The Ramazzini Institute
for Occupational and Environmental Health Research   

Who Are We?

Moral Questions
Human Guinea Pigs and the Sacrifice of 'Susceptible' Populations

     Historian William H. McNeill, in Plagues and Peoples, applies the process of evolution to human societies as well as to our bodies. When logic doesn’t prevail, other tools of survival take over. Long after we rose to the top of the food chain, he points out, cannibalism - a form of macroparasitism - - persisted. It still does.
     Cannibalism raised its ugly head in January of this year at a meeting convened by the National Research Council at the behest of the Environmental Protection Agency. EPA was under pressure from the pesticide industry to relax existing policies and regulations. The Council was asked to examine the use of “human research participants” in determining toxicity. Johns Hopkins University Professor Lynn Goldman, former Assistant Administrator in EPA for pesticides and toxic substances, and Jennifer Sass, Senior Scientist of the Natural Resources Defense Council weighed in. They not only questioned the use of ‘human research subjects‘, they also attacked the threshold or “No Observable Adverse Effect Level” approach to setting standards for pesticides that fail to protect ‘susceptible populations’, such as unborn and born children, the elderly, or heavily exposed farm workers.
     The "threshold" concept attracts some environmental scientists as a way to play the game of ‘as if’ that characterizes science, in a way they consider socially or economically ‘realistic’. Other believe that thresholds or ‘safe levels’ for toxic substances in large, normal populations are not found. “Observable” = what some decide to observe using a method of observation selected to produce a desired result, and “adverse” = what they decide is bad.
     In the January meeting on pesticides, Jennifer Sass showed an instructive slide comparing three different studies of the lowest observable effect levels [LOEL] of aldicarb. In a “scientific study” done by a manufacturer, four healthy adult males experienced lowered levels of the enzyme cholinesterase when dosed with 0.075 mg/ kilogram of body weight.
     Another maker of aldicarb, also tested four healthy adult males and determined that 0.025 mg/kg body weight was the LOEL for cholinesterase inhibition. Sass compared these results with a finding by Lynn Goldman, who found that the lowest dosage associated with illness was 0.0023 mg/kg observed in a 66-year old woman who ate a contaminated cucumber. “Within 45 minutes she experienced nausea, vomiting, sweating, dizziness, loss of balance, disorientation, and fatigue.”
     The standard for aldicarb is based in great part on the cholinesterase study of the healthy males. But those most heavily exposed – farm workers – may in fact include 66-year old women, as well as pregnant women, children, and not-so-healthy males who do not work the eight hour shifts assumed by the standard. They may work from dawn to dusk, unable to wash or change contaminated clothes, or access personal protective equipment [which in hot climates can be worn for only a few hours per day.] Access to health care typically occurs when they collapse and are carted to the nearest emergency center.
     There is another way to play the game of ‘as if’. Well-studied normal populations of tens of thousands exposed to toxic agents such as asbestos and ionizing radiation provide a different risk assessment model. Since in these cases the risk of cancer, the effect best studied, has never been found to completely disappear, even at very low levels of exposure, then a prudent assumption is that for any toxic agent zero risk does not exist. Playing the game with this rule makes elimination of unnecessary exposure to a toxic agent an ethical imperative.
     The no zero risk rule also supports the preference of ethical researchers to use laboratory animals instead of humans, or to do ethically-designed epidemiology and medical surveillance to determine toxicity. Nonetheless, all the health regulators are under pressure to accept the use of data from consciously exposed humans, regardless of the necessity of the agent being tested, and with the claim that the human research “subjects” are “volunteers” who know what they are doing.
     Most of us experience medical procedures, from flu shots to brain surgery, and sign a consent form stating that we voluntarily and with full knowledge agree to what the doctor is about to do. The same applies to both the healthy and the very ill who participate in clinical trials of new drugs or therapies. Most don’t even read the form. We [or our proxy] just sign, whether out of fear or trust or ignorance or lack of real choice, or ‘all of the above’. The nature of the consent – questions of ‘voluntariness’, delivery of information and conflicts of interest among providers or investigators – makes real choice a chimera. Yet, mesmerized by this common experience, we seldom question the use of this model in protecting research subjects. They become still another ‘susceptible’ population sacrificed for the sake of setting environmental standards for exposures and agents that may not be necessary in any case. They also become victims of socially tolerated cannibalism by a subtle means of coercion.
     Previously, when the Environmental Protection Agency issued a policy on the use of data from the testing of human research subjects, they considered a Science Advisory Board report that discussed the coercive nature of financial incentives for "volunteer" research subjects, a practice that clouds the voluntariness in the voluntary informed consent doctrine at the heart of this kind of research. They found that in Holmes County, Mississippi, where median family income is about $11,302, a $40 fee may be adequate to induce volunteers to take a pesticide cocktail. In Nassau County, New York, with a median farnily income of nearly $54,000, the fee might have to be $100.
     Knowledge of the risks, whether adequate or not, is perceived differently by different socio-economic classes, allowing greater opportunities for the exploitation of precisely those humans least able to deal with adverse effects. Professor Goldman documented this kind of exploitation in her statement before the Council’s committee.
     In 1998, Goldman testified, “ it was apparent that manufacturers were beginning to voluntarily submit to the EPA human studies conducted on … organophosphates. These studies were human oral pesticide toxicity studies to determine acute “no effect” levels … A reporter with the Wall Street Journal (Europe) reported on this in a series of rather damning articles detailing how a laboratory in Scotland was carrying them out. He quoted research subjects who said they believed that the test substances were pharmaceuticals and not pesticides. Subjects asserted that they were paid a substantial amount ($1,000) to participate for a few days; they described themselves as penniless students or indigents.” [Underline added]
     EPA at the time declared a moratorium on using data from these tests, put together an ethics review committee, and tightened the procedures now being questioned by EPA and the EPA-chartered Council committee.        

Sheldon W. Samuels