American doctors created history, for the first time in the world, a pig's heart was placed inside a human. Xenografts: are we ready for organ transplants from animals?
Pig Heart Transplant: For the first time in a US hospital, a pig's heart has been implanted inside a human. The patient is named David Bennett and a pig's heart is transplanted in a last-ditch effort to save his life.
Highlights
For the first time in the world, a pig's heart was transplanted to save the life of a human.
In America's Maryland Hospital, doctors transplanted it as a last attempt
The patient is feeling great after 3 days of this amazing surgery
Pig heart being implanted inside patient Bennett at Maryland Hospital
Washington
For the first time in the world, doctors have transplanted a pig's heart as a last-ditch effort to save a human life at a US hospital in Maryland. The hospital said on Monday that the patient who received this pig heart is feeling very well after 3 days of this amazing surgery. Even after this success, it is still too early to say whether it will work or not.
With this operation, doctors have taken a step forward in the long-running effort to transplant animal organs inside humans. Doctors at the Maryland Medical Center said the transplant showed that a genetically modified animal's heart could function in a human's body, without being immediately ruled out. The name of this patient is David Bennett and his age is 57 years.
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Doctors had no other way to save life
Patient David is told that a pig's heart has been implanted in him. His son told that the father knows that there is no guarantee that this experiment will be successful but the doctors had no other way to save his life. Bennett had said a day before this surgery, 'It is either a matter of death or a transplant. I want to stay alive I know it is like shooting an arrow in the dark, but it is my last option.
There is an acute shortage of human organs for transplantation in the world. For this reason, scientists are now trying to use animal parts. Last year alone, 3800 heart transplants were done in the US, which is a record in itself. "If it works, it will allow a steady supply of organs for patients who are sick," says Dr. Mohammad Mohiuddin, a specialist in animal-to-human transplant at the Maryland Center.
Bioethics
Xenografts: are we ready for organ transplants from animals?
The potential of xenotransplantation appears clear, but the transition to clinical practice is far away and there are many questions that scientists and bioethicists will have to answer
In Italy, there are 8,861 patients awaiting transplantation (Source: Data Transplantation System , as of 31/12/2018 - taken from the AIDO website) and in 2018 3,725 organ transplants were performed, carried out by deceased or living donors (Source : National Transplant Center ). In the USA there are 113,346 people waiting for a transplant and 33,177 transplants carried out in 2019 (Data updated to 1/12/2019 - Source: UNOS ). According to these numbers, the need for organs in the world is dramatically high, given that transplantation is a solution for many diseases but there are not enough organs.
Precisely for this reason, xenografts are being studied , i.e. the transplantation of organs and cells from a species other than man.
The history of organ transplants is recent and barely exceeds a century: only in 1902, in fact, a French surgeon developed a technique to join two blood vessels (anastomosis). The research of Alexis Carrel - Nobel Prize for Medicine in 1912 - concerned just experimental surgery and tissue and organ transplantation, and helped to lay the foundations for transplant medicine. The innovation in medicine then allowed the development of new techniques, which led to the first kidney transplant in 1954 in the USA, of the liver in 1963 in the United States and then of the heart in December 1967 in South Africa. However, the results were unsatisfactory and very few patients survived for more than a few days, maximum for a few months (and not always in optimal conditions).The breakthrough in terms of post-transplant survival came with the discovery of cyclosporine , an immunosuppressive drug discovered in the 1970s, capable of blocking the response of the recipient's immune system T lymphocytes and, with them, rejection. To date, it remains a very complex intervention and with possible serious consequences, even if levels of excellence in this field have been reached in Western countries. A little more than 100 years after that Nobel Prize, the techniques in medicine have made great strides and post transplant survival has significantly increased, but the numbers do not add up and perhaps the only hope of solving the problem lies precisely in xenotransplants.
Is it really possible to put a pig's heart in a human being? The answer is yes andthe last case dates back to the 1990s in India, with sadly predictable consequences for the patient and a murder sentence for the doctors involved. Xenotransplants have been part of the history of medicine and research in the field of transplants and, probably, have never completely emerged from it. Already in past centuries, before the discovery of blood groups by Karl Landsteiner (Nobel Prize for Medicine in 1930), animals were used for transfusions to war wounded. The dire consequences led to some countries banning this practice, but doctors and researchers didn't stop there. In the nineteenth century an attempt was made to transplant the skin of other animals onto humans to "cure" wounds; in 1838 the pig's cornea was transplanted; in the 1920s in France a Russian doctor transplanted testicular slices from baboons in patients of a certain age to try to have effects similar to viagra; in the 1960s, 13 people received chimpanzee kidneys and one woman survived for 9 months. The first heart transplant dates back to 1964 and involved the heart of a chimpanzee and an American man in a coma. James Hardy, one of the most famous surgeons of the time and author of the first lung transplant and the first (xenon) heart transplant, managed to make and author of the first lung transplant and the first (xenon) heart transplant, managed to make that heart beat for about an hour and then the patient died. A well-known case in the press is that of The first heart transplant dates back to 1964 and involved the heart of a chimpanzee and an American man in a coma. James Hardy, one of the most famous surgeons of the time and author of the first lung transplant and the first (xenon) heart transplant, managed to make that heart beat for about an hour and then the patient died. A well-known case in the press is that of The first heart transplant dates back to 1964 and involved the heart of a chimpanzee and an American man in a coma. James Hardy, one of the most famous surgeons of the time and author of the first lung transplant and the first (xenon) heart transplant, managed to make that heart beat for about an hour and then the patient died. A well-known case in the press is that ofBaby Fae, a newborn for whom a baboon heart transplant was authorized to try to give her hope, having been born premature and with a severe heart malformation that would have allowed her to live only a few days. The girl survived for 21 days after the operation, the longest period for a xenotransplant, but on an ethical level several controversies arose (see the article "Baby Fae: A beastly business." Published in the Journal of medical ethics , published in 1985). This was allowed because the situation was desperate and because of the lack of transplantable organs suitable for infants.
