Richard Slayman, a 62-year-old man, received the world’s first pig-to-human kidney transplant on March 16 in the United States. The kidney was from a genetically modified pig who was carrying 69 genomic edits. From what we read, the patient is doing well as of now. Previously, surgeons transplanted two gene-edited pig hearts and several gene-edited pig kidneys into brain-dead human patients so as to evaluate and hone the procedure. Earlier this year, a gene-edited pig liver was transplanted in China — this raised huge expectations that xenotransplantation may finally have come of age.
Organ transplantation, one of the biggest medical breakthroughs of the 20th century — and the subject of research even in the preceding century —has prevented thousands of people from dying of end-stage organ failure. Yet a persistent problem is the huge gap between demand and supply; there are simply not enough organs available for transplantation. As a result, there are several more people on waiting lists, and patients dying whilst waiting for lifesaving organs.
According to estimates from the World Health Organization, two million people globally need organ transplants each year, yet only one in 20 of those individuals get a donor organ. When it comes to India, at least 20 individuals pass away every day while waiting for an organ, and there are over 300,000 patients on the waiting list. In our nation, the waiting list is augmented by one person every 10 minutes.
Radical approaches like xenotransplantation thus, can close the supply and demand gap for many patients. While implanted devices and cell or stem cell therapies are among the other kidney replacement techniques under investigation, xenotransplantation might be the most accessible, as well as the easiest to implement, and even the most economical option.
Furthermore, since animal organs are resistant to some viruses, such as the Epstein-Barr virus and Hepatitis B and C, they could potentially introduce extrinsic genetic material to avoid certain diseases.
Pigs are preferred because they can be raised in a controlled environment, mature very quickly, have large litters and their organs are the same size as human organs.
To facilitate successful transplantation, pigs have been genetically engineered to resist the barriers to transplantation: immunity, inflammation and clotting. This included the deletion of pig antigens like Gal 3, which humans can have a hyperacute rejection. What’s more, CRISPR/Cas9 genome editing devices have enabled the process of gene editing (removal as much as addition) with accuracy, efficiency, and affordability.
Most pigs harbour a Porcine Retrovirus (PERV) that is infectious to humans. This too has been modified by genetic engineering, but recipients require close follow-ups for transmission of these viruses which could be a major public health hazard in the same way that the transfer of influenza virus, coronavirus, and the human immunodeficiency virus (HIV) between species generated strains that led to widespread infections.
Despite its potential, xenotransplantation is not without its challenges and ethical considerations. The possibility of infectious disease transmission and cross-species infection rank first among these difficulties. The potential for a xenograft-carrying microbe to mutate and produce a novel infectious pathogen can not be ruled out.
Then there are other ethical concerns with xenotransplantation that need to be addressed. A carefully constructed ethical code concerning the creation and care of animals that will serve as donors needs to be developed. It also needs to be decided when and under what circumstances should children and infants be considered as recipients of xenografts. Moreover, persons who receive xenografts may be required to participate in long-term follow-up programmes. An equitable way to distribute donor animal organs in a society where thousands of people die while waiting for a transplant will need to be formulated.
Xenotransplantation has the potential to completely transform organ transplantation, notwithstanding the difficulties and ethical issues it raises. Xenotransplantation may open the door to a future in which organ shortages are eliminated and patients have access to life-saving organs when they need them most. It is therefore vital that ethical scrutiny goes hand in hand with research.
Dr (professor) Sandeep Guleria is a senior consultant surgeon specialising in transplantation at the Indraprastha Apollo Hospital in New Delhi
