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Of Pigs, Primates and Plagues: A Report by the
I. Introduction The alleged chronic shortage of human organs has led some researchers and federal health officials in the US and elsewhere to consider using animals such as pigs and nonhuman primates as alternate sources of organs for humans.[1] The prospect of commercial cross-species transplantation or xenotransplantation--which has been attempted since the early 20th century--has created huge financial incentives for biotechnology and pharmaceutical companies.[2] While some researchers and animal research advocates are optimistic about xenotransplantation's potential,[3] others are calling for a moratorium on the technology which, they say, is a threat to public health [4] and the environment, has an appalling track record, is expensive, and unnecessary.[5] These concerns have not been satisfactorily addressed by xenotransplantation's proponents, who have overstated the technology's potential benefits to the public. In light of the evidence presented herein, the Medical Research Modernization Committee (MRMC)* advocates a freeze on further xenotransplants. The Public Health Risks Posed by Xenotransplantation
On March 1, 1997 British researchers reported that pig retroviruses (PERVs) [6] infected human kidney cells in vitro and replicated themselves until the viral particles "were no longer susceptible to destruction by the [human] immune system."[7] Retroviruses are life-long infections and many are easily transmissible through blood or sexual contact.[8] Assuming that the numerous problems associated with cellular and vascular rejection were overcome and xenograft recipients survived a xenotransplantation, they could become viral timebombs with the ability to transmit infectious retroviruses to other people. Would public health agencies knowingly expose citizens to such dangers by allowing xenotransplants to be performed? On September 23, 1996, the US Department of Health and Human Services (HHS) published a set of Draft Guidelines on Infectious Disease Issues in Xenotransplantation in the Federal Register (Vol. 61, No. 185, pp. 49920 - 49932). While the risks posed by xenotransplantation were explicitly acknowledged in the guidelines, the HHS nevertheless appeared to endorse the technology. On December 20, 1996, the MRMC submitted a 21-page critique of the HHS's draft guidelines, citing 1) epidemiological and public health risks, 2) medical and scientific shortcomings, 3) concerns that xenotransplantation would diminish the importance of preventive health programs and personal responsibility for health, and that it would 4) consume already scarce resources that should be allocated towards practical, safe, and cost-effective health maintenance measures. Added to this are other concerns including: 1) the enormous investment biotechnology and pharmaceutical companies have made in xenotransplantation, and the tremendous influence such entities exert over federal health authorities, enabling private corporate interests to prevail over public health concerns. (Such was the case with Monsanto's recombinant bovine growth hormone (rBGH) which gained FDA approval despite overwhelming public opposition to the product being forced on consumers, particularly without appropriate labeling). 2) The disturbing genetic reconstruction of life (in this case, the creation of transgenic animals) which is advancing on a commercial scale with almost no informed public discussion or effective oversight. Previous transgenic pig research programs have produced animals with various painful physical abnormalities including arthritis, stomach ulcers, muscular weakness, defective vision, and weakened immunity. Transgenic animals are destined to spend their lives confined in unnatural, sterile environments, unable to fulfill their basic behavioral needs, until death.[9] 3) The environmental problems posed by the disposal of tens or hundreds of thousands of genetically altered animal carcasses has not been addressed, either in the HHS guidelines, or by the federal government on a national scale. The dumping of tens of millions of gallons of animal waste into the environment each year by traditional hog farming operations has created ideal breeding conditions for deadly microorganisms like Pfiesteria piscida which has killed billions of fish, poisoned water systems, and made people sick.[10] The disposal of animal renderings has been recognized as a major problem in traditional farm animal breeding operations.[11] The MRMC believes that the HHS draft guidelines on xenotransplantation are woefully inadequate for several reasons that will be discussed below. II. Epidemiological and Public Health Concerns: The HHS guidelines on xenotransplantation provide few real safeguards against the introduction and spread of new infectious diseases in the human population. The HHS repeatedly raises concerns about infectious disease risks associated with xenograft procedures throughout its draft guidelines. There are several points to be made in this regard. First, it is only possible to test for already identified viruses. All animals have many, perhaps thousands, of viruses within their DNA that remain inactive but could break free by recombination or other means at any time. Second, a zoonotic virus may mutate inside its human host, or recombine with human viral elements, creating new viruses that could be highly lethal.[12] Many viruses (such as HIV) have long incubation periods, often resulting in a manifestation of illness years after an initial exposure. By the time a new virus was finally identified, it could be too late; a new disease may have already begun to spread among the human population. Third, viruses have different disease presentations in humans and animals; an animal host may live perfectly well with a species-specific virus that is deadly to humans. For example, Macaque herpes is harmless to Macaques, but lethal to humans.[13] And finally, unlike animal-derived biologic products like porcine heart valves which are treated with glutaraldehyde [14] (and are, according to some physicians, inferior to their synthetic counterparts),[15] implanting living non-human animal organs directly into humans facilitates the transmission of potentially deadly infectious animal diseases to the human population.[16] The HHS itself admits (in paragraph 1.1 of its guidelines) 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." Moreover "the intimate contact between the recipient and the xenograft, the associated disruption ofanatomical barriers, and immunosuppression of the recipient are more likely to facilitate interspecies transmission of xenogeneic infectious agents than normal contact between humans and animals," a concern echoed by respected immunologists and virologists in the UK.[17] Jonathan Allan, a prominent virologist in the Department of Virology and Immunology at the Southwest Foundation for Biomedical Research in San Antonio, Texas, writes that transplantation of animal organs into humans circumvents the natural barriers (skin, mucosal surfaces and the acid environment of the stomach) that prevent infection by these microorganisms, "which means that viruses not typically thought to be infectious for humans such as blood-borne or sexually transmitted pathogens would now have access to human organ systems."[18] Many kinds of cells behave unnaturally when torn from their familiar surroundings. Because cells from transplanted animal organs migrate in the human body, attempt to adapt to their new environment, and integrate themselves inside human cells, a virus that was transmitted from baboons or pigs to humans, could permanently incorporate itself into human chromosomes. Such a virus would remain in the human body even if the animal organ were subsequently removed, as in the case of "bridge organs."[19] In addition, the guidelines assume (paragraph 2.5.3 ) that zoonotic diseases would only be spread through sexual contact or the sharing of body fluids. But government scientists admit that many viruses can spread via a mere cough or sneeze.[20] The HHS guidelines are voluntary and may be ignored.[21] Furthermore, they inappropriately leave oversight to surgeons and local review boards rather than federal health authorities, and set the stage for unleashing diseases on the human population, with unknown consequences. In 1996, Jonathan Allan stated that "[the HHS] guidelines provide few real safeguards against the introduction and spread of new infectious diseases in the human population."