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More Fun Than Fun: Is Evolutionary Medicine Coming of Age?

More Fun Than Fun: Is Evolutionary Medicine Coming of Age?

H.M.S. Beagle, the ship in which the young Charles Darwin sailed and gathered the raw material for his theory of evolution by natural selection. The frontispiece by Robert Taylor Pritchett from Darwin, Charles (1890), Journal of researches into the natural history and geology of the various countries visited by H.M.S. Beagle etc. Image: The Voyage of the Beagle, John Murray/public domain

  • Basic scientists are good at proposing overarching theories, knocking down paradigms and erecting new ones. These are necessary and provide the raw material for future applications.
  • Unfortunately, the new flurry of activity in evolutionary biology inspired by evolutionary medicine won’t by itself change the professional lives of doctors and the experience of patients.
  • For this new research to have an impact on doctors and patients, evolutionary biology must have an equally salubrious effect on medicine and clinical practice.
  • This can come about only if doctors and medical researchers adopt evolutionary biology as the core principle integrating their entire domain.
  • The Ukrainian-American geneticist Theodosius Dobzhansky galvanised much of biology by noting, “Nothing makes sense in biology except in the light of evolution”.
  • A similar transformation in the spirit of “nothing makes sense in health and disease except in the light of evolution” will be needed for the fruits of evolutionary biology to percolate into medicine.

In the last article, we witnessed the birth of a new discipline called evolutionary medicine, with the promise of creating new forms of knowledge about health and disease and potentially ushering in novel and improved methods of treatment. Now, let us survey the current state of this fledgling discipline.

Evolutionary medicine today

Evolutionary medicine has come a long way since the pioneering efforts of three intrepid scholars, the ornithologist Paul Ewald, the psychiatrist Randolph Nesse and the marine biologist George Williams. Today there are thousands of research papers, dozens of monographs and textbooks, a journal (Evolution, Medicine, and Public Health), an ‘International Society for Evolution, Medicine, and Public Health’, a club for Virtual Evolutionary Medicine Conversations, and even a young child-field called evolutionary psychiatry. This progress has been greatly facilitated by Stephen C. Stearns, the Edward P. Bass Professor of Ecology and Evolutionary Biology at Yale University, who took a deep interest in the new discipline in its early infancy.

Stephen C. Stearns, the Edward P. Bass Professor of Ecology and Evolutionary Biology at Yale University. Photo: Stephen C. Stearns

Before he became interested in evolutionary medicine, Stearns was a well-known evolutionary biologist prominently associated with the discipline of ‘life history evolution’.

Life-history evolution asks why organisms age and die, how they decide how many offspring to have, of what sizes and at what times in their life span, and how the same set of genotypes produce different phenotypes in different environments. It is easy to see why Stearns was attracted to evolutionary medicine: his previous disciplinary expertise had primed him to tackle precisely the issues that concern this new discipline.

Stearns told me in an email: “I got interested in evolutionary medicine in the mid-1990s after reading books by Paul Ewald and Nesse/Williams.  I was intrigued by the insights but not impressed by the speculation and the lack of experimental support for some of the claims”. To fix this problem, Stearns put together – as early as 1999 – an edited volume entitled Evolution in Health and Disease, with “24 chapters written by rigorous scientists with high standards”.

Stearns also told me that although he was not really an expert in the field of evolutionary medicine (at least at that time), because he was the editor of that volume, he began to get invitations to speak about evolutionary medicine. He had no choice but to become an expert, and he did.

Eventually, Stearns teamed up with his Yale University colleague Ruslan Medzhitov, the David W. Wallace Professor of Immunobiology, to write a definitive textbook, Evolutionary Medicine (2018). Stearns and Medzhitov have put the science of evolutionary medicine on a firm theoretical footing and provide impressive empirical support for many of the claims of the discipline.

