Making evolutionary biology a basic science
Randolph M. Nessea,1, Carl T. Bergstromb, Peter T. Ellisonc, Jeffrey S. Flierd, Peter Gluckmane, Diddahally R. Govindarajuf,
Dietrich Niethammerg, Gilbert S. Omennh, Robert L. Perlmani, Mark D. Schwartzj, Mark G. Thomask, Stephen C. Stearnsl,
and David Vallem
aDepartments of Psychiatry and Psychology, University of Michigan, Room 3018, East Hall, 530 Church Street, Ann Arbor, MI 48104;bDepartment of Biology,
University of Washington, Seattle, WA 98195-1800;cDepartment of Human Evolutionary Biology, Harvard University, 11 Divinity Avenue, Cambridge, MA
02138;dOffice of the Dean, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115;eCentre for Human Evolution, Adaptation, and Disease Liggins
Institute, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand;fDepartment of Neurology, Boston University School of Medicine, 72 East
Concord Street, Boston, MA 02118;gDepartment of Hematology, Children’s University Hospital, 72076 Tu ¨bingen, Germany;hCenter for Computational
Medicine and Bioinformatics and Departments of Internal Medicine, Human Genetics, and Public Health, University of Michigan, Room 2017F, Palmer
Commons, 100 Washtenaw Avenue, Ann Arbor, MI 48109;iDepartment of Pediatrics, University of Chicago, 5841 South Maryland Avenue, Chicago, IL
60637;jDivision of General Internal Medicine, Department of Medicine, New York University School of Medicine and VA New York Harbor Healthcare
System, 423 East 23rd Street, Suite 15N, New York, NY 10010;kResearch Department of Genetics, Evolution, and Environment, University College London,
Gower Street, London WC1E 6BT, United Kingdom;lDepartment of Ecology and Evolutionary Biology, Yale University, P.O. Box 208106, 165 Prospect Street,
New Haven, CT 06520-8106; andmMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 519 BRB, 733 North
Broadway, Baltimore, MD 21205
Edited by Daniel L. Hartl, Harvard University, Cambridge, MA, and approved September 29, 2009 (received for review August 2, 2009)
New applications of evolutionary biology in medicine are being
discovered at an accelerating rate, but few physicians have suffi-
cient educational background to use them fully. This article sum-
marizes suggestions from several groups that have considered
how evolutionary biology can be useful in medicine, what physi-
cians should learn about it, and when and how they should learn
it. Our general conclusion is that evolutionary biology is a crucial
basic science for medicine. In addition to looking at established
evolutionary methods and topics, such as population genetics and
pathogen evolution, we highlight questions about why natural
selection leaves bodies vulnerable to disease. Knowledge about
evolution provides physicians with an integrative framework that
links otherwise disparate bits of knowledge. It replaces the prev-
alent view of bodies as machines with a biological view of bodies
shaped by evolutionary processes. Like other basic sciences, evo-
lutionary biology needs to be taught both before and during
medical school. Most introductory biology courses are insufficient
to establish competency in evolutionary biology. Premedical stu-
dents need evolution courses, possibly ones that emphasize med-
ically relevant aspects. In medical school, evolutionary biology
should be taught as one of the basic medical sciences. This will
require a course that reviews basic principles and specific medical
applications, followed by an integrated presentation of evolution-
ary aspects that apply to each disease and organ system. Evolu-
tionary biology is not just another topic vying for inclusion in the
curriculum; it is an essential foundation for a biological under-
standing of health and disease.
curriculum ? Darwinian ? education ? evolution ? health
already have made full use of evolutionary biology. Far from it.
New applications of evolutionary biology to medical problems
are being discovered at an accelerating rate. The other articles
from this Sackler colloquium on ‘‘Evolution in Health and
Medicine’’ illustrate recent research progress. This article con-
siders what changes in medical education are needed to bring the
health problems. For the sake of focus and simplicity, we address
here only medical education; parallel educational recommenda-
Several sources contribute to the recent flowering of evolu-
tionary approaches in medicine. The first is that the basic science
of evolutionary biology continues its rapid development, build-
ne hundred and fifty years after publication of Darwin’s On
The Origin of Species, one might expect that medicine would
ing on the stable foundation of Darwin and Wallace’s theory of
natural selection (1). Genetic variants carried by individuals who
reproduce more than others tend to increase in frequency over
the generations, thus shifting the genetic make-up and mean
phenotype of the population to be more like them and generally
better adapted to their environments. The role of natural
selection in shaping living organisms has been empirically con-
firmed beyond dispute. Selection is by no means the only factor,
however. Mutations are inevitable; DNA is damaged by radia-
tion and toxins, and replication is not perfect. Other random
events are also important; genetic drift can push neutral or even
deleterious alleles to high frequency, whereas a storm might
eliminate all individuals with a useful mutation. Population
bottlenecks, inbreeding, and migrations also shape gene fre-
quencies, which in turn influence the distribution of phenotypes.
Natural selection and these other evolutionary mechanisms
change species, and, equally important, keep them the same via
stabilizing selection that disfavors individuals with extreme
traits (2, 3).
These core principles are, however, only the roots of a rapidly
growing network of explanations based on evolution. One main
branch is phylogeny. Long-established methods for analyzing
relationships within and among species are now being aug-
mented by new methods that use molecular genetic data to test
hypotheses about the relationships among populations and spe-
cies and about the large-scale history of life itself (4). The other
main branch is the study of adaptation. The unity of all life was
only one of Darwin’s greatest discoveries; the other was his
explanation for why organisms have traits that are so well
adapted to the challenges they face. No plan is involved; natural
selection tends to increase the frequencies of alleles of individ-
uals that survive and reproduce better than others in specific
environments (5). Sewall Wright (6) envisioned this process as
a landscape of hills and valleys, where the hills represent peaks
This paper results from the Arthur M. Sackler Colloquium of the National Academy of
are available on the NAS web site at www.nasonline.org/Sacker_Evolution_Health_Medicine.
