THE ALLIANCE FOR HUMAN RESEARCH PROTECTION

Testimony
by
Vera Hassner Sharav

Committee on the Use of Third Party Toxicity Research with Human Research Participants
Science, Technology, and Law Program
The National Academies of Science

January 8, 2003

My name is Vera Sharav and I am the president and founder of The Alliance for Human Research Protection (AHRP) a citizens’ watchdog organization monitoring human research to ensure that the moral principles enshrined in the Nuremberg Code and the Declaration of Helsinki are preserved and followed in experiments involving human beings. The Alliance for Human Research Protection is inalterably opposed to the exploitation of human beings as experimental guinea pigs in nontherapeutic experiments to test poisonous substances.

Pesticide experiments in human beings are morally unconscionable and scientifically dubious – they fail to meet fundamental standards of permissible research – as they offer no potential therapeutic benefit to the subjects or society. Such experiments violate the Nuremberg Code and all subsequent national and international codes of medical research ethics that were adopted precisely to prevent potentially harmful experiments from ever again being conducted on human beings. Thus, it is something of a jolt that the U.S. Environmental Protection Agency (EPA), whose mission is protecting the public from environmental hazards is even contemplating requests to sanction human pesticide experiments inasmuch as they violate those moral and legal standards.

Pesticides are chemicals designed to kill, control, or repel insects, plant diseases, weeds, rodents, and germs. They are used mostly in agriculture, but also for industrial purposes and to kill pests in homes, schools, and hospitals. Because of their inherent toxicity human exposure to poisonous chemicals is always undesirable. Pesticides have absolutely no therapeutic medical use and human beings exposed to pesticides will never derive a benefit from such exposure. Some of the people exposed can expect to experience adverse effects – often emerging long after exposure. Among the grotesque medical atrocities committed by Nazi doctors at Auschwitz and other death camps, were experiments that deliberately exposed human beings to germs and poisonous chemicals. When the experiments were publicly revealed during the Nazi "Doctors Trial" at Nuremberg,[1] sixteen doctors were found guilty of "crimes against humanity." The American military tribunal’s verdict laid down 10 universal principles – The Nuremberg Code – to set boundaries for permissible (i.e., ethical) research involving human beings. The first qualification for permissible research on human experiments: experiments must "conform to the ethics of the medical profession" and be justified by the expectation that they will "yield results for the good of society that are unprocurable by other methods or means of study." [emphasis added]

Pesticide experiments do not meet that ethical standard. Moral principles preclude the deliberate exposure of human beings to such toxic agents. Because of their toxicity, and absence of any therapeutic benefit, moral principles preclude the deliberate exposure of human beings to such toxic agents. The world community recognizes that exposing human beings to chemicals that could potentially kill them is reprehensible. Therefore, pesticides have been fed to rats, mice and guinea pigs in laboratory studies designed to test (indirectly) whether toxicity levels are safe for humans. Regulatory standards of safety of non-therapeutic chemicals are therefore established by risk assessment based almost entirely on predicting human effects by indirect means. (The same is true for simulated automobile crashes.)

In 1972, Congress passed the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA) requiring all pesticides to be tested in animals to ensure the health and safety of human beings are not jeopardized. Laboratory animal studies indicate a variety of adverse effects from exposure to certain pesticides, particularly several organochlorine and organophosphate insecticides.[2] Since the immune system plays a critical role in helping ward off disease, there is growing concern in the scientific community that toxic chemicals, such as pesticides, may damage the immune system of children and infants who are uniquely susceptible to the effects of pesticides because of their physiological immaturity and greater exposure to pesticides. Pesticides have been associated with birth defects, certain childhood cancers – including leukemia, sarcomas, and brain tumors – and found to adversely affect the nervous system.

Of particular concern is that during the first six years of life. Children are also especially susceptible to the impact of carcinogenic pesticides during periods of rapid growth, specifically infancy and adolescence, when cells and tissues are proliferating.[3] The information gained under FIFRA raise concerns about the potential hazards of widespread, unrestrained use of pesticides and a corresponding rise in serious health hazards – particularly in children.