I found it striking that they draw a significant fraction of their concepts and data from disciplines not traditionally thought to be related to evolutionary medicine. In a clever strategy to attract the attention of doctors, they have detailed chapters entitled “What is a Patient?” and “What is a Disease?”, showing how adopting an evolutionary lens can reimagine both the disease and those it afflicts.

Evolutionary Medicine is accompanied by a highly accessible set of lectures by Stearns, freely available on YouTube. I learned a great deal by watching the 65 lectures with the textbook at hand. The combination is a great resource for budding doctors and medical professionals while we wait for evolutionary biology to be widely taught as a standard part of the medical curriculum.

Ancient evolutionary events with medical consequences

Stearns and Medzhitov got me hooked very early in the book in a section they intriguingly labelled “Ancient histories with medical consequences”. They do mean ‘ancient’ even by evolutionary standards and list five events in the history of life ranging from 3 billion to 2-3 million years ago.

The origin of asymmetry – Three billion years ago, single-celled organisms began to divide asymmetrically into one daughter cell that inherits the old contents of the mother cell and the other that inherits the newly synthesised contents. At this point, natural selection inevitably kicked in by improving the ‘new’ daughter cell, which had superior reproductive performance, and neglected the ‘old’ daughter cell, which had relatively inferior reproductive performance.

Thus, deleterious mutations in the ‘old’ daughter cell were not subject to as intense selection and were therefore allowed to accumulate, leading to its ageing and eventual death. On the other hand, deleterious mutations in the ‘new’ daughter cell were eliminated more efficiently, keeping it young and healthy. Such was the origin of ageing that continues to bother us today, not to mention our doctors.

I discovered, to my great surprise, (1) that this idea of the importance of asymmetric cell division was already suggested by the German biologist August Weisman (1834-1914) in 1882 but forgotten (and rediscovered recently), and (2) that such asymmetry in cell division can be seen, and ageing can thus be demonstrated even in laboratory populations of the bacterium E. coli where the two daughter cells are morphologically symmetrical, but it turns out that their contents are not.

This is exciting stuff indeed and opens up avenues for a detailed understanding of the genetic and molecular mechanisms of asymmetric cell division and, thence, of ageing.

A screenshot of Stephen Stearns’s YouTube course on evolutionary medicine. Source: YouTube

The invention of stem cells – Some 1-2 billion years ago, multicellular organisms began to set aside so-called ‘stem cells’ that retained totipotency1 and could therefore come in handy to repair damaged parts. Not so surprisingly, at least in hindsight, it turns out that most cancers originate in stem cells; the innovation of making stem cells appears to have prepared the ground for the development of cancer.

Stearns and Medzhitov evocatively describe the origin of multicellularity as a covenant between cells of the multicellular body, where the somatic cells would stop growing after they make the required tissues and organs; germ cells would carry forward a copy of the genes of somatic cells into the next generation; and the stem cells would retain the capacity to multiply so as to be able to repair damaged tissues and organs whenever needed.

But “cancer breaks that covenant”. Stem cells, being ‘totipotent’, and thus endowed with the capacity to multiply and differentiate into any type of cells that were needed to undertake the required repairs, can misuse that capacity.

The origin of the vertebrate adaptive immune system – In a momentous event 500 million years ago, a transposable element (pieces of DNA that can jump from one location to another in the genome, causing mutations as they do so) carrying two genes got inserted into one of the immunoglobulin genes in one of our fish-like ancestors. This appears to have given the vertebrate adaptive immune system the ability to produce highly variable antibodies that could recognise and eliminate any possible foreign antigen.

The two genes are called RAG1 and RAG2 (where the letters are short for ‘recombination activating genes’). . Some bacterial viruses, such as mu, are transposable elements similar to the so-called jumping genes, whose discovery was recognised by the award of a Nobel Prize to Barbara McClintock in 1983.

The ability of our immune system to produce a nearly infinite variety of antibodies to every conceivable antigen and retain the memory of past infections is based on a similar ability to shuffle the DNA, in a process called somatic recombination. As Stearns remarks in an early lecture in his YouTube course, it is ironic that a kind of viral infection in our ancestors has given us the ability to fight viral infections!

