It goes without saying that medicine is a highly biological subject—how could it be otherwise? It therefore comes as a surprise for many people to learn that medicine is not very evolutionary. That’s why Randolph Nesse and George C. Williams could write a groundbreaking review article in 1991 titled “The Dawn of Darwinian Medicine”1, followed by their trade book Why We Get Sick in 1995.That was over 20 years ago. For most of that time, the medical profession was extraordinarily slow in grasping what it means to be evolutionary. Now, however, there are signs that the pace of acceptance is picking up. Through it all, Randolph Nesse has been at the center of the action, first at the University of Michigan and now at Arizona State University, where he moved in 2014 to become the founding director of the Center for Evolution & Medicine. My interview with Randy covers the past, present, and future of evolutionary medicine.David Sloan Wilson: Welcome, Randy, to TVOL! You must be very gratified to be empowered with your own center, which I look forward to discussing with you as part of our conversation.Randolph Nesse: It is thrilling to finally have a chance to help evolutionary medicine grow fast and well. But I wouldn't call it my center; it is a campus-wide Presidential Initiative, with 12 faculty, and more being recruited now. Let people know we are looking!DSW: This interview will help spread the word! Let’s begin with the central mystery of how medicine can be highly biological in some respects but not very evolutionary. Why was your landmark review article needed? Also, is there a difference between the terms “Darwinian Medicine” and “Evolutionary Medicine”?RN: I have very gradually come to accept that medicine is a practical profession, not a science. It uses science, thank goodness! But the process of incorporating new kinds of science is always slow. Until the early 20th century, basic biology was hardly used. In the mid 20th century, advocates for the utility of biochemistry encountered skepticism. Even genetics has been slow to get into the curriculum. Evolution is inherently more interesting, and it provides a framework for organizing all other knowledge in biology, so I think its incorporation will be faster, but the process is inherently slow.In our 1991 article, George Williams and I posed a new question about disease. Instead of the usual question of “what is broken and why?” we encouraged people to also ask why the body had so many traits that leave us vulnerable to sickness. Natural selection could have eliminated the wisdom teeth and the appendix, and made the birth canal and the coronary arteries wider, but it didn't. Why not? Such questions were not entirely new, of course, but we argued that they should be taken seriously, with testing of alternative hypotheses.The evolutionary outlook expands the perspective of health professionals from that of mechanics to that of engineers. A mechanic, or a doctor who only studies mechanisms, wants to know how things work and what's gone wrong. Engineers and evolutionary biologists also ask why systems are the way they are, specifically, why they have aspects that leave them vulnerable to failures. The deeper understanding that emerges has long been routine in engineering, but is just now being appreciated in medicine.As for Darwinian medicine and evolutionary medicine, they are synonyms. George and I argued for hours about which term to use. George argued, correctly and successfully, that the word evolution was too nonspecific because it can refer to any kind of change, and that “Darwinian” highlights the central role of natural selection, and honors the scientist who inspired us. But as the years have passed, most people have adopted evolutionary medicine as the standard descriptor to avoid the negative associations to “Darwinian.” Even “evolutionary medicine” is problematic because it incorrectly implies a special brand of medical practice. It isn’t. Evolutionary medicine is the field that encompasses all research and teaching at the intersection of the basic science of evolutionary biology and the practical professions of medicine and public health. “Evolution AND Medicine” is more accurate, but has yet to catch on.DSW: Thanks very much for this background. Tell us the story of how you became a pioneer and how you started to work with George Williams. For the benefit of our readers, I also had a lifelong association with George. We were intellectual adversaries on the topic of group selection (except for disease avirulence, which he correctly interpreted as an example of group selection) but very good friends. He was revered among evolutionary biologists and sadly passed away in 2010 after succumbing to Alzheimer’s disease.RN: I had an inspiring invertebrate biology teacher at Carleton College, Patrick Milburn, who encouraged us to write a paper on a challenging