CRT's Comments to the US Food and Drug Administration on "Public Health Issues Posed by the Use of Nonhuman Primate Xenografts"

A fully-referenced hard-copy of the following document, including 102 footnotes, is available from CRT.

Dockets Management Branch (HFA-305)
Food and Drug Administration
5630 Fishers Lane, Rm. 1061
Rockville, MD 20852

Re: Docket No. 99D-0557
Public Health Issues Posed by the Use of Nonhuman Primate Xenografts
Federal Register, April 6, 1999

July 2, 1999

To whom it may concern:

The Campaign for Responsible Transplantation (CRT) is an international coalition of physicians, scientists and 70 public interest groups representing 2 million people. CRT was launched on January 20, 1998 out of concern over the irresponsible rush to commercialize xenotransplantation. CRT believes that xenotransplantation poses a grave danger to public health because of the risk of transferring potentially deadly zoonotic viruses to the human population. If it is developed further, xenotransplantation will also burden society with a host of complex regulatory, administrative, financial, legal, social, ethical, and environmental problems. Despite this, the technology is receiving substantial public and private financing with virtually no public consultation. The public must be given a voice in the debate about xenotransplantation. CRT aims to be that voice.

The FDA's Guidelines on Nonhuman Primate Xenografts are Arbitrary and Irresponsible

"[W]hether the risk of infectious diseases posed by xenografts obtained from pigs is less than that posed by xenografts obtained from nonhuman primates remains unclear."
Eda T. Bloom [FDA], Austine D. Moulton [FDA], Amy P. Patterson [FDA], Louisa E. Chapman [CDC], Judy McCoy, "Xenotransplantation: The Potential and the Challenges," Critical Care Nurse, Vol. 19, No. 2, (April 1999): 80.

"Everybody agrees that xenotransplantation is a risk — even the head of the FDA."
- Fritz H. Bach quoted in Kristine Novak, "US FDA to Issue New Rules on Xenotransplantation," Nature Medicine Vol. 4, No. 8 (August 1998): 876.

CRT would like to comment on the Food and Drug Administration's (FDA's) guidelines on "Public Health Issues Posed by the Use of Nonhuman Primate Xenografts," issued April 6, 1999. The guidelines instituted a de facto ban on nonhuman primate xenografts because they would expose patients and the public to "significant infectious disease risk." Indeed, the risks of using nonhuman primates as donors in xenotransplants have been elucidated in detail in the scientific literature, most notably by virologists like Jonathan Allan, Frederick Murphy, and others.

However, the FDA guidelines regrettably stopped short of banning nonhuman primate xenografts altogether. Instead, they encourage still further research on the risks posed by nonhuman primate xenografts, thereby leaving the door open for such xenografts to be carried out in the future. "On [the] one hand, the real implications of possible harm to people are recognized, while on the other, the need for knowledge, without reference to human consequences, seems to prevail."

CRT believes that, if the FDA was serious about protecting the public from "significant infectious disease risk(s)," it would have banned xenografts outright.

Equally disturbing is the fact that the April 6th guidelines entirely failed to address the dangers to public health posed by the use of xenografts from other nonhuman species such as pigs. This is illogical considering that pigs are being touted as the source animals of choice for xenotransplants, and that scientists within the FDA (and the Centers for Disease Control) have acknowledged the potential dangers posed by porcine xenografts.

The guidelines are also extremely negligent in light of knowledge that:

• several documents have described the nature of porcine infectious diseases; and it is known that pigs can carry bacterial, viral, fungal, protozoal and helminth pathogens,

• most cell lines derived from porcine tissues actively produce type C retroviruses,

• recent studies have demonstrated the infectivity of human cells by porcine endogenous retroviruses (PERVs). (PERVs' replication capacity was found to increase when passaged in human kidney cells), and

• journal articles have suggested possible transmission of porcine viruses, such as pseudorabies, to human recipients of porcine islet cells.

