Evolutionary medicine/Bibliography

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Works of Randolph M. Neese, M.D., University of Michigan

Journal articles

• Nesse RM, Ganten D, Gregory TR, Omenn GS. (2012) Evolutionary molecular medicine. J Mol Med | Published online: 29 April 2012.
  • "This article reviews 15 evolutionary principles and their applications in molecular medicine in hopes that readers will use them and related principles to speed the development of evolutionary molecular medicine."

• Nesse RM (1984) An evolutionary perspective on psychiatry. Compr.Psychiatry 25:575-580.

• Nesse RM. (1988) Life table tests of evolutionary theories of senescence. Exp.Gerontol. 23:445-453.
  • "The phenomenon of senescence requires both evolutionary and proximate explanations. The most widely accepted evolutionary explanation for senescence is that it never gets exposed to natural selection because environmental hazards kill all individuals before the age at which senescence causes decreased fitness. If this explanation is sufficient, wild populations should not demonstrate senescence, and their mortality rates should therefore remain constant during adult life, except when environmental causes of mortality have recently decreased. The alternative explanation for the persistence of the genes that cause senescence is that they have been selected for because they have pleiotropic effects that are beneficial early in life when the force of selection is strongest. Where this is the case, mortality rates should increase with age in wild populations. A method is described for using life table data to calculate an estimate of the intensity of selection acting on senescence in wild populations. This method is applied to a variety of life tables. The results suggest that pleiotropic genes may be important causes of senescence in some populations, but not in others. This has implications for research on the proximate mechanisms of senescence."

• Nesse RM. (1990) The evolutionary functions of repression and the ego defenses. J.Am.Acad.Psychoanal. 18:260-285.

• Wlliams GC & Nesse RM (1991) The dawn of Darwinian medicine. Q.Rev.Biol. 66:1-22. PMID 2052670.

• Abstract: While evolution by natural selection has long been a foundation for biomedical science, it has recently gained new power to explain many aspects of disease. This progress results largely from the disciplined application of what has been called the adaptations program. We show that this increasingly significant research paradigm can predict otherwise unsuspected facets of human biology, and that it provides new insights into the causes of medical disorders, such as those discussed below:

• 1. Infection. Signs and symptoms of the host-parasite contest can be categorized according to whether they represent adaptations or costs for host or parasite. Some host adaptations may have contributed to fitness in the Stone Age but are obsolete today. Others, such as fever and iron sequestration, have been incorrectly considered harmful. Pathogens, with their large populations and many generations in a single host, can evolve very rapidly. Acquisition of resistance to antibiotics is one example. Another is the recently demonstrated tendency to change virulence levels in predictable ways in response to changed conditions imposed incidentally by human activities.
• 2. Injuries and toxins. Mechanical injuries or stressful wear and tear are conceptually simpler than infectious diseases because they are not contests between conflicting interests. Plant-herbivore contests may often underlie chemical injury from the defensive secondary compounds of plant tissues. Nausea in pregnancy, and allergy, may be adaptations against such toxins.
• 3. Genetic factors. Common genetic diseases often result from genes maintained by other beneficial effects in historically normal environments. The diseases of aging are especially likely to be associated with early benefits.
• 4. Abnormal environments. Human biology is designed for Stone Age conditions. Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets, the effects of excess consumption of normally scarce nutrients such as fat and salt, developmental diseases such as myopia, and psychological reactions to novel environments.

• The substantial benefits of evolutionary studies of disease will be realized only if they become central to medical curricula, an advance that may at first require the establishment of one or more research centers dedicated to the further development of Darwinian medicine.

• McGuire MT, Marks I, Nesse RM, & Troisi A. (1992) Evolutionary biology: a basic science for psychiatry? Acta Psychiatr.Scand. 86:89-96.

