Nothing in biology makes sense except in the light of evolution. —Theodosius Dobzhansky
The term evolutionary medicine refers to the study of, teaching of, and application of the concepts, principles and perspectives of evolution and evolutionary biology to the understanding, prevention and management of human disease, both mental and physical, and to the general improvement of human well-being. Advocates of evolutionary medicine regard those projects as stemming from an understanding of human biology as an evolved living system embedded in an environment of diverse other evolved living and non-living systems. They implicitly or explicitly subscribe to the proposition of the 20th century's pioneer geneticist and evolutionary biologist, the Russian-American, Theodosius Dobzhansky, to wit:
Often the advocates of evolution-informed medicine see Dobzhansky's "light of evolution" as shining from the ideas of Charles Darwin and Alfred Russel Wallace, in particular the idea of adaptation due to natural selection, or, as Wallace preferred, 'survival-of-the-fittest'. Hence the term 'Darwinian medicine' finds alternative use for evolutionary medicine. We now know that evolutionary forces comprise a wide range of natural processes in addition to natural selection, and different 'kinds' of selection.  The advance of evolutionary medicine will require an appreciation of all evolutionary processes potentially affecting human health.
Scientists from many different disciplines have contributed in diverse ways to the developing discipline of evolutionary medicine: anthropology, cardiovascular medicine, endocrinology, evolutionary biology, exercise physiology, family medicine, genetics, geriatrics, gynecology, immunology, physiology, metabolism, nutrition, obstetrics, oncology, pediatrics, psychiatry, psychology, and systems biology.
Does medicine without evolution make sense?
This section's question header echoes the title of a recent (April, 2007) editorial in the open-access journal, PLoS Biology,  by senior editor Catriona J. MacCallum.  MacCallum laments the fact that evolution does not figure prominently in the medical community and in the curriculum of medical schools. She notes one of the reasons:As explained at a meeting on evolution and medicine I recently attended in York, United Kingdom (the Society for the Study of Human Biology and the Biosocial Society’s 2006 symposium, “Medicine and Evolution"), medicine is primarily focused on problem-solving and proximate causation, and ultimate explanations can seem irrelevant to clinical practice. Crudely put, does a mechanic need to understand the origins, history, and technological advances that have gone into the modern motor vehicle in order to fix it? 
Editorial comment by the Citizendium Biology Workgroup: As if the modern motor vehicle, or any other human artifact for that matter, could match the organizational constitution of the most complex organism on Earth.
MacCallum continues to highlight the York meeting mentioned in the previous quote:Participants at the York meeting discussed:
- not only how vulnerability to cancer is an inevitable but unfortunate consequence of imperfect human engineering and natural selection (Mel Greaves, Institute of Cancer Research, UK),
- but how life history theory can potentially explain patterns of pregnancy loss (Virginia Vitzthum, Indiana University),
- how a comparative approach applied to different human cultures and different primates can improve rates of breastfeeding (Helen Ball, University of Durham),
- whether clinical depression has an adaptive origin (Lewis Wolpert, University College London), and
- if suicide attempts are really just evolutionary bargaining chips in intense social disputes (Ed Hagen, Humboldt University).
Topics of interest: a selection
2006 symposium, “Medicine and Evolution”
A selection of titles of, and of Abstract excerpts from, the oral presentations at the Society for the Study of Human Biology and the Biosocial Society’s 2006 symposium, “Medicine and Evolution”), help give a sense of the topics of interest to advocates of evolutionary medicine as a separate discipline:
- Randolph Nesse: Darwinian medicine is flowering: will it set seed?
- "[T]he incorrect metaphor of the body as a machine can now be replaced with an evolutionary view of the body as a bundle of tradeoffs shaped by natural selection to maximize Darwinian fitness. This change in perspective is fundamental. It will lead to advances at all levels of analysis in all fields of medicine."
- Sarah Elton: Environments, adaptation and evolutionary medicine
- "In this presentation I will consider the concept of the 'environment of evolutionary adaptedness' [viz., the Stone Age] and its utility in understanding human evolutionary history and current human health. I will also critically review the importance of the selective pressures of the environment in shaping the health and disease profiles of modern human populations, and argue that although ideas such as 'Stone Age' adaptations to diet and consequent implications for human health in the 21st Century are attractive, they do not necessarily stand up to scrutiny."
