Call it the “ick” factor.
Stories like the 2018 bombshell out of China, of a scientist manipulating embryonic DNA to produce the world’s first genetically engineered human babies, make people uneasy, often in ways they find hard to define. Our fear of genetics is diffuse and visceral and surfaces in a range of dystopian visions, from experiments gone wrong, à la Frankenstein’s monster, to worlds dominated by genetically enriched super-people. But while our antennae are attuned to things distant, scary and futuristic, we may be missing the more real and immediate threat: Genetic medicine as we practice it today is poised to alter our concept of disease and responsibility in ways that will make the world fundamentally more unfair.
If you could use reproductive genetic technology to make sure that your child did not have a genetic disease, would you do it? That question is not science fiction anymore for many prospective parents. If you have an increased risk of breast and ovarian cancer because of a variant in your genes, there are now ways to make sure you don’t pass that pathogenic variant along to the next generation. If you and your partner each harbor a single gene for spinal muscular atrophy—and with it a 25 percent chance that each of your children will be born with a life-threatening degenerative disease—we can remake the odds, assuring that all your children will be born healthy.
Is this desirable? Parents-to-be have voted with their feet: A non-invasive way to take a look at fetal DNA, introduced in 2011, is the fastest growing genetic test in medical history. But even as we embrace it, the power of the technology makes many people uncomfortable.
When you put “reproductive” and “genetics” in the same sentence, there’s always a lurking question about where it is all going to lead. Public opinion favors some uses and not others. Polling on this issue has been consistent for decades: The public is okay with the use of technology to prevent disease, but not to alter traits. Americans approve of interventions to reduce a child’s lifetime risk of cancer, but don’t want parents choosing their child’s eye color or selecting for higher intelligence, says an AP-NORC poll from 2018. We are in favor of healthier babies, but not “designer babies.”
“Trait selection” invokes the “ick” factor because it seems like it’s tampering with nature (always risky), and because stacking the deck on a child’s genes feels like cheating, even if it is for something trivial like eye color (fact-check: A child’s eye color is constrained by the genes carried by his or her parents, so don’t look for a sudden fad for purple-eyed toddlers). Designer babies, like designer jeans and designer sunglasses, are for the wealthy, and it rubs people the wrong way to see the playing field grown more uneven even before the players learn to walk. But, ironically, it is the negative ramifications of preventing disease—the one aspect of designer babies that does not make us uncomfortable—that may create the most difficult challenges for society in the near future.
How could preventing disease be bad? Isn’t the ability to prevent or even cure genetic disease a benefit to everyone? The answer, of course, is yes; curing genetic disease is a benefit—but only if it doesn’t reinforce existing imbalances and inequities. Unfortunately, a number of concurrent trends suggest this isn’t going to be the case, and that preventing genetic disease will be a luxury enjoyed by the few, not the many. If that does not change, we will risk segregating genetic disease, reshaping it along the long-vexed axis of access: access to money, to education, to new treatments, to reproductive medicine, to testing, to abortion. If we are not careful, some genetic diseases may soon transition from being a part of our common humanity to something that happens only to “certain people.”
The canary in this particular coal mine is Down syndrome, the most common of the handful of chromosomal conditions for which pregnant women have already been offered testing for decades. Down syndrome, like many genetic conditions we might test for in the future, is complex and variable. Individuals with Down syndrome have some level of developmental delay and characteristic physical features; some, but not all, are born with other health problems like heart defects.
To be very clear, Down syndrome is a difference, not an affliction, and people with Down syndrome have health risks, but should not be defined by them. In 2011, when researchers surveyed 284 individuals with Down syndrome over age 12, 99 percent of them said they were happy with their lives. Parents of children with Down syndrome have spoken movingly to me of the joy their kids bring to them and to their families—but also of their need for resources and support.
It’s a crucial challenge, therefore, to offer prenatal testing for Down syndrome in a way that demonstrates understanding of these lived realities along with a respect for the needs of those born with the condition. That is the goal of genetic counseling in the prenatal setting, but it is an ideal that, in practice, has often not been met. For this reason, expanded screening programs have at times been viewed as an attack on the very humanity of individuals with disabilities. Yet, paradoxically, selective access to screening may prove even more dangerous to the welfare of persons with Down syndrome by changing it from a random event into something that is vanishingly rare in certain communities and relatively commonly in others.
