Is Finding Out Your Baby’s Genetics A New Responsibility of Parenting?
Hours after a baby is born, its heel is pricked with a lancet. Drops of the infant's blood are collected on a porous card, which is then mailed to a state laboratory. The dried blood spots are screened for around thirty conditions, including phenylketonuria (PKU), the metabolic disorder that kick-started this kind of newborn screening over 60 years ago. In the U.S., parents are not asked for permission to screen their child. Newborn screening programs are public health programs, and the assumption is that no good parent would refuse a screening test that could identify a serious yet treatable condition in their baby.
Learning as much as you can about your child's health might seem like a natural obligation of parenting. But it's an assumption that I think needs to be much more closely examined.
Today, with the introduction of genome sequencing into clinical medicine, some are asking whether newborn screening goes far enough. As the cost of sequencing falls, should parents take a more expansive look at their children's health, learning not just whether they have a rare but treatable childhood condition, but also whether they are at risk for untreatable conditions or for diseases that, if they occur at all, will strike only in adulthood? Should genome sequencing be a part of every newborn's care?
It's an idea that appeals to Anne Wojcicki, the founder and CEO of the direct-to-consumer genetic testing company 23andMe, who in a 2016 interview with The Guardian newspaper predicted that having newborns tested would soon be considered standard practice—"as critical as testing your cholesterol"—and a new responsibility of parenting. Wojcicki isn't the only one excited to see everyone's genes examined at birth. Francis Collins, director of the National Institutes of Health and perhaps the most prominent advocate of genomics in the United States, has written that he is "almost certain … that whole-genome sequencing will become part of new-born screening in the next few years." Whether that would happen through state-mandated screening programs, or as part of routine pediatric care—or perhaps as a direct-to-consumer service that parents purchase at birth or receive as a baby-shower gift—is not clear.
Learning as much as you can about your child's health might seem like a natural obligation of parenting. But it's an assumption that I think needs to be much more closely examined, both because the results that genome sequencing can return are more complex and more uncertain than one might expect, and because parents are not actually responsible for their child's lifelong health and well-being.
What is a parent supposed to do about such a risk except worry?
Existing newborn screening tests look for the presence of rare conditions that, if identified early in life, before the child shows any symptoms, can be effectively treated. Sequencing could identify many of these same kinds of conditions (and it might be a good tool if it could be targeted to those conditions alone), but it would also identify gene variants that confer an increased risk rather than a certainty of disease. Occasionally that increased risk will be significant. About 12 percent of women in the general population will develop breast cancer during their lives, while those who have a harmful BRCA1 or BRCA2 gene variant have around a 70 percent chance of developing the disease. But for many—perhaps most—conditions, the increased risk associated with a particular gene variant will be very small. Researchers have identified over 600 genes that appear to be associated with schizophrenia, for example, but any one of those confers only a tiny increase in risk for the disorder. What is a parent supposed to do about such a risk except worry?
Sequencing results are uncertain in other important ways as well. While we now have the ability to map the genome—to create a read-out of the pairs of genetic letters that make up a person's DNA—we are still learning what most of it means for a person's health and well-being. Researchers even have a name for gene variants they think might be associated with a disease or disorder, but for which they don't have enough evidence to be sure. They are called "variants of unknown (or uncertain) significance (VUS), and they pop up in most people's sequencing results. In cancer genetics, where much research has been done, about 1 in 5 gene variants are reclassified over time. Most are downgraded, which means that a good number of VUS are eventually designated benign.
While one parent might reasonably decide to learn about their child's risk for a condition about which nothing can be done medically, a different, yet still thoroughly reasonable, parent might prefer to remain ignorant so that they can enjoy the time before their child is afflicted.
Then there's the puzzle of what to do about results that show increased risk or even certainty for a condition that we have no idea how to prevent. Some genomics advocates argue that even if a result is not "medically actionable," it might have "personal utility" because it allows parents to plan for their child's future needs, to enroll them in research, or to connect with other families whose children carry the same genetic marker.
Finding a certain gene variant in one child might inform parents' decisions about whether to have another—and if they do, about whether to use reproductive technologies or prenatal testing to select against that variant in a future child. I have no doubt that for some parents these personal utility arguments are persuasive, but notice how far we've now strayed from the serious yet treatable conditions that motivated governments to set up newborn screening programs, and to mandate such testing for all.