- Stan Ulijaszek: Human nutrient requirements from a life history perspective
- "In this presentation, human life history tradeoffs will be considered in relation to protein requirements, and the evolutionary implications of protein requirements will be considered in relation to the major nutritional transition that took place at the origins of agriculture."
- Tessa Pollard: Populations with very high rates of type 2 diabetes and cardiovascular disease: competing explanations
- "The finding that people who grow slowly in early life have a greater risk of type 2 diabetes and cardiovascular disease in later life if they are exposed to a western environment, offers a simpler explanation for what has happened in populations that have experienced rapid changes in lifestyle. In addition, these populations are usually exposed to other risk factors such as high rates of infection, racism and poverty. Examination of these different explanations shows how evolutionary theory can be applied in helpful and unhelpful ways by those trying to understand the causation of some of the most important health issues facing humans today."
- Lewis Wolpert: The evolutionary biology of depression
- "It has recently been proposed that depression and suicidality might be bargaining strategies... a hypothesis I test... As predicted by the bargaining hypothesis, in a large subgroup of cases there is clear recognition by all parties involved that suicidality is meant to apply pressure in intense social disputes. In many cases, the strategy works, yielding benefits for the suicidal individual."
- Ed Hagen: The bargaining model of suicidality
- "It has recently been proposed that depression and suicidality might be bargaining strategies... a hypothesis I test... As predicted by the bargaining hypothesis, in a large subgroup of cases there is clear recognition by all parties involved that suicidality is meant to apply pressure in intense social disputes. In many cases, the strategy works, yielding benefits for the suicidal individual."
- Mel Greaves: Volutionary origins of vulnerability to cancer
- "I will outline the argument that vulnerability to cancer, especially in ageing Homo sapiens, can be viewed as unfortunate consequences of several inherent features of evolution by natural selection… As an example of the application of evolutionary logic to the causality of a particular cancer, I will discuss our research on childhood leukaemia. Here a case is made for a mismatch between patterns of common infections during infancy in affluent societies and historical programming of the immune system."
- Virginia Vitzthum: Evolution and Endocrinology: the Regulation of Pregnancy Outcomes
- "Two central challenges in the study of biological and behavioral variation are distinguishing adaptive and non-adaptive responses, and elucidating the physiological pathways that mediate these responses. Evolutionary endocrinology has emerged as a cross-disciplinary field of research that addresses these and other questions regarding the neurophysiological architecture that drives the implementation of life history strategies (the choices made by an organism regarding the timing and magnitude of investment in somatic demands and reproductive efforts). "
- Laurence Shaw: Seasonality, food deprivation and PCOS [polycystic ovary syndrome]
- "If genetics are at the core of such a common condition [PCOS], the question of whether there is an evolutionary advantage to the possession of the gene or genes is inevitably raised. Three hypotheses are proposed. "
- Jon Laman: Evolution as a tool to teach immunology to doctors
- "I will aim to engage you in a discussion whether the following two premises hold, and can successfully withstand your critical review: (a) Evolutionary thinking provides a valuable, if not the best, teaching paradigm for instructing students and doctors on the immune system. (b) Recent scientific progress in evolution of immunity (e.g. signaling principles retained from plant to mouse to human) is so rapid and exciting, that it provides an excellent framework to train doctors and biomedical investigators in translational medicine, a central concept in current models of medical innovation."
Older evolutionary hypotheses
In the provocative debate article entitled "Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?", Eugene E. Harris and Avelin A. Malyango challenge teachers to provide answers that really address student's questions. They provide striking illustrations of the potential of evolutionary medicine :
- Since the 1950s, it is known that sickle cell disease, a disease of hemoglobin, the oxygen-carrying protein in red blood cells, originates from regions where malaria is prevalent and that heterozygotes (persons who have the normal and the abnormal hemoglobin) are more resistant to the malaria parasite Plasmodium falciparum than those who have only normal hemoglobin. Harris and Malyango point out that this explanation is "still not found in many medical and pre-professional health texts, leaving students needlessly wondering 'Why?'"
