- By Rita Rubin
The era of personalized medicine is coming. As genetic profiling, also known as genome sequencing, gets better, cheaper and more widely available, more of us may one day know exactly which chronic diseases we're likely to contract, what medications we should avoid and even what type of diet we should follow. In just a few years, with such data in hand, our doctors might be able to identify our vulnerabilities and target treatments with a greater chance of success than ever before.
We can get a preview of that future today through private services like 23andme, which, for just $99, will analyze a half-teaspoon of your saliva and return a detailed report with some 250 bits of information about your genetic profile and how it could influence your health.
It's far from a full genomic sequencing, but it does provide some potentially valuable data. It's also something of a bargain. When the company launched its service in 2007 — the name is inspired by the 23 pairs of chromosomes that make up the human genome — the analysis was priced at $999 and provided far less information. The clinical cost of complete genome sequencing is more than $3,000, though it is also falling.
"For 99 bucks you have a pretty good set of information," says Dr. Eric Topol, a cardiologist who is the chief academic officer of Scripps Health in San Diego and the author of The Creative Destruction of Medicine: How the Digital Revolution Will Create Better Health Care. "But it's only a partial story."
One Woman's Genome
Misha Angrist, an assistant professor at the Duke Institute for Genome Sciences and Policy and the author of Here Is a Human Being: At the Dawn of Personal Genomics, was one of the first people to view the results of the sequencing of their entire genome, and is one of many who now wonder how popular direct-to-consumer genetic testing will become. "In general, people who give up their credit card numbers and their saliva are a self-selected bunch who are interested in this information," he says. (Testing is available to consumers nationwide, with some exceptions: Maryland bars the shipping of genetic tests to consumers, and New York forbids shipping your sample from within the state.)
I snapped up a 23andMe test kit in December 2011, becoming one of more than 200,000 people so far who has enlisted the service. I was concerned about whether I carried a genetic mutation that would greatly increase my risk of breast and ovarian cancer — my father's mother and one of his sisters had breast cancer. While only about 10 percent of all cases are considered hereditary, scientists have been able to link three genetic mutations to virtually all inherited breast cancers in Ashkenazi (Eastern European-descended) Jews, like me.
Though I rushed to order the kit, I confess to waiting several months before sending my sample to the company's California lab. I was nervous about what I'd find out. After I got the notification that my results were available, I waited until my next doctor's appointment to click on the link that would tell me whether I had one of the Ashkenazi mutations. Much to my relief I was negative for all three, but I'll continue to get mammograms and clinical breast exams because the 23andme assessment doesn't ensure I'll never develop breast cancer.
What You Learn
The information from services like 23andme is not complete. Generally, it can tell you only if your odds of a certain condition are better or worse than the general population. Testing can reveal, for example, if you have a variation in your genes that increases your odds of developing diabetes from one in five — the general population's risk — to one in three. If you discover that you have that variation, you may decide to act on the news by changing your exercise and diet regimens to ward off the condition.
Testing can only reveal what scientists know so far about the link between genes and disease. It can tell you if you have the rare genetic mutation that appears to raise one's lifetime risk of contracting Parkinson's disease to 60 percent, but not having the mutation doesn't at all mean you're in the clear. My own results indicated that my risk of contracting Crohn's disease, an inflammatory bowel condition, was only about half that of the general population — but I've already lived with the disease for more than 20 years.
In the case of heart disease, testing can show you if your ethnicity, or the presence of certain genetic markers, indicate an elevated risk. As is the case with many conditions, though, environment and lifestyle play at least an equally important role in determining your actual risk of heart disease. The company's reports detail which conditions are more or less affected by genetics. There are certain concerns for which research indicates that genetic tendencies play a larger-than-average role in determining one's risk. 23andme estimates, for example, that genetic factors determine at least 60 percent of an individual's risk of developing obesity.
The Best Value in Testing
Perhaps the most reliable, and immediately actionable, component of the 23andMe data is its assessment of how we will respond to certain drugs. For example, the company checks for genetic variations related to how well we metabolize clopidogrel (Plavix), which helps prevent blood clots that could cause heart attack or stroke, and warfarin (Coumadin), a blood-thinner that prevents and treats clots in the veins, lungs and heart.
Clopidogrel needs to be converted into its active form in the liver. Most of us have two functioning copies of the gene that carries the blueprints for the enzyme needed to activate the drug. But some of us have only one, and about 1 in 20 people have none. Those in the latter group are considered to be poor metabolizers of clopidogrel; for them, the drug works about as well as a sugar pill.
About a third of patients prescribed warfarin turn out to be more sensitive to the drug than expected, due in part to genetic mutations. This is why, in 2007, the Food and Drug Administration approved labeling on the drug that suggests doctors use genetic tests to optimize dosing. For people with a heightened sensitivity to warfarin's effects, a dose of the drug that is too high puts them at risk of potentially life-threatening internal bleeding. If a dose is too low, though, potentially lethal blood clots could form.
The Psychological Element
I'm not sure how I would have reacted if I had learned I had a genetic mutation increasing my risk of breast cancer. Experts remain concerned about the psychological impact of finding out that you're at high risk of a potentially fatal disease, especially when companies can send you the information via email without the context and advice your doctor could provide in person.
There's a threat to the health care system, some clinicians believe, in producing a legion of "patients in waiting" — otherwise healthy, asymptomatic people who have found out they may be at risk for chronic disease, then overload hospitals with demands for further testing and treatments that may not be necessary.
Several studies are under way to find out just what actions people — and their doctors — take based on genetic data. Topol says his own research has shown that patients don't necessarily panic when they learn the results of direct-to-consumer genetic testing. (23andMe advises that its information "is intended for research and educational purposes only, and is not for diagnostic use.")
For patients with a risk of disease but no symptoms, the wisest action would be preventive steps, like changes in diet and lifestyle to ward off heart disease. But even with genetic data in hand, many of us may not take steps to improve our health. "I'm fairly comfortable with the conclusion that people don't freak out," Angrist says, "but neither are they likely to change their behavior."
Millions of us resist giving up cigarettes or fatty foods, despite the obvious health risks. When we find out that our genes make us even more susceptible to chronic disease than we thought, will we respond differently? That's one of the things we'll discover as genome sequencing goes mainstream.