A Layperson's Guide to the Problems With Animal-to-Human Organ Transplants

Executive Summary

1. Introduction
The alleged chronic shortage of human organs has led some researchers and federal health officials in the US and elsewhere to consider using animals, such as pigs and nonhuman primates, as alternate sources of organs for humans. The prospect of commercial cross-species transplantation (or xenotransplantation) - attempted since the early 20th century - has created huge financial incentives for biotechnology and pharmaceutical companies. While some researchers and animal research advocates are optimistic about xenotransplantation's potential, others are calling for a moratorium on the technology, which they say threatens public health and the environment, has an appalling track record, and is both expensive and unnecessary. These concerns have not been satisfacto rily addressed by xenotransplantation's proponents, who have overstated the technology's potential benefits.

2.Organ Xenotransplantation's Track Record: 100% Failure
There have been some 55 animal-to-human whole organ transplants attempted since 1906. All have proven unsuccessful, resulting in the suffering and death of all patients and donor animals. The thousands of cross-species experiments (between goats, rats and chickens, rats and hamsters, cats and dogs, pigs and primates) performed since 1906, and continuing today, have not provided reliable information about what would happen to human xenograft recipients. Xenotransplantation is a dangerous and unproven technology.

3. Xenotransplantation Is Expensive
Xenotransplantation is riskier and promises to be even more expensive than human-to-human transplantation ($250,000 per operation in 1995, not including the hidden costs of breeding, housing, feeding, medicating, testing, transporting, rendering, and disposing of the waste and remains of herds of transgenic animals). Institute of Medicine figures from 1996 reveal that xenotransplant costs for all patients who need organs could reach $20.3 billion. These costs are beyond the means of the majority of Americans and an already overburdened health care system. If ever successful, the technology would, at best, benefit a small minority of patients (100,000) while dramatically driving up health care costs for all.

4. We Should Learn From the Past
Responsible public health authorities would steer clear of xenotransplantation in the interest of human health, particularly in light of the knowledge that animal viruses can jump the species barrier and kill humans. HIV - the virus that causes AIDS - may be a simian immunodeficiency virus (SIV) that leapt the species barrier in central Africa. Health authorities were unable to prevent the worldwide spread of HIV infection. Similarly, they were unable to prevent Ebola outbreaks in Sudan, Zaire (1976, 1979, 1995) and the US (1989, 1996). Furthermore, there is evidence that humans have become ill after consuming or being injected with animal materials. There is a reported link between the smallpox vaccine (derived from animal cells) and AIDS, a recently acknowledged link between human lung, brain and bone cancer and the SV (simian virus) 40 (found in old batches of the Salk polio vaccine), and the threat of emerging infectious diseases, including human Creutzfeldt-Jakob Disease (CJD) from the consumption of "mad cows" in Europe, the Netherlands, and the US.

5. Why Nonhuman Primates Should Not Be Used As Organ "Donors"
Baboon viruses flourish on human tissue cultures, before killing the cultures. There are over 20 known, potentially lethal viruses that can be transmitted from nonhuman primates to humans, including Ebola, Marburg, hepatitis A and B, herpes B, SV40, and SIV. Numerous scientists have urged US public health agencies to exclude primates as donors for xenotransplantation.

6. Why Pigs Should Not Be Used As Organ "Donors"
Given the acknowledged danger from nonhuman primate viruses, pigs are being considered as the choice "donor" animals for xenotransplants. However, pig retroviruses have infected human kidney cells in vitro; and virologists believe that many pig viruses have not been adequately studied. Viruses that are harmless to their animal hosts, can be deadly when transmitted to humans. For example, Macaque herpes is harmless to Macaque monkeys, but lethal to humans. The deadly human influenza virus of 1918 that killed more than 20 million people worldwide was a mutation of a swine flu virus that evolved from American pigs and was spread around the world by US troops. Leptospirosis (which produces liver and kidney damage), and erysipelas (a skin infection), are among the a pproximately 25 known diseases that can be acquired from pigs, all of which could easily affect immunosuppressed humans. There may be myriad unknown "pig diseases" still to be discovered.
In addition, physiological and anatomical differences between humans and pigs call into question the rationale for their use. These include differences in life-span, heart rate, blood pressure, metabolism, immunology, and regulatory hormones. A pig heart put into a human will turn black and stop beating in fifteen minutes. There is no clinical evidence to suggest that this acute cellular and vascular rejection will ever be overcome, or that organs from genetically bred pigs are any less likely to be rejected by the human body than those from conventional pigs. Moreover, the massive doses of immunosuppressive drugs that would be required for such an operation would likely cause severe toxicity, and increase the patient's chances of developing cancer.

7. Xenotransplantation Gives Animal Viruses Easy Access to Humans
Transplanting living animal organs into humans circumvents the natural barriers (such as skin and gastrointestinal tract) that prevent infection, thereby facilitating the transmission of infectious diseases from animals to humans.

8. No Way To Screen For Unknown Viruses
There is no way to screen for unknown viruses. Proceeding with xenotransplantation could expose patients and non-patients to a host of new animal viruses which could remain dormant for months or years before being detected.
Many viruses, as innocuous as the common cold or as lethal as Ebola, can be transmitted via a mere cough or sneeze. An animal virus residing in a xenograft recipient might become airborne, infecting scores of people, and causing a potentially deadly viral epidemic of global proportions akin to HIV or worse. It is highly unlikely that scientists and health care workers would be prepared to cope with such a scenario.