CRT hopes that the FDA's failure to address the dangers posed by porcine xenografts was not the result of lobbying by biotechnology companies like Novartis who have made/are making enormous investments in breeding "humanized" pigs for xenotransplants(?) Surely the FDA would not risk the public's health and safety to safeguard corporate profits(?)

Even xenotransplant researcher Fritz Bach, a paid consultant to Novartis, writes:

"[T]he FDA has issued guidelines that essentially exclude the baboon as a donor [in xenotransplants]. This has been done on the basis, at least in part, of the perceived higher risk of infection if baboons rather than pigs are used as donors. The baboon as a donor may well pose a higher infectious risk than the pig, but in fact we do not know the extent of the risk presented by either animal. Given this ignorance, is it not somewhat incongruous to conclude that the risk of using baboons is too great while the risk of using the pig is acceptable? From the ethical point of view, both pose a risk to society . . ."

Indeed numerous scientific articles have warned of the risks of using pigs, transgenic or otherwise, as source animals in xenotransplants (See Tables 1, 2, and 3 below).

Aside from the documented evidence of porcine endogenous retroviruses (PERVs) infecting human cells in vitro, and of possible transmission of porcine viruses to human recipients of porcine islet cells, there is evidence of human contamination and/or infection by:

• porcine rhabdoviruses (i.e. vesicular stomatitis virus),

• picornaviruses (i.e. foot-and-mouth disease, swine vesicular disease virus),

• swine influenza,

• paramyxovirus,

• and the novel "Nipah" viral encephalitis virus that recently infected over 250 people, induced relapses in several patients, killed 111, and led to the mass slaughter of some one million pigs and thousands of dogs, goats and sheep in Malaysia.

Pigs also carry prion proteins that could be transmitted to humans, and are likely to carry numerous viruses and infectious organisms that have yet to be identified.

Borie, et al., write that, in the context of xenotransplantation:

• Bacteria could theoretically be transmitted to humans in the event of bacteremia, occurring during organ harvesting. Current procedures of organ preservation before grafting would not necessarily circumvent the risk because bacterial growth at temperatures close to 0O C has been documented for bacteria like Yersinia. Detection of bacteria with current assays may prove difficult.

• In humans, liver abcesses caused by Entamoeba histolytica, and gastrointestnal infection by Entamoeba polecki, commonly found in pigs, have been documented. Pig organs may be infested with parasites. Such parasites may not currently be recognized as zoonoses and might become established in immunosuppressed patients.

• Numerous fungal infections, in humans and pigs, are latent in healthy individuals, but may become activated after host defenses are weakened by immunosuppression.

• Pigs carry a broad spectrum of potentially zoonotic viruses (See Table 3). These cause a wide range of symptoms in humans, including fever and general malaise, sores on the face or feet, neurological disorders, meningitis, and death. Pigs may also act as "mixing vessels" for viruses from other mammals and birds.

The FDA omitted this evidence in its April 6, 1999 guidelines. CRT believes that such an omission is arbitrary and irresponsible. Moreover, it is inconceivable that the FDA would continue to approve clinical experiments with porcine cells, tissues and organs 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."

Xenotransplantation poses inherent disease risks to patients and non-patients alike. Non-patients include animal handlers, surgical team members who harvest and implant animal organs, lab workers handling clinical specimens from xenotransplant recipients, nurses and others who would provide medical care to the patient(s), relatives and friends of the patient, and the public at large.

CRT therefore believes that, if the FDA's mission is truly to "protect the public health," the agency's April 6, 1999 guidelines should have included a prohibition on all porcine and nonhuman primate xenografts.

Xenotransplantation Will Add to the "Current Disease Burden"

"The primary aim of public health policy should be prevention."
- Jonathan S. Allan, "The Risk of Using Baboons as Transplant Donors: Exogenous and Endogenous Viruses," Annals of the New York Academy of Sciences, Vol. 862 (1998): 95.

