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Breaking Bioethics

This section provides reactions to current and emerging issues in

bioethics.

Germline Modification and the Burden of

Human Existence
JOHN HARRIS

Introduction In my book On Cloning, published

in 2004,1 I traced the roots of the hos-
The very idea of intervening in the
tility to germline modification and,
germline of humans, to modify if not
incidentally, outlined the technique—
human nature at least the genetic
then already widely known—that might
endowment of some humans, contin-
eventually make possible the treatment
ues to encounter hostility that is unre-
of mitochondrial disease. I noted there
lated to the expected benefit or to the
that the panic over germline modifi-
safety and efficacy of such procedures.
To understand the pervasive hostility cation began with IVF:
to the idea of germline modification, we
My interest in cloning was kindled
first need to look at the roots of this
when I started thinking about cloning
hostility in developments in the 1970s.
in the light of the birth of Louise Brown
In this article I do not consider issues on July 25th 1978. I described the tech-
of safety and efficacy specifically but nique that eventually produced Dolly
explore the question of whether there in a paper published in 1983,2 and
exist principled objections to germline discussed some possible advantages of
modification in general and to mito- the technique in my book The Value of
chondrial replacement therapy (MRT) Life which was published in 1985.3
in particular. We start with the modern
history of this hostility and then, in Now that more than 5 million babies4
the second section, examine the argu- have been born via assisted reproduc-
ments against MRT. tion technology (ART), pioneered in

This article is based on three public interventions I made recently in an attempt to defend a new,
valuable, and both life-saving and life-enhancing therapeutic technology. The technology in question is
mitochondrial replacement therapy (MRT). In descending chronological order, these interventions
were (1) a workshop of the United States Institute of Medicine of the National Academies Board
on Health Sciences Policy entitled “Ethical and Social Policy Considerations of Novel Techniques
for Prevention of Maternal Transmission of Mitochondrial DNA Diseases” in Washington, DC
(see http://www.iom.edu/Activities/Research/MitoEthics/2015-MAR-31.aspx); (2) a presenta-
tion in the United Kingdom Parliament, under the auspices of the Progress Educational Trust, on
Monday, February 2, 2015 (on the eve of the historic debate and vote in the U.K. Parliament that
gave the go-ahead for mitochondrial transfer); and (3) an article published in the Guardian news-
paper in 2012 shortly after the U.K. Human Fertilization and Embryology Authority announced a
public consultation on mitochondrial DNA transfer.

Cambridge Quarterly of Healthcare Ethics (2016), 25, 6–18.

© Cambridge University Press 2016.
6 doi:10.1017/S0963180115000237
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Germline Modification and the Burden of Human Existence

the U.K. by Bob Edwards and Patrick creatures was unethical in principle—
Steptoe, the horrified reaction of so not simply because it was unsafe. Bush
many commentators at the time, which did not, for example, note that grow-
I remember well,5 seems hard to credit. ing life for our convenience is the reason
There would, it was widely claimed, be we humans have been cloning plants
unimaginably terrible long-term effects. for millennia and why animal cloning
As Louise Brown herself said recently: has recently taken off in a big way.
“When I was born they all said it
shouldn’t be done and that it was mess- Cloning is already being used com-
ing with God and nature but it worked mercially in the livestock industry in
and obviously it was meant to be.”6 some parts of the world for the repli-
Almost fifteen years after Louise cation of elite breeding animals. It has
Brown appeared, another famous female been widely reported in the media
baby was born in the United Kingdom that products from the offspring of
cloned animals have already entered
thanks to (and despite execrations
the human food chain in the United
directed at) British science. This was a
States and elsewhere. . . . Following
baby called Dolly.7 So famous was she the decision by the US Food and Drug
destined to become and so scientifi- Administration . . . that products from
cally significant was she at birth that cloned animals are safe, food from
her arrival on the scene was announced clones and their offspring can freely
in Nature on February 27, 1997,8 and enter the marketplace in the US and
again the reaction ranged from hostile there is no requirement for these prod-
to hysterical. ucts to be labeled. There remains a
The then president of the United voluntary moratorium in place for
States, Bill Clinton, called immediately clones of species other than cattle,
for an investigation into the ethics of pigs and goats until more informa-
tion is available on these species.12
such procedures9 and announced a mor-
atorium on public spending on human
cloning. President Clinton said, “There And neither Bush nor Clinton criticized
is virtually unanimous consensus in the God for her massive program of human
scientific and medical communities that cloning (more on this later).
attempting to use these cloning tech- Members of the European Parliament
niques to actually clone a human being demanded that each EU member
is untested and unsafe and morally “enact binding legislation prohibiting
unacceptable.”10 George W. Bush reit- all research on human cloning and
erated Clinton’s hostility to cloning. providing criminal sanctions for any
“I strongly oppose human cloning, as breach.”13 The European Parliament
do most Americans. We recoil at the rushed through a resolution on cloning,
idea of growing human beings for spare the preamble of which asserted that
parts, or creating life for our conve-
nience.”11 From 1998 to 2001, the time the cloning of human beings . . . ,
cannot under any circumstances be
span bookended by these two presiden-
justified or tolerated by any society,
tial comments, cloning a large creature
because it is a serious violation of fun-
like a sheep or a human was problematic damental human rights and is con-
and certainly far from “safe enough,” trary to the principle of equality of
given the paucity of reasons that were human beings as it permits a eugenic
then apparent for cloning humans. and racist selection of the human race,
However, their remarks and those of it offends against human dignity and it
others at the time suggested that cloning requires experimentation on humans.

