The Gene Machine, page 1
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For Aviv, Shira, and Orli, who couldn’t be more perfect for me had they been “designer babies”
The unexamined life is not worth living.
—Socrates
Introduction
“He’s perfect,” pronounced the pediatrician at my two-week-old son’s inaugural check-up. I flushed with happiness. What a nice thing for a doctor to say to an insecure first-time mom. And yet he was wrong. We all have genetic mutations. In fact, each human being kicks off life with about sixty new mutations, or changes in their genes.
Some are more obvious than others. Some cause problems, others don’t. Nobody’s perfect, the adage goes. When it comes to our genes, that’s especially true.
In 2007, when I was pregnant with my third child, a routine ultrasound revealed a cyst on my daughter’s developing brain. Flat on my back in a darkened room, ultrasound goo smeared on my belly, I froze. Contending with any ominous-sounding “cyst” would have been bad enough, but processing the idea in conjunction with my baby’s brain, her tiny body’s command center, was chilling. I heard the doctor say that such bubbles frequently go away but may also indicate trisomy 18, a devastating genetic condition that is often fatal soon after birth, if not in utero. I could opt for what doctors call “watchful waiting,” keeping tabs on the cyst via ultrasound as my pregnancy progressed, or I could choose an amniocentesis—a needle inserted into my womb—to suction DNA for analysis from my daughter’s skin cells, free-floating in my amniotic fluid. In skilled hands, the risk of miscarriage is very low, but it still exists. What did I want to do?
I am an information junkie, so for me the decision was clear: my husband and I went straight from my doctor’s office to the office of the specialist who would do the amnio. It was a quick, if sharply painful, assault on my midriff. Predictably, I spent the next day or so panicked that I would miscarry, wondering if I’d made the right choice. Then, on a Saturday afternoon in January, on my middle child’s second birthday, the phone rang. The lab was calling to reassure me that initial results showed all the chromosomes where they should be. I sank onto the couch, folded the birthday girl, Shira, in her purple velvet frock and with her budding blond curls, into my arms, and cried with relief.
Imagine my confusion a few days later when our mail carrier shoved a copy of the lab report, which I’d requested, through the mail slot. The amnio had indeed ruled out trisomy 18, but it had inadvertently revealed that my baby had a different, unrelated condition: inversion 9, a transposed ninth chromosome. For some reason, the top portion of the chromosome had landed on the bottom; the segment that was supposed to be on the bottom had migrated to the top. All the relevant information was still there; it’s akin to putting your underwear in your socks drawer and your socks in the drawer reserved for undies. You could still find the wayward socks and undergarments, arranged neatly—they just wouldn’t be where they ordinarily reside.
It was, I learned, one of the most common genetic errors. Even the lab report dismissed its relevance, its technical language reassuring me that this genetic blooper was benign or, in the language of the lab, “not associated with clinical effects.” Perhaps, but I quickly found that knowing about it was strongly associated with emotional effects. One of my daughter’s chromosomes was upside down and I wasn’t supposed to worry? What’s more, it was highly likely that either my husband or I had the same inversion, considering that the lab report noted that this topsy-turvy presentation was considered a “normal familial variant.”
To allay my fears, I took the ill-advised yet irresistible path that so many of us tread when faced with unfamiliar health-related information: I paged Dr. Google. I came across one small study that indicated an increased risk of schizophrenia, a finding that still makes me blanch when my daughter, Orli, throws a tantrum or acts particularly irrational, traits that—let’s be honest—are not wholly uncharacteristic of the average grade-schooler.
Still, I wasn’t prepared for this surprise genetic discovery; nor are countless other parents who encounter similar situations. And yet our growing reliance on a constantly expanding arsenal of genetic tests to enhance our understanding of our children at their most basic cellular level means that this scenario is becoming routine. It’s not that I wish I didn’t know; I’m glad I know, because now, if new research is published that finds Orli’s error correlates with disease, I’ll be paying close enough attention to delve into that research and see what I can do, if anything, to reduce her risks. Over the years, I’ve assimilated the news of Orli’s genetic anomaly, incorporating it into the vivid panorama that is my tennis-playing, panda-obsessed youngest child. I can’t honestly say that I think about her chromosomal quirk on a daily or even weekly basis, but it does pop into my mind from time to time (remember those tantrums?), and sometimes I wonder: What if the lab report is wrong?
I first started paying attention to the increasing role that genetic testing is playing in children’s health back in 2011. I was covering parenting and pediatrics for Time and received an email from Pediatrics, the official journal of the American Academy of Pediatrics, about an intriguing study. The research explored parents’ eagerness to subject their children to tests that transcended the boundaries of the ever-growing catalog of genetic diseases comprising the routine “newborn screening” regimen that takes place in hospitals across the country. The research in question was fascinating: in a large group-practice health plan, 219 parents were offered testing for themselves for genetic variants associated with increased risk of eight fairly common adult-onset conditions—heart disease, high blood pressure, high cholesterol, Type 2 diabetes, osteoporosis, and cancers of the colon, skin, and lung. Asked if they’d like the same genetic testing for their children under age eighteen, the parents indicated that they thought the benefits of testing their kids outweighed any risks. Their gung-ho attitude seemed to stem from a belief that testing could certify their kids as grade-A healthy.