- Alpha and beta thalassemias, Hemoglobin E (Hb E) syndrome, and Glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), and a "myriad" of other diseases of the blood are appearing in Europe and North America, as a result of migrations. At least for the above mentioned hematological disorders, the link with malaria protection is backed by a fair amount of evidence.
- People of European descent also have their share of serious inherited diseases, such as Tay sachs, cystic fibrosis (CF), hemochromatosis, which might have been retained because they afforded resistance to such epidemics as tuberculosis and/or typhus (Tay sachs, CF) and the plague (hemochromatosis). Amongst these metabolic diseases, cystic fibrosis, the most common life-shortening, childhood onset inherited disorder in Caucasians has been most strongly correlated to recent epidemics (of typhus).
Considering the tragic nature of these conditions, answering "Why" they exist might be indicated.
Furthermore, Harris and Malyango point out that "many (other) evolutionary hypotheses initially advanced a decade or more ago ... have not received rigorous scientific testing." Some evolutionary hypotheses have raised intense interest due to their breadth and their radical implications:
- The inability to produce ascorbate (vitamin C), hypoascorbemia, is described by the Online Mendeleian Inheritance in Man database as human's public inborn error of metabolism, as it affects all members of the human race, in agreement with Irwin Stone's analysis. The broad popular movement in favour of optimal health initiated by Nobel laureate Linus Pauling in the 1970's was founded on Stone's work, but still today, the idea that the discordance between the higher primate's environment [e.g., a diet rich in ascorbic acid-containing foods, which allowed the loss of the ability to produce vitamin C] and the modern food supply, cause a broad range of diseases, has not been addressed centrally by nutritional science, despite strong voices from some quarters. Albert Szent Gyorgyi, who received the Nobel Prize for his discovery of the molecule, comments in familiar terms the situation:
The medical profession itself took a very narrow and wrong view. Lack of ascorbic acid caused scurvy, so if there was no scurvy there was no lack of ascorbic acid. Nothing could be clearer than this. The only trouble was that scurvy is not a first symptom of lack but a final collapse, a premortal syndrome, and there is a very wide gap between scurvy and full health. But nobody knows what full health is! This could be found out by wide statistical studies, but there is no organization which could and would arrange such studies.
- Creighton University Professor of Medicine, Robert P. Heaney, presents a related argument, referred to as "long-latency deficiency disease". The following excerpts from the Abstract of his paper encapsulate the concept:
Nutrient intake recommendations and national nutritional policies have focused primarily on prevention of short-latency deficiency diseases. Most nutrient intake recommendations today are based on prevention of the index disease only. [Scurvey, the index disease of dietary ascorbic acid deficiency, does not take long (years, decades) to develop.] However, inadequate intakes of many nutrients are now recognized as contributing to several of the major chronic diseases that affect the populations of the industrialized nations. Often taking many years to manifest themselves, these disease outcomes should be thought of as long-latency deficiency diseases. Sometimes they come about by the same pathophysiologic mechanism that produces the index disease, but sometimes the mechanisms are completely different.
- Heaney concludes:
Discerning the full role of nutrition in long-latency, multifactorial disorders is probably the principal challenge facing nutritional science today. The first component of this challenge is to recognize that inadequate intakes of specific nutrients may produce more than one disease, may produce diseases by more than one mechanism, and may require several years for the consequent morbidity to be sufficiently evident to be clinically recognizable as “disease.” Because the intakes required to prevent many of the long-latency disorders are higher than those required to prevent the respective index diseases, recommendations based solely on preventing the index diseases are no longer biologically defensible.
- Biological defensibility for nutrient recommendations in long-latency deficiency diseases can, in many cases, derive theoretical foundation from an evolutionary perspective, as Heaney points out for the case of vitamin D, and as others have pointed out for other nutrients.
- The fat utilization hypothesis for schizophrenia, psychopathic manipulation and creativity developped by the late David F. Horrobin, editor of the journal Medical Hypotheses, appealed to many of the public who try to make sense of the relationship between genius and madness. "The Madness of Adam and Eve: How Schizophrenia Shaped Humanity", one of the nominees for the Royal Society Prizes for Science Books (Aventis Prizes), posits that "touches of schizophrenia" were necessary for the development of human culture:
100,000 years ago we became human, and technical, religious, artistic, military and criminal abilities emerged. The first modern humans migrated from Africa to Eurasia and Australasia, carrying with them the genetic basis of schizophrenia, the only major illness found to the same extent in all racial groups. Modern evidence shows that families where schizophrenia is present are also exceptionaly creative in many different fields. Albert Einstein and James Joyce each had a schizophrenic child. David Horrobin draws on his knowledge of evolution, medicine and psychiatry to generate a startling hypothesis: we are human because some of us are schizophrenic and because a "touch of schizophrenia" is associated with that creativity which defines us and separates us from our nearest primate relatives.
