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
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
- 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
- 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
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
What immune problems does xenotransplantation
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
The human immune system has been shown to have four different
- 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
- 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
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
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
- 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
- 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
- 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
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
technologies to xenotransplantation currently being
evaluated globally include:
- Stem cell research (limited in the US by Federal legislation)
- Gene therapy
- Artificial organs