Can you imagine wanting to know whether your newborn baby will fall victim to Alzheimer’s disease decades down the road? What about cancer or diabetes?
Emma Warin can. In August she gave birth to a healthy 8-lb., 3-oz. boy. She agreed to participate in an unprecedented study in which researchers will map out every speck of DNA in her son’s genome, potentially revealing mutations that could cause health problems now and far into the future. Warin, a medical-device sales representative in Falls Church, Va., says the information will help her plan ahead for any issues. Still, she adds, “It’s a little scary.” (TIME Explains: The Science of Genome Sequencing)
When it comes to your health, the debate about how much information is too much is about to get a lot more complicated. Whole-genome sequencing (WGS), a scientific breakthrough less than 10 years old, is on its way to becoming a mainstream medical test. When researchers first mapped a human genome in 2003, the effort cost $2.7 billion. Now the price for analyzing a person’s genetic code is down to $7,500 and falling. As the test gets cheaper, it’s expanding beyond cancer patients seeking tailored therapies and people suffering from mystery illnesses; the government is already starting to consider the possibility of scanning the genome of every newborn baby. Eventually the test could even become available through drugstores, for anyone with curiosity and a credit card.
Experts say this will open an uncharted — and possibly chilling — frontier in medicine. WGS can provide early warnings about some of the deadliest and most debilitating diseases. Those warnings, in turn, can enable timely treatment or at least allow people to make plans about long-term care. But the drawbacks can be significant. Murky findings, for instance, can send patients on odysseys of costly, risky and potentially unnecessary additional tests.
WGS raises tough questions for all patients, but it’s quickly becoming clear that some of the most complicated issues center on one group: kids. After all, the youngest patients have the most to gain from early detection of severe disorders. Many parents naturally want to get as much information as possible about their kids’ health. And this is certainly not the first time they’ve had to decide how much they want to know about their kids’ genetic future: pregnant women are routinely offered tests to detect Down syndrome and other disorders.
(MORE: Complete Genetics Coverage)
But WGS can detect an increased risk not just of childhood diseases but also of disorders that may not manifest for decades, if at all. As the test becomes more widely available, parents who consider sequencing their children will face agonizing decisions. Should apparently healthy kids get screened, or only those whom doctors suspect of having a problem? If a child does get tested, should parents opt to learn all the results — potentially burdening themselves with worries about far-off suffering — or should they choose to remain in the dark about untreatable problems that wouldn’t strike until adulthood? After researchers at the University of Washington announced this summer that they’d successfully performed WGS on a fetus, the decisionmaking process ratcheted up: How much should parents learn about unborn children?
Perhaps the most unnerving choice of all: how much information to share with the child, and at what age. Warin herself, though committed to the testing, hasn’t yet decided how she’ll handle sharing the results with her son. “I probably would wait until he’s older … I’m not sure if I’d let him know,” she says. “Probably. Maybe.”
As medical tests go, WGS is relatively simple for patients. Less than a teaspoon of blood is enough for a human’s DNA to give up its secrets. In the lab, of course, it’s more complicated. Scientists use chemicals to burst open the cells and gather the microscopic threads of DNA that had been housed inside them. Those tiny strands are placed into sophisticated machines that read each of the 3 billion bits of information, called base pairs, that make up a person’s genetic alphabet. Computers then scan the data for the equivalent of spelling mistakes — some “mistakes” cause disease; others don’t.
That’s where things get tricky. WGS reports on all 21,200 genes at once, but science doesn’t know enough yet to interpret all the results. Some genetic mistakes, or variants, are known to be bad (“deleterious mutations”), and some are known to be harmless (“benign polymorphisms”). In between is a vast gray area where scientists just don’t know what the changes mean. In other words, sometimes WGS will turn up something that’s known to affect health, but often the results will simply raise more questions.
Still, demand for the tests for kids appears poised to take off as the cost continues to drop — and as more adults are exposed to the concept. A study last year in the journal Pediatrics found that parents offered genetic tests for adult-onset conditions including diabetes and skin cancer said they’d also like to test their children.
The study participants reflected some common beliefs in today’s society — that more information is always better and that the best parents are the most proactive — and they tended to regard the tests as a way to rule out the bad stuff. “The more [the parents] anticipated feeling good, the more they wanted to test,” says Colleen McBride, the National Human Genome Research Institute (NHGRI) investigator who led the small study. “But the reality is, those parents are going to get bad news. Their kids are going to be at risk for something. So how are they going to react to that?”
