China vs. the West: Who Will Lead the Way in Embryo Editing Research?
The U.S. metaphorically boxing with China over biomedical research.
Junjiu Huang and his team performed a miracle. A few miracles, actually. The researchers at Sun Yat-sen University in Guangzhou, China used the precise new DNA editing tool called CRISPR-CAS9 to edit a human embryo, replacing a single base. In doing so, they edited out beta-thalassemia, a blood disorder that reduces the production of hemoglobin, which can result in pale skin, fatigue, higher risk of blood clots, and other symptoms.
The race is on, and it's one everyone is going to try to win.
Huang's group, which did not respond to an email requesting comment for this story, injected 86 embryos and observed them for 48 hours. After that period -- a time long enough for CRISPR to split the DNA, other molecules to replace the base, and the embryos to grow to eight cells -- they tested 54 of the 71 that survived. Of those, only a few had the replacement base, according to a report of the study published in Protein & Cell. The experiment stopped there as the embryos, which had been acquired from local fertility clinics, were non-viable and not implanted.
But procreation was not the point. Far from it, in fact. The point was to demonstrate that it could be done, that in some far off (or not so far off) future, doctors could use CRISPR to eliminate diseases like Tay-Sachs, Huntington's, and cystic fibrosis that are caused by genetic mutations. Going a step further, perhaps they could eventually even tailor embryos that will develop into adults with specific traits like height and IQ.
Experts agree that we are far from that point, years if not decades away from leveraging CRISPR to cure diseases and decades if not centuries from being able to build designer babies. In that frame, Huang's achievement is just a small step, a blip on the timeline of human achievement. But seen in another light, it's yet another sign that we need to start talking about DNA modification now, establishing protocols, procedures, and plans that guide the subject before we get so far down the road that momentum is impossible to stop.
"The Chinese generally don't have the religious objections to embryo research that have held back research in the West."
It's essential to do so now because the idea of DNA modification -- a realization that humanity can control its evolution -- is compelling and attractive. Imagine a world where doctors and scientists could get rid of disease before it begins or ensure a baby would arrive with an Einstein-level IQ. That's intriguing, and also terrifying. What are the rules? How do we know when to stop? What guides the process? And how can we prevent mistakes or unwanted mutations? To borrow from another famous quotation, with great power comes great responsibility.
These aren't questions for Huang and the Chinese scientific community alone. A team from Oregon recently edited viable human embryos, eliminating a mutation that can lead to heart failure while preventing any unintended consequences. Just as importantly, every embryo they edited produced the intended genetic changes, a vital step since a partial success rate, known as mosaicism, could have devastating consequences to a future child.
In London at the Francis Crick Institute, researcher Kathy Niakan used CRISPR-CAS9 to "turn off" a gene that produces the protein OCT4. Without the protein, the fertilized egg could not produce a blastocyst, which is a key structure in early mammalian development that gives rise to an embryo and placenta. The recent study wasn't designed to go further, but the use of CRISPR was important. "One way to find out what a gene does in the developing embryo is to see what happens when it isn't working," said Dr. Niakan, who was the first scientist in the world to be granted regulatory approval to edit the genes of a human embryo for research. "Now that we have demonstrated an efficient way of doing this, we hope that other scientists will use it to find out the roles of other genes. If we knew the key genes that embryos need to develop successfully, we could improve IVF treatments and understand some causes of pregnancy failure. It may take many years to achieve such an understanding. Our study is just the first step."
The point is, CRISPR is here and it's not going anywhere. Scientists will continue to use it to learn about how humans develop. Yet different rules regarding CRISPR and embryo research in countries around the world will impact who gets there first. "I've heard the U.S.-China gene editing research parallel paths as Sputnik 2.0," said Kevin Doxzen, Science Communications Specialist at the University of California, Berkeley's Innovative Genomics Institute. The race is on, and it's one everyone is going to try to win.
Based on number of researchers and ease of regulations, the Chinese are the favorites to advance the science the furthest, the fastest.
