DEPARTMENT OF HEALTH AND HUMAN SERVICES
TABLE OF CONTENTS
Pursuant to the Right to Petition Government Clause
contained in the First Amendment of the United States Constitution1,
the Administrative Procedure Act2, and the Department of Health
and Human Services' ("HHS") governing statutes and implementing regulations3,
petitioners file this petition for rulemaking with HHS.The issuance of the
"Draft Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation"
(hereinafter "xenotransplantation guidelines") by HHS is arbitrary and capricious,
an abuse of agency discretion, and otherwise not in accordance with law. Furthermore,
before issuing the xenotransplantation guidelines, the agency failed to comply
with the requirements of NEPA. Consistent with HHS' governing statutes and
regulations, petitioners respectfully request the Secretary to undertake the
II. Individual petitioners (home addresses
have been shortened)
Christopher Anderegg, M.D., Ph.D. (physician)
Marc Bekoff, Ph.D. (animal behaviorist, Guggenheim fellow)
Irwin D. Bross, Ph.D., President (biostatistician, epidemiologist,
public health scientist)
Lynda Birke, Ph.D. (biologist)
Geoffrey Campbell, M.D., F.R.C.S., M.B.Ch.B., B.S. (plastic
and reconstructive surgeon)
Claude Emile Chastel, Ph.D. (virologist)
Holly Cheever, D.V.M. (veterinarian)
Murry J. Cohen, M.D., Co-Chair (psychiatrist)
Pietro Croce, M.D. (retired professor of clinical and anatomical
Paul F. Cunningham, Ph.D. (associate professor of psychology)
Patrick Dixon, M.A., M.B.B.S., (Director, Global Change, Ltd.)
Donald Doll, M.D., (hematologist, oncologist)
J. Scott Douglas, (Founding Director, Committee for Children
and victim of AIDS)
Clare Druce (Director, Farm Animal Welfare Network)
Zoe C. Erwin (concerned citizen)
Moneim A. Fadali, M.D., F.A.C.S., F.R.C.S., F.A.C.C., F.A.C.C.P.
Emily A. Fano, M.A. (concerned citizen)
Pamela G. Fernandez, Ph.D.(agronomist)
Roger S. Fouts, Ph.D (professor of psychology)
Jane M. Fraser, B.V.M.S., M.R.C.V.S. (veterinarian)
Helen Fullerton, Ph.D. (biochemist)
Emanuel Goldman, Ph.D. (microbiologist)
James F. Grillo, M.D., F.A.C.S. (head and neck surgeon)
Robert L. Hendley, M.D. (ophthalmology)
Mae-Wan Ho, Ph.D. (biologist)
Jennifer Johnson (concerned citizen)
Leonard J. Karlin, M.D. (pathologist, Medical Director, retired,
Elliot M. Katz, D.V.M. (veterinarian)
Dr. Janne Kuil (concerned citizen)
Lorin Lindner, Ph.D., M.P.H. (Program Director, substance
abuse treatment program)
Deanna Z. Macek, M.D. (veterinarian)
Michael Mansfield, Q.C. (barrister)
Richard G. McLellan, M.D. (trauma surgeon)
Andre Menache, D.V.M., (veterinarian)
David S. Miller, MS, DVM (veterinarian)
Mark C. Niblack, M.D. (physician)
Jack Norris (concerned citizen)
Barbara Lee Perlmutter, M.D., Ph.D., (internal medicine, HIV/AIDS
Neil Ratner, M.D. (anesthesiologist)
Bina Robinson (concerned citizen and senior citizen)
Roy Selby, M.D., (neurosurgeon, heart transplant recipient)
Don Sloan, M.D. (Obstetrics and gynecology)
D. Edwards Smith, M.D., F.A.C.P. (Physician)
Verena Soldati (zoologist)
Les Stewart, D.D.S. (dentist)
Susan Stewart, R.N. (nurse)
Polly Strand (volunteer breast cancer peer counselor)
Robert L. Trimble, Executive Vice President and General Council
Robert J. Vergnani, M.D. (ophthalmology)
Jerry Vlasak, M.D., F.A.C.S., (trauma surgeon)
Richard W. Weiskopf, M.D., F.A.C.P. (primary care physician,
Although there is a shortage of human organs donated for transplantation, there is no convincing evidence "that the United States government and medical communities have consistently and aggressively worked to increase the supply of human organs available for transplantation."4 Instead, researchers are exploring the implantation of animal cells, tissues, and organs called "xenografts" into humans. This procedure is called "xenotransplantation." However, the current scientific information does not show that "xenotransplantation clinical experiments will work as promised or should be conducted on human patients needing realistic and reliable treatment options."5 Xenotransplantation has been repeatedly attempted since 1906, yet there has never been a successful animal-to-human whole organ transplant. Despite this failure rate, the National Institutes of Health ("NIH") has provided funding and the Food and Drug Administration ("FDA") has given approval for several human experiments, including using genetically engineered pig livers to filter human blood.6
Moreover, instead of regulating this dangerous procedure, the HHS agencies including NIH, FDA, and the Center for Disease Control ("CDC") issued voluntary guidelines entitled "Draft Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation."7 Members from the scientific community responded to these voluntary guidelines by stating that "these guidelines are unlikely to protect the public adequately and are insufficient to prevent the possible spread of a new infectious disease."8 Furthermore, many scientists are concerned that the use of xenotransplantation will create a great public health danger because the guidelines do not take seriously enough the likelihood that monkey and pig viruses may be transmitted to humans.9
In the xenotransplantation guidelines, HHS admits that "the spectrum of infectious agents transmitted via human organ transplantation has been well established, while the full spectrum of infectious agents potentially transmitted via xenograft transplantation is not well known. Infectious agents that produce minimal symptoms in animals may cause severe morbidity and mortality in humans."10 Indeed, some viruses may not produce disease until years after a person is infected. Already, scientists have identified several deadly viruses that have jumped from animals to humans, including AIDS11, bird flu12, herpes B13, Ebola, and Creutzfeldt Jakob Disease14. However, many uncertainties still exist regarding the variety and transmission of animal viruses. Many doctors fear that xenotransplantation may "unleash into the human population an AIDS-like virus that you can catch as easily as the common cold."15 Even the World Health Organization cautions that "the field of xenotransplantation brings with it the potential for introducing unwanted animal-origin infectious agents, both known and unknown, into the human population. These agents could cause disease in their new host. Dissemination beyond the original recipient into the general populati>
Transfer interrupted!16 Although cross-species transplants subject the recipient and the public to significant health risks, HHS chose a lenient method for monitoring the health effects from this procedure by constructing voluntary guidelines on xenotransplantation use. Consequently, HHS cannot guarantee that all researchers, institutions, and patients will choose to comply with the guidelines. As a result, human health may be jeopardized.
Despite the significant health concerns and uncertainties raised by the scientific community regarding the use of xenotransplantation, HHS issued the voluntary guidelines without performing either an environmental assessment or an environmental impact statement as required by NEPA. Additionally, contrary to the statutory requirements under NEPA, HHS issued the guidelines without considering any viable alternatives.
Public Health Service Act, 42 U.S.C. § 201 et seq.
When HHS issued the draft xenotransplantation guidelines,
the agency acted contrary to the scientific evidence and failed to consider
important factual issues and statutory requirements. By issuing voluntary
guidelines for a procedure that will most likely cause serious effects on
human health, HHS acted arbitrarily and capriciously.17 Next, HHS
failed to comply with NEPA. The agency should have conducted an environmental
assessment or environmental impact statement because xenotransplantation will
likely cause significant harm to human health and the environment. HHS also
failed to consider alternative methods as required by NEPA. There are several
alternative methods which should have been considered that are not only safer,
but also more cost effective than xenotransplantation. For the reasons discussed
below, the agency should immediately ban xenotransplantation.
An agency's action is judicially reviewable under the arbitrary and capricious standard. Under this standard, an agency must show a "rational connection between the facts found and the choice made."18 An agency action is arbitrary and capricious when the agency has relied on factors which Congress has not intended it to consider, entirely failed to consider an important aspect of the problem, offered an explanation for its decision that runs counter to the evidence before the agency, or is so implausible that it could not be ascribed to a difference in view or the product of agency expertise.19 In determining whether an agency decision was "arbitrary and capricious," a court must consider whether the decision was based on a reasoned evaluation of the relevant factors and whether there has been a clear error of judgment.20
In this case, HHS is required under the Public Health Service Act, 42 U.S.C. § 299a-2(b)(2), to consider certain factors when assessing health care technology. The Act requires the Administrator to consider "the safety, efficacy, and effectiveness, and, as appropriate, the legal, social, and ethical implications, and appropriate uses of such [health care] technologies . . . the Administrator shall also consider the cost effectiveness of such technologies." As described below, HHS did not adequately consider these elements.21 Instead, HHS issued the xenotransplantation guidelines despite the scientific evidence indicating that the xenograft recipient will suffer significant harm from this ineffective procedure. Furthermore, the agency did not adequately consider how to protect the public from contracting xenogeneic diseases or from incurring the large costs associated with the use of this procedure. The information presented below shows that HHS violated the Public Health Service Act by arbitrarily and capriciously publishing the guidelines.
