For years, doctors, scientists, and ethicists have debated whether people will benefit from decoding their DNA, the three billion letters of the genome that spell out traits and predisposition to disease. Now, that complicated conversation is moving to a new venue: the newborn nursery.
The questions swirling around DNA sequencing — how to analyze so much data, what conditions to look for and report back, what to do with unexpected findings — grow even more complicated when the person being sequenced cannot yet be involved in the decision.
Newborn screening is currently used to detect conditions that can have devastating short-term effects on an infant's health, such as metabolic disorders or a deadly immune disorder. It is possible that exhaustive DNA sequencing could be used not just to look for those rare conditions, but to delve more deeply into the child's health.
Seeking to get ahead of a technology that is rapidly advancing, the National Institutes of Health requested and, in November, received a flood of proposals for pilot projects that could provide evidence to guide how, and if, genome sequencing could be used in infancy.
On one hand, researchers speak about the power of one day being able to consult the genetic "book of life" throughout a person's lifetime, if DNA sequencing at birth were to become standard. On the other, doctors worry that the information could lead to issues with medical insurance or simply become a burdensome addition to the medical record that doctors are not ready to handle.
"Are we going to get more bang for the buck if we have this extra information?" said Tiina Urv, program director at the National Institute of Child Health and Human Development. "If you're screening a child at a young age, you might be identifying conditions that don't manifest until they're much older. What do you do with that information? That's why we want to set up pilot studies."
Genetic information is already transforming medical care. Local hospitals routinely use DNA profiles of tumors to refine cancer diagnosis and treatment, and many specialists think it is only a matter of time before full genome sequencing will be used in oncology.
Patients' genomes are being used as a research tool to hunt the source of rare, inherited diseases. At Boston Children's Hospital, 60 children with suspected genetic conditions have been sequenced so far, and nine disease-causing genes have been identified.
"The exact same technology, the ability to sequence the genome, can obviously be used to learn about the makeup of all of us, not just the rare patient with a rare disease," said Alan Beggs, director of the Manton Center for Orphan Disease Research at Children's Hospital. "There are significant potential risks, and I say potential because I think nobody really knows. . . . I think it's a little bit like the genie in the bottle, and it's coming out of the bottle right now."
Susan Wolf — a professor of law, medicine, and public policy at the University of Minnesota — said the prospect of routinely sequencing healthy newborn babies raises an array of new questions and needs careful study, in part because the decisionmaker is not the baby, but the child's parents.
"They have a complicated relationship, a different relationship, to the data than the newborn person themselves," Wolf said.
Historically, medical specialists have believed that such testing should be done in children only if the findings would be of use before individuals are old enough to make the decision to be tested themselves. Otherwise, they have argued, it is important to wait and preserve an "open future" for children.
"Otherwise, the cat's out of the bag, and plus you may have affected parent-child bonding, the dynamics of that family," Wolf said.
To begin to examine some of the logistics and repercussions of such testing, Beggs teamed with Dr. Robert Green, a geneticist at Brigham and Women's Hospital, to design a trial to measure benefits and risks of newborn sequencing.
They proposed a randomized trial in which half the babies would have their DNA analyzed and half would not. Then, researchers would closely track how the information influenced the baby's health and treatments and whether it alters family relationships, causes parents excessive worry, or leads to more visits to the pediatrician. They proposed disclosing only information that would be relevant to the child's health, not risks that might lie decades away.
A version of their proposal, called BabySeq, won $100,000 in seed money from the Brigham this fall, and the researchers are seeking a larger grant from the NIH. The NIH plans early next year to review their proposal and others and decide the recipients of funding. A total of $25 million has been set aside to support several projects over five years.
Some hospitals are already moving forward with trials of DNA sequencing in newborns, both to understand common problems and as a tool to guide health care for babies as they grow up.
After Kathy Tennant's infant, Audrey, was born prematurely at Inova Fairfax Hospital in Virginia earlier this year, she and her husband decided to participate in a study there that would use the genomes of mothers, fathers, and babies to understand more about preterm birth and how to prevent it. During the extensive counseling process, which included signing a 16-page consent form, Tennant said she was told they could choose to learn results unrelated to the study if they emerged.
"We mostly joined to help to see what causes preterm labor," Tennant said, describing the hope that something researchers learned could help spare other families — or even one day, her own children — from spending agonizing weeks as vulnerable infants live in neonatal intensive care units. "If there was any [other] genetic information, we thought that would be OK. But that wasn't the purpose; that was just a little bonus for us."
For example, she said, there were chronic illnesses in her husband's family, and identifying risks early could make their family healthier.
That's what Joseph Vockley — chief scientific officer of the Inova Translational Medicine Institute, headquartered in Falls Church, Va. — said he believes will be the power of newborn sequencing. In addition to studying preterm birth, Inova has launched a large study that involves sequencing families' genomes and following children until age 18, to see if DNA testing can help predict, prevent, and help understand health problems as they develop, such as obesity and diabetes.
"If you're going to do predictive and preventive medicine, the best place to start is with the newborn; it's basically a clean slate," Vockley said.
In his studies, Vockley said, they have thought hard about how to handle unexpected findings. First, they will check a result. For example, if a gene associated with risk of breast cancer was detected, that result would be compared with another test, and that finding would be shared with the pediatrician.
At Children's Hospital, when incidental findings are discovered in inquiries into the genetic underpinnings of rare diseases, the information is presented to a board that reviews the finding and decides whether it should be reported to the family, which can specify whether it wants to receive such information. Beggs said the hospital has so far made only one incidental finding, but the family did not want to be told.