Why genetics is so far a boondoggle.

Health and medicine explained.
Oct. 18 2005 1:05 PM

The Disappointment Gene

Why genetics is so far a boondoggle.

Celebrating the sequencing of the human genome five years ago, President Bill Clinton declared the decipherment of its 3 billion base pairs "the most important, most wondrous map ever produced by mankind." Enthusiasts promised that the genome project heralded an era of personalized medicine. By 2010, predicted Art Caplan, the University of Pennsylvania bioethicist, the "age of one-size-fits-all drugs" would be replaced by an era of "designer drugs" targeted to different biological groups. Soon we would all have records of our own DNA, enabling physicians and counselors to program what we ought to eat, where we should go to school, what kind of life insurance we should buy, and what antidepressants we might use.

In five years, the genome has indeed transformed biological research. Thanks to vast quantities of new genetic information, scientists are revealing unimagined complexity in the molecular workings of the body. Precisely because of this complexity, though, much of the data have little immediately useful meaning, and the research has produced only a trickle of medicine. The drug industry submitted 50 percent fewer applications to the Food and Drug Administration in 2002 and 2003 than in 1997 and 1998, despite the fact that biotech research investment doubled between the two periods.

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But where the angels of established medical science fear to tread, a new industry has arisen. Several companies now offer genetic scans, some available at a supermarket near you, that claim to provide all you need to "take the guesswork" out of living. So, let's get started: In the words of Sciona, a leading "nutrigenetics" company, "It's time to discover The Science of You!"

The Web site of Great Smokies Laboratory of Asheville, N.C., which sells its Genovation "profiles" through alternative practitioners, promises that "seeing the results of your Genovations test is like seeing the cards you've been dealt by Nature." Sciona, a British company that recently moved to the alternative-lifestyles mecca of Boulder, Colo., sells "nutrigenetics" kits, with information on heart, immune system, bone health, endocrinal, and "detoxification" genes. After sending in a cheek-swab sample of DNA, you receive a booklet describing several of your gene variations and their meanings. What can be divined from these double-helixed tea leaves? A 97-page mock-up of a model profile that Sciona showed me (cost: about $500) provided the following advice to "John Doe" based on Sciona's readouts of 34 DNA variants: Eat your vegetables, get exercise, take some vitamins, and lose a few pounds. This your mom also can tell you; Sciona co-founder Rosalynn Gill-Garrison admits as much. The difference, she says, is the magical aura surrounding genetic information, the sense of finality that comes with that knowledge—however partial and even distorted.

Some of the offerings are more tailored,though certainly not more credible. GeneLink, of Margate, N.J., will do your "nutragenic and dermatagenic profile" and direct you to particular skin-care products. Another outfit, Imagene, founded by former University of Texas pharmacologist Kenneth Blum, offers DNA testing for children with "disruptive and addictive personalities." Once the $275 test kit has confirmed that your child has "dopaminergic related Reward Deficiency Syndrome," you can buy a month's supply of pills for $60, along with a $30 oral spray that provides up to two hours of relief from unspecified "cravings."

As snake oil goes, these offerings are mild compared with the product that some biotech companies were putting out to investors a few years back. For a precautionary tale of genetic hype, it's hard to beat the story of Human Genome Sciences, created in the 1990s by William A. Haseltine, a Harvard AIDS researcher. Haseltine had a partnership for several years with Craig Venter, an erstwhile computer brainiac at the National Institutes of Health, to begin sequencing and submitting patents on thousandsof pieces of DNA. To listen to Haseltine was to believe that he had discovered a gold mine. His work, he said in 2000, "speeds up biological discovery a hundredfold, easily. Easily." He talked of finding in genes "the fountain of youth" in the form of "cellular replacement" therapies. Investors rewarded Haseltine with more than $1 billion in 2000. The drugs bombed out early in clinical trials, the stock plummeted, and Haseltine decamped with his millions to become a philanthropist. Three other big genomics companies—Incyte, Celera, and Millenium Pharmaceuticals—also failed to spin genetic discoveries intodrugs.

To be fair, all four are still trying, and drug development takes time. But the failed promise thus far points to the hubris of a simplified view of genetics. Certain powerful genes cause disorders like cystic fibrosis and Tay-Sach's disease. But one-gene diseases are rare, as you may remember from high-school biology; in our primitive past, most humans who carried them died before child-rearing age. (Click here for an explanation of why some of these genes persist.)

Assiduous readers of newspaper science columns will remember the stream of announcements in the 1990s of the discovery of genes "for" everything from impulsive behavior to schizophrenia to heart disease and cancer. (Not to mention the so-called gay gene.) In the fine print, the authors of those studies made clear that they thought the genes they'd located made only small contributions to the condition in question. But even those limited effects failed to hold up in most cases. A recent literature review by Joel Hirschhorn, a geneticist at the Broad Institute in Boston, found that only six of the 166 initially reported associations of genes with a disease or trait had been replicated consistently. It may turn out that many inherited diseases aren't connected to genes at all. The genome project itself showed why this is so. Some geneticists guessed, based on the number of RNA transcripts discovered by the late 1990s, that there were as many as 150,000 genes in the human genome. Genomic companies like Incyte patented many of those transcripts. But the number of genes has proved to be closer to 20,000. A lot of the RNA transcripts, it turns out, play other roles in the cell that are only partially understood. Genes, per se, don't provide the whole biological, and therefore medical, story of inheritance.

New gene-hunting methods involve searching for DNA variations over the entire genome. Within a year or two, for example, scientists will have a catalog of 10 million single nucleotide polymorphisms, or SNPs, which are variations in DNA base pairs at particular stretches of the genome. The hope is that by mapping out these variations, scientists will find similar patterns in people who have predispositions to certain diseases. These variations will lead the way to more genes that make subtle contributions to disease.

Few doubt that SNPs and other collections of biomarkers will help find some meaningful genetic links to illness. But their value for the utopian future of personalized medicine is far from clear. If genetic "errors" occur in common parts of DNA across the human species, thenSNP collection will help us find those errors. But if each subgroup of humans—from Pima Indians to Mongolian shepherds to Icelanders—has a unique way, say, of becoming vulnerable to Alzheimer's, then no matter how many SNPs we collect, it will be difficult to find key genetic variants that we can test for—or treat. The optimistic view is that SNPs and other data collections will locate common genes that contribute to common sources of suffering. But it will be years, if ever, before a comprehensive genetic screen could tell you how specifically to stave off a particular condition. For the foreseeable future, environmental effects will swamp the visible genetic ones. That is, no matter what your genotype is, the best health advice is to eat well and not overmuch, get exercise, and stop smoking. And in general make love, not war.

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