The promised breakthroughs and cures from the Human Genome Project may have been too optimistic from a timing perspective. But Wade may be too pessimistic when he writes, “Indeed, after ten years of effort, geneticists are almost back to square one in knowing where to look.”
Not really. As others in the piece say, the Human Genome Project and the HapMap project growing out of it have been essential to a better understanding of the genetic underpinning of many common diseases. The evidence is clearly with Eric Lander who says in the article, “Having a common scaffold on which one can put all the information has dramatically accelerated progress.”
But why no cures yet? Because in plotting the genetic map, we learn that each step taken teaches us more as well as opens more questions to be resolved. For example, researchers have found that what was commonly regarded as “junk” between pieces of DNA isn’t “junk” at all; it has functions that contribute to biological processes just as the DNA does. And one of the bigger surprises has been that knowing the common genetic variants isn’t enough to find the causes of disease. Researchers must track down the rare variants or mutations with strong biological effects on the disease. As Wade writes, “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.”
Yes; this is a very important finding, and one that would have been years ahead of us without the Human Genome Project and HapMap. And this positions us well to take the next steps to reduce the time for development of effective therapies. Rudolph Tanzi, PhD, head of the Genetics and Aging Unit at Mass General Hospital and primary investigator of the Alzheimer’s Genome Project funded exclusively by Cure Alzheimer’s Fund, says: “Having identified over 200 new Alzheimer’s candidate genes through the Alzheimer’s Genome Project, we can now find the ‘causal’ DNA variants in Alzheimer’s, then determine which biochemical pathways are broken as a result, and discover therapies to “fix what is broken” based on that information.”
Another recent article in the Wall Street Journal reports that “Drug Makers Will Share Data for Failed Alzheimer’s Trials” (WSJ, June 11, 2010). Why so many failures? One major reason is that many of these drugs were developed without the knowledge of these genetic processes and their biological effects.
Yes, it takes time — and much more money than has so far been dedicated to Alzheimer’s research — to discover what genetics has to teach us about the basic causes of disease. But without following that trail, the cost and the failure rate will be much, much higher.