Is Finding Out Your Baby’s Genetics A New Responsibility of Parenting?

A doctor pricks the heel of a newborn for a blood test.
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.
Kirstie Ennis, an Afghanistan veteran who survived a helicopter crash but lost a limb, pictured in May 2021 at Two Rivers Park in Colorado.
In June 2012, Kirstie Ennis was six months into her second deployment to Afghanistan and recently promoted to sergeant. The helicopter gunner and seven others were three hours into a routine mission of combat resupplies and troop transport when their CH-53D helicopter went down hard.
Miraculously, all eight people onboard survived, but Ennis' injuries were many and severe. She had a torn rotator cuff, torn labrum, crushed cervical discs, facial fractures, deep lacerations and traumatic brain injury. Despite a severely fractured ankle, doctors managed to save her foot, for a while at least.
In November 2015, after three years of constant pain and too many surgeries to count, Ennis relented. She elected to undergo a lower leg amputation but only after she completed the 1,000-mile, 72-day Walking with the Wounded journey across the UK.
On Veteran's Day of that year, on the other side of the country, orthopedic surgeon Cato Laurencin announced a moonshot challenge he was setting out to achieve on behalf of wounded warriors like Ennis: the Hartford Engineering A Limb (HEAL) Project.
Laurencin, who is a University of Connecticut professor of chemical, materials and biomedical engineering, teamed up with experts in tissue bioengineering and regenerative medicine from Harvard, Columbia, UC Irvine and SASTRA University in India. Laurencin and his colleagues at the Connecticut Convergence Institute for Translation in Regenerative Engineering made a bold commitment to regenerate an entire limb within 15 years – by the year 2030.
Dr. Cato Laurencin pictured in his office at UConn.
Photo Credit: UConn
Regenerative Engineering -- A Whole New Field
Limb regeneration in humans has been a medical and scientific fascination for decades, with little to show for the effort. However, Laurencin believes that if we are to reach the next level of 21st century medical advances, this puzzle must be solved.
An estimated 185,000 people undergo upper or lower limb amputation every year. Despite the significant advances in electromechanical prosthetics, these individuals still lack the ability to perform complex functions such as sensation for tactile input, normal gait and movement feedback. As far as Laurencin is concerned, the only clinical answer that makes sense is to regenerate a whole functional limb.
Laurencin feels other regeneration efforts were hampered by their siloed research methods with chemists, surgeons, engineers all working separately. Success, he argues, requires a paradigm shift to a trans-disciplinary approach that brings together cutting-edge technologies from disparate fields such as biology, material sciences, physical, chemical and engineering sciences.
As the only surgeon ever inducted into the academies of Science, Medicine and Innovation, Laurencin is uniquely suited for the challenge. He is regarded as the founder of Regenerative Engineering, defined as the convergence of advanced materials sciences, stem cell sciences, physics, developmental biology and clinical translation for the regeneration of complex tissues and organ systems.
But none of this is achievable without early clinician participation across scientific fields to develop new technologies and a deeper understanding of how to harness the body's innate regenerative capabilities. "When I perform a surgical procedure or something is torn or needs to be repaired, I count on the body being involved in regenerating tissue," he says. "So, understanding how the body works to regenerate itself and harnessing that ability is an important factor for the regeneration process."
The Birth of the Vision
Laurencin's passion for regeneration began when he was a sports medicine fellow at Cornell University Medical Center in the early 1990s. There he saw a significant number of injuries to the anterior cruciate ligament (ACL), the major ligament that stabilizes the knee. He believed he could develop a better way to address those injuries using biomaterials to regenerate the ligament. He sketched out a preliminary drawing on a napkin one night over dinner. He has spent the next 30 years regenerating tissues, including the patented L-C ligament.
As chair of Orthopaedic Surgery at the University of Virginia during the peak of the wars in Iraq and Afghanistan, Laurencin treated military personnel who survived because of improved helmets, body armor and battlefield medicine but were left with more devastating injuries, including traumatic brain injuries and limb loss.
"I was so honored to care for them and I so admired their steadfast courage that I became determined to do something big for them," says Laurencin.
When he tells people about his plans to regrow a limb, he gets a lot of eye rolls, which he finds amusing but not discouraging. Growing bone cells was relatively new when he was first focused on regenerating bone in 1987 at MIT; in 2007 he was well on his way to regenerating ligaments at UVA when many still doubted that ligaments could even be reconstructed. He and his team have already regenerated torn rotator cuff tendons and ACL ligaments using a nano-textured fabric seeded with stem cells.
Even as a finalist for the $4 million NIH Pioneer Award for high-risk/high-reward research, he faced a skeptical scientific audience in 2014. "They said, 'Well what do you plan to do?' I said 'I plan to regenerate a whole limb in people.' There was a lot of incredulousness. They stared at me and asked a lot of questions. About three days later, I received probably the best score I've ever gotten on an NIH grant."
In the Thick of the Science
Humans are born with regenerative abilities--two-year-olds have regrown fingertips--but lose that ability with age. Salamanders are the only vertebrates that can regenerate lost body parts as adults; axolotl, the rare Mexican salamander, can grow extra limbs.