The placenta as a mediator of parent-offspring conflict – Next, they discuss another historical event with medical consequences that occurred 15 million years ago during our evolution. This one is particularly intriguing because it potentially connects the mammalian placenta with the possibility of cancer. These kinds of counter-intuitive insights are the pleasing consequence of evolutionary thinking. Unfortunately, the event under discussion is not very pleasing as it makes us more prone to metastatic cancer.

What can be the connection between the placenta and cancer? A related counterintuitive idea from evolutionary biology is that a certain amount of conflict between parents and offspring is inevitable because parents, who are equally related to all their offspring, would be selected to allocate resources fairly to all their offspring. But offspring who are more related to themselves than to their siblings would be selected to demand more than their parents are selected to give.

Parent-offspring conflict, it turns out, takes many forms. In mammals, stem cells from the foetus can invade the mother’s body via the placenta and manipulate the diameter of the mother’s arteries, so that the foetus gets more food than the mother intended.

One can see a flip-flop during mammalian history with the evolution of highly invasive placentas in primitive lineages (foetus wins), the maternal suppression of invasive placentas in some lineages such as cows and horses (mother wins), more invasive placentas in cats and dogs (foetus wins), and the more recent change of fate with the re-evolution of invasive placentas in the ancestors of humans, chimpanzees and gorillas, about 15 million years ago (foetus wins).

Mammalian species with more invasive placentas – including humans – have higher rates of metastatic cancers, while those with less-invasive placentas have lower rates of metastatic cancers. It appears that if foetal stem cells are good at invading the mother’s body, they are also good at invading other parts of their own bodies and metastasising, resulting in an interesting trade-off between foetal success in drawing more nutrition from the mother and being prone to cancer later in life.

Indeed, many of the genes and inter-cellular processes used by the foetus during interaction with the mother are the same that are used by cancer cells during metastasis. The cellular and molecular mechanisms by which foetal stem cells invade and manipulate maternal physiology, and the maternal counter-strategies that suppress invasive placentas, are likely to help understand metastasis and its possible control.

It is reassuring to note that in cows and horses, for example, maternal counter-mechanisms have successfully reversed the foetal excesses and have led to an evolutionarily stable phenotype of less invasive placentas.

Bipedal locomotion – The most recent of these ancient evolutionary events with medical consequences occurred some 2-3 million years ago. After splitting off from the chimpanzees, human ancestors increasingly resorted to upright, bipedal locomotion that helped hunt down large prey cooperatively.

For efficient bipedal locomotion, a considerable remodification of the pelvis was required leading to the present difficulties in childbirth. These difficulties were further exacerbated by the evolution of our large brains, making it necessary to postpone a considerable fraction of brain development to the period after birth. Nevertheless, childbirth remains difficult and requires the foetus to rotate and pass through the human birth canal facing backwards. These difficulties in childbirth leading to high mortality rates may have only been overcome by our capacity to live in cooperative groups and assist each other during childbirth and beyond.

Living in cooperative groups was facilitated by large brains and, in turn, further facilitated the evolution of even larger brains leading to the development of the hunter-gatherer lifestyle that was inextricably linked to walking. Hence, another consequence of our bipedality was that walking became crucial for our survival and health.

David A. Raichlen of the University of Southern California and Daniel E. Lieberman of Harvard University have recently investigated the evolution of human walking behaviour. They have calculated the number of steps taken per day by modern humans as measured by the ubiquitous Fitbit and similar wearable devices. For our non-Fitbit using ancestors, they have calculated the number of steps taken from their hind-limb step lengths and distances covered per day.

Analysing the number of steps taken per day by our non-human great ape ancestors such as orangutans (a little under 1,000 steps/day), gorillas (a little over 1,000 steps/day), chimpanzees (~ 4,000 steps/day), bonobos (~5,000 steps/day), and humans living in small-scale hunter-gatherer societies (up to 18,000-20,000 steps/day), they infer that there was a strong shift in selection pressure during human evolution for increased physical activity in the form of walking, in order to stay fit.