Author contributions: R.M.N., C.T.B., P.T.E., D.R.G., D.N., R.L.P., M.G.T., S.C.S., and D.V.
designed research; R.M.N., C.T.B., P.T.E., P.G., D.R.G., D.N., G.S.O., R.L.P., M.D.S., M.G.T.,
S.C.S., and D.V. performed research; R.M.N. analyzed data; and R.M.N., C.T.B., P.T.E., J.S.F.,
P.G., D.R.G., D.N., G.S.O., R.L.P., M.D.S., M.G.T., S.C.S., and D.V. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
1To whom correspondence should be addressed. E-mail: email@example.com.
www.pnas.org?cgi?doi?10.1073?pnas.0906224106PNAS Early Edition ?
1 of 8
of fitness and the valleys regions of reduced fitness. Selection
tends to move traits up nearby slopes toward fitness hilltops, but
nearby higher peaks can be difficult to reach because the
transition requires moving through ‘‘valleys’’ of decreased
Tinbergen (7) and Mayr (8) provided an important clarifica-
tion of the difference between proximate questions about mech-
anisms and evolutionary questions about origins and functions.
They helped biologists recognize that every trait of every
organism needs two separate and complementary kinds of
explanation, proximate explanations of how mechanisms work,
and evolutionary explanations (sometimes called ‘‘ultimate ex-
planations’’) about how they got to be the way they are. For
instance, the proximate explanation of the adrenal gland in-
cludes its anatomy, tissues, chemical constituents, and the de-
velopmental processes that assemble them. Separate, and
equally important, is an evolutionary explanation: the phylogeny
of the adrenal gland and how it has conferred a selective
advantage. Notice that each kind of question has two subques-
tions. A complete biological explanation requires answers to
what are now known as Tinbergen’s four questions: What is the
mechanism? How did the mechanism develop? How has it given
a selective advantage? What is its phylogeny?
Many advances in evolutionary biology have emerged from
asking evolutionary questions about traits important to medicine
and public health, and the answers provide advances for medi-
cine; the benefits flow in both directions. Rates of aging are
heritable, so why has not selection eliminated or at least greatly
slowed aging? The strength of selection is weaker at older ages,
so deleterious mutations can accumulate, and genes that give
advantages in youth will be selected for even if they have
pleiotropic deleterious effects later in life (9, 10). Populations
with mostly females can have many more offspring than those
with an equal sex ratio, so why are not sex ratios more often
female biased? Because parents maximize their reproductive
success by making offspring of whichever sex is less common,
notwithstanding the penalty to group success, as R. A. Fisher
that nonsexual reproduction is twice as productive? This is a
fascinating problem, only partly solved; most proposed solutions
attribute it to the advantages of having genetically diverse
offspring (12, 13). Reducing the genome to a single copy during
meiosis seems wasteful; why not have oocytes that start with
many cells? Meiosis and crossing-over may have evolved to help
minimize the penetration of superselfish genes that arrange for
their own preferential transmission at the expense of other genes
and an individual’s health (14) and to repair damaged DNA
sequences. Why is cancer so persistent, and why does its prev-
alence increase at older ages? The evolutionary answer arises
from the limits of selection in eliminating deleterious alleles,
tradeoffs with the benefits of tissue repair, and genetic changes
induced by pathogens (15). Why do humans tend to have only
one offspring at a time (16)? Why is first reproduction delayed
for ?20 years? Such traits receive evolutionary analysis in life
history theory (17, 18). Why do individuals often act in ways that
such actions can increase the reproductive success of relatives
who have identical genes (19, 20). Another is that investing in
mate competition has relatively greater fitness payoffs for males,
thus explaining the 300% excess of male vs. female mortality
rates at sexual maturity in modern populations (21). Yet another
is that our dietary and exercise preferences were shaped in
environments fundamentally different from those common now
(22). What are the evolutionary reasons for capacities for pain,
fever, and negative emotions? Although painful and costly, they
are adaptive responses that evolved in conjunction with regula-
tory mechanisms that express them in situations where they are
useful (23, 24).
Investigations into such questions have tested scores of evo-
lutionary hypotheses, many with specific applications in medi-
New Genetic Data and Methods
New progress is also made possible by availability of vast
amounts of genetic data and associated new methods for gen-
erating and analyzing DNA sequence and gene expression data.
This is perhaps most obvious in our new ability to use genetic
information to trace phylogenies of species, subpopulations, and
genealogies of individuals (4). New data and methods also allow
estimation of the strength of selection acting at a given locus,
allowing us to test hypotheses about selection in humans (29, 30).
For example, strong signals of selection surround the locus of the
alcohol dehydrogenase gene in Southeast Asians (31). It is also
now possible to test evolutionary theories about differences in
selection acting on genes derived from paternal and maternal
sources, as in the case of imprinted genes (32). Accurate
measurements of mutation accumulation have also become a
reality (33); this might enable us to address long-standing
questions about the consequences of mutation accumulation or
the load of mutations (34). We are only beginning to discover the
many ways that genetic data can be used to generate and test
evolutionary hypotheses and the ways that evolutionary theory
can guide genetic studies and help to interpret unexpected
Increasing distance from 19th-century theories of degenera-
tion and 20th-century eugenics makes it easier to recognize the
value of modern evolutionary applications in helping individual
patients. In the late 19th century, Spencer’s ideas were more
influential than Darwin’s, with detrimental effects on evolution-
ary biology. In the early 20th century, evolutionary approaches
to health emphasized eugenics, supposed racial superiority, and
fears of degeneration, exploited by the Third Reich (36). When
Nazi horrors were publicized at the end of World War II,
scientific publications on evolution and medicine ceased sud-
denly (37). Although associations linger from previous links to
eugenics, repudiation of such social policies is now so widely
shared that it is easier to recognize the ways that evolutionary
biology can help us understand diseases. New evolutionary
approaches to medicine are almost entirely unconnected with
these earlier movements. Modern approaches tend to distance
themselves actively from concerns about races and the species.