Based on number of researchers and ease of regulations, the Chinese are the favorites to advance the science the furthest, the fastest. "The Chinese generally don't have the religious (predominantly Christian) or moral objections to embryo research that have held back research in the West," said Dr. Julian Savulescu, the Uehiro Professor of Practical Ethics and Director of the Oxford Martin Programme on Collective Responsibility for Infectious Disease at the University of Oxford. "This kind of research should be done, with the right sort of ethical oversight. The concern over China leading the way is that institutional oversight mechanisms are probably not as developed as in the West but so far, there is no evidence of breaches in standards of research ethics around the published research."
Or, put another way by bioethicist Dr. Arthur Caplan, founding director of NYU Langone Health's Division of Medical Ethics: "The Chinese, because they don't care and don't have moral reservations about embryo work, are doing what they want." This lack of aversion to working with embryos manifests itself in a couple of ways. The absence of moral qualms is one. Funding is another. Huang's study, and others like it, receive funding from the government. His, for example, was supported by two grants from the National Basic Research Program and three from the National Natural Science Foundation of China.
The U.S., on the other hand, bans any federal funding for research using human embryos. A law passed in 1996 states that federal dollars can't be used for: "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses." This restriction can shift incentives as many private institutions or commercial enterprises may have financial motivations or other goals beyond furthering basic research for the sake of general knowledge.
Embryo gene modification recently performed in the U.K. would merit 15 years in prison in Australia.
The embryo research ban is even more strict elsewhere. The Oviedo Convention, enacted in 1997, effectively prohibits germline engineering in members of the European Union. "In Italy, you can't destroy an embryo for any reason," said Alessandro Bertero, a postdoctoral fellow at the University of Washington's Department of Pathology who used to study in Italy. "It's illegal, and you'll go to jail." Later, Bertero was one of the researchers who worked with Dr. Niakan in London, an investigation that was allowed by the UK's Human Fertilisation and Embryology Authority. (In Australia, Niakan and her colleagues would face 15 years in jail due to the 2002 Prohibition of Human Cloning Act, which prohibits altering the genomes of embryonic cells.)
Despite the moral and legal reservations in the Western world, every person I spoke with for this story believed that better, more advanced studies and learning is happening in the U.S. and Europe. "The best studies in my opinion are from the labs in California and Oregon," Bertero said. "The quality of the work [in the Chinese study] – not being critical, but to be scientifically critical -- was just quick and dirty. It was, 'Let's just show that we have done it and get it out.' That doesn't mean that the quality of the work was good."
"If the Chinese or someone else starts beating our brains out, we're not going to want to stand by idly and not do these things."
How long that remains the case, however, is an open question. A significant number of groups in China are working on germline editing in human embryos. The concern is that the Chinese will emerge as a leader sooner rather than later because they can do research with embryos more easily than their Western counterparts.
For Caplan, the NYU professor, the embryo ban in the U.S. isn't based on science; it's rooted in something else. "It's 96 percent political," he said, laughing. "It has basically ground to a halt because no one wants to see repercussions take place if federal funding is involved. The NIH isn't involved. And they won't be."
What, in his mind, would get Americans to start realizing the benefits that embryo research would provide? "The perception that other countries were moving quickly to get the advantages of CRISPR and other gene modification techniques, finding more industrial and more medical purposes," he said. "If the Chinese or someone else starts beating our brains out, we're not going to want to stand by idly and not do these things."
Doing so would involve difficult conversations about the role of embryos in research. But these are philosophical questions that need to be approached at some point. From a U.S. perspective, doing so sooner while the American scientists still hold the technological and informational edge, is vital. Ignoring the issue doesn't make it go away.
Experts think a few changes should be made. The ban on federal funding should be lifted. Scientists and regulators should push for things like allowing federal funds to be used for the creation of new embryos for research purposes and the use of spare IVF embryos for research when the embryo would not be implanted into a woman. (Privately funded scientists can proceed in states that encourage embryonic stem cell research, like New York, New Jersey, and California, but not in restrictive ones like Louisiana and South Dakota, which prohibit creating or destroying embryos for research.) Policymakers could ban reproductive gene editing for now but look at it again after a certain period. A highly anticipated report issued earlier this year from an international guidance committee left the door open to eventual clinical trials with edited embryos. As of now, however, Congress will not allow the Food and Drug Administration to consider such trials. This is the future and it's the scientific community's responsibility to develop the ethical framework now.
