The U.S. government is funding an ambitious set of studies into what happens if you screen the entire genome of newborns. The goal is to find out whether such testing brings better health care or unwanted information overload.
Do parents even want to know what fate might await their babies? Can doctors find out anything useful medically? Do you get information that freaks you out? All over the country, thousands of newborns will be enrolled in this experiment, the National Institutes of Health announced on Wednesday.
They’re not necessarily looking for new diseases in the babies yet, says Dr. Eric Green, director of the NIH’s National Human Genome Research Institute (NHGRI). They want to know what happens if you even go down this road of whole-genome sequencing.
Now’s the time, he said, as companies begin offering these tests on the market and as more and more people seek to find out just what their genes say about their health. “Everything is moving so fast,” Green told reporters on a conference call.
“We really want to take advantage of this window of opportunity to answer key questions about the technical, ethical, social implications while we have a chance to do it,” Green added. “If it turns out this is something that is worth doing, we would answer questions about how to make it most effective.”
Green’s genome institute and the National Institute of Child Health and Human Development (NICHD) has set aside $25 million for the next five years to study the matter, starting out with $5 million to four institutions: Brigham and Women's Hospital and Boston Children's Hospital; Children's Mercy Hospital in Kansas City; the University of California, San Francisco and the University of North Carolina at Chapel Hill.
Each center will take a different approach. For example, UCSF will test blood drops previously collected from 1,400 California children who were already given newborn screening tests. Boston Children's will recruit 480 newborns starting early next year, giving half the standard screening and half an extra genome test.
Most of the 4 million children born in the U.S. each year get a heel-prick test that takes a drop of blood to screen for genetic diseases such as phenylketonuria, sickle-cell disease, cystic fibrosis and thyroid disorders. The precise panel differs from state to state but usually covers around 30 disorders.
One reason to do the tests, says NICHD director Dr. Alan Guttmacher, is to intervene early, before the child gets sick. Phenylketonuria or PKU is a classic example. It’s an inability to process an amino acid called phenyl lanine, which can build up in the brain and cause permanent damage. “By knowing the baby has the disease early, parents can modify the baby’s diet to remove phenylalanine and prevent damage,” Guttmacher said. “Prevention is the only effective solution.”
The heel-prick tests cost around $100. Whole-genome screening covers not only known genetic defects, but the entire DNA map. Commercial tests – which don’t look at every stretch of DNA – cost about $5,000.
Each of the four centers will answer slightly different questions about the testing. “We would like to see if genome sequencing can shed light on disorders that we don’t screen for currently,” Guttmacher said. But there are social and legal questions. “How do we protect the baby’s privacy?” he asked. “Where will the baby’s genome data be stored and who will have access to it?”
NIH is clearly sensitive about the matter after settling with the family of Henrietta Lacks, the cervical cancer patient whose tumor cells have been used as the basis of countless medical experiments for more than 60 years, without her family’s knowledge or permission until a few years ago.
Under the settlement, two of Lacks’s grandchildren will help decide which biomedical researchers will have access to the genetic information from her cells, called HeLa cells. Lacks, whose story was told in the 2010 best-selling book "The Immortal Life of Henrietta Lacks," died in 1951.
Some of the genetic diseases that might turn up include Fragile X syndrome, which can cause profound mental retardation, and Rett syndrome, which can cause a developmental disorder similar to autism, Erv said.
UNC's team will test healthy children alongside children who are suspected to have genetic diseases already, while Children's Mercy will work on a test it has already developed to rapidly screen babies fro 750 diseases caused by a single genetic defect, including muscular dystrophy, cystic fibrosis and polycystic kidney disease.
"We believe that 30 percent of the babies in our NICUs (neonatal intensive care units) are likely to benefit from next-day genome sequencing. This grant will generate the critical data to guide the use of rapid genome sequencing in the diagnosis and treatment of acutely ill babies," said Dr. Stephen Kingsmore, director of the Center for Pediatric Genomic Medicine at Children’s Mercy.
It does raise delicate questions. “What should doctors tell parents about what was found? How much will all of this cost?” Guttmacher said.
“What is the best way to deliver and present genome sequencing information to parents and clinicians?” added Green.
Another important question, says NHGRI’s Anastasia Wise, is how to handle what are called incidental findings – something discovered by accident. Do parents want to know, for instance, that their child carries a high genetic risk of a certain cancer?
“How do the parents feel? What do they understand?” added NICHD’S Tiina Urv.
There are medical questions, too. "Some of the disorders we pick up during screening are chemical abnormalities, but we don’t know whether they will actually cause problems for the child," said UCSF's Dr. Robert Nussbaum, who will direct one of the studies. "We’d like to know whether there is something in the children’s genes that determines whether these abnormalities actually will cause disease.”
At least one consumer advocacy group, Public Citizen, expressed some concerns. “It’s actually proceeding to do genomic sequencing in newborns while at the same time trying to determine what are the ethical implications of that. Maybe they are getting ahead of themselves,” said the group’s Dr. Michael Carome.
Carome’s group has petitioned the Health and Human Services Department about different NIH research involving newborns, saying parents were not adequately informed of the dangers. That study involved more than 1,300 premature babies who were given differing amounts of oxygen to see if there was a difference in whether they survived and how healthy they were.
Premature babies given too much oxygen can become blind, while those given too little are more likely to die. In the trial, 20 percent of the babies given lower amounts of oxygen died, compared to 16 percent of those given more. Public Citizen’s complaint was that parent’s weren’t adequately told of the risks to their babies.