Dr. Ian Krantz and Nancy Spinner want to find out. The husband-and-wife team at the Children’s Hospital of Philadelphia (CHOP) are working with an $8.8 million grant from NHGRI to understand what genomic information parents want to know and what they don’t. To do this, they are recruiting families whose children have one of four types of medical conditions: hearing loss, autism or intellectual disabilities, a history of sudden cardiac arrest, and disorders of the mitochondria, the tiny power plants that energize cells.
Many of these parents are looking for something specific: the cause of, say, their child’s inability to walk or talk. “If you tell parents their child also has an increased risk for colon cancer or breast cancer, that’s a whole different level of stress,” says Krantz, a pediatrician who oversees medical genetics training at CHOP.
Krantz and Spinner themselves are divided on what they’d want to know about their own children and about each other. Krantz is game for sequencing himself and learning all the results; not so for Spinner, who notes that many mutations indicate only an increased risk of developing disease, not a guarantee of it. She also points out that environment plays a significant role in disease development. “I’m a worrier,” she says, “and everything you find isn’t necessarily going to turn out to be the truth.”
If they were compelled to do WGS for their kids because they had a severe but undiagnosed disorder, they would. But Spinner says she wouldn’t want to know about any incidental findings; Krantz would want only results that could be acted on in childhood. What they agree on is that sequencing their three kids just out of curiosity is unnecessary.
The stakes are bigger than individual families, though. Some researchers believe sequencing newborns can help identify certain genetic changes that can be addressed early in life — and that determining which mutations cause disease and which don’t will lead to better medical care for everyone.
One of those researchers is Dr. John Niederhuber, the former director of the National Cancer Institute (NCI). While sequencing cancers at NCI, Niederhuber became convinced that understanding our genetic code would transform medicine. In 2010 he established the nonprofit Inova Translational Medicine Institute in northern Virginia to explore the connection between genomics and future health. If we know what health conditions we’re predisposed to, he says, we can theoretically take preventive steps: lose some weight to stave off diabetes, eat more kale to avoid cancer, start screening extra-early for breast cancer.
So what better place to start, Niederhuber figured, then at birth or even before? His study, which is privately funded, is asking pregnant couples if they want to be sequenced and have their newborns sequenced and, if so, whether they want to find out the results. “I wasn’t sure how our young families would react to this,” he says, “but they have been very interested.” The study launched in April and plans to enroll 2,500 families. Emma Warin’s family was among the first to sign up.
Kathi Huddleston, Inova’s director of clinical research, sees the long-term project as “almost like the baby Framingham,” she says, referring to a landmark study of heart health in generations of residents of that Massachusetts town. Still, she’s cautious about what WGS will reveal about all those infants. “Doing whole-genome sequencing is a long ways from putting in a movie about your future,” she says. “There’s more that we don’t understand than we do understand.”
For parents of sick kids, that can be maddening. Janice and Mike Belcher have been trying to figure out what’s wrong with their 8-year-old daughter Juliet since she was three days old. Juliet, who lives in Blue Bell, Pa., can’t walk or talk or eat on her own; she’s fed through a tube that snakes into her intestines. When strangers ask what’s wrong with their daughter, the Belchers don’t have an answer. Doctors have suspected that Juliet has some sort of disorder in which her body’s mitochondria aren’t manufacturing enough energy.
So although Juliet cracks up while listening to her mom read the wacky rhymes in C Is for Clown, her brain activity is hampered. “We suspect the specific genetic disorder in Juliet is one that has never been known to cause disease in any human being before,” says her doctor at CHOP, geneticist Marni Falk. Sequencing could confirm Falk’s hunch. So in August, the Belchers agreed to have Juliet’s exome — the part of her genome that codes for the proteins that do the body’s operational heavy lifting — sequenced at Houston’s Baylor molecular laboratory.
But before Baylor would proceed, the Belchers had to tackle an eight-page consent form. How much, it asked, did they want to know? Should they be told only about findings directly related to her mitochondrial disorder? About genes that increase her childhood risk of other diseases? About mutations that could cause heart disease or cancer when she’s an adult?
The Belchers first said they wanted to learn only about gene mutations that could explain Juliet’s condition. Then, on the car ride home, Janice, a sixth-grade teacher, started having doubts. Had they made the wrong decision? “As she gets older, if she’s going to start having different problems, I want to prepare,” she told Mike, who is a Marine Corps officer. In the end, they asked to be told about anything that could possibly affect Juliet. And just like Emma Warin, they are still waiting for their child’s results.
This is the first in a five-part series exploring the promise and pitfalls of sequencing children’s genomes. Read the full series.
DNA illustration: Getty Images