What happened to the man who received a pig’s heart this year?

A few weeks ago, the scientific world recorded surprising news. For the first time in history, a genetically modified pig heart worked and has allowed a human being to live.

This is David Bennett, a 57-year-old American who did not meet the requirements to receive a human heart transplant, but who had a new opportunity in an experimental procedure that has been investigated for more than three decades. Bennett suffered from ventricular fibrillation, an abnormality that accelerates the heart rate and can be fatal.

Five weeks after the transplant, the medical team monitoring him has not reported any signs of rejection of the new organ, the US magazine The New Yorker reported on February 21. The man still remains at the University of Maryland Medical Center, where the procedure was performed.

According to the World Health Organization, cardiovascular diseases cause the highest number of deaths in the world. In the Americas they represent two million lives a year.

”In the last ten or fifteen years, attempts have been made to develop methods such as ventricular assist devices, which are machines with a motor that replaces cardiac functions. However, its costs are quite high for the health system”, explains Ángel García, head of the Cardiology Unit of the San Ignacio University Hospital.

Transplantation is one of the treatment alternatives in patients with advanced heart failure, in which the patient’s diseased heart is replaced by that of a donor with very similar characteristics. The first such successful procedure was performed 55 years ago in South Africa.

But finding a compatible heart is a complex process. “After the initial studies, the patient enters a waiting list for organs that has specific regulations in each country,” describes García, who is also a specialist in heart failure and heart transplantation.

”There may be between ten and twenty patients on the waiting list for a heart transplant in Colombia”, explains the expert. This would represent a time between one and twelve months.

The Texas Heart Institute estimates that there are 3,000 people in the world waiting for a heart transplant. According to the United States Health Resources and Services Administration, 17 people die daily in that country when they cannot find an organ with biological or anthropometric parameters such as weight, height, blood group or adequate quality.

A historic surgery

That is why, for more than thirty years, scientists have investigated xenotransplantation: the implantation of organs from one species to another, as an option that could save more lives.

“In fact, many of the biological valves that we implant in patients for valve replacement are of bovine origin”, adds Angel Garcia.

Guillermo Rivera, professor of Anatomy at the Pontificia Universidad Javeriana Cali section, affirms that “For two decades, the pig has been used in this type of research due to the high similarities with respect to human structural biological components, particularly in the internal and external form.”

But when transplanting hearts from dogs, monkeys and pigs into humans, the body rejected them and they died within a few days for this reason or from infection. How then was the surgery performed at the University of Maryland possible? The process began with a group of pigs that were raised for several generations in environments with controlled care and a specific diet in order to monitor their growth and that they were suitable for this procedure.

In fact, the heart comes from a genetically modified pig. These modifications have been achieved thanks to the contributions of new genome editing techniques such as CRISPR-Cas9, which allows genes to be inactivated and introduced into gametes and embryonic cells, generating animal organs that are immunologically more likely to be accepted by the human body. body.

This process is not always effective and the offspring may not be born with the expected mutation for a transplant to work, so the project’s researchers continue to monitor the transgenic pigs until after six months, when their organs are similar in size to those of the humans.

For Alejandro Mariño, cardiologist and coordinator of the heart failure and transplant program at the San Ignacio University Hospital, the key was in the genetic engineering used in the research.

”The biggest barrier was immunological. The human immune system rejected the animal organ, so certain genes were removed from the pig’s immune system so that rejection would not occur. This genetic modification alters the immune system of the animal and avoids the hyperacute rejection that had been presenting in previous attempts”, manifest.

The modification made in pigs inactivated a biomolecule that mammals have, and added six human genes to their genome so that they could be compatible. These are concepts developed since the 1997 research that cloned Dolly the sheep.

”It is the first time that a xenotransplantation has been done in the modern era and it works. Thanks to genetic modification, it ends up being a viable graft for the function we want from the transplant”, adds the cardiologist Mariño.

The use of animals to generate organs for humans opens debates on ethical and moral issues in research with animals and their modification at the genetic level. The first is about the destination of certain species for scientific purposes.

the dilemmas

The pigs used are not common, since “they are found in specialized laboratories at universities or in research institutes, called vivariums. This means that they are animals that are born, live and die in controlled and supervised situations”assures the professor of the Javeriana University of Cali Guillermo Rivera.

For certain positions, this type of treatment and use of animals means reaffirming human superiority over animals, a matter of philosophical and political controversy.

“It is an important advance for humanity that we can protect human life, but there is an animal sector that would not agree because for them the human value, in moral terms, is equal to the animal value”, affirms José Edwin Cuéllar, professor at the Institute of Bioethics of the Pontificia Universidad Javeriana.

The philosopher is critical and recognizes that, although it is important to advance in these studies, other aspects must be kept in mind when considering ethics in research. “For a large number of scientists there is no limit because knowledge is the priority and that is why they do many experiments, but the implications in the use of animals cannot lead to the fact that anything can be done. There is a limit, even if we recognize ourselves as morally superior”, Add.

Cuéllar is emphatic that the factors and new information that is being discovered in the process must be taken into account and that research must be constantly reevaluated. Human and animal research ethics committees are very important in this, in which experts must determine the feasibility and methodologies.

For Manuel Góngora, director of the Javeriana Comparative Biology Unit, the social benefit of this project is clear and tangible. However, he is aware that there are considerable ethical implications and that they undoubtedly generate social tension, “but the important thing is to achieve the moral justification that society expects by following the scientific criteria and the ethical framework that regulate research with animals”it states.

For the veterinarian, the scarcity of available organs and the high impact of heart disease justify this type of project, which could become a real option to protect human life and improve its well-being. In addition, he states that these procedures are regulated by international standards that have very demanding welfare and care criteria to minimize the pain or suffering of the animals.

”We, the veterinary doctors, are the most interested in achieving more and more alternative methods. We hope that at some point it will not be necessary to use animals for scientific purposes, but at this time and in this context, they could be saving a significant number of lives.” says Gongora.

From the medical point of view, they also face and open up new dilemmas. Ángel García maintains that the first of them is in the selection of the patient for this type of transplant, because it is not only about the surgery, but also the treatment, the follow-up, the supervision of the subsequent care and the medications that it requires.

Then comes the discussion about what type of treatment to apply: human heart, animal heart, or ventricular assist device. “All patients are already ill, so giving priority to certain conditions or characteristics has ethical dilemmas. In general, the urgency criteria are discussed in a multidisciplinary way to better distribute”it states.

Alejandro Mariño, for his part, points out that another important risk is the possibility of zoonoses, or “Animal-transmitted infections that did not occur before and are now possible. There is a real risk of the development of new diseases and complications that are not known so far”.

All the experts consulted are emphatic that this is a first phase and that although it has responded favorably so far, follow-up should be done in the medium and long term, since it is still at a very early stage.

”Despite the fact that heart transplants emerged more than 50 years ago, from the initial moment it took several decades to be able to standardize the procedure. The investigations will tell what needs to be improved genetically, in the characteristics of transplant management and in the care of transgenic pigs”exposes Marino.

Miguel Martínez Delgadillo, El Tiempo, Colombia/GDA