Xenotransplantation as a Technology

Xenotransplantation could be used to treat severe burns, dealing with the issue of closure and coverage, with the best source currently being fresh cadaver allografts, of which there is a great shortage (Ge, et al., 2010). One promising breakthrough has been using CTLA4Ig (cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin) genetically modified pig skin as a dressing for wounds using Ad5F35 as a viral carrier for delivery (Ge, et al., 2010). However, acute immune rejection means that survival of this skin is always less than 14 days (not long enough to meet needs); therefore, current methods such as autologous split-thickness skin grafts (dermis and epidermis skin layers taken from one part of a patient and transplanted over the burn), cultured epidermal sheets, artificial materials, and cultured cell matrices are preferable (Ge, et al., 2010).

Livers have been engineered for xenotransplant which can produce antibodies against the host’s immune cells, this “gelatinous dewdrop” protects the pancreatic islet cells from the immune system of the host (Reardon, 2015). This is called Diabecell, and is in late-stage clinical trials, with patients surviving 9 years without signs of rejection or infection (Reardon, 2015). Pancreatic islet cells on their own are very promising, being much easier to transplant than solid organs (González, 2012). This could treat diabetes without the need of immunosuppression (María Jorqui Azofra, 2012). Although more life-threatening in the event of failure (15% of heart transplant patients die within one month of surgery (Strachan, 2015)), heart xenotransplants have proven to be more successful than other organs. One baboon received a genetically modified pig heart and survived for 2.5 years (Reardon, 2015); in this case, the α-gal-free heart transplanted by surgeon Muhammad Mohiuddin was not replacing the heart of the baboon itself (Reardon, 2015).

Kidney transplants seem more promising (Reardon, 2015); with an average wait time of 3 years for kidneys, the demand is high (Strachan, 2015). The only alternative is the intrusive and intense treatment that is dialysis; this takes time out of your life, restricts consumption of fluids, and increases risk of heart attack or stroke (Strachan, 2015). Kidney xenotransplants have been relatively successful, with a transplanted kidney functioning in a baboon for 4 months (Reardon, 2015). When I spoke to leading xenotransplant researcher, Dr. David Cooper, he told me, “I believe the first patients to participate in a clinical trial will be those awaiting a kidney transplant. If the trial fails, the pig kidney can be removed, and the patient can go back on to dialysis (if this is still possible).” (Cooper, 2018). This shows that a failure of a kidney xenotransplant wouldn’t always be fatal, making it more suitable for clinical trials.

There are a multitude of organs and tissues hoped to be used for xenotransplantation. The cornea, for example, has already been approved for marketing in China as of April 2015 (Reardon, 2015). The lung is another organ in great demand to which xenotransplantation may hold the solution; however, lung’s large network of blood vessels have proven them “extremely difficult to transplant”, increasing the chance of donor and host blood contact, which increases the risk of rejection (Reardon, 2015). One factory farm has been designed to produce 1,000 pig lungs per year (Mountain, 2015), this could help alleviate the shortage which resulted in 56 deaths in the UK in 2014 alone (Strachan, 2015). Lungs are often unsuitable for transplant (23% not offered), with half of those suffering cystic fibrosis (a genetic condition which affects the functioning of the lungs) needing a lung transplant as adults, the shortage means that 1/3 of these individuals will die before this transplant can happen (Strachan, 2015). Lung xenotransplants are the most difficult organ to transplant, requiring the modification of 12 genes to make it suitable; as of 2014, United Therapeutics had successfully removed 6 of these genes (McNamee, 2014). The source of these organs would most likely be domestic pigs, Sus scrofa domestica (Magdalena Hryhorowicz, 2017).

