Will religious people reject organ transplants from pigs?
The first successful recipient of a human heart transplant lived 18 days. The first artificial heart recipient lived just over 100.
Their brief post-transplant lives paved the way toward vastly greater successes. Former Vice President Dick Cheney relied on an artificial heart for nearly two years before receiving a human heart transplant. It still beats in his chest more than a decade later.
Organ transplantation recently reached its next phase with David Bennett. He survived for two months after becoming the first recipient of a pig’s heart genetically modified to function in a human body in February. Known as a xenotransplant, the procedure could pave the way for greatly expanding the use of transplanted vital organs to extend human lives.
Clinical trials would have to be held in the U.S. before xenotransplants become widespread; Bennett’s surgery was authorized under a special Food and Drug Administration program that addresses patients with life-threatening medical conditions.
German researchers plan to perform eight pig-to-human heart transplants as part of a clinical trial beginning in 2024. According to an email sent to Leaps.org by three scholars working on the German project, these procedures will focus on one of the reasons David Bennett did not survive longer: A porcine infection from his new heart.
The transplant team will conduct more sensitive testing of the donor organs, “which in all likelihood will be able to detect even low levels of virus in the xenograft,” note the scientists, Katharina Ebner, Jochen Ostheimer and Jochen Sautermeister. They are confident that the risk of infection with a porcine virus in the future will be significantly lower.
Moreover, hearts are not the only genetically modified organs that are being xenotransplanted. A team of surgeons at the University of Alabama at Birmingham successfully transplanted genetically modified pig kidneys into a brain-dead human recipient in September. The kidneys functioned normally for more than three days before the experiment ended. The UAB team is now moving forward with clinical trials focusing on transplanting pig kidneys into human patients.
Some experts believe the momentum for xenotransplantation is building, particularly given the recent successes. “I think there is a strong likelihood this will go mainstream,” says Brendan Parent of NYU Langone Health.
Douglas Anderson, a surgeon who is part of that kidney xenotransplant team, observes that, “organ shortages have been the major issue facing transplantation since its inception” and that xenotransplantation is a potential solution to that quandary. “It can’t be understated the number of people waiting for a kidney on dialysis, which has a significant mortality rate,” he says. According to the advocacy group Donate Life America, more than 100,000 people in the U.S. alone are waiting for a donated organ, and 85 percent of them need a kidney.
Other experts believe the momentum for xenotransplantation is building, particularly given the recent successes. “I think there is a strong likelihood this will go mainstream,” says Brendan Parent, director of transplant ethics and policy at NYU Langone Health, a New York City-based hospital system. Like the UAB team, surgeons at NYU Langone have had success coaxing modified pig kidneys to work in deceased humans.
“There is a genuinely good chance that within a generation, (xenotransplantation) might become very common in reasonably wealthy countries,” says Michael Reiss, professor of science education at University College in London. In addition to his academic position, Reiss sits on the Nuffield Council on Bioethics, a nonprofit that is one of Britain’s most prominent watchdogs regarding medical and scientific issues. Reiss is also an Anglican priest and has studied xenotransplantation from both a scientific and religious point of view.
Moreover, genetic modifications could one day lead to organs being specifically optimized for their recipients. That could ensure issues like donor rejection and the calculated risk of artificially suppressing recipient immune systems become concerns of the past.
Major bioethical, religious concerns
Despite the promise of xenotransplantation, numerous bioethical issues swirl around the procedure. They could be magnified if xenotransplantation evolves from one-off experiments to a routine medical procedure.
One of the biggest is the millennia-long prohibitions Islam and Judaism have had regarding the consumption of pork. Will followers of these religions assume such rules extend to those taboo materials being inserted into a human body?
“Initially, one’s instinctual reaction is that, oh, crumbs! – how are Jews and Muslims going to react to that?” Reiss says. But in a world where science and secularism are accepted on an everyday basis, he notes it is not a significant issue. Reiss points out that valves from pig hearts have been used in human patients for decades without any issues. He adds that both Islam and Judaism waive religious dietary restrictions if a human life is at risk.
“While nobody's saying an individual patient is to be forced to have these, the very high proportion of people who identify as Jews or Muslims when given this option are content with it,” he says.
Concurring with Reiss is Michael Gusamano, professor of health policy at Lehigh University and director of its Center for Ethics. He is currently performing research on the ethics of xenotransplantation for the National Institutes of Health.
