String theory

From Wikipedia, the free encyclopedia

For a more accessible and less technical introduction to this topic, see Introduction to M-theory.
In physics, string theory is a theoretical framework in which the point-like particles of particle physics are
replaced by one-dimensionalobjects called strings. It describes how these strings propagate through
space and interact with each other. On distance scales larger than the string scale, a string looks just like
an ordinary particle, with its mass, charge, and other properties determined by the vibrational state of
the string. In string theory, one of the many vibrational states of the string corresponds to the graviton,
a quantum mechanical particle that carries gravitational force. Thus string theory is a theory of quantum
gravity.
String theory is a broad and varied subject that attempts to address a number of deep questions
of fundamental physics. String theory has been applied to a variety of problems in black hole physics,
early universe cosmology, nuclear physics, and condensed matter physics, and it has stimulated a number
of major developments in pure mathematics. Because string theory potentially provides a unified
description of gravity and particle physics, it is a candidate for a theory of everything, a self-
contained mathematical model that describes all fundamental forces and forms of matter. Despite much
work on these problems, it is not known to what extent string theory describes the real world or how
much freedom the theory allows to choose the details.
String theory was first studied in the late 1960s as a theory of the strong nuclear force, before being
abandoned in favor of quantum chromodynamics. Subsequently, it was realized that the very properties
that made string theory unsuitable as a theory of nuclear physics made it a promising candidate for a
quantum theory of gravity. The earliest version of string theory, bosonic string theory, incorporated only
the class of particles known as bosons. It later developed into superstring theory, which posits a
connection called supersymmetry between bosons and the class of particles called fermions. Five
consistent versions of superstring theory were developed before it was conjectured in the mid-1990s that
they were all different limiting cases of a single theory in eleven dimensions known as M-theory. In late
1997, theorists discovered an important relationship called the AdS/CFT correspondence, which relates
string theory to another type of physical theory called a quantum field theory.
One of the challenges of string theory is that the full theory does not have a satisfactory definition in all
circumstances. Another issue is that the theory is thought to describe an enormous landscape of possible
universes, and this has complicated efforts to develop theories of particle physics based on string theory.
These issues have led some in the community to criticize these approaches to physics and question the
value of continued research on string theory unification.
Fundamentals

The fundamental objects of string theory are open and closed strings.
In the twentieth century, two theoretical frameworks emerged for formulating the laws of physics. One of
these frameworks was Albert Einstein's general theory of relativity, a theory that explains the force
of gravity and the structure of space and time. The other was quantum mechanics, a radically different
formalism for describing physical phenomena using probability. By the late 1970s, these two frameworks
had proven to be sufficient to explain most of the observed features of the universe, from elementary
particles to atoms to the evolution of stars and the universe as a whole.[1]
In spite of these successes, there are still many problems that remain to be solved. One of the deepest
problems in modern physics is the problem of quantum gravity.[1] The general theory of relativity is
formulated within the framework of classical physics, whereas the other fundamental forces are
described within the framework of quantum mechanics. A quantum theory of gravity is needed in order
to reconcile general relativity with the principles of quantum mechanics, but difficulties arise when one
attempts to apply the usual prescriptions of quantum theory to the force of gravity.[2] In addition to the
problem of developing a consistent theory of quantum gravity, there are many other fundamental
problems in the physics of atomic nuclei, black holes, and the early universe.[a]
String theory is a theoretical framework that attempts to address these questions and many others. The
starting point for string theory is the idea that the point-like particles of particle physics can also be
modeled as one-dimensional objects called strings. String theory describes how strings propagate
through space and interact with each other. In a given version of string theory, there is only one kind of
string, which may look like a small loop or segment of ordinary string, and it can vibrate in different ways.
On distance scales larger than the string scale, a string will look just like an ordinary particle, with
its mass, charge, and other properties determined by the vibrational state of the string. In this way, all of
the different elementary particles may be viewed as vibrating strings. In string theory, one of the
vibrational states of the string gives rise to the graviton, a quantum mechanical particle that carries
gravitational force. Thus string theory is a theory of quantum gravity.[3]
One of the main developments of the past several decades in string theory was the discovery of certain
"dualities", mathematical transformations that identify one physical theory with another. Physicists
studying string theory have discovered a number of these dualities between different versions of string
theory, and this has led to the conjecture that all consistent versions of string theory are subsumed in a
single framework known as M-theory.[4]
Studies of string theory have also yielded a number of results on the nature of black holes and the
gravitational interaction. There are certain paradoxes that arise when one attempts to understand the
quantum aspects of black holes, and work on string theory has attempted to clarify these issues. In late
1997 this line of work culminated in the discovery of the anti-de Sitter/conformal field theory
correspondence or AdS/CFT.[5] This is a theoretical result which relates string theory to other physical
theories which are better understood theoretically. The AdS/CFT correspondence has implications for the
study of black holes and quantum gravity, and it has been applied to other subjects,
including nuclear[6] and condensed matter physics.[7][8]
Since string theory incorporates all of the fundamental interactions, including gravity, many physicists
hope that it fully describes our universe, making it a theory of everything. One of the goals of current
research in string theory is to find a solution of the theory that reproduces the observed spectrum of
elementary particles, with a small cosmological constant, containing dark matter and a plausible
mechanism for cosmic inflation. While there has been progress toward these goals, it is not known to
what extent string theory describes the real world or how much freedom the theory allows to choose the
details.[9]
One of the challenges of string theory is that the full theory does not have a satisfactory definition in all
circumstances. The scattering of strings is most straightforwardly defined using the techniques
of perturbation theory, but it is not known in general how to define string theory nonperturbatively.[10] It
is also not clear whether there is any principle by which string theory selects its vacuum state, the
physical state that determines the properties of our universe.[11] These problems have led some in the
community to criticize these approaches to the unification of physics and question the value of continued
research on these problems.[12]
Strings
Main article: String (physics)

Interaction in the quantum world: worldlines of point-like particles or a worldsheet swept up by

closed strings in string theory.
The application of quantum mechanics to physical objects such as the electromagnetic field, which are
extended in space and time, is known as quantum field theory. In particle physics, quantum field theories
form the basis for our understanding of elementary particles, which are modeled as excitations in the
fundamental fields.[13]
In quantum field theory, one typically computes the probabilities of various physical events using the
techniques of perturbation theory. Developed by Richard Feynman and others in the first half of the
twentieth century, perturbative quantum field theory uses special diagrams called Feynman diagrams to
organize computations. One imagines that these diagrams depict the paths of point-like particles and
their interactions.[13]
The starting point for string theory is the idea that the point-like particles of quantum field theory can
also be modeled as one-dimensional objects called strings.[14] The interaction of strings is most
straightforwardly defined by generalizing the perturbation theory used in ordinary quantum field theory.
At the level of Feynman diagrams, this means replacing the one-dimensional diagram representing the
path of a point particle by a two-dimensional surface representing the motion of a string.[15] Unlike in
quantum field theory, string theory does not have a full non-perturbative definition, so many of the
theoretical questions that physicists would like to answer remain out of reach.[16]
In theories of particle physics based on string theory, the characteristic length scale of strings is assumed
to be on the order of the Planck length, or 10−35 meters, the scale at which the effects of quantum gravity
are believed to become significant.[15] On much larger length scales, such as the scales visible in physics
laboratories, such objects would be indistinguishable from zero-dimensional point particles, and the
vibrational state of the string would determine the type of particle. One of the vibrational states of a
string corresponds to the graviton, a quantum mechanical particle that carries the gravitational force.[3]
The original version of string theory was bosonic string theory, but this version described only bosons, a
class of particles which transmit forces between the matter particles, or fermions. Bosonic string theory
was eventually superseded by theories called superstring theories. These theories describe both bosons
and fermions, and they incorporate a theoretical idea called supersymmetry. This is a mathematical
relation that exists in certain physical theories between the bosons and fermions. In theories with
supersymmetry, each boson has a counterpart which is a fermion, and vice versa.[17]
There are several versions of superstring theory: type I, type IIA, type IIB, and two flavors of heterotic
string theory (SO(32) and E8×E8). The different theories allow different types of strings, and the particles
that arise at low energies exhibit different symmetries. For example, the type I theory includes both open
strings (which are segments with endpoints) and closed strings (which form closed loops), while types IIA,
IIB and heterotic include only closed strings.[18]
Extra dimensions
An example of compactification: At large distances, a two dimensional surface with one circular
dimension looks one-dimensional.
In everyday life, there are three familiar dimensions of space: height, width and length. Einstein's general
theory of relativity treats time as a dimension on par with the three spatial dimensions; in general
relativity, space and time are not modeled as separate entities but are instead unified to a four-
dimensional spacetime. In this framework, the phenomenon of gravity is viewed as a consequence of the
geometry of spacetime.[19]
In spite of the fact that the universe is well described by four-dimensional spacetime, there are several
reasons why physicists consider theories in other dimensions. In some cases, by modeling spacetime in a
different number of dimensions, a theory becomes more mathematically tractable, and one can perform
calculations and gain general insights more easily.[b] There are also situations where theories in two or
three spacetime dimensions are useful for describing phenomena in condensed matter physics.[20] Finally,
there exist scenarios in which there could actually be more than four dimensions of spacetime which
have nonetheless managed to escape detection.[21]
One notable feature of string theories is that these theories require extra dimensions of spacetime for
their mathematical consistency. In bosonic string theory, spacetime is 26-dimensional, while in
superstring theory it is 10-dimensional, and in M-theory it is 11-dimensional. In order to describe real
physical phenomena using string theory, one must therefore imagine scenarios in which these extra
dimensions would not be observed in experiments.[22]

A cross section of a quintic Calabi–Yau manifold

Compactification is one way of modifying the number of dimensions in a physical theory. In
compactification, some of the extra dimensions are assumed to "close up" on themselves to form
circles.[23] In the limit where these curled up dimensions become very small, one obtains a theory in which
spacetime has effectively a lower number of dimensions. A standard analogy for this is to consider a
multidimensional object such as a garden hose. If the hose is viewed from a sufficient distance, it appears
to have only one dimension, its length. However, as one approaches the hose, one discovers that it
contains a second dimension, its circumference. Thus, an ant crawling on the surface of the hose would
move in two dimensions.[24]
Compactification can be used to construct models in which spacetime is effectively four-dimensional.
However, not every way of compactifying the extra dimensions produces a model with the right
properties to describe nature. In a viable model of particle physics, the compact extra dimensions must
be shaped like a Calabi–Yau manifold.[23] A Calabi–Yau manifold is a special space which is typically taken
to be six-dimensional in applications to string theory. It is named after mathematicians Eugenio
Calabi and Shing-Tung Yau.[25]
Another approach to reducing the number of dimensions is the so-called brane-world scenario. In this
approach, physicists assume that the observable universe is a four-dimensional subspace of a higher
dimensional space. In such models, the force-carrying bosons of particle physics arise from open strings
with endpoints attached to the four-dimensional subspace, while gravity arises from closed strings
propagating through the larger ambient space. This idea plays an important role in attempts to develop
models of real world physics based on string theory, and it provides a natural explanation for the
weakness of gravity compared to the other fundamental forces.[26]
Dualities

