Just a few days after the operation, the 57-year-old patient was doing well, given the circumstances. In January, David Bennett of Hagerstown, Maryland, became the first human to receive a heart from a genetically modified pig.
This was a breakthrough for transplantation medicine, which is also expected to remedy the notorious shortage of donor organs. Organs from specially bred animals could become a substitute for organs from human donors. However, it now turns out that the intervention in Baltimore was only a partial success.
According to the doctors from the University of Maryland, after 20 days a virus was detected in the patient, which came from the donor animal and was transmitted to his organism via the heart. The treating physicians gave the patient antiviral agents to prevent the virus from multiplying. However, his condition worsened and he died two months after the procedure.
It is still unclear to what extent the virus transmission contributed to the death of the patient. “One must not forget that the patient was already very ill before the transplantation,” says Joachim Denner, head of the working group on virus safety in xenotransplantation at the Institute for Virology at Freie Universität Berlin. However, it is striking that the patient developed inflammatory reactions and other symptoms that were also observed in animal experiments with baboons that had received an infected pig heart.
The virus transmitted into the patient with the pig heart was a porcine cytomegalovirus (PCMV). However, this designation is misleading, says Denner. Human cytomegalovirus, which infects humans, is known to cause direct tissue destruction in various organ systems when transmitted with organ transplantation.
However, the animal, “porcine” cytomegalovirus is only distantly related to the human. In fact, it is a roseolovirus that is more closely related to human herpesviruses, which almost everyone is infected with.
Animal experiments have already shown that the infection significantly reduces the survival time of the transplant. “While positive pig hearts did not survive 30 days in baboons, negative donor hearts managed to reach a record of 182 and 195 days,” reports Denner about the work of his team at the Robert Koch Institute in cooperation with researchers from the DFG-funded Transregio- Collaborative Research Center “Xenotransplantation in Germany”.
How the virus works is still unclear. The scientists assume that the virus acts directly on the immune system and cells of the blood vessels and triggers multi-organ failure.
So far there is no evidence of a direct infection of baboon cells or human tissue. “However, it cannot be ruled out that the virus will adapt to the new host, as has also been described for other herpes viruses,” says Denner.
However, Konrad Fischer, head of the Xenotransplantation Section at the Technical University of Munich, considers the risk of new viruses being generated by xenotransplantations that can infect humans to be extremely low: “Although people have been in intensive contact with pigs or pork products on a daily basis for centuries, it was possible no transmission between pigs and humans has been shown to date.”
The donor pig from the Revivicor company had been tested for the virus several times with nasal swabs. The negative results of the tests could have been due to the fact that the pig did not have an acute viral infection but had been infected before. “With such a latent infection, the virus remains below the molecular detection limit,” says Fischer. For future transplants, the virus-free donor pigs must be guaranteed.
Because after the transplantation, in humans, the virus was able to multiply in the pig’s heart because it was no longer suppressed by the pig’s immune system.
“The transmission could have been prevented if the detection strategies available in Germany had been used,” says Denner. However, this apparently did not happen.
The patient could then possibly have lived longer because the transplanted heart was not damaged by an immunological rejection by the human organism. “The genetic modifications intended to prevent this have proven their worth,” says Denner, referring to the two months that it extended the patient’s life.