“Leaders from all major religions have commented on this and have indicated that this is not inconsistent with religious doctrine,” Gusamano says in written remarks to Leaps.org. “Having said that, it is plausible to believe that some people will assume that this is inconsistent with the teaching of their religion and may object to…receiving a xenotransplant as part of routine medical care.”
A history of clashes
Despite those assurances, science has long clashed with theology. Although Galileo proved the planets revolved around the sun, the Catholic Church found him guilty of heresy and rewarded his discovery with house arrest for the last decade of his life. A revolt occurred in mid-19th century India after native-born soldiers believed the ammunition supplied by their British occupiers had been lubricated with pork and beef tallow. Given they had to use their mouths to tear open ammunition pouches, this violated both the tenets of Islam and Hinduism. And one of the conspiracy theories hatched as a result of COVID-19 was that the vaccines developed to fight the disease were the “mark of the beast” – a sign of impending Armageddon under evangelical Christian theology.
The German xenotransplant research team has encountered such potential concerns when the procedure is regarded through a religious lens. “The pastors in our research suspected that many recipients might feel disgust and revulsion,” they write. “Even beyond these special religious reservations, cultural scripts about pigs as inferior living beings are also generally widespread and effective in the western world, so that here too possible disgust reactions cannot be ruled out.”
The German researchers add that “Jewish and Muslim hospital pastoral workers believe possible considerable problems in this respect, which must be dealt with psychosocially, religiously, and pastorally prior to a possible transplantation in order to strengthen the acceptance of the received organ by the patients and their relatives.”
Parent, the director at NYU Langone, shares a concern that xenotransplantation could move “too fast,” although much of his worry is focused on zoonotic disease transmission – pig viruses jumping into humans as a result of such procedures.
Another ethical issue
Moreover, the way pigs and other animals are raised for transplants could pose future ethical dilemmas.
Reiss notes that pigs raised for medical procedures have to be grown and kept in what are known as a designated pathogen-free facility, or DPF. Such facilities are kept painstakingly antiseptic so as to minimize the risk of zoonotic transmissions. But given pigs are fond of outdoor activities such as wallowing in mud and sleeping on hay, they lead “stunningly boring lives” that they probably do not enjoy, Reiss observes.
Ethical concerns with using pigs may push transplantation medicine into its next logical phase: Growing functional organs for transplant in a laboratory setting.
“There’s no doubt that these research pigs have gotten much better veterinary care, et cetera, (compared to farmed pigs). But it’s not a great life,” Reiss says. “And although it hasn’t so far dominated the discussion, I think as the years go by, rather as we’ve seen with the use of apes and now monkeys in medical research, more and more theologians will get uncomfortable about us just assuming we can do this with…pigs.”
The German research team raises the same concerns, but has taken a fairly sanguine view on the topic. “The impairments of the species-typical behavior will certainly provoke criticism and perhaps also public protest. But the number of animals affected is very small in relation to slaughter cattle,” the German researchers note. “Moreover, the conditions there and also in several animal experiments are far worse.”
Observers say that may push transplantation medicine into its next logical phase: Growing functional organs for transplant in a laboratory setting. Anderson, the UAB transplant surgeon, believes such an accomplishment remains decades away.
But other experts believe there is a moral imperative that xenotransplantation remain a temporary solution. “I think we have a duty to go in that direction,” Parent says. “We have to go that way, with the xenotransplantation process (as) a steppingstone and research path that will be useful for bioengineered organs.”
A new injection is helping stave off RSV this season
In November 2021, Mickayla Wininger’s then one-month-old son, Malcolm, endured a terrifying bout with RSV, the respiratory syncytial (sin-SISH-uhl) virus—a common ailment that affects all age groups. Most people recover from mild, cold-like symptoms in a week or two, but RSV can be life-threatening in others, particularly infants.
Wininger, who lives in southern Illinois, was dressing Malcolm for bed when she noticed what seemed to be a minor irregularity with this breathing. She and her fiancé, Gavin McCullough, planned to take him to the hospital the next day. The matter became urgent when, in the morning, the boy’s breathing appeared to have stopped.
After they dialed 911, Malcolm started breathing again, but he ended up being hospitalized three times for RSV and defects in his heart. Eventually, he recovered fully from RSV, but “it was our worst nightmare coming to life,” Wininger recalled.
It’s a scenario that the federal government is taking steps to prevent. In July, the Food and Drug Administration approved a single-dose, long-acting injection to protect babies and toddlers. The injection, called Beyfortus, or nirsevimab, became available this October. It reduces the incidence of RSV in pre-term babies and other infants for their first RSV season. Children at highest risk for severe RSV are those who were born prematurely and have either chronic lung disease of prematurity or congenital heart disease. In those cases, RSV can progress to lower respiratory tract diseases such as pneumonia and bronchiolitis, or swelling of the lung’s small airway passages.
