Improving the Use of Drugs Through Genes

You can only learn so much about your health through genetic testing. But the technology can revolutionize how doctors prescribe pharmaceuticals

By John Carey

Getting a personal gene analysis right now may not tell you much that's useful to your health. But that doesn't mean the technology can't improve medical care and save lives. One of the most promising uses for information is fine-tuning how drugs are prescribed. That's because some genetic variations that turn up in gene testing affect how people respond to pharmaceutical products. My liver enzymes might be speed demons when it comes to clearing drugs from my blood, while yours work far more slowly. So I'll need a higher dose of the drug to get the same medical effect. To take an extreme case, one-third of people with a particular gene die when given a certain AIDS drug. Yet in patients without the genetic variation, the drug works great. So doctors must test for the gene before prescribing the drug.

Similarly, a recent study showed that 36% of colon cancer patients have a mutated gene in their tumors that prevents Erbitux, a cancer drug made by ImClone (IMCL), from working. Testing for that gene will save patients from unnecessary treatment. It will also save the health-care system millions of dollars, since the drug costs more than $60,000 per year.

Another study reported that 40% of people with African ancestry get no benefit from beta-blockers, blockbuster drugs used to treat heart disease and high blood pressure. "For some drugs, this will change medical practice forever," says Dr. Howard McLeod, director of the University of North Carolina's Institute for Pharmacogenomics and Individualized Therapy.

The Right Dosage, Through Genetics

However, McLeod adds, it is "still early days" in using genetic knowledge to prescribe drugs. When you look at the world's 20 top-selling drugs, genetic analysis has only been developed for one or two, and it's the same story if you rank pharmaceuticals by which ones are known to cause adverse effects or hospital admissions. Only a couple of the top 20 come with tests that predict which patients will be harmed. "People who can process the drug faster are underdosed, and people that don't process drugs well get toxicity," explains Dr. David Brailer, a former top health technologist in the Bush Administration and chairman of Health Evolution Partners, a health-care investment firm.

But eventually, this situation will improve, Brailer predicts. Some of the lesser-known personal genomics companies are already going down this more specialized path, developing tests to help doctors prescribe medicines. San Francisco-based DNA Direct tests for the genes that determine a patient's response to warfarin, a blood thinner. Since not enough drug in the blood increases the risk of clots while too much can lead to dangerous bleeding, there is urgent need for a test to help pinpoint the right starting dose. DNA Direct also can spot the gene, found in 7-10% of women, that prevents the cancer drug tamoxifen from helping certain women with breast cancer. "Drug response is an area we're really excited about," says Ryan Phelan, DNA Direct's founder and CEO. Brailer expresses similar enthusiasm. Such uses "will radically alter the prescribing market," he says. "We think there's a lot of value there in giving drugs more efficiently."

Still a Long Road Ahead

This niche—using genes to guide prescribing—may help the young business of personal genomics get off the ground. Ultimately, reading people's genetic codes should bring many other scientific and financial payoffs. "I'm still relentlessly optimistic," says Greg Lennon, co-founder of SNPedia. But it's also clear there will be plenty more false starts and failed investments along the road to this future. In the end, given the complex interactions between genes, environmental factors, and life's vagaries and choices, most people will probably accept that genes do not define our destiny. Says Tera Eerkes, co-founder and chief scientist of Q-Trait, another personal genomics company: "I like that we can learn from our genes, but that is not the end of the story of who we are."

Carey is a senior correspondent for BusinessWeek in Washington.