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John Harris

The resolution went on to claim that identical” to another human being

“each individual has a right to his or her means a human being sharing with
own genetic identity and that human another the same nuclear gene set.
cloning is, and must continue to be,
prohibited.”14 These statements provide no coherent
The European parliamentarians failed basis for objection to cloning, nor indeed
to notice that the same right to “her to germline therapy per se. There are
own genetic identity” is violated with vague references to “human rights” or
the birth of every identical twin. God “dignity” or the importance of “genetic
(or nature) is a habitual and serial identity” with little or no attempt to
cloner, causing such violations of rights explain what these principles are, or to
in 1 in every 270 births; 3 in every 1,000 indicate how they might apply to clon-
human births are clones. This means ing. If, for example, embryo splitting
that, globally, around 400,000 human (the deliberate creation of monozygotic
clones are born every year.15 It is diffi- twins) proved to confer immunity to
cult to avoid the conclusion that neither some lethal genetic diseases, would we
God nor nature has any respect for an ban this deliberate cloning? I hope not!
individual’s “right to her own genetic In 2001 the United Kingdom gov-
identity” as defined by the European ernment outlawed human reproductive
Parliament. cloning in the hastily drafted Human
Following swiftly on the tail of the Reproductive Cloning Act 2001. This
European Parliament, the Additional hostility to cloning followed closely the
Protocol to the Convention for the pronouncements of many other bodies
Protection of Human Rights and Dignity both in Europe and across the world. It
of the Human Being with Regard to the is sometimes claimed16 that the exten-
Application of Biology and Medicine, on sive outlawing of germline alterations
the Prohibition of Cloning Human Beings now in place in many countries was the
of the Council of Europe was promul- result of a long and thoughtful process.
gated in Paris, on January 12, 1998— The available evidence does not sup-
again, one may think, in some haste, if port this. The consensus against germ-
not panic, following the birth of Dolly. line interventions per se, as I have
The protocol states: indicated previously and argued else-
where,17 is ill-conceived and is now
Considering the purpose of the crumbling—witness the recent vote to
Convention on Human Rights and change the law in the U.K. Parliament18
Biomedicine, in particular the prin- and the willingness of the United States
ciple mentioned in Article 1 aiming Institute of Medicine of the National
to protect the dignity and identity of Academies to make a serious and objec-
all human beings, tive reassessment of these issues.19
[The member states] have agreed
The common factors between Louise
as follows:
Brown and the family-name-deficient
Dolly were two. First there is the alleg-
Article 1
edly “synthetic” circumstances of their
conception and birth (as if they weren’t
1. Any intervention seeking to create a
human being genetically identical to real female human and animal individ-
another human being, whether living uals). The second factor is the claim that
or dead, is prohibited. their creation involved some unspecified
2. For the purpose of this article, violation of what was variously described
the term human being “genetically as a right to “genetic identity” and, in

