The researcher counseled the Stetsons on privacy concerns around genome testing and reminded them they were making a decision their grown daughter could very well disagree with. Unlike most of the families given the choice, the Stetsons said yes — intrigued by the possibility that the exhaustive information gleaned from their daughter’s genes might one day help her.
As it turned out, their case was one of the success stories in the “BabySeq” project, a federally sponsored clinical trial intended to test DNA sequencing in newborns — one of the more thought-provoking uses of the technology.
The Stetsons received clear, immediate and actionable information to help Cora. In contrast, 90 percent of the families whose children had their DNA tested found out they did not carry a genetic risk that posed a health threat in childhood, according to a study reported Thursday in the American Journal of Human Genetics.
“I think it’s interesting that medicine can still be playing defense when we’re at this point in the world — I think we should all be playing offense,” Lauren Stetson said.
Their daughter had a genetic enzyme deficiency that, if left untreated, could cause developmental delays and vision problems. Normally, the deficiency is picked up in standard newborn screening, when blood from a heel prick is analyzed for dozens of disorders. But because Cora’s case was borderline and there was no family history, it was missed in the routine screening. Today, she is a normal, happy two-year-old with a simple vitamin regimen to keep her healthy.
“I believe that the child was at risk to grow up with slightly diminished intellectual ability,” said Alan Beggs, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, one of the leaders of the trial. “Whether it would be an amount you could measure and say, ‘Aha, they’re a special-needs child’ — we don’t know the answer, mostly because children like that who’ve been born in the past are so subtle they never get sent to extensive genetic testing.”
Genetic testing has become increasingly routine for people curious about their ancestry, cancer patients seeking treatments targeted to the genetic mutations that drive their disease and people suffering from mysterious, undiagnosed conditions thought to have genetic roots. But the question of how and whether full genome sequencing of healthy people should be done has remained a matter of considerable debate. Genome enthusiasts paint a picture in which DNA information can inform a truly personalized course of medicine for every individual, while skeptics question whether the information is truly useful for everyone.
The tremendous potential — and concerns — over genome sequencing intensify at the beginning of life, when the genetic manual for a person’s entire life could guide their lifelong care, perhaps long before symptoms of disease even develop. But it also raises deep questions: Will the information provide clear, useful answers on what medical actions to take? Are parents sacrificing their children’s autonomy by making such a consequential decision when they are newborns? Does more information improve health and save lives, or increase unnecessary tests and parental worries and, potentially, alter the bond between parent and child?
The BabySeq project randomized children to receive either DNA sequencing or routine care. Researchers decoded the DNA of 159 infants, including 127 healthy newborns and the rest from the neonatal intensive care unit, at a cost of about $1,000 per child. The data was analyzed for aberrant genes that cause diseases in childhood — meaning researchers left out disease risks that could come later in life, such as Alzheimer’s disease.
The researchers found gene mutations strongly linked to diseases treatable in childhood in 10 percent of the babies, none of which would have been detected at that stage based on family history or symptoms. They found that 90 percent of the infants carried gene mutations that had no direct effect on their health, but could affect their offspring’s health in a few decades — if they partnered with someone who happened to carry mutations in the same genes. They also looked for genes that could provide actionable information to parents such as the presence of breast cancer risk genes, and reported that information back to families in three cases.
“I think we’re basically pushing back on the notion that there’s nothing there, or that there’s nothing actionable there,” said Robert C. Green, a medical geneticist at Brigham and Women’s Hospital who co-led the trial. “I think history is going to look back at this time period and say, ‘Didn’t they realize how much meaningful information was in the genome of virtually every single person?’”
But whether this information is ultimately helpful or harmful, whether it saves lives, or drives unnecessary medical care, remains to be seen, in most cases. For those skeptical of the value of testing healthy newborns, the study results were far from a resounding endorsement, seeming to show that most parents weren’t interested in this information, and that in only a small fraction of cases, did they discover immediate health risks. Even then, the utility of the information was not always clear.
“I hope that we will see that this is a tool that can be useful when indicated, in a nuanced way, not the idea of using it on everybody,” said Josephine Johnston, director of research at the Hastings Center, a think tank focused on bioethics. “That’s certainly what studies are showing: It’s not so easy to sequence someone and know what it means.”
For example, multiple babies carried gene mutations thought to cause a heart condition called dilated cardiomyopathy, but it’s unclear whether they will ever develop heart problems. That means the families can get further testing for the child and other family members, or make different decisions about participating in sports that could increase the children’s risk. But it’s also possible that some of those children will never develop the disease because of a fact about genetic testing that is often not appreciated — the information, which has been built up as the blueprint of a human being, is not nearly as deterministic as most people believe.
While many people understand that having high cholesterol or blood pressure are risk factors for a heart attack or stroke, they may not appreciate that for many mutations, not everyone who carries the flaw will develop the disease.
“It’s also the case that genetic information is understood by the public as being somewhat different than blood pressure,” Johnston said. “Maybe there are things that I can do to combat high blood pressure. People don’t understand genes the same way — as things you can change.”