In recent years, there has been new talk of the possibility of using xenografts as a solution to the lack of human organs. Why this return? First, the technologies available have changed and evolved: CRISPR , for example, could help researchers to modify the animal's genome in order to facilitate the integration process of the organ and reduce any risks. New generation drugs, including immunosuppressive ones, may also help in this regard. Over the years of research on the subject, it has been concluded that the animal that could best respond to human needs is the pig . This is for three main reasons: they are easy to breed and reproduce easily, in a few months they are adult individuals and have organs similar in size to human ones. Pigs can be raised in sterile and controlled environments to avoid contamination by infectious agents and, theoretically, we could have an unlimited supply of organs ready for transplantation. This would reduce the deaths of people who wait in vain for their organ and improve the health of patients, since they could be transplanted as soon as the need arises, without waiting long their turn on the transplant list and reducing the effects on the organism.
The discourse on xenotransplantation does not only foresee 'pros', but there are also 'cons'. The first concerns the immune response:an organ belonging to another species is recognized as foreign and attacked by our defense system , causing a massive response and acute rejection. If we think about it, it is already difficult to manage rejection in human-to-human transplants, let alone making a species leap. Another problem is the presence of silent retroviruses, housed in the pig genome, which could theoretically make the leap of species and trigger infections in humans. Last, but not least, is the greater presence of animal rights movements, much more active now than in the past, which could oppose and limit the applicability of this practice, considered despicable as it involves the killing of other animals (compared to only food purposes) and the creation of transgenic organisms, which could have health problems due to the modifications introduced by man. Furthermore, from an economic and regulatory point of view, the necessary considerations must be made: growing animals in protected environments that comply with all hygiene and sanitary standards, genetically modifying them, controlling and feeding them with suitable feed is expensive and regulatory bodies are still struggling to follow the situation. The same is true for bioethical and legal considerations about the risks associated with a new medical technique. First in 2008 and then in 2011, xenografts have also been a topic of interest for theWorld Health Organization - discussed during the First and Second WHO Global Consultation on Regulatory Requirements for Xenotransplantation Clinical Trials - which aims at international collaboration and coordination for the prevention and surveillance of risks associated with interspecies organ transplants.
Before experimenting on humans, the scientific research process involves testing the technique on non-human primates. Studies of this type have already been done and the results seem promising, but some problems remain. Immunosuppressive therapy has certainly helped carry out this research and the use of new genomic editing techniques will facilitate the process by which the human organism will accept the pig organ. They will be 'humanized' pig organs and one possibility is that, initially, xenografts are used as a 'bridge' to keep the patient alive while waiting for a compatible human organ. The question that remains is: how many genetic modifications will it take to overcome the barrier from one species to another? A facility in Germany, MWM biomodels, started breeding genetically modified pigs with 4 mutations that would make their organs more acceptable to the human body. In 2018, 14 pig hearts were transplanted into 14 baboons and two of the specimens survived for 6 months. The study was published in Nature in December of the same year and, recently, MIT Technology Review told the story of this research in depth.
One of the 'CRISPR dads', George Church, is also interested in xenotransplantation. The s tartup eGenesis , founded in 2015 and managed together with its partner Luhan Yang, aims to " create a world where there is no lack of transplantable organs". Unlike the German researchers, who support the theory according to which the final effect is more controllable with fewer changes at the level of the genome, in this case the hypothesized mutations are in greater number. Last November, the news of a loan of 100 million dollars from Fresenius Medical Care Ventures (FMCV), with the participation of other investors (see the press release ).
These two realities are not the only ones doing research on xenotransplantation, even if there are not many dedicated centers, and the investments in the sector underline the global interest in continuing studies in this area. It is a revolutionary field, which has found a possible window of applicability thanks to the introduction of new research tools, including CRISPR. The potential is evident, but today there are even more doubts than certainties.
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