• Abstract: Evolutionary biology has much to offer psychiatry. It distinguishes between ultimate and proximate explanations of behavior and addresses the functional significance of behavior. Subtheories, frequently voiced misconceptions, specific applications, testable hypotheses and limitations of evolutionary theory are reviewed. An evolutionary perspective is likely to improve understanding of psychopathology, refocus some clinical research, influence treatment and help integrate seemingly unrelated findings and theoretical explanations

• Nesse RM & Berridge KC (1997) Psychoactive drug use in evolutionary perspective. Science 278:63-66. PMID 9311928.

• ’Abstract: Pure psychoactive drugs and direct routes of administration are evolutionarily novel features of our environment. They are inherently pathogenic because they bypass adaptive information processing systems and act directly on ancient brain mechanisms that control emotion and behavior. Drugs that induce positive emotions give a false signal of a fitness benefit. This signal hijacks incentive mechanisms of "liking" and "wanting," and can result in continued use of drugs that no longer bring pleasure. Drugs that block negative emotions can impair useful defenses, although there are several reasons why their use is often safe nonetheless. A deeper understanding of the evolutionary origins and functions of the emotions and their neural mechanisms is needed as a basis for decisions about the use of psychoactive drugs.

• Conclusion: Emotional capacities evolved to improve the Darwinian fitness of individuals as they seek resources and avoid dangers. The pursuit of emotion-associated goals tends to move organisms up a hedonic and adaptive gradient, but neurobehavioral systems are designed to maximize Darwinian fitness, not happiness, so our pleasures are often fleeting, and we experience much unnecessary suffering. The neurochemical mechanisms that mediate these states confer intrinsic vulnerability to substance abuse in environments where drugs are available. A better understanding of the mechanisms, origins, and functions of the emotions will enhance our ability to cope with substance abuse and our wisdom in making decisions about the therapeutic use of psychoactive drugs.

• Nesse R (1998) Emotional disorders in evolutionary perspective. Br.J.Med.Psychol. 71:397-415.

• Abstract: Understanding emotional disorders requires understanding the evolutionary origins and functions of normal emotions. They are special states, shaped by natural selection to adjust various aspects of the organism in ways that have tended to give a selective advantage in the face of the adaptive challenges characteristic of a particular kind of situation. They are designed to maximize reproductive success, not happiness. Negative emotions such as anxiety and low mood are not disorders, but, like the capacity for pain, evolved defences. Excessive anxiety or low mood is abnormal, but we will not have confidence about what is excessive until we understand their functions better than we do. Emotional disorders arise often from social emotions because of the conflicts inherent in social life, and because of the strategic advantages of demonstrating commitments to follow through on threats and promises. An evolutionary understanding of individuals in terms of their relationship strategies and the social emotions offers great promise for psychotherapists.

• Nesse R. (1998) Darwinism and psychiatry. Harv.Ment.Health Lett. 14:5-7. PMID 15344231.

• Nesse RM & Williams GC .(1998) Evolution and the origins of disease. Sci.Am. 279:86-93.

• Nesse RM (1999) Proximate and evolutionary studies of anxiety, stress and depression: synergy at the interface..Neurosci.Biobehav.Rev. 23, p 895-903. PMID 10580304.

• Abstract: While enormous progress has been made in unraveling the proximate physiological mechanisms that account for anxiety, stress, and low mood, these states continue to give rise to considerable conceptual confusion. This is, in part, because proximate studies have neither been adequately distinguished from, nor integrated with, evolutionary explanations for the adaptive functions of anxiety, stress, and mood. A complete biological explanation that incorporates both proximate and evolutionary explanations will be of great value to better define the border between normal and pathological, to help to explain why pathological anxiety and depression are so common, and to provide a much-needed basis for sensible decisions about when different pharmacological manipulations are likely to be helpful or harmful. Ideally, evolutionary considerations should provide a conceptual framework within which the biological significance of the proximate mechanisms can be better understood, and the proximate findings should provide tests of evolutionary hypotheses. Studies at the interface between evolutionary and proximate explanations will be difficult, but important to better understand individual differences in vulnerability and the etiology of diseases that result from dysregulation of anxiety and mood.