A diagram of string theory dualities. Yellow arrows indicate S-duality. Blue arrows indicate T-duality.
Main articles: S-duality and T-duality
One notable fact about string theory is that the different versions of the theory all turn out to be related
in highly nontrivial ways. One of the relationships that can exist between different string theories is
called S-duality. This is a relationship which says that a collection of strongly interacting particles in one
theory can, in some cases, be viewed as a collection of weakly interacting particles in a completely
different theory. Roughly speaking, a collection of particles is said to be strongly interacting if they
combine and decay often and weakly interacting if they do so infrequently. Type I string theory turns out
to be equivalent by S-duality to the SO(32) heterotic string theory. Similarly, type IIB string theory is
related to itself in a nontrivial way by S-duality.[27]
Another relationship between different string theories is T-duality. Here one considers strings
propagating around a circular extra dimension. T-duality states that a string propagating around a circle of
radius R is equivalent to a string propagating around a circle of radius 1/R in the sense that all observable
quantities in one description are identified with quantities in the dual description. For example, a string
has momentum as it propagates around a circle, and it can also wind around the circle one or more times.
The number of times the string winds around a circle is called the winding number. If a string has
momentum p and winding number n in one description, it will have momentum n and winding
number p in the dual description. For example, type IIA string theory is equivalent to type IIB string theory
via T-duality, and the two versions of heterotic string theory are also related by T-duality.[27]
In general, the term duality refers to a situation where two seemingly different physical systems turn out
to be equivalent in a nontrivial way. Two theories related by a duality need not be string theories. For
example, Montonen–Olive duality is example of an S-duality relationship between quantum field theories.
The AdS/CFT correspondence is example of a duality which relates string theory to a quantum field
theory. If two theories are related by a duality, it means that one theory can be transformed in some way
so that it ends up looking just like the other theory. The two theories are then said to be dual to one
another under the transformation. Put differently, the two theories are mathematically different
descriptions of the same phenomena.[28]
Branes
Main article: Brane

Open strings attached to a pair of D-branes

In string theory and related theories, a brane is a physical object that generalizes the notion of a point
particle to higher dimensions. For example, a point particle can be viewed as a brane of dimension zero,
while a string can be viewed as a brane of dimension one. It is also possible to consider higher-
dimensional branes. In dimension p, these are called p-branes. The word brane comes from the word
"membrane" which refers to a two-dimensional brane.[29]
Branes are dynamical objects which can propagate through spacetime according to the rules of quantum
mechanics. They have mass and can have other attributes such as charge. A p-brane sweeps out a (p+1)-
dimensional volume in spacetime called its worldvolume. Physicists often study fields analogous to the
electromagnetic field which live on the worldvolume of a brane.[29]
In string theory, D-branes are an important class of branes that arise when one considers open strings. As
an open string propagates through spacetime, its endpoints are required to lie on a D-brane. The letter
"D" in D-brane refers to a certain mathematical condition on the system known as the Dirichlet boundary
condition. The study of D-branes in string theory has led to important results such as the AdS/CFT
correspondence, which has shed light on many problems in quantum field theory.[30]
Branes are also frequently studied from a purely mathematical point of view. Mathematically, branes can
be described as objects of certain categories, such as the derived categoryof coherent sheaves on
a complex algebraic variety, or the Fukaya category of a symplectic manifold.[31] The connection between
the physical notion of a brane and the mathematical notion of a category has led to important
mathematical insights in the fields of algebraic and symplectic geometry[32] and representation theory.[33]
M-theory
Main article: M-theory
Prior to 1995, theorists believed that there were five consistent versions of superstring theory (type I,
type IIA, type IIB, and two versions of heterotic string theory). This understanding changed in 1995
when Edward Witten suggested that the five theories were just special limiting cases of an eleven-
dimensional theory called M-theory. Witten's conjecture was based on the work of a number of other
physicists, including Ashoke Sen, Chris Hull, Paul Townsend, and Michael Duff. His announcement led to a
flurry of research activity now known as the second superstring revolution.[34]
Unification of superstring theories

A schematic illustration of the relationship between M-theory, the five superstring theories, and eleven-
dimensional supergravity. The shaded region represents a family of different physical scenarios that are
possible in M-theory. In certain limiting cases corresponding to the cusps, it is natural to describe the
physics using one of the six theories labeled there.
In the 1970s, many physicists became interested in supergravity theories, which combine general
relativity with supersymmetry. Whereas general relativity makes sense in any number of dimensions,
supergravity places an upper limit on the number of dimensions.[35] In 1978, work by Werner
Nahm showed that the maximum spacetime dimension in which one can formulate a consistent
supersymmetric theory is eleven.[36] In the same year, Eugene Cremmer, Bernard Julia, and Joel Scherk of
the École Normale Supérieure showed that supergravity not only permits up to eleven dimensions but is
in fact most elegant in this maximal number of dimensions.[37][38]
Initially, many physicists hoped that by compactifying eleven-dimensional supergravity, it might be
possible to construct realistic models of our four-dimensional world. The hope was that such models
would provide a unified description of the four fundamental forces of nature: electromagnetism,
the strong and weak nuclear forces, and gravity. Interest in eleven-dimensional supergravity soon waned
as various flaws in this scheme were discovered. One of the problems was that the laws of physics appear
to distinguish between clockwise and counterclockwise, a phenomenon known as chirality. Edward
Witten and others observed this chirality property cannot be readily derived by compactifying from
eleven dimensions.[38]
In the first superstring revolution in 1984, many physicists turned to string theory as a unified theory of
particle physics and quantum gravity. Unlike supergravity theory, string theory was able to accommodate
the chirality of the standard model, and it provided a theory of gravity consistent with quantum
effects.[38] Another feature of string theory that many physicists were drawn to in the 1980s and 1990s
was its high degree of uniqueness. In ordinary particle theories, one can consider any collection of
elementary particles whose classical behavior is described by an arbitrary Lagrangian. In string theory, the
possibilities are much more constrained: by the 1990s, physicists had argued that there were only five
consistent supersymmetric versions of the theory.[38]
Although there were only a handful of consistent superstring theories, it remained a mystery why there
was not just one consistent formulation.[38] However, as physicists began to examine string theory more
closely, they realized that these theories are related in intricate and nontrivial ways. They found that a
system of strongly interacting strings can, in some cases, be viewed as a system of weakly interacting
strings. This phenomenon is known as S-duality. It was studied by Ashoke Sen in the context of heterotic
strings in four dimensions[39][40] and by Chris Hull and Paul Townsend in the context of the type IIB
theory.[41] Theorists also found that different string theories may be related by T-duality. This duality
implies that strings propagating on completely different spacetime geometries may be physically
equivalent.[42]
At around the same time, as many physicists were studying the properties of strings, a small group of
physicists was examining the possible applications of higher dimensional objects. In 1987, Eric Bergshoeff,
Ergin Sezgin, and Paul Townsend showed that eleven-dimensional supergravity includes two-dimensional
branes.[43] Intuitively, these objects look like sheets or membranes propagating through the eleven-
dimensional spacetime. Shortly after this discovery, Michael Duff, Paul Howe, Takeo Inami, and Kellogg
Stelle considered a particular compactification of eleven-dimensional supergravity with one of the
dimensions curled up into a circle.[44] In this setting, one can imagine the membrane wrapping around the
circular dimension. If the radius of the circle is sufficiently small, then this membrane looks just like a
string in ten-dimensional spacetime. In fact, Duff and his collaborators showed that this construction
reproduces exactly the strings appearing in type IIA superstring theory.[45]
Speaking at a string theory conference in 1995, Edward Witten made the surprising suggestion that all
five superstring theories were in fact just different limiting cases of a single theory in eleven spacetime
dimensions. Witten's announcement drew together all of the previous results on S- and T-duality and the
appearance of higher dimensional branes in string theory.[46] In the months following Witten's
announcement, hundreds of new papers appeared on the Internet confirming different parts of his
proposal.[47] Today this flurry of work is known as the second superstring revolution.[48]
Initially, some physicists suggested that the new theory was a fundamental theory of membranes, but
Witten was skeptical of the role of membranes in the theory. In a paper from 1996, Hořava and Witten
wrote "As it has been proposed that the eleven-dimensional theory is a supermembrane theory but there
are some reasons to doubt that interpretation, we will non-committally call it the M-theory, leaving to the
future the relation of M to membranes."[49] In the absence of an understanding of the true meaning and
structure of M-theory, Witten has suggested that the M should stand for "magic", "mystery", or
"membrane" according to taste, and the true meaning of the title should be decided when a more
fundamental formulation of the theory is known.[50]
Matrix theory
Main article: Matrix theory (physics)
In mathematics, a matrix is a rectangular array of numbers or other data. In physics, a matrix model is a
particular kind of physical theory whose mathematical formulation involves the notion of a matrix in an
important way. A matrix model describes the behavior of a set of matrices within the framework of
quantum mechanics.[51]
One important example of a matrix model is the BFSS matrix model proposed by Tom Banks, Willy
Fischler, Stephen Shenker, and Leonard Susskind in 1997. This theory describes the behavior of a set of
nine large matrices. In their original paper, these authors showed, among other things, that the low
energy limit of this matrix model is described by eleven-dimensional supergravity. These calculations led
them to propose that the BFSS matrix model is exactly equivalent to M-theory. The BFSS matrix model
can therefore be used as a prototype for a correct formulation of M-theory and a tool for investigating
the properties of M-theory in a relatively simple setting.[51]
The development of the matrix model formulation of M-theory has led physicists to consider various
connections between string theory and a branch of mathematics called noncommutative geometry. This
subject is a generalization of ordinary geometry in which mathematicians define new geometric notions
using tools from noncommutative algebra.[52]In a paper from 1998, Alain Connes, Michael R. Douglas,
and Albert Schwarz showed that some aspects of matrix models and M-theory are described by
a noncommutative quantum field theory, a special kind of physical theory in which spacetime is described
mathematically using noncommutative geometry.[53] This established a link between matrix models and
M-theory on the one hand, and noncommutative geometry on the other hand. It quickly led to the
discovery of other important links between noncommutative geometry and various physical
theories.[54][55]
Black holes
In general relativity, a black hole is defined as a region of spacetime in which the gravitational field is so
strong that no particle or radiation can escape. In the currently accepted models of stellar evolution,
black holes are thought to arise when massive stars undergo gravitational collapse, and many galaxies are
thought to contain supermassive black holesat their centers. Black holes are also important for
theoretical reasons, as they present profound challenges for theorists attempting to understand the
quantum aspects of gravity. String theory has proved to be an important tool for investigating the
theoretical properties of black holes because it provides a framework in which theorists can study
their thermodynamics.[56]
Bekenstein–Hawking formula
In the branch of physics called statistical mechanics, entropy is a measure of the randomness or disorder
of a physical system. This concept was studied in the 1870s by the Austrian physicist Ludwig Boltzmann,
who showed that the thermodynamic properties of a gas could be derived from the combined properties
of its many constituent molecules. Boltzmann argued that by averaging the behaviors of all the different
molecules in a gas, one can understand macroscopic properties such as volume, temperature, and
pressure. In addition, this perspective led him to give a precise definition of entropy as the natural
logarithm of the number of different states of the molecules (also called microstates) that give rise to the
same macroscopic features.[57]
In the twentieth century, physicists began to apply the same concepts to black holes. In most systems
such as gases, the entropy scales with the volume. In the 1970s, the physicist Jacob Bekenstein suggested
that the entropy of a black hole is instead proportional to the surface area of its event horizon, the
boundary beyond which matter and radiation is lost to its gravitational attraction.[58] When combined
with ideas of the physicist Stephen Hawking,[59] Bekenstein's work yielded a precise formula for the
entropy of a black hole. The Bekenstein–Hawking formula expresses the entropy S as

