Earlier this year, news broke of the first experimental xenotransplantation: a human patient with heart disease received the heart of a pig that had been genetically modified to avoid rejection. Although initially successful, the experiment ended two months later when the transplant failed, resulting in the patient’s death. At the time, the team did not release any details about what went wrong. But this week saw the release of a research paper that reviews everything that went into preparing for the transplant and the weeks that followed.
Critically, this includes the eventual failure of the transplant, which was triggered by the death of many muscle cells in the transplanted heart. But the reason for this death is unclear and the typical signs of rejection by the immune system were not present. So we’ll have to wait a bit to figure out what’s wrong.
A solid start
Overall, the article paints a picture of organ recipient David Bennett as a patient who was on the verge of death when the transplant took place. He was an obvious candidate for a heart transplant and was only kept alive through the use of a device that helped oxygenate his blood outside of his body. But the patient had what the researchers call “poor adherence to treatment,” leading four different transplant programs to deny him a human heart transplant. At that time, he and his family agreed to participate in the experimental xenotransplantation program.
The pig that served as the heart donor came from a population that was extensively genetically modified to limit the possibility of rejection by the human immune system. The line was also free of a specific virus that inserts into the pig genome (endogenous porcine retrovirus C, or PERV-C) and was bred under conditions that should limit exposure to pathogens. The animal was also screened for viruses before the transplant, and the patient was screened for porcine pathogens afterwards.
After the transplant, the patient’s new heart functioned well, displaying a normal rhythm between 70 and 90 beats per minute. More importantly, more than half of the blood that filled the left ventricle of the transplanted heart was pumped into the circulatory system with each contraction; that was up just 10% in the diseased heart he replaced.
About two weeks after the transplant, Bennett began experiencing abdominal pain and weight loss that eventually caused him to lose over 20 kg (40 lb). He was placed on a feeding tube and an exploratory laparoscopy showed potential signs of infection which was resolving, but no action was deemed necessary. Shortly thereafter, screening revealed possible infection with the porcine version of cytomegalovirus; the human version of this virus causes problems like pneumonia and mononucleosis. This was managed with antiviral treatments.
While weight loss was an obvious concern, five weeks after the transplant there was no indication of rejection and the heart was still functioning.