In Memoriam: Jane Ellen Simmons

Vol. 130, No. 10 In MemoriamOpen AccessIn Memoriam: Jane Ellen Simmons Cynthia V. Rider, Linda S. Birnbaum, Michael J. DeVito, Richard C. Hertzberg, Glenn E. Rice, and Linda K. Teuschler Cynthia V. Rider https://orcid.org/0000-0002-4497-518X Division of Translational Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Search for more papers by this author , Linda S. Birnbaum Nicholas School of the Environment, Duke University, Durham, North Carolina, USA Search for more papers by this author , Michael J. DeVito Center for Computational Toxicology and Exposure, Office of Research and Development (ORD), U.S. Environmental Protection Agency (EPA), Research Triangle Park, North Carolina, USA Search for more papers by this author , Richard C. Hertzberg Biomath Consulting, Emory University, Atlanta, Georgia, USA Search for more papers by this author , Glenn E. Rice Center for Public Health and Environmental Assessment, ORD, U.S. EPA, Cincinnati, Ohio, USA Search for more papers by this author , and Linda K. Teuschler Linda Teuschler & Associates, St. Petersburg, Florida, USA Search for more papers by this author Published:27 October 2022CID: 101601https://doi.org/10.1289/EHP12225AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit The sudden loss of Jane Ellen Simmons on 19 March 2022 was felt deeply by the community of scientists, colleagues, friends, and mentees whom she touched over the course of her career. Two things were clear to all who knew her: Jane Ellen dearly cherished her husband and daughter, Roel and Johanna Schaaper, and she had an irrepressible passion for the rigorous scientific pursuit of understanding how exposure to chemical mixtures in the environment affects human health. Jane Ellen was one of a kind, an outstanding laboratory toxicologist at the U.S. Environmental Protection Agency’s Office of Research and Development (EPA ORD) for 36 years, internationally known expert on chemical mixtures, superb liaison across researchers, coordinator and leader of multidisciplinary projects, champion of generating toxicity data useful for environmental health risk assessment, and amazing presenter and author of complex information, all while maintaining the life she loved as a devoted wife and mother.Jane Ellen Simmons, 1952–2022. Image: Courtesy of U.S. EPA photography library.The field of toxicology has traditionally focused on quantifying the impact of individual chemicals on model organisms or cells to inform our understanding of risk to humans or ecosystems. Jane Ellen was a pioneer in the relatively small community of scientists extending the field of toxicology to combined exposures and mixtures. At the beginning of her career, including her graduate work under Van Stee at the National Institute of Environmental Health Sciences in inhalation toxicology, she waded into the nascent field of mixtures toxicology undeterred by the common refrain at the time that it would be “a career-ending pursuit.” Some of her first publications1–3 described her work with David DeMarini, Ezra Berman, and other colleagues at the U.S. EPA exploring the toxicity of complex mixtures collected from the input streams to hazardous waste incinerators. Transitioning from testing complex mixtures to defined environmentally relevant mixtures, she would often cite her collaboration4 with Ray Yang on evaluating the toxicity of a 25-chemical mixture of groundwater contaminants as being a key catalyst for her work in mixtures. The central themes of tackling complex and challenging public health problems and building strong and lasting collaborations were established early in Jane Ellen’s career and defined her path.Jane Ellen’s research interests turned to understanding the toxicities and health risks posed by mixtures of disinfection by-products (DBPs) in chemically treated drinking water. She initially focused on combinations of individual DBPs and, working closely with statisticians, developed a keen understanding of how to efficiently design experimental mixture toxicology studies capable of providing high-quality data. These studies raised important questions about health risks associated with daily exposures to complex DBP mixtures. Combining this interest with a vision of how different parts of the U.S. EPA could collaboratively investigate an environmental health issue, she formed and led a cross-disciplinary project team of agency scientists and engineers that designed and conducted the Four Lab Study. Working tirelessly from the bottom up, she garnered support and resources for this extensive project, often employing her famous Southern charm, gift of diplomacy, and scientific logic. She then meticulously oversaw the coordination of the study, where natural organic matter (NOM) in surface water was concentrated, transported to research laboratories, chemically disinfected to generate DBPs, and tested in multiple in vivo and in vitro toxicity assays. In the primary multigenerational bioassay, the NOM was administered to rodents in their drinking water5; health effects in these animals were subsequently studied by investigators in