- 2015 Award in Excellence in Pharmacology/Toxicology
- 1980 Faculty Award in Pharmacology/Toxicology
David L. Eaton, Ph.D., is Dean and Vice Provost of the University of Washington (UW) Graduate School and Professor of Toxicology in the Department of Environmental and Occupational Health Sciences at UW’s School of Public Health and Community Medicine. In 1978, Dr. Eaton received his Ph.D. in pharmacology from the University of Kansas Medical Center. He joined the faculty at UW as Assistant Professor after a 6-month post-doctoral fellowship, and has since served the university in a range of leadership and research roles.
Dr. Eaton was the first Director of UW’s toxicology program in the Department of Environmental Health. In 1991, he was named Associate Chair of the department. He served as Associate Dean for Research at the School of Public Health from 1999 to 2005, and as Associate Vice Provost for Research from 2006 to 2013. For more than 20 years, Dr. Eaton directed the National Institute of Environmental Health Sciences (NIEHS) P30 Core Center, called the Center for Ecogenetics and Environmental Health, which supports multidisciplinary work on gene–environment interactions.
Dr. Eaton was awarded a PhRMA Foundation New Investigator grant in 1980—recognition that allowed him to compete for his first National Institutes of Health (NIH) Research Project Grant. Since then, he has received numerous awards from NIEHS, the National Cancer Institute, and the National Institute of General Medical Sciences. Dr. Eaton served as Director of the UW–NIEHS Superfund Basic Research Program and NIEHS Toxicogenomics Research Consortium, and as Project Director of the NIEHS Nanotoxicology Consortium.
During his 36-year tenure at UW, Dr. Eaton has fostered innovative, interdisciplinary approaches to graduate research and education. He is an Adjunct Professor of Medicinal Chemistry in the School of Pharmacy, co-teaches a graduate course on the fundamentals of pharmacogenetics and toxicogenomics for UW’s Public Health Genetics program, serves on dissertation and reading committees for doctoral students, and has trained 36 graduate and post-doctoral students—many of whom now hold positions in industry and academia.
For most of his career, Dr. Eaton’s research has focused on understanding species and interindividual differences in the way drugs and non-drug chemicals are metabolized in the liver. Many of his studies have looked at substances that act as human liver carcinogens. He was the first to demonstrate that resistance of laboratory mice to the potent human hepatocarcinogen, aflatoxin B1 (AFB), was due exclusively to the constitutive expression of a form of glutathione S-transferase in the mouse liver. Dr. Eaton’s laboratory cloned and sequenced the gene (mGSTA3) in 1992 and showed it had more than 10,000-fold higher specific activity toward the carcinogenic epoxide of AFB compared with human alpha class GSTA1. His lab further demonstrated that both human CYP1A2 and CYP3A4 effectively form AFB-8,9-epoxide. With these kinetic differences in biotransformation, Dr. Eaton and his team demonstrated that—at relatively low concentrations of AFB encountered in the human diet—human hepatic CYP1A2 is likely responsible for the vast majority of epoxide formation in vivo. His laboratory also showed that human GSTM1 plays an important role in detoxifying AFB-epoxide, even though it has a small fraction of the catalytic function of mouse GSTA3.
Dr. Eaton has published 180 peer-reviewed papers, book chapters, and full-length proceedings, and edited two books. He was a lead author of the “Principles of Toxicology” chapter of Casarett and Doull’s Toxicology for the past four editions.
Recognizing the importance of staying engaged in the field, particularly for the purpose of better disseminating scientific discoveries, Dr. Eaton has served on numerous national advisory boards, panels, and committees and held leadership roles at various professional societies. He served as Secretary and later President of the Society of Toxicology (SOT) and as Treasurer of the American Board of Toxicology. In 1993, he received the SOT Achievement Award, and in 2014, he was recognized with the SOT Public Communications Award and Pacific Northwest Society of Toxicology Achievement Award. Dr. Eaton is an Elected Fellow of the American Association for the Advancement of Science and Academy of Toxicological Sciences. He has served on more than a dozen National Academy of Sciences (NAS) and Institute of Medicine (IOM) committees and as Chair for several important NAS reports, including the National Research Council review of the Environmental Protection Agency’s controversial assessment of dioxin exposure. In 2004, Dr. Eaton’s service to the Academy was recognized with a lifetime appointment as National Associate. He was elected to the IOM in 2011.
