Strange New Organ Transplant Methods Raise Urgent Questions
New techniques use organs from partially resuscitated people and look toward genetically modified pigs
FEATUREDBIOTECHNOLOGY
Martha Rosenberg
Martha Rosenberg
Nov 12 2022
If you or a loved one has needed an organ transplant, you know the problem firsthand: There are not enough organs for those who need them and there is a long waiting period.
That desperate need, and potential profits, have fueled a Frankenstein-like effort to find or create organs to give recipients a longer lease on life.
The need for organs can be a matter of life or death. In the United States, more than 105,000 people sit on the national waiting list, and every nine minutes, a new name is added. Seventeen people die every day while waiting for an organ transplant in the United States, according to the government’s organ donor website.
The most common transplant operations are for hearts, kidneys, livers, pancreases, lungs, bone and bone marrow, skin, and intestines; some such transplants come from living donors, but most are obtained after a donor is deceased.
Different organs remain viable for different amounts of time after the patient has died, or after the organ has been taken from the deceased.
According to Donor Alliance, the liver can remain viable for transplant for up to 12 hours, and kidneys for up to 36 hours. But for other organs, such as the heart or lungs, that window is much shorter, in the range of 4 to 6 hours.
With so few organs available for so many in need, there’s tremendous pressure on scientists and industry to push the boundaries of medical ethics with products and procedures that can sound like mad science.
These vanguard developments raise fundamental questions about human life, the commodification of the human body, and the very definition of “human.”
Let’s put aside the obvious horrors of forced organ harvesting from prisoners of conscience in China, including Tibetans, Uyghurs, and, most notably, Falun Gong practitioners, “the primary victims of this cruel practice,” according to the U.S. Human Rights Commission.
Everyone can agree that this practice is abhorrent, but there are other new practices that raise more complex questions, including a new practice that some fear is being used to curb the dead donor rule.
That rule requires that a patient be dead, and often for several minutes, before their organs are taken. This ensures organs only come from the deceased.
Reviving the Dead—Partially
Doctors are using a relatively new procedure called NRP-cDCD (“normothermic regional perfusion with controlled donation after circulatory death”) to widen the window on organ transplants and make more organs available.
In this procedure, terminal patients are allowed to die and then be partially resurrected. Their blood is circulated with the help of machines that warm it, but the arteries that feed the brain are clamped off and starved.
Writing in the journal Cureus in 2022, pro-NRP researchers say that the method “is an emerging technology, a cost-effective alternative in donation after circulatory death (DCD), and will increase the pool of donors in heart transplantation.”
Among other advantages, NRP “restores heart function” and allows “continuous warm blood perfusion,” the researchers write.
Until now, transplant surgeons wouldn’t remove the organs of patients who are not brain dead, even if they couldn’t survive without life support. The procedure raises questions about what can be done with the body after death and how “death” itself is defined. Other procedures challenge the definition of the human body.
Transplants from Genetically Modified Animals
Scientists are in a race to develop genetically humanized animals for their organs. For example, scientists are currently trying to grow human organs in genetically altered pigs and other animals, and in 2017, the creation of what’s claimed to be the first part-human, part-pig hybrid was announced.
Xenotransplantation—using animal organ donors—is far from new. The first pig-to-human corneal transplant, for example, was performed in 1838, according to the journal EMBO Reports, but xenotransplantation was beset with failures until recently.
With the advent of CRISPR gene editing (clustered, regularly interspaced, short palindromic repeats) and stem cell science, an otherworldly new form of “chimeric” animals boasting human organs has made xenotransplantation viable.
Doctors had all but given up on such procedures after too many experiences like Dr. Keith Reemtsma’s in the 1960s. Reemtsma, a transplant surgeon at Tulane University, inserted rhesus monkey and chimpanzee kidneys into humans, but the transplants all failed.
“An infant known as Baby Fae received a baboon heart at the Loma Linda University Medical Center in California in 1984 but died of rejection 21 days later,” wrote Dr. Joshua Mezrich, a transplant surgeon writing in The Wall Street Journal.
After more mishaps, transplant doctors stopped work with animal organs altogether, Mezrich wrote, and “only implantation of inert tissue from animals, such as heart valves, continued.”
A major risk with transplantation is the human immune system attacking and rejecting the newly transplanted organ as foreign.
According to the government health site MedlinePlus, “all [organ] recipients have some amount of acute rejection,” and if anti-rejection medicines are not used—risky unto themselves—”the body will almost always launch an immune response and destroy the foreign tissue.”
When transplants come from pigs—a preferred animal donor over primates because of size, breeding time, and public acceptance of their use—their intrinsic protein, alpha-gal, leads to rapid human rejection.
In 2020, the FDA approved a pig without alpha-gal, the first intentional genomic alteration. Some researchers and medical scientists want to use pigs that are genetically altered to prevent rejection of their organs in humans.