These hypotheses illustrate how evolutionary medicine can formulate hypotheses of a breadth as great as the timeframe under study. Even more fundamental questions can be raised when considering how lower life forms evolve. Do these modern cosmogonic narratives give credence to the crude interpretation of the survival of the fittest paradigm, which evocate the tragic events of the early XXth century? Or, on the contrary, are evolutionary explanations giving clues to the function of cooperative behaviours? (also see altruism)
(in progress: from Lynn Margulis, in The New World Encyclopedia)
Margulis sees symbiogenesis—the development of new organisms, organelles, and so forth from the merging of two separate organisms—as a fundamental factor in creating genetic variation (more so than mutation) and as a primary force in evolution. In general, and in contrast to neo-Darwinism, Margulis holds that "Life did not take over the globe by combat, but by networking" (Margulis and Sagan 1986)—in other words, more by cooperation than via Darwinian competition.
Medicine needs evolution
"Medicine Needs Evolution" introduces another recent (February, 2006) editorial arguing for the need of a discipline of evolutionary medicine, published in the journal Science, by Randolph M. Nesse, professor of Psychiatry and Psychology at the University of Michigan, working in the field of evolution and medicine; Stephen C. Stearns, Edward P. Bass Professor of Ecology and Evolutionary Biology at Yale University, working in the field of evolutionary biology; and, Gilbert S. Omenn, president of AAAS and professor of Medicine and Genetics at the University of Michigan, working in cancer proteomics, computational biology, and science policy. Those researchers argue the value of evolutionary explanations for:
- the narrowness of the birth canal
- the persistence of genes involved in bipolar disease
- the persistence of genes involved in senescence
- the nature of the arms race among bacteria that account for bacterial resistance to natural plant and artifactual antibiotics
- vector-related increases in pathogen virulence
- the biological role of cough, fever, and diarrhea and when to counter them
- why the commonality of low-back problems
- why the body synthesizes bilirubin
- how the modern diet causes diseases by thwarting evolutionary dietary norms
- why the modern high incidence of breast cancer
Nesse, Stearns and Omenn end their editorial with the argument that "…both the human body and its pathogens are not perfectly designed machines but evolving biological systems shaped by selection under the constraints of tradeoffs that produce specific compromises and vulnerabilities. Powerful insights from evolutionary biology generate new questions whose answers will help improve human health."
Evolutionary medicine in action
Why has Nature not designed the human body and mind better, so that it can remain healthy throughout its life span? Professor Randolph Nesse, University of Michigan, tries to answer that question with examples. We discuss one of them here:
• Why obesity?
The evolutionary explanation for the high prevalence of obesity in modern times relates to the problems human ancestors had to solve during millions of years human evolution in an East African grasslands with scattered trees. Intermittent periods of food shortage encouraged evolution of body mechanisms that kept appetite high and body weight with some reserve whenever possible. The reason for that: when our ancestors ate heartily and gained some fat stores at times when they had plentiful supplies of food, they had a better chance of surviving and reproductively passing on their genes at later times when they had little food to eat. In modern times, where food shortages in many parts of the world do not present a problem, those mechanisms encouraging hearty appetite and building fat stores promote eating too heartily for too long, and consequent long-lasting and ever-increasing building of fat stores — as if the body anticipated an impending famine. Moreover, those mechanisms favored high appetite specifically for fat and sugar, energy-rich foods often in scarce supply in pre-agricultural times and therefore then unlikely to encourage obesity. The agricultural, industrial and fast-food revolutions have eliminated the short supply of those foods in much of the world, and the revolutionaries have exploited the human appetite preferences, with consumer encouragement, by separating fats and oils and refining foods to readily absorbable sugars and readily digestible chains of sugar molecules (e.g., white flour made from wheat).
