Type of paper:Â | Term paper |
Categories:Â | Biology Medicine Genetics |
Pages: | 7 |
Wordcount: | 1691 words |
Introduction
Increasing demand for transplantation of organs and the decreasing number of quality deceased human-made available every year have necessitated the need for interspecies organ usage for clinical transplants. Interspecies organ transplantation, also known as xenotransplantation is not a new concept; there have been tonnes of clinical trials and experiments for over three centuries. However, it has not been flawless as there are still many barriers that still need to be overcome for it to be a viable reliable solution. Xenotransplantation has undergone through massive progress in the recent past thanks to cloning, molecular engineering, surgery immunology, better organ preservation, creation of better immunosuppressants and the ability to create genetically modified pigs that can grow organs that are more compatible with humans. (Ekser & Cooper, 2010)
Evolution of Interspecies Organs Transplant
It is vital to highlight the roots or history of the technique and see how it has evolved based on the available literature to understand the cross-species transplantation of organs. There are multiple cases from the 17th century to the 20th centuries, where blood transfusion from non-human species into patients was done to treat various pathological conditions. In the 17th century, a French researcher, Jean Baptiste Denis did blood transfusion from multiple animals to humans leading to mixed reactions from the public and eventual banning of xeno-transfusion in France for years. (Cooper, 2012)
The 19th century saw the popularization of Skin xenotransplantation. Skin grafts from various animal species were transferred to humans or patients with different pathological issues. The skin grafts were obtained from multiple donor species, e.g., sheep rabbits, dogs, cats, etc. but frogs were the most popular. Unfortunately, none of the skin grafts used provided permanent healing. In the 1920s, Serge Voronoff, a Russian scientist, practicing in France conducted several testicular transplants from baboons and chimpanzees to aging men who had lost their urge for coitus. He firmly believed that hormones generated in the testis could reinvigorate his patients. However, the surgery was not only filled with numerous complications but also wasn't as fruitful as expected.
Furthermore, it left patients with serious psychological issues. Throughout the 20th century, multiple trials and experiments on organ transplants in primates were carried out. Reemtsma transplanted kidneys from chimpanzees into over 13 patients between the year 1963 and 1964. One patient survived for nearly nine months before suddenly dying from the electrolyte imbalance. Hardy performed the first heart transplant obtained from a chimp to a human in 1964. Unfortunately, the patient died after two hours. In 1966, the first liver transplant to a human patient from a chimpanzee was done by Starzl. (Cooper, 2012)
Some of the experiments carried over the years has yielded promising result as highlighted in the historical timeline. However, it is crucial to note that most of the interspecies transplants have failed due to either infectious complications or rejections due to reduced availability of immunosuppressive agents. Invention and inception of cloning and genetic engineering technologies, better research and results are being obtained. Genetically modified pigs have shown better correlation with the human species and therefore provide hope for a limitless supply of various tissues, cells, and organs for transplant.
Potential Recipients and Usage of the Organs
Human organ shortage for transplantation (allografts) is a significant barrier in organ transplantation. As the number of patients requiring allotransplantation increases, there is a decreasing amount of viable donated organs. In America alone, 54% of adults have registered to donate their organs, but only a single person out of 3 die in a manner that allows sourcing of viable organs. As of April 2019, over 115,000 people have registered and waiting for organ transplants in the United States alone (OPTN, 2019). In 2015, over 143000 people were on organ transplantation waiting list in the council of Europe member states (EDQM-European Directorate for the quality of medicines. 2017). Currently, there are thousands of patients across the world hopelessly awaiting organ transplants. Majority of these patients will die even before an organ is obtained. According to OPTN, six people are added to the national waiting list per hour, i.e., one person in every 10 minutes. (OPTN, 2019) Meaning, the number will significantly rise in the coming years unless a solution is found. Interspecies organ transplants is an up-and-coming solution to circumvent this problem and provide organs for thousands of patients worldwide. Furthermore, the cells and organs obtained from the various species can also be used to treat multiple life threating diseases such as diabetes or cancer
Potential Organ Donors
From the first clinical trials, non-human primates were used as donors due to their close relation genetically, physically and behavior to humans. Chimps were commonly used and regarded as the best donor because of similar organ sizes to humans and better blood compatibility. However, chimpanzees are endangered species, and therefore a new source has to be obtained. Baboons were sought after as the closest relatives to chimpanzees but were considered impractical donors due to their small organ sizes, poor blood compatibility and long gestation periods. Furthermore, the main risk of using these animals especially primates is the transmission of diseases due to their close similarities with humans. (Taylor & Burlak, 2018). Most of the other animals are considered incompatible with humans' physiology although some are used for experiments, e.g., mice. Currently, pigs are the most viable human organ donors. First, the Risk of interspecies transmission of infectious diseases and retroviruses from pigs is more decreased compared to non-human primates due to vast phylogenetic distance from humans (Dooldeniya & Warrens, 2003). Secondly, pigs are readily available and plentiful. Third, the organs are large enough almost similar to those of humans, and finally, pigs can be genetically modified to overcome the various biological barriers in transplantation. (Taylor & Burlak, 2018).
