Beginning in the 1960s, doctors attempted to transplant kidneys, hearts, and livers from baboons and chimpanzees—man’s closest genetic relatives—into humans. But the organs failed within weeks, if not days, from rejection or infection. These efforts were largely abandoned after “Baby Fae,” an infant with a fatal heart condition, died within a month of receiving a baboon heart transplant in 1984. (Immune System Her translation refused the heart.)
By the 1990s, researchers turned their attention to pigs. Their organs are similar in size to a human’s and take only a few months to grow to a size suitable for donation. Unlike primates, there is little concern about them transmitting HIV-like viruses to patients (although pigs harbor different viruses). And scientists think pig donors will be more accepted by the general public, since they have been raised for agriculture.
But biological differences between pigs and humans make transplantation much more difficult. So the researchers turned to genetic engineering to make pig organs more suitable for recipients—deleting pig genes and adding human genes to prevent immune rejection, blood clotting, and inflammation.
All of the pig organs used in humans this year have had 10 gene edits — although the exact modifications are slightly different. One thing they have in common is the deletion of a gene called Alpha-gal, which is associated with acute rejection, occurs within minutes of pig tissue transplantation. This means that no transplanted organs are immediately rejected. However, different types of rejection can occur weeks or months later, and scientists don’t know which corrections or how many of them will lead to the best results.
Team Maryland has come up with some theories about why Bennett’s heart finally failed. Although it did not show typical signs of rejection, it did show damage to the capillaries—the smallest and most fragile of blood vessels—during the autopsy. This could be evidence of a pattern of immune rejection that the team has never seen before in baboon recipients of pig hearts, Mohiuddin said.
Another possibility is that the patient was infected with a virus found naturally in pigs, and in immunodeficiency caused by anti-rejection drugs, the virus caused heart failure. The scientists looked for endogenous pig retroviruses, integrated into the pig genome. These viruses were undetectable in Bennett’s heart tissue, but another was: porcine cytomegalovirus, or pCMV. Mohiuddin said infection could also explain the capillary damage.
Since then, the Maryland team has developed a test to detect pig virus DNA in very small amounts, which they have used on baboon tissue transplanted with pig hearts. In lab tests, they found evidence of the virus in several animal species, but no correlation was found between infection and how long the transplanted heart lasted.
The third explanation is that an antibody therapy that Bennett was given attacked his heart. The drug, intravenous immunoglobulin, is for people with weakened immune systems, such as transplant patients. But because it was made from a pool of antibodies from thousands of donors, it may contain natural antibodies that may have attacked the cells in the pig’s heart.
