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MAY 9, 2005
Dr. Francis S. Collins: On The Trail Of Disease Genes Collins is leading the search for DNA variations that can result in illnesses When Dr. Francis S. Collins was a hotshot gene hunter at the University of Michigan in the 1980s and early '90s, his team of researchers used to add a decal to his motorcycle helmet each time they bagged another gene. Now, even though the 55-year-old scientist has weighty responsibilities as leader of the Human Genome project and head of the National Human Genome Research Institute, he keeps on nabbing important new genes. His latest: a genetic variation that helps explain why some people are more likely than others to get diabetes. Collins still enjoys riding his motorcycle and being a hands-on gene sleuth. But what's "really gratifying," he says, is that the latest find is merely one example of an outpouring of new knowledge about biology and disease. The discoveries are being made possible by visionary projects spearheaded by Collins and his institute following the success of the earlier effort to read the entire human genetic code. The Human Genome project was "creating the foundation," Collins says. "Now it is time to put the rest of the building together." Knowing all three billion "letters" of one person's DNA won't reveal whether she is susceptible to heart disease or Alzheimer's. To comprehend disease risks, "the one-tenth of one percent of DNA that differs between people is something you want to understand in great detail," Collins says. So it's necessary to compare the genomes of different people. But it's too big a task to search all the millions of DNA differences. As one architect of the grand building plan, Collins helped launch an effort to figure out how the DNA variations are related, so researchers can search fewer of them. "It's a fantastic shortcut," he says. Among the first fruits -- in addition to the diabetes gene -- is the discovery of an immune-system gene playing a role in macular degeneration, the leading cause of blindness in the elderly. "That is one of the early home runs, and it presages a lot more to come," says Collins. Another part of the vision is painstakingly reading thousands of entire genetic codes. "If I've learned anything in the last 15 years working on the genome project, it is that you shouldn't settle for the 20,000-foot view if you can get down and look at every blade of grass," he says. To understand cancer, he's seeking funding to sequence the DNA of 250 tumors from each of 50 types of cancer. "That's basically 12,500 genome projects," he says. "It seems wildly ambitious. But it's achievable." The payoff: uncovering the biological pathways that make cells malignant. These projects are changing the way science is done. Collins believes gene-sequencing costs are poised to drop by at least a factor of 10. And the National Institutes of Health is setting up centers to screen half a million chemicals in every biological test scientists can dream up, determining which can halt an autoimmune reaction, slow tumor growth, reverse heart disease, or alter other biological systems. The database will be a vast lode of information that any researcher in the world could mine. These efforts will bring an unprecedented look at the genetic hand each of us has been dealt. "You or I should be able to have our genomes sequenced for $1,000 or less within 10 years," Collins says. Each of us may then be able to tailor lifestyles or drug regimens to boost the chances of a long, healthy life. Turning this grand scenario into reality is the most important task Collins can imagine. "This is the most compelling opportunity we have to change the equation of ourselves vs. disease."  By John Carey
BW MALL
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