World Health Organization (WHO) infectious disease experts F.X. Meslin, et al., say that major infectious diseases kill an estimated 52 million people worldwide. Deaths from infectious diseases in the U.S. rose 58% between 1980 and 1992. And the rate at which patients picked up infections in U.S. hospitals rose by 36% in 1995 (the latest year for which figures were available). Xenotransplantation, Meslin et al. say, could spread "novel communicable diseases," thereby adding to the "current disease burden." This is not paranoid speculation. Within the last 30 years, a number of zoonotic agents have been transmitted to humans, resulting in subsequent human-to-human transmission. These include AIDS, (thought to have first been transmitted from chimpanzees to humans), , swine influenza, Marburg filovirus, Ebola virus, and Crimean-Congo hemorrhagic fever virus.

Identifying, treating, and controlling emerging infectious diseases and pathogens have created enormous challenges. The WHO World Health Report, 1996, states that, despite the emergence of some 30 new infectious diseases in the last 20 years, (including new variant Creutzfeldt-Jakob disease ), "there is still a lack of national and international political will and resources to develop and support the systems necessary to detect them and stop their spread. Without doubt, diseases as yet unknown but with the potential to be the AIDS of tomorrow, lurk in the shadows."

Numerous public health and infectious disease experts have expressed their concern about the use of xenotransplantation.

French virologist Claude Chastel has said that xenotransplantation could create "a new infectious Chernobyl." Australian virologist Peter Collignon has said that, "[t]ransplanting organs and tissues from animals to humans is one of the best experiments we could devise to 'create' new infectious agents." Jonathan Stoye, a virologist at the National Institute for Medical Research in London, has said, "[i]t is . . . imperative that we consider the threat posed by [porcine] retrovirus replication both to the individual transplant recipient as well as to society as a whole . . ." Even Imutran, the British firm developing transgenic pigs for xenotransplantation, acknowledges "the risk of transmitting a pig pathogen to a human" via xenotransplants.

American virologist Jonathan Allan has noted that it is impossible to screen for viruses that have yet to be discovered and says, "[s]eldom, if ever, have we had as much knowledge to prevent a future epidemic. What is lacking is the wisdom to act upon that knowledge."

The data that fuel these concerns are numerous and will be presented below.

Risks of Transplanting Porcine Cells, Tissue and Organs into Humans — the Evidence

"[T]he risk of viral transmission from swine to human appears substantial."
- Dominic C. Borie, et al., Infection Control and Hospital Epidemiology, Vol. 19, No. 5 (May 1998): 357.

"PERV infection may have serious impact on the health of not only transplant recipients but also the human population at large, if spread of an undetected infectious agent into the community were to take place."
- Yasuhiro Takeuchi, et al., "Host Range and Interference Studies of Three Classes of Pig Endogenous Retrovirus," Journal of Virology, Vol. 72, No. 12 (December 1998): 9986-91.

"[T]ransplanting an organ carrying endogenous xenotropic provirus is equivalent to injecting a patient with live C-type virus. . . . to casually ignore its virtual certain presence in transplant trials makes little sense."
- Jonathan P. Stoye, John M. Coffin, "The Dangers of Xenotransplantation," Nature Medicine, Vol. 1, No., 11 (November 1995): 1100.

"Even if the risk of producing a "new infection" were as low as one in 1000 there could be at least 10 infections each year. Any one of these outbreaks could become a major public health problem with the potential for intercontinental spread."
- Peter J. Collignon, "Xenotransplantation: Do the Risks Outweigh the Benefits?," Medical Journal of Australia, Vol. 168 (18 May 1998): 519.

All vertebrate species, including humans, harbor endogenous retroviruses, acquired during the course of evolution, some of which are capable of infecting other species. Pigs, like nonhuman primates, harbor endogenous retroviruses. It is estimated that hundreds of different endogenous retroviruses may be present in one animal. Viruses infecting pigs that cannot be guaranteed to be absent from a xenograft include porcine retrovirus, porcine polyomavirus, porcine parvovirus, porcine circovirus, porcine cytomegalovirus, porcine reproductive and respiratory syndrome virus, influenza virus, porcine hepatitis E virus, and porcine herpesvirus. In pigs, the expression of retroviruses has been associated with the development of leukemia and lymphoma. In humans, retroviruses can induce chronic, life-long infections, "long latency malignancies, neurological disorders, wasting diseases and immunodeficiencies, for which treatment is limited or unavailable." Some retroviruses, such as simian foamy virus (SFV) an simian immunodeficiency virus (SIV), have spread to animal handlers with occupational exposures to baboons and rhesus monkeys, proving that transmission of retroviruses can occur under conditions that are less intimate than xenotranslantation.