Instead, they focus on ways that evolutionary biology can help to
solve medical problems of individuals and meet the public health
needs of communities (37).
Finally, evolutionary approaches are growing in medicine
thanks to new publications and broader education of physicians
and researchers. Controversy about teaching evolution in public
schools continues to inhibit evolution education, but it also has
stimulated interest in many of the best students (38). Several
recent books on evolutionary approaches to medicine (25, 27, 28,
39, 40) have given rise to many new undergraduate courses on
the topic, and recent international conferences have brought
together those working in related areas, with predictable synergy
(26, 41, 42).
Recommendations About Education Approaches for Evolution
Despite this progress, few physicians and medical researchers
have had a chance to learn specific applications in medicine and
public health through a course in evolutionary medicine. Many
have never even been exposed to the necessity of finding
evolutionary and proximate explanations. Implementation of
recommendations commissioned by the American Association
of Medical Colleges and the Howard Hughes Medical Institute
(AAMC-HHMI) would help change the situation. Twenty-two
2 of 8 ?
www.pnas.org?cgi?doi?10.1073?pnas.0906224106Nesse et al.
leading scientists, physicians, and medical educators met five
times from 2007 to 2009 to recommend scientific foundations for
future physicians (43). Instead of specific courses, they recom-
mend education that results in eight competencies that should be
mastered by students entering medical education (E 1–8) and
eight more for students in the course of medical education
E 1–7 correspond roughly to mathematics, scientific methods,
physics, chemistry, biochemistry, cell biology, physiology, and
facultative adaptations to internal and external changes. E8 is
recommendation from a major medical education body that
physicians need to master evolutionary biology. The AAMC-
HHMI report frames the evolution competency broadly, ‘‘Dem-
onstrate an understanding of how the organizing principle of
evolution by natural selection explains the diversity of life on
Earth.’’ This could include all of evolutionary biology. The
specific wording seems to emphasize phylogeny and phenomena
at the level of the species and above, however, some especially
important medical applications involve how selection shaped
traits that allow individuals to adapt to their environments and
the role of evolutionary factors other than selection. A more
inclusive global competency could be phrased: ‘‘Demonstrate an
understanding of how natural selection and other evolutionary
processes account for the history of life and the relationships
among species, how these processes have endowed organisms
with traits that promote reproductive success, and why they leave
some aspects of the human body vulnerable to disease.’’
The areas E 1–7 are established components of premedical
education, so much previous thought has gone into how they can
Evolutionary biology, however, is just now being recognized as
a basic science for medicine. Only a few papers address the
issues. Two studies document the absence of evolutionary biol-
ogy from the medical curriculum (44, 45), and several articles
make general recommendations about teaching evolutionary
biology in medicine (46–48). This article is an attempt by a
diverse group of scientists to address the question systematically.
Our suggestions are based on discussions by three overlapping
groups of authors. Some of us spent 2007–2008 at the Berlin
Institute for Advanced Study working together on evolutionary
applications in medicine and optimal education strategies. Four
others had extensive discussions in the course of organizing the
Sackler Colloquium. Finally, four others presented papers at the
colloquium on topics related to the role of evolution in medical
education. Our opinions are, of course, diverse. This article
summarizes major areas of agreement and it attempts to clarify
some issues on which opinions differ. We recognize that evolu-
tion is of equal importance for other health professions, such as
nursing, and that it is especially important for public health.
However, because somewhat different issues arise for each field,
we decided to limit our recommendations here to the field of
General Conclusions and Recommendations
We generally agree on five global points:
1. Better education about evolutionary biology and its appli-
cations in medicine will have substantial benefits for physi-
cians, their patients, public health workers, researchers, and
other health professionals. This conclusion is supported by
other articles in this colloquium and by explanatory material
below in association with specific recommendations.
2. Much of this education needs to be provided or initiated
before beginning formal medical studies. Like mathematics,
chemistry, genetics, and the study of biological mechanisms
(proximate biology), evolutionary biology is a basic science
that should be taught before medical school.
3.The evolution content in introductory biology courses is
insufficient; specialized undergraduate courses will be im-
portant. We hold varying opinions about whether to recom-
mend general overview courses or courses specialized to the
needs of future physicians. All agree that substantial evolu-
tion education is essential.
4. Some aspects of evolutionary biology need to be taught as a
part of the medical curriculum, despite the practical chal-
lenges. The medical curriculum is already overly full. How-
ever, medically relevant principles of evolutionary biology
need to be taught during professional school, just as they are
for other basic sciences such as anatomy, genetics, and
5. Evolutionary biology is a unifying principle that provides a
framework for organizing medical knowledge from other
basic sciences. Attaining a deep understanding of this gen-
eral framework is a worthy learning objective, because much
of the power of evolutionary thinking in medicine comes
from its ability to foster integrative thinking about our bodies
as products of evolutionary processes.