"The US and Europe have the technological history and capacity to lead this research and should do so, ethically. We ought to be revising our laws and ethical guidelines to facilitate this kind of research," Professor Savulescu said. "But the challenge is to think constructively and ethically about this new technology, and to be leaders, not followers."
Are the gains from gain-of-function research worth the risks?
Gain-of-function research can make pathogens more infectious and deadly. It also enables scientists to prepare remedies in advance.
Scientists have long argued that gain-of-function research, which can make viruses and other infectious agents more contagious or more deadly, was necessary to develop therapies and vaccines to counter the pathogens in case they were used for biological warfare. As the SARS-CoV-2 origins are being investigated, one prominent theory suggests it had leaked from a biolab that conducted gain-of-function research, causing a global pandemic that claimed nearly 6.9 million lives. Now some question the wisdom of engaging in this type of research, stating that the risks may far outweigh the benefits.
“Gain-of-function research means genetically changing a genome in a way that might enhance the biological function of its genes, such as its transmissibility or the range of hosts it can infect,” says George Church, professor of genetics at Harvard Medical School. This can occur through direct genetic manipulation as well as by encouraging mutations while growing successive generations of micro-organism in culture. “Some of these changes may impact pathogenesis in a way that is hard to anticipate in advance,” Church says.
In the wake of the global pandemic, the pros and cons of gain-of-function research are being fiercely debated. Some scientists say this type of research is vital for preventing future pandemics or for preparing for bioweapon attacks. Others consider it another disaster waiting to happen. The Government Accounting Office issued a report charging that a framework developed by the U.S. Department of Health & Human Services (HHS) provided inadequate oversight of this potentially deadly research. There’s a movement to stop it altogether. In January, the Viral Gain-of-Function Research Moratorium Act (S. 81) was introduced into the Senate to cease awarding federal research funding to institutions doing gain-of-function studies.
While testifying before the House COVID Origins Select Committee on March 8th, Robert Redfield, former director of the U.S. Centers for Disease Control and Prevention, said that COVID-19 may have resulted from an accidental lab leak involving gain-of-function research. Redfield said his conclusion is based upon the “rapid and high infectivity for human-to-human transmission, which then predicts the rapid evolution of new variants.”
“It is a very, very, very small subset of life science research that could potentially generate a potential pandemic pathogen,” said Gerald Parker, associate dean for Global One Health at Texas A&M University.
“In my opinion,” Redfield continues, “the COVID-19 pandemic presents a case study on the potential dangers of such research. While many believe that gain-of-function research is critical to get ahead of viruses by developing vaccines, in this case, I believe that was the exact opposite.” Consequently, Redfield called for a moratorium on gain-of-function research until there is consensus about the value of such risky science.
What constitutes risky?
The Federal Select Agent Program lists 68 specific infectious agents as risky because they are either very contagious or very deadly. In order to work with these 68 agents, scientists must register with the federal government. Meanwhile, research on deadly pathogens that aren’t easily transmitted, or pathogens that are quite contagious but not deadly, can be conducted without such oversight. “If you’re not working with select agents, you’re not required to register the research with the federal government,” says Gerald Parker, associate dean for Global One Health at Texas A&M University. But the 68-item list may not have everything that could possibly become dangerous or be engineered to be dangerous, thus escaping the government’s scrutiny—an issue that new regulations aim to address.
In January 2017, the White House Office of Science and Technology Policy (OSTP) issued additional guidance. It required federal departments and agencies to follow a series of steps when reviewing proposed research that could create, transfer, or use potential pandemic pathogens resulting from the enhancement of a pathogen’s transmissibility or virulence in humans.