The potential for transmission of porcine retroviruses to xenograft recipients is a significant concern for xenotransplantation.

Pigs harbor type C endogenous retroviruses. At least two infectious variants of porcine endogenous proviruses, dubbed PERV-A and PERV-B, are widely distributed in different organs, cells and tissues (spleen, heart, kidney, liver, lung, thymus) of different breeds of pigs. These retroviruses are passed from mother to offspring and therefore cannot be eliminated by the conventional techniques used to generate specific pathogen-free animals. Furthermore, specific-pathogen-free pigs may be silent carriers of enteric organisms such as micrococci, streptococci D, and colibacillus; and contamination by as-yet unrecognized pathogens will always be possible. More importantly, 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 PERVs and possibly other infectious organisms.

Preliminary results from three separate studies of (a total of 20) patients exposed to porcine cells suggested the absence of PERV infection in those patients.

However, the studies have numerous problems. First, the small number of people used in the studies are not statistically significant. Second, it is generally accepted that screening assays for detecting human infection by pig pathogens are not where they need to be yet. Such assays cannot screen for novel or emerging infectious agents, so that negative results cannot guarantee the absence of a retrovirus; and "assays for retroviruses of veterinary importance are less well developed and characterized than assays for human retroviruses." Moreover, Borie et al write that "most current serological tests probably are of limited value in immunosuppressed patients." Consequently, the antibody-based assays used to detect PERV infections in the afore-mentioned studies may not have been powerful enough to detect PERV infection, the neutralizing assays may have missed infection, and/or may have produced false negatives, for which there is no control mechanism. Third, plasma samples used to analyze patients' xeno ntibody responses are frozen (often at -70 C) and thawed at very high temperatures. Viruses are very unstable; it is unknown whether such extreme temperature changes could alter PERV and impact assay results. Lastly, as pointed out by virologist Jonathan Stoye: "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. Brown, et al., concur that "[w]idespread infections in the human community are established most efficiently when persistent infections with continuous transmissibility, but delayed disease onset, occur. For this reason, the public health consequences of xenogeneic infections could be most profound when the i mediate pathogenicity in the infected individual is least evident. Thus the presence of retroviruses in source animals and xenografts procured from them might pose the greatest concern."

Conventional Human Exposure to Pigs is Not a Predictor of Xenotransplantation's Effects

Some have suggested that humans have co-existed with, and eaten, pigs for centuries with allegedly no ill effects. This statement is inaccurate and ignores several important facts.

First, it ignores the calamitous effects of the 1918 swine flu influenza that killed 20-40 million people worldwide.

Second, pig farmers suffer high rates of respiratory ailments, pneumonia, lung scarring, animal bites and chemical poisoning.

Third, virologists point out that placing animal organs directly into humans circumvents all the natural barriers designed to prevent infection. The genetic modification, or "humanization,"of pigs could provide an opportunity for animal viruses to fool the human immune system and "hide" inside the human body. German virologist Joachim Denner and others point out that retroviral infections from pigs may recombine with human endogenous retroviruses, leading to recombinant "superviruses" with unknown, and possibly more virulent properties. These could become preadapted for human infection and subsequent human-to-human transmission. Some recombinant retroviruses have been shown to induce cancer. Accurate screening for such viruses may be difficult.

In this vein, some scientists are concerned that xenotransplants could alter the human gene pool, favor the evolution of porcine-human chimeras, and result in the production of diseases that are analogous to inborn errors of metabolism — a profoundly disturbing issue that has received little attention.

