Peering Into the Future

Testing is just one piece of the genomic revolution. A major goal is to create new sophisticated therapies that home in on a disease's biological glitch, then fix the problem. Already, genes are helping to predict a patient's response to existing medications. A prime example in this field of pharmacogenetics, says Dr. Wylie Burke of the University of Washington, is a variant of a gene called TPMT, which can lead to life-threatening reactions to certain doses of chemotherapy. A genetic test can guide safe and appropriate treatment. Two genes have been identified that influence a person's response to the anti-blood-clotting drug warfarin. And scientists are uncovering genetic differences in the way people respond to other widely used medications, like antidepressants.

Knowing a patient's genotype, or genetic profile, may also help researchers uncover new preventive therapies for intractable diseases. At Johns Hopkins University School of Medicine, Dr. Christopher Ross has tested several compounds shown to slow the progression of Huntington's in mice. Now he wants to test them in people who are positive for the Huntington's mutation but have not developed symptoms--a novel approach to clinical drug trials, which almost always involve sick people seeking cures. "We're using genetics to move from treating the disease after it happens," he says, "to preventing the worst symptoms of the disease before it happens."

Early on, the targets of genetic medicine were rare, single-gene disorders, like sickle-cell anemia and Tay-Sachs. Now it's time for the big guns--genetically complex but common conditions like heart disease. A number of genes have already been linked to such illnesses, but many more are at work. The human-genome project, which defines the 99.9 percent of DNA we all have in common, was the starting point. Act II: the "Hap Map"--a genetic atlas completed last year that zeroes in on the .1 percent of DNA that differs among individuals. The Hap Map is proving to be a boon to scientists, allowing them to scan whole chunks of DNA, rather than single genes, to isolate mutations responsible for disease. Already, the Hap Map has helped scientists uncover several gene variations that contribute to macular degeneration, the leading cause of vision loss in older people. At Harvard, Dr. Rudolph Tanzi is using the Hap Map to track down gene mutations that cause the common, late-onset form of Alzheimer's, which could strike as many as 16 million Americans by the year 2050. Tanzi's work is funded by the Cure Alzheimer's Fund, a nonprofit that is investing $3 million to unravel the Alzheimer's genome, which it hopes to complete by the summer of 2008. Tanzi says a prototype genetic chip to test for the disease could be available within five years. Dr. Eric Topol, of Case Western Reserve University, is hunting down genes that predispose people to heart attacks.

Private companies, interested in developing drug therapies, are investing in DNA as well. In Iceland, deCode Genetics has pinpointed a gene mutation for type 2 diabetes called TCF7L2. One copy of the mutation increases an individual's risk by 40 percent, two copies by 140 percent, says CEO Kari Stefansson. Stefansson says he expects a genetic test will be available as early as next year. And a joint effort by NIH and Pfizer, announced earlier this year, is searching for genes for a host of diseases, including schizophrenia, bipolar disease and severe depression.

As science advances, business follows. Today genetic testing usually takes place in specialized clinics, where patients undergo thorough counseling both before and after testing so that they--and other family members--understand the emotional and practical implications that might arise. But do-it-yourself online testing companies, advertised directly to consumers, are springing up on the Internet. Ryan Phelan, CEO of DNA Direct, founded in 2004, says her site provides a "virtual genetics clinic," making testing as easy as sending in a cheek swab. (Cost: anywhere from $200 to $3,300.) DNA Direct provides counseling and does not sell remedies after results are in. But other companies are not so scrupulous, marketing tests that have little to no scientific validity, then pushing products as therapy. Critics say they need more oversight. "What you have here," says Dr. Adam Wolfberg, of Tufts-New England Medical Center, "is a real blurring of the lines between medical testing and product marketing."

Scientific revolutions must be tempered by reality. Genes aren't the only factors involved in complex diseases--lifestyle and environmental influences, such as diet or smoking, are too. And predictions about new tests and treatments may not come to pass as fast as researchers hope--they may not come at all. Still, it's hard not to get excited about the future, especially when you consider the medical competition now underway: NIH has challenged researchers to come up with a method, within the next 10 years, to sequence a single human genome for $1,000 (today's cost: $5 million to $10 million). Assuming it works, one day not too far in the future, each of us will go to the doc, hand over our blood and get back our personalized biological blueprints. "It's an astounding curve to be riding," says Collins. Hold on to your DNA.

With Anne Underwood and Jonathan Mummolo

© 2006