[22] He said, ". . . lax guidelines in place in the United States will, in effect, jeopardize the health of individuals not only in the US but also globally as we have seen with the rapid worldwide spread of HIV-1."[23] In 1997 Allan reiterated his concerns in light of new findings about pig retroviruses' ability to infect human cells. He said public health officials "should resist the transplant community's clamour for animal organs in light of this new data. Our first priority must be to protect the public health."[24] Although the HHS presents a detailed array of precautions, including health surveillance plans, human and animal screening programs, and national registries designed to "minimize" and "diminish" the risk of zoonotic disease transmission, these precautions cannot guarantee negligible risk, which should be an absolute requirement for xenotransplantation. We Should Learn From the Past While the HHS reports (p.49920) that live animal cells, tissues and organs are being used in a number of "experimental clinical procedures," they downplay the extremely dangerous nature of such procedures whose clinical value is still unproven. There are a multitude of scientific unknowns with respect to the existence and behavior of zoonotic viruses. Responsible health authorities would steer clear of xenotransplantation in the interest of human health, particularly in light of the knowledge that animal viruses can jump the species barrier and kill humans. HIV - the virus that causes AIDS, may be a simian immunodeficiency virus (SIV) that leapt the species barrier in central Africa. Health authorities were unable to prevent the worldwide spread of HIV infection. Similarly, they were unable to prevent Ebola outbreaks in Sudan, Zaire (1976, 1979, 1995) and the US (1989, 1996).[25] Furthermore, there is evidence that humans have become ill after consuming or being injected with animal materials. There is a reported link between the smallpox vaccine (which used animal cells) and AIDS,[26] a recently acknowledged link between human lung, brain and bone cancer and the SV (simian virus) 40 (found in old batches of the Salk polio vaccine),[27] and the threat of emerging infectious diseases[28] such as human Creutzfeldt-Jakob Disease (CJD) from the consumption of "mad cows" in Europe, the Netherlands, and the US. Baboon viruses have been found to flourish on human tissue cultures in the laboratory - before killing the cultures.[29] Given the acknowledged danger from monkey viruses,[30] pigs are being considered as the choice donor animals for xenotransplants. However, pig retroviruses' ability to infect human kidney cells in vitro has recently been demonstrated.[31] Virologists note that the "biologic and pathogenic features of a type C retrovirus" identified in the blood of pigs used in laboratories have not been adequately studied.[32] The deadly human influenza virus of 1918 that killed more than 20 million people worldwide was a mutation of a swine flu that evolved from American pigs and was spread around the world by US troops mobilized for World War 1.[33] Leptospirosis (which produces liver and kidney damage), erysipelas (a skin infection),[34] and wabah babi, recently discovered in Indonesia,[35] are among the approximately 25 known diseases that can be acquired from pigs, (see attached list) all of which could easily be passed onto immunosuppressed humans. There may be myriad unknown "pig diseases" like wabah babi still to be discovered. Frederick Murphy, Dean and Professor of Virology at the University of California, Davis's School of Veterinary Medicine, reports in the journal Science (1996) that "known pathogenic viruses that might pose a risk in xenotransplantation include many adenoviruses, papovaviruses, papillomaviruses, parvoviruses, hepadnaviruses, morbilliviruses, filoviruses, hantaviruses, arenaviruses, arteriviruses, flaviviruses, and togaviruses . . . certain retroviruses (includingendogenous 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."[36] This is alarming, and it is highly unlikely that the HHS guidelines could prepare scientists and health care workers to cope with such a lengthy list of known dangers. How Would Our Health Care System Cope With the Consequences of Infection? Although the HHS acknowledges the risks of spreading xenogeneic viruses to the human population, it does not examine the long-term implications of unleashing such viruses on society. Prominent virologists note, and history has taught us, that it is easier to prevent a viral epidemic than to contain one. Containment, screening and treatment are extremely costly for governments; treatments are not always successful and cures are rare. Should a xenogeneic agent be discovered at a later date, it could be virtually impossible (as it was during the AIDS crisis) to locate all infected individuals, or those who may have had contact with infected individuals. More importantly, it may be impossible to determine the original source of infection. The HHS concurs that "most acute viral infectious episodes among the general population are never etiologically identified" (paragraph 4.3.2). Several questions therefore arise and they have yet to be adequately addressed: 1. How would federal agencies identify carriers of the virus in the general population once the virus was dispersed? It is naive to believe that the creation of a national registry/database to assess the long-term safety of xenotransplants and the health of xenograft recipients would be adequate to track the progress of a retrovirus, particularly one that is not known. The Vaccine Adverse Event Reporting System (VAERS), for example, established in 1990 and managed by the Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) has been described by epidemiologists at the FDA and CDC as "a reporting system . . . [with] . . . major limitations, including under-reporting, lack of specificity, and a lack of a natural control group." The lack of enforcement or monitoring of reporting practices leads to serious inconsistencies in the data that are collected.[37] The VAERS database is a repository for voluntarily submitted reports, but are there any guarantees that a mandatory reporting system would work? Given the enormous amount of data, paperwork, and filing xenotransplant procedures would generate, it would be naive to assume that human error or negligence won't come into play somewhere along the line in the form of a miscalculation of numbers, misinterpretation of data, misfiling of folders, improper labeling of files or slides, and so on. A San Diego-based food company was recently blamed for mislabeling imported strawberries and shipping them to public schools in seventeen states, resulting in almost 200 cases of hepatitis A, with thousands more possibly affected.[38] The Federal Bureau of Investigation's crime laboratory was recently criticized for submitting flawed scientific findings in at least 55 cases. A report found that scientific examiners (including chemists and toxicologists) had prepared "sloppy reports, exaggerated their findings . . . and inadequately documented their test results." Supervisors had left too much discretion to subordinates "who reached findings that were unsupportable by scientific evidence." Moreover, laboratory managers had failed to respond to internal complaints.[39] These cases illustrate that error and negligence are an inevitable part of human activity. Regulatory mechanisms often fail to prevent or correct these errors and/or behaviors, the consequences of which could be disastrous in the face of a xenogeneic infection. 2. How would federal agencies contain an infectious epidemic caused by an unfamiliar xenogeneic agent, particularly when US doctors are currently not required to report cases of Ebola, nor any other disease they cannot identify, to the CDC? [40] The AIDS Action Council in Washington, DC issued a report in 1991 entitled Good Intentions which evaluated early HIV prevention efforts in the US; the Council found "poor federal inter-agency coordination," poor long-term planning, and insensitivity to women and people of color. If carriers of a zoonotic virus were identified, would they all be quarantined/placed in isolation? What if there were thousands or tens of thousands of carriers? Would special facilities have to be built to accommodate them? If so, who would pay to build these facilities? 3. How would research centers identify unknown and unidentifiable microbes or illnesses? In 1992, there were 744 unexplained deaths attributed to infections in four states across the US.