where c is the speed of light, k is Boltzmann's constant, ħ is the reduced Planck constant, G is Newton's
constant, and A is the surface area of the event horizon.[60]
Like any physical system, a black hole has an entropy defined in terms of the number of different
microstates that lead to the same macroscopic features. The Bekenstein–Hawking entropy formula gives
the expected value of the entropy of a black hole, but by the 1990s, physicists still lacked a derivation of
this formula by counting microstates in a theory of quantum gravity. Finding such a derivation of this
formula was considered an important test of the viability of any theory of quantum gravity such as string
theory.[61]
Derivation within string theory
In a paper from 1996, Andrew Strominger and Cumrun Vafa showed how to derive the Beckenstein–
Hawking formula for certain black holes in string theory.[62] Their calculation was based on the
observation that D-branes—which look like fluctuating membranes when they are weakly interacting—
become dense, massive objects with event horizons when the interactions are strong. In other words, a
system of strongly interacting D-branes in string theory is indistinguishable from a black hole. Strominger
and Vafa analyzed such D-brane systems and calculated the number of different ways of placing D-branes
in spacetime so that their combined mass and charge is equal to a given mass and charge for the resulting
black hole. Their calculation reproduced the Bekenstein–Hawking formula exactly, including the factor
of 1/4.[63] Subsequent work by Strominger, Vafa, and others refined the original calculations and gave the
precise values of the "quantum corrections" needed to describe very small black holes.[64][65]
The black holes that Strominger and Vafa considered in their original work were quite different from real
astrophysical black holes. One difference was that Strominger and Vafa considered only extremal black
holes in order to make the calculation tractable. These are defined as black holes with the lowest possible
mass compatible with a given charge.[66]Strominger and Vafa also restricted attention to black holes in
five-dimensional spacetime with unphysical supersymmetry.[67]
Although it was originally developed in this very particular and physically unrealistic context in string
theory, the entropy calculation of Strominger and Vafa has led to a qualitative understanding of how
black hole entropy can be accounted for in any theory of quantum gravity. Indeed, in 1998, Strominger
argued that the original result could be generalized to an arbitrary consistent theory of quantum gravity
without relying on strings or supersymmetry.[68] In collaboration with several other authors in 2010, he
showed that some results on black hole entropy could be extended to non-extremal astrophysical black
holes.[69][70]
AdS/CFT correspondence
Main article: AdS/CFT correspondence
One approach to formulating string theory and studying its properties is provided by the anti-de
Sitter/conformal field theory (AdS/CFT) correspondence. This is a theoretical result which implies that
string theory is in some cases equivalent to a quantum field theory. In addition to providing insights into
the mathematical structure of string theory, the AdS/CFT correspondence has shed light on many aspects
of quantum field theory in regimes where traditional calculational techniques are ineffective.[6] The
AdS/CFT correspondence was first proposed by Juan Maldacena in late 1997.[71] Important aspects of the
correspondence were elaborated in articles by Steven Gubser, Igor Klebanov, and Alexander Markovich
Polyakov,[72] and by Edward Witten.[73] By 2010, Maldacena's article had over 7000 citations, becoming
the most highly cited article in the field of high energy physics.[c]
Overview of the correspondence

A tessellation of the hyperbolic plane by triangles and squares

In the AdS/CFT correspondence, the geometry of spacetime is described in terms of a certain vacuum
solution of Einstein's equation called anti-de Sitter space.[74] In very elementary terms, anti-de Sitter space
is a mathematical model of spacetime in which the notion of distance between points (the metric) is
different from the notion of distance in ordinary Euclidean geometry. It is closely related to hyperbolic
space, which can be viewed as a disk as illustrated on the left.[75] This image shows a tessellation of a disk
by triangles and squares. One can define the distance between points of this disk in such a way that all
the triangles and squares are the same size and the circular outer boundary is infinitely far from any point
in the interior.[76]
One can imagine a stack of hyperbolic disks where each disk represents the state of the universe at a
given time. The resulting geometric object is three-dimensional anti-de Sitter space.[75] It looks like a
solid cylinder in which any cross section is a copy of the hyperbolic disk. Time runs along the vertical
direction in this picture. The surface of this cylinder plays an important role in the AdS/CFT
correspondence. As with the hyperbolic plane, anti-de Sitter space is curved in such a way that any point
in the interior is actually infinitely far from this boundary surface.[76]

Three-dimensional anti-de Sitter space is like a stack of hyperbolic disks, each one representing the state
of the universe at a given time. The resulting spacetime looks like a solid cylinder.
This construction describes a hypothetical universe with only two space dimensions and one time
dimension, but it can be generalized to any number of dimensions. Indeed, hyperbolic space can have
more than two dimensions and one can "stack up" copies of hyperbolic space to get higher-dimensional
models of anti-de Sitter space.[75]
An important feature of anti-de Sitter space is its boundary (which looks like a cylinder in the case of
three-dimensional anti-de Sitter space). One property of this boundary is that, within a small region on
the surface around any given point, it looks just like Minkowski space, the model of spacetime used in
nongravitational physics.[77] One can therefore consider an auxiliary theory in which "spacetime" is given
by the boundary of anti-de Sitter space. This observation is the starting point for AdS/CFT
correspondence, which states that the boundary of anti-de Sitter space can be regarded as the
"spacetime" for a quantum field theory. The claim is that this quantum field theory is equivalent to a
gravitational theory, such as string theory, in the bulk anti-de Sitter space in the sense that there is a
"dictionary" for translating entities and calculations in one theory into their counterparts in the other
theory. For example, a single particle in the gravitational theory might correspond to some collection of
particles in the boundary theory. In addition, the predictions in the two theories are quantitatively
identical so that if two particles have a 40 percent chance of colliding in the gravitational theory, then the
corresponding collections in the boundary theory would also have a 40 percent chance of colliding.[78]
Applications to quantum gravity
The discovery of the AdS/CFT correspondence was a major advance in physicists' understanding of string
theory and quantum gravity. One reason for this is that the correspondence provides a formulation of
string theory in terms of quantum field theory, which is well understood by comparison. Another reason
is that it provides a general framework in which physicists can study and attempt to resolve the
paradoxes of black holes.[56]
In 1975, Stephen Hawking published a calculation which suggested that black holes are not completely
black but emit a dim radiation due to quantum effects near the event horizon.[59] At first, Hawking's result
posed a problem for theorists because it suggested that black holes destroy information. More precisely,
Hawking's calculation seemed to conflict with one of the basic postulates of quantum mechanics, which
states that physical systems evolve in time according to the Schrödinger equation. This property is usually
referred to as unitarity of time evolution. The apparent contradiction between Hawking's calculation and
the unitarity postulate of quantum mechanics came to be known as the black hole information
paradox.[79]
The AdS/CFT correspondence resolves the black hole information paradox, at least to some extent,
because it shows how a black hole can evolve in a manner consistent with quantum mechanics in some
contexts. Indeed, one can consider black holes in the context of the AdS/CFT correspondence, and any
such black hole corresponds to a configuration of particles on the boundary of anti-de Sitter
space.[80] These particles obey the usual rules of quantum mechanics and in particular evolve in a unitary
fashion, so the black hole must also evolve in a unitary fashion, respecting the principles of quantum
mechanics.[81] In 2005, Hawking announced that the paradox had been settled in favor of information
conservation by the AdS/CFT correspondence, and he suggested a concrete mechanism by which black
holes might preserve information.[82]
Applications to nuclear physics
Main article: AdS/QCD correspondence

A magnet levitating above a high-temperature superconductor. Today some physicists are working to
understand high-temperature superconductivity using the AdS/CFT correspondence.[7]
In addition to its applications to theoretical problems in quantum gravity, the AdS/CFT correspondence
has been applied to a variety of problems in quantum field theory. One physical system that has been
studied using the AdS/CFT correspondence is the quark–gluon plasma, an exotic state of matter produced
in particle accelerators. This state of matter arises for brief instants when heavy ions such
as goldor lead nuclei are collided at high energies. Such collisions cause the quarks that make up atomic
nuclei to deconfine at temperatures of approximately two trillion kelvins, conditions similar to those
present at around 10−11 seconds after the Big Bang.[83]
The physics of the quark–gluon plasma is governed by a theory called quantum chromodynamics, but this
theory is mathematically intractable in problems involving the quark–gluon plasma.[d] In an article
appearing in 2005, Đàm Thanh Sơn and his collaborators showed that the AdS/CFT correspondence could
be used to understand some aspects of the quark–gluon plasma by describing it in the language of string
theory.[84] By applying the AdS/CFT correspondence, Sơn and his collaborators were able to describe the
quark gluon plasma in terms of black holes in five-dimensional spacetime. The calculation showed that
the ratio of two quantities associated with the quark–gluon plasma, the shear viscosity and volume
density of entropy, should be approximately equal to a certain universal constant. In 2008, the predicted
value of this ratio for the quark–gluon plasma was confirmed at the Relativistic Heavy Ion
Collider at Brookhaven National Laboratory.[85][86]
Applications to condensed matter physics
Main article: AdS/CMT correspondence
The AdS/CFT correspondence has also been used to study aspects of condensed matter physics. Over the
decades, experimental condensed matter physicists have discovered a number of exotic states of matter,
including superconductors and superfluids. These states are described using the formalism of quantum
field theory, but some phenomena are difficult to explain using standard field theoretic techniques. Some
condensed matter theorists including Subir Sachdev hope that the AdS/CFT correspondence will make it
possible to describe these systems in the language of string theory and learn more about their
behavior.[85]
So far some success has been achieved in using string theory methods to describe the transition of a
superfluid to an insulator. A superfluid is a system of electrically neutral atomsthat flows without
any friction. Such systems are often produced in the laboratory using liquid helium, but recently
experimentalists have developed new ways of producing artificial superfluids by pouring trillions of cold
atoms into a lattice of criss-crossing lasers. These atoms initially behave as a superfluid, but as
experimentalists increase the intensity of the lasers, they become less mobile and then suddenly
transition to an insulating state. During the transition, the atoms behave in an unusual way. For example,
the atoms slow to a halt at a rate that depends on the temperature and on Planck's constant, the
fundamental parameter of quantum mechanics, which does not enter into the description of the
other phases. This behavior has recently been understood by considering a dual description where
properties of the fluid are described in terms of a higher dimensional black hole.[87]
Phenomenology
Main article: String phenomenology
In addition to being an idea of considerable theoretical interest, string theory provides a framework for
constructing models of real world physics that combine general relativity and particle
physics. Phenomenology is the branch of theoretical physics in which physicists construct realistic models
of nature from more abstract theoretical ideas. String phenomenology is the part of string theory that
attempts to construct realistic or semi-realistic models based on string theory.
Partly because of theoretical and mathematical difficulties and partly because of the extremely high
energies needed to test these theories experimentally, there is so far no experimental evidence that
would unambiguously point to any of these models being a correct fundamental description of nature.
This has led some in the community to criticize these approaches to unification and question the value of
continued research on these problems.[12]
Particle physics
The currently accepted theory describing elementary particles and their interactions is known as
the standard model of particle physics. This theory provides a unified description of three of the
fundamental forces of nature: electromagnetism and the strong and weak nuclear forces. Despite its
remarkable success in explaining a wide range of physical phenomena, the standard model cannot be a
complete description of reality. This is because the standard model fails to incorporate the force of
gravity and because of problems such as the hierarchy problem and the inability to explain the structure
of fermion masses or dark matter.
String theory has been used to construct a variety of models of particle physics going beyond the
standard model. Typically, such models are based on the idea of compactification. Starting with the ten-
or eleven-dimensional spacetime of string or M-theory, physicists postulate a shape for the extra
dimensions. By choosing this shape appropriately, they can construct models roughly similar to the
standard model of particle physics, together with additional undiscovered particles.[88] One popular way
of deriving realistic physics from string theory is to start with the heterotic theory in ten dimensions and
assume that the six extra dimensions of spacetime are shaped like a six-dimensional Calabi–Yau manifold.
Such compactifications offer many ways of extracting realistic physics from string theory. Other similar
methods can be used to construct realistic or semi-realistic models of our four-dimensional world based
on M-theory.[89]
Cosmology
Main article: String cosmology