In fact, researchers had tried to talk the parents out of testing their kids (no kids were actually tested; researchers were simply trying to gauge interest) by telling them that there were no known health benefits to doing so, but the parents were not deterred. They may have assumed that their kids—whose average age was ten—would get a clean bill of health. Yet the fifteen different gene mutations associated with the eight diseases the parents were being screened for are so widespread that any particular child would likely have tested positive for nine mutations.
“What? Really?!” I exclaimed to Colleen McBride, senior author of the study and then chief of the Social and Behavioral Research Branch at the National Human Genome Research Institute (NHGRI). Parents, myself included until that moment, seemed pretty clueless about the stories that genes may whisper or shout within our bodies. Yet more and more genetic tests are being introduced—and more and more genes are being singled out as potential troublemakers. We are learning more and more about our genome, our genetic code, but at the same time we still don’t understand the basics. As McBride characterized the parents when I interviewed her for the Time story: “The more they anticipated feeling good, the more they wanted to test. 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?”
That question is at the heart of this book. Is genetic knowledge empowering or fear-inducing, or both? Will it heighten the anxieties of already hyper-anxious helicopter moms and dads, always waiting for the genetic shoe to drop? Will it make parents more diligent about their child’s health so that they offer broccoli over brownies and slather on the sunscreen? Will it stress parents out or make them savvier?
There’s no indication that parental enthusiasm for genetic information is waning. In fact, a 2014 survey revealed overwhelming support from newly minted parents. In the study, 514 of them were asked within forty-eight hours of their child’s birth if they’d be interested in having their baby’s genome sequenced, its DNA code deciphered and scanned for errors that may be associated with disease. Thirty-seven percent said they were “somewhat” interested, 28 percent indicated they were “very” interested, and 18 percent reported they were “extremely” interested—a total of 83 percent. Factors such as gender, race, education, and income level didn’t seem to make a difference one way or another: four out of five parents thought sequencing their baby’s genome seemed like a pretty sound idea.
Even notoriously nonchalant teenagers want a piece of the action. When 282 Cincinnati students in middle school and high school were asked if they’d want to know genetic results about hypothetical conditions that wouldn
We are accustomed in our tech-savvy world to accumulating data on our children. There are apps to track a baby’s sleep, how often he eats, when she dirties a diaper. But tallying genetic mutations trumps tracking the daily toll of soiled Pampers.
In an information age that compels us to be connected 24/7, no longer do we run to the shelf to pull out a volume of the Encyclopaedia Britannica. We are all encyclopedias now with the help of an Internet connection. But all this information can be disconcerting. When I talk about my work, I find that people are either giddy with the promise of information or quaking at the thought of attempting to divine their destiny and that of their children and grandchildren. Even the scientists who are doing the research in the academic trenches, advancing these technologies from theory into practice, are on the fence about what they want to know about themselves and their loved ones. At one of the most esteemed children’s hospitals in the country, one geneticist I interviewed spoke proudly of having his genome sequenced; another, whose office is within earshot of the first’s, disparaged the trend as self-important and superfluous.
Regardless of differing views, there’s no doubt that genetics is reshaping pregnancy and childhood. In the process, it’s changing the experience of what it means to be a parent.
* * *
Not long ago, having a baby was a fairly straightforward venture. When a couple decided to have a child, they’d ditch the birth control pills and dim the lights. But with no plastic wand with twin purple lines to offer instant at-home confirmation, there was no easy way to gauge success.
The first home pregnancy test—a diagnostic tool now taken for granted by the 4 million women who give birth each year in the United States—wasn’t developed until the 1970s. For centuries before that, women relied on various methods, including the so-called “grain test,” which supposedly had the added benefit of sussing out gender. An Egyptian papyrus from 1350 B.C.E. explains the not-so-scientific theory behind the practice of a would-be mother urinating on wheat and barley seeds: “If the barley grows, it means a male child. If the wheat grows, it means a female child. If both do not grow, she will not bear at all.”
When I was conceived in 1971, my mother learned she was going to become one by heading to her doctor’s office after she missed her period. She was offered no genetic tests, got no real-time sonographic glimpse of her daughter-in-waiting doing weightless flips inside her abdomen, had no clue if I’d be a boy or a girl. She didn’t know if I’d emerge with ten fingers and the same number of toes, let alone the proper number of chromosomes. She was expecting, and she was oblivious to all the things that could go wrong.
