by Ed Cara
In the not-too-distant future, it will be possible to get a complete readout of a person’s genetics with ease, even right after they’re born. A new study published Thursday offers a glimpse of what that future could look, suggesting many children are born with genetic conditions that can’t be found with current screening. But the study also raises important ethical questions about how best to handle the predictions these tests will provide families and their doctors.
Currently, newborns in the U.S. are given blood screening tests that can identify dozens of genetic conditions, including cystic fibrosis and sickle-cell anemia. These tests look for markers, many of which are genetic mutations, seen in people who develop a specific disease. But the genetic markers used in these screening tests represent a tiny slice of a person’s whole set of genes, or genome. The only way to get a (mostly) full picture of a person’s DNA is to sequence it.
Genetic sequencing has long been an extensive, expensive process, but technological advances over the years have made it easier and cheaper to pull off. So doctors and researchers at the Brigham Women’s Hospital and the Boston Children’s Hospital, both in Massachusetts, began a trial in 2015 that would test just how practical and useful sequencing could be if it were regularly done on newborns. They called it the BabySeq Project.
The new study, published in The American Journal of Human Genetics, highlights the initial major findings from the project.
The more than 300 families who volunteered for the BabySeq Project were randomly assigned to two groups. Those in the control group would get the same sort of usual care, including standard genetic screening for the newborns and genetic counseling for caretakers with a family history of genetic disease. Newborns in the second group would get all that and also have their DNA sequenced in whole. Both healthy newborns as well as those who needed intensive care after delivery were included in the project.
Of the 159 babies who received genetic sequencing, 15 (9.4 percent) were found to have mutations that raised their risk of health conditions likely to show up before they turned 18. These conditions included an enlarged heart, hearing loss, or severe kidney disease.
“That was surprising,” study author Ozge Ceyhan-Birsoy, a clinical molecular geneticist at Memorial Sloan Kettering Cancer Center, told Gizmodo. “None of them were anticipated [to have a risk] based on their family or clinical histories.”
The results show the potential of newborn genetic sequencing, but there were plenty of other complicated revelations.
For one, the team was initially allowed to tell the families only about mutations known to raise the risk of childhood genetic conditions. But they could also spot mutations that raised the risk of conditions that would pop up in adulthood, such as breast or colon cancer. Of the 85 families who later consented to having this information disclosed, three newborns had such mutations. And when the parents of these children were tested, they too were found to have the mutations. That’s ostensibly important information to have handy, but it’s worth wondering just how much this kind of screening could change the fundamental doctor-patient relationship.
“There’s typically only one patient per doctor. But in genetics, when you have one member of a family as your patient, you might have to consider that the whole family is potentially under your care,” senior author Alan Beggs, director of the Manton Center for Orphan Disease Research at Boston Children’s Hospital, told Gizmodo. Beggs is the co-lead researcher of the BabySeq Project, alongside his counterpart Robert C. Green at Brigham Women’s Hospital.
The nature of genetic risk is also inherently complicated. Some conditions can be caused by one bad mutation, but others are caused by a mishmash of genetic variations interacting in ways we barely understand. And new risk factors are being discovered every day. Perhaps most confusing is that not everyone genetically at risk for a condition will go on to develop it.
“We might find that everyone with a disease has this particular mutation but not everyone with that mutation gets the disease,” Beggs said. “The uncertainty of that information makes it tricky to return to families in a way they’ll understand.”
The vast majority of children (88 percent) were also carriers of recessive genetic conditions, meaning they had one copy of a gene that might cause disease in future generations, provided their partner also carried a similar copy. A few children (5 percent) had mutations that might influence how they will respond to certain drugs. Are these things need-to-know information, too?
Leaving aside health, should parents be able to know about the potential traits of their children even before they’re delivered out into the world? And if so, should they be allowed to act on it? In many places, including the U.S., there have already been bans proposed or passed on selective abortions based on a child’s sex, race, and genetic risk, though reproductive health advocates have criticized the latter policy as an underhanded attempt to destroy abortion rights by anti-abortion forces.
“I think, as with any technology, it can be used for good or for harm,” said Beggs. “Ultimately, how we use it is going to be up to society.”
It’s unlikely that newborn sequencing will become part of standard care anytime soon, though, according to Ceyhan-Birsoy. Sequencing is still relatively expensive, for one. And it’s uncertain how many people will even want it. Only 7 percent of the families asked to consider participating in the BabySeq Project eventually signed on. The majority who gave a reason for declining simply said they weren’t interested in the research, but others cited genetic privacy or the fear of discrimination as their main concern.
“I think what’s very clear, though,” Beggs said, “is that for a subset of patients, particularly patients who are sick at birth, sequencing might be a cost-effective and beneficial step in today’s world.”
The BabySeq Project will soon formally wind down. But Beggs and his team plan to release more findings from it, including survey results on how the families themselves felt about the project and the information it gave them. They also hope to keep following the families and see what happens to these children as they grow up.
“We feel we have a moral commitment to follow this through. So we expect, in the long term, to stay in touch with these families,” said Beggs.