Harvey Wiley’s Contemporary Vision
April 4, 2012
This essay is in response to the question: How does the environment influence brain development? What are the exposures of greatest concern? What is the latest science and how can we translate that science into protective public health policy?
Picture a dining room where twelve young men, in suits and ties, await a meal. An older man presides over the group. The year is 1902. The older man is Harvey Washington Wiley, chief chemist of the Bureau of Chemistry of the Department of Agriculture. The diners are volunteers from the Department of Agriculture who had agreed to become subjects in a pioneering study of the toxicity of food additives. Wiley had become concerned about food safety and the practice of adulterating products with preservatives such as formaldehyde and concluded that only a controlled experiment could illuminate their potential toxicity. Wiley’s volunteers became known to the public as the “Poison Squad.” They consumed their tainted meals or capsules containing the chemicals and provided urine and feces for analysis. It was a thoroughly modern clinical trial. Wiley’s vision later was translated into the founding of the FDA in 1906, and his naming as its first commissioner.
Leap forward 110 years. Picture the Poison Squad of 2012. Visualize a pregnant woman and a child. She herself provides the meals, not the special kitchens at the Department of Agriculture that prepared them with fresh ingredients. She and her child are not evaluated weekly, like Wiley’s young men, by physicians from the Public Health Service. Instead of the five preservatives tested by Wiley’s volunteers, they consume thousands of chemical products never assessed thoroughly for toxicity. Although the quantities may be minute, quantity, we know, is not a reliable guide to toxicity. Compared to the 1902 diners, our contemporary Poison Squad is participating in a vast, uncontrolled experiment of how exposure to environmental chemicals creates a legacy of developmental disorders, including disorders of the brain and behavior, whose expression extends over the entire lifespan.
This portrait of today’s Poison Squad generates two dilemmas, one scientific and one ethical. The scientific dilemma is straightforward. How can we possibly test the tens of thousands of chemicals that now pervade our environment and whose traces can be found in our tissues? One answer is the movement, termed the 21st century answer to that dilemma, to test these chemicals with massive arrays of in vitro preparations designed to model our own metabolic pathways. It is now underway, but too early to tell if this sweeping change in how we practice toxicology can yield useful information about risks to neurobehavioral development. Can in vitro systems guide us to exposure standards designed on the basis of a small shift in the mean IQ score of a population?
The ethical dilemma is at least equally challenging. My university adheres to policies similar to those of other research organizations. If I wish to conduct an experiment in which I expose human subjects to a toxic chemical, even in trace amounts, I have to submit my plans to our Institutional Review Board. My board members will closely scrutinize my proposal to make sure it abides by the ethical principles now universally accepted for the protection of human subjects. These principles were established by the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.
One is of those principles is "justice," which seeks some correspondence between who receives the benefits of the research and who bears its burdens. A second principle is "beneficence," which requires that researchers maximize the potential benefits to the subjects and minimize the risks of harm. A third is "respect for persons," the source of the directive for informed consent. It mandates that subjects enter into the research voluntarily and with adequate information. Children receive special consideration because they are held to lack adequate capacity for self-determination.
All three guidelines pose ethical dilemmas for industry, government, and the public, when chemicals are created not for therapeutic interventions but, instead, are emitted into our environment by commercial activities.
Justice. Most often, chemicals make their way into the environment to benefit the emitter. If it is a corporation, the objective is to increase earnings. Those who undergo the exposure do not share directly in the profits. Whatever benefits may exist for those of us who undergo exposure cannot be described except in vague economic terms or more general terms as adjuncts to the general welfare.
Beneficence. This principle is based on two conflicting axioms. First, do no harm. Second, if harm is a possibility, as in therapeutic trials, maximize benefits to the individual, as by helping to cure a disease, and minimize harm. Those responsible for imposing the risks, however, incur obligations to justify those risks and to distribute the benefits to those most in need of them. Again, we have no adequate framework for assessing benefits for those exposed to chemicals in the environment. The balance is skewed by our inability to measure both sides of the equation.
Respect for persons. Voluntariness is the key concept. The paramount requirement is informed consent. The subject must be told, in clear language, all of the risks of participation and agree to them. Yet who can argue that most of us expose ourselves voluntarily to environmental toxicants? The exposures are inadvertent and, often, inescapable. The fetus, infant, and child possess essentially no choice at all.
The void between the ethical principles that guide research and the practices that determine environmental exposures greatly expands when we consider informed consent. Few of the 80,000 chemicals registered today with the Environmental Protection Agency have been tested adequately by the current standards of toxicological science. Of the 3,000 chemicals produced or imported at over one million pounds a year, only 43 percent have received even minimal study; and, of those, only 23 percent have been examined for their potential to cause developmental damage in children.
Few of us would be willing subjects in the kinds of environmental experiments we are compelled to take part in. Adults can make changes in diet, or carry out other choices to minimize exposures. The fetus, the infant, and the child can’t choose. They are recruited for massive experiments in risk assessment, and depend on us, as guardians, for protection. We need to again reflect on Harvey Wiley’s vision.