Also of concern is the genetic manipulation of the non-consenting animals themselves. Transgenic manipulation and cloning, (which would both be used to create pigs for xenotransplants), are still imprecise techniques which cause tremendous animal suffering and raise many ethical, social and religious issues. As one bioethicist remarked, "[W]e would have to judge that animals' interests matter very little indeed for the direct harm that xenotransplantation would impose on them . . . "

Lastly, it is ironically because people eat too much pork and other meat, (and drink, smoke, and don't exercise), that pig organ transplants are being considered.

Meat consumption has been definitively linked with the onset of heart disease, diabetes, and many forms of cancer. Meanwhile, lifestyle changes have proven capable of reversing heart disease; and diabetes — the most common condition found in patients who need kidney transplants — is largely controllable through diet and lifestyle changes. An article in the Journal of the American Dietetic Association suggested that $13 billion 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 one to three percentage points. In contrast, a study published in Preventive Medicine (November 1995) revealed that meat-eating is responsible for $61.4 billion in annual health care costs.

Therefore, the notion that xenotransplantation is somehow safe, justifiable, or desirable because of humans' historical agricultural "relationship" with pigs is rejected by CRT.

Public Attitudes Towards Xenotransplantation

It is far from clear, based on the limited number of surveys that have been performed, that the public is in favor of xenotransplantation. In fact, most recent surveys have been performed outside of the U.S. and these have demonstrated an aversion to xenotransplantation. One Australian study found negative attitudes among patients awaiting transplants. Other studies, also from Australia, by Paula J. Mohacsi, et al., found that opposition to xenotransplantation was not limited to acute care nurses, but was also expressed by others, including animal rights activists, actual transplant recipients, potential transplant recipients and the general community. Some British authors have suggested that nurses may have a particular aversion to xenotransplants, and may not want to care for xenograft patients for fear of becoming infected with a zoonotic virus.

A Swedish study of people's attitudes towards receiving organs and tissues from different sources revealed that 77% of respondents preferred organs from living human donors, and only 40% were prepared to accept an animal organ. Women were less prepared than men to accept xenotransplants. A recent European survey on biotechnology indicated that xenotransplantation was perceived to involve unacceptable risks and that the use of transgenic animals as a source was seen as "morally dubious."

In one American study done by the National Kidney Foundation in 1998, and funded by Novartis, it was not surprising to find that 62% of Americans would allegedly favor xenotransplants, however, "opposition to xenotransplantation was strongest among the best informed." Other articles implied that Americans, in fact, had 'visceral reactions against xenotransplants.'

Hence, it is not clear that xenotransplantation is acceptable to the American public. The FDA should be careful about promoting a risky technology like xenotransplantation that is not widely accepted, but that may have widespread deleterious public health effects. Particularly because questions about liability, in the event of a public health disaster resulting from xenotransplantation, have yet to be addressed by FDA or the Department of Health and Human Services.

Xenotransplantation is clearly less acceptable to non-Americans. In January 1999, the Council of Europe, a barometer of public opinion for 40 European countries, recommended a moratorium on xenotransplants due to fears of a threat to public health. The FDA should respect and heed public opinion in other countries since a xenogeneic infection spread from a xenograft recipient in the U.S., should s/he survive, could potentially cause a global pandemic.

Alternative Ways of Solving the Alleged Organ Shortage

There are safer, more cost-effective, and humane alternatives to xenotransplantation that are not being explored by regulatory authorities. The priority should be aggressive investment in, and implementation of population-based preventive medicine programs. If implemented on a grand scale, such programs could drastically curtail disease rates, reduce the demand for human organs (and surgical procedures of all kinds), save money, and eliminate the prospect of dangerous cross-species transplants. (A note to policy-makers: Defeatist attitudes will not successful programs make).

Neither the government nor the medical community have aggressively encouraged human organ donation; and several studies have revealed problems in the overall coordination of organ procurement programs, as well as inadequate training of neuroscience nurses, and administrative problems at the federal level. A General Accounting Office report on organ donation (April 1998) found that the Heath Care Finance Administration (HCFA), which sets performance standards for organ procurement organizations, has not considered all available methods for determining, and thus increasing, the number of potential organ donors. Consequently, HCFA has not accurately evaluated the number of usable organs in the U.S., suggesting that the number of available organs may be much higher than previously thought. The findings of this report must be investigated fully.

