Evolution as medicine

Recently, I’ve encountered two ways in which evolutionary principles can be applied to medicine. Rather than using brute force to kill pathogens, these are more subtle, systemic approaches.

Viruses and bacteria evolve, just like all other living creatures. The difference is that they do it really fast. This means we can use evolution as a way of manipulating them. In the first story, we alter the environmental pressures that they live under, forcing them to adapt accordingly. In the second, we apply the rapid evolution of one microbe (viruses) to counter the the rapid evolution of another (superbugs).

Anyway – here’s the two stories:

1. By controlling the environmental conditions in which pathogenic organisms grow, we can, in principle, exert limited control over their evolution.

In order to be transmitted, some pathogens require a live, or even an active host. For these pathogens, there is evolutionary pressure towards non-lethal or lower intensity infections – infections that keep the host mobile and able to spread the pathogen. Others do not rely on host transmission, and in their case, there is evolutionary pressure towards the full exploitation of the host; that is, high intensity infections that take full advantage of the host as an incubator and food source.

Two examples of these pressures exist and have been studied:

• Cholera can be transmitted through several mechanisms, including water. Of these, water is the only one that doesn’t rely on an active host. Therefore, it is expected that cholera samples taken from a population with high water quality (where disease transmission must occur through active hosts). This effect was demonstrated through the analysis of samples taken from a cholera epidemic in Latin America in the 1990s. Samples of the disease taken from Ecuador (where water quality is low) produced more toxins than those taken from Chile, where water quality is comparatively high.
• Malaria transmits into humans through mosquito bites. Furthermore, the immature parasite is picked up again by mosquitoes through biting infected humans, where it grows, and is eventually injected, mature, into another human host. By protecting those seriously ill with malaria from being bitten again, more intense variants of the disease can be intercepted, and only less intense variants of the disease are transmitted. This was studied in Tennesee in the 1930s & 1940s, when the construction of hydro lakes led to widespread malaria.

This approach does little to prevent disease, but does a lot to reduce its intensity.

Ref: TED talk 2007, Paul Ewald – ‘Can we domesticate germs?’

2. Use viral evolution to counter bacterial evolution of resistance to antibiotics

A major medical problem facing the world today is increased bacterial resistance to antibiotics. It’s generally accepted that the unnecessary use of antibiotics to counter mild infections, and, more importantly, to promote animal growth in farming has led to the rise of anti-biotic resistant ‘super-bugs’, including MRSA, resistant TB, and more. All sorts of diseases once considered controllable are becoming uncontrollable again, and people are dying from them in their thousands.

The principle behind this is simple – bacteria evolve at a rate many orders of magnitude faster than vertebrates. If we exert pressure on bacterial populations (through, say, a particular form of antibiotic), they’ll tend to evolve resistance. We’re stuck in an evolutionary race – we ‘evolve’ attacks (particular drugs), they evolve resistance. Currently, we’re much worse and much slower than the bacteria are at this, and we’re losing.

However, we’re not the only organisms that want to be able to attack and kill bacteria – there’s a whole class of viruses that prey on bacteria, including the famous T4 virus you’ll all have seen pictures of. These are called bacteriophages, and, like us, they’re in an evolutionary race with bacteria. One difference – they’re a lot better at it than we are.

Bacteriophages have another interesting property – they tend to be very specific in what they attack, most only targeting a small number of bacteria. Human cells are quite different to bacteria in many ways, and are effectively ignored by them. Given this, what is to prevent us from using them to target particular types of bacteria? Infected by medicinally resistant staphylococcus aureus (MRSA)? Try this viral cocktail..

OK – it sounds a bit far-fetched, or at least dangerous. There’s almost certainly drawbacks or risks that need to be addressed, but, as a research direction, it sounds really interesting. Several groups have been working with this therapy for quite some time, and some trials are underway. There’s even a book on the subject – Viruses vs. Superbugs.

Ref: Interview on Science Friday, April 4, 2008

I find the idea of this sort of manipulation extremely elegant – the phrase ‘playing god’ seems, to me to apply to this sort of thing even more so than it does to genetic engineering; I think of that as something more akin to hacking than the exertion of any divine powers..