogenetics
Pharmacogenetics can be defined as the study
of the effects (therapeutic, neutral or adverse) of
pharmaceutical drugs on the genetically diverse
members of the human population. Already it is known
that one in ten drugs (e.g. the blood thinner warfarin)
varies in effect depending on differences such as SNPs
in the person’s DNA profile.
In the future it may be possible to use genomic

information and customise medical treatment to suit Figure 5.8 ‘Personalised’ medicine
Related Topic
Rational drug design ● It binds to the particular region of DNA in the mutant
gene that causes the genetic disorder and prevents
Once information from DNA sequencing has been used
transcription of abnormal mRNA.
to identify the genes involved in a disease, the next
● It binds to the abnormal mRNA that has been
challenge is to establish the structure of the gene(s) and
transcr ibed and prevents it from being translated
the protein(s) expressed. Pharmacogeneticists may then
into abnormal protein. (A type of RNA called
tr y to design a drug that will act as an ef fective treatment.
inter fer ing RNA induces post-transcr iptional silencing
The inventive process of creating a new medication based
of genes in this way and is therefore being used to
on knowledge of the structure of the target molecule (e.g.
design new drugs.)
DNA or protein) is called rational drug design.
● It binds to and renders inactive the protein whose
This process involves the synthesis of a specif ic chemical presence would cause the genetic disorder.
(normally an organic molecule) that is complementar y in
An example of a medication produced as a result of
shape (and electr ical charge) to its biomolecular target.
rational drug design is a tyrosine kinase inhibitor (called
If it is ef fective, it provides the patient with a therapeutic
imatinib). This is used to treat chronic myeloid leukaemia
benef it by acting in one of the following ways: 69
➜
Human Cells Unit 1
(see page 61) because it binds with tyrosine kinase and its target molecule before the new compound has even
renders it inactive. been synthesised. This is more ef f icient than traditional
methods of drug discover y where the early stages of
Rational drug design of ten benef its from computer
development are heavily dependent on results from
modelling techniques. In addition, use of computers
trial-and-error testing on cultured cells and laborator y
has accelerated discover y of new drugs by enabling
animals.
scientists to make fairly accurate predictions about the
af f inity of a new compound for (and its likely ef fect on)
Future ethical issues. For example, if a person’s genome

contains genetic markers indicating a high risk of a
Risk prediction debilitating or fatal disease later in life, who should have
access to this information?
Already variations in DNA have been linked to
conditions such as diabetes, heart disease, schizophrenia ● The person’s employer? Perhaps the company
and cancer. In the future, when the locations in the will refuse to employ anyone who is at risk of the
human genome of many more markers for common disorder.
diseases and disorders have been established, it should ● The person’s offspring? Maybe this would tell them
become possible to scan an individual’s genome for more than they want to know about their own
predisposition to a disease and predict risk early genome.
enough to allow suitable action to be taken. Eventually ● The person’s life insurer? Perhaps the insurance
reduction of risk may be achieved through appropriate company will insist on charging a much higher
drug treatment combined with a healthy lifestyle. premium or refuse to provide cover at all.
Many people believe that laws should be introduced to

Ethical issues prevent genetic discrimination based on information
If personal genomic sequencing becomes a routine obtained from an individual’s genome. These issues
predictive medical procedure then this raises many need to be addressed by society before genomic
sequencing becomes inexpensive and widely available.
1 a) i) What information is obtained from the process of 4 Rewr ite the following sentences, choosing only the
genomic sequencing? correct answer from each underlined choice. (4)
ii) Give ONE example of a use to which this a) The role of a sequence of bases can be identif ied by
information can be put. (2) f inding the amino acid/nucleotide sequence of a
b) What is meant by the term bioinformatics? (1) known protein to which it corresponds.
c) Give T WO examples of the type of sequence that b) The study of a group of organisms with respect to
bioinformaticists would look for in a long chain of their diversity, relatedness and classif ication is
bases to identify gene sequences present. (2) called pharmacogenetics/systematics.
2 Br iefly descr ibe the ‘out-of-Africa’ theor y as applied to c) Compar ison of human genome sequence data gives
human beings. (3) information about evolutionar y relationships/
3 a) What is meant by personal genomics? (2) learned behaviour.
b) Give T WO possible benef its of personalised medicine d) An altered gene sequence that fails to code for a
to patients of the future. (2) protein is more likely to be neutral/harmful than one
70 that has no negative ef fect.
Human genomics
first cycle second cycle

5’ 3’ 5’ 3’ 5’ 3’
single copy
of DNA
3’ 5’ 3’ 5’ 3’ 5’
DNA heated to separate the strands DNA heated to separate the strands
5’ 3’ 5’ 3’ 5’ 3’
3’ 5’ 3’ 5’ 3’ 5’
primers bind to DNA

by hydrogen bonding primers bind to DNA by hydrogen bonding
5’ 5’ 3’ 5’ 5’ 3’ 5’ 5’ 3’
3’ 3’ 3’
primer
3’ 3’ 3’
3’ 5’ 5’ 3’ 5’ 5’ 3’ 5’ 5’
DNA polymerase replicates

target section of DNA DNA polymerase replicates target section of DNA
5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’
3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’ 3’ 5’
two identical copies of DNA
at end of first cycle four identical copies of DNA at end of second cycle
Figure 5.9 Polymerase chain reaction
71
Human Cells Unit 1
Amplification and detection of The DNA is heated to break the hydrogen bonds
between base pairs and separate the two strands.
DNA sequences Cooling allows each primer to bind to its target
sequence. During the next step, heat-tolerant DNA
Polymerase chain reaction polymerase adds nucleotides to the primers at the 3′
The polymerase chain reaction (PCR) is a technique end of the original DNA strands.
(see Figure 5.9) that can be used to create many copies
The first cycle of replication produces two identical
of a piece of DNA in vitro (i.e. outside the body of an
molecules of DNA, the second cycle four identical
organism). This amplification of DNA involves the
molecules and so on, giving an exponentially growing
use of primers. In this case, each primer is a piece of
population of DNA molecules. By this means a tiny
single-stranded DNA complementary to a specific
quantity of DNA can be greatly amplified and provide
target sequence at the 3′ end of the DNA strand to be
sufficient material for forensic and medical purposes.
replicated.
Case Study Use of PCR

PCR is used to amplify DNA from sources such as
embryonic cells for prenatal screening of genetic
target (template) DNA added to test tube containing
disorders and blood, semen and other tissues buffer solution + DNA polymerase (heat-tolerant), two
from a crime scene for DNA fingerprinting. PCR types of primer, four types of DNA nucleotide and
co-factor (magnesium chloride)
depends on a process called thermal cycling. A cycle
consists of three steps each carried out at a different
temperature. The earliest designs of this technique
used three water baths and normal DNA polymerase.
mixture taken through first step:
The latter was destroyed during the heating step in short time at 94–96 °C
the cycle and had to be replaced for use in the next (DNA strands separate)
cycle.
The following two important innovations enabled

PCR to become automated: mixture taken through second step:
first short time at 50–65 °C
● the isolation of heat-tolerant DNA polymerase cycle
(primers bond to DNA strands)
from a species of bacterium native to hot springs
● the invention of the thermal cycler, a
computerised heating machine able to control the
repetitive temperature changes needed for PCR. mixture taken through third step:
longer time at 72 °C (polymerase
Figure 5.10 shows a simplified version of the steps builds nucleotides into DNA strands)
carried out during thermal cycling in order to amplify
DNA.
procedure repeated many

times (DNA becomes amplified)
many more
cycles
(e.g. 20–30)
Figure 5.10 Amplif ication of DNA by thermal cycling

72
Human genomics
Related Topic DNA probes and arrays

One of the meanings of the word array is an orderly
‘Needles and haystacks’ arrangement of many items. A DNA microarray is an
Equally as impressive as the amplif ication of DNA by orderly arrangement of thousands of different DNA
PCR is the specificity of the reaction. Each pr imer is a probes as tiny spots attached to a glass slide. A DNA
piece of single-stranded DNA synthesised as the exact probe is a short, single-stranded fragment of DNA. It
complement of a shor t length of the DNA strand to which is used to detect the presence of a specific sequence of
it is to become attached. This enables the pr imer to f ind nucleotide bases in a sample of DNA. The DNA under
‘the needle in the haystack’. In other words it is able to investigation is called the target DNA.
locate, among many dif ferent sites, the specif ic target
DNA sequence that is to be amplif ied. The process then A probe is able to carry out its function because its
goes on to produce millions or even billions of copies of sequence of bases is complementary to the specific
the DNA. Therefore this amplif ication of DNA by PCR is base sequence to be detected in the target DNA.
sometimes descr ibed as being like ‘a haystack from the Fluorescent labelling indicates those spots where a
needle’. probe has successfully detected and combined with its
complementary sequence on the target DNA.
Case Study Medical uses of DNA probes

Figure 5.11 shows a method used to carry out a gene their message into mRNA. It is this subset of
expression microarray. actively coding genes that gives the cell type its
unique properties. A gene expression microarray
● DNA probes (each representing a known gene from
containing DNA probes enables a comparison to be
the human genome) are synthesised and fixed into
made between, for example, healthy and cancerous
position on the glass slide.
cells and shows which genes are active only in the
● Messenger RNA transcripts made by active genes
diseased cells. It also allows the effect of a potential
in the cells of the target tissue are isolated.
treatment on the expression of thousands of genes to
● These mRNA transcripts are used to make lengths
be investigated simultaneously.
of single-stranded, complementary DNA (cDNA) by
a process called reverse transcription, using DNA DNA probes can also be used in genotype
nucleotides containing a fluorescent label. microarrays to compare the genomic content of
● The cDNA mixture is added to the DNA microarray individuals (e.g. healthy individuals compared with
to allow hybridisation to take place. (Hybridisation those suffering a genetic disorder). In addition, the
is the pairing up and bonding that occurs if a probes are employed in microarrays to detect the
length of cDNA comes into contact with a gene presence of certain single nucleotide polymorphisms
probe to which it is exactly complementary.) (SNPs) in the genome of individuals where these may
● Following rinsing, the microarray is examined for indicate predisposition to disease.
fluorescent spots.
False positives and negatives
A spot only gives off fluorescence if hybridisation has
Some genetic tests are not 100% reliable. Most involve
taken place. Each fluorescent spot indicates a gene
a very low incidence of error. If (on rare occasions) a
that is expressed by the cells in the target tissue.
test fails to detect a specific DNA sequence when in
fact it is present, the result is called a false negative.
Applications
If (on rare occasions) the test indicates the presence
Although each cell in the human body, almost
of a specific DNA sequence when, in reality, it is
without exception, contains a full set of identical
absent, the result is called a false positive. (See
genes, within each type of differentiated cell only a
Appendix 4.)
fraction of these genes are active and transcribing
73
➜
Human Cells Unit 1
target tissue sample

containing target DNA spot containing DNA microarray
DNA probe
mRNA isolated from cells
mRNA transcripts from

actively-coding genes
detail of
row of four
spots
reverse transcription of mRNA to make

cDNA using labelled DNA nucleotides
single-stranded cDNA with fluorescent labels
single-stranded DNA
probes each representing a
different known gene
cDNA mixture added to microarray

of DNA probes to allow hybridisation
DNA microarray cDNA complementary to probe
fluorescence indicates
genes expressed
by target tissue
detail of
row of four
spots
74 Figure 5.11 Use of DNA probes

Human genomics
Medical and forensic applications of

amplified DNA 1 2 3 4 5 6
Medical
PCR can be used to amplify the genomic DNA from
a cell sample taken from a patient. By this means
sufficient DNA is generated to allow it to be screened
for the presence or absence of a specific sequence
known to be characteristic of a genetic disease or
disorder. This enables medical experts:
● to estimate the risk of disease onset (for example, by
identifying mutations in the person’s genome that
are known to increase the chance of developing a
particular disease)
● to confirm a diagnosis of the genetic disorder if the
condition is suspected (based on the patient’s family Key:
history and/or the fact that the patient is showing 1 Sample 1 of forensic material from crime scene
early symptoms). 2 Sample 2 of forensic material from crime scene
3 DNA sample from the victim
4 DNA sample from suspect P
Genetic testing for cystic fibrosis 5 DNA sample from suspect Q
6 DNA sample from suspect R
In the UK, it is estimated that 1 in 25 people carries a
recessive mutant allele for cystic fibrosis (see page 58).
Carriers do not suffer the disease but if two carriers Figure 5.12 Forensic application
produce a child, they risk a 1 in 4 chance of the child
suffering cystic fibrosis. Therefore couples planning samples taken from the victim and the suspects are
a family may decide to be tested for the presence of a also amplified. Next the components of the samples are
mutant allele for cystic fibrosis in their genome. This separated using gel electrophoresis and then compared.
can be done by genetic testing using blood cells. DNA is
amplified and tested for the presence of a mutant allele mother father child
using genetic probes.
Forensic
DNA profile
The human genome possesses many short, non-coding
regions of DNA composed of a number of repetitive
sequences. These regions are found to be randomly
distributed throughout the genome and to differ in
length and number of repeats of the DNA sequences
from person to person. Each region of repetitive
sequences is unique to the individual who possesses it.
Therefore these regions of genetic material can be used
to construct a DNA profile for that person.
Crime scene
Forensic scientists make use of the PCR reaction
to amplify DNA samples from a crime scene. DNA 75
Figure 5.13 Genetic ‘f ingerpr ints’
Human Cells Unit 1
In the example shown in Figure 5.12, it is concluded profile (‘genetic fingerprint’) must match one in that of
that the DNA in sample 1 from the crime scene matches their father or their mother. The fact that each person
that of the victim and that the DNA in sample 2 from has 50% of their bands in common with each of their
the crime scene matches that of suspect Q. parents (see Figure 5.13) allows paternity disputes to
be settled.
Paternity dispute
Evidence based on DNA amplified by PCR has also
PCR followed by gel electrophoresis can also be been used to identify missing people from human
employed to generate genetic profiles from DNA remains left at the site of a disaster and to secure the
samples and confirm genetic relationships between release of innocent people who have been wrongly
individuals. Each person inherits 50% of their DNA imprisoned.
from each parent therefore every band in their DNA
1 a) What can be produced in vitro by employing the 2 a) Br iefly descr ibe the structure of a genetic probe. (1)
polymerase chain reaction (PCR)? (1) b) What is a genetic probe used for? (1)
b) In PCR, what is a primer? (2) 3 a) What medical application does the amplif ication of
c) Why is the DNA heated dur ing the PCR process? (1) DNA by PCR make possible? (1)
d) What is the purpose of cooling the DNA sample? (1) b) What feature of the human genome makes each
e) What character istic of the DNA polymerase used in individual unique and allows genetic prof iles to be
PCR prevents it from becoming denatured dur ing the constructed? (1)
process? (1)
1 Proteins consist of subunits called _____ acids of which

altered evolutionar y personalised there are _____ dif ferent types.
amino folded probes 2 Amino acid molecules are joined together by _____
amplif ied forensic prof iles bonds to form polypeptides. Polypeptides are coiled and
bioinformatics frameshif t risk _____ to form protein molecules whose _____ structure,
which is maintained by cross-connections between amino
chain genomic screened
acids, is directly related to their function.
chromosome heat-tolerant sequence
3 A single-gene mutation involves the substitution,
coding insertion three-
inser tion or _____ of nucleotides in the DNA chain.
customised lethal dimensional
Substitutions can result in _____ or nonsense
cycling microarrays translocated mutations. Inser tions or deletions lead to _____
deletion missense twenty mutations. An _____ can cause an expansion of a
diagnosis mutation var iable nucleotide sequence repeat.
disorder or igins 4 A mutation can result in the production of an _____

protein that does not function properly, or in the failure
environmental peptide
of the gene to express the protein, thereby causing a
genetic _____.
Table 5.2 Word bank for chapters 4–5
5 A _____ may undergo a structural mutation if one or
more of its genes becomes deleted, duplicated or _____.
A _____ to a chromosome involves a major change to
the individual’s genome and is of ten _____.
76
Human genomics
6 Determining the sequence of nucleotide bases for 9 DNA can be _____ by the polymerase _____ reaction
individual genes or for a person’s entire genome is called using pr imers, _____ DNA polymerase and repeated
_____ sequencing. Use is made of _____, involving thermal _____.
computing and statistics, to compare sequence data.
10 DNA _____ are shor t, single-stranded fragments of DNA
7 Gene sequences can be identif ied by compar ing them used in _____ to detect the presence of a specif ic base
with those of known genes and looking for similar _____ _____ in DNA samples.
sequences. Human genome sequence data are also
11 In medicine, amplif ied DNA can be _____ for a specif ic
compared to obtain information about human _____
genetic sequence associated with a disease to allow a
and _____ relationships.
_____ or an estimate of r isk to be made.
8 In the future, routine sequencing of an individual’s
12 The existence of _____ numbers of repetitive sequences
genome may lead to _____ medicine. This could involve
of DNA makes each person’s genome unique and allows
predicting _____ of disease through knowledge of a
DNA _____ of individuals to be constructed for _____
person’s genome and administer ing _____ drugs in
use.
appropr iate dosages. Diseases are complex and of ten
af fected by both genetic and _____ factors.
77
Human Cells Unit 1
6 Metabolism and enzymes
Cell metabolism Reversible and irreversible steps

Cell metabolism is the collective term for the thousands Metabolic pathways are regulated by enzymes that
of biochemical reactions that occur within a living catalyse specific reactions. A pathway often contains
cell. The vast majority of these are steps in a complex both reversible and irreversible steps, which allow the
network of connected and integrated pathways that are process to be kept under precise control. Glycolysis
catalysed by enzymes. (see page 101) is the metabolic pathway that converts
glucose to an intermediate metabolite called pyruvate
Metabolic pathways at the start of respiration. Figure 6.2 shows the first
three enzyme-controlled steps in a long pathway.
The biochemical processes upon which life depends
take the form of metabolic pathways, which fall into Glucose diffusing into a cell from a high concentration
two categories: outside to a low concentration inside is irreversibly
converted to intermediate 1 by enzyme A. This process
● Catabolic pathways bring about the breakdown of is of advantage to the cell because it maintains a low
complex molecules to simpler ones, usually releasing
concentration of glucose inside the cell and therefore
energy and often providing building blocks.
promotes continuous diffusion of glucose into the cell
● Anabolic pathways bring about the biosynthesis of
from the high concentration outside.
complex molecules from simpler building blocks
and require energy to do so. The conversion of intermediate 1 to intermediate 2
Such pathways are closely integrated and one often by enzyme B is reversible. If more intermediate 2 is
depends upon the other. For example, aerobic formed than the cell requires for the next step then
respiration in living cells is an example of catabolism, some can be converted back to intermediate 1 and
which releases the energy needed for the synthesis of used in an alternative pathway (for example to build
protein from amino acids (an example of anabolism). glycogen in animal cells or starch in plant cells). The
This close relationship is shown in Figure 6.1. An conversion of intermediate 2 to intermediate 3 by
important chemical called ATP (see chapter 7) plays a enzyme C is irreversible and is a key regulatory point
key role in the transfer of energy between catabolic and in the pathway. There is no going back for the substrate
anabolic reactions. now. It is committed to following glycolysis through all
the steps to pyruvate.
glucose + protein
oxygen
catabolic energy anabolic

pathway pathway
CO2 + amino
water acids
78
Figure 6.1 Two types of metabolic pathway
Metabolism and enzymes
domain
glucose
glucose
archaea
enzyme A enzyme A
alternative
route
glycogen starch intermediate 1

intermediate 1
(in mammals) (in plants)
enzyme B enzyme B sorbitol
intermediate 2 intermediate 2
enzyme C enzyme C
several enzyme-
controlled steps
intermediate 3 intermediate 3
many enzyme- many enzyme-

controlled steps controlled steps
pyruvate pyruvate
Figure 6.2 Example of a metabolic pathway Figure 6.3 Alternative route
Alternative routes The bonds break when the molecules of reactant have
absorbed enough energy to make them unstable. They
Metabolic pathways can also contain alternative routes
are now in the transition state and the reaction can
that allow steps in the pathway to be bypassed.
occur. This energy input often takes the form of heat
Figure 6.3 shows a pathway from glucose via an
energy and the reaction only proceeds at a high rate
intermediate (called sorbitol) that bypasses the steps
if the chemicals are raised to a high temperature (see
controlled by enzymes A, B and C but returns to
Figure 6.4).
glycolysis later in the pathway. This bypass is used when
the cell has a plentiful supply of sugar.
Activation energy and enzyme action high activation

increasing energy level in system
energy required
The rate of a chemical reaction is indicated by the
reactants
amount of chemical change that occurs per unit
time. Such a change may involve the joining together products
of simple molecules into more complex ones or the
splitting of complex molecules into simpler ones.
In either case the energy needed to break chemical progress of reaction
bonds in the reactant chemicals is called the activation
energy. Figure 6.4 Uncatalysed reaction
79
Human Cells Unit 1
Related Activity
Investigating the effect of heat on the placed in f ive water baths at dif ferent temperatures. The
detergent is used to sustain any oxygen bubbles that are
breakdown of hydrogen peroxide released as a froth.
Hydrogen peroxide is a chemical that breaks down into
water and oxygen as shown in the following equation: Af ter 30 minutes the tubes are inspected for the
presence of a froth of oxygen bubbles which indicates the
hydrogen peroxide → water + oxygen
breakdown of hydrogen peroxide. The diagram shows a
2H2O2 → 2H2O + O2 typical set of results where the volume of froth is found to
In the exper iment shown in Figure 6.5, test tubes increase with increase in temperature.
containing hydrogen peroxide and drops of detergent are
initial
froth
hydrogen
peroxide +
detergent in
every tube,
gently mixed
at start
icy water water water water
water at 20°C at 40°C at 60°C at 80°C
at 1°C froth of
AFTER 30 MINUTES oxygen
bubbles
tiny
bubbles
of oxygen
rising to
the surface
no change no change little change
Figure 6.5 Investigating the ef fect of heat on the breakdown of hydrogen peroxide
Related Activity
Investigating the effect of manganese small mass of manganese

dioxide about to be added
dioxide on the breakdown of hydrogen
peroxide A B
In the exper iment shown in Figure 6.6, the bubbles

forming the froth in tube A are found to relight a glowing
splint. This shows that oxygen is being released dur ing
the breakdown of hydrogen peroxide. In tube B, the hydrogen
control, the breakdown process is so slow that no oxygen peroxide
at room
can be detected. A B temperature
It is concluded therefore that manganese dioxide (which
froth of
remains chemically unaltered at the end of the reaction) oxygen no
has increased the rate of this chemical reaction which bubbles detectable
rising up reaction
would otherwise have only proceeded ver y slowly. A test tube
80 substance that has this ef fect on a chemical reaction is
called a catalyst. Figure 6.6 Ef fect of a catalyst
Properties and functions of a catalyst Importance of enzymes

A catalyst is a substance that: Living cells cannot tolerate the high temperatures
needed to make chemical reactions proceed at a rapid
● lowers the activation energy required for a chemical
rate. Therefore they make use of biological catalysts
reaction to proceed (see Figure 6.7)
● speeds up the rate of a chemical reaction called enzymes.
● takes part in the reaction but remains unchanged at Enzymes speed up the rate of the reactions in a
the end of it. metabolic pathway by lowering the activation energy
needed by the reactant(s) to form the transition state. It
is from this unstable state that the end products of the
reaction are produced.
increasing energy level in system
low activation
energy required By this means biochemical reactions are able to proceed
reactants rapidly at the relatively low temperatures (e.g. 5–40°C)
needed by living cells to function properly. In the
products absence of enzymes, biochemical pathways such as
respiration and photosynthesis would proceed so slowly
that life as we know it would cease to exist.
progress of reaction
Enzyme action
Figure 6.7 Catalysed reaction Enzyme molecules are made of protein. Somewhere on
an enzyme’s surface there is a groove or hollow where
its active site is located. This site has a particular shape
Related Activity
Investigating the effect of catalase on fresh liver boiled liver

the breakdown of hydrogen peroxide
Catalase is an enzyme made by living cells. It is especially C D
abundant in fresh liver cells. In the exper iment shown in
Figure 6.8, the bubbles produced in tube C are found to
relight a glowing splint. This shows that oxygen is being
released during the breakdown of hydrogen peroxide as hydrogen
follows: peroxide
at room
catalase C D temperature
hydrogen peroxide → water + oxygen
(substrate) (enzyme) (end products) froth of
oxygen no
bubbles detectable
In tube D, the control, the breakdown process is so slow rising up reaction
that no oxygen can be detected. It is concluded that the the test tube
enzyme catalase has increased the rate of this chemical
reaction, which would otherwise have proceeded only Figure 6.8 Ef fect of catalase
ver y slowly.
81
Human Cells Unit 1
that is determined by the chemical structure of, and substrate are complementary to the enzyme’s active site
bonding between, the amino acids in the polypeptide for which they show an affinity (chemical attraction).
chains that make up the enzyme molecule.
Induced f it
Specif icity The active site is not a rigid structure. It is flexible
An enzyme acts on one type of substance (its substrate) and dynamic. When a molecule of substrate enters
whose molecules exactly fit the enzyme’s active site. The the active site, the shape of the enzyme molecule and
enzyme is specific to its substrate and the molecules of
substrate molecules with high affinity for active site
enzyme substrate with affinity

for active site
active site
active site
enzyme
substrate becomes bound

reactants correctly
to active site
orientated to fit
active site
enzyme–substrate
complex
enzyme holds
reactants closely
enzyme’s shape has with an induced fit
changed creating an
induced fit on
substrate
substrate is broken down
to end products
enzyme weakens chemical
bonds in reactants and
promotes the chemical
reaction by lowering
activation energy
end products end products with

are released low affinity for active
site are released
end products
enzyme
has returned
to original
shape
Figure 6.10 Or ientation of reactants dur ing an enzyme
82
Figure 6.9 Induced f it dur ing an enzyme-catalysed reaction catalysed reaction
the active site change slightly, making the active site fit
all active sites
very closely round the substrate molecule. This is called involved in reaction
induced fit (see Figure 6.9). The process is like a rubber
maximum rate of reaction at
glove, slightly too small, exerting a very tight fit round a this enzyme concentration
hand. Induced fit ensures that the active site comes into
increasing rate of reaction

very close contact with the molecules of substrate and
increases the chance of the reaction taking place.
some active
sites still free
Orientation of reactants
When the reaction involves two (or more) substrates
(see Figure 6.10), the shape of the active site determines
the orientation of the reactants. This ensures that
they are held together in such a way that the reaction
between them can take place. increasing substrate concentration
First the active site holds the two reactants closely

Figure 6.11 Ef fect of increasing substrate concentration
together in an induced fit. Then it acts on them to
weaken chemical bonds that must be broken during the
reaction. This process reduces the activation energy Ef fect of substrate concentration on enzyme
needed by the reactants to reach the transition state
activity
that allows the reaction to take place.
The graph in Figure 6.11 shows the effect of increasing
Once the reaction has occurred, the products have a substrate concentration on the rate of an enzyme-
low affinity for the active site and are released. This controlled reaction for a limited concentration of
leaves the enzyme free to repeat the process with new enzyme. At low concentrations of substrate, the reaction
molecules of substrate. rate is low since there are too few substrate molecules
present to make maximum use of all the active sites
Factors affecting enzyme action on the enzyme molecules. An increase in substrate
concentration results in an increase in reaction rate
To function efficiently, an enzyme requires a suitable
since more and more active sites become involved.
temperature, an appropriate pH and an adequate supply
of substrate. Inhibitors (see page 91) may slow down This upward trend in the graph continues as a straight
the rate of an enzyme-controlled reaction or bring it to line until a point is reached where further increase in
a halt. substrate concentration fails to make the reaction go
any faster. At this point all the active sites are occupied
(the enzyme concentration has become the limiting
factor). The graph levels off since there are now more
substrate molecules present than there are free active
sites with which to combine. The effect of increasing
substrate concentration is summarised at molecular
level in a simplified way in Figure 6.12.
83
Human Cells Unit 1
enzyme substrate enzyme–substrate amount of product
(limited concentration) complex produced per unit time
unused active
sites
low concentration low

unused active
site
medium concentration medium
all active
sites in use
high concentration high
unused
very high concentration high
substrate
Figure 6.12 Ef fect of increasing substrate concentration at a molecular level
Related Activity
piece of fresh liver about to be
dropped into each measuring cylinder
A B C D E F G H I
Investigating the effect of increasing
substrate concentration
Liver cells contain the enzyme catalase which catalyses
the breakdown of hydrogen peroxide to water and
oxygen. In the experiment shown in Figure 6.13, the
one var iable factor is the concentration of the substrate
(hydrogen peroxide). When an equal mass of fresh
liver is added to each cylinder, the results shown in the
diagram are produced. The height of the froth of oxygen
most dilute increasing concentration most
bubbles indicates the activity of the enzyme at each of hydrogen peroxide
solution of concentrated
concentration of substrate. hydrogen solution of
peroxide hydrogen
From the exper iment it is concluded that increase in a few seconds after liver is added peroxide
substrate concentration results in increased enzyme oxygen bubbles
activity until a point is reached (in cylinder G) where A B C D E F G H I
some factor other than substrate concentration has
become the limiting factor.
Figure 6.13 Ef fect of substrate concentration on

84
enzyme activity
enzyme 1 enzyme 2 enzyme 3

metabolite W metabolite X metabolite Y metabolite Z
Figure 6.14 Action of a group of enzymes
Direction of enzyme action A metabolic pathway rarely occurs in isolation.

A metabolic pathway usually involves a group of If, as a result of related biochemical pathways, the
enzymes as shown in Figure 6.14. As substrate W concentration of metabolite Y in Figure 6.14 were to
becomes available, enzyme 1 becomes active and increase to an unusually high level and that of X were
converts W to X. In the presence of metabolite X, to decrease, then enzyme 2 could go into reverse and
enzyme 2 becomes active and converts X to Y and so on. convert some of Y back to X until a balanced state
A continuous supply of W entering the system drives (equilibrium) was restored once more.
the sequence of reactions in the direction W to Z with
the product of one reaction acting as the substrate of Multi-enzyme complexes
the next. Enzymes are often found to act in groups. A group may
take the form of a multi-enzyme complex. Enzymes
Reversibility such as DNA polymerase (see chapter 2) and RNA
Most metabolic reactions are reversible. Often an polymerase (see chapter 3) form parts of multi-enzyme
enzyme can catalyse a reaction in both a forward and complexes.
a reverse direction. The actual direction taken depends
on the relative concentrations of the reactant(s) and
product(s).
1 a) Def ine the term metabolism. (2) The shape of the active site ensures that the
b) Descr ibe T WO ways in which the two types of reactants are correctly or ientated/denatured so that
metabolic pathway dif fer from one another. (2) the reaction can take place. This is made possible by
2 Give THREE reasons why enzymes are referred to as the fact that the enzyme increases/decreases the
biological catalysts. (3) activation energy needed by the reactants to reach
3 a) What determines the structure of an enzyme’s active the transitor y/transition state. (3)
site? (1) 4 a) What is meant by the term rate of reaction? (See page
b) What is meant by the aff inity of substrate molecules 79 for help.) (1)
for an enzyme’s active site? (1) b) i) What ef fect does an increase in concentration of
c) What term means ‘the change in shape of an substrate have on reaction rate when a limited
active site to enable it to bind more snugly to the amount of enzyme is present?
substrate’? (1) ii) Explain why. (4)
d) Rewr ite the following sentences, choosing the
correct answer from each underlined choice.
85
Human Cells Unit 1
Control of metabolic pathways Gene action in Escherichia coli
A metabolic pathway normally consists of several Background information
stages, each of which involves the conversion of one
metabolite to another. Each step in a metabolic pathway ● Glucose is a simple sugar used in respiration by the
is driven by a specific enzyme (see Figure 6.15). Each bacterium E. coli for energy release.
enzyme is coded for by a gene (though complex ● E. coli can only make use of the glucose in lactose if
enzymes composed of several polypeptides require it is released from the galactose.
several genes to be involved in their production). If the ● Lactose is digested to glucose and galactose by the
appropriate enzymes are present, the pathway proceeds. enzyme β-galactosidase.
If one enzyme is absent, the pathway comes to a halt. ● E. coli’s chromosome has a gene that codes for
Enzyme action can be regulated at the level of gene β-galactosidase.
expression (see below) and at the level of enzyme ● E. coli is found to produce β-galactosidase only when
action (see page 91). lactose is present in its nutrient medium and fails to
do so when lactose is absent.
● Somehow the gene that codes for β-galactosidase is
switched on in the presence of lactose and switched
gene(s) gene(s)
off in the absence of lactose.
● The process of switching on a gene only when the
enzyme 1 enzyme 2
enzyme that it codes for is needed is called enzyme
metabolite A metabolite B metabolite C induction.
Lac operon of E. coli

Figure 6.15 Control of two steps in a metabolic pathway An operon (see Figure 6.17) consists of one or more
structural genes (containing the DNA code for the
Control by switching genes on and off enzyme in question) and a neighbouring operator gene,
which controls the structural gene(s). The operator gene
Some metabolic pathways are only required to operate is, in turn, affected by a repressor molecule coded for by
under certain circumstances. To prevent resources being a regulator gene situated further along the DNA chain.
wasted, the genes that code for the enzymes controlling
each of their stages are ‘switched on’ or ‘switched off ’ as
Absence of lactose
required.
Environments inhabited by E. coli normally contain
Lactose metabolism in Escherichia coli glucose but not lactose. The bacterium would waste
Lactose is a sugar found in milk. Each molecule of some of its resources if it made the lactose-digesting
lactose is composed of a molecule of glucose and a enzyme when no lactose was present to digest.
molecule of galactose (see Figure 6.16). Figure 6.17 shows how the bacterium is prevented from
doing so by the repressor molecule combining with the
operator gene. The structural gene remains switched off
glucose galactose and its DNA is not transcribed.
Presence of lactose
When the bacterium finds itself in an environment
containing lactose, the events shown in Figure 6.18
take place and lead to the induction of β-galactosidase.
Lactose (the inducer) prevents the repressor molecule
Figure 6.16 Molecule of lactose
from binding to the operator gene. The system is no
longer blocked, the structural gene becomes switched
86
on and production of β-galactosidase proceeds.
Iac operon
regulator gene operator gene structural gene which

codes for -galactosidase
DNA chain
3
structural gene
‘switched off’
2 repressor
1 transcription and combines
translation to form a with operator 4
repressor protein molecule no -galactosidase
produced
repressor molecule
Figure 6.17 Effect of repressor in absence of lactose
Iac operon
regulator gene operator structural

gene gene
DNA chain
5
transcription and operator free
2 6 successful transcription
translation to form a and translation to form
repressor protein molecule -galactosidase
3 4
some repressor
repressor molecule
lactose unable to
combines combine
with with
1 repressor operator
lactose
(inducer)
enters the
cell
7
enzyme digests lactose
until supply runs out then
repressor combines with
operator and switches the
gene off as in Figure 6.17
Figure 6.18 Effect of inducer (lactose)
87
Human Cells Unit 1
When all the lactose has been digested, the repressor Hypothesis
molecule becomes free again and combines with This hypothesis of gene action was first put forward
the operator as before. The structural gene becomes by two scientists called Jacob and Monod. It is now
switched off and the waste of valuable resources (such supported by extensive experimental evidence from
as amino acids and energy) is prevented. work done using bacteria.
Related Activity
Investigating the lac operon of E. coli

1 2 3 4
ONPG is a colourless synthetic chemical that can be
E.coli E.coli ONPG -g
broken down by the enzyme β-galactosidase as follows: + + +
β -galactosidase lactose lactose -g
+
ONPG ⎯⎯⎯⎯⎯⎯→ galactose + yellow compound ONPG
buffer
solution
The presence of the yellow colour indicates activity by in every
β-galactosidase. The experiment is set up as shown in tube
Figure 6.19.
( -g = -galactosidase)
From the results it is concluded that:
after 1 hour at 35°C
● in tube 1, lactose has acted as an inducer and switched
on the gene in E. coli that codes for β-galactosidase;
this enzyme has acted on the ONPG, forming the
yellow colour
● in tubes 2 and 4, no yellow colour was produced 1 2 3 4
because ONPG was absent
● in tube 3, β-galactosidase has acted on ONPG, forming
the yellow compound.
yellow colourless yellow colourless
Figure 6.19 Investigating the lac operon
Related Topic
The ara operon of E. coli Transformation of the ara operon

Arabinose is a sugar that can be used by E. coli as its sole E. coli cells can be genetically transformed using a
source of carbon and energy in the absence of glucose modif ied plasmid called pGLO. This procedure br ings
and lactose. To be of use to the bacter ium, arabinose about the replacement of the ara operon’s structural
must be broken down by enzymes. The genes for these genes with a gene (or iginally from a fluorescent jellyf ish)
enzymes (the ara operon) are switched off in the absence that codes for green fluorescent protein (GFP) and a
of arabinose (see Figure 6.20) and switched on in its second gene that makes the transformed cells resistant
presence as a result of arabinose acting as an inducer (see to an antibiotic (called ampicillin). In the presence
Figure 6.21). of arabinose, the inducer, these transformed bacter ia
produce GFP instead of arabinose-digesting enzymes, as
88 shown in Figure 6.22.
ara operon
DNA chain group of structural genes which

regulator gene promoter code for arabinose-digesting enzyme
structural genes
3
remain switched off
transcription and
1 2 regulator binds
translation to form
to DNA but
inactive regulator no arabinose-digesting
remains inactive 4
molecule enzyme produced
regulator molecule
Figure 6.20 Situation in a normal bacter ium in the absence of arabinose
ara operon
DNA chain group of structural genes which

regulator gene promoter code for arabinose-digesting enzyme
RNA
4
3 polymerase
transcription and begins
2 arabinose combines
translation to form transcription
with regulator
inactive regulator changing its shape
molecule and making it
act on promoter
5 transcription and
translation of enzymes
arabinose that digest arabinose
1 (inducer)
enters cell
Figure 6.21 Situation in a normal bacter ium in the presence of arabinose
transformed operon
DNA chain GFP gene in place of gene for resistance

regulator gene promoter genes for enzyme to ampicillin
4
RNA
3
transcription and polymerase
arabinose combines
2 translation to form begins
with regulator
inactive regulator transcription
changing its shape
molecule and making it
act on promoter
5 transcription and
translation of GFP
(green fluorescent
arabinose protein)
1 (inducer)
enters cell 89
Figure 6.22 Situation in a transformed bacter ium in the presence of arabinose
Human Cells Unit 1
Related Activity
Investigating the transformed ara Af ter appropr iate treatment to bring about the
transformation, samples of bacter ia are subcultured onto
operon four nutr ient agar plates, as shown. Only transformed
This exper iment is set up as shown in Figure 6.23. pGLO bacter ia with the genes for GFP and ampicillin resistance
plasmids are added to tube 1 to transform the bacteria grow on plates A and B. No bacter ia grow on plate C
into cells containing the genes for GFP and ampicillin because they are not resistant to ampicillin antibiotic.
resistance. Tube 2 is the control.
pGLO plasmid added
tube 1 tube 2
(control)
Escherichia coli
in transformation solution
A B C D
nutrient agar
+ nutrient agar nutrient agar
ampicillin + + nutrient agar
+ ampicillin ampicillin
arabinose
after 36 hours at 37°C
growth of transformed no growth growth of untransformed

E. coli resistant to ampicillin E. coli
result in fluorescence no fluorescence no fluorescence no fluorescence

UV light
presence of arabinose cells lack arabinose cells have been cells lack GFP
reason (inducer) has switched (inducer) needed to killed by ampicillin gene and arabinose
GFP gene on switch GFP gene on
90 Figure 6.23 Investigating the transformed ara operon

Untransformed bacter ia grow on plate D, which lacks

ampicillin.
When the plates are exposed to ultraviolet light,
fluorescence occurs in plate A only (see Figure 6.24). It
is concluded that the presence of arabinose, the inducer,
has switched on the GFP gene in these cells, resulting in
the production of green fluorescent protein.
Figure 6.24 Expression of the GFP gene
Regulation of gene expression by signal Ef fect of signal molecules

molecules The activity of some enzymes is controlled by signal
In the lac operon system of control in E. coli (and the molecules. For example, the hormone epinephrine
ara operon – see Related Activity), a gene that had (adrenaline), released into the bloodstream by the
been switched off becomes switched on in response adrenal glands, binds to receptors in the membrane of
to a signal molecule from the cell’s environment. In liver cells where it acts as a signal molecule. It triggers
the lac operon system, the signal molecule is lactose. It a series of events in the liver cells that results in the
combines with the product of the regulator gene (the activation of an enzyme that converts glycogen to
repressor molecule) enabling the structural gene to be glucose when the body needs energy urgently.
expressed and lead to the production of the required
Signal molecules that affect a cell’s metabolism and
enzyme.
originate within the cell itself are called intracellular
signal molecules. On the other hand, signal
Control by regulation of enzyme molecules such as epinephrine that come from the
action cell’s environment (e.g. from other cells) are called
Some metabolic pathways (e.g. glycolysis – see page extracellular signal molecules.
101) are required to operate continuously. The genes
that code for their enzymes are always switched on and
Ef fect of inhibitors
An inhibitor is a substance that decreases the rate of an
the enzymes that they code for are always present in the
enzyme-controlled reaction.
cell. Control of these metabolic pathways is brought
about by regulating the action of their enzymes as
Competitive inhibitors
follows.
Molecules of a competitive inhibitor compete with
molecules of the substrate for the active sites on the
91
enzyme. The inhibitor is able to do this because its
Human Cells Unit 1
competitive inhibitor absent
end
products
substrate
enzyme enzyme–substrate complex enzyme

showing induced fit
competitive inhibitor present
competitive
inhibitor
unused
substrate
enzyme enzyme–inhibitor
substrate complex
Figure 6.25 Ef fect of a competitive inhibitor
molecular structure is similar to that of the substrate As substrate molecules increase in concentration
and it can attach itself to the enzyme’s active site and outnumber those of the competitive inhibitor,
as shown in Figure 6.25. Since active sites blocked more and more active sites become occupied by true
by competitive inhibitor molecules cannot become substrate rather than inhibitor molecules. The reaction
occupied by substrate molecules, the rate of the reaction rate continues to increase until all the active sites are
is reduced. occupied (almost all of them by substrate).
Ef fect of increasing substrate concentration

The graph in Figure 6.26 shows the effect of increasing
no competitive
substrate concentration on rate of reaction for a limited inhibitor
relative rate of reaction
amount of enzyme affected by a limited amount of

inhibitor. In graph line 1 (the control), increase in
substrate concentration brings about an increase in competitive
reaction rate until a point is reached where all active inhibitor present
sites on the enzyme molecules are occupied and then
the graph levels off.
In graph line 2, increase in substrate concentration

increasing substrate concentration
brings about a gradual increase in reaction rate.
Although the competitive inhibitor is competing for
and occupying some of the enzyme’s active sites, the Figure 6.26 Ef fect of increasing substrate concentration on
true substrate is also occupying some of the sites. competitive inhibition
92
Inhibition of β-galactosidase by galactose

Normally the enzyme β-galactosidase catalyses the reaction:
Investigation
β-galactosidase
lactose ⎯⎯⎯⎯⎯⎯→ glucose + galactose
However, it is also able to break down a colourless, synthetic compound called ONPG, as follows:
β -galactosidase
ONPG ⎯⎯⎯⎯⎯⎯→ galactose + yellow compound
The exper iment shown in Figure 6.27 is set up to investigate the inhibitor y ef fect of galactose on the action of
β-galactosidase as the concentration of the substrate, ONPG, is increased. The independent variable in this
exper iment is substrate concentration.
At the end of the exper iment, an increasing intensity of yellow colour (indicating products of enzyme activity) is
found to be present in the tubes, with tube 1 the least yellow and tube 4 the most yellow. The intensity of colour
can be measured quantitatively using a colorimeter. This allows the results to be displayed as a graph.
A possible explanation for these results is that galactose acts as a competitive inhibitor, having most ef fect at
low concentrations of substrate. As the concentration of substrate increases, more and more active sites on the
enzyme become occupied by substrate, not inhibitor, and reaction rate increases.
equal volume and 1 2 3 4

concentration of
galactose and
-galactosidase
in every tube
buffer solution
in every tube 1 unit 2 units 3 units 4 units
ONPG ONPG ONPG ONPG
1 2 3 4
least yellow most yellow
(least action (most action
of enzyme of enzyme
on ONPG) on ONPG)
increasing intensity of yellow colour
Figure 6.27 Investigating the inhibitor y ef fect of galactose
Regulation by changing the shape of the of the enzyme molecule. This results in the active
active site site becoming altered indirectly and being unable to
combine with the substrate as shown in Figure 6.28.
Non-competitive inhibitors The larger the number of enzyme molecules affected
A non-competitive inhibitor does not combine directly in this way, the slower the enzyme-controlled reaction.
with an enzyme’s active site. Instead it becomes attached Therefore, the non-competitive inhibitor acts as a type
to a non-active (allosteric) site and changes the shape of regulator.
93
Human Cells Unit 1
non-competitive regulatory molecule regulatory molecule
inhibitor (activator) becomes (inhibitor) becomes
attached to an attached to an
allosteric site allosteric site
inhibitor
attached substrate
to enzyme no longer
substrate enzyme’s fits active
enzyme
shape site
becomes
altered
Figure 6.28 Ef fect of a non-competitive inhibitor

enzyme molecule held in enzyme molecule held in
active form by activator inactive form by
non-competitive inhibitor
Some enzyme molecules are composed of several
polypeptide subunits and each subunit has its own
Figure 6.30 Enzyme regulation by an activator and an
active site. The enzyme molecule also has several non
inhibitor
active (allosteric) sites. Depending on circumstances,
the enzyme molecule may exist as an active form or an
inactive form. These have different shapes, as shown in Feedback inhibition by an end product
Figure 6.29. End-product inhibition (see Figure 6.31) is a further
way in which a metabolic pathway can be regulated. As
allosteric site
the concentration of end product (metabolite Z) builds
active site
up, some of it binds to molecules of enzyme 1 in the
pathway. This slows down the conversion of metabolite
W to X and in turn regulates the whole pathway.
metabolite W
enzyme 1
active form of enzyme inactive form of enzyme
Figure 6.29 Active and inactive forms of an enzyme molecule metabolite X
The enzyme molecule changes shape if a regulatory enzyme 2 some of end product
molecule becomes bound to one of its allosteric (metabolite Z) binds to
sites (see Figure 6.30). If the regulatory molecule is enzyme 1 and prevents
conversion from W to X
an activator, the enzyme adopts its active form and metabolite Y
enzyme activity is stimulated. If the regulatory molecule
is a non-competitive inhibitor, the enzyme changes to enzyme 3
its inactive state and enzyme action is inhibited. The
more enzyme molecules affected by activators, the faster
the reaction rate; the more enzyme molecules affected metabolite Z
by inhibitors, the slower the reaction rate.
94 Figure 6.31 Regulation by feedback inhibition

As the concentration of Z drops, fewer molecules of control by this means (called negative feedback
enzyme 1 are affected and more of W is converted to control) and wasteful conversion and accumulation of
X and so on. The pathway is kept under finely tuned intermediates and final products are avoided.
Related Activity
Investigating the effect of phosphate

on phosphatase
Phosphatase is an enzyme that releases the phosphate
group from its substrate for use in cell metabolism.
Phosphatase is present in the extract obtained from
ground-up mung bean sprouts. Phenolphthalein
phosphate is a chemical that can be broken down by
phosphatase as follows:
phosphatase
phenolphthalein phosphate ⎯⎯⎯⎯⎯⎯→ phenolphthalein + phosphate
(pink in alkaline
conditions)
The exper iment is set up as shown in
Figure 6.32. At the end of the experiment a 1 2 3 4 5
decreasing intensity of pink colour is found equal volume and
concentration of
to be present in the tubes. Tube 1 is the most phenolphthalein
pink and tube 5 is the least pink. From these phosphate and
phosphatase in
results it is concluded that tube 1 contains every tube
most free phenolphthalein as a result of most
enzyme activity and that tube 5 contains buffer buffer buffer buffer buffer
(pH5) (pH5) (pH5) (pH5) (pH5)
least free phenolphthalein as a result of least + 0.05 M + 0.10 M + 0.20 M + 0.30 M
enzyme activity. In other words as phosphate sodium sodium sodium sodium
phosphate phosphate phosphate phosphate
concentration increases, the activity of the
enzyme phosphatase decreases. A possible after 20 min at 30°C alkali added to denature
phosphatase enzyme and turn any free phenolphthalein to pink
explanation for this ef fect is that phosphate
acts as an end-product inhibitor of the enzyme
phosphatase. 1 2 3 4 5
most pink decreasing intensity of least pink

(most free pink colour (least free
phenolphthalein present) phenolphthalein present)
Figure 6.32 Investigating the ef fect of phosphate on phosphatase
95
Human Cells Unit 1
1 a) Briefly explain why E. coli is only able to produce the 3 An enzyme molecule may possess several active sites
enzyme β-galactosidase when lactose is present in and several alloster ic sites and exist in an active or an
its food. (2) inactive form. Explain how molecules of such an enzyme
b) What is the benef it of this on/of f mechanism to the could be controlled so that they could br ing about:
bacter ium? (1) a) an increase in reaction rate (1)
c) In this example, does lactose act as an intracellular b) a decrease in reaction rate. (1)
or an extracellular signal molecule? (1) 4 Figure 6.33 shows a metabolic pathway where
2 a) What proper ty of a competitive inhibitor enables it to metabolites P, Q and R are present in equal quantities at
compete with the substrate? (1) the star t.
b) i) What ef fect does an increase in concentration of a) Name enzyme X’s i) substrate, ii) product. (2)
substrate have on rate of reaction when a limited b) Name enzyme Y’s i) substrate, ii) product. (2)
amount of competitive inhibitor and enzyme are c) In which direction will the pathway proceed if more
present? of metabolite P is added to the system? (1)
ii) Explain why. (3) d) i) Metabolite R can act as an end-product inhibitor.
Descr ibe how this would work.
ii) What is the benef it of end-product inhibition? (3)
enzyme X enzyme Y
metabolite P metabolite Q metabolite R
Figure 6.33
96
Cellular respiration
7 Cellular respiration
Cellular respiration is a series of metabolic pathways
that brings about the release of energy from a foodstuff ATP
and the regeneration of the high-energy compound (high-energy
state)
adenosine triphosphate (ATP).
Adenosine triphosphate build-up

requiring energy
breakdown
releasing energy
A molecule of ATP is composed of adenosine and
three inorganic phosphate (Pi) groups, as shown in
Figure 7.1. Energy held in an ATP molecule is released ADP + Pi
when the bond attaching the terminal phosphate is (low-energy
state)
broken by enzyme action. This results in the formation
of adenosine diphosphate (ADP) and inorganic
phosphate (Pi). On the other hand, energy is required Figure 7.2 Relationship between ATP and ADP + Pi
to regenerate ATP from ADP and inorganic phosphate.
This relationship is summarised in Figure 7.2.
Transfer of energy via ATP
ATP is important because it acts as the link between
catabolic energy-releasing reactions (e.g. respiration)
bond which must be
broken to release energy and anabolic energy-consuming reactions (e.g. synthesis
of proteins). It provides the means by which chemical
adenosine Pi Pi Pi
energy is transferred from one type of reaction to the
other in a living cell (see Figures 7.3 and 7.4).
adenosine diphosphate
adenosine triphosphate Turnover of ATP molecules

It has been estimated that an active cell (e.g. a bacterium
Figure 7.1 Structure of ATP undergoing cell division) requires approximately
two million molecules of ATP per second to satisfy
carbon dioxide ATP amino

+ water acids
energy energy
CELLULAR ENERGY SYNTHETIC

RESPIRATION TRANSFER PATHWAY
energy energy
glucose
ADP + Pi protein
+ oxygen
97
Figure 7.3 Transfer of chemical energy by ATP
Human Cells Unit 1
its energy requirements. This is made possible by the
fact that a rapid turnover of ATP molecules occurs
continuously in a cell. At any given moment some ATP
molecules are undergoing breakdown and releasing
the energy needed for cellular processes while others
are being regenerated from ADP and Pi using energy
released during cell respiration.
Fixed quantity of ATP

Since ATP is manufactured at the same time as it is used
up, there is no need for a living organism to possess a
vast store of ATP. The quantity of ATP present in the
Figure 7.4 ‘What do you mean, I need ATP? I thought you said
human body, for example, is found to remain fairly
a teepee!’
constant at around 50 g despite the fact that the body
may be using up and regenerating ATP at a rate of
about 400 g/h.
Related Activity
Measuring ATP using luciferase ● The presence of ATP is essential for the production of
light energy and the reaction does not proceed in its
Background absence.
● Luciferase is an enzyme present in the cells of f ire- ● When lucifer in and luciferase are plentiful and ATP is
flies. It is involved in the process of bioluminescence the limiting factor, the intensity of light emitted is
(the production of light by a living organism). propor tional to the concentration of ATP present.
● Luciferase catalyses the following reaction:
The exper iment is carr ied out as shown in Figure 7.5 and
luciferase the results used to draw a graph of known values of ATP
lucifer in + ATP ⎯⎯⎯⎯⎯→ end products + light energy concentration (see Figure 7.6). When the exper iment is
ATP solution ATP solution ATP solution

(concentration (concentration (concentration
microplate water 1 unit) 5 units) 10 units)
containing
several wells
(to allow
multiple
replication)
equal
volume and
concentration
of luciferin microplate 1 microplate 2 microplate 3 microplate 4
and luciferase
in every well in
every microplate each microplate inserted in luminometer to measure intensity of light given out as luminescence
no light emitted 2 units of light emitted 8 units of light emitted 16 units of light emitted
98
Figure 7.5 Measur ing light emitted from known concentrations of ATP
repeated using mater ial of unknown ATP content, the ATP sample containing
concentration can be determined from the graph. For microplate an unknown
concentration
example, the sample shown in Figure 7.7 would contain of ATP
7.5 units of ATP.
20 equal volume
and concentration
of luciferin and
light intensity (units)
luciferase in
every well
10
microplate inserted
0 in luminometer
0 1 2 3 4 5 6 7 8 9 10
ATP concentration (units)
Figure 7.6 Graph of luciferase results

12 units of
light emitted
Figure 7.7 Measur ing light emitted from unknown

concentrations of ATP
Phosphorylation reactant becomes phosphorylated and energised. In the

early stages of cellular respiration, for example, some
Phosphor ylation is an enzyme-controlled process
reactants must undergo phosphorylation during what is
by which a phosphate group is added to a molecule.
called the energy investment phase. One of these steps is
Phosphorylation occurs, for example, when the reaction
shown in Figure 7.8.
shown in Figure 7.2 goes from bottom to top and
inorganic phosphate (Pi) combines with low-energy
ADP to form high-energy ATP.
ATP
(high energy) ADP
Phosphorylation of a reactant in a pathway
Phosphorylation also occurs when phosphate (Pi) and glucose
glucose-6-phosphate
(high energy)
energy are transferred from ATP to the molecules of a
reactant in a metabolic pathway, making them more
reactive. Often a step in a pathway can proceed only if a Figure 7.8 Phosphor ylation of glucose
99
Human Cells Unit 1
Effect of phosphorylase on a phosphor ylated substrate
Background
Investigation
centrifuge tube
● Glucose-1-phosphate is a phosphor ylated form of glucose.
● A molecule of starch is composed of many glucose molecules linked
together in a long chain. starch-free
potato extract
● Potato tuber cells contain phosphor ylase, an enzyme that promotes
the synthesis of starch.
● Potato extract containing phosphor ylase is prepared by liquidising a heavy cell debris
mixture of potato tuber and water and then centr ifuging the mixture and starch grains
until the potato extract (see Figure 7.9) is starch-free.

The exper iment is set up at room temperature on a spotting tile, as shown
in Figure 7.10. Figure 7.9 Preparation of potato
extract
faint blue-black blue-black

0 min 3 min 6 min 9 min
glucose-1-phosphate A A
+ potato extract
glucose B
+ potato extract B
glucose-1-phosphate
C C
+ distilled water
Figure 7.10 Investigating a phosphor ylated substrate
One dimple from each row is tested at 3-minute inter vals with iodine solution. Starch is found to be formed in
row A only. It is concluded that in row A phosphor ylase has promoted the conversion of the phosphorylated (and
more reactive) form of the substrate, glucose-1-phosphate, to starch, as in the following equation:
phosphor ylase
glucose-1-phosphate ⎯⎯⎯⎯⎯⎯⎯→ starch
(phosphor ylated substrate) (enzyme) (end product)
In row B (a control), phosphor ylase has failed to conver t the more stable (and less reactive) form of the
substrate, glucose, to starch.
In row C (a control), the molecules of glucose-1-phosphate have failed to become bonded together into starch
without the aid of phosphor ylase.
Positive and negative controls

A positive control is set up to assess the validity of a testing procedure or design and ensure that the
equipment and mater ials being used are in working order and appropr iate for use in the experiment being carr ied
out.
100
For example, a positive control for the above exper iment could be set up as row D, which would contain starch
in ever y dimple. If the addition of iodine solution at each 3-minute inter val gave a blue-black colour, this would
conf irm that:
● the iodine solution being used was working properly as a testing reagent for starch
● the exper iment was not adversely af fected in some way, for example by the contamination of the spotting tile
or by changes in room temperature.
If a positive control does not produce the expected result, then this indicates that there is something wrong with
the design of the testing procedure or with the mater ials being used.
A negative control is one that should not work. It is a copy of the exper iment in which all factors are kept exactly
the same except the one being investigated. When the results are compared, any dif ference found between the
exper iment and a negative control must be due to the factor being investigated.
In the above investigation, starch is not synthesised in row B, showing that the glucose must be in a
phosphor ylated state to become conver ted to starch. If row B had not been set up, it would be valid to suggest
that starch would have been formed whether or not the glucose was phosphor ylated. Similarly, starch was not
formed in row C showing that phosphor ylase (in potato extract) must be present for phosphor ylated glucose
to be conver ted to starch. If row C had not been included, it would be valid to suggest that phosphor ylated
glucose would have become starch whether or not phosphor ylase was present. Therefore rows B and C in this
investigation are negative controls.
Synthesis of ATP Metabolic pathways of cellular

When an energy-rich substance such as glucose is respiration
broken down during cellular respiration in a living
cell, it releases energy that is used to synthesise ATP Glycolysis
from ADP and Pi. Cellular respiration consists of many The process of cellular respiration begins in the
enzyme-controlled steps, which ensure that energy cytoplasm of a living cell with a molecule of glucose
release occurs in an orderly fashion. being broken down to form pyruvate. This process of
‘glucose-splitting’ is called glycolysis. It consists of a
A flow of high-energy electrons from the respiratory series of enzyme-controlled steps. Those in the first
pathway is used to pump hydrogen ions (H+) across the half of the chain make up the energy investment phase
inner mitochondrial membrane and maintain a region (where 2ATP are used up per molecule of glucose);
of higher concentration of hydrogen ions on one side of those in the second half of the chain make up an energy
the membrane (see Figure 7.11). payoff phase (where 4ATP are produced per molecule
Embedded in the membrane are molecules of the of glucose), as shown in Figure 7.12.
protein ATP synthase, which is an enzyme. The return Phosphorylation of intermediates occurs twice during
flow of hydrogen ions from the region of higher the first phase:
concentration to the region of lower concentration ● in step 1, where an intermediate is formed that can
takes place via ATP synthase molecules. This makes part connect with other metabolic pathways
of the ATP synthase rotate and catalyse the synthesis of ● in step 3, which is an irreversible reaction leading
ATP from ADP and Pi. ATP synthase molecules operate only to the rest of the glycolytic pathway and
in a similar way in the membranes of chloroplasts. catalysed by the enzyme phosphofructokinase.
The generation of 4ATP that occurs during the second
half of the pathway gives a net gain of 2ATP per
molecule of glucose during glycolysis. In addition,
during the energy payoff phase, H+ ions are released
from the substrate by a dehydrogenase enzyme. These 101
H+ ions are passed to a coenzyme molecule called
Human Cells Unit 1
mitochondrion
enlarge
H+ H+ H+ H+ H+
higher concentration of H+ H+
on this side of membrane H+ H+
inner membrane
H+ H+
lower concentration of H+
on this side of membrane
H+ H+ H+
flow of ‘high energy’ ADP + Pi ATP

electrons used to pump
H+ across membrane ATP synthase
Figure 7.11 ATP synthase in action
NAD (full name, nicotinamide adenine dinucleotide), The acetyl group of acetyl coenzyme A combines
forming NADH. with oxaloacetate to form citrate and enter the citric
acid cycle. This cycle consists of several enzyme-
The process of glycolysis does not require oxygen.
mediated stages, which occur in the central matrix of
However, NADH only leads to the production of
mitochondria and result finally in the regeneration of
further molecules of ATP at a later stage in the
oxaloacetate.
respiratory process if oxygen is present. In the absence
of oxygen, anaerobic respiration occurs (see page 113). In three steps in the cycle, dehydrogenase enzymes
remove H+ ions from the respiratory substrate along
Citr ic acid cycle with associated high-energy electrons. These H+ ions
If oxygen is present, aerobic respiration proceeds and and high-energy electrons are passed to the coenzyme
pyruvate is broken down into carbon dioxide and NAD to form NADH. In one other step a similar
an acetyl group. Each acetyl group combines with reaction occurs but the coenzyme is FAD (full name,
coenzyme A to form acetyl coenzyme A. During this flavine adenine dinucleotide). On accepting H+ ions
process, further H+ ions are released and become bound and electrons it becomes FADH2. In addition, ATP is
102 to NAD, forming NADH. A simplified version of the produced in one of the steps and carbon dioxide is
metabolic pathway is shown in Figure 7.13. released in two of the steps.
pyruvate
glucose
ATP CO2
ADP phosphorylation at step 1 NAD
other
intermediate able to metabolic NADH
continue to other pathways pathways
acetyl
coenzyme A
coenzyme A
energy
investment intermediate
phase
ATP phosphorylation at step 3
ADP catalysed by phosphofructokinase
intermediate citrate
2CO2
2NAD oxaloacetate
2NADH
citric
2ADP acid
2ATP 3NAD
cycle
energy
payoff
phase 3NADH
m s
FADH2 an
y en s tep
2ADP z y m e - c o n t ro ll e d
2ATP
FAD ADP + Pi
pyruvate
ATP
Figure 7.12 Glycolysis Figure 7.13 Citric acid cycle
Related Activity
Demonstrating the effect of malonic succinic dehydrogenase

acid succinate + FAD ⎯⎯⎯⎯⎯⎯⎯⎯⎯→ fumarate + FADH2
Background ● Malonic acid is a chemical that inhibits the action of

● Succinate and fumarate are two of the intermediates succinic dehydrogenase.
in the citric acid cycle. ● In this investigation a chemical called DCPIP is used
● When succinate is converted to fumarate during as the hydrogen acceptor. DCPIP changes colour upon
respiration in a living cell, hydrogen is released and gaining hydrogen as follows:
passed to the coenzyme FAD. The reaction is catalysed dark blue ⎯⎯⎯⎯→ colourless
by the enzyme succinic dehydrogenase as follows: (lacks hydrogen) (has gained hydrogen)
103
➜
Human Cells Unit 1
The exper iment is carr ied out as shown in Figure 7.14.

