U.S. researchers transplant pig kidneys into monkeys

: News; Dr. Johanna Walter; Published: 16 October 2023

About alleged breakthroughs and empty promises in xenotransplantation research

Researchers from the USA have transplanted genetically modified pig kidneys into long-tailed macaques. The fact that 3 out of 21 monkeys have survived the procedure for longer than two years was celebrated as a breakthrough and has received extensive coverage in the media. The organization Doctors Against Animal Experiments (DAAE) is appalled that once again numerous animals had to suffer and die, while giving false hope to patients. There have already been countless such "successes" in xenotransplantation, of which, at best, not much was heard of anymore or the death of patients was reported.

In a study published in October in Nature, various genetically modified pig kidneys were transplanted into 21 long-tailed macaques. The kidneys were taken from cloned pigs, whose genetic material was altered at up to 69 positions using the genetic scissors CRISPR-Cas. These modifications intended to prevent organ rejection by removing structures that could be recognized as foreign by the recipient's immune system. Additionally, seven human genes were inserted into some of the kidneys, and viruses integrated in the pigs' genetic material were removed (1).

The monkeys' kidneys were surgically removed and replaced by pig organs. Prior to and after the procedure, the monkeys received a cocktail of various medications aimed at suppressing their immune systems. Within the first month following the transplantation, ten of the monkeys were killed, primarily due to the failure of the transplanted kidneys. A few of the animals that received "humanized" pig kidneys with inserted human genes, survived the transplantation for a longer time. However, only 3 of the monkeys survived longer than 2 years. One of these animals was killed shortly after crossing the 2-year mark due to tissue fluid buildup and kidney failure. "The suffering endured by these animals is immense. The EU Directive on animal testing classify such experiments as 'severe'," notes Dr. Johanna Walter, scientific officer at DAAE.

The goal of the experiments is to make pig organs available for human transplantation to address the shortage of donor organs. The company eGenesis (USA), which carried out the genetic modification of the pig kidneys, anticipates that the published study will significantly advance their endeavors to test the procedure in humans (2).

"Why these animal experiments are being celebrated as a success is completely incomprehensible," Dr. Walter states. "Even in the case of the most 'optimized' kidneys, the first animal had to be killed after just 6 days, and others shortly thereafter. Only 3 of the animals have survived for more than 2 years. The reasons for the significant variation in survival times are entirely unknown. The experimenters themselves suspect that it may be due to the pig kidneys being humanized, rather than being optimized for long-tailed macaques - thereby admitting the lack of transferability of animal experiments," Walter continues.

Once again, only human trials will provide clarity. The outcome of these human experiments is uncertain, apart from the risks of transplant rejection and viral transmission, as humans and primates significantly differ in terms of size, weight, and blood pressure (3). To date, only two patients have received pig organs. In January 2022, a genetically modified pig heart was transplanted into a human in the United States. The patient died two months later, likely as a virus was transferred along with the heart, against which the recipient's immune system, which was suppressed by drugs, could not defend. Therefore, clinical studies in humans, despite prior animal experiments, pose a completely unpredictable risk to patients who may offer themselves for such experiments out of desperation.

Xenotransplantation research has promised the routine replacement of defective organs for years. In 2018, at the University of Munich (LMU), heart surgeon Bruno Reichart announced that xenotransplantation could reach the clinic within 3 years after a baboon survived the transplantation of a similarly genetically modified pig heart for 6 months. The Munich researchers have been working on refining the procedure for 30 years now (4). And, even today, well after the entry into the clinic as anticipated in 2018, there is no significant progress to be seen.

DAAE calls for an end to xenotransplantation research, which entails immense animal suffering and has failed to deliver on its promises for decades. Abusing pigs as genetically manipulatable spare part depots is unacceptable. Xenotransplantation cannot be a solution to the shortage of donor organs. Instead, people’s health should be strengthened through preventive measures, and treatment options should be advanced through innovative, human-oriented state-of-the-art research.

U.S. researchers transplant pig kidneys into monkeys

About alleged breakthroughs and empty promises in xenotransplantation research

References