A flying pig, with a kind of superhero cape on its back, was projected for a few seconds on the giant screen in the assembly hall of the Sant Pau Hospital in Barcelona: “It used to be said that xenotransplants would work when pigs fly. Well, pigs already fly,” transplant surgeon Muhammad Mohiuddin (Hyderabad, India, 59 years old) decisively resolved to conclude the scientific conference that he gave a couple of weeks ago at the Barcelona center. This doctor, director of the Cardiac Xenotransplantation program at the University of Maryland (Baltimore, USA), is a pioneer in pig heart transplantation to humans: his team successfully performed the first in the world in 2022 on patient David Bennett and repeated the milestone in 2023 with Lawrence Faucette. The doctors managed to transplant the animal organ in both cases and extend the lives of these men, but for a short time: both died a few weeks after receiving the graft. His story, however, was living proof that it could be done. The technique was feasible: a pig’s heart could beat in a man’s chest.
Xenotransplants—transplants of organs or tissues from animals to people—are positioned as an alternative to alleviate the donation deficit in the world. “In the United States, 150,000 people are waiting for a transplant. Every 80 minutes, someone dies due to lack of an organ,” explained Mohiuddin, who visited Barcelona on May 9 to participate in the scientific conferences for the 40th anniversary of the first heart transplant performed in Spain — it was in Sant Pau, in 1984. —. In Spain, one of the world’s leading countries in donation and transplantation, nearly 6,000 interventions were performed in 2023 and, as of December 31 of last year, 4,794 people were on the waiting list to receive an organ.
Mohiuddin has been dedicated to the study and development of xenotransplantations for more than three decades. He assures that they have learned from the experiences with their respective patients and remembers that they were very sick people, almost hopeless, without further therapeutic alternatives. In a quick interview with EL PAÍS between presentations, the surgeon also guarantees that they will continue trying, despite the technical complexity of this procedure and all the ethical considerations it raises: from the threat of rejection – the animal organs used are genetically modified to avoid an unfavorable immune system response—to the eventual risk of introducing animal viruses into humans that become activated or embedded in DNA, to the open debate on animal rights.
Ask. Are you ready for a third xenoheart transplant?
Answer. Yes, we are trying to find a good patient and we are trying to find ways to improve, based on learning from the two transplants we have performed.
Q. What is the objective of xenotransplantation? An infinite supply of organs?
R. Yes. once this is successful and has consistent long-term survival, it will be able to be offered to many people who cannot have [un trasplante de] human heart Anyone who needs a heart or any other organ—because this isn’t just for the heart—can also use other pig organs. It can be used so that whoever needs it can obtain an organ and not have to wait a long time.
Q. Why do they choose pig organs?
R. The pig is not very close to humans, as are baboon monkeys or chimpanzees. But it takes a long time before a monkey reaches the size of a human and, in addition, there are diseases such as HIV (AIDS), which can be transmitted from the monkeys’ organs or their cells. That’s why we don’t use them. In pigs, now, with our genetic manipulation capabilities, we can modify it quickly [para evitar un rechazo del organismo a este órgano]. And pigs grow very quickly: within a year, they grow to a size that would be suitable for adult humans.
Q. What stage of maturity is this technique in?
R. All the previous work was done in animals and now we have started to do it in humans, but there is some difference that we are identifying. We have to overcome those differences and try to keep the heart for a long period of time. Furthermore, the patients where it is being tested are very, very sick. If we have a patient who is a little better, who is not as sick, the result will be better.
Q. And what is the final objective? Buy time with animal organs until they have a human organ to transplant or is the idea to live forever with these animal organs?
R. When you say for a short period of time, that’s called a transplant bridge. Some organs, such as the liver, can be bridged for a short period of time and then receive another organ. In the heart, if the heart is working well, you can leave it until it fails. But if you find another human heart in the meantime, you can exchange it. But, you know that the transplant is very difficult and every time you take that heart out and put it back in, there are other complications. So it is better, if the heart is good, to leave it until it fails and then put in another pig heart or the human heart, if available.