• Concluding Paragraph: The focus of this article has been the adaptive significance f anxiety, low mood and stress, so to prevent misunderstanding, it is important to clearly state that much anxiety and depression results from diseases such as major depression and panic disorder. Furthermore, much physical, and probably mental, illness results from the complications of the stress response. The search for the etiology of these disorders is a high priority. The argument here does not undermine the hard-won recognition that these disorders really are diseases. It does, however, suggest that, like chronic pain and febrile seizures, they probably often involve dysregulation of a normal defense. If that is correct, it implies the need to use special research strategies that begin by elucidating the normal mechanisms that mediate the defense, and then proceed to study the mechanisms that regulate the defense, and finally try to understand the etiological factors that disrupt the normal regulation mechanisms. Understanding the proximate mechanisms that normally regulate these defenses, from molecules to neurons to the transduction of social cues, will provide a solid foundation for understanding why and how they become dysregulated. Evolutionary approaches that focus attention on their normal functions, how they were shaped by natural selection, and how they are regulated, will be essential in this enterprise.

• Nesse RM. (2000) Natural selection, mental modules and intelligence. Novartis.Found.Symp. 233:96-104. PMID 112769132.

• Abstract: The question of whether intelligence is one trait or many has exercised several generations of researchers, but no consensus is in sight. Evolutionary psychology, with its emphasis on domain-specific mental modules, seems to offer hope for advancing understanding of this question. We know that the mind has been shaped by natural selection to maximize reproductive success. This tells us what the mind must do--it must solve the adaptive problems that the organism confronts. However, whether this functional capacity is manifest in congruent anatomic, physiological, genetic, cognitive or psychometric structures is another matter. Examination of how natural selection shaped other mechanisms suggests that knowing functional demands provides only modest guidance as to the structure of mechanisms. None the less, it remains simultaneously clear that these mechanisms are not entirely general, but have been shaped to cope with specific challenges. Our metaphors for the mind, whether as a digital computer or a Swiss army knife, are misleading because computers and tools are products of intelligent design. In contrast, minds are products of natural selection whose intertwined components are products of incorporated genetic mutations whose effects are widespread and constrained by historical precedents. Our tendencies to describe the structure of the mind in terms of discrete components make it difficult for us to comprehend the mind as a mind. One antidote may be to minimize metaphorical descriptions of postulated structures of mind and focus instead on its function.

• Nesse RM. (2000) Is depression an adaptation?.Arch.Gen.Psychiatry 57:14-20. PMID 10632228.

• Abstract: Many functions have been suggested for low mood or depression, including communicating a need for help, signaling yielding in a hierarchy conflict, fostering disengagement from commitments to unreachable goals, and regulating patterns of investment. A more comprehensive evolutionary explanation may emerge from attempts to identify how the characteristics of low mood increase an organism's ability to cope with the adaptive challenges characteristic of unpropitious situations in which effort to pursue a major goal will likely result in danger, loss, bodily damage, or wasted effort. In such situations, pessimism and lack of motivation may give a fitness advantage by inhibiting certain actions, especially futile or dangerous challenges to dominant figures, actions in the absence of a crucial resource or a viable plan, efforts that would damage the body, and actions that would disrupt a currently unsatisfactory major life enterprise when it might recover or the alternative is likely to be even worse. These hypotheses are consistent with considerable evidence and suggest specific tests.

• Conclusion: Is depression an adaptation? At present, we do not have the evidence needed to say for sure. However, it seems likely that low mood and related negative affects were shaped to help organisms cope with unpropitious situations. Some negative and passive aspects of depression may be useful because they inhibit dangerous or wasteful actions in situations characterized by committed pursuit of an unreachable goal, temptations to challenge authority, insufficient internal reserves to allow action without damage, or lack of a viable life strategy. However, it is essential to emphasize that many depressions are clearly disease states: some caused by dysregulations of negative affect and others by brain defects unrelated to low mood. The fact that low mood, and perhaps some depression, may be useful should not distract attention from recognition that depression is one of humanity's most serious medial problems.108 A deeper understanding of the adaptive significance of low mood and depression will improve our ability to prevent and relieve both mood disorders and low moods that are normal, but unnecessary.