Not everyone chooses to test for Down syndrome, and when it is identified in the fetus, not everyone chooses to end the pregnancy. But a significant majority does make that choice. The most comprehensive review of the subject in the United States was published in 2012 by Jaime Natoli of the University of South Carolina and her co-researchers, and their analysis suggests that about two-thirds of pregnant women presented with a diagnosis of Down syndrome will choose to have an abortion. But, significantly, this number is not consistent across the population. The authors point to regional and demographic differences across the country, suggesting that today the odds that someone will carry a baby with Down syndrome to term depends on their culture, their religious beliefs, and where they live. It is shaped by access to prenatal testing and by access to abortion, which varies dramatically by state and income.
What this means is that access to prenatal testing has shifted the incidence of Down syndrome, making it a marker of place and class. As affluent families have fewer children with Down syndrome, it is, relatively speaking, increasingly a condition of other populations—a form of de facto disease segregation that is not good for individuals with Down syndrome.
Crucially, this skew won’t just apply to Down syndrome going forward. There are thousands of other genetic diseases and conditions, and soon we will be able to test for many more of them during pregnancy. Increasingly, tests will give prospective parents information on a variety of threats to the well-being of their potential child. Some of the conditions we will test for will be severe and lethal in childhood; others will be milder, or perhaps present only later in life, like Parkinson’s or Alzheimer’s disease. Sometimes the genetic test results will mean the child is absolutely going to get the disease; most will indicate only an increased risk, like the genes that make certain people more susceptible to heart disease or colon cancer.
How this information gets used will tell us something about what prospective parents consider an intolerable risk. But the impact of testing during pregnancy will be limited by the reality that prospective parents must weigh their concerns against the heartbreak of ending a pregnancy in which they have invested their hopes and dreams.
There is no such limitation, however, when the choice is a matter of selecting between embryos in the IVF setting.
IVF is a major growth industry in part because of something called preimplantation genetic testing, or PGT, which involves taking a small sample of cells from an early-stage embryo to analyze its DNA. This allows people to screen embryos for genetic variation that can cause a disease or condition or susceptibility. The downside is that IVF and PGT are extremely expensive and the process itself is burdensome, since the woman must go through a series of injections to stimulate her ovaries and a minor surgical procedure to extract the eggs.
Despite this, more and more people are using PGT when they are aware of a risk that could affect a potential child. The use of PGT for single gene disorders has grown rapidly in recent years. PGT has been in existence since 1990, but its use in the early years was extremely limited. It was limited by what were considered appropriate targets—usually severe, life-threatening, childhood-onset conditions—and it was limited by our own ability to identify which couples were at increased risk.
Today, we are much more likely to know who is at risk, and why. People who once might have said with a shrug that “heart disease runs in my family” may now be in a position to put a name to the culprit in their genes. The same revolution is taking place in cancer, neurology, and other medical specialties. At the same time, we have improved our ability to identify couples at risk when there is no family history. Recessive conditions are those that occur only when a child receives a disease-causing version of the same gene from each parent, so these diseases can be silent through the generations, and suddenly appear when two carriers have a baby. Until recently, we screened for only a handful of the most common conditions and, as a rule, only after the woman was already pregnant. For most of the vast category of recessive disease, the first sign of risk was the birth of an affected child.
In the past few years, multiple screens have come on the market that identify carriers of hundreds of rare diseases like cystic fibrosis, and ultra-rare diseases like trimethylaminuria, a disorder of the metabolism that makes an affected individual smell like rotting fish. But these expansive carrier screens generally require prospective parents to pay out of pocket. In addition to the cost, getting the information in time to use PGT requires both halves of the couple to be involved in preconception planning.
