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.”
After spaceflight record, NASA looks to protect astronauts on even longer trips
At T-minus six seconds, the main engines of the Atlantis Space Shuttle ignited, rattling its capsule “like a skyscraper in an earthquake,” according to astronaut Tom Jones, describing the 1988 launch. As the rocket lifted off and accelerated to three times the force of Earth's gravity, “It felt as if two of my friends were standing on my chest and wouldn’t get off.” But when Atlantis reached orbit, the main engines cut off, and the astronauts were suddenly weightless.
Since 1961, NASA has sent hundreds of astronauts into space while working to making their voyages safer and smoother. Yet, challenges remain. Weightlessness may look amusing when watched from Earth, but it has myriad effects on cognition, movement and other functions. When missions to space stretch to six months or longer, microgravity can impact astronauts’ health and performance, making it more difficult to operate their spacecraft.
Yesterday, NASA astronaut Frank Rubio returned to Earth after over one year, the longest single spaceflight for a U.S. astronaut. But this is just the start; longer and more complex missions into deep space loom ahead, from returning to the moon in 2025 to eventually sending humans to Mars. To ensure that these missions succeed, NASA is increasing efforts to study the biological effects and prevent harm.
The dangers of microgravity are real
A NASA report published in 2016 details a long list of incidents and near-misses caused – at least partly – by space-induced changes in astronauts’ vision and coordination. These issues make it harder to move with precision and to judge distance and velocity.
According to the report, in 1997, a resupply ship collided with the Mir space station, possibly because a crew member bumped into the commander during the final docking maneuver. This mishap caused significant damage to the space station.
Returns to Earth suffered from problems, too. The same report notes that touchdown speeds during the first 100 space shuttle landings were “outside acceptable limits. The fastest landing on record – 224 knots (258 miles) per hour – was linked to the commander’s momentary spatial disorientation.” Earlier, each of the six Apollo crews that landed on the moon had difficulty recognizing moon landmarks and estimating distances. For example, Apollo 15 landed in an unplanned area, ultimately straddling the rim of a five-foot deep crater on the moon, harming one of its engines.
Spaceflight causes unique stresses on astronauts’ brains and central nervous systems. NASA is working to reduce these harmful effects.
NASA
Space messes up your brain
In space, astronauts face the challenges of microgravity, ionizing radiation, social isolation, high workloads, altered circadian rhythms, monotony, confined living quarters and a high-risk environment. Among these issues, microgravity is one of the most consequential in terms of physiological changes. It changes the brain’s structure and its functioning, which can hurt astronauts’ performance.
The brain shifts upwards within the skull, displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes.
That’s partly because of how being in space alters blood flow. On Earth, gravity pulls our blood and other internal fluids toward our feet, but our circulatory valves ensure that the fluids are evenly distributed throughout the body. In space, there’s not enough gravity to pull the fluids down, and they shift up, says Rachael D. Seidler, a physiologist specializing in spaceflight at the University of Florida and principal investigator on many space-related studies. The head swells and legs appear thinner, causing what astronauts call “puffy face chicken legs.”
“The brain changes at the structural and functional level,” says Steven Jillings, equilibrium and aerospace researcher at the University of Antwerp in Belgium. “The brain shifts upwards within the skull,” displacing the cerebrospinal fluid, which reduces the brain’s cushioning. Essentially, the brain becomes crowded inside the skull like a pair of too-tight shoes. Some of the displaced cerebrospinal fluid goes into cavities within the brain, called ventricles, enlarging them. “The remaining fluids pool near the chest and heart,” explains Jillings. After 12 consecutive months in space, one astronaut had a ventricle that was 25 percent larger than before the mission.
Some changes reverse themselves while others persist for a while. An example of a longer-lasting problem is spaceflight-induced neuro-ocular syndrome, which results in near-sightedness and pressure inside the skull. A study of approximately 300 astronauts shows near-sightedness affects about 60 percent of astronauts after long missions on the International Space Station (ISS) and more than 25 percent after spaceflights of only a few weeks.
Another long-term change could be the decreased ability of cerebrospinal fluid to clear waste products from the brain, Seidler says. That’s because compressing the brain also compresses its waste-removing glymphatic pathways, resulting in inflammation, vulnerability to injuries and worsening its overall health.
The effects of long space missions were best demonstrated on astronaut twins Scott and Mark Kelly. This NASA Twins Study showed multiple, perhaps permanent, changes in Scott after his 340-day mission aboard the ISS, compared to Mark, who remained on Earth. The differences included declines in Scott’s speed, accuracy and cognitive abilities that persisted longer than six months after returning to Earth in March 2016.
By the end of 2020, Scott’s cognitive abilities improved, but structural and physiological changes to his eyes still remained, he said in a BBC interview.
“It seems clear that the upward shift of the brain and compression of the surrounding tissues with ventricular expansion might not be a good thing,” Seidler says. “But, at this point, the long-term consequences to brain health and human performance are not really known.”
NASA astronaut Kate Rubins conducts a session for the Neuromapping investigation.
NASA
Staying sharp in space
To investigate how prolonged space travel affects the brain, NASA launched a new initiative called the Complement of Integrated Protocols for Human Exploration Research (CIPHER). “CIPHER investigates how long-duration spaceflight affects both brain structure and function,” says neurobehavioral scientist Mathias Basner at the University of Pennsylvania, a principal investigator for several NASA studies. “Through it, we can find out how the brain adapts to the spaceflight environment and how certain brain regions (behave) differently after – relative to before – the mission.”