Thus, the reduced walking rates of people living in modern industrialised societies (~5,000 steps/day), though on par with chimpanzees and bonobos, is a mismatch compared to our past hunter-gatherer lifestyle. This reduced walking rate contributes at least partly to the high prevalence of type 2 diabetes and cardiovascular diseases.

More recent evolutionary events of medical consequences

Then there have been several relatively recent evolutionary events with equally significant medical consequences. The most important of these is our migration out of Africa some 150,000 years ago and colonisation of much of the planet, a journey that repeatedly split up and reunited human groups leading to highly complex patterns of the distribution of genetic variation within and between populations.

Genetic variation poses a special challenge to medicine because it means that one treatment doesn’t work for all patients. The challenge of genetic variation to medicine is greatly exacerbated by the social and political implications of human genetic variability, often leading to a great reluctance or opposition to accept or even investigate genetic differences within and between populations for fear of their misuse. It is now widely accepted that most genetic variation occurs within populations and races rather than between them. This is comforting as it undermines the biological basis of races and will hopefully pave the way for an end to racial discrimination.

But the fact that a large amount of genetic variation occurs within populations poses great difficulties for developing individualised medical treatment. Individuals can vary significantly in their susceptibility to different diseases, both infectious diseases and lifestyle diseases, and in their ability to respond to drugs and toxins.

An evolutionary perspective also underscores the importance of human life history traits such as size at birth, size and age at sexual maturity, the ability to respond to nutrition and other environmental factors, to the expression of health and disease. And these traits themselves display considerable variation between different individuals, making the task of doctors extremely difficult.

Even before evolutionary medicine begins to offer tangible benefits in treating diseases, it can already begin to show why our present medical interventions are not as effective as we would like them to be. If their ineffectiveness is at least partly due to inter-patient genetic variability, that would suggest a very different trajectory for medical research than if the present interventions are uniformly effective or ineffective for all patients.

Evolutionary medicine, understood as taking an evolutionary perspective on health and disease, offers exciting opportunities for evolutionary biologists to pursue their science in a vastly expanded domain of problems, questions and model systems. I have little doubt that this will be hugely beneficial to the discipline of evolutionary biology. Indeed, the salubrious influence of evolutionary medicine on evolutionary biology is already underway. There has been and will continue to be a massive expansion in research outputs in terms of papers, books and monographs and much expansion in terms of university departments, courses, faculty positions, conferences, PhDs and so on.

It is to be expected that much of this activity will be in the form of curiosity-driven puzzle-solving research, and success will be largely judged but how beautiful and logical the new findings will be and how they satisfyingly tie together diverse hitherto unconnected phenomena. And that is how it should be for science to flourish. Let us now consider a couple of recent examples of the kinds of ideas and open-ended logical explorations that evolutionary biologists cherish.

Evolutionary origins of pathogenic obesity

I was delighted to learn that my friend, colleague and mentor Mary Jane West-Eberhard had recently become interested in the evolutionary origins of obesity. Mary Jane is a highly-regarded evolutionary biologist whom different kinds of evolutionary biologists would like to claim as one of their own. But I like to think that we social-wasp researchers have a priority over others.

Mary Jane began her career studying social wasps towards her PhD degree under the mentorship of Richard Alexander at the University of Michigan. Her thesis, The Social Biology of Polistine Wasps, was the first definitive study of a social wasp in the light of the new framework of Hamilton’s inclusive fitness theory – and has become both a landmark and a harbinger of numerous similar studies of social wasps and bees.

