The dawn of Darwinian medicine

Following reference 1, I have been reading a paper from the dawn of Darwinian medicine, the paper of that name of reference 2. One of the founding papers of the discipline, thirty years old now, but still a good read. 

The argument being that the medical sciences had been focussed on the proximate causes of physical diseases, when a look at the ultimate evolutionary causes might have been helpful. The paper ending with a plea for evolutionary matters to be given a place in medical syllabuses, a plea which, if reference 3 is anything to go by, has not gone unheeded.

All this by way of providing me with background to another old paper of more immediate interest to me, the one about depression at reference 4. On which more in due course.

The starting point of the adaptationists’ approach is the observation that any (not necessarily human) trait which is widespread across the world is likely to have been the result of selection. The trait, perhaps a long time ago, was adaptive for something. It survived because one did better with it than without it. It was a response, an answer to some life problem or other. In short, an adaptation. Selection would have eliminated traits which caused harm. 

This last elimination does not, however, include traits which cause harm in one context but good in another. Such a trait might be the best design compromise that selection can find for the complicated chunk of machinery called a human being in this or that tricky situation. For example, humans and some apes have lost the ability to metabolise uric acid – which, as uric acid is good at garbage disposal, is good for longevity – but bad for gout, caused by excess of same uric acid.

A corollary to all this is that most traits have functions. So, for example, the snouts of sharks and some other fishes include an odd feature called the ampullae of Lorenzini. It turns out that their function is to detect electrical emanations of prey, which might, for example, be hiding under the sea bed sand. With there having been an interesting dialectic between why the ampullae were there at all, what they did and how they did it. I associate to my father’s ponderings about the dialectic between structure and function both more generally and from a dental point of view, back in the 1930’s, ponderings which meandered on certainly until I was old enough to remember about them.

The paper goes on to demonstrate of how evolution, adaptation and selection interact with physical disorders, many of these last being the result of infections and others the result of old age. With many unpleasant symptoms – such as inflammation, vomiting and coughing – being defences rather than disorders, so if you splat the mechanism in question, perhaps with chemicals, you lose the defence along with the discomfort.

In section II, we get a substantial Table 1 listing about 25 cases, drawn from Volume 42 of the journal ‘Evolution’, where the adaptationists' approach has made predictions, mostly confirmed. The two I checked, seemed to check out, with one of the two being the snakes mentioned below.

In section III, we get a much smaller Table 2 listing heads which can be used to suggest the approach to any particular phenomenon in the world of infectious diseases. We are given examples under each head – with quite a lot of space being given to the possible dangers of blocking unpleasant symptoms, which may also be host defences. All this being summarised in the figure above.

Complemented by section IV on the tricky interactions between hosts and parasites.

The three sections following look at disease from three more points of view: more or less accidental damage to the body; problems caused by genes; and, lastly, problems caused by our rapidly changing external environment.

Then in the closing section VIII the authors summarise by saying that: ‘… Walking upright has a price in back problems. The capacity for tissue repair has a price of cancer. The immune response has a price of immune disorders. The price of anxiety is panic disorder. In each case, natural selection has done the best it can, weighing benefits against costs. Wherever the balance point, however, there will be disease. The adaptationist does not view the body as a perfect creation, but as a bundle of compromises. By understanding them, we will better understand disease…’. 

In which, by way of a short hand, natural selection is portrayed as an intelligent agent. Which short hand many eschewed, preferring more concrete, more proximate explanations. Which might help explain why Darwinian medicine took a while to catch on.

Some odds and ends

The authors turn over all kinds of interesting examples and material. There is, for example, good evidence that eating well when young might improve reproductive fitness but may well also reduce your life expectancy.

An example of adaptation at work was the size and position of eggs in aquatic as opposed to terrestrial snakes, the method of locomotion of the two varieties being different in an egg relevant way. See reference 5 for the details.

We need also to remember that most common traits in humans probably emerged in the Stone Age – or earlier – when conditions were rather different to those now, when the cost-benefit equations might have given a different answer.

I read something of the complicated interactions between hosts and parasites, particularly those involving very small parasites, bacteria and viruses, which reproduce, mutate and evolve very quickly, even within their time in a single host. Very much a topical matter, given the COVID pandemic. As evidenced by reference 6 – sadly incomprehensible to me.

I had been an adherent of the line that such small parasites generally evolve to a state of mutually beneficial symbiosis with the their hosts, dead hosts not being much use to them at all. I now learn that this is not, in general, true. Although perhaps more true in the case of parasites transmitted by person to person contact than in those transmitted by intermediating vector.

Noting here that there are plenty of bacteria on the surface of and more particularly in the cosier environment of the various orifices of the human body, most of which, particularly those in the gut, do not count as parasites. The relationship is indeed one of symbiosis. Thinking with my fingers, I dare say the divide between the two categories is rather fuzzy at the margins.

Natural toxins, most of which come from plants, are a mostly a different kind of war, conducted at a different pace, between plants and the herbivores that want to eat them. Many toxins are bitter in taste, giving humans some defence against them. Later on, we come to know which plants contain toxins, possibly how to deal with them, possibly leaching the toxins out, leaving the useful food behind. Think olives and manioc (or cassava).

In the past, I have often used ‘adaption’ instead of ‘adaptation’. As far as I can make out now from OED, the latter is more correct, the former a convenient shorthand, possibly prompted by the derivation of adoption from adopt.

An unrelated oddment

[An information bearing diagram from reference 7. From the Circos of reference 8. Key follows]

[Key to the diagram above]

It so happened that something on the gene rather than the evolution path turned up a couple of days ago, that is to say advertisement from Medscape of reference 7. From which I learn that maybe 1 in 500 men have an extra sex chromosome, either X or Y, and that this confers a substantially increased risk of contracting various common diseases, including type 2 diabetes, venous thrombosis, pulmonary embolism and chronic obstructive pulmonary disease. With the extra X, aka KS for Klinefelter syndrome, making subjects prone to various reproductive disorders. Of interest to me in that I only recently learned that we don’t all have the same number of chromosomes.

Conclusions

The adaptationist approach to physical disorder and disease in humans does seem to be helpful. With this more or less on board, time to return to reference 4, to find out how adaptation plays there. Does it play as well with mental, as with physical disorders? How does the argument presented here map across?

We also have a handy and accessible introduction to some of the nuts and bolts of evolution.

References

Reference 1: https://psmv5.blogspot.com/2022/07/mourning-form-and-content.html. 

Reference 2: The dawn of Darwinian medicine – Williams GW, Nesse RM – 1991.

Reference 3: https://en.wikipedia.org/wiki/Evolutionary_medicine.

Reference 4: Is Depression an Adaptation? – Randolph M. Nesse – 2000.

Reference 5: Constraints on reproductive investment: a comparison between aquatic and terrestrial snakes – Richard Shine – 1988.

Reference 6: Study on the virulence evolution of SARS‐CoV‐2 and the trend of the epidemics of COVID‐19 - Mengyue Wang, Jiabiao Yi, Wen Jiang - 2022. Authors from China who appear to be engineers of some sort rather than medical people.

Reference 7: Detection and characterization of male sex chromosome abnormalities in the UK Biobank study - Yajie Zhao, Eugene J. Gardner, Marcus A. Tuke, Huairen Zhang, Maik Pietzner, Mine Koprulu, Raina Y. Jia, Katherine S. Ruth, Andrew R. Wood, Robin N. Beaumont, Jessica Tyrrel and others – 2022.

Reference 8: http://www.circos.ca/. The horse’s mouth as far as Circos plots are concerned.