I read an early review of Zoobiquity, the excellent and popular book written by cardiologist and evolutionary medicine colleague Barbara Natterson-Horowitz and Kathy Bowers. I was surprised to see the reviewer dismiss the entire book as a just so story. Where did this criticism come from, and what is a just so story? ” Just So stories for little children” was written by Rudyard Kipling. It included fanciful accounts of how the leopard got it spots, and so on. Gould and Lewontin applied the “just so” insult to adaptationist research in 1979 with their paper “The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme“. Infamously, they argued that adaptationist hypotheses generally are wrongheaded, because a great many traits were byproducts, like spandrels. In architecture, a spandrel is a byproduct of affixing a dome on an arched structure. To assign function to a spandrel, then, would be a mistake. Gould and Lewontin’s paper has been described in great detail elsewhere – read here, here, and here, but its main intent was to ridicule adaptationists as naive dupes who overlook likelier non-adaptationist explanations. They asserted that adaptive hypotheses are just so stories and that adaptationists are Panglossian. Voltaire’s fictional Dr. Pangloss believed that the function of the nose was to hold up spectacles and that everything was for the best in this best of all possible worlds. Ridiculous! Who wants to be the object of derision or ridicule?
Being on the receiving end of “just so” shuts off conversation and puts the recipient on their back foot. It is an insult, not a good faith effort to engage with a scientific claim. This I suspect was the intent of Gould and Lewontin. They believed adaptation to be unimportant. In many respects, Gould and Lewontin won the argument. After all, we are still talking about a 40+ year old paper. Rasmus Nielsen wrote that “Evolutionary biologists are today, arguably, much more reluctant to invent adaptive stories without direct evidence for natural selection acting on the traits in question.” The caricature Gould and Lewontin lampooned is now inverted: non-adaptive arguments require no special justification, but adaptive ones are met with a swift and furious clap back. The pendulum has swung in the opposite direction, but at what cost?
The problem is this: an entire category of explanation has been ruled off limits by the substantial subset of biologists, social scientists, and physicians. Gould & Lewontin might have been pleased with the current state of biomedicine, in which adaptationist arguments are out of favor. As I have noticed at conferences and in the scientific literature, tests of adaptation are relatively rare, owing in part to the legacy of Gould, Lewontin, and their adherents.
In my 2012 paper The emergence of evolutionary medicine, I did an analysis of the published literature in evolutionary medicine, based on US National Library of Science subject heading terms. I wrote that “phylogeny” is one of the more frequently indexed evolutionary terms in PubMed. I went on to say that “publications with adaptation as a main focus were relatively fewer in number and the rate of publication growth has tapered over the last decade.” When I repeated my search today, it looks like papers focusing on adaptation topped out in 2013 at 993 publications and have been in decline since.
Gould and Lewontin are not the only reason why studies about adaptation are rare in PubMed. Another is that many doctors are not steeped in the methods or jargon of evolutionary biology. Evolution takes a back seat in the literature and practice of medicine. Antibiotic resistance in bacteria, for instance, is rarely said to “evolve.” It instead “develops”, or “emerges”, as if from the primordial muck by spontaneous generation. The absence of commonly accepted terms for evolutionary processes in medicine is a detriment, as I pointed out in this 2012 paper. The words adaptive and evolution have different, non-Darwinian, meanings in medicine. Biomedical researchers engage in verbal gymnastics to describe things they might mean are functional or beneficial (aka adaptive). Even “functional” is problematic. Look up “functional constipation” to see what I mean. I see homeostasis and homeostatic being used as a stand-in for adaptation or adaptive function. Homeostasis really means something different from adaptive, of course. No matter, in biomedicine we concern ourselves mostly with the absence of adaptation. Dysregulation, dysfunction, and defects are the main preoccupations. In tilting at adaptive windmills, Gould and Lewontin unwittingly set the stage for a non-evolutionary biomedical science. If selection is far down on the hierarchy of evolutionary explanations, and most of what we observe are spandrels, then why should we bother with evolution as an explanatory or organizing force in the first place?
Here is the rub: To label something as dysregulated or non-adaptive is as much an evolutionary claim as labeling something as adaptive. Specifically, traits thought to be maladaptive or non-adaptive come with the implication that selection does not act on a trait, or selection has not had sufficient time to modify the trait. Here is an example of a problematic claim: In this Nature paper “Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis,” white blood cells were shown to undergo over 2000 changes in gene expression when exposed to lipopolysaccharide. These changes are labeled “defects,” but is it really plausible to think that all these changes throughout evolutionary history were defective and maladaptive? That is an extraordinary claim, requiring extraordinary evidence. In fact, the evidence often goes in the opposite direction.
In Voltaire’s Candide, the character Martin is an extreme pessimist, the opposite of Dr. Pangloss. Researchers who assume that host traits uncovered in diseases are uniformly maladaptive adopt Martin’s pessimistic worldview. A great many molecular pathways and patient parameters observed in diseases – especially sepsis – are conventionally understood to be maladaptive. Channeling Gould and Lewontin, I argue that maladaptive claims should not be accepted unquestioningly and without testing. It is scientifically and logically bankrupt to require an impossibly high bar to make an adaptive claim but no evidence to assert maladaptation.
