Friday, September 29

A man with a pig’s heart: questions and answers about organ transplants from animals to people

These days an unprecedented medical advance has surprised: a 57-year-old man with terminal heart disease received a successful transplant of a genetically modified pig heart on January 7, as announced by the University of Maryland

A long-distance scientific race to turn pigs into organ donors for humans

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The operation lasted eight hours and the patient, David Bennett Sr., of Maryland, was doing well on Monday, according to the surgeons who operated on him. On its Twitter page, the American university He uploaded a photo this Thursday in which you can see the good condition of the patient.

This surgical intervention was the only option available to Bennett and gives hope to hundreds of thousands of people with failing organs waiting for a transplant. We clarify doubts about this historical operation.

What is a xenotransplantation?

The term is used to refer to organ transplants from animals to people. “The idea arose more than 30 years ago as a strategy to alleviate the low rates of organ donation”, comments Lluís Montoliu, a researcher at the National Center for Biotechnology (CNB-CSIC). “This type of intervention applies in particular to the transplantation of organs from genetically modified pigs to non-human primates and humans,” he says.

Beatriz Domínguez-Gil, general director of the National Transplant Organization, assures that “in the past, xenotransplantation was performed on humans that failed due to so-called hyperacute rejection. The genetic modification of animals to ‘humanize’ their organs is what has allowed the qualitative leap that represents the transplant of a pig heart to a patient without available therapeutic options that we have known these days”.

Is the intervention similar to that of a human donor heart transplant?

“Essentially yes, since it is about replacing a damaged human heart with a healthy one from a transgenic pig,” says Montoliu. However, “although very similar, the two organs are not exactly the same and surgeons have had to solve these small anatomical differences to connect the veins, arteries and nerves of the porcine heart in the thorax of the xenotransplanted patient”. Obviously, the biologist points out, “the introduction of a pig’s heart into a human thorax has been a challenge that these surgeons have had to solve”.

For his part, Domínguez-Gil emphasizes that the details of the intervention are still unknown because “all the information we have so far comes from the press and not from the scientific literature.” However, he adds, “the surgery performed is surely similar to that which would be performed for a human heart transplant.”

How can CRISPR technology help make interspecies organ transplantation more viable?

The CNB researcher explains that the pigs used for xenotransplantation are transgenic. “In particular, the one used at the University of Maryland carries up to ten different genetic modifications: four inactivated genes from the porcine genome and six added human genes.”

Montoliu indicates that these genetic modifications can also be carried out with gene-editing CRISPR technology, in particular the specific inactivation of genes. “All these modifications are aimed at preventing, regulating or delaying as much as possible the fulminant rejection and the one that can occur in the medium and long term when placing a non-human organ inside the human body. It is about preventing our immune system from recognizing the pig’s organ as foreign”, he points out.

Regarding the transgenic pig, whose heart was used for the transplant carried out on Bennett, there is still no exact information on the altered genes or the technologies used. So “we don’t know if CRISPR has been used in any of the modifications,” he says.

Is this transplant a first step towards à la carte organs from animals?

This first successful xenotransplantation – as well as the one carried out in September connecting the kidney of a transgenic pig to the blood circulation of a brain-dead woman—represent “a great advance that culminates more than three decades of scientific and technological advances, and analogous experiments carried out transplanting organs from transgenic pigs to primates, such as baboons“explains the biologist.

It is, he says, a step that shows that “it is feasible to use organs from transgenic pigs to replace, at least for a time, damaged human organs. In this way, time could be gained on the waiting lists until there is a compatible human organ”.

However, Montoliu believes that “we are still a long way from à la carte animal organ transplants. These are pioneering experiments that will have to be repeated and analyzed in clinical trials, but we are on the right track.”

The head of the ONT points out that “thanks to the different lines of research that are now open, the future of patients who need to replace a diseased organ with a healthy one is very promising. Xenotransplantation,” she adds, “is closer to becoming into a clinical reality, although there is still a long way to go from a technical, ethical and legal point of view”.

Another option that this expert values ​​as very interesting is the generation of bioartificial organs. “Starting from the recipient’s own cells, it would make it possible to build à la carte organs. Not only in the sense of having the organ, but in that of being able to avoid the use of immunosuppressants in the patient once transplanted,” he stresses.

What do we know about revivicor, the US company that has modified the transplanted heart?

This company, based in Blacksburg (Virginia, USA), “emerged from the dismantling of a previous one, the British PPL Therapeutics, which disappeared in 2003, which was responsible for the creation of Dolly the sheep and for showing the world the technology of cloning in 1997,” says Montoliu.

Precisely, the researcher points out, “it is through cloning techniques that these pigs with multiple genetic modifications continue to be obtained. Therefore, in some way, we owe the success of this first pig-to-human xenotransplantation to the famous Dolly the sheep” . In 2011 Revivicor was in turn bought by United Therapeutics, an American pharmaceutical company.

What ethical problems do xenotranslations pose?

From an ethical point of view, Lluís Montoliu considers that this experimentation is justified, given that “the possible alterations in animal welfare caused to pigs by genetic modifications are amply compensated with the ultimate goal of saving the lives of people who need a new organ to survive.

The biologist explains, “the pig is a common animal that is consumed in enormous quantities. In Spain there are almost as many pigs for consumption, fattening and export as there are inhabitants. For this reason, it does not arouse as much empathy or ethical dilemmas as would occur with the use of non-human primates for the same purpose”. On the other hand, he comments that non-human primates are not as suitable either in size or in ease of breeding and, furthermore, they are animals specially protected by European and national legislation.

For this researcher, “the ethical limits of xenotransplantation are probably beyond the metabolic organs usually involved in these procedures: heart, liver, pancreas, kidney… They would appear – he affirms – if we approached transplanting parts of the central nervous system or of the brain, currently a scientific red line and unacceptable from an ethical point of view”, he concludes.