The test results were crystal clear, and still the doctors didn’t know what to do. A sick baby whose genome was analyzed at the Children’s Hospital of Philadelphia turned out to possess a genetic mutation that indicated dementia would likely take root around age 40. But that lab result was completely unrelated to the reason the baby’s DNA was being tested, leaving the doctors to debate: Should they share the bad news?
When it comes to scanning DNA or sequencing the genome — reading the entire genetic code — what to do with unanticipated results is one of the thorniest issues confronting the medical community. Many conflicted discussions followed the dementia discovery at the Children’s Hospital of Philadelphia (CHOP) before a decision was reached: the parents would not be told that this fatal memory-sapping disease likely lurks in their child’s future. Given the hopelessness of the situation, with no treatment and no cure, the doctors said forwarding such information along felt pointless. “We came around to the realization that we could not divulge that information,” says Nancy Spinner, who directs the hospital laboratory that tested the infant. “One of the basic principles of medicine is to do no harm.”
Around the same time, Spinner’s lab also tested another child — an unusually short 2-year-old referred for kidney disease — and discovered the toddler had a gene linked to a rare form of colon cancer. In some cases, polyps arising from this kind of cancer have been known to develop as early as age 7. This time, the decision to inform the parents was easier: “We feel good about that one,” says Spinner. “Proper screening can make a huge difference.”
Across the country, a small but growing number of doctors are turning to increasingly sensitive genomic tests to pinpoint the root causes of young patients’ mystifying symptoms. But many still don’t know how to handle results unrelated to the ailments that prompted such sequencing. “If you’re looking in the area of chromosome 17 and BRCA1 [a breast-cancer gene] is nearby, you can’t ignore it,” says Barbara Bowles Biesecker, director of the genetic-counseling program at the National Human Genome Research Institute (NHGRI), which is housed on the campus of the National Institutes of Health. “What are you going to do, put blinders on and not look to the left?”
(MORE: Read TIME’s complete series on DNA testing and children)
Encountering all these unexpected results has called into question the traditional approach to bioethics—to share unexpected findings only if they’re life threatening or treatable. “We think that premise is nonsense,” says Misha Angrist of the Duke Institute for Genome Sciences & Policy. Angrist was among the first people to have his genome sequenced in 2009 as part of the Personal Genome Project, which aspires to publish the genetic codes of 100,000 volunteers as a way to boost research into personalized medicine. “Parents should be given access to this information that’s derived from their bodies and their children’s bodies. This information is for everyone. It’s scary because we have chosen to make it scary. We exacerbate it by treating it like the bogeyman.”
As the price of sequencing keeps dropping—it can be done today for as little as $7,500 and there’s talk of a $1,000 genome in the future—many doctors are bracing for the day when large numbers of healthy people start sequencing their genomes. Some worry the trend will translate into mass anxiety over ominous or unclear results.
Perhaps nowhere is the risk of overreaction greater than when it concerns prenatal testing. In June, the University of Washington (UW) announced it had sequenced a fetal genome with 98% accuracy. Consider: If you were to learn your unborn baby had a genetic marker for cancer, might you abort? But markers are not guarantees, notes bioethicist Tom Murray, a visiting scholar at Yale. “Great, we can sequence the genome of a fetus. What the hell does it tell us?” he says. “Much less than most people probably believe. Probabilities are not the same as certainties.”
As sequencing moves from the realm of research labs into doctors’ offices, the medical community is rushing to hammer out guidelines. The American College of Obstetricians and Gynecologists recently discouraged the use of personalized genomic tests to gauge disease risk. “Although genetic profile tests may prove to be important tools in the future, they are not ready for prime time,” the group said in May. Meanwhile, the American Academy of Pediatrics advises that “in the absence of clearly beneficial treatments or effective preventive strategies, genetic testing of children and adolescents may not be justified.” Knowing about disease risk “would almost certainly have an impact on how that parent interacts with that child and how they think about that child’s future,” says Joy Boyer, a senior program analyst at NHGRI, which is devoting $19 million this year to examining the ethical, legal and social implications—or ELSI, for short—of genomic research.
It didn’t take millions of dollars in research for breast-cancer survivor Debbie Horwitz to reach that same conclusion. Horwitz, a mother of two in Raleigh, N.C., tested positive a few years ago for the breast cancer gene. She was hell-bent on testing her then-infant daughter, Jordan,until her husband talked her out of it. She now supports the decision. “I don’t think it’s fair for us to have that information now and have that heaviness in our family or in how we relate to Jordan,” says Horwitz. “I think knowing whether Jordan is positive or negative would also cause a lot of tension and sadness in our family.”