topic. I decided to figure out why natural selection didn’t get rid of aging. Genetic variations influence how fast you age, so natural selection should have gradually eliminated those that cause faster aging. But it didn’t. What a great mystery!I took the bus from Northfield, Minnesota to the Twin Cities, where I spent days looking up references from the thousand page yearly volumes of Index Medicus. I wrote them out on index cards and wandered through the stacks to see which ones where there. Those were the days when scholars got their steps! But it was worth it. I came up with what I thought was a great idea: aging mechanisms that limit the life span of individuals would benefit a species by speeding its evolution when environments changed.All through medical school I kept asking, “Why isn’t the body better designed?” My professors all gave the same answer: natural selection isn’t that great, mutations happen. Finally, when I was a junior faculty member, frustrated with the lack of scientific foundation for psychiatry, I found my way to the Museum of Natural History. It was thrilling to discover that there is a solid science of behavior that explains why animals do what they do, separate from just describing the responsible brain mechanisms.After I got more comfortable with my new biologist friends, I got up my nerve and told them my theory about aging. They laughed and laughed. They were astounded that a doctor could be so ignorant as to think that something like aging could persist because it was good for the species. In moments I realized my whole view of the living world had been wrong, and that my excellent medical education had exposed me to only one half of biology. They told me to go read Williams, 1957.1 I had missed it in my library search. Finally reading it changed my understanding of life. Everyone should read it several times. It is the original source of clear thinking about aging, cooperation, menopause and more.Evolutionary thinking was in full ferment at Michigan then, thanks to Dick Alexander and other great faculty including Bobbi Low and Barb Smuts and Richard Wrangham inviting visitors including Bill Hamilton, George Williams, Martin Daly, Margo Wilson, Nap Chagnon, and Bill Irons. We spent whole days and nights arguing about evolution and human behavior. I met George at one of those gatherings and we immediately found so much in common, especially since I had by then published a couple of papers with a method for testing his theory about aging. Soon we were talking about how much evolution had to offer to medicine. Our 1991 paper got things going, but Why We Get Sick had much more impact.DSW: In my own work, I draw heavily upon another pioneer, the Dutch biologist Niko Tinbergen, who shared the Nobel prize with Konrad Lorenz and Karl von Frisch in 1973 for helping to found the science of ethology (animal behavior). In his effort to establish ethology as a branch of biology, Tinbergen observed that four questions needs to be addressed about all products of evolution, concerning function, mechanism, development, and phylogeny.2 Ever since, “Tinbergen’s four questions” have been cited as a compact summary of a fully rounded evolutionary approach. Do you also draw upon Tinbergen’s four questions, as I do, and do you think they’re a good way to describe the main problem with medicine—namely, that is focuses on the “mechanism” question without paying sufficient attention to the other questions?RN: So you too have been inspired by Tinbergen’s insight! It is so powerful. It still amazes me that so few in the health professions even recognize that both proximate and evolutionary explanations are essential. I first grasped it deeply when I read Ernst Myer’s The Growth of Biological Thought in 1982. Like a flashbulb, it illuminated questions that had been lurking in the dark of my mind. Soon after I become fascinated by the shorter more powerful version: the Four Questions Tinbergen laid out in a 1963 article2 he wrote to honor the 60th birthday of his mentor, Konrad Lorenz. The irony is that Tinbergen's Four Questions has become more central to Ethology than Lorenz’s descriptions of animal behavior.On sabbatical in London, I spent a couple of months just thinking about those four questions, and how they fit together. Two are about evolution: two are about mechanisms. Two of them are about changes over time, two of them are about a cross-section in time. It eventually dawned on me that this makes a very nice matrix. I put it on my website, and within a year was on Wikipedia and everywhere. I published a version in an article celebrating the 50th anniversary of Tinbergen's publication.
