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Health and Disease

Xenotransplantation: Using Animal Organs to Relieve The Human Organ Crisis

The organ crisis is an ever-prominent issue as globally, the demand for healthy and well-functioning organs significantly exceeds the available supply. Xenotransplantation is a medical procedure whereby living cells, tissues or organs are transplanted from one species to another: a potential solution for the human organ crisis.

By Swetha Babu

Published 2:35 EST, Sat November 20th, 2021

Abstract

The organ crisis is an ever-prominent issue as globally, the demand for healthy and well-functioning organs significantly exceeds the available supply. Xenotransplantation is a medical procedure whereby living cells, tissues or organs are transplanted from one species to another: a potential solution for the human organ crisis.

Introduction

In the United States of America alone, ten patients die each day while on the waiting list to receive life saving vital organ transplants.

Xenotransplantation can alleviate this issue, while also providing greater access of transplant organs to ethnic minorities and limiting rejection in grafts. The benefits and risks of this procedure will be evaluated to determine whether xenotransplantation is a potential solution to human organ shortages.

Potential for Xenotransplantation

 Organ Shortages 

Today, organ transplantation is mainly undertaken to treat severe failure of vital organs such as the heart, lungs, liver and kidneys. Population aging and increasing sedentary lifestyles will result in an increase of the prevalence of chronic diseases (such as Type 2 Diabetes Mellitus and Coronary Heart Disease) and, consequently, the demand for transplantation. The strain on transplant organ supplies will encourage advances in biomedical breakthroughs, particularly in diagnostics and genomics, to reduce the occurrence of diseases progressing to life-threatening stages where only organ transplantation is viable. However, currently, xenotransplantation is one of the most readily available options to lessen the organ transplant crisis.

Xenografts: Reducing Risk of Rejection

Xenotransplantation not only enables organ transplantation but also the transplantation of tissue and cells (known as xenografts). Various tissues such as animal bone, skin, and foetal neural tissues for xenotransplantation have been suggested to be viable. Animal-to-human transplantation of tissues is certainly less dangerous than organ xenotransplantation as the animal tissues do not have major blood supplies hence the immune response is less vigorous, and the surgical procedure is less risky. Meaning, less damage to the patient is expected due to the lower risk of rejection and infection.

Image 1

A common example of animal tissue xenotransplantation is biological heart valves. These valves are used since unlike mechanical valves, they are not associated with a higher risk of blood clots, so the intake of blood thinners is not required. Porcine (pig) valves, which are an example of successful xenografts in modern medicine, are frequently used to replace aortic and mitral valves in the heart to treat cardiac valve conditions such as valvular stenosis.

The benefit to Patients of Ethnic Minorities 

In addition, xenotransplantation could be hugely beneficial for patients of ethnic minorities, where locating a suitable organ match is difficult. To reduce the risk of rejection, donors and recipients are ‘matched’ – it is vital for the donor and the recipient to have a matching blood group and antigen tissues type which is generally difficult to coordinate with an ethnic minority group.

In 2017, figures revealed that 21 percent of people in the UK who died on the organ transplant waiting list were from a black, Asian, or ethnic minority background compared with 15 percent a decade ago. This problem is then heightened due to the fact that such ethnic minorities constitute a significantly larger proportion of the organ donation waitlist: patients of ethnic minorities are three to four times more likely to develop end-stage renal failure and therefore require a kidney transplant. The huge stress on the supply of organs for ethnic minority patients is clearly evident here, and xenotransplantation has the potential to curb this issue greatly.

Ethical Concerns Against The Procedure

Animal Mistreatment

Animal mistreatment and disobedience to animal rights is one of the most significant ethical concerns associated with xenotransplantation, and it is argued that xenotransplantation is a violation of nature to exploit animals for their organs.

The welfare of animals is of great concern as these animals will be subject to trials and experiments before xenotransplantation becomes an available medical procedure. In addition, since there is the possibility of virus transference from animal to human, these animals are raised with special diets and in supervised environments specified for their growth. This has resulted in ethical criticism, as keeping animals imprisoned in an area that is not similar to its natural habitat with synthetic food diets and without other animal interaction does not enable the animals to live naturally.

