XENOTRANSPLANTATION 

• Xenotransplantation refers to any medical procedure involving the transplantation, implantation, or infusion of either live cells, tissues, or organs from a nonhuman animal source into a human recipient, or human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs, as defined by the US Food and Drug Administration (FDA). Essentially, it entails utilizing animal cells and organs to treat human illnesses.
• The practice of xenotransplantation dates back to the 1980s when it was first attempted in humans, particularly involving heart transplants. This approach emerged due to the significant disparity between the number of patients in need of transplants and the limited availability of human donor organs.
• With nearly 90,000 individuals awaiting kidney transplants in the United States alone, and over 3,000 deaths occurring annually while on the waiting list, xenotransplantation offers a potential solution to alleviate the shortage of donor organs and save lives.
• Moreover, there's growing evidence, as highlighted by Columbia University’s Department of Surgery, suggesting the effectiveness of xenotransplantation in treating neurodegenerative disorders and diabetes using animal cells and tissues. This underscores its broader therapeutic potential beyond organ transplantation.

3. The Process of Xenotransplantation

Xenotransplantation involves several critical steps to ensure the procedure's success, as explained by experts in the field.

• Before transplantation, the selected animal organ undergoes genetic modifications to minimise the risk of rejection by the human body. This involves employing advanced gene editing technologies like CRISPR-Cas9 to make specific alterations to the organ's genome.
• In the case of Richard "Rick" Slayman's operation, physicians at Harvard Medical School reported making 69 genomic edits to the pig kidney. Using CRISPR-Cas9, they removed pig genes responsible for producing sugars that trigger immune responses in humans. Additionally, human genes were added to enhance the compatibility of the kidney with the human body.
• The actual transplantation process is similar to conventional organ transplants, where the animal organ, in this case, a pig kidney, is sewn into the recipient's body. Following surgery, standard immune-suppressing drugs are administered to prevent rejection.
• Continuous monitoring is crucial after the transplant to evaluate the recipient's immune response to the animal organ. This ongoing assessment helps healthcare professionals make any necessary adjustments to medications and ensure the long-term viability of the transplant.

Pigs have emerged as a preferred source for xenotransplantation due to several key factors

• Pigs exhibit anatomical and physiological characteristics that closely resemble those of humans. This similarity enhances the compatibility and functionality of pig organs when transplanted into human recipients.
• Pigs are extensively bred on farms, providing a readily available and cost-effective source of organs for transplantation. Moreover, the widespread breeding of various pig breeds allows for matching the size of harvested organs with the specific requirements of individual human recipients.
• Pig heart valves have been successfully used in humans for over five decades, demonstrating the compatibility and adaptability of pig organs in transplantation procedures.

Despite the potential benefits of xenotransplantation, several challenges and considerations exist

• There is a concern regarding the potential transmission of infectious agents from pigs to humans during xenotransplantation. This includes both recognized and unrecognized infectious agents, posing a risk to recipients and their close contacts.
• Cross-species transmission of retroviruses from pigs to humans is another significant concern. These viruses may remain latent and manifest as diseases years after infection, highlighting the importance of thorough screening and monitoring protocols.
• To address these challenges, various strategies are being explored. For example, embedding the pig's thymus gland, responsible for educating the immune system, beneath the outer layer of the transplanted organ can help prevent immune responses. Additionally, stringent screening and monitoring protocols are essential to minimize the risk of infectious agent transmission and retrovirus infection.