Medicine can’t beat them; can it join them?

As I was re-reading Jerry Coyne’s Why Evolution Is True the other night, an aside about bacterial resistance to antibiotics set me to thinking. It’s well known, and to be expected from evolutionary theory, that bacteria—and other pathogenic organisms, such as viruses and eukaryotic parasites—tend to evolve resistance to the drugs designed to wipe them out. It’s fairly obvious: Those drugs exert an extreme selection pressure, as strong as we can make it…thus if the variation exists to produce resistance, we’re positively selecting for it and are guaranteed to end up with it in the end.

As Coyne also pointed out, the response is pretty variable: Diseases like polio and measles haven’t seemed to evolve any resistance at all, while common flu strains evolve so quickly that every flu season is a gamble, where the vaccines available are but a best guess as to what will crop up next. HIV takes the prize as the grand champion of rapid evolution: It evolves so quickly inside each carrier that it eventually evolves its way around the immune system.

This of course reminded me of Orgel’s Second Rule: Evolution is cleverer than you are. As long as medical scientists invent drugs to eradicate pathogenic organisms, they will be exerting selective pressures and will tend to select for resistance. I don’t see that there’s a feasible way around this—short of a drug so astonishingly good that it is always 100% effective (even in the face of imperfect patient compliance!), or a set of rotating drugs so large that no strain can evolve resistance to all at once, it seems impossible; and those conditions seem extremely implausible.

So I wonder, how much medicine is being done that is not only aware of evolution (and the dangers it causes in adaptation to resist drugs), but actually uses it? What follows is very speculative—I’m no biologist or medical expert; I’m just thinking out loud, wondering how much of this is done or has been done; and if not, then why.

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One example of a strategy that harnesses evolution would be to design phages. A phage (or bacteriophage), if you don’t know, is a virus that infects a bacterium. This may sound like a rare and exotic sort of being, but phages may well be one of the largest groups of organisms on Earth. Phage therapy makes a sort of intuitive and beautiful sense: Instead of giving a patient a drug that may operate on the basis of differential toxicity (it will damage the bacteria a lot more than the patient), give them something that is absolutely specific to the infectuous agent. (In fact, if Wikipedia is to be believed on this, phage therapy is so specific that this is actually one of the problems: Each phage targets a very specific strain of bacteria, so if the infectuous strain is different…)

But it seems to me that there’s room for so much more. Now that we stand at the early dawn of the age of genetic engineering, perhaps a time will come when phages can be designed to target pathogens for which no useful phages are known. And if the phages we have access to are less than ideal, then why should we not selectively breed them? If we have a disease for which all of Koch’s postulates hold, for instance, and we can retrieve the real, infectuous strains and grow them in culture, then surely we can use those cultures as growth media for phages—evolving phages better able to attack those strains. By wiping out the bacterial cultures and growing subsequent generations of phages on bacteria that lack exposure, the bacteria will have no opportunity to evolve resistance, and we should be able to essentially breed phages to wipe out whatever bacteria we like.

Of course, eventually resistant strains would spread throughout the population. But so what? It’s no big deal. We’d just isolate those strains and selectively breed our phages to target them.

I don’t know whether anything similar could work against viruses. Viruses don’t metabolise, so virophages are pretty damned rare (I’ve only ever heard of one). Are there bacteria that eat viruses? If so, those bacteria could presumably be selectively “bred”…

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Another, more modest, evolution-aware strategy would be to deliberately select against virulence. Consider, for example, a hypothetical drug that targets some, but only some strains of flu. Specifically, it suppresses particularly dangerous strains, but is deliberately designed not to target the less harmful ones. Such a strategy would not wipe out flu, of course—but then, we couldn’t do that in the first place. What it might do is give more “benign” strains of flu a competitive advantage over their deadlier cousins. Since all strains of flu work in similar ways, they could be viewed as competitors for the same ecological niche. (I could be wrong about this; I’m speculating, after all!) If we allow a relatively benign strain to fill this niche, but do our best to keep the deadlier version down, then we basically co-operate with the more benign flu at the expense of the more dangerous one. There will be a selective benefit in being benign.

(The inspiration for this speculation is actually evolution in HIV. HIV tends to spread pretty slowly—its epidemic proportions may not make it seem that way, but you really can’t spread HIV as quickly as you can spread a cold. A sneeze just hits more people than—Let’s just say that airborne diseases can spread more quickly. As a result, a strain of HIV that caused the carrier to drop dead within the week would never get off the ground; it would spread more slowly than it killed, which limits a disease to a small group of carriers. In other words, a disease has to spread slowly enough to infect a bunch of other carriers, and how slowly is enough depends on the disease: In case of HIV, pretty slowly. I have read, though I cannot now find a source for this claim, that some widespread strains of HIV are evolving toward slower development to full-blown AIDS, for these reasons.)

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I harbour no illusion that any of this is revolutionary to anyone at all professionally competent in biology or medical science—I am at best a reasonably well-read layman. But the notion of evolutionary strategies in medicine are intriguing to me, and I really do wonder how much is being done, how much has been done, how much can and will be done with it. For now, I merely jot down these thoughts and speculations. When I have a little more time, I should do some digging and some reading to see what’s out there.