Scientists discover DNA might not be that useful as part of your annual checkup

Since the human genome was first sequenced in 2003, the immense promise of a technology that can reveal the 6 billion letters that make each of us who we are has loomed large as a way to revolutionize nearly every aspect of human health, from what we know about ourselves the day we are born to how to stave off the day that we die. But the ability to peer into the most fundamental biology of a human being has raised a slew of ethical questions and one that is even more simple: when is that information useful?

If people are healthy, the answer seems to be not very often according to a new, four-year clinical trial that exhaustively studied the use of genome sequencing of healthy adults by a primary care doctor, anticipating the day that this information becomes part of everyone's medical record. Learning their genomic results didn't appear to harm anyone, but also didn't provide any clear short-term health benefits -- and it did drive up health spending compared to patients who simply got a detailed family history.

Contrary to longstanding ethical concerns that people will suffer psychological ill effects by learning things they don't want to know in their DNA, people did not experience anxiety or depression in the six months after receiving the results. They racked up an average of $350 more in health care costs, although the relatively small number of people in the study meant the difference wasn't statistically significant. And while 11 in 50 of the people who were sequenced found out they carried rare genetic mutations that put them at risk of a disease, that information had few health implications for the majority of the patients, who showed no signs of the diseases.

In a few cases, patients might still develop those diseases in future, but that was far from certain. And, reflecting the fluid and evolving understanding of DNA, one mutation that was reported back to a patient was reclassified and was no longer considered a risk factor by the end of the study.

"My bottom line: big questions about the medical utility of whole genome sequencing in healthy adults, real concerns about the health care cost increases from doing whole genome sequencing in healthy adults, continued uncertainty about how the primary care docs are going to be able to handle this, and little comfort about the lack of harms if whole genome sequencing rolls out throughout the population," Hank Greely, director of Stanford Law School's Center for Law and the Biosciences, said in an e-mail.

Every new medical invention brings with it excitement around novel capabilities, whether it is a 3-D mammogram or a new kind of joint implant. That always comes balanced against the question of how it should best be used. But genome sequencing has traveled a particularly long red carpet of hype. Its medical uses are unusually diverse and it has been plummeting in price; the cost of sequencing and interpreting the genomes in the study was about $5,315, but today an interpreted genome costs about $1,000, according to Jason Vassy, a primary care physician and researcher at the VA Boston Healthcare System and Brigham and Women's Hospital who led the study published in the Annals of Internal Medicine.

Add to that the fact this type of information is being sold directly to people, whether it is Silicon Valley's 23andMe or a growing crop of startup companies that seek to offer consumers medical advice informed by their genome.

"Today, in 2017, for a healthy individual, I don't recommend that any primary care physician order whole genome sequencing for that patient. But in a way this study kind of models what might be a more common scenario; the patients would bring this to us. The patient gets their whole genome sequenced; they ask us our opinion," Vassy said.

That doesn't mean people don't like learning about their biology. Renee DuChainey-Farkes, 63, runs a school in the Back Bay neighborhood of Boston. She eats a healthy diet and exercises, but was curious about her DNA and decided to sign up for the study. Her mother had heart disease and breast cancer, but she had also smoked. DuChainey-Farkes hoped she'd get into the group that got their DNA sequenced, but she was also nervous when she was picked.

"It was like, 'Uh-oh, what am I going to find out,'" DuChainey-Farkes said. "You can always say information is knowledge, but if it's not the kind of information I want, keep it away."

She found out she has an unusual blood type. She learned about her underlying risk for diabetes and obesity. She also found out that she has a rare gene mutation that causes a disease called variegate porphyria, which can cause blistering skin lesions and acute attacks that cause severe abdominal pain.

She has never had an acute attack, but had blistered skin as a child that was attributed to sunburn. She went to a specialist for a follow-up appointment to get baseline measurements done. That reassures her, because if she ever has an attack there will be information in her medical record about her risk for the disease.

Although Duchainey-Farkes enjoyed the testing and felt like she learned a lot about herself, it's less clear how useful the information is. She's a fair-skinned redhead and has always avoided the sun.

"It's kind of like this secret I have. I don't know what to do about it," said DuChainey-Farkes, who has been trying to get her young adult children interested in her findings. "I'm not going to get a really bad sunburn -- I'm definitely more conscious of that."

Misha Angrist, an associate professor at the Duke Social Science Research Institute who has had his genome sequenced twice said that the study shows just how much effort is needed to create the infrastructure to provide this kind of information to healthy patients. He said it also hints at how much more research it will take to really gain any conclusive evidence on whether genome sequencing is ultimately useful for healthy people.

"I imagine some people, especially people who are skeptical of this, will look at this paper and say, 'You know, this is a nothing-burger,'" Angrist said. "I guess I would probably say I think it's more like an hors d'oeuvres of a meal with many courses."

Peter Ting, 60, signed up because he was curious whether the thyroid problems and diabetes that afflicted his family members lay in his future, too.

His results were less than a revelation. Ting found out he doesn't have a particular genetic predisposition for diabetes or thyroid disease, a fact that came as a relief. But the relief changes very little about his outlook: he still thinks he should continue his efforts to lose weight. Ting also found an explanation for a problem that wasn't really a problem. For his whole life, he has had trouble adjusting from bright to dark environments; he'd be momentarily blinded, for example, when walking into a dark movie theater. When driving, he'd close one eye as he approached a tunnel, then open it once he was inside, so that one half of his vision would be pre-adjusted to darkness.

Finding out the gene mutation doesn't change anything, other than learning his problem has a name: fundus albipunctatus.

"It's good to know, you know," Ting said. "It's not that important -- well, it's important that I adapted already."