[41] Robert Michler, former Director of heart transplant service at New York's Columbia-Presbyterian Medical Center has admitted that "it is difficult to monitor for the unknown."[42] As Jonathan Allan writes, "there is no way to screen for viruses that have yet to be discovered . . . (and there may be several of these)."[43] CDC officials have estimated that before Legionnaire's diseases was identified in 1976, 2,000 -6,000 deaths per year were incorrectly attributed to pneumonia. Similarly, although the HIV virus was identified in 1983, researchers have now discovered cases that may date as far back as 1968. The CDC's Unexplained Illnesses and Deaths Surveillance project was established in 1994 in an attempt to combat emerging infections. The project's two dozen researchers have only been able to explain about 10% of the cases they have reviewed.[44] Failure to identify an emerging zoonotic infection could be catastrophic. 4. Who would pay to develop appropriate screening assays and screening programs for a new virus (assuming one could be developed quickly enough)? The US military spent $43 million between 1986 and 1988 screening 3.2 million new volunteers and existing personnel for HIV.[45] It should be noted that diagnostic, sampling and analytical technologies and equipment are fallible.[46] Assays may fail to detect an infection in an individual, a hospital, or a blood center's blood supply, or they may falsely detect infection where none exists. The HHS admits that "immunosuppressed transplant patients may be unable to mount a sufficient immunological response for serological assays to detect infections reliably" (paragraph 4.3.2 .1). Jonathan Allan points out that the assays used to detect infection in animals, particularly primates, have not been assessed for their specificity or sensitivity.[47] This suggests that a new zoonotic virus may not be detectable in the xenograft recipient until it is too late, and a new disease may have begun to spread. In addition, physicians and/or laboratory personnel may misread or misunderstand lab results. A recently published report in The New England Journal of Medicine revealed that nearly one-third of physicians who referred patients for tests to detect genetic mutations misinterpreted the test results. More importantly, about 32% misunderstood the meaning of a negative result.[48] Failure to identify genetic mutations or other cellular abnormalities in xenograft recipients' test results could lead to another public health crisis akin to AIDS or Ebola. 5. Assuming all of the xenograft recipient's contacts (paragraph 2.4), could be located and identified, and assuming assays gave reliable results and were interpreted correctly, who would pay to screen all of these individuals, presuming they agreed to submit to testing? If they did not agree to testing, would they be forced to submit to it? Experience with HIV has shown that, "where control measures such as mandatory testing are considered by authorities, the level of voluntary requests for testing drops; an atmosphere of coercion has had the effect of frightening people away from testing and treatment centers, driving AIDS underground."[49] Would individuals' behavior and whereabouts be constantly monitored? In this regard, the guidelines fail to take the basic vicissitudes of human nature into account, particularly with respect to the xenograft recipients themselves. The rigorous and "potentially life-long surveillance" program, requiring complete physical exams and sampling regimens (paragraphs 2.5.5, 4), could backfire. Individuals may tire of such a regimen and secretly relocate, never to be found again. Health care workers are also asked to submit to sampling and surveillance regimens (paragraph 4.3.3 .2) which could backfire or be disregarded. Workers who may accidentally prick themselves with an infected needle, for example, (paragraph 4.3.3.3), may not record or report the exposure, or archive it in the "Health Exposure Log," for fear of losing their jobs. The implications for public health of this scenario, which would be compounded if these workers changed jobs or moved to another city or state, are obvious. With respect to carrying out procedures outlined in the guidelines, the guidelines fail to consider that a percentage of laboratory, health care, and surgical personnel may be prone to laziness, carelessness/ sloppiness, fear and outright deceitfulness. 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 brought to light. In May 1997, the Federal Government admitted that "safety had taken a back seat to science" at the Laboratory.[50] The New York Times reported that the Laboratory went about its business "like any other manufacturing site," its workers dumping industrial solvents, low-level radioactive waste and pesticides around its 5,300 -acre property, contaminating private water wells and Suffolk County's aquifer - the sole source of drinking water for three million Long Island residents. The additional discovery of leaks of tritium and other radioactive substances from the Laboratory was attributed to "awry decision-making" according to a DoE official.[51] Other noted examples of institutional malfeasance include the HIV-contaminated blood scandals in France, China and Japan in which medical authorities knowingly allowed HIV-contaminated blood to be used for transfusions and blood-clotting treatments for hemophiliacs.[52] In the 1980s, the Pennsylvania-based Armour Pharmaceutical Company knowingly continued selling a blood-clotting drug in Canada despite warnings that its heat-treatment process wasn't killing the AIDS virus, causing thousands of Canadians to become infected with AIDS and hepatitis C.[53]Similarly, four pharmaceutical companies: Bayer AG (Germany), Baxter International Inc. (Illinois), Rhone-Poulenc Rorer Inc. (France), and Green Cross Corp. (Japan) - infected about 8,000 Americans with HIV in the 1980s through contaminated blood-clotting substances.[54] A report released by the Institute of Medicine in 1995 found that the government, manufacturers and the National Hemophilia Foundation all failed to move swiftly to insure the safety of blood-clotting products in the 1980s.[55] US Food and Drug Administration investigators recently found "continuing violations in blood safety laws and regulations" at the New York Blood Center which supplies 80% of the blood used in New York hospitals. A night shift manager was arrested for "taking short cuts to manipulate the testing of blood for viruses like HIV and hepatitis."[56] A similar scenario with a zoonotic virus would have unforeseeable public health and economic repercussions. 6. Who would pay for long-term treatment and care of infected individuals? Current drug therapies for AIDS (protease inhibitor cocktails) cost up to $20,000 per year in 1997 dollars.[57] To treat all 30 million people with AIDS would cost $6 billion per year.[58] Add to that fees for hospital stays, doctor visits, and blood tests. The hundreds of millions of federal dollars spent on AIDS research, including $129 million recently allocated to develop a vaccine,[59] should also be tallied; such increased spending is an inevitable consequence of an epidemic. Clearly, treating and caring for individuals infected with a new xenogeneic virus would cost the US billions. 7. Because no regulatory system is foolproof, how could public health agencies ensure that xenograft recipients and their families understood, and were adequately informed about, the risks involved in xenotransplantation procedures? The concept of informed consent was developed after World War II, as a result of Nazi experiments conducted on unwilling human prisoners. Rules were consequently designed that were supposed to protect volunteers and patients in medical research. However, Charles Inlander, President of the People's Medical Society in Emmaus, Pennsylvania, has reported that the average person would need 19 years of graduate-level education to read consent forms for experimental procedures, and that they are written more for lawyers than laypersons. The New York Times reported that consent forms, which must be signed by patients or their relatives, do not always fully explain the risks of experimental procedures. Patients have been permanently damaged or killed by treatments that were supposed to heal them, leading some health experts to express concern about "unchecked human experimentation" taking place in hospitals, universities, and private laboratories throughout the US. Legislators have held hearings "to determine the scope of lapses and violations of ethics in experiments."