"A human being with a pig's heart"... Why is organ transplantation from animals the hope of contemporary medicine?

At a distance of about forty kilometers from the German city of Munich, specifically in the middle of the road between it and its international airport, you can notice among the dense trees a somewhat different building, on one side of which is a huge laboratory, where you can see through the windows Outside, people wear white coats and move with great caution and some complex devices. On the other side, you will see a farm with hundreds of pigs.

We are talking here about the Center for Innovative Medical Models (CiMM) in Munich (1) of the Ludwig Maximilian University, which is a unique research environment for generating, characterizing and implementing animal models in medical research. Researchers in this center are particularly interested in generating very special types of pigs, even Their shape is sometimes different from the usual pig, but more important is the organs they contain inside them, and an increasing number of researchers in this field see them as the next hope for medicine.

The story of Mr. David Bennett

David Bennett is a 57-year-old American citizen who has been suffering for years with a serious heart disease that requires a heart replacement, but during the past three months he was bedridden, waiting for death moment after moment, and in At the same time, he did not qualify for a human heart transplant, so he decided to undergo a completely new experimental test of its kind, which is to receive a pig's heart instead of his human heart. "Either I die, or I do this transplant," Bennett(2) says. "I want to live. I know it's a shot in the dark, but it's my last option."

The operation was performed several days ago, during the first half of January 2022, at the American University of Maryland Hospitals, and the US Food and Drug Administration granted emergency authorization to perform this exceptional surgery on New Year's Eve through the policy of "compassionate use" of experimental medical procedures In this case, a pig's heart was the only option available to a patient facing a serious, life-threatening medical condition, but it wasn't just an ordinary pig's heart.

Like the pigs that the Center for Innovative Medical Models in Munich is working on, this pig is genetically modified. In fact, if it were a normal pig's heart, the body would reject it immediately and the patient might die, because the surfaces of pig cells contain sugar molecules that immediately stimulate the human immune system to deal with With it, just as it deals with infection and injuries, and therefore we will be facing a physiological disaster.

But this Mr. Bennett pig received 10 genetic modifications(3) while still in the embryonic stage, before growing into an adult animal. Three of these modifications were sufficient to turn off the genes responsible for the rapid rejection of pig organs by the human body, and then six human genes responsible for the immune acceptance of the pig heart were inserted into the human genome. Finally, it knocks out one extra gene in the pig to prevent overgrowth of pig heart tissue, a major problem noted in previous animal experiments.

Genetic modification (4) is simply a process of cutting and pasting, but within the scope of genes, and genes are the codes of life, imagine that the genetic material, that which is found in every cell in your body, is a huge book with instructions for building millions of things that you inherit from your father and mother Like the color or degree of curl in your hair, the length of your bones, the curvature of your nose, this extends to the instructions for building the tiny proteins in your body's cells. Each of these instructions is called a "gene." If we put new genes in between existing ones, or disable or delete others, then The instructions change and new traits are created within the body, in this case the pig's body. (For more rich details about genetic modification, you can consider a previous report by the author entitled Nobel for Chemistry 2022 .. What if we could control the code of life?).

But things will not stop there. Although Mr. Bennett received a pig's heart fully equipped to be accepted by the human body, he will also receive immunosuppressive drugs that help his body accept the new organ as smoothly as the researchers wish, including a new experimental drug from an American company called "Kenexa Pharmaceutical Products", specifically designed to help with Cases such as those of Mr. Bennet, involving a non-human heart.

The beating heart of a baboon

This is not the first time that attempts have been made to transfer organs from animals to humans. For example, in the sixties of the last century, (5) the great American surgeon Keith Rimitsma conducted 13 medical experiments to transplant a kidney from monkeys baboon to humans. Most of these operations failed and the baboon's kidney was rejected within a few weeks, but one woman lived for nine months.

Most attempts to transplant other organs, especially hearts and lungs, achieved similar degrees of survival in the body of the recipients, and in 1984 the American physician Leonard Bailey transplanted a heart from a baboon into the body of the infant Stephanie Faye Buckler (6), known in the media at the time as "Baby Faye" The infant was born with hypoplastic left heart syndrome, and although she died within 20 days of the operation, she lived longer overall than any previous non-human heart recipient.