From the results it is concluded that in tube A succinic A B
dehydrogenase in respir ing mung bean cells has conver ted

malonic
succinate to fumarate and that the hydrogen released distilled
acid
water mung
has been accepted by DCPIP, turning it colourless. It is solution
beans
concluded that in tube B, the respirator y pathway has
been blocked and no hydrogen has been released for DCPIP
to accept because malonic acid has inhibited the action of
after 24 hours mung after 24 hours mung
succinic dehydrogenase. beans cut in half beans cut in half
dark blue
DCPIP
dark
colourless
blue
Figure 7.14 Ef fect of malonic acid
Electron transpor t chain of hydrogen ions is maintained. The return flow of

An electron transport chain consists of a group of hydrogen ions to the matrix (the region of lower H+
protein molecules. There are many of these chains in a concentration) via molecules of ATP synthase drives
cell. They are found attached to the inner membrane of this enzyme to synthesise ATP from ADP and Pi. Most
mitochondria. NADH and FADH2 from the glycolytic of the ATP generated by cellular respiration is produced
and citric acid pathways release high-energy electrons in mitochondria in this way.
and pass them to the electron transport chains (see
When the electrons come to the end of the electron
Figure 7.15).
transport chain, they combine with oxygen, the
The electrons begin in a high-energy state. As they final electron acceptor. At the same time, the oxygen
flow along a chain of electron acceptors, they release combines with a pair of hydrogen ions to form water.
energy. This is used to pump hydrogen ions across the In the absence of oxygen, the electron transport chains
membrane from the inner cavity (matrix) side to the do not operate and this major source of ATP becomes
intermembrane space, where a higher concentration unavailable to the cell.
104
mitochondrion
outer
membrane
enlarge
inner cavity (matrix)

inner
membrane
intermembrane space
enlarge
INTERMEMBRANE SPACE
electron transport chain
H+ H+ H+ H+ H+ H+ H+
flow of ‘high H+ H+ H+ H+ H+
energy’ electrons return flow of H+
energy from electrons used
H+ H + makes part of the
to pump H+ across membrane
ATP synthase rotate
inner
mitochondrial
membrane
H+ H+
H+ H+ H+ ATP synthase
NADH
FADH2 ADP + Pi ATP
FAD
NAD
low-energy hydrogen
+ oxygen + water
electrons ions
MATRIX
Figure 7.15 Electron transpor t chain
Related Activity
Investigating the activity of ● Yeast cells contain small quantities of stored food that
can be used as a respirator y substrate.
dehydrogenase enzyme in yeast ● Resazur in dye is a chemical that changes colour upon
Background gaining hydrogen, as follows:
● Dur ing respiration, glucose is gradually broken down blue ⎯⎯→ pink ⎯⎯→ colourless
and hydrogen released at various stages along the (lacks (some (much
pathway. Each of these stages is controlled by an hydrogen) hydrogen hydrogen
enzyme called a dehydrogenase. gained) gained) 105
➜
Human Cells Unit 1
● Before setting up the exper iment shown in Figure 7.16,
dr ied yeast is added to water and aerated for an hour at A B C
35°C to ensure that the yeast is in an active state.
blue
Once the experiment has been set up, the contents resazurin glucose water glucose
of tube A are found to change from blue via pink to dye in each boiled yeast
tube suspension
colourless much faster than those of tube B. Tube C, the
live yeast
control, remains unchanged. suspension
It is concluded that in tube A, hydrogen has been rapidly
released and has acted on and changed the colour of the tubes shaken vigorously for 20
resazur in dye. For this to be possible, dehydrogenase seconds and placed in water bath
enzymes present in the yeast cells must have acted on
glucose, the respirator y substrate.
In tube B, the reaction was slower because no glucose was A B C
added and the dehydrogenase enzymes could only act on

any small amount of respirator y substrate already present contents water bath
of each at 35°C
in the yeast cells. tube begin
blue
In tube C, boiling has killed the cells and denatured the
dehydrogenase enzymes.
after a few minutes
colourless pink blue
Figure 7.16 Dehydrogenase activity
1 a) What compound is represented by the letters ATP? (1) 3 Using the letters G, C and E, indicate whether each of
b) What is the structural dif ference between ATP and the following statements refers to glycolysis (G), citr ic
ADP? (1) acid cycle (C) or electron transpor t chain (E). (Some
c) Give a simple equation to indicate how ATP is statements may need more than one letter.) (8)
regenerated in a cell. (2) a) It br ings about the breakdown of glucose to
2 Explain each of the following: pyruvate.
a) Dur ing the glycolysis of one molecule of glucose, the b) It ends with the production of water.
net gain is two and not four molecules of ATP. (1) c) It begins with acetyl from acetyl coenzyme A
b) Living organisms have only small quantities of combining with oxaloacetate.
oxaloacetate in their cells. (1) d) It involves a cascade of electrons, which are f inally
c) A human body can produce ATP at a rate of around accepted by oxygen.
400 g/h, yet at any given moment there are only e) It has an energy investment and energy payof f
about 50 g present in the body. (2) phase.
f) It results in the production of NADH.
106
g) It involves the release of carbon dioxide.
h) It results in the production of ATP.
Substrates for respiration

glucose
Carbohydrates
Starch (a complex carbohydrate stored by plants) and
glycogen (a complex carbohydrate stored by animals) glycerol intermediate
are composed of chains of glucose molecules. They act

as respiratory substrates since they can be broken down
fat pyruvate
to release glucose as required (see Figure 7.17). Other
sugar molecules such as maltose and sucrose can also be
converted to glucose or intermediates in the glycolytic acetyl
pathway and used as respiratory substrates. fatty acids coenzyme A
Fats
When required for use as a respiratory substrate, a citric
acid
molecule of fat is broken down into glycerol and fatty cycle
acids. These products then become available for use in
cellular respiration. Glycerol is converted to a glycolytic
intermediate (see Figure 7.18) and fatty acids are
metabolised into molecular fragments that enter the Figure 7.18 Fat as a respirator y substrate
pathway as acetyl coenzyme A for use in the citric acid
cycle.
requirements for protein synthesis undergo
deamination, forming urea and respiratory pathway
Proteins intermediates, as shown in Figure 7.19. These
Proteins in the diet are broken down to their intermediates then enter the metabolic pathway and
component amino acids by the action of digestive act as respiratory substrates, regenerating ATP as
enzymes. Amino acids in excess of the body’s before.
starch glycogen
maltose glucose sucrose
fructose
pyruvate
107
Figure 7.17 Carbohydrates as respirator y substrates
Human Cells Unit 1
glucose
amino acids
pyruvate
(e.g. alanine)
urea
amino acids acetyl

protein (e.g. leucine) coenzyme A
urea
amino acids citric

(e.g. aspartic intermediate acid
acid) cycle
deamination of amino
urea
acid to respiratory
pathway intermediate
urea
Figure 7.19 Protein as a respirator y substrate
Practical Activity and Report
Investigating the use of three different sugars as respiratory substrates for yeast
Information ● 1 container of glucose solution (10 g in 90 ml water)
● Figure 7.20 shows, in a simple way, the molecular ● 1 container of maltose solution (10 g in 90 ml water)
structure of three types of sugar and the digestive
enzymes needed to break down maltose and sucrose. ● 1 container of sucrose solution (10 g in 90 ml water)
● Str ictly speaking, this activity is really three ● 3 conical flasks (250 ml) each with rubber stopper and
investigations being carr ied out simultaneously. deliver y tube
● In each case the independent var iable is time. ● 3 labels
● The dependent var iable that you are going to measure ● 3 portions of dr ied yeast, each 1 g
is the volume of carbon dioxide released as a result of ● clock
yeast using a par ticular type of sugar as its respirator y
substrate. What to do
1 Read all of the instructions in this section and prepare
You need your results table before carr ying out the exper iment.
● 3 graduated tubes
2 Fill each graduated tube with coloured tap water and
● 3 large beakers (e.g. 500 ml) of coloured tap water clamp it in an inver ted position in a beaker of coloured
108 water, as shown in Figure 7.21.
● 3 clamp stands
glucose
maltose
maltase
glucose glucose glucose glucose
sucrose sucrase
glucose fructose glucose fructose
Figure 7.20 Relationship between three sugars
3 Label the conical flasks ‘glucose’, ‘maltose’ and ‘sucrose’

respectively and add your initials.
4 Pour the appropr iate sugar solution into each conical
flask and add a por tion of dr ied yeast.
graduated
tube 5 Assemble the stoppers and deliver y tubes as shown in
Figure 7.21.
6 Star t the clock and record, at 5-minute inter vals, the
total volume of carbon dioxide that has been released
for each flask over a period of 2 hours.
7 If other students have carr ied out the same exper iment,
pool the results.
Reporting
Wr ite up your repor t by doing the following:
1 Rewr ite the title given at the star t of this activity.
2 Wr ite the subheading ‘Aim’ and state the aim of your
exper iment.
coloured 3 a) Wr ite the subheading ‘Method’.

tap water
b) Draw a diagram of your apparatus set-up at the star t
of the exper iment af ter the yeast has been added
and bubbles of carbon dioxide are being released.
c) Br iefly descr ibe the experimental procedure that you
followed using the impersonal passive tense. Note:
The impersonal passive tense avoids the use of ‘I’ and
‘we’. Instead it makes the apparatus the subject of
the sentence. In this exper iment, for example, you
could begin your repor t by saying ‘Three graduated
tubes were f illed with coloured water. . . (not ‘I f illed
three graduated tubes with coloured water. . .).
sugar
solution + d) Continuing in the impersonal passive tense, state
live yeast
how your results were obtained.
4 Wr ite the subheading ‘Results’ and draw a f inal version
Figure 7.21 Yeast investigation set-up of your table of results. 109
➜
Human Cells Unit 1
5 Wr ite the subheading ‘Analysis and Presentation of 7 Wr ite the f inal subheading ‘Evaluation of Experimental
Results’. Present your results as three line graphs with Procedure’. Give an evaluation of your exper iment
shared axes on the same sheet of graph paper. (keeping in mind that you may comment on any stage
of the exper iment that you wish). Tr y to incorporate
6 Wr ite the subheading ‘Conclusion’ and a shor t
answers to the following questions in your evaluation,
paragraph to state what you have found out from a
making sure that at least one of your answers includes a
study of your results. This should include answers to the
suppor ting statement.
following questions:
a) Why is the same mass of yeast and the same mass of
a) Which respirator y substrate(s) was yeast able to use
sugar used in ever y flask?
ef fectively?
b) Why is the same genetic strain of yeast used in each
b) Which enzyme (see Figure 7.20) is probably produced
flask?
by yeast cells in adequate quantities to digest its
substrate before its use in cellular respiration? c) Why must the rubber stoppers be tightly f itting?
c) Which respirator y substrate(s) was yeast not able to d) Why should a control flask containing distilled water
use ef fectively? and yeast have been included in this investigation?
d) Which enzyme is probably not produced by yeast in e) What is the purpose of pooling results with other
adequate quantities within the 2-hour timescale to groups?
digest its substrate and make it suitable for use in
cellular respiration?
Research Topic Use of respiratory substrates during exercise and starvation
Carbohydrate, fat and protein can all be used as sources of energy. Blood glucose (largely from liver
respiratory substrates. Their individual contr ibutions to glycogen) and slower-acting fatty acids provide most of the
the body’s overall energy supply depends upon the body’s energy over the next 30 minutes or so. In the later stages
circumstances. of the race, fatty acids become increasingly impor tant as
supplies of glucose decrease.
Exercise
For several minutes, from the star t of aerobic exercise, the A marathon runner therefore depends on a combination of
body burns pr imar ily carbohydrates. Af ter 20–30 minutes of carbohydrate and fat. The relative contr ibution made by
continuous exercise, respirator y substrate usage shif ts to a each fuel depends on availability. The athlete might decide
balance of around 50% carbohydrate and 50% fat. Dur ing to ‘load up’ with carbohydrate dur ing pre-race meals. He or
the f irst hour of exercise, protein makes up less than 2% of she might consume an approved refreshment of glucose
the respirator y substrate but its utilisation increases dur ing solution af ter 11 km and thereaf ter at inter vals of 5 km.
prolonged exercise. It can reach 5–15% of fuel usage during Under these circumstances the degree of dependency on fat
the latter stages of prolonged exercise lasting 5 hours or reser ves is greatly reduced.
more.
Starvation
Marathon running
Starvation results when the body continuously expends
The respirator y substrates used in this lengthy athletic more energy than it takes in as food. During the early
event (42.2 km) are glucose, glycogen and fat, as shown in stages of star vation, the body uses up its store of glycogen
Figure 7.22. Dur ing the f irst few minutes of the race, readily and then mobilises its fat reser ves. As star vation becomes
available glucose from muscle glycogen is the main fuel prolonged, liver cells continue to use fatty acids from stored
used to generate energy. However, as the race continues fats to form acetyl coenzyme A. Some acetyl coenzyme A
and the rate of blood flow increases, blood-borne fuels enters the citr ic acid cycle (see Figure 7.18) and is used in
carr ied to the exercising muscles become the dominant the normal way; some becomes conver ted to water-soluble
110
glycogen fat in adipose

in liver tissue
release of release of
glucose fatty acids
glycogen
in muscle
glucose in fatty acids

release of glucose blood in blood
in muscle cells
rapid release slower release of

rapid release of energy over energy sustained
of energy over a short time over a long time
a short time
energy for
muscular
contraction
Figure 7.22 Fuelling a marathon
ketones, which are transpor ted in the bloodstream to the fat have become exhausted. Then skeletal muscle and other
brain and provide it with a vital source of energy. tissues r ich in protein are used up to provide energy dur ing
the cr isis. Eventually the person becomes emaciated and
Tissue protein is used as a source of energy only dur ing death soon follows.
prolonged star vation when the reser ves of glycogen and
Regulation of the respirator y slows down glycolysis. When the concentration of ATP
decreases again, the enzyme is no longer inhibited and
pathway glycolysis speeds up. Phosphofructokinase is similarly
Refer back to Figure 7.12, which shows glycolysis. The inhibited by high concentrations of citrate. However, if
third step in this process is catalysed by the enzyme the citrate concentration drops (because other pathways
phosphofructokinase. It is an irreversible step and are using citric-acid-cycle intermediates) then the
the intermediate formed as a result of enzyme action enzyme is no longer inhibited and the rate of glycolysis
is committed to continuing glycolysis. This third step increases.
is regarded as a key regulatory point in the pathway
because the activity of the enzyme can be regulated as This process of feedback inhibition regulates
follows. and synchronises the rates of the glycolytic and
citric acid cycle pathways. It is important
When the cell contains more ATP than it needs to meet because:
its current demands, the high concentration of ATP ● the needless build-up of an intermediate is 111
inhibits phosphofructokinase (see Figure 7.23) and prevented
Human Cells Unit 1
glucose
phosphofructokinase
high concentration of ATP high concentration of citrate

has an inhibitory effect has an inhibitory effect
pyruvate
citrate
citric acid
ATP cycle
electron transport chain

(and ATP synthase)
Figure 7.23 Regulation of the respirator y pathway
● ATP is only produced from respiratory pathways as contraction comes from a chemical called creatine
required phosphate, which plays a key role in the coupled
● resources are conserved. reactions shown in Figure 7.24.
During strenuous muscular activity, creatine phosphate

Creatine phosphate system in muscle cells breaks down, releasing energy and
ATP is the source of immediately-available chemical phosphate, which are used to convert ADP to ATP by
energy needed for muscular contraction. During phosphorylation. The ATP formed is used to sustain
intense muscular activity, muscle cells break down ATP maximal muscular contraction for a few more seconds
to ADP and phosphate. This process is accompanied by following the original intense muscular effort. Therefore
the release of energy to do work. However, each muscle sufficient energy is generated to fuel a short burst of
112 cell only stores sufficient ATP for a few contractions. intense activity such as a 100-metre sprint, a golf swing
Much of the energy needed for repetitive muscular or the lifting and lowering of a heavy weight.
During a rest period when demand for energy by

a) during strenuous activity
muscle cells is low, little of the ATP produced by cellular
respiration is required for muscular contraction. Under
y
creatine
en
erg ATP these circumstances ATP is used to generate creatine
phosphate. Enzymes bring about the breakdown of
ATP, releasing phosphate and energy, which are used
phosphorylation of ADP to produce creatine phosphate by phosphorylation.
This creatine phosphate acts as a high-energy reserve
available to muscle cells during the next period of
creatine
phosphate
ADP strenuous activity.
Lactic acid metabolism

b) during rest period During strenuous exercise, the tiny quantity of ATP
present in muscle cells lasts for about 3 seconds.
creatine Resynthesis of ATP from creatine phosphate continues
ATP to provide energy for a few more seconds until the
creatine phosphate store is depleted. As the intensive
exercise continues, the cells respire anaerobically
phosphorylation of creatine
because they do not receive an adequate supply of
gy oxygen from the bloodstream to support an increased
er
creatine en level of aerobic respiration.
phosphate
ADP
Neither the citric acid cycle nor the electron transport
chain can generate the additional ATP required; only
Figure 7.24 Creatine phosphate system glycolysis is able to provide more ATP. It generates
Case Study Creatine supplements

Creatine present naturally in muscle cells has been It is now known that different people respond
manufactured by liver cells or has been derived from to creatine supplements in different ways. For
items in the diet such as meat. A 70 kg adult has example, those who have a naturally high store of
about 120 g of creatine in their muscles. creatine in their muscles do not receive an energy-
boosting effect from a supplement. Many medical
Supplements and sporting performance
experts consider that claims for creatine as a
Increased intake of creatine as supplements has been
muscle performance enhancer have been greatly
shown to increase the store in the body by up to an
exaggerated.
upper limit of around 20%. Excess creatine is excreted
in urine. Various studies have been carried out to
Side effects
investigate if a relationship exists between increased
No adverse effects have been reported for short-
creatine levels in muscle cells (following supplements
term studies. However, many athletes are taking
taken over a 5–6 day loading period) and improved
creatine supplements over extended periods and no
athletic performance.
long-term studies have been carried out. It is known
Creatine supplements were found to improve the that the kidneys of athletes taking the supplements
performance of many ‘power’ athletes engaged in often have to produce urine containing creatine at
exercise of a brief, high-intensity nature such as concentrations of up to 90 times the normal level.
sprinting and weight-lifting. However, those studies This may be doing their kidneys long-lasting damage.
that examined the effect of creatine supplements on At present no one can state confidently that taking
performance of events involving endurance exercise creatine supplements over an extended period is
such as long-distance running showed no significant safe. People are advised to avoid doing so until more 113
improvement. research has been carried out.
Human Cells Unit 1
2NADH and 2ATP from each molecule of glucose as
it is broken down to pyruvic acid (see Figure 7.25).
This process is followed by the conversion of pyruvic
acid (pyruvate) to lactic acid (lactate) accompanied
by the transfer of hydrogen from the NADH and the
regeneration of NAD. NAD must be present to enable
glycolysis to continue and produce more ATP.
Figure 7.26 Repayment of oxygen debt

lactic acid
glucose
(lactate)
ATP totals
Lactic acid metabolism (anaerobic respiration) is a
less efficient process since it produces only 2ATP per
molecule of glucose compared with around 38ATP
formed by cellular respiration in the presence of oxygen
2ADP (aerobic respiration).
2NAD
+ 2Pi
Types of skeletal muscle fibre

oxygen debt builds up
oxygen debt repaid
All physical activities require parts of the body to move.

These movements are brought about by the action of
2ATP 2NADH skeletal muscle fibres, which fall into two categories
based on the duration of their twitches:
● type 1 – slow-twitch muscle fibres

● type 2 – fast-twitch muscle fibres
The two types differ in many ways, as shown in
Table 7.1.
pyruvic acid
(pyruvate) Myoglobin
Myoglobin is an oxygen-storing protein present in
muscle cells. It has a stronger affinity for oxygen than
haemoglobin. (Affinity means tendency to combine
with a substance.) Therefore myoglobin is able to
Figure 7.25 Lactic acid metabolism extract oxygen from blood for use by muscle cells,
especially those in slow-twitch muscle fibres.
However, as lactic acid gathers in muscle cells, it causes
fatigue and an oxygen debt builds up. This is repaid Dif ferent f ibres for dif ferent events
when exercise comes to a halt (see Figure 7.26). Energy Slow-twitch muscle fibres depend on aerobic
generated by aerobic respiration is now used to convert respiration to generate most of their ATP and are
lactic acid (transported in the bloodstream to the liver) especially effective when put to use during endurance
back to pyruvic acid and glucose. events such as rowing, cycling and long-distance
running. Fast-twitch muscle fibres depend on glycolysis
to generate ATP and are especially effective when put
114 to use during power events such as weight-lifting and
sprinting.
Feature Type of skeletal muscle fibre

1 (slow-twitch) 2 (fast-twitch)
Speed of contraction Slow Fast
Length of time for which contraction is sustained Long Shor t
Speed at which f ibre becomes fatigued Slow Fast
Respirator y pathway(s) normally used to generate ATP Glycolysis and aerobic pathways Glycolysis only
Number of mitochondr ia present Large Small
Density of blood capillar ies associated with f ibre High Low
Concentration of myoglobin in cells High Low
Major storage fuels used Fats Glycogen and creatine phosphate
Table 7.1 Compar ison of slow- and fast-twitch muscle f ibres
Skeletal muscles contain a genetically determined For example, the muscles in the back responsible for
mixture of slow-twitch and fast-twitch fibres. In most maintaining posture contain mostly slow-twitch fibres,
muscles, a fairly even balance exists between the two but whereas the muscles that move the eyeballs are made up
in some muscles, one type predominates over the other. mainly of fast-twitch fibres.
Case Study Muscle fibre types in elite athletes

Skeletal muscles normally contain a balanced world-class level and the genetically determined ratio
mixture of slow- and fast-twitch fibres. The actual of their slow to fast muscle fibres. Olympic sprinters,
composition of an individual’s muscles is genetically for example, have been shown to possess up to
determined. Some people inherit a higher than 80% fast-twitch fibres in their leg muscles whereas
average percentage of type 1; others a higher than elite athletes who excel in marathons often have
average percentage of type 2. It is thought therefore around 80% slow-twitch fibres in the same muscles.
that the former are more suited to endurance sports It must also be kept in mind that athletic success
whereas the latter have an edge in power sports. is also closely related to the quantity and quality of
intensive practice undertaken by the athlete during
It is certainly the case that a correlation exists
training.
between the type of sporting event performed by
athletes who eventually excel in their field at a
115
Human Cells Unit 1
1 Name T WO complex carbohydrates composed of chains

of glucose molecules. (2) carbohydrate 2
1
2 Figure 7.27 shows the relationship between
carbohydrate and two other classes of food that can act
as alternative sources of energy. Identify blanks 1–5. (5)
3 The equation in Figure 7.28 represents the creatine
phosphate system.
3 intermediate 4
a) Identify which chemical undergoes phosphor ylation
dur ing i) reaction X, ii) reaction Y. (2)
b) Which of reactions X and Y is the per iod of rest and pyruvate
which is the per iod of strenuous activity? (1) fatty acids

4 Compare fast- and slow-twitch muscle f ibres with
reference to major storage fuels used, relative 5
number of mitochondria and relative concentration of

myoglobin. (3)
citric
acid
cycle
Figure 7.27
X
creatine phosphate ADP creatine ATP
Y
Figure 7.28
acetyl competitive FAD irreversible phosphate substrate

activation complex fatigue lactic phosphofructo synchronise
ADP concentration f ibres lower ing kinase transferred
af f inity creatine genetic metabolism phosphor ylation transition
anabolism debt glycolysis NADH product transpor t
ATP electron hydrogen negative proteins twitch
ATP synthase endurance induced of f pyruvate wasted
break energy inhibit on regulated water
catabolism environment inhibition or ientation shape
citrate enzymes investment oxygen structure
116 Table 7.2 Word bank for chapters 6–7

1 Cell ______ encompasses all the enzyme-catalysed phosphor ylation using energy released dur ing cellular
reactions that occur in a cell. respiration. ______ also occurs when Pi and energy are
______ from ATP to a reactant in a pathway.
2 ______ consists of biosynthetic metabolic pathways
that build up ______ molecules from simpler 12 Cellular respiration begins with ______, the breakdown
constituents and need a supply of energy; ______ of glucose to ______. This consists of an energy ______
consists of metabolic pathways that ______ down larger phase and an energy payof f phase with a net gain of two
molecules into smaller ones and usually release ______. molecules of ATP.
3 For a metabolic reaction to occur, ______ energy is 13 In the presence of oxygen, pyruvate is broken down into
needed to form a ______ state from which end products carbon dioxide and an ______ group. With the help of
are produced. ______ catalyse biochemical reactions by coenzyme A, the acetyl group enters the citr ic acid cycle
______ the activation energy needed by the reactants by combining with oxaloacetate to become ______.
to form their transition state.
14 As one respirator y substrate is conver ted to another in
4 Substrate molecules have an ______ for the active the citr ic acid cycle, carbon dioxide is released, ATP is
site on an enzyme. The active site’s shape determines formed and pairs of ______ ions along with high-energy
the ______ of the reactants on it and it binds to them electrons are removed and passed to coenzymes NAD
closely with an ______ f it. and ______, forming NADH and FADH2.
5 The enzymes controlling a metabolic pathway usually 15 ______ and FADH2 pass their high-energy electrons to
work as a group. Although some steps are ______, ______ transpor t chains where the energy released is
most metabolic reactions are reversible. The direction used to pump hydrogen ions across inner mitochondr ial
in which the reaction occurs depends on factors such as membranes. The return flow of these hydrogen ions
concentration of the ______ and removal of a ______ makes par t of each ______ molecule rotate and
as it becomes conver ted to another metabolite. catalyse the synthesis of ATP. ______, the f inal electron
6 Each step in a metabolic pathway is ______ by an acceptor, combines with hydrogen ions and electrons to
enzyme that catalyses a specif ic reaction. Each enzyme form ______.
is under ______ control. 16 Complex carbohydrates, ______ and fats can all be used
7 Some metabolic pathways are required continuously as respirator y substrates if they are f irst conver ted to
and the genes that code for their enzymes are always suitable intermediates able to enter the pathway.
switched ______. Other pathways are only needed on 17 ______ is an enzyme that catalyses an irreversible step
cer tain occasions. To prevent resources being ______, in glycolysis. Its activity is inhibited by high levels of ATP
the genes that code for their enzymes are switched on and citrate. These inhibitor y feedback mechanisms help
or ______ as required in response to signals from within to ______ and regulate the respirator y pathway.
the cell and from its ______.
18 Dur ing strenuous activity, ______ phosphate in muscle
8 Molecules of a ______ inhibitor resemble the substrate cells breaks down, releasing energy and ______ used
in ______. They become attached to the active site to conver t ADP to ATP. The ATP formed fuels muscle
and slow down the reaction. Their ef fect is reversed by contraction for a few seconds.
increasing the ______ of substrate.
19 Dur ing a per iod of vigorous exercise, muscle cells do not
9 Some regulator y molecules stimulate enzyme activity or receive the adequate supply of oxygen needed for the
______ it non-competitively by changing the ______ of electron ______ chain to operate. Instead of enter ing
the enzyme molecule and its active site(s). the citr ic acid cycle, pyruvate is converted to ______
10 Some metabolic pathways are controlled by end product acid, which causes ______ of muscles. Any oxygen
______, a form of ______ feedback control. ______ that develops is repaid when the vigorous
exercise comes to a halt.
11 ______ is a high-energy compound able to release
and transfer energy when it is required for cellular 20 Skeletal muscle contains fast-twitch ______, good for
processes. ATP is regenerated from ______ and Pi by shor t-lived power events, and slow-______ f ibres, good
for ______ activities.
117
Human Cells Unit 1
Applying Your Knowledge and Skills
Chapters 1–7 vi) nucleus inser ted into egg

1 Figure 7.29 shows a possible use of stem cells in the
b) Which of the following is not represented in
future.
Figure 7.29? (1)
A cytoplasmic hybr id cell
a) Match blank boxes P, Q, R, S, T and U with the
B amniotic stem cell line

following possible answers. (5)
C undif ferentiated stem cells
i) stem cells induced to dif ferentiate
D nuclear transfer technique
ii) nucleus removed and retained
iii) stem cells removed and cultured in laborator y c) i) Name a source of the donor egg cells used at
iv) egg lacking nucleus retained present in this line of research.
v) matching tissue transplanted to patient without ii) Why does this prevent the ser ies of events shown
fear of rejection in the diagram being put into practice? (2)
adult patient
cells
taken
U
cardiac cell
brain discarded P Q nucleus removed
tissue tissue and discarded
T
embryo
mitosis and cell division
stem cell
colony of
stem cells
Figure 7.29
2 Refer back to Figure 2.8 on page 19, which shows b) Why did the transforming principle treated with
Gr if f ith’s transformation experiment. Aver y continued DNAase have no ef fect on the mouse? (2)
this line of investigation and isolated a chemically c) Why did the transforming principle treated with
pur if ied form of the ‘pr inciple’ that transformed live R protease still work and af fect the mouse? (2)
to live S cells. He then carr ied out the exper iment shown d) Identify T WO factors from Figure 7.30 that must be
in Figure 7.30. kept constant throughout the exper iment. (2)
a) Find out and state the ef fect that: e) State the means by which the reliability of the
i) the enzyme DNAase has on DNA, its substrate experiment could be checked. (1)
ii) the enzyme protease has on protein, its
118 substrate. (2)
3 Refer back to Figure 2.19 on page 27 and then draw a

labelled diagram to show both the DNA strands and the
test tube contents that would result af ter three DNA transforming principle
replications involving semi-conser vative replication

only. (4)
4 Figure 7.31 on page 120 shows mRNA’s codons and the
amino acids that they code for. treated with treated with left
DNAase and protease and untreated and
a) Which letters should have been inserted at positions then injected then injected injected into
into mouse into mouse mouse
X and Y in the wheel? (2)
b) How many codons are able to tr igger the process of
translation? (1)
c) Identify the codons that can br ing translation to a
halt. (3)
d) Which amino acid is coded for by codon:
i) UUU; ii) ACC; iii) GGU? (3)
e) Name all the codons that code for leucine. (2)
f) Refer back to Figure 3.9 on page 38 and then state
which amino acid would become attached to this
tRNA’s site of attachment. (Remember that tRNA
has an anticodon and that the wheel shows mRNA
codons.) (1)
5 Figure 7.32 on page 120 shows the base sequence on a
region of DNA undergoing a type of point mutation.
a) i) Identify the type of point mutation that occurred.
ii) Descr ibe the way in which the DNA has been
altered. (2) mouse unaffected mouse dies mouse dies
b) Refer to Table 3.2 on page 39 and Appendix 1 and

work out the amino acid sequence for: Figure 7.30
i) the or iginal DNA 8 The graph in Figure 7.34 on page 121 shows the
ii) the mutant DNA. (2) expected number of copies of DNA that would be
c) i) State whether this mutation would be generated by the polymerase chain reaction (PCR) under
missensical or nonsensical. ideal conditions.
ii) Explain your choice. (2) a) i) What name is given to the type of graph paper
6 Copy and complete Table 7.3 on page 121, which refers used here to present the data?
to three genetic disorders descr ibed in case studies ii) Why has this type of graph paper been used? (2)
chapter 4 (pages 56–59). (12) b) How many cycles of PCR are required to produce
7 The DNA fragments shown in Figure 7.33 on page 121 10 000 000 copies of the DNA? (1)
were formed dur ing the type of sequencing technique c) How many cycles are required to increase the number
illustrated in Figure 5.1 on page 64. Each fluorescent tag of copies of DNA already present at ten cycles by a
indicates the point on the strand where replication of factor of 103? (1)
complementar y DNA was brought to a halt by a modif ied d) i) How many copies of the DNA were present af ter
nucleotide. 30 cycles?
a) Work out the sequence of the bases in the ii) Now state your answer in words. (2)
complementar y DNA strand. (1) e) Refer back to Figure 5.9 on page 71 and, with the
b) Deduce the sequence of bases in the or iginal DNA aid of coloured pencils, draw a diagram of the DNA
strand. (1) that would be present at the end of the third cycle of
PCR. (4)
119
➜
Human Cells Unit 1
ine
phenylalan
glycine
ine
glu
leuc
tam
as
e
ic a
r in
pa
cid
se
rti
ca
C A G U C A G
G U ine
cid
U
A C os
ala
nin C A tyr
e U G OP
G G U U ST
A C P
A C STO
C A
[X] G ine
G C A U cyste
valine A C
STOP
C U G U G A
U G tryptophan
G U
arginine A G A C U C
C A leucine
U C G
e A
serin G U
A C
C C A A
ne U U [Y] G
lysi G U
pro
A lin
C e
ine C A
r ag U G G
pa A C U G A C U
as
his
e
tid
nin
glu
ine
STA ine or
reo
tam
th
arginin
RT
isoleucin
hion
ine
met
Figure 7.31
Figure 7.35 on page 122 shows an exper iment set up

triplet of to investigate the lac operon in E. coli (where β-g =
bases
β-galactosidase).
C T C A G G A A C T G C a) Explain the yellow colour in i) tube C, ii) tube E. (2)
b) Explain the faint yellow colour in tube A. (1)
c) It could be argued that ONPG acts as an inducer.
mutation Draw a diagram of the control that should be set up
to check out this possibility. (1)
d) How could the reliability of the results be improved? (1)
C T C A G G A T C T G C
e) Return to page 90 and consider the experiment
shown in Figure 6.23. Imagine that bacter ia from
plates B and D have been grown on plates E and F
Figure 7.32 respectively, which both contain nutrient agar and
9 ONPG is a chemical that can be broken down as follows: arabinose.
β -galactosidase i) Predict the ef fect of exposing plates E and F to
ONPG ⎯⎯⎯⎯⎯⎯⎯→ galactose + yellow compound ultraviolet light.
120 ii) Explain your answer. (3)
Genetic disorder Type of single- Effect of mutation Effect of mutation Effect of mutation
gene mutation on structure of on functioning of on phenotype of
responsible protein expressed protein untreated, affected
individual
Phenylketonur ia (PKU)
Cystic f ibrosis
Huntington’s disease
Table 7.3
1 000 000 000
Key
complementary DNA
A 100 000 000

primer modified nucleotide
with fluorescent tag
10 000 000
G
C
T 1 000 000
G C
number of copies of DNA
100 000
10 000
T
T
A
1000
T
Figure 7.33
10 Give an account of enzyme activity under the headings: 100
a) induced f it (3)
b) activation energy (3)
c) ef fect of substrate concentration. (4) 10
11 Refer back to the investigation shown in Figure 7.14

on page 104. Based only on these results, it could be
argued that malonic acid has simply killed the cells.
0
0 5 10 15 20 25 30
a) How could the exper iment be adapted to investigate number of cycles of PCR
if malonic acid really does act as a competitive
inhibitor? (1) (Hint: see chapter 6, pages 91–92.) 121
Figure 7.34 ➜
Human Cells Unit 1
b) Explain how you would know from the results of your
redesigned exper iment whether or not malonic acid
had acted as a competitive inhibitor. (2)
E. coli in nutrient
broth + low E. coli in
concentration of nutrient broth
lactose
small small small small

sample sample sample sample
A B C D E F
E. coli E. coli ONPG -g E. coli E. coli

+ + + +
ONPG -g lactose lactose
+
ONPG
buffer
solution in
every tube after one hour at 35°C
A B C D E F
faint yellow colourless yellow colourless yellow colourless
Figure 7.35
122
Physiology and
Unit
2 Health
Physiology and Health Unit 2
8 Reproductive organs and hormonal control
Testes is by the sperm duct that free-swimming sperm leave

the testis. Testosterone is produced by interstitial cells
The reproductive system of the human male is shown in located in the tissue between the seminiferous tubules.
Figure 8.1. The testes are the site of sperm production Testosterone passes directly into the bloodstream.
and the manufacture of the male sex hormone
testosterone. Sperm (full name spermatozoa) are Sperm are motile. On being released during sexual
male gametes formed from germline cells in tiny tubes intercourse inside the female body, they move through
called seminiferous tubules. These tubules unite to the uterus and along the oviducts where they may meet
form coiled tubes that connect to the sperm duct. It an egg. The process of fertilisation is dependent upon
bladder
seminal vesicle
(one of two)
penis prostate gland
urethra sperm duct
testis
scrotum
close-up
seminiferous close-up of
tubule seminiferous
tubule
germline cell
spermatozoa
sperm interstitial cell

duct
blood capillary
124
Figure 8.1 Male reproductive system
Reproductive organs and hormonal control
the motility of sperm, which brings the two gametes The prostate gland (see Figure 8.1) secretes a thin,
together to form a zygote. Such motility requires a fluid lubricating liquid containing enzymes whose action
medium and a source of energy. maintains the fluid medium at the optimum viscosity
for sperm motility. Semen is the collective name given
Accessory glands to the milky liquid released by the male. It contains
The seminal vesicles (see Figure 8.1) secrete a liquid sperm from the testes and the fluid secretions from the
rich in fructose. This sugar provides sperm with the seminal vesicles and prostate gland that maintain the
energy needed for motility following their release by mobility and viability of sperm.
the male at ejaculation. The liquid secreted by the
seminal vesicles also contains hormone-like compounds Ovaries
that stimulate contractions of the female reproductive
The reproductive system of the human female is shown
tract. These movements help the sperm to reach the
in Figure 8.2. Eggs (ova) are formed from germline
oviduct at a much faster rate than could be achieved by
cells in the ovaries. The ovaries contain immature eggs
swimming alone.
oviduct (uterine tube)
ovary muscular coat

uterus
endometrium
cervix
vagina
enlarge
ovary
corpus luteum
immature
follicle
follicle mature ovum

developing released into
oviduct at ovulation
egg cell follicular liquid
(ovum)
125
Figure 8.2 Female reproductive system
at various stages of development. Each egg (ovum) is
surrounded by a follicle, which secretes the hormone
Hormonal control of sperm
oestrogen and protects the developing egg. Following production
ovulation (release of an egg), the follicle develops into Influence of pituitary hormones on testes
a corpus luteum (see Figure 8.2), which secretes the The two functions of the testes are regulated by
hormone progesterone. the pituitary hormones. When FSH arrives in the
bloodstream, it promotes sperm production in the
Hormonal control seminiferous tubules. When ICSH arrives, it stimulates
interstitial cells to produce the male sex hormone
Hormones are chemical messengers produced by an testosterone.
animal’s endocrine (ductless) glands and secreted
directly into the bloodstream. When a hormone Influence of testosterone
reaches a certain target tissue, it brings about a specific
Testosterone stimulates sperm production in the
effect. Hormones control the onset of puberty, sperm
seminiferous tubules. It also activates the prostate gland
production and the menstrual cycle.
and seminal vesicles to produce their secretions.
Hormonal onset of puberty Self-regulation of testosterone production

At puberty, the hypothalamus (see Figure 8.3) secretes As the concentration of testosterone builds up in the
a releaser hormone whose target is the pituitary bloodstream, it reaches a level where it inhibits the
gland. On being stimulated the pituitary responds by secretion of FSH and ICSH by the pituitary gland (see
producing two hormones. The first of these is called Figure 8.4). Since this leads in turn to a decrease in
FSH (follicle-stimulating hormone); the second is testosterone concentration, it is soon followed by a
known in men as ICSH (interstitial cell-stimulating
hormone) and in women as LH (luteinising hormone).
The release of these hormones at puberty triggers the
PITUITARY
onset of sperm production in men and the menstrual GLAND
cycle in women.
hypothalamus
FSH
brain ICSH
pituitary
high concentration
gland
of testosterone
TESTIS
stimulates stimulates
sperm testosterone
production production
SEMINIFEROUS INTERSTITIAL
TUBULES CELLS
= release of hormone
= stimulatory effect
= inhibitory effect
126
Figure 8.3 Location of hypothalamus and pituitar y gland Figure 8.4 Self-regulation of testosterone production
resumption of activity by the pituitary gland, which Influence of ovarian hormones on uterus
makes FSH and ICSH again, and so on. This type of and pituitar y gland
self-regulating mechanism is called negative feedback
control. Oestrogen
Oestrogen stimulates proliferation (cell division) of
Hormonal control of the menstrual the inner layer of the uterus, called the endometrium,
cycle thereby effecting its repair following menstruation and
preparing it for implantation. This ovarian hormone
Influence of pituitary hormones on ovar ies also stimulates the secretion of LH by the pituitary
FSH and LH from the pituitary gland affect the ovaries gland (see Figure 8.6).
in several ways. FSH stimulates the development and
maturation of each follicle (see Figure 8.5). It also Progesterone
stimulates ovary tissue to secrete the sex hormone Progesterone promotes the further development and
oestrogen. vascularisation of the endometrium into a spongy
layer rich in blood vessels, making it ready to receive a
LH triggers ovulation. It also brings about the
blastocyst (embryo) if fertilisation occurs. Progesterone
development of the corpus luteum from the follicle
also inhibits the secretion of FSH and LH by the
and then stimulates the corpus luteum to secrete the sex
pituitary gland (see Figure 8.7).
hormone progesterone. Oestrogen and progesterone
are known as the ovarian hormones.
The menstrual cycle
The events described above that are under hormonal
releaser
control in the human female fit together as
hypothalamus hormone
interacting parts of a synchronised system – the

menstrual cycle.
stimulates secretion
of FSH and LH
pituitary gland = release of hormone
= release of
hormone = stimulatory effect
pituitary gland
= stimulatory
effect stimulates
FSH LH secretion of LH
LH uterus
ovary
ovary
stimulates development
of corpus luteum
stimulates
maturation
triggers
of follicle ovulation
oestrogen
stimulates
proliferation of
endometrium
secretion of secretion of
oestrogen progesterone
127
Figure 8.5 Ef fect of pituitar y hormones on ovar y Figure 8.6 Ef fect of oestrogen on uterus and pituitar y
pituitary gland
inhibits
secretion of
FSH and LH
uterus
ovary
endometrium
progesterone
promotes
vascularisation
of endometrium
= release of hormone
= stimulatory effect
= inhibitory effect
Figure 8.7 Ef fect of progesterone on uterus and pituitar y
A cycle lasts for about 28 days though this can vary egg. The egg is then moved slowly along the oviduct.
from woman to woman. Each cycle is continuous with During a short period of about 3–4 days, fertilisation
the one that went before and the one about to follow. may occur if the egg meets a sperm.
For convenience the first day of menstruation (as
indicated by menstrual blood flow) is regarded as ‘day Luteal phase
one’ of the cycle. The menstrual cycle is summarised in During this second half of the cycle (following
Figure 8.8. It is made up of two phases. ovulation), LH stimulates the follicle to become the
corpus luteum. This gland-like structure secretes
Follicular phase progesterone and oestrogen. The subsequent rise
During this first half of the cycle, FSH from the in progesterone concentration stimulates further
pituitary gland stimulates: development of the endometrium. It becomes thick
(with an increase in vascular blood vessels) and spongy,
● the development and maturation of a follicle ready to accept and nourish a blastocyst if fertilisation
● the production of oestrogen by the ovarian tissues. takes place and the blastocyst becomes implanted.
As the concentration of the oestrogen builds up, The combined high levels of oestrogen and
it brings about the repair and proliferation of the progesterone during this luteal phase also trigger an
endometrium. Eventually the high concentration of inhibitor y effect on the pituitary gland. Concentrations
oestrogen triggers a surge in the production of LH (and of FSH and LH drop as a result and no new follicles
FSH) by the pituitary gland at about day 14. This surge develop at this time. This is a further example of
128 of LH is the direct cause of ovulation since it makes the negative feedback control.
blister-like wall of the follicle rupture and release the
pituitary hormones
FSH LH
FSH
LH
ovary
developing follicle corpus luteum
follicular phase ovulation luteal phase
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 1 2
ovarian hormones
oestrogen
progesterone
progesterone
oestrogen
endometrium vascularisation
proliferation
menstruation
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 1 2
day
Figure 8.8 Menstrual cycle
If fertilisation does not occur, lack of LH leads, in turn,

to the degeneration of the corpus luteum by about
day 22 in the cycle. This is followed by a rapid drop in
progesterone (and oestrogen). By day 28 in the cycle,
these ovarian hormones are at such a low level that
the endometrium can no longer be maintained and
menstruation begins. This involves the loss of the inner
layer of the endometrium accompanied by a small
volume of blood. This stage continues for a few days.
129
Related Topic
Fertilisation the highest concentration of oestrogen immediately

precedes ovulation, the secretion of thin mucus at this
If fer tilisation does occur, the embr yo secretes a hormone
time increases the chance of fer tilisation by facilitating
called human chor ionic gonadotrophin (HCG) which has
the entr y of sperm into the female reproductive tract.
the same ef fect as LH. HCG maintains the corpus luteum
which continues to secrete progesterone and prevent High levels of progesterone cause the cer vical mucus to
menstruation from taking place. Af ter about 6 weeks the become viscous and in the event of pregnancy change
placenta takes on the job of secreting progesterone. The into a semi-solid ‘plug’. This protects the fer tilised egg
presence of HCG in ur ine is the basis of pregnancy testing. from possible infection.
Role of the cervix in fertility Changes in body temperature

The cells lining the cer vix at the neck of the uterus (see Body temperature r ises by about 0.5°C at ovulation and
Figure 8.2) secrete mucus, which lubricates the vagina. remains at this higher level dur ing the luteal phase of the
These cells are stimulated by high levels of oestrogen to cycle.
secrete water y mucus easily penetrated by sperm. Since
Testing Your Knowledge
1 a) i) Where in a testis are sperm produced? 4 Decide whether each of the following statements is
ii) Which hormone is produced by interstitial true or false and then use T or F to indicate your choice.
cells? (2) Where a statement is false, give the word that should
b) i) Which accessor y glands secrete a liquid r ich in have been used in place of the word in bold print. (6)
hormone-like chemicals? a) The menstrual cycle consists of the endometrial
ii) Describe the contribution to fertilisation made phase and the luteal phase.
by these chemicals. (2) b) FSH stimulates ovar y tissue to secrete oestrogen.
c) Oestrogen stimulates the proliferation of the
2 a) Name the structure that surrounds an egg in an
endometrium.
ovar y. (1)
d) LH tr iggers the process of menstruation.
b) What does this structure develop into, following
e) Progesterone inhibits secretion of FSH and LH by the
ovulation? (1)
ovaries.
3 Copy and complete Table 8.1, which refers to four
f) Lack of LH leads to degeneration of the corpus
hormones in the female body. (8)
luteum.
Hormone Site of production One function of the hormone

Stimulates the development and
maturation of each follicle
Br ings about development of the
corpus luteum
Stimulates secretion of LH by the
pituitar y gland
Promotes vascular isation of the
endometr ium
Table 8.1
130
Biology of fertility control
9 Biology of fertility control

Knowledge of the biology of fertilisation is put to The period of fertility lasts for about 1–2 days. The
effective use when designing treatments for infertility infertile phase is resumed, on average, after the third
and devising methods of contraception. daily recording of the higher temperature by which time
the unfertilised egg has disintegrated.
Fertile periods Mucus

The cervical mucus secreted into the vagina during the
Continuous versus cyclical fertility fertile period is thin and watery to allow sperm easy
The negative feedback effect of testosterone (see access to the female reproductive system. However, after
Figure 8.4, page 126) maintains a relatively constant ovulation, the mucus gradually increases in viscosity
level of the pituitary hormones (FSH and ICSH) in under the action of progesterone, showing that the
the bloodstream of men. This results in a fairly steady system has returned to the infertile phase.
quantity of testosterone being secreted and sperm being
produced. Therefore men are continuously fertile. Use of indicators
The above indicators can be used by a woman to
This contrasts markedly with the cyclical fertility of calculate her fertile period. This knowledge is useful
women. The delicate interplay of pituitary and ovarian to a couple who wish to have a child and want to
hormones that occurs in their body normally results in know when sexual intercourse is most likely to achieve
the period of fertility being restricted to the 1–2 days fertilisation.
immediately following ovulation.
Calculation of the fertile period Treatments for infertility

Temperature Stimulating ovulation
Within the menstrual cycle, the alternating processes
A woman may fail to ovulate because of an underlying
of menstruation and ovulation are separated by
factor, such as failure of the pituitary gland to secrete
intervals of about 2 weeks. Approximately 1 day after
adequate FSH or LH. In such cases, ovulation can be
the LH surge that triggers ovulation, the woman’s body
successfully stimulated by:
temperature rises by about 0.2–0.5°C under the action
of progesterone. It remains at this elevated level for the ● drugs that mimic the normal action of FSH and LH
duration of the luteal phase of the cycle (see Figure 9.1). ● drugs that prevent the negative feedback effect of
follicular phase luteal phase

mouth temperature (°C)
37.0
36.6
36.2
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 2122 23 24 25 26 27 28
day in menstrual cycle
131
Figure 9.1 Rise in temperature dur ing the luteal phase
oestrogen on FSH secretion during the luteal phase
of the menstrual cycle.
On some occasions these drugs are so effective that
they bring about ‘super-ovulation’ and this can lead to a
multiple birth such as quintuplets (see Figures 9.2 and
9.3). Drugs that cause super-ovulation are also used
to promote the release of eggs to be used for IVF (see
below).
Artificial insemination
Insemination is the introduction of semen into the
female reproductive tract. It occurs naturally as a result
of sexual intercourse.
Figure 9.3 Ef fect of ‘super-ovulation’
Figure 9.2 Quintuplets
oviduct
sperm injected
into uterus
tube
ovary
sperm in
syringe
uterus
support to allow
entry of syringe tube
132
Figure 9.4 Artif icial insemination
Artificial insemination is the insertion of semen into

the female tract by some means other than sexual 1 blockage
intercourse. Artificial insemination may be employed in oviduct
as a method of treating infertility. If a man has a low

sperm count, several samples of his semen can be
collected over a period of time and each preserved by several eggs
released
freezing until required. They are then defrosted and following
released together into his partner’s cervical region at the hormonal
treatment
time when she is most likely to be fertile (see Figure 9.4).
Artificial insemination can also be used to insert semen 2
of a donor who has a normal sperm count into the

cervical region of a woman whose partner is sterile.
eggs removed from
In vitro fertilisation (IVF) woman’s body
This method of treatment attempts to solve the

3
problem of infertility caused by a blockage of the egg
oviducts (uterine tubes). It enables fertilisation to occur
outside the bodies of the would-be parents in a culture nutrient
dish. Figure 9.5 shows some of the stages involved in the sperm medium
procedure.
4
embryo
● At stage 1, the woman is given hormonal treatment
to stimulate multiple ovulation.
● At stage 2, a surgical procedure is employed to
remove several of these eggs from around her ovary
using a piece of equipment similar to a syringe. 5
● At stage 3, the eggs are mixed with sperm in a culture
dish of nutrient medium to allow fertilisation to
occur. Alternatively a sperm may be injected directly
into an egg at this stage (see ICSI below).
● At stage 4, the fertilised eggs are incubated in the
nutrient medium for 2–3 days to allow cell division
to occur and form embryos each composed of eight
(or more) cells.
● At stage 5, two (or three) of the embryos are chosen
and then inserted via the vagina into the mother’s
uterus (which is now ready for implantation).
● At stage 6, the remaining embryos are frozen and 6
stored in case a second attempt at implantation is
required.
embryo inserted
Pre-implantation genetic screening and into uterus frozen
embryo
diagnosis
Before stage 5 is carried out, one or two cells may be
removed and tested for genetic abnormalities. The test Figure 9.5 In vitro fer tilisation (IVF)
may take one of two forms:
133
● pre-implantation genetic screening (PGS) – a
non-specific approach that checks the embryo for
single gene disorders and common chromosomal Intracytoplasmic sperm injection
abnormalities in general
During IVF, eggs and sperm are mixed together in a
● pre-implantation genetic diagnosis (PGD) – a
culture dish. There is only a good chance of fertilisation
specific approach that is used to check for a known
chromosomal or gene defect. occurring if a large number of active sperm are present.
In those cases where the man’s sperm count is low
These tests enable experts to select which embryos
or many of his mature sperm are defective in some
should and which should not be allowed to become
way, intracytoplasmic sperm injection (ICSI) can be
implanted in the mother’s endometrium.
employed.
Related Topic This procedure involves drawing a healthy sperm into

a syringe needle and then injecting it directly into an
Ethics of PGS and PGD egg to bring about fertilisation (see Figure 9.6). During
the procedure the egg is held in place by a holding tool.
Some people strongly suppor t the practices of PGS and
ICSI is commonly used as part of IVF treatment.
PGD because they of fer reassurance to couples who
would otherwise be at high r isk of producing children
with ser ious genetic disorders. In the absence of these
techniques, many of these couples would probably choose
to remain childless. The suppor ters also claim that in
addition to helping the individual families af fected, a
reduced frequency of genetic diseases and disorders is of
great benefit to society as a whole.
Other people are opposed to PGS and PGD. They insist

that it is morally wrong to inter fere with the process of
conception by making it selective. They argue that these
procedures are the star t of eugenics, whereby the human
race would be subjected to selective breeding in order to
‘improve its quality’. They speculate that this route could
lead to a world of ‘designer’ children in which genetic
engineer ing of of fspr ing would become routine practice.
egg membrane
sperm holding tool
injection needle
egg cytoplasm
134 Figure 9.6 Intracytoplasmic sperm injection

Related Activity
Examining data on success rate for IVF From Table 9.1 it can be concluded that the number
of patients receiving IVF treatment and the number
and its effect on long-term health of babies born as a result of it increased signif icantly
Success rate over the per iod of time considered. These changes were
Tables 9.1, 9.2 and 9.3 show data that refer to IVF success accompanied by a slight increase in IVF success rate
rates for the UK. when measured as percentage live bir th rate per cycle.
Year
2006 2007 2008
Number of patients 34 855 36 861 39 879
Number of cycles 44 275 46 829 50 687
Number of bir ths as a result of IVF 10 242 11 091 12 211
Number of babies born 12 596 13 672 15 082
IVF success rate as live bir th rate per cycle (%) 23.1 23.7 24.1
Table 9.1 Success rate for IVF over 3 years
IVF success rate as live birth rate per cycle (%)

Age of patient (years)
Year 2007 Year 2008
Under 35 32.3 33.1
35–37 27.7 27.2
38–39 19.2 19.3
40–42 11.9 12.5
43–44 3.4 4.9
Over 44 3.1 2.5
Table 9.2 Ef fect of age on IVF success rate
State of embr yo used in IVF

Fresh Frozen
Number of patients 33 520 7 792
Number of cycles 39 334 8 959
Number of bir ths as a result of IVF 10 010 1 618
Number of babies born 12 480 1 855
Under 35 years 33.1 22.2
IVF success rates as percentage 35–37 27.2 17.8

of live bir th rates by age 38–39 19.3 15.8
Over 39 years 10.7 11.9
Table 9.3 Ef fect of freezing on success rate for IVF ➜ 135
(It should be noted that the number of successful bir ths exposing many women to an increased r isk of uter ine
is smaller than the number of babies born because some cancer in later life and urge that research be carr ied out
bir ths are multiple.) in this area. They also recommend that patients consider
natural-cycle IVF in place of stimulated-cycle IVF despite
From Table 9.2 it can be concluded that the chance of
the fact that the former’s success rate is only 7–10%
successfully giving bir th following IVF treatment is
compared with 25–30% for the latter.
highest for women under the age of 35 and decreases
steadily with increasing age of patient. Child
From Table 9.3 it can be concluded that dur ing the per iod Most children conceived through IVF tend to have a body
studied more fresh than frozen embr yos were used. In mass at bir th that is significantly lower than the average
addition the success rate for IVF using fresh embr yos was for full-term babies conceived naturally, and of ten closer
much higher for women of 39 and under but slightly lower to that of premature babies.
for women over the age of 39. In general, children born with a low body mass are more
likely to suf fer long-term health problems such as
Long-term health issues of IVF obesity, diabetes, hear t conditions and hyper tension in
later life at around 50 or more years of age. Exper ts are
Mother
concerned that children conceived through IVF will also
Many thousands of children are born annually using IVF
be more prone to these conditions. However, the f irst
treatment involving drugs that stimulate the mother’s
successful IVF treatment was not carr ied out until 1978.
ovaries to release a large number of eggs. About 6% of
Therefore no IVF-born people are old enough yet to allow
patients undergoing this form of IVF are found to suf fer
a sur vey to be conducted and tentative conclusions to be
hyperstimulation of their ovar ies. In addition, medical
drawn.
exper ts are concerned that stimulated-cycle IVF may be
Contraception Intra-uterine devices

An intra-uterine device (IUD) is a T-shaped structure
Contraception is the intentional prevention of
(see Case Study – Example of a physical contraceptive)
conception or pregnancy by natural or artificial means.
that is fitted into the uterus for many months or even
years to prevent the implantation of an embryo into the
Physical methods of contraception endometrium.
Barrier methods
A barrier method makes use of a device that physically Sterilisation procedures
blocks the ability of sperm to reach an ovum. These In men, vasectomy involves the cutting and tying of
devices include: the two sperm ducts, thereby preventing sperm being
released during sexual activity. (Sperm produced
● the condom – a rubber sheath that fits over the after this sterilisation procedure normally undergo
man’s penis phagocytosis and are destroyed.)
● the diaphragm – a dome-shaped rubber cap that is
inserted into the woman’s vagina to block the cervix In women, tubal ligation involves the cutting and tying
before each act of sexual intercourse of the two oviducts (see Figure 9.7) to prevent eggs
● the cervical cap – a rubber structure that fits tightly meeting sperm and reaching the uterus. Sterilisation
round the cervix and can be left in position for a few is a highly effective means of contraception but it is
days. normally irreversible.
These methods are very effective but they are not as
successful as chemical methods (see page 137).
136
procedure makes the concentration of progesterone

and oestrogen in her bloodstream increase and exert
oviduct cut and tied
negative feedback control.
Therefore, secretion of FSH and LH by the pituitary

gland is inhibited. Since little or no FSH is present,
follicle maturation remains inhibited and ovulation
ovary fails to occur. Dummy (placebo) pills are usually taken
during the fourth week to allow the levels of oestrogen
uterus and progesterone to drop and menstruation to occur.
‘Morning-af ter’ pills

These are also known as emergency hormonal
contraception pills. They often contain higher doses of
the hormones (progesterone and oestrogen) found in
standard oral contraceptive pills. They are taken by the
woman after unprotected sexual intercourse to prevent
Figure 9.7 Ster ilisation by tubal ligation
implantation from occurring if fertilisation has taken
place unintentionally. Ideally these pills should be taken
as soon after unprotected sex as possible but may be
effective up to about 72 hours.
Chemical methods of contraception
Pills containing a combination of hormones ‘Mini pills’
These oral contraceptive pills normally contain These are also known as progesterone-only pills
synthetic progesterone combined with synthetic because they contain synthetic progesterone but not
oestrogen. One common method requires the woman oestrogen. They work by causing thickening of cervical
to take a pill every day without fail for 3 weeks from mucus, which reduces the viability of sperm and their
the final day of the previous menstrual period. This access to the uterus.
Case Study Example of a physical contraceptive

Although widely used to mean any system of birth are hostile to sperm (and perhaps to the very early
control that prevents pregnancy, strictly speaking the embryo).
word contraception means prevention of conception. ● It impairs the mobility of sperm and prevents them
If this definition is adhered to strictly, then an reaching the egg.
intra-uterine device (IUD) has to be described as a ● It irritates the lining of the uterus making it
contragestic device since it prevents the gestation of unreceptive to an embryo, which therefore fails to
an already conceived embryo. become implanted in the endometrium.
In the UK, the term intra-uterine device (IUD) refers There is no denying that the IUD is an effective
to a T-shaped plastic structure with copper wound contraceptive device but it has tended to be less
around its outside (see Figure 9.8). It also has threads popular than other forms of contraception. This is
attached to it that can be used by a medical expert probably due to the fact that it has had a history of
to gently remove the device when required. An IUD causing complications, including inflammation of
works in several ways: the uterus and oviducts and also ectopic pregnancies
(those that result from the implantation of an embryo
● Its presence in the uterus stimulates the release
at a site other than the uterus).
of white blood cells and various substances that
➜ 137
In addition, many people feel uneasy about the ethics
involved in preventing an already conceived embryo oviduct
from becoming implanted in the endometrium. They

prefer to use a method of contraception that stops
sperm reaching an egg in the first place and therefore
prevents any chance of conception taking place.
ovary copper on
outside of IUD
uterus
Figure 9.8 Intra-uter ine device
Case Study Example of a chemical contraceptive

Although ‘mini pills’ are also called progesterone- ● It can be used during breast feeding and does not
only pills, strictly speaking this is a misnomer affect the milk supply.
because they contain a synthetic form of ● It can reduce the cramp and heavy bleeding
progesterone. In addition, this form of chemical suffered by some women during menstruation.
contraception may be taken by the woman in the ● It can be taken by women who cannot take
form of pills or be given as an implant the size of a oestrogen.
matchstick. The latter is inserted under the skin on ● It can be taken by women who suffer health
the inside of the upper arm and can give protection problems such as high blood pressure.
against pregnancy for up to 3 years.
Some of the disadvantages of the ‘mini pill’ are as
The chemical’s method of activity varies with dosage. follows:
At low doses it inhibits ovulation in only about 50% ● It must be taken at the same time every day.
of cycles. Therefore the woman is largely dependent ● It can cause breast tenderness and mood swings.
on progesterone’s thickening effect on cervical mucus ● It can lead to irregular menstrual cycles.
for protection against pregnancy. At higher doses, it ● It can lead to weight gain.
inhibits ovulation in the majority of cycles and brings
about thickening of cervical mucus. This form of contraception is not necessarily suitable
for all women. Individuals are advised to seek expert
Advantages and disadvantages advice before using it.
Some advantages of the ‘mini pill’ are as follows:
● It does not interfere with sexual spontaneity.
138
1 a) Distinguish clearly between the terms continuous b) What treatment is used in step C? (1)
fertility and cyclical fertility with reference to human c) What is the purpose of carr ying out steps A and B? (2)
beings. (2) 4 Rewr ite the following sentences about contraception
b) i) For how long does a woman’s per iod of fer tility using the correct answer from each underlined
last dur ing each menstrual cycle, on average? choice. (5)
ii) Describe T WO signs that give an approximate a) The use of a cer vical cap is a barr ier/cyclical method
indication of when this time occurs. (3) of contraception.
2 a) What is ar tif icial insemination? (1) b) The ‘morning af ter’ pill is a physical/chemical means
b) Under what T WO sets of circumstances might of preventing pregnancy.
ar tif icial insemination be used as a means of treating c) An intrauterine device prevents implantation of an
infer tility? (2) embr yo in the oviduct/endometrium.
3 a) The following list gives the steps in the procedure d) The ‘mini pill’ contains synthetic oestrogen/
employed dur ing in vitro fer tilisation. Arrange them progesterone, which works by making cer vical mucus
into the correct order. (1) thicker.
A Incubation of fer tilised eggs in nutr ient medium. e) Ster ilisation in a woman involves a procedure called
tubal ligation/vasectomy.
B Deep-freezing of unused fer tilised eggs.
C Stimulation of ovar ies to br ing about multiple
ovulation.
D Mixing of eggs with sperm in a dish.
E Inser tion of two or three fer tilised eggs into the
uterus.
F Removal of eggs from the mother’s body.
139
10 Ante- and postnatal screening

The health of a pregnant woman and her developing
fetus can be monitored using a variety of techniques
and tests. Several methods of antenatal (prenatal)
screening can be employed to identify the risk of the
fetus inheriting a genetic disorder or chromosomal
abnormality. Further tests can then be carried out if
necessary.
Antenatal care
With her consent, the mother’s blood pressure is
monitored, her blood type identified and general health
checks such as blood and urine tests carried out.
Ultrasound imaging
When an ultrasound scanner is held against a pregnant
woman’s abdomen, it picks up high-frequency sounds
that have bounced off the fetus. These are converted to Figure 10.2 The bad old days before ultrasound scanning
an ultrasound image on a computer screen.
Dating scan scan is used to determine the stage of the pregnancy

Ultrasound imaging is carried out at 8–14 weeks to (gestational age assessment) and to calculate the date
produce a dating scan (see Figures 10.1 and 10.2). This when the baby is due to be born. Dating scans are
used in conjunction with biochemical tests for marker
chemicals (see below).
Anomaly scan
Further ultrasound imaging is performed at 18–20
weeks to produce an anomaly scan. This allows a check
to be made for the presence of any serious physical
abnormalities in the fetus.
Biochemical tests
A woman’s body undergoes many physiological changes
during pregnancy. This is the normal course of events.
Many of these changes, such as the concentration
of human chorionic gonadotrophin (HCG), can be
monitored by biochemical tests. (The detection of
HCG in blood and urine following implantation of an
embryo is also the basis of early pregnancy tests.)
140 At 16–18 weeks, the pregnant woman is offered a series

Figure 10.1 Ultrasound image at 14 weeks of biochemical tests that check for three markers.
Ante- and postnatal screening
(One of these markers is AFP. See Related Topic –

Assessing the risk of Down’s syndrome using screening 1000
tests.) The results of these tests, used in conjunction 500
with the mother’s age, enable medical experts to assess
chorionic gonadotrophin (units)

the risk of chromosomal abnormalities being present in 100
concentration of human
the fetus. 50
Normally other routine tests are also carried out to

check the health of the pregnant woman and the 10
developing fetus by monitoring altered renal, liver 5
and thyroid functions and other biochemical changes.
(See Related Activity – Examining data on altered
1
biochemistry during pre-eclampsia.)
0.5
4 8 12 16 20 24 28 32 36 40
False positives and false negatives weeks of gestation
Some medical conditions are indicated by the
presence of certain marker chemicals in blood and Figure 10.3 HCG levels dur ing normal pregnancy
urine. However, these marker chemicals vary during
pregnancy. At one stage the presence of a high (or low) If a marker chemical was measured at an inappropriate
concentration of a certain marker may indicate the point in the timescale and found to be high, significance
presence of a genetic disorder in the fetus, whereas at could be attributed to it mistakenly. This would lead
another stage in the pregnancy, a high (or low) level to a false positive result where the test would show
of the marker may be of no significance. For example, the fetus to have the condition when, in fact, it does
in a normal pregnancy, the level of human chorionic not have it. Similarly, if the test for the marker was
gonadotrophin (HCG) increases during weeks 6–10 and carried out and found to be low at a time when the
then decreases to a steady low level later in gestation, normal value is also low, this could give a false negative
as shown in Figure 10.3. However, it remains at a high result. It would suggest that the fetus does not have
level if the fetus has Down’s syndrome. Risk assessment the condition when in fact it might really have it (see
based on a result at 10 weeks would be meaningless Appendix 4). It is for this reason that the times chosen
since both a normal pregnancy and a Down’s syndrome for biochemical tests are closely synchronised with
one would show an elevated result. information deduced from ultrasound dating scans.
Related Activity
Examining data on altered The data in Table 10.1 refer to a ser ies of studies carr ied
out on a large population of women. Some were non
biochemistry during pre-eclampsia pregnant (NP), some pregnant but not suf fer ing pre
Pre-eclampsia is a medical condition that af fects a eclampsia (P) and some pregnant and suf fer ing pre
minor ity of pregnant women. It is regarded as the most eclampsia (PE).
common cause of several dangerous complications that
can ar ise dur ing pregnancy. A woman suf fer ing pre From the table it is concluded that the concentration
eclampsia displays some or all of the following symptoms: of urea in blood plasma is signif icantly higher for the
PE women than for the NP and P women. Also, the
● high blood pressure (hyper tension) concentration of calcium in ur ine is signif icantly lower
● excess protein in blood plasma for the PE women than for the NP and P women. This latter
● changes to blood biochemistr y caused by factors such dif ference becomes even more apparent when the data
as altered liver or renal function. are presented as the bar char t shown in Figure 10.4 and
drawn to include error bars (see Appendix 3). 141
➜
Group Urea in blood plasma Calcium in urine 220
(mg l -1) (mg l -1)
210
NP 189.3 ± 13.7 163.4 ± 24.8
P 187.0 ± 14.1 177.5 ± 39.1 200
PE 228.7 ± 20.2 91.8 ± 21.2

190
Table 10.1 Results of biochemical tests
180
The dif ferences are thought to be the result of a decrease
concentration of calcium in urine (mg l–1)

in renal blood flow and glomerular f iltrate rate in PE 170
women causing them to retain higher concentrations of
160
urea and calcium in their blood. Altered levels of these
chemicals are just two of many possible indicators of pre
150
eclampsia. At present there is no cure for the condition
and in ser ious cases the baby may be induced early or be 140
delivered by Caesarean section to avoid the mother’s life
being put in danger and the baby suf fer ing long-term 130
adverse ef fects.
120
110
100
90
80
70
0 NP P PE
group
Figure 10.4 Ef fect of pre-eclampsia on renal function
Diagnostic testing specific condition or disorder. Certain diagnostic tests

A screening test is one that is used to detect signs may be offered to a pregnant woman if:
and symptoms associated with a certain condition or ● evidence of a potential problem has already emerged
disorder. If the signs are found, the probability that the from the results of earlier routine screening tests
individual is suffering the condition can be assessed as a ● there is a history of a harmful genetic disorder in her
degree of risk. (See Related Topic – Assessing the risk of family

Down’s syndrome using screening tests.) ● she is already known to belong to a high-risk
category (e.g. women over the age of 35). (See
A diagnostic test, on the other hand, is a definitive Related Topic – Risks associated with Down’s
test that produces results that can be used to establish syndrome testing.)
142
without doubt whether or not the person is suffering a
Related Topic
Assessing the risk of Down’s syndrome

using screening tests
Blood test for alpha-fetoprotein
During pregnancy alpha-fetoprotein (AFP) is produced
by the fetus and its concentration in the mother’s blood
increases. The level in the mother’s blood decreases
sharply soon af ter the baby is born. Low levels of AFP
(lower than 0.4 where 0.5–2.49 is the normal range of
values dur ing pregnancy) are found in cases of Down’s
syndrome (tr isomy 21) and Edwards syndrome (trisomy
18). However, this test marker is par t of a biochemical
screening test and not a diagnostic one. Therefore, even
if a result shows a low level of AFP to be present and Figure 10.5 Nuchal translucency scan
indicates high risk, it does not mean that a chromosomal
abnormality has been diagnosed. Nuchal translucency scan (NT)
A nuchal translucency scan helps experts to estimate
Multiple gestation more accurately the r isk of a woman having a Down’s
The predictive power of biochemical tests for a multiple syndrome baby than by consider ing her age alone (as
gestation such as twins is much lower than for a single shown in Table 10.2 on page 144). The test is carr ied
fetus. This is because the tests depend on analysis of the out at 11–14 weeks (the time found to give the most
mother’s blood and may still give normal results even if reliable results). It enables an assessment to be made
one of the fetuses is abnormal. The nuchal translucency of the thickness of the fluid in the tissue at the nape of
ultrasound test (see below) is much more reliable since it the fetus’s neck by viewing it as a nuchal translucency
examines each fetus individually. (see Figure 10.5). If the nuchal translucency exceeds
the normal value, there is a r isk of a chromosomal
abnormality in the fetus. However, as before, this is not a
diagnostic test.
Related Information
Risks associated with Down’s syndrome translucency all indicate a high risk of Down’s syndrome,
testing the woman may be advised to have an amniocentesis
or a chor ionic villus sampling test, both of which are
There are two dif ferent aspects of r isk associated with diagnostic but invasive.
Down’s syndrome. The f irst relates to the mother’s age
and the associated r isk of her having a baby with this The second aspect of r isk relates to the tests themselves.
condition. In older women the germline cells that produce Amniocentesis (carried out at a later stage in gestation)
eggs are found to be more prone to a type of mutation slightly increases the r isk of miscarr iage, whereas
that leads to eggs being formed that contain an extra chor ionic villus sampling (carr ied out at an earlier stage
copy of chromosome 21. Therefore, the older the woman, in gestation) runs a much higher r isk of losing the baby.
the higher the r isk that she will have a baby with Down’s Therefore when making a choice, the pregnant woman has
syndrome, as shown in Table 10.2. When a combination of to weigh up the r isk of a miscarr iage against the risk of
maternal age, biochemical tests and thickness of nuchal wanting to seek a termination fairly late in the pregnancy.
➜ 143
Maternal age at full term of gestation period (years) Risk of Down’s syndrome
20 1:1450
22 1:1450
24 1:1400
26 1:1300
28 1:1150
30 1:940
32 1:700
34 1:460
36 1:270
38 1:150
40 1:85
42 1:55
44 1:40
46 1:30
Table 10.2 Risk of Down’s syndrome with increasing maternal age
Use of kar yotype Amniocentesis

A person’s karyotype is a visual display of their Amniocentesis is carried out at about 14–16 weeks.
complete chromosome complement, with the It involves the withdrawal of a little amniotic fluid
chromosomes arranged as pairs showing their size, containing fetal cells (see Figure 1.15 on page 12).
form and number. The two diagnostic tests described These are cultured, stained and examined under
below depend on fetal material being obtained to allow the microscope. A full chromosome complement is
a karyotype to be prepared for examination. photographed and the chromosomes arranged into
pairs to form the karyotype, as shown in Figure 10.6.
This technique, which takes about 2 weeks, allows
1 2 3 4 5 1 2 3 4 5
6 7 8 9 10 11 12 6 7 8 9 10 11 12
13 14 15 16 17 18 13 14 15 16 17 18
19 20 21 22 X X 19 20 21 22 X X
normal female Down’s syndrome female extra copy of

chromosome 21
144
Figure 10.6 Normal and Down’s syndrome kar yotypes
chromosomal abnormalities to be detected. A karyotype

fetus
containing an extra copy of chromosome 21, for
example, indicates Down’s syndrome. The parents may uterus
then elect to have the pregnancy terminated.
Chorionic villus sampling

Chorionic villus sampling (CVS) involves taking a
vagina stop
tiny sample of placental cells using a fine tube inserted
into the mother’s reproductive tract (see Figure 10.7).
The cells are then cultured and used for karyotyping as chorionic villus
before. One benefit of CVS is that it can be carried out
as early as 8 weeks into the pregnancy. The prospect syringe long flexible tube
of a termination at this stage is much less traumatic
for many would-be parents than at 16 or more weeks
Figure 10.7 Chor ionic villus sampling
following amniocentesis. However, CVS causes a higher
incidence of miscarriages than amniocentesis.
Related Topic
Karyotypes indicating genetic disorders Figure 10.8 shows the kar yotype of a person with
Turner’s syndrome, caused by the lack of one of the two
Figure 10.6 on page 144 compares the kar yotypes of
X chromosomes. It occurs with a frequency of about 1 in
a normal female with a female with Down’s syndrome
2500 female live bir ths. Individuals af fected in this way
(trisomy 21). This condition, caused by the presence
are always female and shor t in stature. Since their ovar ies
of an extra copy of chromosome 21, is character ised by
do not develop, they are infer tile and fail to develop
learning dif f iculties and distinctive physical features. It
secondar y sexual character istics at puber ty.
occurs in 1 in 800 live bir ths.
1 2 3 4 5
1 2 3 4 5
6 7 8 9 10 11 12
6 7 8 9 10 11 12
13 14 15 16 17 18
13 14 15 16 17 18
19 20 21 22 X
19 20 21 22 X X Y
Figure 10.8 Turner’s syndrome kar yotype Figure 10.9 Klinefelter’s syndrome kar yotype ➜ 145
Figure 10.9 shows the kar yotype of a person with
Klinefelter’s syndrome, caused by the presence of an
extra sex chromosome to give the grouping XXY. It occurs
with a frequency of about 1 in 1000 male live bir ths. An
individual with this unusual chromosome complement
is always male and possesses male sex organs. However, 1 2 3 4 5
people af fected in this way are infer tile because their
testes are ver y small and fail to produce sperm.
Figure 10.10 shows the kar yotype of a person with
6 7 8 9 10 11 12
Edwards’ syndrome (tr isomy 18), caused by the
presence of an extra copy of chromosome 18. It occurs
with a frequency of about 1 in 3000 live bir ths. The
13 14 15 16 17 18
condition is character ised by unusual skull shape
and small chin accompanied by hear t and kidney
malformations. Ver y few suf ferers sur vive beyond their
f irst year and all show profound delay in all aspects of 19 20 21 22 X Y
development.
Figure 10.10 Edwards’ syndrome kar yotype
Rhesus antibody testing Postnatal (after birth) screening

When a Rhesus-negative mother is pregnant with a
Rhesus-positive fetus, a potential problem arises (see Diagnostic testing for metabolic
chapter 22, page 316 for full details). Rhesus antigens
on the surface of the fetus’s red blood cells are regarded
disorders
as foreign by the mother’s immune system if she comes At present almost none of the inherited disorders can be
into contact with them at a sensitising event such as the successfully treated. An exception is phenylketonuria
birth of the baby. (PKU). This inborn error of metabolism occurs with a
frequency of about 1 in 10 000 in the UK (see chapter
After an event of this type, the mother is given anti- 4, page 56.) If PKU is not detected soon after birth, the
Rhesus antibodies to destroy any Rhesus antigens left baby’s mental development is affected adversely.
behind by the baby before the mother’s immune system
has time to respond to them. In order to manage this In the UK, all newborn babies are routinely screened
treatment successfully, medical staff need to run tests for PKU by having their blood tested for the presence
on the mother’s blood and establish its type well in of excess phenylalanine within the first few days of
advance. life. PKU sufferers are then placed on a restricted diet
containing the minimum quantity of phenylalanine
1 What is meant by the term antenatal screening? (1) 3 Distinguish clearly between the terms screening test and
2 a) At approximately what stage in pregnancy is diagnostic test. (2)
i) a dating scan, ii) an anomaly scan performed? (2) 4 Give T WO dif ferences between amniocentesis and
b) What is the purpose of each of these scans? (2) chorionic villus sampling. (2)
c) What name is given to the technique used to obtain
146 these scans? (1)
needed for normal growth. Provided that a PKU brain is still developing), mental deficiency is prevented
sufferer continues to consume this diet low in and other adverse effects are kept to a minimum.
phenylalanine (especially during childhood when the
Related Topic
Screening newborn babies for inherited In the UK, newborn babies are routinely screened for
galactosaemia. The test checks the infant’s blood for
diseases the presence of the three enzymes needed to conver t
Galactosaemia galactose to glucose. Af fected babies that go untreated
may suf fer serious ef fects which can be fatal and lead
Under normal circumstances, lactose (the sugar in milk
to the death of the baby within a few days of bir th. The
products) is broken down in the human body to glucose
condition is treated by eliminating lactose and galactose
and galactose by enzyme action. The galactose formed
from the infant’s diet. However, some suf ferers still go on
is then conver ted to glucose under the action of three
to exper ience learning dif f iculties even though they are
enzymes, as shown in Figure 10.11.
on a restr icted diet.
Galactosaemia is an inher ited disorder with an incidence
of about 1 in 60 000 births. It occurs when one or more of Congenital hypothyroidism
the enzymes in the pathway is non-functional or absent The pituitar y gland (see Figure 10.12) produces thyroid-
as a result of a mutation. In one form of the disorder, for stimulating hormone (TSH), which stimulates the
example, where the suf ferer lacks the normal form of thyroid gland to release thyroxine. This hormone is
enzyme 2, intermediate 1 accumulates to toxic levels in essential for proper development of the ner vous system,
var ious tissues. This causes damage to the body including regulation of the body’s metabolic processes and normal
enlargement and cirrhosis of the liver, failure of the growth and development.
kidneys and damage to the brain.
Congenital hypothyroidism is an inherited disorder
caused by a defect in the biochemical pathway that leads
galactose
enzyme 1
intermediate 1
pituitary
enzyme 2
TSH
intermediate 2
thyroid gland
enzyme 3
glucose thyroxine
➜ 147
Figure 10.11 Normal conversion of galactose to glucose Figure 10.12 Release of thyroxine
to the synthesis of thyroxine. It occurs in about 1 in 4000 measures thyroxine level 2–3 days af ter bir th. If the
bir ths. Although the child is born with a severe def iciency level of thyroxine is low (or that of TSH is high) fur ther
in the functioning of the thyroid gland, initially they show tests are carr ied out. Where a diagnosis is conf irmed,
no symptoms that would identify this specif ic problem. the infant is given a daily dose of thyroxine, which is
However, af ter a few months, lack of thyroxine leads increased as the child grows. Most children treated in this
to obvious failure of normal growth and to permanent way show normal growth and development.
impairment of the brain of an untreated suf ferer.
In the UK, almost all cases of congenital hypothyroidism
are detected by screening newborn babies. The test
Genetic screening and

counselling affected O
Standardised human pedigree unaffected O
nomenclature and symbols affected O
In humans, the X and Y chromosomes are the sex carrier O

chromosomes. All the other chromosomes in the
unaffected O
genotype are called autosomes. The most commonly
used forms of the nomenclature and symbols used for
human pedigrees are shown in Figures 10.13, 10.14 and
Figure 10.15 Symbols in a sex-linked pedigree
10.15. Further information about sex-linked inheritance
is given in the Related Topic on page 153. Pedigree charts
mating (relationship) line
A pattern of inheritance can be revealed by collecting
male female
parent parent
homozygous information about a particular characteristic from the
genotype
members of a family and then using it to construct a
BB bb line of family tree (pedigree chart). Once the phenotypes are
descent
known, most of the genotypes can be deduced.
Such construction of a family tree is carried out by

a genetic counsellor when information and advice
Bb Bb Bb Bb Bb Bb
are required by a couple who are worried about the
twins deceased 2 of 6 siblings possibility of passing a genetic disorder (known to exist
male
in their family) on to their children.
heterozygous genotype
Figure 10.13 Human pedigree nomenclature and symbols

Different patterns of inheritance
Autosomal recessive inheritance
Figure 10.16 shows a family history of cystic fibrosis.
affected O
The geneticist recognises that such a trait shows a
unaffected O
typical autosomal recessive pattern of inheritance
affected O because:
● the trait is expressed relatively rarely
unaffected O
● the trait may skip generations
● the trait is expressed in some of the offspring of a
148
Figure 10.14 Symbols in an autosomal recessive pedigree consanguineous marriage (in this case cousins)
O sufferer of cystic fibrosis
O sufferer of cystic fibrosis
O non-sufferer
O non-sufferer
Figure 10.16 Autosomal recessive inher itance
Cc Cc
CC/Cc CC/Cc cc CC/Cc CC/Cc
Cc Cc Cc Cc CC/Cc
CC/Cc cc CC/Cc CC/Cc cc cc CC/Cc CC/Cc ?

