Genetic tests are everywhere, but how reliable are they?
The Greeks asked their oracles to predict future fortunes and future losses. The Romans studied the entrails of sacrificed animals for similar reasons. In modern-day medicine, though, soothsayers come in the form of genetic tests.
Ever since the human genome was sequenced almost 15 years ago, tens of thousands of genetic tests have flooded the marketplace. By analyzing someone’s DNA, often through a blood sample or cheek swab, these tests promise to foretell whether a patient is prone to certain cancers, blessed with the potential to become a star soccer player, or at an elevated risk of having an opioid addiction.
These types of genetic tests are finding an eager audience. The North American genetic testing market, already the largest in the world, was worth $11.9 billion in 2016, by one estimate, and is expected to grow at more than 15 percent a year for the foreseeable future. Companies such as LabCorp, which offer genetic tests via doctor recommendations, and the healthcare giant Roche have moved aggressively into the field. The company 23andMe, a household name because of its ancestry tests, sells health-related tests directly to consumers.
But for a source of medical information to be legally sold in the United States, just how accurate does it need to be?
Like a prediction from a crystal ball, genetic test results are sometimes wrong. Some tests that predict the likelihood a young pregnant woman will have a child with a genetic condition such as Down syndrome may only be correct only 60 percent of the time. Most genetic tests, and many other lab tests, go unvetted by the Food and Drug Administration. That means these tests may not undergo any independent review to make sure they accurately pick up the disease or genetic conditions they claim to be seeking.
The FDA has been wrestling for years with whether and how to do more. During the Obama administration, the agency proposed a new set of draft limits on a whole class of tests, and then put them on hold immediately after Donald Trump’s election. This spring, the FDA gave 23andMe permission to market genetic screenings for susceptibility to Alzheimer’s, Parkinson’s, and other conditions. It was the first time the agency blessed direct-to-consumer tests for genetic health risks.
While the debate over genetic testing often follows a pattern familiar from countless other industries — business groups want less regulation, and consumer advocates favor more — it also raises more cosmic questions: Is a medical test just a piece of information? Or is it something more, if its result leads to dramatic or irreversible action such as chemotherapy or an abortion? And if a data point is factually suspect, or ripe for misinterpretation, when and how should it be offered to consumers?
Especially if regulators stand aside, Americans may soon be swimming in even more tests that vary greatly in their reliability. Yet for some people contemplating a current ailment or their future well-being, getting an answer — even an unreliable one — may be better than no answer at all.
Especially for people expecting a baby, genetic tests can be hard to resist. “I think we all are wanting to know our child doesn’t have something. . . we want them to be healthy,”’ said Mischa Livingstone, a filmmaker and professor who lives in California. Without asking for it, his pregnant wife, Jessica, was given a genetic test that predicted a 99 percent chance their child would have Turner syndrome, a genetic condition that can lead to short stature, heart defects, and other symptoms. But genetic tests for Turner are more often wrong than right — a fact the couple didn’t know at the time.
They were devastated, and immediately went for more invasive testing, which showed the fetus was fine. But their sense of dread didn’t lift until their daughter, now 2 1/2, was born perfectly healthy.
Despite the heartache a faulty genetic test result caused, Livingstone says he’d consider asking for one again. “I think it feeds into that need for certainty,’’ he said.
Both individuals and society as a whole are intolerant of the unknown, medical sociologists say.
Long before genetic screenings, there was a critical relationship between lab tests and medical treatment. Doctors often won’t prescribe drugs or treatment without a positive test result. Insurance payments are rarely processed without diagnostic codes. The rise of genetic testing won’t change, and may even amplify, that dynamic.
While some diagnoses may still carry social stigma — think schizophrenia, for example — they more often may confer legitimacy. Having a gene for alcoholism, for example, can make people view the problem as biological, as opposed to a character flaw. For patients, genetic tests promote a “therapeutic optimism” — a hope that they can be treated and cured for an immediate problem or a future one, according to Michael Bury, professor emeritus at Royal Holloway, University of London, who studies society and illness.
A test alone can feel like a step forward. Undergoing a screening, said Natalie Armstrong, professor of healthcare improvement research at the University of Leicester, “can make people feel that at least they are doing something proactive.”
Interestingly, one study indicated that certain direct-to-consumer genetic tests don’t affect users’ behavior or anxiety levels, bolstering the argument that people may use the information as data points, not a surefire prediction of their own fate.
Many bioethicists are unpersuaded. “On an individual basis, it is tempting to discount the pitfalls of ‘a little extra information,’” says Beth Peshkin, an oncology professor and genetic counselor at Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C. But on a population level “the implications of inaccurate results can be costly and, sometimes, deadly.”
One of the most cited examples of this harm is from a 2008 genetic test for ovarian cancer that misdiagnosed women, some of whom had their ovaries removed unnecessarily before the test was pulled from the market. Because test makers do not have to report when a test turns out to be wrong — in fact many people may never know when a test result is a false positive or negative — FDA officials have said it has been almost impossible to assess the overall harm from all unregulated tests.
Cost is another concern that may arise from the overuse of genetic tests that proliferate without meaningful oversight. Tests often beget more tests that cost an ever-escalating amount of money. Enough testing, will invariably pick up something abnormal in a patient, even though it may not harm them, some experts believe.
“In some ways it’s easy for us to try and find something definitive and act on that even though it has nothing to do with what is wrong with the patient,’’ said H. Gilbert Welch, a cancer research at Dartmouth College who has written extensively on the dangers of overtesting. “Genetics is an amazing tool. . . but to what extent does that data predict something that you care about? Is it useful knowledge?”
The American Clinical Laboratory Association, the key trade group for genetic test makers, and other advocates of lighter regulation argue that bad tests are rare, and that it’s more important for the free market to allow innovation. With more tests in place to identify disease, cures come next, they say.
So far, the public has shown little concern about the fallout of genetic testing. While a 2016 poll showed only 6 percent of American adults have undergone genetic testing, 56 percent of them said they would want to if it could predict cancer or a disease like Alzheimer’s. Most Americans, the poll found, believe genetic tests for predicting disease are mostly accurate and reliable.
Safety advocates’ best chance to tighten regulation may have already passed. The world of genetic testing becomes more free-wheeling and consumer-driven all the time. By one industry estimate, 10 new genetic testing products enter the market each day. Despite considerable skepticism from medical experts, new apps purport to use data from gene sequencing to develop personalized diet plans and fitness routines.
The FDA’s now-shelved rules would have classified genetic and other tests according to how much harm they could cause if their result was wrong. For example, a new genetic test for colon cancer, which requires intrusive and costly treatment, likely would have been subject to full FDA review; the maker of a test that predicts mere baldness might only have had to register it with the agency and report any known problems with it. Under the Trump administration, the agency appears less likely to draw such distinctions — or impose new restrictions at all.
People want answers soon, and their inclination is to believe what appears to be solid, unassailable medicine, said Robert Klitzman, a Columbia University bioethicist. Individuals will need to evaluate these tests carefully. “The notion of being able to tell your fortune has great lure. But it’s a little bit of hubris. We still don’t know so much.”
Genetic testing, still in its infancy, promises a measure of clarity about the future of our bodies. But as genetic science rapidly evolves, that modern-day crystal ball raises vexing new questions and creates its own kind of uncertainty.
Beth Daley is a freelance writer and former reporter for the Globe and the New England Center for Investigative Reporting. This piece was produced with support from the National Institute for Health Care Management Foundation.