Friday, December 4, 2009

Competing causes everywhere

We've written about recent studies in which one has to do risk-benefit analysis in order to statistically determine the least (or most) beneficial treatment outcome, as in the currently hot debate about mammography. Risk-benefit concepts are a manifestation of causal complexity, in which many factors are at play.

The problem arises when a cause doesn't act alone to produce an outcome of interest, or when a factor is causally associated with more than one outcome, in which other such causes are also involved. Thus, lowering exposure to the cause may reduce the likelihood of outcome A, but increase the likelihood of outcome B.Genetic pleiotropy, in which a gene has more than one biological effect, is widespread if not nearly universal. Indeed, it is difficult even to determine all of a gene's 'functions' since even the definition of what a gene is is expanding rapidly as we learn more and realize how much more we have to learn about genomes.Biological traits are universally the result of many genetic factors interacting (signals and their receptors, genes and the transcription factors that activate or repress them, the mechanism that translates them into active protein, etc.).

Evolution works on the net result and while one manifestation of a gene's action may be favorable to survival or reproductive success, some other action of the gene may be unfavorable. Evolution takes some viable middle ground.This is one major reason why genetic causation is often so difficult to work out. It is likely why many drugs work well for their intended purpose, but have negative side effects in some people. It's why some drugs turn out not to work as well as expected on their intended target, while having a surprising Viagra effect that one might say makes hope 'rise' in other aspects of life.

In biomedical research, investigators study one disease, like diabetes, aiming to prevent or cure it. But inevitably, if they succeed, the rates of some other diseases will increase. If you've effectively dodged the diabetes bullet you’ll live longer, or be more active, or eat more, or drive more aggressively at night (because your vision’s not impaired), and so on. Each of those things increases risks of other negative outcomes.A commentary on page 1731 of the Nov 21 issue of the Lancet is by a Dr Nutt, a British doctor sacked from his position on the governments Advisory Council on the Misuse of Drugs, illustrates some of these issues. Dr Nutt stated what is rather obviously true, that "alcohol was more dangerous than many illegal drugs, including cannabis, ecstasy, and LSD." This apparently outrageous if true statement -- a threat, if implemented in regulatory policy, to every pub owner in the Kingdom! -- was simply too much.

But it's timely for us, because the fact of societal and other consequences of alcohol abuse is, along with a number of diseases for which alcohol abuse seems a clear risk factor, goes against the findings that risk of other diseases, like heart disease, seems to be reduced by alcohol consumption. And this does not include the moral side of alcohol use, which to many can even be a religious issue of abusing the body--the temple of the soul, or damage that the cost and results of drinking does to innocent family members.

Once again, we have competing causes to deal with. Were there a single standard, alcohol might be regulated like tobacco or even currently illegal drugs, given the societal harm it causes. Yet at the same time it might be prescribed as a preventive medicine. Neither science nor society has a good way of deciding how to respond to this mix of factors. This is an unavoidable dilemma, a philosophical or even existential conundrum.

Even if biomedical research were to reach its oft-hinted goal of near-immortality (yes, leading geneticists have seriously and publicly promised even centuries of healthy life as the payoff from our NIH dollars), the consequences might not be so rosy. The earth would be deeper in humans than Darwin’s estimated elephant-jammed world (in the Origin of Species). Food supplies would inevitably be threatened. There would be fights over other resources, adding violence to the causes of death and misery. New York apartments would become even smaller than the closets they are now. Psychological existence might be much worse.

Unless, of course, we colonize outer space? Though probably not, because if science is right about the universe, the same laws of complexity will operate on Mars as they do here at home. So when science has social or policy implications, it's always a balancing act.


Arjun said...

One reason I don't 'entirely' support biomedical research. The same moral quandary excised me from such a research project.

I feel as though we have an explicit tendency to ignore long-long-term dynamics. A prime example would be the global warming debate: if we are to believe paleoclimatologists, Earth's temperature has fluctuated over millions of years.

That said, we must contend right now with the impact on our lifestyles of the current supposed upward trend of global temperature, and I guess that somewhat justifies the myopia.

Ken Weiss said...

I would say that we don't hold the kind of discussion we should. What are we willing to give up, in terms of our own personal consumption, for what gain for our descendants? Since murder and mayhem and dislocation have always been (and are) part of human 'civilized' society, will serious curtailing today really make life better a century from now?

In the really long term, we're going to lose to bacteria anyway, even if they're the ones that NASA promises are on Mars (after all, we're going bankrupt to find 'life' on Mars!).

So, if we're all ant food one way or another, why give up our Hummers today? Let our grand-kids deal with life as they find it in their time. It's a viable viewpoint, even if I don't happen to share it.

I'm really just sour grapes because I missed my chance to buy cheap future beach-front property in Nevada.