Sandra Ian
}
see text page 154
Figure 10.17 Genotypes for autosomal recessive example
● males and females are affected in approximately ● Non-sufferers are homozygous dominant (e.g.
equal numbers. CC) or heterozygous (e.g. Cc) and most of these
The geneticist can therefore add genotypes to the family genotypes can be deduced by referring to other
tree by applying the following rules governing any closely related members of the tree.
characteristic showing autosomal recessive inheritance: The outcome of the cystic fibrosis example is shown in
149
● All sufferers of the trait are homozygous recessive Figure 10.17.
(e.g. cc).
Autosomal dominant inheritance
Figure 10.18 shows a family history of Huntington’s
disease (chorea).
O sufferer of Huntington’s chorea
O sufferer of Huntington’s chorea
O non-sufferer
O non-sufferer
Figure 10.18 Autosomal dominant inher itance
Hh hh
hh Hh hh
hh hh Hh hh Hh hh Hh hh
hh hh hh Hh hh Hh hh ? ? Hh
Juan Zara
}
see text page 154
150
Figure 10.19 Genotypes for autosomal dominant example
The geneticist recognises that such a trait shows a ● the fully expressed form of the disorder occurs
typical autosomal dominant pattern of inheritance relatively rarely
because: ● the partly expressed form occurs much more
● the trait appears in every generation frequently
● each sufferer of the trait has an affected parent ● each sufferer of the fully expressed form has two
● when a branch of the family does not express the parents who suffer the partly expressed form of the
trait, the trait fails to reappear in future generations disorder
of that branch ● males and females are affected in approximately
● males and females are affected in approximately
equal numbers.
equal numbers. The geneticist can therefore add genotypes to the
The geneticist can therefore add genotypes to the family family tree by applying the following rules governing
tree by applying the following rules governing any any characteristic showing autosomal incomplete
characteristic showing autosomal dominant inheritance: dominance:
● All non-sufferers are homozygous recessive (e.g. hh). ● All non-sufferers are homozygous for one
● Sufferers are homozygous dominant (e.g. HH) or incompletely dominant allele (e.g. HH).
heterozygous (e.g. Hh) and most of these genotypes ● All sufferers of the fully expressed form of the
can be deduced by referring to other closely related disorder are homozygous for the other incompletely
members of the tree. dominant allele (e.g. SS).
The outcome of the Huntington’s disease example is ● All sufferers of the partly expressed form of the
shown in Figure 10.19. disorder are heterozygous for the two alleles (e.g. HS)
and most or all of the genotypes can be deduced by
referring to other closely related members of the tree.
Autosomal incomplete dominance
Figure 10.20 shows a family tree with a history of sickle- The outcome of the sickle-cell disease example is shown
cell disease and sickle-cell trait (see also page 55). in Figure 10.21.
The geneticist recognises that such a disorder shows a Sex-linked recessive trait
typical autosomal incompletely dominant pattern of Figure 10.22 shows a family with a history of
inheritance because: haemophilia. (Further information about sex-linked
inheritance is given in the Related Topic on page 153.)
O sufferer of sickle-cell anaemia
O sufferer of sickle-cell anaemia
O sufferer of sickle-cell trait
O sufferer of sickle-cell trait
O non-sufferer
O non
non-su
-suffe
fferer
rer
151
Figure 10.20 Autosomal incomplete dominance inheritance
HS HH HS HS
HS HS HH HS HH HS SS HH
HH SS HS HS HS HS
HH HS SS SS HH HH SS HS HS
Chika Sabato
}
see text page 154
Figure 10.21 Genotypes for autosomal incomplete dominance example
O sufferer of haemophilia
O non-sufferer
O non-sufferer
Figure 10.22 Sex-linked recessive inher itance
The geneticist recognises that such a trait shows a The geneticist can therefore add genotypes to the family
typical sex-linked recessive pattern of inheritance tree by applying the following rules governing any
because: characteristic showing sex-linked recessive inheritance:
● many more males are affected than females (if any) ● All sufferers of the trait are ‘homozygous’ recessive
● none of the sons of an affected male shows the trait (normally male, e.g. XhY, and very rarely female
● some grandsons of an affected male do show the XhXh).
152
trait. ● Non-sufferers are ‘homozygous’ dominant
(e.g. XHY or XHXH) or heterozygous carrier females

(e.g. XHXh) and most or all of these genotypes can
O carrier
be deduced by referring to other closely related
X X /X X
H H H h
XYh
members of the tree.
The outcome of the haemophilia example is shown in
Figure 10.23, where symbols for the female carriers can
XHY XHXh XHY now be added.
XHY XHXh XhY XHY XHXH/XHXh XHY

Jane Hamish
XhY
}
see text page 154
Figure 10.23 Genotypes of sex-linked recessive example
Related Topic
Sex-linked inheritance One of these blood-clotting agents is a protein called

factor VIII. In humans the genetic information for
Although the X and Y sex chromosomes make up a pair,
factor VIII is carr ied on the X chromosome. However, a
an X chromosome dif fers from a Y in that the X has many
defective version of the factor VIII protein is formed if
genes that are absent from the Y. These genes are said to
the gene is changed by a mutation. A person who inher its
be sex-linked (see Figure 10.24). When an X chromosome
meets a Y chromosome at fer tilisation, each sex-linked
gene on the X chromosome becomes expressed in the
phenotype of the human male produced. This is because normal O normal O
the Y chromosome does not possess alleles of any of these carrier O haemophiliac O
sex-linked genes and cannot of fer dominance to them.
haemophiliac O
Haemophilia
Clotting of blood is the result of a complex ser ies of
biochemical reactions involving many essential chemicals.
carrier haemophiliac
mother father
sex-linked
genes
carrier haemophiliac normal haemophiliac

daughter daughter son son
X Y
Figure 10.25 Haemophilia A cross using alternative symbols

➜ 153
Figure 10.24 Sex-linked genes
the altered genetic mater ial suf fers a condition called
haemophilia A (see page 180). The suf ferer’s blood carrier haemophiliac
mother father
takes a ver y long time (or even fails) to clot, resulting in
prolonged bleeding from even the tiniest wound. Internal XHXh XhY
bleeding may occur and continue unchecked, leading to
ser ious consequences.
Since haemophilia A is caused by a recessive allele carr ied

on the X but not the Y chromosome, it is a sex-linked
condition. The genotypes of individuals in crosses
involving haemophilia A are normally represented by the
following symbols: XH (normal blood-clotting allele), Xh XHXh XhXh XHY XhY
(haemophilia) and Y (no allele for this gene). carrier haemophiliac normal haemophiliac
Figure 10.25 shows the outcome of a cross between daughter daughter son son
a carr ier woman and a haemophiliac man using
standardised human pedigree symbols. Figure 10.26 Figure 10.26 Haemophilia A cross using superscr ipt
shows the same cross using symbols where the sex symbols
chromosomes are represented by X and Y and the alleles
of the sex-linked gene by appropr iate superscr ipts.
Related Activity
Assessing the risk for the condition and destined to develop it later in life.
From the information available, the genetic counsellor
Once the genetic counsellor has constructed the
would conclude that there is a high r isk that each of
pedigree char t and established as many genotypes as
their children would suf fer this debilitating disease. For
possible, they are in a position to assess r isk and state
example, if both Juan and Zara turn out to be Hh then 3 in
probabilities.
4 of their children on average would suf fer Huntington’s
Autosomal recessive disease.
Returning to the cystic fibrosis example shown in
Autosomal incompletely dominant
Figure 10.17, consider the situation that Sandra and Ian
Returning to the sickle-cell disease example shown in
f ind themselves in. Cystic f ibrosis is known to exist in
Figure 10.21, consider the situation that Chika and Sabato
Sandra’s family but not that of Ian. The genetic counsellor
f ind themselves in. The genetic counsellor would explain
would work out from the family tree that Sandra has a
to them that each of their children would have a 1 in 4
2 in 3 chance of being a carr ier. The counsellor would
chance of suf fer ing the fully expressed condition of the
already know that the frequency among the Br itish
disease, a 1 in 2 chance of suf fer ing the milder condition
population of an individual being heterozygous for the
and a 1 in 4 chance of being unaf fected.
cystic f ibrosis allele is 1 in 25, and would therefore regard
this as the r isk of Ian being a carr ier. Combining all these Sex-linked recessive
probabilities, they would conclude that the r isk of Sandra Returning to the haemophilia example shown in
and Ian having a child with cystic f ibrosis is fairly low. Figure 10.23, consider the position that Jane and Hamish
f ind themselves in. Jane is anxious to know if she could
Autosomal dominant
pass the trait on to her sons. There is no histor y of the
Returning to the Huntington’s disease example shown
disorder in Hamish’s family. From the information in the
in Figure 10.19, consider the situation that Juan and
family tree, the genetic counsellor would note that Jane’s
Zara f ind themselves in. Unlike their siblings, both
brother and nephew have developed this sex-linked
are still too young to know whether or not they have
disorder. This shows that Jane’s mother and sister are
received the harmful allele from an af fected parent. At
carr iers. They would conclude therefore that there is a 1
present it is a 1 in 2 chance that each is heterozygous
154 in 2 chance of Jane being a carr ier. If she does turn out
to be a carr ier, then each of her sons (but none of her

daughters) would stand a 1 in 2 chance of developing
haemophilia. However, from the information presently
available, the counsellor would assess the r isk of each son
being a haemophiliac as a 1 in 4 chance.
Case Study Risk evaluation in polygenic (multiple gene) inheritance

When a trait shows an autosomal recessive This is because the condition is determined partly
pattern of inheritance involving only one gene, a by the effects of multiple genes and partly by
straightforward assessment of risk can be made environmental influences.
based on the family’s pedigree chart. However, when
Risk evaluation in such cases is usually empirical.
a genetic defect or disorder shows a polygenic
This means that it is based on data derived from
pattern of inheritance, an evaluation of risk is much
many real case histories rather than on genetic
more difficult to make with any degree of accuracy.
theory alone. A few examples are shown in Table 10.3.
Disorder Incidence Risk of normal parents Risk of affected parent having:

(per 100) having a second affected an affected child a second affected
child (per 100) (per 100) child (per 100)
Asthma 4.0 10 26 *
Cleft palate 0.1 2 7 15
Congenital 0.5 1–4 1–4 10
heart disease
Epilepsy 0.5 5 5 10
Manic-depressive 0.4 10–15 10–15 *
psychosis
Schizophrenia 1.0 10 16 *
Table 10.3 Empir ical risk for multiple-gene disorders (* = data unavailable)
1 a) By what means is postnatal screening for b) Give ONE rule that the geneticist would apply when
phenylketonur ia (PKU) carr ied out? (1) adding genotypes to a family tree showing a pattern
b) Why is PKU described as an inborn error of of autosomal recessive inher itance. (1)
metabolism? (Hint: see chapter 4, page 56.) (2) 3 a) Name T WO character istics of a family’s pedigree
c) What treatment is given to suf ferers of PKU? (1) char t that would enable a geneticist to recognise
2 a) Name T WO character istics of a family’s pedigree that it showed a pattern of sex-linked recessive
char t that would enable a geneticist to recognise inher itance. (2)
that it showed a pattern of autosomal recessive b) Give ONE rule that the geneticist would apply when
inheritance. (2) adding genotypes to a family tree showing a pattern
of sex-linked recessive inher itance. (1)
155
9 Fer tility in men is ______; fer tility in women is ______,

amniocentesis follicle- ovar ies being restr icted to the 1–2 days following ovulation in
anomaly stimulating oviducts each monthly cycle.
antigens genetic ovulation 10 Infer tility may be caused by failure to ovulate, blockage
anti-Rhesus germline pedigree of ______ or failure of ______ in women, and low
implantation ______ count in men.
avoidance phase
barr iers injection postnatal 11 Methods of treatment of infer tility include the use of
insemination drugs that ______ ovulation, artif icial ______, in
biological progesterone
______ fer tilisation (IVF) and intracytoplasmic sperm
chemical interstitial prostate ______ (ICSI). Pre-implantation ______ diagnosis may
chor ionic kar yotype seminal be used dur ing IVF to check an embr yo for chromosomal
chromosomal luteinising sperm defects before implantation.
continuous luteum ster ilisation 12 Some methods of contraception are based on ______
cyclical marker stimulate knowledge of the menstrual cycle and the ______ of
menstrual fer tile per iods. Other physical methods depend on
dating testes
______, intra-uter ine devices or ______. Some ______
diagnostic miscarr iage testosterone methods prevent follicles from being stimulated and
endometrium mucus vascular isation eggs from being released. Others cause thickening of
follicle negative vitro cer vical ______.
oestrogen 13 Dur ing antenatal care, a ______ scan is made by
ultrasound imaging to determine the stage the
Table 10.4 Word bank for chapters 8–10 pregnancy has reached. An ______ scan is used to
1 The ______ of the human male produce sperm from detect physical problems in the fetus.
germline cells in seminiferous tubules and make 14 Signs of medical conditions suf fered by pregnant women
testosterone in ______ cells. can be detected using screening tests for ______
2 The mobility and viability of sperm are maintained by chemicals. These allow r isk of genetic disorders in the fetus
fluids secreted by the ______ gland and ______ vesicles. to be assessed and may be followed up by ______ tests.
3 The ______ of the human female contain ______ cells that 15 A ______ is a display of a complement of chromosomes
produce ova (eggs) each surrounded by a protective ______. arranged in pairs to show their form, size and number.
Hormones made by the ovary are oestrogen and ______. 16 Dur ing ______, a sample of amniotic fluid is taken
4 The pituitar y gland releases ______ hormone (FSH) and to obtain cells for kar yotyping to check for ______
interstitial-cell-stimulating hormone (ICSH)/______ abnormalities. Dur ing ______ villus sampling, cells
hormone (LH). for the same purpose are obtained from the placenta.
This procedure carries a higher r isk of ______ than
5 In men, FSH stimulates sperm production and ICSH promotes
amniocentesis.
______ production. The concentration of testosterone is
maintained at a steady level by ______ feedback control. 17 A Rhesus-negative mother is given ______ antibodies
af ter the bir th of a Rhesus-positive baby to destroy any
6 In women, FSH stimulates the development of a follicle
Rhesus ______ before her immune system has time to
containing an ovum (egg) and the secretion of ______.
respond to them.
LH tr iggers ______ and br ings about the development
of the corpus ______ which secretes progesterone. 18 ______ screening is carr ied out on newborn babies to
check for metabolic disorders such as PKU. Information
7 Oestrogen stimulates the proliferation of the ______ and
about a par ticular characteristic can be collected from
progesterone promotes its further development and ______.
the members of a family and be used to construct a
156 8 The ______ cycle lasts for about 28 days and involves a ______ char t. Single gene disorders show dif ferent
follicular ______ and a luteal phase. patterns of inheritance, such as autosomal recessive.
Structure of the cardiovascular system
11 Structure of the cardiovascular system
Cardiovascular system as a whole and the external environment. These

requirements are met by the cardiovascular system,
In the human body, substances need to be exchanged which contains a fluid connective tissue (blood)
continuously between the different structures that confined to tubes (vessels). The smallest of these
make up the body’s internal environment. In addition, vessels transport materials to within rapid diffusion
exchanges must be made between the organism distance of every living cell. A muscular pump (heart)
Related Topic
pulmonary lungs pulmonary
Circulation of blood artery vein
Figure 11.1 shows the route taken by blood as it

passes from the hear t to a region of the body and
then back to the hear t. Arter ial branches of the head
carotid
aor ta supply oxygenated blood to all parts of the artery
body. Deoxygenated blood leaves the organs in jugular
veins. These unite to form the vena cava, which vein
returns blood to the hear t.
aorta
Pulmonar y system coronary
coronary artery
This is the route by which blood is circulated from
vein
the hear t to the lungs and back to the hear t.
It should be noted that as a rule arter ies carr y vena
oxygenated blood and veins carr y deoxygenated cava
blood. However, the pulmonar y system is
exceptional in that the ar ter y carr ies deoxygenated heart
blood and the vein carr ies oxygenated blood. hepatic
hepatic artery
vein liver
Hepatic portal vein
Whereas veins normally carr y blood from a capillar y hepatic
bed in an organ directly back to the hear t, the portal
gut
vein
hepatic portal vein is exceptional in that it carr ies gut arteries
blood from the capillar y bed of one organ (the
intestine) to the capillar y bed of a second organ renal
renal
(the liver). This means that the liver has three blood vein artery
kidneys
vessels associated with it.
other
other
other parts arteries
veins
of body
= oxygenated blood
= deoxygemated blood
= capillary bed
Figure 11.1 Human circulator y system 157

continuously circulates blood round the system. Vasoconstriction and vasodilation
(Remarkably there are approximately 60 000 miles of The smooth muscle in the walls of arterioles (small
vessels in a human adult!) arteries) can contract (or become relaxed) depending
The distribution of blood is under efficient control at on the body’s requirements. This process allows the
all times, allowing the cardiovascular system to work in changing demands of different tissues to be met by
close harmony with the digestive, respiratory, excretory, finely tuned adjustments in the local distribution of
locomotor and endocrine systems. (See Related Topic – blood. For example, during strenuous exercise, arterioles
Circulation of blood.) leading to working muscles undergo vasodilation (see
Figure 11.3). This allows an increase in blood flow to the
Structure and function of blood skeletal muscles involved in the strenuous exercise. At
vessels the same time the arterioles leading to abdominal organs
such as the small intestine undergo vasoconstriction,
The lumen (central cavity) of a blood vessel is
which reduces blood flow to these parts.
lined with a thin layer of epithelial cells called the
endothelium. The composition of the vessel wall
Capillaries
surrounding the endothelium is found to be different in
Blood is transported from arterioles to venules (small
an artery compared with a vein, as shown in Figure 11.2.
veins) by passing through a dense network of tiny
microscopic vessels called capillaries (see Figure 11.4).
Arter ies Capillaries are the most numerous type of blood vessel
Arteries carry blood away from the heart. Each
in the body. They are referred to as the exchange vessels
possesses a thick middle layer of smooth muscle in its
since all exchanges of substances between blood and
wall and an inner and outer layer of elastic fibres. The
living tissues take place through their thin walls. These
elastic fibres enable the walls of an artery to pulsate
are composed of epithelium and are only one cell thick.
(stretch and recoil with a rhythmical beat) thereby
accommodating the surge of blood received after each VASOCONSTRICTION
heartbeat. ‘circular’ muscle
arteriole in arteriole wall
contracted
artery
narrow
thick muscular layer lumen
ARTERY narrow capillary

lumen
VASODILATION
‘circular’ muscle
outer inner arteriole in arteriole wall
layer middle lining
layer layer relaxed
(elastic of
(muscle) (elastic artery
fibres) endothelium
fibres)
valve wide
lumen
VEIN
capillary
wide lumen
thin muscular layer
Figure 11.3 Simplif ied version of vasoconstr iction and

158
Figure 11.2 Comparison of structure of an ar ter y and a vein vasodilation
Veins
Veins carry blood back to the heart. The muscular layer
and the layers of elastic fibres in the wall of a vein are
thinner than those in an artery because blood flows
thin wall
along a vein at low pressure. Compared with an artery,
(endothelium)
is only one cell thick
the lumen of a vein is wider. This reduces resistance to

flow of blood to a minimum. Valves are present in veins
(but not in arteries) to prevent backflow of blood. (See
Related Activity – Demonstrating the presence of valves
in veins.)
Figure 11.4 Capillar y
Related Activity
Demonstrating the presence of valves

in veins
The presence of a valve in a vein in the arm can be
demonstrated by the method shown in Figure 11.5.
scarf tied tightly

round arm
vein
small region of vein remains ‘empty’

finger B removed
closed valve
fingers A and B placed on a vein
A
detail
A B
bulge shows position

of closed valve
finger A removed
finger A pressed down hard; finger B open valve

used to squeeze blood out of vein
detail
A
B
bulge decreases
as valve opens
blood from hand flows
into vein again
Figure 11.5 Demonstrating the presence of valves in a vein 159

Related Activity
Measuring the degree of

stretching in arteries and veins
Figure 11.6 shows the apparatus set up and
ready for use. The r ings of ar ter y and vein used
in this experiment are cut from the aor ta and
vena cava of a cow or sheep. The length of a
r ing of ar ter y with a mass carr ier attached to
it is measured. This is regarded as the ‘or iginal
length’ for all calculations. A 10 g mass is added
to the carrier. The new length of the r ing of
arter y is recorded and the percentage change paperclip hook
in length (compared with the or iginal length)
calculated. The procedure is continued using
additional 10 g masses up to 50 g and then
repeated using a r ing of vein.
ring of blood vessel
A greater percentage increase in length is
obtained for ar ter ies than for veins in response
to increasing mass added. This shows that
arter ies are able to stretch more than veins and
it is explained by the fact that ar teries contain
more elastic f ibres in their walls than veins.
mass carrier
When the experiment is extended to measure
percentage change in length on removing each
applied mass, ar ter ies are found to return to
their or iginal length more readily than veins,
showing that they are capable of more elastic
recoil.
10 g mass
Figure 11.6 Measur ing the stretching of a blood vessel
Tissue fluid Blood arriving at the arteriole side of a capillary bed

(see Figure 11.7) is at a higher pressure than blood in
Blood consists of red blood cells, white cells and
the capillaries. As blood is forced into these narrow
platelets bathed in plasma. Plasma is a watery yellow
exchange vessels, it undergoes a form of pressure
fluid that contains many dissolved substances such as
filtration and much of the plasma (containing small
glucose, amino acids, respiratory gases, plasma proteins
dissolved molecules) is squeezed out through the thin
160 and useful ions.
walls. This liquid is called tissue fluid. It differs from
blood plasma in that it contains little or no protein.
lymph passes into

lymphatic system
(see Figure 11.8)
respiring cells lymph vessel
blood arriving
in arteriole at
high pressure
blood leaving

in venule at

low pressure

capillary
some tissue fluid

enters capillary

by osmosis some plasma

forced out
of capillary
some tissue fluid

enters lymphatic
vessel
Figure 11.7 Exchange of materials in a capillar y bed
Exchange of materials Lymphatic return of tissue fluid

The network of capillaries in a capillary bed is so dense Some of the tissue fluid does not return to the blood
that every living cell in the body is located close to a in the capillaries. Instead this excess tissue fluid is
blood capillary and is constantly bathed in tissue fluid. absorbed by thin-walled lymphatic vessels, which have
Since tissue fluid contains a high concentration of blind ends and are located in the connective tissue
soluble food molecules, dissolved oxygen and useful among the living cells (see Figure 11.7). Once in a
ions, these diffuse down a concentration gradient into lymphatic vessel, the tissue fluid is called lymph.
nearby cells, supplying them with their requirements.
At the same time, carbon dioxide and other metabolic Lymphatic system
wastes diffuse out of the cells into the tissue fluid to be
Lymph is collected by a vast network of tiny lymph
excreted.
vessels, which unite to form larger vessels, a few of
which are shown in Figure 11.8. Flow of lymph through
Osmotic return of tissue fluid
the lymphatic system is brought about mainly by the
Much of the tissue fluid returns to the blood in the
vessels being periodically compressed when muscles
capillaries at the venule side of the capillary bed. This
contract during breathing, locomotion and other body
process is brought about by osmosis, with water passing
movements. Backflow of lymph is prevented by the
from a region of higher water concentration (tissue
presence of valves in the larger vessels. These vessels
fluid lacking plasma proteins) to a region of lower
eventually return their contents via two lymphatic
water concentration (blood plasma rich in soluble
ducts, which enter the veins coming from the arms (see
proteins) down a water concentration gradient. Carbon
Figure 11.8).
dioxide and metabolic wastes enter the bloodstream by 161
diffusion.
The lymphatic system is regarded as a specialised part
of the cardiovascular system because it consists of:
lymphatic duct
opens into vein ● lymph fluid that is derived from blood
from right arm lymphatic duct opens
into vein from left arm ● a system of vessels that returns lymph to the
bloodstream.
vein from
left arm
heart
lacteals in villi
of small intestine spleen
absorb products lymphatic
of lipid digestion vessels (only
a few are
shown)
lymph node
groups of
lymph nodes
(lymph ‘gland’)
direction of movement of lymph
Figure 11.8 Lymphatic system
Case Study Disorders of the lymphatic system
Oedema abdominal region. An abdomen swollen in this way

Oedema is the name given to the condition where is a symptom of kwashiorkor (see Figure 11.9). This
tissue fluid accumulates in the spaces between cells is a severe form of malnutrition suffered by young
and blood capillaries, causing tissues to swell up. children (especially infants weaned off breast milk by
Oedema can be caused by several factors, including a mother with a newborn baby to feed).
the following.
Parasites
Blood pressure The tiny larvae of one type of parasitic worm are
High blood pressure can result in tissue fluid being transmitted by mosquitoes. Once inside the body,
produced at a rate faster than it is drained away by they invade the lymphatic system. When they
the lymphatic system. mature into adult worms, they take up residence
in, and block, lymph vessels, especially those in the
Malnutrition
legs. This obstruction along with excessive growth
A prolonged dietary deficiency of protein can result
of neighbouring tissues in the infected area results
in the plasma protein level in the blood being so
in elephantiasis (see Figure 11.10), an enormous
low that it is similar in concentration to that of the
enlargement of the affected extremity.
tissue fluid. Under these circumstances, little or no
tissue fluid is returned osmotically to the blood.
The lymphatic system is unable to remove the
extra volume of fluid, which tends to gather in the
162
some parts of Africa USA
Figure 11.10 Elephantiasis
Figure 11.9 Kwashiorkor
1 Decide whether each of the following statements is true 2 a) Give T WO structural dif ferences between an ar ter y
or false and then wr ite T or F to indicate your choice. and a vein. (2)
Where a statement is false, give the word that should b) Give ONE functional dif ference between an ar ter y
have been used in place of the word in bold pr int. (6) and a vein. (1)
a) The carotid vein returns deoxygenated blood from 3 a) What is tissue fluid? (2)
the head to the vena cava. b) Name a substance that passes from body cells into
b) The renal ar ter y carr ies blood to the kidneys to be tissue fluid. (1)
pur if ied. c) Br iefly descr ibe T WO methods by which tissue fluid
c) The pulmonar y vein carr ies deoxygenated blood returns to the bloodstream. (2)
from the hear t to the lungs. 4 a) Br iefly descr ibe the means by which lymph in a
d) The hepatic portal vein carr ies deoxygenated blood lymph vessel is forced along through the lymphatic
from the gut to the liver. system. (1)
e) The coronary vein carr ies oxygenated blood from the b) What structures prevent backflow of lymph in the
lungs to the hear t. lymphatic system? (1)
f) The hepatic arter y carr ies deoxygenated blood from c) Which structures enable lymph to return to the blood
the liver to the vena cava. circulator y system? (1)
163
Structure of the heart Thickness of ventricle walls
The continuous circulation of blood round the body is The wall of the left ventricle is particularly thick and
maintained by a powerful muscular pump, the heart. muscular since it is required to pump blood all round
This organ is divided into four chambers, two atria the body. The wall of the right ventricle is less thick
and two ventricles (see Figure 11.11). The right atrium since it only pumps blood to the lungs.
receives deoxygenated blood from all parts of the
body via two main veins called the venae cavae. This Valves
deoxygenated blood passes into the right ventricle and Figure 11.11 shows the four heart valves. Two of these,
then leaves the heart by the pulmonary artery which situated between the atria and the ventricles, are called
divides into two branches each leading to a lung. the atrio-ventricular (AV) valves. They allow blood to
flow from atria to ventricles but prevent backflow from
Following oxygenation in the lungs, blood returns ventricles to atria.
to the heart by the pulmonary veins and enters the
left atrium. It flows from the left atrium into the left The other two heart valves, situated at the origins of the
ventricle and leaves the heart by the aorta, the largest pulmonary artery and aorta, are called semi-lunar (SL)
artery in the body. valves. These valves open during ventricular contraction
allowing blood to flow into the arteries. When arterial
pressure exceeds ventricular pressure, they close,
aorta
preventing backflow. The presence of the valves ensures
pulmonary arteries
that blood is only able to flow in one direction through
the heart.
pulmonary veins Cardiac function

vena cava
At each contraction of the heart, the right ventricle
pumps the same volume of blood through the
right atrium pulmonary artery (and round to the lungs) as the left
left atrium
ventricle pumps through the aorta (and round the
left AV valve
body).
vena cava
Heart rate (pulse) is the number of heartbeats that
semi-lunar
valves occurs per minute. (See Related Activity – Measuring
left ventricle pulse rate using a pulsometer.)
right AV valve
Stroke volume is the volume of blood expelled by each
right ventricle
very thick ventricle on contraction. The stronger the contraction,
muscular the greater the stroke volume.
thick muscular wall wall
Cardiac output is the volume of blood pumped out of a

= direction of blood flow
ventricle per minute. Thus cardiac output (CO) = heart
rate (HR) × stroke volume (SV).
Figure 11.11 Human hear t
Table 11.1 shows an example of the effect of exercise on
cardiac output for a human adult.
State of body Heart rate (beats/min) Stroke volume (ml) Cardiac output by each ventricle (l/min)
At rest 60 60 3.6
Dur ing exercise 120 70 8.4
Dur ing strenuous exercise 180 80 14.4
164
Table 11.1 Ef fect of exercise on cardiac output
Related Activity
Measuring pulse rate using a

pulsometer
Pulse rate can be measured by using a pulsometer, as
shown in Figure 11.12. Resting pulse rate is a measure
of pulse rate when the body is at rest and has not been
exercising for some time. On average, resting pulse rate
for men is approximately 75 beats/minute and slightly
higher for women, although any value between 60 and 90 Attach the equipment to your wrist.
is regarded as being within the normal range.

Pulse as a health indicator
If a person is f it, the relative quantity of cardiac muscle
present in their hear t wall is greater and more ef f icient
than that of an unf it person. A ver y f it person tends to
have a lower pulse rate than an unf it person because the
f it person’s hear t is larger and stronger. Therefore it does
not need to contract as of ten to pump an equal volume of
blood round the body. (In other words, the stroke volume Insert your finger into the sensor.
is greater.)
Attach the connector to the main unit.
Press button P to take your pulse.
Figure 11.12 Using a pulsometer
1 Construct a table that names the four chambers of 2 Compare the location and function of an AV valve with
the human hear t, the type of blood (oxygenated/ those of an SL valve. (2)
deoxygenated) that it contains, where this blood has 3 Distinguish clearly between the terms stroke volume,
come from and where this blood is going. (8) cardiac output and heart rate. (3) 165
1
12 The cardiovascular system in action
Chapter Head
Cardiac cycle blood in the atria to increase. Eventually atrial pressure

exceeds that in the ventricles, the AV valves are pushed
The term cardiac cycle refers to the pattern of open and blood starts to enter the ventricles.
contraction (systole) and relaxation (diastole) shown
by the heart during one complete heartbeat. On average, During atrial systole (see Figure 12.2) the two atria
the length of one cardiac cycle is 0.8 seconds, as shown contract simultaneously and send the remainder of
in Figure 12.1 which is based on a heart rate of 75 beats the blood down into the ventricles through the open
per minute. AV valves. The ventricles (still in the relaxed state of
ventricular diastole) fill up with blood and the SL valves
During diastole, the return of blood via the venae cavae remain closed.
and pulmonary veins to the atria causes the volume of
Atrial systole is followed about 0.1 seconds later by
= systole (contraction) ventricular systole. This stage involves the contraction
of the ventricles and the closure of the AV valves. The
= diastole (relaxation)
pressure exerted on the blood in the ventricles (as
the cardiac muscle contracts) soon exceeds the blood
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
time (seconds) pressure in the arteries. The SL valves are pushed open
situation and blood is pumped out of the heart and into the aorta
in atria
and pulmonary arteries.
situation in
ventricles
During diastole the higher pressure of blood in the
arteries closes the SL valves again and the next cardiac
cycle begins. The closing of the AV and SL valves are
state of atrial systole ventricular systole diastole
heart (and ventricular (and atrial

responsible for the sounds that can be heard during
diastole) diastole)
each cardiac cycle. (See Related Topic – Valves and heart
Figure 12.1 One cardiac cycle sounds.)
ATRIAL SYSTOLE VENTRICULAR SYSTOLE ATRIAL AND VENTRICULAR

(and ventricular diastole) (and atrial diastole) DIASTOLE
atrium and
atrium atrium ventricle
contracting relaxed relaxed
ventricle ventricle
relaxed contracting
AV valves open AV valves closed AV valves opening

SL valves closed SL valves open SL valves closed
166
Figure 12.2 Systole and diastole
The cardiovascular system in action
Related Topic
WX Y Z
120
Valves and heart sounds SL valve closes
Figure 12.3 refers to some of the changes that occur during SL

100 valve aortic pressure
the cardiac cycle. At point W in the graph (which refers opens
to the lef t side of the hear t only), ventr icular pressure 80
pressure (mm Hg)

exceeds atr ial pressure forcing the AV valve to close. This left ventricular
produces the f irst hear t sound (‘lubb’) which can be heard pressure
using a stethoscope. It can also be detected as a pattern 60
shown on a phonocardiogram (see Figure 12.3).

40 AV
At point X, ventr icular pressure exceeds aor tic pressure valve
closes AV valve opens
forcing open the SL valve. At point Y, ventricular pressure 20
falls below aor tic pressure causing the SL valve to close. left atrial pressure
This produces the second hear t sound (‘dupp’) heard
0
through a stethoscope. At point Z, ventr icular pressure 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
falls below atr ial pressure and the AV valve opens. time (s)
The hear t sound ‘lubb’ is heard at the star t of ventr icular

ATRIA
systole and ‘dupp’ at the start of ventr icular diastole.
VENTRICLES
Abnormal hear t sounds produced by abnormal patterns
= systole = diastole
of cardiac blood flow are called heart murmurs. These
are of ten caused by defective valves, which fail to open
or close fully. This type of condition can be inher ited or ‘lubb’ ‘dupp’
result from diseases such as rheumatic fever. heart sounds
on phono
cardiogram
Figure 12.3 Pressure changes and hear t sounds
wave of excitation
Cardiac conducting system sino-atrial node (SAN) makes atria contract
The sequence of events that occurs during each

heartbeat is brought about by the activity of the
pacemaker and the conducting system of the heart
right atrium
(see Figure 12.4). The pacemaker, also known as
the sino-atrial node (SAN), is located in the wall of
the right atrium. It is a small region of specialised atrio-ventricular
node (AVN)
tissue (composed of autorhythmic cells) that exhibits
spontaneous excitation. This means that the pacemaker
bundle of
initiates electrical impulses that make cardiac muscle conducting fibres
cells contract at a certain rate. This rate can be regulated
by other factors to suit the body’s requirements (see network of
conducting fibres
below). The pacemaker works automatically and would
continue to function even in the absence of nerve
contraction of ventricles
connections from the rest of the body. spreads upwards from apex
apex
A wave of excitation originating in the SAN spreads 167
through the muscle cells in the wall of the two atria Figure 12.4 Conducting system of the heart
making them contract simultaneously (atrial systole). Autonomic nervous control
The impulse is then picked up by the atrio-ventricular The heart is supplied with branches of the opposing parts
node (AVN) located centrally near the base of the atria. of the autonomic nervous system (see page 203).
The impulse passes from the AVN into a bundle of Control centres located in the medulla of the brain
conducting fibres, which divides into left and right regulate heart rate (see Figure 12.5). The cardio
branches. Each of these branches is continuous with accelerator centre sends its nerve impulses via a
a dense network of tiny conducting fibres in the sympathetic nerve to the heart; the cardio-inhibitor
ventricular walls. Stimulation of these fibres causes centre sends its information via a parasympathetic nerve.
simultaneous contraction of the two ventricles The two pathways are antagonistic to one another
(ventricular systole) starting from the heart apex and in that they have opposite effects on heart rate. An
spreading upwards. increase in the relative number of nerve impulses
Such coordination of heartbeat ensures that each type arriving at the SAN (pacemaker) via the sympathetic
of systole involves the combined effect of many muscle nerve results in an increase in heart rate. An increase
cells contracting and that ventricular systole occurs in the relative number of impulses arriving at the SAN
slightly later than atrial systole, allowing time for the via the parasympathetic nerve results in a decrease in
ventricles to fill completely before they contract. heart rate. The actual rate at which the heart beats is
determined by which system exerts the greater influence
Regulation over the heart at any given moment.
The pacemaker tissue alone initiates each heartbeat.
Neurotransmitter substances released by these
However, heart rate is not fixed as it is altered by
nerves influence the SAN. Sympathetic accelerator
nervous and hormonal activity.
nerves release the neurotransmitter norepinephrine
(noradrenaline), whereas slowing parasympathetic
nerves release acetylcholine (see page 253).
psychic and emotional
factors can sometimes
electrocardiogram
influence heart’s action
cerebrum
voltage
time
medulla
cardio-inhibitor centre close-up of one

cardio cardiac cycle
accelerator slowing
centre parasympathetic R
nerve
SAN
(pacemaker)
T
AV node P
spinal cord S
accelerator 0 0.2 0.4 0.6 0.8

sympathetic nerve
time (s)
168
Figure 12.5 Autonomic ner vous control of hear t rate Figure 12.6 Normal electrocardiogram
Hormonal control The normal ECG pattern is shown in Figure 12.6. It

Under certain circumstances (such as exercise or stress), consists of three distinct waves normally referred to
the sympathetic nervous system acts on the adrenal as P, QRS and T. The P wave corresponds to the wave
glands, making them release the hormone epinephrine of electrical excitation spreading over the atria from
(adrenaline) into the bloodstream. On reaching the the SAN. The QRS complex represents the wave of
SAN, this hormone makes the pacemaker generate excitation passing through the ventricles. The T wave
cardiac impulses at a higher rate and bring about an corresponds to the electrical recovery of the ventricles
increase in heart rate. occurring towards the end of ventricular systole.
Electrocardiogram Blood pressure

The electrical activity of the heart generates tiny Blood pressure is the force exerted by blood against
currents that can be picked up by electrodes placed on the walls of the blood vessels. It is measured in
the skin surface. The electrical signals, once amplified millimetres of mercury (mm Hg) as described below.
and displayed on an oscilloscope screen, produce a Blood pressure is generated by the contraction of the
pattern called an electrocardiogram (ECG). ventricles and it is therefore highest in the large elastic
arteries (aorta and pulmonary artery). As the heart
Related Activity
Examining abnormal ECGs atrial flutter

Abnormal hear t rhythms and some forms of hear t disease
can be detected and diagnosed using ECGs because
these produce unusual but identif iable patterns. Some
examples are shown in Figure 12.7.
When extremely rapid rates of electr ical excitation occur,
these lead to an increase in rate of contraction of either
atr ia or ventr icles. In an atr ial flutter, for example, the
contractions occur much more rapidly than normal but ventricular fibrillation
do remain coordinated. The example in Figure 12.7 shows
three P waves for ever y one QRS complex.
In a fibrillation, contractions of dif ferent groups of hear t
muscle cells occur at dif ferent times, making it impossible
for coordinated pumping of the hear t chambers to take
place. Ventr icular f ibr illation, for example, produces an
ECG with an irregular pattern. This condition is lethal if it
is not corrected. ventricular tachycardia
During ventricular tachycardia, abnormal cells in the

ventricle walls act like pacemakers and make these chambers
beat rapidly and independently of the atria. The P (atrial)
waves are absent and the wide QRS waves are abnormal.
Relief for some suf ferers of abnormal hear t rhythms can be
Figure 12.7 Abnormal ECGs
provided by f itting them with an artificial pacemaker. This
acts as a stimulator and sends out small electr ic impulses to a person who has suf fered a cardiac arrest. If it is followed
the hear t, making it beat in a normal, regular manner. soon af ter by defibrillation (the administration of an
electr ic shock to the subject’s heart by trained staf f), the
Emergency person’s chance of sur vival is increased by up to 30%.
CPR (cardiopulmonar y resuscitation) is an emergency Def ibr illation is only ef fective for cer tain abnormal hear t
procedure involving chest compressions administered to rhythms such as f ibr illation and ventricular tachycardia. 169
(for example, 80 mm Hg). Figure 12.8 shows the blood
150
pressure trace for a normal 18-year-old at rest.
blood pressure (mm Hg)
125
100 Decreasing blood pressure during

75
circulation
Although the pumping action of the heart causes
50
fluctuations in aortic blood pressure, the average
25 pressure in the aorta remains fairly constant. Figure 12.9
0
shows how a progressive decrease in pressure occurs
0 0.5 1.0 1.5 2.0 as blood travels round the circulatory system dropping
time (s)
to almost zero by the time it reaches the right atrium
Figure 12.8 Blood pressure trace again.
goes through systole and diastole during each cardiac As blood flows through a narrow blood vessel, friction
cycle, the arterial pressure rises and falls. For example, occurs between the blood and the vessel wall making
during ventricular systole, the pressure of blood in the the wall resist blood flow to some extent. It is this
aorta rises to a maximum (for example, 120 mm Hg); resistance by vessel walls to the flow of blood that causes
during ventricular diastole, it drops to a minimum the decrease in its pressure.
systolic
120 pressure
= average pressure
in arteries
100
85 mm
blood pressure (mm Hg)
80
diastolic
60 pressure
40 35 mm
20 15 mm
6 mm
1 mm
0
aorta arteries arterioles capillaries venules veins vena cava
direction of
blood flow
170
Figure 12.9 Decrease in blood pressure
Step 1 Step 2 Step 3
arm
artery
column of
mercury (Hg)
cuff
mm Hg
hand pump
Figure 12.10 Measur ing blood pressure
Measurement of blood pressure Hypertension

Systolic and diastolic pressures can be measured using Hypertension (high blood pressure) is the prolonged
an inflatable sphygmomanometer, which makes use of elevation of blood pressure when at rest. It is normally
a column of mercury to give the pressure readings as indicated by values of systolic pressure greater than
shown in Figure 12.10. (A sphygmomanometer can be 140 mm Hg and diastolic pressure greater than 90 mm Hg.
digital, as shown in Figure 18.1 on page 265.) It is rare in young people but fairly common in adults over
the age of 35. It is a major risk factor for many diseases
● In step 1, the cuff is inflated until the pressure that it that have a relatively high incidence later in life such as
exerts stops blood flowing through the arm artery. coronary heart disease and strokes.
● In step 2, the cuff is allowed to deflate gradually
until the pressure of blood in the artery exceeds the Hypertension is commonly found in people with an
pressure in the cuff. A pulse can now be felt and unhealthy lifestyle that includes some or all of the
blood can be heard to spurt through the arm artery following:
again using a stethoscope. The pressure at which this
● being overweight
first occurs is a measure of systolic pressure.
● not taking enough exercise
● In step 3, more air is released from the cuff until the
sound of spurting blood disappears and a pulse is ● eating a diet excessively rich in fatty food especially
no longer detected. The pressure at which this first animal fat
occurs is a measure of diastolic pressure. ● consuming too much salt
● drinking alcohol to excess regularly
Blood pressure is found to vary considerably from ● being under continuous stress.
person to person. A typical set of values for a healthy
young adult would be a systolic pressure of 120 mm Hg
and a diastolic pressure of 70 mm Hg. These values are
normally written as 120/70 mm Hg and referred to as
‘120 over 70’. 171
1 a) Distinguish between the terms systole and 3 a) What is an electrocardiogram? (1)

diastole. (2) b) i) Of how many waves does a normal ECG consist?
b) Construct a table to compare atr ial systole and ii) How many of these represent waves of electr ical
ventr icular systole with reference to state of atr ial excitation af fecting regions of the hear t? (2)
wall, state of ventr icular wall, state of AV valves and 4 a) i) Is the pressure of blood in the aor ta at its
state of SL valves. (4) maximum dur ing ventr icular systole or
2 a) i) By what other name is the hear t’s pacemaker ventr icular diastole?
known? ii) Explain your answer. (2)
ii) Br iefly descr ibe the function per formed by the
b) What name is given to an instrument used to
pacemaker. (2)
measure blood pressure? (1)
b) i) What hear t structure is represented by the letters c) Give ONE reason why prolonged hyper tension is
AVN? dangerous. (1)
ii) This structure passes impulses on to the
conducting f ibres. In which region of the hear t
are these f ibres located?
iii)Which stage of the cardiac cycle occurs as a direct
result of the conducting f ibres passing on the
impulses? (3)
1 The ______ is the inner cellular layer of a blood vessel’s

aorta endothelium semi-lunar wall that lines the central cavity (______).
ar ter ioles f ibres sino-atrial 2 Ar ter ies carr y blood away from the hear t at ______
atria heartbeats sounds pressure and their walls are thicker, more muscular and
atrio-ventr icular high sphygmomano more ______ than those of ______ which carr y blood
autorhythmic hormonal meter back to the hear t at ______ pressure.
backflow hyper tension stretch 3 The elasticity of ar ter ial walls enables them to ______
capillar y low stroke and recoil in response to the surge of blood that arr ives
cardiovascular lumen systole af ter each ______ of the hear t. Veins have ______ to
tissue fluid prevent backflow of blood.
chambers lymph
circulator y ner ves valves 4 Flow of blood to par ticular body par ts can be controlled
closing osmosis vasoconstr iction by ______ and vasodilation of ______.
contraction output veins 5 When blood is forced through a ______ bed, some
decrease protein venae cavae plasma passes out through the vessel walls. This liquid,
diastole pulmonar y ventr icles which bathes the cells, is called ______. It dif fers from
ar ter ies plasma in that it contains little or no plasma ______.
elastic
electro pulmonar y veins 6 Some tissue fluid returns to blood capillar ies by ______;
cardiogram pulse the remainder is absorbed by tiny lymphatic vessels and
becomes ______.
172
7 The hear t has two upper ______ called atria and two 11 Hear tbeat is initiated in the hear t itself by the ______
lower chambers called ______. Deoxygenated blood cells of the ______ node (pacemaker) which set it at a
returns to the hear t from the body by the ______; it cer tain rate. This rate of hear tbeat is then regulated by
is pumped by the heart to the lungs via the ______. autonomic ______ and ______ control.
Oxygenated blood returns to the hear t from the lungs
12 Impulses from the SAN spread through the atria and
by the ______; it is pumped by the hear t to the body via
are picked up by the ______ node and passed via
the ______.
conducting ______ to the ventr icular walls which
8 The atr io-ventr icular (AV) valves in the hear t prevent respond by contracting.
______ of blood from the ventr icles to the ______.
13 The electr ical activity of the hear t can be displayed on a
The ______ (SL) valves prevent backflow from the large
screen as an ______.
ar teries to the ventricles.
14 Blood pressure shows a progressive ______ as blood
9 Hear t rate (______) is the number of ______ that
travels round the ______ system.
occurs per minute. ______ volume is the volume of
blood expelled by each ventr icle on contraction. Cardiac 15 Ar ter ial blood pressure can be measured using a
______ is the volume of blood pumped out of a ventr icle ______. High blood pressure (______) is a major r isk
per minute. factor for ______ disease.
10 A cardiac cycle consists of a period of contraction called

______ and a period of relaxation called ______.
Dur ing a cardiac cycle two separate heart ______ can be
heard; each indicates the ______ of a set of valves.
173
1
13 Cardiovascular disease, diabetes and obesity
Chapter Head
Pathology of cardiovascular wall of an artery. Initially plaques are composed largely

of fatty material (mainly cholesterol – see page 182),
disease (CVD) but as the years go by they become enlarged by the
In the UK, cardiovascular diseases are responsible addition of fibrous material, calcium and more
for a high proportion of deaths annually, as shown in cholesterol (see Figure 13.2).
Figure 13.1.
The presence of these larger atheromas leads to:
● a significant reduction in the diameter of the
Atherosclerosis affected artery’s lumen
Atherosclerosis is the formation of plaques called ● the restriction of blood flow to the capillary bed
atheromas beneath the inner lining (endothelium) in the served by that artery
● an increase in blood pressure.
Women respiratory
In addition, large plaques hardened by deposits of
injuries and disease calcium cause arterial walls to become thicker and lose
poisoning (15%)
(3%) their elasticity. This process, which occurs as a direct
other cancers (14%)
result of atherosclerosis, is often called hardening of
the arteries. Symptoms of atherosclerosis normally
all other remain absent until later in life when problems can
causes
breast cancer (4%) arise. Then the condition can lead to the development
(23%)
lung cancer (5%)
of various cardiovascular diseases such as coronary
bowel cancer (2%)
heart disease (including angina), strokes and heart
diabetes (1%) attacks (myocardial infarctions). Atherosclerosis is
also the root cause of peripheral vascular disease (see
stroke (8%)
page 180).
other CVD including
coronary heart disease heart attacks (12%)
including angina (13%)
Men respiratory artery

injuries and disease
poisoning (13%)
(5%)
other cancers (20%)
muscular
layer
all other
causes
(18%)
lumen of
lung cancer (7%)
vessel
bowel cancer (3%) inner lining
diabetes (1%) (endothelium)
stroke (7%)
other CVD including
heart attacks (8%) atheroma
coronary heart disease
including angina (18%)
174
Figure 13.1 Causes of death in the UK Figure 13.2 Atheroma in an ar ter y
Cardiovascular disease, diabetes and obesity
Related Topic
Coronary heart disease atherosclerosis. Coronar y ar ter ies obstructed to such an

extent that their diameter is reduced by about 70% allow
Coronary ar ter ies suf f icient blood to flow to the cardiac muscle only when
The f irst two branches of the aor ta are the lef t and the person is at rest.
r ight coronar y arteries (see Figure 13.3). These vessels
However, dur ing exercise or stress, the hear t beats
spread out over the sur face of the hear t and divide into
faster and the demand for oxygen by cardiac muscle
an enormous number of tiny branches leading to a dense
cells increases accordingly. This demand cannot be met
network of capillar ies among the cardiac muscle cells that
because of the reduced blood flow through the narrowed
make up the wall of the hear t.
coronar y ar ter ies. Therefore a sudden pain occurs in the
chest, of ten accompanied by feelings of suf focation.
aorta Examining league tables

CHD is the most common cause of premature death in
many developed countr ies. Table 13.1 contains data from
a European sur vey. It compares death rates from CHD per
100 000 population in men (all ages) for several European
countr ies for two dif ferent years.
From the data it can be seen that the countr ies occupying
the six positions at the ‘undesirable’ top of the ‘league
table’ have remained unchanged over the 8-year per iod
but that all of these countr ies have shown a decrease
in CHD deaths except Hungar y, which remains the
undisputed leader.
coronary
The data also show that the four positions at the
arteries ‘desirable’ bottom end of the table have also remained
unchanged and that all four countries have shown a
Figure 13.3 Coronar y ar ter ies decrease in CHD deaths. The four countr ies in positions
7–10 in the league have also shown an improvement over
Each cardiac muscle cell is within 10 µm of a capillar y, the 8-year per iod and the UK has moved to a slightly
compared with the average distance of 60–80 µm in other better position (though its new position still leaves plenty
organs. This close proximity to exchange vessels allows of room for improvement).
ver y rapid dif fusion of oxygen and food into the actively
Table 13.2 contains data collected in the UK. It compares
respir ing cardiac muscle cells.
death rates from CHD per 100 000 population from the
Coronary hear t disease (CHD) four par ts of the UK over a 10-year per iod. From the data
it can be concluded that the number of deaths caused by
This general term refers to any disease that results in
CHD is decreasing in all par ts of the UK with time. It can
restriction or blockage of the coronar y blood supply to
also be seen that death rate per 100 000 population is
par t of the hear t’s muscular wall. It of ten takes the form
always higher for men than for women in any year in any
of angina, a condition character ised by a crushing pain
par t of the UK. In addition, the death rate in Scotland
in the centre of the chest, which tends to radiate out into
for both men and women is always higher than that in any
the lef t arm and up to the neck and jaws. It is suf fered by
other par t of the UK in any given year.
people whose coronar y ar ter ies have become narrowed by
175
➜

Year
2000 2008
Countr y Deaths per 100 000 population Country Deaths per 100 000 population
Hungar y 302 Hungar y 303
Czech Republic 256 Czech Republic 239
Finland 255 Finland 193
Bulgaria 247 Bulgar ia 190
Ireland 234 Ireland 155
Poland 205 Poland 151
UK 200 Austr ia 142
Austria 183 Iceland 138
Sweden 176 UK 132
Iceland 166 Sweden 130
Nor way 164 Norway 103
Switzerland 129 Switzerland 93
Netherlands 125 Netherlands 73
France 76 France 55
Table 13.1 Deaths rates from coronar y hear t disease for European men
Year
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
UK mean 39 36 35 32 30 27 24 22 21 20
Women England 37 34 32 30 28 25 23 21 19 19
aged Wales 41 40 39 36 33 32 27 25 23 21
35–74 Scotland 54 50 45 41 41 37 35 33 30 28
N. Ireland 46 41 38 36 30 30 28 27 23 22
UK mean 112 104 98 92 87 80 74 69 65 61
Men England 108 100 94 88 83 77 71 66 62 59

aged Wales 128 113 109 104 95 83 82 75 69 65
35–74 Scotland 146 133 120 113 112 101 98 88 89 81
N. Ireland 133 115 105 99 90 89 80 76 74 65
Table 13.2 Deaths from coronar y heart disease for Br itish men and women per 100 000 population
176
Clotting of blood
artery
Blood clotting is a protective device triggered by platelet
damage to cells. Normally it occurs to prevent loss of
endothelium
blood at a wound. The presence of damaged cells leads
atheroma
to the release of blood clotting factors that activate the
cascade of reactions shown in Figure 13.4. The enzyme
prothrombin, which is always present in blood plasma
but inactive, now becomes converted to its active form
called thrombin. Thrombin promotes the conversion of atheroma becomes ruptured
molecules of fibrinogen (a soluble plasma protein) into
threads of fibrin (an insoluble protein). These fibrin
threads become interwoven into a framework to which
platelets adhere, forming a blood clot. By this means
damaged
the wound is sealed and a scaffold is produced upon endothelium
which scar tissue can be formed.
prothrombin clotting factors released

(inactive enzyme)
clotting factors
(e.g. vitamin K)
platelets stick
together forming
a temporary plug
thrombin
(active enzyme)
clotting of blood
fibrinogen fibrin
(soluble) (insoluble) wound sealed
by blood clot
(thrombus)
Figure 13.4 Chemical reactions resulting in f ibr in formation fibrin threads
Thrombosis
Atheromas on the inside lining of an artery make Figure 13.5 Formation of a thrombus in a blood vessel
the surface uneven and disturb the smooth flow of
blood. As an atheroma gradually becomes enlarged it
may eventually burst through the endothelium and
muscular layer
damage it (see Figure 13.5). Under these circumstances,
coronary atheroma
thrombosis may occur. Thrombosis is the formation of artery endothelium
a blood clot (thrombus) in a vessel. (in blood clot
longitudinal (embolus)
section)
Embolus
The presence of a thrombus in an artery causes further
blockage in addition to that caused by atheromas. If
177
a thrombus breaks loose, it is known as an embolus. Figure 13.6 Coronar y thrombosis
An embolus is carried along by the blood until it blocks myocardial infarction (heart attack). A thrombus that
some narrow vessel and causes blood flow to be severely causes a blockage in an artery in the brain may lead to a
restricted or even brought to a complete halt. Blockage stroke. This normally results in the death of some of the
of a coronary artery by this type of thrombus is called tissues served by that artery because they are deprived
coronar y thrombosis (see Figure 13.6). It deprives of oxygen.
part of the heart muscle of oxygen and may lead to a
Research Topic Use of thrombolytic medications
Background
The main constituent of a thrombus is f ibr in. Under normal tissue plasminogen
circumstances, once a blood clot has ser ved its purpose, the activator
clot is broken down and removed. For this to happen,
plasminogen, the inactive form of the necessar y enzyme,
must f irst be conver ted to plasmin, the active form. This fibrin
conversion is brought about by a fur ther enzyme called (insoluble)
tissue plasminogen activator (tPA) present on the
endothelial cells lining blood vessels. The series of reactions
involved is shown in Figure 13.7.
plasminogen plasmin
Thrombolysis (inactive enzyme) (active enzyme)
The formation of a blood clot in a blood vessel and its

subsequent movement through the circulator y system as
an embolus that f inally blocks a narrow blood vessel is the products of fibrin
root cause of several ser ious conditions such as myocardial degradation
infarction, stroke and deep vein thrombosis (see page
180). Thrombolysis is the process by which such a clot is
broken down using a special medication in order to limit the Figure 13.7 Action of tissue plasminogen activator
damage caused by the blockage. Examples of thrombolytic
intravenously as soon as possible af ter the onset of the
drugs are streptokinase (or iginally extracted from
hear t attack or stroke. However, great care must be taken
bacteria) and tissue plasminogen activator (produced by
to ensure that their use is appropr iate. For example, they
recombinant DNA technology).
are suitable for treatment of a stroke caused by an embolus
Both of the above drugs work by conver ting inactive (blood clot) but not for a stroke caused by a haemorrhage
plasminogen to active plasmin and they are given (bleeding from a ruptured blood vessel).
Related Topic
Comparison of use of antiplatelet and clot by inhibiting the sticking together of platelets.
Therefore antiplatelet drugs are used to prevent the
anticoagulant therapies formation of a thrombus that could cause a coronar y
Both of these forms of medication are used to prevent the thrombosis or a stroke in people who run a signif icant r isk
formation of clots in the circulator y system. of developing such a condition.
Antiplatelet drugs Aspirin is an example of a relatively mild antiplatelet

drug. It inhibits the action of an enzyme essential
An antiplatelet drug is a form of pharmaceutical
for the production of a chemical that makes platelets
178 medication that interferes with the formation of a blood
stick together. However, daily use of aspir in, even calcif ication (hardening) of the arter ies. Hepar in is
in low-to-moderate doses, is accompanied by the another anticoagulant. It works by preventing thrombin
r isk of gastrointestinal bleeding in some individuals. from playing its role in the pathway.
Glycoprotein inhibitors are a more potent form of
antiplatelet drug. They also cause gastrointestinal Side effects
bleeding in some patients and their use is restr icted to Like antiplatelet drugs, the most ser ious side ef fect
a hospital setting because they can cause complications of anticoagulants is bleeding. This may take the form
such as low blood pressure. of prolonged nosebleeds, gastrointestinal bleeding or
increased bleeding during menstruation.
Anticoagulants
Anticoagulants are used in the treatment of thrombotic Clinical investigation
disorders such as deep vein thrombosis (see page
Table 13.3 shows the results of a randomised tr ial
180) and pulmonar y embolism (see page 181). An
comparing the two types of treatment on a large
anticoagulant dif fers from an antiplatelet drug in that
population of patients recovering from the implantation
it reduces or prevents blood clotting by inter fer ing with
of metallic stents (suppor ts) in their coronar y ar ter ies.
a stage in the biochemical pathway that leads to f ibr in
From these results it was concluded that in this tr ial,
production (see Figure 13.4).
three of the side ef fects occurred signif icantly less
In the UK, warfarin is the most commonly used frequently in antiplatelet therapy compared with
anticoagulant. It works by preventing vitamin K from anticoagulation therapy. However, there is insuf f icient
carr ying out its function in the pathway. However, evidence available at present to enable exper ts to favour
excessive depletion of vitamin K increases the r isk of conclusively one type of therapy over the other.
Percentage of patients in sample affected by side effect

Side effect
Antiplatelet therapy Anticoagulation therapy
Swelling caused by partially clotted blood 25 34
Discoloured ‘bruised’ areas of skin 16 38
Prolonged bleeding dur ing surgical repair 1 2
All bleeding complications 33 48
Table 13.3 Side ef fects of two therapies
Research Topic Bleeding disorders
Von Willebrand disease circumstances such as dental surger y or nosebleeds and

Von Willebrand disease (vWD) is caused by def iciency dur ing menstruation when bleeding may be prolonged.
of a protein called von Willebrand factor (vWF) needed In a rarer form of vWD, af fected individuals are
to make platelets stick together dur ing blood clotting. homozygous for the defective gene. They lack vWF and are
There are several forms of this inher ited condition. In the more seriously af fected. They can even suf fer bleeding of
most common one the person is heterozygous for the the joints. Never theless, individuals with vWD normally do
defective gene and their level of vWF is signif icantly lower not require regular treatment. However, they may be given
than normal. However, their blood still clots normally and a synthetic form of vWF in exceptional circumstances, for
they are unaware of the condition except dur ing unusual example immediately prior to undergoing major surger y.
➜ 179
Haemophilia A, B and C The less severe form, haemophilia C, af fects about 1 in
Haemophilia is a group of inher ited disorders, each 100 000 of the population (male and female equally).
of which impairs the body’s blood clotting mechanism Up until the 1950s, people with severe haemophilia rarely
and leads to prolonged bleeding from even the tiniest lived beyond the age of 10–11 years. Since the 1960s,
wound. The three forms of the condition are summar ised when ef fective treatment f irst became available, the life
in Table 13.4. expectancy of haemophiliacs has been extended to near
Haemophilia A and B occur in approximately 1 in 5000 normal levels. Modern treatments make use of versions
males (and ver y rarely in females). Of these males about of Factors VIII, IX and XI produced by recombinant DNA
85% suf fer haemophilia A and about 15% haemophilia B. technology.
Haemophilia Genetics Cause of the problem Symptoms Treatment