A map of the cosmic microwave backgroundproduced by the Wilkinson Microwave Anisotropy Probe
The Big Bang theory is the prevailing cosmological model for the universe from the earliest known periods
through its subsequent large-scale evolution. Despite its success in explaining many observed features of
the universe including galactic redshifts, the relative abundance of light elements such
as hydrogen and helium, and the existence of a cosmic microwave background, there are several
questions that remain unanswered. For example, the standard Big Bang model does not explain why the
universe appears to be same in all directions, why it appears flat on very large distance scales, or why
certain hypothesized particles such as magnetic monopoles are not observed in experiments.[90]
Currently, the leading candidate for a theory going beyond the Big Bang is the theory of cosmic inflation.
Developed by Alan Guth and others in the 1980s, inflation postulates a period of extremely rapid
accelerated expansion of the universe prior to the expansion described by the standard Big Bang theory.
The theory of cosmic inflation preserves the successes of the Big Bang while providing a natural
explanation for some of the mysterious features of the universe.[91] The theory has also received striking
support from observations of the cosmic microwave background, the radiation that has filled the sky
since around 380,000 years after the Big Bang.[92]
In the theory of inflation, the rapid initial expansion of the universe is caused by a hypothetical particle
called the inflaton. The exact properties of this particle are not fixed by the theory but should ultimately
be derived from a more fundamental theory such as string theory.[93] Indeed, there have been a number
of attempts to identify an inflaton within the spectrum of particles described by string theory, and to
study inflation using string theory. While these approaches might eventually find support in observational
data such as measurements of the cosmic microwave background, the application of string theory to
cosmology is still in its early stages.[94]
Connections to mathematics
In addition to influencing research in theoretical physics, string theory has stimulated a number of major
developments in pure mathematics. Like many developing ideas in theoretical physics, string theory does
not at present have a mathematically rigorous formulation in which all of its concepts can be defined
precisely. As a result, physicists who study string theory are often guided by physical intuition to
conjecture relationships between the seemingly different mathematical structures that are used to
formalize different parts of the theory. These conjectures are later proved by mathematicians, and in this
way, string theory serves as a source of new ideas in pure mathematics.[95]
Mirror symmetry
Main article: Mirror symmetry (string theory)

The Clebsch cubic is an example of a kind of geometric object called an algebraic variety. A classical result
of enumerative geometry states that there are exactly 27 straight lines that lie entirely on this surface.
After Calabi–Yau manifolds had entered physics as a way to compactify extra dimensions in string theory,
many physicists began studying these manifolds. In the late 1980s, several physicists noticed that given
such a compactification of string theory, it is not possible to reconstruct uniquely a corresponding Calabi–
Yau manifold.[96] Instead, two different versions of string theory, type IIA and type IIB, can be compactified
on completely different Calabi–Yau manifolds giving rise to the same physics. In this situation, the
manifolds are called mirror manifolds, and the relationship between the two physical theories is
called mirror symmetry.[97]
Regardless of whether Calabi–Yau compactifications of string theory provide a correct description of
nature, the existence of the mirror duality between different string theories has significant mathematical
consequences. The Calabi–Yau manifolds used in string theory are of interest in pure mathematics, and
mirror symmetry allows mathematicians to solve problems in enumerative geometry, a branch of
mathematics concerned with counting the numbers of solutions to geometric questions.[31][98]
Enumerative geometry studies a class of geometric objects called algebraic varieties which are defined by
the vanishing of polynomials. For example, the Clebsch cubic illustrated on the right is an algebraic variety
defined using a certain polynomial of degree three in four variables. A celebrated result of nineteenth-
century mathematicians Arthur Cayley and George Salmon states that there are exactly 27 straight lines
that lie entirely on such a surface.[99]
Generalizing this problem, one can ask how many lines can be drawn on a quintic Calabi–Yau manifold,
such as the one illustrated above, which is defined by a polynomial of degree five. This problem was
solved by the nineteenth-century German mathematician Hermann Schubert, who found that there are
exactly 2,875 such lines. In 1986, geometer Sheldon Katz proved that the number of curves, such as
circles, that are defined by polynomials of degree two and lie entirely in the quintic is 609,250.[100]
By the year 1991, most of the classical problems of enumerative geometry had been solved and interest
in enumerative geometry had begun to diminish.[101] The field was reinvigorated in May 1991 when
physicists Philip Candelas, Xenia de la Ossa, Paul Green, and Linda Parks showed that mirror symmetry
could be used to translate difficult mathematical questions about one Calabi–Yau manifold into easier
questions about its mirror.[102] In particular, they used mirror symmetry to show that a six-dimensional
Calabi–Yau manifold can contain exactly 317,206,375 curves of degree three.[101] In addition to counting
degree-three curves, Candelas and his collaborators obtained a number of more general results for
counting rational curves which went far beyond the results obtained by mathematicians.[103]
Originally, these results of Candelas were justified on physical grounds. However, mathematicians
generally prefer rigorous proofs that do not require an appeal to physical intuition. Inspired by physicists'
work on mirror symmetry, mathematicians have therefore constructed their own arguments proving the
enumerative predictions of mirror symmetry.[e] Today mirror symmetry is an active area of research in
mathematics, and mathematicians are working to develop a more complete mathematical understanding
of mirror symmetry based on physicists' intuition.[104] Major approaches to mirror symmetry include
the homological mirror symmetry program of Maxim Kontsevich[32] and the SYZ conjecture of Andrew
Strominger, Shing-Tung Yau, and Eric Zaslow.[105]
Monstrous moonshine
Main article: Monstrous moonshine

An equilateral triangle can be rotated through 120°, 240°, or 360°, or reflected in any of the three lines
pictured without changing its shape.
Group theory is the branch of mathematics that studies the concept of symmetry. For example, one can
consider a geometric shape such as an equilateral triangle. There are various operations that one can
perform on this triangle without changing its shape. One can rotate it through 120°, 240°, or 360°, or one
can reflect in any of the lines labeled S0, S1, or S2 in the picture. Each of these operations is called
a symmetry, and the collection of these symmetries satisfies certain technical properties making it into
what mathematicians call a group. In this particular example, the group is known as the dihedral
group of order 6 because it has six elements. A general group may describe finitely many or infinitely
many symmetries; if there are only finitely many symmetries, it is called a finite group.[106]
Mathematicians often strive for a classification (or list) of all mathematical objects of a given type. It is
generally believed that finite groups are too diverse to admit a useful classification. A more modest but
still challenging problem is to classify all finite simple groups. These are finite groups which may be used
as building blocks for constructing arbitrary finite groups in the same way that prime numbers can be
used to construct arbitrary whole numbers by taking products.[f] One of the major achievements of
contemporary group theory is the classification of finite simple groups, a mathematical theorem which
provides a list of all possible finite simple groups.[107]
This classification theorem identifies several infinite families of groups as well as 26 additional groups
which do not fit into any family. The latter groups are called the "sporadic" groups, and each one owes its
existence to a remarkable combination of circumstances. The largest sporadic group, the so-
called monster group, has over 1053 elements, more than a thousand times the number of atoms in the
Earth.[108]
A graph of the j-function in the complex plane
A seemingly unrelated construction is the j-function of number theory. This object belongs to a special
class of functions called modular functions, whose graphs form a certain kind of repeating
pattern.[109] Although this function appears in a branch of mathematics which seems very different from
the theory of finite groups, the two subjects turn out to be intimately related. In the late 1970s,
mathematicians John McKay and John Thompson noticed that certain numbers arising in the analysis of
the monster group (namely, the dimensions of its irreducible representations) are related to numbers
that appear in a formula for the j-function (namely, the coefficients of its Fourier series).[110] This
relationship was further developed by John Horton Conwayand Simon Norton[111] who called it monstrous
moonshine because it seemed so far fetched.[112]
In 1992, Richard Borcherds constructed a bridge between the theory of modular functions and finite
groups and, in the process, explained the observations of McKay and Thompson.[113][114] Borcherds' work
used ideas from string theory in an essential way, extending earlier results of Igor Frenkel, James
Lepowsky, and Arne Meurman, who had realized the monster group as the symmetries of a
particular[which?] version of string theory.[115] In 1998, Borcherds was awarded the Fields medal for his
work.[116]
Since the 1990s, the connection between string theory and moonshine has led to further results in
mathematics and physics.[108] In 2010, physicists Tohru Eguchi, Hirosi Ooguri, and Yuji
Tachikawa discovered connections between a different sporadic group, the Mathieu group M24, and a
certain version[which?] of string theory.[117] Miranda Cheng, John Duncan, and Jeffrey A. Harvey proposed a
generalization of this moonshine phenomenon called umbral moonshine,[118] and their conjecture was
proved mathematically by Duncan, Michael Griffin, and Ken Ono.[119] Witten has also speculated that the
version of string theory appearing in monstrous moonshine might be related to a certain simplified model
of gravity in three spacetime dimensions.[120]
History
Main article: History of string theory
Early results
Some of the structures reintroduced by string theory arose for the first time much earlier as part of the
program of classical unification started by Albert Einstein. The first person to add a fifth dimension to a
theory of gravity was Gunnar Nordström in 1914, who noted that gravity in five dimensions describes
both gravity and electromagnetism in four. Nordström attempted to unify electromagnetism with his
theory of gravitation, which was however superseded by Einstein's general relativity in 1919. Thereafter,
German mathematician Theodor Kaluza combined the fifth dimension with general relativity, and only
Kaluza is usually credited with the idea. In 1926, the Swedish physicist Oskar Klein gave a physical
interpretation of the unobservable extra dimension—it is wrapped into a small circle. Einstein introduced
a non-symmetric metric tensor, while much later Brans and Dicke added a scalar component to gravity.
These ideas would be revived within string theory, where they are demanded by consistency conditions.