DSW: Excellent! Am I correct that the medical profession was initially slow to grasp the evolutionary perspective but that acceptance is now picking up? If so, then how do you explain the “initially slow” part?RN: I wish the field of medicine was only initially slow! I don’t know of any medical school in the world that teaches the basics of evolutionary biology and how to apply them to problems in medicine. This is, of course, outrageous. It’s also understandable. Medicine should be somewhat slow to change, to avoid getting caught up in fads. Also, medical school deans pay attention, first and foremost, to budgets and reputations. Investing in evolutionary biology won’t make a school rich, and it risks arousing protests from some students and donors. It won’t be long, however, before some school takes the lead and discovers that an evolutionary approach provides a superior framework for organizing medical knowledge, and that a curriculum that features evolution attracts the best students, leaving other school scrambling to catch up.DSW: Let’s hope so! Now, how about the “picking up” part?RN: Except in medical schools, evolutionary medicine has grown exponentially. Courses are offered in scores of universities, and new textbooks on the topic come out every year. But no medical school teaches evolution as a basic science, and only a few have even one lecture on the topic in the entire curriculum.When I’m invited to travel to give a lecture, I often agree to come only if the Dean or curriculum head expresses an interest in having a conversation about evolution in the medical school curriculum. The first question is always the same. "How does understanding evolutionary biology improve the quality of care doctors provide?” I previously replied with practical examples, such as how to minimize antibiotic resistance, and how to make better decisions about when to use drugs to block cough and fever. But why should we demand more from evolutionary biology than other basic sciences? We don't demand instant clinical improvements to justify teaching embryology, biochemistry, or genetics. We want doctors who are educated about the body and disease. Evolution provides not just a few core concepts, but also a framework for organizing medical knowledge.More than one medical school dean has told me, always on the condition that I not mention the name of the school, that adding evolution to the curriculum would bring complaints from evangelical students, and the possible loss of contributions from some donors. Plus, medical schools do not have evolutionary biologists on the faculty to do the necessary teaching, and research. Medical schools are silos with very thick walls. But I’m not pessimistic at all. Undergraduates find enormous enthusiasm and interest when they study evolutionary approaches to medicine, and they will grow up to be deans and heads of foundations.DSW: Tell us about your move to ASU and what you have been empowered to accomplish there. Also, your move is not an isolated event. ASU appears to have become a Mecca for the study of evolution in relation to human affairs. Tell us about that also.RN: U.S. News & World Report recently named Arizona State University as the most innovative university in the country. I'm usually skeptical of such hype, but at ASU it's for real. Our president, Michael Crow, is a genuine intellectual. He and his team look for exciting areas ready to blossom, and the make major investments long before other universities see the opportunity, and even before funding agencies get up to speed.I was initially skeptical about whether ASU would follow through on its large commitments to our Center, but I was soon reassured by talking with old friends who also recently been lured to ASU—Kim Hill, Magdalena Hurtado, Joan Silk, and Rob Boyd. The University decided to become the center of the world for evolutionary anthropology, got the best people to come, and they are now recruiting still more top scientists. Just having a chance to talk with people in that group every week has made intellectual life here nearly as exciting as University of Michigan in the 1980s. Now, with four new faculty joining six great scientists already at our Center, it is more exciting yet. One of our faculty members, Katie Hinde, describes it as “the science party in the desert.”As for our mission, the university has accepted and supported its grand scope. We aim to establish evolutionary biology as a basic science for medicine, worldwide. That requires both great research and also major investments in creating teaching resources and connecting far flung people working on similar topics.DSW: Your center includes both “Medicine” and “Public Health” in its title. Why is this distinction important and do they become evolutionary in different ways?RN: For simplicity, we are "The Center for Evolution and Medicine.” But we are well aware, thanks especially to Gil Omenn, the chair of our scientific advisory board, that the opportunities in public health may be even greater than those in medicine. Public health takes a population perspective, and it offers