In defining risky pathogens, OSTP included viruses that were likely to be highly transmissible and highly virulent, and thus very deadly. The Proposed Biosecurity Oversight Framework for the Future of Science, outlined in 2023, broadened the scope to require federal review of research “that is reasonably anticipated to enhance the transmissibility and/or virulence of any pathogen” likely to pose a threat to public health, health systems or national security. Those types of experiments also include the pathogens’ ability to evade vaccines or therapeutics, or diagnostic detection.
However, Parker says that dangers of generating a pandemic-level germ are tiny. “It is a very, very, very small subset of life science research that could potentially generate a potential pandemic pathogen.” Since gain-of-function guidelines were first issued in 2017, only three such research projects have met those requirements for HHS review. They aimed to study influenza and bird flu. Only two of those projects were funded, according to the NIH Office of Science Policy. For context, NIH funded approximately 11,000 of the 54,000 grant applications it received in 2022.
Guidelines governing gain-of-function research are being strengthened, but Church points out they aren’t ideal yet. “They need to be much clearer about penalties and avoiding positive uses before they would be enforceable.”
What do we gain from gain-of-function research?
The most commonly cited reason to conduct gain-of-function research is for biodefense—the government’s ability to deal with organisms that may pose threats to public health.
In the era of mRNA vaccines, the advance preparedness argument may be even less relevant.
“The need to work with potentially dangerous viruses is central to our preparedness,” Parker says. “It’s essential that we know and understand the basic biology, microbiology, etc. of some of these dangerous pathogens.” That includes increasing our knowledge of the molecular mechanisms by which a virus could become a sustained threat to humans. “Knowing that could help us detect [risks] earlier,” Parker says—and could make it possible to have medical countermeasures, like vaccines and therapeutics, ready.
Most vaccines, however, aren’t affected by this type of research. Essentially, scientists hope they will never need to use it. Moreover, Paul Mango, HSS former deputy chief of staff for policy, and author of the 2022 book Warp Speed, says he believes that in the era of mRNA vaccines, the advance preparedness argument may be even less relevant. “That’s because these vaccines can be developed and produced in less than 12 months, unlike traditional vaccines that require years of development,” he says.
Can better oversight guarantee safety?
Another situation, which Parker calls unnecessarily dangerous, is when regulatory bodies cannot verify that the appropriate biosafety and biosecurity controls are in place.
Gain-of-function studies, Parker points out, are conducted at the basic research level, and they’re performed in high-containment labs. “As long as all the processes, procedures and protocols are followed and there’s appropriate oversight at the institutional and scientific level, it can be conducted safely.”
Globally, there are 69 Biosafety Level 4 (BSL4) labs operating, under construction or being planned, according to recent research from King’s College London and George Mason University for Global BioLabs. Eleven of these 18 high-containment facilities that are planned or under construction are in Asia. Overall, three-quarters of the BSL4 labs are in cities, increasing public health risks if leaks occur.
Researchers say they are confident in the oversight system for BSL4 labs within the U.S. They are less confident in international labs. Global BioLabs’ report concurs. It gives the highest scores for biosafety to industrialized nations, led by France, Australia, Canada, the U.S. and Japan, and the lowest scores to Saudi Arabia, India and some developing African nations. Scores for biosecurity followed similar patterns.
“There are no harmonized international biosafety and biosecurity standards,” Parker notes. That issue has been discussed for at least a decade. Now, in the wake of SARS and the COVID-19 pandemic, scientists and regulators are likely to push for unified oversight standards. “It’s time we got serious about international harmonization of biosafety and biosecurity standards and guidelines,” Parker says. New guidelines are being worked on. The National Science Advisory Board for Biosecurity (NSABB) outlined its proposed recommendations in the document titled Proposed Biosecurity Oversight Framework for the Future of Science.
The debates about whether gain-of-function research is useful or poses unnecessary risks to humanity are likely to rage on for a while. The public too has a voice in this debate and should weigh in by communicating with their representatives in government, or by partaking in educational forums or initiatives offered by universities and other institutions. In the meantime, scientists should focus on improving the research regulations, Parker notes. “We need to continue to look for lessons learned and for gaps in our oversight system,” he says. “That’s what we need to do right now.”