The axolotl is important as a model organism because it is a four-footed vertebrate with a similar body plan to humans. Mapping the axolotl genome in 2018 enhanced scientists' genetic understanding of their evolution, development, and regeneration. Being easy to breed in captivity allowed the HEAL team to closely study these amphibians and discover a new cell type they believe may shed light on how to mimic the process in humans.
"Whenever limb regeneration takes place in the salamander, there is a huge amount of something called heparan sulfate around that area," explains Laurencin. "We thought, 'What if this heparan sulfate is the key ingredient to allowing regeneration to take place?' We found these groups of cells that were interspersed in tissues during the time of regeneration that seemed to have connections to each other that expressed this heparan sulfate."
Called GRID (Groups that are Regenerative, Interspersed and Dendritic), these cells were also recently discovered in mice. While GRID cells don't regenerate as well in mice as in salamanders, finding them in mammals was significant.
"If they're found in mice. we might be able to find these in humans in some form," Laurencin says. "We think maybe it will help us figure out regeneration or we can create cells that mimic what grid cells do and create an artificial grid cell."
What Comes Next?
Laurencin and his team have individually engineered and made every single tissue in the lower limb, including bone, cartilage, ligament, skin, nerve, blood vessels. Regenerating joints and joint tissue is the next big mile marker, which Laurencin sees as essential to regenerating a limb that functions and performs in the way he envisions.
"Using stem cells and amnion tissue, we can regenerate joints that are damaged, and have severe arthritis," he says. "We're making progress on all fronts, and making discoveries we believe are going to be helping people along the way."
That focus and advancement is vital to Ennis. After laboring over the decision to have her leg amputated below the knee, she contracted MRSA two weeks post-surgery. In less than a month, she went from a below-the-knee-amputee to a through-the-knee amputee to an above-the-knee amputee.
"A below-the-knee amputation is night-and-day from above-the-knee," she said. "You have to relearn everything. You're basically a toddler."
Kirstie Ennis pictured in July 2020.
Photo Credit: Ennis' Instagram
The clock is ticking on the timeline Laurencin set for himself. Nine years might seem like forever if you're doing time but it might appear fleeting when you're trying to create something that's never been done before. But Laurencin isn't worried. He's convinced time is on his side.
"Every week, I receive an email or a call from someone, maybe a mother whose child has lost a finger or I'm in communication with a disabled American veteran who wants to know how the progress is going. That energizes me to continue to work hard to try to create these sorts of solutions because we're talking about people and their lives."
He devotes about 60 hours a week to the project and the roughly 100 students, faculty and staff who make up the HEAL team at the Convergence Institute seem acutely aware of what's at stake and appear equally dedicated.
"We're in the thick of the science in terms of making this happen," says Laurencin. "We've moved from making the impossible possible to making the possible a reality. That's what science is all about."
7 Reasons Why We Should Not Need Boosters for COVID-19
A top infectious disease physician explains why immunity derived from natural infection and the vaccines should be long-lasting.
There are at least 7 reasons why immunity after vaccination or infection with COVID-19 should likely be long-lived. If durable, I do not think boosters will be necessary in the future, despite CEOs of pharmaceutical companies (who stand to profit from boosters) messaging that they may and readying such boosters. To explain these reasons, let's orient ourselves to the main components of the immune system.
There are two major arms of the immune system: B cells (which produce antibodies) and T cells (which are formed specifically to attack and kill pathogens). T cells are divided into two types, CD4 cells ("helper" T cells) and CD8 cells ("cytotoxic" T cells).
Each arm, once stimulated by infection or vaccine, should hopefully make "memory" banks. So if the body sees the pathogen in the future, these defenses should come roaring back to attack the virus and protect you from getting sick. Plenty of research in COVID-19 indicates a likely long-lasting response to the vaccine or infection. Here are seven of the most compelling reasons:
REASON 1: Memory B Cells Are Produced By Vaccines and Natural Infection
In one study, 12 volunteers who had never had Covid-19--and were fully vaccinated with two Pfizer/BioNTech shots-- underwent biopsies of their lymph nodes. This is where memory B cells are stored in places called "germinal centers". The biopsies were performed three, four, six, and seven weeks after the first mRNA vaccine shot, and were stained to reveal that germinal center memory B cells in the lymph nodes increased in concentration over time.
Natural infection also generates memory B cells. Even after antibody levels wane over time, strong memory B cells were detected in the blood of individuals six and eight months after infection in different studies. Indeed, the half-lives of the memory B cells seen in the study examining patients 8 months after COVID-19 led the authors to conclude that "B cell memory to SARS-CoV-2 was robust and is likely long-lasting." Reason #2 tells us that memory B cells can be active for a very long time indeed.
REASON #2: Memory B Cells Can Produce Neutralizing Antibodies If They See Infection Again Decades Later
Demonstrated production of memory B cells after vaccination or natural infection with COVID-19 is so important because memory B cells, once generated, can be activated to produce high levels of neutralizing antibodies against the pathogen even if encountered many years after the initial exposure. In one amazing study (published in 2008), researchers isolated memory B cells against the 1918 flu strain from the blood of 32 individuals aged 91-101 years. These people had been born on or before 1915 and had survived that pandemic.