The use of xenotransplantation is encouraged by HHS, yet
the agency repeatedly cautions throughout the voluntary guidelines that the
recipient is at risk of harm. HHS admits that "[t]he intimate contact between
the recipient and the xenograft, the associated disruption of anatomical barriers,
and immunosuppression of the recipient are more likely to facilitate interspecies
transmission of xenogeneic infectious agents than normalcontact between humans
and animals."22 Furthermore, the U.S. Committee on Xenograft Transplantation
warns that the risk of disease transmission through xenografts "must be considered
a real threat."23 By failing to adequately consider the safety
of the xenograft recipient before issuing the xenotransplantation guidelines,
HHS acted arbitrarily and capriciously.
The Institute of Medicine report on xenotransplantation concluded that "[b]ecause xenotransplants involve the direct insertion of potentially infected cells, tissues, or organs into humans, there is every reason to believe that the potential for transmission of infectious agents (some of which may not even now be recognized) from animals to human recipients is real."24 Scientists are currently aware of several animal viruses that have jumped the species barrier and caused illness in humans. For example, there is a reported link between: (1) the smallpox vaccine (which used animal cells) and AIDS25, (2) human lung, brain, and bone cancer and the simian virus 40 (found in old batches of the Salk polio vaccine)26, and (3) human Creutzfeldt Jakob Disease and the consumption of "mad cows."27
Some of the known pathogenic viruses that may pose a risk to xenotransplant recipients include: many adenoviruses, papovaviruses, papillomaviruses, parvoviruses, hepadnaviruses, morbilliviruses, filoviruses, hantaviruses, arenaviruses, arteriviruses, flaviviruses, and togaviruses . . . certain retroviruses (including endogenous retroviruses, mammalian type C and D retroviruses, lentiviruses, and human T cell leukemia virus/bovine leukemia virus-like viruses) and certain animal herpesviruses (including herpes simplex-like viruses, Epstein-Barr-like viruses, cytomegaloviruses, and HHV6-, 7-, and 8-like viruses) must be considered further.28
Based on the current scientific information, the number of known viruses is alarming. Thus, it is highly unlikely that any type of government guideline could prepare scientists and health care workers to cope with such a lengthy list of known and unknown dangers.
Any evidence showing that xenotransplantation is safe, should be highly scrutinized. For example, many scientists are skeptical of a recent study showing that no pig virus DNA or antibodies to pig viruses were found in patients who received xenografts. Critics point out that the study was small, short, and none of the patients received a whole organ, which provides a much larger reservoir of viruses.29 Furthermore, no one can say conclusively whether pig viruses are incubating in these patients.30 British scientist Robin Weiss asked, "If there are negative results does it mean no one's infected, or that you can't detect it?"31 Virologist Jonathan Allan explains that "[e]ven if the transplant recipient failed to develop any signs of disease associated with PERV [porcine endogenous retrovirus], it may still be 20 years or more before detailed epidemiological studies can be completed to ascertain what the pathogenic potential might be of a virus that begins to circulate in the human population."32
Unfortunately, the scientific unknowns regarding the existence and behavior of zoonotic viruses are numerous. In 1998, virologist Frederick Murphy wrote, "[n]o one could have predicted the emergence or zoonotic nature of the bovine spongiform encephalopathy prion in cattle . . . and certainly not . . .AIDS . . . [S]omewhat distinct strategies are needed to deal specifically with emerging zoonotic diseases, and these strategies have not been fully developed."33 In 1998, xenotransplant researcher Fritz Bach said, "Everybody agrees that xenotransplantation is a risk - even the head of the FDA. We don't know whether the first or any other patient receiving a [xeno]transplant could start an epidemic."34 In light of the numerous known and unknown animal viruses, the transmission of animal viruses to xenograft recipients is a real threat that HHS should have adequately considered.
HHS unsuccessfully attempts to minimize the dangers to human health from xenotransplantation by screening source animals. In the xenotransplantation guidelines, HHS outlines a section on "animal sources" designed to "minimize" the risk of transmitting infectious animal diseases to humans.35 Animals are to be screened for "infectious agents" and then maintained in a biosecure environment to minimize exposure to infectious vectors.36 The surveillance programs are supposed to be "adequate" although the term "adequate" is not defined anywhere in the guidelines.37 Furthermore, the precautions taken for screening animals for infectious diseases are illusory because HHS concedes that the source animals and "all procured cells, tissues and organs intended for clinical use" should be "as free as possible of infectious agents."38 In effect, HHS admits that a "germ-free" animal is impossible. Additionally admitting that potentially pathogenic organisms are difficult to exclude in specially bred animals "without extraordinary measures" is a breeder of laboratory animals, Charles River. Charles River also acknowledges that labs must select the agents for which they wish to screen due to the "prevalence of agents" and the "cost of screening."40 Furthermore, the Institute of Medicine report on xenotransplantation states 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."41 Similarly, scientists Jonathan Stoye and John Coffin explain that endogenous retroviruses "are widely distributed in mammalian species including pigs and baboons, potential donors for [xenotransplants]. Since they are inherited in the germ line in the form of proviral DNA, they are impossible to remove using the usual methods for deriving pathogen-free animals."42
Regardless of the scientific evidence described above along with HHS's own admission that it is impossible to obtain a "germ-free" animal, the agency provides minimal protection in the xenotransplantation guidelines for limiting animal viruses. In fact, HHS states that extensive screening of the source animal(s) may sometimes be limited "to ensure graft viability," and that imported animals and their offspring may be used if the animals belong to "a species or strain not available for use in the United States."43 History has shown, however, that this is dangerous advice. For example, importing monkeys into the United States for biomedical research has already placed the safety of Americans in jeopardy by exposing them to the deadly Ebola-Reston, Marburg and herpes B viruses. Monkey STLV may have resulted in cross-species HTLV-2, which causes human leukemia. Moreover, the hepatitis B virus may have originated from human exposure to asymptomatic chimpanzee carriers.44 These examples show that the use of imported animals is dangerous. Due to the impossibility of obtaining "germ-free" animal sources for xenograft recipients, HHS's limited screening method will not prevent the transmission of animal viruses.
The scientific evidence shows that no animal, whether transgenic or otherwise, can remain completely free of parasites or endogenous viruses. Some scientists believe that pigs may provide a safer source of tissues and organs for xenotransplantation than primates, particularly because humans and pigs have co-existed for centuries. However, scientific research demonstrates that this theory is erroneous. Placing a live pig organ directly into the body of an immunosuppressed patient creates an ideal condition for the transfer of porcine viruses to humans.45 Pigs can carry a number of bacterial, viral, fungal, protozoal, and helminth pathogens, and may even harbor prion diseases. Indeed, xenotransplant proponents admit that transmissible spongiform encephalopathy (TSE) "is a cause for concern in transgenic animals bred for xenotransplants.46
"Within the last year, several new viruses, or strains of viruses in pigs have emerged in experimental and farm settings. In 1997, British scientists discovered a pig C-type endogenous retrovirus called PERV-PK whose genes were scattered throughout the pig genome.47 The scientists found PERV in the hearts, spleens and kidneys of several breeds of pigs. They also found that PERV infected human kidney cells in vitro and replicated themselves until the viral particles "were no longer susceptible to destruction by the [human] immune system."48
After this discovery, two related but distinct classes of PERV (A and B) were identified. Both were found in several breeds of pigs and both infected human cells in culture.49 In response to this finding, many scientists voiced their concerns. British scientist Jonathan Stoye said, "[o]ur findings suggest that a xenotransplantation would increase the likelihood of the transmission of a pig virus."50 Virologist Jonathan Allan stated that "[t]hese results should compel public health agencies in the United States and elsewhere to regard animal to human transplantation as a melting pot for retroviruses that might result in recombinant viruses with altered pathogenicities."51 Norman Levinsky, a Boston University medical professor who chaired the Institute of Medicine's xenotransplantation committee, described the PERV findings as "scary."52
Later, in August 1998, scientists from Hannover Medical School in Germany reported that PERV is also produced by cells from pig aortas, livers, lungs, and skin - all tissues likely to be used for transplants. They suggested a "serious risk of retrovirus transfer after xenotransplantation."53 Also in 1998, an American team reportedly found another PERV, PERV MSL, embedded in the genes of white blood cells of miniature pigs.54
PERV are not the only concern for xenotransplant recipients. Other porcine viruses that could pose a danger to humans through xenotransplants include paramyxovirus (which causes flu-like symptoms in humans)55, porcine torovirus56, porcine rotavirus57, porcine circovirus (a wasting syndrome in young pigs)58, porcine reproductive and respiratory syndrome virus (PRRS)59, porcine pseudorabies virus60, an H3N2 swine virus which is entering humans more often than previously thought, and is a descendant of swine flu viruses from over a decade ago61, and a previously unrecognized strain of Hepatitis E virus that is very similar to the strain that causes disease in humans.
