(Image via ihv.org)
Staff Writer: Maya Arruda
Heart disease is notorious in America, being one of the most common causes of death. Lifestyle, unfortunate genetics, and plain bad luck can triple whammy a person into a heart attack.
Many people know someone with heart problems, friends and relatives alike.
Unfortunately, severe heart damage can mean that the only method of recourse for survival is a heart transplant. Patients likely to get a heart attack are put on the transplant list preferentially based on lifestyle, age, and other factors.
However, there aren’t necessarily enough hearts to transplant for everyone who needs one, hence the transplant list. Human hearts don’t exactly grow on trees, and they aren’t like kidneys; everyone only has one heart, and they tend to all be using it.
Consequently, instead of allotransplants (human-to-human transplants), xenotransplants (animal-to-human transplants) look like a more feasible option to save more human lives.
Hearts of similar sizes to humans are used like pigs or primates because they are relatively compatible with human physiology. However, heart xenotransplants are still in the research phase and are not readily available.
And perhaps for good reason.
A patient with terminal heart failure from Maryland, Lawrence Faucette, died at age 58 due to complications with a heart xenotransplant six weeks after the surgery. He underwent an experimental pig xenotransplant on September 20th, 2023, after being deemed ineligible for an allotransplant.
He passed away on October 30th.
Faucette leaves behind his wife, Ann, and his two sons.
He was a Navy veteran and scientist who was much beloved by the people in his life. A complete memorial from his doctors and wife can be found here.
“He knew his time with us was short, and this was his last chance to do for others. He never imagined he would survive as long as he did, or provide as much data to the xenotransplant program. He was a man who was always thinking of others, especially myself and his two sons,” Ann Faucette stated after her husband’s passing.
Faucette was the second-ever person to undergo this xenotransplant procedure. The first, David Bennett Sr., also died over a month after the initial surgery. There were traces of a pig virus in Bennett’s transplanted heart, which may have caused a fatal infection.
Under normal conditions, the immune system should have dealt with the virus; however, transplant recipients are almost always placed on immunosuppressive drugs to prevent transplant rejection (exceptions are for autografts, which come from another part of the patient’s body, or for isografts, where the donor is an identical twin). Xenotransplants absolutely require immunosuppressants to prevent rejection.
But why? Well, it all comes down to a protein called MHC (Major Histocompatibility Complex), also known as HLA (Human Leukocyte Antigen), depending on the paper. This protein designates things as self or nonself (I.e., an invader or threat) so that the immune system attacks the nonself but not the self.
MHC is essential for transplant compatibility among allotransplants. There is a wide variety of MHCs in the human species. More compatible MHCs mean a lower chance of transplant rejection, which means a better outcome for the patient. However, it is challenging to have perfect MHC compatibility between non-related individuals (even within a family is a bit iffy, except in the case of identical twins).
Understandably, humans and animals have different-looking MHC, so human immune cells typically recognize animal cells (or animal organs) as “nonself” and attack them. However, an overly strict immunosuppressant regimen would be too damaging to the patient, so instead of dying of heart failure, they’d instead die of common pneumonia or some other infection.
In an attempt to mitigate some of the need for immunosuppressants, the pig hearts for these xenotransplant experiments have been genetically modified to be less egregious to the human immune system. The researchers behind the experiment have removed some identifying antigens (not MHC, but molecules that evoke an immune response by human cells) and the pig SLA (Swine Leukocyte Antigen, the MHC for pigs). The researchers have also added human proteins to the pig hearts to entice the human immune system to view the pig heart as “self.”
For those interested in the scientific details, the paper about Bennett’s xenotransplant can be found here.
While both Bennett and Faucette have passed, heart xenotransplantation remains a promising research field for human medicine. Both patients of this procedure did not experience rejection until after a month, which is an encouraging sign that the patients avoided hyperacute and some forms of acute transplantation rejection.
With further research and development, xenotransplants could help the millions of Americans on the heart transplant list. Bennett and Faucette will help save lives.