A Mutant allele of Factor Lack of suf f icient Regular intravenous
VIII gene which is clotting Factor VIII infusion of Factor VIII
recessive and sex- External and internal
linked bleeding post
operatively and
B Mutant allele of Factor Lack of suf f icient spontaneously into sof t Regular intravenous
IX gene which is clotting Factor IX tissues and joints infusion of Factor IX
recessive and sex-
linked
C Mutant allele of Factor Lack of suf f icient Mild form of condition Normally no treatment
XI gene which is clotting Factor XI character ised by some required except in
incompletely dominant prolonged bleeding advance of surger y
and autosomal when Factor XI is given
Table 13.4 Types of haemophilia
Peripheral vascular disorders

The peripheral arteries are those other than the aorta
and coronary and carotid arteries. When any of the
peripheral arteries are affected by atherosclerosis, their
central cavity becomes narrower (see Figure 13.2).
This leads to peripheral vascular disease, which most
commonly affects the leg arteries. When these blood
vessels suffer an obstruction of this type, blood flow is
restricted and pain is felt in the leg muscles because they
are receiving an inadequate supply of oxygen.
swelling caused by
deep vein thrombosis
Deep vein thrombosis
Deep vein thrombosis is the formation of a thrombus
(blood clot) in a vein, most commonly one in the calf
of the lower leg. Normally this causes the affected
extremity to become painful and swell up (see
Figure 13.8). In addition, veins close to the skin surface
180
can become engorged with blood. Figure 13.8 Deep vein thrombosis
Pulmonar y embolism
If a thrombus in a vein breaks free, a serious left lung
complication may arise. The clot (now an embolus) is

transported via the vena cava and heart chambers to the pulmonary artery
containing
pulmonary artery where it may block a small arterial deoxygenated
branch. This serious situation is called a pulmonary blood
embolism (see Figure 13.9) and is characterised by detail of branch
of pulmonary
symptoms such as chest pains, breathing difficulties and artery
palpitations. Treatment takes the form of anticoagulant embolus
drugs or, in severe cases, thrombolytic drugs. If blocking
blood
untreated, a pulmonary embolism can lead to collapse vessel
and sudden death.
heart
Figure 13.9 Pulmonar y embolism

blood from liver
blood circulatory system
molecule of LDL-cholesterol
some LDL-cholesterol
engulfed by body cells
close-up
body cells
LDL-cholesterol
LDL receptor excess LDL-cholesterol
LDL-cholesterol
atheroma
attached
to receptor
LDL-cholesterol
engulfed
LDL-cholesterol
by cell
released from receptor
LDL receptor
used to synthesise
new receptors
cholesterol released
and used by cell
181
Figure 13.10 Transpor t of cholesterol by LDL
Cholesterol ● eats a diet rich in saturated fat throughout their life
● suffers an inherited condition called familial
The term lipid refers to a diverse group of organic hypercholesterolaemia (see page 184).
compounds which includes simple lipids such as
fats (saturated and unsaturated) and more complex High-density lipoprotein (HDL)
substances such as steroids. Cholesterol is an important Some excess cholesterol is transported by high-density
substance because it is a precursor for the synthesis lipoproteins (HDL) from body cells to the liver for
of steroids (such as sex hormones) and it is a basic elimination. Under normal circumstances, this process
component of cell membranes. Therefore its presence prevents a high level of cholesterol accumulating in
in the bloodstream at an appropriate concentration the bloodstream. In addition, HDL-cholesterol is
is essential to the health and well-being of the human not taken into artery walls and therefore does not
body. It is produced in liver cells from saturated fats contribute to atherosclerosis. However, these benefits
present in a normal balanced diet. are dependent on a healthy balance existing between
the HDL-cholesterol molecules (sometimes called
Transpor t of cholesterol ‘good cholesterol’) and the LDL-cholesterol molecules
Lipoproteins are molecules containing a combination (sometimes called ‘bad cholesterol’). (It should be noted
of lipid and protein. They are present in blood plasma that the cholesterol attached to a molecule of LDL is
and transport lipids from one part of the body to identical to that attached to HDL.)
another.
Normally HDL molecules carry about 20–30% of
Low-density lipoprotein (LDL) blood cholesterol and LDL molecules carry about
60–70%. A higher ratio of HDL to LDL results in a
Cholesterol is transported to body cells by low-density
decrease in blood cholesterol and a reduced chance of
lipoproteins (LDL) produced by the liver. Most body
atherosclerosis and cardiovascular disease. The reverse
cells synthesise LDL receptors which then become
is true of a lower ratio of HDL to LDL.
inserted in their cell membrane. When a molecule of
LDL carrying cholesterol (LDL-cholesterol) becomes The concentration of HDL-cholesterol in the
attached to a receptor, the cell engulfs the LDL- bloodstream is normally higher and the risk of CVD
cholesterol and the cholesterol is released for use by the lower in people who exercise regularly. In addition,
cell (see Figure 13.10). evidence suggests that HDL levels may also be raised by
the replacement of some saturated fat with unsaturated
Atherosclerosis fat in the diet and the consumption of less total fat.
Once a body cell contains an adequate supply of
cholesterol, a negative feedback system is triggered Statins
which inhibits the synthesis of new LDL receptors. The level of cholesterol in the blood can be reduced
Therefore less of the LDL-cholesterol circulating in the by medication. Drugs such as statins bring about this
bloodstream is absorbed by body cells. Instead, some of effect by inhibiting an enzyme essential for the synthesis
it is taken up by endothelial cells lining the inside of an of cholesterol by liver cells. (See Research Topic – Action
artery. The cholesterol is then deposited in an atheroma of cholesterol-reducing drugs.)
in the wall of the artery. This process is very likely to
occur if the person:
182
Research Topic Action of cholesterol-reducing drugs
HMG-CoA reductase is an enzyme found in liver cells that in the level of cholesterol in the blood. Statins also act
promotes the f irst step in a long chain of biochemical by increasing the number of LDL receptors made by liver
reactions that leads to the production of cholesterol cells. These receptors br ing about a reduction in the level
(see Figure 13.11). Statins are the most widely used of ‘bad cholesterol’ by removing some molecules of LDL-
cholesterol-reducing drugs. They act by competing with cholesterol from the bloodstream.
the enzyme’s substrate (HMG-CoA) for the active sites on
the molecules of the enzyme. This process of competitive Night or day
inhibition reduces the rate at which the enzyme is able Normally cholesterol synthesis occurs mainly at night.
to produce intermediate 1 and subsequently reduces the Therefore statins that only act over a shor t time span
rate at which the cell is able to make cholesterol. are more ef fective if taken at bedtime rather than in the
Since more cholesterol or iginates from internal morning.
manufacture in liver cells than from the diet, a drop in Clinical trials
cholesterol production by the liver soon results in a drop
Several clinical tr ials have shown the benef its of statins
in reducing death rates among patients suf fer ing
cardiovascular disease (CVD). In recent years, fur ther
HMG-CoA
clinical tr ials have been carr ied out to investigate if
statins reduce coronar y and cerebrovascular events in
enzyme (HMG-CoA reductase)
people who are at risk of, but are not suf fer ing, CVD.
Table 13.5 shows the results from one of these tr ials.
It was carr ied out over a period of 4 years on many
thousands of par ticipants of average age 63 years. About
25% were suf fer ing diabetes but none of them was
intermediate 1
suf fer ing CVD at the star t of the tr ial.
The results from this trial and many others have been
many more enzymes collated. From the vast quantity of data produced, it has
and intermediates
been concluded that statins, by reducing cholesterol
levels in patients at r isk of CVD, br ing about a signif icant
reduction in the r isk of major cardiovascular events and a
signif icant decrease in mor tality caused by CVD.
cholesterol
Figure 13.11 Production of cholesterol
Condition Percentage of group affected after 4 years Percentage risk

Control group Statin group reduction
Major coronar y event 5.4 4.1 24

Major cerebrovascular event 2.3 1.9 17
All-cause mor tality 5.7 5.1 11
Table 13.5 Results of clinical tr ial investigating action of statin
183
Related Activity
Investigating current views on the use concer ted ef for ts by pharmaceutical companies, there is
no suggestion at present that people who have elevated
of statins LDL-cholesterol levels but are not at risk of CVD should be
In the UK, advice to NHS staf f includes the following taking statins.
guidelines:
Although most people f ind the guidelines helpful,
● Statin therapy is recommended for adults with clinical some people f ind them unsatisfactor y. They are
evidence of CVD. concerned that the ‘20% 10-year r isk of developing
● Statin therapy is recommended as par t of the CVD’ is dif f icult to def ine quantitatively and is open to
management strategy for pr imar y prevention of CVD var ious interpretations. In their opinion many doctors,
for adults who have a 20% or greater 10-year risk of under pressure from pharmaceutical companies and
developing CVD. (Risk assessment is based on factors from increased public awareness of a ‘potential health
such as whether the individual is elderly, suf fers problem’, may be disposed to prescr ibe statins for people
diabetes or belongs to a high-r isk ethnic group.) whose LDL-cholesterol is above a notional target level
● Any decision to initiate therapy should only be made but who are otherwise perfectly healthy and not at
following an informed discussion between the doctor risk of CVD. The critics add that these people would be
and the patient about the r isks and benef its of statin undergoing many years of unnecessary drug therapy.
treatment. They stress that it is impor tant that each person makes an
Therefore the current view in the UK is that the use of informed decision before embarking on a course of statin
statins should be restr icted to the treatment of patients therapy.
who are at r isk of or are already suffering CVD. Despite
Familial hypercholesterolaemia (FH) the possession of ver y high LDL-cholesterol levels in

Familial hypercholesterolaemia is an inherited the bloodstream.
disorder that shows an autosomal dominant pattern of
If the condition is left untreated, large quantities of
inheritance. (See Related Activity – Analysing an FH
cholesterol are deposited in the walls of arteries from
pedigree.)
an early age. Therefore affected individuals suffer
Under normal circumstances, molecules of LDL- cardiovascular problems such as coronary artery
cholesterol bind to LDL receptors on cell membranes. disease at a much younger age than the members of
However, in sufferers of FH, the mutated gene causes the population as a whole. People whose family has a
a decrease in the number of LDL receptors present in history of FH can take a genetic test to determine if
the cell membranes or a change in their structure that they have inherited an FH allele. The condition can be
renders them non-functional. Either way, molecules of treated by the individual adopting a modified lifestyle
LDL-cholesterol are unable to unload their cholesterol and taking medication such as statins. (See Related
in cells. It is for this reason that FH is characterised by Topic – Investigating treatments for FH.)
184
Related Activity
Analysing an FH pedigree Therefore, on average, there is a 1 in 2 (50%) chance that

each of their children will be af fected.
Figure 13.12 shows the pedigree of Laura, a suf ferer of
familial hypercholesterolaemia (FH). Members of Laura’s FH shows typical features of autosomal dominant
generation and Laura’s father’s generation af fected by inheritance:
this inher ited disorder have all received treatment and
● The trait appears in ever y generation.
are still alive. However, af fected members of Laura’s
● Each suf ferer of the trait has an af fected parent.
grandmother’s generation (and earlier generations) did
● When a branch of the family does not express the
not receive treatment and died prematurely compared
trait, the trait fails to reappear in future generations
with the non-suf ferers of their own generation.
of that branch.
In this family tree, the mutant allele for FH is dominant ● Males and females are af fected in approximately equal
and each af fected person is a heterozygote. Each numbers.
heterozygote has marr ied an unaf fected homozygote.
Key
= affected O
= unaffected O
= affected O
= unaffected O
= deceased
Laura
Figure 13.12 Pedigree of familial hypercholesterolaemia
Related Topic
Investigating treatments for familial Suf ferers are also encouraged to take regular exercise
because this is thought to lower levels of LDL-cholesterol.
hypercholesterolaemia (FH)
Change in lifestyle Medication
For the treatment to be successful, the suf ferer has to If a dietar y change does not succeed in lower ing LDL-
follow a diet that reduces total fat intake to less than cholesterol level suf f iciently, the suf ferer of FH is given
30% of their total intake of kilojoules. In addition, this medication. Some drugs such as statins work by lower ing
diet concentrates on a reduction in saturated fats by the the level of LDL-cholesterol (‘bad cholesterol’); others
af fected individual: such as nicotinic acid (a form of vitamin B3) may help to
increase the level of HDL-cholesterol (‘good cholesterol’).
● decreasing the quantities of beef, pork, lamb and
chicken that they eat
● replacing full-fat dair y products with low-fat dair y and Filtration
soy products Suf ferers of ver y extreme forms of FH are treated by
● eliminating foods r ich in oils such as palm and having their blood f iltered to remove excess LDL-
coconut. cholesterol. 185
1 a) What is meant by the term atherosclerosis? (2) c) By what means do drugs such as statins reduce blood
b) Identify T WO ways in which the structure of an ar ter y cholesterol level? (1)
is altered by atherosclerosis. (2) 4 Decide whether each of the following statements is
2 a) Arrange the following four stages that occur dur ing true or false and then use T or F to indicate your choice.
thrombosis into the correct order. (1) Where a statement is false, give the word that should
A clotting factors are released have been used in place of the word in bold print. (5)
B soluble f ibrinogen changes into threads of a) Atherosclerosis causes the lumen of an af fected
insoluble f ibr in arter y to become wider.
b) A thrombus that has broken loose and is free to
C an atheroma bursts and damages the
travel through the bloodstream is called an angina.
endothelium
c) The development of an atheroma in the wall of an
D inactive prothrombin becomes active thrombin arter y results in an increase in blood pressure.
b) What might be the result of a thrombus blocking: d) Per ipheral vascular disease is character ised by the
i) an ar ter y in the brain narrowing of capillaries in body extremities.
ii) a coronar y arter y? (2) e) If a small clot formed by deep vein thrombosis travels
3 a) Give ONE reason why all cells need a supply of through the bloodstream it may cause a pulmonar y
cholesterol. (1) embolism.
b) How is cholesterol transpor ted:
i) from the liver to body cells
ii) from body cells to the liver? (2)
Blood glucose levels and vascular A tissue may be affected either by being flooded with
leaked blood or by not receiving an adequate oxygen
disease supply. Microvascular disease can cause damage to the
Normally blood plasma contains glucose at a
concentration of around 5 millimoles per litre (mmol/l)
with this glucose concentration varying slightly
depending on demand by respiring tissues. However, if
a person is suffering untreated diabetes (see page 188) wall of arteriole
their level of blood glucose may become elevated to an
abnormal and chronic level such as 30 mmol/l. Under
these circumstances endothelial cells lining blood vessels
absorb far more glucose than normal. This process causes
enlarge
damage to blood vessels and may lead to peripheral
vascular disease, CVD or stroke.
Microvascular (small vessel) disease

endothelial
When the endothelial cells lining a small blood vessel cell
such as an arteriole (see Figure 13.13) take in more
glucose than normal, their basement membrane
becomes thicker but weaker. Therefore, as the walls
of an affected blood vessel become abnormally thick,
they lose their strength and may burst and bleed basement membrane
(haemorrhage) into the surrounding tissues. This
186
leakage reduces rate of flow of blood through the body. Figure 13.13 Endothelium of an ar ter iole
Related Activity
Investigating symptoms associated the kidneys are eventually no longer able to per form their
function of f ilter ing and purifying blood. This form of
with microvascular disease kidney disease is common among people with diabetes
Whereas macrovascular (large vessel) disease is caused who do not control their condition strictly. Its symptoms
by an obstruction blocking a main ar ter y, microvascular include:
disease results from damage to small blood vessels.
Symptoms of a macrovascular problem such as coronar y ● swelling of the ankles, feet and lower legs
hear t disease tend to be readily apparent, severe and ● production of darker urine, containing traces of blood
of ten life-threatening. Symptoms of a microvascular ● shor tage of breath when climbing stairs.
problem such as per ipheral ner ve dysfunction tend to lack
specif ic expression for a long time but to become severe In order to have kidney disease diagnosed and treated
eventually. They tend to be restr icted to localised areas before it reaches an extreme stage, people with
and to respond to treatment if an associated condition diabetes are advised to be screened annually for kidney
such as elevated blood glucose level is controlled in time. complications.
Microvascular complications are common among long- Peripheral neuropathy (per ipheral ner ve dysfunction)
term suf ferers of poorly controlled diabetes. Diabetic is a condition resulting from microvascular disease of
retinopathy resulting from prolonged high blood glucose blood vessels closely associated with ner ves that ser ve
levels, for example, causes small vessels in the retina to the body’s extremities such as hands and feet. These
haemorrhage and leak into the back of the eye. This early ner ves are damaged by prolonged exposure to elevated
sign of diabetes is normally picked up dur ing a routine levels of blood glucose. Symptoms can take the form of
eye test. In its early stages, diabetic retinopathy can numbness, tingling or pain in hands, arms, toes, feet
occur without obvious symptoms or pain. As the condition or legs. Per ipheral neuropathy is common among older,
becomes more ser ious, vision is af fected and, if lef t overweight diabetics who continue to exer t poor control
untreated, it eventually causes blindness. over their condition. If lef t untreated, it can lead to the
development of ulcers and eventually to the amputation
Microvascular disease that causes damage to kidney of the af fected extremity.
ar terioles can lead to renal failure. This occurs because
retina, affecting vision, and to the kidneys, causing Liver as a storehouse

renal failure. In addition it affects nerves in the body’s
About one hundred grams of glucose are stored as
extremities, which suffer peripheral nerve dysfunction.
glycogen in the liver. Glucose can be added to or
(See Related Activity – Investigating symptoms
removed from this reservoir of stored carbohydrate
associated with microvascular disease.)
depending on changes in supply or demand.
Regulation of blood glucose level Insulin and glucagon

All living cells in the human body need a continuous A rise in blood glucose concentration to above its
supply of energy released from the breakdown of normal level (for example, following a meal) is
glucose during tissue respiration. However, the body detected by receptor cells in the pancreas. These cells
obtains supplies of glucose only on those occasions produce insulin. This hormone is transported in the
when food is eaten. To guarantee that a regular supply bloodstream to the liver where it is picked up by insulin
of glucose is present in the bloodstream and available receptors. Excess glucose is absorbed by the liver cells
for use by cells regardless of when and how often food and an enzyme is activated that catalyses the reaction:
is consumed, the body employs a system of negative
feedback control. glucose → glycogen
This process brings about a decrease in blood glucose
187
concentration to around its normal level. If the blood
more insulin
(less glucagon)
receptor cells
liver
in pancreas
increase in blood excess glucose

glucose concentration stored as glycogen
normal glucose normal glucose

concentration concentration
in bloodstream in bloodstream
decrease in blood glycogen converted

glucose concentration to glucose
more glucagon
(less insulin)
receptor cells liver
in pancreas
Figure 13.14 Regulation of blood glucose level by negative feedback control
glucose drops below its normal level (for example, glands secrete an increased quantity of the hormone
between meals or during the night), different receptor epinephrine (adrenaline) into the bloodstream.
cells in the pancreas detect this change and release Epinephrine overrides the normal homeostatic control
glucagon. This second hormone is transported to the of blood glucose level by inhibiting the secretion of
liver and activates a different enzyme, which catalyses insulin and promoting the breakdown of glycogen to
the reaction: glucose. Once the crisis is over, secretion of epinephrine
glycogen → glucose is reduced to a minimum and blood glucose level
is returned to normal by the appropriate corrective
Now glucose is released from liver cells and the blood
mechanism involving insulin or glucagon.
glucose concentration rises to around its normal value.
Figure 13.14 gives a summary of this homeostatic
system and shows how insulin and glucagon act Diabetes
antagonistically. People who suffer diabetes are unable to control
their blood glucose level. If untreated, it can rise to
Epinephrine 10–30 mmol/l compared with the normal blood glucose
concentration of around 5 mmol/l. There are two types
During exercise or ‘fight or flight’ reactions (see
of diabetes and they are compared in Table 13.6.
page 205) when the body needs additional supplies
of glucose to provide energy quickly, the adrenal
188
HE31928.indb 188 26/02/2013 10:14

Type 1 diabetes Type 2 diabetes

Percentage of all cases 5–10 90–95
Stage of life at which condition Childhood or early teens (therefore Adulthood (therefore of ten referred to
normally first occurs of ten referred to as ‘juvenile onset’ as ‘adult onset’ diabetes)
diabetes)
Typical body mass of sufferer Normal or underweight Overweight or obese
Ability of pancreatic cells to produce Absent Present
insulin
Sensitivity of cells (e.g. liver and Cells have the normal number of insulin Cells have a decreased number of insulin
skeletal muscle) to insulin receptors on their surfaces. They receptors on their surfaces, making
respond to the presence of insulin (if them less sensitive (or even resistant)
given as treatment) and br ing about the to insulin. Therefore few (or no) glucose
opening of glucose channels into the channels are opened, much glucose
cells. fails to enter the cells and normal
conversion of glucose to glycogen is
prevented.
Treatment Regular injections of insulin and a Exercise, weight loss, diet control (and
careful diet insulin in some cases)
Table 13.6 Compar ison of two types of diabetes
Both types of diabetes, if untreated, result in a rapid Glucose tolerance test

increase in blood glucose level following a meal. The
Glucose tolerance is the capacity of the body to deal
filtrate formed in the kidneys of an untreated diabetic
with ingested glucose. This depends on the body
is so rich in glucose that much of the glucose is not
being able to produce adequate quantities of insulin.
reabsorbed into the bloodstream but instead excreted in
Measurement of glucose tolerance is a clinical test used
urine. Therefore, testing urine for glucose is often used
to diagnose diabetes. It investigates by indirect means
as an indicator of diabetes.
whether (or not) insulin production is normal. After
Many vascular diseases are closely associated with fasting for 8 hours, a person has their blood glucose
chronic (long-lasting) complications of diabetes. level measured and then consumes a known mass of
Whereas it used to be a fatal disorder, diabetes can glucose to give a glucose load. Their blood glucose level
now be successfully treated provided that the affected is monitored over a period of 2½ hours and the results
individual is prepared to adopt a healthy lifestyle. plotted to give a glucose tolerance curve. (See Related
Activity – Analysing glucose tolerance curves.)
Related Activity
Analysing glucose tolerance curves that insulin production is normal. The increase in blood
glucose concentration has tr iggered the sequence of
Figure 13.15 shows three dif ferent glucose tolerance
events shown in Figure 13.14 and has been brought back
cur ves resulting from glucose tolerance tests.
to normal by negative feedback control. In this example,
Curve 1 the process is so ef fective that the blood glucose level
The person’s glucose concentration r ises to a maximum close to the end of the test dips below the initial fasting
at around 30 minutes and then quickly drops to its initial level for a shor t time.
low level well within the 2½ hour per iod. This indicates
➜ 189
18 Cur ve 2
The person’s blood glucose concentration begins at the
16 curve 3 normal fasting level but continues to r ise to a maximum
at around 60 minutes (or even later) before beginning to
14
decrease. The delay in insulin response to glucose load
blood glucose concentration (m mol/l)
indicates a mild form of type 2 diabetes. This condition

12
will probably respond to a careful diet and not require
treatment with insulin.
10
Cur ve 3
Af ter fasting, the person’s blood glucose concentration
8
is still at an abnormally high level. Af ter ingestion of
curve 2 glucose, it continues to rise for 60 minutes (or more) and
6
then shows a slight decrease but fails to drop even to its
curve 1
initial high level. This sequence of events indicates severe
4
diabetes (probably type 1). The person is either producing
no insulin or their cells are failing to make a normal
2
insulin response to glucose load. Regular injections of
insulin and a carefully controlled diet will probably be
0
0 30 60 90 120 150 needed to control this condition.
time (minutes)
glucose
ingested
Figure 13.15 Glucose tolerance cur ves
Obesity
Obesity is a condition characterised by the
accumulation of excess body fat in relation to lean
tissue such as muscle. Being obese greatly increases cardiovascular disease
the individual’s risk of suffering a variety of health kidney failure
problems (see Figure 13.16). type 2 diabetes
osteoarthritis
Body mass index (BMI)
There is an ideal body mass (weight) for each person.
This varies from one individual to another. A person’s Figure 13.16 Obesity and health problems
body mass index (BMI) is calculated using the formula:
body mass (where body mass is measured in kg and height is
BMI = _________ measured in m). The currently accepted classification of
height2
BMI values is shown in Table 13.7.
BMI value Opinion of experts Risk of associated health problems

20–25 Ideal for height Average
26–30 Overweight Increased
31–40 Obese (ver y overweight) Greatly increased
Over 40 Ver y obese (grossly overweight) Ver y greatly increased
190
Table 13.7 BMI values
Limitation of BMI method classified as obese by the BMI method. To measure

Some individuals such as body-builders, who have a body fat accurately, a measurement of body density is
relatively low percentage of body fat and an unusually required. (See Related Topic – Methods of measuring
high percentage of muscle bulk, would be wrongly body composition.)
Related Topic
Methods of measuring body sum of these measurements is used, with the aid of a
mathematical formula, to estimate body density and
composition percentage fat content.
Densitometr y
This method assumes that the body’s fat mass (all Bioelectr ical impedance
chemical fat in the body) and the fat-free mass (muscle, The body’s fat-free mass of fers little resistance (or, more
bone, etc.) have densities of 0.9 g/cm3 and 1.11 g/cm3 accurately, impedance) to the flow of a small electric
respectively. Measurements of the person’s body weight in current compared with the fat mass, which is an insulator
air and then under water provide information that can be and of fers a high resistance. Therefore, an estimate
used with the aid of a mathematical formula to estimate of ratio of fat-free mass to fat mass can be made by
the percentage of total body mass made of fat. applying a small electr ic current to par ts of the body and
measur ing bioelectr ical impedance.
Skin-fold thickness
A skin-fold calliper is used to measure the thickness of Waist/hip ratio
a fold of skin containing a layer of subcutaneous fat at Although the total quantity of fat in the body is a
four specif ic sites in the body (see Figure 13.17). The ver y impor tant factor when assessing health r isk, the
back of upper arm front of upper arm
below shoulder blade side of waist
Figure 13.17 Positions used for taking skin fold measurements 191
➜
distribution pattern of the fat is even more impor tant. ‘pear’ ‘apple’
‘Apple-shaped’ people (see Figure 13.18) with excess
abdominal fat are now known to be, on average, at
a greater r isk of type 2 diabetes and CVD than ‘pear-
shaped’ people with excess fat round their hips. Women
are considered to be at r isk when their waist/hip ratio
is greater than 0.8 and men are considered to be at r isk
when their waist/hip ratio is greater than 1.0.
Figure 13.18 Two patterns of fat distr ibution
Causes of obesity intake by limiting their consumption of fat (which has

Genetic, psychological, environmental, metabolic a high calorific value relative to other foods) and free
and dietary factors are all thought to be possible sugars (which do not need any metabolic energy to be
contributors to obesity. However, the most common expended to digest them). They are also encouraged
cause is the excessive consumption of food rich in fats to take regular exercise in order to expend some of the
and free sugars combined with lack of physical activity. energy in their body fat while keeping their muscle
tissue lean. Increased exercise also helps to bring about:
Treatment
● a reduction in the risk factors associated with CVD
A reduction in energy intake and an increase in energy
● an increase in the level of HDL-cholesterol (‘good
expenditure are the mainstays of treatment for obesity.
cholesterol’) in the blood
Affected individuals are advised to reduce energy
● a decrease in hypertension and stress.
Related Topic
Effect of exercise on body composition If this person adopts a lifestyle that includes some gentle
exercise, making their energy output exceed their energy
Exercise does not need to be strenuous to br ing about a
input by 210 kJ per day, then af ter 1 week their energy
loss in weight. However, total energy intake must be less
def icit will be 1470 kJ, af ter 10 weeks 14 700 kJ and
than total energy output for weight loss to occur.
af ter 40 weeks 58 800 kJ, which is equivalent to 2 kg of
body fat.
Worked example
On the other hand, if the person adopts a lifestyle that
1 kg of body fat contains 29.4 megajoules (MJ) of energy.
includes more vigorous exercise, making their energy
1 MJ = 1000 kJ. Therefore, 29.4 MJ = 29 400 kJ. output exceed their energy input by 840 kJ per day, then
af ter 1 week their energy def icit will be 5880 kJ and
Imagine an individual wants to lose 2 kg of body fat af ter 10 weeks 58 800 kJ, which is equivalent to 2 kg of
(equivalent to 58 800 kJ). body fat.
192
Related Activity
Examining risk factors and remedial Treatment of cardiovascular disease

measures in treating CVD Medication
People who are suf fer ing cardiovascular disease or have
Risk factors
suf fered a hear t attack may be given:
The main CVD risk factors are:
● nitroglycerin to improve blood flow to hear t muscle
● high LDL-cholesterol level
by making coronar y ar ter ies become dilated
● obesity
● heparin to act as an anticoagulant and reduce the
● unhealthy diet high in saturated fat and cholesterol
tendency of blood to clot in coronar y ar teries
● physical inactivity
● tissue plasminogen activator to dissolve blood clots
● high blood pressure
in vessels
● smoking
● beta-blockers to reduce the hear t’s workload by
● diabetes
decreasing heart rate and blood pressure.
● dr inking alcohol to excess
● ver y stressful lifestyle.
All of these r isk factors can be reduced signif icantly by
adopting a healthy lifestyle suppor ted by medication
where necessar y.
blockage in probe of
catheter balloon blood coronary artery catheter vessel
wall
probe pushed through blockage

and balloon inflated
balloon deflated and

catheter removed lumen of
vessel unblocked
Figure 13.19 Balloon angioplasty ➜ 193

Medical intervention
Angioplasty
Where par tial or almost complete blockage of a coronar y aorta
ar ter y is detected, angioplasty may be used. Figure 13.19
shows the tip of a balloon catheter reaching a blockage.
vein grafts
When the balloon is inflated, it disperses the fatty
deposits and opens up the vessel. The balloon is then
sites of
deflated and removed. partial
blockage
Stenting
A stent (see Figure 13.20) is a suppor ting device that
may be inser ted dur ing balloon angioplasty of a coronar y
ar ter y to hold the vessel open.
Coronar y bypass
coronary arteries
In cases of extensive coronar y ar ter y disease, a coronary carrying normal
blood supply
bypass operation may be per formed. This is done by
connecting the aor ta to the coronar y arter y using a
length of vein from the patient’s leg (see Figure 13.21). Figure 13.21 Double bypass of blocked coronar y ar teries
blockage stent mounted on

vessel balloon catheter
blood wall
balloon inflated and

stent expanded
balloon catheter removed

and stent left in vessel
194
Figure 13.20 Stenting
1 a) i) In what way do the endothelial cells lining an b) Construct a table to show THREE dif ferences between
ar ter iole respond to chronic elevation of blood type 1 and type 2 diabetes. (3)
glucose level? c) i) What is meant by the term glucose tolerance?
ii) What ef fect can this process have on the ii) What is the purpose of a glucose tolerance
structure of the ar ter iole? (2) test? (2)
b) Identify T WO par ts of the body that would be 3 a) What is meant by the term obesity? (1)
ser iously af fected if one or more of the small blood b) Give the formula used to calculate body mass index
vessels supplying them with blood were to burst. (2) (BMI). (1)
2 a) Which hormone promotes the conversion of: c) What are the T WO main ways in which an obese
i) glucose to glycogen person can reduce the r isk factors for CVD? (2)
ii) glycogen to glucose?
iii)Where in the body are these hormones produced?
iv) In which organ do the conversions promoted by
these hormones occur? (4)
What You Should Know Chapter 13
reactions. These result in the formation of threads of

activity embolism lean ______ that clot blood and seal the wound.
ar terioles embolus liver 3 A thrombus that travels through the bloodstream and
atheromas endothelium low-density eventually blocks a blood vessel is called an ______. If it
atherosclerosis exercise membranes blocks the ______ ar ter y, it can cause a hear t ______.
attack familial negative If it blocks an ar ter y to the brain, it can cause a ______.
burst f ibr in obesity 4 The narrowing of ar ter ies other than those supplying
cardiac glucagon peripheral par ts of the body core, such as the ______ muscle and
cardiovascular glycogen receptors brain, causes ______ vascular disease.
cholesterol high restr icted 5 The formation of a blood clot in a large per ipheral vein
clotting high-density statins is called ______ vein thrombosis. If the clot travels
coronar y hormone stroke to a blood vessel supplying the lungs, it can cause a
pulmonar y ______.
deep indicator thrombosis
diabetes insulin tissues 6 Cholesterol is a fatty substance made in the ______ and
diagnosed kidneys tolerance needed as a component of cell ______. It is transpor ted
to body cells by ______ lipoproteins (LDL) and back to
the liver by ______ lipoproteins (HDL).
Table 13.8 Word bank for chapter 13
7 Excess LDL-cholesterol in the blood can result in ______
1 Atherosclerosis is the accumulation of plaques (______) being deposited in atheromas causing ______. Drugs
under the ______ in the walls of ar ter ies. The diameter such as ______ reduce blood cholesterol levels.
of an af fected ar ter y becomes reduced and blood flow
8 ______ hypercholesterolaemia is an inher ited disorder
is ______. The condition is the root cause of many
that causes suf ferers to develop abnormally ______
cardiovascular diseases.
levels of cholesterol.
2 ______ is the formation of a blood clot (thrombus).
Cells damaged by the rupture of an atheroma release
______ factors that activate a ser ies of chemical ➜ 195
9 Ver y high levels of blood glucose can cause damage to 13 The fact that, in both types of diabetes, the ______
______ and lead to vascular disease. Damage to small cannot cope with the elevated blood glucose level and
blood vessels can make them ______ and leak their release glucose in ur ine, is used as an ______ of the
contents into nearby ______. condition.
10 Blood glucose level is regulated by ______ feedback 14 Diabetes is ______ using the glucose ______ test.
control. When the glucose level is too high, the ______
15 ______ is character ised by the accumulation of excess
insulin promotes the conversion of glucose to ______;
body fat relative to ______ body tissue. Obesity is
when it is too low, the hormone ______ promotes the
closely associated with lack of physical ______ and a
conversion of glycogen to glucose.
diet r ich in fat.
11 People with ______ are unable to control their blood
16 Risk factors for ______ disease are reduced by taking
glucose level ef fectively.
______ and keeping body weight at an optimum level.
12 Those with type 1 diabetes are unable to make ______.
Those with type 2 diabetes are able to make insulin but
their cells lack an adequate number of insulin ______
and fail to allow enough glucose to enter.
Chapters 8–13
1 The male reproductive system is shown in Figure 13.22.
a) Using only the appropr iate letters, indicate the route
taken by sperm from site of production to point of
exit from the male body. (1)
b) Copy and complete Table 13.9. (8) A F
2 Figure 13.23 represents some of the events that G
occurred dur ing a complete menstrual cycle in a woman. B
C H
a) i) On which dates would sexual intercourse have
I
been most likely to result in fertilisation in this
woman? D
ii) Give T WO reasons to explain how you arr ived at J
your answer. (3)
b) Give a fur ther physical sign unrelated to the graph K
that might have helped the woman to identify her E

most fer tile time. (1)
c) What evidence from the graph tells you that
fer tilisation did not occur dur ing the cycle

L
shown? (1)
Figure 13.22
Letter in Figure 13.22 Name of this Example of substance secreted by Way in which named substance
indicating accessory accessor y gland accessory gland that contributes to contributes to fertilisation
gland fertilisation
196 Table 13.9

37.2
temperature (°C)
37.0
36.8
36.6
36.4
body 36.2
of progesterone
concentration
increasing
13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 1 2 3 4 5 6 7 8 9 10
September October
start of menstrual flow
Figure 13.23
d) i) Assuming that the cycle remains the same
20
length, on which dates in October will sexual

intercourse be most likely to lead to conception
18
in this woman?
ii) If fer tilisation were to occur, in what way would 16
incidence of Down’s syndrome per 1000 births
the progesterone cur ve dif fer from the one in

Figure 13.23? (2) 14
e) i) Instead of tr ying to avoid the fer tile phase, the
woman decided to use a hormonal method of 12
contraception containing progesterone. Explain
how this prevents fertilisation. 10
ii) Why do women ‘on the pill’ take pills lacking sex
hormones 1 week in ever y four? 8
iii) Suggest why women are recommended to take
the placebo pills rather than no pills at all dur ing 6
that week. (4)

4
3 The graph in Figure 13.24 shows the relationship between
incidence of Down’s syndrome and maternal age.
2
a) Use the graph to estimate the chance of a woman at
each of the following ages having a Down’s syndrome 0
baby: i) 20 years, ii) 30 years, iii) 40 years. (3) 15 20 25 30 35 40 45
b) Account for the trend shown by the graph. (1) age of mother (years)
4 Figure 13.25 shows a pedigree char t for the inher ited

Figure 13.24
trait of deaf-mutism.
a) i) Which of the following patterns of inher itance is c) If X marr ies a man who is homozygous for the normal
shown by this trait? allele, what is the percentage chance of each child of
A autosomal recessive this union being:
B autosomal dominant i) a deaf mute
C sex-linked recessive ii) a carr ier of the deaf-mute allele? (2)
ii) Give ONE reason to suppor t your choice.

d) If Y marr ies a woman who is homozygous for the
iii) Give ONE reason for deciding against each of the

normal allele, what is the chance of each child of this
other choices. (4)

union being:
b) Copy the pedigree char t and, using symbols of i) a deaf mute
your choice, attempt to supply the genotype of ii) a carr ier of the deaf-mute allele? (2)
197
each person (giving both possibilities in uncer tain
cases). (9) ➜
deaf mute O normal O
heart
deaf mute O normal O
lymph
node
respiring cells
X Y Q
Figure 13.25 R
e) If X marr ies Y, what is the chance of each child being: Figure 13.26
i) a deaf mute a) i) Copy or trace the diagram and label it using the
ii) a carr ier of the deaf-mute allele? (2) terms arter y, capillary, lymphatic vessel, lymphatic
5 Table 13.10 shows a set of results for the exper iment duct and vein.
shown in Figure 11.6 on page 160 using a 2 mm-thick ii) Add at least f ive arrows to your diagram to
r ing of ar ter y and a 2 mm-thick r ing of vein from a cow. show the direction of flow of the liquids in the
Mass added (g) Change in length (%) vessels. (7)
Vein Arter y b) Which letter in the diagram indicates the presence
of: i) blood plasma, ii) lymph, iii) tissue fluid? (3)
0 0.0 0.0
7 Figure 13.27 represents the repeated ser ies of events
10 72.5 75.0 that occurs dur ing the human hear tbeat.
20 79.0 84.5 0 1.0 2.0
time (s)
30 91.5 95.0
40 95.0 102.0 atria X
ventricles Y
50 94.5 105.5 = systole
Table 13.10
Figure 13.27
a) Plot the data on the same sheet of graph paper and
draw cur ves of best f it. (4) a) i) Which lasts longer, atr ial or ventr icular systole?
b) i) Draw T WO conclusions from the data. ii) Explain why this dif ference is necessar y. (2)
ii) Relate your answer to i) to the structure of b) i) Name the stages of the cardiac cycle represented
ar ter ies and veins. (3) by X and Y.
c) Identify T WO points of procedure relating to the ii) In what state is cardiac muscle in the atr ia during
animal material being used that were carr ied out stage X? (3)
to eliminate additional var iable factors from the c) i) How many complete hear tbeats are represented
exper iment. (2) by the diagram?
d) State T WO ways in which the exper iment could be ii) Express the person’s pulse rate in beats per
improved to increase the reliability of the results. (2) minute. (2)
6 Figure 13.26 shows a simplif ied version of the
198 circulator y system.
d) Redraw par t of the diagram to represent one 9 Figure 13.28 shows box plots of body weight for three
complete hear tbeat and then add the letters L and populations of Br itish men of average height at three
D and arrows to indicate when the two hear t sounds dif ferent times in recent histor y.
would be heard. (3)
8 The data in Table 13.11 refer to normal systolic blood 130
description
pressures found in humans at dif ferent ages.
120
Age (years) Systolic blood pressure (mm Hg)
110
Male Female obese
100
0–4 93 93
body weight (kg)

90
5–9 97 97
over
10–14 106 106 80
weight
15–19 119 116 70
20–24 123 116 normal

60
25–29 125 117
50
30–34 126 120 under
40 weight
35–39 127 124
40–44 129 127 30
population 1 population 2 population 3
45–49 130 131 from 1950 from 1980 from 2010
50–54 135 137

55–59 138 139 Figure 13.28
60–64 142 144 a) What percentage of data is contained in the box in a

65–69 143 154 box plot? (See Appendix 2 for help.) (1)
b) i) By what means is the median value of the data
70–74 145 159 indicated in a box plot?
75–79 146 158 ii) State the median value for each of the
Table 13.11 populations. (2)
c) i) Which box set shows the widest distr ibution of
a) Present the data as a two-tone bar char t. (4) values between its median and its upper
b) i) Make a generalisation about the ef fect of age on quar tile?
blood pressure. ii) Which box set shows the smallest overall
ii) Give a possible explanation (related to lifestyle) distr ibution of values? (2)
to account for this trend. (2) d) Does a whisker represent a 95% level of conf idence
c) It has been suggested that female sex hormones or an actual value? (1)
may in some way of fer protection against high blood e) What was the lowest value recorded? (1)
pressure. What information from the table seems to f) If the data were plotted as a graph of number of
suppor t this theor y? (1) individuals against body weight, which population
would give a symmetr ical, bell-shaped cur ve? (1)
g) i) What trend is shown by the three box plots?
ii) Suggest a reason for this trend that does not
refer to food intake. (2)
10 Give an account of thrombosis following the rupture of
an atheroma. (10)
199
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Neurobiology and
Unit
3 Communication
Neurobiology and Communication Unit 3
14 Nervous system
Sensory information from receptors in contact with the
external environment and the internal environment
brain
(the inside of the body) is collected by the nervous
cranial
system and analysed. Some of this information is CNS nerve
stored for possible future use. Meanwhile, appropriate spinal
cord PNS
voluntary and involuntary motor responses are initiated spinal
which lead to muscular contractions or glandular nerve
secretions.
Divisions of the nervous system

Based on structure and location of component parts,
the nervous system can be divided as shown in
Figure 14.1. Figure 14.2 shows, in a simple way, where
these parts are located in the human body.
nervous system
central nervous peripheral nervous

system (CNS) system (PNS)
Figure 14.2 Location of CNS and PNS
spinal
brain cord carotid arteries and thermoreceptors in the cerebellum
– see page 209). Sensory pathways keep the brain in
touch with what is going on in the body’s external and
Figure 14.1 Structural division of the ner vous system internal environments.
The brain analyses, interprets, processes and stores

Sensory and motor pathways some of this constant stream of information, which
Peripheral nerves contain a sensory pathway consisting is based on stimuli such as sounds, sights, colours,
of sensory nerve cells and/or a motor pathway tastes, temperature of skin and blood and CO2
consisting of motor nerve cells. Sensory pathways concentration and water concentration of blood. The
carry nerve impulses to the CNS from receptors. Some brain’s association centres (see page 212) may act on
receptors are located in external sense organs (such as this information by sending nerve impulses via the
202
the skin, eye retina and ear cochlea); others are found motor pathways to effectors (e.g. muscles and glands).
in internal sense organs (such as CO2 receptors in These then bring about the appropriate response, such
Nervous system
Somatic ner vous system

The somatic nervous system (SNS), which includes the
CNS
spinal nerves, controls the body’s skeletal muscles. This
involves sensory and motor pathways, as outlined in
Figure 14.3. The somatic nervous system is responsible
nerve impulses carried for bringing about certain involuntary reflex actions
by motor neurons in
nerve impulses carried motor pathways (for example, limb withdrawal), but most of the control
by sensory neurons in
sensory pathways that it exerts is over voluntary movements of skeletal
muscles.
Imagine, for example, that you are invited to select your

receptors effectors four favourite chocolates from a large box of a familiar
make. The displayed chocolates act as visual stimuli.
Nerve impulses pass from each retina via sensory nerve
stimuli responses
cells in the optic nerve to the brain. There, association
centres process the information and compare it with
previous experiences. Decisions are taken and nerve
Figure 14.3 Flow of information through the ner vous system impulses pass to the brain’s motor area (see page 212).
This in turn sends impulses via motor nerve cells to
as muscular contraction or enzyme secretion. This the appropriate skeletal muscles of the arm and hand
relationship is summarised in Figure 14.3. allowing the voluntary responses needed to pick out the
four sweets. This series of events involves the somatic
Functional division nervous system.
A further method of dividing up the nervous system is
based on the different functions performed by the two Autonomic nervous system
separate branches of the peripheral nervous system, as The autonomic nervous system (ANS) (see
shown in Figure 14.4. Figure 14.5) regulates the internal environment by
controlling structures and organs such as the heart,
blood vessels, bronchioles and alimentary canal. This
peripheral nervous control is generally involuntary because it normally
system
works automatically without the person’s conscious
control being involved (although, under exceptional
circumstances, some people are able to heighten or
suppress certain autonomic responses intentionally).
somatic nervous autonomic nervous The nerves that comprise the autonomic nervous
system (mostly voluntary) system (involuntary)
system arise from nerve cells in the brain and emerge
at various points down the spinal cord to reach the
effectors (cardiac muscle, smooth muscle and glands)
that they stimulate with nerve impulses.
Antagonistic nature of autonomic nervous system

parasympathetic system
sympathetic system The sympathetic and parasympathetic systems that
(calms body down
(prepares body for action)
returning it to normal state) make up the autonomic nervous system are described as
being antagonistic. This means that they affect many of
Figure 14.4 Functional divisions of the ner vous system the same structures but exert opposite effects on them.
Figure 14.5 shows only a few of the many tissues and
organs controlled in this way. 203
SYMPATHETIC NERVES PARASYMPATHETIC NERVES

(many not shown) (many not shown)
rate and force of contraction rate and force of contraction

of cardiac muscle increases of cardiac muscle decreases
result: increased cardiac result: decreased cardiac

output of blood output of blood
smooth muscle in wall of smooth muscle in wall of

bronchioles becomes relaxed bronchioles becomes contracted
result: bore of tube result: bore of tube
becomes dilated becomes constricted
allowing increased allowing decreased
volume of air to enter lung volume of air to enter lung
rate of contraction of smooth rate of contraction of smooth

muscle in wall of digestive muscle in wall of digestive
tract decreases tract increases
result: decreased rate result: increased rate

of peristalsis of peristalsis
activity of secretory glands activity of secretory glands

in intestinal wall is inhibited in intestinal wall is stimulated
result: decreased result: increased

production of production of
intestinal secretions intestinal secretions
no parasympathetic nerve
adrenal gland is stimulated connection to adrenal gland
result: increased rate of

secretion of hormone no effect
epinephrine (adrenaline)
Figure 14.5 Autonomic ner vous system
Harmonious balance constantly working in an equal but opposite manner,

The autonomic nervous system is concerned with with neither gaining the upper hand. The activity of a
maintaining a stable internal environment by playing tissue or organ under their control is the result of the
its part in the process of homeostasis (see Related two opposing influences. It is therefore normally in a
Topic – Homeostasis). Under normal circumstances state somewhere between the extremes of hypo- and
204 hyperactivity.
the sympathetic and parasympathetic systems are
Nervous system
Finely tuned control oxygen) and away from the gut and skin (which require
The stimulation of an effector by both sympathetic minimal servicing during the crisis). Rate of nervous
and parasympathetic nerves provides a fine degree perspiration also increases. Hence a thudding heart, a
of control over the effector. The system works like face white with fear and a clammy sensation in localised
a vehicle equipped with both an accelerator and a areas of the body that are in a ‘cold sweat’ (e.g. armpits
brake. If the car had an accelerator but no brake then and palms of hands) are all characteristic responses to a
the process of reducing speed would depend solely on crisis.
decreasing the pressure on the accelerator. This method The hormone epinephrine helps to sustain the arousal
would require too much time to elapse before the car effects until the emergency is dealt with. This might
responded and slowed down. Use of a brake, which can involve taking a determined and defensive stand,
be applied in addition to decreasing the pressure on the perhaps involving a fight or cutting your losses and
accelerator, allows for a much more rapid and effective running away. In either case the vast amount of energy
means of regulating the car’s speed. required by the skeletal muscles is supplied by their
There are exceptions to the rule of dual innervation of increased blood flow.
an effector by both parasympathetic and sympathetic Rest and digest
nerves. For example, the adrenal gland, which secretes When the excitement is over, the parasympathetic
the hormone epinephrine (adrenaline), receives a system takes over for a brief spell, calming the body
supply of sympathetic nerves only (see Figure 14.5). down and returning it to normal for ‘rest and digest’.
Fight or flight Heart rate and blood pressure drop to normal. Rate of
On being stimulated and briefly gaining the upper peristaltic contractions in the digestive tract increases.
hand, the sympathetic system arouses the body in Blood is diverted to the intestines where it can resume
preparation for action and the expenditure of energy its job of absorbing the end products of digestion now
during ‘fight or flight’. The heart rate and blood that the crisis is over. The effects brought about by the
pressure increase. Blood supplies are diverted to the parasympathetic nerves help the body to conserve
skeletal muscles (in great need of an increased supply of resources and store energy.
Related Topic
Homeostasis the body’s community of living cells to function ef f iciently

and sur vive.
Homeostasis is the maintenance of the body’s internal
environment within cer tain tolerable limits despite
changes in the body’s external environment (or changes Ef fect of exercise on respirator y system
in the body’s rate of activity). Rate and depth of breathing increase during exercise.
This results in increased ventilation of the lungs which
Pr inciple of negative feedback control promotes the uptake of oxygen and the removal of carbon
dioxide.
When some factor af fecting the body’s internal
environment deviates from its normal optimum level
(called the norm or set point), this change in the factor is Carbon dioxide as the stimulus
detected by receptors. These send out ner ve or hormonal The graph in Figure 14.7 shows the results from an
messages which are received by effectors. The ef fectors exper iment to compare the ef fect on breathing rate of
then br ing about cer tain responses that counteract the inhaling normal air, ‘abnormal’ air type 1 and ‘abnormal’
or iginal deviation from the norm and return the system air type 2. Only the ‘abnormal’ air type 2 is found to cause
to its set point. This corrective homeostatic mechanism breathing rate to increase sharply. It is concluded that it
is called negative feedback control (see Figure 14.6). It is the high level of carbon dioxide in the ‘abnormal’ air
provides the stable environmental conditions needed by type 2 (and not the low level of oxygen in ‘abnormal’ air
205
➜
messages
receptors effectors
corrective responses
increase in factor bringing about negative
feedback control
factor affecting factor affecting

internal environment internal environment
at norm/set point at norm/set point
corrective responses
decrease in factor bringing about negative
feedback control
messages
receptors effectors
Figure 14.6 Pr inciple of negative feedback control
normal air abnormal air 1 normal air abnormal air 2 normal air
50 21% oxygen 13% oxygen 21% oxygen 21% oxygen 21% oxygen
0.04% CO2 0.04% CO2 0.04% CO2 8% CO2 0.04% CO2
rate of breathing (breaths/min)
40
30
20
10
0
0 1 2 3 4 5 6 7 8 9 10 11 12
time (minutes)
Figure 14.7 Ef fect of gases on breathing rate
type 1) that acts as the stimulus tr igger ing increased rate Homeostatic control
of breathing. Chemoreceptors in the carotid ar teries and aor ta
(see Figure 14.8) are sensitive to the concentration of
Fur ther exper iments show that the depth of breathing
carbon dioxide present in the bloodstream. A rise in
also increases in response to inhalation of air r ich
carbon dioxide level dur ing vigorous exercise causes
in carbon dioxide. Similarly in the body of a person
these sensor y cells to send an increased number of
undergoing vigorous exercise, it is the increased level of
ner ve impulses via sensor y neurons to the respiratory
carbon dioxide in the bloodstream that acts as the main
control centre in the medulla. This region of the brain
stimulus br inging about an increase in rate and depth of
responds by sending a greater number of ner ve impulses
breathing. However, severe lack of oxygen eventually also
via motor neurons to the intercostal muscles and
206 causes increased rate and depth of breathing.
Nervous system
diaphragm. The subsequent increased activity of these

structures brings about an increase in rate and depth
of breathing. Excess carbon dioxide is removed and the
internal environment is kept within tolerable limits. This
homeostatic pathway is summar ised in Figure 14.9.
brain
group of
chemoreceptors
carotid respiratory
artery control centre
in medulla
aorta
intercostal
muscle
diaphragm
Figure 14.8 Ner ve pathway tr iggered by chemoreceptors 207

➜
chemoreceptors many medulla

(carotid bodies) sensory
at bases of impulses (at base of
carotid arteries hind brain)
in neck few
sensory
impulses
decrease in increase in
blood CO2 blood CO2
concentration concentration
many motor few motor
impulses impulses
increase in decrease in
rate and depth rate and depth
of breathing of breathing
diaphragm
and intercostal
muscles
(in thorax)
Figure 14.9 Homeostatic control of CO2 concentration of blood
1 a) Name the T WO components of the central ner vous 4 Rewr ite the following sentences, choosing the correct
system (CNS). (2) word from each underlined choice.
b) What collective name is given to all the ner ves The body becomes aroused ready for ‘f ight or flight’ by
excluding the central ner vous system? (1) the action of the sympathetic/parasympathetic ner ves.
2 Dif ferentiate between the following pairs of terms: As a result, rate of blood flow to the heart increases/
a) sensory and motor pathways (2) decreases, rate of per istalsis increases/decreases and
b) receptors and effectors. (2) rate of breathing increases/decreases. (4)
3 a) Name the T WO branches of the autonomic ner vous
system. (2)
b) State the ef fect of each branch of the autonomic
ner vous system on:
i) cardiac output
ii) width of bore of the bronchioles. (4)
208
Nervous system
Brain possesses structures (not shown in the diagram) that

project deep into the cerebral cortex. The structures that
The brain (see Figure 14.10) is a complex organ
make up the limbic system are involved in a variety of
composed of three interconnected, concentric layers:
functions such as:
● the central core ● processing information needed to form long-term
● the limbic system memories
● the cerebral cortex (outer layer of cerebrum). ● regulating emotional states (e.g. anxiety, fear and
aggression)
Central core ● influencing biological motivation (e.g. hunger, thirst
The central core contains several important regions of and sex drive).
the brain. One of these is the medulla, which controls
many essential processes of life such as breathing, heart Hypothalamus
rate, sleep and arousal (the state of being awake and The limbic system also contains the hypothalamus (see
aware of the external environment). The cerebellum is Figure 14.10). This is a physically small but functionally
also part of the brain’s central core. It controls balance significant region of the brain.
and muscular coordination, enabling the body to move
and to adopt appropriate posture. Pituitary gland
The hypothalamus is connected to the pituitary
Limbic system gland, as shown in Figure 14.11, and therefore acts as
The limbic system is a composite region of the brain
a link between the nervous system and the hormonal
illustrated in a simple way in Figure 14.10. It also
(endocrine) system.
cerebral cortex
right cerebral hemisphere left cerebral hemisphere

corpus callosum
right cerebral (see Figure 14.14)
hemisphere
left hemisphere
removed
cerebellum
pituitary medulla
REAR gland
FRONT hypothalamus
spinal cord
= central core
= limbic system
= cerebral cortex
209
Figure 14.10 Human brain
● gonadotrophic hormones – first released during
puberty to stimulate reproductive organs to produce
and release gametes (see chapter 8).
hypothalamus
Contraction of smooth muscle
blood vessel
Axons of neurons whose cell bodies lie in the
taking releaser
hypothalamus extend to the sympathetic and
nerves
hormone
to anterior pituitary
parasympathetic centres in the brain’s central core.
This enables the hypothalamus to regulate autonomic
posterior (rear)
anterior (front) of
of pituitary
activities such as the contraction and relaxation of
pituitary gland
gland smooth (involuntary) muscle involved in homeostatic
mechanisms. These include vasoconstriction and
vasodilation of blood vessels during control of body
blood vessel taking pituitary temperature.
hormones to body
Figure 14.11 Pituitar y gland Control of body temperature

The hypothalamus contains the thermoreceptors,
The hypothalamus contains secretory cells that produce which are sensitive to changes in temperature of
releaser hormones. These are transported in the blood that reflect changes in the temperature of
bloodstream to the anterior pituitary gland where they the body core. The thermoregulatory centre in the
trigger the release of pituitary hormones such as: hypothalamus responds to this information by sending
● growth hormone – essential for the normal growth appropriate nerve impulses to effectors such as sweat
of the body and development of long bones glands and the blood vessels involved in vasodilation
● thyroid stimulating hormone – needed to make the and vasoconstriction (see Figure 14.12). These trigger
thyroid gland produce thyroxin, which is essential corrective feedback mechanisms and return the body
for the control of metabolism temperature to its normal level.
much heat lost by radiation very little heat lost by radiation
capillaries capillaries
receive large receive
volume of small volume
overheated of blood
blood
arteriole becomes
constricted as
shunt vessel
arteriole smooth muscle (receives large
becomes becomes volume of blood)
dilated as contracted
smooth muscle shunt vessel
becomes relaxed (not always present)
nerve impulses arteriole venule

arteriole venule from hypothalamus
nerve impulses
from hypothalamus
vasodilation vasoconstriction
210
Figure 14.12 Vasodilation and vasoconstr iction of skin ar ter ioles
Nervous system
Control of water balance Cerebral cor tex

If the water concentration of the blood decreases due to The cerebral cortex is the outer layer of the cerebrum,
increased sweating or consumption of salty food, then which forms the largest and most complex part of the
osmoreceptors in the hypothalamus are stimulated. brain. The cerebrum is split by a deep cleft into two
These trigger the secretion of antidiuretic hormone halves called cerebral hemispheres. The left hemisphere
(ADH) by the posterior pituitary gland into the processes information from the right visual field and
bloodstream. On arriving in the kidneys, ADH increases controls the right side of the body. The reverse is true of
the permeability of the tubules and collecting ducts to the right hemisphere.
water. As a result, more water is reabsorbed into the The two hemispheres are not completely separated but
bloodstream and its water concentration is returned to are connected by a large bundle of nerve fibres called
normal.
Case Study Role of the limbic system

Researchers have developed partial maps of the On the other hand, people whose limbic system has
regions of the brain responsible for emotions. Much been seriously damaged by, for example, a tumour,
of this information has been obtained from studies of are often found to suffer an absence of certain
people who have suffered some form of brain damage emotions and desires. Figure 14.13 shows further
or disorder. For example, some people whose limbic details of the limbic system.
system undergoes excessive activity as a result of a
disorder such as an epileptic seizure are often found Amygdala
to exhibit one or more of the following ‘emotional’ This region of the limbic system is closely associated
behaviours: with the ability to experience and express emotions
such as fear, anger and aggression, each of which
● unaccountable fear responses
plays its part in the survival of a human in a crisis.
● unreasonable, aggressive impulses and actions
Lesioning of the amygdala on each side of the limbic
● uncontrollable laughter
system is found to make mammals emotionally
● strong sexual arousal
unresponsive and unaggressive. For example,
● feelings of bliss and ‘at oneness’ with the universe.
monkeys who had previously responded to the
presence of snakes with terror were found to show no
fear of the same snakes following lesioning of their
amygdalae.
Among humans, some people suffer epileptic

seizures that cause abnormally high levels of
activity of certain neurons in the amygdala.
Evidence suggests that this results in feelings of
pleasure
hyper-aggressiveness, leading to violent behaviour.
centre
hypothalamus Removal of part of each amygdala by neurosurgery
has been found to change the person’s behaviour and
eliminate rage attacks. The amygdala is also thought
to be critical in the formation of memories associated
amygdala with fear of dangerous objects and situations.
pleasure
centre Pleasure centres
Several areas of the limbic system are found to be
hippocampus
associated with feelings of pleasure. Two of these
are shown in Figure 14.13. (See also Figure 18.2 on
page 266.)
Figure 14.13 Details of the limbic system 211
right cerebral left cerebral
hemisphere hemisphere
horizontal section cross-section
of cerebrum of cerebrum
cleft
corpus corpus
callosum callosum
Figure 14.14 Location of the corpus callosum
the corpus callosum (see Figure 14.14). This fibrous effectors (such as muscles). By this means, coordination
link between the two hemispheres is important to allow of voluntary movement is effected.
information to be transferred from one to the other.
Whatever happens in one side of the brain is quickly As a simple example, imagine that you are blindfolded
communicated to the other side, thereby coordinating and a very large ice cube is placed in your hand. Sensory
brain functions and enabling the brain to act as an areas in your cerebral cortex receive information from
integrated whole. touch, pressure and cold receptors in your skin. By
analysing and interpreting these impulses, association
Functional areas of the cerebral cortex centres in your cerebral cortex gain an impression of
The cerebral cortex contains three types of functional the size, shape, weight, texture and temperature of the
area: sensor y, association and motor. Each area ‘mystery object’. When they put all this information
performs its own particular function distinct from together, it results in you experiencing the sensation of
the others. The sensory areas receive information holding a very large ice cube. As the ice cube becomes
as sensory impulses from the body’s receptors (e.g. uncomfortably cold and heavy, you reach a decision
touch receptors in the skin and thermoreceptors in to let it go. The appropriate motor centre carries out
the hypothalamus). The association areas analyse and orders by sending out impulses to the muscles that
interpret these impulses, ‘make sense’ of them and operate the hand, causing your grip on the ice cube to
‘take decisions’ if necessary. The motor areas receive relax.
information from the association areas and ‘carry out
212
orders’ by sending motor impulses to the appropriate
Nervous system
Localisation of function
premotor motor
A cerebral hemisphere consists of several distinct association area
area somatosensory
regions, as shown in Figure 14.15, which refers to the area
left side of the cerebrum. Each of these areas has a somatosensory
particular function to perform, as described below (see association
FRONT area
Related Topic – Functions of cerebral areas).
Every area shown in Figure 14.15 is duplicated (in REAR
mirror image) in the right cerebral hemisphere with

the exception of the speech motor area. Each person
has only one such region; it is situated on the left
cerebral hemisphere in 90% of the population. Of
speech visual
particular importance for normal sensations are the motor area visual area
auditory
somatosensor y, visual and auditory areas. These area
association
auditory area
localised regions receive separate sets of sensory
association
impulses and register sensations that are evaluated in area
their association centres.
Figure 14.15 Detail of the lef t cerebral hemisphere
Related Topic
Functions of cerebral areas

The dif ferent functions of the var ious areas of the cerebral cor tex are summar ised in Table 14.1.
Area of cerebral cortex Function

Somatosensor y Receives impulses from receptors in skin, organs and muscles
Somatosensor y association Receives impulses from somatosensor y area, which it analyses, interprets and may ‘act
on’; also stores memor ies of previous exper iences
Visual Receives impulses from retina and interprets these as images involving shape, colour and
so on
Visual association Receives impulses from visual area and br ings about recognition of obser ved objects by
referr ing to memor ies of previous visual exper iences
Auditor y Receives impulses from cochlea and interprets these as sounds involving pitch, volume and
so on
Auditor y association Receives impulses from auditor y area and brings about conversion of sounds into
recognisable patterns, which can be understood depending on previous experience
Premotor association Receives messages from other association areas and stores memor ies of past motor
exper iences, enabling it to plan and control complex sequences of motor activities such as
wr iting, running down stairs and so on, in the light of past exper ience
Motor Receives messages from premotor association area and obeys orders by sending motor
impulses to appropr iate skeletal muscles
Speech motor Receives messages from other par ts of cerebrum; translates thoughts into speech by
sending impulses to the appropr iate par ts of the motor area which in turn send motor
impulses to muscles controlling lips, tongue and vocal chords
Table 14.1 Functions of cerebral cor tex 213
Interconnections sensory impulse and the ability to make an integrated
The cerebral cortex is the centre of conscious thought response. The cerebrum is also able to recall stored
and no part of it works in complete isolation. memories and then alter future behaviour in the light
Interconnections in the form of tiny nerve fibres link of past experience. In addition there are areas of the
up the different areas and messages are constantly cerebral cortex that are responsible for higher mental
passing between them from sensory areas to motor processes such as intelligence, personality, creativity,
areas via association areas. This allows for sophisticated imagination and conscience.
perception of a situation involving several types of
Related Topic
Evidence from brain injuries rod entered beneath his lef t eye and exited through the
top of his head (see Figure 14.16). Amazingly the man
Some forms of tumour and disease can injure cer tain
sur vived and was able to speak, think, remember and
areas of the brain. Similarly, specif ic regions of the brain
eventually return to work. However, he had changed.
can be damaged by accidents. Careful study of the ef fects
From having been mild-mannered and dependable, he had
of such injuries sometimes allows exper ts to infer the
become ill-tempered, unreliable and no longer able to
role played by a par ticular par t of the brain.
stick to a plan. This case and others involving damage to
the frontal lobes of the brain show that they are involved
Damaged frontal lobe in planning, goal setting and personality.
In 1848, an accident led to an inch-thick rod being dr iven
into the head of a young Amer ican railroad worker. The Wife or hat?
In another case, a musician of great ability developed
a problem in later life. He no longer recognised people
or objects and failed to remember the past visually. He
would chat to pieces of furniture thinking that they were
people. On one occasion he reached out, took hold of his
wife’s head and tr ied to lif t it to put it on, thinking that it
was his hat! The problem was due to damage to his visual
association centres.
Lesions
Lesions are small regions of damage. The location of the
brain’s language areas is ver if ied by the fact that lesions
in these regions give r ise to speech defects. For example,
extensive damage to the speech motor areas results in the
person being unable to ar ticulate words despite the fact
Figure 14.16 This brain damage was not fatal that they fully understand the words that they hear.
214
Nervous system
Related Topic
Electroencephalograms (EEGs) EEGs are useful but not ver y precise since they reflect
the simultaneous activity of many cells all over the
An EEG is a record of the cerebrum’s electrical activity
brain. Although an EEG may show an abnormal pattern
over a shor t per iod of time (e.g. 20–30 minutes). It is
indicating a possible problem, it fails to pinpoint the
made using information from impulses picked up by
par ticular region of the brain responsible. However,
electrodes placed on dif ferent regions of the scalp (see
reliable use can be made of EEGs in the diagnosis of comas
Figure 14.17). Dif ferent brain wave patterns indicate
and brain death.
dif ferent levels of mental activity, as shown in
Figure 14.18.
relaxed
awake and
concentrating
suffering an
epileptic attack
asleep
Figure 14.17 Prepar ing for an EEG
Compare the long, rolling wave pattern typical of sleep in a deep sleep
with the concentrated non-rolling pattern obtained when
the subject is awake and concentrating. The more densely
packed the ‘spikes’ in the pattern, the higher the level
of electr ical activity present in the brain. An extreme
in a coma
version of this is seen in the EEG of the person suf fer ing
an epileptic attack. In addition, patients who suf fer
personality problems accompanied by extreme changes of
behaviour are of ten found to produce abnormal EEGs. Figure 14.18 EEG wave patterns
215
Related Topic
Split-brain studies orange in the diagram) is represented in the lef t cerebral

hemisphere.
Visual pathways
This occurs because half of the ner ve f ibres in each optic
Normal situation ner ve cross over to the opposite side of the brain at
Each cerebral hemisphere controls the opposite side the optic chiasma. Normally each side of the cerebrum
of the body. When the two eyes are focused on the quickly communicates its share of the information with
centre of a two-tone f ield of view, each eye receives the other side via the corpus callosum. As a result, both
light from both sides of the f ield of view, as shown in hemispheres perceive the whole f ield of view.
Figure 14.19. However, each cerebral hemisphere only
receives information from about half of this visual f ield. Abnormal situation
Ever ything to the lef t of the central line (the lef t f ield of A person whose corpus callosum has been cut (for
view – blue in the diagram) is represented in the visual example, dur ing an operation to tr y to relieve intractable
area of the right cerebral hemisphere; ever ything to epilepsy) is descr ibed as a ‘split-brain’ patient. In such a
the r ight of the central line (the r ight f ield of view – person the exchange of information between the cerebral
two-tone field of view being observed two-tone field of view being observed
right eye right eye
optic nerve optic nerve
optic chiasma optic chiasma
right cerebral right cerebral

hemisphere hemisphere
corpus callosum corpus callosum severed
visual area of right hemisphere

visual area of right hemisphere
no information exchanged between hemispheres

information exchanged between hemispheres
each hemisphere perceives

both hemispheres half of information only
perceive all information
216 Figure 14.19 Normal visual pathway Figure 14.20 Abnormal visual pathway
Nervous system
hemispheres as described above cannot take place and hemisphere only and that this is the lef t side of the
each hemisphere receives only half of the information brain ‘talking’. However, when asked to point with the
about the f ield of view (see Figure 14.20). left hand to what they saw from a selection of possible
f ields of view, the person chooses a f ield of view that is
When asked to say what they see, the split-brain patient completely blue since the lef t hand is controlled by the
descr ibes a f ield of view that is completely orange. This is right side of the brain, which is now indicating its version
fur ther evidence of the localisation of brain function. It of events.
indicates that the motor speech area is in the lef t cerebral
Related Topic
Imaging the brain metabolic rates and lower levels of brain activity in a
person who is af fected by AD.
Several techniques are now available that enable medical
exper ts to create clear, visual images of inside the brain PET scans can also be used to identify those par ts of
without involving surger y. These are used to study the the brain that show highest metabolic activity dur ing
normal workings of the brain and to diagnose var ious par ticular actions and emotions. For example, a scan
disorders. Two such techniques are descr ibed below. will show which area of the brain is most active when
the person is, say, listening to music or stroking a
PET (positron-emission tomography) furr y object or suddenly feeling angr y. These f indings
provide convincing evidence for the localisation of brain
This type of brain scan reveals the location of active
functions.
areas of the brain, showing high metabolic activity
(an increased demand for glucose and oxygen). In
Language areas
preparation for a PET scan, the person receives an
injection of glucose (or an appropr iate alternative) The process of speech is found to involve several specif ic
labelled with a harmless isotope that shows up at the regions of the brain. These dif ferent ’language’ areas
most active areas of the brain. These areas are detected also show up on brain scans as regions of high metabolic
by a PET camera and conver ted to a colour ised image by a activity (see Figure 14.22). When the information from
computer. several scans is put together, it gives a map of the brain’s
language areas, as shown in Figure 14.23.
PET scans are used to diagnose abnormalities such as
brain tumours (areas of high metabolic activity) and areas fMRI (functional magnetic resonance imaging)
of neuron damage (low metabolic activity) that may lead This technique employs radio waves and magnetic f ields
to forms of dementia such as Alzheimer’s disease (AD). to produce images of the brain. It also depends on
For example, the PET scan in Figure 14.21 shows lower properties of haemoglobin present in blood that enable
Figure 14.21 PET scans 217