Tolerance levels for the majority of pesticides on the market have been established based on adult eating habits, but risk assessments have failed to take into account the fact that children are exposed to pesticides from multiple sources. A growing body of evidence – from case reports and epidemiological studies – shows links between pesticide exposure and the development of adverse health effects:

• A 1992 National Cancer Institute review of two dozen epidemiological studies found pesticides to be one of five likely carcinogens explaining why farmers had elevated risks of several forms of cancer including Hodgkin’s disease, multiple myeloma, leukemia, melanoma, and cancers of the lip.[4]
• According to the Office of Technology Assessment, [5] an estimated 4 to 9 percent of agricultural and other workers acutely poisoned by pesticides experience delayed persistent neurological and psychiatric effects including agitation, insomnia, weakness, nervousness, irritation, forgetfulness, confusion, and depression.
• In 1993 the National Academy of Sciences issued a report3 documenting the special vulnerability of children to pesticides, and that government standards for residues in food do not adequately protect children. Children’s exposure to pesticides is greater than adults because of their distinctive diet and play activities.
• Based on experiments in laboratory animals, the EPA has identified at least 96 different pesticide ingredients registered for use that are potential human carcinogens.[6]
• The California Department of Pesticide Regulation[7] Of the sixty-three chemicals evaluated by the DPR, fifteen have tested positive for birth defects and twenty-two have tested positive for other reproductive effects in experimental studies.
• According to the National Research Council, [8] concern about children’s exposure to pesticides is valid because "exposure to neurotoxic compounds at levels believed to be safe for adults could result in permanent loss of brain function if it occurred during the prenatal and early childhood period of brain development."

These concerns led Congress to enact the 1996 Food Quality Protection Act (FQPA) for the protection of children. Under FQPA standards pesticides must be evaluated to ascertain a safe level of exposure that will protect children from health risks. Following the enactment of FQPA, EPA focused on the most widely used pesticides, the organophosphates consisting of 40 different compounds used in dozens of combinations on wheat products, fruits, and found in air, water, furniture, even toys. Organophosphates clearly saturate a child’s environment, thus posing cumulative risks of harm. EPA’s preliminary assessments found that organophosphates, as currently used, already exceed the risk level allocated to all others.[9]

EPA’s findings of toxicity validate the concerns for children’s health.[10] However, the toxicity findings present an economic threat to pesticide manufacturers whose profits and liability may be affected. The assessment of safety in animal studies is determined by the "no observable effect level," NOEL, baseline. A 10-fold margin of safety below NOEL is then calculated as safe for humans. Because of the greater risk for children the 1996 law required those pesticides that children may be exposed to – e.g., organophosphates – must be further reduced by 10-fold.

But the law aimed at protecting children’s health is under siege. Giant corporate bullies of the chemical industry have embarked on an aggressive strategy aimed at derailing those legal protections for children. Pesticide companies have seized the opportunity to exert pressure on a waffling EPA.[11] They have introduced a flawed rationale for exposing human beings instead of rats to poisonous products, in order to escape from compliance with FQPA safety standards. The purpose of this "Trojan Horse" strategy is to circumvent legal restrictions on allowable toxic levels and to lift the ban on human pesticide experiments. If this strategy works, this special interest group will succeed in sweeping aside painfully won international standards for protection of research subjects. If EPA accepts valid or invalid data from unethical human studies to set lower safety standards, industry will escape from liability.

Human pesticide experiment, Scotland:

In 1998 Bayer AG conducted an experiment in Scotland in which eight students were doused with the insecticide, Azynphos-methyl (AZM), for the purpose of obtaining "favorable" data to persuade the EPA to weaken federal safety standards that had been established by animal studies. AZM has been widely used in agriculture, but its neurotoxic hazards to agricultural workers, children and the environment, have led the EPA to greatly restrict its use.[12] The World Health Organization has declared AZM "highly hazardous." In 1991, a thunder storm caused azinphos-methyl to run off sugar cane into rivers, killing up to a million fish, along with turtles, alligators, snakes and birds. And in 2002 Canada reported that high concentrations of AZM were found in the Wilmot River, killing 15,000 fish.[13]

Organophosphate pesticides – such as Azinphos-Methyl – are hazardous substances that originated as military weapons designed to kill people.15 Experiments involving such pesticides have nothing in common with bone fide medical research: they have much in common with the experimental atrocities committed by Nazi doctors and scientists. It is significant that the German pharmaceutical / pesticide company that was most intimately involved in experiments that tested its products on inmates in the Nazi concentration camps, [14] is the catalyst for affecting a radical policy change to further its business interests. Azinphos-methyl, manufactured by Bayer AG, was developed during World War II by Bayer scientists who were among those who conducted experimental atrocities at Auschwitz and other Nazi death camps when the company was a subsidiary of I.G. Farben, the manufacturer of Zylcon B, the very gas used to exterminate millions of Jewish people.13 The experiments were classified: "medical and scientific experiments in the service of science."[15]

