[Paleopsych] Slate: The Disappointment Gene

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The Disappointment Gene
http://slate.msn.com/id/2128292

Why genetics is so far a boondoggle.
By Arthur Allen
Updated Tuesday, Oct. 18, 2005, at 10:05 AM PT

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.

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 thousands of 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 into drugs.

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, then SNP 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.

For this you should pay $500?