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.
[Editor's Note: This video is the fourth of a five-part series titled "The Future Is Now: The Revolutionary Power of Stem Cell Research." Produced in partnership with the Regenerative Medicine Foundation, and filmed at the annual 2019 World Stem Cell Summit, this series illustrates how stem cell research will profoundly impact human life.]
Kira Peikoff was the editor-in-chief of Leaps.org from 2017 to 2021. As a journalist, her work has appeared in The New York Times, Newsweek, Nautilus, Popular Mechanics, The New York Academy of Sciences, and other outlets. She is also the author of four suspense novels that explore controversial issues arising from scientific innovation: Living Proof, No Time to Die, Die Again Tomorrow, and Mother Knows Best. Peikoff holds a B.A. in Journalism from New York University and an M.S. in Bioethics from Columbia University. She lives in New Jersey with her husband and two young sons. Follow her on Twitter @KiraPeikoff.
He Almost Died from a Deadly Superbug. A Virus Saved Him.
An attacking rogue hippo, giant jumping spiders, even a coup in Timbuktu couldn't knock out Tom Patterson, but now he was losing the fight against a microscopic bacteria.
Death seemed inevitable, perhaps hours away, despite heroic efforts to keep him alive.
It was the deadly drug-resistant superbug Acinetobacter baumannii. The infection struck during a holiday trip with his wife to the pyramids in Egypt and had sent his body into toxic shock. His health was deteriorating so rapidly that his insurance company paid to medevac him first to Germany, then home to San Diego.
Weeks passed as he lay in a coma, shedding more than a hundred pounds. Several major organs were on the precipice of collapse, and death seemed inevitable, perhaps hours away despite heroic efforts by a major research university hospital to keep Tom alive.
Tom Patterson in a deep coma on March 14, 2016, the day before phage therapy was initiated.
(Courtesy Steffanie Strathdee)
Then doctors tried something boldly experimental -- injecting him with a cocktail of bacteriophages, tiny viruses that might infect and kill the bacteria ravaging his body.
It worked. Days later Tom's eyes fluttered open for a few brief seconds, signaling that the corner had been turned. Recovery would take more weeks in the hospital and about a year of rehabilitation before life began to resemble anything near normal.
In her new book The Perfect Predator, Tom's wife, Steffanie Strathdee, recounts the personal and scientific ordeal from twin perspectives as not only his spouse but also as a research epidemiologist who has traveled the world to track down diseases.
Part of the reason why Steff wrote the book is that both she and Tom suffered severe PTSD after his illness. She says they also felt it was "part of our mission, to ensure that phage therapy wasn't going to be forgotten for another hundred years."
Tom Patterson and Steffanie Strathdee taking a first breath of fresh air during recovery outside the UCSD hospital.
(Courtesy Steffanie Strathdee)
From Prehistoric Arms Race to Medical Marvel
Bacteriophages, or phages for short, evolved as part of the natural ecosystem. They are viruses that infect bacteria, hijacking their host's cellular mechanisms to reproduce themselves, and in the process destroying the bacteria. The entire cycle plays out in about 20-60 minutes, explains Ben Chan, a phage research scientist at Yale University.
They were first used to treat bacterial infections a century ago. But the development of antibiotics soon eclipsed their use as medicine and a combination of scientific, economic, and political factors relegated them to a dusty corner of science. The emergence of multidrug-resistant bacteria has highlighted the limitations of antibiotics and prompted a search for new approaches, including a revived interest in phages.
Most phages are very picky, seeking out not just a specific type of bacteria, but often a specific strain within a family of bacteria. They also prefer to infect healthy replicating bacteria, not those that are at rest. That's what makes them so intriguing to tap as potential therapy.
Tom's case was one of the first times that phages were successfully infused into the bloodstream of a human.
