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:: Xenotransplantation Fact Sheet

What is xenotransplantation?

Xenotransplantation (pronounced ZEENO-transplantation) is the process of transferring (transplanting) organs, tissues, or cells from one species to another.   The term comes from combining "xeno", the Greek world for stranger, with the word "transplant". An example is the transplant of a kidney from a pig into a human.

Why would anyone ever want to resort to using an animal donor's organ? Don't people donate enough organs?

The shortage of available, healthy human organs for transplantation is enormous and shows no signs of decreasing in the foreseeable future.   Click on the links below to see the waiting lists for:

What are the potential benefits of xenotransplantation?

Xenotransplantation could potentially provide an unlimited supply of cells, tissues, and organs for humans. Any disease that is treated by human-to-human transplantation could potentially be treated by xenotransplantation. Organ xenotransplants could include whole hearts, lungs, livers, kidneys or pancreases. Tissue xenotransplants could include skin grafts for burn patients, corneal transplants for the visually impaired, or bone transplants for limb reconstruction. Cellular xenotransplants may provide treatment for people with diabetes, Alzheimer's or Parkinson's diseases.

Are there different types of xenotransplants?

There are four basic types.

  • Solid Organ Xenotransplant: removing an organ, such as a kidney, liver, lung, or heart, from a donor animal and transplanting it into a recipient animal (or human)
  • Cellular or Tissue Xenotransplant: grafting tissues or cells (such as islet [insulin-producing] cells) from a donor animal and grafting or implanting it directly into the organ of a recipient (such as the pancreas of a person with type 1 diabetes)
  • External Therapies: filtering/purifying human blood cells outside of the body through an animal organ (such as a kidney) or cells in an external device
  • Human/Animal Hybrid: human cells grown in culture with non-human animal cells that are transplanted back into human patients

Have animal organs or tissues been used for transplants before?

Medical science already uses animal parts for various therapeutic reasons, such as replacement heart valves from pigs. However, these therapeutic products have been chemically treated and are not functional, living tissue. This distinguishes them from the viable organs used in xenotransplantation.

Have any solid organ xenotransplants been performed on people?

In 1984, Dr. Leonard Bailey transplanted a baboon heart into a newborn infant dubbed "Baby Fae".   The baby died after 20 days.   In 1992, Dr. Thomas Starzl at the University of Pittsburgh transplanted a baboon kidney into a patient with AIDS and hepatitis B.   The patient died after 70 days.   In 1993, the procedure was repeated on a patient with hepatitis B, but the patient never regained consciousness.

What are the potential risks of xenotransplantation?

The most serious risk appears to be cross-species transmission of undetected or unidentified animal infectious agents to patients, that could in turn, be transmitted to the general public. The worst-case scenario would be a major new epidemic. The potential risk of cross-species infection is largely compounded by the practices of patient immunosuppression for transplantation. Some of the other scientific concerns surrounding xenotransplantation include immune rejection, uncertain efficacy/viability (whether it will work), and whether high levels of immunosuppression will leave the patient vulnerable to more frequent infectious diseases or cancer.

Scientists are attempting to overcome immune rejection by inserting human genes into animal cells to make them more acceptable to a patient's immune system. Some experts believe that moving to clinical trials is the only way the uncertainties surrounding xenotransplantation can be answered. Others say experimental results show that a clinical trial at present would be premature and that these trials should be undertaken only if and when the risks have been shown to be minimal.

What animals could be used for xenotransplants?

While it may seem logical to choose animals that are genetically similar to humans, such as apes or baboons, it is becoming clear that more distant mammals may be preferred. Pigs have been viewed as the preferred choice of source animal due to the fact that they are inexpensive and easy to breed, can produce large litters in months as opposed to years, have organs that are about the right size, and may confer less risk of infection to humans than non-human primates. Pigs are also easier to raise in conditions that are free of disease-causing organisms and can be genetically manipulated to reduce the risk of organ rejection.

