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.
Your Privacy vs. the Public's Health: High-Tech Tracking to Fight COVID-19 Evokes Orwell
The COVID-19 pandemic has placed public health and personal privacy on a collision course, as smartphone technology has completely rewritten the book on contact tracing.
It's not surprising that an autocratic regime like China would adopt such measures, but democracies such as Israel have taken a similar path.
The gold standard – patient interviews and detective work – had been in place for more than a century. It's been all but replaced by GPS data in smartphones, which allows contact tracing to occur not only virtually in real time, but with vastly more precision.
China has gone the furthest in using such tech to monitor and prevent the spread of the coronavirus. It developed an app called Health Code to determine which of its citizens are infected or at risk of becoming infected. It has assigned each individual a color code – red, yellow or green – and restricts their movement depending on their assignment. It has also leveraged its millions of public video cameras in conjunction with facial recognition tech to identify people in public who are not wearing masks.
It's not surprising that an autocratic regime like China would adopt such measures, but democracies such as Israel have taken a similar path. The national security agency Shin Bet this week began analyzing all personal cellphone data under emergency measures approved by the government. It texts individuals when it's determined they had been in contact with someone who had the coronavirus. In Spain and China, police have sent drones aloft searching for people violating stay-at-home orders. Commands to disperse can be issued through audio systems built into the aircraft. In the U.S., efforts are underway to lift federal restrictions on drones so that police can use them to prevent people from gathering.
The chief executive of a drone manufacturer in the U.S. aptly summed up the situation in an interview with the Financial Times: "It seems a little Orwellian, but this could save lives."
Epidemics and how they're surveilled often pose thorny dilemmas, according to Craig Klugman, a bioethicist and professor of health sciences at DePaul University in Chicago. "There's always a moral issue to contact tracing," he said, adding that the issue doesn't change by nation, only in the way it's resolved.
"Once certain privacy barriers have been breached, it can be difficult to roll them back again."
In China, there's little to no expectation for privacy, so their decision to take the most extreme measures makes sense to Klugman. "In China, the community comes first. In the U.S., individual rights come first," he said.
As the U.S. has scrambled to develop testing kits and manufacture ventilators to identify potential patients and treat them, individual rights have mostly not received any scrutiny. However, that could change in the coming weeks.
The American approach is also leaning toward using smartphone apps, but in a way that may preserve the privacy of users. Researchers at MIT have released a prototype known as Private Kit: Safe Paths. Patients diagnosed with the coronavirus can use the app to disclose their location trail for the prior 28 days to other users without releasing their specific identity. They also have the option of sharing the data with public health officials. But such an app would only be effective if there is a significant number of users.
Singapore is offering a similar app to its citizens known as TraceTogether, which uses both GPS and Bluetooth pings among users to trace potential encounters. It's being offered on a voluntary basis.
The Electronic Frontier Foundation, the leading nonprofit organization defending civil liberties in the digital world, said it is monitoring how these apps are developed and deployed. "Governments around the world are demanding new dragnet location surveillance powers to contain the COVID-19 outbreak," it said in a statement. "But before the public allows their governments to implement such systems, governments must explain to the public how these systems would be effective in stopping the spread of COVID-19. There's no questioning the need for far-reaching public health measures to meet this urgent challenge, but those measures must be scientifically rigorous, and based on the expertise of public health professionals."
Andrew Geronimo, director of the intellectual property venture clinic at the Case Western University School of Law, said that the U.S. government is currently in talks with Facebook, Google and other tech companies about using deidentified location data from smartphones to better monitor the progress of the outbreak. He was hesitant to endorse such a step.
"These companies may say that all of this data is anonymized," he said, "but studies have shown that it is difficult to fully anonymize data sets that contain so much information about us."
Beyond the technical issues, social attitudes may mount another challenge. Epic events such as 9/11 tend to loosen vigilance toward protecting privacy, according to Klugman and Geronimo. And as more people are sickened and hospitalized in the U.S. with COVID-19, Klugman believes more Americans will be willing to allow themselves to be tracked. "If that happens, there needs to be a time limitation," he said.
However, even if time limits are put in place, Geronimo believes it would lead to an even greater rollback of privacy during the next crisis.
"Once certain privacy barriers have been breached, it can be difficult to roll them back again," he warned. "And the prior incidents could always be used as a precedent – or as proof of concept."
Stem Cell Therapy for COVID-19 Is Gaining Steam in China, But Some Skeptical Scientists Urge Caution
Over the past two months, China's frantic search for an effective COVID-19 treatment has seen doctors trying everything from influenza drugs to traditional herbal remedies and even acupuncture, in a bid to help patients suffering from coronavirus-induced pneumonia.
"This treatment is particularly aimed at older patients who are seriously ill. These kinds of patients are in the danger zone."
Since mid February, one approach that has gained increasing traction is stem cell therapies, treatments that have often been viewed as a potential panacea by desperate patients suffering from degenerative incurable conditions ranging from Parkinson's to ALS. In many of these diseases, reality has yet to match the hype.