➜
association centre
(seen words converted to
from brain scans while subject was hearing words mental sound patterns)
motor area
(control of lips, visual association
tongue etc.) centre
(seen words
recognised)
FRONT REAR
speech
motor
area
(speech visual centre
preparation) (words seen)
auditory area
area of high activity area of high activity (words heard) auditory association area
when words are when words are (words understood)
being heard being understood
from brain scans while subject was seeing words Figure 14.23 Map of the brain’s language areas
changes in patterns of blood flow to be followed. These

indicate activity of brain cells. By this means, exper ts are
able to create anatomical and functional images of the
brain.
FRONT REAR
Dur ing an fMRI scan (see Figure 14.24), a person might,
for example, be subjected to a variety of visual, auditor y
or tactile stimuli. The scan would then reveal those
area of high activity
areas of the brain involved in vision, hear ing or touch.
when words are being area of high activity area of high activity In addition to research using healthy volunteers, fMRI
converted into mental when words are when words are
being recognised being read
is used to diagnose disease and disorders such as brain
sound patterns
tumours.
from brain scans while subject was speaking words
FRONT REAR
area of high activity area of high activity

when words are being
prepared for speech
when words are being
spoken and lips, tongue
active
and vocal cords are in use areas
of
Figure 14.22 Language areas from brain scans brain
Figure 14.24 fMRI scan
218
Nervous system
1 Decide whether each of the following statements is e) The hypothalamus influences the secretion of
true or false and then use T or F to indicate your choice. hormones by the cerebral cortex.
Where a statement is false, give the word(s) that should f) Homeostatic mechanisms involving contraction of
have been used in place of those in bold pr int. (6) smooth muscle are regulated by the hypothalamus.
a) The brain’s central core contains the medulla and the 2 a) Name THREE dif ferent types of functional area
cerebrum. present in the cerebral cor tex. (3)
b) Balance and muscular coordination are controlled by b) Br iefly descr ibe the function carr ied out by each of
the cerebellum. these dif ferent types of area. (3)
c) Rate of breathing and hear tbeat are regulated by the 3 a) Which cerebral hemisphere controls
pituitary gland. i) the lef t, ii) the r ight side of the body? (1)
d) Emotional and motivational states are influenced by b) i) What is the corpus callosum?
the limbic system. ii) State its function. (2)
What You Should Know Chapter 14
such as the hear t and alimentar y canal.

autonomic exper ience ner vous 6 The ANS is made up of the ______ system which arouses
central external parasympathetic the body in preparation for ‘f ight or flight’ and the
cerebellum hemisphere per ipheral ______ system which calms the body and promotes ‘rest
cerebral hypothalamus pituitar y and digest’.
conscious integrated recalled 7 The brain is composed of the central core, the ______
contractions involuntar y receptors system and the ______ cor tex.
corpus lef t somatic 8 The central core contains the ______ which regulates
cortex limbic sympathetic hear tbeat and breathing, and the ______ which
ef fectors long-term voluntar y controls balance, movement and posture.
emotional medulla water 9 The limbic system processes information needed for
______ memories and influences biological motivation
Table 14.2 Word bank for chapter 14 and ______ states. It contains the ______ which
produces releaser hormones. These make the ______
1 Sensor y information from the body’s internal and
gland secrete fur ther hormones. The hypothalamus also
______ environment is analysed by the ______ system.
regulates ______ balance and body temperature.
Appropr iate motor responses are then initiated which
lead to muscular ______ and glandular secretions. 10 The cerebral ______ is the centre of conscious thought.
Its sensor y areas receive sensor y impulses from ______.
2 The ner vous system can be divided on a structural basis
Its association areas analyse and interpret information
into the ______ ner vous system (CNS) and the ______
and its motor areas send motor impulses to ______.
ner vous system (PNS).
11 The r ight cerebral ______ receives information from
3 The ner vous system can be divided on a functional basis
the lef t visual f ield and controls the ______ side of the
into the ______ ner vous system (SNS) and the ______
body. The reverse is true of the lef t cerebral hemisphere.
ner vous system (ANS).
Information is transferred from one hemisphere to the
4 The SNS controls ______ movement of the skeletal other via the ______ callosum, enabling the brain to
muscles. work as an ______ whole.
5 The ANS works automatically without involving the 12 Ner ve cell activity in the cerebral cor tex enables
person’s ______ thought. It regulates the internal decisions to be made, memor ies to be ______ and
environment by exer ting ______ control over structures 219
behaviour to be altered in the light of ______.
1
15 Perception
Chapter Head
A person’s awareness of the components of their shape is recognised as representing an object appears to
external environment is based on information picked stand out from the background in an obvious manner.
up by receptors in sensory organs and passed to the This form of perceptual organisation is called the
brain. This information is then subjected to analysis ‘figure-ground’ phenomenon. For example, Figure 15.1
and interpretation by the brain and converted into the shows a black triangular figure that stands out from the
person’s perception of their surroundings. Although white background. The part seen as the figure tends to
many perceptual experiences depend on information appear slightly in front of the ‘ground’, although they
from sense organs other than the eyes, this chapter are printed on the same two-dimensional surface. Any
concentrates on visual perception. This form of field of view that contains contrasting components is
perception enables a person: perceived as ‘figural’. One or more parts of it become
segregated as figures that stand out from the rest of the
● to segregate objects from one another and from their field (that forms the ground).
background
● to judge how near or far various objects are situated
from the person
● to recognise different objects.
Segregation of objects
Perceptual organisation into figure
and ground
The first stage in the development of visual perception
is the appreciation of certain aspects of an object’s
shape. In drawing, any line that encloses an area whose Figure 15.1 Figure-ground phenomenon
Related Activity
Analysing reversible figure-and-ground

images
Although shapes that are prominent, interesting, str iking
or central in the f ield of view tend, more readily, to
become f igural, there is no hard-and-fast rule. Nor must
the same object or par t of the f ield of view always remain
the f igure. By f ixedly gazing at one par t of the f ield of
view or by employing a ‘switch of attention’ to dif ferent
par ts of the f ield of view, an alternation of ten occurs
between the f igure and the ground, as in the following
examples.
Identif iable shapes
Close examination of Figure 15.2 reveals both a black
vase f igure against a white ground and twin white human
220 prof ile f igures against a black ground. Figure 15.2 Vase or faces?
Perception
Non-identif iable shapes

Geometr ic shapes and patterns seen against a background
appear object-like with contours and boundar ies. Ver y
of ten these f igure-ground relationships are reversible.
Figure 15.3 shows a flag-like image. Is it a white ‘cross’ on
a black ground or a black ‘four-leafed clover’ on a white
ground? Figure 15.4 shows a pattern of abstract white
plant-like shapes against a black ground. Or is it black
washing dr ying on a line against a white ground? The
reversible f igure-ground ef fect works best when the two
par ts of the image are equally meaningful.
Figure 15.3 Reversible geometr ic shapes
Figure 15.4 Reversible abstract pattern
Perceptual organisation into

coherent patterns
The brain tends to organise visual stimuli that it receives
into a coherent pattern rather than into many different
parts. Even simple patterns of dots or lines tend to fall
into ordered relationships when viewed. Figure 15.5
Figure 15.5 Perception of pattern
appears to consist of three pairs of lines with an extra
unpaired line at the right. Figure 15.6 shows how a
modification to the lines tends to reorganise the image
as three pairs of lines beginning at the right, with an
extra unpaired line at the left.
Figure 15.6 Reorganisation of perceived pattern following

modif ication
221
Related Activity
Grouping of visual stimuli Similar ity

Several factors are thought to determine how the visual The brain organises similar visual stimuli into groups
system organises stimuli into patterns. They include based on factors such as colour, size, shape and tone.
proximity, similar ity, closure, and orientation. In Figure 15.9 some of the dots are blue and some are
orange. The brain perceives the dots as three distinct
Proximity groups based on similarity of colour of the members
The mind groups visual stimuli that are close together as within each group.
par t of the same object. Conversely, it groups stimuli that
are far apar t as separate objects. Consider Figure 15.7.
In the lef t box the dots are close together and form one
group (a ‘square’). In the box on the r ight, the spacing
of the same set of dots has been changed. Some dots are
in closer proximity to one another than to the rest of the
dots. The brain now perceives the set as four groups based
on the close proximity of the members within each group.
Similarly, the brain perceives pictures composed entirely
of dots as several distinct groups or clusters rather than
individual dots. This enables the brain to make sense of a
‘dot picture’, such as the one in Figure 15.8.
Figure 15.9 Ef fect of similar ity
Closure
When a f igure is incomplete or par tially hidden by another
object, the brain ‘f ills in’ the elements that it does not
perceive as visual stimuli. This process is called closure
Figure 15.7 Ef fect of proximity
222 Figure 15.8 Groups of dots as distinct images Figure 15.10 Closure
Perception
and it is the means by which a whole rather than an

incomplete object is perceived. For example, the image
in Figure 15.10 is perceived as a circle (rather than just a
ser ies of cur ved, broken lines) as a result of closure.
Or ientation
The brain organises visual stimuli from elements that
are all seen moving in the same direction at the same
rate as one object. For example, the individual birds in a
migrating flock are perceived collectively as one object
(see Figure 15.11).
Figure 15.11 Orientation
Related Activity A B
Grouping of stimuli by proximity and

similarity
Figure 15.12 is composed of eight par ts (A–H), each of
which is a set of objects. Study each set and decide:
i) the number of separate groups of objects present
within the set
C D
ii) whether your brain employed proximity of objects
within a group or similarity of objects within a group
to arr ive at your answer to i).
(Answers below)
E F
G H
A = S, B = P, C = P, D = S, E = P, F = P, G = S, H = S ii)
A = 3, B = 3, C = 3, D = 6, E = 2, F = 3, G = 4, H = 3 i)
Answers: Figure 15.12 Grouping of stimuli by proximity or similar ity 223
Related Activity
Closure
Study the eight images in Figure 15.13 and work out
what the brain perceives when it has f illed in the gaps by
closure in each case.
Figure 15.13 Closure activity
224
Perception
Perception of distance
Y
Visual cues
X
The distance of one or more objects from the eye is
indicated by the presence of one or more visual cues
present in the scene being viewed.
Relative size
The further away an object is situated from the eye, the
smaller it is perceived to be. For example, by appearing
to decrease in size, the sleepers in the railway line in
Figure 15.14 indicate their increasing distance from
the eye.
Figure 15.15 Ef fect of relative height
Relative height in hor izontal f ield

A
Among a group of objects whose bases are below the
horizon, those with their base in a relatively higher
position appear to be further away and those with their
base in a relatively lower position seem to be nearer
the eye. For example, in Figure 15.15 the base of fence
post X is relatively higher than that of fence post Y. This
makes X seem further away than Y. This figure also
shows the effect of relative size on the perception of
distance.
Texture gradient
A change in the relative size and density of objects
is perceived when they are viewed from different
distances. The fact that the stones on the left in
Figure 15.15 become smaller and less textured leads to
Figure 15.14 Visual cues the perception that they are more distant.
Superimposition Linear perspective

When one object partially blocks the view of another, Parallel lines such as the railway line in Figure 15.14
the blocked object is perceived to be further away. In and the road in Figure 15.15 appear to converge in the
Figure 15.14, hill A at the front overlaps and cuts off distance.
part of the view of hill B behind it. Therefore hill A is
perceived to be nearer than hill B.
225
Related Activity
Analysing images of depth perception

Identify and discuss the visual cues that enable the brain
to perceive depth in Figure 15.16.
Figure 15.16 Identifying visual cues
Műller-Lyer illusion
For the most par t our visual perception ser ves us ver y well and
Investigation
seeing really is believing. However, on some occasions such as the

viewing of an optical (visual) illusion, perception can be misleading.
The Műller-Lyer illusion is an optical illusion based on two arrow-
like f igures. One has two ‘tails’, the other has two ‘heads’, as shown
in Figure 15.17. Each head or tail is composed of two shor t lines
called fins. The length of the arrow with two ‘tails’ is perceived to Figure 15.17 Műller-Lyer illusion
be longer than the arrow with two ‘heads’.
Figure 15.18 shows the char t used in this investigation. It has an ‘arrow’ XY (called the standard stimulus line)
and a blank line below XY. The f igure also shows cards A and B. These begin each tr ial in boxes A and B. They are
picked up simultaneously by the subject and placed onto the blank unlabelled line in an attempt to create ‘arrow’
AB (the comparison stimulus line) which appears equal in length to arrow XY. The length of AB is carefully
measured and the reading recorded. The same person repeats the procedure a fur ther four times and an average
value is calculated. The dif ference between the average value for the length of AB and the actual length of XY is
calculated. The results are pooled and presented as a graph.
Alternative designs
The investigation can be carried out using arrow heads and tails with f ins of dif ferent relative length from those
in Figure 15.18 or drawn at a dif ferent angle, or the arrows drawn using relatively thicker lines. It can also be
repeated using the arrows arranged ver tically instead of hor izontally. Table 15.1 gives the reasons for adopting
certain procedures dur ing the investigation.
Procedure Reason for adopting procedure

The char t and cards A and B are drawn on plain (not To prevent the presence of squares or lines helping
squared or lined) paper the subject to judge distance
Cards A and B begin at the same star ting positions To prevent each new attempt to create line AB being
each time before being picked up influenced by the result of the previous attempt
Each person makes f ive attempts
To increase the reliability of the results
Many students are tested
226
Table 15.1 Reasons for adopting procedures dur ing investigation
Perception
chart
X Y
BOX A BOX B
CARD A CARD B
A B
Figure 15.18 Char t and cards for investigating the Műller-Lyer illusion
Binocular disparity into one in the brain by the process of fusion producing
a binocular image. This image indicates depth and
Each eye looks at an object from a slightly different
distance of the object more effectively than either
position relative to the other eye. Therefore a slight
single-eye, monocular image. The process may fail
disparity (difference) occurs between the images of
to occur if excessive quantities of alcohol have been
the same object formed by the two eyes. The closer
consumed. Then the person may ‘see double’. 227
the object is to the viewer, the greater the disparity
between the two images. The two images are merged
Related Activity
Investigating binocular disparity It is also easier to quickly locate and touch the tip of
the same pen (using a f ingertip of your free hand) when
Hold a pen about 300 mm away from your face with its
both eyes are open rather than when just one is open.
tip angled slightly downwards and pointing towards your
This is because the fused binocular image gives a better
nose. Close each eye in turn repeatedly. The pen seems
indication of depth and distance of the pen tip from the
to jump from side to side as the disparate images are
eyes than either single-eye, monocular image.
perceived time about. With both eyes open, the images
become fused and the pen is seen to be positioned
straight ahead.
Related Topic
Stereoscopy
Stereoscopy is the process by which an image, created positions for two pictures
by fusing two two-dimensional images, is given the of the same object
illusion of three-dimensional depth. Stereoscopy occurs

naturally dur ing binocular vision when the disparate
images formed by the two eyes are fused together into
a three-dimensional image by the brain. Stereoscopy binocular
eyepiece
can be used to enhance ar tif icially the illusion of depth
in a diagram, a photograph or a movie. This is done by
presenting each eye with a slightly dif ferent image of the
object.
Stereoscope magnifying lens
A stereoscope is a simple optical instrument (see

Figure 15.19). It has a binocular eyepiece containing
magnifying lenses through which two slightly dif ferent Figure 15.19 Stereoscope
pictures of the same object are viewed, each with one eye.
This creates a three-dimensional image of the object.
3-D movies
Over 100 years ago, stereoscopes were a popular form In a three-dimensional motion picture, two moving
of enter tainment and stereograms (pairs of appropr iate images of the object are super imposed on one another
photographs) were produced commercially for this and projected onto the screen. The viewer wears
purpose. Some stereograms can be viewed without a eyeglasses that contain a pair of f ilters. Each f ilter only
stereoscope. Figure 15.20 shows two slightly dif ferent allows light through from one of the moving images. The
images of a molecular model of a channel in a cell brain fuses the two disparate images as before, creating a
membrane. Hold the picture 100–200 mm from your eyes, three-dimensional illusion.
stare at the space between the two images and allow your
eyes to relax. Some people f ind that the images fuse,
producing a third, centrally located, three-dimensional
version of the molecular model.
228
Perception
Figure 15.20 Stereogram of molecular model
Perceptual constancy experience and stored knowledge and, in part, on the

cue of relative size. Imagine that you move towards
A person’s visual perception of their surroundings
a bookcase to fetch a particular book. The retinal
remains stable despite the changing images landing on
image of the book becomes larger as you approach it.
their retinas as they move their eyes or body around. If
However, the retinal image of the bookcase and the
retinal images were taken at face value, objects would
other books also becomes larger, so the relative size of
appear to increase or decrease in size as they moved
the various objects to one another does not change. The
towards or away from us. Similarly objects would
book appears constant because it maintains the same
appear to change in shape when viewed from different
size relative to the objects that surround it.
angles (and colours would seem to alter in response to
different levels of illumination).
Shape constancy
The perception that an object remains the same shape
Size constancy regardless of the changes in the angle at which it is
The perception that an object remains the same size
viewed is called shape constancy. For example, when a
regardless of the size of the image on the retina is called
door is viewed as it swings open, it goes through a series
size constancy. Imagine you throw a ball for a dog to
of changes with respect to the images of it that land
fetch. As the dog runs away from you, its image on your
on the retina (see Figure 15.21). However, you do not
retina becomes smaller and as it runs towards you, its
believe that the door’s shape has actually changed from
image on your retina becomes larger. However, you do
a rectangle to a trapezoid. You perceive an unchanging
not believe that the dog has shrunk and then increased
door. Similarly, the rim of a glass is perceived as round
in size again.
whether it is viewed from above or from the side.
229
Size constancy is thought to depend, in part, on past Shape constancy is thought to depend largely on past
experience and stored knowledge.
to be more important than details such as colour or
texture. Figure 15.22 represents eight different types of
fruit based on their colour. However, it is not possible
to identify the fruits using colour as the sole visual
cue. Figure 15.23 represents the same eight fruits using
their shape as the visual cue. Now it becomes possible
to recognise pear, plum, pomegranate, banana, apple,
lemon, orange and grapes.
It is by means of their shape that objects are initially

characterised and differentiated from one another
during early learning. This information is then stored
in the long-term memory (see page 239). The most
Figure 15.21 Shape constancy important feature of an object’s shape is its general
outline. Young children, in particular, gain details
Recognition about this characteristic by both viewing the object and

running their fingers around its edge.
Importance of shape
The ability to perceive an object’s physical properties
Matching perceived shapes
such as shape, colour and texture is called object When a person perceives a shape, a subconscious
recognition. Of these properties, shape is considered attempt is made to match this shape with one of the
230
Figure 15.22 Colour as a recognition cue Figure 15.23 Shape as a recognition cue
Perception
‘visual descriptions’ already stored in the brain. If the Expectation and context
shape is a familiar one, it will be quickly matched and Figure 15.26 shows a deliberately ambiguous figure
the object recognised. If the shape is unfamiliar it may in the context of both letters and numbers. When the
draw a complete blank. letters A and C are covered up and the information
is read horizontally, the central figure is perceived to
On the other hand, it may be recognised as being
be the number 13 because of the context of the other
similar but not identical to one or more visual
numbers. When the numbers 12 and 14 are covered up
descriptions held in the brain. The brain then infers
and the information is read vertically, the central figure
that the object is related in some way to one or more of
is perceived to be the letter B because of the context of
these visual images. It may then recognise that the shape
the other letters. In each case the stimulus is the same
represents a familiar object shown from an unusual
but it is perceived differently because the viewer expects
angle (see Figure 15.24) or it may recognise that the
to see numbers along with other numbers and letters
object is a further member of an already familiar group
along with other letters.
of objects. Imagine, for example, that you have never
seen a pink grapefruit (see Figure 15.25). Your brain
would not be able to name this type of fruit but it
would recognise from its shape and general appearance
that it is similar to oranges and yellow grapefruit and
therefore it is a type of citrus fruit.
Figure 15.26 Letter or number?
Figure 15.24 Familiar object, unfamiliar angle (answer below)

Past exper ience
Expectations are often, at least in part, the result of
previous experience. In an investigation, the people in
test group A were shown a series of pictures of small
mammals (some of them rodents) and those in group B
were shown a series of pictures of humans (some bald
and some wearing glasses). The members of each group
were then shown the ambiguous ‘ratman’ diagram (see
Figure 15.27).
Figure 15.25 Pink grapefruit

Answer to Figure 15.24: Screwdr iver
Perceptual set
Perceptual set is the tendency of a person to perceive
certain aspects of available sensory information and
ignore others. Perceptual set is affected by expectation,
context and past experience. It influences the way in
231
which a stimulus is perceived. Figure 15.27 ‘Ratman’
Most people in group A perceived the picture as It is interesting to note that when the members of each
a mouse or a rat whereas most people in group B group were then shown the other set of pictures, it did
perceived it as the face of a bald man wearing glasses. not change their perception of ‘ratman’ in most cases.
In each case, perceptual set, brought about by previous
experience, had influenced which sensory data were
perceived and which were ignored.
Influence of perceptual set using ambiguous stimuli

In this investigation, the class is divided into two separate groups, A and B, and are not allowed to communicate
Investigation
with one another. The members of each group view only the set of pictures indicated in Table 15.2 for exper iment 1.
Then the members of both groups view the f irst ambiguous picture (see Figure 15.28). Without conferr ing with one
another, the members of both groups wr ite down what they perceive in response to its caption. This procedure is
repeated for exper iments 2 and 3 and then the results are pooled and tabulated.
Experiment Theme of ten pictures to be viewed during prior treatment Ambiguous

Group A Group B picture to be
viewed
1 Human females aged Human females aged Figure 15.28
approximately 10–30 approximately 60–90
2 Birds, some of which are ducks, Small mammals, some of which Figure 15.29
geese and swans are hares and rabbits
3 Two-dimensional geometr ic Two-dimensional geometr ic Figure 15.30
shapes, each containing a smaller, shapes, each containing a
dif ferent geometr ic shape at its smaller, dif ferent geometr ic
centre shape near its edge
Table 15.2 Treatments intended to create perceptual set
232 Figure 15.28 Young woman or old woman? Figure 15.29 Duck or rabbit?
Perception
Table 15.3 shows a typical set of results for this investigation. In

each case, perceptual set brought about by previous experience
has influenced the perception of the ambiguous image. For
example, in exper iment 1, most students in group A exposed
in advance to pictures of younger women saw a young woman,
whereas those in group B exposed to pictures of older women
perceived an older woman. Table 15.4 gives some procedures
adopted dur ing this investigation and the reasons for doing so.
Is the ball in the centre of the back surface or

in the corner of the front surface?
Figure 15.30 Where is the ball?
Exper iment Image perceived Group A Group B

Number of % number of Number of % number of
students students students students
1 Young woman 9 90 2 20
Old woman 1 10 8 80
2 Duck 10 100 3 30
Rabbit 0 0 7 70
3 Ball in centre 7 70 1 10
Ball in corner 3 30 9 90
Table 15.3 Results for perceptual set investigation
Procedure Reason for adopting procedure

No communication allowed between groups A and B To prevent members of one group viewing the
other group’s preparator y pictures so that optimal
conditions are created to br ing about two types of
perceptual set
No collaboration allowed among the members of a To prevent group members influencing one another’s
group once the ambiguous f igure has been viewed perception of the ambiguous image
Large number of students invited to take par t To increase the reliability of the results
Several ambiguous images used
Table 15.4 Reasons for adopting procedures dur ing investigation
233
1 Decide whether each of the following statements is true 2 a) Name THREE types of visual cue that enable the brain
or false and then use T or F to indicate your choice. When to perceive distance. (3)
a statement is false, give the word that should have b) i) What is meant by the term binocular disparity?
been used in place of the one(s) in bold pr int. (6) ii) By what means is a binocular image formed? (3)
a) The process by which the brain analyses and makes 3 Identify T WO aspects of an object that are perceived
sense of incoming sensor y information is called to remain constant despite the fact that the person
sensitivity. viewing it is moving towards it. (2)
b) A form of perceptual organisation where a shape 4 a) Briefly descr ibe how the brain makes use of stored
stands out from its surroundings is called the figure- visual descr iptions in order to recognise objects. (2)
ground phenomenon. b) In Figure 15.31, the central f igure could be seen
c) Visual stimuli are organised into coherent patterns as the letter I or the number 1. Br iefly explain this
by the brain. ambiguity in terms of perceptual set. (3)
d) The perception that an object remains the same
shape regardless of changes in the angle at which it
is viewed is called shape segregation.
e) The most impor tant visual cue in the recognition of
an object is its texture.
f) The tendency to perceive some aspects of sensor y
information and ignore others is called perceptual
set.
Figure 15.31
234
Memory
16
1 Memory
Chapter Head
Memor y is one of our major mental faculties. It is the

capacity of the brain to store information, retain it and
Different levels of memory
Memory is thought to involve three separate interacting
then retrieve it when required. The brain is so versatile
levels, as shown in Figure 16.1. All information that
that it can capture images of sights, sounds, smells,
gains access to the brain must first pass through the
tactile sensations and emotions all experienced at the
sensory memory (SM) and then, if selected, enter the
one time and retain them as memories. For example,
short-term memory (STM). From there it may be
a child receiving a present of a new puppy remembers
transferred to the long-term memory (LTM) or be
various details of the experience vividly for a long time.
discarded.
The brain is able to store a vast quantity of knowledge,
thoughts and detailed information relating to past
experiences as memories. Memory enables us to deal Level 1 – sensory memor y (SM)
with future situations in the light of past experience. In Stimuli from the outside world are continuously
the absence of memory we would be helpless, unable to being perceived as sensory images by the brain. These
manage even the simplest task without having to first impressions are very short-lived (e.g. 0.5 seconds for
relearn it. visual and 2 seconds for auditory) and only a few are
selected and transferred to level 2. The SM provides a
detailed representation of the person’s entire sensory
Selective memory experience from which relevant pieces of information
The receptors in the human sense organs are are sent to the STM.
continuously picking up stimuli and transmitting
sensory impulses to the brain. However, only a fraction Level 2 – short-term memor y (STM)
of the sensory images formed become committed to
Most of the information encoded into this second
memor y because the process is highly selective. If this
level of the system consists of visual and auditory
were not the case the mind would become cluttered
images. However, the STM holds only a limited
with useless information such as every phone number
amount of information – about seven items at the
ever used, every musical note of every tune ever heard
one time (see Investigation – Length of memory
whether liked or disliked, and so on.
span). Not only does the STM have a limited capacity
but, in addition, the items are held for a short time
Encoding, storage and retrieval (approximately 30 seconds). During this time,
To become part of the memory, the selected sensory retrieval of items is very accurate. Thereafter they are
image must first become encoded (converted to a form either transferred to level 3 or lost by displacement
that the brain can process and store). Storage is the (the pushing out of ‘old’ by new incoming
retention of information over a period of time. This information) or by decay (the breakdown of a fragile
may last for only a brief spell such as 30 seconds or for a ‘memory trace’ formed when a group of neurons
very long period, perhaps a complete lifetime. briefly became activated).
Retrieval is the recovery of stored material. This
involves the recall of information that has been
committed to either the short-term or the long-
term memory (see page 239). Thus when memory
is functioning properly, encoding leads to storage of
information that can be retrieved later when required.
235
LEVEL 3
LEVEL 1 LEVEL 2
sensory short-term long-term

continuous flow memory (SM) selected sensory memory (STM) some images memory (LTM)
of information
from environment brain constantly images transferred with limited transferred thought to have
forming sensory capacity unlimited capacity
images
most sensory many items discarded

images quickly lost following loss by
displacement or decay
Figure 16.1 Three levels of memor y
Length of memory span

A person’s short-term memor y span can be measured by f inding out the number of individual ‘meaningless’
Investigation
items that they can reproduce correctly, and in order, immediately af ter seeing or hear ing them once.
Ser ies Number of digits in series

741 3
2835 4
46279 5
584153 6
9082637 7
16136209 8
592403517 9
8076148362 10
78501942493 11
512367509308 12
6821496708754 13
236
Table 16.1 List of ser ies of digits
Memory
In the following investigation there is one tester

(e.g. the teacher) and many subjects (the members 100
of the class). The tester reads out the f irst ser ies of 90
percentage of subjects able to

remember the series correctly
80
digits (see Table 16.1) clearly and at uniform speed.
70
Immediately af ter reading out the last digit of
60
at least once
the f irst ser ies, the tester signals that all subjects
50
should lif t their pencils, wr ite down the ser ies of
40
digits that they have just heard and then lay their
30
pencils down again.
20
10
The tester then reads out the next ser ies, and so on
0
until the end of the list. The responses are checked 3 4 5 6 7 8 9 10 11 12 13
and each subject’s memor y span for the f irst list is number of digits in series
established. The procedure is repeated twice using
dif ferent lists. Each subject’s best overall score Figure 16.2 Graph of memor y span results
is taken to represent his or her memor y span. The
class results are pooled and graphed. Figure 16.2
char ts a typical set of results for a class of 20 pupils. Table 16.2 outlines the design features of this investigation
and the reasons for employing them.
From the results in Figure 16.2, it is concluded that for this group of pupils, the poorest (minimum) memor y
span was 5 digits (one pupil), the best (maximum) memor y span was 9 digits (one pupil) and that all of the other
subjects had a memor y span somewhere in between. On average, the human shor t-term memor y span is found to
be 7 ± 2 digits, though some amazing exceptions have been recorded.
Design feature or precaution Reason

Ser ies of random numbers used To eliminate easily remembered sequences or groups
of numbers
All information read out clearly at uniform speed by To ensure that the only var iable factor is the number
the same tester of digits in the ser ies
Pencils laid down between responses To prevent over-eager subjects star ting to wr ite down
the ser ies before it has been completely read out
Each subject given three attempts To obtain a more reliable result for each subject’s
best score
Many pupils tested and the results pooled as a graph To fur ther increase the reliability of the results
Table 16.2 Design features for memor y span investigation
Chunking provide users with means to transfer an 11-digit

A chunk is a meaningful unit of information made up number from directory to telephone by chunking.
of several smaller units. To most people familiar with
Imagine, for example, that a business woman in
the dates of the Second World War, 1945 is one chunk of
Aberdeen wishes to phone an unfamiliar Glasgow
information not four chunks. However, to most people
number (e.g. 01416293801). If she already knows that
4951 is four chunks of information (unless it happens
Glasgow’s national code is 0141 then that chunk reduces
to be something significant such as the PIN number of
her task to remembering 8 items. If in addition she has
their bank account). Since short-term memory is only
cause to phone Glasgow fairly regularly and recognises
capable of holding about seven new items at one time,
629 as a district code then this becomes a second chunk.
chunking is a useful method of increasing its memory 237
The job now demands a memory span of 6 items, which
span. The compilers of all-digit telephone numbers
many people can manage comfortably.
Related Activity
Investigating the effect of chunking on List 1 List 2

memory span ICL PIN
In this investigation, the subjects view list 1 only (in TPT KGB
Table 16.3) for 2 minutes and are then allowed 4 minutes OML HIV
to write down as many of the 3-lettered items as they can MVM SQA
remember. The procedure is repeated for list 2. The items EZQ VAT
in list 2 are found to be much more easily remembered CPG FBI
than those in list 1. This is because each is an acronym UPR PTO
that acts as a meaningful chunk of information. DUL USA
MCA RAC
SUT NYC
ATX UFO
NSE BBC
RPA MOT
YAD RIP
BCU PLC
Table 16.3 Ef fect of chunking
Rehearsal Ser ial position ef fect

Rehearsal involves repeating to yourself over and over From the results in Related Activity – Investigating the
again (silently or out loud) a piece of information serial position effect, it can be seen that recall is best for
that you are trying to memorise. This process helps the objects shown at the end (recency effect), closely
to extend the time for which the information is followed by those shown at the start (primacy effect).
maintained in the STM. Those in the middle of the viewing sequence gain a very
poor score. This memory pattern is called the serial
position effect.
Related Activity
Investigating the serial position effect

100
percentage of subjects who
In this investigation, the tester informs the subjects that primacy effect recency effect
remembered each object
90
they will be required to memor ise 20 fairly similar objects. 80
The tester reveals the f irst object and allows the subjects 70
60
to view it for 5 seconds. Object 1 is then removed and 50
object 2 revealed for 5 seconds. 40
30
This procedure is repeated for the remaining objects. As 20
10
soon as the last one has been removed, the subjects are 0
invited to pick up their pencils and write down as many 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
of the objects as they can recall in any order. Figure 16.3 position of object in viewing sequence
shows a graph of a typical set of results for a group of 100
subjects.
238 Figure 16.3 Ser ial position ef fect
Memory
Explanation Working memor y

Images of the first few objects can be remembered Working memory is an extension of the short-term
because during the experiment there has been memory. It actively processes, manipulates and controls
enough time for them to have been well rehearsed. information while it is held in the STM. This enables
In many cases they have therefore become encoded simple cognitive tasks to be carried out. Imagine, for
and transferred to the LTM from where they can be example, that you have been asked to think of all the
retrieved at the end of the experiment. pieces of furniture containing drawers that are present
in your home and then calculate the total number of
The last seven or so objects are remembered because drawers. To do this, you form a mental image of your
images of them are still present in the STM and are home and then go for a visuo-spatial tour, room by
quickly ‘dumped’ onto paper by the subjects as soon room. As you come to each relevant piece of furniture,
as they start writing. (If there is a 1 minute delay and you employ your working memory to count the
rehearsal is prevented before subjects are allowed to number of drawers and add this value to the running
write down the objects that they recall, the recency total in your STM.
effect vanishes.) Images of the objects in the middle of
the sequence are not well retained by the vast majority
of subjects because, by the time these images enter
Level 3 – long-term memory (LTM)
the STM, it is already crowded. Therefore many are This third level in the system (see Figure 16.4) is
forgotten before they can be rehearsed, encoded and thought to be able to hold an unlimited amount of
stored in the LTM. information. During encoding, the items are organised
into categories such as personal facts and useful skills.
LTM
items rehearsed and

retained for longer than 30 seconds
episodic memories
(relating to personal facts,
experiences and events)
semantic memories
(relating to general knowledge,
non-personal facts and concepts)
selected sensory item encoded ready procedural memories

STM
information encoded for storage in LTM (relating to skills)
item retrieved
from LTM emotional memories
(resulting from positive or negative
associations with certain stimuli)
item displaced
while in STM spatial memories
(relating to one’s environment
and its spatial orientation)
item forgotten
239
Figure 16.4 Transfer of information
These are then stored for a long time, perhaps even Benef it of rehearsal
permanently. It must be stressed that this multi-level In addition to extending the length of time for which
model of memory and how it works is probably an a piece of information is held in the STM, rehearsal
oversimplification. In addition, the three levels of facilitates its transfer from STM to LTM. Research
memory should not be thought of as occupying three shows that students who regularly stop and rehearse
distinct regions of the brain. what they are reading (and try to learn) are much more
successful at committing the information to memory
Transfer of information between STM and than students who read continuously and resist taking
LTM rehearsal breaks. Reciting in your own words what you
A hypothetical representation of this process is have just read forces your attention (probably starting
shown in Figure 16.4. Information is constantly being to wander) back to the material. Several short rehearsal
transferred between the brain’s two storage ‘depots’ breaks during the learning process are found to be
– the STM and the LTM. If, during its brief stay in the more effective than one long rehearsal at the end of a
STM, an item is successfully encoded (see page 241) marathon learning session.
then this enables it to be transferred for storage in
the LTM which has an enormous, perhaps unlimited, Organisation
capacity. This item may later be retrieved from the LTM Information that is organised into logical categories is
when required. Successful transfer of information from more easily transferred from the STM to the LTM (see
the STM to the LTM is promoted by the processes of Investigation – Effect of organisation on retrieval from
rehearsal, organisation and elaboration of meaning. LTM).
Effect of organisation on retrieval from LTM

In this investigation, the subjects are divided into two groups, A and B. The members of group A are given
Investigation
1 minute to memor ise the 20 words in list 1 (in Table 16.4). The members of group B are given 1 minute to
memor ise list 2. All par ticipants then count backwards from 50 to 0 out loud in unison. Finally, all subjects are
given 2 minutes to wr ite down as many words as they can remember from their list.
List 1 List 2
apple apple
skir t orange
autumn banana
father pear
pear spring
iron summer
brother autumn
summer winter
jacket mother
lead father
trousers sister
winter brother
orange copper
tin lead
sister iron
shir t tin
spr ing jacket
copper shir t
banana trousers
mother skirt
240
Table 16.4 Ef fect of organisation
Memory
The members of group B are found to be much more successful. This is because the words in list 2 are much
easier to memor ise than those in list 1. The reason for this is that the items in list 2 have been organised into
categories. Grouping items of information in an organised fashion increases their chance of being successfully
encoded and transferred from STM to LTM. The group headings (‘fruit’, ‘seasons’, ‘family’, etc.) act as contextual
cues (see page 242), which facilitate the retr ieval of the information from LTM to STM at a later stage. Thus
organisation of mater ial helps to transfer it in both directions.
The exper iment is repeated using new lists and giving group A the organised list and group B the disorganised list
to memor ise. Table 16.5 gives some design features of this investigation and the reasons for employing them.

Large number of subjects used To increase the reliability of the results
20 items present on each list To make the task beyond the scope of the STM
Only 1 minute allowed to memor ise list To reduce the ef fect of other memor y aids such as
rehearsal
Subjects count backwards from 50 before wr iting To prevent the STM contributing answers
answers
Exper iment repeated with new lists and groups To increase the reliability of the results
reversed
Table 16.5 Design features for organisation investigation
Elaboration of meaning of encoding are shallow; others are deeper. Information

Elaboration is a further means of aiding the encoding encoded by repetition is an example of shallow
and transfer of information from STM to LTM. It encoding. Information encoded by associating it with
involves analysing the meaning of the item to be other information such as meaning or linking it with
memorised and taking note of its various features and previous memories is called elaborative encoding. It is
properties. Let us imagine, for example, that you are regarded as a deeper form of encoding.
trying to commit the idea ‘limbic system’ to your LTM.
It is for this reason that rehearsing material (such as
You could try rehearsing ‘limbic system – important part
a group of words in a foreign language) simply by
of the brain’ a few times and it might become encoded.
repetition (shallow encoding) can be a less effective way
However, as it stands, this information is sparse and
of memorising the words than by linking them to their
lacking in interest. Therefore it will probably make little
meaning and to other related words already known
impression and is unlikely to be well retained.
(elaborative encoding).
Successful long-term retention is much more likely
if elaboration of meaning is employed, as shown
Classif ication of information in the LTM
The system of storage in the LTM is analogous to a
in Figure 16.5. By being analysed and elaborated,
filing cabinet of unlimited capacity, organised into
the idea ‘limbic system’ becomes more interesting
distinct categories of information. As items are
and meaningful, enabling it to make a long-lasting
encoded and transferred to the LTM, they are classified
impression.
and filed in the appropriate section(s).
Encoding
Encoding is the conversion of one or more nerve Retr ieval of items from the LTM
impulses into a form that can be received and held by The LTM contains a vast and permanent store of
the brain and retrieved later from the STM or LTM. remembered experience which is constantly being
The quality of the memory is affected by the attention revised, reorganised and enlarged as new material flows
into it. When a piece of information needs to be called 241
given to the task of encoding the material. Some forms
limbic system
It is an important
region of the brain
impoverished encoding (often poorly retained)
It regulates
emotional states
It processes
It influences
information
biological
needed for LTM
motivation
limbic system
It makes up
It has structures
one of three
that project into
inter-connected
the cerebrum
layers of the brain

It is an important
region of the brain
elaborative encoding (usually well retained)
Figure 16.5 Elaboration of meaning
up and retrieved from the LTM, a search is mounted

(see Figure 16.6). This is aided by contextual cues. (A
cue is a signal or reminder; contextual means relating
to the conditions or circumstances that were present
at the time when the information was encoded and
committed to the LTM.) It is thought that a contextual
cue somehow triggers an impulse through a ‘memory
circuit’.
If a memory has been stored under several different

categories (e.g. dandelion might feature under ‘plants’,
‘flowers’, ‘leaves’, clocks’, ‘weeds’, etc.) then it can
be retrieved in various ways. This is because many
contextual cues for it exist and lead to the different files
relating to it. These can then be checked out to see if
one contains the information being sought (e.g. names
of common weeds with yellow flowers).
It is more difficult to retrieve a memory that has been

Figure 16.6 Attempting retr ieval
filed under a few categories only, since it will have few
contextual cues relating to it. Hence the beneficial
242
effects of organisation and elaboration when trying to
Memory
memorise information. A memory whose encoding possesses powerful contextual cues. These enable
in the LTM is accompanied by unusual, emotional the experience to be retrieved and recalled clearly
or dramatic events (e.g. the person’s wedding day) throughout life.
Case Study Alzheimer’s disease

Alzheimer’s disease (AD) is the most common type progressively lost but the cause of this breakdown is
of dementia (mental deterioration). It is diagnosed not clearly understood. One hypothesis proposes that
most often among people over the age of 65. AD is caused by reduced synthesis of acetylcholine,
a neurotransmitter substance. But drugs that are
Symptoms
used to treat this deficiency are not very effective.
The earliest symptoms often take the form of
A second hypothesis suggests that AD is caused
problems with attentiveness, planning and abstract
by the accumulation of proteins called β-amyloids
thought, accompanied by partial memory loss. The
as plaques. However, a vaccine that was found to
latter is observed as an inability by the person to
clear the plaques in a clinical trial did not have any
acquire new memories (for example, they cannot
effect on dementia. Further studies have shown that
recall recently observed events). This state is often
deposition of the plaques is not closely correlated
wrongly attributed simply to aging.
to loss of neurons. A third hypothesis proposes that
As the condition continues to develop, some or all of
the formation of tangles of tiny fibres inside the cell
the following symptoms develop:
bodies of neurons leads to their degeneration and
● confusion that the resultant breakdown of synapses (neuron
● mood swings connections) in the cerebrum causes AD.
● irritability
Management
● aggression
At present no drug that halts or even delays the
● loss of LTM
progression of the disease is available, although some
● loss of speech.
antipsychotic drugs are used to reduce aggression
AD is incurable and gradually leads to death as bodily and psychosis in AD patients with behavioural
functions are lost. problems. Care for an AD patient is often provided by
the person’s partner or close relative. However, this
Diagnosis places an enormous burden on the carer, especially
AD is normally diagnosed using information based when the condition progresses and the patient
on the patient’s medical history and on the results of becomes incapable of tending to their own basic
behavioural assessments and neuropsychological needs such as feeding themselves.
screening tests. Figure 16.7, for example, shows a
diagram that a patient would be asked to copy as part Future
of a test. Many AD patients find the task difficult. When Approximately half of new dementia cases each
AD is suspected, the diagnosis is often followed by a year are AD. Every 5 years after the age of 65, the risk
brain scan such as a PET (see chapter 14, page 217). of acquiring AD doubles. As people live longer, the
incidence of dementia (including AD) is expected to
Cause increase (see Table 16.6).
In AD, cell-to-cell connections in the brain are
Year Estimated percentage of people
worldwide with dementia
2005 0.379
2015 0.441
2030 0.556
Table 16.6
Figure 16.7 Test item ➜ 243

Prevention activities that promote mental stimulation may
Some studies suggest that factors such as regular reduce the risk of AD. However, no causal relationship
exercise, balanced diet, social interaction and has been established.
Location of memor y in the brain words. Patients who have undergone a right temporal
lobectomy have great difficulty remembering unfamiliar
Several different types of memory exist within the LTM geometrical figures, new faces and musical sequences.
(see Figure 16.4). These are associated with particular These findings suggest that memories of different
areas of the brain, although evidence suggests that there categories of general facts are stored in different sides
is a degree of overlap. Close communication certainly of the brain.
exists between these areas of the brain.
Many experts now believe that stores of episodic and
Episodic and semantic memories semantic memories may be widely distributed across
many areas of the cerebral cortex, with each memory
(‘remembering that. . .’) being stored in the cortical region that first received the
Episodic memory is the recall of personal facts, information.
experiences and events. Semantic memory is the recall
of general knowledge, non-personal facts and concepts Procedural memories (‘remembering
(e.g. abstract ideas). These two forms of memory are
closely associated with specific regions of the cerebral
how to. . .’)
cortex such as the temporal lobes at the sides of the Procedural memories contain the information needed
cerebrum (see Figure 16.8). to perform motor skills (e.g. remembering how to
swim) and mental skills (e.g. remembering how to
read). Procedural memories are retrieved and put to
use without the need for conscious control. Many
FRONT REAR
of these skills (especially those involved in muscular
coordination) are closely linked to the cerebellum and
to long-term modifications of the motor area of the
cerebral cortex.
Emotional memor y
Emotional memories are formed as a result of positive
temporal lobe or negative associations with certain stimuli. Often
these are not recalled consciously but may be invoked
Figure 16.8 Temporal lobe of lef t cerebral hemisphere
subconsciously during ‘automatic’ attraction towards,
or avoidance of, a previously met stimulus. Emotional
Electrical stimulation
memories involve the cerebral cortex and the limbic
Electrical stimulation of the temporal lobes of patients
system (see chapter 14) and close links between the two
undergoing brain surgery (to relieve epilepsy) resulted
regions.
in them recalling, in minute detail, personal facts and
events (and even songs) from their distant past. This
suggests that the temporal lobes were the site of at least Spatial memory
some of their episodic memor y. Spatial memory is responsible for holding a record
of information that can be recalled about a person’s
Lef t or right temporal lobe environment and its spatial orientation. Think of the
Patients who have had their left temporal lobe removed kitchen in your home. Where is the sink in relation to
244
are found to have great difficulty remembering the cooker and the fridge? You can immediately bring
unfamiliar words and associations between pairs of to mind their spatial relationship. In doing so you are
Memory
retrieving information stored in your spatial memory. information. Damage to one part may have a knock-on
This type of memory is located in the limbic system. effect on another. Most investigators believe that many
Amnesiac patients suffering damage to part of the different regions of the brain are involved in memory
limbic system called the hippocampus (see chapter 14, with some regions playing larger roles than others.
page 211) cannot remember spatial layouts and are
often severely impaired with respect to their spatial Type of memory Possible location in the brain
navigation. episodic and semantic many regions of cerebral cor tex
Table 16.7 summarises the possible locations of the procedural motor region of cerebral cor tex
different types of memory. However, care must be taken emotional limbic system and cerebral cor tex
when attempting to draw conclusions about their exact spatial limbic system
locations since the many brain circuits involved are
Table 16.7 Possible locations of memor y types
intimately interconnected and constantly exchanging
Related Topic
Smart drugs Some other memor y-enhancing drugs called cholinergics

work by increasing the level of acetylcholine present
Smart drugs improve mental functions such as memory,
at the junctions between ner ve cells in the brain.
cognition (the mental process by which knowledge is
Acetylcholine is a neurotransmitter substance (see
acquired) and concentration. They are used to treat
page 253). Its presence at the junction of two neurons
people with Alzheimer’s disease, Parkinson’s disease
enables a ner ve impulse to pass from one neuron to
and attention-def icit hyperactivity disorder (ADHD). For
another. It is therefore descr ibed as a ‘memor y facilitator’
example, methylphenidate (Ritalin – see Figure 16.9) acts
since memor ies can only be formed, stored and retr ieved
by causing an increase in the level of dopamine at ner ve
if ner ve impulses can pass from one par t of the brain
cell junctions. This enhances the flow of ner ve impulses
to another. Cholinesterase is an enzyme that breaks
between certain neurons in the brain and improves
acetylcholine down to non-active products under natural
attention levels in ADHD patients.
conditions in the cell. Under these circumstances a
ner ve impulse is unable to pass across the junction in
the absence of acetylcholine. Cholinergic drugs act by
inhibiting cholinesterase, thereby sustaining the ef fect
of acetylcholine.
Smar t drugs such as Modaf inil (known to boost memor y
and brain power) are used by some soldiers and pilots to
help them stay awake on long missions. Sleep-depr ived
surgeons have been found to think more clearly and be
better at solving problems and carr ying out simulated
operations when given Modaf inil. However, this smar t
drug has not yet been subjected to long-term safety
Figure 16.9 Ritalin tests. Some students have also begun taking smart
drugs in an attempt to improve their memor y and level
of concentration. But this is a r isky business because
the ef f icacy of these drugs and the extent of their side
ef fects on healthy people have not yet been established
conclusively.
245
1 a) Approximately how many items can be held in the 3 a) What is meant by the term rehearsal in relation to
STM at any one time? (1) pieces of information to be memor ised? (1)
b) Is the memor y capacity of the STM limited or b) Suggest why rehearsal aids the transfer of
unlimited? (1) information from the STM to the LTM. (1)
c) For approximately how long are items held in the 4 a) Explain the meaning of the terms organisation and
STM? (1) elaboration in relation to the transfer of information
d) Identify T WO ways in which items may be lost from from the STM to the LTM. (4)
the STM. (2) b) Why is it easier to retr ieve information from the LTM
e) Explain what is meant by the term chunking and if its components were organised and elaborated
include an example in your answer. (2) pr ior to their transfer to the LTM? (1)
2 a) The three stages involved in memor ising facts are 5 a) Distinguish between the terms episodic, semantic
storage, retrieval and encoding. Arrange these into and procedural memor y. (3)
the order in which they occur. (1) b) Where in the brain is the spatial memor y thought to
b) Explain the reasons for the primacy and recency be located? (1)
ef fects found to occur dur ing an investigation into
the ser ial position ef fect. (2)
4 The distance of an object from the eye is indicated by

binocular height retain visual cues such as its _______ size and its relative
brain long-term retr ieval ______ in the hor izontal f ield.
chunking memor y segregate 5 The two dif ferent images of the same object formed by
contextual organisation semantic the eyes are merged by the brain into one ______ image
that indicates depth and ______.
displacement past sensor y
distance patterns shape 6 The most impor tant characteristic in the recognition of
an object is its ______.
elaboration perception shor t-term
emotional perceptual span 7 The tendency to perceive cer tain aspects of available
sensor y information and ignore others as a result of
episodic procedural spatial
______ experience, context or ______ is called ______
expectation rehearsal visual set.
ground relative working
8 ______ is the capacity of the brain to store, _______
and then retr ieve information when required.
9 Information enter ing the ______ memor y lasts for a few
1 The process by which the ______ analyses and seconds on its way to the ______ memor y (STM).
interprets incoming sensor y information is called
______. 10 The STM has a memor y ______ of about seven items
which it holds for about 30 seconds. This time can
2 ______ perception enables a person to ______ objects be increased by ______ and the number of items
from their background, judge how far away they are and remembered can be increased by ______.
recognise them.
11 If information is not passed to the ______ memor y it is
3 Images may be perceived as f igure and ______, and as lost by ______ or decay.
coherent ______.
246
Memory
12 An extension of the STM used to per form cognitive tasks 15 Dif ferent types of memor y exist. ______ memor y
is called ______ memor y. (personal facts) and ______ memor y (general
knowledge and concepts) are stored in the cerebral
13 Transfer of information from STM to LTM and its ______
cortex. ______ memor ies (motor skills) are stored in
from LTM at a later stage are aided by rehearsal, ______
the motor area of the cerebral cor tex. ______ memor ies
of meaning and ______ dur ing encoding.
involve both the limbic system and the cerebral cor tex.
14 ______ cues aid the retr ieval of information from LTM. ______ memor y is located in the limbic system.
247
1
17 Nerve cells and neural pathways
Chapter Head
Cells of the nervous system neurons. These cells provide the body with rapid means
of communication and control. They are structurally
The nervous system consists of a complex network of adapted to suit their function of conducting nerve
nerve cells called neurons which receive and transmit impulses from one part of the body to another. There
electrical signals (nerve impulses), and glial cells which are three types of neuron – sensory, inter and motor –
support and maintain the neurons. as shown in Figure 17.1.
Neurons Although these appear to be very different, they all

share the same basic structures. Each consists of a
The efficient working of the human body and all of its
cell body and associated processes: one axon and
parts depends on the coordinated activity of billions of
cell body of inter neuron
dendrite cell body of

motor neuron
tiny branch
of axon
cell body of
sensory neuron
axon
synaptic axon
cleft (’space’)
synaptic
cleft (’space’)
dendrite
axon
direction
of nerve
impulses
myelin sheath myelin sheath
node
(gap lacking
myelin)
dendrite
NERVE IMPULSE NERVE IMPULSE
RECEPTOR EFFECTOR
STIMULUS RESPONSE
248
Figure 17.1 Three types of neuron
Nerve cells and neural pathways
several dendrites (see Figure 17.2). These thread-like parts of the body (e.g. toes) can be more than a metre
extensions of the cytoplasm are often referred to as in length! Each axon from a motor neuron carries a
nerve fibres. message from the cell body to an effector.
The direction in which a nerve impulse travels is always:

dendrites → cell body → axon
At the two points in Figure 17.1 where information
passes from the axon of one neuron to the dendrites
of the next, there is great potential for successful
transmission because in reality one neuron ends
in many tiny axon ‘branches’ and the next neuron
normally begins as many tiny dendrite ‘branches’.
Myelin sheath
The myelin sheath is the layer of fatty material that
insulates an axon. The small gaps in the myelin sheath
along an axon are called nodes. A nerve fibre lacking
myelin is described as unmyelinated.
Speed of transmission of impulse

Figure 17.2 Neuron The presence of the myelin sheath greatly increases the
speed at which impulses can be transmitted from node
to node along the axon of a neuron. In unmyelinated
Dendrites fibres, the axon is exposed to the surrounding medium
Dendrites are nerve fibres that receive nerve impulses and the velocity at which impulses are conducted is
and pass them towards a cell body. A sensory neuron’s greatly reduced.
dendrites gather into one elongated fibre, which
transmits information from receptors (in contact with Myelination
the environment) and sends it to the cell body. Inter
Myelination, the development of myelin round axon
and motor neurons have several short dendrites that
fibres of individual neurons (see Figure 17.3), takes
collect messages from other neurons and send them to
time and is not complete at birth but continues during
their respective cell bodies.
postnatal development until adolescence.
Cell body The hypothalamus is not fully myelinated until about
The cell body of a neuron contains the nucleus 6 months. For this reason a very young baby does not
and most of the cytoplasm. It is the control centre have a fully effective ‘thermostat’ able to bring about
of the cell’s metabolism and contains clusters of finely tuned control of body temperature. Similarly,
ribosomes. These are required to make various proteins an infant is unable to control fully the lower body
including the enzymes needed for the synthesis of because the neurons in the spinal cord that transmit
neurotransmitters (see page 253). The cell bodies of impulses from the brain to the lower body are not fully
inter neurons are situated in the central nervous system. myelinated until the child is about 2 years old.
Axon Diseases
An axon is a single nerve fibre that carries nerve In some diseases the myelin sheath around axons
impulses away from a cell body and, in the case of becomes damaged or destroyed. This leads to problems
sensory and inter neurons, on to the next neuron in the such as a loss of muscular coordination. (See Related
sequence. The axons of motor neurons are extremely Topic – Analysis of three diseases.) 249
long. For example, those that connect with distant
nucleus glial cell
axon
glial cell closes

around axon
glial cell lays down

layers of plasma
membrane
around axon
myelin sheath
Figure 17.3 Myelination
Glial cells around an axon (see Figures 17.3 and 17.4).

There are several types of glial cell. They do not Other glial cells provide neurons with some of the
transmit nerve impulses but are essential to provide chemicals that they need to function. They also help
neurons with physical support. Some are responsible to control the chemical composition of the fluid
for the process of myelination. This production of the surrounding the neurons. By this means these glial
myelin sheath occurs when a type of glial cell lays down cells maintain a homeostatic environment around the
successive, tightly packed layers of plasma membrane neurons.
250
close-up
direction of
nerve impulse plasma
membrane of
mitochondrion presynaptic
neuron
vesicle
containing synaptic
neuro- terminal
transmitter (axon
direction of ending)
nerve impulse synaptic
from inter neuron cleft
axon of
inter neuron neurotransmitter plasma
molecules membrane of
axon ending being postsynaptic
synaptic cleft released neuron
dendrite containing
receptor sites
Figure 17.4 Myelin sheath
The intimate association between projections from cell body

of motor neuron
certain glial cells (see Figure 17.5) and the cells forming
the walls of capillary blood vessels is thought to
contribute to the make-up of the blood-brain barrier
(BBB). This is a layer that lines blood capillaries and is myelin sheath
composed of cells that fit together very closely. It keeps
blood that is circulating in capillaries separate from the axon of motor
neuron
extracellular fluid in the brain and prevents movement
of microorganisms and large molecules into the fluid
from the bloodstream. Some glial cells are phagocytic.
They remove foreign and degenerate material from the
CNS by phagocytosis.
muscle fibre axon ending
direction of cell body of

nerve impulse inter neuron
close-up
in brain
extracellular direction of
nerve impulse
fluid (chemical
composition
controlled by mitochondrion
glial cell vesicle containing

projections) neurotransmitter

molecules

cell body of
glial cell
in brain
projection
skeletal
of glial cell
muscle fibre
intimate contact
between glial cell
projections and
capillary wall
Figure 17.6 Synaptic clef t
blood capillary in brain
blood-brain barrier
251
Figure 17.5 Role of glial cell
Related Topic
Analysis of three diseases

Table 17.1 gives an analysis of three diseases that result from problems af fecting neurons.
Poliomyelitis (polio) Multiple sclerosis (MS) Tay-Sachs disease (TSD)

Cause Caused by a virus that is The cause is unknown. It This is a genetic disorder involving
transmitted via oral-to-oral is thought that a complex a single mutated gene. The
and faecal-to-oral routes. interaction between the person’s suf ferer inherits a copy of the
In a minor ity of cases the genotype and some unidentif ied defective recessive allele from both
virus spreads along ner ve environmental factor or agent parents. The mutation leads to
pathways destroying motor results in the person’s own insuf f icient activity of an enzyme
neurons in the spinal cord immune system damaging the that normally breaks down certain
and brain. myelin sheaths around axons. fatty acid der ivatives. In a TSD
This produces demyelinated ner ve suf ferer, harmful quantities of
f ibres unable to transmit ner ve these molecules gather in neurons
impulses ef f iciently (especially of the CNS, making the neurons
between the brain and spinal become distended and incapable of
cord). per forming their function.
Symptoms These take the form of The patient suf fers numbness, In TSD patients, a region of the
fever and pains in the walking dif f iculties, impaired retina shows up as a red spot.
neck and back muscles. vision and progressive loss of This is the centre of the fovea, the
In a minor ity of cases, coordination as the ability to only par t of the retina whose cells
asymmetr ical weakness control muscles is lost. Some are not distended by fatty acid
of certain muscles occurs, forms of MS involve episodic der ivatives. The most common form
followed by paralysis of attacks interspersed with spells of the disease (infantile TSD) results
one or more body parts, when symptoms decrease and may in the continuous deter ioration
commonly a limb. disappear temporarily. In other of physical and mental abilities
forms the symptoms persist and from the age of around 6 months.
slowly accumulate. The child becomes deaf and blind.
Muscles fail to work and paralysis
follows. The child normally dies at
about age 4 years.
Treatment There is no cure. Treatment There is no cure for MS. Treatment There is no cure. Treatment takes
focuses on providing relief involves tr ying to prevent the the form of palliative care given to
of symptoms by using patient from suf fer ing new patients to ease their symptoms.
painkillers and promoting attacks and helping them to
moderate exercise and regain function when they have
consumption of a healthy suf fered an attack. Several types of
diet. In most cases, medication are available that help
paralysis is temporar y, to decrease the number of attacks
though complete recover y but they are of ten accompanied by
may take years. In a adverse side ef fects. Some patients
few cases paralysis is resor t to alternative treatments
permanent. unsuppor ted by clinical evidence,
such as medicinal cannabis.
Table 17.1 Analysis of three diseases
252
Synaptic clefts and neurotransmitter (see Figures 17.6 and 17.7). When a
nerve impulse passes through the presynaptic neuron
neurotransmitters and reaches the synaptic terminal, it stimulates several
The tiny region of functional contact between an axon vesicles. These simultaneously move to the terminal’s
ending of one neuron and a dendrite (or sometimes surface, fuse with its membrane, form openings and
cell body) of the next neuron in a pathway is called a discharge their contents (about 10 000 molecules of
synapse. The plasma membranes of the two neurons at neurotransmitter per vesicle) into the synaptic cleft.
a synapse are very close to one another and separated
only by a narrow space called a synaptic cleft (see Once in the cleft, the neurotransmitter molecules
Figure 17.6). briefly combine with receptor molecules at sites on
the membrane of the postsynaptic dendrite. This
The nerve cell before the synaptic cleft is called the process alters the membrane and its electrical state. For
presynaptic neuron; the one after the synaptic cleft example, the binding of acetylcholine to receptor sites
the postsynaptic neuron. Neurons also connect makes ‘gates’ in the postsynaptic membrane open (see
with muscle fibres and endocrine gland cells via Figure 17.8). This allows increased flow of ions to occur
spaces similar to synaptic clefts. Messages are relayed through the membrane, resulting in a nerve impulse
across synaptic clefts from neuron to neuron both being initiated in the postsynaptic membrane.
inside and outside the brain by chemicals called
neurotransmitters. Two examples are acetylcholine and
norepinephrine (noradrenaline).
acetylcholine in
Action of neurotransmitter synaptic cleft postsynaptic
membrane
Each synaptic terminal of an axon holds a rich
supply of vesicles containing a store of one type of receptor site
mitochondrion
‘gate’ closed
acetylcholine binds
to receptor site
vesicles in synaptic
terminal containing
neurotransmitter
synaptic cleft
‘gate’ opens allowing
flow of ions which results
in a new impulse
being initiated
253
Figure 17.7 Electron micrograph of a synaptic clef t Figure 17.8 Neurotransmitter in action
Excitator y and inhibiting signals only the brief moment required to pass on that impulse.
This is achieved by the neurotransmitter being rapidly
The type of alteration to a postsynaptic membrane that
removed as soon as the impulse has been transmitted,
occurs following the binding of a neurotransmitter to
thereby preventing continuous stimulation of
its receptors depends on the type of receptor present.
postsynaptic neurons.
The signal generated is determined by the receptor
and may be excitatory or inhibitory. The same There are two types of mechanism for the removal of
neurotransmitter may even have an excitatory effect in neurotransmitters. These are enzyme degradation and
one situation and an inhibitory effect in another, as in re-uptake.
the following example.
Acetylcholine, for example, is broken down into
Acetylcholine released into the cleft between a motor non-active products by an enzyme present on the
neuron and a skeletal muscle fibre binds to receptors postsynaptic membrane, as in the following equation:
that have an excitatory effect on the muscle fibre and
make it contract. Acetylcholine released into the cleft cholinesterase
acetylcholine ⎯⎯⎯⎯⎯⎯⎯→ non-active products
between a motor neuron and a heart muscle fibre
binds with receptors that have an inhibitory effect. This The non-active products are reabsorbed by the
reduces the rate and strength of contraction of cardiac presynaptic neuron and resynthesised into active
muscle (and heart beat). neurotransmitter, which is stored in vesicles ready
for reuse. The energy required is supplied by the
Direction of impulses mitochondria present in the synaptic terminal.
Vesicles containing neurotransmitter occur on one side Norapinephine (noradrenaline), on the other hand,
only of a synapse. This ensures that nerve impulses are undergoes re-uptake by being reabsorbed directly by
transmitted in one direction only. the presynaptic membrane that secreted it and is stored
in the vesicle ready for reuse.
Need for removal of neurotransmitter Filtering out weak stimuli

after transmission of impulse A nerve impulse is only transmitted across a synapse
To ensure precise control of the system and allow for and on through the postsynaptic neuron if it first
the successful transmission of each short-lived impulse, brings about the release of a certain minimum number
the postsynaptic membrane must remain excited for of neurotransmitter molecules. This critical number
is needed to affect a sufficient number of receptor
Related Information
Mode of action of neurotransmitters
Table 17.2 gives some examples of neurotransmitters and their modes of action.
Neurotransmitter Mode of action
Acetylcholine Excitator y at ver tebrate skeletal muscle sites; excitator y or inhibitor y at other sites
depending on type of receptor present
Norepinephr ine (noradrenaline) Excitator y or inhibitor y depending on type of receptor present
Serotonin Excitator y or inhibitor y depending on type of receptor present
GABA (gamma aminobutyr ic acid) Inhibitor y
Dopamine Excitator y or inhibitor y depending on type of receptor present
Glycine Inhibitor y
254 Table 17.2 Neurotransmitters and their mode of action
sites on the membrane of the postsynaptic neuron. Summation

Achievement of this is called reaching the membrane’s
The electrical change in a postsynaptic membrane that
threshold.
results from the binding of a neurotransmitter to its
Weak stimuli that fail to do so are called subthreshold receptors is called an EPSP (excitatory postsynaptic
stimuli. They are filtered out by the synapse acting as potential). An EPSP at a synapse can be too weak
an unbridgeable gap. The continuous low-level drone to enable threshold to be reached. However, a
of machinery, for example, fails to evoke a response postsynaptic cell may receive information via synapses
because the weak ‘background’ stimuli do not bring from several neighbouring neurons. If many synaptic
about the release of enough neurotransmitter to create terminals of many presynaptic neurons discharge their
an impulse in the postsynaptic membrane. However, a neurotransmitter simultaneously or in rapid succession,
sudden change in the stimulus (such as an increase in then enough of the chemical is released to fire an
volume) brings about the normal response and makes impulse. This cumulative effect of a series of weak
the person aware of the machinery. stimuli that together bring about an impulse is called
summation (see Figure 17.9).
direction of
nerve impulse axon of

axon of
presynaptic neuron many weak presynaptic neuron
stimuli in
few weak stimuli
total are
inadequate to
adequate to
fire an impulse
fire an
impulse
cell body of postsynaptic neuron
no nerve nerve impulse

impulse transmitted following
transmitted summation
of weak stimuli
Figure 17.9 Summation
Related Topic
Action of curare and strychnine or injected with curare, the poison binds to acetylcholine
receptors on the postsynaptic membranes of muscle
Curare f ibres. This results in the neural pathway becoming
Curare is the general name given to several poisons

blocked and no ner ve impulses reaching the muscles.
or iginally found in South Amer ica. These are produced by

Therefore these fail to contract and remain relaxed and
cer tain plants and have been used traditionally as arrow

in a state of paralysis. Curare is therefore descr ibed as a
and dar t poisons by South Amer ican native forest dwellers

muscle relaxant.
to paralyse prey (see Figure 17.10).