Pigs would be more suitable for a number of reasons, mainly that pigs have organs of a similar size and function to human organs (Griffin, 2017). Although they are not the perfect genetic match, primates, which are the alternative (better genetic match), have organs that are too small and therefore not suitable donors for xenotransplantation (Girasole, 2014). Pig-breeding poses fewer logistical and ethical issues as they mature quickly, produce large litters, and can be bred to a high standard in sterile conditions (Werner, n.d.); this makes the use of pigs more cost-effective (Magdalena Hryhorowicz, 2017). There is a complication of using pigs, since they have a much shorter gestation period than humans (1/3 that of humans), meaning human cells would have to be inserted in correspondence to the developmental stage of the pig foetus (Knapton, 2017); attempts at this have been successful, with the human cell being allowed to develop for 3-4 weeks (Knapton, 2017). In addition to all of this, the variety in pig breeds means an organ could be matched to a specific patient (Magdalena Hryhorowicz, 2017), reducing the risk of rejection.

In this essay, I will explore xenotransplantation as a technology, looking at its flaws, ethical issues, and any alternatives that may be used instead of or alongside this prominent technology. Experiments continued into the 1980s; there were some ‘successes’, such as a 9-month survival of a chimpanzee kidney into a human (the other 12 of 13 patients died within 2 months) under surgeon Keith Reemtsma in 1964 (Heggie, 2016). The technology gained publicity in 1983 when a baby (Baby Fae) died after a failed attempt at a baboon heart transplant (McNamee, 2014). It was the fear of rejection and of PERVs (something I will discuss later), which halted the technology completely by the late 1990s. Xenotransplantation may seem like something from fiction (such as HG Wells’ classic novel, The Island of Dr Moreau), but has been attempted since the 17th Century (Heggie, 2016), with heart valve transplants being used right now (Griffin, 2017).

Ian McConnell, emeritus professor of veterinary science at Cambridge University said that, “there are several medical procedures using pig tissues such as heart valves in cardiac surgery, insulin producing pancreatic cells to correct diabetes in man and corneal transplants which have been used safely in man for many years”; showing that xenotransplantation is a very current technology. For larger organs (such as kidneys and hearts), new problems arise; attempts at solid organ transplants from primates into humans in the 1960s resulted in little success, with organs being rejected by the human immune system (Reardon, 2015). As early as 1845, surgeons like Dr. Samuel Bigger, were attempting to transplant corneas between species to cure blindness (Heggie, 2016); very few of these were successful.

By 1885, there had been 5 attempts of whole organ transplants into humans; 4 using dog eyes were unsuccessful, but in Boston there was a report of a successful transplant using the eye of a rabbit (Heggie, 2016). However, there is a possible solution: xenotransplantation. Defined by the United States Public Health Service as: “any procedure that involves the transplantation, implantation, or infusion into a human recipient of live cells, tissues, or organs from a nonhuman animal source or human body fluids, cells, tissues, or organs that have had ex vivo contact with live nonhuman animal cells, tissues, or organs.”(Magdalena C. Kimsa, 2014), xenotransplantation, combined with other strategies to increase the number of donors (such as an opt-out system), could potentially save thousands of lives. This is not just an issue limited to the UK. In the US, there are over 120,000 people waiting for an organ transplant, with someone being added every 10 minutes (McNamee, 2014). Tragically, the lack of donors means around 20 people die waiting for an organ they desperately need every day in the USA (McNamee, 2014).

Life on the waiting list is extremely difficult, both physically and emotionally. In the UK, the average wait time for a kidney for adults is 1,022 days (Transplant, 2015), an extremely long time to wait. Waiting for the phone call saying an organ is available can put your entire life on hold, restricting what you do and how you interact with those around you (Strachan, 2015). One patient waiting for a lung transplant said, “I can’t plan anything. All I’m doing is waiting on this phone call” (Strachan, 2015); this epitomises life on the UK waiting list, an experience shared by about 10,000 people in the UK right now (Strachan, 2015), 3 of whom die every day. Advances in modern medicine and improvements to car safety have meant that the number of available (deceased) organ donors is falling (Knapton, 2017), but the number of people requiring new organs is increasing by about 15% every year (A Ravelingien, 2004). One of the main reasons for this increase in demand is the UK’s ageing population (Xenotransplantation, 2016), combined with improvements to medicine (e.g. post-op treatment), meaning those previously unsuitable for transplant are now eligible (e.g. people with diabetes) (Werner, n.d.); and fewer young people being involved in fatal car collisions, previously a major source of organs for transplant (Xenotransplantation, 2016)