[60] Patients undergoing xenotransplantation procedures would have to be informed of the risks to themselves, their families, friends, and society at large. But how would the process of informed consent in xenograft procedures be monitored? Who would ensure that patients and their families were fully informed of all the risks? What of patients who may choose to participate in privately-funded research where there are no mechanisms of accountability to federal health authorities, and little chance of receiving remuneration for injury or death? Is the field of xenotransplantation immune from "unchecked human experimentation" and "violations of ethics?" 8. A majority of non-smokers feel that their rights and their health[61] are compromised when they are forced to breathe second-hand cigarette smoke. What of the rights of people who may inadvertently come into contact with xenograft recipients harboring potentially pathogenic agents? While patients may give their consent to undergo xenotransplants, it would be impossible to obtain consent from every person the xenograft recipients may come into contact with (should they survive). This situation raises serious legal questions because it could constitute a form of involuntary human experimentation, in violation of the 1964 UN "Helsinki Declaration" on Biomedical Research Involving Human Subjects as well as the 1993 International Guidelines for Biomedical Research Involving Human Subjects, the US rules of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, and new rules adopted by the US government to prohibit secret experiments on unwitting human subjects.[62] 9. Would the US government be prepared to compensate victims of xenogeneic infections (such as people who may have inadvertently contracted an infection from a xenograft recipient)? HIV-1 and HIV-2, two immunodeficiency viruses linked to monkey viruses, infected more than 12,000 people through blood transfusions before the disease was recognized and discovered.[63]The French government was forced to establish a $2.2 billion fund to compensate victims of AIDS-contaminated blood transfusions administered between 1980 and 1985.[64] Compensation claims in the US have been filed by Persian Gulf War veterans,[65] victims of secret government-sanctioned radiation[66] and syphilis experiments,[67] Vietnam war veterans exposed to Agent Orange,[68] and parents of vaccine-damaged children.[69] The government may now also be held liable for failing to protect citizens from SV (simian virus) 40-contaminated polio vaccine.[70] In addition, it has been pointed out that the harmful consequences of global epidemics are almost always more lethal in poor, undernourished communities.[71] Has any thought been given to the ethical and economic ramifications of unleashing a new retroviral illness in developing countries? Can our government afford such a global public health catastrophe? 10. Where would potentially infectious animal tissues be stored? What about power failures? What if computer hackers or intruders were to destroy the health records of all the source animal herds, and/or the clinical data relevant to xenograft recipients? The Limited Value of Risk Assessment Although the HHS admits (p.49922) that "the introduction of xenogeneic infectious agents into and propagation through the general human population is a risk that must be addressed, "ultimately, writes Frederick Murphy, "risk may be revealed only through ongoing surveillance and clinical observation,"[72] - in other words, after disaster has already struck, as with the AIDS crisis. Paragraph 2.3, the "Clinical Protocol Review," recommends that local Institutional Review Boards have expertise in risk assessment vis-a-vis the transmission of zoonotic viruses to humans. But risk assessment is a precarious "science" which is often subject to enormous political manipulation. The outcome of most risk assessments depends on a risk assessor's subjective selection and interpretation of data (including statistical analyses). According to David G. Hoel et al., different statistical models can yield risk estimates that vary over a wide range.[73] Performing a risk assessment does not reduce the risk of a dangerous occurrence, it is merely an attempt to assess the danger. Ultimately, risk assessment is a hypothesis that can only be tested and validated by the occurrence of the very event one is trying to prevent.[74] Some risks, such as the disease risk to "health care workers who provide direct/indirect post-transplantation care for xenograft recipients" (paragraph 4.3.3) remain undefined and maybe heightened or diminished by the adequacy of "biosafety standards" that are employed. Here again, steps are suggested that may "minimize," rather than eliminate exposure and transmission of zoonotic and nosocomial agents between the (xenograft) recipient(s) and health care workers (paragraph 4.3.3.1). But risk must be negligible when the public health implications are so great. Animal Viruses and the Myth of the "Germ-Free" Animal In paragraph 3, the HHS outlines detailed "source animal" breeding, husbandry, and screening protocols designed to "minimize" the risk of transmitting infectious animal diseases to humans. The surveillance programs are to be "adequate" (paragraph 3.4) though the term adequate is not defined anywhere. Not only is the assessment of the "adequacy of the screening program" left to the discretion of the xenotransplant team (for whom objectivity may be difficult), but the precautions are illusory. Indeed, the 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" (emphasis added), (paragraphs 3.1.2 and 3.5.2). Moreover, it is recognized that animals may contract diseases during transport. It has also been shown that animals whose food, water and bedding are sterilized, who live in barren sterile environments in which temperature, humidity, lighting are controlled, and who are kept in isolation/deprived of social interaction, are far more susceptible to immunosuppression and a host of diseases including cancer, than their wild counterparts.[75] Undoubtedly, that is why pigs, who are very social, playful, sensitive, and intelligent animals,[76] possessing high IQs,[77] do not thrive in such sterile, artificial environments[78] - a problem for those who would seek to breed them in large numbers for xenotransplantation. Indeed, of 49 transgenic pigs bred by Imutran, a UK-based biotechnology company, 20% - 25% were either stillborn, died or were killed soon after birth.[79] A report by the (British) Advisory Group on the Ethics of Xenotransplantation concluded that the risks of animal organs being infected with bacteria, fungi, parasites, and prions were "ethically acceptable" provided that donor animals were bred in specific pathogen free (SPF) environments.[80] That is an irresponsible statement. Prions -abnormal forms of proteins that enter the brain and force normal proteins to mutate - have been identified as the agents that can cause Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy (BSE) in cows. Prions are resistant to boiling, formaldehyde, and ultraviolet and gamma-irradiation, and prion-related diseases remain latent for long periods of time.[81] Prions occur naturally in the brains of all mammals, hence no animal can be free of them.[82] In fact, no animal, whether transgenic or otherwise, can remain completely free of parasites or endogenous viruses. Clive Patience et al. say, for example, that it would be "a daunting task to eliminate infectious retroviruses from pigs to be used for xenotransplantation, given that [they] estimate approximately 50 PERV [pig endogenous retroviruses] per pig genome."[83] In its June 1996 report, the Institute of Medicine acknowledged that "it is not possible to have completely pathogen-free animals, even those derived by Cesarean section, because some potentially infectious agents are passed in the genome and others may be passed transplacentally." Even Charles River Laboratories, (which breeds animals for laboratories) in Wilmington, Massachusetts, admits that potentially pathogenic organisms are difficult to exclude in specially bred animals "without extraordinary measures." The company recommends a detailed health monitoring and diagnostic evaluation program which requires the expertise of parasitologists, microbiologists, pathologists and serologists. Charles River acknowledges that labs must select the agents for which they wish to screen due to the "prevalence of agents" and the "cost of screening."