An Interview with Dr. Eaton
Q: How did receiving the PhRMA Foundation Faculty Award in Pharmacology/Toxicology affect your research and career development?
A: This award came at a very important time in my career—just as I was starting a new career as an assistant professor, with only a short post-doctoral experience to build on. The award provided me with the resources necessary to collect some preliminary data that subsequently led to my first NIH R01 grant. Without the NIH grant success, I likely would have had a difficult time getting the publications needed for promotion and tenure. So I view the PhRMA award as very important to my early career, which then set the stage for the rest of it.
Q: What is your advice for a young investigator planning to pursue an academic career?
A: Stay focused and build on your strengths. Learn to say no to too many outside commitments/committees that will distract you from your research. Of course you have to be judicious in your choices, and it is not advisable to say no to everything, as being a “team player” is also very important to your success in academia. Be persistent in your efforts to obtain NIH funding, and look for alternative sources of funding beyond NIH for your research. Support from “non–NIH” sources can be extremely important to your success and may allow you to succeed even without getting an NIH R01 grant in your first few years of independent research. Finally, find some good collaborators who can help you take your research to the next level. There is strong interest in interdisciplinary research, and seasoned investigators in peripheral but related areas may help you find an innovative twist to your work that will help you land that grant!
Q: Could you put some of your cancer and environmental toxins research into layman’s terms?
A: Although most people traditionally think of environmental and food contaminants, especially potential cancer-causing chemicals as a by-product of industrial activities, Mother Nature has crafted some remarkably toxic substances. One of these is produced by a common mold that grows on corn, peanuts, and other common foods. The mold is called aspergillus flavus, and the toxin it produces is called aflatoxin (Aspergillus FLAvus TOXIN). The most potent form of this natural chemical is called Aflatoxin B1, or AFB for short. AFB was first discovered when it was identified as the chemical responsible for poisonings and liver cancer in farm-raised turkeys and trout. It was subsequently shown to be a common contaminant of the human diet in regions of the world where subsistence farming of corn and/or peanuts is common and where high heat and humidity are common. Many of these same areas (certain regions in China, Southeast Asia, and Central Africa) have among the world’s highest rates of mortality from liver cancer, and numerous epidemiological studies have demonstrated that AFB contamination of the diet is a very important contributor to this.
Early in my career, I was fascinated by the finding that rats were exquisitely sensitive to the cancer-causing effects of AFB, whereas mice were almost completely resistant. This suggested a genetic susceptibility potential, so my lab set out to discover the molecular basis for the species difference and determine where humans fit—are we more like rats, or more like mice, and if we are more like rats (highly sensitive, as suggested by epidemiological data), is there something we could do to make us more like mice (resistant to the cancerous effects of AFB)? We discovered adult mice are highly resistant to the cancer-causing effects of AFB because they express a special form of a common gene called glutathione-S-transferase (mGSTa3), which is remarkably effective at detoxifying the carcinogenic form of AFB (called AFBO, readily made in the livers of rats, mice, and humans). Rats had a GST gene (rGSTA5) very similar to the form of the mouse GST that made mice resistant, but rats did not normally express that gene in their liver and thus were not good at detoxifying AFBO. However, we and others showed the gene for rat GSTA5 could actually be turned on [to start producing] the GST enzyme that could detoxify AFBO, making rats resistant.
Q: You have written that toxicological evidence should be “presented in a courtroom.” How can toxicology aid decisions in chemical exposure cases?