Mary Jane West-Eberhard, with a copy of her magnum opus ‘Developmental Plasticity and Evolution’ in her hand, and some wasp nests close at hand. Photo: Mary Jane West-Eberhard

Never one to be tied down to a narrow discipline, Mary Jane’s scientific work has been characterised by bold and expansive syntheses and generalisations across all forms of life and covering myriad biological phenomena. Her magnum opus, Developmental Plasticity and Evolution (2003), established her as a major contemporary thinker in evolutionary biology. George C. Williams, one of the founders of evolutionary medicine, said of her book:

“This is a brilliant new synthesis of evolutionary biology, full of novel and convincing arguments and important lessons for workers in a great diversity of biological fields. I think this book will be a classic that people will be quoting decades from now…”

Luckily, such an author has now focused her attention on a problem in evolutionary medicine.

In a 2019 perspective article in PNAS entitled ‘Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity’, Mary Jane proposed the novel“VAT prioritisation” hypothesis. Her main plea is to distinguish between abdominal fat and subcutaneous fat and not lump them together, as is done when we measure body mass index (BMI) as the total body mass divided by the square of the body height.

BMI is not useful to describe and diagnose conditions of overweight and obesity and understand the myriad diseases associated with them, such as type-2 diabetes and cardiovascular disease. This is because abdominal fat, technically called visceral adipose tissue (VAT), and subcutaneous fat, or subcutaneous adipose tissue (SAT), have different functions, respond differently to environmental stressors and have different health, social and evolutionary consequences.

Therefore, “Trying to analyse the diseases of obesity without understanding the biological functions of these key structures is like trying to analyse circulatory disease without understanding the biological functions of the heart,” says Mary Jane.

VAT has important immune functions involving storing certain fatty acids required to mount an immune response and responding to signals that suggest the need for an immune response. VAT is, therefore, crucial to deal with abdominal infections. SAT, on the other hand, is not useful in fighting infection and has other functions, as we shall see below.

The VAT prioritisation hypothesis, therefore, proposes that the body should prioritise investment in VAT over SAT when the foetus experiences poor nutrition and is expected to have a low birth weight, which is associated with a high risk of infection.

However, when the prediction of a poor adult environment based on a poor foetal environment fails, as it happens when low-weight babies are fed well, especially when they emigrate to nutritionally rich environments, there is a problem, another kind of mismatch. Excess and unnecessary abdominal fat accumulates, leading to obesity, which is significantly associated with diabetes and cardiovascular disease.

The problem of excess abdominal fat is further exaggerated when the adults have access to a diet rich in fats and sugars, which stimulate the VAT to mount inflammatory responses. And the latter appears to happen because excess fats and sugars affect intestinal bacteria, increasing the permeability to visceral pathogens.

The knowledge of complex interactions of various physiological body components should caution us against medical interventions without adequate knowledge.

I was particularly struck by a study Mary Jane cited in which Dr Neena Modi and her colleagues at the Imperial College London and the King Edward Memorial Hospital, Pune, compared Indian and European babies. Noting that “the adult Asian Indian phenotype is characterised by central adiposity despite a lower body mass index”, they measured the total and regional adipose tissue content using whole-body magnetic resonance imaging.

Their results were striking. The Asian Indian neonates had significantly greater VAT adiposity in their abdomens compared to the white European babies, despite similar overall adipose content in the whole body. They concluded that “differences in adipose tissue partitioning exist at birth” and perceptively advised that “investigative, screening and preventive measures must involve maternal health, intrauterine life and infancy.”

Thus, prioritising VAT over SAT may be a useful evolved adaptive response of the body – but attempts to compensate for poor nutrition during pregnancy with high fat and sugar-rich adult diets only serve to make matters worse. It is a sobering thought that vastly improving our situation at one time of life cannot always overcome the ill effects of poor conditions at other times; indeed, it may make it worse.

Here, again, is an illustration that medicine and health care should take into consideration the body’s evolved mechanisms to cope with adversity and attempt to augment them rather than ignore them and try something altogether new.

Excess SAT, on the other hand, is considered good for health, so individuals with more SAT get the happy label “metabolically healthy obese”. An important component of the VAT prioritisation hypothesis is that the VAT-SAT trade-off is adaptively tuned by phenotypic plasticity – that is,  by the ability of the same genotype to produce different phenotypes based on the environment: more VAT if the situation is bad and more SAT if it looks good out there. But what is the good of more SAT?

