Last week, surgeons announced that they had conducted the first pig heart transplant on a human. The surgery was a defining moment in the field of xenotransplantation, or transplants between species. It's uncertain how well or how long the heart will function, but researchers hope that the procedure will one day compensate for a scarcity of human organs for sick patients.
The procedure, performed by a team from the University of Maryland School of Medicine (UMSOM), was a major test for several experimental innovations aimed at keeping the pig heart functioning in a human chest, including 10 genetic changes in the pigs, a novel immunosuppressant given to the recipient, and a cocaine-laced solution used to incubate the heart.
Here's how the complicated procedure was influenced by science and ethical considerations.
David Bennett, 57, had severe heart failure and ventricular fibrillation, a kind of arrhythmia. Physicians at the University of Maryland Medical Center and other institutions ruled him ineligible for a human heart transplant because he had not taken steps to treat his high blood pressure and other health issues.
Instead, with Bennett's approval, the UMSOM team applied to the U.S. Food and Drug Administration (FDA) for a "compassionate use" authorization to give him a heart from a genetically modified pig created by Revivicor, a biotech company.
Rejection, an immunological response in the recipient that might cause the organ from another species to fail, is a risk of xenotransplantation. One major issue is that antibodies produced by humans identify specific sugars on the surface of pig cells as alien.Revivicor therefore took off three genes for enzymes that allow pig cells to generate those sugars in one of its lines of modified pigs.
Human genes were used to make six changes: two anti-inflammatory genes, two genes that promote normal blood coagulation and prevent blood vessel damage, and two other regulatory proteins that aid to suppress antibody response.
The gene for a growth hormone receptor was removed as a final tweak to lessen the likelihood that a pig organ, nearly matched in size to the patient's chest, would outgrow it once transplanted.
Muhammad Mohiuddin, director of UMSOM's cardiac xenotransplantation program, and colleagues announced in September 2021 that this modification reduced the growth of pig hearts transplanted into baboons, a change they hope will help people avoid heart failure.
Aside from immune rejection, pig hearts transplanted into baboons appear to sputter out in a matter of days unless they are perfused with a nutritional solution before to the transplant, according to Mohiuddin. The processes underlying the hearts' failure are unknown, but he speculates that removing the organ from the pig's chest depletes the energy-producing mitochondria in the organ's cells.
The UMSOM team used a technique invented by Lund University surgeon Stig Steen and marketed by the Swedish business XVIVO for keeping and treating donor hearts after they were harvested. The heart is immersed in a flowing broth containing water, chemicals such as adrenaline and cortisol, as well as dissolved cocaine.
It's unclear how cocaine keeps the bodiless heart healthy, according to Mohiuddin, but its presence in the solution causes complications when his team imports a new batch from Sweden; each shipment requires a permission from the U.S. Drug Enforcement Administration.
Asked about the breakthrough surgery, Revivicor CEO David Ayares said that it won't be the first only xenotransplantation.
"We're going to take this all the way through to human clinical trials, and hopefully have an unlimited supply of donor organs," Ayares said.