On the other hand, animal experiments found similar survival rates, and the main problem was the direct rejection of the transplanted organ in the human body, but with time the survival days of the organ transferred from pigs to baboons improved significantly, especially with the emergence of genetic modification at the beginning Millennium, since that time the transfer member's stay has escalated to 400 days, and it's up to two years in 2020.

Why a pig?

Since the 1990s, scientists have been favoring pigs over other animals such as chimpanzees and baboons as potential organ donors. At present, the domestic pig (Sus scrofa domestica) is the best donor of biological resources for transplantation.

There are multiple reasons (7, 8) that make pigs the best organ donor. Pigs have been well studied over many years in terms of physiological and anatomical aspects. They are also relatively easier to genetically modify compared to other animals. Genetic modification experiments on pigs in particular are numerous. , and established a degree of sobriety in the study of pigs in this respect, which had already allowed previous successful surgeries on smaller scales of organs.

In China, for example(9), researchers transplanted insulin-producing pancreatic cells from genetically modified pigs into diabetic patients. And at Massachusetts General Hospital in the United States of America, researchers announced last October that they had used genetically modified pig skin as a temporary wound cover for a person with severe burns, and it worked as effectively as human skin better than any other animal skin, and pig valves are already used successfully in current heart operations.

Moreover, the organs of pigs are similar in terms of size and anatomical structure to human organs, which facilitates their placement in the human body, and pigs also come with different strains, and are easy to reproduce, and in each “belly” they produce a large number of offspring (such as rabbits), They also reach adulthood in about six months, much faster than primates.

Add to this the fact that millions of pigs are slaughtered annually for human consumption, there can be no ethical objection to the use of pig organs to treat human diseases, unlike other animals whose extinction is feared or ethical objections can arise to their use. In fact, ethical aspects are important in the context of issues such as these, and they are often raised on a global level as soon as a case arises of an organ being passed from an animal to a human.

Pig, Ethics and Religion

For example, Baby Fay's short life and quick death received worldwide attention in the 1980s, and (10) many condemned the idea of ​​killing animals to save ourselves. The procedure for the child was described as a "medical adventure" with very undesirable consequences, and another team said that what happened in the case of this child was an "abhorrent act".

On the other hand, some raise an additional ethical problem, which is the long-term risks of these techniques, and therefore we sacrifice the first donors for this type of surgery, and in fact there are complex legal determinants in this particular context. The case of Mr. Bennett, for example, as he had announced himself a short time ago and as indicated by his medical examinations, was hopeless, and it was expected that he would die at any moment. The same is true for another case that was announced last October and caused a global uproar when a pig's kidney was transferred to a woman. Hospitals of the Langone Center for Organ Transplantation at the American University of New York (11).

The medical condition of this woman was undoubtedly more complicated than that of Mr. Bennett, as she was brain dead and the doctors were preparing to remove her medical devices and announce her death, and she - before entering a coma - had stated that she wanted to donate her organs, and her family agreed to perform the experimental operation for her And indeed, the operation was completed and was announced as a success, as the doctors, led by Robert Montgomery, the surgeon at the same center, followed the lady’s kidney parameters for about 56 hours, and she was completely normal.

Montgomery is one of the world's leading names in transgenic pig organ transplantation, and believes that if human organ transplantation is seen as a fossil fuel, depletable and often problematic, then pork organ transplantation is one aspect of sustainable energy. The other side, as suggested, is a new research scope as well, but has not yet witnessed similar achievements, which is the creation of human organs such as the pancreas in the laboratory, in a manner that is completely genetically compatible with the patient's body, and that will inevitably be an unparalleled revolution in the history of medicine.

Another ethical aspect pertaining to the Islamic world, where Islam forbade eating pork, and a large group of jurists said that everything in pork is forbidden, but despite this, this particular issue may find smooth solutions in cases of life-threatening necessity, for example, the center Al-Azhar International for Electronic Fatwa and Dar Al-Iftaa Al-Masria have announced (12) that “Although the principle in benefiting from the pig or its parts is sanctity, it is permissible to benefit from it and treat with part of its parts, or one of its organs, provided that necessity calls for that, and that there is nothing to support it.” His position is among the pure ones in terms of healing and relieving harm.”