Already, studies have shown that veterinarians and laboratory researchers who work with pigs have a high risk of infection from zoonotic agents. Some of the porcine diseases that are known to be transmissible to humans include swine flu, leptospirosis, brucellosis, listeriosis, anthrax, erysipelas, herpes, toxoplasmosis, and ascariasis62. The use of pig organs for human transplantation raises public health concerns according to Robert H. Purcell, M.D., chief of the hepatitis viruses section in the National Institute of Allergy and Infectious Diseases in Bethesda who states that "[n]onpathogenic pig viruses could possibly become pathogenic in human transplant recipients [receiving] immuno-suppressing drugs."63
The above scientific information shows that xenotransplantation is not a safe procedure for the xenograft recipient. Considering the agency's admission that it is impossible to obtain a "germ-free" animal for xenotransplantation use, HHS is acting arbitrarily and capriciously in violation of the Public Health Service Act by issuing the xenotransplantation guidelines. Without demonstrating that there are any effective methods to protect the health of the transplant patient, HHS is jeopardizing the safety of the xenograft recipient by allowing the use of this procedure. Thus, there is no rational reason to permit xenotransplantation, and as a result, HHS should immediately ban its use.
HHS's issuance of the guidelines on the use of xenotransplantation without adequately considering the effectiveness and efficacy of this procedure is arbitrary and capricious. Instead of cautiously examining the scientific evidence, HHS has opened the door for researchers to actively transplant xenografts into humans. The history of xenotransplantation use demonstrates the ineffectiveness of this procedure, yet HHS endorses xenotransplantation by stating in the guidelines that "xenotransplantation shows promise for a wide range of diseases . . . and as an alternative source of cells, tissues and organs for clinical transplantations."64 HHS also encouraged the use of this procedure by providing millions of dollars in grant money to researchers.65
HHS's endorsement of xenotransplantation is inconsistent with the history and clinical evidence which shows that xenotransplantation is doomed to failure. Alexis Carrel, the French surgeon who was one of the first to transplant organs, graft veins, and skin between dogs, cats, and monkeys in the early 1900s, discouraged other surgeons from conducting similar experiments because his had all failed. Later, in 1984, Jacques Losman, a cardiac surgeon from the Beth Israel Hospital in Newark, who had worked with Christian Barnard's heart transplant team in South Africa said, "all animal experiments have shown that transplants from one species to another fail . . . I don't think there was much scientific basis to believe that this would work."66 Bioethicist Arthur Caplan, explains that "there's absolutely no basis in basic research for trying a pig liver in a human being given the differences in biology between people and pigs."67
These statements against the use of xenotransplantation
are supported by xenotransplantation's unsuccessful history. There have been
approximately 60 documented animal-to-human whole organ transplants since
1906 and all have proven unsuccessful.68 The following examples
illustrate these failures.
Due to the numerous differences between humans and animals,
xenotransplantation is not an effective procedure.87 Xenografts
are dangerous for human patients because the responses of grafted animal organs
to human pituitary, adrenal, thyroid, pancreatic, and sex hormones are unpredictable.88
Moreover, in a 1996 report, the U.K.'s Advisory Group on the Ethics of Xenotransplantation
The FDA's active support for xenotransplant research and development is inconsistent with the agency's previous decisions. For example, in 1991, the FDA ordered a recall of a disinfectant, Sporicidin, used by dentists and doctors worldwide to sterilize equipment, claiming that it did not adequately protect patients from infectious microorganisms. The FDA Commissioner at that time, David Kessler, stated that "[w]e will not tolerate products that would permit the transmission of disease from one patient to another."93 However, when nine noted scientists asked the agency to enact a moratorium on xenotransplantation in the interest of public health in January 1998, the FDA refused.94 Instead of imposing a moratorium, the FDA approved the following clinical trials: pig neuronal cells into Parkinson's and Huntington's Disease patients, cow adrenal cells into cancer patients, pig liver cells for liver failure patients, and pig pancreas cells into diabetes patients.95
FDA approved these clinical trials in 1997, even though a team of xenotransplant researchers acknowledged that "[pig islet cell transplantation] . . . has to date not been successful in providing long-term insulin production by pig islet cells."96 In addition, staff scientists at the FDA's Center for Biologics Evaluation and Research (CBER) explained that transplantation of nonhuman live cells presents a risk of introducing novel pathogens into the human population.97 Experiments conducted by CBER scientists show that "activation of immune cells derived from pig blood resulted in release and transfer of an infectious retrovirus which could infect human cells."98 The FDA also approved in 1997, a phase 1 multicenter trial using transgenic pig livers as temporary "bridges" to filter the blood of patients awaiting human liver transplants.99 These experiments are neither safe nor effective. In response to this FDA approval, British scientist Jonathan Stoye said, "If you're going to hook someone up to a pig liver outside their body for a long period, I don't think it's much safer than an actual [whole organ] transplant."100 Other xenotransplant researchers stated that "[a]lthough there has been one relatively recent attempt at pig heart transplantation in a human and another of auxilliary pig liver transplantation, these both proved unsuccessful, and the problem of hyperacute rejection is yet to be resolved."101
Another agency involved with the research and development of xenotransplantation is the CDC. Although the CDC is working to develop the use of xenotransplantation, this action is inconsistent with the agency's own policies and scientific evidence. The CDC's mission is to "place the benefits of society above the benefits to the institution; develop and advocate sound public health policies; implement prevention strategies; and foster safe and healthful environments."102 The CDC admits that the risk of creating an infectious new human disease through xenotransplantation "does not go to zero,"103 yet the agency continues to promote the use of xenotransplantation. This action is contrary to the agency's mission to protect public health.
Furthermore, despite the advice by numerous scientists to exclude primates as source animals in xenotransplants, the CDC has not provided species-specific regulations in HHS's xenotransplantation guidelines. Nonhuman primate (NHP) species used in biomedical research may be infected with a variety of retroviruses including simian immunodeficiency virus (SIV), simian spumaviruses (such as SFV), simian T-lymphotrophic viruses (STLV), and/or simian type D retroviruses (SERV).104 All of these viruses cause life-long infections in NHPs and may be transmitted to humans.105
Many scientists fear the transmission of animal viruses to humans. For example, virologist Jonathan Allan states that foamy viruses represent "the greatest immediate threat to humans among the known simian retroviruses" because their pathogenic potential may not become known until after they are well-established in the human population.106 British scientist Robin Weiss points out that "we understand all too little about what allows viruses to adopt and spread in a new host" and explains that by breaking down the immune system barriers that cause animal to human transplant rejection, we may help foreign viruses transfer into the human population.107
In March 1998, CDC discovered that active viral particles of a Simian Foamy Virus (SFV) were found in the bloodstream of four laboratory workers exposed to green monkeys and baboons over the course of several years.108 Although none of the workers showed signs of disease, and known partners tested negative for SFV, CDC scientist Heneine stated that there is a potential for SFV transmission and adaptation, especially through donated blood.109 Although permitting the use of xenotransplantation is inconsistent with FDA and CDC's own policies and scientific evidence, these agencies are allowing the use of this procedure.
The above information shows that HHS has not adequately
considered the effectiveness and efficacy of xenotransplantation as required
by the Public Health Service Act. Therefore, by allowing the use of this procedure,
HHS is acting arbitrarily and capriciously in violation of its statutory obligations.
HHS failed to adequately consider the legal, social, and ethical implications of xenotransplantation before issuing the guidelines.110 Without adequately considering the effects of xenotransplantation on the public, HHS is acting arbitrarily and capriciously.
HHS admits that the "contact between the recipient and the xenograft . . . [is] more likely to facilitate interspecies transmission of xenogeneic infectious agents than normal contact between humans and animals" and "infectious agents may not be readily identifiable with current techniques."111 Nevertheless, the agency went ahead and issued guidelines for xenotransplantation use despite the dangerous consequences. As explained above, it is highly probable that HHS will be unable to protect the xenograft recipient or the public from being infected by an animal virus. As a result, HHS should have considered how the government will handle an infectious epidemic before the guidelines for xenotransplantation use were issued.
