What is xenotransplantation?

Indications and Procedures

The transplantation of organs from human donors to human recipients has been established practice in medicine since the first successful kidney transplant was performed in 1954. Its applications have been limited, however, for two major reasons. First, the demand for human-donated organs always exceeds the supply. Second, the human body naturally rejects transplants. When the immune system recognizes compounds on the surfaces of cells from any source that is “not self,” a chain reaction begins. Antibodies attack foreign proteins and mark them for destruction by white blood cells. Enzymes attack the walls of blood vessels in a transplanted organ, destroying it within hours. To prevent rejection, transplant recipients must take immunosuppressive drugs for months or years. Blocking their immune response, however, makes transplant patients susceptible to infections, some of which can be deadly.

Xenotransplantation—the transfer of cells, tissues, or organs from nonhuman animal donors to human recipients for therapeutic purposes—might solve both of these problems. A large supply of organs can, in theory, be farmed in animals such as pigs. Also, theoretically, organs can be tailor-made to prevent rejection. Genetic engineering
techniques should be able to replace animal proteins and sugars on the surfaces of cells with human ones, thus creating an organ that the recipient’s immune system is tricked into accepting as “self.”

This genetic engineering is accomplished by transferring genes from humans to animals specially bred and farmed to serve as organ donors. To achieve this, a fertilized egg is removed from the uterus of a female donor animal. Next, human protein-coding genes are inserted into the nucleus of the fertilized egg. Finally, the egg is returned to the animal’s uterus and allowed to develop normally. If the human genetic material is preserved and activated, then the cells of the animal that develops from the egg will manufacture human proteins on the surfaces of its cells.

Uses and Complications

One concern about xenotransplantation is that new diseases might be introduced into humans from other animals. All animals carry endogenous viruses
that are part of their genetic makeup. Endogenous viruses are harmless in their natural hosts, but they can prove deadly when they cross from one species to another. For example, the Hong Kong flu virus lay harmlessly in waterbirds for many years. It then struck chickens and caused massive deaths on poultry farms, and now it infects and sometimes kills people. How the virus migrated to humans remains unknown. Also, diseases can be minor in some animals but major in humans. The herpesvirus B is one example. It gives monkeys mild cold sores but causes fatal encephalitis in people. The concern is that a virus imported into the human population through xenotransplantation might subsequently spread through other means, such as blood, air, water, or
food.

Issues of morality, ethics, and religion also arise. Although the genetic makeup of other primates most closely matches that of humans, many people believe that using apes and monkeys as organ donors would be morally unacceptable. One answer to such objections is to use animals that are routinely raised and slaughtered for food. Pigs are easy to breed and care for, and they produce large litters. Their size and weight are similar to humans. Few people object to killing pigs. Much xenotransplantation research involves the development of pigs as potential organ donors. If pig cells can be induced to display human proteins on their surfaces, then the human body will, in theory, accept organs donated from them.

Animals used as transplant donors could not come from ordinary farms because the possibility of transferring infections would be too great. The animals would need to be raised in germ-free medical facilities. Animal rights advocates condemn organ farms as cruel. Despite such objections, public opinion supports further research on xenotransplantation. In a 1998 survey sponsored by the National Kidney Foundation, nearly two-thirds of respondents judged xenotransplantation an acceptable alternative to human donor transplants.

Perspective and Prospects

Xenotransplantation is not a new idea. In 1906, with no knowledge of the immune system, French surgeon Mathieu Jaboulay transplanted a kidney from a pig and a liver from a goat to human patients, both of whom died. In 1964, Thomas Starzl at the University of Pittsburgh transplanted baboon kidneys into two humans. Both patients died from infections accompanied by kidney failure. That same year, a chimpanzee-to-human transplant fared a little better. The patient lived for nine months before the kidney failed.

In 1984, a child the press called “Baby Fae” was born prematurely with a severely malformed heart. She could not live long without a transplant. No human heart small enough was available, so surgeons at Loma Linda University in California gave Baby Fae the heart of a baboon. The operation went well, but Fae died of organ rejection and infection after the surgery.

In 1992, two liver transplants from baboons were attempted. The livers functioned well, but the patients died from infections. That same year, two women received livers from pigs. The transplants were not meant to be permanent but were intended as “bridges” until human donors could be found. In both women, the livers functioned well, but one woman died before a human organ could be located.

In 1995, British scientists succeeded in transplanting pig hearts into monkeys. Half the monkeys survived for forty days, but long-term survival was not achieved, and attempts to transplant whole organs declined after that. Instead, researchers turned to cell transplants. Since 1995, brain cells from pigs have been used with some success in the experimental treatment of people with Parkinson’s disease. In 2002, researchers in Virginia announced that they had successfully bred pigs lacking a specific sugar molecule on their cell surfaces known to trigger the rejection response in humans. Xenotransplantation advocates hope that this and similar developments will spur further progress in the field.

Bibliography

Brynie, Faith Hickman. 101 Questions About Your Immune System You Felt Defenseless to Answer . . . Until Now. Brookfield, Conn.: Twenty-first Century Books, 2000.

Cooper, David K. C., and Robert P. Lanza. Xeno: The Promise of Transplanting Animal Organs into Humans. New York: Oxford University Press, 2003.

Fovargue, Sara. Xenotransplantation and Risk: Regulating a Developing Biotechnology. New York: Cambridge University Press, 2012.

Munson, Ronald. Raising the Dead: Organ Transplants, Ethics, and Society. New York: Oxford University Press, 2004.

"Organ Transplantation." MedlinePlus, May 23, 2013.

Schicktanz, Silke, et al. Teaching Ethics in Organ Transplantation and Tissue Donation. Akron, Ohio: University of Akron Press, 2011.

Tramper, Johannes, and Yang Zhu. Modern Biotechnology: Panacea or New Pandora's Box? Wageningen, the Netherlands: Wageningen Academic Publishers, 2011.

"Xenotransplantation." US Food and Drug Administration, Feb. 4, 2010.