Harriet Hall on Darwinian medicine: it is a useless endeavor?

In one of my very first posts on this site I questioned the value of “Darwinian medicine”—that area of inquiry that tries to explain disease and the behavior of pathogens as results of natural selection.  Cold viruses, for example, are supposed to make you sneeze to facilitate their spreading, while malaria parasites make you prostrate so that mosquitoes can transmit them to the next host without being swatted. We shouldn’t dismiss these as idle speculations, for we know from the case of the zombie ants that very simple pathogens can do complicated things to their hosts to facilitate the parasites’ transmission.

This is a popular area of evolutionary study, but I’ve sometimes questioned its value in helping us treat disease.  After all, how does knowing that we crave fats and sweets because they were valuable to our ancestors on the savanna help us deal with heart disease?  I find the value of the discipline more in raising interesting questions about the evolution of pathogens than in really dealing with the problems of human health.  Perhaps the malaria protist has indeed evolved to debilitate us as a way of spreading its genes.  But those speculations are difficult to test, and I’m not sure how, if confirmed, they’d help us deal with the disease.  But I can’t resist thinking that thinking about these things is fascinating, and could one day lead to medical payoffs. As we all know, pure science often has unexpected practical consequences.

In response to my questions about evolutionary medicine, David Hillis, an evolutionary biologist, at the University of Texas at Austin, gave a number of practical applications of evolutionary medicine (see his list at the link above). Most of David’s examples involved tracking disease epidemics by using molecular markers or using similar markers to identify, say, the strain of influenza most likely to cause future outbreaks.  And yes, these are useful contributions of evolutionary biology to medicine, though the flu method hasn’t worked all that well.

Darwinian medicine includes other fascinating speculations, like Margie Profet‘s famous theory that morning sickness is a way to protect fetuses from ingestion of damaging toxins by the mother, and therefore doctors shouldn’t try to prevent that nausea lest the alleviation cause birth defects.  I’m not sure where that’s led, though: do doctors now allow morning sickness to proceed untreated? (Profet’s personal story, by the way, is a sad one; you can read a precis here.)

Other studies have shown that fever might be adaptive: the body’s way of killing pathogens by raising its temperature to levels that kill infections. Work on lizards, who can cure themselves of infectious disease by basking in the sun, and hence raising their body temperature, show that preventing that basking allows the disease to persist. The adaptive strategy, then, would be for doctors not to try reducing non-dangerous fevers in their patients, but I’m not sure whether they do that.

So there are two ways to regard Darwinian medicine.  First, as a way to frame evolutionary hypothesis about disease that might be testable.  Second, as a way to cure disease.  But even understanding the first won’t necessarily lead to the second. We know with certainty, for example, the molecular cause of sickle-cell anemia, and are nearly certain how the gene for that disease (a form of beta-hemoglobin with a unique mutation) came to be in such high frequencies (see below), but that knowledge hasn’t lead to a cure or new advances in treatment.  But in other cases doctors simply might be unaware of the potential value of Darwinian analysis, in which case they should be educated in those aspects of evolutionary medicine that promise real benefit.

In a recent post on Science-Based Medicine, “Do we need ‘evolutionary medicine?,” Dr. Harriet Hall discusses the value of these endeavors. The impetus for her piece was reading the 1994 book Why We Get Sick: The New Science of Darwinian Medicine, by Randolph M. Nesse and George C. Williams. My own take on the book was that it was a fascinating read, and did help open up a new area of evolutionary thinking, though it’s early days to expect practical results. (Let me add here that Hall has been a tremendously important voice in the battle for scientific medicine versus quackery.)

Hall’s is a strange article in one respect: she argues both that many evolutionary speculations are untestable or untested, and thus constitute useless “just so stories,” but at the same time claims that doctors have already incorporated evolutionary principles into their practice.

As an example of Hall’s dismissal of evolutionary explanations, here’s what she says about Profet’s Darwinian theory of morning sickness:

This is a testable prediction and there is some evidence to support it; but there is no way to prove that this is the true explanation or the only one. They suggest that suppressing morning sickness might increase the risk of congenital defects. But there is no evidence for that. They recommend that women “respect their nausea” and remember that it may be beneficial. (It would likely decrease your survival prospects if you said that to your wife while she was throwing up for the umpteenth time!) They admit that relieving suffering is important too, but they recommend that any anti-nausea medicine should be carefully evaluated to make sure it doesn’t cause any harm. Of course, we already do that for all medications used during pregnancy. I fail to see how evolutionary thinking adds anything to the care of pregnant women. In fact, I can see how it might result in unnecessary worry and suffering.

But of course one could in principle test that explanation—if not in humans then in animals. (Has that been done? If not, somebody should do it.) That’s the only way to truly show that anti-nausea medication “doesn’t cause any harm.” And Hall says this about fever:

Should we treat fevers? Fever probably evolved as a defense mechanism: it may do something towards helping fight off the infection. Evolutionary thinking makes us ask why we developed this adaptation and whether it is wise to interfere. But do we need evolutionary thinking for this? Doctors have already questioned the need to lower a fever, recognizing that it is not the fever but the infection that needs to be treated, that fever itself doesn’t do much harm, and that lowering a fever might have adverse effects in some cases. I’ve read many discussions of those points, and nowhere did they mention wondering about why we evolved to have fevers. I don’t see that evolutionary thinking adds anything useful to the discussion. Fever is what it is, and we can study it and deal with it without speculating about how it came to be that way.