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Germline Modification and the Burden of Human Existence

the case of human cloning (that is, the and there are, with suitable safety cave-
deliberate creation of monozygotic ats, moral reasons—in addition to
twins), of a right in essence plucked from some of the appropriate safety mea-
the air to suit prejudice and scientific sures I have discussed elsewhere23—
illiteracy. This imperative, invented by to make use of these methods. We now
UNESCO’s Bioethics Committee to jus- turn to one specific existing possibil-
tify its condemnation of cloning, involves ity for improvement that involves a
the claim that the human genome must germline intervention—namely, mito-
be preserved as “the common heritage of chondrial replacement therapy.
humanity.”20 Those who appeal to
this concept not only have come to see
The Argument: What Are the Pros
the present evolved state of the human
and Cons of MRT Whereby Healthy
genome as the common heritage of
Mitochondria from an Unrelated
humanity but also draw on the almost
Donor Are Included in an Embryo
always unargued claim that the human
Containing the Nuclear DNA of Two
genome must be frozen, as far as is
Other People?
possible, in perpetuity at this particu-
lar evolutionary stage. We should note, before concentrating
UNESCO conveniently ignored the on MRT, that a recent flurry of papers
fact that cloning is the only reproduc- in Nature and Science discussing pos-
tive method that actually does pre- sible research and therapy using various
serve the human genome intact. Indeed, genome modification techniques—
it copies it (sometimes only almost) which were almost immediately fol-
exactly. Other forms of human repro- lowed by the announcement that a group
duction, on the other hand, randomly in China had used such techniques in
vary the human genome with each human embryos24—are further evidence
combination of the genetic material of not only of the scientific viability of
two or more different individuals. What methods of modifying the human germ-
human reproduction does not do very line but also of the need to reassess the
well is improve it. As I argued in my safety, efficacy, and ethics of the use of
book Enhancing Evolution,21 the human such techniques in humans and to
genome in its present state is a very move toward a new consensus as to the
imperfect work in progress. The prob- appropriate conditions for their ulti-
lem is that progress via Darwinian mate acceptability.25
evolution is extremely slow, and the In particular, the paper by David
direction unpredictable; all we know Baltimore et al. emphasizes the need for
is that it will facilitate gene survival.22 such work to be carried out “in coun-
It is probable that, in the interests of tries with a highly developed biosci-
human survival and certainly those of ence capacity” and ones in which “tight
human welfare and well-being, we may regulation” of such science exists or can
simply not be able to wait. For example, be established.26 In the U.K. context, for
we will need to accelerate the devel- example, any further such modifica-
opment of better resistance to bacteria, tions that would end up in the genome
disease, viruses, or hostile environ- of an implanted human embryo would
ments or of the technologies that will have to be licensed by the U.K. regula-
be eventually necessary to find, and tory body Human Fertilization and
travel to, habitats alternative to the Embryology Authority (HFEA), which
earth. There are methods to push evolu- was established by act of Parliament in
tion a little harder in the right direction, 1990.27 Such measures would probably

