Just about every day, genetic counselor Shawn Fayer heads to the maternity ward at Brigham and Women's Hospital in Boston and tries to convince new parents to give him a blood sample.
Fayer is offering gene sequencing for newborns. It gives parents a tantalizing look at their baby's genetic information.
New parents Lauren and Ian Patrick, from Marion, Mass., were excited when they were first approached earlier this month.
"My initial reaction — why wouldn't someone do this? Why wouldn't they want the information?" Ian Patrick says as he cradles his newborn son, Finn. "For me, more information is better, even if it's not always good."
If his parents sign him up, Finn would join the BabySeq project, an NIH-funded study led by Dr. Robert Green, a medical geneticist at Brigham and Women's Hospital, and Alan Beggs at Boston Children's Hospital. With genetic testing getting cheaper and cheaper, Green wants to figure out what happens when parents know their child's genetic blueprint from day one.
Half of the babies who join the study will have their protein-coding genes sequenced and screened for variants that are associated with diseases of childhood, with a method called whole-exome sequencing. The other half will get the regular heel-prick blood test offered to all newborns, which screens for major genetic disorders like cystic fibrosis.
Researchers will follow both sets of babies to figure out how genetic sequencing impacts them. They want to find out if knowing the kids' genetic makeup could actually make them healthier, or if it could increase their health care costs, or even change their relationship with their parents.
"We are looking for all sorts of unanticipated variations in DNA," Green says, "and we say right up front we don't know what they all mean. We don't know what they're all going to mean for your baby."
Green is particularly interested in a list of 1,514 genes where there are good reasons to reveal a mutation because a disease might be treated or prevented. But there are so many changes in everyone's DNA, he says, he's finding something to report in every baby he sequences.
Right now, that's a pretty small number of babies. Green has sequenced the genes of 51 newborns so far, and he's found five who have genetic mutations families wouldn't have known about otherwise. Two babies have pharmacogenetic variants — mutations that mean certain drugs might not work as well on them. Three have mutations associated with heart conditions they inherited from a parent. Both the babies and their parents appears to be totally healthy.
One of those babies is Kai Gracia. His parents, Alyssa and Jason Gracia, agreed to the test when Kai was just a few days old. They didn't expect to find much. Alyssa was genotyped a few years before, and the information she got was mostly trivial — she learned she metabolized caffeine particularly quickly and she discovered she didn't have the photic sneeze reflex, meaning she wasn't likely to sneeze when suddenly exposed to bright light. So when the results on her baby came back, she was shocked. Right there in Kai's genetic report was this: supravalvular aortic stenosis.
It turns out Kai has a mutation in a gene that codes for a protein called elastin. Elastin helps heart muscles bend and stretch. Not producing enough of it can cause the aorta to narrow. People can die from this, or need multiple surgeries as they grow.
Now that she knew her baby might get sick, Alyssa Gracia had lots of questions. Would Kai be able to play sports when he got older? Did he need surgery? Could crying too much be dangerous?
She made appointments with pediatric cardiologists and brought in Kai's genetic report. One doctor said he looked fine, and only needed to be monitored every few years. Another said his parents should bring him back after just a few months. Usually, a condition like Kai's isn't diagnosed until a child is showing symptoms. That means doctors still aren't quite sure how to treat Kai.
This is the kind of story that both thrills and terrifies the observers of this new technology, according to Green.
"There's no consensus on how to manage these findings," he says. And it's unclear if the follow-up is worth it, or if it might actually do harm.
Gene sequencing reveals medical information about not just one person, but potentially a whole family. So all that follow-up is being done not just on Kai, but on his dad and his grandmother — all people who might be carrying this gene and might be at risk themselves.
So what can families do with all this information? Dr. Green says that for one family, this genetic report was potentially lifesaving.
It showed an inherited mutation in the baby's BRCA2 gene, which increases the risk of breast, ovarian, prostate and pancreatic cancers. This means not only is the baby at risk, but the child's mother or father could be, too.