Voluntarily trying to limit food intake for weight reduction leads to the body's reacting against such foolhardiness from the body's perspective gained by millions of years of experience, thereby stimulating those evolved appetite-activating mechanisms, acting against the willpower resolve. No wonder dieters feel hungry and typically regain their weight losses after a period of dieting.
Though our human ancestors undoubtedly led a life of high physical activity, hunting, gathering, and often relocating to greener pastures, their body mechanisms nevertheless evolved to encourage minimizing, as much as practical, wasteful expenditures of the energy required for physical activity — an evolved tendency to inactivity that can operate unopposed when food supplies do not present a problem and when modern transportation minimizes the need for human-powered locomotion. Too often Americans, for example, have too big a load of food to carry home from the grocery store not to drive their cars the few blocks between home and store. With an evolved mechanism to encourage minimizing physical activity, in combination with the evolved mechanisms for high appetite and food preferences for sweet and fat, obesity comes easily in modern times.
Anthropologist Melvin Konner adds a sociocultural component to the evolutionary perspective on obesity. He points out that historically plump women represented the ideal of female beauty, that the plump young women models of Renaissance painters had just enough reserve of stored energy to pay the costs of gestating and breastfeeding a baby — contributing to her and the father's reproductive fitness. Professor Konner adds: "Little wonder, then, that evolution caused men to find it [female plumpness] attractive."
♦ ’Overweight' vs. 'Obesity'
Commonly, nutritionists and healthcare workers classify body fat into categories (underweight, normal weight, overweight, obesity, morbid obesity) by how much a person weighs (in kilograms, kg) relative to his/her height (in meters, m) multiplied by itself (meters squared, m2) — the so-call body mass index, or BMI, (kg/m2) = weight in kilograms ÷ height in meters2.
Intriguingly, some medical studies suggest that carrying a small amount of excess weight — viz., a body fat status termed ‘overweight’ (BMI 18.5 to < [less than] 25) as opposed to ‘obesity’ (BMI > [greater than] 30 — may not associate with increased mortality, considering “all causes” of mortality. Flegal and colleagues, analyzing national survey data over some thirty years found that:
"Relative to the normal weight category (BMI 18.5 to <25), obesity (BMI >30) was associated with 111,909 excess deaths (95% confidence interval [CI], 53,754-170,064) and underweight [BMI <18.5] with 33,746 excess deaths (95% CI, 15 726-51 766). Overweight was not associated with excess mortality (-86,094 deaths; 95% CI, -161, 223 to -10 966)."  [Emphasis added] [The 95% CI values in a BMI category give the range of excess deaths — i.e., relative to the normal weight category — for 95% of the individuals in that category]
Flegal and colleagues cite other studies consistent with their findings in ‘overweight’ individuals and other not consistent. In a subsequent study, looking at specific causes of death, as opposed to all-cause mortality, Flegal and colleagues found that overweight individuals had fewer deaths from diseases other than cancer and cardiovascular disease than normal weight individuals, and failed to find a strong association of overweight with cancer or cardiovascular disease.  Regarding overweight, they state:
"Some evidence suggests that modestly higher weights may improve survival in a number of circumstances [citations given], which may partly explain our findings regarding overweight. Overweight is not strongly associated with increased cancer or CVD risk, but may be associated with improved survival during recovery from adverse conditions, such as infections or medical procedures, and with improved prognosis for some diseases. Such findings may be due to greater nutritional reserves or higher lean body mass associated with overweight." 
Considering that our hunter-gatherer ancestors had to recover from infections and trauma acquired during their reproductive years, the possibility that the extra reserves accompanying the overweight state improves recovery and survival would make sense from an evolutionary perspective.
BMI does not give a perfect index of body fat status, inasmuch as lean body mass (e.g., muscle) contributes to body weight, so that some ‘overweight’ individuals may qualify so in part because of greater lean body mass. Likewise, in elderly persons, with reduced muscle mass, BMI may underestimate body fat stores. Flegal et al.'s conclusion need interpretation in the light of BMI's less than perfect specificity for body fat mass.