Providing a Rationale for Evolutionary Content
in Medical Education
The relevance of evolutionary biology in medical education is by
no means universally recognized. Medical school deans and
other educators often ask for evidence that knowledge about
evolutionary biology will improve the effectiveness of health-
care professionals. A simple response is to cite direct applica-
tions. For instance, doctors need to understand the evolution of
antibiotic resistance, methods for tracing pathogen phylogenies,
how selection shaped mechanisms that regulate protective re-
sponses such as pain and fever, and the intimate connections
between evolution, environment, and diseases of aging. How-
ever, limiting the discussion to such direct applications sells short
the utility of evolutionary biology in medicine.
Much basic science education in medicine is required, not
because it has direct daily applications, but because it is essential
for understanding the body and disease. As summarized in
overarching principle 2 in the AAMC-HHMI report, ‘‘The
principles that underlie biological complexity, genetic diversity,
interactions of systems within the body, human development,
and influence of the environment guide our understanding of
human health, and the diagnosis and treatment of human
disease.’’ We require competence in calculus, physics and chem-
istry, not because they are needed every day in the clinic, but
because physicians with competence in these areas will better
understand the body and will make better medical decisions.
For instance, most medical schools provide an extensive
course on developmental biology because understanding how a
zygote develops into an adult organism is an important founda-
to disease. Understanding how natural selection and other
evolutionary processes have shaped the body and its components
across evolutionary time is equally valuable. Like developmental
biology, it describes patterns of development that explain why
the body is the way it is and why certain aspects leave us
vulnerable to diseases. So far, however, no medical school
teaches evolutionary biology as a basic science comparable to
The large-scale structure of evolutionary applications in med-
icine can be organized into 10 areas by intersecting the two
subfields of evolutionary biology (phylogeny and adaptation)
with five different targets of selection: human genes, human
traits, pathogen traits, pathogen genes, and somatic cell lines
such as those in cancer and the immune system (26). Some of
these areas are well developed and extensively taught. For
instance, population genetics is the foundation for all evolution-
ary approaches to disease, and phylogenetic methods are widely
Nesse et al. PNAS Early Edition ?
3 of 8
applied to pathogen evolution. Others are less well developed.
For instance, asking questions about why selection has left the
body vulnerable to disease is a newer enterprise that offers
methodological challenges, and opportunities for deeper under-
standing (40, 49, 50).
General recommendations like those above provide a foun-
dation for more specific suggestions for about what would be
taught, when, and how. The AAMC-HHMI report eschews
course recommendations in favor of suggesting specific compe-
tencies and learning objectives. We follow this same format,
expanding on occasion to illustrate how physicians who master
specific learning objectives will practice superior medicine.
Learning objective 1 for the evolution competency in the
AAMC-HHMI report requires students to be capable of ex-
plaining ‘‘how genomic variability and mutation contribute to
the success of populations.’’ This is a valuable objective, but its
implementation requires sophistication to avoid confusion. The
wording could lead some to think that mutations exist to speed
evolution or that the evolutionary explanation for maintained
genetic variation is well understood, when it is actually an issue
of intensive study in evolutionary biology, as illustrated by
articles by Valle and Eyre-Walker (51) and Houle (52) in this
work, and drift brings added complications. Also, although the
success of populations is important, one of the great achieve-
ments of 20th-century evolutionary biology is recognition that
selection generally acts to maximize benefits to individuals and
their genes, not species or populations (53, 54). The other
learning objective, ‘‘explain how evolutionary mechanisms con-
tribute to change in gene frequencies in populations and to
reproductive isolation,’’ encompasses a breadth of important
material. Neither of these learning objectives focuses explicitly
on issues of bodily adaptation and maladaptation that are crucial
More detailed learning objectives for evolutionary biology
would make them more similar to those for other basic sciences.
For instance, among the six learning objectives for E3 (physics),
students are expected to ‘‘demonstrate knowledge of the prin-
ciples of thermodynamics and fluid motion,’’ and ‘‘demonstrate
knowledge of principles of quantum mechanics, such as atomic
and molecular energy levels, spin, and ionizing radiation.’’ With
these in mind, we offer several comparably specific learning
objectives for evolutionary biology. We recognize that our
opinions are no substitute for a representative body of experts
convened to address these issues; nonetheless, they may be
Learning Objectives for Premedical Competencies in
1. Demonstrate an understanding of how natural selection
shapes traits in organisms. Grasping how selection works
turns out to be quite difficult, in part because it requires
replacing intuitive thinking about species-typical normal
types with population thinking that views a species as a
collection of genetically diverse individuals. It also requires
recognizing how evolutionary explanations are different
from proximate explanations; instead of describing struc-
tures and mechanisms, they describe how a process changes
the distribution of characteristics of a population over the
Y Describe how the beaks of the many species of finches of the
Galapagos have come to be well-matched to the usual foods
of each species and the evidence that supports your thesis.
Y Describe the differences between human and chimpanzee
teeth and guts and the evolutionary forces that are likely
Y Describe distinctive aspects of human facial musculature, and
the evolutionary forces likely to have shaped them.
Y Show how selection can account for a species staying mostly
the same across thousands of generations.
2. Describe the differences between proximate and evolution-
ary explanations, and the two subtypes under each.
Y Provide proximate and evolutionary explanations for the
metabolic pathways that synthesize bilirubin.
Y Provide proximate and evolutionary explanations for the
retention of fluid in congestive heart failure.
Y Provide proximate and evolutionary explanations for the
cessation of sexual cycling in young human females who
regularly exercise intensely.
3. Describe the relative roles of mutation, selection, drift, and
migration in accounting for genotypes and phenotypes.
Y Explain the origins of lactase persistence into adulthood in
certain populations and the factors that explain its current
Y Discuss the prevalence of blue eyes in different populations,
and how you would investigate possible evolutionary expla-
4. Describe the mathematical formulations that describe the
rate of change of an allele’s frequency under different
strengths of selection, and the implications for hypotheses
about the role of selection in accounting for differences
among human populations.