Human pesticide experiments that have been conducted by industry are, by their nature immoral and scientifically dubious. The experiments fail to meet scientific standards: A statistical power analysis by Dr. Herbert Needleman[16] demonstrated that to detect a 1% increased risk for mental deficits linked to pesticides would require 2,500 subjects per dose. A 1% increased risk would mean that 160,000 children under the age of five would suffer cognitive impairment, learning disabilities and behavioral problems. Dr. Needleman’s power analysis shows that human pesticide studies done so far have "virtually no chance to find an effect, and therefore are exposing Îvolunteers’ to poisons for no scientific reason."[17]

Documents obtained by Natural Resource Defense Council (NRDC) reveal the experiment failed to comply with rudimentary ethical requirements. It was conducted without regard for the health, welfare, and dignity of the subjects – who were not informed about the purpose, nature or risks involved. The experiment has been severely criticized for its disregard for human rights, ethical research standards, and scientific integrity.[18] Given these egregious violations the experiment does not deserve serious consideration by EPA. Experiments such as this are designed to promote pesticides as safe by pretending that the information obtained from a miniscule number of subjects provides generalizable information about the health hazards these pesticides pose for children and fetuses.

If the EPA were to accept the specious arguments for the removal of safety standards that reduce permissible exposure levels based on animal data, the consequences for children will be disastrous. Children will be placed at higher risk of exposure to neurotoxic pesticides, and pesticide companies would benefit from an added bonanza – protection against liability claims. Valid information about the safety of pesticides and pollutants is obtained from epidemiological studies and animal studies. Yet, Bayer’s submission of this pesticide experiment in August 2001 is the catalyst for a possible major change in public policy. [19]

To understand the corporate culture that motivates chemical corporations to conduct poisonous chemical experiments on human beings, it is instructive to examine the historic record of one of the industry’s giants. Bayer’s history reveals a long and infamous record of human rights violations, including slave labor and inhumane human experimentation.[20] [21] In 1948, the International War Crimes Tribunal at Nuremberg found thirteen Bayer executives guilty of war crimes, slavery, and crimes against humanity. The American Chemical Association notes that all IG Farben pharmaceuticals were marketed under the Bayer trademark.[22] Throughout the Nazi era, Bayer was the control center for IG Farben human experiments. Bayer’s products – including drugs, pesticides, and nerve gases – were tested on helpless death camp inmates.14

Holocaust survivor sues Bayer AG:

On February 17, 1999, a lawsuit was filed in U.S. District on behalf of Eva Mozes Kor, one of 180 surviving twin children (out of 1,500) who had been subjected to medical experiments at Auschwitz. The suit charged Bayer, of collaborating with Dr. Josef Mengele (the "Angel of Death") to commit medical atrocities for profit.[23] The suit claimed that Auschwitz inmates were injected with toxic chemicals and germs provided by Bayer "to intentionally make them sick in order to test the effectiveness of its experimental medicines."23 And the suit claimed that Bayer officials personally monitored and supervised some of the experiments. According to Irwin B. Levin, one of several lawyers who handled the class action suit for the plaintiffs, Bayer paid Nazi officials to gain access to those confined in the death camps and collaborated in Nazi experiments as a form of "research and development."

On June 11, 1999, ABC News 20/20 reported that new documents not available to the tribunal at Nuremberg directly link Bayer to the Nazi experiments. The documents are chilling evidence of the culture of utilitarian ethics in which human beings had been reduced to commodities and referred to as "test objects" A letter in which Bayer sales director, Wilhelm Mann, praised Mengele’s experiments and promised to discuss financing from the company:14 "I have enclosed the first check," Mann wrote. "Dr. Mengele’s experiments should, as we both agreed, be pursued. Heil Hitler!"23 ABC reported that "Bayer says there’s no evidence any money was actually sent." ABC’s Brian Ross reported that a longtime Bayer employee, Dr. Helmut Vetter was involved in testing Bayer experimental vaccines and medicines on Auschwitz inmates. He was later executed for giving inmates fatal injections. Levin stated: "Bayer actually performed some of those atrocities." He went on to say, "this case represents the worst example of individual and corporate evil that the legal system may ever see."[24]

Since the Nazi era, a pattern of corrupt practices and indifference to human life – especially in the Third World – have continued the legacy. I cite but a few examples.

Pesticide poisons 42 Peruvian Children:

In August 2002, the Pesticide Action Network [25] reported that a Peruvian Congressional Subcommittee found "significant evidence of criminal responsibility" by both Bayer and the Peruvian Ministry of Agriculture in the poisoning of 42 children in the remote Andean village of Auccamrca in Octboer 1999. Twenty-four of the children died, and eighteen others suffered significant long-term health and developmental problems after eating a school breakfast contaminated with the organophosphate pesticide methyl parathion. The families filed a suit against Bayer asserting the company should have taken steps to prevent foreseeable misuse of this extremely hazardous chemical. Bayer packaged the pesticide, a white powder that resembles powdered milk, in small plastic bags, labeled in Spanish and displaying a picture of vegetables without indication of danger and no usable safety information.