The Livers of Arabs

Since these medical problems are usually very serious, the fatwa in its entirety permits surgeries of this kind absolutely, and it is expected that other similar fatwas will follow from various official authorities in the Islamic world, which I have always dealt with problems similar to the method of paying damage, and it remains for some people to receive these organs until surgeries of this kind become socially familiar.

In fact, issuing legislation related to the transplantation of animal organs into human bodies would be an important solution to major problems facing the Arab world in this particular context, which is one of the lowest regions in the world in terms of organ transplantation for patients on the brink of death. Compare, for example (13), between the rate of Organ transplantation per million individuals in a country such as Libya (0.1 to 2.4) or Egypt (10 to 24.9) at the rate in the United States of America, which reaches more than a hundred cases, and yet we know that almost half of the cases in the United States will not receive organ transplantation. Because of the sharp rise in demand versus supply, let alone the Arab world!

Between 1990-2013, 3,804 liver transplants (14) were performed only in 11 Arab countries, namely Egypt, Saudi Arabia, Tunisia, Algeria, Kuwait, the United Arab Emirates, Qatar, Jordan, Libya, Iraq and Lebanon, in 27 medical centers, with Saudi Arabia being the highest in terms of coverage. On liver transplantation, that's only 25% of what needs to be achieved. In Egypt specifically, this is happening in the midst of the spread of viral hepatitis, which has killed hundreds of thousands of citizens due to cirrhosis, and a good part of them could have been saved through an organ transplant.

The Future of Medicine

As you read this article, researchers from another company called Revivacor(15) are raising pigs that have some genetic similarities to humans on a very neat farm in Virginia, and they call them pigs. In "Jal-Save", they added five human genes to it through gene editing techniques, specifically to their livers, kidneys and hearts, in the hope that they could harvest these organs and use them in transplants and avoid rejection by human bodies. Revavicor is the company that modified Mr. Bennett's pig.

At some point, this seemed like science fiction, but "ReviviCore" is the daughter of the British medical company "BBL" that produced the famous cloned sheep "Dolly", which seemed like science fiction at the time, but it seems that we are now close to achieving it. This extends to everything you might think is far from you, but do you know someone who has a problem with their heart, kidneys or lungs? Do you know a relative or loved one with diabetes? You must know someone, and you may notice their suffering, and you may even notice the deterioration of their condition day after day with the passage of time. The incidence of this disease reaches 25% of people in some of our Arab countries, but these modern technologies tell us that there is still hope.

As of this writing, Mr. Bennett has spent a few days alive with the new pig's heart, the doctors are following his health standards moment by moment, and everyone, with us, hopes that the man will live a normal life for as long as possible.

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Resources

1. Center for Innovative Medical Models (CiMM)
2. University of Maryland School of Medicine Faculty Scientists and Clinicians Perform Historic First Successful Transplant of Porcine Heart into Adult Human with End-Stage Heart Disease
3. Previous Source
4. Nobel Prize for Chemistry 2022... What if we could control the code of life?
5. Xenotransplantation: A Historical Perspective
6. li>
7. Leonard L Bailey: in 1984 he transplanted a baboon heart into a human infant known as “Baby Fae”
8. The potential advantages of transplanting organs from pig to man: A transplant Surgeon's view
9. li>
10. Genetically Modified Pigs as Organ Donors for Xenotransplantation
11. Meet the pigs that could solve the human organ transplant crisis
12. Is it okay to harvest pig kidneys to save human lives?
13. In a First, Surgeons Attached a Pig Kidney to a Human
14. Al-Azhar Fatwa: The ruling on transferring a pig’s kidney to a human being is “haram” except in one case (get to know it)
15. The global database on donation and transplantation
16. Status of Liver Transplantation in the Arab World
17. First GM pigs for allergies. Could xenotransplants be next?