Is transplanting a pig’s heart ethical?
In Switzerland, in 2021, 1,434 people were waiting to receive an organ, 72 of whom died while waiting. Some people sometimes wait several years before a transplant. If animals like pigs could supply the missing organs, would it be ethical to harvest them? For Leo Bühler, professor of surgery at the Cantonal Hospital and the University of Friborg and specialist in xenotransplantation, the answer is positive. “We eat meat and animals are already used in the clinic, especially for heart vessels and valves.” Another argument in favor of this therapy is that it would reduce international organ trafficking and the exploitation of poor donors, a consequence of the global shortage.
In January, a pig’s heart was transplanted for the first time in a patient with heart disease. He survived two months. The use of organs, tissues or cells of animal origin in humans, or xenotransplantation, began about a hundred years ago with the aim of addressing the shortage of organs available for transplants. Today, this approach has taken a decisive turn. How was this new kind of transplant made possible? Will it soon be common? Analysis with two specialists.
The pig, both close to and different from us
During the research, scientists tested xenografts from organs of different animals, such as baboon or sheep. But the pig is the most suitable donor, as Franz Immer, specialist in cardiac surgery and director of Swisstransplant, explains: “His heart is very similar to ours. It has the same weight, the same size and functions in a similar way. It is therefore technically easy to transplant into humans.”
But once this heart is in place, the question of rejection arises, as for a human heart transplant. Indeed, our immune system recognizes the presence of antigens different from ours on the surface of foreign cells and attacks them immediately to destroy them. To avoid such rejection, recipients are prescribed immunosuppressants. But in the case of an animal organ, the antigens are so different that this treatment is not enough. This is why the pig has been genetically modified to, on the one hand, no longer produce the antigens likely to trigger rejection and, on the other hand, to express human genes which block part of the immune reaction. These modifications are facilitated by the very short generation time of the pig in comparison with other animals closer to us: they reach their sexual maturity in less than a year and give birth to about ten young per litter, while they takes ten years for a monkey to reproduce and give birth to one or two young.
Alongside the risk of rejection of the heart, there is another major risk: that of infection of the recipient by pig viruses. To minimize this, the pigs are reared under sterile conditions for two generations.
A first step towards xenotransplantation
During the research, the modified pig heart was first transplanted into monkeys, which survived for three years. In the human patient transplanted in January, “the heart functioned very well for several weeks and with no signs of rejection,” according to a statement from the University of Maryland Medical Center in the United States. The causes of death are currently unknown, but the patient was not an ideal recipient, as his condition was already critical at the start. For Leo Bühler, professor of surgery at the Cantonal Hospital and at the University of Friborg and specialist in xenotransplantation, “it is nevertheless a major step that has been taken in the field of xenografts. But before this approach becomes clinical routine, the experiment will have to be repeated several times, in highly specialized centres, which will probably take many years.”
Besides the heart, other organs could be transplanted, such as the kidneys. This is the organ in greatest need: more than 70% of people awaiting a transplant are for the kidney. Late last year, a team successfully implanted pig kidneys into a brain-dead patient to test the technique. However, the pig kidney does not secrete erythropoietin (EPO), the hormone responsible for the production of red blood cells. The recipient therefore needs to receive it for life. For more complex organs, transplantation remains unlikely for the moment, according to Franz Immer: “The liver or the pancreas, for example, produce many metabolic reactions specific to humans that those of the pig cannot replace. In the case of the heart, the operation is simpler, we can see it as a pump.
Another major challenge lies in the production of organs from pigs. “The logistics are very complex, because obtaining enough organs would require large breeding centers that meet impeccable sterility standards,” explains Leo Bühler. For the moment, it is not yet possible to guarantee the safety of organs in terms of infection and the risk of their transmission in humans. For the specialist, “it will take at least 5 to 10 years before xenotransplantation becomes clinically concrete. But we have been talking about this deadline for many years,” he said.
To other tracks
Some therapies are now as advanced as whole-organ xenografts. « This is the case with the artificial heart (or ventricular assistance), which is implanted more and more from the age of 60, instead of a heart transplant or while waiting for it », explains Franz Immer, doctor specializing in cardiac surgery and director of Swisstransplant. This small pump placed in the left ventricle collects blood from the lungs to bring it into the aorta. Stem cells and cultured tissues of human origin are also a promising avenue, according to Leo Bühler, professor of surgery at the Cantonal Hospital and at the University of Friborg and specialist in xenotransplantation: « A clinical phase has started with diabetics receiving stem cells modified to produce insulin.” Xenotransplantation research is also supported at the Swiss level, where scientists have worked on the isolation of pig liver and pancreas cells. Once coated in a biogel, they are transfused to treat acute liver failure or diabetes. After trials on mammals, clinical trials are now planned in humans.
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Published in Le Matin Dimanche on 04/17/2022.
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