Their memory B cells, when exposed to the 1918 flu strain in a test tube, generated high levels of neutralizing antibodies against the virus -- antibodies that then protected mice from lethal infection with this deadly strain. The ability of memory B cells to produce complex antibody responses against an infection nine decades after exposure speaks to their durability.
REASON #3: Vaccines or Natural Infection Trigger Strong Memory T Cell Immunity
All of the trials of the major COVID-19 vaccine candidates measured strong T cell immunity following vaccination, most often assessed by measuring SARS-CoV-2 specific T cells in the phase I/II safety and immunogenicity studies. There are a number of studies that demonstrate the production of strong T cell immunity to COVID-19 after natural infection as well, even when the infection was mild or asymptomatic.
The same study that showed us robust memory B cell production 8 months after natural infection also demonstrated strong and sustained memory T cell production. In fact, the half-lives of the memory T cells in this cohort were long (~125-225 days for CD8+ and ~94-153 days for CD4+ T cells), comparable to the 123-day half-life observed for memory CD8+ T cells after yellow fever immunization (a vaccine usually given once over a lifetime).
A recent study of individuals recovered from COVID-19 show that the initial T cells generated by natural infection mature and differentiate over time into memory T cells that will be "put in the bank" for sustained periods.
REASON #4: T Cell Immunity Following Vaccinations for Other Infections Is Long-Lasting
Last year, we were fortunate to be able to measure how T cell immunity is generated by COVID-19 vaccines, which was not possible in earlier eras when vaccine trials were done for other infections (such as measles, mumps, rubella, pertussis, diphtheria). Antibodies are just the "tip of the iceberg" when assessing the response to vaccination, but were the only arm of the immune response that could be measured following vaccination in the past.
Measuring pathogen-specific T cell responses takes sophisticated technology. However, T cell responses, when assessed years after vaccination for other pathogens, has been shown to be long-lasting. For example, in one study of 56 volunteers who had undergone measles vaccination when they were much younger, strong CD8 and CD4 cell responses to vaccination could be detected up to 34 years later.
REASON #5: T Cell Immunity to Related Coronaviruses That Caused Severe Disease is Long-Lasting
SARS-CoV-2 is a coronavirus that causes severe disease, unlike coronaviruses that cause the common cold. Two other coronaviruses in the recent past caused severe disease, specifically Severely Acute Respiratory Distress Syndrome (SARS) in late 2002-2003 and Middle East Respiratory Syndrome (MERS) in 2011.
A study performed in 2020 demonstrated that the blood of 23 recovered SARS patients possess long-lasting memory T cells that were still reactive to SARS 17 years after the outbreak in 2003. Many scientists expect that T cell immunity to SARS-CoV-2 will be equally durable to that of its cousin.
REASON #6: T Cell Responses from Vaccination and Natural Infection With the Ancestral Strain of COVID-19 Are Robust Against Variants
Even though antibody responses from vaccination may be slightly lower against various COVID-19 variants of concern that have emerged in recent months, T cell immunity after vaccination has been shown to be unperturbed by mutations in the spike protein (in the variants). For instance, T cell responses after mRNA vaccines maintained strong activity against different variants (including P.1 Brazil variant, B.1.1.7 UK variant, B.1.351 South Africa variant and the CA.20.C California variant) in a recent study.
Another study showed that the vaccines generated robust T cell immunity that was unfazed by different variants, including B.1.351 and B.1.1.7. The CD4 and CD8 responses generated after natural infection are equally robust, showing activity against multiple "epitopes" (little segments) of the spike protein of the virus. For instance, CD8 cells responds to 52 epitopes and CD4 cells respond to 57 epitopes across the spike protein, so that a few mutations in the variants cannot knock out such a robust and in-breadth T cell response. Indeed, a recent paper showed that mRNA vaccines were 97.4 percent effective against severe COVID-19 disease in Qatar, even when the majority of circulating virus there was from variants of concern (B.1.351 and B.1.1.7).
REASON #7: Coronaviruses Don't Mutate Quickly Like Influenza, Which Requires Annual Booster Shots
Coronaviruses are RNA viruses, like influenza and HIV (which is actually a retrovirus), but do not mutate as quickly as either one. The reason that coronaviruses don't mutate very rapidly is that their replicating mechanism (polymerase) has a strong proofreading mechanism: If the virus mutates, it usually goes back and self-corrects. Mutations can arise with high rates of replication when transmission is very frequent -- as has been seen in recent months with the emergence of SARS-CoV-2 variants during surges. However, the COVID-19 virus will not be mutating like this when we tamp down transmission with mass vaccination.
In conclusion, I and many of my infectious disease colleagues expect the immunity from natural infection or vaccination to COVID-19 to be durable. Let's put discussion of boosters aside and work hard on global vaccine equity and distribution since the pandemic is not over until it is over for us all.