Before they told the family, the researchers had to deal with "a really pernicious ethical problem," says Green. He and his colleagues had agreed they would only tell parents about genetic variants that could impact babies in childhood, since the children weren't able to decide for themselves whether they wanted to know their genetic risks. BRCA2 causes cancer in adults, not children.
But this information was so important, Green decided to break protocol.
"You know what the first four words were out of the mother's mouth when she was told?" Green asks. " 'Oh, that explains it.' "
It turns out the mother knew distant relatives who had died from cancer, but she hadn't thought it meant anything for her. Without her baby's test, she might never have learned about her own risk.
Not every mutation is actionable like this. Green is also finding a lot of single recessive mutations for conditions like cystic fibrosis, Tay-Sachs and sickle cell. Since it takes two mutations, one each from mother and father, to cause the disease, it becomes an issue only when these babies grow up and decide to have children themselves.
One thing Green hadn't anticipated is how hard it has been to convince new parents to do this screening in the first place. Early research showed the majority of parents were interested in the medical information. But 94 percent of parents Green and his team are approaching are saying no.
Lauren and Ian Patrick, the parents of baby Finn, are a good case study.
Initially, they were convinced they wanted the screening. But after an hour talking to a genetic counselor about all the ways this sequencing could go wrong, they decided against it.
They learned that any genetic sequencing would go in their son's medical record, and it wouldn't be able to be removed. And while federal law prohibits genetic discrimination by health care providers and in the workplace, life insurers can still use genetic information to pick and choose whom they'll sell policies to. By the time the meeting was over, the Patricks' excitement had been replaced with concern.
"It really gave me pause that this would be part of the medical record that private companies would have access to," Lauren Patrick says. "That was my full stop in the end."
After all, for the first time she's making a decision for someone who has no say, she says. "That's the biggest thing on my mind, this new dynamic."
RENEE MONTAGNE, HOST:
Today in Your Health, we take you to the cutting edge of medicine - the maternity ward at Brigham and Women's Hospital in Boston. That's where a team of genetic counselors is trying to convince new mothers and fathers to let them genetically sequence their newborns. Mary Harris from member station WNYC reports.
MARY HARRIS, BYLINE: So imagine you've just had a baby, like Lauren and Ian Patrick have.
LAUREN PATRICK: You're getting your birth certificate.
HARRIS: This is Finn. He's just 4 days old.
(SOUNDBITE OF KNOCKING)
HARRIS: Then there's a knock on the door from a genetic counselor, Shawn Fayer.
SHAWN FAYER: Hello.
IAN PATRICK: Hey, how are you?
FAYER: I'm Shawn of the BabySeq project. How are you?
HARRIS: And he offers you the chance to do something that sounds pretty cool.
FAYER: Shall we get started?
HARRIS: He wants to analyze your baby's genome and tell you what's in there.
FAYER: Now we can sequence all genes all at once for a relatively lower cost than years ago.
HARRIS: If Lauren and Ian say yes, they'll be part of a study called BabySeq, and they'll have a chance to get a glimpse at baby Finn's genetic blueprint.
FAYER: How does that sort of information sound to both of you?
L. PATRICK: I think it sounds like something that we'd be interested in having.
HARRIS: They won't give parents their baby's full genetic code, more like the executive summary. Doctors will tell families if a baby's genes point to a problem that might impact him as he grows or if genetic mutations mean certain drugs won't work as well on him. Researchers will then follow families for years to see whether getting sequenced actually makes babies like Finn any healthier.
I. PATRICK: My initial reaction was that why wouldn't somebody do this or why wouldn't they want the information?
HARRIS: This is Finn's dad, Ian.
I. PATRICK: For me, more information is better, even if it's not always good, I think.
HARRIS: It depends on what you find. Dr. Robert Green is leading this study.
Do you remember the first time someone called you up and said, looks like we've found something?