Y Intestinal lactase persistence has given selective advantages as
large as 8% in dairying cultures. Compare this strength of
selection to that for other traits.
Y Apply these methods to myopia to conclude whether the
recent use of eyeglasses has likely increased rates of near-
5. Explain how the comparative method and other strategies
can be used to test evolutionary explanations.
Y High uric acid levels have been hypothesized to give an
advantage by slowing rates of aging arising from oxidative
damage. How could you use comparative data to assess this
of other primates to assess this hypothesis.
6. Be able to describe the role of tradeoffs in traits shaped by
Y Explain why natural selection has not made the head of the
radius thicker to protect against fracture.
Y What tradeoffs are likely to have shaped mechanisms that
regulate fat storage in humans?
7. Understand the core principles of behavioral ecology.
Y What are the main areas to which a pathogen, such as
tapeworm, allocates energy, and the tradeoffs among them?
Y Explain the basic principles of foraging theory in patches and
how these might apply to the distribution of a disease vector.
8. Describe phenomena explained by kin selection and inclusive
fitness more generally.
Y Kin selection is said to explain ‘‘altruism.’’ What are some
4 of 8 ?
www.pnas.org?cgi?doi?10.1073?pnas.0906224106 Nesse et al.
Y A colleague suggests that aging might be valuable for the
species to speed evolution. How would you assess this idea?
Y Explain how an individual’s actions can influence his or her
fitness even after reproduction has ended.
9. Understand sexual selection, and how it can shape sex
Y Provide proximate and evolutionary explanations for sex
differences in life span.
Y Why does oogenesis in females end during fetal life, whereas
spermatogenesis in males continues into old age? What ge-
netic diseases are associated with father’s age?
Such detailed objectives may seem to be asking too much. They
are, however, simpler and more directly relevant to medicine
than other proposed learning objectives such as the principles of
quantum mechanics, and being able to explain how molecular
easily be expanded and refined. We hope others will attempt to
The AAMC-HHMI report lists eight competencies to be at-
tained in medical education, including applications of physics
and chemistry (M2) and genetics (M3). It does not include any
specific applications of evolution. Competency M1 is ‘‘apply
knowledge of molecular, biochemical, cellular, and systems-level
mechanisms that maintain homeostasis, and of the dysregulation
of these mechanisms, to the prevention, diagnosis, and manage-
ment of disease.’’ This describes the application of proximate
knowledge to the body and disease. A parallel competency to
bring in the evolutionary half of biology, perhaps M1b, would be
‘‘apply knowledge of evolutionary factors that have shaped the
body and its regulatory systems to the prevention, diagnosis, and
management of disease.’’
Learning Objectives for Medical Competencies in Evolutionary
1. Explain what is meant by facultative adaptation (phenotypic
plasticity) and how such adaptations are shaped by natural
Y Explain tanning in response to sunlight.
Y Explain the effects of early life experiences of caloric depri-
vation and stress on later metabolism and how you would
investigate if these effects are facultative adaptations or
2. Explain how to calculate heritability and what it means.
Y Height is highly heritable, yet genomewide association studies
have so far found no common genetic variants that account for
more than a few percent of the variation for height. Explain.
Y Explain why high heritability for a common disease is likely to
indicate strong effects of novel environmental factors.
3. Describe why the concept of tradeoffs means that no trait in
the body can be perfect.
Y A strong immune response would seem to be useful. Explain
tradeoffs and other reasons why we remain so vulnerable to
Y A narrow birth canal has serious costs to mother and infant.
What evolutionary tradeoffs likely account for the narrowness
of the birth canal?
4. Understand the role of modern environments in causing
Y The past hundred years have seen an ‘‘epidemiological tran-
sition’’ in which chronic disease has come to overshadow acute
infectious disease. Describe the responsible chronic diseases,
for some aspects of our modern environment.
Y Describe how the rise of agriculture has influenced disease
vulnerability and if there is evidence that agriculture has
5. Describe how path dependence makes evolved bodies fun-
damentally different from designed machines.
Y The human spine is a source of much trouble; propose some
possible evolutionary explanations.
Y A twisted omentum can cut off blood supply to the gut.
Describe the evolutionary reasons for human vulnerability to
volvulus and a comparative test of your hypothesis.
6. Demonstrate understanding of how methods for tracing
phylogenies can be applied to genetic data.
Y Show how to use genetic data to determine which of several
possible pathogen populations is the most likely source of a
Y Describe how genetic data can be used to show our relatedness
to other primates.
7. Explain how coevolution of hosts and pathogens results in
arms races that shape traits prone to contribute to disease.
Y Streptococcus has evolved with primates for millions of years.
Describe a disease complication that may arise from the
coevolution of host defenses and pathogen strategies.
Y Cholera kills by dehydration. Describe the proximate mech-
anism and the selective processes likely to have shaped it. Use
this information to comment on the likely costs and benefits,
for pathogen and host, of using drugs to block this mechanism.
8. Understand how the absence of pathogen exposures can
Y Why does normal development of the vertebrate gut require
the presence of signals from gut bacteria?
Y What are some medical consequences of modern hygiene and
antibiotics that eliminate such signals?
Y Describe why the absence of helminths in the human gut is
associated with certain diseases.
9. Demonstrate understanding of the processes that shape
pathogen virulence and antibiotic resistance.
Y Antibiotic resistance can emerge and spread in just a matter
of months. Describe the responsible proximate and evolution-
Y Explain why pathogens spread by vectors such as mosquitoes
tend to be more virulent than those spread by respiratory
Y Bacteria from deep soil samples show resistance to many
10. Describe how the principles of signal detection theory
explain how selection shapes mechanisms that regulate
guide research about when it is safe to use drugs to block
Y Costs of fever include tissue damage, the risk of seizures, and
metabolic costs. Describe how high you would expect these
costs to be in comparison with the benefits if fever is con-
trolled by a regulatory mechanism that is near optimal.