What have other countries done about xenotransplantation?

In the United States, the regulatory responsibility lies with the Food and Drug Administration (FDA) which has updated its "Public Health Service Guidelines on Infectious Disease Issues in Xenotransplantation" that were first released in September 1996. Clinical trials involving xenotransplantation have been approved by the FDA.

In Great Britain, a moratorium on clinical trials was introduced in January 1997, but clinical trial applications may now be submitted for review to the United Kingdom Xenotransplantation Interim Regulatory Authority (UKXIRA). UKXIRA was established in May 1997, to advise the UK Health departments on actions necessary to regulate xenotransplantation and to advise on the acceptability of clinical trial applications. UKXIRA has not approved any clinical trials to date.

The World Health Organization, in its efforts to foster international consensus on issues related to human health, hosted a consultation with international experts and published guidelines in 1998 on preventing and managing infectious diseases associated with xenotransplantation.

In January 1999, the Council of Europe's Parliamentary Assembly called for a moratorium on xenotransplantation until this new technology is evaluated and guidelines are established and agreed upon. The Assembly also asked the Council of Europe Public Health and Bioethics Committees to work hand in hand with the World Health Organization on a strategy which balances ethical, medical, scientific, legal, social and public health issues before human clinical trials continue.   Limited clinical trials involving xenotransplantation are planned or ongoing in some countries, such as the U.S., Belgium, Spain, and Germany.

Why are scientists having difficulty making xenotransplantation work in humans?

There are two main challenges: keeping the human body's immune system from rejecting the animal organ and ensuring that the new organ functions after xenotransplantation. To date, overcoming the human immune system appears to be the greatest challenge.

What immune problems does xenotransplantation face?

The human immune system is the product of hundreds of millions of years of development. Provided by nature, it protects us against infection by reacting to anything it doesn't recognize as part of the human body (self). We live in an ocean of microorganisms (bacterial, viruses, etc.), both helpful and harmful. Without an immune system, every microorganism is potentially lethal and without constant effective treatment, we would die within days. But the human immune system was designed to attack anything it recognizes as "foreign". It wasn't designed to accommodate potentially life-saving transplanted organs.

The human immune system has been shown to have four different rejection processes:

  • Hyperacute: The body quickly destroys the organ, often within hours, because it recognizes a specific sugar molecule called gal [galactose-(alpha 1,3)-galactose] and other key molecules on the organ cells that it considers "foreign".
  • Delayed (vascular): Over months, the blood vessels of the transplanted organ are attacked by antibodies and immune cells. The cause is not fully understood.
  • Acute (cellular): Over months, the T-cells of the immune system attack the transplanted organ.
  • Chronic: The progressive destruction of the transplanted organ over months to years, possibly due to antibodies to the organ. The process is not fully understood.

What's being done to overcome the immune problem?

  • To make animal organs more compatible with the humans, animals are being genetically modified to "knock out" genes that produce cell parts which the human immune system would reject.   There has already been some success: the gal gene has been knocked out of pig DNA.
  • Pigs being cloned to produce new lines of pigs which are closer to human size (miniature swine) and have genetically more compatible organs.
  • For some cell xenotransplants, cells are being encapsulated so that they are far less likely to be rejected

Does xenotransplantation pose a risk to the community as a whole (that is, people other than patients)?

Yes. The greatest danger is from what are known as "porcine endogenous retroviruses" (PERVs).   PERVs are retroviruses that are embedded in pig DNA and could be potentially transmitted to patients, and spread beyond just patients, following xenotransplantation, especially from solid organs.

As described by the Australian Government's National Health and Medical Research Council, PERVS are "...present in almost all strains of pigs and cannot be removed by raising pigs in sterile conditions.   Although PERV is inactive, and therefore harmless in pigs, there are concerns that transplantation into humans may activate the virus, creating a new human disease that could spread to those close to the transplant recipient and eventually to the wider community.   PERVs can infect human cells in the laboratory, suggesting that they could infection humans through xenotransplantation..."