ROBERT GREEN: Well, there are so many changes in everyone's DNA that we actually find something on everybody's sequence.
HARRIS: Which may or may not cause any harm. So far, he's sequenced about 50 babies. Five of those have had congenital conditions their parents wouldn't have known about otherwise, heart problems mostly, and two babies had pharmacogenetic variants, meaning certain drugs might not work as well on them.
But most of what Green is finding in just about every baby he screens are recessive genes that would only be passed on if these babies have kids of their own with a partner who is also a carrier. Green says that means parents might want to think more seriously about how genetically compatible they are with their partners before they have kids.
GREEN: If you think about it, we're just leaving it up to chance to decide whether two people who meet and decide to have a baby are actually carrying a mutation in the same gene.
HARRIS: The potential in all this genetic information gets Green excited. He spent years in a completely different field, neurology, but he went back into training at 52 years old to study genetics. He's had his own genome sequenced three times, so he's been surprised at how hard it's been to convince new parents to take this test.
GREEN: Overall, about 6 percent of the families that we approach are saying yes.
HARRIS: Wow. That seems really low.
GREEN: It does seem really low.
HARRIS: So far, they've spoken to more than 2,400 families. Fewer than 200 have said yes. Parents are worried about bad results or results that aren't clear, and there's good reasons for that. The babies, Green says, might have heart problems. None of them have symptoms, so it's hard to say if they're sick or not.
GREEN: We're very clear with parents about the fact they might get unpleasant information. They might get information that they didn't expect. They might get information that's really hard to interpret. It's quite confusing. They might get information that could theoretically be used against their child in the future.
HARRIS: And when you're a new parent, all that information can feel overwhelming.
(SOUNDBITE OF PHONE RINGING)
HARRIS: Back in the maternity ward, new mom Lauren and her husband, Ian, who started out so bullish about screening, spend almost an hour talking to their genetic counselor about all the ways this sequencing can go wrong.
I. PATRICK: What are most people's sort of reluctancies into doing this type of...
HARRIS: They're worried about their son's privacy and also discrimination.
I. PATRICK: What are they afraid of or what are they - I don't know how to put it the right way.
FAYER: Yeah, no, that's a very good question. So there's actually...
HARRIS: The genetic counselor tells Lauren and Ian that while federal law actually prevents genetic discrimination when it comes to health insurance in the workplace, it isn't against the law for life insurers to use this information to pick and choose who they'll sell their plans to, and that worries them.
FAYER: So at this point, what are we thinking? Is it something you would like to have a little bit more time to think about? Or we can go over the consent forms now if you would like, whatever works for you.
L. PATRICK: I think take a day. Do you want to take a day?
I. PATRICK: Good. That would be great, yeah. Just the insurance thing's an interesting question.
L. PATRICK: Yeah, for me, too.
I. PATRICK: And I'd hate to put him in that position but...
L. PATRICK: Yeah, exactly.
I. PATRICK: ...At the same time, I sort of believe in it, but...
L. PATRICK: Yeah.
HARRIS: Lauren and Ian went through six failed rounds of IVF before this surprise pregnancy, so Finn is a much-hoped-for baby. They say they just want what's best for this little guy.
L. PATRICK: I think we pretty much left that conversation thinking it wasn't for us.
HARRIS: I called Lauren a couple weeks later to see what they decided. In the end, she just didn't feel comfortable with all the unknowns.
L. PATRICK: It really gave me pause that this would be a permanent medical record that private companies would have access to, so that was just my full stop in the end.
HARRIS: Green says he gets this hesitation.
GREEN: We are looking for all sorts of unanticipated variations in DNA. And we say right up front, we don't know what they all mean. We don't know what they're all going to mean for your baby. Would you still like to participate?
HARRIS: Right now, a lot of parents just aren't sure. For NPR News, I'm Mary Harris in Boston. Transcript provided by NPR, Copyright NPR.