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John Harris

also need to be approved separately by all reproduction of whatever kind. This

Parliament, as has recently happened so-called uncharted territory (so called
in the case of MRT. In other words, in by Lisa Jardine, current chair of the
the U.K. we have—and for more than HFEA, when she announced the HFEA’s
25 years have had—so far adequate and consultation on these issues in 2012)30
robust safeguards in place. However, presents the usual trade-offs between
these safeguards in the U.K. are the result benefits to people now and known
of prior years of wide public consulta- unknowns concerning future dangers.
tion, punctuated by scholarly research The introduction of all new technolo-
and the commissioning of authoritative gies involves uncertainty about long-
reports,28 and the emergence of a consen- term and unforeseen events.
sus on the way forward should be estab- This is, of course, also true of
lished and continually reviewed by “normal” sexual reproduction—a very
Parliament where necessary. dangerous activity indeed, and one
I shall now concentrate on the ethics often described as a “genetic lottery.”
of MRT, which is, from a safety per- Human reproduction involves genes
spective, widely regarded as now good being recklessly combined—sometimes
to go. But a number of the consider- literally but always figuratively—in the
ations we are about to discuss will also dark, with unforeseeable consequences
apply to the other techniques described for the resulting children, parents, and
in the literature cited previously. the generations to come.
There is a large degree of despera-
tion and not a little callousness in Every year an estimated 7.9 million
the objections that have been made so children—6 percent of total birth
far to mitochondrial donation. This worldwide—are born with a serious
procedure—which will pave the way birth defect of genetic or partially
genetic origin. Additional hundreds
to helping some 2,500 women in the
of thousands more are born with seri-
U.K. have children related to them ous birth defects of post-conception
and avoid some terrible diseases—is, origin, including maternal exposure
I believe, to be unreservedly welcomed. to environmental agents, (teratogens)
Unfortunately, some people seem to such as alcohol, rubella, syphilis and
object regardless of the evidence and iodine deficiency that can harm a
are willing to defend absurdly high developing fetus.31
standards of safety, standards that are
not met by normal sexual reproduc- It is doubtful that natural sexual repro-
tion, let alone by ARTs. duction, with its risk of sexually trans-
Mitochondrial disease can be very mitted disease, its high abnormality rate
serious, causing conditions like Leigh’s in the resulting children, and its gross
disease, a fatal infant encephalopathy, inefficiency in terms of the death and
and others that waste muscles or cause destruction of embryos (estimated to be
diabetes and deafness. one in three to one in five deaths per live
birth),32 would ever have been approved
by regulatory bodies if it had been
Future Generations
invented as a reproductive technology
Of course, this new technology is to rather than simply “found” as part of our
some extent about consequences for evolved biology.
“generations down the line”29—but so Of course, this is not a reason to add
what? This is true not only of all assisted insult to injury, but it puts the peril of
reproductive technologies but also of the uncharted future posed by this

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Germline Modification and the Burden of Human Existence

technology into some perspective. If the the first time. If impractically high
gold standard is sexual reproduction, precautionary thresholds were deci-
new reproductive methods would have sive we would not have vaccines,
to be pretty bad to fail. MRT will pre- nor IVF, nor any other advance.
Nothing is entirely safe. We have to
vent serious mitochondrial disease and
decide what’s “safe enough” given
the suffering it causes for women with the balance of risks and benefits.
mitochondrial disease, for their own Sometimes this decision must be left
children, and for countless future gen- to those who wish to use the proce-
erations. As always, we have to balance dure and on whom the risk falls. . . .
possible unknown future risks with It is true that reproductive risks
known future dangers. also fall on potential offspring. But
that is true of all reproduction, and
yet we do not ban it. Indeed, it is
The Alternative to MRT Involves Greater important to realise that we are already
Known Risk deeply engaged in a mass experiment33
on the quality of our gametes. This
An important point is that, in the case
is particularly true for men, for whom
of mitochondrial disease, we know ample evidence indicates that older
that many women for many different age lowers the quality of gametes
reasons will continue to desire their (most likely through the accumulation
own genetically related children and of DNA damage), with a clear correla-
will continue to have them if denied tion between older father’s age and
or unable to access MRT. The denial of increased risk for several neuropsychi-
access to MRT will not prevent seri- atric disorders like schizophrenia.34
ous disease being transmitted indefi-
nitely through the generations, whereas Three-Parent Families
access to MRT can be expected signifi-
cantly to reduce this risk. The choice The “three genetic parents” label that has
here is not between a germline inter- been applied by many commentators is
vention that might go wrong and as a also grossly misleading. The third-party
result perpetuate a problem indefinitely DNA contained in the donated mito-
and a safe alternative. It is between chondria makes up much less than 1
such a technique and no current alter- percent of the total genetic contribu-
native for women who want their tion and does not transmit any of the
own genetically related offspring and traits that confer the usual family
who will also act so as to perpetuate resemblances and distinctive personal
the occurrence of disease. features in which both parents and
children are interested. The mitochon-
dria provide energy to cells and when
Safety and Uncertainty they are diseased cause inheritable
We have always to decide not what is harm—hence the need for mitochon-
safe but what is safe enough, given the dria replacement therapy. No identity-
balance of risks and benefits. As I noted conferring features are transmitted by
with colleagues elsewhere: the mitochondria.
In any event, to be a parent properly
[It] is worth reminding ourselves so called, as opposed to a mere progeni-
that uncertainty is the defining fea- tor, involves much more than a genetic
ture of knowledge-intensive societ- contribution to the child and often
ies and applies, quite obviously, to any does not entail a genetic contribution
procedure contemplated in humans for at all (for example, adoption, fostering,