• Nesse RM (2001) On the difficulty of defining disease: a Darwinian perspective..Med.Health Care Philos. 4, p 37-46. PMID 11315418.

• Abstract: Most attempts to craft a definition of disease seem to have tackled two tasks simultaneously: 1) trying to create a series of inclusion and exclusion criteria that correspond to medical usage of the word disease and 2) using this definition to understand the essence of what disease is. The first task has been somewhat accomplished, but cannot reach closure because the concept of "disease" is based on a prototype, not a logical category. The second task cannot be accomplished by deduction, but only by understanding how the body works and what each component is for, in evolutionary detail. An evolutionary view of the origins of the body and its vulnerabilities that result in disease provides an objective foundation for recognizing pathology. Our social definition of disease will remain contentious, however, because values vary, and because the label "disease" changes judgments about the moral status of people with various conditions, and their rights to medical and social resources.
• Concluding Paragraph: So, what is disease? It seems to me that philosophers have answered the question relatively well, given the constraints of trying to provide a definition in words. Yes, there is disagreement, but for the reasons mentioned, no single definition will serve all the functions demanded of it. An individual has a disease when a bodily mechanism is defective, damaged, or incapable of performing its function. The continuing debates about the definition of disease arise partly from the hope that a logical definition can be found that conforms to common usage based on prototypes, partly from attempts to seek the essence of disease without reference to all the complexity of the mechanisms of the body and their origins and functions, and partly from the political and moral implications of labeling a condition a disease. We will undoubtedly see if further pursuit of these debates will, or will not, deepen our understanding of what is disease, and what disease is.

• Nesse RM (2001) How is Darwinian medicine useful? West J.Med. 174:358-360. PMID 11342524.

• Conclusion: Everyone uses metaphors to understand the world. The dominant metaphor for the body has been a machine. Disease has been viewed as a defect arising in an otherwise perfect device. An evolutionary view offers a richer and more nuanced view of the body as a product of natural selection: extraordinary in many ways, but also flawed in many ways, for good evolutionary reasons. Furthermore, it reveals that the body has no master plan and there is no such thing as "the" human genome. Humans have genes that make phenotypes that effectively make new copies of themselves. We care less about the fate of our genes, however, and more about the health and welfare of individuals....Darwinian medicine will most powerfully advance our goal of helping individuals by inspiring research that yields solid new findings to guide health care practice. Even at this early stage, however, Darwinian medicine can help clinicians answer old questions, pose new questions, and provide a more natural view of disease.

• Nesse RM (2001) Motivation and melancholy: a darwinian perspective.</u.> Nebr.Symp.Motiv. 47:179-203. PMID: 11759348.

• Eaton SB, Strassman BI, Nesse RM et al. (2002) Evolutionary health promotion. Prev.Med. 34:109-5118. PMID 11817903.

• Abstract: Health promotion's promise is enormous, but its potential is, as yet, unmatched by accomplishment. Life expectancy increases track more closely with economic prosperity and sanitary engineering than with strictly medical advances. Notable achievements in the past century--the decreased incidences of epidemic infections, dental caries, and stomach cancer--are owed to virologists, dentists, and (probably) refrigeration more than to physicians. Prevention speaks against tobacco abuse with a single voice, but in many other areas contradictory research findings have generated skepticism and even indifference among the general public for whom recommendations are targeted. Health promotion's shortcomings may reflect lack of an overall conceptual framework, a deficiency that might be corrected by adopting evolutionary premises:

• (1) The human genome was selected in past environments far different from those of the present.
• (2) Cultural evolution now proceeds too rapidly for genetic accommodation--resulting in dissociation between our genes and our lives.
• (3) This mismatch between biology and lifestyle fosters development of degenerative diseases.