A: It is very difficult to know with a high level of confidence whether an exposure to a particular chemical caused or contributed to a specific disease in a specific individual. However, the scientific principles that underlie pharmacology/toxicology and epidemiology are very useful in helping judges and jurors understand the likelihood that a particular exposure caused or contributed to a disease. Because the science is complex and usually has a significant degree of uncertainty around it, it is important that qualified scientists be willing to assist jurors in understanding. The nature of the legal process is such that experts are generally called upon by lawyers for one side or the other to present the evidence that supports their case. There are always two sides to every story, and it is important that both sides be aired, hopefully with truth and honesty. Some years ago I was invited to give a presentation to about 50 federal and state judges as part of an AAS symposium on Science in the Courtroom. Following my presentation, I was asked if I would write up the “basic principles of toxicology for judges and lawyers” for a law review article. That article was written to assist judges and lawyers in understanding how to assess toxicological evidence presented in the courtroom, and it has been fairly widely cited by judges in “toxic tort” litigation opinions.
Q: As someone who is very involved with medical societies and environmental health committees and boards, could you talk about the importance of staying engaged and giving back to the scientific community?
A: Research and the scientific discoveries that come from research are important, but their value is greatly diminished if the science that is produced is not effectively disseminated to the boundaries of the academy. Thus, it is imperative researchers become engaged in ways that facilitate the dissemination of discoveries to the rest of the world. Participating in professional societies, public interest groups, industry trade associations, and governmental agency committees and nonprofit organizations that have as one of their goals the dissemination of scientific information to the public can be very rewarding personally and professionally. Many federally funded research programs, especially center grants from the NIH, have as a requirement some community outreach and engagement activities. One of the most rewarding and impactful (and time consuming!) opportunities for scientists to put their knowledge and experience to use is to serve on National Academies of Sciences/National Research Council committees that address important policy implications where science can be an integral component of important decisions made by the federal government.
Q: How has the field of toxicology changed over the years?
A: The biggest change has been the remarkable insights and understanding of the molecular mechanisms of biological action of chemicals that have come from the rapid development of molecular approaches (so-called “omics” tools) applied to toxicology. With this knowledge has come a fundamental shift in the way scientists view toxicological effects of chemical substances, especially the dose–response relationship. It is now evident that many chemicals can induce subtle changes in cell signaling at doses well below those that cause an immediate or evident toxic response. Often, these changes represent an adaptive response to an external stressor, but we are beginning to recognize that such changes, especially if occurring continuously over a long period, may have important consequences in health by promoting—or in some instances inhibiting—disease processes associated with normal aging. This is perhaps best evident in the relatively new field of endocrine disruption, where seemingly non-toxic doses of certain chemicals that interfere with normal hormonal signaling processes may eventually alter the incidence of hormonally related chronic diseases such as breast cancer. Such changes are often too small to be of apparent significance to an individual, but they may have public health implications for large populations that are exposed for many years. In these circumstances, the chemical exposure is not causing the disease, but it may modify the disease process such that the ultimate incidence of disease in a large population is altered. This, of course, also provides opportunities for developing new drugs that favorably alter the disease outcome in a population.
Q: What is the most rewarding part of your job?
A: In my current position as Dean and Vice Provost of Graduate Education at a large public research university, the most rewarding part of my job is seeing the incredible potential of the next generation of scientists, who, with the remarkable gain in technologies and “big data,” will literally change the world. Having the opportunity to foster the development of innovative, interdisciplinary approaches to graduate research and education in a variety of fields is very rewarding. In my current job, I get to see this happen across fields that extend well beyond biomedical sciences and into engineering, social sciences, and even arts and humanities. From a scientific perspective, I’ve been blessed with the opportunity to collaborate with many really smart people across various fields, and this has made my own research career much more rewarding than if I’d stayed within my own silo of biochemical toxicology. And of course, having the opportunity to work with and mentor outstanding young scientists seeking their master’s and doctoral degrees remains a highlight of my professional life.