HHS needs to address how infected individuals will be identified and how those infected will be prevented from spreading diseases. HHS also needs to address who will pay for treatment and care for those infected.112 Treating and caring for individuals infected with animal viruses will most likely cost the U.S. billions of dollars. So far, HHS has not stated whether it would compensate victims who inadvertently come into contact with a lethal animal virus. However, this should be a consideration because the government has already had to respond to compensation claims filed by Persian Gulf War veterans113, victims of Agent Orange114, hemophiliacs infected by HIV-tainted blood115, and parents of vaccine-damaged children.116 The government may now be held liable for failing to protect citizens from potentially lethal xenogeneic viruses.117
Before issuing the xenotransplantation guidelines, HHS failed to adequately consider the social implications from the use of xenotransplantation, including the protection of public health from the transmission of infectious diseases. The Institute of Medicine report on xenotransplantation states that "[h]istoric experience with many zoonotic diseases suggests that the potential for human infection with xenogeneic pathogens has implications for the community that extend beyond the individual transplant recipient."118 Even HHS admits that there is a public health concern over the transmission of unknown zoonoses from the xenograft recipient to the public,119 yet despite this admission, the xenotransplantation guidelines provide ineffective safeguards to protect public health from the introduction and spread of infectious diseases. In the xenotransplantation guidelines, HHS discusses a surveillance plan to monitor xenograft recipients, but the agency fails to discuss the issue of noncompliance with the guidelines.
HHS's recommended monitoring practices will most likely not be implemented effectively because HHS fails to take the basic vicissitudes of human nature into account.120 The rigorous and "potentially life-long surveillance" program, requiring complete physical exams and sampling regimens will probably not succeed.121 If individuals choose to sporadically participate or entirely withdraw from the monitoring program, HHS will not be able to detect an infectious disease. Consequently, the disease may spread rapidly to the public before HHS recognizes its existence.
HHS also did not discuss the possibility that a percentage of laboratory, health care, and surgical personnel may purposefully or negligently not comply with the surveillance procedures. There have been several examples where public health was compromised due to personnel problems. For example, decades of secrecy, mismanagement, and conscious violations of public health and environmental laws by personnel at the Department of Energy's Brookhaven National Laboratory in Long Island were recently uncovered. In May 1997, the federal government admitted that safety had taken a back seat to science at the Laboratory.122
Most importantly, HHS is not able to effectively protect public health because the xenotransplantation guidelines are only voluntary. By issuing voluntary guidelines, instead of promulgating federal regulations, HHS has chosen the most lenient method possible to policeand monitor the outbreak of a potentially infectious epidemic. Oversight of the entire xenotransplant operation and surveillance monitoring is left to the discretion of local review boards, surgical staff, and health care workers, many of whom do not have the necessary expertise to evaluate xenotransplantation protocols. For example, speaking at a National Institutes of Health meeting on January 22, 1998, in Bethesda on Developing US Public Health Policy on Xenotransplantation, Dr. Ernest Prentice of the University of Nebraska Medical Center said, "We approved a xenoperfusion protocol at my institution . . . and quite frankly, we didn't know what we were doing." Furthermore, even HHS' Inspector General, June Gibbs Brown, concluded in a draft report that the institutional review boards, whose members are unpaid, and who are charged with monitoring the treatment of participants in clinical trials, "face crushing workloads, inadequate training and potential conflicts of interest."123 The Inspector General further indicated that these findings were "a warning signal of a system that is in jeopardy."124
Based upon this information, allowing local review boards to have oversight authority for xenotransplantation use raises major concerns. Consequently, Louisa Chapman from the CDC indicated that the FDA will monitor all clinical xenotransplantation trials.125 This information, however, has yet to be made final in the Federal Register. Even with this change in authority, it may not help to improve the safety of public health because FDA has already failed to successfully provide public health oversight. For example, in December 1997, the General Accounting Office issued a report indicating many oversight problems by FDA, including FDA's failure to monitor transplant patients who may have received human tissues infected with HIV and other viruses.126 According to the report, the FDA has no register of approximately 400 U.S. centers which process several hundred types of human tissue.127 Moreover, the agency does not require these centers to report "errors and accidents" involving the distribution of infected tissue.128 Consequently, FDA is setting the stage for a potential public health disaster.
Even if HHS implemented regulations prohibiting noncompliance with the surveillance program, HHS will most likely be unable to stop an outbreak of infectious diseases. As discussed earlier, scientists are not aware of all of the potential animal viruses. Furthermore, new viruses may develop because zoonotic viruses may mutate inside their human hosts, or recombine with human viral elements, creating new viruses that could be highly lethal.129 By the time a new virus is identified, it may be too late. A new disease may have already begun to spread among the human population. Because HHS's safeguards for preventing the transmission of infectious viruses will not protect public health, HHS has failed to adequately consider the social implications of xenotransplantation before issuing the guidelines.
Although HHS identifies procedures for obtaining informed consent in the xenotransplantation guidelines, the agency failed to consider important issues dealing with this ethical issue.130 In fact, the Institute of Medicine report on xenotransplantation indicates that "more research needs to be done on the psychological, religious, and social interpretations of xenotransplants for patients and their families."131 HHS should have considered that xenograftpatients will most likely be very ill when they decide to take part in this procedure.132 In light of these patients' desperate situations, they must understand highly complex issues, including the experimental nature of xenotransplantation and the health risks to not only themselves, but also their close personal contacts.
The Institute of Medicine report also states that there are numerous instances where the medical community's enthusiasm for a new medical and surgical invention leads to an underestimation of the risks and an over exaggeration of the benefits.133 In response to this statement, HHS should proceed cautiously by thoroughly considering all of the ethical issues before allowing xenotransplant patients to participate in this procedure. By issuing these guidelines before adequately considering the ethical implications of xenotransplantation, HHS acted arbitrarily and capriciously.
HHS acted arbitrarily and capriciously in issuing xenotransplantation guidelines because it is not a cost effective technology. The FDA plans on establishing a registry to archive xenograft patient and source animal tissue samples.134 This archive is to be funded by the FDA and the NIH--in other words, by taxpayers. FDA officials estimate the cost of the registry at $250,000 to $300,000 a year, and the cost for the archive at $1 million a year.135
Xenotransplant researchers acknowledge that "rearing pigs under gnotobiotic [germ-free] conditions, [is] extremely expensive and time-consuming [and] the production of gnotobiotic pigs would greatly add to the cost of providing donor organs."136 Currently it costs from $25,000 to $100,000 to test just one pig for the presence of known bacteria and viruses.137 The biotechnology company Nextran explains that one of its pig organs will eventually cost the same as a human organ.138 Based upon this estimate, xenotransplantation is not cost effective because the current transplant costs for human organs range form $116,000 for a kidney to more than $300,000 for a liver.139 Factoring in years of follow-up care and immunosuppressive drugs, the cost rises to about $400,000 for a liver transplant and over $300,000 each for heart and lung transplants.140 The Institute of Medicine report predicts that xenotransplantation will push annual transplant cost from $3 billion to $20.3 billion.141 Based on this information, HHS should have considered that xenotransplantation is not cost effective.
In sum, HHS issued xenotransplantation guidelines despite scientific evidence showing that: (1) xenotransplantation is not a safe procedure for either the xenograft recipient or close contacts of the xenograft patient; (2) xenotransplantation is an unsuccessful and ineffective procedure; (3) xenotransplantation has unresolved legal, social, and ethical implications; and (4) xenotransplantation has negative economic consequences. Based on the above information, there is no "rational connection between the facts found and the choice made."142 Thus, by issuing the guidelines, HHS acted arbitrarily and capriciously in violation of the Public Health Service Act.
NEPA was designed to "promote efforts which will prevent
or eliminate damage to the environment and biosphere and stimulate the health
and welfare of man."143 NEPA's purposes are to "help public officials
make decisions that are based on understanding of environmental consequences,
and to take actions that protect, restore and enhance the environment," and
to "insure that environmental information is available to public officials
and citizens before decisions are made and before actions are taken."144
To accomplish these purposes, NEPA requires all federal agencies to prepare
a "detailed statement" regarding all "major federal actions significantly
affecting the quality of the human environment . . ."145 This statement
is called an environmental impact statement (EIS) and it is required to contain:
The regulations further provide that EAs shall discuss the need for the proposal, alternatives, the environmental impacts of the proposed action, and a listing of agencies and persons consulted.149 The CEQ regulations also mandate public involvement in the preparation of EAs and public availability and review of EAs and any Findings of No Significant Impact ("FONSIs"). The regulations specifically state that a federal agency "shall involve . . .the public, to the extent practicable, in preparing [environmental] assessments" and "[t]he agency shall make the finding of no significant impact available to the affected public . . ."150 CEQ has advised federal agencies that public comment on FONSIs and EAs is essential in a number of circumstances, including unusual proposals and cases involving public controversy over the proposal.151
In this case, HHS issued guidelines on the use of xenotransplantation, in light of the serious health and environmental effects, without complying with any of the NEPA requirements. NEPA requires that agencies "take a 'hard look' at the environmental consequences before taking a major action."152 HHS failed to take the required "hard look" at the environmental and health consequences of its actions because no EA or EIS was performed.