To do this, he says, “Astronauts will perform NASA’s cognition test battery before, during and after six- to 12-month missions, and will also perform the same test battery in an MRI scanner before and after the mission. We have to make sure we better understand the functional consequences of spaceflight on the human brain before we can send humans safely to the moon and, especially, to Mars.”
As we go deeper into space, astronauts cognitive and physical functions will be even more important. “A trip to Mars will take about one year…and will introduce long communication delays,” Seidler says. “If you are on that mission and have a problem, it may take eight to 10 minutes for your message to reach mission control, and another eight to 10 minutes for the response to get back to you.” In an emergency situation, that may be too late for the response to matter.
“On a mission to Mars, astronauts will be exposed to stressors for unprecedented amounts of time,” Basner says. To counter them, NASA is considering the continuous use of artificial gravity during the journey, and Seidler is studying whether artificial gravity can reduce the harmful effects of microgravity. Some scientists are looking at precision brain stimulation as a way to improve memory and reduce anxiety due to prolonged exposure to radiation in space.
Other scientists are exploring how to protect neural stem cells (which create brain cells) from radiation damage, developing drugs to repair damaged brain cells and protect cells from radiation.
To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
Additionally, NASA is scrutinizing each aspect of the mission, including astronaut exercise, nutrition and intellectual engagement. “We need to give astronauts meaningful work. We need to stimulate their sensory, cognitive and other systems appropriately,” Basner says, especially given their extreme confinement and isolation. The scientific experiments performed on the ISS – like studying how microgravity affects the ability of tissue to regenerate is a good example.
“We need to keep them engaged socially, too,” he continues. The ISS crew, for example, regularly broadcasts from space and answers prerecorded questions from students on Earth, and can engage with social media in real time. And, despite tight quarters, NASA is ensuring the crew capsule and living quarters on the moon or Mars include private space, which is critical for good mental health.
Exploring deep space builds on a foundation that began when astronauts first left the planet. With each mission, scientists learn more about spaceflight effects on astronauts’ bodies. NASA will be using these lessons to succeed with its plans to build science stations on the moon and, eventually, Mars.
“Through internally and externally led research, investigations implemented in space and in spaceflight simulations on Earth, we are striving to reduce the likelihood and potential impacts of neurostructural changes in future, extended spaceflight,” summarizes NASA scientist Alexandra Whitmire. To boldly go where no astronauts have gone before, they must have optimal reflexes, vision and decision-making. In the era of deep space exploration, the brain—without a doubt—is the final frontier.
A newly discovered brain cell may lead to better treatments for cognitive disorders
Swiss researchers have discovered a third type of brain cell that appears to be a hybrid of the two other primary types — and it could lead to new treatments for many brain disorders.
The challenge: Most of the cells in the brain are either neurons or glial cells. While neurons use electrical and chemical signals to send messages to one another across small gaps called synapses, glial cells exist to support and protect neurons.
Astrocytes are a type of glial cell found near synapses. This close proximity to the place where brain signals are sent and received has led researchers to suspect that astrocytes might play an active role in the transmission of information inside the brain — a.k.a. “neurotransmission” — but no one has been able to prove the theory.
A new brain cell: Researchers at the Wyss Center for Bio and Neuroengineering and the University of Lausanne believe they’ve definitively proven that some astrocytes do actively participate in neurotransmission, making them a sort of hybrid of neurons and glial cells.
According to the researchers, this third type of brain cell, which they call a “glutamatergic astrocyte,” could offer a way to treat Alzheimer’s, Parkinson’s, and other disorders of the nervous system.
“Its discovery opens up immense research prospects,” said study co-director Andrea Volterra.
The study: Neurotransmission starts with a neuron releasing a chemical called a neurotransmitter, so the first thing the researchers did in their study was look at whether astrocytes can release the main neurotransmitter used by neurons: glutamate.
By analyzing astrocytes taken from the brains of mice, they discovered that certain astrocytes in the brain’s hippocampus did include the “molecular machinery” needed to excrete glutamate. They found evidence of the same machinery when they looked at datasets of human glial cells.
Finally, to demonstrate that these hybrid cells are actually playing a role in brain signaling, the researchers suppressed their ability to secrete glutamate in the brains of mice. This caused the rodents to experience memory problems.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Andrea Volterra, University of Lausanne.
But why? The researchers aren’t sure why the brain needs glutamatergic astrocytes when it already has neurons, but Volterra suspects the hybrid brain cells may help with the distribution of signals — a single astrocyte can be in contact with thousands of synapses.
“Often, we have neuronal information that needs to spread to larger ensembles, and neurons are not very good for the coordination of this,” researcher Ludovic Telley told New Scientist.
Looking ahead: More research is needed to see how the new brain cell functions in people, but the discovery that it plays a role in memory in mice suggests it might be a worthwhile target for Alzheimer’s disease treatments.
The researchers also found evidence during their study that the cell might play a role in brain circuits linked to seizures and voluntary movements, meaning it’s also a new lead in the hunt for better epilepsy and Parkinson’s treatments.
“Our next studies will explore the potential protective role of this type of cell against memory impairment in Alzheimer’s disease, as well as its role in other regions and pathologies than those explored here,” said Volterra.