On January 7, a team of surgeons from the University of Maryland School of Medicine (UMSOM) transplanted a genetically modified pig heart into 57-year-old David Bennett, a man with terminal heart disease and arrhythmia.
Bennett was terminally ill and had been hospitalized for over six weeks, relying on a heart-lung bypass machine to keep him alive. The groundbreaking surgery was Bennett’s only chance at extending his life, as multiple transplantation centres in the United States had deemed him ineligible for a human heart transplant due to a history of ignoring doctors’ attempts to manage his high blood pressure and other comorbidities. With transplantable organs in such short supply and over 100,000 people on the national transplant waiting list, these institutions only give organs to people who they believe will care for them.
Medical professionals at UMSOM filed a petition to the US Food and Drug Administration (FDA) to transplant a genetically modified pig heart into their patient, on the grounds that this experimental procedure was the only option to extend his life. They received emergency authorization on December 31, and began preparations to perform the surgery in a week from then.
Animal-human fusion
Xenotransplantation is the transplantation of animal cells, tissues, and organs into human recipients, and it may help solve the organ shortage crisis. Pig heart valves have been used to replace human heart valves for many years, but, if we measure success by whether the patient survived and their body did not immediately reject the organ, there have been no other successful animal-to-human organ transplants to date. In 1984, a baboon heart was transplanted into a newborn human with fatal heart defects. The baby died within a month because her body mounted a strong immune response against the foreign heart and, since then, xenotransplants have been largely abandoned.
The heart used for Bennett’s revolutionary transplant, however, was no ordinary pig heart. The heart was developed by the biotechnology company Revivicor, a subsidiary of United Therapeutics Corporation. The company disabled the effect of three genes in the donor pig so that its cells could not produce certain membrane-bound sugars that human antibodies would recognize as foreign, and which could therefore trigger an immune reaction. They also inserted six human genes into the pig genome to reduce inflammation, protect blood vessels, maintain regular blood coagulation, and suppress antibody responses in Bennett’s body. Lastly, they deleted a gene in the pig genome that governs growth hormones so that the heart would not grow in size, once transplanted into its human host.
On the day of the surgery, the surgical team excised the heart from the pig, placed it into a perfusion machine, and bathed it in a solution containing dissolved cocaine and other chemicals. Previous studies have found that cocaine helps to maintain heart function in the time between excision and transplantation, although the underlying reason for this is unknown.
The transplantation was performed by Dr. Bartley P. Griffith, a distinguished surgeon and the director of the Cardiac Transplant Program at the University of Maryland Medical Centre. Bennett has been recovering well, according to a statement published three days after the surgery.
His body’s response to the heart will provide scientists with invaluable data about what still needs to be done before xenotransplantation can become a standard option for patients.
Looking forward
What could this surgery mean for the future of animal-to-human organ transplantation? Well, it might mean that more government-approved xenotransplants will be performed on terminally ill patients. While the one-time authorization applied only to Bennett’s case, it is likely that surgeons at UMSOM or other medical centres will apply for similar authorization in the future. Nonetheless, there is still much research to conduct before xenotransplantation becomes more widely used.
The xenoheart used in this surgery is still in the preclinical development stage, and Revivicor is also developing a xenokidney, xenolobe, and xenolung. Other biotechnology companies are also working on producing animal organs suitable for human transplantation, although none have currently reached human trials. These kinds of organs are often first tailored for use in baboons or other test animals. Moreover, these genetically modified organs are very expensive to produce.
While the successful transplant at UMSOM has saved a man’s life, and is bound to result in a lot of new information for scientists, xenotransplantation still has a long way to go before reaching clinical and public acceptance.