Drawing on diverse literature, Mary Jane argued that SAT allows individuals to store fat in regions such as breasts and buttocks, thus displaying body shape and other signs of beauty and fertility and gaining reproductive success through sexual and social selection. Sexual and social selection – phenomena that Mary Jane has extensively studied before – are variants of natural selection where individuals achieve evolutionary success by being favoured as partners in reproduction or for social cooperation.

Thus, Mary Jane concluded that “the VAT–SAT trade-off can be seen, in evolutionary terms, as involving to some degree a trade-off between the immune functions of VAT and the social (body shape) functions of SAT”.

Mary Jane West-Eberhard’s VAT prioritisation hypothesis is, at present,

“… the most coherent view of the relationships between (1) the immune functions of VAT, (2) its connection with chronic inflammatory disease, (3) population differences in disease incidence, (4) the role played by modern mass-marketed foods, and (5) the evolutionary setting that may have favored adaptive fetal effects on patterns of fat allocation…”

These ideas should no doubt be treated as plausible hypotheses worthy of further testing. The more diverse and counter-intuitive observations that a hypothesis can connect into a single coherent explanation, the more attractive that hypothesis should be. However, high attractiveness does not necessarily mean that it is correct but merely that it deserves to be put to the test on priority.

Do we need a paradigm shift in understanding type-2 diabetes?

While proposing coherent general theories represents one kind of passion for basic scientists, overturning existing paradigms is another, and that is prized even more highly. The historian of science Thomas Kuhn famously described the history of science as consisting of long periods of ‘normal science’ interrupted occasionally by revolutions that rapidly ushered in a new paradigm, followed by a return to normal science.

Although the Kuhnian view of the history of science has been much criticised, it still holds great appeal to those who wish to start revolutions and change the paradigm in their discipline. I always welcome attempts to create revolutions and change paradigms because I put the onus on the prevailing paradigms and their practitioners to survive the assaults. A battle-scarred paradigm that has survived many assaults inspires more confidence compared to one that has remained glibly accepted without a challenge.

My friend and colleague Milind Watve has spent the past two decades challenging our understanding of type-2 diabetes and suggesting the way to a possible new paradigm. In a book entitled Doves, Diplomats, and Diabetes, Watve employed the format of a set of undergraduate lectures to take the reader through his arguments. This is not surprising because Watve has spent most of his career teaching undergraduates and has done so with a passion that is hard to match.

I remember numerous applicants for the PhD programme at the Indian Institute of Science frequently telling us during the interviews that they had been trained and inspired by Milind Watve. Some years later, Watve himself appeared for the same interviews and told us that he had spent all his time training undergraduates, but now he wished to get a PhD!

Watve’s style of training was not restricted to lectures and conversations. He engaged undergrads in research and published fascinating papers with his undergrads as co-authors in well-known journals. After getting a PhD from the Indian Institute of Science, he promptly returned to his undergraduate teaching career.

In step one of his argument, Watve summarises our traditional understanding of type-2 diabetes as paraphrased below:

1. Obesity is a consequence of positive energy balance, i.e., we eat more than we can burn.

2. Obesity is the main cause of insulin resistance.

3. The body tries to compensate for insulin resistance by making more insulin.

4. A progressive decline in the ability to make insulin and the development of insulin resistance lead to elevated blood sugar.

5. Increased blood sugar leads to the pathophysiological consequences of diabetes.

In step two, he draws upon a vast body of literature to question the robustness of each of the above statements in the following way, paraphrased by me again:

1. The cause of the positive energy balance is unclear; is it that we eat more or burn less? If we don’t know which, the idea of positive energy balance is not useful. In other words, we really do not understand the cause of modern-day obesity.

2. Obesity and insulin resistance are correlated, but it is unclear which is the cause and which is the effect. Even if there is a causal connection, the mechanism by which obesity causes insulin resistance is far from clear.