Physician scientists and their interdisciplinary colleagues will need to carry out further studies to definitively answer the question whether moderately increased body fat stores have beneficial health effects, and if they do, under what circumstances. An evolutionary perspective might guide the direction of such studies. For example, an evolutionary biologist might ask: Does the overweight condition have more beneficial effects if present continuously or if occurring intermittently, and if the latter, what patterns yield the best effects?
The evolutionary perspective on obesity's ultimate causal factors presented here would predict a high degree of heritability for obesity and for the tendency to obesity. Epidemiologic studies indeed tend to confirm that prediction. Reviewing the scientific literature, Yang and colleagues in the departments of Epidemiology and Medicine at Tulane University report:
"Twin, adoption, and family studies have established that obesity is highly heritable, and an individual’s risk of obesity is increased when one has relatives who are obese [citations given]. Heritability estimates ranged from 16 percent to 85 percent for body mass index [citations given], from 37 percent to 81 percent for waist circumference [citations given], from 6 percent to 30 percent for WHR [citations given], and from 35 percent to 63 percent for percentage body fat [citations given]. The Framingham Heart Study reported a moderate heritability estimate for body mass index (40–50 percent) [citations given]. In contrast, the National Heart, Lung, and Blood Institute family heart study and twin studies observed higher estimates of heritability for body mass index (40–80 percent), and they also reported a heritability of 70–80 percent for weight gain [citations given]." 
♦ Healthcare costs
Should we factor in healthcare costs in considering national/global policies for prevention of obesity? A simulation study from the Netherlands suggests that in the long run, obesity reduces healthcare costs, because increased healthcare costs due to non-obesity-related disease associated with greater longevity in the non-obese offset the healthcare costs of obesity-related disease associated with lesser longevity in the obese.
♦ Prevalence of Overweight and Obesity
From the Abstract of their 2006 study in the Journal of the American Medical Association (JAMA), Cynthia L. Ogden and her colleagues at the National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, Md, and the Epidemic Intelligence Service, Centers for Disease Control and Prevention, Atlanta, Ga, reported that:
- In 2003-2004, 17.1% of US children and adolescents were overweight and 32.2% of adults were obese.
- Tests for trend were significant for male and female children and adolescents, indicating an increase in the prevalence of overweight in female children and adolescents from 13.8% in 1999-2000 to 16.0% in 2003-2004 and an increase in the prevalence of overweight in male children and adolescents from 14.0% to 18.2%.
- Among men, the prevalence of obesity increased significantly between 1999-2000 (27.5%) and 2003-2004 (31.1%).
- Among women, no significant increase in obesity was observed between 1999-2000 (33.4%) and 2003-2004 (33.2%).
- The prevalence of extreme obesity (body mass index ≥40) in 2003-2004 was 2.8% in men and 6.9% in women.
- In 2003-2004, significant differences in obesity prevalence remained by race/ethnicity and by age.
- Approximately 30% of non-Hispanic white adults were obese as were 45.0% of non-Hispanic black adults and 36.8% of Mexican Americans.
- Among adults aged 20 to 39 years, 28.5% were obese while 36.8% of adults aged 40 to 59 years and 31.0% of those aged 60 years or older were obese in 2003-2004.
Thus obesity prevalence in the US increased significantly between 1999 and 2004, in men; in children and adolescents overweight prevalence increased. In 2003-2004, obese adults made up 32.2% of the adult population, and overweight children and adolescents made up 17.1% of their age group. If the upward trend continues, the maturation of children and adolescents may increase the prevalence of obesity. In 2003-204, nearly 7% of women qualify as extremely obese (body mass index [BMI] of 40 or more, whereas overweight becomes obesity at BMI of 35), and nearly 3% of men qualified.
♦ An "integrative" view of obesity
In their 2007 report in Science, Brent E. Wisse, Francis Kim, and Michael W. Schwartz, of the Department of Medicine, Harborview Medical Center and University of Washington, Seattle, present what they entitle "An Integrative View of Obesity", in which they begin:
Obesity is a serious concern because it increases the risk of cardiovascular disease, type 2 diabetes, and some cancers, among other health problems. The evolution of public health policies and treatment options depends upon an improved understanding of how genetic and environmental factors interact to favor weight gain, and how excessive weight disrupts metabolism. But getting at the causes of obesity and related metabolic disorders is a formidable challenge, in part because so many body systems are affected. Because disturbances in one organ or tissue can compromise the function of several others, separating cause and effect is often difficult. Yet common themes are emerging that may offer a new viewpoint. Among these is the notion that metabolic dysfunction arises from exposure of the body's cells to an excess of nutrients (citation).