As explained above, the use of xenotransplantation is a "significant" action because this procedure is highly controversial and poses unique and unknown health effects to the xenograft recipient and the general public.153 Furthermore, this action affects "the quality of the human environment."154 The CEQ regulations define "the quality of the human environment" to include "the natural and physical environment and the relationship of people with that environment."155 In this case, the relationship of people to their environment is affected by the agency action because the use of xenotransplantation may create deadly new animal viruses. Due to this significant public health concern, HHS should have prepared an EIS.
Xenotransplantation also poses significant threats to the environment. HHS should have considered in an EIS/EA that the animals needed for xenotransplantation will increase the environmental problems caused by animal-based agriculture. For example, U.S. farms generate about 1.4 billion tons of animal manure a year, 130 times the quantity of U.S. human sewage, according to a 1997 report by the Senate Agriculture Committee entitled, Animal Waste Pollution in America: An Emerging National Problem. This untreated and largely unregulated manure, contaminated with bacteria, parasites, chemicals and heavy metals, is washed off farmland by rain and discharged into streams and rivers, killing fish, and making people who eventually drink it, bathe in it, and wash their clothes with it, sick.156
Surveys find animal waste is degrading 1,785 bodies of water in 39 states.157 Pesticides, insecticides and antibiotics which are commonly used in agriculture may also contribute to soil and ground water contamination and consequently, harm human health.158 Pollution from factory farms impairs more miles of U.S. rivers than all other industry sources and municipal sewers combined.159 During the past two decades, the number of coastal waters that host major and recurring attacks by harmful microbes has doubled.160 Pigs and pig waste pose a particular danger because they contract and transmit many human diseases including meningitis, salmonella, chlamydia, giardia, cryptosporidiosis, brucella, worms and influenza. The hazards from hogs increases when they are packed closely together.161
Hog farms also pollute the air. In Minnesota, tests showed eight of 32 air samples taken near manure lagoons exceeded air quality standards for hydrogen sulfide.162 A study done at Duke University Medical Center revealed that those who lived downwind from hog factory farms suffered from a variety of illnesses including increased tension, depression, flu-like symptoms, fatigue, dizziness, blackouts, loss of appetite, and sleep disturbances.163
HHS also failed to discuss in an EIS/EA the environmental and health impacts caused by the disposal of numerous remains of genetically modified animals. Conventional agricultural operations continuously wrestle with the problems of how to dispose of millions of tons of perishable animal tissue each year.164 Incineration, burial, and composting are all expensive, unhygienic, and environmentally problematic.165 In fact, in 1997, the Sierra Club filed a lawsuit against a hog farm, citing 50 violations of federal environmental laws, including the farm's illegal pits for disposing dead pigs.166 Disposing of transgenic pigs is an important issue because if these animals are disposed of improperly, the DNA can replicate, spread, and recombine, picking up genes from viruses in other species, and consequently, create new pathogens.167 Thus, disposing of genetically modified animals is a significant environmental and health concern that should have been addressed in an EIS/EA.
HHS issued guidelines on xenotransplantation use that pose "significant" public health and environmental concerns. The public should have been involved in the NEPA process, especially considering the controversial nature of xenotransplantation. By completely ignoring the entire EIS/EA requirements, HHS has violated NEPA.
Before issuing the guidelines on the use of xenotransplantation, HHS should have complied with the requirements of NEPA for considering alternative methods.168 However, nowhere in the guidelines did HHS explore the option of using any alternative methods. Under NEPA, HHS is mandated to take a "hard look at the alternatives and explain its reasons for rejecting them" in either an EIS or an EA.169
Many methods exist to improve human health that are not only more effective, but are also safer than xenotransplantation. These methods should have been seriously considered by HHS. For example, HHS could have increased education on disease prevention.170 The U.S. spends $425 billion per year - about two thirds of all medical expenditures - to treat the six leading chronic diseases that cause nearly three quarters of all deaths: heart disease, cancer, stroke, diabetes, chronic obstructive pulmonary disease, and liver disease.171 Patients with these diseases may become transplant candidates, yet many of these conditions could be diminished or prevented by improvements in the American diet.172 If Americans simply reduced their average saturated fat intake by one to three percentage points, then $13 billion dollars in medical costs could be saved and 100,000 first-time heart attacks averted by the year 2005.173 Even xenotransplant proponents have acknowledged that "the incidence of diabetes is rising steeply in developing economies, probably because of the adoption of a western diet."174 It is estimated that promoting healthy diet and lifestyle changes could curb the nation's $1 trillion spending on health care by one third.175 Thus, preventive medicine could drastically reduce the demand for human organs which would eliminate any argument for needing to use cross-species transplants.176
Another alternative method that HHS should have considered involves increasing awareness on the importance of organ donation. Although infection and rejection are still problems in human-to-human transplantation, using human organs for transplants is a method that has saved or at least prolonged human lives. Xenotransplantation, on the other hand, has never saved a single life. Neither the U.S. government nor the medical community has aggressively encouraged human organ donation.177 Currently, only 20% of individuals who die with healthy organs have arranged to donate their organs, even though a 1993 Gallup Poll showed that 85% of the public supports organ donation.178
Improving the success rate of human transplant operations would also increase the number of available human organs because many people on the transplant waiting lists are in need of new organs to replace failed organs from previous transplants.179 Boosting low rates of cadaveric organ donation could also increase the supply of human organs. Doctors in Europe and Japan say that cadaveric organ donation could increase the supply of human kidneys two-to-five fold.180 An operation called ventricular remodeling, in which a portion of a patient's diseased heart muscle is removed, can keep 75% of patients who undergo the procedure off the transplant waiting lists.181 Moreover, researchers at the Albert Einstein College of Medicine in New York explains that an injection of liver cells may prove to be just as effective as a whole liver transplant.182 Furthermore, researchers predict that, in the future, live human organs could be grown in vitro from a scraping of human tissue.183 Due to the controversial nature of xenotransplantation, HHS should have considered the viable alternative methods available as required by an EIS/EA before issuing the xenotransplantation guidelines.
In sum, due to the possible creation of new lethal animal viruses and the degradation of the environment from the use of xenotransplantation, HHS' issuance of the xenotransplantation guidelines is a major federal action significant affecting the quality of the human environmental. Consequently, HHS should have performed an EA/EIS. If HHS had performed an EA/EIS, then the agency would have discovered that xenotransplantation should not be permitted because viable alternatives exist.
The specific action requested by petitioners, banning xenotransplantation and revoking HHS' guidelines for xenotransplantation, is categorically excluded under 21 C.F.R. § 25.30(h) and therefore does not require the preparation of an EA or EIS.
HHS admits that "public health concerns exist regarding the potential transmission of xenogeneic infectious agents not recognized as classical zoonoses from xenografts to recipients, and then from the recipient to other persons."184 Despite this admission and contrary to the scientific evidence, HHS issued guidelines on xenotransplantation. Within these guidelines, HHS failed to consider important health issues and also failed to provide the required environmental documentation. Based on the information in this petition, HHS should comply with its statutory requirements and immediately rescind its guidelines and institute a comprehensive U.S. ban on the use of xenotransplantation.
Except as described above, petitioners know of no other similar issue, act, or transaction to this petition currently being considered or investigated by any HHS office, other federal agency, department, or instrumentality, state municipal agency, court, or any law enforcement agency. Petitioners are requesting a substantive response to this petition within one hundred and eighty (180) calendar days. In the absence of an affirmative response, petitioners will be compelled to consider litigation in order to achieve the agency action requested.
The undersigned certifies, that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to the petitioner which are unfavorable to the petition.
On behalf of the petitioners,
CC: Dockets Management Branch
Dr. Harold E. Varmus
Gene Matthews, Legal Advisor to CDC and ATSDR
December 10, 1998
** This petition has been modified from its original version
25 U.S.C. § 553(e) (1994).
321 C.F.R. § 10.30.
4John McArdle, PhD, Director/Scientific Advisor, Alternatives Research and Development Foundation, Comments to HHS’ Draft Guidelines On Xenotransplantation (Dec. 20, 1996).
