Tuesday, October 11, 2011

Arthashastra and Antibiotics: Alternative approaches to disease control

The latest news in the public health sphere in India is the fear of a new antibiotic-resistant "superbug"- namely the NDM-1 gene http://bit.ly/rdihtz.

In many ways, this is the latest illustration of how we may need to try alternative approaches to the field of communicable disease control.

First, the context: "Superbugs" are newly evolved species of bacteria that are antibiotic-resistant. To defeat the menace of superbugs, we need to understand what fundamentally leads them to arise.

The answer is antibiotics itself! In essence. the mechanism is as follows: "Simple" forms of bacteria infect us, and if their effects are malign (not all bacteria are harmful to human beings), we seek to treat them with antibiotics.

The use of these antibiotics effectively causes the evolution of superbugs.

Now, it so happens that the rate of bacterial evolution is high. The "rate" of evolution is governed by 2 things- how often an organism mutates (scientists still do not understand what governs this) and how efficient natural selection is in weeding out "bad" mutations ("Bad" here refers only to the ability of the mutated organism to survive and reproduce, not to its effects on other organisms)

We don't have control on the first mechanism (that is, the rate of mutation)- it so happens that bacteria mutate really fast. But in using antibiotics, we are ensuring that "weak" or "bad" mutations are weeded out even more efficiently.  In other words, we are helping the superbugs develop faster!

Another way to explain this is to say that our use of antibiotics makes bacteria "want" to develop antibiotic-resistant forms (this is the shorthand that we often use, which is misleading since evolution has no agency, or purpose- it just is. But using this shorthand helps us understand the phenomenon better)

This is an arms race that we are condemned to lose- for example, the rampant use of methicilin  to treat staph infections led to the rise of MRSA (methicilin resistant staph infection), the use of vancomycin to treat MRSA then has led to the the evolution of VRSA (vancomycin resistant staph). We are chasing a moving target, one that moves much faster than we can.

But then, what choice do we have? Clearly, the answer cannot be to leave bacterial infections untreated.

An alternative approach is to actually help the evolution of less malign bacteria- to come to some kind of mutual accommodation with bacteria rather than look to vanquish them.

Let me use a concept from Kautilya's Arthashastra (the seminal text on the use of pragmatic realpolitik to achieve one's strategic goals) to illustrate the point.

In Arthashastra, Kautilya delineates 4 ways to deal with any adversary- "sama" (use of logic or argument), "dama" (gift, bribery or blandishment), "bheda" (sow dissension or confusion) and "danda" (use of force)

Fundamentally, our way of dealing with bacterial disease control is "danda"- destroy the adversary with force.

Now, that is a smart strategy only if the power asymmetry is disproportionately in your favor, and the costs of using force are low.

This is clearly not the case with the use of antibiotics.

So why not try an alternative approach- one inspired by "dama"? Can we bribe our way towards more benign forms of bacteria?

One radical approach in disease control (pioneered by the evolutionary biologist Paul Ewald) actually is looking to do that.

The basic concept to understand is on how diseases spread. Some diseases, like a common cold, are deliberately not virulent- the reason is that by not debilitating you severely, it can keep you up and moving, sneezing all the way so that you can infect other people (translation: help it survive and reproduce). Other diseases such as African sleeping sickness or malaria are virulent since by incapacitating us it increases the probability of its own spread (since the mosquitoes that spread it from one host to another can get to you easier if you are pushed to the brink of death and are unable to move).

So in many ways, the degree of virulence of a disease is determined by the modes of transmission.

Hence, if we were to attack not the disease directly, but the modes of transmissions, we can effectively bribe the infections towards lower virulence.

For example if we spend our medical research money, not on developing antibiotics, but on cleaning water supply or on providing mosquito nets, there is evolutionary pressure on the infectious agents to move towards lower virulence, since for their own spread they need us to be moving around. History also suggests this- when cholera outbreaks spread from Peru to Ecuador (where the water supply was poorly protected), the bacteria became more virulent; when it moved to Chile (where the water supply was much better protected), it became less virulent since it needed people to be alive and mobile, in order for it to spread. (Source: Survival of the Sickest by Sharon Moalem)

Effectively this is a policy of accommodation with the infectious agents- we will not fight you, we will cooperate with you to help you spread, but you need to make your effect on us more benign! By bribing them thus, we may have a far better chance at survival.

I was thinking about this also when I was watching the movie "Contagion". Communicable disease control is really hard- the movie brought out the point not only of the large scale destruction that a single "Black swan" (low probability, high impact) event can bring about, but also that even after a "cure" is discovered, the time to market is so high due to the stringent requirements on testing by the FDA, as also the scale of production and distribution required.

We need multiple approaches to deal with this problem, and the wisdom from the Arthashastra of how deal with adversaries may have useful pointers on what kind of approach we may consider!

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