David Bennett is perhaps a name you’ve heard quite frequently since the last week or so. On the 7th of January 2022, he became the first man in the world to successfully receive a transplant of a pig’s heart. The eight-hour-long operation took place at the University of Maryland Medical Center in Baltimore, USA, and the success was viewed by some as the beacon of light for the future of organ transplant surgery.
Though the surgical breakthrough was the first-of-its-kind, xenotransplantation, the goal of transplanting animal organs into people, has been pursued by scientists and doctors alike since more than 60 years ago. It was the summer of 1940, when Peter Medawar and his wife, Jean, and eldest daughter, Caroline’s peaceful Sunday afternoon was broken by a plane crashing violently just 200m away in a garden. Although the pilot survived the crash, he suffered horrific burns.
A zoologist by training, the Oxford researcher Medawar was conducting studies on which antibiotics were best at treating burns. For the pilot who just crashed, doctors soon came to Medawar for help on deciding what medications to use. During a time where the war left many airmen in agony with much of their skin incinerated, while medical advances such as blood transfusions and antibiotics were able to prolong their lives, there was no way of actually treating these burns. And when the doctors transplanted healthy skin from one person to another to cover the burn-wound, it was all destroyed soon after.
At the time, the doctors believed it to be merely a matter of skill that the skins were destroyed – the cutting and sewing were yet to be perfected, but Medawar saw something more. Through tireless experimentation with 25 rabbits, he grafted pieces of skin from each one onto every other one. 625 operations on 25 rabbits later, he showed that skin could not be grafted between different rabbits. More interestingly, during the second round of grafting, it turned out that the rejection happened even faster than during the first transplant, indicative of an immune reaction. Fundamentally, Medawar and his team showed that transplantation can be successful as long as the immune reactions can be stopped.
Fast forward to a few decades later, in the 1960s, chimpanzee kidneys were transplanted into some human patients, but the longest a recipient lived was nine months. Then in 1983, a baboon heart was transplanted into an infant named Baby Fae, who died 20 days later. In order to increase the chance of a successful transplantation, scientists looked to gene editing and cloning technologies to genetically alter the organs so that it’s less likely to be rejected by the patient. Specifically, pigs are often chosen over other primates for organ procurement because they are easier to raise and their organs are able to reach adult human size in just around six months.
Before the pig’s heart was transplanted into David Bennett, Revivicor, a regenerative medicine company that provided the pig’s heart for surgery, made 10 genetic modifications to the organ. Firstly, 3 genes were knocked out or inactivated, including one gene that encodes a molecule which would cause an aggressive human rejection response. Then, the growth gene was inactivated to stop the pig’s heart from growing further in size after it was implanted. Finally, six tweaks were made to the pig’s heart as additions of human genes: two anti-inflammatory genes, two genes that promote normal blood coagulation and prevent blood vessel damage, and two other regulatory proteins that help tamp down antibody response, says the Science magazine.
Despite the initial challenges, scientists are hoping that its success will enable them to give more people animal organs. However, if Bennett’s success were to be replicated, regulators and ethicists will need to define what makes a person eligible for a pig organ. For instance, most people waiting for kidney transplants can be put on dialysis, and organ harvesting from animals raises animal welfare concerns. PETA, the non-for-profit organisation People for the Ethical Treatment of Animals, warns of the mistreatment of animals as “warehouses of spare parts”, citing protocols documenting that baboons and macaques were caged alone, subjected to multiple major survival surgeries, numerous biopsies, and repeated blood draws in clinical trials for organ transplantation. Furthermore, in these days of the pandemic, all of us are only too aware of the very real danger of transmitting unknown viruses during such a procedure, as pigs often carry zoonotic and other infectious pathogens that could be introduced to the human patient.