• These principles could inform a research agenda and, ultimately, public policy:

• (1) Better characterize differences between ancient and modern life patterns.
• (2) Identify which of these affect the development of disease.
• (3) Integrate epidemiological, mechanistic, and genetic data with evolutionary principles to create an overarching formulation upon which to base persuasive, consistent, and effective recommendations

• Nesse RM (2002) Evolutionary biology: a basic science for psychiatry. World Psychiatry 1:7-9. PMID 16946805.

• Concluding Paragraph: There is a strong human tendency to seek unitary explanations for diseases, and to think of multiple explanations as competing. This mistake has left most investigations of mental disorders seeking only one half of a full biological explanation. The remedy is to carefully pursue both evolutionary and proximate explanations for each disease. Our bodies are amazingly well designed in many respects, but they also have flaws that leave us vulnerable, flaws that make sense in an evolutionary perspective. There is every reason to think that the synergy between evolutionary and proximate approaches will soon bring major advances in our understanding of mental disorders (12).

• Nesse RM. (2004) Natural selection and the elusiveness of happiness.. Philos.Trans.R.Soc.Lond B Biol.Sci. 359:1333-1347. PMID 15347525.

• Abstract: The quest for happiness has expanded from a focus on relieving suffering to also considering how to promote happiness. However, both approaches have yet to be conducted in an evolutionary framework based on the situations that shaped the capacities for happiness and sadness. Because of this, the emphasis has almost all been on the disadvantages of negative states and the benefits of positive states, to the nearly total neglect of 'diagonal psychology', which also considers the dangers of unwarranted positive states and the benefits of negative emotions in certain situations. The situations that arise in goal pursuit contain adaptive challenges that have shaped domain-general positive and negative emotions that were partially differentiated by natural selection to cope with the more specific situations that arise in the pursuit of different kinds of goals. In cultures where large social groups give rise to specialized and competitive social roles, depression may be common because regulation systems are pushed far beyond the bounds for which they were designed. Research on the evolutionary origins of the capacities for positive and negative emotions is urgently needed to provide a foundation for sensible decisions about the use of new mood-manipulating technologies.

• Keller MC & Nesse RM. (2005) Is low mood an adaptation? Evidence for subtypes with symptoms that match precipitants.. J.Affect.Disord. 86:27-35. PMID 15820268.

• BACKGROUND: Although severe depression is dysfunctional, the capacity to experience normal low mood may be useful in certain fitness-threatening situations. Moreover, if specific kinds of situations recurred often enough in the course of evolution, natural selection may have shaped partially differentiated subtypes of low mood that are parallel to the subtypes of anxiety that protect against different kinds of danger. To test this hypothesis, we examined how symptoms of low mood differ depending upon the precipitating situation, and whether these differences match expectations of symptoms useful in each kind of situation.
• METHOD: 337 subjects who experienced a period of low mood within the last year wrote accounts describing perceived causes of their low mood and they filled out the CES-D depression inventory. Seven symptom scales were derived from analysis of CES-D data. Independent judges blindly coded the accounts into one of six precipitant categories.
• RESULTS: Different untoward situations were associated with different symptoms that were predicted to be useful in those situations. Social losses (death of a loved one, romantic breakups, and social isolation) were associated with greater crying and arousal. Failure to reach a goal, stress, and winter seasons were associated with more fatigue and pessimism.
• DISCUSSION: These results suggest that natural selection shaped not only a generic state of low mood but also partially differentiated subtypes shaped to cope with specific situations that were associated with fitness losses among our ancestors.

