Parents’ desires for genetic information about their children can vary widely. The big question is what genetics experts and institutions think they should know—and how we might empower parents to take control of their children’s genetic data. An Excerpt From The Gene Machine by Bonnie Rochman (Scientific American /Farrow, Straus and Giroux, 2017)
In 2010, Mike Bamshad, the chief of pediatric genetic medicine at the University of Washington, co-led a team that was the first to sequence the DNA of an entire family—a mother, a father, and their two grown children—to find the cause of their condition. The researchers succeeded in pinpointing the gene that was responsible for Miller syndrome, a condition that caused the limb deformities and recessed chins of Debbie Jorde’s two children. In accordance with standard research protocol, they engaged in the time-consuming task of obtaining formal consent from the family to share with them each potential finding. But once the results came back, the researchers were frustrated by the cumbersome process of returning those results, one by one. Complicating matters was a secondary, or incidental, finding—primary ciliary dyskinesia, a condition that resembles cystic fibrosis. As Bamshad recalls, some family members wanted some results and others wanted different ones, and some of their preferences evolved over time. Bamshad figured there had to be a more efficient way for people being sequenced to select their preferences and receive their results.
For a baby being sequenced, parents can choose to learn only about results that affect their child in the near term—or opt to access everything.
In the past, Bamshad would have performed a particular genetic test on a child and the family would come back to the clinic to get the result—testing one gene would yield one result. But sequencing scans all 19,000 or so of a person’s genes. With sequencing moving toward the mainstream, the deluge of data generated from each sequencing test would mean that no provider would have the time to go over each and every potential result with each family member, asking: “Do you want this type of information? What about that type of information?” “We can’t do this,” he declared at the time to his colleagues. “This is highly impractical.” Together they started brainstorming solutions.
Bamshad sees exome and genome sequencing not so much as a test but more as a resource. Bamshad isn’t conflicted about what results to share because he believes the solution is simple: make everything available, but empower the patient to decide which results to access.
Preventive Genetic Medicine
That’s just what patients can do through My46, a Web-based program developed by Bamshad and his colleague Holly Tabor, a geneticist and bioethicist. My46 takes its name from the number of chromosomes common to humans. Akin to an online file folder, it allows patients to manage their data, store their genetic testing results, and access particular findings when they deem it appropriate. With My46, results indicating risks for cancer or other diseases that could develop years later could be stored online in a confidential, password-protected account.
Users can choose what they want to know and when. “If you are at the pediatrician’s office and you are with your eight-year-old child, you can decide to pull down that result,” says Bamshad. “Eventually, everyone will have their genome stored in the cloud.”
For a baby being sequenced, parents can choose to learn only about results that affect their child in the near term—or opt to access everything.
Meanwhile, the results remain in an online vault, where parents—or the children themselves, once they’re older— can choose to tap into them at will. The tool has been used locally at the University of Washington for research results and will be licensed for free to researchers and nonprofit groups; empirical data show that families like the format. “If you generate genome information on a newborn, people wonder what to do with it,” says Bamshad. “It makes no sense. We don’t think it’s a problem because we have this tool to deliver results.”
..the conventional wisdom—not to mention professional guidelines—advises against genetic tests for children younger than eighteen unless they’re medically necessary.
Parents’ desires for genetic information about their children can vary widely. The big question is what genetics experts and institutions think they should know—and how we might empower parents to take control of their children’s genetic data.
Bamshad readily admits he’s got a radically different mind-set from many of his colleagues around the country about divulging health data. He’s not asking if we should be returning results; he’s asking how. His belief that having access to genomic information early in life is useful comes from the research that he and his colleagues have conducted; from the vantage point of having sequenced the first nuclear family, Bamshad and his team have been thinking about sequencing and the information it generates for longer than nearly anyone else. “We already have demonstrated the utility of having access to genomic information early in life, even information about a fetal genome,” says Bamshad. “We’ve already made the decision that this is information of potential interest to families.”
And yet the conventional wisdom—not to mention professional guidelines—advises against genetic tests for children younger than eighteen unless they’re medically necessary. “We are recommending that parents be left with the ambiguity that their infant is at higher risk for breast cancer because they have breast cancer in their family, but we are unwilling to test the baby to know for sure,” says Bamshad, citing the familiar example of the BRCA genes. “If we’re counseling someone in clinic and they are at high risk for breast cancer and they have their infant daughter with them, why should we wait to talk again when she’s eighteen? Why would we not test and say she’s not a BRCA carrier or she is, and here’s what you should do about it? We should use this information to improve health care, and one of the clearest ways to improve health care is to prevent disease. It’s very clear-cut.” If parents find out their child is not a carrier, they can heave a big sigh of relief. “That’s huge,” says Bamshad.
“We should use this information to improve health care, and one of the clearest ways to improve health care is to prevent disease. It’s very clear-cut.”
The Right to An Open Future
“Naysayers emphasize the right to an open future,” say Tabor. “Will you think differently about your child if you know she has a BRCA mutation? But a mother may already treat her daughter differently because she knows that she, the mom, has a mutation in the gene. We already make assumptions about our children. There is no evidence I’m aware of that getting genetic information about your child results in a negative outcome. In most cases, there are more likely to be benefits rather than harms.”