3. Once again, insulin resistance and insulin overproduction are correlated, but the cause-effect relationship is unclear. If overproduction of insulin causes insulin resistance, then that is a whole different story casting doubts on the roles of diet and obesity.

4. All evidence in the literature indicates that insulin insufficiency and insulin resistance are both important, but they are neither necessary nor sufficient to cause elevated blood sugar.

5. The proposed link between high blood sugar and the pathophysiological effects of diabetes is the weakest of all making it more a belief than a proven fact.

Being dissatisfied with the prevailing paradigm, Watve attempted to usher in a new paradigm. Very briefly, the essence of Watve’s new paradigm is that our behavioural strategies are an important component of health and disease, especially metabolic diseases.

Drawing on the literature from animal behaviour, he noted the differences between behavioural strategies that have been metaphorically called Hawk and Dove. Broadly speaking, Hawks are aggressive, behaviourally dominant and have “high levels of sex hormones, low serotonin and higher dopamine activity in the brain, lower plasma cholesterol, and corticosteroids as well as low plasma insulin”. Doves, on the other hand, are meek and subordinate and “low sex hormones, high serotonin, low dopamine, and higher plasma levels of corticosteroids and cholesterol.”

Compared to Hawks, it is the physiology of Doves that appears to mirror the metabolic syndrome in humans. But this is not a problem for the doves because they will not have access to the lifestyle, especially the diets, of Hawks.

Watve then translated this animal behaviour scenario of Hawks and Doves to humans and suggested that our contrasting behavioural strategies may be metaphorically called ‘Soldiers’ and ‘Diplomats’ with corresponding physiological correlates.

In particular, Watve hypothesised that “a combination of behavioral strategies and diet is what matters and not diet alone”, and predicted that “diet-induced insulin resistance should be seen only in the diplomat class of people and not in the soldier class”. But the trouble with humans is that Diplomats have access to the diets of Soldiers. Thus, he said, “the obesity epidemic seen today is because we have transitioned from the Hawk-Dove dichotomy in animals to the Soldier-Diplomat dichotomy in humans”.

Based on a vast literature that I have not studied or discussed here, Watve summarised the main difference between his hypothesis and the present paradigm as follows:

“The classical theory argues that sedentary life leads to obesity, and obesity leads to insulin resistance. [My] new hypothesis states that physical activities and particularly intensive and aggressive activities by themselves are insulin sensitizing independent of obesity…”

Thus, Watve’s causal arrow goes from ‘lifestyle to insulin resistance to obesity’, rather than the previously conceived ‘lifestyle to obesity to insulin resistance’. It is easy to see that the new causal postulate leads to very different policy prescriptions.

Not one to waste any time, Watve has already begun working with clinicians at the recently established Behavioural Intervention for Lifestyle Disorders (BILD) at the Deenanath Mangeshkar Hospital and Research Centre, a multi-speciality hospital in Pune. In a recent publication, he and his colleagues demonstrated that “a multidimensional functional fitness score has a stronger association with type 2 diabetes than obesity parameters in cross sectional data”.

I am not really competent to evaluate Watve’s criticism of the prevailing paradigm nor the merits of his alternate paradigm. My greater interest here is to describe the process of science and to demonstrate the potential of evolutionary thinking to change paradigms of health and disease. Watve’s verdict is that changing paradigms is an uphill task. He told me in a recent email:

“I have been publishing research on diabetes (over 20 papers and two books by now), but I am amazed by the response of the diabetes research community. Nobody counter-argued, and nobody doubted or questioned what I said. I gave talks at places like the Joslin Diabetes Centre of Harvard Medical School. People listened to me with interest and responded positively in an individual capacity. But nothing happens at the level of science. No change in the old paradigm in spite of multiple experiments clearly falsifying it. Very few citations of my papers. No change in clinical practice. Things are going exactly as per Thomas Kuhn’s description”.