Each year, RSV is responsible for 2.1 million outpatient visits among children younger than five-years-old, 58,000 to 80,000 hospitalizations in this age group, and between 100 and 300 deaths, according to the Centers for Disease Control and Prevention. Transmitted through close contact with an infected person, the virus circulates on a seasonal basis in most regions of the country, typically emerging in the fall and peaking in the winter.
In August, however, the CDC issued a health advisory on a late-summer surge in severe cases of RSV among young children in Florida and Georgia. The agency predicts "increased RSV activity spreading north and west over the following two to three months.”
Infants are generally more susceptible to RSV than older people because their airways are very small, and their mechanisms to clear these passages are underdeveloped. RSV also causes mucus production and inflammation, which is more of a problem when the airway is smaller, said Jennifer Duchon, an associate professor of newborn medicine and pediatrics in the Icahn School of Medicine at Mount Sinai in New York.
In 2021 and 2022, RSV cases spiked, sending many to emergency departments. “RSV can cause serious disease in infants and some children and results in a large number of emergency department and physician office visits each year,” John Farley, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, said in a news release announcing the approval of the RSV drug. The decision “addresses the great need for products to help reduce the impact of RSV disease on children, families and the health care system.”
Sean O’Leary, chair of the committee on infectious diseases for the American Academy of Pediatrics, says that “we’ve never had a product like this for routine use in children, so this is very exciting news.” It is recommended for all kids under eight months old for their first RSV season. “I would encourage nirsevimab for all eligible children when it becomes available,” O’Leary said.
For those children at elevated risk of severe RSV and between the ages of 8 and 19 months, the CDC recommends one dose in their second RSV season.
The drug will be “really helpful to keep babies healthy and out of the hospital,” said O’Leary, a professor of pediatrics at the University of Colorado Anschutz Medical Campus/Children’s Hospital Colorado in Denver.
An antiviral drug called Synagis (palivizumab) has been an option to prevent serious RSV illness in high-risk infants since it was approved by the FDA in 1998. The injection must be given monthly during RSV season. However, its use is limited to “certain children considered at high risk for complications, does not help cure or treat children already suffering from serious RSV disease, and cannot prevent RSV infection,” according to the National Foundation for Infectious Diseases.
Until the approval this summer of the new monoclonal antibody, nirsevimab, there wasn’t a reliable method to prevent infection in most healthy infants.
Both nirsevimab and palivizumab are monoclonal antibodies that act against RSV. Monoclonal antibodies are lab-made proteins that mimic the immune system’s ability to fight off harmful pathogens such as viruses. A single intramuscular injection of nirsevimab preceding or during RSV season may provide protection.
The strategy with the new monoclonal antibody is “to extend protection to healthy infants who nonetheless are at risk because of their age, as well as infants with additional medical risk factors,” said Philippa Gordon, a pediatrician and infectious disease specialist in Brooklyn, New York, and medical adviser to Park Slope Parents, an online community support group.
No specific preventive measure is needed for older and healthier kids because they will develop active immunity, which is more durable. Meanwhile, older adults, who are also vulnerable to RSV, can receive one of two new vaccines. So can pregnant women, who pass on immunity to the fetus, Gordon said.
Until the approval this summer of the new monoclonal antibody, nirsevimab, there wasn’t a reliable method to prevent infection in most healthy infants, “nor is there any treatment other than giving oxygen or supportive care,” said Stanley Spinner, chief medical officer and vice president of Texas Children’s Pediatrics and Texas Children’s Urgent Care.
As with any virus, washing hands frequently and keeping infants and children away from sick people are the best defenses, Duchon said. This approach isn’t foolproof because viruses can run rampant in daycare centers, schools and parents’ workplaces, she added.
Mickayla Wininger, Malcolm’s mother, insists that family and friends wear masks, wash their hands and use hand sanitizer when they’re around her daughter and two sons. She doesn’t allow them to kiss or touch the children. Some people take it personally, but she would rather be safe than sorry.
Wininger recalls the severe anxiety caused by Malcolm's ordeal with RSV. After returning with her infant from his hospital stays, she was terrified to go to sleep. “My fiancé and I would trade shifts, so that someone was watching over our son 24 hours a day,” she said. “I was doing a night shift, so I would take caffeine pills to try and keep myself awake and would end up crashing early hours in the morning and wake up frantically thinking something happened to my son.”