My46’s role as a virtual file drawer is particularly useful in complex cases in which results are of undetermined significance. As genetic tests become more powerful, results are not always crystal clear. With gene discoveries announced regularly, it becomes even more important to store results so that they can be reinterpreted in light of new genetic insights or treatments.
We stand at a crossroads where we must decide how to share, comprehend, and make use of information about our genomes. Forget fretting about Google knowing your shopping habits or the wisdom of accessing your bank account via the Wi-Fi connection at Starbucks: those conventional concerns about privacy pale next to the biochemical secrets housed in your DNA.
“This area is like a Rorschach test,” says Robert Green, a medical geneticist at Brigham and Women’s Hospital and Harvard Medical School. “One group of people says, of course, all this information is potentially valuable to people and we should share it all. The other group is saying, don’t return any incidental findings; it’s inappropriate.”
Achieving Consensus
Trying to achieve consensus may have been a naïve undertaking, but that was Green’s charge from the American College of Medical Genetics and Genomics. In 2013, an ACMG committee that he co-chaired announced with much fanfare its recommended list of incidental findings that labs across the country should always return to the patient, regardless of the reason for testing or the preferences of the family. The list was originally known as the “ACMG 56” for the number of genes for which the group said labs should scour the genome.
In practice, it means that a child being sequenced, say, to help diagnose a mysterious disorder, should also have fifty-six genes scanned for changes that are associated with twenty-four or so other conditions that have potential treatments or interventions. In other words, if you wanted exome or genome testing, you had to accept the return of incidental findings from these genes.
Incidental or secondary findings aren’t new. We’ve all heard of cancer diagnoses made by chance when a person comes in for an unrelated scan. “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,” says Green. What’s changed is the scope. While a scan of an injured bicyclist could, in theory, pick up the occasional tumor, a scan of a genome, with its thousands of genes, is far more likely to pick up something suspicious.
Green’s niche is examining what it means to apply genetics and genomics in the practice of medicine and more broadly in society. “Everyone will have incidental findings, depending upon what you determine to be an incidental finding,” says Green, who notes that the situation is even more complicated in children. “Results that you return may never trouble the child as a child, but they could trouble that child as an adult. That then starts to get entangled with an ethical principle that’s been out there for a long time that says you don’t share with families medical findings if you find something that indicates a child will get cancer in their forties or fifties.”
Many in the genetics community, bioethicists in particular, pounced once they reviewed the new guidelines. The stipulation that patients must be tested for certain conditions, whatever their wishes, especially troubled them. “It’s not ‘incidental’ if you have a mandatory hunt,” says Lainie Friedman Ross, a pediatrician and bioethicist at the University of Chicago.
It’s little surprise that Ross disagreed so vehemently with the ACMG recommendations. Around the same time the ACMG 56 guidelines were announced, Ross had authored an eagerly awaited policy issued jointly by the ACMG and the American Academy of Pediatrics, the nation’s professional association for pediatricians, about genetic testing in children. The statement differs rather starkly from the ACMG 56 guidelines, even though the ACMG was one of two parties to its development. Casting a wide net for potential disease-causing gene changes is not advised; for the most part, genetic testing should be performed only for diagnostic reasons, because testing should be in a child’s “best interest.”
What’s tricky is that not everyone agrees on how to define that concept, especially since what’s in the best interest of the child may, in a broader context, encompass what’s in the best interest of other relatives. The ACMG recommendations, recall, direct labs to scan children’s genomes for a multitude of disease-linked variants that parents did not request. As a result, not only could disease or risk for disease be caught early in a child, but it could be identified in an unsuspecting adult as well. That theoretical BRCA mutation that Bamshad and Tabor referenced may be of little consequence for a young girl who is years away from developing breasts. But it could be of grave consequence to her mother or father, who is likely to have passed it on to her. “Especially if it is the mother, this information could be life-saving,” says Green. “There is no way that losing a mother to breast cancer is in the best interests of the child.”
The Best Interests of the Child
Be that as it may, requiring that kids be automatically tested for disease risk feels coercive to others. “A typical pediatric ethics framework [asks what is in] the best interests of the child, but here it’s about helping the family members,” Ellen Wright Clayton, the Vanderbilt University pediatrician and bioethicist, told a small group gathered for a 2013 bioethics seminar at Seattle Children’s Research Institute. “In other settings, I have talked about the child as a canary in a coal mine here. It feels that way to me. From a pediatric ethics perspective, [the ACMG recommendation] is a stunning deviation from what pediatric ethics has been based on.”
Whether you agree or not with the marching orders to look for additional findings, Ross raises a good point: Can something rightfully be considered “incidental” if it’s intentionally sought out?
In 2014, the ACMG officially concurred. The organization now refers to “incidental findings” as “secondary findings.” The geneticist Sherri Bale, who served on the ACMG committee that made the decision, believes the distinction is important and more than just a matter of semantics. “We are looking for this stuff,” she says. “It’s not incidental. So let’s just call a spade a spade.” With that hurdle out of the way, debate has continued to percolate within the genetics community over which genes, if any, should routinely be scrutinized. (The list of genes recently expanded to fifty-nine.) After considerable uproar, the ACMG revised its guidelines in 2014, backpedaling to say that parents— indeed, anyone—may opt out of additional genome screening. If you don’t want surplus screening, you won’t automatically get it.
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