Xenotransplantation benefits humankind by potentially saving lives and elongating life expectancies to the detriment of animals.

Religious Concerns

From a religious perspective, a fundamental value is to protect and preserve human life.

Xenotransplantation could be difficult in some religious cultures, such as Judaism and Islam, as swine is prohibited to be consumed, and to receive an organ for transplant from this animal could be considered sinful, disobeying their religious ideologies. Hence, locating another appropriate animal species’ organs for transplantation into humans. However, according to some perspectives of Christianity, Judaism, and Islam, there are not any specific religious fundamental binding reasons which prohibit xenotransplantation to treat grave and life-threatening organ insufficiencies.

If a patient refuses xenotransplanted organs on religious or cultural grounds and still requires an organ to treat their condition, they may need to be prioritized for allotransplantation (human to human transplants), stimulating another ethical dilemma. In the event that xenotransplantation is a reality, the allocation of human and animal organs would have to be thoroughly evaluated, ensuring that allocation is based on clinical need and that the maximum number of people continue to receive transplant organs. 

Scientific Concerns Against The Procedure

Physiological Differences in Organs 

Size and longevity are two main issues regarding animal organs for xenotransplantation. For example, a pig heart or kidney, when of suitable size for donation, may still have the potential for rapid growth, and the rate of growth of animal organs compared to the growth of human organs is most likely to be significantly different. The differences in organ size will limit the range of potential recipients of xenotransplants. Furthermore, the natural lifestyle is roughly 15 years, and aging in xenotransplanted organs is unknown.

Introduction of Unknown Infections

Xenozoonosis is the transmission of infectious agents between species via xenotransplants and xenografts. Animal to human transmission of pathogens can be extremely rare but past occurrences include avian influenza.

The main reason for the increased likelihood of disease transmission in xenotransplantation is that the implantation of foreign tissues into the human body breaches the physical barriers that usually prevent the transmission of disease. This potentially leaves the recipient of the xenotransplant exposed to a myriad of unknown pathogens which will most likely leave the recipient severely immunosuppressed 

Impact on Psychological Well Being

It is possible for the transgenic animal organ transplantation into the human recipient to cause major psychological and personality issues for the recipient. In 2010, a study revealed that individuals can form certain perceptions about their physical shape and their identity, as they struggle with the acceptance of an animal organ transplant, providing controversies for both the patients and society.

Hyperacute Rejection

Hyperacute rejection occurs because the human antibodies in the blood recognize the foreign antigens on the cells of the xenograft/xenotransplant, which are cells of pigs and all other distantly related species, triggering a rapid immune response. These antibodies bind to the cells lining the blood vessels of the organs as blood flows through the animal tissues, which activates the complement system, attacking the xenograft/xenotransplant. White blood cells are also activated by the complement proteins, and within a few minutes, the animal tissues are reduced to a black, swollen mass: the xenograft/xenotransplant has been rejected.

Image 2
Example of hyperacute rejection after renal transplantation: Kidney is no longer able to function as tissues are destroyed.

Although hyperacute rejection can occur in allotransplantation, it is significantly more likely to occur in xenotransplant recipients as the tissues originate from an individual of a different species, resulting in notably different antigens on its cells’ surface. Hyperacute rejection is probably the most difficult scientific concern against xenotransplantation, however, many promising methods to tackle this issue have arisen. One method includes the genetic modification of pigs (transgenic pigs), where, when an organ of the modified pig is transplanted in a human, the human complement regulatory proteins on the cells of the pig organ to inhibit the activation of complement, inhibiting hyperacute rejection.

Application to Fundamentals of Medical Ethics

Autonomy

It is clear that the nature of informed consent is the permission of the patient about the procedure after receiving thorough information about the side effects, and in return, the patient will be safe from treatments that are incompatible with their beliefs or unwanted. Informed consent is infinitesimally significant when regarding medical procedures, particularly ethically and medically controversial procedures such as xenotransplantation.

