“Here it is,” I thought. “Mortality in an e-mail.” It had been almost four months since I walked into a lab at a Harvard research facility, rolled up my sleeve, and gave a vial of blood to have my genome sequenced.
Now my deciphered genome was complete. It appeared to be a good report. For one thing, I didn’t see the word “Alzheimer’s”—not that dementia runs in my family. I saw a variant linked to slightly higher-than-normal risk of macular degeneration. No surprise; about 10 percent of Americans develop this condition, and my mother has it. There was a variant linked to higher risk of schizophrenia, which I’m probably too old to develop. But then my eyes wandered back to the top of the report and an unfamiliar series of letters and numbers: JAK2-V617F. The JAK2 gene variant was classified as “well-established pathogenic,” meaning harmful. It appears frequently in people with rare, “cancer-like” blood diseases. Although most are treatable, this wasn’t the best news. My wife, Judi, and I agreed we would have to look into this further before starting to worry.
Genome sequencing will become more widely used as the cost drops to $1,000 in coming months, manufacturers and researchers say. Navigenics, 23andMe, and other companies that offer test kits for home use and post results on a secure site have been scanning the genome for individual markers of ancestry and health risks for years. These companies, whose services are branded as “recreational” and cost anywhere from $100 to thousands of dollars, have taken criticism for lacking precision and overstating the weight of their findings. Now whole genome sequencing, which provides a far more detailed view of an individual’s protein-making machinery, is becoming affordable enough to become a routine diagnostic tool—on par, price-wise, with an MRI—as well as a way to find out how much Neanderthal DNA one has, or whether one is likely to go bald. (At age 53, I no longer need confirmation on that last count.) Google (GOOG) and Amazon.com (AMZN) are both investing in technologies to manage the information tidal wave expected from powerful new sequencers. But while the ever-growing library of the human genome will prove an invaluable reference to science—not to mention marketers—it’s still unclear how individuals will react to having their genetic fortunes read.
Three days after getting my results, I took a seat in the office of George Church, the Harvard scientist who started the Personal Genome Project and arranged my sequencing. Church is one of the pioneers of gene sequencing whose technologies have influenced or been adopted by almost every company in the industry. Joseph Thakuria, the project medical director, was there to lead the team’s discussion of my results. After a short review of my report, the scientists turned to the JAK2 variant.
“This is probably the most serious variant that we’ve actually seen to date in the study,” Thakuria said. About two out of 1,000 people have the JAK2 variant, which encourages blood cells to grow and divide. The variant is used to diagnose three rare blood disorders, including primary myelofibrosis, which is potentially lethal. “I don’t want you to fret about this,” Thakuria said, before giving me fresh cause for worry: a study, published in 2010, in which 10,507 people in Copenhagen gave blood samples and were followed for as long as 18 years. The Copenhagen researchers went back and analyzed the blood samples: 18 had the JAK2 variant; 14 of those 18 with the variant developed cancer in their lifetimes, and all 18 died within the study period. How, exactly, was this helping?
“That’s a very scary figure,” Thakuria allowed. He calmed me with a few observations. It wasn’t clear, for instance, whether people with the variant had died of the conditions they had been diagnosed with, he said. Most of the 18 lived into their 70s or 80s. “Half of them could have died of bicycle accidents,” he said, smiling.
I struggled to digest all this new information. While I was glad to be contributing to health research, I had entered an area where even experts don’t have answers. What will happen as more people get results from broad genome sequencing? Gathering genetic data from thousands of people can help researchers understand health by correlating gene variations with diseases, says Dr. Harold Varmus, director of the U.S. National Cancer Institute. He worries, however, that companies doing these studies may not always ensure that customers get a full understanding of their results. “My concern is whether individuals are getting guidance on how to deal with the information,” he says.
Back home, I compulsively reloaded and reread my report. I noticed it had been updated electronically. Now the second entry on my list of variants was labeled “APOE-C130R”—that’s another name for the ApoE4 gene associated with increased risk of Alzheimer’s disease. “Sorry this was missed earlier,” one of the Harvard researchers said in a follow-up e-mail. I began running memory tests in my head.
Back in May, before I’d surrendered my vial of blood, Aubrey Milunsky, director of the Boston University Center for Human Genetics, had warned me that having my genome sequenced would cause me to worry needlessly about ailments that might never strike. “Why would you want to know that?” he had asked me then. “You know [the variant] is there, but you don’t know what it means,” he said. “You’re smack in the territory of inviting anxiety into your life.” Now, with the results in hand, I called on him again and told him the report had actually taken some uncertainty out of my life. I explained that I had a rare mutation linked to conditions that are often treatable. Wouldn’t it make sense for me to undergo a blood test regularly to see whether my blood counts had changed? Not necessarily. Researchers are still trying to determine when to do more common tests for breast and prostate cancer, for example. Some people who get positive results on these screening exams will undergo unneeded treatment that may actually cause harm. In October, a government panel recommended that blood tests used to screen for prostate cancer should be restricted to men with symptoms. The same panel said in 2009 that routine mammograms for women should begin at age 50, rather than 40.
My genomic exercise had uncovered things I’d rather not know, Milunsky pointed out. Others who undergo the same procedure may learn of mutations that practically guarantee serious, and perhaps even fatal, diseases. Indeed, a 1999 study in the American Journal of Human Genetics found that about 1 percent of 4,527 people who were told they had the gene that causes Huntington’s disease, a progressive nervous system disorder, attempted or committed suicide or were hospitalized for psychiatric reasons. Yet there are many people who, threatened with mortality, achieve great things. (Would that I could channel Steve Jobs.)
“I’m not going to lie to you: I’d rather you didn’t have it,” Thakuria said. “This isn’t like one of those mutations that have specific recommendations. There are no guidelines here. This is part of being on the frontier.”
Whether or not individuals want to know what their genome reveals, there are innumerable interested parties who do. Considering how avidly advertisers scour the personal information we divulge to social networks, one can only imagine how much they’ll want to know about the needs, desires, and weaknesses coded into our DNA. Here’s a thought: If only I hadn’t agreed to make my results public through the Harvard project. I could have sold them to Big Pharma to prepare for those Alzheimer’s bills.