A patient whose failing heart had been replaced with the heart of a genetically altered pig in a landmark surgery at the University of Maryland Medical Centre in Baltimore, United States, died on 8 March 2022, two months after the operation.

The successful transplantation surgery was announced on 10 January 2022, a few days after it was carried out on 57-year-old David Bennett, who was suffering from severe arrhythmia, a life-threatening disorder affecting the rhythm of his heartbeats.

The experimental procedure was done after the US Food and Drug Administration (FDA) granted emergency authorization for it on 31 December 2021. Bennett had been ruled ineligible for a conventional heart transplant or an artificial heart by major transplant centres.

Cross-species transplant

According to the FDA, xenotransplantation is “any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues, or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs”.

Xenotransplantation is seen as an alternative to the clinical transplantation of human organs whose demand around the world exceeds supply by a long distance.

Xenotransplantation involving the heart was first tried in humans in the 1980s. A well known case was that of an American baby, Stephanie Fae Beauclair, better known as Baby Fae, who was born with a congenital heart defect, and who received a baboon heart in 1984.

The surgery was successful, but Baby Fae died within a month of the transplant after the baboon heart was rejected by her body’s immune system. Even so, Baby Fae managed to survive the xenotransplantation for much longer than in earlier experiments.

Xenotransplantation if found compatible in the long run, could help provide an alternative supply of organs to those with life-threatening diseases. The pig’s heart transplanted into Bennett did well initially, and he showed no signs of rejection for several weeks. Bennett spent time with his family, did physical therapy and watched the Super Bowl, The New York Times reported, quoting hospital officials.

It was not immediately clear if his death ultimately occurred due to rejection of the xenotransplanted heart by his body.

Why the heart of a pig?

Pig heart valves have been used for replacing damaged valves in humans for over 50 years now. There are several advantages to using the domesticated or farmed pig (Sus scrofa domestica) as the donor animal for xenotransplantation.

The pig’s anatomical and physiological parameters are similar to that of humans, and the breeding of pigs in farms is widespread and cost-effective. Also, many varieties of pig breeds are farmed, which provides an opportunity for the size of the harvested organs to be matched with the specific needs of the human recipient.

Genetically engineered pig

The molecular incompatibility between pigs and humans can trigger several immune complications after the transplant, which might lead to rejection of the xenograft. To preempt that situation, genetic engineering is used to tweak the genome of the pig so as to ‘disguise’ it, so that the immune system of the human recipient fails to recognise it, and the reactions that lead to xenograft rejection are not triggered.

In the case of Bennett, the donor pig had been put through 10 genetic modifications intended to ‘deactivate’ or knock out four pig genes, and add six human genes. A “GalSafe” pig was used, from which a gene that codes for Alpha-gal (a sugar molecule) was removed. Alpha-gal can elicit a devastating immune response in humans, and GalSafe pigs have been well studied, and are approved by the USFDA for use in pharmacology.

The pig was provided by Revivicor, a regenerative medicine company. On the morning of the surgery, the team removed the pig’s heart and placed it in a special machine to keep the heart preserved until surgery.