Xenotransplantation: progress and promiseBMJ 1999; 319 doi: https://doi.org/10.1136/bmj.319.7220.1311 (Published 13 November 1999) Cite this as: BMJ 1999;319:1311
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Re: “Xenotransplantation: Progress and Promise” (BMJ 13 November 1999;
To the Editor:
In the American newspaper, Newsday, (Nov. 5, 1999, p.A53),
bioethicist Art Caplan wrote, “Nature is making it very clear that lurking
out in our world are still more mutating viruses and pestilent bacteria .
. . Medicine has to learn an important lesson. The lowliest organisms can
confound even the mightiest medical experts. Whatever medicine's
achievements . . . humility is a better guide to dealing with the dangers
and risks in the world around us than is hubris.” These are wise words
which should be heeded by pro-xenotransplantation “bioethicists” like
It is naiive to believe that extensive research in
xenotransplantation “is being propelled” by drug companies’ beneficent
desire to alleviate human suffering, rather than the promise of billions
of dollars in profits from the sale of “humanized” pig parts and expensive
anti-rejection drugs. For there would be much safer and more-cost-
effective ways of dealing with the perceived human organ and tissue
shortage. One would be aggressive investment in population-based
prevention programs to prevent organ disease in the first place; another
would be passage of presumed consent laws, which have increased organ
donation rates in Austria, Belgium, Singapore and other countries.
Cultivating human tissues for transplantation would provide a much safer
source than animals.
It is ironic, given the multitude of known and unknown viruses
lurking in animals, that proponents of xenotransplantation continue to
claim the technology can be made “safe.” It will be impossible to breed
animals that are free of all infectious pathogens and endogenous
retroviruses. Moreover veterinarian M.M. Swindle asserts that “it will be
impossible to provide complete individual animal screening in a timely
fashion prior to performing a xenograft transplant.” Therefore, all
recipients of porcine cells, tissue, or organs would be exposed to viruses
and possibly other infectious organisms.
Public health authorities admit that xenotransplantation could
transmit deadly animal viruses to humans. Known pig viruses include the
porcine endogenous retroviruses (PERVs) – a family of AIDS-like viruses
that have infected human cells. And there may be dozens of unknown
viruses, many with long latency periods, waiting to be discovered.
None of the alleged “safety” studies performed to date account for latent
or unknown viruses. Virologist Jonathan Stoye says: “the absence of
infectious virus in, say, the first two hundred patients does not mean it
will not occur in the two hundred and first. This implies that the chance
of some hazard arising can never be zero . . . The greatest danger would
come from something causing disease with a very long latency period.”
HIV-1, for example, was transmitted silently from human to human until it
was recognized as a causative agent for AIDS in the early 1980s.
A retrospective Novartis/CDC study, designed to allay safety concerns
about porcine xenotransplants, raised more questions than it answered: 30
patients who underwent “splenic perfusions” in Russia tested positive for
Porcine Endogenous Retrovirus (or PERV) DNA; 23 had pig cells circulating
in their bodies 8.5 years after treatment; and four patients injected with
pig cells produced antibodies against pig PERV – suggesting a potential
active infection by pig viruses. Data from some patients were deemed
“uninterpretable” due to a lack of sufficient DNA for analysis, and
technological limitations; none of the patients were exposed to tissue or
organs from transgenic pigs; a majority of the study samples tested were
from extracorporeal perfusion patients, exposed for very short periods -
on the order of minutes to hours. Data from such experiments are hardly
relevant to the kinds of conditions that would apply in whole organ
xenotransplants. Only 14 patients were actually injected with porcine
pancreatic islet cells, but important information about these patients’
exposure times and health and immunological status was missing.
This is hardly a solid study, and certainly not one to base claims of
“safety” upon, particularly in light of the fact that “our understanding
of the retrovirology of xenotransplant source animals is incomplete,” and
that “little or nothing is known about the pathogenic potential of
endogenous retroviruses introduced directly into other species.”