Beneficence

With future scientific breakthroughs to reduce the risk of rejection and to alter the rate of aging of the tissues, xenotransplantation can become commercially available like allotransplantation, as the risk of further disease to the recipient will be much lower. However, in this age, xenotransplantation of organs remains extremely difficult as more harm to the patient will be done, even if the organ does not remain in the patient’s body on a long-term basis but just to elongate the patient’s life expectancy while they wait for a human transplant organ. 

Non-Maleficence

Currently, the risks associated with xenotransplantation potentially outweigh the benefits, mainly due to the lack of scientific uncertainty of whether the transplanted organ can function as desired in the recipient’s body. 

Justice

The physical risks of xenotransplantation can be life-threatening, hence,  the recipient should be under close follow-up for an indefinite period of time, which can affect many aspects of human life, including sexual relationships and nutrition. In addition, recipients may have compromised immune systems and an increased risk of contracting infections, resulting in complete isolation and quarantine from others. This situation is undoubtedly against the most basic human rights – freedom and the establishment of relationships with others.

Conclusion

Several solutions against medical issues concerning xenotransplantation have arisen in recent years, including genetic modification and using transgenic pigs. However, an abundance of research and funding for clinical trials is still required to ensure that the procedure is well understood for the safety of potential recipients.  

But currently, in the face of difficulties, such as the unmet balance between organ demand and supply, xenotransplantation may be an attractive option shortly as ethical concerns around anthropocentric views and animal mistreatment still remain. But, if society can accept the ethical obligations associated with xenotransplantation, this procedure undoubtedly has the potential to develop into a legitimate solution to organ shortages.

Swetha Babu, Youth Medical Journal 2021

References

US Food and Drug Administration. (2021, Mar 3.) “Xenotransplantation” https://www.fda.gov/vaccines-blood-biologics/xenotransplantation

Cascalho, M., & Platt, J. L. (2008). “Challenges and potentials of xenotransplantation” Clinical Immunology, 1215–1222. https://doi.org/10.1016/B978-0-323-04404-2.10081-8

Nuffield Council on Bioethics. (1996) “Animal-to-Human Transplants. The ethics of xenotransplantation” 5-6. https://www.who.int/ethics/en/ETH_Nuffiled_xenotransplantation.pdf

Morgan, M., Kenten, C., Deedat, S., Farsides, B., Newton, T., Randhawa, G., Sims, J., & Sque, M. (2016). “Increasing the acceptability and rates of organ donation among minority ethnic groups: a programme of observational and evaluative research on Donation, Transplantation and Ethnicity (DonaTE)” NIHR Journals Library.

NHS Blood and Transplant. Organ Donation. (2018, Jul 18.) “Government campaign will focus on urgent shortage of black, Asian and minority ethnic organ donors” https://www.organdonation.nhs.uk/get-involved/news/government-campaign-focus-on-bame-organ-shortage/

Behnam Manesh, S., Omani Samani, R., & Behnam Manesh, S. (2014). “Ethical issues of transplanting organs from transgenic animals into human beings” Cell journal, 16(3), 353–360.

Sautermeister, J., Mathieu, R., & Bogner, V. (2015). “Xenotransplantation-theological-ethical considerations in an interdisciplinary symposium” Xenotransplantation, 22(3), 174–182. https://doi.org/10.1111/xen.12163

Dooldeniya, M. D., & Warrens, A. N. (2003). “Xenotransplantation: where are we today?” Journal of the Royal Society of Medicine, 96(3), 111–117. https://doi.org/10.1258/jrsm.96.3.111

George J. F. (2006). Xenotransplantation: an ethical dilemma. Current opinion in cardiology, 21(2), 138–141. https://doi.org/10.1097/01.hco.0000203183.81534.f9

Image 1 – https://images.theconversation.com/files/196741/original/file-20171128-28856-5zra8q.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=668&h=324&fit=crop

Image 2 – https://static.cambridge.org/binary/version/id/urn:cambridge.org:id:binary:20181009125204364-0075:9781107281981:61398fig16_3.png?pub-status=live

By Swetha Babu

Swetha Babu is a student at Wycombe High School in Buckinghamshire, UK. She is an aspiring medic with particular interests in rheumatology and neurology.

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