Phages and bacteria evolved measures and countermeasures to each other in an "arms race" that began near the dawn of life on the planet. It is not that one consciously tries to thwart the other, says Chan, it's that countless variations of each exists in the world and when a phage gains the upper hand and kills off susceptible bacteria, it opens up a space in the ecosystem for similar bacteria that are not vulnerable to the phage to increase in numbers. Then a new phage variant comes along and the cycle repeats.
Robert "Chip" Schooley is head of infectious diseases at the University of California San Diego (UCSD) School of Medicine and a leading expert on treating HIV. He had no background with phages but when Steff, a friend and colleague, approached him in desperation about using them with Tom, he sprang into action to learn all he could, and to create a network of experts who might provide phages capable of killing Acinetobacter.
"There is very little evidence that phage[s] are dangerous," Chip concluded after first reviewing the literature and now after a few years of experience using them. He compares broad-spectrum antibiotics to using a bazooka, where every time you use them, less and less of the "good" bacteria in the body are left. "With a phage cocktail what you're really doing is more of a laser."
Collaborating labs were able to identify two sets of phage cocktails that were sensitive to Tom's particular bacterial infection. And the FDA acted with lightning speed to authorize the experimental treatment.
A bag of a four-phage "cocktail" before being infused into Tom Patterson.
(Courtesy Steffanie Strathdee)
Tom's case was scientifically important because it was one of the first times that phages were successfully infused into the bloodstream of a human. Most prior use of phages involved swallowing them or placing them directly on the area of infection.
The success has since sparked a renewed interest in phages and a reexamination of their possible role in medicine.
Over the two years since Tom awoke from his coma, several other people around the world have been successfully treated with phages as part of their regimen, after antibiotics have failed.
The Future of Phage Therapy
The experience treating Tom prompted UCSD to create the Center for Innovative Phage Applications and Therapeutics (IPATH), with Chip and Steff as co-directors. Previous labs have engaged in basic research on phages, but this is the first clinical center in North America to focus on translating that knowledge into treating patients.
In January, IPATH announced the first phase 2 clinical trial approved by the FDA that will use phages intravenously. The viruses are being developed by AmpliPhi Biosciences, a San Diego-based company that supplied one of the phages used to treat Tom. The new study takes on drug resistant Staph aureus bacteria. Experimental phage therapy treatment using the company's product candidates was recently completed in 21 patients at seven hospitals who had been suffering from serious infections that did not respond to antibiotics. The reported success rate was 84 percent.
The new era of phage research is applying cutting-edge biologic and informatics tools to better understand and reshape the viruses to better attack bacteria, evade resistance, and perhaps broaden their reach a bit within a bacterial family.
Genetic engineering tools are being used to enhance the phages' ability to infect targeted bacteria.
"As we learn more and more about which biological activities are critical and in which clinical settings, there are going to be ways to optimize these activities," says Chip. Sometimes phages may be used alone, other times in combination with antibiotics.
Genetic engineering using tools are being used to enhance the phages' ability to infect targeted bacteria and better counter evolving forms of bacterial resistance in the ongoing "arms race" between the two. It isn't just theory. A patient recently was successfully treated with a genetically modified phage as part of the regimen, and the paper is in press.
In reality, given the trillions of phages in the world and the endless encounters they have had with bacteria over the millennia, it is likely that the exact phages needed to kill off certain bacteria already exist in nature. Using CRISPR to modify a phage is simply a quick way to identify the right phage useful for a given patient and produce it in the necessary quantities, rather than go search for the proverbial phage needle in a sewage haystack, says Chan.
One non-medical reason why using modified phages could be significant is that it creates an intellectual property stake, something that is patentable with a period of exclusive use. Major pharmaceutical companies and venture capitalists have been hesitant to invest in organisms found in nature; but a patentable modification may be enough to draw their interest to phage development and provide the funding for large-scale clinical trials necessary for FDA approval and broader use.
"There are 10 million trillion trillion phages on the planet, 10 to the power of 31. And the fact is that this ongoing evolutionary arms race between bacteria and phage, they've been at it for a millennia," says Steff. "We just need to exploit it."