You're born, your heel is pricked, your blood is taken. The sample is fed into a machine which decodes your entire genome, all 6 billion bases, tiny pieces of chemical material found in every cell of your body – half from your mother, half from your father – that make up your genes. The machine spits out its results, detailing every single genetic mutation: good, bad and uncertain.
It sounds like a scene from a futuristic science-fiction novel, but it’s a reality that's closer than you think.
In 1990, scientists began to decode the entire human genome. It took hundreds of thousands of research hours, more than a billion dollars and nearly 13 years to complete, explained Dr. Eric Green, director of the National Human Genome Research Institute (NHGRI), while speaking at a recent genomics panel and debate in Washington, D.C. By August of 2003, scientists had a complete human blueprint.
Today, because of rapid technological advances, an entire human genome can be sequenced in a day or two for a few thousand dollars, and that price will continue to drop, Green said. So instead of doing targeted tests looking at specific genes, patients may turn to whole genome sequencing as a more economical solution.
“We are at a point now where powerful new genome sequencing technologies are making it faster and more affordable than ever to access genomic information about patients,” Green said in a press release.
In the fall of 2013, researchers at four different institutions – Brigham and Women’s Hospital in Boston, Children’s Mercy Hospital in Kansas City, Mo., the University of California, San Francisco and the University of North Carolina at Chapel Hill – received funding from the National Institutes of Health to launch pilot studies of newborns’ genomes. The Eunice Kennedy Shriver National Institute of Child Health and Human Development and the NHGRI invested $20 million into the five-year program.
Hospitals already do basic newborn screening tests to evaluate infants’ risks for rare diseases, mostly those of a metabolic nature, says Dr. Jonathan Berg, a geneticist and principal investigator with the newborn genome project at UNC. Typically, doctors only consult parents when the test shows something may be wrong.
“It is an incredibly effective tool for saving the lives of babies who you would never have suspected to have a metabolic disorder because they’re so rare,” Berg says.
But when researchers begin whole genome sequencing, some argue that partnering with patients and helping them make "informed decisions" about which results they want to know will be a critical part of the process. Most specialized clinics currently offering whole genome sequencing require extensive genetic counseling and oblige patients to give their "informed consent."
"There is a very legitimate need to know or want to know by many people and I don’t think we, the academic center, should play the deciders of this information." says Dr. Gianrico Farrugia, director of the Center for Individualized Medicine at the Mayo Clinic.
Each of the four studies has chosen its own focus and takes a slightly different perspective. Berg’s team targets newborn sequencing in the public health setting. They plan to evaluate parents' preferences regarding results they wish to know and those they don’t.
All of the parents will be given results that meet the team's criteria for diseases where intervention begins in childhood. Those in an experimental group also would have the option of learning their newborns' risk for diseases in certain categories: diseases that begin in childhood and are not treatable; diseases that begin in adulthood and are treatable, like gene mutations associated with breast cancer; and diseases that would not affect their newborns but could impact their newborns' children – a status that would make the newborn a "carrier."
None of the parents will be able to learn about diseases that begin in adulthood and are not medically treatable. Berg said the team will avoid risk predictions for certain other diseases where sequencing does not always effectively detect the disease.
“The goal is to see if we can identify the conditions that would make sense to add as part of a routine screening, and that would not create additional concerns in terms of adding information that may be outside of the scope of what we consider traditional newborn screening," Berg says regarding his research team's work.
Unlike with targeted genetic testing – in which researchers pinpoint specific genes – the return of results in whole genome sequencing includes massive amounts of data, and thus far there is no standardized method for how to interpret results and how to decide which results to share with patients. The American College of Medical Genetics and Genomics published recommendations regarding what results doctors should and shouldn’t share in 2013, but those have been widely disputed and outright rejected by some clinics.
“We’re living right now in the wild Wild West, but we’re at the frontier,” says Dr. Bruce Blumberg, director of graduate medical education for Kaiser Permanente Northern California.
Testing children or infants for disorders that don’t occur until adulthood runs counter to long-established guidelines set for children.
“Since 1995 there’s been a standing consensus that we don’t test kids for adult-onset disorders until they themselves reach the age of majority,” says Susan Wolf, a professor of law, medicine and public policy at the University of Minnesota Law School, in reference to recommendations set by the American Academy of Pediatrics which hold that children under 18 have the right to what experts call "an open future," and should wait until they are of age to decide whether or not to find out their risk for adult-onset diseases. But the AAP hasn’t set specific guidelines for whole genome sequencing.