Leonard Susskind
String theory was originally developed during the late 1960s and early 1970s as a never completely
successful theory of hadrons, the subatomic particles like the proton and neutron that feel the strong
interaction. In the 1960s, Geoffrey Chew and Steven Frautschi discovered that the mesonsmake families
called Regge trajectories with masses related to spins in a way that was later understood by Yoichiro
Nambu, Holger Bech Nielsen and Leonard Susskind to be the relationship expected from rotating strings.
Chew advocated making a theory for the interactions of these trajectories that did not presume that they
were composed of any fundamental particles, but would construct their interactions from self-
consistency conditions on the S-matrix. The S-matrix approach was started by Werner Heisenberg in the
1940s as a way of constructing a theory that did not rely on the local notions of space and time, which
Heisenberg believed break down at the nuclear scale. While the scale was off by many orders of
magnitude, the approach he advocated was ideally suited for a theory of quantum gravity.
Working with experimental data, R. Dolen, D. Horn and C. Schmid developed some sum rules for hadron
exchange. When a particle and antiparticlescatter, virtual particles can be exchanged in two qualitatively
different ways. In the s-channel, the two particles annihilate to make temporary intermediate states that
fall apart into the final state particles. In the t-channel, the particles exchange intermediate states by
emission and absorption. In field theory, the two contributions add together, one giving a continuous
background contribution, the other giving peaks at certain energies. In the data, it was clear that the
peaks were stealing from the background—the authors interpreted this as saying that the t-channel
contribution was dual to the s-channel one, meaning both described the whole amplitude and included
the other.
Gabriele Veneziano
The result was widely advertised by Murray Gell-Mann, leading Gabriele Veneziano to construct
a scattering amplitude that had the property of Dolen-Horn-Schmid duality, later renamed world-sheet
duality. The amplitude needed poles where the particles appear, on straight line trajectories, and there is
a special mathematical function whose poles are evenly spaced on half the real line—the gamma
function— which was widely used in Regge theory. By manipulating combinations of gamma functions,
Veneziano was able to find a consistent scattering amplitude with poles on straight lines, with mostly
positive residues, which obeyed duality and had the appropriate Regge scaling at high energy. The
amplitude could fit near-beam scattering data as well as other Regge type fits, and had a suggestive
integral representation that could be used for generalization.
Over the next years, hundreds of physicists worked to complete the bootstrap program for this model,
with many surprises. Veneziano himself discovered that for the scattering amplitude to describe the
scattering of a particle that appears in the theory, an obvious self-consistency condition, the lightest
particle must be a tachyon. Miguel Virasoro and Joel Shapiro found a different amplitude now understood
to be that of closed strings, while Ziro Koba and Holger Nielsen generalized Veneziano's integral
representation to multiparticle scattering. Veneziano and Sergio Fubiniintroduced an operator formalism
for computing the scattering amplitudes that was a forerunner of world-sheet conformal theory, while
Virasoro understood how to remove the poles with wrong-sign residues using a constraint on the
states. Claud Lovelace calculated a loop amplitude, and noted that there is an inconsistency unless the
dimension of the theory is 26. Charles Thorn, Peter Goddard and Richard Brower went on to prove that
there are no wrong-sign propagating states in dimensions less than or equal to 26.
In 1969–70, Yoichiro Nambu, Holger Bech Nielsen, and Leonard Susskind recognized that the theory could
be given a description in space and time in terms of strings. The scattering amplitudes were derived
systematically from the action principle by Peter Goddard, Jeffrey Goldstone, Claudio Rebbi, and Charles
Thorn, giving a space-time picture to the vertex operators introduced by Veneziano and Fubini and a
geometrical interpretation to the Virasoro conditions.
In 1971, Pierre Ramond added fermions to the model, which led him to formulate a two-dimensional
supersymmetry to cancel the wrong-sign states. John Schwarz and André Neveuadded another sector to
the fermi theory a short time later. In the fermion theories, the critical dimension was 10. Stanley
Mandelstam formulated a world sheet conformal theory for both the bose and fermi case, giving a two-
dimensional field theoretic path-integral to generate the operator formalism. Michio Kaku and Keiji
Kikkawa gave a different formulation of the bosonic string, as a string field theory, with infinitely many
particle types and with fields taking values not on points, but on loops and curves.
In 1974, Tamiaki Yoneya discovered that all the known string theories included a massless spin-two
particle that obeyed the correct Ward identities to be a graviton. John Schwarz and Joel Scherk came to
the same conclusion and made the bold leap to suggest that string theory was a theory of gravity, not a
theory of hadrons. They reintroduced Kaluza–Klein theory as a way of making sense of the extra
dimensions. At the same time, quantum chromodynamics was recognized as the correct theory of
hadrons, shifting the attention of physicists and apparently leaving the bootstrap program in the dustbin
of history.
String theory eventually made it out of the dustbin, but for the following decade all work on the theory
was completely ignored. Still, the theory continued to develop at a steady pace thanks to the work of a
handful of devotees. Ferdinando Gliozzi, Joel Scherk, and David Olive realized in 1977 that the original
Ramond and Neveu Schwarz-strings were separately inconsistent and needed to be combined. The
resulting theory did not have a tachyon, and was proven to have space-time supersymmetry by John
Schwarz and Michael Green in 1984. The same year, Alexander Polyakov gave the theory a modern path
integral formulation, and went on to develop conformal field theory extensively. In 1979, Daniel
Friedanshowed that the equations of motions of string theory, which are generalizations of the Einstein
equations of general relativity, emerge from the renormalization group equations for the two-
dimensional field theory. Schwarz and Green discovered T-duality, and constructed two superstring
theories—IIA and IIB related by T-duality, and type I theories with open strings. The consistency
conditions had been so strong, that the entire theory was nearly uniquely determined, with only a few
discrete choices.
First superstring revolution

Edward Witten
In the early 1980s, Edward Witten discovered that most theories of quantum gravity could not
accommodate chiral fermions like the neutrino. This led him, in collaboration with Luis Álvarez-Gaumé, to
study violations of the conservation laws in gravity theories with anomalies, concluding that type I string
theories were inconsistent. Green and Schwarz discovered a contribution to the anomaly that Witten and
Alvarez-Gaumé had missed, which restricted the gauge group of the type I string theory to be SO(32). In
coming to understand this calculation, Edward Witten became convinced that string theory was truly a
consistent theory of gravity, and he became a high-profile advocate. Following Witten's lead, between
1984 and 1986, hundreds of physicists started to work in this field, and this is sometimes called the first
superstring revolution.
During this period, David Gross, Jeffrey Harvey, Emil Martinec, and Ryan Rohm discovered heterotic
strings. The gauge group of these closed strings was two copies of E8, and either copy could easily and
naturally include the standard model. Philip Candelas, Gary Horowitz, Andrew Strominger and Edward
Witten found that the Calabi–Yau manifolds are the compactifications that preserve a realistic amount of
supersymmetry, while Lance Dixon and others worked out the physical properties of orbifolds, distinctive
geometrical singularities allowed in string theory. Cumrun Vafa generalized T-duality from circles to
arbitrary manifolds, creating the mathematical field of mirror symmetry. Daniel Friedan, Emil
Martinec and Stephen Shenker further developed the covariant quantization of the superstring using
conformal field theory techniques. David Gross and Vipul Periwal discovered that string perturbation
theory was divergent. Stephen Shenker showed it diverged much faster than in field theory suggesting
that new non-perturbative objects were missing.

Joseph Polchinski
In the 1990s, Joseph Polchinski discovered that the theory requires higher-dimensional objects, called D-
branes and identified these with the black-hole solutions of supergravity. These were understood to be
the new objects suggested by the perturbative divergences, and they opened up a new field with rich
mathematical structure. It quickly became clear that D-branes and other p-branes, not just strings,
formed the matter content of the string theories, and the physical interpretation of the strings and
branes was revealed—they are a type of black hole. Leonard Susskind had incorporated the holographic
principle of Gerardus 't Hooft into string theory, identifying the long highly excited string states with
ordinary thermal black hole states. As suggested by 't Hooft, the fluctuations of the black hole horizon,
the world-sheet or world-volume theory, describes not only the degrees of freedom of the black hole, but
all nearby objects too.
Second superstring revolution
In 1995, at the annual conference of string theorists at the University of Southern California
(USC), Edward Witten gave a speech on string theory that in essence united the five string theories that
existed at the time, and giving birth to a new 11-dimensional theory called M-theory. M-theory was also
foreshadowed in the work of Paul Townsend at approximately the same time. The flurry of activity that
began at this time is sometimes called the second superstring revolution.[34]

