On Dec. 3, 1967, doctors performed the world’s first heart transplant. They took the heart out of a deceased donor and surgically implanted it in an ill recipient in South Africa. Just over 51 years after scientists created the field, they’re on the verge of transforming it—this time, with pig organs.
In a landmark study published today (Dec. 5), scientists based in Germany report that baboons with transplanted hearts from genetically-engineered pigs can survive for over six months. “It is time to reconsider what preclinical results should be required before pig-to-human clinical trials can be initiated,” Christoph Knosalla, a heart surgeon at the German Heart Center in Berlin who was not involved with the study but reviewed the work, wrote in an accompanying commentary.
The possibility of xenotransplantation, involving animal-to-human transplants, has been on the minds of the medical community for centuries. Although there have been short-term successes—including one case of a patient surviving with a chimpanzee kidney for nine months—xenotransplants are still considered too risky for clinical use.
However, xenoplantation is a tantalizing option given the current organ shortage in the US. The problem is particularly acute for those in need of a heart transplant, who must receive an organ from a donor who was declared brain-dead in a hospital setting (some organs like kidneys or parts of livers can be given from people who are still alive). Right now, there are over 114,000 people on the waitlist for organs in the US, almost 4,000 of which are for new hearts, according to the United Network for Organ Sharing, a US-based nonprofit. The same organization estimates that about 7,000 people will die waiting for an organ annually. Anywhere between 1.6% and 16% of patients waiting for hearts may die before they receive one, depending on other risk factors like age and kidney health.
In theory, xenotransplants from pigs, which have hearts similar in size to those of humans, could alleviate this shortage. However, so far pig-heart transplants in baboons have only kept the animals alive for a maximum of 57 days—much shorter than guidelines set almost two decades ago by the International Society for Heart and Lung Transplantation (ISHLT), and still in use today. In 2000, the organization stated that clinical trials for xenotransplantation “should be considered when approximately 60% survival of life-supporting pig organs in non-human primates has been achieved for a minimum of three months, with at least 10 animals surviving for this minimum period.” There should be some indication that the organs could last for longer, too, and the procedure should only be considered as a last resort.
The study published today reports that baboons survived with genetically-modified pig hearts for over six months, edging closer to the ISHLT guidelines. The team surgically implanted 16 baboons with hearts that had been removed from pigs that had been genetically modified to have more in common with a primate’s body.
The baboons were divided into three groups to test out different transplant techniques. In the first group, the longest-surviving baboon only made it 30 days. The scientists believe this is because the hearts had been damaged due to temperature and other environmental factors before they were implanted.
In the second group, surgeons kept the hearts in better condition at cooler temperatures in a blood-based solution, but didn’t give the baboons the right combinations of immunosuppressants; although the transplant recipients in some cases survived 40 days, the transplanted hearts swelled up to an average of 249% their original size, which led to other organ failures.
In the third group, the surgeons effectively protected the organ before the transplant, tweaked the immunosuppressant regimen, and prepped the baboons’ bodies by giving the primates medication to lower their blood pressure to similar levels as a pig to help counteract the possibility of swelling. One baboon in this group was euthanized after 50 days, because it developed fluid in the chest cavity, and two more were euthanized after three months in order to examine how their transplanted hearts were doing. After the scientists determined that those two baboons were relatively healthy, they continued the remaining two animals’ medications until days 161 and 175. They died roughly three weeks later.
The ability for a patient to survive with a heart from another person once seemed impossible. In less than a century, science has lunged forward to make living with a heart from another species a possibility in our lifetimes.