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Tech VisionariesChris Hartlove

Tech Visionaries

A Map of the Human Toxome

We like to think that manufactured products have grown safer over the last century, that careful toxicological testing and stringent regulation now protect us from medicines that can poison and cosmetics that can blind us. The reality is not so rosy. Humans are potentially exposed to 80,000 chemicals for which no toxicological assessment has ever taken place. And the current methods of evaluation—high-dose animal tests extrapolated to human beings—are at best crude and at worst unscientific.

“The current toolbox simply doesn’t allow us to do the testing we want,” says Thomas Hartung, MD, PhD, who saw the limitations of these approaches in his previous work as director of the European Center for the Validation of Alternative Methods. Now the Doerenkamp-Zbinden Endowed Chair in Evidence-Based Toxicology and director of the Center for Alternatives to Animal Testing (CAAT), he says he was drawn to the Bloomberg School in 2009 by “the opportunity to become involved in something that could revolutionize the field.”

The opportunity he envisioned was to identify and catalog comprehensively what are known as “pathways of toxicity” (PoT): the molecular pathways that, when perturbed, produce adverse health effects. Whereas current toxicological tests typically expose animals to a substance in order to provide a crude characterization of its toxicity, Hartung wants to comprehensively document the substance’s interactions with human cells and compile the results in an open-source database.

“There are a couple of hundred ways to kill a cell," says Thomas Hartung. "If we had a map of this, we could start to look into which cell has which of these pathways, and we might start to understand why a substance is toxic for mice and not for rats, or why it affects liver cells and not heart cells.”

With a $6 million NIH Director’s Grant, he has set out to do just that. “The first step,” he says, “is to develop a language to describe toxicity—describing these pathways in relation to the genes that are involved and metabolic pathways that are involved.” With this shared vocabulary, a global consortium can begin contributing to the database and building what he calls a “human toxome.”

The need to improve present-day toxicological testing is apparent. From food additives to medications to the ubiquitous materials of our built environments, we are both surrounded by and dependent on novel substances of unknown toxicological safety. “Products worth $10 trillion are rated with [the old] suite of toxicological tests, and people know they aren’t necessarily making the best business decisions,” says Hartung, a professor of Environmental Health Sciences (EHS). “But technologies that are young, from the last few decades, offer a new approach to solving this problem.”

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