Juan Maldacena
During this period, Tom Banks, Willy Fischler, Stephen Shenker and Leonard Susskind formulated matrix
theory, a full holographic description of M-theory using IIA D0 branes.[51] This was the first definition of
string theory that was fully non-perturbative and a concrete mathematical realization of the holographic
principle. It is an example of a gauge-gravity duality and is now understood to be a special case of
the AdS/CFT correspondence. Andrew Strominger and Cumrun Vafa calculated the entropy of certain
configurations of D-branes and found agreement with the semi-classical answer for extreme charged
black holes.[62] Petr Hořava and Witten found the eleven-dimensional formulation of the heterotic string
theories, showing that orbifolds solve the chirality problem. Witten noted that the effective description of
the physics of D-branes at low energies is by a supersymmetric gauge theory, and found geometrical
interpretations of mathematical structures in gauge theory that he and Nathan Seiberg had earlier
discovered in terms of the location of the branes.
In 1997, Juan Maldacena noted that the low energy excitations of a theory near a black hole consist of
objects close to the horizon, which for extreme charged black holes looks like an anti-de Sitter
space.[71] He noted that in this limit the gauge theory describes the string excitations near the branes. So
he hypothesized that string theory on a near-horizon extreme-charged black-hole geometry, an anti-de
Sitter space times a sphere with flux, is equally well described by the low-energy limiting gauge theory,
the N = 4 supersymmetric Yang–Mills theory. This hypothesis, which is called the AdS/CFT
correspondence, was further developed by Steven Gubser, Igor Klebanov and Alexander Polyakov,[72] and
by Edward Witten,[73] and it is now well-accepted. It is a concrete realization of the holographic principle,
which has far-reaching implications for black holes, locality and information in physics, as well as the
nature of the gravitational interaction.[56] Through this relationship, string theory has been shown to be
related to gauge theories like quantum chromodynamics and this has led to more quantitative
understanding of the behavior of hadrons, bringing string theory back to its roots.[84]
Criticism
Number of solutions
Main article: String theory landscape
To construct models of particle physics based on string theory, physicists typically begin by specifying a
shape for the extra dimensions of spacetime. Each of these different shapes corresponds to a different
possible universe, or "vacuum state", with a different collection of particles and forces. String theory as it
is currently understood has an enormous number of vacuum states, typically estimated to be
around 10500, and these might be sufficiently diverse to accommodate almost any phenomena that might
be observed at low energies.[121]
Many critics of string theory have expressed concerns about the large number of possible universes
described by string theory. In his book Not Even Wrong, Peter Woit, a lecturer in the mathematics
department at Columbia University, has argued that the large number of different physical scenarios
renders string theory vacuous as a framework for constructing models of particle physics. According to
Woit,
The possible existence of, say, 10500 consistent different vacuum states for superstring theory probably
destroys the hope of using the theory to predict anything. If one picks among this large set just those
states whose properties agree with present experimental observations, it is likely there still will be such a
large number of these that one can get just about whatever value one wants for the results of any new
observation.[122]
Some physicists believe this large number of solutions is actually a virtue because it may allow a natural
anthropic explanation of the observed values of physical constants, in particular the small value of the
cosmological constant.[122] The anthropic principle is the idea that some of the numbers appearing in the
laws of physics are not fixed by any fundamental principle but must be compatible with the evolution of
intelligent life. In 1987, Steven Weinberg published an article in which he argued that the cosmological
constant could not have been too large, or else galaxies and intelligent life would not have been able to
develop.[123] Weinberg suggested that there might be a huge number of possible consistent universes,
each with a different value of the cosmological constant, and observations indicate a small value of the
cosmological constant only because humans happen to live in a universe that has allowed intelligent life,
and hence observers, to exist.[124]
String theorist Leonard Susskind has argued that string theory provides a natural anthropic explanation of
the small value of the cosmological constant.[125] According to Susskind, the different vacuum states of
string theory might be realized as different universes within a larger multiverse. The fact that the
observed universe has a small cosmological constant is just a tautological consequence of the fact that a
small value is required for life to exist.[126] Many prominent theorists and critics have disagreed with
Susskind's conclusions.[127]According to Woit, "in this case [anthropic reasoning] is nothing more than an
excuse for failure. Speculative scientific ideas fail not just when they make incorrect predictions, but also
when they turn out to be vacuous and incapable of predicting anything."[128]
Background independence
Main article: Background independence
One of the fundamental properties of Einstein's general theory of relativity is that it is background
independent, meaning that the formulation of the theory does not in any way privilege a particular
spacetime geometry.[129]
One of the main criticisms of string theory from early on is that it is not manifestly background
independent. In string theory, one must typically specify a fixed reference geometry for spacetime, and all
other possible geometries are described as perturbations of this fixed one. In his book The Trouble With
Physics, physicist Lee Smolin of the Perimeter Institute for Theoretical Physics claims that this is the
principal weakness of string theory as a theory of quantum gravity, saying that string theory has failed to
incorporate this important insight from general relativity.[130]
Others have disagreed with Smolin's characterization of string theory. In a review of Smolin's book, string
theorist Joseph Polchinski writes
[Smolin] is mistaking an aspect of the mathematical language being used for one of the physics being
described. New physical theories are often discovered using a mathematical language that is not the most
suitable for them… In string theory it has always been clear that the physics is background-independent
even if the language being used is not, and the search for more suitable language continues. Indeed, as
Smolin belatedly notes, [AdS/CFT] provides a solution to this problem, one that is unexpected and
powerful.[131]
Polchinski notes that an important open problem in quantum gravity is to develop holographic
descriptions of gravity which do not require the gravitational field to be asymptotically anti-de
Sitter.[131] Smolin has responded by saying that the AdS/CFT correspondence, as it is currently understood,
may not be strong enough to resolve all concerns about background independence.[g]
Sociological issues
Since the superstring revolutions of the 1980s and 1990s, string theory has become the dominant
paradigm of high energy theoretical physics.[132] Some string theorists have expressed the view that there
does not exist an equally successful alternative theory addressing the deep questions of fundamental
physics. In an interview from 1987, Nobel laureate David Gross made the following controversial
comments about the reasons for the popularity of string theory:
The most important [reason] is that there are no other good ideas around. That's what gets most people
into it. When people started to get interested in string theory they didn't know anything about it. In fact,
the first reaction of most people is that the theory is extremely ugly and unpleasant, at least that was the
case a few years ago when the understanding of string theory was much less developed. It was difficult
for people to learn about it and to be turned on. So I think the real reason why people have got attracted
by it is because there is no other game in town. All other approaches of constructing grand unified
theories, which were more conservative to begin with, and only gradually became more and more radical,
have failed, and this game hasn't failed yet.[133]
Several other high-profile theorists and commentators have expressed similar views, suggesting that
there are no viable alternatives to string theory.[134]
Many critics of string theory have commented on this state of affairs. In his book criticizing string theory,
Peter Woit views the status of string theory research as unhealthy and detrimental to the future of
fundamental physics. He argues that the extreme popularity of string theory among theoretical physicists
is partly a consequence of the financial structure of academia and the fierce competition for scarce
resources.[135] In his book The Road to Reality, mathematical physicist Roger Penrose expresses similar
views, stating "The often frantic competitiveness that this ease of communication engenders leads to
'bandwagon' effects, where researchers fear to be left behind if they do not join in."[136] Penrose also
claims that the technical difficulty of modern physics forces young scientists to rely on the preferences of
established researchers, rather than forging new paths of their own.[137] Lee Smolin expresses a slightly
different position in his critique, claiming that string theory grew out of a tradition of particle physics
which discourages speculation about the foundations of physics, while his preferred approach, loop
quantum gravity, encourages more radical thinking. According to Smolin,
String theory is a powerful, well-motivated idea and deserves much of the work that has been devoted to
it. If it has so far failed, the principal reason is that its intrinsic flaws are closely tied to its strengths—and,
of course, the story is unfinished, since string theory may well turn out to be part of the truth. The real
question is not why we have expended so much energy on string theory but why we haven't expended
nearly enough on alternative approaches.[138]
Smolin goes on to offer a number of prescriptions for how scientists might encourage a greater diversity
of approaches to quantum gravity research.[139]
Placebo
From Wikipedia, the free encyclopedia
For other uses, see Placebo (disambiguation) and Placebo effect (disambiguation).
The placebo effect can be produced by inert tablets, by sham surgery, and by false information, such as
when electrical stimulation is turned "off" in those who have implanted brain electrodes due
to Parkinson's disease.[1]
A placebo (/pləˈsiːboʊ/ plə-SEE-boh; Latin placēbō, "I shall please"[2] from placeō, "I please")[3][4] is a
substance or treatment with no active therapeutic effect.[5] A placebo may be given to a person in order
to deceive the recipient into thinking that it is an active treatment. In drug testing and medical research, a
placebo can be made to resemble an active medication or therapy so that it functions as a control; this is
to prevent the recipient(s) and/or others from knowing (with their consent) whether a treatment is active
or inactive, as expectations about efficacy can influence results.[6][7] This psychological phenomenon, in
which the recipient perceives an improvement in condition due to personal expectations, rather than the
treatment itself, is known as the placebo effect or placebo response.[8][9] Research about the effect is
ongoing.[10]
Placebos are an important methodological tool in medical research.[11] Common placebos include inert
tablets (like sugar pills), vehicle infusions, sham surgery,[12] and other procedures based on false
information.[1] There is also some evidence that patients who know they are receiving a placebo still
report subjective improvement in their condition if they are told that the placebo can make them feel
better.[13] It has further been observed that use of therapies about which patients are unaware may
generally be less effective than using ones that patients are informed about, regardless of whether or not
a placebo is involved.[14]
Placebo effects are the subject of scientific research aiming to understand underlying neurobiological
mechanisms of action in pain relief, immunosuppression, Parkinson's disease and depression.[15] Brain
imaging techniques done by Emeran Mayer, Johanna Jarco and Matt Lieberman showed that placebo can
have real, measurable effects on physiological changes in the brain.[16] Placebos can produce some
objective physiological changes, such as changes in heart rate, blood pressure, and chemical activity in
the brain, in cases involving pain, depression, anxiety, fatigue, and some symptoms of Parkinson’s. In
other cases, like asthma, the effect is purely subjective, when the patient reports improvement despite
no objective change in the underlying condition.[16][17]
The placebo effect is a pervasive phenomenon;[18] in fact, it is part of the response to any active medical
intervention.[19] The placebo effect points to the importance of perception and the brain's role in physical
health. The use of placebos as treatment in clinical medicine (as opposed to laboratory research) is
ethically problematic as it introduces deception and dishonesty into the doctor-patient
relationship.[20] The United Kingdom Parliamentary Committee on Science and Technology has stated
that: "...prescribing placebos... usually relies on some degree of patient deception" and "prescribing pure
placebos is bad medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of
any treatment on the NHS."[21]
In 1955, Henry K. Beecher proposed that placebos could have clinically important effects.[22][23] This view
was notably challenged when, in 2001, a systematic review of clinical trials concluded that there was no
evidence of clinically important effects, except perhaps in the treatment of pain and continuous
subjective outcomes.[23] The article received a flurry of criticism,[24] but the authors later published
a Cochrane review with similar conclusions (updated as of 2010).[25] Most studies have attributed the
difference from baseline until the end of the trial to a placebo effect, but the reviewers examined studies
which had both placebo and untreated groups in order to distinguish the placebo effect from the natural
progression of the disease.[23]
Contents
[hide]
1Types
2Effects
3Ethics
4Mechanism of the effect
4.1Expectancy and conditioning
4.2Placebo effect and the brain
4.3Brain and body
4.4Evolved health regulation
5Clinical utility
5.1Clinical significance
5.2Negative effects
5.3Doctor-patient relationship
5.4Changes over time
6Individual differences
6.1Genes
7Symptoms and conditions
7.1Pain
7.2Depression
7.3Chronic fatigue syndrome
7.4List of medical conditions
8Endocannabinoid system involvement
9History
9.1Placebo-controlled studies
9.2Nocebo
9.3Ingredients
10See also
11References
12External links
Types[edit]
In a 1983 article, Clement J. McDonald, Steven A. Mazzuca, and George P. McCabe Jr. defined a placebo
as "a substance or procedure... that is objectively without specific activity for the condition being
treated".[26] Under this definition, a wide variety of things can be placebos and exhibit a placebo effect.
However, the placebo effect may be a component of legitimate pharmacological therapies: Pain-
killing and anxiety-reducing drugs that are infused secretly without an individual's knowledge are less
effective than when a patient knows they are receiving them. Likewise, the effects of stimulation from
implanted electrodes in the brains of those with advanced Parkinson's disease are greater when they are
aware they are receiving this stimulation.[27] Sometimes administering or prescribing a placebo merges
into fake medicine. Common placebos include pills ("sugar pills") or saline injections. Fake surgeries have
also seen some use. An example is the Finish Meniscal Legion Study Group’s trial published in The New
England Journal of Medicine, which found a sham meniscal surgery to be equally effective to the actual
procedure.[28][29] While examples of placebo treatments can be found, defining the placebo concept
remains elusive.[30]
Effects[edit]
The placebo effect has sometimes been defined as a physiological effect caused by the placebo, but
Moerman and Jonas have pointed out that this seems illogical, as a placebo is an inert substance that
does not directly cause anything. Instead they introduced the term "meaning response" for the meaning
that the brain associates with the placebo, which causes a physiological placebo effect. They propose that
the placebo, which may be unethical, could be avoided entirely if doctors comfort and encourage their
patients' health.[24]Ernst and Resch also attempted to distinguish between the "true" and "perceived"
placebo effect, as they argued that some of the effects attributed to the placebo effect could be due to
other factors.[31]
Research suggests that for psychological reasons, some placebos are more effective than others. Large
pills seem to work better than small pills, colored pills work better than white pills, an injection is more
powerful than a pill, and surgery gives a stronger placebo effect than injections do.[32]
Research has also shown when it comes to specific psychological disorders, such as mild or moderate
depression, placebos have the same effects compared to antidepressants.[33]
Ethics[edit]
See also: Medical ethics and Philosophy of medicine
The placebo effect has been controversial throughout history. Notable medical organizations have
endorsed it,[11] but in 1903 Richard Cabot concluded that it should be avoided because it is deceptive.
Newman points out the "placebo paradox" – it may be unethical to use a placebo, but also unethical
"not to use something that heals". He suggests to solve this dilemma by appropriating the meaning
response in medicine, that is make use of the placebo effect, as long as the "one administering... is
honest, open, and believes in its potential healing power".[20]
Mechanism of the effect[edit]
Because the placebo response is simply the patient response that cannot be attributed to an
investigational intervention, there are multiple possible components of a measured placebo effect. These
components have varying relevance depending on study design and the types of observations. [34] While
there is some evidence that placebo interventions can alter levels
of hormones,[35] endocannabinoids[36] or endogenous opioids,[37] other prominent components
include expectancy effects, regression to the mean,[26][38] and flawed research methodologies.
Expectancy and conditioning[edit]
The placebo effect is related to expectations
The placebo effect is related to the perceptions and expectations of the patient; if the substance is
viewed as helpful, it can heal, but, if it is viewed as harmful, it can cause negative effects, which is known
as the nocebo effect. In 1985, Irving Kirsch hypothesized that placebo effects are produced by the self-
fulfilling effects of response expectancies, in which the belief that one will feel different leads a person to
actually feel different.[39] According to this theory, the belief that one has received an active treatment
can produce the subjective changes thought to be produced by the real treatment. Placebos can act
similarly through classical conditioning, wherein a placebo and an actual stimulus are used simultaneously
until the placebo is associated with the effect from the actual stimulus.[40] Both conditioning and
expectations play a role in placebo effect,[41] and make different kinds of contribution. Conditioning has a
longer-lasting effect,[42] and can affect earlier stages of information processing.[43] Those that think that a
treatment will work display a stronger placebo effect than those that do not, as evidenced by a study of
acupuncture.[44][45]
A placebo presented as a stimulant will have this effect on heart rhythm and blood pressure, but when
administered as a depressant, the opposite effect.[46] Perceived ergogenic aids can increase
endurance,[47] speed[48] and weight-lifting ability,[49] leading to the question of whether placebos should
be allowed in sport competition.[50] In addition, there are ethical and moral concerns related to their use
and we must be cautious of policies and practices that exploit placebos to the detriment of athletes’
health and well-being.[51]
Because placebos are dependent upon perception and expectation, various factors that change the
perception can increase the magnitude of the placebo response. For example, studies have found that
the color and size of the placebo pill makes a difference, with "hot-colored" pills working better as
stimulants while "cool-colored" pills work better as depressants. Capsules rather than tablets seem to be
more effective, and size can make a difference.[52] One researcher has found that big pills increase the
effect[53] while another has argued that the effect is dependent upon cultural background.[54]
Motivation may contribute to the placebo effect. The active goals of an individual changes their somatic
experience by altering the detection and interpretation of expectation-congruent symptoms, and by
changing the behavioral strategies a person pursues.[55][56] Motivation may link to the meaning through
which people experience illness and treatment. Such meaning is derived from the culture in which they
live and which informs them about the nature of illness and how it responds to treatment. Research into
the placebo treatment of gastric and duodenal ulcers shows that this varies widely with society.[24] The
placebo effect in treating gastric ulcers is low in Brazil, higher in northern Europe (Denmark,
Netherlands), and extremely high in Germany. However, the placebo effect in treating hypertension is
lower in Germany than elsewhere.[57]
Though the placebo effect is typically associated with deception in order to invoke positive expectations,
studies carried out by Harvard Medical School have suggested that placebos can work even without
deception. In an attempt to implement placebos honestly, 80 patients suffering from IBS were divided
into two groups, one of which receiving no treatment, while the other were provided with placebo pills.
Though it was made clear the pills had no active ingredient, patients still reported adequate symptom