Curare-poisoned prey normally dies as a result of
asphyxiation since its respirator y muscles no longer
Acetylcholine is a neurotransmitter that relays messages
work. Curare-poisoned prey is safe to eat because curare
needed to br ing about muscular contraction in
molecules are unable to pass through the lining of the
ver tebrates. When a muscle is wounded by a poison dar t 255
consumer’s gut and into their bloodstream. ➜
Glycine is a neurotransmitter that occurs naturally in the
bodies of many types of animal including mammals. When
it binds to its receptors on the postsynaptic membranes
of motor neurons in the brain and spinal cord, it has an
inhibitor y ef fect, which prevents excessive contraction
of skeletal muscles. Str ychnine acts as an antagonist
(see page 266) and competes with glycine for the same
receptor sites. The higher the concentration of str ychnine
absorbed into the body, the fewer the number of glycine
molecules that manage to combine with their receptors
and br ing about the normal, natural inhibitor y ef fect.
In the absence of the inhibitor y ef fect, an excitatory
state results and motor neurons are able to transmit an
unchecked flow of ner ve impulses to skeletal muscles.
Figure 17.10 Curare is used on blowpipe dar ts Therefore the victim suf fers continuous spasms of
muscular contraction that can af fect the whole body. In
addition, skeletal muscles may become fully contracted.
Str ychnine In ver y low doses str ychnine acts as a stimulant and some
Strychnine is a highly poisonous chemical made by Olympic athletes in the past have r isked using it in an
many members of the plant genus Strychnos. It is used attempt to improve their per formance.
to control pests such as rats, which suf fer muscular
convulsions and eventually die of asphyxiation.
1 a) Draw a simple diagram of a motor neuron and label

the par ts: cell body, dendrite and axon. (3) 1
b) State the function of each of the labelled par ts in
P
your diagram. (3)
2 a) What ef fect does the presence of a myelin sheath
3
around a ner ve f ibre have on the speed at which the 4
f ibre can transmit a ner ve impulse? (1)
b) Why are children unable to exer t full control of their
lower body before the age of 2 years? (1)
2
3 Figure 17.11 shows a synapse.
a) Match numbered par ts 1–4 with the following terms:
synaptic cleft, axon, synaptic terminal, membrane of Q
dendrite. (4)
b) i) Identify structure P. R
ii) Give the name of a neurotransmitter that could
be released at Q.
part of postsynaptic part of presynaptic neuron
iii) To what structures would these neurotransmitter neuron
molecules br iefly combine?
iv) In which direction would the ner ve impulse pass Figure 17.11
in this diagram? 4 What is meant by the term summation with reference to
v) State the fate of the neurotransmitter that you ner ve impulses? (2)
gave as your answer to par t ii) once the ner ve
256 impulse has been transmitted.
vi) Identify structure R and state its function. (7)
Complex neural pathways

Neurons are found to be connected to one another
in many different ways in the CNS. The various
combinations allow many types of complicated
interaction to occur between neurons. This enables direction
of nerve
the nervous system to carry out its many complex impulse
functions. Examples of neural pathways are as outlined
below.
Converging neural pathway

To converge means to come together and meet at
a common point. In a convergent neural pathway, cell body of neuron
receiving converging
impulses from several sources are channelled towards, nerve impulses
and meet at, a common destination, as shown in
Figure 17.12. This brings about a concentration of
excitatory or inhibitory signals at a common neuron.
(See Related Topic – Convergence of neurons from
rods.)
Figure 17.12 Converging neural pathway
Related Topic
Convergence of neurons from rods pathway, as shown in Figure 17.13. The ner ve impulse
transmitted by one rod in dim light is weak. On its own it
Rods and cones would be unable to br ing about the release at the synapse
Rods and cones are visual receptors present in the retina of enough neurotransmitter to raise the postsynaptic
of the eye. They contain pigments that break down in the membrane to threshold. However, the convergent
presence of light. In each case, this breakdown forms a arrangement of several rods allows several impulses
chemical that tr iggers ner ve impulses along a pathway to be transmitted simultaneously and these have the
of neurons. The pigment present in cones is not ver y combined ef fect of releasing enough neurotransmitter.
sensitive to light. Br ight light (e.g. daylight) is needed The postsynaptic membrane now reaches threshold
to break it down and tr igger the transmission of ner ve and transmits the ner ve impulse on through the neural
impulses. The pigment in rods, on the other hand, is so pathway of the optic ner ve to the brain.
sensitive to light that it even reacts in ver y dim light
This process increases the human eye’s sensitivity to low
and f ires of f impulses. It is quickly rendered temporar ily
levels of illumination and allows vision in conditions of
inactive in br ight light.
almost total darkness. Fur thermore, we gain a reasonably
comprehensive view of the surroundings because the rods
Convergence of signals from rods are thoroughly distr ibuted throughout the retina (except
As the intensity of light enter ing the eye decreases, for the fovea).
cones cease to respond and rods take over. Unlike cones,
several rods form synapses with the next neuron in the
➜ 257
human eye
direction of
nerve impulse
fovea
retina
optic nerve
enlarge
direction of light
entering eye
to
optic
nerve

direction cell body of neuron

of nerve receiving converging
impulse signals from five rods
cell body of rod
cone
rod containing
light-sensitive
pigment
Figure 17.13 Rods and cones
three motor neurons leading

to separate destinations
Figure 17.14 Diverging neural pathway
Diverging neural pathway from the original single source to be transmitted to

several destinations. Figure 17.14 shows a simplified
To diverge means to branch out from a common point.
version of this principle.
In a diverging neural pathway, the route along which an
impulse is travelling divides. This allows information
258
Related Topic
Examples of diverging neural pathways Temperature control

Similarly, a neural pathway that begins in the
Fine motor control hypothalamus is found to diverge into branches that lead
Movement of those par ts of the body operated by skeletal to sweat glands, skin arter ioles and skeletal muscles. This
muscles is controlled by the motor area of the cerebrum enables the hypothalamus to exert coordinated control
(see Figure 14.15, page 213). The cerebrum communicates over the structures involved in temperature regulation.
with the muscles by sending impulses via motor neurons For example, vasoconstriction, shivering and decreased
in neural pathways. Divergence of these pathways rate of sweating can all be initiated simultaneously if the
from a common star ting point allows impulses to be body temperature begins to drop.
simultaneously transmitted to dif ferent muscles of the
hand, for example. This br ings about f ine motor control
of the f ingers and thumb by allowing them to operate in
unison when required to do so.
Reverberating pathway
A reverberation means a sound that occurs
repeatedly, as in an echo or a vibrating tuning fork. In
a reverberating neural pathway, neurons later in the
pathway possess axon branches that form synapses with direction of
neurons earlier in the pathway (see Figure 17.15). This nerve impulse
arrangement enables nerve impulses to be recycled and

to repeatedly stimulate the presynaptic neurons. Once
the circuit is activated and reverberating as a result
of this feedback of impulses, it continues to give out
signals until the process is brought to a halt when no
longer required.
Related Information
axon branch
allowing positive
Examples of reverberating pathways feedback of
nerve impulses
Complex reverberating circuits in the brain are involved in
the control of rhythmic activities such as breathing. They
are also thought to be involved in shor t-term memor y
but not long-term memor y. Electroconvulsive shock,
which br ings electr ical activity in the ner vous system
to a temporar y halt, af fects breathing and STM but not
LTM. A pathway can reverberate and transmit impulses
for seconds, for hours or, in the case of breathing, for a
lifetime.
259
Figure 17.15 Reverberating pathway

Development of new neural pathways new environmental experiences is called plasticity
of response. (Plastic in this biological sense means
The brain is a dynamic structure containing a profusion
able to be influenced or become changed.) Plasticity
of neural connections at synapses. It is not ‘hard-wired’
of response enables new neural pathways to form,
with fixed, immutable neural pathways. In fact, neurons
especially during:
in the brain undergo change in their synaptic network
during a person’s lifetime. Depending on sensory input, ● early development of the brain
some synapses lose connections while others retain ● the learning of new skills
them or even develop additional ones. This remarkable ● response to brain injury.
ability of brain cells to become altered as a result of
Related Topic
Effect of type of environment on early not used, they become redundant and are removed by
‘pruning’. If the young mammal’s environment is one
development of brain of sensor y and/or social depr ivation (e.g. small, bare
As a young mammal, such as a rat, develops and interacts cage, no toys, solitar y conf inement, etc.) then few new
with its environment, neurons in its brain are activated. synaptic connections are made between brain neurons
If the environment is enr iched and stimulating (e.g. and many of the or iginal dendr ite connections are
contains ladders to climb, wheels to spin, other rats pruned. The animal’s brain does not develop as fully
to play with, etc.) then cer tain synaptic connections and the animal is found to be less intelligent than the
between brain neurons are made frequently. As a result, animal in the stimulating environment. It is thought that,
the synaptic connections become reinforced and increase in a similar way, the brains of human babies reared in
in number as the neurons develop extra dendr ites. By seriously deprived environments fail to develop to their
this means new neural pathways develop, some of which full potential. The process of neural plasticity in response
endow the animal with increased cognitive skills. to new environmental stimuli is never completely lost. It
continues throughout life but becomes more limited later
When synaptic connections between brain cells are
in adulthood.
Related Activity
Analysing data on neural development

in rat brains
increasing number of synapses per neuron
The graph in Figure 17.16 shows the results from stimulating

environment
an investigation into the ef fect of two dif ferent
environments on brain development in rats. Those reared
in a stimulating, enr iched environment were found to
have a larger number of synapses (up to 25% more) than
rats reared in a depr ived environment. In addition, the deprived environment
former were found to possess a cerebral cor tex that was
3.3–7.0% thicker than that of the latter.
In a fur ther investigation, one group of rats was reared

in an enr iched environment and another group in an
unenr iched environment. The rats were in turn released
increasing age
individually into a maze (see Figure 17.17) several times a
day for 20 days.
260 Figure 17.16 Stimulating versus depr ived environment
in
5 10
4 8
3 6
mean
time 5 mean
in number
maze 2 4 of errors
(min)
3
1 2
0 0
rats from rats from

enriched unenriched
environment environment
Figure 17.18 Results from maze exper iment

out
Figure 17.17 Typical rat maze unenr iched environment at solving maze problems. They
were also found to have a signif icantly thicker cerebral
The bar graph in Figure 17.18 shows the results for the cortex, containing enlarged neurons (with a greater
f inal maze run. From the results it is concluded that spread of dendr ites) and a higher number of glial cells
members of the group from the enr iched environment than the depr ived rats.
were much more successful than those from the
Related Topic
Brain development and sensory Feral children

deprivation These are children who have lived in the wild without any
Failure of environmental stimulation during cr itical human contact dur ing their formative years. Of ten this
per iods of brain development can lead to irreversible sur vival has depended upon the suppor t of wild animals
def iciencies in cer tain functions of the brain. that have taken them into their group. The normal
development by young children of human communication
skills (e.g. spoken language, meaningful eye contact,
‘Blind’ kitten physical gestures, etc.) is dependent upon continuous:
In one of several related exper iments, scientists ● obser vation of the activities of other human models
temporarily blocked the visual input to one eye of a ● hear ing of sounds made by other humans
kitten dur ing a period of brain development when neural ● mimicking of human sounds and gestures that evoke
connections were being formed in response to sensor y responses (e.g. praise) from other humans.
exper iences. They found that this led to irreversible
structural and functional changes in the visual cortex of By growing up in conditions of sensory depr ivation and
the animal’s brain. It caused permanent impairment of lack of human contact, feral children fail to develop
vision in the af fected eye because in the absence of visual these communication skills. Even if the children are
stimuli, the requisite neurons had been pruned of their successfully retr ieved from the wild, they may not be able
unused synaptic connections and were unable to develop to develop the skills fully because the requisite brain
these connections again (when visual input returned). neurons have passed their cr itical per iod of development
When the exper iment was repeated using adult cats, it and are no longer suf f iciently plastic to form all the
261
had no ef fect on their vision. necessar y synaptic connections.
Plasticity of response following brain injur y
Figure 17.19 shows a brain scan of a person who has
suffered a stroke. The black area indicated by the arrow
region of brain
shows the region of the brain affected in this case.
affected by
stroke People who have suffered serious brain damage of this
type are found to be severely affected. Depending on the
specific area affected, they may, for example, be unable
to speak or be unable to move one or more of their
limbs.
However, during the first few months following the

injury, some sufferers are found to make a significant
recovery and regain speech or use of the limb, at least in
part. Neurons in the damaged region of the brain have
not regained their functional state. What has happened
is that neurons in some other region of the brain that
has escaped damage have formed new neural pathways
enabling them to take on these jobs. People who show
this type of improvement are demonstrating major
plasticity of response where new neural pathways
enable an area of brain damage to be bypassed. (See
Figure 17.19 Brain scan of stroke victim Case History – Brain injury and sensory substitution.)
Case History Brain injury and sensor y substitution

After surgery, a patient was given an antibiotic to her tongue. This in turn sent impulses to her brain.
aid her recovery from an infection. A few days later Eventually the woman regained her balance and no
she found that she had completely lost her sense of longer needed to use the brainport.
balance. The antibiotic had damaged the region of her
Her recovery is attributed to neuroplasticity of the
brain responsible for visual and gravitational stability.
brain in response to sensory substitution. The region
Four years later, the woman volunteered for an of the brain normally responsible for processing
experimental treatment devised by a leading sensory information from chemoreceptors on the
exponent of neuroplasticity. He used an apparatus tongue was able to respond and adapt to the arrival
called a brainport. This consisted of a strip of tape of the completely new set of impulses. By doing
containing microelectrodes wired to a ‘spirit-level’ so, that region of the brain became able to process
structure attached to a hard hat. When the strip was information and send impulses to the effectors
attached to the woman’s tongue and the hard hat put responsible for balance. Remarkably, that region
in place, the level on the hat was able to determine of the brain also continued to perform its normal
her spatial coordinates and send information to function and the woman did not lose her sense of
taste.
262
Minor plasticity
The ability of the brain to suppress reflexes (such
as blinking) or responses to sensory impulses (such
as visual distractions) is called minor plasticity of
response. It is investigated in the Investigations that
follow.
The brain’s capacity to suppress the blinking reflex

A reflex action is a rapid, automatic, involuntar y response to a stimulus. Blinking the eye by contraction of the
Investigation
eyelid muscle in response to a real or imaginar y danger is a reflex action. In the exper iment shown in
Figure 17.20, ten attempts are made to make the volunteer blink using their r ight eyelid. An inter val of 10
seconds is allowed between each tr ial to allow the volunteer to compose themselves and summon maximum
willpower. The eye is held at the same distance from the pipette at each tr ial.
fingers of clamp stand
sterile plastic pipette

eye of volunteer
who is to try to
hand about to squeeze resist blinking
pipette and expel air
Figure 17.20 Resisting blinking
It is found that some people are ver y good at suppressing this reflex action while others cannot resist blinking,
however hard they tr y. This form of minor plasticity is thought to occur in the following way. Since the ner vous
system consists of many interconnecting ner ve cells, two conflicting types of message (one ‘saying’ Blink!; the
other ‘saying’ Resist blinking!) meet in a converging pathway. If the overall ef fect at the synapses af fected is
excitatory then an impulse is f ired and the blinking response occurs. If the overall ef fect is inhibitory then no
impulse is f ired and blinking fails to occur. Thus some people cannot resist blinking while others can successfully
‘stare out’ the stimulus.
The ability of the brain to suppress sensory impulses

The person being tested is given 2 minutes to attempt a task that requires a reasonable amount of concentration
Investigation
(e.g. to correctly solve as many simple ar ithmetical problems as possible from a long list). The f irst tr ial is
conducted in optimum conditions (e.g. silence, good lighting, etc.). The second tr ial, using a fresh list of
problems of equal dif f iculty to the f irst, is carr ied out under conditions of auditory distraction (e.g. sound of a
car alarm). The f inal trial is performed under conditions of visual distraction (e.g. flashing light).
Some people are found to be ver y good at suppressing the sensor y impulses from the distractions and perform
ver y well each time. Other people f ind it ver y dif f icult to concentrate when distracted and fail to block out the
sensor y impulses. 263
Discussion
From the above two investigations, it can be
concluded that responses shown by a normal, healthy
person’s nervous system are not necessarily fixed and
unchangeable. Sometimes the brain can be persuaded to
temporarily suppress a reflex action or block out certain
sensory impulses. This demonstrates minor plasticity
of response of the nervous system.
1 Br iefly explain what is meant by the terms converging 2 a) Give an example of major plasticity of response of
neural pathway, diverging neural pathway and the brain. (1)
reverberating neural pathway. (6) b) Give an example of minor plasticity of response of
the brain. (1)
264
Neurotransmitters, mood and behaviour
18
1 Neurotransmitters, mood and behaviour
Chapter Head
Endorphins Dopamine and the reward

When the body is injured or affected by illness, nerve pathway
impulses pass to the brain, resulting in the sensation
Dopamine is a neurotransmitter produced in several
of pain. Endorphins are chemicals that function like
regions of the brain. Two of these centres, ‘V’ and ‘N’,
neurotransmitters and act as natural painkillers by
are shown in a simplified way in Figure 18.2. They are
combining with receptors at synapses and blocking the
located in the limbic system and are connected by nerve
transmission of pain signals. Endorphins are produced
fibres which form a neural circuit. When a survival-
in the hypothalamus and their level of production
related urge such as hunger, thirst or sexual need is
increases in response to:
being satisfied by current behaviour, neurons in centre
● physical and emotional stress ‘V’ release dopamine which is carried to centre ‘N’.
● severe injury Neurons in centre ‘N’ also release dopamine and induce
● lengthy periods of vigorous exercise a pleasurable feeling. It is for this reason that V and N
● certain foodstuffs such as chocolate. are often referred to as pleasure centres and the route
from V to N is called the brain’s reward pathway. It is
Depending upon circumstances, increased levels of thought to have evolved because it reinforces forms of
endorphins may bring about: beneficial behaviour (such as eating when hungry) that
are of survival value. Several other circuits that release
● regulation of appetite
dopamine are also present in the brain, although only
● release of sex hormones
one of these is shown in Figure 18.2. It leads to the
● feelings of euphoria.
frontal area of the cerebral cortex which is responsible
for cognitive appreciation of pleasure.
Related Topic
Endorphins and pain threshold

In an investigation, the endorphin level in the blood
plasma of each of the par ticipants was measured. Then cuff
each person’s pain threshold was tested. This was done
using a blood-pressure cuf f (see Figure 18.1) pumped up
until the volunteer indicated that they could not take any
more pressure. The par ticipants were split into groups A
and B. The members of group A exercised vigorously for
10 minutes whereas those in group B remained at rest. hand
pump
Af ter exercise, the endorphin level of the members of

group A was found to have r isen in ever y case and, when
the blood-pressure cuf f test was repeated, their pain
digital sphygmomanometer
threshold was found to have increased. They were, on
average, able to stand the cuf f at a higher pressure for
a longer time. The endorphin level and pain threshold Figure 18.1 Digital sphygmomanometer with manually inflated
of group B was found to have remained unchanged. The cuf f
result of this and many similar experiments suppor t the
theor y that endorphins act as natural painkillers.
265
centre ‘N’ releases reward
Treatment of neurotransmitter-
dopamine and induces
pleasurable feeling
pathway
centre ‘V’ releases related disorders
dopamine when
a need is satisfied
Agonists and antagonists
An agonist is a chemical that binds to and stimulates
specific receptors on the membrane of postsynaptic
neurons in a neural pathway. Since the agonist mimics
the action of a naturally occurring neurotransmitter, it
triggers the normal cellular response. Therefore, nerve
impulses are transmitted, sometimes at an enhanced
level (see Figure 18.3).
An antagonist is a chemical that binds to specific

frontal area of cerebral cortex
responsible for cognitive receptors on the membrane of postsynaptic neurons
appreciation of pleasure in a neural pathway. By blocking the receptor sites,
an antagonist prevents the normal neurotransmitter
Figure 18.2 Reward pathway from acting on them. Therefore normal transmission of
nerve impulses in that neural pathway is greatly reduced
or brought to a halt.
Addiction
Many drugs used to treat neurotransmitter-related
When rats were allowed to press a lever that stimulated disorders are very similar in chemical structure to
area N in their brain, they became addicted to this form neurotransmitters. Therefore some are employed to act
of stimulation of their pleasure centre. Even when kept as agonists where appropriate and others are used as
on a starvation diet, they chose the brain-stimulation antagonists.
lever over food until completely exhausted. Female rats,
addicted in this way, even abandoned their young in
order to gain access to the lever.
Inhibitors
Other drugs act in a different way by preventing
the removal of the neurotransmitter from synaptic
clefts. Some of these work by inhibiting the enzyme
normal situation without drug effect of agonist drug effect of antagonist drug
natural natural
natural chemical in chemical
synaptic cleft chemical
agonist
drug
antagonist
membrane of drug
postsynaptic
neuron
receptor
site
normal cellular activity enhanced cellular activity cellular activity blocked
266
Figure 18.3 Action of agonist and antagonist
(e.g. cholinesterase) that would normally degrade the neurotransmitter (for example, norepinephrine) by
the neurotransmitter (for example, acetylcholine). presynaptic neurons.
Others act by inhibiting the normal reabsorption of
Related Information
Examples of neurotransmitter-related Parkinson’s disease
disorders and their treatment Parkinson’s disease (PD) is a major cause of neurological
disability in older people. It is caused by the loss of
Alzheimer’s disease neurons in the midbrain that synthesise dopamine. In
Alzheimer’s disease (AD) is a form of dementia that addition to activating the brain’s reward pathway, this
is incurable and eventually terminal (see also page neurotransmitter has other functions. For example,
243). The suf ferer’s brain gradually degenerates (see it plays a key role in the control and coordination of
Figure 18.4). One theor y proposes that AD is caused movement. Therefore, severe loss of dopamine-producing
by the loss, in several par ts of the brain, of neurons cells can lead to:
that make acetylcholine. Under normal circumstances ● muscle tremors (shaking)
this neurotransmitter crosses synaptic clef ts, binds to ● r igidity (stif fening of muscles)
receptors and allows ner ve impulses to be transmitted ● dif f iculty in the initiation of movement and speech
through neural pathways. Af ter transmission of the ner ve ● slowness of movement
impulse, acetylcholine in a synaptic clef t is broken down ● reduced control over f ine motor movement.
by the enzyme cholinesterase (see page 254). These are all symptoms typical of PD.
Several drugs have been developed to treat AD by acting
as cholinesterase inhibitors. The intention is that the
Production of dopamine
use of one of these drugs will br ing about an increase Under normal circumstances, dopamine is synthesised
in concentration of acetylcholine in the suf ferer’s from tyrosine (an amino acid), as shown in Figure 18.5.
synaptic clef ts and lead to improved communication The dopamine is stored in vesicles in neurons in
between those neurons that use acetylcholine as a preparation for release into a synaptic clef t when required
neurotransmitter. These treatments do improve symptoms
in some patients and may temporar ily slow down the
tyrosine
progression of the condition, but for the most par t they
have not been found to be ver y ef fective.
enzyme 1
healthy brain advanced AD
L-dopa
enzyme 2
dopamine
breakdown by monoamine oxidase

(following nerve impulse transmission)
breakdown products
of dopamine
267
Figure 18.4 Degeneration of the brain Figure 18.5 Synthesis and breakdown of dopamine ➜
to combine with receptors and br ing about transmission It is thought to be caused by a combination of inherited
of a ner ve impulse. Following transmission, dopamine factors and environmental factors (such as the use of
is broken down by an enzyme called monoamine oxidase cer tain recreational drugs) that lead to a biochemical
(MAO). imbalance in the brain.
Treatment Dopamine antagonists

L-dopa An overactive dopamine system contr ibutes at least
Patients suf fer ing PD are not given dopamine to treat in par t to some forms of schizophrenia when specif ic
their condition because dopamine cannot cross the pathways in the brain (responsible for memor y, self-
blood–brain barr ier (see page 251). However, L-dopa can awareness and social behaviour) become blocked. Drugs
be used as a treatment because it is able to pass through that act as dopamine antagonists br ing about relief of
the barr ier and is then conver ted to dopamine. In a this condition.
healthy brain, dopamine is released only in ver y specif ic
Generalised anxiety disorders
areas. Unfor tunately, the use of L-dopa is accompanied by
unpleasant side ef fects such as involuntar y movements Chronic anxiety is the central component of this group of
and nausea because it penetrates the whole brain. conditions which is expressed by symptoms of impaired
concentration, sleep disturbance, irr itability, restlessness
Inhibition of MAO and panic attacks.
Drugs that act by inhibiting the action of MAO (see
Serotonin and GABA agonists
Figure 18.5) are also used in the treatment of PD.
By preventing the action of MAO, an MAO inhibitor Serotonin is a neurotransmitter with var ious functions
makes any dopamine that is present (for example, from including regulation of mood, appetite, sleep and
administered L-dopa) have a longer-lasting ef fect. intestinal movements. It is known to contr ibute to
feelings of well-being when it is at the optimum level.
Dopamine agonists When an imbalance occurs, this may tr igger a generalised
Agonists that mimic the action of dopamine are also used anxiety disorder.
to treat PD but they can lead to unpleasant side ef fects. GABA is the body’s chief inhibitor y neurotransmitter.
When it combines with its receptors, it causes an
Potential use of adult stem cells inhibitor y ef fect on neurotransmission. GABA agonists
Researchers have taken samples of skin cells from many (such as valium) are drugs that mimic the ef fect of
patients at an early stage of PD. These skin cells are GABA. By suppressing neural f iring, they inhibit other
being used to produce induced plur ipotent stem cells neurotransmitters when an imbalance exists. This results
(see chapter 1 page 12) which are then induced in vitro in a reduction of anxiety in the patient.
to develop into cultures of brain neurons af fected by PD.
This work enables scientists to compare normal with Norepinephrine and beta blockers
diseased nerve cells and gain a better understanding of Norepinephrine is a neurotransmitter that promotes
why dopamine-synthesising neurons die and PD develops. the transmission of ner ve impulses, some of which have
In the future, stem cells themselves may be used to treat an excitator y ef fect on cer tain parts of the body. For
PD which at present remains incurable. example, it brings about the increase in force and rate of
Schizophrenia hear tbeat that occurs dur ing the ‘f ight or flight’ response
(see chapter 14). An imbalance in norepinephrine is
Schizophrenia is a complex psychotic disorder in which
also implicated in generalised anxiety disorders. This
the suf ferer’s contact with reality may become highly
condition can be treated using beta blockers which bind
distor ted. The condition is character ised by:
with receptor sites and prevent them being stimulated by
● emotional instability norepinephrine. This treatment results in a signif icant
● delusions reduction in anxiety and in some cases it may even
● hallucinations enhance performance such as that of musicians, actors
● social apathy or dancers suf fer ing from per formance anxiety (stage
● progressive deter ioration of personality. fr ight).
268
Depression that it remains in the synaptic clef ts of the depressed

person’s neural circuits.
MAO and re-uptake inhibitors
Ver y low levels of serotonin and/or norepinephr ine of ten Some drugs called selective serotonin re-uptake
cause depression. Many prescr ibed antidepressant drugs inhibitors (such as Prozac) decrease the re-uptake of
alter serotonin levels. Like dopamine and norepinephr ine, serotonin, making it stay longer in the synapses. Other
serotonin is broken down by monoamine oxidase (MAO). antidepressant drugs inhibit re-uptake of both serotonin
Therefore MAO inhibitors are used to prevent the and norepinephr ine enabling them to sustain their
breakdown of serotonin and increase the length of time ef fects for a longer per iod.
Mode of action of recreational stimuli – sounds, colours, and sense of time seem
altered)
drugs ● behaviour (the person is able to stay awake for
Many people choose to alter their state of consciousness longer and talk about him/herself endlessly).
by using recreational drugs (some legal, some illegal) Recreational drugs interact with neurotransmitters in
that affect the transmission of nerve impulses in the different ways. For example, they can:
reward circuit of the brain. The subsequent alteration in
the person’s neurochemistry may lead to changes in: ● stimulate the release of a natural neurotransmitter
● act as an agonist by initiating the action of a
● mood (the person feels happier, more confident or neurotransmitter
more aggressive) ● act as an antagonist by binding with receptors and
● cognitive thinking (the person becomes poorer at blocking the action of a neurotransmitter
carrying out complex mental tasks such as problem ● inhibit the re-uptake of a neurotransmitter
solving and decision making) ● inhibit the breakdown of a neurotransmitter by an
● perception (the person misinterprets environmental enzyme.
Related Information
Examples of mode of action of recreational
drugs
Cocaine
This drug, extracted from the coca plant, acts as a
psychostimulant. It produces feelings of well-being in
the user and gives the person the impression that they
have untapped reser ves of energy available to tackle
any task with conf idence (usually overconf idence – see
Figure 18.6). Cocaine can induce hallucinations, such as
the sensation that there is sand under the skin sur face
or that thousands of bugs are crawling over it. Continued
use of cocaine leads to social withdrawal, depression and
dependence on ever higher dosages. People intoxicated
with cocaine, especially ‘crack’ (the form that is smoked),
readily become aggressive and violent. They also r isk
taking a life-threatening overdose.
Figure 18.6 Cocaine-fuelled delusions of self-impor tance 269

➜
Cocaine works by inhibiting the dopamine re-uptake The nature and intensity of the ef fects of cannabis depend
channels (see Figure 18.7). This creates an over on:
abundance of dopamine in neural pathways such ● the dose
as the reward circuit and causes them to become ● the strain of the source plant
overstimulated. Drugs such as cocaine that can increase ● the method of consumption
normal dopamine levels by more than 10 times can cause ● the physical and mental state of the user.
severe mental disorders such as paranoia.
Like cigarette smoke, cannabis smoke contains chemicals
Cannabis that cause lung diseases. Heavy use of cannabis may tr igger
schizophrenia in some susceptible individuals.
This drug, obtained from the Indian hemp plant (see
Figure 18.8), acts f irst as a pleasurable stimulant and Cannabis contains chemicals called cannabinoids, which
then as a sedative. work by binding to cannabinoid receptors. Under normal
conditions, these receptors become occupied by a natural
The user may feel excited, restless and uninhibited at f irst
neurotransmitter dur ing the transmission of ner ve impulses
but later feels drowsy and normally falls into a deep sleep.
cocaine absent cocaine present
arrival of nerve impulse

at axon terminal
vesicle containing
dopamine
dopamine
re-uptake of re-uptake
dopamine channel blocked
by cocaine
dopamine dopamine
transporter released
(channel
forming cocaine
protein)
dopamine
released
over-abundance of
dopamine builds up
dopamine combines
with receptor on
postsynaptic
membrane
nerve impulse many more

transmitted impulses
transmitted
270 Figure 18.7 Ef fect of cocaine on dopamine re-uptake

that br ing about control of muscles and regulation of pain

sensitivity. Since cannabis mimics these ef fects, its use
in a medical context (for example, in the treatment of
multiple sclerosis and ar thritis) is approved of in many
countr ies.
MDMA
MDMA (‘ecstasy’) is a synthetic drug sold illegally in
tablet form (see Figure 18.9). It makes the users feel
more aler t, energetic and in tune with their surroundings
and the people around them. Dancing for long periods
while under the influence of MDMA increases the chance
of overheating and ser ious dehydration. Other adverse
ef fects include anxiety, panic attacks and feelings of
paranoia and depression dur ing the days that follow use
of the drug.
Canna
Serotonin is a natural neurotransmitter whose ef fects

include a contribution towards feelings of well-being (see
bis sat
also page 268). Under normal circumstances re-uptake of

serotonin occurs in synapses following the transmission
iva
of ner ve impulses. MDMA works by inhibiting serotonin’s

re-uptake, thereby causing an increase in its level in
synaptic clef ts and promoting temporar ily heightened
sensations of well-being.
Nicotine
This drug is the active ingredient of tobacco plant
products. Cigarette smokers repor t that nicotine has a
soothing ef fect and helps them to concentrate. However,
Figure 18.8 Indian hemp plant nicotine is highly addictive and cigarette smoke (see
Figure 18.10) is responsible for many diseases, including
lung cancer.
Under normal circumstances nicotinic acetylcholine
receptors on brain neurons become occupied by the
Figure 18.9 MDMA tablets
Figure 18.10 Not long to go! 271

➜
BAC = 0
BAC = 0.10
DEPENDABLE
BAC = 0.15
DEVILISH
BAC = 0.20
DIZZY
BAC = 0.25
DAZED
BAC = 0.30
DISGUSTING
(BAC = blood alcohol concentration

in g/100 ml blood) DEAD DRUNK
272 Figure 18.11 Stages of drunkenness

neurotransmitter acetylcholine causing transmission of brain var ies from feelings of relaxation and good humour
ner ve impulses. Such transmission leads to an increase af ter a dr ink or two, to complete loss of consciousness
in the level of dopamine, serotonin and norepinephr ine. following excessive consumption (see Figure 18.11).
Since nicotine mimics this ef fect and increases the Shor t-term ef fects of dr inking alcohol include decreased
activity of these nicotinic acetylcholine receptors, inhibitions, motor impairment, confusion and drowsiness.
one of its ef fects is to increase the level of dopamine in Long-term ef fects include liver and brain damage.
the reward circuit of the brain, resulting in euphor ia,
GABA receptors normally have an inhibitor y ef fect
relaxation and eventual addiction.
on neural pathways when the neurotransmitter GABA
Alcohol binds to them. Alcohol mimics the effect of GABA and
reduces feelings of anxiety. Alcohol can also lead to
Alcohol, which is a depressant, is one of the most widely
activation of dopamine-synthesising neurons thereby
used recreational drugs in the world. Although its use is
elevating dopamine levels and making the person feel
almost universally legal, it is not safer than many other
good temporar ily while the reward system in the brain
drugs that remain illegal. The ef fect of alcohol on the
continues to be over-stimulated.
Related Topic
Alcohol and reaction time Reaction time is the time between the occurrence of an
event and a person’s reaction to it. Figure 18.12 shows the
Alcohol is a water-soluble drug that is rapidly absorbed
results of an investigation into the ef fect of alcohol on
through the mouth and stomach linings into the blood. It
the reaction time to complete a simulated emergency stop
af fects brain functions within minutes of consumption.
Key
100 unimpaired
reaction time
impaired
reaction time
80
percentage of subjects tested
60
40
20
0
0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09
BAC (g/100 ml blood)
Figure 18.12 Ef fect of alcohol on reaction time 273

➜
of a vehicle. 10% of subjects were found to show impaired the safer option might be to brake, provided that there
reaction time with a BAC (blood alcohol concentration) are no vehicles behind the dr iver. The average dr iver’s
as low as 0.02 g/100 ml. From a BAC of 0.06 g/100 ml, reaction time in such a situation doubles from 1.5 to
the number of subjects showing impaired reaction time 3.0 seconds when their BAC is 0.08 g/100 ml. Exper ts
outnumbered those showing no impairment. estimate that this makes the person about four times
more likely to crash than if their BAC had been zero.
Dr iving In UK the maximum legal BAC threshold for dr iving is
Imagine a person dr iving down a street when a car 0.08 g/100 ml (i.e. 80 mg/100 ml blood). Some people
suddenly pulls out of a dr iveway in front of them. The would like to see this limit reduced to a lower level or even
dr iver is faced with a choice of braking or swer ving round to zero.
the vehicle. However, there could be oncoming traf f ic and
Drug addiction and tolerance become less sensitive to the agonist drug. This leads
to drug tolerance because a larger dose of the drug is
Drug addiction can be defined as a chronic disease now required to stimulate the reduced number of less
that causes the sufferer to compulsively seek out and sensitive receptors. This process involving a decrease
use the drug regardless of the consequences. Although in number and sensitivity of receptors as a result of
the initial decision to take the drug is voluntary, repeated exposure to a drug acting as an agonist is
subsequent changes that take place in the person’s brain called desensitisation (and is also referred to as drug
soon override their self-control. This makes the person tolerance).
incapable of resisting the overpowering urge to take
more of the drug.
Drug sensitisation
A drug user is said to have built up a drug tolerance Repeated use of a drug that acts as an antagonist (see
when their reaction to an addictive drug is found to page 266) by blocking certain neuroreceptors prevents
have decreased in intensity compared with previous the normal neurotransmitter from acting on them.
times, even though the concentration of the drug has The nervous system compensates for the reduced
remained unaltered. A larger dose is now required to stimulation of the receptors by increasing their number.
bring about the original effect. In addition, the receptors themselves become sensitive
Drug desensitisation to the antagonist drug.
Repeated use of a drug that acts as an agonist (see This process involving an increase in number
page 266) results in certain neuroreceptors (e.g. those and sensitivity of receptors as a result of repeated
that promote the release of dopamine) being repeatedly exposure to a drug acting as an antagonist is called
stimulated, causing increased feelings of well-being sensitisation. It appears that sensitisation results in
or euphoria. The nervous system compensates for other psychological changes, which transform ordinary
the overstimulation of these receptors by reducing sensations of ‘wanting’ into excessive drug-craving and
their number. In addition, the remaining receptors addiction.
274
Related Topic
Genetic components of addiction Cocaine addiction

Dopamine transporter (DAT) is the channel-forming
Alcoholism protein that controls the re-uptake of dopamine through
The development of alcoholism among individuals with a its channels (see Figure 18.7) following the transmission
family histor y of this problem is found to be four to eight of ner ve impulses at synapses. Cocaine blocks the re-
times more common than among individuals with no such uptake channels and this leads to an over-abundance of
family histor y. So is alcoholism the result of inherited dopamine in the synaptic clef ts and over-stimulation of
factors or environmental factors (such as imitation of the brain’s reward pathway.
parental behaviour) or a combination of both?
A mutant allele for the gene that codes for DAT has now
Twin studies been identif ied. People who are homozygous for this
mutant allele are found to make less DAT and to be even
Many studies involving identical and non-identical twin
more susceptible to the ef fects of cocaine. Evidence
pairs have been carr ied out. The results indicated that
suggests that they are 50% more likely to become
when one identical twin was addicted to alcohol, there
addicted to the drug (if they choose to consume it).
was a high probability (about 76%) of the other twin
also being an alcoholic. When one non-identical twin Work with mice
was an alcoholic, on average, the other twin ran a much
Several genes involved in drug addiction have been
lower r isk (about 26%) of being an alcoholic. These
discovered in mice. Some examples are given in
studies suggest that there is a large genetic component
Table 18.1. Researchers are attempting to identify
to addiction to alcohol. Clearly environmental factors
comparable genes in humans. This work may eventually
also play a large par t in the process. This relationship is
lead to the development of treatments for drug addiction.
thought to be true for other addictive drugs.
It must be kept in mind that inher iting some genes for
susceptibility to addiction does not mean that addiction is
inevitable. Environmental factors also contr ibute largely
to the r isk of addiction.
Type of mutant mouse Result

Bred with defective Per2 gene Animals found to consume three times more alcohol than
normal mice
Bred to lack serotonin receptor gene Htr1b Animals display a greater urge to consume alcohol and
cocaine than normal mice
Bred to lack cannabinoid receptor gene Cnr1 Animals display a reduced reward response to morphine
compared with normal mice
Table 18.1 Genetic factors involved in drug addiction in mice
275
Related Topic
Drug rehabilitation programmes Psychological dependency

Drug rehabilitation programmes (‘rehab’) are forms This problem is addressed by encouraging addicts to carr y
of treatment for people who have become addicted to out some or all of the following:
psychoactive drugs. The aim of the programme is to
enable the addict to recover and to cease substance ● Stop using the drug.
abuse. Some programmes specialise in combating ● Disassociate themselves from fr iends who are still
physical tolerance, others in dealing with psychological using the drug.
dependency. ● Adopt the twelve-step programme.
● Receive counselling to identify behaviours and
problems related to their addiction.
Physical tolerance ● Examine their habits and lifestyle and make changes
This problem is tackled using medications. For example, in relation to their addiction.
methadone and buprenorphine are used to treat people ● Accept that complete abstention from the drug (not
addicted to opiates such as heroin and morphine. The moderate use of it) is necessar y for recover y.
medications are intended to stabilise the patient, prevent ● Adopt a cognitive-behavioural approach to prevent
withdrawal symptoms and br ing use of the illegal drug relapse in the future.
to a halt. The patient, sustained on doses of medication,
Success of the cognitive-behavioural approach depends
is able to lead a ‘normal’ life, free from the pressure of
on the patient’s ability to deal ef fectively with high-
f inancing the next ‘f ix’.
r isk, relapse-provoking situations. The former addict is
instructed on how to develop and employ problem-solving
and decision-making skills in order to resist temptation
and prevent a relapse.
1 a) Identify the chemical substances made in the to and stimulating cer tain receptors is called an
hypothalamus that function like neurotransmitters agonist/antagonist.
and act as natural painkillers. (1) d) A chemical that binds to specif ic receptors and
b) Give T WO examples of situations to which the body blocks the action of the neurotransmitter is called an
would respond by increasing the level of production agonist/antagonist.
of these chemicals. (2) e) Some drugs work by promoting/inhibiting the action
2 Choose the correct answer from the underlined choice of enzymes that degrade neurotransmitters.
given in each of the following statements. (7) f) The euphor ic ef fect of recreational drugs is the
a) Acetylcholine/dopamine is a neurotransmitter that result of altered neurotransmission in the brain’s
activates the reward pathway and induces feelings of cognitive/reward pathway.
pleasure. g) An increase in the number and sensitivity of
b) Endorphin production is increased/decreased in neurotransmitter receptors as a result of exposure
response to physical and emotional stress. to a drug acting as an agonist is called sensitisation/
c) A drug that mimics a neuroreceptor by binding desensitisation.
276
8 To prevent continuous stimulation of ______ neurons,

addiction endorphins presynaptic neurotransmitters are ______ from the synaptic clef t by
agonist enzyme receptor ______ action or re-uptake.
altered excitator y recreational 9 The cumulative ef fect of a ser ies of ______ stimuli that
antagonist glial removed together br ing about an impulse is called ______.
back inhibiting re-uptake 10 In a ______ neural pathway, ner ve impulses from

behaviour mimics reverberating several sources meet at a common destination.
body mood reward 11 In a ______ neural pathway, the route along which a
clef t myelin sensitisation ner ve impulse travels divides, allowing information to
pass to several destinations.
converging myelination sheath
dendr ites neurons speed 12 In a ______ pathway, later neurons form synapses with
earlier ones, allowing the ner ve impulse to be sent
desensitisation neurotransmitter summation
______ through the circuit.
diseases painkillers support
13 The ability of brain cells to become ______ as a result
diverging plasticity tolerance
of new environmental experiences is called ______ of
dopamine postsynaptic weak response.
Table 18.2 Word bank for chapters 17–18 14 ______ are chemicals that function like
neurotransmitters and act as natural ______.
1 The ner vous system is composed of sensor y, inter and
motor ______ which transmit electr ical signals, and 15 ______ is a neurotransmitter secreted by neurons in the
______ cells. brain’s ______ pathway which is activated by cer tain
types of benef icial behaviour.
2 Each neuron consists of a cell ______ and associated
ner ve f ibres: one axon and several ______. 16 Chemicals that act like neurotransmitters are used in the
treatment of some disorders. An ______ is a chemical
3 An axon is surrounded by a ______ sheath of insulating that stimulates specif ic receptors on postsynaptic
mater ial whose presence greatly increases the ______ neurons and ______ the action of the naturally
at which ner ve impulses can be transmitted through the occurr ing neurotransmitter. An ______ blocks receptors
f ibre. and prevents the neurotransmitter from acting on them.
4 Glial cells ______ neurons, maintain a stable 17 Some drugs act by ______ the enzyme that degrades the
environment around neurons and produce the myelin natural neurotransmitter or by inhibiting its ______.
______.
18 Many ______ drugs br ing about their ef fect by af fecting
5 ______ continues until adolescence. The myelin the brain’s reward circuit thereby alter ing the person’s
sheath is destroyed by cer tain ______ causing loss of ______, perception and ______. The drugs may act as
coordination. agonists, antagonists or inhibitors.
6 A synaptic ______ is a tiny space between two neurons. 19 An increase in the number and sensitivity of
Information is transmitted at a synapse by a chemical neurotransmitter receptors following repeated exposure
called a ______ being released from vesicles in the to a drug that is an antagonist is called ______ and
______ neuron. The neurotransmitter combines with leads to ______.
______ sites on the postsynaptic membrane.
20 A decrease in the number and sensitivity of
7 The receptor determines whether the signal generated is neurotransmitter receptors following repeated exposure
______ or inhibitor y. to a drug that is an agonist is called ______ and leads to
drug ______.
277
1
19 Communication and social behaviour
Chapter Head
Humans are social animals. The vast majority prefer part but as the months go by the baby narrows down
to live in communities rather than lead a solitary its interest to selected people. Specific attachment to
existence. To operate successfully the members of a the mother (and a few other carers) becomes evident
group must be able to communicate with one another. between 6 and 9 months. As specific attachment
Such social behaviour involves transmitting and develops, indiscriminate attachment weakens. This is
receiving information using signs and signals (such as shown in Figure 19.1 where attachment is measured
verbal, written and body language). Communication as the amount of protest shown by the baby on being
between humans begins at birth and continues separated from the carer.
throughout life.
Infant attachment
7 indiscriminate attachment
attachment intensity score (units) specific attachment
In humans the period of dependency of the infant upon 6
the adult members of the species is a very lengthy one. 5
Under normal circumstances nature provides the newly
4
born infant with a mother (or other primary carer)
who is able to satisfy the baby’s needs such as food and 3
contact comfort. The newborn baby’s activities, such 2

as suckling, clinging and crying, help to trigger in the 1
mother a desire to protect and care for the child. As she
0
does, a strong emotional tie develops between the baby
5–8
9–12
13–16
17–20
21–24
25–28
29–32
33–36
37–40
41–44
45–48
49–52
and the mother. The tie that binds the baby to the carer
is called infant attachment. age (weeks)
At first, attachment is indiscriminate on the baby’s Figure 19.1 Infant attachment
Related Topic
Contact comfort
For many years it was thought that babies became
attached to their parents principally because the parents
provide food. However, in recent years, the additional
impor tance of contact comfort has become appreciated.
This was f irst demonstrated exper imentally using infant
monkeys exposed to two types of substitute mother. The
f irst ‘mother’ was constructed of bare wire; the second
‘mother’ was made of the same wire covered in thick, sof t
towelling (see Figure 19.2).
In one exper iment, only the bare wire mother supplied

food. However, once the infant monkeys had f inished
feeding, they spent much more of their time clinging to
the cloth mother than the bare one. They always ran to Figure 19.2 Contact comfor t with cloth ‘mother’
278 the cloth mother when fr ightened. Cuddling the cloth
Communication and social behaviour
mother’s sof t towelling material calmed the infants down. Ef fects of depr ivation
These exper iments demonstrate a high-level need for In a var iation of the exper iment illustrated in Figure 19.2,
close bodily contact and the sensation of physical well- some infant monkeys were denied access to the cloth
being and safety. Contact comfor t similarly plays a basic mother. Such deprivation of contact comfort led to the
role in establishing attachment between human infants development of disturbed adults. Some were over-
and their pr imar y carers. aggressive, others withdrawn and uncommunicative and
all became inadequate parents. Human infants who
receive plenty of food and warmth but are denied contact
comfor t may also exhibit maladjusted behaviour.
The ‘strange situation’ Importance of secure attachment

The ‘strange situation’ is a research tool devised to The long period of dependency on the parent provides
investigate infant attachment. It allows experts to assess the infant with a secure base from which to operate. The
whether a child is securely or insecurely attached to more secure the attachment of infant to their mother,
their primary carer. It involves the following sequence the more likely they are to explore their immediate
of events (each of which lasts 3 minutes, except the first environment, all the time safe in the knowledge that
one): the parent is present as a haven of safety. During
these explorations the infant will come across many
● A mother brings her baby into an unfamiliar room opportunities for learning and for the development of
supplied with toys. cognitive abilities. The number and variety of these
● The mother and child are left alone in the room and opportunities, and the level of stimulation that they
the child may explore and investigate the toys if they provide, will depend on what the infant’s environment
wish to do so. has to offer (see Figure 19.3). A securely attached infant
● A stranger enters the room, talks with the mother is more likely to benefit from these opportunities than
and after a few moments tries to play with the infant. an insecurely attached one.
● The mother leaves the baby with the stranger who
tries to interact with the child. (This stage is called Infant attachment is of fundamental importance
the first separation episode.) because it lays down the foundations for the formation
● The mother returns and plays with the child while of stable, trusting relationships in the future. In
the stranger leaves. (This stage is called the first addition it provides the basis for social, linguistic
reunion episode.) and intellectual skills to develop and be built upon
● The mother leaves the baby alone. (This stage is for the rest of life. Happy, securely attached infants
called the second separation episode.)
● The stranger returns and tries to engage with the
child.
● The mother returns as the stranger leaves. (This
stage is called the second reunion episode.)
This series of episodes allows hidden observers to study

the behaviour of the baby:
● with the mother
● with the stranger
● alone.
Table 19.1 shows different categories of children

279
identified by the experts. Figure 19.3 Early development of cognitive abilities
Type of attachment
Secure Insecure
Detached Resistant
(avoidant) (ambivalent)
Response to toys and Child explores freely Child hardly explores Child does not explore
chance to explore new and plays with toys if or plays with toys freely or play with toys
environment mother is present regardless of who is even when mother is
present present
Response to Displays major distress Displays indif ference Displays major distress
departure of mother or mild distress
Response to presence Resists of fers of Accepts comfor t from Resists of fers of
of stranger in absence comfor t from stranger stranger if required comfor t from stranger
Examples of baby’s of mother
behaviour dur ing
Response to mother’s Goes to mother Ignores mother or Displays inconsistent
the ‘strange
return immediately for approaches her while behaviour by seeking
situation’
comfor t and then calms looking away and resisting comfor t
down and returns to at the same time (e.g.
play approaches mother
to be picked up but
then struggles to
be released again);
may show signs of
resentment or anger
and tr y to hit mother
Baby is more attached Baby treats mother Baby is more attached
to mother than to and stranger equally to mother but in
stranger. This situation in a detached manner. an erratic way. This
is thought to ar ise This situation is situation is thought
because the mother is thought to ar ise to arise because the
capable, demonstrative because the mother is mother tends to be
of her love and inept and insensitive irr itated by the baby.
Psychologists’ interpretation from the study
sensitive to the baby’s to the baby’s needs, On occasions she is
of many case histor ies
needs (she can of ten though not rejecting insensitive to the
interpret these from him/her. (Of ten baby’s needs and, by
the baby’s var ious the mother lacks expressing controlled
forms of cr ying). perception and does anger towards the
not know how to baby, is rejecting him/
relieve the baby’s her.
distress.)
Table 19.1 Results of the ‘strange situation’
280
begin life with an excellent start. Insecurely attached levels of social competence than those exposed to
infants deprived of normal social contact, affection and authoritarian or permissive control. Children with
cuddling often suffer long-lasting ill effects. authoritative parents are more likely to develop into
self-reliant, academically successful and socially accepted
Socialisation and social adults.
competence Method of control Behaviour adopted by parent

Socialisation is the gradual modification of a Author itar ian • exer ts an extremely high level of
developing individual’s behaviour in order to (‘unreasonably control
accommodate the demands of an active social life str ict’) • never explains the reasons for the
led within the community. Compared with other rules to the child
mammals, young humans are dependent on adults for a • expects the child to obey orders
very long period of development during childhood and without question
adolescence. This is advantageous in that it provides • does not engage in verbal give
time for socialisation and learning to occur and for and-take
• demonstrates little or no warmth
social competence to develop. Social competence is
towards the child
the foundation upon which successful interaction with
• uses shaming or withdrawal of
others depends. A socially competent person possesses a love as a means of discipline
combination of attributes, such as those shown in
Author itative • is warm, nur tur ing and
Table 19.2.
(‘demanding but emotionally suppor tive towards
responsive’) the child
Attribute Details
• sets limits, rules and high
Behavioural Ability to react appropr iately in social standards and explains the
skills situations, for example by being reasons for them
sympathetic, assertive, submissive, • gives direction and expects
forceful, af fectionate, demanding, responsible behaviour and
modest, approving or suppor tive, cooperation in return
depending on circumstances • explains the consequences of
Cognitive Ability to gain the knowledge and develop unacceptable behaviour
skills the problem-solving skills necessar y to • reasons with the child and
function ef fectively, for example to gain encourages verbal give-and-take
employment within society • demonstrates respect for the child
as an independent individual
Emotional Ability to form stable relationships and
Permissive • is warm and nur tur ing towards the
skills demonstrate feelings towards others
(‘excessively child
Table 19.2 Attr ibutes of social competence lenient’) • is responsive to the child’s needs
and wishes
Methods of control • does not set limits, lay down rules
or assign responsibilities
The quality of a developing child’s social competence • adopts a ‘no discipline’ approach
is affected by the method of control adopted by their and does not tr y to keep the child
parents (and other influential adults in their life). Three under control
different methods of control are shown in Table 19.3. • does not encourage the child
Research indicates that children raised by parents who to aim for high standards of
exert authoritative control, on average, show higher behaviour
• allows the child to regulate their
own behaviour
Table 19.3 Methods of control
281
1 What is social behaviour? (1) c) Suggest ONE possible ef fect on individuals in later
2 a) In general, what is meant by the term infant life of social depr ivation dur ing infancy. (1)
attachment? (1) 4 a) Identify T WO methods of parental control that can
b) In addition to food, what other factor, provided by influence the social competence of a developing
the pr imar y carer, is important in the development child. (2)
of infant attachment? (1) b) Give T WO dif ferences between the two methods of
3 a) Name T WO forms of insecure infant attachment. (2) control you named in a). (2)
b) Describe br iefly the way in which psychologists
believe that each of these ar ises. (4)
Effect of communication their degree of like or dislike for something). It may

display emotion (for example, as a facial expression).
Communication is the exchange of information, Non-verbal communication comes in many forms.
facts, feelings, ideas and opinions between people.
Most people spend a large part of their time each day Smiling in infants
communicating (at various levels) with other people. To A baby is capable of taking part in a non-verbal
do so they make use of verbal and non-verbal means of dialogue based on sounds and visual signals such as
contact. smiling. At about 6 months, smiling becomes a selective
social act normally reserved for the mother (and other
Non-verbal communication close members of the family) whom the baby recognises
Non-verbal communication (sending and receiving (see Figure 19.5). Smiling is important because it makes
wordless messages) plays an important part in the the baby especially appealing and lovable, thereby
establishment of relationships between individuals. strengthening the bond between the carers and the
On some occasions, it reinforces verbal messages, on baby. This is of survival value because it helps to ensure
others, it adds to the information being transmitted that the baby (who is almost totally helpless at this
(see Figure 19.4). This form of communication may stage) will receive the food, care and attention that they
also indicate an individual’s attitude (for example, need.
www.Car toonStock.com
282
Figure 19.4 Non-verbal communication Figure 19.5 Smiling as a social act
Facial expressions
A facial expression is the result of the activity of many
‘Don’t hurt him!’
muscles. It conveys the emotional state of the individual
to observers. Smiling, for example, indicates pleasure
shared by the people exchanging smiles. Many other
facial expressions are also used to act as indicators of
emotions. The six main types are shown in Figure 19.6.
It is interesting to note in particular the varied use to
which the eyes and mouth are put to convey these non
verbal messages. Cartoonists are especially skilful at
employing facial expressions to communicate attitudes
and emotions essential to the understanding of a
joke (see Figure 19.7). Surveys show that on average
Figure 19.7 Car toonists use facial expressions to good ef fect
women are better than men at correctly recognising the
emotion represented by a facial expression.
making contact with those of another person. This
Eye contact maintenance of gaze between two people is called eye
The eyes are used to communicate information by contact (see Figure 19.8). People who are in a close
the length of time that they are allowed to continue relationship exchange glances and meet one another’s
direct gaze much more often than people who are
strangers. Extended eye contact is one method by which
people communicate sexual interest in one another.
Therefore strangers (who wish to remain strangers)
feel embarrassed if eye contact extends beyond a mere
exchange of glances. They tend to play safe by avoiding
unnecessary eye contact.
happiness sadness
disgust fear
anger surprise
Figure 19.8 Eye contact can be used to communicate sexual
283
Figure 19.6 Facial expressions indicating emotion interest
Related Topic
Looking as signalling One way of indicating this is for A to catch B’s eye. If,
in return, B wishes to signal that she is not interested
In addition to various eye movements such as eyes
in making contact, she will avoid his gaze. Then A will
popping, eyes narrowing, etc., the eyes are used to
either give up or persist. If he persists, B may then decide
convey signals by simply looking at another person in a
to adopt an angr y def iant stare to signal rejection. On
meaningful way. For example, winking (see Figure 19.9)
the other hand, B may wish to signal that she does want
at someone only slightly known to you might indicate
to make contact with A and therefore will allow him to
friendliness (or over fr iendliness!) and the wish to become
catch her eye. This may lead to a conversation (verbal
better acquainted. On the other hand, winking discreetly
communication).
at a good fr iend in the company of others might indicate
the mutual enjoyment of a pr ivate joke.
person A person B
A signals interest
by attempting to
make eye contact
with B
B signals lack
of interest by
avoiding A’s
gaze
Figure 19.9 Winking provides a quick signal

A persists and
B responds
When the process of looking normally at another person by adopting
a defiant
continues for a per iod of time beyond that required stare
for routine information gathering, the signals become
loaded with fur ther meaning. Consider an individual
(e.g. male person A in Figure 19.10) who wants to make
contact with another individual (e.g. female person B). Figure 19.10 Looking as signalling
284
Related Topic
Body language Figure 19.11) all give clear signals. Other gestures
indicate emotional states of mind. For example,
Of ten people are unaware of the extent to which they
continuous drumming of the f ingers or f idgeting suggests
use their bodies to communicate with one another non-
tension or boredom; wr inging of the hands indicates
verbally. Such body language is expressed by posture,
anguish; clenched f ists signal pent-up anger. Some
gestures and certain other activities. Several examples of
people engage in cer tain activities that give an indication
posture and the possible attitude of the person adopting
of their state of mind. Nail-biting and hair-chewing are
the bodily position are given in Table 19.4.
outward signs of ner vous tension or stress.
Posture Suggested attitude

Sprawled back in easy chair Relaxed
with legs spread
Sitting up stif fly with legs Tense
together
Standing with feet apart and Confrontational
arms akimbo
Slumped for ward in chair with Bored or sad
arms folded
Lying curled in ‘fetal’ position Fr ightened
Table 19.4 Communication by posture

Some gestures have def inite meaning. Beckoning
someone forward, nodding the head and pointing (see Figure 19.11 Pointing is an ef fective gesture
Physical proximity between the two participants; decrease in the distance

Within each culture there is a generally accepted may indicate sexual attraction or aggression (in other
distance that two people keep between them while words an invasion of someone’s ‘personal space’ – the
conducting a normal conversation. Increase in this invisible ‘bubble’ that surrounds each human body).
distance may suggest dislike or even repugnance
Related Topic 80
percentage of time during which
Effect of physical proximity on eye

eye contact was maintained
contact 70
In an exper iment, a group of female volunteers each
agreed to take par t in three br ief inter views with a female
stranger who would be sitting at a dif ferent distance
60
from the volunteer each time. The inter viewer had been
trained to stare continuously at the volunteer dur ing each
inter view. Each volunteer’s percentage eye contact was
measured for each inter view. The results are shown as a 50
graph in Figure 19.12. 3.0 2.5 2.0 1.5 1.0 0.5
distance between subjects (m)
Figure 19.12 Ef fect of physical proximity on eye contact 285

➜
As distance between the two people decreased, the aggression or sexual attraction. In each case the specially
amount of eye contact also decreased. At a distance of trained inter viewer continued to stare while talking; the
0.5 m the two people were physically and psychologically volunteer appeared uncomfor table and embarrassed, and
much closer than the generally accepted level for tr ied to avoid making eye contact.
strangers. They were within the region associated with
Touching The process of touching may communicate different

Touch is a powerful form of non-verbal meanings including support (see Figure 19.13),
communication. An impersonal situation, such as an playfulness, appreciation, affection and sexual interest.
interview for a job, may begin or end with a handshake
between employer and potential employee. If the person
Mode of deliver y of speech as a form of non
gets the job and a satisfactory working relationship verbal communication
develops over time, the dominant employer may feel Tone of voice, accent, emphasis, speed of delivery and
free to touch, as a supportive gesture, the arm, for timing of speech are auditory signals that depend
example, or shoulder of the subordinate employee. on spoken language for their existence. They often
However, the employee knows that they are not free to indicate the person’s frame of mind. A monotonous
touch their employer. voice suggests fatigue and boredom, loudness may
indicate anger and high speed often signals excitement
An increased amount of touching occurs between or nervousness.
people who have close personal relationships, such as
the members of a family.
Verbal communication
Language
A language is a system that combines basic sounds (in
themselves meaningless) into spoken words usually
also represented by written symbols (see Figure 19.15).
These sounds and symbols represent information that
can then be arranged into simple categories (words)
and more complex hierarchies (phrases, sentences
and paragraphs). Since the sounds and symbols have
meaning to the members of the society in question,
they enable its members to express thoughts and
feelings and convey information to one another. The
ability to make sophisticated use of language is one
of the distinguishing features that make much of our
Figure 19.13 Touching as a form of non-verbal communication behaviour unique and set us apart from other animals.
Related Topic
Go and no-go touch areas touchable areas. Other par ts, especially those close to sex
organs, are regarded as ‘vulnerable’ and untouchable by
The results of detailed research indicate that people
most people. Figure 19.14 shows the results of a sur vey
regard dif ferent areas of their body in dif ferent ways with
carr ied out among a large group of college students.
respect to accessibility to others to touch. In general,
Some par ts of the body were touchable to one categor y of
arms and shoulders are regarded as ‘non-vulnerable’,
person but not to another.
286
where where
mothers fathers
may may
touch touch
where where
friends partners
of the of the
same opposite
sex may sex may
touch touch
‘taboo’ area commonly ‘neutral’ area commonly ‘accessible’ area commonly

touched in less than touched in 25%–50% touched in over 75%
25% of students in survey of students in survey of students in survey
Figure 19.14 Go and no-go touch areas 287

Transfer of information
On a short-term basis, language allows humans to
convey to one another the information necessary for
successful day-to-day living. We are able, for example,
to request our basic needs, express feelings about others
and handle a variety of interpersonal situations. We
soon learn how to employ certain linguistic strategies
to our advantage. For example, adopting a friendly
tone of voice, speaking clearly and not too quickly,
varying the tone of voice and listening to other people’s
point of view are all techniques employed by good
communicators.
On a long-term basis, language allows the transfer and

receipt of information from generation to generation.
For most people in Britain this occurs during 11 or
more years of schooling, often followed by several years
of further education.
Knowledge possessed and discoveries made by one

generation are passed on by spoken and written word
to the next generation without each new generation
having to make each discovery for itself. This saves
time and enables successive generations to go on and
make new discoveries which then become added to the
existing body of human knowledge.
Figure 19.15 Language as written symbols Thus language promotes the acceleration of learning
and the development of intellect. It allows us to make
detailed plans that, in turn, affect and benefit future
generations by promoting their continued cultural and
scientific progress and social evolution.
1 a) In general, what is meant by the term communication referr ing to T WO examples of ways in which
in relation to human social behaviour? (1) information can be communicated by non-verbal
b) Identify the T WO types of communication. (2) means. (2)
c) Why is smiling by an infant of sur vival value? (2) b) Other people are descr ibed as having an ‘excellent
2 a) Give T WO examples of emotions that are of ten telephone manner’. Suggest T WO possible features
indicated by facial expressions. (2) of such a person’s verbal skills that this might
b) For each of these expressions, descr ibe the state of include. (2)
the person’s mouth when the facial expression is 4 a) What is language? (2)
adopted. (2) b) State T WO methods by which language can be
3 a) Some people f ind it more dif f icult to communicate transferred from person to person. (2)
impor tant information to a stranger by telephone c) Why is transfer of language from generation to
than by talking face to face. Suggest why, by generation impor tant? (2)
288
Effect of experience and group behaviour
20
1 Effect of experience and group behaviour
Chapter Head
Learning Effect of practice on motor skills

The term learning is often used to mean knowledge Once a motor skill (e.g. riding a bicycle) has been
gained by study or the act of gaining knowledge by mastered, repeated use of it promotes the establishment
studying. However, psychologists define learning as any of a motor pathway in the nervous system. Repetition
relatively permanent change in behaviour that occurs of the skill is thought to result in an increased number
as a direct result of experience. of synaptic connections being formed between the
neurons in the pathway. This leads to the formation
of a ‘motor memory’ for the skill. Practice improves
performance; lack of practice results in the skill
becoming ‘rusty’ (but not being completely lost).
Learning using a finger maze

exit
The apparatus shown in Figure 20.1 is used by
Investigation
a learner who is blindfolded throughout the

exper iment. The learner’s task is to proceed
through the maze from entrance to exit using
the tip of their foref inger. The obser ver’s job is
to measure the time taken for each tr ial by the
learner. The procedure is repeated to give a total
of 10 trials. Table 20.1 lists some design features
(and precautions) and the reasons for adopting
them in this investigation.
Af ter several tr ials, the time required to pass

through the maze is found to decrease until
eventually a minimum is reached. When graphed,
the results give a learning cur ve (see Figure 20.2).
From this investigation it is concluded that practice
improves performance of a motor skill. In the
case of the f inger maze, a best time is eventually
reached and this cannot be improved upon. By space to comfortably
accommodate one finger tip
tr ial-and-error learning, the person has formed a entrance
picture (cognitive map) of the route through the
maze in their ‘mind’s eye’ and a certain minimum
Figure 20.1 Finger maze
amount of time is required to physically run the
f inger tip through it.
➜ 289
Same learner used for each group of 10 tr ials; same To ensure that only one var iable factor is included in
f inger used each time; same design of maze used the investigation
each time
10 tr ials per learner To give learner oppor tunity to reach best score
Learner blindfolded throughout all 10 tr ials To prevent learner improving their per formance
ar tif icially
Path between matchsticks just wide enough to To prevent two f ingers being used to explore
accommodate one f inger tip comfor tably simultaneously two routes at a junction and establish
the correct one more quickly
Experiment repeated with many learners and To obtain a more reliable set of results
learning cur ves compared
Table 20.1 Design features for investigation
Types of learning curve

The cur ve shown in Figure 20.2 from the results of a f inger maze investigation char ts the decrease in time taken
as an indication of the ef fect of practice on learning. Counting the decreasing number of errors made by the
learner in successive tr ials is an alternative method of carr ying out this investigation and gives a learning cur ve
of similar shape.
Learning can also be measured as an increase in the number of correct responses achieved per unit time (e.g.
the number of three-lettered words that a person unfamiliar with a keyboard can key in in 1 minute from a long
list). When graphed, the results give a second type of learning cur ve (see Figure 20.3). Again practice is found to
improve per formance. Eventually, af ter much practice, a maximum level of per formance is reached that cannot
be improved upon. However skilled the person, there is a physical limit to the number of words that he or she can
key in in 1 minute.
200 10
180 9
number of words correctly keyed in
160 8
140 7
time taken (seconds)
120 6
100 5
80 4
60 3
40 2
20 1
0 0
1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 7 8 9 10
trial number
trial number
Figure 20.2 Learning cur ve of typical set of results Figure 20.3 Second type of learning cur ve
290
Imitation Imitation is an especially effective method of learning

if the expert breaks up the demonstration into several
Children learn by observing and imitating (copying)
small parts and allows the learner to try to repeat
adults and other older children. This often occurs
what they have seen after each part. Learning by
during play. A child dressing up in adult clothes
imitation is further promoted if the expert is perceived
(see Figure 20.4) is imitating the behaviour of adult
by the learner as an attractive role model whose
relatives and friends. Learning by imitation is not
status is enhanced by the possession of the skill being
restricted to children. Throughout life, many aspects
demonstrated.
of human behaviour are learned by observing and
imitating the behaviour of others. When faced with a For most people, copying a demonstration is the
new task (e.g. learning how to operate a smart phone), preferred method of learning a new skill. To try to
it is much easier and takes less time to learn by compensate for the lack of a live expert to imitate,
watching and then imitating an expert than by reading instruction manuals often include many diagrams of
the manual. human models which aid comprehension.
Imitation of social skills

Behaviour acquired by imitation is not restricted to the
learning of physical tasks and skills; it is also involved in
the learning of social skills and attitudes. Parents, other
adults and perhaps older brothers and sisters provide
children with a variety of possible models to imitate.
Children tend to imitate many aspects of cultural and

social behaviour. Once learned, many of these values
and traditions (such as being kind and generous to
others, belonging to a certain religion and so on)
might be adopted for life. Some might be accepted
during childhood (for example, the belief that smoking
damages health) but be rejected during adolescence
(when smoking might be made to seem attractive by a
peer group). However, in adulthood the person might
resume the original belief. Most people eventually
embrace many of the cultural and social traditions and
Figure 20.4 Learning by imitation values held by their parents.
Speed of performance of a new task

The task in this investigation is learning to f ind the way through a tr ial-and-error cavity maze. The class, working
Investigation
in pairs, is divided into two groups, A and B. Each pair in group A is given a copy of Figure 20.5 and timed as they
carr y out the task by following wr itten instructions. Each pair in group B is timed as they f irst watch the teacher
demonstrate the task and then carr y it out by imitation.
On average it is found that the members of group B are faster at per forming the task than those in group A. It is
therefore concluded that imitation is more ef fective than following a set of wr itten instructions. It is interesting
to note that no signif icant dif ference is found between the groups in terms of the number of errors made dur ing
the f irst attempt or the reduction in number of mistakes made dur ing the second attempt. This suggests that the
two methods of instruction are equally ef fective.
➜ 291
maze board
cavity 1 Ask your partner
to use the two
paper clips to fit a
maze blank over
the maze board.
maze blank
2 Start at the green arrow.

