I really didn’t know what to expect when I started my internship at the Natural Resources Defense Council’s (NRDC) San Francisco office in September, 2017. Sure, I’d had a good interview and discussed a handful of interesting potential projects with my future supervisor, Dr. Miriam Rotkin-Ellman – but on that first day, I didn’t know what it meant to do advocacy work as a scientist. This isn’t a fault of the NRDC, but rather, an artifact of the academic structures that guide fledgling scientists through their doctoral research: advocacy just isn’t on the curriculum. In my (highly-subjective) experience most discussions among Molecular Toxicology PhD students and their advisors, professors, or mentors emphasize the intellectual prestige of staying in academia. These discussions present a false binary: you can stay in the ivory tower and remain a “real” scientist, or you can sell out and flee to industry where all the money is. A few of the more open-minded professors might concede the existence of a third option – government work – but using my training to support an advocacy organization isn’t even a consideration.
Fortunately, my research interests had led me to the Berkeley Center For Green Chemistry (BCGC), which would, in turn, lead me to the NRDC. The BCGC is a interdisciplinary organization by necessity, and it is due to the expansiveness and complexities of the field. Green chemistry is a highly integrative field that uses elements of engineering, physics, and toxicology to improve human and environmental health from a chemistry perspective. To fully achieve the promise of this gestalt discipline, however, we must consider not only which chemicals are used and in what their effects are, but also why are they used in the ways that they are, and what are the social, economic, and regulatory forces that foster their use. By addressing these questions through coursework, internships, mentorship, and seminars, the BCGC helps toxicology researchers like me place chemicals in their proper societal contexts, and highlights the power of toxicological research outside the lab.
Interning at the NRDC these past few months has been an incredible opportunity to contextualize my work on chemical hazard assessment within the vast and sprawling maze that is the US chemicals regulatory system. Much like the cells that make up the human body, chemicals regulation is a complex and dynamic network of systems within systems. Just as cells take in food and nutrients to produce energy and biological molecules, various groups such as companies, government groups, and advocacy organizations apply inputs to the chemical regulatory system with the hope of achieving a desired output. In most cases it is, either the prohibition or the exoneration of a chemical used in commerce. In the case of chemicals regulation, inputs may include public health studies, lobbying efforts, court cases, science advisory panels, and public comments. These create myriad and subtle changes throughout the systems within systems. While I’d had a vague sense of the complexity of this regulatory ecosystem due to my public health training, it wasn’t until I was in the thick of it that I truly understood its sophistication and scope. At the NRDC, I learned quickly about the different actors involved, and where they fit in; I learned about the legal frameworks and policies that gave structure to the ecosystem; I learned about the places where science and law were most applicable, and that they weren’t often the same places; and finally, I learned about new possibilities for applying my training as a toxicologist.
Working with Dr. Kristi Pullen Fedinick, my primary project required me to assess a new model that the EPA has proposed as an alternative testing method for an androgen disruption screening assay, and to determine its strengths and weaknesses. On its surface, the project seemed straightforward: decide if this model works well enough as a replacement for an existing test and provide an assessment in time for a science advisory panel at the EPA headquarters in Washington DC – a panel that the NRDC sent me to attend. Below the surface, however, there were several aspects of the project which carried much greater weight when placed in the context of the present regulatory environment, the most significant of which also featured prominently in my dissertation: the applicability of high-throughput screening (HTS) methods for chemical hazard screening.
HTS methods for chemical testing use advances in robotics to automate biochemical tests such that they can be conducted rapidly and in high volume; this allows thousands of chemicals to be tested fairly quickly and is common practice in the pharmaceutical industry as researchers hunt for new potential drugs. The EPA and other regulators have been expanding their use of HTS for years in an effort accelerate the pace of regulatory decision-making and to address a backlog of tens of thousands of chemicals for which very little hazard data is available. Scaling the testing process also has the benefit of significantly lowering the cost of testing. Certainly, HTS is the most practical solution to chemicals testing and is likely to play a significant role in hazard assessment for years to come. There remain significant limitations to the technology, however, in the use of HTS for regulatory purpose – as Dr. Pullen Fedinick and I determined during our evaluation of the Androgen Receptor (AR) Pathway model proposed by the EPA.
Dr. Pullen Fedinick and I are currently developing a manuscript based on our considerations of HTS used in regulatory practice, but there are a few simple conclusions that we derived over the course of my internship. The most significant point is that HTS only accommodates very simple assays that are not capable of recapitulating the complexity of biological systems. Put simply: a cell is not a person, and a single receptor does not a biochemical pathway make. Our evaluation of the EPA’s AR pathway model convinced us that even a dozen or so assays were not sufficient to capture the tremendous complexity of the endocrine signaling process, and that while HTS may be useful to supplement the hazard assessment procedure, it should not be used in lieu of standard tests. Additionally, HTS is still quite limited in terms of the “chemical space” that it can be used to evaluate, that is, metals and chemicals at the far ends of the spectrum of water solubility may not be suitable for HTS testing strategies.
In 2016, Congress passed a massive piece of legislation to update the rules for chemicals testing in the United States, and as I learned during my internship, precedent plays an outsized role in our country’s legal system. The initial implementation of this regulatory scheme, then, will have enormous consequences for the law’s future use. Given the speed and cost of HTS methods, it is easy to see their appeal in chemical hazard assessment, particularly as the EPA considers how it will employ the new rules at its disposal. Unfortunately, HTS has many limitations, and if it is not used judiciously, the potential to erroneously classify a chemical as “safe” or even “low priority for future testing” is great. This could allow hazardous chemicals to slip through the cracks and not be detected as dangerous for years following their misclassification. Therefore, in this context, it is vital that toxicologists work with advocacy organizations and regulators to ensure that chemical hazard testing is conducted in a scientifically-robust and responsible fashion to ensure the greatest possible protection of human and environmental health.
I may not have known what to expect on my first day at NRDC in September, but the last three months have given me invaluable perspective on the role of my work in the broader societal context. The work was difficult at times, but always interesting, and certainly nothing like anything I’d learned in any of my courses. I am now convinced that advocacy is an incredibly important and interesting career path for toxicologists, and that toxicology students at all levels would benefit from an earlier introduction to such opportunities. I’m extremely grateful to Drs. Rotkin-Ellman and Pullen Fedinick for their mentorship and guidance during my time at NRDC and to the Wareham Group for providing support funding. And I’m excited to be joining the ranks of the BCGC in January, where I will continue to work on challenging problems related to chemicals, society, and human and environmental health.
I first fell in love with molecules in my sophomore organic chemistry course. I remember commenting to my lab partner that organic chemistry problems were much more interesting than crossword puzzles, and they should be included in newspapers (with spelling as poor as mine, crosswords were never very fun). After failing to convince others of the merits of Sunday chemistry problems in the newspaper, I entertained myself by digging into the chemistry of the materials and products in our everyday world. Understanding the design and use of molecules has become a life-long endeavor. These last five years at the Berkeley Center for Green Chemistry (BCGC) have been wonderful, providing me with the opportunity to deepen my appreciation of chemistry and the larger social, economic, and political structures that influence the selection of chemicals.
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