Which brings me to the other problem with the call for sequencing newborn babies: the idea that even if it's not what the law requires, it's what good parents should do. That idea is very compelling when we're talking about sequencing results that show a serious threat to the child's health, especially when interventions are available to prevent or treat that condition. But as I have shown, many sequencing results are not of this type.
While one parent might reasonably decide to learn about their child's risk for a condition about which nothing can be done medically, a different, yet still thoroughly reasonable, parent might prefer to remain ignorant so that they can enjoy the time before their child is afflicted. This parent might decide that the worry—and the hypervigilence it could inspire in them—is not in their child's best interest, or indeed in their own. This parent might also think that it should be up to the child, when he or she is older, to decide whether to learn about his or her risk for adult-onset conditions, especially given that many adults at high familial risk for conditions like Alzheimer's or Huntington's disease choose never to be tested. This parent will value the child's future autonomy and right not to know more than they value the chance to prepare for a health risk that won't strike the child until 40 or 50 years in the future.
Parents are not obligated to learn about their children's risk for a condition that cannot be prevented, has a small risk of occurring, or that would appear only in adulthood.
Contemporary understandings of parenting are famously demanding. We are asked to do everything within our power to advance our children's health and well-being—to act always in our children's best interests. Against that backdrop, the need to sequence every newborn baby's genome might seem obvious. But we should be skeptical. Many sequencing results are complex and uncertain. Parents are not obligated to learn about their children's risk for a condition that cannot be prevented, has a small risk of occurring, or that would appear only in adulthood. To suggest otherwise is to stretch parental responsibilities beyond the realm of childhood and beyond factors that parents can control.
With millions of people left feeling helpless as COVID-19 sweeps across the U.S. and the rest of the planet, there is one way in which absolutely anyone can help fight the pandemic -- all you need is a computer and an Internet connection.
"The more donors that participate, the more science we're able to do."
The Folding@home project allows members of the public to contribute a portion of their computing power to a gigantic virtual network which has mushroomed over the past month to become the most powerful supercomputer on the planet.
As of April 6, more than one million people across the globe have donated some of their home computing resources to the project. Combined, this gives Folding@home processing powers that dwarf even NASA and IBM's most powerful devices. To join, all you have to do is go to this website and click 'Download Now' to load the Folding@home software on your computer. This runs in the background, and only adds your unused computing power to the project, so it will not drain resources from tasks you're trying to do.
"It's totally crazy," said Vincent Voelz, associate professor of chemistry at Temple University, Philadelphia, and one of the scientists leading the project. "A month ago, we had around 30,000 to 40,000 participants. And then last week, it rose up 400,000 and now we've hit a million. But the more donors that participate, the more science we're able to do."
Voelz and the other scientists behind Folding@home are using these vast resources to model the ever-changing shapes of the coronavirus's proteins, in the hopes of identifying vulnerabilities or 'pockets' in its structure that can be targeted with new drugs.
One of the reasons it's difficult to find treatments for viruses like COVID-19 and Ebola is because the proteins, the innate building blocks of the viral structure, have notoriously smooth surfaces, making it hard for drugs to bind to them.
But viral proteins don't stay still. They are constantly evolving and changing shape as the atoms within push and pull against each other. Having a supercomputer enables scientists to simulate all these different shapes, revealing potential weaknesses which were not immediately visible. And the more powerful the supercomputer, the faster these simulations can happen.
"Simulating these protein motions also enables us to answer basic questions such as what makes this new coronavirus strain different from previous strains," said Voelz. "Is there something about the dynamics of these proteins that makes it more virulent?"
Finding a genuinely novel drug for COVID-19 is particularly critical.
Once they have identified suitable pockets within the proteins of COVID-19, the Folding@home scientists can then take the many compounds being identified by chemists around the world as potential drugs, and try to predict which ones will stand the best chance of binding to those pockets and inhibiting the virus's ability to invade and take over human cells.
"We have so much bandwidth now with Folding@home that we really think we can make a dent with screening these, and prioritizing which compounds are then going to get experimentally tested," said Voeltz.
The team are particularly hopeful they can succeed, having already used the supercomputer to identify a new vulnerability in the Ebola virus, which could go on to yield a new treatment for the disease.