Nesse et al. PNAS Early Edition ?
5 of 8
Y If natural selection shaped optimal regulatory mechanisms,
why do not more problems arise from using drugs that block
normal defense responses such as cough and vomiting?
11. Understand somatic selection.
Y Describe how selection among immune cells results in adap-
tive responses to infection.
Y Describe the importance of somatic selection in explaining
cancer and planning chemotherapy strategies.
12. Understand the evolutionary origins of senescence.
Y Explain some of the evidence that aging rates are life history
traits shaped by selection.
Y The physiological reserve declines with age at remarkably
similar rates in multiple organ systems. Explain why.
Y A colleague says that nothing can be influenced by natural
selection after reproduction ends. Why is this incorrect?
13. Explain the origins and significance of genetic variations
that influence responses to pharmaceutical drugs.
Y What do drug metabolizing enzymes do, and what are the
medical consequences of variation in their activity among
Y What was the role of drug metabolizing enzymes in our
evolutionary past and why might this have generated the
variation we see today?
14. Demonstrate understanding of the aspects of microbial
genetics that affect medical outcomes.
Y What is the evolutionary significance to an RNA virus of a
mutation rate 1,000 times greater than that of a DNA virus?
What implications does this have for the design of vaccines
against HIV and influenza?
Y How can DNA be exchanged among bacteria? What is the
functional significance for the bacteria? What are the impli-
cations for the development of antibiotic resistance?
Once again, we emphasize that the above learning objectives and
examples are only suggestions. We hope they will encourage
more systematic investigations of optimal policies about evolu-
tion education in medicine. We know we have omitted important
items, and a sophisticated committee would edit many items to
a more suitable format. While we await such more comprehen-
sive assessment, some will ask what specific topics should be
covered in the medical curriculum. Remarkably few suggestions
have appeared (46, 55). Ours appear in the next section.
Topics That Should Be Covered in a Medical School Course on
1. A review of core principles of evolutionary biology.
2. Common misunderstandings about evolution: how to recog-
nize and avoid them.
3. Evolutionary explanations: importance, formulation, testing.
4. Cooperation, kin selection, levels of selection.
5. Evolutionary genetics, signals of selection, drift, pleiotropy,
6. Evolutionary considerations in epidemiology, and genome-
wide association studies.
7. Life history theory applied to humans.
8. Senescence and late-onset diseases.
9. Reproduction, sexual selection, and related medical prob-
10. Antibiotic resistance and virulence evolution.
11. Coevolution, arms races, and related aspects of infectious
12. The ecology and evolution of emerging diseases.
13. Somatic evolution in cancer, and immunology.
14. Diseases of modern environments and the epidemiological
15. Defenses, their regulation, and their costs.
16. Tradeoffs, at levels from genes, to physiology, to behavior.
17. Development as a product of and contributor to evolution-
18. Facultative adaptations (phenotype plasticity) and related
19. Human evolution and ancestral environments.
20. Genetic differences among human populations and rates of
21. Heritability and an understanding of how genes interact
22. Behavioral ecology, behavior, and the origins and functions
The Integrative Power of Evolutionary Understanding
Two things about medical education are widely acknowledged;
there is more to learn than anyone can learn, and much of what
we teach students now will be obsolete soon. The usual conclu-
sion is that we need to teach students general principles, and we
need to teach them how to find specific information when they
need it (43).
stretches beyond any specific discipline. It does not address one
level, such as biochemistry, or one system, such as the immune
system. Rather, it offers principles that apply to every biological
system at every level. As a recent overview of another Sackler
Colloquium on Darwin noted, ‘‘Most scientists agree that evo-
lution provides the unifying framework for interpreting biolog-
ical phenomena that otherwise can often seem unrelated and
perhaps unintelligible’’ (56). It offers a sturdy integrative frame-
work, one on which myriad facts can be hung in retrievable
locations. Bilirubin metabolic pathways become much more
memorable when integrated with the evolutionary reasons for
those pathways. The role of cholera toxin in the small bowel
makes more sense when considered in light of factors shaping
virulence. The tendency of certain strains of Streptococcus to
cause rheumatic fever makes more sense when integrated with
the arms races that shaped the vulnerability. Proximate mech-
anisms that explain our vulnerability to obesity and substance
abuse make more sense when framed in terms of the environ-
ments that shaped those mechanisms.
Beyond a framework for organizing medical knowledge, a
deep evolutionary understanding also helps to correct the prev-
alent dependency on the metaphor of the body as a designed
machine (47). Of course, the body is a system of interlocking
mechanisms, with levers, pulleys, and chemicals and feedback
regulation at all levels. It is not, however, a machine built from
blueprints created by an engineer. Instead, it is a jury-rigged
system that generally works, despite serious ‘‘design’’ flaws such
as the inside-out eye and the double curve in the spine (57). Its
complexity goes far beyond complexity we can readily describe,
because it emerged from layer on layer of systems built from tiny
variations over hundreds of millions of years. Many wish it was
easy to map modules in the brain to specific functions, but we are
finding functions distributed among various areas in ways that
defy common sense and any ability to come up with a clear
description (58). We strive to characterize the function of a gene,
only to discover that most do more than one thing, and some
have very different functions depending on the tissue and the
phase of development. Thus, as Childs et al. (47) pointed out so
well, the body is not a designed machine; it is a soma shaped by
selection, and that is something very different. As students
become increasingly able to understand the limits of the de-
signed machine metaphor, and as they grasp the body as a
6 of 8 ?
www.pnas.org?cgi?doi?10.1073?pnas.0906224106Nesse et al.
product of natural selection, they will have a deeper understand-
ing of the body and why it is vulnerable to disease.