Yes, we do need evolutionary thinking for this, because it makes more doctors question the value of lowering fevers.  When you have a cold, treating the infection is useless, so maybe we should contemplate not taking fever-reducing medicine.  Such studies could be done (indeed, perhaps they have been—this is not my area of study!), and one would predict that colds would last longer in those individuals who didn’t try to reduce their fevers.  Low fever may not be harmful, but it’s still debilitating, and we need to know whether or not to treat it beyond wiping out the underlying infection.

But then Hall reverses her argument and says that doctors already appreciate the value of evolutionary thinking:

Evolutionary thinking is already an integral part of medicine and an essential element of all biology. E. O. Wilson’s description of medicine as “one of the last unconquered provinces” simply is not true. Doctors regularly think about evolution and study its effects. The evolution of drug resistance in bacteria is the best-known example but there are many others. For instance, we think that sickle-cell anemia has persisted because it only affects those who inherit the gene from both parents, while those with only one copy of the gene (heterozygotes) have an increased resistance to malaria.  G6PD deficiency causes hemolytic anemia but also offers protection against malaria.

But consider this: malaria is a credible explanation, but we can’t prove that it is the real one. Some other factor that we have not considered might be the true explanation, and malaria resistance might be a coincidence. And the malaria explanation is intellectually satisfying to those who ask “why” but it has had no practical impact on diagnosis or treatment.

I’m not sure that I agree with Hall’s characterization of doctors as deeply educated in evolution and its usefulness in medicine.  Certainly drug resistance in bacteria is something that most doctors know about (but many still give in to importuning patients and prescribe unneeded antibiotics), but that’s a rare example.  Beyond drug resistance, I doubt that most doctors know a lot about the application of evolution to medicine.

And Hall’s dismissal of the “malaria” hypothesis for sickle-cell anemia is unfortunate: there is lots of evidence that being a heterozygote for the sickle-cell gene helps stave off malaria.  These include studies of direct fitness of patients. “Normal” individuals carrying two copies of the nonmutant gene have about 85% of the reproductive output of heterozygotes carrying only one copy, because homozygotes are at higher risk for lethal malaria.  Individuals with two copies of the sickle-cell gene usually die before reproducing, because they have the illness, and their evolutionary fitness is zero. When carriers of a single copy have higher evolutionary fitness than either normal or mutant homozygotes, this heterozygote advantage (we geneticists call it “overdominance” or “heterosis”) keeps the disease gene at fairly high frequency in the population. This is one example of how evolution can’t produce absolute perfection, and indeed can lead to considerable suffering. (A beneficent God would have never allowed that mutation to occur).  Too, in U.S. blacks, who are not subject to the selective pressures of malaria, the frequency of the sickle-cell gene has decreased, just as evolutionary theory predicts (there’s also some reduction via intermarriage with whites.)  Finally, there is the remarkable concordance between the distribution of malaria in Africa and the distribution of the sickle-cell gene.

When Hall says that we can’t “prove” that malaria is the evolutionary cause of high frequencies of sickle-cell anemia, she’s asking for too much. Science can’t “prove” anything.  But the evidence is strong that the evolutionary theory is correct.  Of course, as I noted above, in this case it hasn’t helped us treat the disease.

Hall concludes again that evolutionary thinking is deeply ingrained in doctors, but also that that this thinking hasn’t helped us much:

I’m sorry, but I just don’t “get it.” Am I missing something? Am I just a contrary curmudgeon? Evolution is already an essential part of all science. Medical scientists already understand evolution and apply its principles appropriately. I didn’t see a single example in their book of any significant practical development in medical care that would not have occurred in the general course of medical science as it is commonly practiced, without any need for a separate discipline of “Darwinian medicine.” Evolutionary explanations, whether true or speculative, may satisfy our wish to understand “why,” but I can’t see that they have much objective usefulness.  Instead, they have produced at least one major annoyance: a movement that preaches to us how we ought to revert to the supposed diet of our ancestors (the Cave Man Diet, etc.).

The answer to Hall’s question is “yes,” she is being somewhat of a curmudgeon. She makes some good points in her piece—the most important being that understanding the evolutionary basis of disease or pathogen behavior may not help us find cures—but I think she’s wrong in believing that most doctors are deeply ingrained with principles of evolution. Many doctors haven’t taken a course in evolution in college, and certainly don’t learn about it in medical school. (Readers who are physicians may want to weigh in here.) And I’m pretty sure that some evolutionary hypotheses will lead to testable treatments that might not have arisen without an evolutionary viewpoint.  Just because an idea remains a speculation rather than graduating to a full blown theory with some empirical support does not mean that we’ll find a way to test it.  I haven’t given up on Darwinian medicine.