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A week later, I drove to my doctor’s office. She showed me a single-page document with a chart listing some of the drugs metabolized by the relevant enzymes, as well as definitions of poor and ultrarapid metabolizers. Near the top of the page was a small box containing the sum total of my results: “CYP2D6, extensive metabolizer, CYP2C19, extensive metabolizer.” Much to my surprise, I am totally normal. My DNA sequences encoding both enzymes contain none of the known variants that would render them less effective in metabolizing drugs like codeine and the ingredients in NyQuil.

Did this mean I had imagined the side effects of various drugs? Were the nausea and headaches really a kind of negative placebo effect? After consulting with several experts, I still don’t know the answer. Walter Koch, head of research at Roche Molecular Diagnostics, explains that a complex network of factors can influence an individual’s response to drugs, including “age, gender, diet, hormone levels, concurrent medications, and inherited variations [in genes other than those tested for by the AmpliChip].”

It’s also possible that I possess a rare mutation in CYP2D6 or CYP2C19, one the AmpliChip test doesn’t look for. Although the AmpliChip detects the majority of known clinically relevant mutations in these genes, new variants of the genes are still being discovered, according to Miami’s Licinio. Ultimately, my conundrum points out a limitation of diagnostic testing. “These tests are just one of the pieces of information that should be part of a patient’s history, along with your age, your parents’ medical history, and other factors,” says Lesko.

Who Pays?

But at more than a thousand dollars a test, the AmpliChip is not just another easily gained piece of information. For most patients, genetic testing remains expensive and exotic, both economically and logistically inaccessible. So what will it take for pharmacogenomics information to become a standard part of our medical charts? Experts say educating physicians is one of the biggest obstacles. “When most doctors were in medical school, pharmacogenomics was not part of their training,” says Licinio.

Already, though, more and more physicians do want to use these tests. David Mrazek, chair of the psychiatry and psychology department at the Mayo Clinic in Rochester, MN, uses them routinely in clinical practice. He says the benefit of pharmacogenomics in psychiatry is clear: people vary enormously in their response to antidepressants and antipsychotics, both of which can cause troublesome side effects. Some patients spend weeks or months or even years trying different doses of various drugs to find the one that brings the most relief with the fewest problems. By testing for genetic variants in drug-metabolizing enzymes, Mrazek is able to save his patients much of that trial and error. “If a patient is a poor metabolizer of Prozac, I’ll start them on a different drug,” he says.

The real hurdle, then, will be financial. Insurance companies still consider the AmpliChip experimental and are unlikely to cover it until large clinical trials prove that it can both help patients and cut costs. Such studies, which are already under way for psychiatric disorders, will also help determine how best to use the test.

Whatever the economic and insurance considerations, however, the advent of genetic tests like AmpliChip seems all but inevitable. And for patients, that is a good thing.

Emily Singer is the biotechnology and life sciences editor of Technology Review.

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