At the Sackler Colloquium, leaders from Harvard, Yale, and
Johns Hopkins discussed plans to incorporate evolutionary
biology into their medical curricula. Other institutions are
making similar efforts. Some countries, such as Norway, seem to
be ahead (59), while the United Kingdom faces different chal-
lenges (60). Variations among such plans will soon reveal what
works better and not so well, and curricula will evolve. As is the
case for a rare beneficial allele, however, the initial spread is the
momentum continues, and some thoughts about how to get
initial efforts going in healthy directions.
First, additional formal investigations into the role of evolu-
tionary biology in medical and public health curricula are
needed. Our opinions, however considered, are no substitute for
the conclusions of diverse groups of experts convened to address
these issues. We hope the AAMC, perhaps in conjunction with
the HHMI, the Institute of Medicine (IOM), and a major
scientific society of evolutionary biologists, will convene groups
to address this issue.
medical curricula. Some are newly available (27, 28, 61), but it
is important to recognize that these efforts are early; developing
a selection of teaching materials will take time. Free web-
accessible educational resources would be very helpful.
Third, with curricula already overly full, and without evolu-
tionary biologists on the faculty, few medical schools are posi-
tioned to take advantage of these opportunities. Strong leader-
ship will be essential. Creating new courses and integrating
cogent evolutionary examples into existing courses will also be
essential. Time for needed new courses will have to come from
existing courses, but it is difficult to get disciplines to give up
teaching time no matter how compelling the case for new
content. Some initial implementations will likely be by dean’s
decision, but perhaps some faculties will cooperate to take
advantage of the opportunity. The incorporation of evolutionary
content in existing courses, done well, should recruit support for
finding time to give students the basics early in medical school.
Fourth, we recommend that the impact of implemented
changes be subject to rigorous investigation from the start. This
will require careful research designs to measure the knowledge
and performance of students who have and have not received
teaching about evolutionary applications in medicine. In addi-
tion to measuring knowledge about evolution and its medical
applications, we suggest measuring changes in their ability to
explain diseases to patients, their ability to evaluate evolutionary
hypotheses critically, their ability to integrate knowledge from
the organism,’’ that informs their intuition about conditions they
have not specifically studied.
Implementation could be accelerated by the simple and
on medical certification examinations at all levels. The Medical
College Admission Test will soon include questions about evo-
lutionary biology. Step 1 of the U.S. medical licensing exami-
nation includes questions from each of the traditional basic
sciences for medicine, but does not cover content related to
evolutionary biology. Students know they need to learn details
about anatomy, physiology, and biochemistry to become certi-
fied. No such questions ensure that physicians understand the
principles of evolutionary biology. We recommend adding such
One hundred and fifty years after publication of The Origin of
Species, new advances demonstrate the utility of evolutionary
biology in medicine, but few physicians and medical researchers
have taken a course on evolutionary biology, and no medical
school teaches evolutionary biology as a basic science for med-
icine. It is as if engineering students never learned physics.
Filling this gap will require substantial changes in medical
education policies and practices. Our suggestions about content,
and when and how best to teach it, are only a beginning. National
and international organizations such as the AAMC, IOM,
HHMI, and the Wellcome Trust have crucial roles to play in
deciding what evolution education is needed, how to provide it,
and how to implement it. A private foundation could, for a
remarkably small investment, have a major positive impact on
the future of medicine. Many physicians, researchers, and edu-
cators stand ready to help do what needs to be done so that
human health gets full benefit from the basic science of evolu-
ACKNOWLEDMENTS. The Berlin Institute for Advanced Study sponsored
much of the research reported here.
1. Futuyma D (2001) Evolution, science, and society. Am Nat 158(Suppl 4):S1–S46.
2. Stearns SC, Hoekstra RF (2005) Evolution: An introduction (Oxford Univ Press, Oxford),
3. Futuyma DJ (2005) Evolution (Sinauer, Sunderland, MA).
4. Felsenstein J (2004) Inferring Phylogenies (Sinauer, Sunderland, MA).
5. Williams GC (1966) Adaptation and Natural Selection: A Critique of Some Current
Evolutionary Thought (Princeton Univ Press, Princeton).
6. Wright S (1932) The roles of mutation, inbreeding, cross-breeding, and selection in
evolution. Proceedings of the 6th International Congress of Genetics, ed Jones DF
(Genetics Society of America, Bethesda), pp 356–366.
7. Tinbergen N (1963) On the aims and methods of ethology. Zeitschrift Tierpsychol
8. Mayr E (1974) Teleological and teleonomic: A new analysis. Boston Stud Philo Sci
9. Williams GC (1957) Pleiotropy, natural selection, and the evolution of senescence.
Evolution (Lawrence, Kans) 11:398–411.
10. Kirkwood T, Austad S (2000) Why do we age? Nature 408:233–238.
11. Fisher RA (1930) The Genetical Theory of Natural Selection (Clarendon, Oxford).
12. Williams GC (1975) Sex and Evolution (Princeton Univ Press, Princeton).
13. Stearns SC (1987) The Evolution of Sex and Its Consequences (Birkha ¨user, Boston).
14. Hurst LD (1995) Selfish genetic elements and their role in evolution: The evolution of
sex and some of what that entails. Philos Trans R Soc London Ser B 349:321–332.