Creating Genomic Standards
Genomics isn’t the first emerging technology to wrestle with ELSI issues. New prenatal tests can detect Down syndrome as early as 10 weeks into pregnancy, which has led some to worry that more women will simply abort and try again. Similarly, there are no prohibitions against hand-picking embryos based on gender nor the creation of a “sibling savior” — a baby conceived as a genetic match for a sick brother or sister in need of healthy stem cells. “Whenever there’s a new evolving technology, we have to decide whether existing approaches to oversight ought to apply or whether we need novel ways to address novel technologies,” says Jeffrey Kahn, a professor of bioethics and public policy at Johns Hopkins University.
Notes Dr. Wylie Burke, a geneticist who chairs the Department of Bioethics and Humanities at UW: “If we open the door to a test that has no clear, well-defined purpose, that is a recipe for unnecessary medical care. Instead, we could say, here are the 1,000 mutations we should check in everyone.”
The American College of Medical Genetics and Genomics is working on just that, painstakingly assembling a list of a few dozen conditions that it says should be routinely looked for during genome sequencing. “We are struggling with this,” says Dr. Robert Green, a medical geneticist at Harvard Medical School, who is co-chairing the group developing the list. “If you fall off your bike and get an X-ray looking for a fractured rib, the radiologist scans the entire X-ray and automatically reports back to your doctor if something else is going on. More than a few cancers have gotten picked up this way. The problem with genomics is that everyone could have incidental findings.”
In March, Green presented a draft list at a conference, where participants pelted him with questions. Lab directors asked if the list would be mandatory. Geneticists wanted to know if the recommendations for children would differ from those for adults. Others inquired whether patients would meet with genetic counselors before learning about disturbing results. “People had strong opinions,” says Green. “These questions are on everyone’s mind.”
There’s another question being asked too: what should be done with genomic transcripts so massive that labs typically FedEx hard drives filled with data? All that information overload is complicated by a steady stream of new genetic discoveries; sequencing results that are head-scratchers today could be meaningful tomorrow.
Three years ago, Dr. Mike Bamshad, chief of genetic medicine at Seattle Children’s Hospital, and his colleagues at UW were the first to sequence all the genes of a family: mom, dad and their two children. The sequencing was a success—the team discovered a new gene for a condition called Miller syndrome—but they also discovered genetic changes that caused other diseases in the family. Some members of the family wanted these results, others didn’t and, over time, some changed their mind about what they wanted. Bamshad recalls that explaining and sharing each potential finding and returning every last result to the family took too long. “We can’t do this,” he told his colleagues at the time. “We need to find a way to give people a way to choose the results they want and do it in a private, convenient way.”
Out of that experience emerged My46, a web-based solution to the problem of what to do with the deluge of data generated by sequencing. Named after the number of chromosomes in human DNA, the non-profit My46 allows people to store their sequencing results online and choose what they want to know and when. For example, parents of a baby who gets sequenced could opt to learn right away any findings about childhood diseases and put everything else—from unclear results to increased risks of adult-onset diseases—inside the digital equivalent of a locked drawer, where it can be stored forever and accessed whenever they want to open it.
My46 is now in the testing phase; early users are part of a study to assess, among other things, how strong the temptation is to look in, say, the cancer drawer and how parents react when they find out their baby is likely to develop a disease later in life.
How Much Information Is Too Much?
Spinner has thought deeply about those reactions, not only in terms of other people’s children but also through the prism of her own three kids.
She thinks doctors should not divulge that a child is at greater risk for an illness if it can’t be treated or prevented. She says she wouldn’t want to know that information about her own children. Meanwhile, her husband, Dr. Ian Krantz, a pediatrician at CHOP, says he might be up for sequencing himself and learning everything. The couple has teamed up to analyze the ethical implications of sequencing children, and in January they will begin enrolling the first of 240 families in their study. In preliminary focus groups held to gauge parents’ attitudes toward unanticipated findings, nearly all the parents said they would be eager to know about every potential disease risk, even if there is no available treatment.
Those attitudes contradict the opinions voiced in other focus groups by bioethicists, lab directors, doctors and genetic counselors, most of whom said that only results that could be immediately acted upon should be shared with families. “The genetics community is anxious to do the right thing by families,” says Spinner, “but what the right thing is isn’t exactly clear.”
This ambiguity haunts Spinner — particularly when it comes to scenarios like the baby who is likely to develop early-onset dementia. “That gene wasn’t on my radar,” she says. “Whenever it comes up, I can feel my anxiety rising.” Through the years, Spinner has gotten used to communicating less-than-cheerful news, but this time the burden felt different, heavier. “In my lab, we diagnose a lot of bad things that tell parents right away that their child will not have the life they’d hoped,” she says. Since there’s nothing to be done to alter the outcome in this baby’s case, the parents will remain oblivious to the misery that seems to lie ahead.
Will the parents ever think to inquire about the unexpected findings of their child’s analysis? Probably not. But either way, the data is all there, saved for posterity in the lab’s private files, its genetic secret untold.
This is the fourth in a five-part series exploring the promise and pitfalls of sequencing children’s genomes. Read the full series.