Xenotransplantation Case Study
Organ failure is undeniably one of the most significant health problems in today’s world. Heart, kidney, lung, liver, and other organ failures are responsible for hundreds of thousands of deaths each year. Heart failure, for instance, claims an especially high number of lives. The Center for Disease Control (CDC) reported in 1996 that heart failure kills four times as many
1 Organ transplantation has proved to be the most efficient and people as does HIV infection.
cost-effective solution to organ failures. In almost all cases, continual medical treatment for affected patients is appreciably more expensive than organ transplants. It is estimated that the
2cost of treatment for heart failure patients ranges from 8 to 35 billion dollars per year. However,
if xenotransplantation (later defined) became a viable permanent option, a potential six billion
3dollar market, a cost significantly less than the afore mentioned treatment cost, would emerge.
Though organ transplantation is clearly the single most viable option to treat organ failures, there exist certain complications in the very system of organ donation. The essence of the problem is that the demand for organs far exceeds the supply. Dr. Anthony Warrens of Imperial College London estimates that for every human organ that is donated, there are five people on the waiting
4list who could benefit from it. Furthermore, the gap is not closing. Transplant surgeons only expect the organ shortage to grow. The issue of sparse organ donations is rooted in the fact that the potential donor pool is not large at all. Many people approve of organ transplants but refuse to donate. Only twenty percent of families actually permit their deceased loved ones to become
5organ donors. So even though transplantation has great promise as a method for treating organ
1 http://www.cdc.gov, "Xenotransplantation: Risks, Clinical Potential, and Future Prospects" 2 Ibid, See 1 3 Title: Organ farm [videorecording] / produced by Ben Loeterman [and] Frank Simmonds ; directed by Frank Simmonds : a Carlton Television Production for WGBH/Frontline in Association with Lion's Den Production and Ben Loeterman Productions, Inc. Publication info: [Alexandria, Va.] : PBS Video, c2001. 4 http://www.guardian.co.uk/uk_news/story/0,3604,1566712,00.html, “Animal organ trials 'within five years'” 5 http://www.fda.gov/fdac/features/596_xeno.html, “Organ Transplants from Animals: Examining the Possibilities”
failure, it has been kept from reaching its full potential by the scant supply of organs. Unfortunately, the CDC reports that heart failure patients are more likely to die on the waiting
6list than they are in the first two years following transplantation surgery. In fact, each year
60,000 to 70,000 new cases of heart failures arise in which heart transplants would be an
7appropriate response, while only 2,000 of them receive heart transplants.
To increase the quantity of available organs, a variety of solutions have been examined. However, one particular option has received superior amounts of attention, research, and development. This developing practice is called xenotransplantation and involves the transfer of tissues and/or organs from one species to another. More specifically, efforts have consisted of transplanting certain organs from other mammals into humans. Research and experimentation have especially focused on the transfer of pig and baboon organs due to their physiological similarity to human organs. It is important to note that, despite much development and promise, xenotransplantation has not yet become a long-term solution to organ failure for any one individual. It has either served merely as a temporary solution (bridge-to-transplantation) or has failed shortly after surgery. Still, xenotransplantation as a permanent solution has only progressed closer and closer to reality. The mastery of this practice would largely increase the supply of organs. In fact, Dr. Warrens commented in September of 2005 that “if it were feasible to use animals as organ donors, an unlimited supply would potentially become instantly
Early Attempts at Xenotransplantation
Though xenotransplantation is a cutting edge procedure likely on the brink of solving a momentous medical issue, it does have a noteworthy past. In 1963 and 1964, Dr. Thomas Starzl
6 Ibid, See 1 7 Ibid, See 3; Dr. Rober Michler; Ohio State Medical Center Surgeon 8 Ibid, See 4
performed six xenotransplantations of baboon kidneys into humans. Survival rates among the
9 patients ranged from 19 to 98 days.
In 1984 baby Fae was born. She suffered an inevitably fatal condition of hypoplastic left heart syndrome – an underdeveloped left side of the heart. Doctors quickly determined that all was lost unless they attempted an emergency heart transplant from an infant baboon to Fae. After gaining permission and even after Fae was required to be placed on a respirator after heart failure, on October 26 in Loma Linda University Medical Center in California, Dr. Leonard Bailey placed the baboon heart into baby Fae’s chest during the critical, four hour surgery. Following the operation Fae was observed as doing well for a few days. However, a massive attack on the foreign tissue of the baboon heart ensued, resulting in Fae’s death. For twenty days baby Fae had survived with the transplanted heart, until she died from organ rejection. Doctors had thought baby Fae would be the ideal candidate for a xenotransplant, given she was just an infant and her immune system had not fully developed – theoretically eliminating the greatest
barrier to xenotransplantation, immune system rejection. Even in 1984 controversy arose with 75 complaints being received in regard to cruelty to baby Fae and 13,000 complaints received for
10cruelty to the baboon.