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John Harris

informal families, and nonpaternity— rate of 2 percent, nonpaternity rates in

more of this anon). the United Kingdom account for more
Although children might be con- than 12,785 births registered annually
fused if they are told that they have to men who are not in fact the genetic
three genetic parents, only a very con- father.
fused person would think—let alone Is this a cause for concern? I doubt it,
say—any such thing. If I were a child and I doubt even more the wisdom of
for whom the alternative to having any measures to “correct” this state
some third-party DNA in my genome— of affairs. More mischief and anxiety
DNA that influences nothing about would certainly be caused by recogniz-
my nature, save only my susceptibility ing a right to know, or indeed a duty
to disease and suffering—was mito- to disclose, all contributors to a given
chondrial disease, I doubt I would be genome. These will of course also
complaining about an identity crisis. include contributors in even earlier
If, on the other hand, I were con- generations, and the contributions of
demned unnecessarily to a life of pain our ape ancestors.
and illness, I would really have some-
thing to complain of, and indeed
Consent or Permission to Influence or
somebody to blame. And among those
Create a Particular Genome
somebodies to blame would be any-
one who opposes the introduction of Finally we should consider the claim
this new technology. that because the future children who
will be affected by use of MRT cannot
consent, the requirement for informed
The Alleged Right to Know Genetic
consent of relevant parties to any medi-
Origins
cal intervention will be breached in the
A problem is often raised about whether case of MRT. In its background briefing
or not resulting children have a right or paper to the public meeting (held
a need to know the identity of the mito- March 31 to April 1, 201535) referred to
chondria donor. It is true that many earlier, the United States Institute of
people think that children have a right Medicine refers to part of its task in con-
to know the identity of their progeni- sidering ethical implications as includ-
tors. But this is dangerous nonsense: ing consideration of the “ethical issues
the right to access information about in providing ‘consent’ or ‘permission’ to
progenitors implies universal paternity accept risks on behalf of a child who
testing, with all the mischief that this does not exist.”36
would entail. This is because of the I am afraid that I fail to see any ethi-
widespread phenomenon known as cal issues that arise in connection with
nonpaternity. future generations as involving issues
“Nonpaternity” refers to cases in of consent. They do not, for the simple
which children in a family are not in and sufficient reason that there are no
fact genetically related to the person such people in existence capable of
they believe to be their father, who usu- either giving or withholding consent.
ally also believes he is the children’s All would be/might be parents make
genetic father. Nonpaternity rates are numerous decisions about issues that
quoted with wildly differing values might affect their future children. They
(from less than 1% to more than 30%). do this all the time without thinking
A modest, and probably reliable, figure about the consent of the children; how
is 2 percent. However, even at a modest could they not do so? In most cases of

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Germline Modification and the Burden of Human Existence