Worse, retroviruses do not always initially cause obvious signs of a disease.   If a retrovirus were present in a xenotransplant organ and were to infect the human recipient of that organ, it could spread to close contacts, caregivers, and even the general population before it had even become obvious that an infection had occurred.

On the other hand, a study of some 150 patients who have had pig transplanted tissue or had their blood pass through pig cells have shown no evidence of infection with PERVs.   Another study has shown no transfer of PERVs from pig to human cells in cell cultures.   However, there have been no studies demonstrating that the risk from PERVs is minimal or can be entirely eliminated.   Tests are available to test for the presence of PERVs, and new tests are being developed.   However, these will only be able to test for those elements of PERVs for which they are designed; they cannot prove the absence of all PERVs.

The risk from PERVs is sufficiently serious that the US Food and Drug Administration Guidelines call for establishing a national data bank for xenotransplantation, maintaining specimens from animals and recipients for as long as 50 years, lifetime monitoring of xenotransplant patients and mandatory autopsy upon death, repeated monitoring of health care providers, and all (intimate) contacts of the patient for life.

Have viruses ever "jumped" from animals to people?

There are many examples of viruses moving from one species to another -- some with widespread, deadly consequences.   Probably the best examples are:

  • HIV (AIDS-causing virus) which appears to have originated in non-human primates from SIV (simian immunovirus)
  • The 1918 influenza that killed millions worldwide appears to have originated from pig viruses.   (There has been some debate that it originated in birds.   In either case, the deadly virus jumped from animals to people.)

In addition, many flu strains that arise annually appear to originate in animals, often in the far East.

What is "xenotourism"?

"Xenotourism", is defined by the US Secretary Advisory Committee on Xenotransplantation (SACX) as describing personal travel outside of a country of residence for the purpose of participating in xenotransplantation programs or attending clinics to obtain therapies not presently available or acceptable in the home country."   In short, it describes people who go to another country to obtain an organ (for transplantation) to circumvent the waiting list that exists in their home country.   If xenotransplantation becomes an acceptable practice, xenotourism could lead to severe health problems, both for the recipient and the community at large because of the enormous number of safeguards that would be required for this technology.

What are the ethical arguments for and against the use of (solid organ) xenotransplantation?

The arguments, on both sides, are numerous, complicated, and often based on personal beliefs.   Unlike most medical procedures in which arguments are often based on weighing the risks and benefits for the patient, we also need to consider the risks versus the benefits for the community at large .   Animal rights issues often come into play.

Pro-xenotransplantation arguments include (but are not limited to):

  • Hundreds of thousands of lives could be saved
  • Patients (such as with cancer) who might not otherwise be eligible could receive organs
  • Minimal time on waiting lists which might lead to patients (in improved conditions) having a better chance at survival
  • Easier to obtain a second organ for transplantation
  • Could eliminate many, lengthy, poor quality of life situations for patients, such as kidney dialysis
  • Decrease likelihood of receiving "partially damaged" organs
  • Could eliminate "black market" in human donor organs

Anti-xenotransplantation arguments include (but are not limited to):

  • Potentially create and spread serious disease(s) from animals to humans, perhaps developing into plagues that may inflict the community at large
  • Long-term monitoring as proposed by FDA and other regulatory agencies likely unenforceable, leading to potential abuse, and leading to new global diseases
  • Animal rights issues (e.g., cruelty, inappropriate use of animals)

What are the alternatives to xenotransplantation?

There are an insufficient number of human organs currently available for donation, and there are no projections that increasing the donor rate will cover the growing shortage.   Alternative technologies to xenotransplantation currently being evaluated globally include:

  • Stem cell research (limited in the US by Federal legislation)
  • Gene therapy
  • Artificial organs




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