China vs. the West: Who Will Lead the Way in Embryo Editing 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."
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.
Breakthrough drones deliver breast milk in rural Uruguay
Until three months ago, nurse Leopoldina Castelli used to send bottles of breast milk to nourish babies in the remote areas of Tacuarembó, in northern Uruguay, by way of ambulances or military trucks. That is, if the vehicles were available and the roads were passable, which wasn’t always the case. Now, five days per week, she stands by a runway at the hospital, located in Tacuarembó’s capital, watching a drone take off and disappear from view, carrying the milk to clinics that serve the babies’ families.
The drones can fly as far as 62 miles. Long distances and rough roads are no obstacles. The babies, whose mothers struggle to produce sufficient milk and cannot afford formula, now receive ample supplies for healthy growth. “Today we provided nourishment to a significantly larger number of children, and this is something that deeply moves me,” Castelli says.
About two decades ago, the Tacuarembó hospital established its own milk bank, supported by donations from mothers across Tacuarembó. Over the years, the bank has provided milk to infants immediately after birth. It's helped drive a “significant and sustained” decrease in infant mortality, says the hospital director, Ciro Ferreira.
But these children need breast milk throughout their first six months, if not longer, to prevent malnutrition and other illnesses that are prevalent in rural Tacuarembó. Ground transport isn't quick or reliable enough to meet this goal. It can take several hours, during which the milk may spoil due to a lack of refrigeration.
The battery-powered drones have been the difference-maker. The project to develop them, financed by the UNICEF Innovation Fund, is the first of its kind in Latin America. To Castelli, it's nothing short of a revolution. Tacuarembó Hospital, along with three rural clinics in the most impoverished part of Uruguay, are its leaders.
"This marks the first occasion when the public health system has been directly impacted [by our technology]," says Sebastián Macías, the CEO and co-founder of Cielum, an engineer at the University Republic, which collaborated on the technology with a Uruguayan company called Cielum and a Swiss company, Rigitech.
The drone can achieve a top speed of up to 68 miles per hour, is capable of flying in light rain, and can withstand winds of up to 30 miles per hour at a maximum altitude of 120 meters.
"We have succeeded in embracing the mothers from rural areas who were previously slipping through the cracks of the system," says Ferreira, the hospital director. He envisions an expansion of the service so it can improve health for children in other rural areas.
Nurses load the drone for breast milk delivery.
Sebastián Macías - Cielum
The star aircraft
The drone, which costs approximately $70,000, was specifically designed for the transportation of biological materials. Constructed from carbon fiber, it's three meters wide, two meters long and weighs 42 pounds when fully loaded. Additionally, it is equipped with a ballistic parachute to ensure a safe descent in case the technology fails in midair. Furthermore, it can achieve a top speed of 68 miles per hour, fly in light rain, and withstand winds of 30 miles per hour at a height of 120 meters.
Inside, the drones feature three refrigerated compartments that maintain a stable temperature and adhere to the United Nations’ standards for transporting perishable products. These compartments accommodate four gallons or 6.5 pounds of cargo. According to Macías, that's more than sufficient to carry a week’s worth of milk for one infant on just two flights, or 3.3 pounds of blood samples collected in a rural clinic.
“From an energy perspective, it serves as an efficient mode of transportation and helps reduce the carbon emissions associated with using an ambulance,” said Macías. Plus, the ambulance can remain available in the town.
Macías, who has led software development for the drone, and three other technicians have been trained to operate it. They ensure that the drone stays on course, monitor weather conditions and implement emergency changes when needed. The software displays the in-flight positions of the drones in relation to other aircraft. All agricultural planes in the region receive notification about the drone's flight path, departure and arrival times, and current location.
The future: doubling the drone's reach
Forty-five days after its inaugural flight, the drone is now making five flights per week. It serves two routes: 34 miles to Curtina and 31 miles to Tambores. The drone reaches Curtina in 50 minutes while ambulances take double that time, partly due to the subpar road conditions. Pueblo Ansina, located 40 miles from the state capital, will soon be introduced as the third destination.
Overall, the drone’s schedule is expected to become much busier, with plans to accomplish 20 weekly flights by the end of October and over 30 in 2024. Given the drone’s speed, Macías is contemplating using it to transport cancer medications as well.
“When it comes to using drones to save lives, for us, the sky is not the limit," says Ciro Ferreira, Tacuarembó hospital director.
In future trips to clinics in San Gregorio de Polanco and Caraguatá, the drone will be pushed to the limit. At these locations, a battery change will be necessary, but it's worth it. The route will cover up to 10 rural Tacuarembó clinics plus one hospital outside Tacuarembó, in Rivera, close to the border with Brazil. Currently, because of a shortage of ambulances, the delivery of pasteurized breast milk to Rivera only occurs every 15 days.
“The expansion to Rivera will include 100,000 more inhabitants, doubling the healthcare reach,” said Ferreira, the director of the Tacuarembó Hospital. In itself, Ferreira's hospital serves the medical needs of 500,000 people as one of the largest in Uruguay's interior.
Alejandro Del Estal, an aeronautical engineer at Rigitech, traveled from Europe to Tacuarembó to oversee the construction of the vertiports – the defined areas that can support drones’ take-off and landing – and the first flights. He pointed out that once the flight network between hospitals and rural polyclinics is complete in Uruguay, it will rank among the five most extensive drone routes in the world for any activity, including healthcare and commercial uses.
Cielum is already working on the long-term sustainability of the project. The aim is to have more drones operating in other rural regions in the western and northern parts of the country. The company has received inquiries from Argentina and Colombia, but, as Macías pointed out, they are exercising caution when making commitments. Expansion will depend on the development of each country’s regulations for airspace use.
For Ferreira, the advantages in Uruguay are evident: "This approach enables us to bridge the geographical gap, enhance healthcare accessibility, and reduce the time required for diagnosing and treating rural inhabitants, all without the necessity of them traveling to the hospital,” he says. "When it comes to using drones to save lives, for us, the sky is not the limit."