“Why are we leaping to newborns who are the most vulnerable and the least able to participate in the decision?” Wolf asks. An alternative would be to run the study in adults first and then potentially in adolescents. Robbing infants of their "right not to know" to satisfy their parents’ curiosity seems unjustifiable, Wolf argues.
Others aren't so sure.
“If you believe as I do that some predictive information is good as an adult, then perhaps it’s even better as a child,” Dr. Robert Green, a principal investigator of the Brigham and Women’s Hospital newborn genome project, said at the D.C. panel, where he debated Wolf.
"But this is only a testable question,” he added. “I’m not sure that’s right, but we’re gathering evidence.”
Berg considers the perspective of his study’s critics, granting that many may see newborn genome sequencing in a "dystopian" light.
“If this became a technology where every newborn had their genome sequenced at birth, then that would mean that from then on in every generation, you would have no decision-making capacity as an adult about whether or not to learn that information," he says. But “if parents can feel like they’re taking better care of their child by having this information, then it could be beneficial ... The jury is out on whether there’s a net benefit or a net harm to doing that.”
Blumberg, a practicing physician and geneticist whose research interests include the psychosocial and emotional aspects of prenatal diagnoses, sees the science outpacing the ethics.
"Genetics are not as deterministic as geneticists would like to believe," he says. "There’s all kinds of modifications that happen to your genome over the course of your life in response to environmental exposure." He worries that the so-called “predictive” data parents receive could create self-fulfilling prophecies.
When Blumberg finds a condition that could place a child at risk for a mild learning disorder, he says he tells the family but warns them not to share the information with the child’s school unless they themselves see the child struggling.
“Because once the school has that information, they will see learning disabilities," he says. "They’ll be primed to treat the child as if they have a learning disability whether they do or not."
But some doctors view genetic information as no more sensitive or personal than other data.
“One of the arguments that has been raised in the literature has been, if you go to get a chest X-ray on your heart and the radiologist finds a spot in your lungs, nobody argues that the radiologist shouldn't say, 'There’s a spot in your lungs, you need to know about it,'" Farrugia says. "Why is it in genomics we tend to be much more careful and we don’t say the same thing, which is, 'We’re testing your genome for cancer and we find you have an increased risk of Alzheimer's.' Why should we not tell you?"
"On the other hand, we've done quite at lot of research with our patients that shows that patients think of their genome as a very private [thing], kind of fundamentally closer to what they consider to be their core," he adds.
One frequently mentioned study series that addresses these questions – known as The Risk Evaluation and Education for Alzheimer's Disease (Reveal) study – explored how people coped after learning their risk for Alzheimer's disease. Subjects handled positive results better than researchers anticipated.
But critics warn against over-generalizing those results. Catharine Wang, a professor in the community health sciences department at Boston University, says the study used "early adopters" who were getting the best possible counseling. These results might not be transferable in a less motivated sample of subjects.
"The people who wouldn't do OK probably wouldn't come in the door in the first place," she says.
In addition to concerns over the impact of sharing genomic data, there are also serious doubts about its validity. Wang says current newborn screenings help identify diseases in cases where there’s solid evidence linking gene mutations and diseases, but with whole genome sequencing, researchers cannot definitively say whether certain variants are disease-related.
“You’re not doing parents a service by saying, 'We found all these variants, but we don’t know what they mean,'” she says.
Using a small sample size also can be problematic.
“Most of our understanding of those variants is from sequencing in symptomatic populations or populations that are from families that have those disorders in them,” Wolf says.
Wang believes whole genome sequencing is effective when used for diagnostic purposes, such as when a child has a condition that doctors are struggling to diagnose, but she’s baffled by the idea of screening basically healthy newborns for diseases.
“We do not understand what we’re finding. We don’t know how to interpret it,” she says.
There aren’t any simple answers that would resolve everyone’s concerns, but one suggestion might be to release portions of the information about an individual’s genome as the individual meets certain life stages. In that case, a newborn or her parents wouldn’t learn about her breast cancer risk until she reaches an age at which she is equipped to address it. By applying certain filters, doctors could interpret genetic information at birth and re-interpret it later in life in the appropriate context.
But beyond the ethical questions, of which there are many, making whole genome sequencing available to literally every newborn poses practical concerns as well. For one thing, the number of genetic counselors and laboratory analysts would have to be drastically increased.
“Every child being born would have to be consented,” Berg says. And explaining to parents their child’s genetic risks and their right to know or to reject that data isn’t easy. Studies like his try to address whether this is a responsible and useful application of public health funds.
“There’s going to be lots and lots of discussion and
consternation and passionate arguments on one side and the other about the
extent to which parents should be able to peek into their infant's genome,”
Berg says. “It’s going to be a fascinating decade to see how everything plays