9. Unanswered Medico-Legal Questions
Would the US government be prepared to compensate victims of xenogeneic infections (such as people who may inadvertently contract an infection from a xenograft recipient)? The French government was forced to establish a $2.2 billion fund to compensate victims of AIDS-contaminated blood transfusions administered between 1980 and 1985. Compensation claims in the US have been filed by Persian Gulf War veterans, victims of secret government-sanctioned radiation and syphilis experiments, Vietnam war veterans exposed to Agent Orange, and parents of vaccine-damaged children. The government may now also be held liable for failing to protect citizens from SV40-contaminated polio vaccine. And what about patients who may choose to participate in privately-funded research where there are no mechanisms of accountability to federal health authorities, and little chance (for patients and non-patients) of receiving remuneration for injury or death. Can we afford another public health catastrophe?

10. The Myth of the "Germ-Free" Animal
Xenotransplant proponents claim that they will breed "germ-free" animals to diminish the risk of viral transmission. But in its June 1996 report, the Institute of Medicine acknowledged that "it is not possible to have completely pathogen-free animals, even those derived by Cesarean section, because some potentially infectious agents are passed in the genome and others may be passed transplacentally." Some British virologists say that it would be "a daunting task to eliminate infectious retroviruses from pigs to be used for xenotransplantation, given that [they] estimate approximately 50 PERV [pig endogenous retroviruses] per pig genome."

11. Weak Regulatory Oversight, and Human Error and Negligence, Would Facilitate Disease Transmission
Proposed regulatory oversight of xenotransplantation procedures is weak and would likely be highly flawed. Virologist Jonathan Allan has stated that, "in choosing voluntary guidelines to be enforced at a local level [via local institutional review boards], . . . the FDA/CDC committee has chosen the least stringent and possibly least successful method of policing these transplant procedures.
Moreover, in all areas of human activity, particularly when money is involved, the potential for fraud, error, and negligence exists. In the past, such behavior has placed human health at considerable risk. Witness the HIV-contaminated blood scandals in France, China, Japan, and the US, for example, in which employees and/or medical authorities knowingly allowed HIV-contaminated blood to be used for transfusions and blood-clotting treatments for hemophiliacs.
Given the enormous amount of data, paperwork, and filing xenotransplant procedures would generate, it would be naive (given human nature) to assume that data will be properly recorded, stored, reviewed, and updated. Regulatory mechanisms often fail to prevent or correct these errors and/or behaviors, the consequences of which could be disastrous in the face of a xenogeneic infection.

12. The Environmental Problems Posed By Xenotransplantation
Breeding animals for xenotransplantation would create a host of environmental problems (including soil and groundwater contamination) associated with the disposal of animal waste, and the carcasses of genetically modified animals and their offspring. Conventional farming and rendering operations have yet to solve these problems which continue to threaten public health across the US.

13. Eating Pigs Fuels Demand For Pig Organs
Ironically, it is precisely because people eat too many pigs (and other factory-farmed animals), and have unhealthy lifestyles, that pig organ transplants are being considered. A large majority of heart, liver, and kidney transplants could be prevented if people reduced their meat, alcohol, and tobacco consumption. Federal health authorities should be encouraging Americans to take responsibility for their health by eating properly, exercising, and avoiding cigarettes and alcohol.

14. We Should Be Investing In Alternatives To Xenotransplantation
Before allocating US funds to such an extreme technology as xenotransplantation, federal public health agencies have a duty to explore proven, less costly, and less risky alternatives. These include 1) preventive health and health maintenance programs aimed at reducing the need for transplants of all kinds, 2) administrative programs to increase human organ donations, 3) clinical research aimed at improving allotransplant technology, and 4) technologies which lessen our dependence on animals.
Lifestyle changes can reverse heart disease. Thirteen billion dollars in medical costs could be saved and 100,000 first-time heart attacks averted by the year 2005 if Americans simply reduced their average saturated fat intake by 3 percentage points.
Launching government-funded education campaigns aimed at increasing the pool of human organs should be considered. Neither the government nor the medical community have aggressively encouraged human organ donation. Currently, only 20% of those individuals who die "healthy" have arranged to donate their organs, even though 85% of the public supports organ donation.
Organ availability quadrupled in Austria when its 'presumed consent' law was enacted, and similar results prevail in other European countries. The law assumes that everyone is an organ donor unless they specify otherwise. If presumed consent legislation were enacted in the US, 75% of the adult US population (210,000,000) might become committed potential organ donors. Another approach involves creating a legal system of financial incentives to increase organ donation.
Finally, we could be investing in surgical techniques to repair malformed or poorly functioning organs. About 75% of patients who undergo a procedure called ventricular remodeling - in which a section of heart muscle is removed and reshaped - can be taken off the transplant waiting list.

15. Conclusion
Xenotransplantation places public health at substantial risk and hence is an unacceptable technology. Given our society's poor track record in managing the consequences of modern science and technology, including the increasing lethality of military weapons, environmental pollution, rainforest destruction, exponential population growth, and AIDS, we must honestly ask ourselves whether we have the wisdom and moral maturity needed to deal with the consequences of xenotransplantation and related genetic technologies. Until that question is publicly debated and, if ever, answered, logic dictates a policy of restraint and humility. In light of epidemiological, public health, medical, scientific, economic, and environmental issues surrounding xenotransplantation, the Medical Research Modernization Committee advocates an indefinite freeze on all forms of experimentation and clinical application of the technology.

All points made in this essay are documented in the full report, which is available from the MRMC. Send check or money order in the amount of $5 (or $3 each for 10 copies or more) to: MRMC at:

MRMC
P.O. Box 201791
Cleveland, Ohio 44120
(216) 283-6702 (phone and fax)