opportunities to improve health on a much larger scale than medicine.DSW: Advancing evolutionary medicine requires a lot of institution changing, such as the pre-med and medical school curriculum and the questions asked on the MCAT exams. In addition, what advice would you give to individuals who want to become self-taught in evolutionary medicine and to make informed decisions about adopting a healthy lifestyle?RN: Yes, human organizations certainly do defend whatever they are already doing, don't they? Several of us have convinced the Medical College Admissions Test to include questions on evolution and medicine. Many biology majors headed for medicine never take an evolution course. The new MCAT requirements should change that.Our Center is making a large investment in developing education resources for anyone in the world to use without cost. In particular, we are collaborating with the International Society for Evolution and Medicine and Public Health to provide links to all relevant high quality education resources at EvMedEd.org. The site has long videos, short clips that can be inserted into lectures, syllabuses, podcasts, and even rap music about evolution and medicine, thanks to an album we commissioned by Baba Brinkman. We will spend the next year adding more content, and creating guides for educators who want to incorporate modules into their courses, and people who just want to learn on their own.As for helping people to adopt a healthy lifestyle, evolution does offer some general principles, such as being wary of ways of eating and exercising that are vastly different from those of our ancestors. However, I think it is a mistake for evolutionary medicine to make direct clinical recommendations. Clinical recommendations should be derived from clinical trials.DSW: Some diet regimes such as Paleo and exercise regimes such as Crossfit are given an evolutionary rationale but are also accused of being fads and not healthy after all. What’s your opinion of these two particular “fads” and how can popular health movements remain science-based? How can the layperson separate the wheat from the chaff?RN: While it is dangerous to derive clinical recommendations directly from theory, it is essential to use theory to generate new hypotheses that can be tested. That is happening. Yes, there is hype about Paleo this and Paleo that, but the interest is generating good data. Melvin Konnor, one of the authors of the original papers and book about Paleo diets, gave a talk for us last year on "Paleo Diet and Lifestyle: After 30 Years, Is There Any Science Left in All the Hype?" You can watch it here. We also heard a talk by Marlene Zuk that was a model of balanced skepticism.DSW: It has been great touching base with you! Is there anything else you would like to relate about the future of evolutionary medicine?RN: The field is on a fine trajectory to improve human health, but it will get sidetracked if people get the idea that it is some kind of alternative to regular medicine. It’s just uses a basic science to better understand, prevent, and treat disease.Testing evolutionary hypotheses, offers subtle challenges, as you well know. Human minds have a tendency to attribute functions to most everything, even diseases! This is a common serious mistake. The focus on functions makes evolutionary medicine fascinating, but it also means that we must be careful to state hypotheses clearly, consider all alternatives, and not give too much preference to our own pet theories. This is really hard for humans. To help my students, I wrote a paper called "Ten Questions for Evolutionary Studies of Disease Vulnerability." Asking them helps to avoid many elementary mistakes. I ask them myself when I am working on new topic.Finally, it’s important for evolutionary medicine to broaden its scope and apply everything in evolutionary biology to every aspect of medicine, public health, dentistry, veterinary medicine, and plant pathology. George and I started things off with excess emphasis on trying to explain why bodies have vulnerabilities to disease. Many other opportunities are ripe, such as applying phylogeny, co-evolution and other evolutionary principles. There are also opportunities for studies of disease to advance basic evolutionary theory.Those interested in learning more should consider joining The Evolution and Medicine Network for free, in order to stay abreast of new advances, and to learn about conferences and other ways to connect with others who share their interests.DSW: Great! I look forward to covering progress in evolutionary medicine, along with so many other topics, on TVOL.RN: Thanks for the chat, it is great to catch up!1. Williams, C.G. (1957) Pleiotropy, Natural Selection, and the Evolution of Senescence. Evolution, 11, 398-411.2. Tinbergen, N. (1963). On Aims and Methods of Ethology. Zeitschrift Für Tierpsychologie, 20, 410–433.
