To be or not to be xenotransplantation?

This article tells about the history of experiments on animal organ transplantation to humans, the current state of research in this field, and also provides arguments for and against the further development of this technology.

Recently, information appeared in the media about a breakthrough in the field of xenotransplantation – a direction that studies the possibility of transplanting functioning organs of one species to representatives of another species. Researchers from the National Institute of Heart, Lung and Blood Diseases of the USA successfully maintained the functioning of the hearts of genetically modified pigs in the abdominal cavity of baboon monkeys for a year.

While for some this statement may seem absurd, if not a nightmare, xenotransplantation is a serious scientific direction, on which well-known scientists from respected research institutions and large private pharmaceutical companies are working.

Moreover, this trend is far from a new trend, and experiments on interspecific blood transfusion were carried out already in the 17th century. However, why transplant animal organs to a living person?

The reason for the relevance of xenotransplantation is extremely clear: due to the acute shortage of donor organs available for transplantation, many patients in need of them die without waiting for their turn.

According to government statistics, an average of 79 organ transplants are performed daily in the United States, while 18 people die daily due to the lack of suitable donor material.

Researchers are trying to solve this problem by developing mechanical devices capable of supporting the functioning of affected organs, but their use is accompanied by an increased risk of infection, thrombosis and bleeding.

Scientists working with stem cells are also actively developing methods for growing organs suitable for transplantation in the laboratory, however, despite regular breakthroughs in this field, today the creation of a fully functional organ outside the body is still very far from reality.

Therefore, experts believe that xenotransplantation is a viable approach that can at least partially solve the problem of the shortage of donor organs.

The eccentric history of xenotransplantationThe earliest known example of the use of animal body parts to replace diseased or defective components of the human body dates back to the 17th century, when Jean Baptiste Denis began to practice the clinical practice of transfusion of animal blood to humans.

It is quite predictable that these procedures did not bring the expected results and xenotransfusion was banned in Denis's homeland, France.

Much later, in the 19th century, an unexpected trend appeared dedicated to xenotransplantation of the skin. Various animals were used as donors, including sheep, rabbits, dogs, cats, rats, chickens and pigeons, but the transplant procedure was classified as "not for the faint of heart".

According to medical records, to ensure the vascularization (formation of capillaries) of the donor skin, a live donor animal was tied to the patient for several days. However, the most commonly used donor, the frog, was usually skinned alive, which was immediately applied to the affected area of the patient's skin.

Despite a number of successful outcomes recorded in history, modern doctors are skeptical about claims that such transplants could bring any benefit to patients.

The first xenotransplantation of a pig's cornea to a human was carried out in 1838. However, after that, researchers for a long time did not take the potential of xenotransplantation seriously. This issue was returned only in the 20th century after the first successes in human organ transplantation.

In 1907, the Nobel Prize-winning surgeon Alexis Carrel, whose experiments on blood vessels made organ transplantation a reality, wrote: "The ideal approach would be to transplant organs to humans from animals that are easy to maintain and operate on, for example, pigs. However, most likely, pig organs will need to be immunized against human blood serum. The future of organ transplantation for therapeutic purposes depends on the possibility of hetero [xeno] transplantation."

These words can be called prophetic, since Carrel accurately describes the direction that xenotransplantology researchers took a century later.

A few years later, French scientist Serge Voronoff (born Sergey Voronov) also predicted the interest of modern science in the use of pancreatic islets of pigs for the treatment of severe forms of type 1 diabetes in humans. However, his other xeno-experiments did not stand up to critical evaluation.

The main scientific interest for Voronov was the restoration of the "taste for life" in older men. He tried to achieve this by transplanting fragments of the seminal glands of chimpanzees or baboons into the seminal glands of his aging patients.

It seems incredible, but this procedure became very popular, and in the 1920s several hundred similar operations were performed in Europe and the USA.

By the 1960s, despite the limited availability of donor material, surgeons in France and the USA began to practice kidney transplantation of dead donors.

At that time, the dialysis procedure had not yet been used in clinical practice and, considering that in the absence of donor kidneys, his patients with kidney failure would inevitably have died, Louisiana surgeon Keith Reemtsma made an unprecedented attempt to transplant animal kidneys to them. As donors, he chose chimpanzees, as the closest relatives of humans from an evolutionary point of view.