They continue with a state-of-the-art summary of the ways the adverse metabolic consequences "from exposure of the body's cells to an excess of nutrients" arise, but they do not provide a truly "integrative" view of obesity as they do not mention the evolutionary history of Nature's reasons for generating and selecting the metabolic networks that happen to lead to those adverse consequences.
Evolutionary medicine suggests we get fat because of built-in encouragements to eat heartily when we have plenty to eat and to restrict energy expenditures in preparation for inevitable food shortages. It may also suggest we consider the effect of the types of food we eat compared to those evolution adapted us to eat. We’ve only recently, on an evolutionary timescale, begun to eat readily absorbable carbohydrates in disproportionate amounts. Our hunter-gatherer ancestors had little access to such food items, with the exception of a bit of honey. Now we have so-called refined carbohydrates readily available and much consumed. Those include granulated sugar and sucrose dissolved in soft drinks; syrups and candies; milled cereal grain flours and their host pastries, pastas and breads; and many other processed ‘high glycemic’ foods. Those foods stimulate the secretion of insulin as control for glucose homeostasis, and induce other hormonal changes that influence appetite and efficiency of energy utilization. Science writer Gary Taubes summarizes the argument:
“There is considerable evidence that the obesity epidemic is caused by a hormonal phenomenon, specifically by the consumption of refined carbohydrates, starches and sugars, all of which prompt (sooner or later) excessive insulin secretion. Insulin is the primary regulator of fat storage. When insulin levels are elevated, fat accumulates in our body tissue; when they fall, fat is released and we use it for fuel. By stimulating insulin secretion, carbohydrates make us fat; by driving us to accumulate fat, they increase hunger and decrease the energy we expend in metabolism and physical activity. In short, obesity is caused not by overeating or sedentary behaviour, but by hormonal malfunctioning triggered by the consumption of particular types of carbohydrate-containing foods.”
Themes in evolutionary medicine
In Professor Nesse's article cited earlier, Professor Nesse summarizes some of the major themes in evolutionary medicine. He points out that an evolutionary view of medicine recognizes natural selection as a major factor designing the characteristics of the human body, wondrous but also flawed, from the human perspective, for plausible evolutionary reasons. He sees evolutionary medicine as seeking to know why evolution has not better designed the body, in particular to avoid illnesses. Obesity and its complications, for example, as discussed above, arises because evolution did not design our bodies to live in the modern food-available environment. As other examples, he argues that natural selection adjusts pathogen virulence to levels optimal for the pathogen, whether that requires killing the host or not. And he notes that symptoms such as fever, cough, and anxiety cause pain but have useful defensive value explained in an evolutionary perspective.
One example of the major themes in evolutionary medicine
Many leading themes in evolutionary considerations relates to the history of human evolution, which we can exemplify in the context of human nutrition.
The human lineage extends back as many as 5-7 million years of hominin evolution before scientists can recognize an ancestor that humans have in common with their closest relative, the chimpanzee. The environmental conditions the human lineage survived in during that entire period of evolution undoubtedly contributed importantly to the modern human genetic composition, with eating preferences and patterns counting as major genetic selection determinants of the environment. Paraphrasing the Oxford historian, Felipe Fernandez-Armesto, a species’ most intimate contact with its natural environment occurs when the species eats it. 
The nutritional requirements for human survival and reproductive fitness therefore presumably established themselves, at least in part, through the natural selection of genes over millions of years. Homo species first appeared at the beginning of the Stone Age approximately 2 million years ago—the Stone Age [a.k.a., the Paleolithic epoch] extended from ~2 million years ago to the beginnings of agriculture ~10 thousand years ago. During that period ancestral Homo species (Homo habilis, Homo erectus, Homo ergaster, inter alia) adapted to a profile of diets markedly different from that of the diets of contemporary humans.   