Q. There may come a day when animal organ transplants coexist normally with human organ transplants. How do you decide that this pig heart goes to this patient and this other human organ goes to another patient?
R. There is already a committee that decides who receives a human organ. The two patients I treated were denied, they could not obtain a human organ. Therefore, they either keep the pig organ or die. One day, when this process becomes common, perhaps the patient will be able to decide if she wants a human organ from an elderly or sick person, or if she wants a new organ from a healthy pig. Everything will be presented to the patient and he can decide.
Q. You transplanted pig hearts into two patients: David Bennett and Lawrence Faucette. And they both died. How is that interpreted in scientific terms?
R. What it means is that we are learning what happens in these patients. All the previous experiments were done on healthy baboons, they did not have any disease, we transplanted them and learned from them. But these patients were very, very sick. Therefore, we are now learning how to change our drug regimen and what additional changes we should make and what not to use in these patients to keep the heart alive for longer periods of time. What we learned from the first patient, we did not do and improved with the second patient. Therefore, it will be a gradual process.
Q. In these two cases, specifically, what went wrong?
R. We think that the antibodies that are present in our human system can attack and kill the organ. This is what we believe has happened.
Q. Are they able to handle potential rejection well? How can you improve in this field?
R. The same thing happened from human to human. At the beginning, when the heart transplant was performed [entre humanos], the heart did not usually survive long. But, then, new drugs appeared that suppress this rejection very well. Therefore, we believe that we will be able to avoid this rejection because there are many drugs that work very well in animals, but are not approved for humans. One day, they will be approved for humans and will be able to suppress rejection very well.
Q. One of the potential risks associated with xenotransplantations is the introduction of new viruses into the human population. The heart transplanted to Bennet had a swine virus. Is there a real risk of this happening?
R. There is no evidence that these viruses can infect humans. They can infect pigs if activated. However, so far there is no evidence that they can infect humans. But our regulatory agencies want us to monitor the patient as long as he lives and continue to monitor not only him, but also his family and anyone he comes into contact with to make sure this virus does not activate and infect humans. . There hasn’t been much work done on humans, but in the slaughterhouse where they slaughter pigs for meat and all that, they get cuts and bruises, they come into contact with blood… There have been studies that have shown that they have never had any viruses of porcine origin.
Q. Another controversy in this field is about animal rights. There are people who denounce or criticize the use of these animals for medical purposes or as a simple tool at the service of humans. What do you think?
R. Yes, there is a concern. Nobody wants to kill more animals. But all the research done so far, all the drugs we use, have been tested in animal models, whether rats, mice or large animal models. And also pigs have been used as food in many countries and are the most widely used meat in the world. In the US alone, 90,000 pigs are killed for food every day. We would be talking about less than a thousand pigs and with each one you can save about seven lives [humanas]with different organs.
Q. What are the big knowledge gaps in this field?
R. Although we knew these patients might not live long, we wanted them to live at least six months because our baboons live nine months or more. That’s why we want to discover the difference between what we learned in the animal model and what we learned in the human model and try to overcome it. Antibodies are one of the things we keep thinking about, that they are not well controlled in sick patients because we cannot give enough of that medicine [para evitar el rechazo] because that drug also generates its own problems.
Q. David Bennett’s pig heart, for example, was supplied by a private company, Revivicor. If private companies enter this field, could altruism in donation and transplants be at risk?
R. Like any medicine, these pig organs will be sold to save lives. And it’s thanks to these companies that we can do it, because research is so expensive that not even the United States government can afford to give us enough money to do it. Although these companies have a motive, because they want to produce these pigs and then sell their organs, they are also trying to save human lives. So, I think this should give these companies the benefit of the doubt, because they are helping us save these lives.
Q. Would you undergo an animal organ transplant if you needed it? A pig’s heart, for example.
R. That’s the question people ask themselves. When you ask a healthy person if they would have a pig transplant, they may say no, but if I reach a stage where I need a heart transplant and I have no other life alternative, if I feel that that animal can save my life, maybe yes.
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