Finding a genuinely novel drug for COVID-19 is particularly critical. While researchers are also looking at repurposing existing medications, like the antimalarials Hydroxychloroquine and Chloroquine (which have just been approved by the FDA for emergency use in coronavirus patients), concerns remain about the safety of these treatments. Researchers at the Mayo Clinic recently warned that the use of these drugs could have the side effect of inducing heart problems and run the risk of sudden cardiac arrest.
But with the death toll increasing by the day, speed is of the essence. Voelz explains that the scientific community has been left playing catch-up, because a drug was never actually developed for the original SARS outbreak in the early 2000s. The enormous computational power of the Folding@home project has the potential to allow scientists to quickly answer some of the key questions needed to get a new treatment into the pipeline.
"We don't have a SARS drug for whatever reason," said Voelz. "So the missing ingredient really, is the basic science to reveal possible drug targets and then the pharma can take that information and do the engineering work and optimizing and clinically testing drugs. But we now have a lot of basic science going on in response to this pandemic."
Stefania Sterling was just 21 when she had her son, Charlie. She was young and healthy, with no genetic issues apparent in either her or her husband's family, so she expected Charlie to be typical.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period."
It wasn't until she went to a Mommy and Me music class when he was one, and she saw all the other one-year-olds walking, that she realized how different her son was. He could barely crawl, didn't speak, and made no eye contact. By the time he was three, he was diagnosed as being on the lower functioning end of the autism spectrum.
She isn't sure why it happened – and researchers, too, are still trying to understand the basis of the complex condition. Studies suggest that genes can act together with influences from the environment to affect development in ways that lead to Autism Spectrum Disorder (ASD). But rates of ASD are rising dramatically, making the need to figure out why it's happening all the more urgent.
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Indeed, the CDC's latest autism report, released last week, which uses 2016 data, found that the prevalence of ASD in four-year-old children was one in 64 children, or 15.6 affected children per 1,000. That's more than the 14.1 rate they found in 2014, for the 11 states included in the study. New Jersey, as in years past, was the highest, with 25.3 per 1,000, compared to Missouri, which had just 8.8 per 1,000.
The rate for eight-year-olds had risen as well. Researchers found the ASD prevalence nationwide was 18.5 per 1,000, or one in 54, about 10 percent higher than the 16.8 rate found in 2014. New Jersey, again, was the highest, at one in 32 kids, compared to Colorado, which had the lowest rate, at one in 76 kids. For New Jersey, that's a 175 percent rise from the baseline number taken in 2000, when the state had just one in 101 kids.
"It is surprising that the prevalence of a significant disorder like autism has risen so consistently over a relatively brief period," said Walter Zahorodny, an associate professor of pediatrics at Rutgers New Jersey Medical School, who was involved in collecting the data.
The study echoed the findings of a surprising 2011 study in South Korea that found 1 in every 38 students had ASD. That was the the first comprehensive study of autism prevalence using a total population sample: A team of investigators from the U.S., South Korea, and Canada looked at 55,000 children ages 7 to 12 living in a community in South Korea and found that 2.64 percent of them had some level of autism.
Searching for Answers
Scientists can't put their finger on why rates are rising. Some say it's better diagnosis. That is, it's not that more people have autism. It's that we're better at detecting it. Others attribute it to changes in the diagnostic criteria. Specifically, the May 2013 update of the Diagnostic and Statistical Manual of Mental Disorders-5 -- the standard classification of mental disorders -- removed the communication deficit from the autism definition, which made more children fall under that category. Cynical observers believe physicians and therapists are handing out the diagnosis more freely to allow access to services available only to children with autism, but that are also effective for other children.
Alycia Halladay, chief science officer for the Autism Science Foundation in New York, said she wishes there were just one answer, but there's not. While she believes the rising ASD numbers are due in part to factors like better diagnosis and a change in the definition, she does not believe that accounts for the entire rise in prevalence. As for the high numbers in New Jersey, she said the state has always had a higher prevalence of autism compared to other states. It is also one of the few states that does a good job at recording cases of autism in its educational records, meaning that children in New Jersey are more likely to be counted compared to kids in other states.
"Not every state is as good as New Jersey," she said. "That accounts for some of the difference compared to elsewhere, but we don't know if it's all of the difference in prevalence, or most of it, or what."
"What we do know is that vaccinations do not cause autism."