15. Greaves MF (2000) Cancer: The Evolutionary Legacy (Oxford Univ Press, Oxford).
16. Low BS (2000) Why Sex Matters (Princeton Univ Press, Princeton).
17. Stearns SC (1992) The Evolution of Life Histories (Oxford Univ Press, Oxford).
18. Hill K, Hurtado A (1991) The evolution of premature reproductive senescence and
menopause in human females. Hum Nat 2:313–350.
19. Hamilton WD (1964) The genetical evolution of social behavior I and II. J Theor Biol
20. Hammerstein P (2003) Genetic and Cultural Evolution of Cooperation (MIT Press,
sex differences in human mortality rates. Hum Nat 17:74–97.
23. Nesse RM (1990) Evolutionary explanations of emotions. Hum Nat 1:261–289.
24. Nesse RM (2005) Natural selection and the regulation of defenses: A signal detection
analysis of the smoke detector principle. Evol Hum Behav 26:88–105.
25. Trevathan WR, McKenna JJ, Smith EO, eds (2007) Evolutionary Medicine (Oxford Univ
Press, New York), 2nd Ed.
26. Nesse RM, Stearns SC (2008) The great opportunity: Evolutionary applications to
medicine and public health. Evol Appl 1:28–48.
27. Stearns SC, Koella JK, eds (2007) Evolution in Health and Disease (Oxford Univ Press,
Oxford), 2nd Ed.
28. Gluckman PD, Beedle A, Hanson MA (2009) Principles of Evolutionary Medicine
(Oxford Univ Press, Oxford).
29. McVean G, Spencer CC (2006) Scanning the human genome for signals of selection.
Curr Opin Genet Dev 16:624–629.
30. Sabeti PC, et al. (2006) Positive natural selection in the human lineage. Science
31. Li H, et al. (2008) Ethnic-related selection for an ADH class I variant within East Asia.
PLoS ONE 3:e1881.
32. Crespi B, Badcock C (2007) Psychosis and autism as diametrical disorders of the social
brain. Behav Brain Sci 31:241–261.
Nesse et al.PNAS Early Edition ?
7 of 8
33. Baer CF, Miyamoto MM, Denver DR (2007) Mutation rate variation in multicellular Download full-text
eukaryotes: Causes and consequences. Nat Rev Genet 8:619–631.
34. Muller HJ (1950) Our load of mutations. Am J Hum Genet 2:111–176.
35. Weiss KM (2008) Tilting at quixotic trait loci (QTL): An evolutionary perspective on
genetic causation. Genetics 179:1741–1756.
36. Proctor RN (1988) Racial Hygiene: Medicine Under the Nazis (Harvard Univ Press,
Rev Biol 84:1–23.
38. Alters B, Nelson C (2002) Perspective: Teaching evolution in higher education. Evolu-
tion (Lawrence, Kans) 56:1891–1901.
39. Ewald PW (1994) Evolution of Infectious Disease (Oxford Univ Press, Oxford).
40. Nesse RM, Williams GC (1994) Why We Get Sick: The New Science of Darwinian
Medicine (Times Books, New York).
41. Stearns SC, Ebert D (2001) Evolution in health and disease. Q Rev Biol 76:417–432.
42. MacCallum CJ (2007) Does medicine without evolution make sense? PLoS Biol 5:e112.
43. AAMC-HHMI Scientific Foundation for Future Physicians Committee (2009) Scientific
Foundations for Future Physicians (American Association of Medical Colleges and
Howard Hughes Medical Institute, Washington, DC).
44. Nesse RM, Schiffman JD (2003) Evolutionary biology in the medical school curriculum.
45. Downie JR (2004) Evolution in health and disease: The role of evolutionary biology in
the medical curriculum. Biosci Ed Elect J 4:1–18.
46. Nesse RM, Williams GC (1997) Evolutionary biology in the medical curriculum: What
every physician should know. BioScience 47:664–666.
school curriculum. Annu Rev Genomics Hum Genet 6:313–330.
48. Harris EE, Malyango AA (2005) Evolutionary explanations in medical and health
profession courses: Are you answering your students’ ‘‘why’’ questions? BMC Med
49. Perlman RL (2005) Why disease persists: An evolutionary nosology. Med Health Care
50. Nesse RM (2005) Maladaptation and natural selection. Q Rev Biol 80:62–70.
51. Valle D, Eyre-Walker A (2009) ●●● Proc Natl Acad Sci USA ●●●.
52. Houle D (2009) Numbering the hairs on our heads: The shared challenge and promise
of phenomics. Proc Natl Acad Sci USA, 10.1073/PNAS.0906195106.
53. Williams GC (1996) Adaptation and Natural Selection: A Critique of Some Current
Evolutionary Thought (Princeton Univ Press, Princeton).
54. Dawkins R (1989) The Selfish Gene (Oxford Univ Press, Oxford).
55. Charlton BG (1997) A syllabus for evolutionary medicine. J R Soc Med 90:397–399.
Acad Sci USA 106(Suppl 1):9933–9938.
57. Held LI (2009) Quirks of Human Anatomy: An Evo-Devo Look at the Human Body
(Cambridge Univ Press, Cambridge).
58. Pessoa L (2008) On the relationship between emotion and cognition. Nat Rev Neurosci
59. Mysterud I (1998) The history, status, and teaching of Darwinian medicine in Norway.
Norsk Epidemiol 8:101–108.
60. Elton S, O’Higgins P (2008) Is there a place for evolutionary medicine in UK medical
education? Medicine and Evolution: Current Applications, Future Prospects, eds Elton
S, O’Higgins P (CRC, Boca Raton, FL), Vol 48, pp 257–269.
practice. Henry Stewart Talks, ed Nesse RM (Henry Stewart, Inc., London), Available at
8 of 8 ?
www.pnas.org?cgi?doi?10.1073?pnas.0906224106 Nesse et al.