Launching education campaigns and hospital training programs aimed at increasing human organ donation should be considered. One study found that families of potential organ donors are receiving inadequate information to make informed choices about organ donation, and their emotional needs are not always met. Another found that, the investment of dedicated race-sensitive personnel in large urban county trauma facilities can result in a significant increase in donor conversion rates. Another study suggested instituting nationally standardized hospital procedures to ensure that all potential donors are identified, that every family is approached about the possibility of organ donation, and that the request is properly structured.

Several suggestions for increasing overall organ donation rates have been proposed: increasing recovery of organs from non-heart beating donors, re-evaluating the criteria for brain death, and expanding the donor criteria to include older donors, for example. A study in the January 22, 1998 issue of the New England Journal of Medicine, reported that cadaveric organ donation — using kidneys from newly deceased people whose hearts have stopped beating — could increase the supply of kidneys two-to-five fold. Others have suggested using market incentives to increase organ donation.

In Norway, between 45-50% of transplanted kidneys come from living donors. Renal transplantation from living donors has been successfully performed in the U.S., and is associated with an 85% increase in rate of organ donations from living donors. Split organ transplants of livers from cadaveric donors have been successfully performed in Israel and elsewhere. These transplants could save two lives instead of one and reduce the number of people on transplant waiting lists. Some surgeons have proposed surgical techniques, such as ventricular remodeling, to avert transplantation. About 75% of patients who undergo this procedure — in which a section of heart muscle is removed and reshaped — can be taken off the transplant waiting list. The use of temporary "bionic hearts," placed alongside patients' ailing hearts, and removed upon recovery, have been successfully used in Britain to treat heart failure and avert heart transplants.

Many nations, including Austria, Spain, Belgium, and Singapore, have seen organ donation rates triple and quadruple after the passage of "presumed consent" or "opt out" legislative schemes, which assume that a person will donate his/her organs after death unless s/he specifies otherwise. Very little research has been done to determine the feasibility of such legislation in the United States. Clearly, if passed, such a law would solve the alleged organ shortage.

CRT believes that, before considering a technology as extreme, dangerous, expensive and inequitable as xenotransplantation, the Department of Health and Human Services (HHS) has an obligation to explore all the options available for increasing the supply of human organs, as well as investigate the utility of surgical techniques described above.

The Precautionary Principle: Ignored by FDA

"Do we really need xenotransplantation?"
- Gilles Beauchamp, "Ethics and Xenotransplantation," Canadian Journal of Surgery, Vol. 42, No. 1 (February 1999): 5-6.

As a federal agency with a mandate to "protect the public health," the FDA should honor the Precautionary Principle. The Precautionary Principle has been defined and incorporated into numerous international charters including the World Charter for Nature (1982), the Economic Summit of Industrialized Nations (1990), the Hague Recommendation on International Environmental Law (1991), Agenda 21 (Rio, 1992), and the Convention on Biological Diversity (1992), among others.

It instructs that:

1. People have a duty to take anticipatory action to prevent harm. When an activity poses threats to human health or the environment, precautionary measures should be taken to avoid that risk, even if some cause and effect relationships are not fully established scientifically. "This challenges the view that, until there is evidence that a new technology is harmful, it is acceptable to proceed with its development."

2. The burden of proof of harmlessness of a new technology, process, or activity lies with its proponents, not with the general public. Taxpayers should not have to pay for the development of xenotransplantation, nor should they pay to assess its safety.

3. Before using a new and potentially dangerous technology, process, or activity, those with decision-making authority have an obligation to examine a full range of non-harmful alternatives, including the alternative of doing nothing.

4. Some technologies pose too great a risk and should simply not be pursued. CRT believes that xenotransplantation falls into this category.

5. Decisions applying the precautionary principle must be open, informed and democratic and must include affected parties.