Within the last 20 years, 30 novel infectious diseases, including
AIDS, Ebola, and Creutzfeldt Jakob Disease, have been discovered. In 1998
-99, the Malaysian “Nipah” viral encephalitis virus jumped from pigs to
humans, infected 269 people, killed 102, left dozens brain-damaged, and
led to the mass slaughter of one million pigs. The swine flu epidemic of
1918 killed 20-40 million people worldwide. A novel pig virus, contracted
via xenotransplantation, could spread to other humans undetected, causing
a world-wide plague.
We continue to be baffled as to why xenotransplant researchers and
drug companies insist on going down this perilous path, rather than focus
their energies on safer, less problematic and humane solutions to the
perceived organ shortage. And we are even more baffled that our public
health authorities, mandated to protect public health and prevent disease,
are encouraging the development and application of xenotransplantation,
while simultaneously acknowledging that it could unleash deadly viruses
upon society. This may prove to be legally problematic for these
Let’s not kid ourselves, xenotransplantation will never be “safe” for
human beings, and its long-term efficacy has yet to be proven. All human
recipients of whole animal organs have died, most within hours or days.
Transplanting pig organs into nonhuman primates, as several biotech
companies are doing, cannot tell us how pig organs and tissues will
perform in human beings, whose physiology, metabolism, and immune
responses are different from other animals.
Last year (May 1998), a group of international physicians pointed out
in the British Medical Journal, that “the number of people living in
absolute poverty has more than doubled since 1975.” Global poverty, they
said (and resultant lack of access to basic health care and adequate
sanitation) is the world’s number one health problem. Today, some 50
million Americans (over a third of them minorities and the working poor)
lack access to basic health care, and another 50 million are underinsured.
If we really wanted to save lives, we would be improving access to basic
health care and sanitation, investing in disease prevention, and (in the
case of organ failure patients) passing legislation to increase human
organ donation. If we are not doing these things, we are simply lining
the drug industry’s pockets.
1. Preliminary cost-benefit analyses (using industry’s own figures) reveal
that first-year implementation costs for xenotransplants in the U.S. would
be $35 billion (see Alan Berger, MBA, CPA “Animal-to-Human Transplants: A
Frightening Cost-Benefit Analysis,”.Animal Protection Institute, Sacramento,
California, October 1999, available on www.crt-online.org) This excludes
expensive follow-up care, regimens of anti-rejection drugs, screening assays
and screening programs for new viruses, hidden costs of breeding,
maintaining, testing, and disposing of herds of transgenic animals, the
costs of hiring skilled hospital personnel, surgical staff, infectious
disease experts and veterinarians capable of properly monitoring xenograft
patients and source animals. And there may be unpredictable legal and
medical costs associated with disease outbreaks as a result of
2. M.F.X. Gnant, “The Impact of the Presumed Consent Law . . .:
Quadruplication in the Number of Organ Donors,” Transplantation Proceedings,
Vol. 23, No. 5 (October 1991): 2685-6. L. Roels, et al., “Effect of a
Presumed Consent Law on Organ Retrieval in Belgium,” Transplantation
Proceedings, Vol. 22, (1990): 2078-9.
3.Dominic C. Borie, et al., “Microbiological Hazards Related to
Xenotransplantation of Porcine Organs Into Man,” Vol. 19, No. 5 (May 1998):
355-65; Frederick A. Murphy, “The Public Health Risk of Animal Organ and
Tissue Transplantation Into Humans,” Science, Vol. 273 1996): 746-7;
Jennifer Brown, et al., “Xenotransplantation and the Risk of Retroviral
Zoonosis,” Trends in Microbiology, Vol. 6, No. 10 (October 1998): 411-14.
4. M.M. Swindle, “Defining appropriate health status and management programs
for specific-pathogen-free swine for xenotransplantation,” Ann NY Acad Sci,
Vol. 862 (December 1998): 111-20.
5. See Dominic Borie, et al., “Microbiological Hazards Related to
Xenotransplantation of Porcine Organs into Man,” Infection Control and
Hospital Epidemiology, Vol. 19, No. 5 (May 1998): 355-65, for an extensive
description of porcine viruses, bacteria, parasites, fungi that could be
transferred to humans via xenotransplantation.