Photo: Milind Watve

To be fair to Watve, his claims as well as his expectations are modest. He ended his book by saying that he may be wrong and would be happy if someone pointed out his errors or conducted experiments to test his predictions.

Can evolutionary medicine affect doctors and patients?

Basic scientists are good at proposing overarching theories, knocking down paradigms and erecting new ones. These are necessary and provide the raw material for future applications. But unfortunately, the new flurry of activity in evolutionary biology inspired by the idea of evolutionary medicine will not by itself make much tangible difference to the practice of medicine, the professional lives of doctors and the experience of patients in the clinic.

For the new research in evolutionary biology inspired by evolutionary medicine to have an impact on doctors and patients, evolutionary biology must have an equally salubrious effect on medicine and clinical practice. This can come about only if doctors and medical researchers adopt evolutionary biology as the core principle integrating their entire domain.

The Ukrainian-American geneticist Theodosius Dobzhansky galvanised much of biology by noting, “Nothing makes sense in biology except in the light of evolution”. A similar transformation in the spirit of “nothing makes sense in health and disease except in the light of evolution” will be needed for the fruits of evolutionary biology to percolate into medicine.

This will require that evolutionary biology becomes an integral part of medical education so that medical researchers and clinicians themselves set the agenda for developing evolution-inspired medicine. To recapitulate the perceptive remarks of George Williams and Randolph Nesse in their landmark paper, The Dawn of Darwinian Medicine (1991):

“New applications of evolutionary principles to medical problems show that advances would be even more rapid if medical professionals were as attuned to Darwin as they have been to Pasteur.”

Stephen Stearns said to me in a recent email:

“I think the main contribution made by evolutionary thought to medical science is an intellectual framework that integrates insights across levels of explanation, from genomics, biochemistry, physiology, and immunobiology to host-pathogen interactions, the emergence of diseases, and the evolutionary implications of public health policies.

Having that framework makes it easier for physicians and public health professionals to makes sense of the immense amount of information that they have to deal with.”

Can evolutionary biology become a foundational subject in medical school curricula?

Discussing the evolutionary biology of cancer, Bernard J. Crespi and Kyle Summers remind us that “Cancer cells and cancer-related genes evolve under the same rules as peppered moths and finches” but lament that “the training and specializations of cancer biologists, evolutionary biologists and ecologists have thus far largely precluded innovative interactions among these disciplines”.

There have been many efforts to persuade medical schools to include evolutionary biology in the medical curriculum but without much success. Randolph Nesse told me in a recent email:

“No medical school teaches the subject, although a few have one lecture. Why not?  A real investigation is needed, but mostly it is that doctors don’t know evolutionary biology, and medical schools have no evolutionary biologists on the faculty … and medicine is a profession that focuses on fixing, promoting understanding only when it advances fixing … or the careers of established medical scientists. My PNAS article about why evolution is needed in the medical curriculum had the deans of Harvard and Yale medical schools as co-authors, but it has had almost no effect.”

Curriculum reform is always fraught with contentious turf battles among the custodians of different disciplines. In the case of evolution, there is, of course, the added problem of religious objections to evolution and political considerations of appeasing interest groups in some societies. Making doctors and clinical researchers internalise evolutionary thinking cannot happen without curriculum reform, but I am afraid that is the one area in which the least progress has been made, and the future does not look very promising.

There is an urgent need for educationists and administrators to find ways to break the deadlock, for the stakes are very high indeed. Here is a rare opportunity for countries like India, where teaching evolution is not a problem, to take the lead for once!

Perhaps this is not so far-fetched a dream. After I wrote this, I received an email from Milind Watve saying, “I found many, if not all, physicians and surgeons showing keen interest in what I said. Lay people were even more responsive. I thought if clinical implementation of evolutionary ideas were to begin, it would begin in India first!!”

Raghavendra Gadagkar is a Department of Science and Technology (DST) Year of Science Chair Professor at the Centre for Ecological Sciences at the Indian Institute of Science, Bengaluru.

  1. Capable of developing into any cell type

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