• Penultimate Paragraph: The hypothesis that low mood is an adaptation raises the question of why depression (extreme low mood) is so prevalent. When depression is caused by an extreme situation, the situation is so abnormal that it is difficult to tell if the reaction is adaptive, albeit extreme, or merely maladaptive. Additionally, as with many defenses, low mood may be activated more often or more intensely than seems necessary because false alarms are often less costly than failing to respond when a response was warranted (Nesse, 2001). Furthermore, low mood evolved to deal with contexts much different than modern ones, which may explain why much normal low mood may nevertheless be maladaptive now (Glantz and Pearce, 1989). Finally, mood regulation mechanisms can be disrupted by many factors including toxins, injuries, extreme experiences, and especially genes. A robust finding from evolutionary genetics is that traits influenced by many genes tend to show high levels of maladaptive genetic variance (Houle, 1998; Charlesworth and Hughes, 1999). If mood reactions are influenced by many genes, recurrent mutation could lead to dysfunction of mood regulation mechanisms (Keller and Miller, 2004).

• Nesse RM. (2005) Maladaptation and natural selection. Q.Rev.Biol. 80:62-70. PMID 15884737.

• Abstract: The transformations George Williams initiated in evolutionary biology seem so blindingly obvious in retrospect that they spur the question of why he saw what no one else did. While most humans are prone to see only what theory predicts, Williams sees in bold relief whatever does not fit. Not an adaptationist or an anti-adaptationist, Williams is better described as a maladaptionist. The challenge of finding evolutionary explanations for apparent maladaptations has been overlooked with casualness akin to that once typical for group selection. Suboptimal traits tend to be dismissed as illustrations of the weakness and stochastic nature of selection compared with mutation and drift. A closer look suggests that such constraints are only one of six possible kinds of explanations for apparently suboptimal designs: mismatch, coevolution, tradeoffs, constraints, reproductive advantage at the expense of the individual, and defenses that are aversive but useful Medicine has asked proximate questions at every possible level but has only begun to ask evolutionary questions about why bodies are vulnerable to disease. Considering all six possible evolutionary reasons for apparently suboptimal traits will spur progress not only in medicine but also more generally in biology. 'Williams Vision" may not yield a net benefit to the possessor, but it is invaluable for the species

• Keller MC & Nesse RM. (2006) The evolutionary significance of depressive symptoms: different adverse situations lead to different depressive symptom patterns. J.Pers.Soc.Psychol. 91:316-5330. PMID 16881767.

• Abstract: Although much depression may be dysfunctional, the capacity to experience normal depressive symptoms in response to certain adverse situations appears to have been shaped by natural selection. If this is true, then different kinds of situations may evoke different patterns of depressive symptoms that are well suited to solving the adaptive challenges specific to each situation. The authors called this the situation-symptom congruence hypothesis. They tested this hypothesis by asking 445 participants to identify depressive symptoms that followed a recent adverse situation. Guilt, rumination, fatigue, and pessimism were prominent following failed efforts; crying, sadness, and desire for social support were prominent following social losses. These significant differences were replicated in an experiment in which 113 students were randomly assigned to visualize a major failure or the death of a loved one

• Nesse RM, Stearns SC, & Omenn GS. (2006) Medicine needs evolution.. Science 311:1071. PMID 16497889.

• Excerpt: The triumphs of molecular biology call attention to evolutionary factors responsible for certain genetic diseases. The textbook example is sickle-cell disease, whose carriers are resistant to malaria. Similar protection against infection has been hypothesized for other disorders. Which aspects of the modern environment are pathogenic? We need to find out. Increases in breast cancer have been attributed to hormone exposure in modern women who have four times as many menstrual cycles as women in cultures without birth control. Other studies suggest that nighttime exposure to light increases the risk of breast cancer by inhibiting the normal nighttime surge of melatonin, which may decrease tumor growth. Evolution has also provided some explanations for conditions such as infertility. The process that eliminates 99.99% of oocytes may have evolved to protect against common genetic defects. And some recurrent spontaneous miscarriages may arise from a system evolved to protect against investing in offspring with combinations of specific genes that predispose to early death from infection.

• Nesse RM. (2007) Evolution is the scientific foundation for diagnosis: psychiatry should use it.. World Psychiatry 6:160-161. PMID 18188435.