[84] Indeed, who would pay for these elaborate and extremely costly animal breeding, "life-long monitoring" and tissue and data archiving programs (see paragraph 3.4 - 3.7.4)? The HHS states that extensive screening of the source animal(s) may sometimes be limited "to ensure graft viability," (paragraph 3) 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" (paragraph 3.1.5). However, importing monkeys, for example, into the United States for biomedical research has placed the safety of Americans in jeopardy before, 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; and the hepatitis B virus may have originated from human exposure to asymptomatic chimpanzee carriers.[85] Hence the practice of importing animals from other countries for medical purposes should be stopped in the interest of public health. In paragraph 3.3, the HHS recommends a "characterization of the human pathogenicity of xenotropic endogenous retroviruses and persistent viral infections present in source animal cells, tissues, and organs." This is feasible for known infectious agents, but as was previously pointed out, there is no way to screen for viruses that have yet to be discovered. The HHS also states that "the use of live vaccines . . . may be justified when dead or acellular vaccines are not available" (paragraph 3.4.1, 3.5). As discussed, live vaccines are a public health concern because they can contain potentially deadly infectious agents. The clinical impact of administering live vaccines to "source animals" whose organs may then be transplanted into humans, can never be assessed in advance. Scientists have recently reported that the accidental transmission of Creutzfeldt-Jakob Disease (CJD) to patients, transplant surgeons, and histopathology technicians is becoming more common "in the high-technology milieu of modern medicine."[86] Given the health threat posed by bovine spongiform encephalopathy (BSE) (which causes human CJD),[87] it is irresponsible for the HHS to suggest that bovine tissue be used for transplantation (paragraph 3.1.6), despite the warning that such tissues not be obtained from countries where BSE exists. First, CJD is making unannounced appearances in the US, the UK, France, Italy,[88] and the Netherlands,[89] and it is unknown how many citizens in other countries may be harboring the illness. It is unknown how many countries monitor their herds for BSE, and how many would admit to having the problem, particularly if such an announcement would result in the compulsory destruction of entire cow herds, thereby incurring large economic losses.[90] Britain, for example, has been eager to proclaim that its cow herds are healthy; but reductions in compensation payments for infected cattle in Britain resulted in fewer farmers reporting cases of BSE and then sending diseased cattle to market, rather than risk losing money by reporting them to the Ministry of Agriculture.[91] In March 1997 the British Government was accused of suppressing a year-old report that found slaughterhouses guilty of practices that could contribute to the spread of mad cow disease.[92] According to The Economist, the study of BSE "has been hobbled by secrecy and government bungling." Basic questions about how the disease is transmitted remain unanswered.[93] When the Foxes Guard the Henhouse It should be noted, and the HHS readily admits (p.49921), that all animal-to-human transplants executed prior to 1996 were performed without the existence of guidelines regarding the "adequate screening of donor animal cells, tissues, and organs intended for human transplant or recommendations for post-transplantation patient monitoring." There was also no federal oversight, with research centers being left to their own devices. Xenograft researchers have opposed federal oversight. For example, Suzanne Ildstad[94] praised the FDA for drafting (unenforceable) guidelines, as opposed to legislation, for the research.[95] The current climate of deregulation in biotechnology favors the unhindered continuation of xenotransplantation research, despite the risks to human health. Jonathan Allan writes that, "in choosing voluntary guidelines to be enforced at a local level, rather than federal regulations, the FDA/CDC committee has chosen the least stringent and possibly least successful method of policing these transplant procedures."[96] Oversight of the entire xenotransplant operation and its aftermath would be 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. Speaking at a National Institutes of Health meeting in Bethesda on Developing US Public Health Policy on Xenotransplantation,' January 22, 1998, 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." Moreover, The New York Times reported that legislators have been "startled" by accounts of "ethics panels, institutional review boards, [IRBs] . . . set up as profit-making ventures to evaluate proposed experiments for research groups that pay them." Researchers, particularly those receiving money from private industry, allegedly "shop" for IRBs that will approve their research.[97] Although the HHS has proposed allowing local IRBs to oversee xenotransplantation procedures, federal health authorities would be called upon to respond to a potential public health disaster resulting from the procedures (paragraph 4.1.1 .6). These authorities will, until that point, have been completely out of the loop with respect to the facts, methods, and risks involved in the xenotransplantation(s). From a public health and public policy standpoint, the MRMC believes that this scenario is unacceptable. In summary, the HHS recognizes the risk of unleashing a viral epidemic upon society through acknowledging that: an infectious agent may be identified in the source animal or herd"subsequent to xenograft harvest" (paragraph 3.5.5); that "necropsy findings [may] reveal infections pertinent to the xenograft recipient" (paragraph 3.6.5); that archived source animal biologic samples are essential for public health investigation and "containment of emergent xenogeneic infections" (paragraph 3.7); that "post-transplantation clinical and laboratory surveillance of xenograft recipients is critical to monitor for the introduction and propagation of xenogeneic and infectious agents in the general population" (paragraph 4.1.1 ); that biological specimens of xenograft recipients should be collected and archived to allow "retrospective investigation of possible xenogeneic infections" (paragraphs 4.1.1.2, 4.3.2.2), and to detect "sentinel human infections prior to dissemination in the general population" (paragraph 4.1.1.5).We do not share the HHS's view that these risks are acceptable. III. Medical and Scientific Concerns: Xenotransplantation is biologically irrational because it falsely assumes that human and non-human body parts are interchangeable. The dismal track record of previous animal-to-human organ transplant attempts is being ignored by the technology's proponents. Animal-to-human transplants have been deadly in some 55 recipients and ineffectual in one (Jeff Getty). The technology is dangerous and unproven. Xenotransplantation is Dangerous and Unproven The HHS states (p.49920) that "xenotransplantation shows promise for a wide range of diseases .. . and as an alternative source of cells, tissues and organs for clinical transplantations." This statement is powerfully contradicted by clinical evidence. In fact, the history of basic animal research, and extremely limited clinical research with humans in the field of xenotransplantation, has been marred by failure. Alexis Carrel, the French surgeon who had transplanted organs, and grafted veins and skin between dogs, cats and monkeys in the early 1900s, discouraged other surgeons from trying the experiments because his had all failed. Arthur Caplan, professor of bioethics and Director of the Center for Bioethics at the University of Pennsylvania School of Medicine has said, "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."[98] Similarly, 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."[99] There have been some 55 documented
animal-to-human whole organ transplants since 1906.[100] All have proven
unsuccessful. For example:
Researchers have suggested performing xenotransplants on chronically ill patients, on infants and children without access to mechanical assist devices, on "large" (or overweight) patients with type O blood, and on patients with conditions which make them ineligible for allotransplants.[140]As in the majority of earlier xenograft cases, this appears to be a select group of patients with little hope of survival to begin with. Should our society condone this kind of human experimentation, the "premature use of unproven procedures in fellow humans,"[141] before exploring safer alternatives? Robert Michler, formerly of New York's Columbia-Presbyterian Medical Center suggests that, as was the case with allotransplantation, the clinical "success" of xenotransplantation could be measured in terms of short-term survival rates, with the goal to strive for "extended graft survival."[142] In other words, if a xenograft recipient survives for ten days with a pig organ, that operation could be deemed a "success." Is that an acceptable standard for such a dangerous and expensive technology? Ultimately, it is the public, not a select group of research scientists, or pharmaceutical or biotechnology executives, who must answer such questions. Pigs Vs. Baboons: Logic or Convenience? The notion that pigs, because of their genetic dissimilarity to humans, could provide a safer source of tissues and organs for xenotransplantation than primates, for example,[143] is erroneous and has been discredited by the incidents of malaria, Dengue and yellow fever (from mosquitoes), Lyme disease (from ticks), rabies (from dogs, raccoons), human brucellosis (from cows, sheep, goats, pigs), bubonic plague, and the 50% human mortality rates associated with hantavirus pulmonary syndrome (from rodents).[144] Moreover, pigs' genetic dissimilarity to humans raises important questions. Ethical issues and disease risks have virtually precluded the use of chimpanzees and other great apes as organ donors. Are pigs the next best thing for those determined to implement the technology, or is there truly a scientific rationale for using pigs? The fact that they breed quickly, or have been "extensively farmed," or have organs that are "similar" in size to ours,[145] does not qualify as scientific justification for their use. It has been suggested that pigs are anatomically and physiologically "similar" to humans.[146] But there are differences in life-span, heart rate, blood pressure, and the structure of the regulatory hormones which maintain the basic physiological stability of the animal.[147] The author of an article in Nursing Times asks, "Can a pig's heart - normally on the same level as its head - pump enough blood to a human brain 15 - 18 inches above? Will a pig kidney filter human blood effectively, or will the pig's different uric acid metabolism lead to biochemical aberrations? And will the human recipient's immune system work in a transplanted pig organ?..."[148] A pig heart put into a human will turn black and stop beating in about fifteen minutes[149] and there is no evidence that this acute cellular and vascular rejection will ever be overcome. Nor is there any clinical evidence to suggest that organs from genetically bred pigs are any less likely to be rejected by the human body than those from conventional pigs. The massive doses of immunosuppressive drugs that would be required for such an operation would likely cause toxicity, increase the patient's chances of developing cancer,[150] and, as discussed, would likely facilitate the transmission of a xenogeneic virus from the animal to the patient.[151] Scientists from the FDA and the CDC have also pointed out that "the short life expectancy of the average pig minimizes the opportunity to observe the clinical manifestations of infections with agents that have long periods of clinical latency."[152] Xenotransplantation remains an unproven, highly experimental, and potentially virulent procedure. IV. The Power and Wisdom of Prevention: Emphasizing xenotransplantation promotes an unsustainable spare-parts approach to health care. It deemphasizes the importance of preventive health programs and lifestyle changes such as dieting, exercise and smoking cessation which could reduce the need for transplants of all kinds. Breeding Animals For Food is Unhealthy and Does Not Justify Xenotransplantation The HHS maintains that using animals such as pigs as xenograft donors is justified because pigs are "currently commercially bred and raised as a source of food" (p.49920). However, the same industry which disregards farm animals and views them as exploitable commodities, will likely disregard animals raised for xenotransplantation. Our traditional agricultural sector currently engages in unsanitary practices which place the health of both animals and humans at risk. Animal feeding practices have come under increasing scrutiny for their ability to cause disease in animals and humans.[153] The American Association of Feed Control Officials lists dried poultry manure, dried broiler litter, dried cattle waste, and pig waste as approved feed ingredients. Manure, animal remains and garbage are known to contain pathogens such as E Coli, salmonella, Lsteria monocytogenes, Campylobacter jejuni, Yersina enterocolitica, Clostridium botulinum, tapeworms, as well as drug residues, toxic chemicals, and a variety of viruses.[154] Human Creutzfeldt-Jakob Disease has been linked to the practice of feeding cows the ground up remains of other animals.[155] While the HHS specifies that "recycled or rendered animal materials" should be excluded from the feed of "source animals" (paragraph 3.2.1.3), such practices may be impossible to monitor and control since breeding facilities will largely be self-monitoring operations. This is not reassuring because feed laws are routinely violated in traditional animal husbandry operations as farmers seek to cut costs, in spite of federal oversight.[156] Because breeding and/or cloning animals for the xenotransplantation market would be undertaken as a for-profit venture, the industry would be subject to the same economic pressures that currently exist in the traditional agricultural sector. It will be difficult, therefore, to maintain sanitary conditions in the source animal breeding facilities. Regulations, which will likely be heavily influenced by the xenotransplant industry to begin with, may not be complied with rigorously, leading to breaches of protocol, with potentially devastating consequences for human health, animal health, and the environment. Eating and Breeding Animals is What Makes People Sick; Prevention is Essential The message that transplantation sends to doctors and scientists is that disease prevention needn't be emphasized; the message conveyed to the public is that it is not necessary to take responsibility for our own health by eating properly and exercising, or avoiding cigarettes and alcohol, because we can expect medical "miracles" to save us. Indeed, the number of patients with preventable diseases for which transplants are prescribed as a treatment, is growing.[157] The number of transplants performed continues to grow, with demand outstripping supply, all ofwhich places a tremendous strain on our health care system and economy. Ironically, it is precisely because people eat too many pigs (and other factory-farmed animals), and have unhealthy lifestyles, that pig organ transplants are being considered. Alcohol-related cirrhosis and alcoholic hepatitis are the most common forms of fatal liver disease in the US, which could be prevented through avoidance of alcohol.[158] Similarly, about 5,000 intravenous drug users develop a chronic and potentially fatal form of hepatitis C every year[159] which could be prevented through avoidance of drugs, or needle sharing. A study published in Preventive Medicine (November 1995) revealed that meat-eating is responsible for $61.4 billion in annual health care costs.[160] Diabetes is the most common condition found in patients who need kidney transplants,[161] and it is largely controllable through diet and lifestyle changes. Scholars, scientists and physicians[162] have criticized the current animal-centered food production system as environmentally destructive, inhumane, unhealthy, and unsustainable. Pig farmers suffer high rates of respiratory ailments, pneumonia, lung scarring, animal bites, and chemical poisoning.[163] New deadly, antibiotic-resistant strains of salmonella (DT104) - linked to farm animals, pork sausage, meat paste and raw chicken,[164] and E-Coli (0157:H7) - long-associated with tainted beef,[165] are invading the US. We Should Be Investing In Alternatives to Xenotransplantation It is unclear who would pay to implement the HHS's extremely costly guidelines. Before allocating US funds to such an undesirable technology as xenotransplantation, federal public health agencies have a duty to explore proven, less costly and less risky alternatives. These include investing in preventive health and health maintenance programs. Lifestyle changes have proven capable of reversing heart disease.