The cost of screening is nothing compared to the cost of making use of the information. Let’s say that Joe and Jane learn via preconception screening that they are each carriers for hypophosphatasia, which means they run a 25 percent chance of having a baby with soft, misshapen bones who will likely die in infancy. If they are interested in using PGT to make sure that doesn’t happen, their IVF costs will run around $20,000 per cycle, with an added $10,000 in custom lab work to identify which of their embryos will not have the disease. Will insurance pay for it? Insurance coverage is extremely inconsistent. Their policy may cover the IVF procedure and stimulation drugs but not the laboratory work required to do PGT, or it may cover PGT but not IVF—a combination one IVF doctor described to me as “like paying for coronary bypass surgery, but not to crack the chest.” Most policies pay for nothing, and those that do may not cover Joe and Jane, because they are not technically infertile.
For some families, these costs will seem like a bargain. For less than the cost of a year at college, they can insure themselves against disaster. A wealthy family dogged by breast and ovarian cancer because of a BRCA 1 or 2 mutation can rid themselves of this scourge in a single generation. While they’re at it, if they produce enough embryos, they may be able to reduce their child’s risk of late-onset Alzheimer’s disease as well, or perhaps pick an embryo less prone to coronary artery disease.
For other families, even the out-of-pocket expenses associated with IVF will make it a nonstarter, no matter what the risk. Access may improve, but evidence to date suggests otherwise. In the United States, just under 2 percent of all babies born are conceived using IVF, while in countries that offer public funds for assisted reproductive technology like Israel, Denmark, and Belgium, it is two or three times that number. The implication: More than half of the people who would like to use IVF in this country can’t afford it. Forty years after its introduction in the United States, IVF remains out of reach for a substantial portion of the American public.
It’s not news that there are inequities in the US health care system, and to some extent this is just another example. But when you take a step back and consider the potential consequences of a world where people with means can reduce or eliminate the threat of genetic disease and others cannot, the stakes are very high. Certain genetic diseases have always occurred more often in specific populations—sickle cell anemia in African Americans, Tay-Sachs in Ashkenazi Jews, a rare type of dwarfism among the Amish. But increasingly, we can expect to see the burden of genetic disease as a category disproportionately born by discrete regional, cultural, and socioeconomic groups—and these groups will be, by and large, those who are already among our most vulnerable populations.
This matters for fundamental moral reasons, but also for practical ones. Families with resources are rainmakers and cheerleaders for disease communities, raising the profile of a condition that affects one of their own. They fund researchers and support groups. Families with fewer resources who are already coping with a sick child or parent will be hard-pressed to add in the roles of activist and educator, but advocacy is crucial in what science writer Virginia Hughes called “the disease Olympics,” the zero-sum game by which funds are allocated for research and care.
And worst of all, these families may face a growing empathy deficit. A public that does not see their own loved ones as hypothetically at risk may not have the “there but for the grace of God go I” impulse that prompts a compassionate response. Rather, they may feel that insulating their children from risk is a reflection of better parenting or better planning, adding a new kind of stigma to the burden of affected individuals. Where society once saw misfortune, they may see instead malfeasance, and balk at the burden of paying for “other people’s mistakes.”
In the field of clinical genetics, we are excited about our growing arsenal of interventions to prevent, treat, or even cure genetic disease. Our goal is to make the world a better place, not to make it more fundamentally unfair. But that could be our legacy if we allow the ghettoization of genetic disease. Put aside Frankenstein and Gattaca for a moment; this is the real, immediate threat.
We can’t respond to it by ignoring all the potential of genetic medicine. The answer can’t be that everyone should suffer from things we can prevent. But we need to be thinking about how to prevent the ghettoization of genetic disease right now.
One clear solution is to link our expanding use of genetic technology to a commitment to preconception screening and prenatal testing for any woman who wants it. We can seek to make sure that abortion is an option for all following prenatal diagnosis of a life-threatening or life-limiting prenatal condition in the fetus, understanding that at times that may require a more complicated or later procedure. We can work on ensuring access to assisted reproductive technology for those whose children are at increased risk of a serious medical risk—a process that begins by defining what is a “serious medical risk” and what is merely an acceptable level of risk associated with being human.
But most of all, we need to work on maintaining empathy for all affected individuals and their families, regardless of our own sense of vulnerability. With the expanding use of genetic technology, we must not only worry that we don’t create monsters; we must worry that we don’t become them.