There is simply no defined proven reason for these increases, said Scott Badesch, outgoing president and CEO of the Autism Society of America.
"There are suggestions that it is based on better diagnosis, but there are also suggestions that the incidence of autism is in fact increasing due to reasons that have yet been determined," he said, adding, "What we do know is that vaccinations do not cause autism."
Zahorodny, the pediatrics professor, believes something is going on beyond better detection or evolving definitions.
"Changes in awareness and shifts in how children are identified or diagnosed are relevant, but they only take you so far in accounting for an increase of this magnitude," he said. "We don't know what is driving the surge in autism recorded by the ADDM Network and others."
He suggested that the increase in prevalence could be due to non-genetic environmental triggers or risk factors we do not yet know about, citing possibilities including parental age, prematurity, low birth rate, multiplicity, breech presentation, or C-section delivery. It may not be one, but rather several factors combined, he said.
"Increases in ASD prevalence have affected the whole population, so the triggers or risks must be very widely dispersed across all strata," he added.
There are studies that find new risk factors for ASD almost on a daily basis, said Idan Menashe, assistant professor in the Department of Health at Ben-Gurion University of the Negev, the fastest growing research university in Israel.
"There are plenty of studies that find new genetic variants (and new genes)," he said. In addition, various prenatal and perinatal risk factors are associated with a risk of ASD. He cited a study his university conducted last year on the relationship between C-section births and ASD, which found that exposure to general anesthesia may explain the association.
Whatever the cause, health practitioners are seeing the consequences in real time.
"People say rates are higher because of the changes in the diagnostic criteria," said Dr. Roseann Capanna-Hodge, a psychologist in Ridgefield, CT. "And they say it's easier for children to get identified. I say that's not the truth and that I've been doing this for 30 years, and that even 10 years ago, I did not see the level of autism that I do see today."
Sure, we're better at detecting autism, she added, but the detection improvements have largely occurred at the low- to mid- level part of the spectrum. The higher rates of autism are occurring at the more severe end, in her experience.
A Polarizing Theory
Among the more controversial risk factors scientists are exploring is the role environmental toxins may play in the development of autism. Some scientists, doctors and mental health experts suspect that toxins like heavy metals, pesticides, chemicals, or pollution may interrupt the way genes are expressed or the way endocrine systems function, manifesting in symptoms of autism. But others firmly resist such claims, at least until more evidence comes forth. To date, studies have been mixed and many have been more associative than causative.
"Today, scientists are still trying to figure out whether there are other environmental changes that can explain this rise, but studies of this question didn't provide any conclusive answer," said Menashe, who also serves as the scientific director of the National Autism Research Center at BGU.
"It's not everything that makes Charlie. He's just like any other kid."
That inconclusiveness has not dissuaded some doctors from taking the perspective that toxins do play a role. "Autism rates are rising because there is a mismatch between our genes and our environment," said Julia Getzelman, a pediatrician in San Francisco. "The majority of our evolution didn't include the kinds of toxic hits we are experiencing. The planet has changed drastically in just the last 75 years –- it has become more and more polluted with tens of thousands of unregulated chemicals being used by industry that are having effects on our most vulnerable."
She cites BPA, an industrial chemical that has been used since the 1960s to make certain plastics and resins. A large body of research, she says, has shown its impact on human health and the endocrine system. BPA binds to our own hormone receptors, so it may negatively impact the thyroid and brain. A study in 2015 was the first to identify a link between BPA and some children with autism, but the relationship was associative, not causative. Meanwhile, the Food and Drug Administration maintains that BPA is safe at the current levels occurring in food, based on its ongoing review of the available scientific evidence.
Michael Mooney, President of St. Louis-based Delta Genesis, a non-profit organization that treats children struggling with neurodevelopmental delays like autism, suspects a strong role for epigenetics, which refers to changes in how genes are expressed as a result of environmental influences, lifestyle behaviors, age, or disease states.
He believes some children are genetically predisposed to the disorder, and some unknown influence or combination of influences pushes them over the edge, triggering epigenetic changes that result in symptoms of autism.
For Stefania Sterling, it doesn't really matter how or why she had an autistic child. That's only one part of Charlie.
"It's not everything that makes Charlie," she said. "He's just like any other kid. He comes with happy moments. He comes with sad moments. Just like my other three kids."