6. See footnotes 16 and 17 in H. Vanderpool, BMJ, 13 November 1999.
7. Jonathan P. Stoye, et al., “Endogenous Retroviruses: A Potential Problem
for Xenotransplantation,” Annals of the New York Academy of Sciences, Vol.
862 (1998): 73.
8. K. Paradis, et al., “Search for Cross-Species Transmission of Porcine
Endogenous Retrovirus in Patients Treated With Living Pig Tissue,” Science,
Vol. 285 (20 August 1999): 1236-41.
9. Jonathan P. Stoye, et al., “Endogenous Retroviruses: A Potential Problem
for Xenotransplantation,” Annals of the New York Academy of Sciences, Vol.
862 (1998): 68.
Competing interests: No competing interests
Xenotransplantation of organs from animals to try to save sick humans
is a very seductive, but inherently dangerous idea. The risk is not just
to the patient, who, if past precedent is any guide, will likely die in
the short term after the procedure. The stakes are much higher than the
fate of one individual, because the entire human population on this planet
is put at risk by this kind of procedure. Viruses that inhabit animals,
some of which are even intrinsic to the animal's own genetic material,
will gain a route of entry into the human population which is not
ordinarily available to them. As noted by Dr. Vanderpool, pig DNA contains
endogenous retroviruses (the same class of viruses which cause AIDS), and
these have been shown to be able to infect human cells in tissue culture.(1)
Dr. Vanderpool does not mention that post-mortem analyses of two human
patients who died 70 and 27 days after receiving baboon livers revealed
two simian viruses which had apparently replicated following the
transplant.(2) Our state of knowledge is far too incomplete to suggest that
it might be possible to breed totally virus-free animals, because it is
almost certain that we do not even know all of the viruses there are which
would need to be eliminated.
We do know that viruses can and do jump species even without our
help, and there are enough frightening precedents of animal to human virus
transmission, as far back as the swine influenza pandemic of 1918 which
killed 20 million world-wide, to scare anyone contemplating
xenotransplantation. In more recent times, one need only recall the
millions of chickens which had to be slaughtered in Hong Kong two years
ago, because of the unexpected jump to humans of an avian influenza virus;
or the tens of thousands of English cattle destroyed because of the
apparent jump to humans of the prion-based bovine spongiform
encephalopathy ("mad cow disease").
The spectacular advance of one of the great scourges of our era,
AIDS, resulted from a virus given new routes of entry into recipient
hosts: the widespread increase in certain lifestyle practices provided a
conduit for efficient transmission without which the virus would likely
have had much less impact, if at all, at least in Western countries. HIV-
1, the virus responsible for AIDS, also likely resulted from a virus jump
from simian to human. The deadly Ebola virus is another example of a virus
which can be transmitted to humans from primates, and there are at least
another 10 known primate viruses which can infect humans, including a
deadly form of herpes. Pigs aren't much safer: there are about a dozen
known pig viruses which can be transmitted to humans, often with serious
Not considered by Dr. Vanderpool is that there are much better
alternative approaches, including lifestyle alterations (diet and
exercise) which would significantly reduce the numbers of transplant
candidates, and presumed consent policies for human donors, which would
significantly expand the pool of available organs. Finally, research on
unwanted human embryos is much more promising as a solution, but this is
held hostage to the abortion politics in the USA. The medical potential of
human tissue and organ cultures seems unlimited and at negligible risk
compared to xenotransplantation, but research on this cannot presently be
federally funded. So instead of pursuing an avenue for transplantation
that really might work, without introducing new viruses into humans, we
are absurdly rushing down a path fraught with danger. Have we learned
nothing from the AIDS epidemic?
(No competing interests.)
(1) Patience C, et al. (1997) Infection of human cells by an endogenous
retrovirus of pigs. Nat. Med. 3:282-6.
(2) Allan JS, et al. (1998) Amplification of simian retroviral sequences
from human recipients of baboon liver transplants. AIDS Res Hum
Competing interests: No competing interests