relief.[58] Another similar study, in which patients suffering from migraines were given pills clearly labeled
placebo, but still reported improvements of their symptoms.[59]
Placebo effect and the brain[edit]
Functional imaging upon placebo analgesia shows that it links to the activation, and increased functional
correlation between this activation, in the anterior
cingulate, prefrontal, orbitofrontal and insular cortices, nucleus accumbens, amygdala, the
brainstem periaqueductal gray matter,[60][61][62] and the spinal cord.[63][64][65][66]
The higher brain works by regulating subcortical processes. High placebo responses link with
enhanced dopamine and mu-opioid activity in the circuitry for reward responses and motivated behavior
of the nucleus accumbens, and, on the converse, anti-analgesic nocebos responses were associated with
deactivation in this part of the brain of dopamine and opioid release.[61] (It has been known that placebo
analgesia depends upon the release in the brain of endogenous opioids since 1978.[67]) Such analgesic
placebos activation changes processing lower down in the brain by enhancing the descending inhibition
through the periaqueductal gray[61] on spinal nociceptive reflexes, while the expectations of anti-analgesic
nocebos acts in the opposite way to block this.[63]
The brain is also involved in less-studied ways upon nonanalgesic placebo effects:
Parkinson's disease: Placebo relief is associated with the release of dopamine in the brain.[68]
Depression: Placebos reducing depression affect many of the same areas that are activated by
antidepressants with the addition of the prefrontal cortex[69][70]
Caffeine: Placebo-caffeinated coffee causes an increase in bilateral dopamine release in the thalamus.[71]
Glucose: The expectation of an intravenous injection of glucose increases the release of dopamine in the
basal ganglia of men (but not women).[72]
Methylphenidate: The expectation of intravenous injection of this drug in inexperienced drug users
increased the release of dopamine in the ventral cingulate gyrus and nucleus accumbens, with this effect
being largest in those with no prior experience of the drug.[73]
Functional imaging upon placebo analgesia has been summarized as showing that the placebo response is
"mediated by "top-down" processes dependent on frontal cortical areas that generate and maintain
cognitive expectancies. Dopaminergic reward pathways may underlie these expectancies".[74] "Diseases
lacking major 'top-down' or cortically based regulation may be less prone to placebo-related
improvement".[75]
Brain and body[edit]
For more details on this topic, see neural top down control of physiology.
The brain has control over the body processes affected by placebos.
In conditioning, a neutral stimulus saccharin is paired in a drink with an agent that produces an
unconditioned response. For example, that agent might be cyclophosphamide, which
causes immunosuppression. After learning this pairing, the taste of saccharin by itself is able to cause
immunosuppression, as a new conditioned response via neural top-down control.[76] Such conditioning
has been found to affect a diverse variety of not just basic physiological processes in the immune system
but ones such as serum iron levels, oxidative DNA damage levels, and insulin secretion. Recent reviews
have argued that the placebo effect is due to top-down control by the brain for immunity[77] and
pain.[78] Pacheco-López and colleagues have raised the possibility of "neocortical-sympathetic-immune
axis providing neuroanatomical substrates that might explain the link between placebo/conditioned and
placebo/expectation responses."[77]:441
A recent fMRI study has shown that a placebo can reduce pain-related neural activity in the spinal cord,
indicating that placebo effects can extend beyond the brain.[79]
Dopaminergic pathways have been implicated in the placebo response in pain and depression. [80]
Evolved health regulation[edit]
Evolutionary medicine identifies many symptoms such as fever, pain, and sickness behavior as evolved
responses to protect or enhance the recovery from infection and injury. Fever, for example, is an evolved
self-treatment that removes bacteria or viruses through raised body temperature.
These evolved responses, however, also have a cost that depending upon circumstances can outweigh
their benefit (due to this, for example, there is a reduction in fever during malnutrition or late pregnancy).
According to the health management system theory proposed by Nicholas Humphrey, the brain has been
selected to ensure that evolved responses are deployed only when the cost benefit is
biologically advantageous. To do this, the brain factors in a variety of information sources, including the
likelihood derived from beliefs that the body will get well without deploying its costly evolved responses.
One such source of information is the knowledge the body is receiving care and treatment. The placebo
effect in this perspective arises when false information about medications misleads the health
management system about the likelihood of getting well so that it selects not to deploy an evolved self-
treatment.[81]
Clinical utility[edit]
Clinical significance[edit]
Asbjørn Hróbjartsson and Peter Gøtzsche published a study in 2001[23] and a follow-up study in
2004[82] questioning the nature of the placebo effect. The studies were performed as two meta-analyses.
They found that in studies with a binary outcome, meaning patients were classified as improved or not
improved, the placebo group had no statistically significantimprovement over the no-treatment group.
Likewise, there was no significant placebo effect in studies in which objective outcomes (such as blood
pressure) were measured by an independent observer. The placebo effect could be documented only in
studies in which the outcomes (improvement or failure to improve) were reported by the subjects
themselves. The authors concluded that the placebo effect does not have "powerful clinical effects,"
(objective effects) and that patient-reported improvements (subjective effects) in pain were small and
could not be clearly distinguished from reporting bias. Other researchers (Wampold et al.) re-analysed
the same data from the 2001 meta-analysis and concluded that the placebo effects for objective
symptom measures are comparable to placebo effects for subjective ones and that the placebo effect can
exceed the effect of the active treatment by 20% for disorders amenable to the placebo effect,[83][84] a
conclusion which Hróbjartsson & Gøtzsche described as "powerful spin".[85] Another group of researchers
noted the dramatically different conclusions between these two sets of authors despite nearly identical
meta-analytic results, and suggested that placebo effects are indeed significant but small in magnitude.[86]
Hróbjartsson and Gøtzsche's conclusion has been criticised on several grounds. Their meta-analysis
covered studies into a highly mixed group of conditions. It has been reported that for measurements in
peripheral organs the placebo effect seems to be more effective in achieving improvements in physical
parameters (such as decreasing hypertension, improving FEV1 in asthma sufferers, or decreasing
prostatic hyperplasia or anal fissure) than in improving biochemical parameters (such
as cholesterol or cortisol) in various conditions such as venous leg ulcers, Crohn's disease, urinary tract
infection, and chronic heart failure.[87] Placebos also do not work as strongly in clinical trials because the
subjects do not know whether they might be getting a real treatment or a sham one. Where studies are
made of placebos in which people think they are receiving actual treatment (rather than merely its
possibility) the placebo effect has been observed.[88] Other writers have argued that the placebo effect
can be reliably demonstrated under appropriate conditions.[89]
In another update by Hróbjartsson & Gøtzsche, published as a 2010 Cochrane systematic review which
confirms and modifies their previous work, over 200 trials investigating 60 clinical conditions were
included. Placebo interventions were again not found to have important clinical effects in general but
may influence patient-reported outcomes in some situations, especially pain and nausea, although it was
"difficult to distinguish patient-reported effects of placebo from response bias". The pooled relative
risk they calculated for placebo was 0.93 (effect of only 7%) but significant. Effects were also found for
phobia and asthma but were uncertain due to high risk of bias. In other conditions involving three or
more trials, there was no statistically significant effect for smoking, dementia, depression, obesity,
hypertension, insomnia and anxiety, although confidence intervals were wide. Several clinical (physical
placebos, patient-involved outcomes, falsely informing patients there was no placebo) and
methodological (small sample size, explicit aim of studying the placebo effect) factors were associated
with higher effects of placebo. Despite low effects in general and the risk of bias, the authors
acknowledged that large effects of placebo interventions may occur in certain situations.[90]
In 2013 Jeremy Howick and colleagues used Hróbjartsson & Gøtzsche's data to compare the magnitude of
placebo effects with the magnitude of treatment effects.[91] They found a statistically significant
difference between placebo and treatment effect sizes in trials with binary outcomes but not in trials with
subjective outcomes.
Negative effects[edit]
Similar to the placebo effect, inert substances have the potential to cause negative effects via the
"nocebo effect" (Latin nocebo = "I will harm"). In this effect, giving an inert substance has negative
consequences.[92]
Another negative consequence is that placebos can cause side-effects associated with real
treatment.[93] One example of this is with those that have already taken an opiate, can then
show respiratory depression when given it again in the form of a placebo.[94]
Withdrawal symptoms can also occur after placebo treatment. This was found, for example, after the
discontinuation of the Women's Health Initiative study of hormone replacement therapy for menopause.
Women had been on placebo for an average of 5.7 years. Moderate or severe withdrawal symptoms
were reported by 4.8% of those on placebo compared to 21.3% of those on hormone replacement.[95]
It is also often ethically challenging in practice to use placebos as a form of treatment.[96]
Doctor-patient relationship[edit]
A study of Danish general practitioners found that 48% had prescribed a placebo at least 10 times in the
past year.[18] The most frequently prescribed placebos were presented as antibiotics for viral infections,
and vitamins for fatigue. Specialists and hospital-based physicians reported much lower rates of placebo
use. A 2004 study in the British Medical Journal of physicians in Israel found that 60% used placebos in
their medical practice, most commonly to "fend off" requests for unjustified medications or to calm a
patient.[97] The accompanying editorial concluded, "We cannot afford to dispense with any treatment that
works, even if we are not certain how it does."[98] Other researchers have argued that open provision of
placebos for treating ADHD in children can be effective in maintaining ADHD children on lower stimulant
doses in the short term.[99]
Critics of the practice responded that it is unethical to prescribe treatments that do not work, and that
telling a patient (as opposed to a research test subject) that a placebo is a real medication is deceptive
and harms the doctor-patient relationship in the long run. Critics also argued that using placebos can
delay the proper diagnosis and treatment of serious medical conditions.[100] Legitimate doctors and
pharmacists could open themselves up to charges of fraud or malpractice by using a placebo.
About 25% of physicians in both the Danish and Israeli studies used placebos as a diagnostic tool to
determine if a patient's symptoms were real, or if the patient was malingering. Both the critics and
defenders of the medical use of placebos agreed that this was unethical.[98] The British Medical
Journal editorial said, "That a patient gets pain relief from a placebo does not imply that the pain is not
real or organic in origin...the use of the placebo for 'diagnosis' of whether or not pain is real is misguided."
The placebo administration may prove to be a useful treatment in some specific cases where
recommended drugs cannot be used. For example, burn patients who are experiencing respiratory
problems cannot often be prescribed opioid (morphine) or opioid derivatives (pethidine), as these can
cause further respiratory depression. In such cases placebo injections (normal saline, etc.) are of use in
providing real pain relief to burn patients if those not in delirium are told they are being given a powerful
dose of painkiller.
Referring specifically to homeopathy, the House of Commons of the United Kingdom Science and
Technology Committee has stated:
In the Committee's view, homeopathy is a placebo treatment and the Government should have a policy
on prescribing placebos. The Government is reluctant to address the appropriateness and ethics of
prescribing placebos to patients, which usually relies on some degree of patient deception. Prescribing of
placebos is not consistent with informed patient choice—which the Government claims is very
important—as it means patients do not have all the information needed to make choice meaningful.
Beyond ethical issues and the integrity of the doctor-patient relationship, prescribing pure placebos is bad
medicine. Their effect is unreliable and unpredictable and cannot form the sole basis of any treatment on
the NHS.[21]
A survey in the United States of more than 10,000 physicians came to the result that while 24% of
physicians would prescribe a treatment that is a placebo simply because the patient wanted treatment,
58% would not, and for the remaining 18%, it would depend on the circumstances.[101]
Changes over time[edit]
A review published in JAMA Psychiatry found that, in trials of antipsychotic medications, the change in
response to receiving a placebo had increased significantly between 1960 and 2013. The review's authors
identified several factors that could be responsible for this change, including inflation of baseline scores
and enrollment of fewer severely ill patients.[102]Another analysis published in Pain in 2015 found that
placebo responses had increased considerably in neuropathic pain clinical trials conducted in the United
States from 1990 to 2013. The researchers suggested that this may be because such trials have
"increased in study size and length" during this time period.[103]
Individual differences[edit]
Placebos do not work for everyone.[104][105] Henry K. Beecher, in a paper in 1955,[22] suggested placebo
effects occurred in about 35% of people. However, this paper has been criticized for failing to distinguish
the placebo effect from other factors, and for thereby encouraging an inflated notion of the placebo
effect.[106]
In the 1950s, there was considerable research to find whether there was a specific personality to those
that responded to placebos. The findings could not be replicated[107] and it is now thought to have no
effect.[108]
The desire for relief from pain, "goal motivation", and how far pain is expected to be relieved increases
placebo analgesia.[55] Another factor increasing the effectiveness of placebos is the degree to which a
person attends to their symptoms, "somatic focus".[56] Individual variation in response to analgesic
placebos has been linked to regional neurochemical differences in the internal affective state of the
individuals experiencing pain.[109]
Those with Alzheimer's disease lose the capacity to be influenced by placebos, and this is attributed to
the loss of their prefrontal cortex dependent capacity to have expectations.[110]
Children seem to have greater response than adults to placebos.[111]
Genes[edit]
In social anxiety disorder (SAD) an inherited variant of the gene for tryptophan hydroxylase
2 (enzyme that synthesizes the neurotransmitter serotonin) is linked to reduced amygdalaactivity and
greater susceptibility to the placebo effect.[112][113][114] The authors note "additional work is necessary to
elucidate the generalizability of the findings".
In a 2012 study, variations on the COMT (catechol-O-methyltransferase) gene related
to dopamine release are found to be critical in the placebo effect among the patients with irritable bowel
syndrome participating in the trial, a research group in Harvard Medical School reported. Patients with a
variation of met/met, for having two copies of the methionineallele were shown to be more likely to
respond to the placebo treatment, while the variation of val/val, for their two copies of valine allele
responded the least. The response of patients with one copy each of methionine and valine fell in the
middle. Release of dopamine in patients with the met/met variations is thought to link to reward and
'confirmation bias' which enhance the sense that the treatment is working. The role of the COMT gene
variations are expected to be more prominent in studies where patients report more subjective
conditions such as pain and fatigue rather than objective physiological measurements.[115][116]
Symptoms and conditions[edit]
The placebo effect occurs more strongly in some conditions than others. Dylan Evans has suggested that
placebos work most strongly upon conditions such as pain, swelling, stomach ulcers, depression, and
anxiety that have been linked with activation of the acute-phase response.[117]
Pain[edit]
The placebo effect is believed to reduce pain—a phenomenon known as placebo analgesia—in two
different ways. One way is by the placebo initiating the release of endorphins, which are natural pain
killers produced by the brain.[118] The other way is the placebo changing the patient's perception of pain.
"A person might reinterpret a sharp pain as uncomfortable tingling."[119]
One way in which the magnitude of placebo analgesia can be measured is by conducting "open/hidden"
studies, in which some patients receive an analgesic and are informed that they will be receiving it (open),
while others are administered the same drug without their knowledge (hidden). Such studies have found
that analgesics are considerably more effective when the patient knows they are receiving them.[120]
When administered orally, placebos have clinically meaningful effects with regard to lower back pain.[121]
Depression[edit]
In 2008, a controversial meta-analysis led by psychologist Irving Kirsch, analyzing data from the FDA,
concluded that 82% of the response to antidepressants was accounted for by placebos.[122] However,
there are serious doubts about the used methods and the interpretation of the results, especially the use
of 0.5 as cut-off point for the effect-size.[123] A complete reanalysis and recalculation based on the same
FDA data discovered that the Kirsch study suffered from important flaws in the calculations. The authors
concluded that although a large percentage of the placebo response was due to expectancy, this was not
true for the active drug. Besides confirming drug effectiveness, they found that the drug effect was not
related to depression severity.[124]
Another meta-analysis found that 79% of depressed patients receiving placebo remained well (for 12
weeks after an initial 6–8 weeks of successful therapy) compared to 93% of those receiving
antidepressants. In the continuation phase however, patients on placebo relapsed significantly more
often than patients on antidepressants.[125] A 2009 meta-analysis reported that in 2005 68% of the effects
of antidepressants was due to the placebo effect, which was more than double the placebo response rate
in 1980.[126]
While some say that blanket consent, or the general consent to unspecified treatment given by patients
beforehand, is ethical, others argue that patients should always obtain specific information about the
name of the drug they are receiving, its side effects, and other treatment options.[127] Even though some
patients do not want to be informed, health professionals are ethically bound to give proper information
about the treatment given. There is such a debate over the use of placebos because while placebos are
used for the good of many to test the effectiveness of drugs, some argue that it is unethical to ever
deprive individual patients of effective drugs.[128]
Chronic fatigue syndrome[edit]
It was previously assumed that placebo response rates in patients with chronic fatigue syndrome (CFS)
are unusually high, "at least 30% to 50%", because of the subjective reporting of symptoms and the
fluctuating nature of the condition. According to a meta-analysis and contrary to conventional wisdom,
the pooled response rate in the placebo group was 19.6%, even lower than in some other medical
conditions. The authors offer possible explanations for this result: CFS is widely understood to be difficult
to treat, which could reduce expectations of improvement. In context of evidence showing placebos do
not have powerful clinical effects when compared to no treatment, a low rate of spontaneous remission
in CFS could contribute to reduced improvement rates in the placebo group. Intervention type also
contributed to the heterogeneity of the response. Low patient and provider expectations regarding
psychological treatment may explain particularly low placebo responses to psychiatric treatments.[129]
List of medical conditions[edit]
The effect of placebo treatments (an inert pill unless otherwise noted) has been studied for the following
medical conditions. Many of these citations concern research showing that active treatments are
effective, but that placebo effects exist as well.
Acne[130][131] Dyspepsia and Stomach motility[145] Itch[154]
Anxiety disorders[130][131] Epilepsy[146] Irritable
[132][133]
Asthma Erectile dysfunction[147] Lower u
Autism: language and behavior problems[134][135] Fibromyalgia[148] Migraine
[136]
Benign prostatic enlargement Food allergy: ability to eat ill-making foods[57] p. 54 Multiple
[137]
Binge eating disorder Gastric and duodenal ulcers[57][149] Nausea:
Bipolar mania[138] Headache[150] Nausea:
[139]
Burning mouth syndrome Heart failure, congestive[151] Osteoar
[19]
Cough Hypertension[152] Overact
Crohn's disease[140] Intellectual disability[153]
[141][142][143][144]
Depression
Endocannabinoid system involvement[edit]
It is found, that the endocannabinoid system may have a key role in nonopioid and NSAIDs-induced
placebo responses, as well as both the therapeutic and adverse effects of NSAIDs.[178]
History[edit]
Main article: Placebo in history