6Ravi S. Chari, et al., Brief Report: Treatment of Hepatic Failure With Ex Vivo Pig-Liver Perfusion Followed by Liver Transplantation, 331 New England Journal of Medicine 234-7 (July 28, 1994)[hereinafter Chari](explaining that three out of four research patients died).
761 Fed. Reg. 49920 (1996).
8Jonathan S. Allan, D.V.M., Southwest Foundation for Biomedical Research, Comments on HHS Draft Guidelines On Xenotransplantation (Dec. 20, 1996)(signed by 44 scientists).
9Ronald Charles Desrosiers, Professor of Microbiology and Molecular Genetics, Harvard Medical School, Comments on HHS Draft Guidelines On Xenotransplantation (Dec. 11, 1996); see Jonathan Allan, Silk Purse or Sow’s Ear, 3 Nature Medicine 275-6 (Mar. 1997).
1061 Fed. Reg. at 49920.
11Jonathan Allan, Xenotransplantation and Possible Emerging Infectious Diseases, 1 Molecular Diagnosis 209-217 (1996).
12Murry Cohen, Alix Fano, Bird Flu a Warning to Stop Animal-Organ Transplants, The Houston Chronicle, (Jan. 15, 1998).
13Jeffrey Ball and Motoko Rich, Did Emory Monkey-Research Lab Do Enough to Protect a Worker?, The Wall Street Journal, (Mar. 18, 1998)(explaining that in December 1997, a 22-year-old research assistant died from herpes B after being splashed in the eye with body fluids from a caged monkey at the Yerkes Regional Primate Research Center in Atlanta).
14Richard Rhodes, Mad Cows and Americans, The Washington Post Magazine 34 (Mar. 9, 1997).
15Animal-Organ Transplants Could Lead to New AIDS, Group Warns, Reuters News Service (Mar. 19, 1998)(emphasis added).
16World Health Organization, Global Aspects of Emerging and Potential Zoonoses: A WHO Perspective, 3 Emerging Infectious Diseases (Apr.-June 1997), [hereinafter WHO Perspective].
17Even if HHS attempts to regulate xenotransplantation, the numerous uncertainties that exist concerning the variety and transmission of infectious diseases would render the regulations meaningless for protecting human health.
18Motor Vehicle Manufacturers Association v. State Farm Mutual Automobile Insurance Co., 463 U.S. 29 (1983).
19Id. at 43.
20Marsh v. Oregon Natural Resources Council, 490 U.S. 360, 378 (1989).
21Although HHS supported a study by the Institute of Medicine on the scientific, ethical, and public health implications of xenotransplantation, HHS failed to adequately consider these issues before issuing the guidelines. Institute of Medicine, Xenotransplantation, Science, Ethics and Public Policy (Washington, DC: National Academy Press, 1996)[hereinafter Institute of Medicine report].
2261 Fed. Reg. at 49922.
23Medical Research Modernization Committee, 10 MRMC Report 4 (Dec. 97).
24Institute of Medicine report, supra note 21, at 92.
25Pearce Wright, Smallpox Vaccine "Triggered" AIDS Virus, London Times (May 1, 1987).
26Pat Wechsler, A Shot in the Dark, New York Magazine 38-43, 85 (Nov. 1996); Anon, Monkey Virus in Polio Vaccine, 277 JAMA 873 (Mar. 1997).
27S.S. Morse, A. Schluederberg, Emerging Viruses: The Evolution of Viruses and Viral Diseases 162 J. of Infectious Diseases 1-7 (1990); World Health Organization, World Health Report (Geneva: WHO, 1996).
28Frederick A. Murphy, The Public Health Risk of Animal Organ and Tissue Transplantation into Humans, 273 Science 746-747 (Aug. 1996).
29A. Coghlan, So Far, So Good, 159 New Scientist 4 (Aug. 8, 1998); Anon, A Double-Edged Sword, 159 New Scientist 3 (Aug. 8, 1998).
31Transfer of Animal Cells to Humans Shows Promise, Reuters London (Aug. 5, 1998).
32Jon Allan, Silk Purse or Sow's Ear, 3 Nature Medicine 276 (Mar. 1997).
33Frederick A. Murphy, 4 Emerging Zoonoses, 3 (July-Sept. 1998).
34Fritz Bach, quoted in Kristine Novak , U.S. FDA to Issue New Rules on Xenotransplantation, 4 Nature Medicine 876 (Aug. 1998) [hereafter Novak (1998)].
3561 Fed. Reg. at 49923.
37Id. at 49925.
38Id. at 49923, 49926 (emphasis added).
39Charles River Laboratories, A Laboratory Animal Health Monitoring Program: Rationale and Development, (Winter 1990), http://www.criver.com/techdocs/hmradev.h.
41Institute of Medicine report, supra note 21, at 49.
42J. P. Stoye, J. M. Coffin, The Dangers of Xenotransplantation, 1 Nature Medicine 1100 (1995).
43Fed. Reg. at 49923.
44Murry J. Cohen, Risks of Importing Monkeys, The Washington Post (May 6, 1996); Barbara Nasto, Philippine Monkey Facility Closed, 3 Nature Medicine 263 (Mar. 1997).
45Using transgenic pigs may facilitate the transfer of viruses to humans, because a virus could use the new genes to disguise itself from the patient's immune system. In addition, pig organs are being bred to suppress the activity of human complement, bloodborne proteins that trigger the immediate rejection of a pig organ. Hence, a pig virus unhindered by human complement would potentially copy itself and spread much more easily. Robin A. Weiss, Transgenic Pigs and Virus Adaptation, 391 Nature 327-8 (Jan. 22 1998).
46Peter Laing, The Unrecognized Potential of Xenotransplantation 37 (Jan. 1996) [hereafter Laing].
47Retroviruses are life-long infections that are easily transmissible through blood or sexual contact.
48Clive Patience, et al, Infection of Human Cells By an Endogenous Retrovirus of Pigs, 3 Nature Medicine 282-6 (Mar. 1997).
49P. Le Tissier, et al., Two Sets of Human-Tropic Pig Retrovirus, 389 Nature 681-2 (Oct. 16, 1997).
50Anita Manning, Doctors See Risk in Animal Organs,USA Today (Oct. 16, 1997).
51Jon Allan, Silk Purse or Sow's Ear, 3 Nature Medicine 275-6 (Mar. 1997).
52Rick Weiss, Viruses in Pig Organs Could Infect Humans, Washington Post (Oct. 16, 1997).
53Xenotransplantation May Bring Risk of Infection, Doctor’s Guide online, http://www.pslgroup.com/dg/abd3e.htm).
54D. E. Akiyoshi, et al., Identification of a Full Length DNA for an Endogenous Retrovirus of Miniature Swine, 72 J. Virology 4503-7 (1998)..
55Rada Rouse, 4 Nature Medicine 378 (Apr. 1998)..
56A. Kroneman, et al., Identification and Characterization of a Porcine Torovirus, 72 J. Virol. 3507-11 (May 1998).
57J. C. Bridger, et al., Viral Determinants of Rotavirus Pathogenicity in Pigs, 72 J. Virol, 6929-31 (Aug. 1998).
58G. Allan, et al., Novel Porcine Circovirus . . ., 142 Vet Rec. 467-8 (Apr. 1998).
59K. D. Rossow, Porcine Reproductive and Respiratory Syndrome, 35 Vet Pathol 1-20 (Jan. 1998).
60Tim Grenda, Swine Virus Prompts Alert at Fairgrounds, The Daily Pilot (S. California) (May 29, 1998).
61L. Campitelli, et al., Continued Evolution of H1N1 and H3N2 Influenza Viruses in Pigs in Italy, 232 Virology 310-8 (June 1997).
62Dr. Gill Langley and Joyce D’Silva, Animal Organs in Humans: Uncalculated Risks and Unanswered Questions 10 (BUAV) (1998) [hereinafter BUAV]. The British Advisory Group on the Ethics of Xenotransplantation compiled a list of porcine viruses, bacteria, and parasites that it felt could not be guaranteed to be absent from a xenograft organ. The viruses included porcine retrovirus, polyomavirus, parvovirus, congenital tremor virus, cytomegalovirus, and influenza virus. N.R. Webster, Animal Tissues Into Humans, 80 British J. of Anaesthesia 281-2 (Mar. 3, 1998). N. Nowotny, et al., Prevalence of Swine Flu Influenza and Other Viral, Bacterial, and Parasitic Zoonoses in Veterinarians, 176 J. Infect. Dis.,. 1414-15 (Nov. 1997). David E. Wentworth, et al., Transmission of Swine Influenza Virus to Humans After Exposure to Experimentally Infected Pigs, 175 J. Infect. Dis., 7-15 (1997).
