The Genome Is Mapped. Now What?

It will be decades before scientists identify and understand all of our genes. But that hasn't stopped them from making dramatic discoveries

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The findings are now being prepared for scientific publication, and thus can't be revealed in detail. But Gene Logic will say that based on the genes active in this patient's cancer, antiangiogenesis drugs and most chemotherapy wouldn't work but three drugs would. Moreover, the scientists discovered that this cancer was producing enormous quantities of a particular enzyme that happens to be the target of yet another experimental drug--something to try if chemotherapy failed. The patient is now in remission.

Mounting this kind of operation for a single patient is hugely expensive--this case ran up a bill of $37,000--and the advice that works for one patient wouldn't apply to someone whose genetic makeup is different. That's why scientists at Gene Logic and other firms--Millennium Pharmaceuticals in Massachusetts and Glaxo Wellcome (both in England and the U.S.) are just two examples--are putting together databases of tissue samples to look for one-letter genetic differences. (These differences are formally known as single-nucleotide polymorphisms, or SNPs.) Fourteen drug companies and the philanthropic Wellcome Trust (not affiliated with Glaxo Wellcome) organized an SNPs consortium last year to begin building a publicly available SNP database. Both the Human Genome Project and Celera are currently sequencing the genomes of many different people, of both sexes and all sorts of ethnic backgrounds, to get a better sense of where the SNPs are.

The strategy clearly works. Last October scientists at Glaxo Wellcome announced that their patient database and SNP mapping information had yielded four genes that were promising drug targets: one each for Alzheimer's, diabetes, psoriasis and migraine. "We've already done what people are proposing to do in the future," says Roses. Glaxo isn't alone. Dozens of firms are concentrating on this subcategory of gene-based medicine, known as functional genomics.

Almost everyone agrees that the complete genome sequence is essential to functional genomics--everyone, that is, except William Haseltine, CEO of Human Genome Sciences, a firm he started with Craig Venter in 1992. "Human genome sequencing [of the entire genome] helps us understand the deep and interesting questions of how our genome relates to those of other species," says Haseltine dismissively. "But it isn't particularly practical."

Following his lead, HGS scientists are ignoring most of the genetic code and concentrating on the mRNA that puts the code into action. During the 1990s the company amassed a huge library of mRNA and used microarrays to see which of these molecular snippets was active in disease. Haseltine's scientists were able to isolate 10 proteins, made from strands of mRNA, that are active in the healing of intractable wounds. Of these, nine were discarded because they may promote cancer.

The remaining candidate, known as repifermin, is currently in FDA-approved clinical trials for patients with skin ulcers, ulcerative colitis and mucosal damage due to chemotherapy, and may be expanded to burn and smoke-inhalation sufferers. And while most scientists disagree with his iconoclastic views, Haseltine is getting results: besides repifermin, his firm has three drugs in clinical trials and expects to add two or three more next year. That puts HGS far ahead of any other company.

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