A quack treating a patient with Perkins Patent Tractors by James Gillray, 1801. John Haygarth used this
remedy to illustrate the power of the placebo effect.
The word 'placebo', Latin for "I will please", dates back to a Latin translation of the Bible by St
Jerome.[179] In 1811, Hooper’s Quincy’s Lexicon-Medicum defined placebo as "[any medicine] adapted
more to please than to benefit the patient".[180][181]
Early implementations of placebo controls date back to 16th-century Europe with Catholic efforts to
discredit exorcisms. Individuals who claimed to be possessed by demonic forces were given false holy
objects. If the person reacted with violent contortions, it was concluded that the possession was purely
imagination.[182]
John Haygarth was the first to investigate the efficacy of the placebo effect in the 18th century.[183] He
tested a popular medical treatment of his time, called "Perkins tractors", and concluded that the remedy
was ineffectual by demonstrating that the results from a dummy remedy were just as useful as from the
alleged "active" remedy.[184]
Émile Coué, a French pharmacist, working as an apothecary at Troyes between 1882 and 1910, also
advocated the effectiveness of the "Placebo Effect". He became known for reassuring his clients by
praising each remedy's efficiency and leaving a small positive notice with each given medication. His
book Self-Mastery Through Conscious Autosuggestion was published in England (1920) and in the United
States (1922).
Placebos remained widespread in medicine until the 20th century, and they were sometimes endorsed as
necessary deceptions.[11] In 1903, Richard Cabot said that he was brought up to use placebos,[11] but he
ultimately concluded by saying that "I have not yet found any case in which a lie does not do more harm
than good".[20]
In modern times, T. C. Graves first defined the "placebo effect" in a published paper in The Lancet in
1920.[185] He spoke of "the placebo effects of drugs" being manifested in those cases where "a real
psychotherapeutic effect appears to have been produced".[186] In 1961 Henry K.
Beecher concluded[187] that surgeons he categorized as enthusiasts relieved their patients' chest pain and
heart problems more than skeptic surgeons.[20] Beginning in the 1960s, the placebo effect became widely
recognized and placebo-controlled trials became the norm in the approval of new medications.[188]
Placebo-controlled studies[edit]
Main article: Placebo-controlled studies
The placebo effect makes it more difficult to evaluate new treatments. Clinical trials control for this effect
by including a group of subjects that receives a sham treatment. The subjects in such trials are blinded as
to whether they receive the treatment or a placebo. If a person is given a placebo under one name, and
they respond, they will respond in the same way on a later occasion to that placebo under that name but
not if under another.[189] Clinical trials are often double-blinded so that the researchers also do not know
which test subjects are receiving the active or placebo treatment. The placebo effect in such clinical trials
is weaker than in normal therapy since the subjects are not sure whether the treatment they are
receiving is active.[88]
Knowingly giving a person a placebo when there is an effective treatment available is a bioethically
complex issue. While placebo-controlled trials might provide information about the effectiveness of a
treatment, it denies some patients what could be the best available (if unproven) treatment. Informed
consent is usually required for a study to be considered ethical, including the disclosure that some test
subjects will receive placebo treatments.
The ethics of placebo-controlled studies have been debated in the revision process of the Declaration of
Helsinki.[190] Of particular concern has been the difference between trials comparing inert placebos with
experimental treatments, versus comparing the best available treatment with an experimental treatment;
and differences between trials in the sponsor's developed countries versus the trial's targeted developing
countries.[191]
Nocebo[edit]
Main article: Nocebo
A phenomenon opposite to the placebo effect has also been observed. When an inactive substance or
treatment is administered to a recipient who has an expectation of it having a negative impact, this
intervention is known as a nocebo (Latin nocebo = "I shall harm").[192] A nocebo effect occurs when the
recipient of an inert substance reports a negative effect and/or a worsening of symptoms, with the
outcome resulting not from the substance itself, but from negative expectations about the treatment.[193]
Ingredients[edit]
Placebos used in clinical trials have sometimes had unintended consequences. A report in the Annals of
Internal Medicine that looked at details from 150 clinical trials found that certain placebos used in the
trials affected the results. For example, one study on cholesterol-lowering drugs used olive oil and corn
oil in the placebo pills. However, according to the report, this "may lead to an understatement of drug
benefit: The monounsaturated and polyunsaturated fatty acids of these 'placebos,' and their antioxidant
and anti-inflammatory effects, can reduce lipid levels and heart disease." Another example researchers
reported in the study was a clinical trial of a new therapy for cancer patients suffering from anorexia. The
placebo that was used included lactose. However, since cancer patients typically face a higher risk
of lactose intolerance, the placebo pill might actually have caused unintended side-effects that made the
experimental drug look better in comparison.[194]