Two years later, her anxiety has become more manageable, and Malcolm is doing well. “He is thriving now,” Wininger said. He recently had his second birthday and "is just the spunkiest boy you will ever meet. He looked death straight in the eyes and fought to be here today.”
Story by Big Think
For most of history, artificial intelligence (AI) has been relegated almost entirely to the realm of science fiction. Then, in late 2022, it burst into reality — seemingly out of nowhere — with the popular launch of ChatGPT, the generative AI chatbot that solves tricky problems, designs rockets, has deep conversations with users, and even aces the Bar exam.
But the truth is that before ChatGPT nabbed the public’s attention, AI was already here, and it was doing more important things than writing essays for lazy college students. Case in point: It was key to saving the lives of tens of millions of people.
AI-designed mRNA vaccines
As Dave Johnson, chief data and AI officer at Moderna, told MIT Technology Review‘s In Machines We Trust podcast in 2022, AI was integral to creating the company’s highly effective mRNA vaccine against COVID. Moderna and Pfizer/BioNTech’s mRNA vaccines collectively saved between 15 and 20 million lives, according to one estimate from 2022.
Johnson described how AI was hard at work at Moderna, well before COVID arose to infect billions. The pharmaceutical company focuses on finding mRNA therapies to fight off infectious disease, treat cancer, or thwart genetic illness, among other medical applications. Messenger RNA molecules are essentially molecular instructions for cells that tell them how to create specific proteins, which do everything from fighting infection, to catalyzing reactions, to relaying cellular messages.
Johnson and his team put AI and automated robots to work making lots of different mRNAs for scientists to experiment with. Moderna quickly went from making about 30 per month to more than one thousand. They then created AI algorithms to optimize mRNA to maximize protein production in the body — more bang for the biological buck.
For Johnson and his team’s next trick, they used AI to automate science, itself. Once Moderna’s scientists have an mRNA to experiment with, they do pre-clinical tests in the lab. They then pore over reams of data to see which mRNAs could progress to the next stage: animal trials. This process is long, repetitive, and soul-sucking — ill-suited to a creative scientist but great for a mindless AI algorithm. With scientists’ input, models were made to automate this tedious process.
“We don’t think about AI in the context of replacing humans,” says Dave Johnson, chief data and AI officer at Moderna. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
All these AI systems were in put in place over the past decade. Then COVID showed up. So when the genome sequence of the coronavirus was made public in January 2020, Moderna was off to the races pumping out and testing mRNAs that would tell cells how to manufacture the coronavirus’s spike protein so that the body’s immune system would recognize and destroy it. Within 42 days, the company had an mRNA vaccine ready to be tested in humans. It eventually went into hundreds of millions of arms.
Biotech harnesses the power of AI
Moderna is now turning its attention to other ailments that could be solved with mRNA, and the company is continuing to lean on AI. Scientists are still coming to Johnson with automation requests, which he happily obliges.
“We don’t think about AI in the context of replacing humans,” he told the Me, Myself, and AI podcast. “We always think about it in terms of this human-machine collaboration, because they’re good at different things. Humans are really good at creativity and flexibility and insight, whereas machines are really good at precision and giving the exact same result every single time and doing it at scale and speed.”
Moderna, which was founded as a “digital biotech,” is undoubtedly the poster child of AI use in mRNA vaccines. Moderna recently signed a deal with IBM to use the company’s quantum computers as well as its proprietary generative AI, MoLFormer.
Moderna’s success is encouraging other companies to follow its example. In January, BioNTech, which partnered with Pfizer to make the other highly effective mRNA vaccine against COVID, acquired the company InstaDeep for $440 million to implement its machine learning AI across its mRNA medicine platform. And in May, Chinese technology giant Baidu announced an AI tool that designs super-optimized mRNA sequences in minutes. A nearly countless number of mRNA molecules can code for the same protein, but some are more stable and result in the production of more proteins. Baidu’s AI, called “LinearDesign,” finds these mRNAs. The company licensed the tool to French pharmaceutical company Sanofi.
Writing in the journal Accounts of Chemical Research in late 2021, Sebastian M. Castillo-Hair and Georg Seelig, computer engineers who focus on synthetic biology at the University of Washington, forecast that AI machine learning models will further accelerate the biotechnology research process, putting mRNA medicine into overdrive to the benefit of all.
This article originally appeared on Big Think, home of the brightest minds and biggest ideas of all time.