Given the risks posed by porcine xenografts and the FDA's apparent refusal to acknowledge them in its April 6th guidelines, CRT believes that the FDA has ignored the Precautionary Principle. This is unacceptable in light of the dangers posed by a technology like xenotransplantation.

Proposed Xenograft Registry is Problematic: Reports Cite FDA's "Weak Oversight"

FDA claims that it will establish a (taxpayer-funded) registry to archive patient and source animal tissue and serum samples into eternity, allowing the agency to (retrospectively) track new infections. Such a registry raises legal issues about jurisdiction, funding and privacy rights. Some lawyers believe that FDA is "already overburdened, under-budgeted, and is not in a position to accept responsibility for creating a registry of this nature without Congressional approval and backing." The American Society of Transplant Surgeons has objected to the registry due to "the magnitude of the task."

Furthermore, a registry can only do so much. For example, xenograft recipients, should they survive, may engage in risky behavior that cannot be controlled without placing potentially illegal restrictions on their freedoms. And yet Frederickson writes: "The ignorance of close contacts that is fostered by the present regulatory scheme ultimately will place the public health at greatest risk."

More importantly, there is no guarantee that the FDA will be able to successfully monitor xenograft tissues since it has already failed to provide oversight for human tissue banks and was cited for "weak oversight" of tracking and recall systems for defective medical devices.

Finally, there are questions about whether the FDA can be trusted to assess the safety of xenotransplants and protect the public from harm that may result. FDA regulations allowed Baxter International to conduct an ill-fated blood substitute trial in 1998, without the informed consent of patients in the study, leading to the death of 24 patients. In 1996, FDA approved the use of a bioengineered plasma product that transmitted hepatitis A to several hemophiliacs. And U.S. consumer groups recently challenged the FDA's decision to approve a controversial recombinant bovine growth hormone (rBGH), suspected of increasing the risk of human breast and prostate cancer. Experts charged that the FDA concealed and/or misrepresented scientific data relevant to the hormone's safety; rBGH was approved and marketed, despite widespread consumer objections, and without appropriate labeling.

Conclusion

The FDA's guidelines on "Public Health Issues Posed by the Use of Nonhuman Primate Xenografts" are arbitrary and irresponsible due to their intentional exclusion of pigs as a species of concern for public health.

This document has primarily discussed the risks posed by pigs as source animals for xenotransplants. CRT believes that the risk of transmitting nonhuman animal viruses to patients and non-patients through xenotransplants, whether from pigs, nonhuman primates, or other animals, though presently unquantifiable, is unacceptable. To disregard this risk to public health and dismiss it in favor of continuing clinical trials, is negligent and flies in the face of the Precautionary Principle. In addition to creating a potential public health nightmare, xenotransplantation would burden society with complex regulatory, administrative, financial, legal, social, ethical, and environmental problems that society should not have to deal with. Xenotransplantation imposes unacceptable suffering on highly intelligent, social, and sensitive animals such as pigs and baboons. The costs of xenotransplantation, in terms of animal and human suffering, do not outweigh its alleged benefits, which have yet to be demonstrated.

We have described a range of safer, more humane and cost-effective ways to solve the alleged human organ shortage. These options should be exhaustively explored by public health agencies before xenotransplantation is even considered. CRT believes, in any case, that a technology as fraught with problems as xenotranspantation, should not be considered by responsible health authorities.

At least two General Accounting Office reports, and several news reports, have raised doubts about the FDA's ability to protect the public health. Industry has successfully pressured the agency to bring new products to market, regardless of the costs to human health. It is doubtful that the FDA's regulatory record would magically improve, particularly since xenotransplantation presents an entirely new and difficult set of regulatory challenges.

The Department of Health and Human Services has, so far, not addressed liability issues vis-a-vis xenotransplantation, (i.e. regarding the handling of claims arising from injury, illness or death resulting from activities or procedures involving xenotransplantation),

Given the above, CRT demands that the FDA institute a formal ban on xenotransplantation, from all nonhuman species immediately.

Sincerely,

Alix Fano, MA
Director
On behalf of CRT's 2 million members