[166] 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.[167] Many examples of preventive medicine could drastically reduce the demand for human organs (and surgical procedures of all kinds), thereby eliminating the prospect of cross-species transplants. The American Society of Primatologists, and several animal advocacy organizations, strongly encourage their members to become organ donors, either through the mechanism of driver's license renewal or through signing an organ donor card (available through the United Network for Organ Sharing).[168] Launching government-funded education campaigns aimed at increasing the pool of human organs should be considered. Neither the government nor the medical community have aggressively encouraged human organ donation.[169] Currently, only 20% of those individuals who die "healthy" have arranged to donate their organs, even though a 1993 Gallup Poll showed that 85% of the public supports organ donation.[170] Presumed consent legislation has been enacted in several countries. The law presumes that everyone is an organ donor unless they specify otherwise. When Belgium enacted its presumed consent law in 1986, organ donation increased by 183% in a two-year period.[171] Organ availability quadrupled in Austria when its law was enacted.[172] A 1996 Swedish law requires all citizens to make a decision regarding the use of their organs after death, and has increased the donor pool by 600,000. A similar Danish law increased the donor population by 150,000.[173] If presumed consent legislation were enacted in the US, researchers contend that 75% of the adult US population (210,000,000) would become committed potential organ donors.[174] But Lloyd Cohen, Professor of law at George Mason University in Virginia, claims that, the US organ shortage (of some 50,000 organs per year) could easily be alleviated by creating financial incentives or rewards for donors. Potential donors would sign a contractual agreement, similar to a life insurance policy, designating beneficiaries of their choice (relatives or friends). Should a donor die and his/her organs be harvested to save another person's life, the donor's beneficiaries would collect the proceeds from the "sale" of those organs.[175] In addition, in the January 22, 1998 issue of the New England Journal of Medicine (1/22/98) doctors 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. We could also be investing in the development of synthetic organs and other surgical techniques to repair malformed or poorly functioning organs. About 75% of patients who undergo a procedure called ventricular remodeling - in which a section of heart muscle is removed and reshaped - can be taken off the transplant waiting list.[176] Ultimately, the MRMC believes that transplantation is a dangerous and expensive approach to healthcare which should not become a normative treatment modality. Physicians and health care agencies need to focus their energies and resources on education and prevention programs to avoid the need for transplants of all kinds. V. Economic Concerns: Because of its exorbitant price tag, xenotransplantation threatens to drive up health care costs for a majority of Americans, placing an unacceptable financial burden on the federal government, both in terms of financing the procedures and the postoperative care, and in dealing with the consequences of a potential viral epidemic akin to HIV or worse. Less costly alternatives to xenotransplantation exist and should be explored. Human-to-Human Transplants Are Expensive Approximately 76,000 patients were referred for organ transplants in 1996, with the majority of those (45,545) being corneal transplants.[177] But human-to-human transplants are in and ofthemselves expensive, with average hospital and first-year postoperative care averaging $200,000 per patient in 1996 dollars[178] - more than double what it cost to treat a person with HIV from diagnosis to death in 1994 (circa $60,000).[179] Costs are rising and five-year survival rates have decreased slightly.[180] Estimated postoperative costs (for liver patients), including anti-rejection drugs and other medications, are approximately $11,000 in the first year, and up to $18,500 annually in the years to follow. Immunosuppressive medications are required for the rest of the recipient's life; he/she must also be continually monitored for infection, rejection, and graft arteriopathy.[181] There are fees for lab tests, child care, physical and occupational therapy and rehabilitation, among other things.[182] Some patients must have several transplants during their lifetimes to replace failing organs.[183] Despite the use of immunosuppressive drugs, roughly 50% of transplanted human organs are rejected and fail within five years.[184] (Rejection problems would clearly be worse for xenotransplants). Besides the problems of rejection, and toxicity from immunosuppressive drugs (doses of which would likely be increased in xenotransplants), the threat of infectious disease is also an issue in allotransplantation. The HHS admits (p.49921) that "transmission of infections (HIV/AIDS, Creutzfeldt-Jakob Disease, rabies, hepatitis B, hepatitis C) via transplanted human allografts has been well documented."[185] Given the above, one must question whether the costs associated with allotransplantation are presently justifiable, particularly when a majority of these procedures could be avoided. Procuring human organs for transplantation is not without its ethical controversies either. Concerns have been raised that poor people in developing countries are being killed so their organs can be harvested and exported to the developed world.[186] Between 1990 and 1995, more than 2000 kidneys, were sold annually to wealthy Middle Eastern recipients.[187] Questions have resurfaced about whether terminally ill patients' deaths are being hastened at some US hospitals to obtain their organs for transplant.[188] In addition, the concept of brain death has been questioned, which has stirred debates about "when to call someone dead."[189] Some have said that current criteria offer no guarantee that a patient is indisputably dead.[190] Surgeons and others in the transplant community fear that the publicity surrounding this issue will frighten people anddiscourage them from becoming organ donors.[191] Xenotransplants Will Be Even More Expensive Xenotransplantation is riskier and promises to be even more expensive than allotransplantation ($250,000 per operation in 1995,[192] not including the costs of breeding, housing, feeding, medicating, testing, transporting, rendering, and disposing of the waste and remains of herds of transgenic animals).[193] Institute of Medicine figures from 1996 reveal that xenotransplant costs for all patients who need organs could reach $20.3 billion.[194] These costs are beyond the means of the average health care consumer and an already overburdened health care system. Xenotransplantation is excluded by Medicare and Medicaid and denied by health maintenance and preferred-provider organizations. If ever successful, xenotransplantation would, at best, benefit a small minority of patients (100,000) while dramatically driving up health care costs for all Americans. This is fiscally irresponsible. Ironically, the AIDS epidemic appears to have reduced the number of potential (human) organ donors due to the threat of infection.[195] Unleashing a xenogeneic infection in the human population via xenotransplantation could have a similar effect: as more and more people became infected with a new zoonotic virus, the number of available human organs for transplantation would shrink accordingly. Thus, in an attempt to solve one problem, xenotransplantation could create another, driving costs for conventional (human) organ transplants even higher. Xenotransplants Are Not a Given Yet The Institute of Medicine's June 1996 report, Xenotransplantation: Science, Ethics, and Public Policy, concluded that "the potential benefits of xenotransplants are great enough to justify the risk." The report was funded by parties who are hardly neutral in this debate, including the FDA, the National Institutes of Health through the National Cancer Institute, and the US Department of Defense (all champions of animal-based research), Charles River Laboratories (breeders of animals used in experimentation), and W. R. Grace and Company (whose subsidiary, American Breeders Service (ABS) filed a patent (WO 95/17500) in 1993 to cover clones and chimeras from pigs, horses, cows, antelopes, goats, and sheep bred with desirable traits for agricultural purposes). Researchers and biotechnology companies are eager to begin mass producing herds of transgenic animals, to provide a potentially limitless supply of organs for transplantation into humans. The HHS seems to hint that, despite the inherent public health risks, "the commercialization of xenograft production . . . throughout the US and the world" (p.49920) is imminent and inevitable - an inappropriate stance for an allegedly neutral public health agency. The HHS fails to speak of the lobbying power of special interests in the decision-making process. A recent issue of Fortune magazine revealed that biotechnology and pharmaceutical companies are eager to cash in on the promise of a booming xenotransplantation market - worth $6 billion annually (and 450,000 pig organ transplants) by 2010.