U.S. EPA and academic laboratories. It remains among the best examples of a toxicological study of a whole mixture.Jane Ellen was a leading force in contributing to the foundation of mixtures science and cumulative risk assessment by focusing much-needed attention on proper study design. In a field rife with confusing terminology (e.g., different definitions for the same term) and poorly designed studies, Jane Ellen was dedicated to improving the landscape and making mixtures studies more useful in regulatory decision making. In a forward she wrote6 for a 2013 Special Issue of Toxicology on mixtures, she noted that all contributing authors were asked to carefully define terms and the models that served as the basis for determining interactions among mixture constituents. She hated the word “synergy” and campaigned for switching to “greater than additive” (with the type of additivity clearly stated, of course). She collaborated with experts in biostatistics to design mixtures studies with adequate power and appropriate tests for deviation from additivity. Furthermore, she made it her life’s mission to advocate for proper study design, writing several papers focused on experimental design, emphasizing design details in her research papers, and teaching about study design in numerous continuing education courses. Committed to helping practitioners navigate the complexities of study design, she quite literally wrote the book on mixtures, co-editing and contributing chapters to the 2018 book Chemical Mixtures and Combined Chemical and Nonchemical Stressors.7Her collaboration with statisticians and modelers also explored the quantitative aspects of mixture dose–response analysis. During many years of such joint research, she gradually began asking math questions of her colleagues, who readily responded with probing toxicological questions of their own. She would ask, “Is there enough statistical power to detect an interaction?” Her mathematicians would ask in return, “But are those deviations toxicologically important?” That crossover of disciplinary thought and jargon is still rare in the biology–mathematics realm and was indeed treasured by all who were fortunate to take part.Beyond her tremendous scientific contributions, Jane Ellen was dedicated to mentoring and supporting both trainees and colleagues, and to building a scientific community in mixtures toxicology. She was active in the Society of Toxicology and was a founding member of the Mixtures Specialty Section, serving in the inaugural presidential chain from 2007 to 2010. She was an exuberant teacher and communicator, with a completely unique voice. As a sought-after speaker, she kept listeners enraptured as she joyfully discussed mixtures, transitioning seamlessly from conspiratorial whisper to emphatic boom. Central to all of Jane Ellen’s accomplishments was her ability to communicate complex ideas in plain language, personally connect with people, and extend tremendous compassion to those around her. Jane Ellen made a lasting impression on both the field of mixtures toxicology and all who knew her.References1. DeMarini DM, Gallagher JE, Houk VS, Simmons JE. 1989. Toxicological evaluation of complex industrial wastes: implications for exposure assessment. Toxicol Lett 49(2–3):199–214, PMID: 2690404, 10.1016/0378-4274(89)90033-7. Crossref, Medline, Google Scholar2. Simmons JE, DeMarini DM, Berman E. 1988. Lethality and hepatotoxicity of complex waste mixtures. Environ Res 46(1):74–85, PMID: 3371293, 10.1016/S0013-9351(88)80060-4. Crossref, Medline, Google Scholar3. DeMarini DM, Inmon JP, Simmons JE, Berman E, Pasley TC, Warren SH, et al.1987. Mutagenicity in Salmonella of hazardous wastes and urine from rats fed these wastes. Mutat Res 189(3):205–216, PMID: 3313035, 10.1016/0165-1218(87)90054-1. Crossref, Medline, Google Scholar4. Simmons JE, Yang RS, Svendsgaard DJ, Thompson MB, Seely JC, McDonald A. 1994. Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction. J Toxicol Environ Health 43(3):305–325, PMID: 7966440, 10.1080/15287399409531923. Crossref, Medline, Google Scholar5. Narotsky MG, Klinefelter GR, Goldman JM, Best DS, McDonald A, Strader LF, et al.2013. Comprehensive assessment of a chlorinated drinking water concentrate in a rat multigenerational reproductive toxicity study. Environ Sci Technol 47(18):10653–10659, 10.1021/es402646c. Crossref, Medline, Google Scholar6. Simmons JE. 2013. ToxMix 2011: International Toxicology of Mixtures Conference. A selection of papers. Preface. Toxicology 313(2–3):71–72, PMID: 24286990, 10.1016/j.tox.2013.11.001. Crossref, Medline, Google Scholar7. Rider CV, Simmons JE, eds. 2018. Chemical Mixtures and Combined Chemical and Nonchemical Stressors: Exposure, Toxicity, Analysis, and Risk. Cham, Switzerland: Springer Cham. Crossref, Google ScholarFiguresReferencesRelatedDetails Vol. 130, No. 10 October 2022Metrics About Article Metrics Publication History Manuscript received2 October 2022Manuscript accepted10 October 2022Originally published27 October 2022 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. 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