When our present Homo species took up agriculture and animal husbandry about 10,000 years ago, Homo sapiens began to forsake their lifestyle as hunter-gatherers—wherein they ate only wild animal and plant foods—and began settling down as farmers and animal husbanders, and, significantly, began introducing foods that they or their hominin ancestors had had no or negligible exposure to: cereal grains, legumes, animal milk and milk-products, and fatty meats. 
Evolutionary biologists have argued that the 10,000-year (300 generation) interval between the beginnings of agriculture and the present time offered natural selection too little time to produce the comprehensive restructuring of our physiology and metabolism for optimal functioning in the face of such a major shift in dietary patterns. "Natural selection can never redesign a mechanism. It can only bring about slight quantitative shifts in its parameters"  An even shorter period has natural selection had to adapt modern humans to dietary novelties since the more recent industrial and fast-food revolutions that further drastically changed the human dietary environment.
With respect to integrated metabolic and physiologic functioning, Homo sapiens’ genome, it is argued, therefore has remained at core unchanged since agriculture and animal husbandry began. Accordingly, students of evolutionary medicine look to the hominin ancestral diets, especially during the Paleolithic, and compare them with modern diets, to try to discover similarities that presumably would favor optimal functionality, or to discover important differences that might render aspects of human metabolism and physiology maladapted. Accumulating evidence suggests that the large-scale mismatch between the modern diet and the nutritional requirements set by the Paleolithic genome contributes importantly in the pathogenesis of obesity, hypertension, diabetes, certain forms of cancer, atherosclerotic cardiovascular disease, kidney stones, age-related muscle wasting, and osteoporosis.  
An evolutionary perspective on several modern diseases
• Anxiety disorders
Holding reference: 
Citations and notes
- Dobzhanskt T. (1973) Nothing in biology makes sense except in the light of evolution. Am Biol Teach, pages=125-9.
- Note article title page misspells Professor Dobzhansky's surname: missing the terminal 'y'.
- Jablonka E, Lamb MJ (2005) Evolution in Four Dimension: Genetic, Epigenetic, Behavioral, and Symbolic Variation in the History of Life. Cambridge: MIT Press. ISBN 978-0-262-10107-3 MIT Press summary Table of Contents and Downloadable Sample Chapters
- MacCallum CJ. (2007) Does Medicine without Evolution Make Sense? PLoS Biol 5(4): e112
- PLoS Biology Editorial Staff Biosketches
- Note: Read summary report of the Society for the Study of Human Biology and the Biosocial Society’s 2006 symposium, “Medicine and Evolution”
- Hagen, Edward H (2003) The Bargaining Model of Depression. (Book Chapter)
- Harris EE, Malyango AA (2005). "Evolutionary explanations in medical and health profession courses: are you answering your students' "why" questions?". BMC Med Educ 5: 16. PMID 15885137.
- OMIM - HYPOASCORBEMIA. Retrieved on 2007-11-13.
- Stone I (1967). "The genetic disease, Hypoascorbemia. A fresh approach to an ancient disease and some of its medical implications". Acta Genet Med Gemellol (Roma) 16: 52–62. PMID 6063937.
- Eaton,S.B.; Konner,M.; Shostak,M. (1988). Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective. Am J Med 84:739-749. PMID 3135745 Cite error: Invalid
<ref>tag; name "eaton88" defined multiple times with different content
- Heaney RP. (2003) [http://www.ajcn.org/cgi/content/abstract/78/5/912 Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 78:912-919. PMID 14594776.
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- Note:To obtain BMI in kg/m2 from weight in pounds (e.g., 150 lbs) and height in inches (e.g., 65 inches [5 feet 5 inches), calculate 150÷ 652, then multiply by a conversion factor, 703, yielding 24.96 kg/m2
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- Abstract: Anxiety-related disorders are among the more common ailments of modern societies. Presumably, their prevalence is partly due to environmental factors, which suggests that anxiety may be one of the health problems that are aggravated by discords (adverse mismatches) between the present way of life and what our genes are adapted to. Consequently, it may be possible to find preventive measures by using the perspective of evolutionary medicine. I shall argue that the prevalence of anxiety-related problems reflects that the nerve circuitry and endocrine activity associated with the fear function have developed beyond normal. Moreover, that this expansion is due to excessive or abnormal triggering, particularly at an early age. Possible discords that may be responsible, such as present child care practices, will be discussed.