The rise of remote work is a win-win for people with disabilities and employers
Disability advocates see remote work as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike.
Any corporate leader would jump at the opportunity to increase their talent pool of potential employees by 15 percent, with all these new hires belonging to an underrepresented minority. That’s especially true given tight labor markets and CEO desires to increase headcount. Yet, too few leaders realize that people with disabilities are the largest minority group in this country, numbering 50 million.
Some executives may dread the extra investments in accommodating people’s disabilities. Yet, providing full-time remote work could suffice, according to a new study by the Economic Innovation Group think tank. The authors found that the employment rate for people with disabilities did not simply reach the pre-pandemic level by mid-2022, but far surpassed it, to the highest rate in over a decade. “Remote work and a strong labor market are helping [individuals with disabilities] find work,” said Adam Ozimek, who led the research and is chief economist at the Economic Innovation Group.
Disability advocates see this development as a silver lining of the pandemic, a win-win for adults with disabilities and the business world alike. For decades before the pandemic, employers had refused requests from workers with disabilities to work remotely, according to Thomas Foley, executive director of the National Disability Institute. During the pandemic, "we all realized that...many of us could work remotely,” Foley says. “[T]hat was disproportionately positive for people with disabilities."
Charles-Edouard Catherine, director of corporate and government relations for the National Organization on Disability, said that remote-work options had been advocated for many years to accommodate disabilities. “It’s a little frustrating that for decades corporate America was saying it’s too complicated, we’ll lose productivity, and now suddenly it’s like, sure, let’s do it.”
The pandemic opened doors for people with disabilities
Early in the pandemic, employment rates dropped for everyone, including people with disabilities, according to Ozimek’s research. However, these rates recovered quickly. In the second quarter of 2022, people with disabilities aged 25 to 54, the prime working age, are 3.5 percent more likely to be employed, compared to before the pandemic.
What about people without disabilites? They are still 1.1 percent less likely to be employed.
These numbers suggest that remote work has enabled a substantial number of people with disabilities to find and retain employment.
“We have a last-in, first-out labor market, and [people with disabilities] are often among the last in and the first out,” Ozimek says. However, this dynamic has changed, with adults with disabilities seeing employment rates recover much faster. Now, the question is whether the new trend will endure, Ozimek adds. “And my conclusion is that not only is it a permanent thing, but it’s going to improve.”
Gene Boes, president and chief executive of the Northwest Center, a Seattle organization that helps people with disabilities become more independent, confirms this finding. “The new world we live in has opened the door a little bit more…because there’s just more demand for labor.”
Long COVID disabilities put a premium on remote work
Remote work can help mitigate the impact of long COVID. The U.S. Centers for Disease Control and Prevention reports that about 19 percent of those who had COVID developed long COVID. Recent Census Bureau data indicates that 16 million working age Americans suffer from it, with economic costs estimated at $3.7 trillion.
Certainly, many of these so-called long-haulers experience relatively mild symptoms - such as loss of smell - which, while troublesome, are not disabling. But other symptoms are serious enough to be disabilities.
According to a recent study from the Federal Reserve Bank of Minneapolis, about a quarter of those with long COVID changed their employment status or working hours. That means long COVID was serious enough to interfere with work for 4 million people. For many, the issue was serious enough to qualify them as disabled.
Indeed, the Federal Reserve Bank of New York found in a just-released study that the number of individuals with disabilities in the U.S. grew by 1.7 million. That growth stemmed mainly from long COVID conditions such as fatigue and brain fog, meaning difficulties with concentration or memory, with 1.3 million people reporting an increase in brain fog since mid-2020.
Many had to drop out of the labor force due to long COVID. Yet, about 900,000 people who are newly disabled have managed to continue working. Without remote work, they might have lost these jobs.