Issues With Transplantation Research
As the human body becomes more manipulatable by surgeons and scientists, the extent to which transplant research requires “living” human bodies also increases. This can complicate the mourning process for family members or play on the emotions of the organ recipients themselves.
In one example, earlier this year, scientists at NYU Langone Health in New York City announced the plan to study pig kidney behavior in brain-dead individuals for two to four weeks.
After a pig heart was transplanted into Alva Capuano, who was brain dead, as part of a study at Langone medical center, her husband, Richard Capuano, told The Wall Street Journal that the decision “was monumentally hard on the entire family.”
“Even though we realized she had already died and wasn’t coming back, there is still a respirator on and there is still a heartbeat. Psychologically it plays a game with you,” he said.
Many remember the recent saga of 57-year-old David Bennett, the first human recipient of a pig heart, who died weeks after his transplant, apparently from porcine cytomegalovirus (though human herpesvirus 6, which may cross-react with cytomegalovirus, was also found in Bennett).
According to a study published in The New England Journal of Medicine, the pigs used in recent failed human heart transplants at Langone, were significantly altered.
“The genetic modifications of the donor pig (including its heart) fell into two categories: those that inactivated pig genes and those that introduced human genes. In total, 10 different modifications were introduced, most to prevent graft rejection by the human immune system,” noted the journal.
The pig heart recipient, Bennett, had a criminal history and was denied a human heart because he was known to not follow medical guidance, raising other transplantation questions.
Scientific and Ethical Experts Weigh In
While many applaud scientific breakthroughs that allow more organs for human transplants (and these developments can certainly be lucrative), others question the direction in which we are going. In a 2021 statement, the American College of Physicians (ACP) raised serious concerns about NRP-cDCD.
The procedure, it said “is more accurately described as organ retrieval after cardiopulmonary arrest and the induction of brain death. It raises significant ethical concerns and questions regarding the dead donor rule, fundamental ethical obligations of respect, beneficence, and justice, and the imperative to never use one individual merely as a means to serve the ends of another, no matter how noble or good those ends may be.”
ACP is the largest medical-specialty society in the world, with 160,000 members internationally.
‘Humanized’ Animals
In a 2018 paper in the journal Embo Reports, authors worry that human stem cells transplanted into genetically altered pig embryos “will migrate to the animal’s brain and alter its behavior or cognitive state.” While such a brain presence could propel Alzheimer’s and Parkinson’s disease research, “there is no consensus on accurately assessing what it means to possess a human-like cognitive state,” wrote the researchers.
“Should personhood be defined as the percent of human brain cells expressed in a human-animal chimera…?” ask the researchers.
The U.S. National Institutes of Health has refused to support the transplantation of human-animal chimeras for this reason.
Moreover, could the advanced genetic technology we have today be used on “healthy human embryos to create designer babies for behavioral or cosmetic enhancements?” they asked.
Nita Farahany, a professor of law and philosophy at Duke Law School, agrees about the slippery slope that genetic engineering allows, she said in a recent interview with The Wall Street Journal. Scientists still don’t have a grasp on how insertion of human genes through gene editing affects animals’ cognitive capabilities, so “you’re starting to blur the line essentially between humans and non-human animals,” she says.
Disease Transmission
Research in the magazine Philosophy Now raises another ethical question: The possibility of disease transmission and future pandemics occasioned by transplantation.
“Diseases like HIV, Ebola, Hepatitis B, and, most recently, bird flu, originated in animals,” wrote co-author Laura Purdy in the magazine. “Pigs, where current xeno research is now focused, are thought to have been the vector of the devastating 1918 influenza epidemic.”
Known and unknown viruses are embedded in pigs’ DNA as they are in all mammals, says Purdy, and “currently harmless organisms, like the E. coli that lives in our guts, could pick up new, possibly harmful traits from the micro-organisms that came along for the ride on pig organs.”
Whether extreme NRP-cDCD surgery or the creation of pig-human chimeras, the race to harvest new organs has a dark side, according to experts.
“In some ways, the legal determination of death and medical practice are starting to diverge in ways that raise complex ethical and legal challenges we will increasingly face as a society,” Farahany of Duke University told The Epoch Times.
Beyond the moral issues of giving further intelligence to genetically modified pigs, or the health issues of inserting animal organs into people, there are fundamental questions about how we are commodifying the body and what it will mean for the sanctity of the body for future generations.
In a time when people can be fired or censured for not getting injected with a relatively new and unverified mRNA vaccine, which some describe as a gene therapy, these questions take on particular urgency.
And given that many of these organ failures are driven by preventable lifestyle factors, such as stress, diet, and a lack of natural movement, one has to wonder if we are putting scientific and commercial interests ahead of the human beings they are supposed to serve.
