While everyone’s attention has been drawn to the debate over stem cell research, another—perhaps more controversial—type of research is taking place.
Xenotransplantation is the transplantation of tissue or organs from one species to another, for example, the transplanting of pig cells into humans. Transplanting animal cells into humans is banned in many nations. Currently in the United States, xenotransplantation researchers are required to abide by stringent safety standards issued by the U.S. Food and Drug Administration.
Xenotransplantation research focuses on what may arguably be a promising method of replacing human organs, one that has the potential to provide an unlimited supply of cells and organs intended to cure illnesses such as diabetes, Parkinson’s and heart disease.
However, xenotransplantation is also said to be expensive, difficult and dangerous.
One type of xenotransplantation involves transplanting islets from pigs into humans in an attempt to cure type 1 diabetes. Several research teams throughout the world are conducting animal trials to determine whether pig islets can be transplanted without initiating hyper acute rejection (HAR), which is seen as one of the biggest obstacles to success in using pig cells in humans.
One Team Is Performing Human Testing
One team is jumping ahead of the pack, initiating tests with humans by implanting encapsulated piglet islets into adolescents with type 1 diabetes.
In May 2001, Rafael Valdes, MD, FACS, and colleagues from the Children’s Hospital of Mexico in Mexico City took islets from customized, disease-free, one-week-old piglets that had been bred specifically for xenotransplantation research purposes. The islets were transplanted into insulin-using adolescents ages 11 to 17 who had had type 1 diabetes for at least three years. The subjects had been on insulin regimens that ranged from 50 to 78 units daily.
Dr. Valdes employed a special method of inserting the pig islets. A 3-cm stainless-steel mesh capsule containing a removable Teflon cylinder was inserted into the abdominal cavity of each patient. Two months later, after a collagen membrane had formed around the capsule, the cylinder was removed and approximately one million pig islets were injected into the tube. The pig islets were mixed with sertoli cells—cells of the testes, which nourish and protect developing sperm cells—to keep the immune system from attacking the pig islets.
In August 2002, at the meeting of the Nineteenth International Congress of the Transplantation Society in Miami, Florida, David White, FRCPath, PhD, professor of xenotransplantation at Roberts Research Institute in London, Ontario, reported on the progress of the 12 children who received the pig islets.
According to the Fall 2002 issue of Insulin-FreeTIMES (available at www. insulinfreetimes.org/02_fall/xeno.htm), Dr. White—a member of Dr. Valdes’s transplant team for this series of operations—stated that only one child remains insulin-independent one year after the transplant. Another was insulin-independent for six months and now requires 75 percent less insulin than before the procedure.
Most important, noted Dr. White, was that no adverse reactions from the pig cells were observed.
The most significant safety issue in xenotransplantation is the possibility of transferring infectious diseases from an animal to a human. With pig islet transplantation, in particular, scientists fear transmitting a disease unique to pigs, called porcine endogenous retrovirus (PERV).
In a landmark study published in the October 19, 1997, issue of Nature, researchers were able to show that PERV could infect human cells in a controlled environment using cells in culture. Despite this finding, no actual cases of PERV have been reported, and research shows no evidence that the transfer of such a retrovirus has ever occurred.
“To date, there are no recognized infections that have resulted from xenotransplantation in the U.S. in regulated trials,” says Louis Chapman of the U.S. Centers for Disease Control and Prevention.
An additional risk is that a disease could be passed to third parties, such as the family or friends of the person who received the transplant. Many experts, including Norman Daniels, MD, of Tufts University in Medford, Massachusetts, oppose all clinical trials of pig islet transplantation for this reason.
“Xenotransplantation poses potential risks to these third parties as well as to the public as a whole if the infectious disease turns out to be a widely transmittable illness,” Dr. Daniels warns.
Guidelines have not been developed in the United States to assess the risk of passing a disease to family and friends of a transplant recipient, he argues.
“I doubt they have addressed this issue,” he says about the Mexican trial.
Fritz Bach, MD, of the Beth Deaconess Medical Center in Boston, agrees that guidelines to protect the public from third-party infection are not yet good enough.
“I personally do not see the background information that would encourage me to do clinical trials with porcine islets in humans at present,” he states.
“One approach that I really do not favor and I find objectionable is for investigators from one country to do trials in countries in which the regulations are less well developed or nonexistent.
“Xenotransplantation that puts people other than the patients at potential risk requires a discussion with an informed public to assess the concerns of that public.”
A Transplant Recipient Argues for Xenotransplantation
Diatranz Ltd., of Auckland, New Zealand, harvested the pig islets used by Dr. Rafael Valdes in his Mexico City research. Currently, pig islet transplantation is illegal in New Zealand, which is why Robert Elliot, MD, FRACP, CNZM, and medical director of Diatranz, chose to conduct the trials in Mexico.
But past patients of Dr. Elliott, who were treated with earlier versions of his transplantation methods as far back as the early 1990s, are speaking out to the New Zealand parliament in favor of his work.
One such patient, Nicki Raffills, is a 25-year-old lawyer with type 1 diabetes who lives in Auckland. Raffills received a pig islet transplant as part of a clinical trial led by Dr. Elliott in 1994. After her transplant, she was able to lower the dosage of her daily insulin injections by 40 percent. This improvement lasted for only three months, however, before the injected islets stopped functioning and she had to return to her original insulin dose.
“I experienced the best three-month period of diabetic control,” she recalls. “I also had the best level of general health, in terms of energy and so on, that I have ever had.”