From the NYT, a plea for not getting carried away with the vision of 'moonshot medicine' as precision engineering. The op-ed is written by Michael Joyner, a doctor at the Mayo Clinic and takes issue with Obama's precision medicine initiative which he apparently underlined in his state of the union address earlier this month. Obama's proposal is nothing new and has been echoed by proponents since the beginnings of the Human Genome Project. The idea of identifying specific genetic variants in patients and then targeting them with specific drugs seems logical enough. But as the article indicates, we have clearly spoken too soon:
The basic idea behind it is that we each have genetic variants that put us at increased or decreased risk of getting various diseases, or that make us more or less responsive to specific treatments. If we can read someone’s genetic code, then we should be able to provide him or her with more effective therapeutic and preventive strategies.
But for most common diseases, hundreds of genetic risk variants with small effects have been identified, and it is hard to develop a clear picture of who is really at risk for what. This was actually one of the major and unexpected findings of the Human Genome Project. In the 1990s and early 2000s, it was thought that a few genetic variants would be found to account for a lot of disease risk. But for widespread diseases like diabetes, heart disease and most cancers, no clear genetic story has emerged for a vast majority of cases.
Then there's the psychological aspect:
The push toward precision medicine could also lead to unintended consequences based on how humans respond to perceptions of risk. There is evidence that if people believe they are less at risk for a given disease, they feel excessively protected and their behavior gets worse, putting them at increased risk. Likewise, those who feel they are at greater risk, even if the increased risk is small, might become fatalistic, making their behavior worse as well. Then there are the worriers, who might embark on a course of excessive tests and biopsies “just in case.” In a medical system already marked by the overuse of diagnostic tests and procedures, this could lead to even more wasteful spending.
And finally, the whole idea that biology can be thought of as a linear engineering systems is fraught with flaws and uncertainty (it's also not everyday that you hear the word 'omertà'):
Given the general omertà about researchers’ criticizing funding initiatives, you probably won’t hear too many objections from the research community about President Obama’s plan for precision medicine. But I am deeply skeptical. Like most “moonshot” medical research initiatives, precision medicine is likely to fall short of expectations. Medical problems and their underlying biology are not linear engineering exercises, and solving them is more than a matter of vision, money and will.
This is not the first time that complex medical endeavors have been made to sound much simpler than what they are. The breathless initial promise of the ability of gene sequencing to directly lead to new drugs has not been somewhat dampened, but other efforts still echo this promise, most notably the Brain Initiative announced with much fanfare a few years ago. The goals of the initiative are laudable and some of the technologies that are being envisaged are fascinating, but we are still light years away in any incarnation whatever to "mapping the brain", let alone using that information for direct therapeutic intervention.
Unlike precision engineering where we are dealing with moving parts whose behavior is a matter of well-understood physical principles, the emergent chaos of biological systems is a very different matter. We should certainly not stop trying to conquer this frontier but we should also make sure everyone knows how far the horizons are. Biology is not physics.