[196] Pharmaceutical giants like Sandoz Pharma AG (US and Switzerland) which is owned by Novartis - the biggest corporate xenotransplantation investor, Bristol-Meyers Squibb, Hoechst, Fujisawa, and biotechnology companies like Alexion Pharmaceuticals Inc. (New Haven, CT), Nextran Corp. (Princeton, NJ), Biotransplant, Inc. (Charlestown, MA), and Imutran (recently acquired by Sandoz and hence owned by Novartis), all have a stake in this market. Public health authorities should not be placing the interests of these private corporations and their lobbyists over the interests of the American public. The Environmental Problems Posed By Xenotransplantation The adverse environmental and health impacts of animal-based agriculture have been well-documented.[197] Nonpoint source pollution, such as agricultural waste, is now the principle threat to surface and ground water quality in the US.[198] North Carolina State University estimates that hundreds of hog manure lagoons, needed as part of hog productions in the state are leaking contaminants such as nitrate - a chemical linked to "blue baby syndrome" - into the groundwater.[199] No mechanical method of retrieval exists to clean contaminants from groundwater. In the summer of 1995, a hog manure lagoon broke open and released 25 million gallons of waste from 10,000 hogs into nearby waters and on to neighboring soybean and tobacco fields.[200] A deadly microscopic phytoplankton named Pfiesteria piscida (latin for fish-killer) thrives in waters polluted by hog manure. The organism can change into 22 different forms - from an amoeba to a two-tailed killer that drugs schools of fish and sucks off their skin. It has been blamed for killing half the fish stocks in North Carolina in the 1990s. After allegedly becoming airborne, Pfiesteria caused North Carolina University freshwater botanist Joann Burkholder and a colleague to become ill with headaches, asthma, stomach cramps, nausea, vomiting, memory loss, and muscle weakness. Fearing a loss of tourism and retribution from the hog farming industry, state officials have refused to accept the existence of a problem or to issue health warnings, accusing Burkholder and others of being drunk or fabricating their ailments.[201] Many experts have addressed the problem of farm animal carcass and waste disposal. Kenneth Steele, Professor in the Department of Geology at the University of Arkansas, Fayetteville, writes that "the use or disposal of animal wastes directly impacts the quality of the land and water."[202] Charles D. Fulhage, of the Department of Agricultural Engineering at the University of Missouri, Columbia writes that "Improper disposal of dead animals can result in surface water or groundwater contamination."[203] John M. Sweeten, extension agricultural engineer specializing in waste management at Texas A & M University reported that livestock manure (from holding ponds, treatment and storage lagoons, and manure stockpiles), contains pathogenic organisms, nitrates, ammonia [and bacteria and viruses] that can contaminate groundwater.[204] Pathogenic water-borne organisms in manure include Salmonella, listeria, vibrio, brucella, cryptosporidium, coxiella, chlamydia, and mycoplasma.[205] Cryptosporidium in calf waste was blamed for a 1993 outbreak in Milwaukee that left 400,[000] people sick and more than 100 dead.[206] Pesticides and insecticides (commonly used in agriculture), and their by-products may also contribute to soil and groundwater contamination.[207] How would facilities breeding pigs for xenotransplants deal with the waste generated by their facilities, particularly in light of recent knowledge about microorganisms like Pfiesteria? Would they deny or try to cover up public health dangers? And how would they dispose of transgenic pigs' bodies once their organs were harvested? Conventional agricultural operations and rendering plants continuously wrestle with the problem of how to dispose of millions of tons of perishable animal tissue each year.[208] A February 1992 article by Kenneth B. Kephart, Extension Swine Specialist for the Department of Dairy and Animal Science at Penn State University, exposed Pennsylvanian farmers' concerns about how to dispose of 100,000 dead hogs annually: by-products of their industry. Incineration,[209] burial, and composting[210] were all described as expensive, unhygienic, and environmentally problematic options. Burial is recognized as an undesirable option due to the potential for groundwater contamination by rotting and diseased flesh.[211] HHS seems to favor the marriage of agriculture and medicine by way of a close collaboration between animal breeding facilities and hospitals/research centers. But in paragraph 3.2.1 of its guidelines, HHS makes no mention of how biomedical animal facilities are to dispose of the numerous remains of genetically modified animals and their offspring. Nor does it make any mention of the environmental impact such facilities would have on local communities - an extremely important omission in the context of the potential disease risks posed by the disposal of such remains. The responsibility is left to the facility, which is not reassuring given the numerous institutional scandals described herein. VI. Conclusion Research has demonstrated that the risk of transmitting animal viruses to humans is real. This is a concern to scientists worldwide. In a letter to the journal Emerging Infectious Diseases, French virologist Claude Chastel wrote that, "while we face the terrific threat of AIDS . . . we are preparing a new infectious Chernobyl.'" Chastel is among dozens of virologists who have publicly advocated a moratorium on xenotransplantation.[212] The HHS proposed guidelines on xenotransplantation procedures acknowledge the dangers the technology could pose to xenograft recipients, laboratory and health care workers, and society at large. Despite this fact, federal health authorities have yielded to the positions held by biotechnology companies, anti-regulation forces, and transplant lobbies, excluding the public and xenotransplantation's critics from debates.[213] This has led to irresponsible policy-making and to the development of unnecessary, expensive, clinically unproven, and potentially dangerous new drugs and technologies. Before supporting a treatment option like xenotransplantation, government and private granting agencies should be allocating funds to 1) prevention programs aimed at reducing the need for transplants of all kinds, 2) administrative programs to increase human organ donations, and 3) - reflecting society's' growing respect and compassion for the nonhuman world[214] - technologies which lessen our dependence on animals. Given our society's poor track record in managing modern global threats including the increasing lethality of military weapons, environmental pollution, rainforest destruction, exponential population growth, and diseases like AIDS, we must honestly ask ourselves whether we have the wisdom and moral maturity needed to deal with the consequences of xenotransplantation and related genetic technology. Until that question is publicly debated and, if ever, answered, logic dictates a policy of restraint and humility. In light of the epidemiological, public health, medical, scientific, economic, and environmental issues outlined in this critique, the MRMC advocates an indefinite freeze on all forms of experimentation and clinical application of xenotransplantation technology. Federal funds should not be used to fund any stage of xenotransplantation's development. Alix Fano, M.A.
References 1 Anthony Dorling, et al., Clinical Xenotransplantation of Solid Organs,'
The Lancet 349 (March 22, 1997): 867-71. |