sexual reproduction, decisions are made, often not even then!). The same is true
first and foremost, about what genetic of medical and judicial decisionmaking
endowment is likely to result from a on behalf of children who lack compe-
particular paring (or more complex tence. The issue is not what the children
combination) of sets of chromosomes; want (although that may be relevant in
about where parents live and in what some circumstances) but what is in
conditions (poverty, luxury, disease their best interests.
and health state, etc.) and hence about Furthermore, in most cases, if the
the environment into which any future potential child’s consent or assent were
children will be born; about maternal to be deemed necessary for creation,
diet during pregnancy; and so on. Once there will never ever be such an actual
children are born, decisions are made child. And because such consents can-
about what food and drink to give them not be obtained, it is in the interests of
and about what stimuli to provide (or the child who would have been born,
withhold)—whether, for example, to insofar as it makes any sense to talk
allow children to ride bikes in the street of such interests, that its consent or
or cross roads unaccompanied; and so assent should be deemed irrelevant.
on. All of this is necessarily accom- This is Derek Parfit’s famous “non-
plished without the necessity for the identity problem.”37 Thus utter disre-
consent of the children—born or unborn, gard of the relevance of such consents
conceived or mere twinkles in their is this potential child’s only chance of
would-be parents’ eyes. existence, and therefore so long as the
To give just one personal example: best guess is that the child’s eventual
I am a so-called baby boomer. That life would not be intolerably ghastly,
means, in my own case, that my Jewish it would be in that child’s interests to
parents living in the U.K. during World be created.
War II decided not to have any further It is significant that those who raise
children until the outcome of the war issues of consent in relation to nonexis-
was clear; they decided it would not be tent beings only do so in circumstances
in the interests of any further children in which they wish to claim that the
that they had to be born into an envi- children would not, or should not, have
ronment controlled by German Nazis. consented, rather than the reverse, and
As a result, I was born in 1945. I am sure therefore should not have been born.
they were not troubled by issues of my But the opposite is true. If the interests
absent consent but, rather, were con- and probable wishes of such children
cerned with what would be in the best are to be considered, they will (if they
interests of any future children that are rational, and who is rational at
they had, and indeed in their own inter- minus more than nine months?—not
ests. The same is true of all parents of one in a thousand) vote “yes please.”
existing children who lack capacity in What is clear is that this attitude cannot
the legal sense—that is, children who be of benefit to the child whose exis-
lack autonomy. Parents, when deciding tence is at issue. It is better for all,
what food to feed infants, what educa- surely, to ignore the issue of consents or
tion to give them, what religious obser- assents and talk about the interests of
vance to inculcate, and what practices the child that will be born, and make
to forbid or to encourage, rarely ask for sure that child is as healthy as possible.
consent or even permission until chil- That child will almost certainly be
dren reach an age of discretion appro- pleased to have been “spared” mito-
priate to the decision in question (and chondrial disease. It might well also

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John Harris

wish to have had such a disease if that as politely as possible, irrelevant and
is the price of existence. Our duty— misleading.
by that I mean every citizen’s duty— Collins concludes the quotation cited
therefore is, because neither child has previously by mentioning “a current
a right to be the one created, surely to lack of compelling medical applications
create the best possible child. That is justifying the use of CRISPR/Cas9 in
what it is to act for the best, all things embryos”41 as a further reason to ban
considered.38 This we have moral rea- them. If, and insofar as, this is true, it
sons to do, but they are not overriding would constitute a powerful reason for
reasons. Parents who choose other- caution in the case of CRISPR/Cas9
wise, although not acting for the best, and other gene modification techniques
are still acting in ways with which it in embryos but, we should note, would
would be wrong to interfere.39 not constitute an objection to further
research using human embryos in juris-
Other Gene Modification Techniques dictions like the U.K. that permit human
embryo research with the 14-day limit—
The Use of CRISPR/Cas9 in Embryos that is, on embryos that have not devel-
oped beyond 14 days from creation and
Many of the arguments rehearsed pre- will not subsequently be implanted in a
viously also apply to objections to other human and brought to birth.
germline modification techniques. In a
recent “statement on NIH funding of
research using gene-editing technolo- Transgenerational Epigenetic Inheritance
gies in human embryos” issued offi- As Sarah Reardon reported recently
cially by the National Institutes of (June 25, 2015) in Nature News,
Health (NIH), Francis S. Collins, M.D.,
Ph.D., director of the NIH, stated: The US House of Representatives is
“The strong arguments against engaging wading into the debate over whether
in this activity remain. These include human embryos should be modified
the serious and unquantifiable safety to introduce heritable changes. Its
issues, ethical issues presented by alter- fiscal year 2016 spending bill for the
ing the germline in a way that affects the US Food and Drug Administration
next generation without their consent.”40 (FDA) would prohibit the agency
We have seen that these arguments from spending money to evaluate
are not only not strong but also patheti- research or clinical applications for
cally weak. “Serious and unquantifi- such products.
able” safety issues are present in all In an unusual twist, the bill—
introduced on 17 June—would also
new technologies, and thus objections
direct the FDA to create a committee
on these grounds need to be spelled out
that includes religious experts to
in detail and weighed against possible review a forthcoming report from the
benefits. Moreover, consent issues, as US Institute of Medicine (IOM). The
we have noted, are irrelevant because IOM’s analysis, which considers the
consent is never available from the ethics of creating embryos that have
unborn or for things that might affect three genetic parents, was commis-
future generations. We have to address sioned by the FDA.42
dangers to future generations and to
the planet in quite another way; the A parallel development has been the
raising of the issue of consent or its dramatic rise in interest in epigenetics
absence in such cases is, to put the point and the increasing speculation that

