FAQs on Xenotransplantation
- What is xenotransplantation?
Xenotransplantation (pronounced
ZEENO-transplantation) is the process of transferring
(transplanting) organs, tissues, or cells from one animal
to another. The term comes
from combining "xeno", the Greek world for stranger, with
the word "transplant".
- Transplantation between which animals?
Xenotransplantation may apply to transferring (transplanting,
implanting, or infusing) organs, tissues, or cells from one
species of animal to another, such as from a pig to a baboon,
or from an animal (such as a pig) to a human.
- Are there different type of xenotransplants?
Yes. 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
In addition, there are non-living animal tissues, such as
pig heart valves, that have been used for repairing hearts
in humans for many years.
- Why would anyone ever want to perform animal-to-animal
xenotransplantation?
Reasons include:
- Treating Cancer: human tumor
cells for breast cancer and other diseases are often
injected into mice as a "preclinical model" for determining the effectiveness of
an anti-cancer treatment. At present, although
the use of animals for these kinds of experiments may
be minimized, it is difficult, if not impossible, to
eliminate them altogether.
- Experiments for Transplanting
Organs into Humans: many, if not most, animal-to-animal
solid organ xenotransplants that have been performed
to date have been to prepare the way for transplanting
kidneys, livers, and hearts from animals, typically
pigs, into humans
- 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 great and shows
no signs of decreasing in the foreseeable future. Click
on the links below to see the waiting list for (the):
- What kinds of animals are potential donor organs for
human beings?
Pigs (including miniature swine)
- Why not use (non-human) primates,
such as chimpanzees and/or baboons, for donor organs?
They are closer to human beings than pigs.
It is precisely because they are,
in an evolutionary sense, closer to us than pigs. The
reasons include safety, ethics, and economics:
- Safety: Because primates
are similar to us, they are more likely to harbor diseases,
including deadly viruses that might easily jump from
their species to ours. Because pigs are substantially
different from us on the evolutionary scale, the thought
is that the infectious agents afflicting pigs would
be less likely to affect humans.
- Ethics: Because primates
are similar to us, there is generally greater reluctance
at using them as source organs. The term "cannibalism" has
been mentioned.
- Economics: Baboons
and chimpanzees require years before becoming fertile
and produce smal litters.
- Why use pigs (including miniature
swine) for donor organs?
- They can reproduce
large litters in months
- Their organ sizes are
generally similar those in humans
- They are easier to
rear in conditions that are free of disease-causing
organisms
- Their risk of infecting
humans with pathogens is much smaller than those
of non-human primates
- They can be genetically
manipulated to reduce the risk of organ rejection
- What health problems could xenotransplantation solve?
People with organ failure and in desperate need of a:
- Kidney (such as patients
on dialysis and/or in end-stage renal disease)
- Liver
- Heart
- Lung
- In addition, cell or tissue xenotransplants could be
used to treat:
- Diabetes
- Alzheimer's disease
- Parkinson disease
- Huntington disease
- Are solid animal organs being transplanted into human
beings today?
No. (At least none have been
authorized or reported in sanctioned medical or scientific
circles.) Research today is all preclinical, that is to
say, xenotransplants of organs from one animal to another---primarily,
from miniature swine or pigs to baboons.
- When were the last xenotransplanted organs in people?
In 1984, Dr. Leonard Bailey transplanted
a baboon heart into a newborn infant dubbed "Baby Fae".
They 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 scientists having difficulty making xenotransplanting
organs work in people?
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 but 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,
however, 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 was never designed
in mind 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
it 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 infect humans
through xenotransplantation..."
Worse, retroviruses do not always
initially cause obvious signs of a disease. If
a retrovirus were present in a xenotransplant organ 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 database for xenotransplantation,
maintaining specimens from animals and xenotransplant 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---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 bird (avian)
viruses. (For years, it had been thought to have originated
in pigs. In either case, the deadly virus jumped from
animals to people.)
As well, 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 describe 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)
There is an excellent, debate
on xenotransplantation available here.
- 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
Want to know more on xenotransplantation?
Background Information
on Xenotransplantation
Scientific/Scholarly Sources of Information
on Xenotransplantation
Government/Regulatory/Guideline Documents on
Xenotransplantation
Transplant-Related Professional/Medical Organizations
Organ Transplant Donor/Recipient Networks and
Registries
Industry & Companies
Involved in Xenotransplantation Research
Organizations Whose Members Might Benefit From
Xenotransplantation
Organizations Supporting Xenotransplantation
Organizations Opposing Xenotransplantation
Animal Rights Organizations Opposing Xenotransplantation
Bioethics: Sites/Articles/Perspectives
Xenotransplantation Articles on the Web |
