In a medical first, a gene-edited pig heart has been transplanted into a human patient

After exhausting all available options, doctors approached David Bennett Sr with a last-ditch effort to save his life – receive a heart transplant from a gene-edited pig. Three days after the transplant, David remains in stable condition, a positive sign that some experts suggest may foreshadow a new era of organ transplantation.

The transplantation of organs from one species to another, known as xenotransplantation, has been the target of medical curiosity for centuries. In 1905, a French scientist attempted to transplant slices of rabbit kidney into a child suffering from chronic kidney disease. Although unsuccessful, this procedure was followed by decades of attempts to transfer organs from lambs, pigs, and primates into human patients.

Scientists would discover that xenotransplantation frequently triggers deadly immune responses in organ recipients. The presence of foreign animal cells sets off a cascade of molecular signals that can kill patients in a matter of days or even minutes.

Advancements in genetics and immunology have uncovered the genes, proteins, and molecular pathways linked to organ rejection. In parallel, rapid improvements in gene-editing technologies like CRISPR have given scientists the ability to precisely edit dozens of sequences across an animal’s genome. In theory, targeted genetic changes could camouflage foreign organs and prevent a deadly immune response, a proposition that multiple companies are pursuing.

In October 2021, surgeons at New York University's Langone Health completed a proof-of-concept experiment by attaching a pig kidney to a brain-dead human body. The organ continued to function normally for two days post-treatment. The kidney came from the Virginia-based regenerative medicine company Revivicor. A year prior, Revivicor had received regulatory approval to genetically-engineer pigs for both food and medical uses.

The issue, however, is that pigs produce a sugar in their cells, which causes an immune response in humans during an organ transplant. By eliminating that sugar through genetic engineering, Revivicor created organs capable of evading an immune response.

On January 7 2022, xenotransplantation took another monumental leap forward with the successful transferring of a gene-edited pig heart into a living human. This time Revivicor provided a heart from a donor pig, engineered to have 10 genetic alterations. They eliminated three genes responsible for organ rejection within the pig's genome while introducing six human genes to help the patient’s body accept the new heart. They knocked out one additional gene to prevent the pig heart from growing too large.

Scientists are hesitant to draw conclusions from this procedure since the surgery was not part of a formal clinical trial and the patient was on novel immunosuppressive drugs. Further monitoring and evaluation of the patient’s health and recovery will reveal whether this one-off experiment is a glimpse of what’s to come. Companies like eGenesis and Qihan Biotech see this as a step in the right direction and are moving their xenotransplantation research closer to the clinic.

Thousands of people die every year waiting for an organ transplant. Demand for organs outpace supply. Where precious organs are available, the distance between donor and recipient can create huge hurdles. Xenotransplantation is, therefore, an applauded technological innovation, but the benefits are not without concern.

David Bennett Sr’s heart transplant has renewed debates on the ethics of using animals for organs. Pigs are historically the donors of choice thanks to their human-sized organs, short gestation periods, and the opinion that pigs are less ethically fraught than primates. Some animal activists contest these arguments, arguing that pigs shouldn’t be engineered or used as organ donors.

Instead of xenotransplantation, experts suggest alternatives for society and governments to address organ donation shortages. One long-fought policy change involves switching organ donation systems from “opt-in” to “opt-out.” Some countries, like the USA, give citizens a choice to become organ donors. Others, like the UK, automatically enrol people with the option to “opt-out” of the programme. This simple change can dramatically increase the number of available donors and shorten the long waiting list.

Next-generation artificial organs may one day act as an alternative to human organ donation. Compared to earlier generations, which use mechanical pumps, advances in 3D printing and tissue engineering are propelling the creation of new artificial hearts made of flesh and blood. Even with an emerging class of organs that blur the line between artificial and natural, there will still be patients who may not meet eligibility requirements, leaving a demand for xenotransplantation.