For example, a software engineer at one of my client companies has struggled with brain fog related to long COVID. With remote work, this employee can work during the hours when she feels most mentally alert and focused, even if that means short bursts of productivity throughout the day. With flexible scheduling, she can take rests, meditate, or engage in activities that help her regain focus and energy. Without the need to commute to the office, she can save energy and time and reduce stress, which is crucial when dealing with brain fog.
In fact, the author of the Federal Reserve Bank of New York study notes that long COVID can be considered a disability under the Americans with Disability Act, depending on the specifics of the condition. That means the law can require private employers with fifteen or more staff, as well as government agencies, to make reasonable accommodations for those with long COVID. Richard Deitz, the author of this study, writes in the paper that “telework and flexible scheduling are two accommodations that can be particularly beneficial for workers dealing with fatigue and brain fog.”
The current drive to return to the office, led by many C-suite executives, may need to be reconsidered in light of legal and HR considerations. Arlene S. Kanter, director of the disability law and policy program at the Syracuse University College of Law, said that the question should depend on whether people with disabilities can perform their work well at home, as they did during Covid outbreaks. “[T]hen people with disabilities, as a matter of accommodation, shouldn’t be denied that right,” Kanter said.
Diversity benefits
But companies shouldn’t need to worry about legal regulations. It simply makes dollars and sense to expand their talent pool by 15% of an underrepresented minority. After all, extensive research shows that improving diversity boosts both decision-making and financial performance.
Companies that are offering more flexible work options have already gained significant benefits in terms of diverse hires. In its efforts to adapt to the post-pandemic environment, Meta, the owner of Facebook and Instagram, decided to offer permanent fully remote work options to its entire workforce. And according to Meta chief diversity officer Maxine Williams, the candidates who accepted job offers for remote positions were “substantially more likely” to come from diverse communities: people with disabilities, Black, Hispanic, Alaskan Native, Native American, veterans, and women. The numbers bear out these claims: people with disabilities increased from 4.7 to 6.2 percent of Meta’s employees.
Having consulted for 21 companies to help them transition to hybrid work arrangements, I can confirm that Meta’s numbers aren’t a fluke. The more my clients proved willing to offer remote work, the more staff with disabilities they recruited - and retained. That includes employees with mobility challenges. But it also includes employees with less visible disabilities, such as people with long COVID and immunocompromised people who feel reluctant to put themselves at risk of getting COVID by coming into the office.
Unfortunately, many leaders fail to see the benefits of remote work for underrepresented groups, such as those with disabilities. Some even say the opposite is true, with JP Morgan CEO Jamie Dimon claiming that returning to the office will aid diversity.
What explains this poor executive decision making? Part of the answer comes from a mental blindspot called the in-group bias. Our minds tend to favor and pay attention to the concerns of those in the group of people who seem to look and think like us. Dimon and other executives without disabilities don’t perceive people with disabilities to be part of their in-group. They thus are blind to the concerns of those with disabilities, which leads to misperceptions such as Dimon’s that returning to the office will aid diversity.
In-group bias is one of many dangerous judgment errors known as cognitive biases. They impact decision making in all life areas, ranging from the future of work to relationships.
Another relevant cognitive bias is the empathy gap. This term refers to our difficulty empathizing with those outside of our in-group. The lack of empathy combines with the blindness from the in-group bias, causing executives to ignore the feelings of employees with disabilities and prospective hires.
Omission bias also plays a role. This dangerous judgment error causes us to perceive failure to act as less problematic than acting. Consequently, executives perceive a failure to support the needs of those with disabilities as a minor matter.
Conclusion
The failure to empower people with disabilities through remote work options will prove costly to the bottom lines of companies. Not only are limiting their talent pool by 15 percent, they’re harming their ability to recruit and retain diverse candidates. And as their lawyers and HR departments will tell them, by violating the ADA, they are putting themselves in legal jeopardy.
By contrast, companies like Meta - and my clients - that offer remote work opportunities are seizing a competitive advantage by recruiting these underrepresented candidates. They’re lowering costs of labor while increasing diversity. The future belongs to the savvy companies that offer the flexibility that people with disabilities need.