Xenotransplantation: The Future of Organ Transplantation

by Imaz Athar

Bob suffers from heart disease and is in dire need of a transplant. Unfortunately for Bob, receiving a transplant is not so easy. First off, doctors need to run a series of tests to see if he is a suitable candidate for heart transplantation. There are times when the patient fails these examinations and is deemed ineligible for a transplant, but let’s say Bob passes them. Now, doctors need to find the ideal heart for Bob. His blood type, heart size and his degree of sickness are only a few of the factors that come into play in this decision.

There are approximately 3,500 people in the United States who are waiting for a heart, and there are not nearly enough donors to meet this demand. As a result, Bob is placed on the waiting list. The amount of time he’ll have to wait is uncertain—it could be months, or even over a year. In the meantime, Bob may have to spend days in the hospital to receive medical treatment that will support his ailing heart. Not only is this inconvenient for him, but realizing that he could die while waiting for a vital organ is tremendously frightening.

Imagine if Bob could avoid the long, life-threatening wait. Imagine if he could receive a clean, disease-free heart within days. Dr. David Cooper, of the Thomas E. Starzl Transplantation Institute in Pittsburgh, believes that this may become a reality. The potential solution? Transplanting a pig’s heart into a human, through a process known as xenotransplantation—the transplantation of living organs, cells, or tissues from one species to a different species.

Currently, there are close to 110,000 patients waiting for an organ donation. However, only around 30,000 organs are transplanted each year. The gap between patients on the waiting list and the number of donors has increased dramatically since 1989, when there were roughly 18,000 patients waiting and a little over 13,000 transplants (much closer to a 1:1 ratio).

As a heart transplant surgeon, Cooper realized that the supply of heart donors did not meet the demand. When running a heart transplant program, Cooper could already only choose 70 patients out of the 140 that were referred to him each year. However, according to Cooper, “well under half” of the 70 patients were actually able to receive a transplant “because [they] didn’t have enough donors.” According to him, the other half “would generally die unless they could be staggered on for another year or so.”

It became clear to him that it was important to direct his attention towards finding a different source of organs, cells and tissues. And the surprising candidate? Pigs.

While primates are more immunologically similar to humans than pigs are, throughout history, humans have not picked up any serious infections from pigs. Pigs can also be bred in larger groups. This is extremely important; pigs could provide an almost unlimited supply of organs.

According to Cooper, an unmodified pig heart lasts only five to 10 minutes in a baboon or human. This is because all pig cells have a galactose component. Three to four months into human development, we create anti-galactose antibodies in our bloodstream to fight disease. When a pig heart is transplanted into a human, these anti-galactose antibodies bind to the galactose components of the pig cells, initiating a process called complement cascade activation, which destroys the pig organ.

Cooper and other researchers have corrected this problem by genetically engineering pigs, so that their cells do not express galactose sugars. Furthermore, research groups in Minneapolis and in Cambridge, England, have developed genetically engineered pigs that possess human complement-regulatory proteins that also protect the pig organ.

With both of these factors combined, Cooper has found that a pig heart can last six or eight months without rejection in a baboon. Although the baboon does not reject the pig heart, blood clotting still occurs. In order to reduce the rate of clotting, Cooper and researchers have put a human coagulation-regulatory protein in the pig. Although this has yet to completely eliminate the clotting, Cooper believes more coagulation-regulatory proteins will prevent this complication. Although there is still progress to be made, six or eight months is already a significant increase in survival rate from five to 10 minutes.

The fact that pigs can provide an unlimited supply of organs is significant on its own. Yet another advantage of using a pig xenotransplant is that doctors will not have to worry about whether or not the pig organ carries infections that can harm the patient. With human donors, doctors have to remove the organs within 24 hours of death, and they only have a few hours to determine whether or not the organs carry disease. At times, according to Cooper, risks have to be taken or else there would not be any donors at all.

This worry is partially alleviated with pigs because they can be raised in clean conditions. They would be kept in separate groups and breathe filtered air; their food would be sterile, and their caretakers would wear suits to eliminate any direct contact with the pigs. This would hopefully mean that the pigs would not contract infections, and produce only non-infected organs. This way, patients would avoid complications that arise from inheriting an unhealthy human organ.

Pigs can be a source of a variety of organs that could potentially help millions of patients with a number of health problems. Despite this, there are people opposed to xenotransplantation because they believe genetic engineering is a violation of animal rights. In fact, in 1999, People for the Ethical Treatment for Animals called xenotransplantation “Frankenstein science” and asked the Food and Drug Administration (FDA) to ban it. Although the FDA did not ban xenotransplantation, they asked that xenotransplant patients be closely monitored throughout their lives.

Despite critics like People for the Ethical Treatment of Animals (PETA), Cooper believes that we need to measure the usage of animals against the outcome it can have for humans. “We can either sit and watch [people] die, or do something about it,” he said.

Cooper disagrees with PETA’s description of xenotransplantation. According to him, the genes that researchers are knocking out (or in) in pigs have “no real effect” on their behavior or well-being.

Others protest against xenotransplantation because they are worried about the pigs’ living situation. However, according to Cooper, the pigs that would be used for xenotransplantation would be treated with respect because they are “commercially valuable.” They would be housed in “perfect” conditions, unlike pigs that are passed through slaughterhouses as sources of food. Organ-source pigs will be anesthetized like humans, euthanized humanely, and die a more “honorable” death than the 100 million pigs that are slaughtered for food each year in the United States.

There are also those that question xenotransplantation for fear that the endogenous retroviruses in pig organs, cells, or tissues will grow in humans. Cooper does not believe that this will happen. In fact, virologists at an FDA committee that Cooper attended stated that the retroviruses, in Cooper’s words, “won’t do any harm.” Others were worried that xenotransplantation could cause an AIDS epidemic, but Cooper also finds this “exceedingly unlikely.”

Despite the evidence that xenotransplantation has the potential of benefiting thousands – if not millions – of patients, the critics remain. But there are always critics. It is the enduring vision that is important. In the late 1970’s, the mortality rate for patients of human heart transplants each a year was extremely high—according to Cooper, it was 50 percent or more. Although this incited criticism, researchers and doctors stuck to their vision, and the mortality rate for patients who receive these transplants is now quite low. This kind of perseverance is significant, and with the amount of research Cooper and others have conducted, and the number of advances that have been made, Cooper believes xenotransplantation will revolutionize medicine and might become commonplace in even just 50 years.