What are xenotransplants?

History

The idea of xenotransplants is actually quite old. During the eighteenth century, for example, transfusions of sheep’s blood were believed to be therapeutic for certain human illnesses. As the science of organ transplants between humans progressed, researchers became increasingly interested in experimenting with using animals as donors. Organ transplantation is an accepted medical treatment in humans, but there are not enough donor organs from humans available to treat every patient who could benefit from the procedure. In 2013, more than 120,000 people in the United States were waiting for an organ, according to the US Department of Health and Human Services. As the demand for transplant surgery grows, the pool of available donor organs shrinks in relation. One of the ethical dilemmas inherent in human organ transplant is that, in most cases, for one person to receive a transplant, another person must die. Bone marrow, partial liver, and kidney transplants are among the few exceptions; donors can usually donate bone marrow, a lobe of their liver, or one kidney and still survive. Nevertheless, for most organs the dilemma remains.

Researchers are interested in using organs harvested from compatible animals, eliminating both the need to wait for a compatible human donor and the shortage of usable organs. This is one form of xenotransplant, and it could eliminate the shortage of donor organs. However, researchers have encountered two major barriers to xenotransplantation; organ rejection by the human body’s immune system and the risk of xenosis, or the transmission of infectious agents, like viruses, between species.

Early research focused on potential donor animals that were similar to humans—that is, primates such as baboons and chimpanzees. Perhaps the most publicized example of such a xenotransplant was the 1984 Baby Fae case, in which doctors in California transplanted a baboon heart into a newborn human infant who otherwise had no chance for survival. The infant survived for several days before succumbing to complications. In 1993, a baboon liver was transplanted to a patient with liver failure. The patient lived for seventy days before dying of an infection. Researchers quickly learned that primates were not ideal candidates for organ donation; not only might the human body reject these organs, but primate organs are small in comparison to those of humans. Chimpanzee kidneys, for example, are too small to perform adequately in an adult human.

Researchers then turned their attention to pigs as possible donors. Swine make ideal donor candidates because they are physically large enough to have organs that can sustain humans, have a short gestation cycle, produce large litters of offspring, and, because they are routinely raised for meat production, are viewed as expendable by the general public. Pig heart valves are already routinely used in humans, with thousands implanted annually, and pig skin is often grafted onto burns. In a clinical trial, pig pancreas cells were injected into patients with Type I (juvenile) diabetes mellitus and several patients required less insulin afterward. People with liver failure have also been hooked up to pigs’ livers to keep them alive until a human liver was available for transplant.

In preliminary trials in humans conducted in the 1990s, neural crest cells (embryonic cells that eventually form part of the nervous system) from fetal pigs were injected into the brains of patients who had experienced a stroke or who had Parkinson’s disease. While a few patients had side effects that could have been the result of this treatment, some patients also seemed to get better. Later, another clinical trial was conducted in patients with Parkinson’s disease. In this trial, all patients underwent a surgical procedure, but only half of the eighteen patients in the study had pig cells injected into their brains, while the other half did not. Neither the patients nor the neurologists who evaluated the patients for improvement knew who had gotten the cell treatment. When the trial was complete, the results showed that there was no difference between patients who got the cells and those who did not, indicating that the pig cells did not improve Parkinson’s disease.

Despite the possible benefit of using pig cells to treat some human diseases, the use of larger organs from pigs has been less successful. Transplant recipients experienced hyperacute rejection; that is, their bodies immediately reacted to the foreign tissue by shutting off the flow of blood to it.

Transgenic Pigs

In 1992, researchers in the United Kingdom announced the creation of Astrid, the first transgenic pig. A transgenic animal is one who has been genetically modified with genes from another species. Since then, several groups have worked to create pigs with organs that have been genetically modified to be human compatible so that they are not rejected by the human immune system. Another goal of this kind of research is to create pigs with organs that are not susceptible to pig viruses.

Ethical and Medical Concerns

Xenotransplantation presents a number of ethical and medical dilemmas. The possibility that a virus, harmless to the donor animal, might be transmitted to the human host and then prove fatal is a major concern. Scientists worry that a potentially deadly disease epidemic could result from using organs or other tissue from either swine or primates. While many researchers are confident that careful screening of donor animals would eliminate or minimize such risks, critics remain convinced that it is possible a virus could lie dormant and undetected in animals, causing problems only after the transplants occurred. Baboons, for example, carry a virus that has the potential to cause cancer in humans.

In addition to the medical issues raised, many bioethicists question the morality of using animals as a source of “spare parts” for humans. They are particularly troubled by the idea of genetically altering a species such as swine in order to make their organs more compatible with human hosts. Proponents of xenotransplants counter these arguments by noting that humans have selectively bred animals for various purposes for thousands of years to eliminate certain characteristics while enhancing others. In addition, animals such as swine are already routinely slaughtered for human consumption.

Finally, there is the problem of human perceptions. While many people support the idea of xenotransplants on the genetic or cellular level, they are less enthusiastic about possible organ transplants. That is, while a majority of people surveyed said they would have no problem accepting a xenotransplant if it were part of gene therapy, far fewer were interested in possibly receiving a pig’s heart if the need arose. If researchers do achieve successful xenotransplants using such organs, however, public perceptions could change. It is easy to question a medical procedure when it is still theoretical; it becomes much more difficult to do so after it becomes a reality.

Impact

An immediate and plentiful source of organs from swine could improve and save many human lives. Overcoming the immunological problems and infectious disease risks are serious barriers to xenotransplantation, and remain active areas of research. Creating transgenic pigs with human-compatible organs is a main thrust of research in xenotransplantation. However, human stem cells from unused embryos or adult stem cells is a competing line of research that may offer an alternative source of organs for transplantation, or a means to repair diseased ones.

Key terms



hyperacute rejection

:

when a transplanted organ or tissue is immediately (within minutes) rejected by the body of the transplant recipient




neural crest cells

:

embryonic cells that eventually form part of the nervous system and other tissues





stem cells


:

multipotent cells that can differentiate into a diverse range of specialized cells




transgenic

:

involving the deliberate incorporation of foreign genes into an animal, such as human genes incorporated into the pig genome




xenosis

:

the transmission of infectious agents between species





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