In the United States alone, over 100 000 people are on the organ transplant waiting list. This overwhelming number of patients cannot be accommodated by the number of organs available for transplant. As a result, 20-35% of patients in need of a transplant die while still on the waiting list.
How can these deaths be prevented? One might say that more people need to sign up for organ donation. While that is true, and 60% of U.S. adults are already signed up for organ donation, several doctors and researchers have begun to research another solution: xenotransplantation.
Xenotransplantation, also known as heterologous transplantation, is the process by which living cells, tissues, or organs, are transplanted into the body of a different species. More specifically, this could be used to transplant animal and human cells, tissues, or organs, amongst each other.
While it may seem modern and futuristic, this therapy has actually been experimented with for many years. The first attempts date back to the early 20th century, with slices of rabbit kidney transplanted into a child suffering from chronic kidney disease. After this, there were also attempts with lambs, pigs, and primates, however none were successful.
Although these trials were innovative discoveries, true progress did not manifest itself until the 1960s, when immunosuppressive drugs were discovered and developed. These drugs are used to treat autoimmune diseases, diseases where the body attacks its own parts, by weakening the immune system, incapacitating it from attacking cells it deems foreign or harmful. Logically, it can also be used to prevent organ rejection after a transplant, as it prevents the body from having the strength to damage the transplanted organ. However, these procedures were yet to be successful.
Xenotransplantation has been in development for almost a century, but does it impact modern medicine?
Recently, there have been two xenotransplants of pig hearts into live human patients.
In January 2022, patient David Bennett Sr. received a genetically modified pig heart. This surgery was conducted at the University of Maryland Medical Center at the hands of some of the best suited people for the task : Dr Muhammad M. Mohiuddin, a professor at University of Maryland School of Medicine (UMSOM) who founded the Cardiac Xenotransplantation Program and is one of the world’s most knowledgeable experts in the field; Dr Bartley P. Griffith, Clinical Director of the Cardiac Xenotransplantation Program at UMSOM; and their team of skillful surgeons, technicians and nurses. After being deemed ineligible for a heart transplant due to having terminal heart disease, the pig heart xenotransplant was Bennett’s only option.
The pig whose heart was used for this procedure had undergone a gene editing procedure to remove certain enzymes that produced sugar antigens, making the pig’s heart less likely to cause organ rejection despite the use of immunosuppressive drugs. The genetic modifications removed and altered certain genes that weren’t compatible with a human body. Therefore, the heart would, in theory, be able to properly resume its function.
Unfortunately, the patient passed away two months after the surgery, due to organ failure. What brought on this sudden heart failure? There are two possible answers.
Firstly, the organ could have been damaged by a drug used to prevent the rejection of the muscle. The effects of this were observed as the heart muscle thickened and stiffened, becoming unable to properly pump blood.
The second possible cause would be a virus found within the heart: porcine cytomegalovirus. This virus is extremely dangerous to newborn and adult pigs, but, under normal circumstances, would not touch humans. However, when the contaminated organ is being directly placed into a human body, it is normal for the body to be under attack, and, not having the antibodies to fight the disease, let the virus harm it. This infection was not detected in the heart until autopsy despite heavy testing of the organ before xenotransplantation.
These two potential causes of death were carefully analyzed by the xenotransplantation and surgical team, so that those mistakes would not be repeated when a future xenotransplant was needed.
This occasion arose in September of 2023, just over a year later.
A new patient, Lawrence Faucette, was in need of a new heart, as he was suffering from end stage heart disease. This procedure occurred in the same way as its predecessor. At the University of Maryland Medical Center, the same team of doctors, led by Dr Bartley P. Griffith and Dr Muhammad M. Mohiuddin, performed the world’s second heart xenotransplant. Faucette was deemed unsuited for a heart transplant due to several health complications, so the xenotransplant was the only option left for him. This pig heart had undergone genetic modifications and was also profused with a special solution of different drugs to hopefully prevent organ rejection.
The surgical team operating on Laurence Faucette.
According to Dr Muhammad M. Mohiuddin, many improvements had been made to the procedure since the previous one. The anti-rejection regimen was modified, the heart was put through many additional screenings to eliminate the possibility of viruses or infections. This time, the procedure would hopefully extend Faucette’s life by more than two months, surpassing the previous trial.
Unfortunately, Faucette passed away in late October, surviving only six weeks, harboring signs of organ rejection. This cause of death was equally likely to have occured with a human heart transplant. Despite these two deaths, Dr Bartley P. Griffith states that “we are still on the precipice of a potentially really important therapy, but it’s yet to prove itself”.
Xenotransplantation could truly be revolutionary to the world of organ transplants, and save millions of lives of those who aren’t in a position to receive a transplant from a human donor. In the future, we can hope to see this therapy evolve into one that could be standard procedure.
To read more about this topic, check out articles on the University of Maryland School of Medicine website, where there is more information about the two procedures. Organ transplant statistics are from the United States Health Resources and Services Administration.
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