Because of indifference and hostility to adaptive evolutionary arguments, we are handicapped in discovering the role of selection and adaptation in health and disease. SARS-CoV-2 provides an example.
Early in the pandemic there was almost an allergy to the suggestion that mutations in the SARS-CoV-2 genome might be functional or adaptive in promoting transmission. After intense scrutiny and an immense volume of research, adaptive evolution in SARS-CoV-2 became abundantly clear. Because of selective pressure from the human immune system, the virus has evolved to evade immune defenses with horrific consequences for public health. Selection and adaptation drive the evolution that we should worry about the most, because successful adaptation in pathogens has the biggest impact on patients. For a moving target like SARS-CoV-2, evolving from one immune-escaping variant to the next, adaptive evolution is what really matters.
Adaptive and maladaptive hypotheses both require rigorous interrogation, but because many believe that adaptation is off limits, few such hypotheses are subjected to analysis. This is a shame, because an overlooked challenge in developing novel therapeutics is determining whether a trait is either a host defense or pathogen virulence feature. Getting that right will have a profound effect on whether a drug will help or harm. If we are wrong, the consequences can be immense, and patients can suffer. At the end of the day, it is vitally important to understand whether evolved traits are adaptive or not. It is useful to know how powerfully natural selection acts on biologic agents of disease.
Returning to Zoobiquity, it is an award-winning New York Times bestseller and has received excellent reviews from the lay public and from scientific audiences. It is ironic that it was tarred with just so, since the main idea of the book is not an adaptive one. Instead Zoobiquity argues that shared phylogeny explains commonalities between human and veterinary medicine. Adaptation does come up in the book, where it is treated appropriately, as a hypothesis generating heuristic.
Finally, Alasdair Houston argued that spandrels are not the byproduct they appeared to Gould and Lewontin. According to Houston and others, spandrels are an “invention rather than a necessary side-effect,” with a design function. This observation is in line with my view that we should avoid assuming automatically that all our observations in human diseases are maladaptive and somehow immune to selection. A more parsimonious reading of human biology is that selection has acted on many disease traits, even ones that are presumed to be dysfunctional. Inevitably, some of these traits will be discovered (or rediscovered) to be adaptive, but we won’t know that without studying those possibilities.
Categories: Uncategorized
Joe Alcock
Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine
EvolutionMedicine 
Ernst Mayr wrote in 1983 “How to carry out the adaptationist program” in the American Naturalist. Of Gould and Lewontin, he wrote that he would “dissent vigorously” and proceeded to provide a methodology.
Thanks for the comment Cynthia. I have debated whether to dive into this, since so many, including Ernst Mayr, have before. I think evolutionary medicine is undeserving of “just so” attacks. I also think there is great value in thinking about how selection affects a wide variety of traits, including pathological ones, in addition to protective ones in health and disease. I’d go further and say that the evolution that matters most to doctors and patients is essentially adaptationist – recent evolution of SARS-CoV-2 that makes it transmit more efficiently and evade defenses. The other point I want to make are that arguments that traits are non-adaptive and non-functional are themselves evolutionary arguments, and they are often wrong. Evolutionary medicine is the potential corrective, with the caveat that these competing ideas need to be assessed thoughtfully and rigorously. I will detail some of these in the post, if I ever get around to finishing it!
The “just so” stories come largely from those who know selection may have been involved, but, don’t know how to evaluate the hypothesis. They speculate and if the topic is sufficiently alluring that journalists pick it up, then commentary becomes shakier and shakier.
Take the recent Nature article on the evolution of lactase persistence. It’s a welcome tour de force of data, but not of interpretation. The authors report on the use of milk by detecting milk fats and assume that the milk was in a liquid form containing lactose. It could have been yogurt, cheese, fermented milk, etc. And they speculate that periods of famine caused people to rely on milk for survival. As if the animals were not affected by the famine, too!
I had some of the same reaction to the milk paper. Of course some of the milk was fermented. I hadn’t thought about the animals being affected by famine. But you are right!
It occurred to me that “just so” stories made up by Kipling or modern day children are almost exclusively Lamarckian rather than Darwinian. Made up stories about how the tiger got its stripes or how the elephant got its trunk invariably involve an event that happened to a single grown animal, with the trait continuing from there.
I read some of the stories today. I agree with this take.
Upon re-reading this excellent essay (yes, well worth the re-read), I was struck by the sentence: “To label something as dysregulated or non-adaptive is as much an evolutionary claim as labeling something as adaptive.“ As you say, since their claim is actually more extraordinary than an adaptationist claim, the burden of proof is on them to elaborate on their claim. They may protest that evolutionary hypotheses are out of bounds as being mere guesses, but do they have anything better to offer? At least with a hypothesis, as opposing to mere handwaving in ignorance and frustration, there’s at least a path for further searching and testing. There’s a wonderful sentence, “It is the gift of theory that helps us realize what needs explanation,” under the heading, “How to Identify Darwinian Puzzles Worth Solving”—page 33 in the book, The Triumph of Sociobiology (2001) by John Alcock.