Join the dots with pencil
lines to get home. You
are only allowed to go
horizontally or vertically.
If your pencil goes down
into a cavity, return to
the previous square and
continue in a different
direction.
3 Every time you go

down into a cavity,
you have made a
mistake. Ask your
partner to keep a
record of the
number of errors
that you make.
4 Having reached
home, ask your
partner to remove
the maze blank
and clip a new
maze blank onto
the maze board.
new maze
blank for
second trial
5 Repeat steps 2 and 3.
Figure 20.5 Investigation procedure

292
Social techniques sexual drive and curiosity. The effect of motivation

Among adults, imitation is an especially effective on an animal’s ability to learn can be investigated
method of learning certain social techniques. For by comparing hungry and well-fed rats, which must
example, tone of voice, sympathetic manner and oral negotiate a maze before receiving a food reward.
delivery carrying authority cannot be described easily. From the graph in Figure 20.7, it can be seen that the
They need to be experienced to be learned. number of errors made per trial by the hungry rats
quickly decreased since they were motivated to learn.
The performance of the well-fed rats failed to improve
Trial-and-error learning because they lacked motivation.
If a rat is placed in a specially designed box (see
Figure 20.6) it responds in various ways such as
exploring the box, touching the floor and leaning
200
against the sides. Sooner or later the animal pushes well fed rats
average number of errors

the lever and food immediately appears in the food
150
tray. If the rat is only rewarded with food when it
presses the lever, it soon learns to associate its own
100
behaviour with the delivery of food. hungry rats
50
0
1 2 3 4 5 6 7 8 9 10 11 12
trial number
Figure 20.7 Ef fect of motivation on learning
lever Reinforcement of behaviour

food reward In the above examples, the behaviour pattern (trial
hungry rat and-error learning) has positive consequences for
the animal (it gets fed). The behaviour is therefore
Figure 20.6 Tr ial-and-error learning in rats repeated and, as a result, becomes reinforced.
Reinforcement (see Figure 20.8) is the process that
Motivation makes an organism tend to repeat a certain piece of
Motivation is the ‘inner drive’ that makes an animal behaviour. During reinforcement, the reinforcer (such
want to participate in the learning process. Animals as a food reward) increases the probability of the
are motivated by many factors such as hunger, thirst, response being repeated.
reinforcement
stimulus response
(e.g. motivational (e.g. behaviour reinforcer
factor such as such as rat (e.g. food reward)
hunger or curiosity) pressing lever)
Figure 20.8 Reinforcement
293
Related Information
Positive and negative reinforcement Negative reinforcement occurs when something
unpleasant or negative is brought to a halt when the
Positive reinforcement occurs when something pleasant
organism makes a par ticular response, thereby increasing
or positive is received by the organism af ter a par ticular
the chance of the response being repeated. For example,
response has been made, thereby increasing the chance
a human discover ing that a painkiller cures a headache is
of the response being repeated. For example, a hungr y
likely to use this remedy when pain str ikes in the future.
rat rewarded with food for pressing the lever repeats the
(Negative reinforcement should not be confused with
operation.
punishment, which is the application of a penalty or
sanction following the wrong response by the learner.)
Related Information
Continuous and intermittent reinforcement Superstition
Behaviour is said to be continuously reinforced when the People develop a superstition as a result of a favourable
response is always reinforced (for example, the hungr y event (which has occurred merely by chance) apparently
rat receives food ever y time it presses the lever). occurr ing in response to some piece of behaviour by
the person. The person repeats the behaviour and
Behaviour is said to be intermittently reinforced if the occasionally the favourable event also occurs thereby
response is reinforced on only some of the occasions that it reinforcing the probability of the person repeating the
occurs. For example, a child’s mother is not always present behaviour. A gambler who blows on the dice muttering
to reward him or her with praise for following the Green ‘Luck, be a lady tonight’, might be rewarded with a
Cross Code. However, the influence of the reinforcements win suf f iciently of ten to reinforce the belief that their
that do occur is (hopefully) strong enough to persist and behaviour is af fecting the response.
make the child cross the road safely when on their own.
Shaping of behaviour trainer reinforcing successive approximations of the

desired response. Normally the desired response would
Shaping is the process by which a desired pattern of
have a low probability of occurring spontaneously.
behaviour is eventually obtained from the learner by the
Case Study Shaping in learning

The proper use of a knife and fork by a child has also features in toilet-training, learning to dress
almost no probability of occurring of its own oneself, tying shoe laces and many other skills.
accord. By using shaping, the parents direct
the child’s behaviour along the desired route Animals
by praising (and therefore reinforcing) those Animal trainers use shaping to teach dolphins to
responses that are approximations of the required balance balloons on their snouts, pigeons to dance in
response. patterns, and parrots to ride bicycles. An especially
useful application of shaping is the training of dogs to
The flow chart in Figure 20.9 shows how
act as the eyes of the blind (see Figure 20.10).
reinforcement of responses that are successively
more and more similar to the final desired response
294 results in the child learning the new skill. Shaping
knife and fork held in separate hands
reinforced by praise
knife and fork held the correct way up
successive
knife and fork used to pick up some food approximations
of desired
response
knife and fork used to pick up
suitable amounts of food
food cut up and prepared
by child for her/himself
entire operation managed final desired Figure 20.10 Guide dogs are trained by shaping
by child unaided response
Figure 20.9 Shaping a desired response
Extinction of behaviour pressing the lever fails to give food, the rat is found to
press it less and less frequently. Eventually the rat does
Extinction is the name given to the eventual
not press it at all and the earlier behaviour pattern
disappearance of a behaviour pattern when it is no
(which had been reinforced continuously and learned
longer reinforced. Consider the rat in Figure 20.6,
quickly) is said to have become extinct.
which has learned that pressing the lever gives food
every time. If this rat is now put into a situation where
Related Information
Effect of intermittent reinforcement on
behaviour pattern but also take much longer to give it
extinction
up completely. They tend to persist in giving the lever an
occasional ‘hopeful’ press. They had learned not to expect
Rats that have learned that pressing the lever sometimes food ever y single time and are not so easily put of f by the
gives food (in other words, have been subjected to lack of reward. Thus, intermittent reinforcement is more
intermittent reinforcement) take longer to learn the resistant to extinction than continuous reinforcement.
295
Related Topic
Rewarded and unrewarded behaviour

Responsible parents tr y to teach their children the
dif ference between acceptable and unacceptable
behaviour. They tend to encourage the development of
‘good’ behaviour by reinforcing it. For example, parents
might be of the opinion that being truthful, showing
consideration for others and tr ying hard at school are
all forms of desirable behaviour. They would therefore
reinforce these behaviour patterns with rewards such as
attention, praise, outings, bir thday presents and pocket
money.
Parents also have to deal with their children when their

behaviour is unacceptable. In theor y, behaviour that
goes unrewarded should become extinct. In some cases
unacceptable behaviour (such as a child nagging a parent
for sweets ever y time they arrive at the supermarket
checkout) does disappear provided that the parent can
summon the patience to ignore it and ensure that the
behaviour always goes unrewarded.
However, most parents f ind that many forms of
unacceptable behaviour shown by their children are
impossible to ignore. Responsible parents normally
attempt to modify such behaviour on the par t of their Figure 20.11 Grounded!
children by resor ting to punishment. This might involve
a long talk followed by removal of the rewards stated
above, accompanied perhaps by fur ther sanctions such as
being ‘grounded’ (see Figure 20.11).
Generalisation Discrimination
Generalisation is the ability to respond in the same way Discrimination is the ability to distinguish between
to many different but related stimuli. In an experiment, different but related stimuli and give different
an 11-month-old boy who liked furry animals was put responses. Discrimination is taught by reinforcing
in a room with a tame white rat. He reached out for the the desired response (for example, a mother giving
rat showing no fear. Each time just as his hand went her baby hugs and kisses when she is addressed as
to touch the animal, a very loud noise was deliberately ‘Mama’) and by not reinforcing the wrong response
made using a steel bar. As a result, the child developed (for example, the father not responding when he is
an aversion for white rats. It was also discovered that the addressed by the baby as ‘Mama’).
child had developed a fear for many other furry objects
The baby is soon able to tell the difference between
that he had not seen before (see Figure 20.12). The
similar stimuli (such as adult family members) and
spread of the response (in this case fear) to different but
determine whether or not the correct stimulus (the
related stimuli is an example of generalisation.
mother) is present before saying ‘Mama’. The baby has
learned to discriminate. Learning to discriminate is an
296 essential part of a child’s preparation for coping with
everyday life. It is important for the child to appreciate,

for example, that some loud noises such as thunder
Social influence
do not indicate danger, that some green fruit such as Social groups
Granny Smith apples are ripe and ready for eating and
Human beings are social animals. A large part of the
that some dogs are unfriendly and might bite.
average person’s life is spent interacting with other
stimulus response by child people who act as stimuli and offer responses to the
person’s behaviour. Almost without exception, people
belong to one or more social groups of different types
reaches out and sizes. These could include, for example, the family,
to rat showing the teenage gang, the sports team, the trade union, the
no fear
army regiment, the cub pack, the football supporters’
club, the political party, the religious sect, the school
orchestra, and so on.
Social groupings provide people with a feeling of

refuses to belonging and of being accepted. Many groups are
reach out
and shows held together by rules, written and unwritten, and
fear of
white rats symbolism such as a uniform that sets the group apart
from the non-members. Groups provide support for
their members especially in times of need. However,
the group also affects the behaviour of the individual
members by setting standards and even deciding what
refuses to
reach out should be done in certain situations. An individual who
and touch
any furry accepts these conditions must behave in the same way
object as the other members of the group.
Social facilitation
One of the factors that motivates many people is the
Figure 20.12 Generalisation need for status. They want to impress and be admired
1 a) Give an example of a motor skill. (1) 5 Choose the correct answer from the underlined choice
b) Why does practice improve the performance of motor given in each of the following statements. (6)
skills? (1) a) Knowledge/learning is a change in behaviour as a
2 a) With reference to the learning of a new skill, what is result of exper ience.
meant by the term imitation? (1) b) Repeated use of a motor skill establishes a motor/
b) Give an example of a cultural tradition that a person sensor y pathway in the ner vous system.
may learn by imitation from their parents and adopt c) Learning can be measured as an increase/a decrease
for life. (1) in the number of errors made per unit time.
3 a) What is meant by the term reinforcement? (1) d) For most people, the preferred method of learning a
b) What name is given to the rewarding of behaviour new skill is to copy a demonstration/manual.
that approximates to the desired behaviour? (1) e) If a behaviour pattern is not rewarded, it is likely to
c) What is meant by the extinction of behaviour? (1) become extinct/reinforced.
4 a) Def ine generalisation and give an example to f) When a child who has been bitten by a dog fears all
illustrate your answer. (3) dogs, this is called discr imination/generalisation.
b) Def ine discrimination and give an example to
illustrate your answer. (3) 297
by other members of a social group to which they Familiar ity with the task
belong. It is interesting therefore to consider whether or The presence of others is especially effective at
not the presence of other people affects an individual’s improving an individual’s performance if they are
performance. Research shows that in competitive already very familiar with the task or the task is very
situations, subjects do tend to work faster and achieve simple. However, the presence of others tends to
a higher level of productivity and energy output than interfere with progress when the person is trying to
they do when working alone. learn something new or perform a more complex
task. Then they imagine that the others are monitoring
Figure 20.13 shows the results from a survey done by
their progress, feel stressed and tend to make more
an athletics club on its members (in the absence of
mistakes. Both of these aspects of social facilitation are
spectators). The presence of other competitors seems
summarised in Figure 20.14.
to spur the individual on to heights not achieved on
their own. This increased performance in the presence
of others (especially when the situation is competitive)
is called social facilitation. Even in non-competitive
presence of others
situations, individuals are found to achieve more when
working in a group than when working in isolation.
70
increased
60 arousal
of individual
average time required to complete
50
400 metres (seconds)
40
30 impaired
enhanced
performance of

performance of
20 complex or

simple or familiar
unfamiliar
tasks by individual
tasks by individual

who feels confident
10 who feels
and self-assured
apprehensive

and
0 self-conscious

competing competing training training
with alone with alone
others others
Figure 20.13 Ef fects of social facilitation Figure 20.14 Contrasting aspects of social facilitation
Related Topic
Group pressure advance to give wrong answer C. When it came to the

turn of number eight (the exper imental subject), they
The following exper iment was set up to investigate the
were placed in the position of having to disagree with
ef fect on an individual of major ity opinion even when it
the major ity or doubt their own judgement suf f iciently
was clearly contrary to the fact. A group of eight people
to conform to group opinion. The exper iment was carried
together in the same room were invited in turn to solve
out on many subjects and repeated many times with each
the problem of visual judgement shown in Figure 20.15.
one. The results are shown in Figure 20.16.
Unknown to the eighth member of the group, the other
seven were par t of the exper iment and had agreed in
298
Dur ing the discussion sessions that followed the The process of exer ting such a strong influence on an
investigation, some interesting points emerged. Many of individual that they abandon their own views or ideas in
the subjects who had agreed with the major ity had not favour of those held by the social group is called group
done so simply to br ing the confusing episode to an end. pressure. If susceptible individuals can be pressur ised
At the time they had expressed genuine respect for the into agreeing to the wrong answer in a straightforward
(wrong) judgement of the major ity! They had come to the situation like the one above, the possibility of influencing
conclusion that there had been something wrong with a person’s judgement is increased dramatically when the
their own eyesight or that they had been exper iencing an controversial subject is an opinion or an attitude.
optical illusion.
held on to their own opinion during every trial and

C refused to be swayed by the majority
X B varied in their response
A
gave in every time and agreed with
the opinion of the majority
28%
27%
To which line is X equal in length? 45%
Figure 20.15 Visual judgement problem Figure 20.16 Results of group pressure exper iment
Deindividuation
In real life, group pressure is a powerful force. People
find it difficult to resist going along with the decisions
made by the group. Members of a group conform
because they:
● identify with other group members and want to be

like them
● desire the personal gain that membership often
brings
● want to be liked and not to be thought of as
unpopular.
Once under the influence of group pressure, individuals

think and act differently from the way that they would
if they were on their own. Decisions and behaviour now
depend less on the members’ individual personalities Figure 20.17 Deindividuation
and more on the collective influence of the group.
This loss by an individual of personal identity when Deindividuated people feel indistinguishable from
in a group is called deindividuation and it can lead to others in the group and are more likely to act
299
diminished restraints on behaviour. mindlessly and do things that they would never
consider doing on their own. This often takes the possible protection from punishment. If the members
form of anti-social, aggressive behaviour by a ‘faceless’ of a mob do not have to worry about being caught
mob whose members have temporarily lost awareness breaking the law, then they are more likely to pursue
of their own individuality and responsibility (see their irresponsible activities.
Figure 20.17).
Influences that change beliefs
Risk-taking
The members of a group will take bigger risks when in Internalisation
the group than when alone. A gang of teenagers will Internalisation is the process by which an individual
taunt and dare one another into pursuing extreme incorporates within him or herself an enduring changed
activities (such as playing ‘chicken’ on a railway line, set of beliefs, values or attitudes. Radio, television and
experimenting with drugs, fighting a rival gang and so newspapers subject listeners, viewers and readers to
on) which they would be unlikely to attempt on their a mass of information that may or may not become
own. internalised. By attempting to persuade people to
change their current beliefs and adopt a different set
Anonymity of beliefs, politicians, government departments and big
Being an anonymous member of a crowd (for example, businesses try to effect internalisation.
by being hooded or masked) offers the individuals
Related Information
Examples of internalisation ● presents a two-sided argument but favours one side
● gives convincing reasons for suppor ting their side
Televised party political broadcast ● appears to be an exper t on the subject being
Politicians regularly use this method to tr y to persuade discussed.
viewers to vote for their par ty. Research shows that

However, it is debatable how many people actually alter
viewers are most likely to pay attention if the presenter:

their beliefs and vote for the speaker’s political par ty,
● has a pleasant appearance having been fully convinced that unemployment will
● has a good vocal deliver y, including warmth and
humour
300 Figure 20.18 Anti-drugs message Figure 20.19 Anti-smoking message

plummet, the economy will boom, the national debt will Internalisation and advertising
shr ink and so on. One method of adver tising attempts to create a feeling
Health warning of dissatisfaction with our current situation while at
the same time presenting us with the allegedly better
Drug education programmes and anti-smoking campaigns
alternative. By this means big businesses tr y to br ing
of ten use posters (see Figures 20.18 and 20.19) in an
about internalisation and persuade us that a par ticular
attempt to persuade people to alter their behaviour.
brand is faster, smoother, sexier, cheaper, etc. than the
‘inferior’ one that we are currently using. Table 20.2 lists
a few products and suggests the altered belief that the
advertiser is hoping to create.
Product Altered belief intended by advertiser

Foodstuf f It will nour ish the family and make the person who ser ves it a ‘good mum or dad’
Soap powder It will get clothes cleaner and sof ter than ever before
Item of clothing It will make the wearer fashionably dressed and the envy of their peer group
Toothpaste It will clean teeth and reduce f illings because it has been proved scientif ically
Double-glazing It will improve the quality of life and make the neighbours envious
Af tershave It will make a man smell so sexy that women will f ind him irresistible
Cosmetic It will make a woman look so beautiful that men will f ind her irresistible
Motor car It will of fer excitement, freedom and escapism previously only dreamed of
Table 20.2 The power of advertising
Identif ication enhance their self-esteem by behaving, in fantasy and/or

Identification is the process by which person A in real life, as if they actually were person B. To a greater
deliberately changes their beliefs in an attempt to be like or lesser extent most people tend to identify with one or
person B. Person B exerts a strong influence over person more of the personalities who dominate the worlds of
A, because A admires B enormously and makes B the entertainment, big business, politics and sport.
object of hero-worship. In extreme cases, A attempts to
Related Information
Identification and advertising
One method of adver tising sets out to exploit the process
of identification by employing a personality with whom
an enormous number of potential customers (with
disposable income) identify. This ‘superstar’ is made the
focus of a massive, nationwide (or even international)
adver tising campaign cover ing all sections of the mass
media.
If the superstar is a reasonable actor, he or she will be

able to endorse the product with apparent sincerity,
perhaps combined with humour and other memorable
Figure 20.20 Celebr ity endorsement 301
➜
gimmickr y. Such endorsement greatly increases the
product’s desirability (see Figure 20.20). It is therefore
eagerly purchased by the legions of fans who identify with
Ms or Mr ‘Wonder ful’ and their achievements, beliefs and
lifestyle.
1 a) Give T WO examples of a social group. (2) 3 a) Give T WO reasons why the members of a social group
b) Give ONE reason why people like being members of a agree to go along with the decisions and rules made
social group. (1) by the group. (2)
2 a) Explain what is meant by the term facilitation. (2) b) What term is used to refer to the loss by an individual
b) Under what circumstances does competition not of personal identity when subjected to group
result in increased per formance? (1) pressure? (1)
5 The per iod of ______ of children on adults is lengthy

attachment emotions linguistic and provides the basis for the development of social,
author itative explore motivated ______ and intellectual skills.
beliefs extinction motor 6 Compared with author itar ian and permissive control of
cognitive facilitation non-verbal children, ______ control normally produces adults with
greater social ______.
communicate foundations pathway
competence groups reinforcement 7 People communicate by verbal and ______ means.
competitive identif ication response 8 Adults communicate non-verbally by employing facial

contact identity shaping expressions, eye ______, postures and touching to
express attitudes and ______.
deindividuation imitating signals
dependency internalisation stable 9 Adults communicate ______ by using language that
allows information to be transferred from generation
depr ived learning verbally
to generation, thereby accelerating ______ and the
development of culture and social evolution.
10 Once a ______ skill has been mastered, its repeated use
1 Humans are social animals and ______ with one another results in the establishment of a motor ______.
throughout life by means of signs and signals.
11 Most people learn a new task more quickly by ______ an
2 The strong emotional tie that binds a baby to the mother exper t than by following written instructions.
is called ______.
12 Dur ing tr ial-and-error learning, animals are ______ to
3 Early infant attachment allows ______ to be laid for the learn by factors such as hunger and thirst.
development of ______ relationships later in life.
13 ______ is the process that makes an animal tend to
4 Securely attached infants are likely to ______ their repeat a cer tain piece of behaviour.
environment which helps them to develop their
______ skills; insecurely attached infants, ______ of 14 ______ is the process by which a desired pattern of
normal social contact, tend to suf fer long-lasting ill behaviour is eventually obtained from the learner by
ef fects. the trainer reinforcing successive approximations of a
302 desired ______.
15 ______ is the eventual disappearance of a behaviour with the behaviour of the group regardless of whether it
pattern when it is no longer reinforced. is acceptable or not.
16 Most people belong to one or more social ______ of 19 ______ is the process by which an individual
dif ferent types and sizes. incorporates within her/himself a set of ______.
17 In general, individuals are found to perform familiar 20 Dur ing ______, individuals deliberately change their
tasks better in ______ situations than on their own. beliefs to tr y to be like some other person whom they
This process is called social ______. strongly admire.
18 ______ occurs when an individual undergoes loss of
personal ______ and is unable to resist going along
Chapters 14–20 Figure 20.21. State your reasons for carr ying out the
var ious procedures that would need to be adopted
1 Imagine that you are at home when the doorbell r ings. You dur ing this investigation. (10)
respond by heading towards the door. Identify FOUR areas 4 In an investigation into memor y span, 40 students were
of the cerebral cor tex shown in Figure 14.15 on page 213 asked to listen to and then attempt to write down each
that are in use dur ing this entire operation and, for each, of several ser ies of letters, the f irst series containing
br iefly descr ibe the role that it plays in the process. (8) three letters. The results are shown in Figure 20.22.
2 Descr ibe the antagonistic nature of the autonomic a) What relationship exists between the number of
ner vous system and compare the ef fect of its two letters in a ser ies and the percentage of students
branches on heart beat and blood distr ibution. (10) able to remember the series? (1)
3 Design an investigation into the ef fect of perceptual b) i) What was the best memor y span recorded in this
set on the perception of the ambiguous picture in exper iment?
ii) How many students possessed this memor y
span? (2)
c) i) What was the poorest memor y span recorded in
this experiment?
ii) What percentage of students possessed this
memor y span? (2)
100
90
percentage of students able
80
70
to remember series
60
50
40
30
20
10
0
3 4 5 6 7 8 9 1011 1211 10 9 8 7 6 5 4 3
number of letters in series
Figure 20.21 Figure 20.22 303

➜
d) i) Does presenting the ser ies of letters in d) i) Why are the two types of distraction investigated
descending order of length produce a dif ferent separately rather than simultaneously?
set of results from presenting them in ascending ii) Why is a fresh set of problems needed for each
order of length? tr ial?
ii) Explain how you arr ived at your answer to i). (2) iii)Identify a possible source of error in this
e) Give a reason for the adoption of each of the exper iment.
following design features in this investigation: iv) Suggest T WO ways in which the reliability of the
i) nonsense groups of letters used to make up the exper iment could be improved. (5)
ser ies rather than proper words 6 Table 20.5 shows the results from four sur veys
ii) each ser ies of letters read out by the same tester investigating the incidence of schizophrenia among
at a uniform speed twins. The members of each pair of twins were raised
iii)40 students invited to take par t rather than just together by their natural parents.
a few. (3) a) What is schizophrenia? (1)
5 In an exper iment to investigate minor plasticity of b) Calculate the average percentage (accurate to
response of the brain, six students were each given two decimal places) of twin pairs af fected with
2 minutes to correctly solve as many mathematical schizophrenia when the twins are i) identical,
problems as possible under three dif ferent sets of ii) non-identical. (2)
conditions. The results are shown in Table 20.4. c) What conclusion about the par t played by inher ited
a) Identify the i) auditor y, ii) visual distraction. (2) factors can be drawn from these f indings? (1)
b) i) Which student(s) demonstrated plasticity of d) Which sur vey’s data do you consider to be:
response of the brain? i) the most reliable
ii) Explain how you arr ived at your answer. (2) ii) the least reliable?
c) Br iefly explain how such plasticity is thought to iii)Explain your choices for i) and ii). (4)
occur. (4)
Student Number of problems solved in 2 minutes

Silence + uninterrupted Car alarm + uninterrupted Silence + flashing light
lighting lighting
A 20 18 21
B 12 12 11
C 14 3 5
D 18 5 7
E 22 23 21
F 25 8 6
Table 20.4
Sur vey Identical twins Non-identical twins

Number of twin pairs Percentage of affected Number of twin Percentage of affected
twin pairs pairs twin pairs
1 21 66.69 60 4.67
2 41 68.32 101 14.91
3 41 76.07 115 14.06
4 268 85.16 685 14.52
304 Table 20.5
7 Figure 20.23 shows the results from a sur vey in which a 8 Two exper iments investigating the ef fect of physical
large number of mothers of newborn babies were asked to proximity on eye contact were carr ied out using male
indicate the side on which they normally held their infant. inter viewers (trained to stare continuously) f irst with
male volunteers and then, later, with female volunteers.
baby held on left side baby held on right side The results are summar ised in the graph in Figure 20.25.
70
60
100 80 60 40 20 0 20 40 60 80 100
percentage of time during which

eye contact was maintained
percentage of mothers
male
volunteers
= right-handed mothers = left-handed mothers
50
Figure 20.23
40
a) i) On which side did the major ity of r ight-handed
mothers hold their babies?
ii) On which side did the major ity of lef t-handed
female
mothers hold their babies? (2) volunteers
30
Based on these results, scientists constructed the 3.0 2.5 2.0 1.5 1.0 0.5
hypothesis that the mother’s hear tbeat of fers a familiar
rhythm and comfor ts the infant. This hypothesis was put distance between subjects (m)
to the test in a large maternity hospital over a per iod of

several days. Babies in group A were exposed night and Figure 20.25
day to the sound of normal heartbeat; those in group a) i) State the reduction in the percentage of eye
B were exposed to irregular sounds. The bar graph in contact time that occurred when distance
Figure 20.24 shows the results. decreased from 3 to 0.5 metres for male
b) Draw T WO conclusions from the graph. (2) volunteers.
c) Was the hypothesis suppor ted? (1) ii) By how many more times did the percentage eye
d) Identify THREE factors that should be kept constant contact time decrease for female volunteers over
dur ing an investigation of this type. (3) the same distance? (2)
b) i) Give a possible reason why male volunteers show
= time spent crying
a decrease in percentage eye contact time as
70 70 distance decreases.
= increase in weight
60 60 ii) Give an additional possible reason why female
volunteers show an even greater decrease
increase in weight (g)
50 50 in percentage eye contact time as distance

percentage time
decreases. (2)
40 40
9 Each of the following paragraphs describes a situation
30 30
involving some aspect of behaviour. Give a br ief
20 20 explanation for each using one or more of the terms that
you have met in chapter 20.
10 10
a) Cer tain animals can be trained to do ‘clever’ tricks.
0 0 A group of rats, for example, were taught to cross a
group A group B drawbr idge, climb a ladder, crawl through a tunnel,
slide down a chute and f inally press a lever for a food
Figure 20.24 pellet. (2) 305
➜
b) Many years ago, cigarette smoking was regarded d) A small girl was bitten by a Scots terr ier (a small
by most people as a harmless habit. A sur vey taken black dog). She developed a fear of all small black
at the time showed that there was a much higher dogs. Her younger brother was bitten by a West
incidence of smoking among people who had grown Highland terr ier (a small white dog). He developed a
up in a family of smokers than those raised by non fear of all dogs. (2)
smoking parents. (1)
10 The posters shown in Figures 20.18 and 20.19 on page
c) A girl suf fer ing from anorexia ner vosa was admitted
300 are designed to attempt to change people’s beliefs.
to hospital and put in a private room on her own
a) For each poster, state a possible version of the
without magazines, mobile phone or T V. She was
altered belief. (2)
only allowed a visitor, a phone call, a magazine or a
b) What name is given to this type of social
T V programme if she agreed to eat something. She
influence? (1)
gained 3 kg in 10 days. (2)
306
Immunology and
Unit
4 Public Health
Immunology and Public Health Unit 4
21 Immune system
The body defends itself against disease-causing immune system. Immunity is the ability of the body to
organisms (pathogens), some toxins (poisons produced resist infection by a pathogen or to destroy the organism
by living things) and cancer cells by means of its if it succeeds in invading and infecting the body.
Line of Specific or Mechanisms employed Location
defence non-specific in Figure
21.1
First Non-specific Use of skin as a physical 1
barrier to keep pathogens 1 skin
out trachea 3
Secretion of acid by internal 2
lining of stomach to kill
microbes boil in skin 4
Secretion of mucus by 3
epithelial lining of trachea thymus
gland
to trap microbes
5
Second Non-specif ic Inf lammator y response 4
bone
Cellular response – 4 marrow
phagocytosis 6
Cellular response – action 4
of natural killer cells
Third Specif ic Response by T lymphocytes 5
from thymus gland
(see page 321)
Production of antibodies by 6 2 stomach
B lymphocytes from bone

marrow (see page 323)
Figure 21.1 Lines of defence in the human body
Table 21.1 Three lines of defence
mucus and
fold gastric juice
secreted
gastric gland into mucus-secreting
stomach cell
close-up of
inner gastric gland acid-secreting
lining of cell
stomach
enzyme-secreting
cell
308
Figure 21.2 Epithelial lining of the stomach
Immune system
Three lines of defence employed by the body are shown

in Table 21.1 and Figure 21.1. The first two are non skin surface pathogenic
bacterium
specific. This means that they work against any type tip of pin
pathogen
of disease-causing agent. The third line of defence is enters body
specific, meaning that its components each work against damaged mast cell
a particular pathogen. histamine released

by mast cell

Non-specific defences red blood white capillary

cell blood cell
Physical and chemical defences by

skin and mucous membranes
The surface of the skin is composed of layers of closely
packed epithelial cells, which offer physical protection swollen, inflamed clotted blood in wound
tissue from damaged
against bacteria and viruses provided that the skin capillaries
remains intact. In addition, mucous membranes that line
the body’s digestive and respiratory tracts are composed phagocyte
in action
of epithelial cells that form a protective physical barrier. phagocytes (and

antimicrobial proteins

The skin and mucous membranes also provide chemical and clotting chemicals)

move to site of infection swollen,
defences against potential pathogenic microorganisms. more

permeable
Secretions from the skin’s sweat glands and sebaceous capillary
glands keep the skin at a pH that is too low for most
microbes to thrive. Secretions such as tears and saliva
contain the enzyme lysozyme, which digests the cell
walls of bacteria and destroys them.
Cells in the mucous membranes secrete sticky mucus, wound is healing
which traps microorganisms. The epithelial cells lining phagocytes engulf

pathogens and
the trachea are ciliated and sweep the mucus and dead cells and
clean up site
trapped microbes up and away from the lungs. Acid of infection
secreted by cells in the epithelial lining of the stomach
(see Figure 21.2) destroys many of the microbes that
have been swallowed. However, some do survive the
al state
acid conditions and may gain further access to the body. return ed to norm
capillary
Inflammatory response
When the body suffers a physical injury such as a cut
and/or invasion by microorganisms, it responds with a Figure 21.3 Inflammator y response
localised defence mechanism called the inflammator y
response at the affected site (see Figure 21.3).
Following injury, mast cells become activated and
Mast cells and histamine release large quantities of histamine. This results
Mast cells are present in connective tissue throughout in blood vessels in the injured area undergoing
the body. They are closely related to (and arise from the vasodilation and capillaries becoming swollen with
same stem cells as) white blood cells. Mast cells possess blood. The additional supply of blood makes the
many granules containing histamine. Histamine is a injured area red and inflamed. It swells up because the
chemical that causes blood vessels to dilate (become stretched capillary walls become more permeable and
309
wider) and capillaries to become more permeable. leak fluid into neighbouring tissues.
bacterium phagocyte
giving out (nucleus not
chemical shown)
lysosomes
(organelles containing
digestive enzymes)
vacuole forming
Figure 21.4 Phagocyte engulf ing bacter ia
trapped bacterium
Cytokines
some lysosomes
Cytokines are cell-signalling protein molecules secreted move towards and
by many types of cell, including white blood cells that fuse with vacuole
have arrived at a site of injury or infection. Cytokines

feature in both non-specific and specific defences.
bacterium being
digested by enzymes
During the inflammatory response, increased flow of from lysosomes
blood and permeability of capillary walls at the site of
injury bring about the following beneficial effects:
● Enhanced migration of phagocytes to the damaged breakdown products
pass into cytoplasm
tissue, attracted by cytokines. Within a short time, of phagocyte
a variety of phagocytes have arrived at the scene and
are engaged in engulfing pathogens by phagocytosis
(see Figure 21.4). Some also clean up the injured site. Figure 21.5 Phagocytosis
● Speedy delivery of antimicrobial proteins to the
infected site. These proteins amplify the immune
response.
● Rapid delivery of blood-clotting chemicals
(clotting elements) to the injured area. Coagulation
of blood stops loss of blood, helps to prevent further
infection of the wound and marks the start of the
tissue repair process.
Non-specific cellular responses

Several types of specialised white blood cells protect the
body against pathogenic microorganisms.
Phagocytosis
The process of phagocytosis is illustrated in Figure 21.5.
A phagocyte is motile. When it detects chemicals released
by a pathogen such as a bacterium, or antigens present on
310 the surface of a pathogen (also see chapter 22), it moves
towards the pathogen. It then engulfs the invader in an Figure 21.6 Cancer cell under attack by NK cell
Immune system
infolding of the cell membrane which becomes pinched

1 protein from NK cell
off to form a vacuole (sometimes called a phagocytic creates a pore in target
vesicle). cell’s membrane
A phagocyte’s cytoplasm contains a rich supply of

lysosomes which contain digestive enzymes (such as
ne
lysozyme, proteases and nucleases). Some lysosomes bra
m em cell
er t signal molecule from
fuse with the vacuole and release their enzymes into it. out f targe 2
NK cell enters target cell
o
The bacterium becomes digested and the breakdown 3 signal relayed and genes switched on
products are absorbed by the phagocyte. ‘suicide’ gene
‘suicide’ gene
Following digestion of the microorganism, the
phagocyte releases cytokines which attract more
phagocytes to the infected area to continue the battle
against the pathogenic invasion. Dead bacteria and
4 ‘suicide’ proteins formed
phagocytes may accumulate at an infected site as pus.
Natural killer cells 5 ‘suicide’ proteins function as

self-destructive (degradative) enzymes
Natural killer (NK) cells (see Figure 1.4, page 4) also
play a non-specific role in defence but they are not vital cell
DNA DNAase
phagocytic. They mount an attack on virus-infected protein protease
cells in general and cancer cells (see Figure 21.6) by

the following means. An NK cell releases molecules
of a protein which forms pores in the target cell’s
membrane. These allow a ‘signal’ molecule from the
NK cell to enter the target cell and trigger the genetically
controlled series of events shown in Figure 21.7.
The subsequent production by the target cell of self-
destructive enzymes results in the cell’s DNA and vital
proteins being broken down into useless fragments. The
cell then shrinks and dies. This process of programmed
cell death is called apoptosis. useless fragments useless fragments
of protein of DNA
Cytokines
Figure 21.7 Events leading to apoptosis in an infected cell
In addition to their role in non-specific immunity, natural
killer cells and phagocytes release cytokines following
contact with a pathogen. These molecules circulate in the
bloodstream and stimulate the specific immune response Testing Your Knowledge
by activating lymphocytes (see page 313).
1 a) i) Identify the protective secretion produced by
the epithelial lining of the trachea.
ii) Name a dif ferent protective secretion made by
the stomach lining.
iii)Br iefly descr ibe how each of these secretions
defends the body against attack by
pathogens. (4)
b) Against which other type of unwanted cell does the
body defend itself? (1)
➜ 311
2 a) What are mast cells? (1)
b) i) Why does injured tissue at a cut quickly become
red and swollen?
ii) What name is given to this response to injur y?
iii)Br iefly explain why it is of benef it to the
body. (5)
3 a) Phagocytosis and antibody production are cellular
responses to invasion by pathogens. Which of
these is i) specif ic, ii) non-specif ic? (1)
b) Briefly explain what is meant by the term
phagocytosis. (2)
4 Decide whether each of the following statements
is true or false and then use T or F to indicate your
choice. Where a statement is false, give the word that
should have been used in place of the word in bold
pr int. (5)
a) The process of programmed cell death of a
pathogen, induced by a chemical from a natural
killer cell, is called phagocytosis.
b) If white blood cells detect tissue damage, they
release cytokines which attract other white blood
cells to the site of injur y.
c) A phagocyte’s cytoplasm contains ribosomes full
of digestive enzymes.
d) Following injur y, mast cells in connective tissue
release histamine which causes vasodilation.
e) Decreased capillar y permeability occurs at an
infected site showing inflammation.
312
Specific cellular defences
22
1 Specific cellular defences
Chapter Head
Lymphocytes
The third line of defence – the specific immune
response – is brought about by lymphocytes derived
from stem cells in bone marrow (see Figure 1.4, page 4).
Some lymphocytes pass to the thymus (a gland in the
chest cavity – see Figure 21.1) where they develop into
T lymphocytes (T cells). Those that remain and mature
in bone marrow become B lymphocytes (B cells).
Immune surveillance
A range of different types of white blood cell move
round the body in the circulatory system and
continuously monitor the state of the tissues. If
damage or invasion by microorganisms is detected,
some types of white blood cell release cytokines
into the bloodstream. This results in large numbers
of phagocytes (non-specific defence) and T cells
(specific defence – see page 321) being attracted to, and
accumulating at, the damaged or infected site.
Figure 22.2 Pool of lymphocytes showing var iety of antigen

blood capillary receptors
White blood cells often squeeze out through tiny

spaces in the capillary wall in order to gain access to
surrounding tissues, as shown in Figure 22.1.
white blood cell
Clonal selection theor y

Any foreign molecule that is recognised by, and able to
elicit a specific response from, a lymphocyte is called
surrounding an antigen. Viruses, bacteria, bacterial toxins and
tissue
molecules on the surfaces of transplanted cells and
cancer cells can all act as antigens.
The body possesses an enormous number of different

lymphocytes. Each lymphocyte has, on the surface of
its cell membrane, several copies of a single type of
antigen receptor. This antigen receptor is specific for
one antigen and is different from that of any other
type of lymphocyte (see Figure 22.2). Therefore, each
lymphocyte is able to become attached to and be 313
Figure 22.1 Exit of white blood cells from a capillar y activated by only one type of antigen. When this occurs
the lymphocyte is said to have been ‘selected’ by the as antigens and attack them. Normally this does not
antigen. The lymphocyte then responds by dividing happen because, during the maturation of B cells and
repeatedly to form a clonal population of identical T cells, any lymphocyte bearing an antigen receptor that
lymphocytes. This process is called clonal selection. would fit a body cell surface protein is weeded out and
rendered non-functional or destroyed by apoptosis.
Although each lymphocyte can only be activated by one
type of antigen, when taken as a group, all of the body’s T lymphocytes have specific surface proteins that enable
lymphocytes possess such an enormous range and them to distinguish between:
variety of cell surface antigen receptors that almost any ● ‘self ’ molecules on the surfaces of the body’s own
antigen is recognised by one of them. cells (and therefore take no action)
● foreign molecules on the surfaces of cells not
Recognition of self and non-self belonging to the body (and therefore initiate an
Each person’s body cells are different because they immune response).
possess a combination of cell surface proteins (their This ability to recognise self and non-self means that
‘antigen signature’) that is unique to that person. It is normally there are no lymphocytes acting against the
of critical importance that a person’s lymphocytes do proteins on the surfaces of ‘self ’ body cells.
not regard that person’s own body cells’ surface proteins
Related Topic
ABO blood-grouping system group B donor

Four types of blood group exist among human beings. cells agglutinated
by anti-B
These are A, B, AB and O. antibodies of
recipient
Antigens
On the surfaces of their red blood cells, people with blood
group A have A antigens, people with blood group B have
B antigens, people with blood group AB have both A and
B antigens and people with blood group O have neither A
nor B antigens (see Figure 22.4)
Antibodies
In their plasma, people with blood group A have anti-B
antibodies, people with blood group B have anti-A
antibodies, people with blood group AB have neither
anti-A nor anti-B antibodies and people with blood group
O have both anti-A and anti-B antibodies. Figure 22.3 Agglutination of red blood cells
Although the blood given in the above transfusion would
Agglutination of blood
also contain anti-A antibodies, these would be so diluted
Cer tain combinations of dif ferent blood types are non- relative to the person’s own red cells that they would have
compatible. If, for example, a person with group A blood no signif icant ef fect. It is incompatibility between the
were to be given a transfusion of group B blood then donor’s cells and the recipient’s plasma which results in
anti-B antibodies in their plasma would combine with agglutination. Cer tain combinations of dif ferent blood
the B antigens on the sur faces of the donated red blood group types are perfectly compatible. For example, a person
cells. This would result in clumping (agglutination) of red with blood group B can receive blood of type O without r isk
blood cells (see Figure 22.3), which would cause major of agglutination. Possible donors and recipients are given
314 problems by blocking small blood vessels. in Figure 22.4.
can percentage
blood antigen(s) on naturally-occurring can donate receive
of
group red blood cell antibodies blood to blood from Scottish
in plasma groups groups population
antigen A
A anti-B
A and AB A and O 35
antibody
antigen B
B anti-A B and AB B and O 11
antibody
antigen A neither anti-A

nor anti-B A, B, AB 3
AB AB
antibodies and O
antigen B present
both
neither anti-A
antigen A and anti-B A, B, AB O 51
O nor antibodies and O
antigen B present
present
Figure 22.4 The ABO blood group system
Related Topic
Rh blood typing Incompatibility

Transfusion of Rh+ blood cells to a Rh– person must be
Rhesus D-antigen avoided because the recipient’s immune system would
In addition to the ABO system of antigens, most people respond and produce anti-D antibodies, which would
have a further antigen on the sur face of their red blood persist, leaving the person ‘sensitised’. Any subsequent
cells. This is called antigen D and people who possess transfusion of Rh+ red blood cells would be liable to cause
it are said to be Rhesus positive (Rh+). A minority of the sensitised Rh– person to suf fer severe or even fatal
people are descr ibed as being Rhesus negative (Rh–) agglutination.
because they lack antigen D but react to its presence by
forming anti-D antibodies. Antigen D is genetically determined by a dominant ➜ 315
allele (D) and lack of antigen D by a recessive allele (d). Risk factor
Thus Rh+ individuals have genotype DD or Dd and Rh– If a Rh– woman (dd) marr ies a Rh+ man (DD), each of
individuals have genotype dd. their children will be Rh+. If a Rh– woman (dd) marr ies
a Rh+ man (Dd), there is a 50% chance that each of their
children will be Rh+ (Dd), as shown in Figure 22.5.
FIRST PREGNANCY
Rh– mother
maternal red
blood cells
close-up of maternal blood lacking
antigen D
no exchange of
red blood cells
across placenta
close-up of fetal blood
close-up of maternal
blood after birth of baby
Rh+ D antigen on surface
fetus of fetal red blood cell
maternal red
blood cell
lacking antigen D
some fetal red
blood cells added
to maternal blood
SUBSEQUENT PREGNANCIES during next few months
maternal immune system
sensitised Rh– mother responds to antigen D
D antibodies cross placenta

and enter fetal blood
close-up of D antibodies produced
maternal blood
maternal red
blood cell lacking
antigen D
D antibodies present
Rh+
fetus
close-up of fetal blood
D antigens and antibodies

combine causing many fetal
red blood cells to become
agglutinated and be destroyed
316 Figure 22.6 Rhesus-incompatible pregnancies

Medical management destroy fetal red blood cells. The resulting condition is
When a Rh– mother has a Rh+ fetus developing inside her called haemolytic disease of the newborn.
body (see Figure 22.6) the baby has antigen D on its red In the past the condition was treated by giving the baby
blood cells which is regarded as foreign by the mother’s transfusions of blood. Nowadays it is usually prevented
immune system. Normally the placenta prevents maternal by injecting the mother with anti-Rhesus antibodies
and fetal bloodstreams from coming into direct contact. soon af ter the bir th of each Rh+ baby. These antibodies
As a result, only a ver y tiny number of fetal blood cells destroy any D antigens from the fetus before the mother’s
(if any) reach the maternal circulation. Therefore the immune system has time to respond to them.
mother’s immune system normally remains ‘unaware’
of the presence of the ‘foreign’ fetus dur ing the f irst
woman man woman man
pregnancy and does not attempt to reject it. dd DD dd Dd
(Rh–) (Rh+) (Rh–) (Rh+)
However, at the time of bir th (or dur ing a miscarriage)
a small quantity of fetal blood does of ten become mixed
with the mother’s blood. The mother’s immune system all Dd Dd and dd
(Rh+) (Rh+) and (Rh–)
responds to this sensitising event by producing anti-D
(100% risk factor) (50% risk factor)
antibodies and she becomes sensitised. If, dur ing
subsequent pregnancies, the fetus is Rh+, antibodies
against antigen D cross the placenta and attack and Figure 22.5 Inher itance of Rhesus D antigen
Autoimmunity cells. This is called autoimmunity and it is the cause of

autoimmune diseases (see Case Studies on rheumatoid
Sometimes the body no longer tolerates the antigens
arthritis, type 1 diabetes and multiple sclerosis).
that make up the self message on cell surfaces and
T lymphocytes launch an attack on the body’s own
Case Study Rheumatoid arthritis

Rheumatoid arthritis is an autoimmune disease certain combination of cytokines occurs in a synovial
that causes chronic inflammation of the synovial joint of a potential sufferer, it promotes an immune
membranes in joints. The membrane swells up and response and white blood cells are stimulated to
the cartilage and bone underneath are gradually migrate to the joint. This creates a state of chronic
destroyed (see Figure 22.7). They are replaced by inflammation that is followed by damage to bone and
fibrous tissue that, in advanced cases, joins the two cartilage.
bones together making the joint immovable.
Treatment
Rheumatoid arthritis is a painful, disabling condition Anti-inflammatory drugs and painkillers are used to
that can result in substantial loss of mobility. It is suppress the symptoms. Immunosuppressant drugs
suffered by about 1% of the population (with women may be used to inhibit the immune response in order
being three times more likely to be affected than to prevent irreversible, long-term damage to the
men) and onset occurs most frequently between the joint’s bone and cartilage.
ages of 40 and 50.
Role of cytokines
The cause of rheumatoid arthritis is unknown
but cytokines are known to play a key role in its
progression. Cytokines are chemical messengers that
allow cells to communicate with one another. When a 317
➜
erosion of bone
loss of cartilage
synovial membrane
synovial sac
swollen joint
cartilage
synovial membrane
bone
inflamed
capsule capsule synovial membrane
inflamed
synovial membrane
swollen joint
bone
synovial sac
loss of cartilage
cartilage
erosion of bone
Figure 22.7 Ef fect of rheumatoid ar thr itis on a joint

inflamed
synovial membrane
swollen joint
Case Study Type 1 diabetes
loss of cartilage
Type 1 diabetes (diabetes mellitus) is an autoimmune The inheritance of particular cell surface proteins
disease where insulin-producing beta cells in the that make up a person’s ‘antigen signature’ is
erosion of bone
pancreas are attacked and destroyed by T cells from associated with susceptibility to this autoimmune
the body’s immune system. condition. However, studies of identical twins have
shown that where one suffered type 1 diabetes, the
A continuous supply of insulin is essential for
other suffered it in only around 40% of the cases
regulation of blood glucose concentration (see page 187).
studied. This suggests that, in addition to inherited
Therefore, sufferers must inject insulin on a regular
factors, environmental factors also play a part in this
basis or risk diabetic shock and death. Poorly controlled
autoimmune disease.
diabetes increases the risk of further problems such as
blindness and kidney disease.
Case Study Multiple sclerosis

Multiple sclerosis is an autoimmune disease that destruction of the myelin, resulting in the ability of
affects the nervous system (see Table 17.1 on page 252). the nerve cells to transmit impulses being seriously
Each motor neuron possesses a long axon surrounded impaired.
by a sheath of myelin which acts as an electrically
Sufferers gradually develop symptoms such as
insulating layer. The myelin sheath is interrupted by
numbness, walking difficulties and diminished
nodes which allow nerve impulses to pass rapidly
vision as the ability to control muscles decreases.
through the nervous system.
Although the trigger for multiple sclerosis is thought
In multiple sclerosis, some unknown trigger (perhaps to be environmental, evidence from twin studies
a virus) activates T cells which then regard molecules suggests that genetic factors also play a part in the
on the myelin sheath as antigens and launch an development of this autoimmune disease.
attack on them. Clones of these T cells continue the
318
Allergy such as pollen, dust or feathers, or even a helpful

substance such as the antibiotic penicillin. Such
The immune system responds to a wide variety of
hypersensitivity in the form of an exaggerated (and
agents that are molecularly foreign to it. This enables
sometimes damaging) immune response is called
it to defend itself against pathogenic bacteria, fungi,
an allergic reaction (see Case Studies on hay fever,
viruses, worms etc. However, sometimes it over-reacts
anaphylactic shock and allergic asthma).
by B lymphocytes responding to harmless substances
Case Study Hay fever

When airborne pollen grains (see Figure 22.8) enter
the nose, throat and upper respiratory passages, they
cells come in contact with harmless
can act as an allergen by causing certain B cells to
substance (e.g. pollen grains)
release antibodies. These become attached to mast
cells in connective tissue causing the release of
histamine. When stimulated in this way, the cells
immune system over-reacts
secrete excessive quantities of histamine, which
produce the inflammatory response (see page 309).
The sequence of events leading to this allergic
reaction are summarised in Figure 22.9. certain B cells are stimulated
The symptoms typical of hay fever are:
● nasal congestion
● running nose antibodies are produced
● red, itchy, watering eyes
● constriction of bronchioles.
They can be relieved by antihistamine drugs and antibodies become attached to

‘mast’ cells in connective tissue
other anti-inflammatory medication.
‘mast’ cells secrete histamine
nasal congestion, running nose,

constriction of bronchioles
Figure 22.9 Events leading to an allergic reaction such as

hay fever
Figure 22.8 Pollen grains are essentially harmless but some

of us react to them
319
Case Study Anaphylactic shock
Anaphylactic shock is a life-threatening allergic
response to an allergen that has been injected (for
example, penicillin or bee venom) or consumed (for
example, peanuts). The person is so allergic to the
antigenic substance that many mast cells respond
and secrete large quantities of histamine and
other inflammatory agents. This triggers sudden
dilation of peripheral blood vessels, loss of much
circulatory fluid to surrounding tissues and a drop in
blood pressure. Death can occur within minutes of
exposure to the allergen.
People who know that they are hypersensitive to

such allergens make every effort to avoid them
and should always carry a preloaded epinephrine
(adrenaline) syringe (see Figure 22.10) to counteract
the allergic response and give symptomatic relief in
an emergency. Figure 22.10 Pre-loaded epinephr ine syr inge
Case Study Allergic asthma

Asthma is a respiratory condition in which the Depending on the allergy, this might include:
sufferer’s air passages become narrower (see
● controlling dust mites
Figure 22.11). This makes it more difficult for the
● avoiding foods to which they are allergic
person to breathe. In addition to suffering shortness
● warming up gently before exercise
of breath, the person tends to wheeze, especially
● using a bronchial dilator (see Figure 22.12) to inhale
after exercise. In extreme situations their chest
a drug that gives symptomatic relief by causing
becomes so tight that they feel as if they are going to
muscles in the bronchioles to relax and open the
airways wider.
muscular
wall
bronchial
dilator
(inhaler)
air space
normal airway untreated bronchiole of an

in cross section asthma sufferer in cross section
Figure 22.11 Ef fect of asthma on a bronchiole
suffocate.
An asthmatic attack can be caused by an allergic

reaction to dust mites, pollen, animal fur and certain
foodstuffs such as peanuts and wheat. It can also be
brought on by nervous tension. In the UK, boys below
the age of 10 are twice as likely to be affected as girls
320 of the same age. Asthma sufferers are able to control
the condition if they follow a management plan. Figure 22.12 Bronchial dilator (inhaler)
Action of lymphocytes helper T cell

(TH cell)
T lymphocytes (T cells)
Two groups of T lymphocytes possessed by the human
body are:
antigen
● helper T cells (TH cells), which secrete cytokines receptor
that activate phagocytes, TC cells and B cells pathogen’s
● cytotoxic T cells (TC cells), which destroy infected antigen
presented by
cells by several methods including the induction of phagocyte
apoptosis.
antigen-receptor binds with antigen
Antigen-presenting cell making TH cell become activated
Once a phagocyte has captured and destroyed an

invading pathogen, it normally presents fragments of activated
TH cell
the pathogen’s antigens at its surface, as shown in
Figure 22.13. Such a phagocyte is described as an
antigen-presenting cell. Other cells in the body infected
with the pathogen also become antigen-presenting cells.
Action of helper T cells

Among the body’s vast pool of helper T cells
(TH cells) there will be a type of TH cell that bears clonal selection and
multiplication of TH cells
antigen receptors able to recognise and bind with the
foreign antigens on the surface of an antigen-presenting
cell, such as the phagocyte shown in Figure 22.14. When
this happens, the TH cell becomes activated, triggering clone of
clone of
activated
the formation of a clone of activated TH cells and a memory
TH cells
TH cells
clone of memory TH cells. release of cytokines
The activated TH cells secrete cytokines, which stimulate

other cells, including TC cells and B cells. Proper stimulation stimulation
functioning of the TC cells and B cells depends on this of TC cells of B cells
stimulation.
Figure 22.14 Activation of a TH cell
pathogen’s antigens
pathogen engulfed fragments of digested presented at surface
by phagocytosis pathogen of phagocyte
phagocyte
321
Figure 22.13 Phagocyte becoming an antigen-presenting cell
Action of cytotoxic T cells as chemical attractants) released by helper T cells and
Within the body’s pool of cytotoxic T cells (TC cells) attack infected cells, as shown in Figure 22.16.
there will be a type of TC cell bearing copies of one type Some types of TC cell bring about the death of infected,
of antigen receptor on its surface that are specific to, antigen-presenting cells at the site of infection by
and able to bind with, the type of foreign antigen on the inducing them to undergo apoptosis (see page 311).
surface of an antigen-presenting phagocyte, as shown in Once a TC cell has killed one target cell, it disengages
Figure 22.15. This binding process results in the TC cell from that cell and moves on to destroy another infected
becoming activated by the antigen-presenting cell and cell. An infected cell’s membrane is not destroyed by
then proliferating and differentiating. By this means it apoptosis. Therefore its cell contents and pathogenic
gives rise to a clone of activated TC cells and a clone antigens remain enclosed and are not dispersed. Instead,
of memor y TC cells. The activated TC cells move to the the dead cell, which has shrunk, becomes engulfed and
site of infection under the influence of cytokines (acting digested by a phagocyte.
cytotoxic T cell
(TC cell)
members of clone of activated

antigen Tc cells become
receptor bound to infected
cells
pathogen’s antigen
presented by phagocyte
pathogen’s
antigen
antigen-receptor binds with antigen

making TC cell become activated
activated
TC cell
infected cell
clonal selection and

multiplication of TC cells
chemical
from Tc cell
perforates
clone of clone of membrane of
activated memory infected cell
TC cells TC cells
infected cell
stimulation by cytokine
from activated TH cells

undergoes
apoptosis
followed by
destruction of infected cells phagocytosis
(see Figure 22.16)
322
Figure 22.15 Activation of a TC cell Figure 22.16 Destruction of infected cells by TC cells
Other TC cells recognise antigens on the surface of Role of helper T cell

cancer cells and attack them. In Figure 22.17, the An antibody-producing response by a B cell specific
smaller TC cell is releasing chemicals that bring about to a foreign antigen can occur following direct contact
the lysis (bursting) of the larger cancer cell. between the B cell and the antigen but normally it
only occurs with the help of a TH cell. The B cell (see
Figure 22.19) displays molecules of foreign antigen
that it has taken in. These antigens are recognised by
an activated TH cell. It responds by releasing cytokines
which stimulate the B cell to multiply and produce:
● a clone of activated B cells which make antibodies
for immediate use
● a clone of memory B cells capable of making
antibodies in the future if required.
activated
TH cell
cytokine
B cell
becomes
Figure 22.17 Lysis of a cancer cell by TC cells stimulated
B lymphocytes (B cells)
foreign antigen
Antigens and antibodies presented by
An antigen is a complex molecule, such as a protein, B cell
that is recognised by the body as non-self and foreign.

multiplication of B cells
The antigen’s presence triggers the production of
antibodies by B lymphocytes (B cells). An antibody is
a Y-shaped protein molecule, as shown in Figure 22.18.
Each of its arms bears a receptor (binding site) that is
specific to a particular antigen.
receptor (binding) clone of activated B cells clone of

sites which produce memory B cells
antibodies
Figure 22.19 Cloning of B cells
323
Figure 22.18 Antibody
Production of antibodies binding of an antibody to an antigen does not in itself
Each clone of B cells produces one type of antibody bring about destruction of the pathogen. However, the
molecule that is specific to one type of antigen surface formation of an antigen–antibody complex inactivates
molecule on a pathogenic cell (or toxin). A clone of the pathogen (or its toxin) and renders it more
B cells that produce antibodies is like a protein factory. susceptible to phagocytosis. In some cases the antigen–
Each B cell produces about 2000 antibody molecules antibody complex itself stimulates the activation of
per second during its 4–5-day life span. Once released proteins that bring about lysis of the pathogen.
into the blood and lymph systems, the antibodies are
transported round the body and make their way to the
infected area. Immunological memory
Pr imar y and secondar y responses
Action of antibodies When a person is infected by a disease-causing
The antibodies recognise and combine with the organism, the body responds by producing antibodies.
antigens at the site of infection (see Figure 22.20). The This is called the primary response (see Figure 22.21).
one of a clone
of activated B cells
antibodies mass-produced
pathogen possessing by B cells and released
antigens multiplying inside
the body and causing disease
antibody
receptor site
antigen on
surface of
pathogen
antibodies meet antigens

at site of infection
antibodies
become bound
to antigens
and block their activity
phagocytes become involved
antigen–antibody
complex engulfed
phagocyte and digested
by phagocytosis
324
Figure 22.20 Action of antibodies
secondary response
increasing concentration of
antibodies in blood plasma
primary response
0 10 20 30 40 0 10 20 30
time (days) some later time in
person’s life (days)
first exposure second exposure
to antigen to antigen
Figure 22.21 Pr imar y and secondar y responses
Due to a latent period elapsing before the appearance of Memor y cells

the antibodies, this primary response is often unable to The secondary response is made possible by the presence
prevent the person from becoming ill. of memor y cells. These are B and T lymphocytes
If the person survives, exposure to the same antigen at a specific to the antigen and produced in response to it by
later date results in the secondary response. This time clonal selection following the body’s first exposure to it.
the disease is usually prevented because: When the body becomes exposed to the disease-causing
microorganism for a second time, the memory cells
● antibody production is much more rapid
quickly proliferate and differentiate, producing clones of
● the concentration of antibodies produced reaches a
T cells and antibody-forming B cells.
higher level
● the higher concentration of antibodies is maintained A summary of some of the many interrelated
for a longer time. components of the specific immune response is given in
Figure 22.22.
sample of pathogen’s antigen

engulfed by phagocyte
and presented at its surface
activation of activation of activation of

TC cell TH cell B cell
stimulation
by cytokine
formation formation of formation formation formation formation

of clone of clone of of clone of of clone of of clone of of clone of
memory activated TC memory activated memory antibody-
TC cells cells which TH cells TH cells B cells producing
destroy B cells
infected or
cancer cells stimulation
by cytokine
325
Figure 22.22 Summar y of the specif ic immune response
1 a) i) Name two types of lymphocyte. lymphocyte, having been selected by an antigen,

ii) Which of these is involved in the specif ic immune divides repeatedly to form a population of identical
response to invasion by a pathogen? (2) lymphocytes? (1)
b) Why do white blood cells at a damaged or infected 3 a) From each of the following pairs, choose the words
site release cytokines? (1) that apply to the term allergic reaction and then use
c) How do white blood cells gain access to damaged all three to explain what the term means. (3)
tissue not directly in contact with blood underreacts/overreacts, hypersensitive response/
capillar ies? (1) hyposensitive response, normally harmful substance/
2 a) i) What is meant by the term antigen? normally harmless substance
ii) Give T WO examples of antigens. (3) b) Explain what is meant by the term autoimmunity. (2)
4 a) Outline the ser ies of events that takes place when a
b) If each lymphocyte can only recognise one specif ic
TC cell binds to an antigen-presenting cell. (4)
antigen, how is it possible that lymphocytes of fer
b) Outline the ser ies of events that occurs when
ef fective protection against a vast var iety of
cytokine from an activated TH cell stimulates a B cell
pathogens? (2)
displaying foreign antigens. (2)
c) What name is given to the process by which a
1 The human body uses its _____ system to protect itself

activated complexes lymphocytes against _____, some toxins and cancer cells.
allergic cytokines lysis 2 The body surface and cavity linings are covered with
antibody dilate memor y _____ cells that provide physical defence against
antigen display non-specif ic infection and produce secretions that give _____
defence.
antigen- distinguish own
presenting epithelial pathogens 3 The body responds to an injur y by making an _____
antimicrobial response. _____ released by mast cells causes blood
faster permeable
vessels to _____ and capillar ies to become more _____.
apoptosis harmless phagocytosis Enhanced migration of phagocytes to the damaged
autoimmune helper receptor site is accompanied by the rapid deliver y of clotting
bloodstream histamine selection elements and _____ proteins.
capture immune specif ic 4 Cer tain specialised white blood cells display _____
cells immunological susceptible responses to pathogens. Phagocytes destroy them by
cell-signalling _____. Natural _____ cells make the pathogen destroy
infected tolerate
itself by apoptosis.
chemical inflammator y
clonal 5 Phagocytes and NK cells release _____ molecules called
killer
cytokines. These stimulate the _____ immune response,
which is brought about by T _____ (T cells) and
Table 22.1 Word bank for chapters 21–22 B lymphocytes (B _____).
326
6 A foreign molecule able to elicit a specif ic response 10 On becoming activated, one group of T lymphocytes
from a lymphocyte is called an _____. When an antigen destroys _____ cells by inducing them to undergo
binds to a _____ on the type of lymphocyte to which it _____.
is specif ic, the lymphocyte becomes _____ and divides,
11 A second group of T lymphocytes (_____ T cells) releases
forming a _____ population.
_____ that activate B lymphocytes.
7 Specif ic proteins present on T cells enable them to
12 Each clone of B cells produces one type of _____ specif ic
_____ between the body’s _____ cells and cells bearing
to one type of antigen sur face molecule on a pathogen.
foreign antigens.
These antibodies are secreted into the _____ and
8 Failure to _____ the body’s own antigens (that make up transpor ted to the site of infection.
the ‘self message’ on cell sur faces) leads to an _____
13 The subsequent formation of antigen–antibody _____
disease. Over-reaction by the immune system to a _____
inactivates the pathogen and makes it more _____ to
substance results in an _____ reaction.
phagocytosis or leads to its destruction following cell
9 Following infection of the body by a pathogen, some _____.
phagocytes _____ the microbe and _____ its antigen on
14 Some of the T and B cells formed by clonal _____ in
their surface. These _____ cells activate T lymphocytes.
response to antigens persist as _____ cells. If the body
is exposed to the same antigen, these cells produce new
clones, which give a _____ and greater _____ response
than dur ing the f irst exposure.
327
1
23 Infectious diseases and epidemiology
Chapter Head
An infectious disease is one that is capable of being

transmitted from one person to another by direct or
indirect contact.
Pathogens
Infectious diseases are caused by many types of
pathogen including:
● viruses (e.g. measles – see Figure 23.1a)
● bacteria (e.g. cholera – see Figure 23.1b)
● fungi (e.g. athlete’s foot – see Figure 23.1c)
● protozoa (e.g. malaria – see Figure 23.1d)
● multicellular parasites (e.g. hookworm – see
Figure 23.2).
Figure 23.2 Head of a hookworm
a) c)
b) d)
328
Figure 23.1 Pathogens associated with human diseases
Infectious diseases and epidemiology
Transmission ● inhaled air (e.g. by breathing in microbes or

droplets contaminated with microbes released by an
Infectious diseases are transmitted by many methods. infected person during coughing or sneezing – see
Some of these are given in the following list: Figure 23.4)
● direct physical contact (e.g. by shaking hands – see
Figure 23.3)
microbes
carried in
droplets microbes carried
in air in the air with
dust particles
microbes carried
directly via air
microbes
passed
from hand
to hand Figure 23.4 Transmission by sneezing
● indirect physical contact (e.g. by sharing

contaminated items such as cups or syringe needles)
● body fluids (e.g. by exchanging saliva during kissing
or seminal fluids during sexual contact)
● faecal–oral route (e.g. by consuming food or drink
contaminated with microorganisms from an infected
person)
Figure 23.3 Methods of disease transmission ● vector organisms (e.g. by being bitten by a mosquito
infected with malaria or yellow fever pathogens).
Case Study Comparison of transmission methods

Different pathogens are transmitted by different Cholera
means. This infectious disease is caused by a bacterium
that is water-borne. In regions of the world where
Measles
sanitation conditions are poor or where a natural
The virus responsible for this infectious disease
disaster (e.g. severe flooding) has occurred, the local
is air-borne. It is transmitted in droplets released
water supply may become polluted with sewage
during coughing and also directly into the air during
contaminated with cholera bacteria. If the water
laboured breathing when the infected person’s nasal
is used for drinking without first being boiled, the
passages are heavily congested.
pathogen gains access to the local population and
HIV a disease epidemic results. The epidemic may gain
HIV (human immunodeficiency virus) responsible further momentum by the pathogen being spread
for AIDS (acquired immune deficiency syndrome by direct contact and by the consumption of food
– see chapter 24, page 342) is transmitted in body contaminated by insect vectors (e.g. flies) that have
fluids such as blood (on a syringe needle shared by previously been in contact with sewage containing
drug addicts) and semen (during unprotected sexual cholera microbes.
intercourse).
329
Control of transmission Appropriate handling and storage of food
Adoption of good practices such as handling foods
Quarantine with clean hands, storing uncooked meats separately
This is a period of compulsory isolation of a person
from cooked meats and sterilising knives and work
suffering a serious communicable disease or of those
surfaces in butchers’ shops and abattoirs help to prevent
who have been in contact with an infected person. It is
the transmission of microbes.
carried out in order to prevent the spread of the disease.
Usually the length of the quarantine period is planned Community responsibility
to match the length of the maximum known incubation
period of the disease. Quality water supply
In the UK, transmission of pathogens from wild
Antisepsis animals to humans in drinking water is prevented
Asepsis is the state of being completely free of by a series of treatments including filtration and
live microorganisms. Antisepsis is the inhibition chlorination to ensure that the water is free of
or destruction of microorganisms that cause pathogens.
disease or decay (in an attempt to approach a
state of asepsis). The growth and multiplication of Safe food webs
pathogens is arrested by adopting procedures such Food manufacturers in the UK are obliged to adopt
as the sterilisation of equipment, the application good manufacturing practice to ensure that harmful
of antiseptics (see Figure 23.5) to wounds and the microorganisms do not enter the food chain. Milk, for
wearing of sterile gloves and surgical masks. example, is pasteurised (heated to 72°C for 15 seconds)
to kill most microorganisms including those that would
cause tuberculosis.
In general, systems of control including inspection,

risk analysis and traceability of food sources are
employed to make the entire process from ‘stable to
table’ safe. However, on rare occasions the system does
break down. Toxins produced by algae, for example,
sometimes manage to enter the food chain via shellfish.
Consumption of these, in extreme cases, can lead to
severe conditions such as paralysis and even death.
Appropriate waste disposal mechanisms

