Friday, 5 October 2007

Genetics' Super Summer

Date: October 02, 2007

The hunt for new genes has suddenly gone into overdrive.
Between the end of May and the beginning of September, scientists discovered telltale genetic markers that help predict the risk of nine major diseases, including breast cancer, multiple sclerosis, rheumatoid arthritis and heart disease. Some of these newly discovered markers will be used soon in diagnostic tests; others will help researchers better understand the diseases in order to invent new treatments.
"There is a new paper out every week. The pace of discovery continues to increase," says Dietrich Stephan of TGEN in Phoenix, Ariz. "It is just amazing."

Until now genetic "discoveries" often turned out to be just plain wrong upon further examination, mostly because they haven't been done in enough people to make sure the result is correct. Samples from thousands of patients are needed to make sure that a finding is not the play of chance; getting that much data used to be impossible.
Now DNA chips, tiny devices made by biotech companies Affymetrix and Illumina, allow scientists to sample the DNA blueprint for a person at 500,000 different places where differences are likely to occur, and to do so cheaply enough that tens of thousands of people can be tested. When they find a genetic variant that occurs in people with, say, multiple sclerosis, but not in those who don't, it is likely that that difference is linked to the disease.

A genetic difference is occasionally so predictive of disease risk that it can immediately be packaged as part of a diagnostic test to tell people whether they are going to get sick. Decode Genetics, a biotech company in Iceland that is running its own gene-finding experiments, sells tests for heart disease and diabetes, and hopes to market a glaucoma test too. The other use for the data is to invent drugs. Stephan, the TGEN researcher, founded a company called Amnestix in Burlingame, Calif., to develop medicines based on his discoveries of genes involved in memory disorders.

Eric Topol, the chief academic officer of Scripps Health, says the string of results this summer is "unprecedented," but warns, "we've just started this whole process. There's so much more work to be done to understand cause and effect."
It is not clear that society is ready for a flood of new genetic tests for common ailments. Myriad Genetics Salt Lake City recently started an ad campaign in major cities in the Northeast for its genetic test for flaws in a gene called BRCA. Most women with a bad version will get breast or ovarian cancer, and many take the radical step of having their breasts and ovaries removed before the disease occurs. But even with this test, which has been around a decade, commentators questioned whether people were ready to deal with being bombarded by TV advertisements.

There are going to be a lot more genetic tests, and they are going to give much muddier forecasts than BRCA. “I am very skeptical that genome-wide association studies will give us much of anything at all that will be useful for patients,” Leroy Hood, one of the pioneers of studying DNA and head of the Institute for Systems Biology in Seattle. He argues that knowing about the risks conferred by one gene are not very useful until you know what other genes play a role in causing the disease. Only then could patients know if they are really at risk.

Despite their power, the DNA chips only give scientists a limited view of the genome. They only allow researchers to look at 500,000 individual signposts scattered across 3 billion letters of DNA. Sometimes this locates a bad gene; other times, they find a marker that isn't part of the gene but is near it, allowing them to sleuth out what DNA difference is causing the disease.
A far more complete approach would be to sequence all 1 billion DNA letters and compare them. Until now, that's been impossible, but now scientists are starting to try. The Personal Genome Project at Harvard Medical School aims to sequence 1% of the genes of 100,000 people. The National Institutes of Health is funding a study that aims to sequence the genomes of up to 100 people to find genes involved in heart disease.

One use for new gene tests that is likely to come fast is in predicting which patients will be helped or harmed by a particular drug. This summer, a Pfizer AIDS drug, Selzentry, is approved only for patients who carry a particular version of an immune system gene, CCR5. The Food and Drug Administration is expected to approve more drugs only for use with people with particular genes, and is drafting guidelines for companies. Clinical Data, the latest effort from billionaire biotech investor R.J. Kirk, is being built around the idea of pairing drugs for depression and schizophrenia with gene tests.

An iffier area is predicting who will benefit or be hurt by a long-existing drug. The FDA added guidance suggesting the use of a gene test in picking the right dose of the blood-thinner warfarin, which is life-saving at the right dose but causes dangerous bleeding if a patient gets too much. Another promising area is the use of a gene test to keep from giving antidepressants to patients who might get suicidal thoughts from the medicines. But often these new findings aren't tested as rigorously. Janet Woodcock, the FDA's chief medical officer, predicts "a lot of scientific uncertainty."

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