Since the 1960s, doctors have attempted to transplant kidneys, hearts and livers from baboons and chimpanzees (humans’ closest genetic relatives) into humans. However, the organ failed within weeks, if not days, due to rejection or infection. These efforts were all but abandoned in 1984 after infant “Baby Faye”, who had a fatal heart condition, died within a month of receiving a baboon heart transplant (her immunity system rejected her heart).
By the 1990s, researchers turned their attention to pigs. Their organs are similar in size to human organs and take only a few months to grow to a size suitable for donation. Unlike primates, there is little concern about transmitting HIV-like viruses to patients (although pigs carry a wide variety of viruses). Scientists also believed that pig donors were generally acceptable because pigs were already bred for agriculture.
However, the biological differences between pigs and humans make transplantation much more difficult. So researchers turned to genetic engineering to make pig organs more suitable for human recipients. Removed pig genes and added human genes to prevent immune rejection, blood clotting and inflammation.
All pig organs used in humans this year had 10 gene edits, but the exact changes were slightly different. What each had in common was the deletion of a gene called . alpha galIt is involved in hyperacute rejection that occurs within minutes of transplanting porcine tissue. This means that the transplanted organ was not immediately rejected. Still, rejections of various kinds can occur weeks or months later, and scientists don’t know which edits, or how many of them, will lead to the best results.
A team from Maryland put forward several theories as to why Bennett’s heart eventually failed. Damage was seen in the capillaries (the smallest and most delicate blood vessels). Mohiuddin says this could be evidence of a type of immune rejection the team has never seen in baboons that received pig hearts.
Another possibility is that the patient was infected with a virus found naturally in pigs, and in an immunocompromised state caused by an anti-rejection drug, the virus caused heart failure. We were looking for an endogenous retrovirus in porcine that integrates into the genome. These viruses were not detected in Bennett’s heart tissue, but another type of virus was porcine cytomegalovirus (pCMV). Infection could also explain the damage to the capillaries, Mohiuddin said.
A team in Maryland then developed a test to detect minute amounts of porcine viral DNA in tissue from baboons transplanted with pig hearts. Laboratory tests found evidence of the virus in several animals, but found no correlation between infection and transplanted heart duration.
A third explanation is that the antibody therapy Bennett received attacked his heart. The drug intravenous immunoglobulin is for people with a weakened immune system, such as transplant patients. However, because it was made from a pool of antibodies from thousands of donors, it may have contained naturally occurring antibodies that could have attacked the cells in the pig’s heart.
