02
Dec
09

Genetics backlash

Uh-oh. I ran across a couple of articles yesterday that are indicative of what I’d call a backlash about genetics that has cropped up over the last couple of  years. Let’s just say that after the enthusiasm generated by the Human Genome Project and the establishment of a number of personal genomics companies, the bloom is off the rose. After all the high expectations for genomics earlier this decade, there is a lot of disappointment right now.

David Freedman’s article in last month’s Fast Company is titled: “The Gene Bubble: Why We  Still Aren’t Disease Free.” (The term “disease free” in the title perhaps shows how exaggerated the expectations for miracles from genetics have become.) The article describes how biotech companies and investors were ardently hoping that decoding the human genome would lead to specific genetic markers that would provide shortcuts in the process of developing drugs for companies desperately seeking an alternative to the drawn-out, expensive process of testing huge numbers of compounds for drug candidates.

But, Freeman points out, that’s not how things have worked out so far. Only a handful of therapeutics have come forth that can be directly linked to genomic evidence, and many of the companies that were founded on the prospect of genetic paths to products have gone out of business, been bought up, or gone to other approaches. Instead what we’ve found is that virtually all complex diseases have many genetic associations, none of which is a keystone to the illness, and additional complex mechanisms are involved in gene expression.

Freeman quotes Bryan Walser, CEO of gene-discovery company Perlegen Sciences, as he sums up his perspective:

Gattaca got it totally wrong… In the movie, genes have 100% penetration,” meaning that if you have a flawed gene, it’s certain you’ll get the disease it’s associated with. For most major common diseases, he explains, specific genes are almost never associated with more than a 20% to 30% increased chance of getting sick. Indeed, the notion that a small number of genes represents a large component of the risk for a particular disorder has simply turned out to be untrue for almost all major illnesses. And the weakness of these correlations extends to other attributes as well. The gene most strongly linked to intelligence accounts for less than 0.4% of the observed variation, while the top six intelligence genes together predict 1% of the variation. A 2009 study of about 6,000 people came up with a technique for predicting a person’s height by looking at the 54 height-related genes; the results turned out to be one-tenth as accurate as averaging the heights of both parents and adjusting for sex, a technique introduced in 1886 by statistician Sir Francis Galton.

There’s a “we’ve been had” tone to this article, not unlike the backlash against the machinations on Wall Street in the last couple of years. Freeman lays the blame for overselling genetics projects on life science companies that wanted shortcuts to profits paid for by taxpayers and to scientists who wanted to sustain themselves on a pipeline of government research grants. That’s all a bit too conspiratorial for my tastes, and it’s a perspective that comes with the clarity of hindsight. The Human Genome Project and a lot of its proffered benefits also reflect the state of knowledge — or lack thereof — at the time they were proposed. The complexity we now see reflects a lot we’ve learned from tools and techniques of quite recent origin. As has happened a number of times in life science history, we’ve learned that the fundamental processes of life are a lot more complex that we imagined.

More about this matter in the next post.

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