63NIAID, Office of Communications, Researchers Discover First Animal Strain of Hepatitis E Virus, NIAID News (Sept. 2, 1997).
6461 Fed. Reg. at 49920.
65One team of researchers at Duke University in North Carolina, received almost $2.5 million from 1997-1998 to transplant pig hearts into monkeys and other animals in an effort to elucidate the "immunological barrier to cardiac xenotransplantation." Will McLemore, Alexion Gets $2 Million Grant, The Yale Daily News (Oct. 26, 1995) (explaining that the Commerce Department’s Advanced Technology Program awarded the biotechnology firm, Alexion Pharmaceuticals, a $2 million grant in 1995 to study the interaction between human tissue and tissue from other animals). A perusal of the National Institutes of Health Research Grants database via the Internet at www.nih.gov, as well as the Compute>
Transfer interrupted!fic Projects (CRISP) database, reveals that the HHS, through the National Institutes of Health and its various agencies, has dispensed millions of dollars to researchers developing xenotransplantation. On August 8, 1997, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Heart, Lung and Blood Institute published an announcement in the NIH Guide, soliciting "applications [from researchers] to enhance [the] ability to transplant organs and tissues across species barriers (xenotransplantation) . . . This research would lead to the development of new therapies to allow xenografts to survive and function in humans . . ." This announcement, entitled, "Mechanisms of the Immune Response to Xenotransplant Antigens," was ironically posted as part of the Public Health Service's Healthy People 2000 initiative which allegedly seeks to achieve "health promotion and disease prevention." It invited applications from "domestic, foreign, for-profit and non-profit organizations, universities, colleges, hospitals, laboratories, units of state and local governments, and eligible agencies of the Federal government."
66Tony Stark, Knife to the Heart: the Story of Transplant Surgery 233 (1996) [hereinafter "Stark"].
68See generally, S. Taniguchi, Clinical Xenotransplantation: Past, Present and Future, 79 Ann R. Coll. Surg. Engl. (1997)[hereinafter Taniguchi].
69Stark, supra note 66, at 19-20.
70Id. at 20.
71Id. at 21.
72Id. at 158.
73Id. at 156-159.
74Stark, supra note 66, at 231.
76Id. at 158-162.
77Id. at 233.
78Id. at 231.
79Anon, Grandstand Medicine, 312 Nature 88 (Nov. 1984).
80Thomas E. Starzl, Baboon-to-Human Liver Transplantation, 341 Lancet 65-71 (Jan. 1993); Richard L. Worsnop, Organ Transplants Can the Number of Donors Be Increased, 5 CQ Researcher 719 (Aug. 1995) [hereinafter "Worsnop"]
81Worsnop, supra note 80, at 719-20.
82Taniguchi, supra note 68, at 13-19 citing J. Czaplicki, et al., The Lack of Hyperacute Xenogeneic Heart Transplant Rejection in a Human, 11 J. Heart Lung Transplant 393 (1992).
83Worsnop, supra note 80, at 719.
84Chari, supra note 6, at 234-7.
85Richard Cole, Baboon Marrow Transplant Deemed Failure, Star-Ledger (Feb. 8, 1996).
86K.S. Jayaraman, Pig Heart Transplant Surgeon Held In Jail, 385 Nature 398 (Jan. 1996).
87BUAV, supra note 62, at 4-9(explaining that very little attention has been paid to the question of whether animal organs are functionally able to sustain human life -- anatomically, biochemically, physiologically, metabolically, and pharmacologically).
88Id. at 20.
89Id. at 25.
90J. Platt, New Directions for Organ Transplantation, 392 Nature 11-17 (1998).
91Anthony Dorling, et al., Clinical Xenotransplantation of Solid Organs, 349 The Lancet 867-71 (Mar. 22 1997).
92Laing, supra note 46, at 34-37.
93Reuters, Medical Disinfectant is Seized by FDA, Newark Star-Ledger (Dec. 14, 1991).
94Meredith Wadman, FDA Turns Down Moratorium Demand on Xenotransplants, 391Nature 423 (Jan. 29, 1998)[hereinafter Wadman].
95Associated Press, Current Transplant Experiments, (Jan. 21, 1998). Richard Knox, Boston Doctors Transplant Pig Cells Into Epilepsy Patient, Boston Globe A13 (Jan. 21, 1998).
96Taniguchi supra note 68, at 13-19.
97CBER’s Research Initiatives Into Xenotransplantation, http://www.verity.fda.gov/search97cgi/97
98C. Wilson, et al., Type C Retroviruses Released From Porcine Primary Peripheral Blood Mononuclear Cells Infects Human Cells, 72 J. Virology 3082-7 (1998).
99Deborah Spak, Northwestern Joins Baxter in Transgenic Pig Liver Trial, (Northwestern University press release) (Oct. 6, 1997).
100Michael Day, Tainted Transplants, 156 New Scientist (Oct. 18, 1997).
101Taniguchi, supra note 68.
102CDC homepage, www.cdc.gov
103Richard A. Knox, Caution Urged on Animal-to-Human Transplants, The Boston Globe A16 (Jan. 22, 1998).
104C. Holden, SIV Hunt Leads to Baboon Virus Discovery, 276 Science 685 (1997).
105Centers for Disease Control and Prevention, Nonhuman Primate Spumavirus Infections Among Persons with Occupational Exposure - United States, 1996, 46 Morbidity and Mortality Weekly Report (Feb. 14, 1997).
106Jonathan Allan, 3 Molecular Diagnosis 211 (Sept. 1996)..
107Helen Phillips, Infection: Assessing the Risks From Animal Infections, Nature, (15 Apr. 1998).
108Phillip Cohen, Once Bitten, 156 New Scientist 23 (Apr. 4, 1998); Walid Heneine, et al. Identification of a Human Population Infection With Simian Foamy Virus, 4 Nature Medicine 403-407 (Apr. 1998); T. E. Starzl, et al., Baboon-to-Human Liver Transplantation, 341 The Lancet 65-71 (1993); J. S. Allan, et al., Amplification of Simian Retroviral Sequences from Human recipients of Baboon Liver Transplants, 14 AIDS Res. Human Retroviruses 821-24 (1998).
110Institute of Medicine report, supra note 21.
11161 Fed. Reg. at 49922.
112Current drug therapies for AIDS cost up to $20,000 per year. Philip Elmer-Dewitt, Turning the Tide, Time, 64 (Dec. 301996/Jan 6, 1997). Hundreds of millions of dollars have been spent on AIDS research. Christine Gorman, The Disease DetectiveTime 64 (Dec. 30, 1996/Jan. 6, 1997).
113Marc Kimball, Daschle Says Bill to Provide Compensation to Gulf War Veterans Suffering From Unexplained Illnesses Included in Omnibus Spending Bill, Press release from Senator Tom Daschle's Office (Oct. 21, 1998).
114Senate Record Vote Analysis, 101st Congress, 1st session, S-9676, Veterans' Agent Orange Exposure and Vietnam Services Benefits Act of 1989 (S.1153) (Aug. 3, 1989)(explaining the bill to provide benefits to Veterans exposed to Agent Orange), http://www.senate.gov/~rpc/rva/1011/1011/62.
115James Dao, Pataki Signs Bill Letting Hemophiliacs Sue Over Blood Clotting Products, The New York Times B4 (Dec. 2, 1997). New York state Governor George Pataki recently signed a bill into law allowing people to sue the makers of blood-clotting products that are widely thought to have infected thousands of hemophiliacs with HIV in the 1980s. The signing came after a class action suit brought by hemophiliacs against manufacturers of blood products. The suit cost manufacturers $650 million.
116Harry Nelson, Claims Swamp US Agency That Pays For Vaccine Injuries, Los Angeles Times A5 (June 20, 1991).
117Mary Lee Grant, Wife, Daughter of Kingsville Veterinarian Who Worked at Alice Facility to Receive Money, Caller-Times, Corpus Christi, (June 4, 1998)(explaining that the Texas Primate Center, a facility breeding monkeys for medical research in Alice, recently settled a suit with the family of a veterinarian who died after contracting herpes B at the facility).
118Id. at 42.
11961 Fed. Reg. at 49922.
120Novak, supra note 34 (explaining that virologist Jonathan Allan says, "The guidelines can outline a tracking program, but they can't limit the behavior of transplant recipients and their close contacts.")
121Id. at 49923, 49926.