Figure 23.5 Familiar antiseptics
Dry refuse is collected on a regular basis and recycled,
incinerated or buried under approximately 250 mm of
Individual responsibility
soil.
Good hygiene
Hygienic practices such as hand-washing, teeth- Control of vectors
brushing and daily showering help to control Many methods are employed to eradicate animals that
populations of microbes and reduce the chance of transmit microbial pathogens.
a pathogen causing an infection and then being
transmitted to another person. The rat flea (see Figure 23.6) transmits bubonic plague
(the ‘Black Death’) from rats to humans. When an
Care in sexual health infected rat is bitten by a flea, the plague bacterium
(see Figure 23.7) passes from the rat’s blood to the
Use of condoms gives protection against sexually
flea. If that flea then bites a human, the pathogenic
transmitted diseases (STDs) such as gonorrhoea and
330 bacterium is transmitted to the person in the flea bite.
HIV/AIDS.
One pandemic in the fourteenth century wiped out

about 25% of the European population. Nowadays
the control of rats (and their fleas) has reduced the
incidence of bubonic plague to a very low level.
Figure 23.8 Mosquitoes are vectors for a number of diseases
Epidemiology of infectious
Figure 23.6 Rat flea diseases
The epidemiology of an infectious disease is the study
of its characteristics such as:
● the location associated with its initial outbreak
● its pattern and speed of spread
● its geographical distribution.
This work is done by epidemiologists who are able

to determine the factors that affect the spread of the
disease. The spread patterns of infectious diseases are
classified as shown in Table 23.1.
Spread pattern Description

of disease
Sporadic Occurs in scattered or isolated instances
with no connection between them
Figure 23.7 Bacter ium that causes bubonic plague Endemic Recurs as a regular number of cases in a
par ticular area
Millions of people die every year of malaria caused by Epidemic Simultaneously af fects an unusually
a protozoan carried by mosquitoes (see Figure 23.8) large number of people in a particular
acting as vectors. Control of mosquitoes is attempted area
by: Pandemic Occurs as a ser ies of epidemics that
● draining stagnant water to remove breeding sites spreads across whole continents or even
● introducing sterile male mosquitoes to reduce the throughout the world
breeding rate Table 23.1 Spread patterns of infectious diseases
● using chemicals such as insecticides and larvicides.
Epidemiologists conduct a thorough surveillance
(close observation) of the disease and collect data that
are subjected to statistical analysis. From this work 331
they attempt to discover possible causal relationships if the person is exposed to the normal disease-causing
that will enable them to identify appropriate control antigen at a later date. The person has acquired active
measures. These could include: immunity by artificial means.
● suggested means of preventing transmission from
person to person and region to region Vaccine clinical tr ials
● appropriate drug therapy for people already infected
Like other new pharmaceutical medicines, vaccines
● immunisation for people not yet infected. must be subjected to clinical trials on humans to
establish that they are safe and efficacious (capable of
Active immunisation and vaccination producing the intended result). Only then can they be
Immunisation is the process by which a person licensed for use.
develops immunity to a disease-causing organism. Before a clinical trial is carried out, the potential
Active immunity refers to the protection gained treatment undergoes extensive testing on cells and on
as a result of the person’s body producing its own animals in the laboratory. If the new treatment works
antibodies. on them, approval for the next stage is sought from the
regulatory authority. This group checks that the clinical
Naturally acquired active immunity trial’s proposed design involving humans matches
If a person survives infection by a pathogen, subsequent European protocol (a procedural method whose design
exposure to the same antigen at a later date results in a and implementation meet certain agreed standards).
secondary response (see page 325) which prevents the
disease from recurring. The person has acquired active
immunity by natural means.
Artif icially acquired active immunity PHASE I

small doses of treatment tested
Vaccination is the method of immunisation by which on a very small number (e.g. 25–50)
a weakened or altered form of the pathogen or its toxin of volunteers to check that it is safe
(see Table 23.2) is deliberately introduced into the body if phase I is successful
by injection, ingestion or nasal spray in order to act as
an antigen and initiate the immune response. PHASE II
treatment tested on a large number
Form of antigen Examples of diseases to which (e.g. 150–300) of people who have
the illness to test if the treatment
in vaccine active immunity is acquired is safe and effective and to find out
what the optimum dose may be
Dead pathogens Hepatitis A and poliomyelitis
if phase II is successful
Parts of pathogens Hepatitis B and HPV (human
papilloma virus)
Weakened Rubella, mumps and measles PHASE III
pathogens treatment tested on a very large number
(e.g. 1000–2000) of people who have
Inactivated Diphther ia and tetanus the illness using a randomised,
bacter ial toxin placebo-controlled, double-blind protocol
Table 23.2 Antigens in vaccines

if phase III is successful
Normally the antigen is mixed with an adjuvant. This
is a chemical substance that promotes the activity of
results submitted
the antigen and enhances the immune response. In and licence sought to
each case the antigen induces the production of B and manufacture the
new treatment
T cells and the formation of antibodies but does not
cause the disease. Some B and T cells persist in the body
332 as memory cells. These initiate the secondary response Figure 23.9 Phases in a clinical tr ial
Phases in the clinical trial A double-blind trial is used at phase III to eliminate
Once the protocol has been approved, testing on bias (an irrational preference or prejudice). For
humans can take place. The three phases that make up a example, if the trial was not double-blind, then a
clinical trial are shown in Figure 23.9. doctor’s belief in the value of the new treatment could,
consciously or subconsciously, affect their behaviour
Design of phase III towards a patient if they knew who was receiving which
‘treatment’.
In phase III of the trial, the target population is split
into two groups – those in the test group who will Randomisation
receive the treatment and those in the control group
who will not. The protocol employed at this stage is: Normally the gender, age and other relevant details
of each subject taking part in phase III of the trial are
● placebo-controlled
entered into a computer. This then puts each person
● double-blind
● randomised.
into one or other of the two groups at random. This
procedure further eliminates bias.
Placebo effect
In its absence a doctor might subconsciously avoid
Instead of the treatment, the members of the control putting more seriously ill patients into the group
group are given a placebo. This is a ‘sham’ treatment receiving the new treatment. Therefore, at the end of
that takes the same form as the real treatment except the trial the new treatment would appear to be more
that it lacks the active ingredient being tested. This effective than it really was because the members of the
procedure is carried out to assess the placebo effect, test group would have begun in better health than those
that is the effect from receiving the treatment that in the control group.
does not depend on the active ingredient in the real
treatment. For example, some patients receiving the Experimental error
placebo may show an improvement in their condition.
The computer also ensures that the composition of the
This could be a result of the psychological effect of:
two groups is as similar as possible. Figure 23.10 shows
● thinking that they were receiving the real treatment
this process in a very simple way. In the test population
● receiving expert attention from health care staff
about to be split up, there are more females than males.
● expecting the treatment to be efficacious.
The computer ensures that this difference is reflected
The use of the placebo allows a valid comparison to in the two groups formed. Similarly, among males
be made between the test group and the control group there are more older than younger subjects. Again this
to assess the effect of the new treatment. If the control difference is maintained in the two groups formed and
group had not been given the placebo, then there would so on. This process reduces experimental error to a
be no way of knowing how many members of the group minimum.
receiving the real treatment showed improvement in
If the process were not adopted, one group might
their condition for one of the above ‘placebo effect’
receive, for example, an atypically large number of older
reasons and not as a result of the active ingredient
subjects who are heavier in weight and more seriously
present in the new treatment itself.
ill. This could invalidate the results. Experimental
error is also reduced by using a very large sample
Double-blind trial
population. (The patient in Figure 23.11 has completely
A blind trial is one in which the human subjects do not misunderstood the reasons for the protocol adopted in
know whether they are receiving the active treatment a clinical trial.)
or the placebo. A double-blind trial is one in which
neither the subjects nor the doctors know who is
receiving what.
333
}
phase III population
group 1
(test group)
The composition
}
of the two groups
is very similar
therefore
divided into two
groups by computer experimental
error is reduced
to a minimum.
group 2
(control group)
male older
female younger
more ill heavier
less ill lighter
Figure 23.10 Using a computer to form test and control groups
Statistical analysis
It is also important to use a very large population of
patients at phase III so that the results obtained can be
subjected to statistical analysis with confidence. The
results for the two groups can then be compared to find
out if significant differences exist between them that
indicate that the new treatment is efficacious. If so, the
researchers would then seek a licence to manufacture it.
Figure 23.11 A misunderstanding
334
1 a) Identify THREE types of pathogenic 3 a) Br iefly descr ibe how active immunisation can be
microorganism. (3) acquired by ar tif icial means. (2)
b) Name the vector that transmits the malar ial b) Copy and complete Table 23.3. (3)
parasite and br iefly descr ibe a method used to tr y to
Feature of design of Reason for inclusion of design
control it. (2)
clinical trial feature
2 a) What is meant by each of the following terms:
antisepsis, quarantine, epidemiology? (3) Randomised
b) Distinguish between the following patterns of Double-blind
disease spread:
i) sporadic and endemic Placebo-controlled
ii) epidemic and pandemic. (4) Table 23.3
335
1
24 Herd immunity and antigenic variation
Chapter Head
Herd immunity individuals who have

When most of the members of a population already suffered the disease
and acquired immunity naturally
have been immunised by vaccination against a non-immune
pathogen, the probability of the few remaining non- individual
immune individuals coming into contact with an
infected individual becomes very low. Under these a human
circumstances, non-immune individuals are protected population
because the normal chain of infection has been
disrupted. This form of protection, given indirectly to
the non-immune minority by the immune majority, is
called herd immunity (see Figure 24.1). immunisation of a very large percentage of
population by vaccination
The greater the percentage of individuals in the
population who are immune, the lower the chance immune
individual
that a non-immune person will come into contact most of
with an infected person. Herd (community) immunity population
now
provides protection for vulnerable sub-groups of the immune
population. These include people who must not be to the
pathogen
vaccinated because of a medical condition such as an non-immune
individuals who
immune disorder. have not been
vaccinated
Mass vaccination arrival of pathogen
(e.g. measles virus)
Herd immunity resulting from mass-vaccination immune
individual
programmes has successfully reduced the spread of
diseases and even eradicated some (see the Case Studies
on tuberculosis, poliomyelitis and smallpox).
non-immune
individuals protected individual who suffers the disease
by herd immunity and acquires immunity naturally
Figure 24.1 Herd immunity
336
Herd immunity and antigenic variation
Case Study Tuberculosis mass vaccination programme

Tuberculosis (TB) is caused by a bacterium that is Vaccination
inhaled in droplets released by an infected person A programme of mass vaccination (accompanied by
during coughing. The disease most commonly affects antibiotic treatment for infected people) was begun
the lungs but many other organs can also become in the UK in the 1950s. The vaccine was routinely
infected. In its later stages, sputum containing blood administered to school children aged 10–13 years. It
is coughed up. This stage of the disease was formerly has been so successful in achieving herd immunity
called consumption. Tuberculosis used to be a over the years that it is no longer delivered to
common cause of death in the UK. A close correlation everyone. Instead, it has been replaced by targeted
existed between incidence of the disease and poor vaccination for those infants, school children, health
social conditions. Poverty-stricken people eating a care workers and older people considered to be at
poor diet and living in overcrowded conditions with greatest risk.
poor sanitation were much more likely to develop the
In recent times the number of cases of TB has begun
disease than wealthier members of society. As social
to rise again as it gains a foothold among problem
conditions gradually improved with time, the death
drug and alcohol users and homeless people with an
rate decreased, as shown in Figure 24.2.
extremely low quality of life and very poor general
health.
4000
3500
causal organism
3000 identified
death rate per million
2500
2000
1500 BCG
1000 vaccination
500
0
1840 1860 1880 1900 1920 1940 1960 1980
year
Figure 24.2 Decline in death rate from tuberculosis
Case Study Poliomyelitis mass vaccination programme

Poliomyelitis (polio for short) is a disease caused introduced in 1956. It reduced the incidence of the
by a virus. Its principal mode of transmission is disease among vaccinated children to about 25% of
the faecal–oral route, but it can be passed on in that of non-vaccinated children. In 1962 an improved
exhaled droplets. In severe cases of the disease, the vaccine containing attenuated (weakened) virus was
virus attacks motor neurons in the spinal cord and introduced. It was administered orally rather than by
hindbrain. This often leads to paralysis of limbs. In injection and has proved to be so effective that herd
very severe cases, the disease can be fatal. immunity has now been established and polio has been
almost completely eradicated in developed countries
A summer epidemic of the disease developed in the such as the UK (see Figure 24.3). Experts have calculated
UK in 1947 and then recurred in subsequent years. that an infant immunisation rate of 80–86% must be
Therefore concerted efforts were made to develop maintained to keep polio in check. It is for this reason
a vaccine. The first type containing dead virus was 337
that polio vaccine is given to babies aged 2 months. ➜
It must be kept in mind, however, that this successful
0
outcome in the battle against polio was not due
solely to the mass vaccination programme. In the UK, 10
percentage decrease in polio death rate for UK

over the years, ever-improving standards of living
and hygiene, including effective means of sewage 20
disposal, have also played their parts in wiping out dead

30 vaccine
the disease. Poliomyelitis is still common in many
developing countries that lack mass vaccination 40 live
programmes and effective sanitation. vaccine
50
60
70
80
90
1930 1940 1950 1960 1970
year
Figure 24.3 Ef fect of vaccination against polio
Case Study Smallpox mass vaccination programme

Up until the end of the eighteenth century, smallpox suffered cowpox (a similar, but milder, non-fatal
was widespread in the UK. This infectious disease disease) were immune to smallpox. He inoculated
caused severe fever and was fatal in about one out a healthy boy with cowpox. Once the boy had
of every five cases. Survivors were left permanently recovered, Jenner inoculated him with what would
scarred. It was known at that time that smallpox normally have been a deadly strain of smallpox virus.
could sometimes be prevented by deliberately Fortunately for everyone concerned, the boy did not
inoculating people with pus from a pustule of a contract smallpox, showing that he was immune. The
person suffering a mild form of the disease. However, science of artificially acquired, active immunity had
this method of immunisation was not reliable and begun.
often produced the fatal form of the disease.
Eradication of smallpox
In 1796, a British doctor called Edward Jenner decided
Free vaccination against smallpox became available
to act on observations that milkmaids who had
in the UK in the 1840s and was made compulsory for
500 babies 10 years later. In Britain and other developed
450 countries, the death rate gradually decreased to a
low level. However, it was not until many years later
number of cases (thousands)
400
350 that one of the greatest triumphs in medical history
300 WHO campaign was achieved. This was the complete eradication
250 began worldwide of smallpox which was brought about by a
last
200 recorded World Health Organization (WHO) programme begun
150 case in 1967. It involved vaccinating as many people as
100 possible shortly after birth and quickly homing in on
50 fresh outbreaks of the disease and then vaccinating
0 all known and suspected contacts. This surveillance-
1950 52 54 56 58 60 62 64 66 68 70 72 74 76 78
containment campaign was so successful that the
year
last recorded case of smallpox occurred in Somalia in
338 1977 (see Figure 24.4).
Figure 24.4 Worldwide eradication of smallpox
HE31928.indb 338 26/02/2013 10:16

Herd immunity threshold of widespread mass vaccination. Under these

circumstances herd immunity cannot be established.
For herd immunity to be effective, only a minority of
the population can be left unvaccinated. The percentage In a developed country, herd immunity for a vaccine-
of immune individuals in a population above which a preventable disease (e.g. measles) may be compromised
disease no longer manages to persist is called the herd if parents believe adverse publicity about the vaccine
immunity threshold. Its value varies from disease to and refuse to have their children vaccinated. Under
disease (see Table 24.1) and depends on factors such as: these circumstances the level of herd immunity can
● the extent of the pathogen’s virulence (its capacity slip below its threshold value. As a result, the incidence
for causing disease) of the disease among non-vaccinated individuals will
● the vaccine’s efficacy (its effectiveness) increase rapidly.
● the population’s contact parameters (e.g. degree of
population density that affects the pathogen’s ability
to spread).
Evasion of specific immune
responses
Public health medicine Over the course of evolution, many pathogens have
evolved mechanisms that enable them to evade specific
In many countries, the public health policy for immune responses made to them by the human
combating a number of common diseases is to use mass body. These often make it possible for a new version
vaccination programmes that create herd immunity to of the pathogen to appear that is ‘one step ahead’ of
them. In the UK, for example, a person’s vaccination the current vaccination programme intended to give
schedule normally begins around the age of 2 months protection against it.
(when they are vaccinated against diphtheria, tetanus,
poliomyelitis, influenza and whooping cough) and
continues for many years. Change in genotype
Pathogenic microorganisms have vast powers of
Absence of herd immunity reproduction. Given suitable conditions, they increase
rapidly in number. Within a population of a pathogen,
In some developing countries where the majority of new strains arise continuously as a result of changes
the population are impoverished and malnourished, occurring in the microbe’s genotype. These changes are
it may not be possible to introduce a programme brought about, for example, by mutations and genetic
Related Topic
Comparison of herd immunity thresholds

Table 24.1 shows herd immunity thresholds for several diseases.
Disease Mode of transmission Herd immunity threshold (%)

Diphther ia Airborne droplets of saliva 85
Measles Airborne 83–94
Mumps Saliva and airborne droplets 75–86
Poliomyelitis Faecal–oral route 80–86
Rubella Airborne droplets 80–85
Whooping cough Airborne droplets 92–94
Table 24.1 Estimated herd immunity thresholds for vaccine-preventable diseases 339
340
antigen
antigen antibody
(surface protein)
1 Influenza The person suffers the

virus disease. Antibodies are
arrives... virus enters body made and eventually the
disease is contained as
antibodies bind to antigens.
Memory cells are produced.
Immunology and Public Health
antigen
Figure 24.5 Ef fect of antigenic variation in influenza virus

2 If the identical Memory cells recognise the
strain of antigens on the virus and
influenza trigger antibody production.
virus arrives the virus enters body Antibodies bind to antigens
next year... and prevent reinfection.
new version of
3 antigen
If a newly Memory cells do not recognise
mutated strain the new antigen. Antibodies
of influenza from before do not fit new
virus arrives antigens. The person suffers the
the next virus enters body disease. Antibodies and memory
year… cells specific to this new antigen
are eventually made, the person
survives and so on…
Unit
4
recombination (such as a combination of genetic trypanosomiasis (‘sleeping sickness’ – see Figure 24.8)
material from two different strains). when it gains access to the bloodstream of humans and
some other mammals. The pathogen is surrounded
Antigenic variation by a coat of glycoprotein molecules that varies in
chemical composition depending on which of the
The new strains of a pathogen are described as
many hundreds of genes that code for variants of the
demonstrating antigenic variation if they have antigens
glycoprotein are switched on.
on their surface that are different from those of the
original strain. A new strain of the pathogen showing
antigenic variation is genetically and immunologically
distinct from its parent strain(s) and succeeds because
it enjoys a selective advantage.
Influenza virus
Production of new antigens enable the influenza virus,
for example, to avoid the effects of the human body’s
immunological memory. This allows it to re-infect the
person because its new antigens are not recognised by
their memory cells (see Figure 24.5). It is for this reason
that influenza remains a major public health problem.
At-risk individuals need to be vaccinated every year
with a new version of the vaccine to give protection (see
Figure 24.7 Tr ypanosoma brucei and red blood cells
Figure 24.6).
Pathogenic protozoa
Antigenic variation is not restricted to viruses and
bacteria. It also occurs in pathogenic protozoa
(unicellular animals), as in the following two examples.
Trypanosomiasis
Trypanosoma brucei (see Figure 24.7) is a protozoan
that causes a fatal neurological disease called
Figure 24.8 A sleeping sickness suf ferer
The infected host responds to the pathogen by making

antibodies against the antigen (the glycoprotein in the
pathogen’s coat). This process results in about 99% of
the protozoa being neutralised and killed. However, 1%
of them manage to shed their coat, switch on a different
gene that codes for a variant of glycoprotein and
produce a new, antigenically distinct coat.
This antigenic variation enables the remaining 1% of
341
Figure 24.6 Epidemic or pandemic? the pathogens to evade detection and give rise to a new
population where each individual is surrounded by a Tuberculosis
coat of the glycoprotein variant. The host’s immune The above strategy is employed by Mycobacterium
system responds by producing a new set of antibodies tuberculosis, the bacterium that causes tuberculosis
that again deal successfully with about 99% of the (see the Case Study on page 337). Mycobacterium
pathogens. But, as before, 1% of the pathogens switch tuberculosis is described as an intracellular pathogen
to a different variant of glycoprotein and survive. because it is able to survive inside phagocytes. When
This cycle of events continues until, eventually, in the a macrophage engulfs a tuberculosis bacterium into
absence of treatment, the host dies. a phagocytic vesicle, the microbe prevents lysosomes
(containing digestive enzymes – see page 310) from
Malaria fusing with the vesicle. The bacterial cell wall contains
Plasmodium falciparum (see Figure 23.1d on page 328) certain molecules that, on release, are thought to modify
is a protozoan that causes malaria. It has a complex life lysosomal membranes in a way that normally inhibits
cycle involving both humans and mosquitoes. For most fusion.
of the time that the pathogen is in a human host, it is
found inside red blood cells. Even if fusion does occur, M. tuberculosis is not easily
attacked by lysosomal enzymes because it is protected
Great antigenic variation exists amongst the members by a waxy cell wall. Therefore the pathogen remains
of the population of the pathogen. This genetic alive inside the macrophage and avoids immune
variability enables the parasite to evade the host’s detection (see Figure 24.9). Other macrophages often
immune response. In addition, individual pathogenic surround and wall off the infected macrophage to try to
cells produce a protein that is transported to an infected keep it contained.
red blood cell’s surface. The protein makes the red
blood cell adhere to the lining of the blood vessel and
prevents it from being removed and destroyed by the
body. The parasite is able to switch between the many
genes that code for variants of this protein, making
it impossible for the host to produce appropriate
antibodies within the limited time available.
Antigenic variation in Plasmodium falciparum has so

far prevented scientists from producing an effective
vaccine. Malaria continues to kill millions of people
annually.
Direct attack on the immune system

Figure 24.9 TB bacter ia can thr ive inside phagocytes
Microorganisms that invade the body soon come into
contact with phagocytes. These might be the phagocytes
present in the bloodstream or larger phagocytic cells Immunodef iciency disease
called macrophages derived from blood cells but An immunodeficiency disease results from the absence
resident in connective tissues. or failure of some component of the immune system
which leaves the person susceptible to infection.
Bacteria that succeed as pathogens have often evolved
a means of mounting a direct attack on the host’s
AIDS and HIV
immune system. For example, by interfering with the
host cell’s phagocytic response, the pathogen manages AIDS (acquired immune deficiency syndrome)
to block an essential step in the process and bring it to is a deficiency disease caused by HIV (human
a halt. immunodeficiency virus) – see Figure 24.10.
342
helper T cell by budding (see Figure 24.12) and move

glycoprotein
off to infect other cells. This can cause destruction of
lipid bilayer the cell or it may undergo apoptosis (see page 311)
(made from
membrane of
following an attack by a TC cell that recognises it as an
previous host cell) infected cell.
B cells do make antibodies in response to HIV but
protein coat (capsid) these are ineffective against viral particles ‘hiding’
viral RNA
inside the helper T cells. Helper T cells are of critical
importance to the immune system since they activate
B cells and cytotoxic T cells. As the number of helper T
reverse transcriptase
cells gradually drops, the body’s immunological activity
decreases, leaving the person susceptible to serious
opportunistic infections such as pneumonia and rare
Figure 24.10 Human immunodef iciency virus (HIV)
forms of cancer. At this point, after several years of
infection by HIV, the person is suffering from AIDS.
HIV infection
HIV attacks helper T lymphocytes. It becomes attached
by glycoprotein on its surface to specific receptors
on the helper T cell surface (see Figure 24.11). The
envelope surrounding the HIV particle fuses with the viral membrane
fuses with cell
membrane of the helper T cell and the virus enters the membrane
host cell.
HIV is described as a retrovirus because it contains

RNA. Since it lacks DNA to transcribe into mRNA,
it adopts a different strategy. Along with its RNA, it virus enters host cell
introduces an enzyme called reverse transcriptase into

the host cell. Using the RNA as a template, this enzyme viral DNA produced by helper
reverse transcription T cell
brings about a reverse version of normal transcription
and produces viral DNA from viral RNA.
viral DNA becomes incorporated
Viral DNA becomes incorporated into the host cell’s into host cell’s DNA
DNA where it can remain dormant for many years

eventually viral DNA directs
before directing the synthesis of new viral particles synthesis of new viral particles
inside the host cells. These escape from the infected

viral RNA
reverse
HIV transcriptase
glycoprotein
binder
receptor on cell
membrane
of helper T cell
virus escapes
from host cell
by budding
343
Figure 24.11 Attachment of HIV to a helper T cell Figure 24.12 Life cycle of HIV
Case Study HIV
Public health measures ● educate people about how the virus is spread
An opportunity for HIV to be transmitted arises when ● supply drug addicts with sterile needles while
a body fluid such as blood, semen or breast milk trying to persuade them to seek treatment for their
containing HIV from one person comes into contact addiction
with the mucous membranes or bloodstream of ● promote the practice of safe sex and the use of
another person. Shared use of non-sterile needles by condoms.
intravenous drug users and unprotected sex account
In the UK, screening of blood and blood products for
for most cases of AIDS.
HIV has eliminated, almost completely, the chance
Public health measures to control the spread of AIDS of the virus being transmitted via blood transfusions
set out to: and blood products.
● raise public awareness of the problem (see
Drug therapies
Figure 24.13)
At present there is no cure for AIDS. Some drugs do
slow down the onset of AIDS but they are expensive
and not available to many HIV-positive people,
especially those living in developing countries.
Drugs developed to disrupt the action of HIV are

called anti-retrovirals. They are designed to target
different stages of the HIV life cycle by acting as:
● reverse transcriptase inhibitors
● DNA-synthesis inhibitors
● protease inhibitors (which prevent key steps in the
synthesis of HIV proteins from occurring).
Combinations of these drugs, accompanied by

medicines to treat opportunistic infections, prolong
the life of an AIDS sufferer but do not offer a cure.
Production of a successful vaccine has so far eluded
scientists because the genetic material in HIV
Figure 24.13 Raising awareness
mutates frequently, forming many new variants with
different antigenic properties.
344
1 a) Explain how a minority of people in a population can 3 Decide whether each of the following statements is
be protected from an infectious disease even if they true or false and then use T or F to indicate your choice.
have not been immunised against it. (2) Where a statement is false, give the word that should
b) Identify T WO factors that af fect the herd immunity have been used in place of the word in bold print. (5)
threshold of an infectious disease. (2) a) The more virulent a pathogen, the higher the
c) Give T WO examples of situations where herd percentage of the population that needs to be
immunity to an infectious disease cannot be vaccinated to establish herd immunity.
established, and explain why in each case. (4) b) The creation of herd immunity is par ticularly
2 a) Name T WO ways by which antigenic var iation impor tant in sparsely populated environments.
can arise in a population of a pathogenic c) Some pathogens can change their antibodies
microorganism. (2) and evade the ef fect of the host’s immunological
b) Explain why at-r isk individuals need to be vaccinated memor y.
against influenza ever y year. (2) d) HIV, which attacks phagocytes, causes acquired
c) Why does the development of an ef fective vaccine immunodef iciency syndrome.
against malar ia continue to elude scientists? (1) e) Antigenic variation occurs in the ‘sleeping sickness’
d) By what means does the bacter ium responsible for pathogen, enabling its var iants to avoid the ef fect of
tuberculosis avoid immune detection? (1) the host’s antibodies.
3 The study of an infectious disease’s outbreak and the

antigens helper T cells phagocytes factors that af fect its spread is called _____. The spread
attack herd poor of a disease that occurs occasionally is descr ibed as
_____, one that occurs as a regular number of cases
bias host quarantine
in a par ticular area as _____, one that occurs as an
clinical hygiene randomised unusually high number of cases in an area as _____ and
compar ison immunity rejected one that occurs as a global epidemic as _____.
detection influenza sporadic 4 Weakened or altered forms of an infectious pathogen or
ef f icacy inhaled threshold its _____ are used as _____. These are administered to
endemic malaria toxin people by _____ so that they will develop active _____
to the disease but not suf fer the disease.
epidemic non-immune vaccination
epidemiology pandemic var iation 5 The safety and _____ of new vaccines must be
established by _____ trials before they can be licensed
evade parameters vector
for use.
exper imental pathogens virulence
6 A clinical tr ial is _____ and double-blind to eliminate
_____ and placebo-controlled to allow a valid _____ to
be made. _____ error is reduced by using a ver y large
1 Infectious diseases caused by _____ such as bacter ia number of people.
and viruses are transmitted by many means including
7 Within a population where most individuals are immune
_____ air, body fluids and _____ organisms.
to an infectious disease, vulnerable _____ individuals
2 _____, antisepsis, good _____, clean water and removal are protected from it by _____ immunity.
of vectors are some of the ways by which transmission of
8 The percentage of immune individuals in a population
infectious diseases can be controlled.
above which a disease no longer persists is called the
➜ 345
herd immunity _____. It depends on the pathogen’s 11 Extensive antigenic _____ in the pathogens that
_____, the vaccine’s ef f icacy and the population’s cause _____ and tr ypanosomiasis has so far prevented
contact _____. scientists from developing a successful vaccine against
them. Antigenic var iation in the _____ virus makes it
9 Herd immunity can be dif f icult to establish if the
necessar y to keep developing new vaccines.
countr y is too _____ to af ford mass vaccination or
if the vaccine is _____ by a large percentage of the 12 Some pathogens take advantage of some par t of the
population. human immune system and launch a direct _____ on
it. HIV attacks _____ and causes AIDS. Tuberculosis
10 By alter ing their antigens, some pathogens are able to
bacter ia avoid immune _____ by sur viving inside
_____ the immune responses made by their _____.
_____.
Chapters 21–24
1 Figure 24.14 shows a simplif ied version of some of the
events associated with the inflammator y response.
tip of knife blade
surface
skin
s of s
kin 1 connective tissue
layer
6
3
blood capillary
engorged
with blood
346 Figure 24.14

a) Match the following answers with blank boxes 1–6 in a) i) Which immunoglobulin in the table would be
the diagram. (5) found in the blood of an unborn baby?
A release of histamine by mast cell ii) Suggest why these antibodies are only needed by
B exit of phagocyte from blood capillar y the baby for a few months af ter bir th. (2)
C entr y of microorganisms at cut b) Of the f ive types of immunoglobulin molecule, which
D attraction of newly arr ived phagocyte to infected is the i) largest, ii) rarest? (2)
area c) State the normal serum concentration of IgA in
E action by phagocyte already present in mg/ml. (1)
connective tissue d) With reference to IgM and IgG, state ONE feature
F increased capillar y permeability allowing common to both the pr imar y and secondar y
increased flow of fluid out of capillar y response shown in the graph. (1)
b) Pain, redness and swelling are features of an inflamed e) With reference to IgG, state THREE dif ferences
area. Copy and complete Table 24.3 using these three between the pr imar y and the secondar y response. (3)
words. (2) f) Antibodies such as IgG are now known to be
produced by the activity of long-lived lymphocytes.
2 Table 24.4 refers to antibody proteins called
With reference to the graph, suggest why the latter
immunoglobulins found in human blood. The graph
are called memor y cells. (1)
in Figure 24.15 refers to the sequence of events that
occurs in response to two separate injections of a type of 3 Give an account of the role played by T lymphocytes in
antigen into a small mammal. the defence of the body. (10)
4 Table 24.5 shows the results for phase II of a clinical tr ial
secondary response
on an influenza vaccine.
a) Present the data as a bar char t, including error bars.
increasing concentration
(See Appendix 3 for help.) (4)

of antibody in plasma
primary response b) i) Based on these results, should this clinical tr ial

proceed to phase III?
ii) Explain your answer. (2)
0 5 10 15 20 25
first second time (days)

injection injection
Key = lgM
= lgG
Figure 24.15
Feature of an inflamed area Reason

An increased blood supply is sent to the af fected area
Fluid is forced out of blood vessels into the tissues at the site of injur y
Swollen tissues press against ner ve receptors and ner ves
Table 24.3
Immunoglobulin (Ig)
IgA IgD IgE IgG IgM
Molecular weight 170 000 184 000 188 100 150 000 960 000
Normal serum concentration 1.4–4.0 g/l 0.1–0.4 g/l 0.1–1.3 mg/l 8.0–16.0 g/l 0.5–2.0 g/l
Ability to cross placenta No No No Yes No
➜ 347
Table 24.4
Time from vaccination (days) Relative viral load in blood plasma (units)
Vaccine group Control group
1 39 ± 6 51 ± 8
2 38 ± 6 48 ± 7
3 23 ± 5 31 ± 5
4 12 ± 3 18 ± 4
Table 24.5
Year Number of notifications of disease Uptake of vaccine (%)

1965 34 000 No vaccine available
1967 31 000 No vaccine available
1969 32 000 80
1971 28 000 80
1973 29 000 80
1975 30 000 40
1977 48 000 32
1979 35 000 44
1981 28 000 54
1983 25 000 58
1985 22 000 64
1987 15 000 74
1989 31 000 78
1991 13 000 84
1993 4 000 86
1995 1 000 90
Table 24.6
5 The data in Table 24.6 refer to the disease per tussis d) i) Descr ibe the pattern of uptake of vaccine dur ing
(whooping cough) in a European countr y. years 1977–92.
a) Plot the data as two line graphs on the same sheet of ii) In general, what ef fect did this have on incidence
graph paper with one x-axis and two y-axes. (4) of the disease? (2)
b) i) Dur ing which years were there 22 000 e) i) Which year required the introduction of a new
notif ications of the disease? vaccine for per tussis?
ii) What was the percentage uptake of the vaccine in ii) Suggest why. (2)
1982? (2)
c) i) Descr ibe the pattern of uptake of vaccine dur ing
years 1973–77.
ii) What ef fect did this have on incidence of the
disease? (2)
348
6 The graph in Figure 24.16 refers to a person infected ii) Why does the relative antibody concentration
with HIV. remain constant between years 1–9 af ter infection
yet the relative HIV concentration increases? (2)
a) i) What happens to the relative concentration of
d) i) At which of the following times af ter infection
HIV between 6 months and 1 year af ter infection?
would this person be most likely to be suf fer ing
ii) Suggest why. (2)
AIDS?
b) i) What relationship exists between the relative
A 6 months B 1 year, 3 months
HIV concentration and relative helper T cell
C 4 years, 6 months D 10 years
concentration from 2 years af ter infection
ii) Explain your choice of answer. (2)
onwards?
e) Why has it proved impossible so far to make people
ii) Explain why. (2)
immune to HIV by vaccination? (1)
c) i) Which type of white blood cell makes antibodies?
antibody concentration
increasing relative concentration
helper T cell concentration
HIV concentration
1 2 3 4 5 6 7 8 9 10
infection time (years)
Figure 24.16
349
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Appendix 1
The genetic code

Abbreviation Amino acid
Second letter of triplet ala alanine
A G T C arg arginine
AAA AGA ATA ACA A asp aspar tic acid

asn asparagine
AAG AGG ATG ACG G
A cys cysteine
AAT AGT ATT ACT T glu glutamic acid
AAC AGC ATC ACC C gln glutamine
GAA GGA GTA GCA A gly glycine

his histidine
GAG GGG GTG GCG G
G ile isoleucine
GAT GGT GTT GCT T leu leucine
First Third
letter GAC GGC GTC GCC C letter lys lysine
of TAA TGA TTA TCA A of met methionine
triplet triplet
phe phenylalanine
TAG TGG TTG TCG G
T pro proline
TAT TGT TTT TCT T
ser ser ine
TAC TGC TTC TCC C thr threonine
CAA CGA CTA CCA A trp tr yptophan
CAG CGG CTG CCG G tyr tyrosine

C val valine
CAT CGT CTT CCT T
Table Ap 1.2 Key to amino acids
CAC CGC CTC CCC C
Table Ap 1.1 The DNA bases grouped into 64 (43) triplets
(A = adenine, G = guanine, T = thymine, C = cytosine)
351
Appendix 2
Box plots A box plot is a way of presenting information that
allows differences between groups, sets, populations, etc.
The data in Table Ap 2.1 refer to the birth weights of to be compared easily. Each box plot shows the median,
babies in three different groups. Each group contains which is the central value in the series of values when
15 babies selected at random from a large number of they are arranged in order. A box plot also displays the
individuals. The mothers of group A were non-smokers, upper quartile (in this case the value 25% above the
those of group B smoked 20 cigarettes per day while median) and the lower quartile (the value 25% below
pregnant and those of group C smoked 40 cigarettes the median). The maximum and minimum values are
per day while pregnant. It is difficult to compare the called upper and lower whiskers. Figure Ap 2.1 shows
variability in birth weight between the three groups how the data for group A are converted into a box plot.
from the data table alone.
Figure Ap 2.2 shows group A’s box plot drawn alongside
Baby Birth weight of baby (kg) those for groups B and C. The box plots give a clear,
number Group A Group B Group C visual representation that allows the variability between
the three groups to be compared more easily than by
15 3.98 3.71 3.42
studying the table of data alone.
14 3.75 3.53 3.30
In this case, the box plots show, at a glance, the
13 3.72 3.49 3.29 depressant effect of smoking on the birth weight of
babies.
12 3.69 3.45 3.24
11 3.62 3.32 3.20
10 3.55 3.27 3.18
9 3.46 3.18 3.15
8 3.38 3.10 3.01
7 3.24 3.06 2.96
6 3.15 2.97 2.92
5 3.12 2.90 2.88
4 3.04 2.86 2.84
3 3.00 2.82 2.78
2 2.96 2.77 2.66
1 2.74 2.53 2.38

Table Ap 2.1
352
Appendix 2
birth weight
of baby (kg) 4.0
baby 15
4.0 upper whisker
3.8
3.8
baby 14
baby 13
baby 12
3.6
upper quartile
baby 11
3.6 (0.75 15 = 11.25
baby 10 = baby 11)
3.4
baby 9
baby 8
3.4 median
weight of baby (kg)

3.2
baby 7
3.2
baby 6
baby 5
lower quartile 3.0
baby 4
baby 3 3.0 (0.25 15 = 3.75
= baby 4)
baby 2
2.8
2.8
baby 1
lower whisker
2.6
2.6
2.4
2.4
2.2
A B C
2.2
group A group
Figure Ap 2.1 Figure Ap 2.2
353
Appendix 3
Statistical concepts Standard deviation
A scientist needs to organise the data collected as results Standard deviation is a measure of the spread of
from an investigation into a manageable form from individual data values around their mean and shows
which conclusions can be drawn. how much variation from the mean exists. A normal
distribution of results can be divided into intervals of
Mean standard deviation as shown in Figure Ap 3.2. 68%
of the values fall within plus or minus one standard
The mean is often referred to as the average. It is the deviation from the mean; 95% of the values fall within
most widely used measure of the central tendency of plus or minus two standard deviations from the mean.
a set of data. It is found by adding up all the values
obtained and dividing them by the total number of The standard deviation of a set of data is calculated
values. For example, for the two populations of British using a mathematical formula (often with the aid of
miners shown in the scatter graphs in Figure Ap 3.1, the an appropriate calculator or computer software). The
mean for population A = 11 830/70 = 169 cm and the deviation (as two standard deviations above or below
mean for population B = 12 530/70 = 179 cm. the mean) for population A in Figure Ap 3.1 equals
9 cm. This low level of deviation reflects the clustering
Range of the values around the mean, with 95% of values lying
within the range 160–178 cm.
The range is the difference between the two most
extreme values in a set of data. For example, for The deviation (as two standard deviations above or
population A the range = 180 – 158 = 22 cm and for below the mean) for population B in Figure Ap 3.1
population B the range = 192 – 164 = 28 cm. equals 11 cm. This higher level of deviation reflects the
Population A (British coal miners in 1910) Population B (British coal miners in 2010)
200 200
190 190 SD 2
180 180
SD 2 mean
height of miner (cm)
height of miner (cm)
170 mean 170

SD 2
160 SD 2 160
150 150
140 140
0 0
0 10 20 30 40 50 60 70 0 10 20 30 40 50 60 70
miner number miner number
(Note: SD 2 = 2 standard deviations)

354
Figure Ap 3.1
Appendix 3
mean
one standard one standard

deviation from deviation from
the mean the mean
frequency
two standard two standard

deviations from deviations from
the mean the mean
68%
2.5% 95% 2.5% Figure Ap 3.3
values
In an investigation into perceptual set (see page 231),

Figure Ap 3.2
three groups of 50 volunteers were used. Before seeing
and being asked to identify the ambiguous image shown
wider spread of the values around the mean, with 95% in Figure Ap 3.3, the members of group A were shown
of values lying within the range 168–190 cm. images of birds, those of group B images of small
Quality of data mammals and those of group C no images. Table Ap 3.1
shows the results.
In a properly designed scientific investigation, several
replicates of each treatment are set up to allow for A plus sign after a result indicates that the significance
experimental error. These replicates produce results test shows the value to be significantly higher than
with a central tendency around the mean. A set of would be expected by chance alone; a minus sign after
results that are clustered around the mean indicates a result indicates a value to be significantly lower than
data of high quality. A comparable set of results (from would be expected by chance alone.
a replicate of the same treatment) that are widespread
are of lower quality. The results from groups A and B (each affected by a
different form of perceptual set) both differ significantly
from what would be expected by chance alone. The
Significant difference results from group C (not affected by perceptual set)
In biology, an experiment is carried out to test a show no such significant difference.
hypothesis. Once results have been obtained, the
scientist needs to know whether these data (which Error bars
rarely conform exactly to the expected outcome) When a bar chart of mean values of data is drawn, it is
support the hypothesis or not. A significance test (a often important to be able to show variability on the
type of statistical analysis) can be used to find out if chart. This can be done using error bars. These are lines
the observed differences between two sets of data are that extend outside and inside each bar and indicate
statistically significant or simply the result of chance. how far from the mean value the true error-free value
Number of people in Number of people in Number of people in

group A who said: group B who said: group C who said:
Bird Rabbit Bird Rabbit Bird Rabbit
47 (+) 3 (–) 5 (–) 45 (+) 24 26
355
Table Ap 3.1
Appendix 3
is likely to be. Error bars can be based on aspects of

variability such as 95% level of confidence and standard 250
deviation.
Figure Ap 3.4 shows a bar chart of the results from a 240

survey carried out on several thousand young people in
a country to estimate the incidence of asthma. Each bar
230
represents a mean value with a 95% level of confidence
whose range is indicated by error bars. Based on the
information in the bar chart, health care experts 220
urea in blood plasma (mg l–1)

could be 95% confident that the percentage number
of asthma cases for the whole population would be
between 13% and 21% for 2–4-year-old males, between 210
7 and 14% for 9–15-year-old females, etc.

200
Error bars also allow a comparison to be made between
two means to determine if they are significantly
different from one another. If their error bars (based on 190
95% level of confidence) do not overlap, the difference
between the two means is regarded as being significant.
180
Figure Ap 3.5 shows a bar chart of the results from
Table 10.1 on page 142 of mean concentration of urea
in the blood plasma of non-pregnant women (NP), 170
pregnant women (P) and pregnant women suffering

pre-eclampsia (PE). Each bar represents a mean value 0
with its variability indicated by error bars. The mean NP P PE
for PE is seen to be significantly different from those group
for both NP and P, which are not significantly different

from one another. Figure Ap 3.5
age
females (years) males
error bar
16–24
9–15
5–8
2–4
16 15 14 13 12 11 10 9 8 7 6 5 4 3 2 1 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21
percentage asthma sufferers percentage asthma sufferers
Figure Ap 3.4
356
Appendix 4
False positives and negatives The results in row 3 of the table are examples of
false positives because the procedure (screening for
A false positive is a result that indicates that the malformations) has produced results indicating that
outcome of an investigative procedure is a positive these fetuses had inherited malformations when in fact
result when in reality the outcome for the set of the babies were found to be normal at birth.
conditions being tested is negative.
The results in row 4 are examples of false negatives
A false negative is a result that indicates that the because the procedure (screening for malformations)
outcome of an investigative procedure is a negative has produced results indicating that these fetuses had
result when in reality the outcome for the set of not inherited malformations when in fact the babies
conditions being tested is positive. were found at birth to possess them.
Table Ap 4.1 shows data from an investigation into the
effectiveness of ultrasound imaging on the antenatal
detection of inherited malformations in babies born in
a region of the UK.
Row Category Year

2001 2005 2009
1 Total number of bir ths 36 433 33 292 29 779
2 Number of babies born with malformations 790 785 762
3 Number of babies repor ted antenatally as having 151 119 52
malformations but normal at bir th
4 Number of babies repor ted antenatally as being 487 464 398
normal but born with malformations
Table Ap 4.1
357
Index
3-D movies 228 antiplatelet therapy 178–9

blood 5, 157
chemical methods, of contraception
antisepsis 330
blood-brain barrier (BBB) 251
137, 138
A chimpanzees 68
anxiety disorders 268

blood cells 4
accessory glands 125

cholera 329
aorta 164, 175

blood clotting 177–81, 310
acetylcholine 168, 245, 253, 254,

cholesterol 181–5
apoptosis 311, 322
blood glucose levels 186–90
267
arteries 158, 159, 160

blood-grouping system 314–15
cholinergics 245
activation energy 79
arterioles 158
blood pressure 162, 169–71
cholinesterase inhibitors 267
activators 94
artificial insemination 132–3

blood vessels 158–9
chorea (Huntingdon’s disease) see
active immunity 332
Huntingdon’s disease (chorea)
aspirin 178–9
BMI (body mass index) 190
AD (Alzheimer’s disease) 65, 217,

chorionic villus sampling (CVS)
243–4, 267
atheromas 174
body composition, measuring
191–2
143, 145
addiction 266, 274–6

atherosclerosis 174, 182
body language 284–5

chromosome structure mutations
adenine 16
ATP (adenosine triphospate) 31,
59–62
97–106, 111–13
body mass index (BMI) 190
adenosine diphospate (ADP) 97

chromosomes 6, 23
ATP synthase 101–2

body temperature 210
adenosine triphospate (ATP) see

chronic anxiety 268
ATP
atria 164
bone 5, 49
chronic myeloid leukaemia (CML)

ADH (antidiuretic hormone) 211
atrial systole 166, 168
‘bone marrow’ transplants 9, 10
61, 69–70
ADP (adenosine diphospate) 97
atrio-ventricular node (AVN) 168
box plots 351–2
chunking 237–8
adrenaline (epinephrine) 169, 188,
atrio-ventricular (AV) valves see
brain 209–18
circulatory system 157
205
AV valves brain development 260–1
citric acid cycle 102–3, 111
AFP (alpha-fetoprotein) 143

autoimmunity 317–18 brain injuries 262
cleavage 42
agonists 266
autonomic nervous system (ANS) bubonic plague 330–1
168, 203–5
clinical trials, vaccine 332–4
AIDS 329, 342–4
closure 222–3, 224
alcohol 272, 273–4
autosomal dominant inheritance

C
150–1, 154
CML (chronic myeloid leukaemia)
alcoholism 275
cancer cells 14–15, 323
61, 69–70
autosomal incomplete dominance
allergic asthma 320

cannabis 270–1
cocaine 269–70, 275
151, 152, 154
allergy 319–20
capillaries 158
codons 38
autosomal recessive inheritance
alpha-fetoprotein (AFP) 143

148–9, 154
capillary beds 157, 160, 161
cognitive-behavioural approach
alternative routes 79
autosomes 148
carbohydrates 107
276
alternative splicing 41–2

AV valves 164, 166, 167
cardiac conducting system 167–9
communication 282–8
Alzheimer’s disease (AD) 65, 217,
AVN (atrio-ventricular node) 168
cardiac function 164–5
competitive inhibitors 91–2
243–4, 267
axons 248, 249
cardiac muscle 6
condoms 136
amino acids 34, 45–6, 351

cardiac output 164
conducting system, of the heart
amniocentesis 143, 144–5
B cardio-accelerator centre 168
167–9
amniotic fluid 12
B cells (B lymphocytes) 313, 323–4,
cardio-inhibitor centre 168
cones 257–8
amplification of DNA 71–2
343
cardiovascular diseases 174–88
congenital hypothyroidism 147–8
amygdala 211
B lymphocytes (B cells) 313, 323–4,
emedial measures 193–4 connective tissue 5
anabolic pathways 78
343
risk factors 193–4 contact comfort 278–9
anaphylactic shock 320
bacteria 328
cardiovascular system continuous fertility 131
angina 175
bacterial transformation 18–19
cardiac cycle 166–71 contraception 136–8
angioplasty 193, 194
balloon angioplasty 193, 194
structure 157–65 converging neural pathway 257–8
anomaly scans 140
barrier methods, of contraception
cartilage 5
cornea repair 10
ANS (autonomic nervous system)

136
catabolic pathways 78
coronary arteries 175
168, 203–5
base-pairing 16–17
catalase 81, 84
coronary bypasses 194
antagonists 266
BBB (blood-brain barrier) 251
catalysts 80–1
coronary heart disease 174, 175–6
antenatal screening 140–6
beliefs, changing 300–2
cell bodies 248–9
coronary thrombosis 177–8
antibodies 49, 323–4
beta blockers 268
cell metabolism 78
corpus callosum 212, 216
anticoagulants 179
beta (β) thalassemia 57
cellular respiration 97, 111–12
corpus luteum 125, 126, 127, 128
anticodons 38
binding sites 39–41
central core 209
creatine phosphate 112–13
antidiuretic hormone (ADH) 211
binocular disparity 227–8
cerebellum 209, 244
cri-du-chat syndrome 61
antigen-presenting cells 321

biochemical tests 140–6
cerebral cortex 211–18, 244
crime scenes 75
antigen receptors 313–14

bioelectrical impedance 191
cerebral hemispheres 211–18
curare 255–6
antigenic variation 340–2
bioinformatics 65, 66–7
cervical caps 136
CVS (chorionic villus sampling)
358 antigens 323

blastocysts 3
cervical mucus 130, 131
143, 145
antiparallel strands 16–18

blind trial 333
cervix 130
cyclical fertility 131
Index
cystic fibrosis 7, 58, 75, 148–9, 154

Edward’s syndrome 146
FH (familial
HDL (high-density lipoproteins)
cytokines 310, 311, 313, 317

EEGs (electroencephalograms) 215
hypercholesterolaemia) 182,
182
cytoplasmic hybrid cells 12–13

eggs (ova) 125–6
184–5
heart
cytosine 16
elaboration of meaning 241
fibrin 177
conducting system 167–9
cytotoxic T cells 321, 322–3

elaborative encoding 241–2
fibrinogen 177
function 164–5
electrocardiograms (ECGs) 169

figure-ground phenomenon structure 164
D 220–1 heart attacks (myocardial
electroencephalograms (EEGs)
dating scans 140

215
fish protein, separation 47–8 infarctions) 174, 178
death rates, coronary heart disease

electron transport chain 104–5
fMRI (functional magnetic heart murmurs 167
175–6
resonance) 217–18 heart rate 164
electrophoresis 63
deep vein thrombosis 180

follicle-stimulating hormone (FSH)
heart sounds 167
elephantiasis 162–3
dehydrogenase enzyme 105–6

126, 128, 137
embolus 177–8
helper T cells 321, 323, 343
deindividuation 299–300
follicles 125, 126, 127
embryonic cells 2
heparin 179
deletion 59
food handling 330
embryonic stem cells 3, 10, 11–12

hepatic portal vein 157
dementia 217, 267

forensic applications, amplified
emergency hormonal contraceptive
herd immunity 336–9
dendrites 248–9
DNA 75–6
pills 137
Hershey and Chase, phage
densitometry 191
fragile X syndrome 58
emotional memories 239, 244

experiments 21
deoxyribonucleic acid (DNA) see

frameshift mutation 54–5, 57, 58
emotions 211
HGP (human genome project)
DNA
FSH (follicle-stimulating hormone) 63–4
encoding 241–2
126, 128, 137
deoxyribose 16
high-density lipoproteins (HDL)
end-product inhibition 94–5

functional magnetic resonance
depression 269
182
endocrine glands 126

(fMRI) 217–18
diabetes 186, 188–90, 318
hippocampus 245
endometrium 127, 128

fungi 328
diabetic retinopathy 187

histamine 309, 319, 320
endorphins 265
diagnostic testing 142, 146–7

HIV 329, 342–4
endothelium 159
G
diaphragms 136
homeostasis 204–8
enzyme control, DNA replication
GABA (gamma aminobutyric acid)
diastole 166
29–31
hormone control 126–9
254, 268
differentiation 2–3
enzyme induction 86
hormones 49, 126
galactosaemia 147
discrimination 296–7
enzymes 49, 81–5
HSCs (haematopoietic stem cells) 9
gamma aminobutyric acid (GABA)
distribution pattern, obesity 192

epidemiology, of infectious diseases
254, 268
human chorionic gonadotrophin
diverging neural pathway 258–9

331–4
(HCG) 130, 140, 141
gel electrophoresis 47–8

division of labour 2
epinephrine (adrenaline) 169, 188,
human genome project (HGP)
gene expression 2
DMD (Duchenne muscular

205
63–4
generalisation 296
dystrophy) 57
episodic memories 239, 244
Huntingdon’s disease (chorea) 59,
genetic code 34, 351

150–1, 154
DNA (deoxyribonucleic acid) epithelial cells 309

genetic counselling 148–55 hybridisation 73
amplification 71–3 epithelial tissue 4

genetic disorders 52, 69
hydrogen bonds 45
arrangement in chromosomes epithelium 4

genetic ‘fingerprints’ 74–5 hydrogen peroxide 80, 84
23
EPSP (excitatory postsynaptic
genetic material, identification hygiene 330
double helix 18
potential) 255
18–21
replication 24–31
error bars 355–6
hypertension 171
genetic screening 148–55

structure 16–18, 22
ethical issues 10–14, 70, 134, 138
hypothalamus 126, 209–11
genetic testing 75
DNA bases 351

eugenics 134
genomic sequencing 63–5 I
DNA microarray 73–5

exchange vessels 158
genotypes 33
ICSH (interstitial cell-stimulating
DNA polymerase 30
excitatory postsynaptic potential
germline cells 7–8 hormone) 126
DNA probes 73–5

(EPSP) 255
glial cells 250–1 ICSI (intracytoplasmic sperm
DNA profiles 75–6

excitatory signals 254
glucagon 187–8 injection) 134
dopamine 245, 254, 265–6, 267–8,

exercise 192
glucose tolerance test 189

identification 301–2
270
exons 36
glycine 254, 256

imitation 291–3
double-blind trial 333
experimental error 333
glycogen 187
immune system 308–11 see also
double helix 18
extinction of behaviour 295–6
glycolysis 78–9, 101–2, 103, 111–12 specific immune response

Down’s syndrome 141, 143–4
eye contact 283–4
glycoprotein inhibitors 179

immunisation 332–3
drug addiction 274–6
drug rehabilitation programmes
F glycoproteins 49
immunodeficiency diseases 342–4
facial expressions 283
group pressure 298–9 immunological memory 323–5
276
false negatives 141, 357

guanine 16
in vitro fertilisation (IVF) 133–6
drug tolerance 274
false positives 141, 357

induced fit 82–3
drugs, recreational 269–76
Duchenne muscular dystrophy

familial Down’s syndrome 62
H induced pluripotent stem cell
haematopoietic stem cells (HSCs) 9

technology 11, 12
(DMD) 57
familial hypercholesterolaemia
(FH) 182, 184–5

haemoglobin 49, 55
infant attachment 278–81
duplication 59–60
family trees 148

haemophilia 151–4, 154–5, 180
infectious diseases 328–34
E fats 107
hardening of the arteries 174
infertility treatments 131–6
E. coli 86–8
feedback inhibition 94–5, 111
hay fever 319
inflammatory response 309–10
ECGs (electrocardiograms) 169
fertile periods 131
HCG (human chorionic
influenza virus 340, 341
359
‘ecstasy’ (MDA) 271
fertilisation 128, 130
gonadotrophin) 130, 140, 141
inherited diseases 147–8
Index
inhibitors 91–2, 266–7

matching shapes 230–1
sensory pathways 202–3
perceptual set 231
inhibitory signals 254

MDA (‘ecstasy’) 271
nervous tissue 6
peripheral neuropathy 187
insulin 42, 187–8

mean 354
neural pathways 257–64
peripheral vascular disease 174,
inter neurons 248

measles 329
neurons 248–50
180–1
internalisation 300–1
medical applications, amplified
neuroplasticity 259–64
personal genome sequence 68
interstitial cell-stimulating
DNA 75
neurotransmitter-related disorders
personalised medicine 68–70
hormone (ICSH) 126

medulla 209
266–9
PET (positron-emission
interstitial cells 124, 126

meiosis 7
neurotransmitters 253–6
tomography) 217
intra-uterine devices (IUD) 136,

membranes 49
nicotine 271, 273
PGD (pre-implantation genetic
137–8 memory
NK (natural killer) cells 4, 310, 311
diagnosis) 134
intracytoplasmic sperm injection levels 235–44

non-competitive inhibitors 93–4
PGS (pre-implantation genetic
(ICSI) 134
screening) 133–4
location in the brain 244–5

non-verbal communication 282–6
introns 36
phage experiments, Hershey and
selective 235
nonsense mutation 54, 57
IUD (intra-uterine devices) 136,

Chase 21
memory cells 325, 332

noradrenaline (norepinephrine)
137–8 phagocytes 4, 310–11
menstrual cycle 126, 127–9

168, 254, 268, 269
IVF (in vitro fertilisation) 133–6 phagocytosis 251, 310–11
Meselson and Stahl’s experiment 28

norepinephrine (noradrenaline)
168, 268, 269

pharmacogenetics 69–70
messenger RNA (mRNA) see
K nuchal translucency scan (NT) 143

phenotypes 33
mRNA
karyotype 144–5
nuclear division (mitosis) 6, 7
phenylketonuria (PKU) 56, 146–7
metabolic disorders 146–7

Klinefelter’s syndrome 145–6
nuclear transfer technique 12–13
phosphate 97
metabolic pathways 78–9, 86–95,

kwashiorkor 162
101–2 nucleotide sequence repeat
phosphofructokinase 111–12
methods of control, and social expansion 55, 59

phosphorylation 97–101, 112
L competence 281
nucleotides 16
physical proximity 285–6
lactic acid metabolism 113–14 methylphenidate 245

pituitary glands 126, 127, 147–8,
lactose metabolism 86–8 O 209–10
microvascular disease 186–7
lagging strands, of replicated DNA obesity 190–2

pituitary hormones 131
‘mini pills’ 137, 138
31
object recognition 230
PKU (phenylketonuria) 56, 146–7
minor plasticity 263–4
language 285–6, 288

oedema 162
placebo effect 333
missense mutation 54, 55–6
language areas 217–18

oestrogen 126, 127, 130, 137
plasma 160
mitochondria 254
LDL (low-density lipoproteins) 182

operator genes 86–8
plasticity of response 259–64
mitochondrial DNA 68
learning 289–97
operons 86–7
platelets 4
mitosis (nuclear division) 6, 7
learning curves 290

oral contraceptive pills 137
pleasure centres 211
model organisms 9
lethal effect 60
ordered relationships 221–3
point mutation 52–3
molecular addition 42
leukaemia 9, 61, 69–70

organic bases 16
poisons 255–6
‘morning after’ pills 137
LH (luteinising hormone) 126,

organisation, and LTM 240–1
poliomyelitis 252, 337–8
mosquitoes 331
128, 137
organs 6
polygenic inheritance 154–5
motor neurons 248
ligase 31
orientation 223
polymerase chain reaction (PCR)
motor skills 289–90
limbic system 209, 244, 245

osmoreceptors 211
71–2
mRNA (messenger RNA) 34–7, 38
linear perspective 225

‘out-of-Africa’ theory 67, 68
polypeptide bonds 45
MS (multiple sclerosis) 252, 318
lipids 182
ova (eggs) 125–6
polypeptides 34, 41, 45–6
mucous membranes 309
lipoproteins 182
ovarian hormones 127
polyribosomes 41
mucus 42, 49, 130, 131, 309
liver 187
ovaries 125–6, 127
positron-emission tomography
Müller-Lyer illusion 226
long-term memory (LTM) 239–43

ovulation 127, 131–2
(PET) 217
multi-enzyme complexes 85
low-density lipoproteins (LDL) 182

post-translational modifications 42
luteinising hormone (LH) 126,
multicellular parasites 328

P
postnatal screening 146–8
128, 137
multiple sclerosis (MS) 252, 318
pacemakers 167–8
postsynaptic neurons 253, 254
lymphatic system 161–3

muscle tissue 5–6, 49, 114–15
pain threshold 265
pre-eclampsia 141–2
lymphocytes 4, 311, 313–25

mutagenic agents 50–1
pancreas 187
pre-implantation genetic diagnosis
lymphoma 9
mutations 7–8, 14–15, 50–62,
parasites 162–3
(PGD) 134
339–40
parasympathetic systems 203–5
lysozymes 309, 311

pre-implantation genetic screening
myelin sheath 248, 249–50, 251

Parkinson’s disease 267–8
(PGS) 133–4
M myelination 249
paternity disputes 75
pregnancy testing 130
macrophages 342
myocardial infarctions (heart
pathogenic protozoa 341–2
pressure filtration 160
attacks) 174, 178
major plasticity 262

pathogens 328–31
presynaptic neurons 253
myoglobin 114
malaria 56, 331, 342

PCR (polymerase chain reaction)
primary response 323–5
male reproductive system 124–5

N 71–2
primary transcript 36
malnutrition 162–3
natural killer (NK) cells 4, 310, 311
pedigree charts 148
primers 30, 31, 71–2
malonic acid 103–4

negative feedback control 127, 128,
peptide bonds 41
procedural memories 239, 244
manganese dioxide 80
131, 187, 188, 205
perception
progesterone 126, 127, 130, 137
MAO inhibitors 269

nerve cells 248–52
distance 225–30 prostate gland 124, 125, 126
marker chemicals 140–1

nervous system 248–52
recognition 230–3 protein synthesis 34
360 mass vaccination 336–9

functional division 203–8 segregation of objects 220–4 proteins
mast cells 309, 320

motor pathways 202–3 perceptual constancy 229
and DNA 34
Index
function 49
S specific immune response 313–25, tissue (adult) stem cells 3
as respiratory substrate 107

SAN (sino-atrial node) 167–8
339–44 touch 286, 287
structure 45–9
schizophrenia 268
sperm 124–5 transcription 33, 35–7
prothrombin 177
secondary response 325, 332
sperm duct 124
transfer RNA (tRNA) see tRNA
protozoa 328, 341–2

selective memory 235
sperm production 126–7 translation 33, 38–41
proximity 222
self-destructive enzymes 311
splice-site mutation 53, 54
translocation 60
puberty 126
semantic memories 239, 244
splicing 36–7 transmission of diseases 329–31
public health medicine 339

semen 125
split-brain studies 216–17 trial-and-error learning 293
pulmonary artery 164

semi-lunar (SL) valves 164, 167
standard deviation 354–5 trinucleotide repeat expansion
pulmonary embolism 181

seminal vessels 124, 125, 126
start codons 38, 41
mutation 53–4
pulmonary system 157

seminiferous tubules 124, 126
statins 182, 183–4 tRNA (transfer RNA) 34, 38
pulse rate 164–5

sensory deprivation, and brain
statistical analysis 333
trypanosomiasis 341
punishment 296
development 261
statistical concepts 354–6 tubal ligation 136–7
sensory memory (SM) 235

STDs (sexually transmitted
tuberculosis (TB) 337, 342
Q diseases) 330
tumours 14–15, 217
sensory neurons 248
quality of data 355

stem cells
Turner’s syndrome 145
serial position effect 238–9
quarantine 330
ethical issues 10–14
serotonin 254, 268, 269

U
R sex chromosomes 148
regulation 13–14
and research 9
ultrasound imaging 140
randomisation 333
sex-linked recessive trait 151–4,
sources of 12
unrewarded behaviour 296
range 354
154–5
therapeutic value 9–10
UV radiation 50–1
rat fleas 330–1

sexually transmitted diseases
rational drug design 69–70
(STDs) 330
types 3–8
V
shape constancy 229

stenting 194
vaccination 332–4, 336–9
receptor molecules 253
shaping of behaviour 294–5

stereoscopy 228–9 vacuoles 311
receptors 202
short-term memory (STM) 235–9

STM (short-term memory) 235–9 valves 159, 164, 166
recreational drugs 269–76
sickle cell disease 55–6, 151, 154

stop codons 38, 41
vascular disease, and blood glucose
regulator genes 86–7
sickle cell trait 151

‘strange situation’ research tool
levels 186–90
rehearsal 238, 240
signal molecules 91
279, 280
vasectomies 136
reinforcement 293–4
significant difference 355

sterilisation procedures 136
vasoconstriction 158
relative height 225
similarity 222
stroke volume 164
vasodilation 158, 309
relative size 225
single-gene mutation 52
strokes 174, 178, 262
veins 159, 160
releaser hormones 210
single nucleotide polymorphism

structural proteins 49
venae cavae 164
renal failure 187
(SNP) 65
strychnine 256
ventricles 164
replication, of DNA 24–31
sino-atrial node (SAN) 167–8

substrate concentration 92–3 ventricular diastole 166
replication forks 30, 31
size constancy 229

sugar-phosphate backbone 16–17 ventricular systole 168
repressor molecules 86–8
skeletal muscle 5–6, 114–15

summation 255
verbal communication 286–8
reproductive organs
skin 309
superimposition 225
vesicles 253
ovaries 125–6
skin-fold thickness 191
sympathetic systems 203–5 viruses 328
testes 124–5
skin grafts 9
synaptic clefts 248, 251, 253–6
visual cues 225
respiratory substrates 107–11
SL valves 166, 167

systematics 67
visual stimuli, grouping 222–4
retrieval, from LTM 241–2
SM (sensory memory) 235

systems 6
von Willebrand disease (vWD) 179
retro viruses 343
smallpox 338
systole 166
von Willebrand factor (vWF) 179
reverberating pathway 259–60
smart drugs 245
reward pathway 265–6

T W
smiling (in babies) 282
rewards 296
T cells (T lymphocytes) 313, 317,
waist/hip ratio 191
smooth (involuntary) muscle 6
Rh blood typing 315–16

321–3
SNP (single nucleotide

warfarin 179
rhesus antibody testing 146

Tay-Sachs disease 57, 252
polymorphism) 65
warts 14
rhesus D-antigen 315–17

TB (tuberculosis) 337, 342
SNS (somatic nervous system) 203

waste disposal 330
rheumatoid arthritis 317–18

testes 124–5
social competence 281
water balance 211
ribosomes 34, 39–41

testosterone 124, 126
social facilitation 297–9

water supply 330
risk evaluation 154–5

texture gradient 225
social groups 297

working memory 239
risk prediction 70
thermal cycling 72
social influence 297–302
Ritalin 245
thrombin 177
X
social skills 289–90
RNA (ribonucleic acid) 33

thrombolysis 178
X-ray crystallography 22
socialisation 281
RNA polymerase 36
thrombosis 177–8
somatic cells 4–6, 8
Z
rods 257–8
thymine 16
somatic nervous system (SNS) 203

zygotes 2
thyroxine 147–8
spatial memories 239, 244–5
tissue fluid 160–1
361

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Unit 1 Human Cells 19 Communication and social behaviour 278

2 DNA and its replication 16

Unit 4 Immunology and Public Health

4 Proteins, mutations and genetic disorders 45 21 Immune system 308

5 Human genomics 63 22 Specif ic cellular defences 313

6 Metabolism and enzymes 78 23 Infectious diseases and epidemiology 328

7 Cellular respiration 97 24 Herd immunity and antigenic variation 336

Unit 2 Physiology and Health Appendix 1

8 Reproductive organs and hormonal control 124

9 Biology of fer tility control 131

10 Ante- and postnatal screening 140

11 Structure of the cardiovascular system 157 Appendix 3

12 The cardiovascular system in action 166

Statistical concepts 354

13 Cardiovascular disease, diabetes and obesity 174

Unit 3 Neurobiology and False positives and negatives 357

14 Ner vous system 202

17 Ner ve cells and neural pathways 248

18 Neurotransmitters, mood and behaviour 265

1 Differentiation and stem cells

Differentiation in human cells unspecialised

As embryological development proceeds, the

Selective gene expression motor fibre

the genes that code (see chapter 3) for the proteins

● reproduce themselves by repeated mitosis and cell

Embr yonic stem cells

Figure 1.3 Embr yonic stem cells

Origin of blood cells

marrow (see Figure 1.4) give r ise to red

natural killer cells and B and T

white blood cells (after staining)

Figure 1.4 Origin of blood cells

Differentiation in somatic cells oesophagus

All differentiated cells (except reproductive cells)

Epithelium lining of cells

Connective tissue Cartilage

one of two pads of

Figure 1.8 Car tilage

flexible fibres live bone cell

blood vessel calcified

Figure 1.11 Cardiac muscle cells

Increasing levels of complexity

Differentiation in germline cells between haploid and diploid cells as summarised in

diploid zygote diploid zygote

repeated mitosis and differentiation to repeated mitosis and differentiation

diploid germline diploid

mitosis diploid mitosis

Figure 1.13 Transmission of mutation in germline cell

Testing Your Knowledge 1

Case Study Therapeutic use of stem cells

Bone marrow transplantation Although umbilical cord blood is rich in HSCs,

stem cells collected bone marrow or

bone marrow or blood

Figure 1.14 Bone marrow transplantation

Cornea repair source of temporary skin while the patient is waiting