In 1992 and 1993, Dr. Starzl oversaw the transplantation of two baboon livers to two different male patients (whose names were withheld from public disclosure). The liver transplants were performed because the patients suffered from Hepatitis B, and a human organ transplant would surely fail because the disease would simply destroy the new organ. Baboons are naturally resilient to Hepatitis B, and thus were thought to be the ideal donor species candidates. The first patient, a 35 year old male, survived for 26 days while the second lived for
9 Ibid, See 3 10 http://www.geocities.com/organdonate/AAACh18HistoryofHumanandXeno.html
70 days, both eventually succumbing to the effects of taking too many immunosuppressants. There was also some data pointing to inadequate function of the livers, but the possibility
11remained that animal organs could function in humans for extended periods of time.
Also in 1992, two women were scheduled to receive liver transplants from pigs. The surgeries were performed with the goal of using the organs to serve as short-term solutions until human livers became available for transplantation. In one of these cases, xenotransplantation successfully achieved the defined goal with the woman surviving on the pig liver, set outside the body and connected to liver arteries, long enough to receive a human liver. However, in the second case, the pig liver, implanted next to the original liver, failed within 32 hours, before a
12human liver transplant could be obtained, resulting in her death. Nevertheless, observation
suggested that both pig livers functioned inside the women for some duration of time. The early history of xenotransplantation has served as the foundation for more recent applications that are responsible for even greater advances.
Donor Species Research
In 1985 two British scientists, Drs. David White and John Wallwork founded a xenotransplant research company, Imutran. Since its founding, Imutran has pioneered the development of transgenic donor species specimens. In 1992, the first transgenic pig, Astrid, was born, causing a media frenzy. Many were eager to know what the pig might look like because as an egg cell, Astrid was injected with human DNA. However, transgenic pigs look and act no less like normal pigs. Only one millionth of Astrid’s DNA is composed of human
11 Ibid, See 3 12
DNA. Imutran was simply breaking down the barrier of immune system rejection of non-human
13 organs in human recipients.
Of recent developments in the study of xenotransplantation, an experiment conducted by
14doctors and researchers of the Mayo Clinic in Rochester, Minnesota is particularly significant.
The purpose was to examine the potential success of cardiac transplantation from one species to another as a precursor to clinical trials with human subjects. The plan was to transplant pig hearts into baboons, because this transplantation would be similar to proposed transplants from pigs to humans. In this experiment, the researchers derived hearts from seven transgenic pigs and used a myriad of immunosuppressant drugs to surgically graft the hearts into receiving baboons. In the presence of all of the medications, the baboons survived a median of three months. Five of the seven died from complications other than rejection. All of the transplants were heterotopic, which means that the hearts were grafted in an abnormal location or position, and the baboons were not kept on life-support afterwards.
The results of this cardiac xenotransplantation experiment suggest that human clinical application is not a distant concept. Under the same conditions with the addition of life support and normal graft positioning and location, the expected median survival period among subjects would be much higher. Here we are again presented with the viable option of using xenotransplantation in combination with life support as a means of life extension rather than a permanent fix. Not only would this allow some of the more seriously ill patients the time to wait for a human transplant donor, but it would be a significant step in the development of permanent animal-to-human solutions. Is this field of experimentation worth spending time and money on?
13 Ibid, See 3 14 http://jtcs.ctsnetjournals.org/cgi/content/abstract/130/3/844, “Cardiac xenotransplantation: Recent preclinical progress with 3-month median survival”
Should clinical trials with seriously ill humans be pursued as soon as this method of transplantation has been repeated and refined?
Dilemma Point 1 – Is the furthering of research in the field of xenotransplantation an acceptable justification for the exploitation of thousands of pigs and baboons? Precursors to Xenotransplantation: Piglet Cells
In 1999 21-year-old college student, Amanda Davis was driving home when suffered a stroke to the right side of her brain. She lost muscle control and had blurred vision to the point of driving off the road even though at the time she was unaware that she had suffered a stroke. When she awoke later at the hospital she was informed that she suffered a stroke which paralyzed the left side of her body. Two years following the incident, Amanda elected to undergo a clinical trial which would involve the injection of neural cells from pig fetuses into her brain. Surgery proceeded with doctors drilling a small hole into the upper right side of Amanda’s cranium. Approximately 80 million neural cells were then injected to the location between the site of the stroke and the healthy brain cells. All seemed well following the operation, but Amanda soon suffered a seizure although it was unable to be linked to the procedure. However, ten months later Amanda’s condition improved greatly. She had previously required the use of a leg brace on her left leg, but now she could easily walk without 15 it.