Fast-forward four decades. We are a generation fueled by information, and at no time in our lives do we crave it more than when we are poised to become parents—and once we have our babe in arms. We snap up pregnancy books and memorize developmental milestones as we steep ourselves in the minutiae of a world so unfamiliar it might as well be another country. Even the language is foreign—hyperemesis gravidarum? Reciprocal babbling? As we struggle to find our footing in this strange new place, the cluster of cells nested deep inside is already under scrutiny.
Indeed, at a pregnant woman’s first prenatal visit, she rolls up her sleeve and lab techs promptly divest her of multiple vials of blood destined for testing. Soon after, more tests are offered via ultrasound and additional blood draws, and via samples of placental tissue and amniotic fluid, revealing a depth of information that scientists couldn’t have fathomed a generation, even a decade, ago. Nor is baby herself exempt.
Across the United States, before parents leave the hospital with their new charges, the infants have taken what a newborn screening education website cleverly dubs Baby’s First Test. No one, of course, is suggesting that infants be quizzed on their ABCs. This first test doesn’t require much of them, just a couple of drops of blood extracted from a pinprick of their heel. The blood is smeared on specially prepared filter paper, then sent to state labs, where it’s screened for rare genetic and metabolic conditions, some of which may quickly prove fatal if not detected.
Newborn screening has been a pillar of public health since 1963, when Massachusetts became the first state to routinely screen infants for phenylketonuria, or PKU, an inherited metabolic disorder that causes brain damage if left untreated. PKU achieved this distinction not because the condition is any more devastating than scores of other genetic diseases, but because it is treatable if detected early—and because the microbiologist Robert Guthrie developed a cheap, effective way to screen for it. This one test spawned the development of others, and what began as a public health measure to detect just PKU has expanded to include dozens of diseases.
There’s little question that newborn screening has saved countless lives. Each year, screening identifies more than 5,000 infants who have genetic disorders with severe, frequently deadly, consequences. Babies who screen positive undergo further testing to confirm a diagnosis and are referred for treatment.
The newborn screening program is a government-funded safety net designed to ensure a healthy start for the newest members of society. “Newborn screening occupies a very privileged place,” says Robert Nussbaum, former chief of the Division of Medical Genetics at the University of California, San Francisco. “It is a form of testing that undergoes the least amount of scrutiny of any genetic testing we offer in society. Newborn screening is a social contract between the population and the government.”
It’s a contract of which many parents remain unaware. Although newborn screening is technically optional, parents often have no memory of being asked about it. Detecting sick babies before they have symptoms is so critical for successful outcomes that parents are not specifically asked to consent. Most newborn screening is done in the hospital between twenty-four and forty-eight hours after birth, when a baby’s enzyme and metabolic levels are within a measurable, age-dependent range; babies born outside the hospital can have their testing done by a nurse midwife or a pediatrician. “It’s an opt-out model,” says Natasha Bonhomme, director of Baby’s First Test, a federally funded clearinghouse for information and education about newborn screening in all fifty states, administered by the health advocacy organization Genetic Alliance. “It’s considered so important that you just go and do it.”
That’s not the case with the ever-growing array of testing available prenatally, postnatally, and even pre-conception. The expanding number of options means that the act of parenting, of making choices for and about a child, now starts long before a baby’s first breath. Mothers and fathers are urged to leave less and less to chance. More testing, earlier than ever, means they don’t have to.
Now, not only do most parents know ahead of time what color to paint the nursery, but technology exists to tell them whether their developing cluster of cells has Down syndrome or a genetic deletion so tiny that it wouldn’t have been detected even a few years ago. Mutations that heighten the lifetime likelihood of developing a great variety of diseases can also be identified, a dicey dance considering that many conditions, such as early-onset Alzheimer’s, cannot be treated: What good is it to know about a risk of disease if there’s nothing that can be done to help? This information exchange about possible or actual progeny is often taking place before the end of the first trimester, maybe even before an embryo implants, forcing parents to make difficult decisions based on an unprecedented deluge of data. Information is usually seen as a good thing, especially in this digital age. But is it possible to have too much information?
* * *
Do parents like Laura—flat on her back on an exam table in midtown Manhattan, pants off, shirt on but pushed up over her pregnant belly, silver lamé high-tops glinting in the darkened room—really want to know their child’s future?
Laura is thirty-three and has come to see Ronald Wapner for chorionic villus sampling, or CVS, in which Wapner, director of maternal-fetal medicine at Columbia University Medical Center, will plunge a needle through her abdomen into her uterus to collect enough placental tissue (its genetic makeup reflects the fetus’s DNA) to determine whether her pregnancy is healthy. He snaps on clear latex gloves, small-talking as he swabs her belly with Betadine, and compliments her shimmery shoes while warning her she’s about to feel a “really strange sensation of pressure.” Laura grimaces. Wapner inserts the needle. When he removes it seconds later, the attached syringe is filled with whitish specks floating in a clear pinkish liquid. The white specks are placental cells; they look like goose down. The fluid is tissue culture media that was present in the syringe from the start. “This could not have been easier,” Wapner reassures Laura.