Barriers
Despite the promising results of interspecies organ transplants over the years, it is crucial to note that there several barriers that hinder progress in the research. The main barriers hindering progress and full realization of xenotransplantation are:
- Medical or biological barriers
- Regulations and guidelines
- Ethical issues
- Animal rights and
- Psychosocial effects.
Medical/Biological Barriers
There are three main biological/medical barriers and include immunological rejection, physiological incompatibilities, and risk of infectious disease transmission. (Pierson et al., 2009)
Immunological Barriers
The main issues with interspecies organ transplants are rejection by the recipient's body. Rejection occurs in several stages. From HAR (Hyperacute rejection), AVR (Acute vascular rejection), cellular rejection and finally chronic rejection. (Pierson et al., 2009)
Physiological Barriers
Most of the clinical trials are done to check for physiological compatibility of the organs from various animal species in humans. The main areas of focus in the research are metabolic functions, hormonal function, coagulation, and general anatomy. Organs from pigs have shown proper functioning in primates but lack compatibility because of significant differences in EPO (Erythropoietin) role in the two species. Some pig to human organ transplants have indicated sound physiological compatibilities such as kidneys and hearts, but full organ liver and lung transplants are still a long way from psychological compatibility (Nguyen, Zwets, Schroeder, Pierson III, & Azimzadeh, 2005). Inflammation and coagulation are the leading causes of physiological failures in humans and primates. (Ramackers et al., 2008)
Infectious Diseases Risks
Interspecies organ donation and transplant poses a substantial public health risk. Many research experiments have shown that porcine endogenous retroviruses do infect the human cells. (Wilson, 2008) This creates a considerable possibility of creating and transmitting new epidemic diseases or virus, e.g., similar to HIV which is believed to have originated from chimpanzees and led to the AIDS Pandemic worldwide. The human immunodeficiency virus is found to have mutated from the Simian immune-deficiency virus in chimps. This is a credible threat which led to the FDA creating stringent regulations and guidelines for drug development and organ transplants, clinical trials and usage from other animal species. (Bloom, 2001) Therefore, any clinical trial involving xenografts must be adequately addressed in terms of its safety concerns to public health.
Regulations and Guidelines
Interspecies transplantation is subject to many regulatory standards due to various medical risks and ethical standards. For any clinical trial to be conducted, they must comply with all the stipulated regulations and rules. Transplants can only be carried out if all the proper authorizations are obtained from regulatory bodies such as IXA (International Xenotransplantation Association), FDA (Food and Drug Administration) and EMEA (European Medicines Agency), Standards and regulations are one of the most significant barriers of process in the field and they vary from country to country. It is essential to note that the main focus of these regulations is to ensure public interest & safety and consider all the ethical issues related to the subject matter including animal rights. (Schuurman, 2015)
Ethical Considerations and Concerns
There are Ethical concerns regarding interspecies organ transplantation. The ethical arguments presented are of a vast and varying range based on their nature and subject. From a public perspective, most people view the use of non-human organs for medical purposes as wrong and unethical. Medics see it as the right thing to do as it will save thousands of human lives in the future. Several people view it as beneficial. Others believe that interspecies organ transplant is a way of biotech companies to extort public money without having their interests at heart and make profits.
On the other hand, terminally ill patients have no choice because they are desperately trying to live. The varying perspectives can be broadly classified into two categories for ease of understanding. That is consequentialists and deontological groups (Manesh, Samani, & Manesh, 2014). The consequentialist group views the interspecies organ donation and transplantation as unacceptable and impractical due to the lack of reliable and valid data or information that can fully warrant its widespread implementation and usage. They claim that transplantation yields inconsistent results on both species and therefore unreliable due to its non- linear nature.
The deontological groups are entirely against the process of interspecies organ usage and claim that the process is unnatural and similar to playing God. From this perspective, interspecies organ usage is seen as unethical regardless of the consequence and effect on both species. This view is mainly expressed by religious entities and affiliated persons who believe that in this time and age, humans have become too arrogant and rebellious trying to replace god and act as creators.
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