In COVID-19, there are hopes it might, though some experts are warning not to count on it. At Beijing's YouAn Hospital, doctors have been treating patients at various stages of the illness with intravenous infusions of so-called mesenchymal stem cells taken from umbilical cord tissue, as part of an ongoing clinical trial since January 21. The outcomes of the initial seven patients – published last month – appeared promising and the trial has since been expanded to 31 patients according to Dr. Kunlin Jin, a researcher at University of North Texas Health Science Center who is collaborating with the doctors in Beijing.
"Sixteen of these patients had mild symptoms, eight are severe, and seven are critically severe," Jin told leapsmag. "But all patients have shown improvements in lung function following the treatment, based on CT scans -- most of them in the first three days and seven have now been completely discharged from hospital. This treatment is particularly aimed at older patients who are seriously ill. These kinds of patients are in the danger zone; it's essential that they receive treatment, but right now we have nothing for most of them. No drugs or anything."
The apparent success of the very small Beijing trial has since led to a nationwide initiative to fast-track stem cell therapies for COVID-19. Across China, there are currently 36 clinical trials intending to use mesenchymal stem cells to treat COVID-19 patients that are either in the planning or recruiting phases. The Chinese Medical Association has now issued guidelines to standardize stem cell treatment for COVID-19, while Zhang Xinmin, an official in China's Ministry of Science and Technology, revealed in a press conference last week that a stem cell-based drug has been approved for clinical trials.
The thinking behind why stem cells could be a fast-acting and effective treatment is due to the nature of COVID-19. The thousands of fatalities worldwide are not from the virus directly, but from a dysfunctional immune response to the infection. Patients die because their respiratory systems become overwhelmed by a storm of inflammatory molecules called cytokines, causing lung damage and failure. However, studies in mice have long shown that stem cells have anti-inflammatory properties with the ability to switch off such cytokine storms, reducing such virus-induced lung injuries.
"There has been an enormous amount of hype about these cells, and there is scant scientific evidence that they have any therapeutic effect in any situation. "
"The therapy can inhibit the overactivation of the immune system and promote repair by improving the pulmonary microenvironment and improve lung function," explained Wei Hou, one of the doctors conducting the trial at YouAn Hospital.
However not everyone is convinced, citing the small number of patients treated to date, and potential risks from such therapy. "We just don't know enough to believe that stem cells might be helpful with COVID-19," said Paul Knoepfler, professor of cell biology at UC Davis. "The new stem cell studies are too small and lack controls, making it impossible to come to any solid conclusions. The chance of benefit is low based on the little we know so far and there are going to be risks that are hard to pin down. For instance, what if a stem cell infusion impairs some kind of needed immune response?"
Other scientists are even more skeptical. "I am concerned about all treatments that use mesenchymal stem cells," warned Jeanne Loring, the Director of the Center for Regenerative Medicine at Scripps Research in La Jolla, Calif. "There has been an enormous amount of hype about these cells, and there is scant scientific evidence that they have any therapeutic effect in any situation. Typically, these treatments are offered to people who have diseases without cures. I'm certain that there will be evidence-based treatments for COVID19, but I understand that they are not yet available, people are desperate, and they will try anything. I hope the sick are not taken advantage of because of their desperation."
Despite such concerns, the steadily rising death toll from COVID-19 means other nations are preparing to proceed with their own clinical trials of mesenchymal stem cells. Jin said he has been contacted by researchers and clinicians around the world seeking information on how to conduct their own trials, with the University of Cambridge's Stem Cell Institute in the U.K. reportedly looking to initiate a trial.
The scale of the global emergency has seen governments repeatedly calling on the corporate world to invest in the search for a cure, and the Australian company Mesoblast – a global leader in cell-based therapies for a range of diseases – are expecting to receive the green light to initiate clinical trials of their own stem cell based product against COVID-19.
"We're talking to at least three major governments," said Silviu Itescu, CEO and Managing Director of Mesoblast. "We are working with groups in Australia, the U.S. and the U.K., and I expect there'll be trials starting imminently in all those jurisdictions."
Itescu is bullish that the therapy has a good chance of proving effective, as it recently successfully completed Phase III trials for severe steroid-refractory acute graft versus host disease (GVHD) – a condition which leads to a very similar disease profile to COVID-19.
"The exact same cytokine profile is occurring in the lungs of COVID-19 infected patients as in GVHD which is destructive to the local lung environment," he said. "If our cells are able to target that in GVHD, they ought to be able to switch off the cytokine response in COVID lung disease as well."
"What we should be focusing on now is not the possible boost to the stem cell field, but rather doing rigorous science to test whether stem cells can help COVID-19 patients."
Jin is hopeful that if the imminent trials yield successful results, the U.S. FDA could fast-track mesenchymal stem cells as an approved emergency therapy for COVID-19. However, Knoepfler cautions that there is a need for far more concrete and widespread proof of the benefit before regulatory bodies start ushering through the green light.
"What we should be focusing on now is not the possible boost to the stem cell field, but rather doing rigorous science to test whether stem cells can help COVID-19 patients," he said. "During a pandemic, it's reasonable to do some testing of unproven interventions like stem cells in small studies, but results from them should be discussed in a sober, conservative manner until there is more evidence."