Turning animals into organ donors for humans.
On average, every day in the United States twentytwo people die waiting for organ transplants, and someone is added to the waiting list every ten minutes. Organs must be taken from donors and quickly transported to recipients. In addition to the time limit, donors and recipients must be matched according to blood type and other factors to decrease the chances of transplant rejection. Donating the organs of a deceased loved one is an extremely difficult and emotional decision for grieving families, and many choose not to do so. All these factors contribute to the shortage of available organs for transplantation. High demand for donor organs has led to the investigation of other organ sources. Xenotransplantation is the transfer of organs between species. While it sounds like something from The Island of Dr. Moreau, physicians and research scientists are convinced that clinical trials will be underway in the near future.
To give you an idea
Human-animal hybrids sound glamorous and exotic, a little like Spiderman. In reality, dabbling with using animal tissues to treat people has resulted in some gruesome stories. In the 1800s, doctors performed skin transplants using all sorts of animals as donors, though the preferred source was frogs. A Russian physician, Serge Voronoff, was famous for transplanting testicular tissue from baboons or chimpanzees into elderly men – the Victorian era form of Viagra.
Medicine has come a long way in the last 200 years. Improving surgical techniques and patient care led to successful human-to-human transplants, though doctors continued to attempt xenotransplants:
- In 1984, an infant born with a cardiac condition called hypoplastic left heart syndrome received a baboon heart. Doctors intended the baboon heart to be a “bridge”, or a temporary solution, until a suitable human heart could be found. Unfortunately, no donor organ became available and the baby died a month later.
- In 1992, two patients received pig livers as bridges. One lived long enough to receive a human liver, while the other did not.
- In 1995 an AIDS patient received a bone marrow transplant from a baboon. His doctors hoped he might achieve resistance to the virus, which is common in primates. Though the transplant was not effective in fighting the AIDS virus, the patient lived another 10 years.
Organ transplants between humans didn’t become successful for the long term until the late 1960s, when immunosuppressive drugs were developed. One of the biggest problems with any transplant is rejection, which occurs when the recipient’s body recognizes the donor organ as foreign (or not self) and the immune system attacks the new organ. The immune attack can ultimately lead to death of the tissue, which results in rejection. This is why all transplant patients must remain on immunosuppressive drugs for the rest of their lives. Graft rejection occurs even in transplants between human donors and recipients. It’s an even bigger problem with xenotransplants because there are more differences between donor and recipient tissues.
A big difference between donors and recipients in xenotransplants is the type of sugar molecules present on the blood vessels in animals. These sugars are not present in humans, and can trigger an immune response. A company called Revivicor succeeded in knocking out the gene coding for the enzyme which adds the sugar molecule to cells in pigs. The knockout pigs have organs free of the triggering sugar, which have been transplanted into baboons. Last month, scientists reported that a baboon which received a kidney from a knockout pig survived 136 days. This beats the previous record of ninety days, and is highly encouraging to researchers.
In addition to removing the differing sugar molecules, scientists have also made other changes to these genetically modified pigs. The animals have been engineered to express human proteins, such as CD46 and thrombomodulin. CD46 helps stop immune responses, while thrombomodulin prevents blood clotting. These changes enable the organ itself to help repress the immune response in the recipient, which means patients may need fewer immunosuppressive drugs or lower dosages. More human genes are being added to further humanize the animal organs. While the results of the pig to baboon transplant were encouraging, widespread use of genetically modified organs in humans must be further investigated. Initial transplants will likely be bridges, designed as temporary measures. Clinical trials may be pursued if those results are positive.
Given the dramatic shortage of human donors, it is almost certain that scientists will continue pursuing xenotransplants from genetically modified animals. And while they may not give you superpowers, any patient on a waiting list will tell you that receiving a donor organ is even better than being Spiderman.
Iwase, H., Liu, H., Wijkstrom, M., Zhou, H., Singh, J., Hara, H., Ezzelarab, M., Long, C., Klein, E., Wagner, R., Phelps, C., Ayares, D., Shapiro, R., Humar, A., & Cooper, D. (2015). Pig kidney graft survival in a baboon for 136 days: longest life-supporting organ graft survival to date Xenotransplantation, 22 (4), 302-309 DOI: 10.1111/xen.12174
Cooper, DKC. A brief history of xenotransplantation. Proc (Bayl Univ Med Cent). 2012 Jan; 25(1): 49–57.
\Cooper, D., Ekser, B., & Tector, A. (2015). A brief history of clinical xenotransplantation International Journal of Surgery DOI: 10.1016/j.ijsu.2015.06.060
Cooper DK (2012). A brief history of cross-species organ transplantation. Proceedings (Baylor University. Medical Center), 25 (1), 49-57 PMID: 22275786
Regalado, Antonio. Surgeons smash records with pig-to-primate organ transplants. MIT Technology Review. 2015.
US Dept of Health and Human Services
Image Credit: Keith Weller, acquired from USDA ARS