Beginning in May of 2001, Dr. Rafael Valdes and an international team of researchers in Mexico City began a controversial experiment as a precursor to xenotransplantation involving human subjects. Clusters of cells from the pancreases of piglets can potentially produce enough insulin to satisfy the needs of a diabetic human being. In their experimental therapy, the researchers extracted islet cells, which are insulin-producing, from several piglets. These cells
15 Ibid, See 3
were then transplanted into the abdomens of 12 insulin-dependent type 1 diabetic adolescents encapsulated by a cylinder of steel mesh. The capsules eliminated the need for immunosuppressive medication, with the idea being to escape the need for daily medication and increase the quality of life of type 1 diabetics.
The therapy showed very promising results. According to Dr. Valdes, many of the first twelve patients exhibited significant improvements or became totally independent of insulin injections for several months. A second group of eleven adolescents has showed similar progress. In September 2005, Valdes reported that the team was still able to detect live islet cells in the devices from the first study.
A particular safety concern with the implantation of islet cells from piglets is the transmission of a disease known as porcine endogenous retrovirus. This disease could then spread to third parties and potentially become a dangerous problem on a wider scale. Recent
16 Many countries research on this topic, however, suggests that there is little reason for fear.have stringent regulations and bans on xenotransplantation of islet cells from piglets because of the risk. In Mexico, the regulations are relaxed, providing the researchers the opportunity to legally do as they pleased. Was the group’s choice to go ahead with human testing without exploring the consequences a safe one? Should this type of research be legally restricted?
Dilemma Point 2 – Even though significant progress has been made as displayed in these two stories, do we still have the right use animals for the practice of xenotransplantation? The Future
For the most part, technical barriers to performing a successful xenotransplantation have
17almost been overcome. To define success for this case, the desired end state of the recipient
16 http://www.timesonline.co.uk/article/0,,2087-1807019,00.html, “Piglet implants help diabetic children recover” 17 Ibid, See 4
would be for him or her to live with the donated organ from the baboon or pig, permanently –
without the need for ultimately seeking a replacement human organ or extensive therapy.
The largest technical barrier which needs to be overcome in a xenotransplant is making certain the donated organ is acceptable to human antibodies in order to avoid organ rejection. The means for accomplishing this task would be to genetically alter the donor specimen through,
18 It is almost definitive that new breed as simply as it can be put, gene therapy or gene splicing.
of pigs and/or baboons would need to be developed solely for harvesting of their organs.
Pigs are seen to be the best candidate as a donor species for various reasons. They are easily bred in large numbers in clean facilities. Physiologically their organs are similar enough to those of humans to allow the possibility of a xenotransplant procedure. Meanwhile the genetics of pigs are distant enough from that of humans to reduce the likelihood of introducing viruses to the human species. Baboons on the other hand breed slowly, only producing one offspring at a time, and are predisposed to hosting a wide variety of viruses and bacteria. However, as primates they would seem to be better suited as donors given the greater physical similarities between them and humans. Ideally, chimpanzees would be used in xenotransplantation research, however, their endangered species status eliminates the possibility.
Dr. Warrens believes that clinical trials in transplanting animal organs to humans is only five years away because of the recent success in nearly overcoming hurdles such as developing
19non-human species’ organs to be compatible with human bodies .
Gaining public acceptance is another hinge for the success of practicing
xenotransplantation as a more routine procedure in the future. In 1998 the National Kidney
18 Annals of the New York Academy of Science; Vol. 862; Xenotransplantation: Scientific Frontiers and Public Policy, “Genetic Engineering in the Pig” 19 Ibid, See 4
Foundation published a press release with results to a comprehensive survey in regard to the
20 Some of the results were as follows: public attitude toward xenotransplantation.
- 50% of healthy persons would themselves accept organs from other species
- 62% considered xenotransplantation a viable option
- 75% of respondents would consider xenotransplantation for a loved one if there were
no human organs available.
There is a potential outcome of performing these xenotransplantations which could have widespread negative impact. Many bacteria and viruses indigenous to pigs and baboons – given
are not harmful to humans. In the event a successful they are the most likely donor species –
procedure is performed many of these viruses could remain in the donated organ, although no immediate harm would come to the recipient. Over time a virus could mutate into a strain which would be harmful to the human species. In the case of Amanda Davis, Dr. Hugh Auchincloss, the FDA subcommittee chairman on xenotransplantation, mentioned the possibility of pig DNA recombining with the human DNA opening the door to a whole host of new viruses. Humankind would be unprepared for an outbreak of potentially global proportions. This is perhaps the most overt ethical issue derived from this developing medical procedure particularly because HIV is believed to have derived from simian sources, and baboon organs transplanted to humans could lead to a whole host of unfamiliar, mutant, viral infections in humans.
Dilemma Point 3 – Is the potential for saving lives of those in need of transplants outweighed by the risk of creating a public health hazard through these types of procedures? Other Ethical Perspectives
The religious community will certainly have something to say about this issue. Giving patients medicine is one thing, but mixing body parts of two species is another. By having some
20 Ibid, See 18, “Analysis of Factors for the Prediction of the Response to Xenotransplantation”