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Germline Modification and the Burden of Human Existence

epigenetic inheritance can occur across deriving from its originating role in the
generations. As the agenda for a work- resulting human. And if it does, does it
shop on “transgenerational epigenetic matter ethically whether or not that
inheritance” hosted by the Company of original source or trigger was a human
Biologists announced: individual or was produced by a human
individual or by an inanimate or organic
The transmission of epigenetic states nonhuman trigger?
across cell divisions in somatic tissues Oscar Wilde’s formidable Lady
is now well accepted and the mecha- Bracknell was, as usual, considerably
nisms are starting to be unveiled. The ahead of the game. As she famously
extent to which epigenetic inheritance remarked, having received the news
can occur across generations is less that Jack—or “Ernest”—Worthing was
clear, but represents a very exciting discovered in a handbag left in the
area with major implications for human
cloakroom at a London railway termi-
health, plant and animal breeding
nus (the Brighton Line): “You can hardly
and evolution. . . . Some of the out-
standing questions include: What trig-
imagine that I and Lord Bracknell would
gers heritable epigenetic changes and dream of allowing our only daughter—
how stably are they propagated? To a girl brought up with the utmost
what extent can one exclude a DNA care—to marry into a cloak-room, and
sequence based mechanism? What are form an alliance with a parcel? Good
the types of covariates that must be morning, Mr. Worthing!”44 And later,
taken into account in epidemiological “Until yesterday I had no idea that there
studies? What types of strategies will were any families or persons whose ori-
be required to define the nature, extent gin was a Terminus.”45
and mechanisms of non-Mendelian So far there are many millions of
transgenerational inheritance?43 humans who are blissfully unaware that
their origins might include, or that their
What have so far escaped critical existence has been triggered by, the func-
notice are the peculiar ethical issues tional equivalent of a terminus or a
raised by the possibility of epigenetic parcel. Perhaps those who believe
inheritance operating across genera- that having three (or more) genetic or
tions. Many people, in the context of indeed epigenetic “parents” is wrong-
MRT, have become accustomed to hear- ful or problematic also share Lady
ing MRT referred to as creating so-called Bracknell’s social prejudices? If not,
three-parent families because the provi- are we entitled to know what other
sion of the—albeit minute—amount of objections there might be to such epi-
inheritable material contained in the genetic ancestry and if such objections
donated mitochondria is considered by ground the implementation of preven-
those who use this term to constitute tive measures or criminal sanctions
a form of parenting, and any number against these would-be or happen-to-
of parents above two consequently be parents and license the prevention
involved is judged by many to be objec- of such random, but socially disas-
tionable. The question thus arises as to trous, antecedents?
whether the source of the epigenetic
material that may also be transferred
Conclusion
“across generations” or the nature of
the “thing” or the event that “triggers In his Life of Galileo, another play-
heritable epigenetic changes” might wright, Bertolt Brecht, gives a memo-
similarly qualify for parental status rable insight into the justification of

