The New York Times has an interesting article about how sequencing the human genome has led to very few cures.
Ten years after President Bill Clinton announced that the first draft of the human genome was complete, medicine has yet to see any large part of the promised benefits.
For biologists, the genome has yielded one insightful surprise after another. But the primary goal of the $3 billion Human Genome Project — to ferret out the genetic roots of common diseases like cancer and Alzheimer’s and then generate treatments — remains largely elusive. Indeed, after 10 years of effort, geneticists are almost back to square one in knowing where to look for the roots of common disease.
But what the Times and maybe many scientists fail to grasp -- and what Ray Kurzweil would be quick to point out -- is that genetic medicine is still on the flat part of the exponential growth curve. If you examine the green line on the chart below (which represents exponential growth) you will see that it begins very flat. This flatness is an illusion of scale, and as progress is made down the curve the slope steepens eventually and surpasses the linear and quadratic curves.
The benefits of technology follow an exponential curve. It is a mistake to judge the results of the Human Genome Project before we reach the elbow in the curve.
Additionally, I will add that what appears to have been quite a surprise to many medical researchers is no surprise to me at all.
It was far too expensive at that time to think of sequencing patients’ whole genomes. So the National Institutes of Health embraced the idea for a clever shortcut, that of looking just at sites on the genome where many people have a variant DNA unit. But that shortcut appears to have been less than successful.
The theory behind the shortcut was that since the major diseases are common, so too would be the genetic variants that caused them. Natural selection keeps the human genome free of variants that damage health before children are grown, the theory held, but fails against variants that strike later in life, allowing them to become quite common. In 2002 the National Institutes of Health started a $138 million project called the HapMap to catalog the common variants in European, East Asian and African genomes.
With the catalog in hand, the second stage was to see if any of the variants were more common in the patients with a given disease than in healthy people. These studies required large numbers of patients and cost several million dollars apiece. Nearly 400 of them had been completed by 2009. The upshot is that hundreds of common genetic variants have now been statistically linked with various diseases.
But with most diseases, the common variants have turned out to explain just a fraction of the genetic risk. It now seems more likely that each common disease is mostly caused by large numbers of rare variants, ones too rare to have been cataloged by the HapMap.
Old (Wrong) Theory: Most common diseases are caused by a few localized, common, genetic variants. Implication: the human genome is generally in a stable equilibrium that is occasionally disturbed by small numbers of large genetic failures.
New (Right?) Theory: Most common diseases are caused by a large number of small problematic genetic variants. Implication: the human genome is generally unstable and all these genes that we think aren't doing anything are actually quite important. Small variations in these "supporting" genes cause the unstable equilibrium to break down. Human life is like a water tower that collapses if you remove enough cross-beams, even if you don't touch the uprights.
It's no surprise to me at life is an unstable equilibrium, and the only reason I can think of for biologists to assume differently because the theory of evolution completely breaks down if genetic viability isn't inherently stable. (Or so it would seem to me.)