Xenotransplantation

Xenotransplantation: Animals Organs for Human Transplantation: How Close are We?

The earliest known documentation of xenotransplantation was in the year 1667 when a French doctor by the name of Jean-Baptiste Denys made use of blood collected from farm animals to perform human blood transfusions. This animal-to-human transplantation had some initial success, as Denys’ first patient, a fifteen-year-old boy, survived upon receiving sheep’s blood into his system. Nonetheless, his xenotransplant practices were eventually sanctioned and banned as two subsequent patients of his died.

In the 19th century, different types of xenotransplantation emerged as surgeons began actively exploring the possibility of skin xenografts, making use of rabbits, dogs, and pigeons as donors. There is however no substantial evidence to prove the success of these practices. As with the other instances of interspecific transplantation, the accounts of attempted xenotransplants in recorded history all carry the common hue of failure.

Nonetheless, despite the shortcomings of the past, research has been and still is being done on the feasibility of these practices which could in success, prove to be a saving grace for the human race.

Xenotransplantation, by definition, is any procedure involving the transplantation, implantation, or infusion into a human recipient of either

  1. Live Cells, tissues, or organs from a non-human source or
  2. Human body fluids, cells, tissues, or organs that have had ex-vivo contact with live non-human cells, tissues, or organs.

Organ transplantation between human beings had been a feature of modern medicine since the mid 20th century, with the results being favorable thus far. The shortage of donors available for said transplants has always been a problem, and one increasing in severity. Countless are on waiting lists for organ transplants, in the United States of America, ten patients die every day on these waiting lists. The demand overwhelmingly outweighs the supply. Therefore, one doesn’t have to think too far before coming to terms with the reasoning behind the reconsideration of xenotransplantation as an option.

It should be stated that research on xenotransplantation never ceased, in fact, it in many ways improved over the last two decades. However, judging this research as a success would be quite a stretch. Strides have been made, significantly so no less, but in truth, we are some ways away from what we would consider as a success. Nonetheless, an attempt to identify where exactly we stand as a society in our progress on this subject of study is the purpose of this article. Returning to the 20th century, the bulk of scientific interest in interspecific transplantation was centered on primates. Larger primates happen to share a 98% genetic similarity with humans so it was hypothesized that their organic nature should be to a reasonable extent, compatible with ours.

The first to test this theory out on live patients was Professor Keith Reemtsman from Tulane University, Louisiana. Being one of the leading researchers on the subject at the time, he pioneered the concept and between the years of 1963-1964, Reemtsman carried out 13 chimpanzee-to-human kidney transplantations. However, on par with the documented efforts of his pioneering predecessors, those of Professor Reemtsman were marred with failure as none of the patients lived longer than nine months. Almost all of them died within a fortnight, which maybe could raise some questions as to the reasoning behind his continued attempts, the generalized failure again demonstrates the complexity of the human immune system.

Dr. Thomas Starzl; often referred to as the father of modern transplantation, himself had a notable foray into the field. He made several attempts to successfully transplant livers from chimpanzees into infants, and in one particularly notable case, a heart transplant was carried out. Needless to say, they all failed.

This continued trend of failure led the world to think in a different direction. In the late 1980s, Dr. David Cooper, a pioneering heart transplant surgeon, argued that primates are not the best donors for humans. His most important argument was the size of the organ – the fact is that a monkey’s heart simply is not large enough for the human adult. He then brought up pigs as a potentially more suitable alternative. At inception, Dr. Cooper’s attempts to transplant organs from pigs to humans proved to be unsuccessful. Nonetheless, his with proved to be the backbone of the outstanding research being conducted today.

The outlying issue with the use of porcine parts was the response of the human immune system to the introduction of foreign organs. Dr. Cooper’s laboratory found the triggers of this immuno-response to be a certain sugar found on the surface of the pig cells. Work then began and soon after, the first set of genetically modified pigs, deemed to be workable had surfaced. Biotechnological companies allowed for large investments into “developing” an animal whose organs would be satisfactory for xenotransplantation.

However, just as things seemed to be going near perfectly, researchers were hit with a harsh reality- the existence of an endogenous pig retrovirus virus that has since been termed the Porcine Endogenous Retrovirus (PERV), a virus that if mismanaged, could infect human cells and easily lead to a deadly epidemic. Due to this reason, nearly all biotech companies terminated their research experiments and most laboratories were shut down around 2001.

Unsurprisingly though, probably in turn due to the overly resilient nature of the human species, research on xenotransplantation it’s still a very active area of interest. Due to significant advancements in technological genetics and engineering, additional porcine sugars and key antigens have been identified, and pigs lacking them have been developed.  The group of Professor Muhammad Mohiuddin at the National Heart Lung and Blood Institute inserted two human genes into the pig genome: one that protects cells from an attack by the complement system, and another that prevents harmful coagulation, taking a significant step forward in nullifying this ill effect

Most recently, in August 2017, researchers from the George Church and Luhan Yang lab at Harvard announced quite a breakthrough in their research: using the CRISPR-cas9 system, a cutting-edge gene-editing technique, they succeeded in inactivating 62 PERV genes in pig cells. From these fetal cells they cloned embryos, and out of the 37 piglets born, NONE showed any trace of the PERV virus.

Even greater strides were made in 2018 when surgical trials showed promising signs: hearts transplanted from these genetically engineered pigs into baboons proved to be sustainable throughout the three-month study period. It is noteworthy that the only issue faced in this study was the size difference between the subjects. Baboons, being significantly smaller than pigs cannot ordinarily allocate porcine organs. The baboons had to be filled with a drug called temsirolimus, which prevents the proliferation and growth of cells.

Another development in the ongoing research on xenotransplantation is the potential use of chimeras. Scientists have opened up about the possibility of using human-animal hybrids as nursing grounds for human-compatible organs. While this may or may not be a practical possibility, ethicists have been very actively spoken in their detestation of this idea.

On a final note, speaking again on the ethics of xenotransplants, animal rights, allocation of resources, distributive justice, and the seemingly obvious subject of consent for xenotransplants from individual patients are also met by demands of consent from the general populace, given the potential public health risks.

It is indisputable that the potential benefits are more than considerable and potentially paramount to the survival of our species, in the long run, it should be noted that the use of xenotransplantation could raise some concerns ranging from the obvious biological to the emerging ethical. 

Like every other innovation, xenotransplantation has accounted for mortality and other risks that cannot be sidelined when weighing its efficacy. On a general note nonetheless, as far as the research heads in the right direction, it’s safe to say that the future of biotechnological development is ever so slightly brighter.

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