Although in 12 out of 13 cases, within 2 months after the procedure, patients developed rejection of the donor organ or an infectious complication, one patient continued to live and work with good health for 9 months, after which he suddenly died from an acute violation of the water-salt balance. The autopsy showed that the kidneys of the chimpanzees had no signs of rejection and functioned normally.

Experiments on xenotransplantation of vital organs to living patients continued until the 1980s, but did not bring long-term success. However, these procedures attracted the attention of the general public (one of the most famous was the unsuccessful transplantation of a baboon heart to a newborn girl in 1983), which led to an increase in organ donation.

At what stage are modern research?Despite the obvious similarities between humans and other primates, pigs are currently considered the most suitable donor for xenotransplantation.

The roads of pigs and humans on the evolutionary path diverged about 80 million years ago, however, genome–wide sequencing showed that the DNA of these two species are very similar, while pig organs are anatomically and physiologically - both in size and function – comparable to human ones.

However, perhaps the greatest advantage of pigs as donors is their availability, in theory providing an almost unlimited number of donor organs. The introduction of pig organ transplantation into clinical practice would simultaneously solve the problem of shortage of donor material.

Adherents of the idea of xenotransplantation also believe that this will improve the results of the procedure. They argue that maintaining good health of pigs, their regular check for infectious diseases and receiving organs from live animals under anesthesia will reduce the likelihood of undesirable side effects, such as the development of insufficiency of transplanted organs or infection of the recipient.

However, there are still serious barriers on the way of xenotransplantation to the clinic.

United Therapeutics, whose specialists began to engage in xenotransplantation research after the daughter of Chief executive Officer Martine Rothblatt was diagnosed with pulmonary hypertension, a disease in which the shortage of donor lungs reaches 90%, said that she had made serious progress in overcoming these barriers.

According to Rotblatt, the company plans to perform the first human pig lung transplant before the end of this decade. According to the company's experts, in order to prevent the rejection of donor lungs by the human body, 12 modifications should be made to the pig genome. Rotblatt assures that there are already animals whose DNA contains 6 of these modifications.

The company's ambitions are not limited to xenotransplantation of lungs and extend to the creation of pig kidneys, liver, heart and retina suitable for human transplantation. However, Rotblatt argues that, apparently, it is the lungs that are the most difficult task.

It should also be noted that the genetically modified piglets whose hearts were transplanted to baboons in the above-mentioned study were provided by United Therapeutics.

Opponents of xenotransplantationHowever, solving research problems is not enough to introduce xenotransplantation into practice.

Despite coordinating each stage of work with ethics committees, Rotblatt, who has a PhD in medical ethics, admits that this will not happen without solving unforeseen regulatory dilemmas and ethical disputes.

Some critics of xenotransplantation believe that instead of developing this direction, more efforts should be made to increase the volume of human organ donation.

In 2004, the Institute for Strategic Studies of Great Britain conducted the first large-scale public opinion poll on potential solutions to the crisis caused by a shortage of donor organs. The obtained data demonstrated the predominance of the negative attitude of the public towards xenotransplantation.

The reaction to the question about the possibility of animal organ transplantation to humans was so hostile that some respondents even demanded to remove it from the list of solutions to the problem. While a number of respondents noted the unethical nature of xenotransplantation, the main reason for the negative attitude was the fear that animal viruses could infect humans and spread in the population.

After the publication of the survey results, a very interesting dispute broke out on the pages of Philosophy Now about xenotransplantation. The opponent of this trend, philosophy professor Laura Purdy, wrote that the dispute over xenotransplantation continues under the slogan "saving lives is our first priority." However, according to her, this means that the lives lost in the future due to the improvement of the xenotransplantation procedure are not taken into account.

She further explained that the resources allocated to healthcare are limited, so it is much more appropriate to use them to carry out simple measures that will save millions of children who die annually from diarrhea, malaria, measles, pneumonia, AIDS and malnutrition, as well as half a million women who die annually during pregnancy and childbirth.

Moreover, she believes that xenotransplantation is only a temporary measure, the need for which will eventually disappear due to future developments (such as partially or completely artificial heart) or public health achievements (for example, prevention of diabetes mellitus). In this context, the large costs that the development and implementation of xenotransplantation will inevitably require seem impractical.

To date, it is unknown whether the public's attitude to xenotransplantation has warmed over the past decade. However, against the background of the development of this research area and an increase in the likelihood of introducing the results of such developments into clinical practice, it is necessary to conduct public surveys that will help avoid ethical problems in the future.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru according to Medical News Today:
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