National Toxicology Program

National Toxicology Program

UPDATE NewsletterUPDATE NewsletterNovember 2015

Variability among individuals spurs decision makers

By John Yewell
Reprinted from Environmental Factor, November 2015

How individuals react to toxins, and how this influences the regulation of environmental pollutants, were the topics of an NIEHS-sponsored workshop in Washington, D.C. on Sept. 30 and Oct. 1.

“Interindividual Variability: New Ways to Study and Implications for Decision Making” was hosted by the Committee on the Use of Emerging Science for Environmental Health Decisions (see sidebar).

Changes in our understanding of risk

Workshop chair Lauren Zeise, Ph.D., acting director of the Office of the Environmental Health Hazard Assessment of the California Environmental Protection Agency, summarized the factors decision makers consider when writing regulations, and the role of scientists in helping them.

“Risk is balanced by technical feasibility, cost assessment, and a variety of other things,” she said. “If you really understand the risk and the benefit of different options, you have a much firmer ground for making decisions.”

NIEHS and National Toxicology Program (NTP) Director Linda Birnbaum, Ph.D., shed light on changes in our understanding of the complex interplay between genetics and environmental stressors. That interplay is key to the variable response that different individuals show to stressors or exposures, also known as interindividual variability.

“The tobacco companies blocked regulation of cigarette smoking for 50 or 60 years by pointing out that only 11 percent of people who smoke get lung cancer,” Birnbaum said. We now understand that susceptibility among people varies for genetic and environmental reasons, she explained. “We have to think about things like our diet, socioeconomic status, the totality of exposures, and stress, which can result in biochemical changes.”

The Four Ps

The revolution now underway in health care, known as personalized medicine, strives to take that variability into account. “Health care today is expensive, reactive, inefficient, and focused largely on one-size-fits-all treatments for events of late stage disease,” said Jon Cook, Ph.D., senior director of investigative toxicology at Pfizer, Inc. “The answer is personalized, predictive, preventive, participatory medicine. The four Ps.”

Recalling Birnbaum’s figures on the percentage of people who may be naturally resistant to certain diseases, Cook explained that some patients get no benefit from drugs developed for wide use. “But they are still at risk for the drug’s side effects,” he said. “They have no benefit and all risk. As much as we think we know about science,” he added, “Mother Nature humbles us.”

Science supporting regulation

Because of the approach to human health that is moving toward the individual, several speakers raised questions about the regulatory mechanisms designed to protect the broader population.

“In the arena ofTox 21, for example,” said Michael DeVito, Ph.D., acting head of the NTP Laboratory at NIEHS, “we are talking about reinventing risk assessment. Fundamental shifts in the science underlie those decisions, but those decisions will always come back to the regulatory context.”

John Vandenberg, Ph.D. and director of the Research Triangle Park Division of the U.S. Environmental Protection Agency National Center for Environmental Assessment, used the example of ozone exposure to underscore the direction of targeted research. “About 15 percent are high responders, and about 15 percent have cast-iron lungs. Why are normals different? That is a key question that the research community has an opportunity to address.”

(John Yewell is a contract writer for the NIEHS Office of Communications and Public Liaison)


Jon Cook

“Diseases are complex. They are multifactorial,” said Cook. “The tools being developed by precision medicine will allow us to dissect disease into subclasses so we can target more effective treatments.” (Photo courtesy of the National Academies)


Linda Birnbaum

Birnbaum encouraged taking a broad view of the environment. “I am defining environment in big terms, not only chemicals,” she said. (Photo courtesy of the National Academies)


Vindiagram of Exposure biology program and Genetics program

Birnbaum’s presentation touched on the complex interactions between genetics and environmental exposure (GxE) in human health. GWA stands for genome-wide association. (Photo courtesy of NIEHS)


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