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John Harris

science to Galileo. Talking to Andrea com/society/2013/jul/12/story-ivf-five-

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5. I organized a public lecture in Manchester
tific colleague who is about to smug- shortly after the birth of Louise Brown was
gle the Discorsi, Galileo’s heretical treatise announced at which Patrick Steptoe spoke.
on mechanics and local motion, out of I remember the university had to lay on spe-
Italy—Galileo says: cial security for him because of the contro-
versy the first test-tube baby had caused.
6. “Test-tube baby” Brown hails pioneers on
A human race which shambles around
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own powers, will never be able to 7. I have not forgotten that this particular baby
develop those powers of nature which was an angelic-looking sheep. The subse-
[scientists] are revealing to it. To what quent discussion follows lines I first devel-
end are you working? Presumably oped back in 2004 in On Cloning (see note 1,
for the principle that science’s sole Harris 2004).
aim must be to lighten the burden of 8. Wilmut I, Schnieke AE, McWhir J, Kind AJ,
human existence.46 Campbell KHS. Viable offspring derived from
fetal and adult mammalian cells. Cloning and
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I agree with Brecht’s Galileo, and most 9. See National Bioethics Advisory Commission.
scientists, that the joy and the hope of Cloning Human Beings: Report and Recom-
science, although definitely not its mendations of the National Bioethics Advisory
sole purpose, is to lighten the burden Commission. Rockville, MD; 1997 Jun; avail-
able at https://bioethicsarchive.georgetown.
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drial replacement therapy can, and in accessed 8 Apr 2015).
the U.K. hopefully will, achieve. The 10. Quoted from President Clinton’s weekly
jury is perhaps still out on other gene radio broadcast, reported in Bioworld Today
modification techniques that affect 1998 Jan 13;9(7). Interestingly, the National
Bioethics Advisory Commission (see note 9)
the germline, but here we have a clas-
stated that it was unethical because it was
sic baby-and-bathwater problem, and unsafe. Clinton either misread his advisors’
we should be cautious about ruling report or decided to add “morally unaccept-
out as unethical the future use of such able” on top of the fact that it was untested
techniques. In the case of MRT, let’s and unsafe, rather than simply stating that it
celebrate the advent of a new and life- was unsafe because it was untested.
11. Bush GW. President discusses stem cell
enhancing therapy and the impressive research. The White House; 2001 Aug 9; available
science that enables this generation, at http://georgewbush-whitehouse.archives.
and future ones, to correct the mistakes gov/news/releases/2001/08/20010809-2.html
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reproduction and to continue to lighten, 12. Compassion in World Farming. Farm Animal
Cloning: A Compassion in World Farming Report;
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July 12; available at http://www.theguardian. workshop of the United States Institute of

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http://news.sciencemag.org/biology/2015/ 26. See note 25, Baltimore et al. forthcoming, at 2.
02/u-k-parliament-approves-controversial- 27. The Human Fertilization and Embryology
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Novel Techniques for Prevention of Maternal Embryology Act 2008 c.22; available at http://
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heritage of humanity.” ments. The Guardian 2012 Sep 17; available at
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2015 Apr 24; available at http://www.nature. The Basic Components. Chicago: University of
com/news/ethics-of-embryo-editing-paper- Chicago Press; 1977; Green RM. The Human
divides-scientists-1.17410 (last accessed 25 Apr Embryo Research Debates. New York: Oxford
2015), for some of my comments on this University Press; 2001, at n185. A figure of
development. 70 percent total embryo loss is confirmed

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John Harris

by Macklon NS, Geraedts JP, Fauser BC. 38. I develop the importance of this imperative—
Conception to ongoing pregnancy: The “black “to act for the best all things considered”—in
box” of early pregnancy loss. Human Repro- my new book: Harris J. How to Be Good. Oxford:
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rical & Gynecological Survey 1983;38(7):433–4. tive choice. In: Harris J, Holm S, eds. The
Edmonds et al. give a figure of 61.9 percent Future of Human Reproduction: Choice and
loss before 12 weeks, but because this figure Regulation. Oxford: Oxford University Press;
does not include embryo loss before implan- 1998:5–37. See also Harris J. The Value of Life.
tation or from miscarriage after 12 weeks, London: Routledge; 1985.
the figure of 80 percent may be more accu- 40. National Institutes of Health. Statement on
rate. Roberts CJ, Lowe CR. Where have all NIH funding of research using gene-editing
the conceptions gone? Lancet 1975;1:498–9. technologies in human embryos. The NIH
See also Bovens L. The rhythm method and Director; 2015 Apr 29; available at http://
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2006;32(6):355–7. statement_gene_editing_technologies.htm
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