Ciproxin clinical trial caused life-threatening infection:

Reports in the United Kingdom press revealed that perhaps 650 people who underwent surgery in a multi-site clinical trial involving Ciproxin, were put at risk of potentially fatal infections because Bayer, the sponsor of the experiment failed to disclose the risks of serious post-operative infection to the hospitals or patients involved. According to the Sunday Times, in previous studies the drug reacted badly when combined with others prior to bowel surgery. It was found that taken orally seriously impaired the drug’s ability to kill bacteria, thereby leading to serious infections.[26] According to the Sunday Times this information was not revealed at the start of the study to the hospitals involved.

The case was revealed by a retired surgeon in Southampton, Dr. Stephen Karran, who is quoted stating: "The Bayer ciproxin trial in Southampton, of which I have first-hand knowledge, was scientifically, clinically and financially fraudulent. It exposed patients to serious risk of infection and violated their basic human rights." [27] On May 14, 2000, the Sunday Times (UK) reported: "Last week Bayer confirmed that it knew of the absorption problems associated with Ciproxin before the study began. It also confirmed that the study’s protocol did not take account of the problem and that it was changed at an unspecified point during the study. Bayer declined to reveal overall numbers for post-operative infections and fatalities, on the grounds that the data remained confidential."26

Human pesticide experiments are morally repugnant. They are designed to promote pesticides as safe by pretending that the information obtained from a miniscule number of subjects provides generalizable information about the health hazards these pesticides pose for children and fetuses. To obtain valid information about the safety of pesticides and pollutants one must conduct epidemiological studies and animal studies. However, as a concession, The Alliance for Human Research Protection would not object to pesticide experiments if the subjects were selected as The Nuremberg Code allows (principle 5): namely, "where the experimental physicians also serve as subjects" along with the sponsors of the trials.

I would like to convey a cautionary note to this and other advisory committees called upon to consider whether to lend support to policy changes that will weaken the fragile, and hard won protections governing research with human subjects. Let us be absolutely clear about the driving force behind the current demand for the legitimization of human pesticide experiments. Market driven, utilitarian ethics threaten to derail medicine and science from their humanitarian focus for the public good. The logical, if murderous end point of utilitarian ethics was embodied at Auschwitz where every scrap of material value was catalogued and utilized while all humane values were annihilated. In a utilitarian universe human beings who are disadvantaged, weak, disabled, needy, or alien, have no rights, they are conscripted to serve as means to an end.

A democratic society can be transformed into a society guided by utilitarian ethics of expediency by the collaborative effort of advisory committees which suffer from the same shortcomings as institutional research review boards – they are not independent, nor do they represent the moral values of the community or the interest of the individuals and groups who will be affected by their recommendations. Advisory panels are often influenced and manipulated by the governing administration and powerful corporate stakeholders that financed their election campaigns. Advisory panels are convened mostly for the purpose of lending legitimacy to policy shifts that contradict existing, public sanctioned policies. Thus, they engage in a process of rationalization, disingenuously paying lip service to truisms, while they weaken individual safeguards.

Several examples come to mind:

The co-chairman of the EPA Science Advisory Board in 1998 had conducted air pollutant experiments on human subjects at the University of Rochester, resulting in the death of an 18 year old student.19 A March 2001 Minority Report by members of the Data Testing Human Subjects Subcommittee, validates the observation that the advisory committee process is tainted, and its recommendations do not even reflect the members’ stated views.15 Notwithstanding the Nuremberg Code mandate – "the voluntary consent of the human subject is essential" – the National Human Research Protection Advisory Committee (NHRPAC) in 2001 recommended legitimizing research conducted on so-called, third party subjects about whom information is gathered without their knowledge or consent. NHRPAC redefined the status of a "human subject" to the exclusion of third-party subjects. Another advisory panel convened by the Secretary of Health and Human Services recently gave approval for a smallpox vaccine trial that would expose 40 non-consenting children aged 2 to 5 to the risks of live vaccinia virus despite the fact the vaccine posed serious risks whereas there is no evidence of their ever being exposed to smallpox. The overwhelming rejection of the idea by the public is noteworthy[28] and is likely to prevent this experiment from going forward.

 

The essential question before this committee and the Environmental Protection Agency is whether the committee will uphold FQPA standards for the protection of children or facilitate the descent of American research down that slippery slope. If we are to preserve a democratic society, we must reject data obtained by unethical means whether it is scientifically valid or invalid.