122J. Raloff, Science's Role in Shake-Up of DOE Lab, Science News Online (May 10, 1997).
123Laurie McKinley, System for Conducting Clinical Trials on Patients Needs Reform, Report Says, Wall Street Journal, (June 1, 1998).
125Moratorium In Xenotransplantation Urged, Marketletter (Feb. 2 1998).
126GAO, Human Tissue Banks: FDA Taking Steps to Improve Safety, but Some Concerns Remain, GAO/HEHS-98-25 (Dec. 1997); also see GAO, Medical Devices: FDA Can Improve Oversight of Tracking and Recall Systems, GAO/HEHS-98-211 (Sept. 24, 1998) (explaining that FDA's oversight authority over manufacturers who are required to track medical devices such as heart valves and pacemakers was weak and "threatens the Food and Drug Administration's (FDA) ability to adequately protect the public.").
129J.P. Stoye, J.M. Coffin, The Dangers of Xenotransplantation, 1 Nature Medicine 1100 (1995); D.M. Smith, Endogenous Retroviruses in Xenografts, 328 New Eng. J. Med. 142-3 (1993).
130Institute of Medicine report, supra note 21, at 57-64.
131Id. at 62.
132HHS also needs to consider the ethical issue that not all patients will be able to give informed consent. For example, a pig liver trial in 1994 involved four patients who were all too ill to give their informed consent to the experiments. Consent was obtained from next of kin. Ravi S. Chari, supra note--,. There is also a larger question concerning whether it would be ethical to expose the public to the risk of infection without its consent. Public exposure to animal viruses may constitute a form of involuntary human experimentation.
133Id. (explaining that "[o]verly optimistic judgments have appeared repeatedly in public statements by treating physicians and in consent forms").
134Novak, supra note 34.
135Wadman, supra note 94.
136Taniguchi, supra note 68, at 13-19.
137Richard A. Knox, Caution Urged on Animal-to-Human Transplants, The Boston Globe A16 (Jan. 22, 1998).
138Kitta MacPherson, Edward R. Silverman, Weighing Risks of Pig Transplants, New Jersey Online, (Mar. 15, 1998).
139Richard H. Hauboldt, Cost Implications of Human Organ and Tissue Transplantation, An Update (Minneapolis, MN: Milliman & Robertson, Inc., 1996).
141Institute of Medicine report, supra note 21, at 79-84.
142Motor Vehicle Manufacturers Ass'n v. State Farm Mutual Automobile Insurance Co., 463 U.S. 29 (1983).
14342 U.S.C. § 4321.
14440 C.F.R. § 1500.1(b)-(c)(emphasis added).
14542 U.S.C. § 4332(C).
14740 C.F.R. §§ 1500-1517.
14840 C.F.R. § 1508.27.
149Id. at § 1509.9(b).
150Id. at §§ 1501.4(b), 1501.4(a)(1).
15146 Fed. Reg. 18028, 18038.
152Baltimore Gas & Electric Co. v. NRC, 462 U.S. 87, 97-98 (1983) quoting Kleppe v. Sierra Club, 427 U.S. 390, 410 n.21 (1976).
153See 40 C.F.R. § 1508.27.
15442 U.S.C. § 102(2)(C).
15540 C.F.R. § 1508.14.
156In February 1998, a liquefied hog waste spill contaminated Oklahoma City's drinking water, a lake, and a refuge area for migratory waterfowl. Anon, Hog Waste Spill May Foul Oklahoma City Water, Tulsa World (Feb. 21, 1998). In Utah, in 1997, at a farm with 32,000 hogs, some 80,000 gallons of manure spilled into the ground water when a pump failed and the waste backed into a water supply well. Anon, Manure Proves to be Massive Environmental Problem, Scripps Howard (Apr. 24, 1998) [hereafter Scripps Howard]; Neal D. Barnard, M.D., Sickened by U.S. "Factory Farms" Bangor Daily News A9 (May 20, 1998). A 100,000 gallon hog manure spill in Olivia, Minneapolis in 1997 killed 60,000 fish. A 1995 manure spill - almost twice the volume of the Exxon Valdez oil spill - dumped some 40 million gallons of pig manure into North Carolina waters, killing 10 million fish. Agricultural runoff from the Mississippi River has created a 7,000 square mile "dead zone" in the Gulf of Mexico. Neal D. Barnard, M.D., Sickened by U.S. "Factory Farms" Bangor Daily News A9 (May 20, 1998)
161Scripps Howard, supra note 156, at A9.
163Nancy Harvell, Hog Factory Stinks . . ., The Capital Times 7A (Mar. 10, 1998)..
164Due to the controversial nature of xenotransplantation, HHS should have considered alternative methods in an EIS/EA before issuing the xenotransplantation guidelines.
165In a 1996 article, Kenneth B. Kephart, (an Extension Swine Specialist for the Department of Dairy and Animal Science at Pennsylvania State University), addresses Pennsylvania farmers's concerns about how to dispose of 100,000 dead hogs annually.
166Stan Grossfeld, Regulations Fall Short in Protecting Water Quality, Report Finds, Boston Globe A1 (Sept. 21, 1998).
167Mae-Wan Ho, The Unholy Alliance, 27 The Ecologist 157 (July-Aug. 1997).
16842 U.S.C. § 4332(c). HHS should have also consider the requirements under National Institutes of Health Revitalization Act, 42 U.S.C. § 283e(a) (requires NIH to develop a plan to eliminate or reduce the number of animals used in research along with encouraging alternative methods).
169Coalition on Sensible Transportation, Inc. v. Dole, 642 F. Supp. 573, 593 (D.D.C. 1986) aff'd, 826 F.2d 60 (D.C. Cir. 1987).Furthermore, in the Animal Welfare Act (AWA), principal investigators are mandated to "consider alternatives to any procedure likely to produce pain to or distress in an experimental animal." 7 U.S.C. § 2143. Developing herds of transgenic pigs for xenotransplantation will involve much suffering. One British scientist wrote that, "[m]any inherently distressing processes are involved, including genetic engineering, cloning, reproductive manipulations, surgical operations, the separation of sows from piglets, close confinement in unnatural indoor conditions and invasive health status monitoring [including blood tests, swabs of the nose and tonsils, tissue and organ biopsies]." Critics charge that the suffering endured by these animals cannot be justified. BUAV, supra note--, at 66.
170Most other affluent countries do a better job than the U.S. in low-cost preventive medicine. "No other country does so little to limit the use of . . . expensive . . . technology" yet "there is a growing body of evidence that many of these expensive procedures and therapies . . . are harmful to patients." Humphrey Taylor, U.S. Health Care: Built for Waste, The New York Times (Apr. 17, 1990).
171Chronic Disease Costs Could Soar, San Francisco Chronicle (Apr. 4, 1997).
172W.R. Bidlack, Interrelationships of Food, Nutrition, Diet and Health: the National Association of State Universities and Land Grant Colleges White Paper, 15 J Am Coll Nutr 422-33 (Oct. 1996).
173Gerry Oster, David Thompson, Estimated Effects of Reducing Dietary Saturated Fat intake on the Incident and Cost of Coronary Heart Disease in the U.S. 96 J. of the American Dietetic Association 127-31 (1996).
174Peter Laing, supra note 46, at.47.
175Peter T. Kilborn, The Uninsured Find Fewer Doctors in the House, The New York Times 14wk (Aug. 30, 1998).
176For a cost/benefit analysis on xenotransplantation seeXenotransplantation Research: A Cost-Benefit Analysis, Xenotransplantation Concern (Apr. 1998).
177Personal statement from Roy Selby, M.D., physician and heart transplant recipient (Nov. 18, 1998); R. W. Evans, Need, Demand, and Supply In Organ Transplantation, 24 Transplantation Proceedings 2152-4 (Oct. 1992) (explaining that organ procurement is "only between 37% to 58% efficient"); Alan Bavley, Doctors Pump Life Into New Ideas for Healing Heart Failure Patients, San Francisco Chronicle, (Dec. 1, 1996).
178Worsnop, supra note 80, at 710.
179Anon, Alternative Ways of Meeting Demand 391 Nature 325 (Jan. 22, 1998).
180F. Valderrabano, Cadaver Transplantation As An Ethical And Cost-Effective Alternative To Living Donor Transplantation: The Spanish Experience, 24 Transplantation Proceedings 2103-5 (Oct. 1992).
181Reuters, Surgery Staves Off Heart Transplant, (Mar. 17, 1997).
182Reuters, Cell Injection May Help Some Liver Diseases, (May 14, 1998).
183John Gearhart, New Potential for Human Embyonic Stem Cells, 282 Science (Nov., 1998).
18461 Fed. Reg. at 49922.