Ivan Rusyn

Vicki Dellarco

Vicki Dellarco, Ph.D., has provided strong leadership within the U.S. EPA and the international community for risk assessments that utilize the best scientific information available.

Dr. Dellarco, a senior science advisor in the Office of Pesticide Programs, has worked effectively to develop methods for mode of action analyses in risk assessment and to implement those methods through case studies and Agency assessments for specific chemicals. She has promoted revisions of toxicity testing guidelines including the thyroid developmental toxicity study guidance, development of toxicity testing strategies for improving and refining approaches to health risk assessment, development of common mechanism policy decisions and cumulative risk assessment methods and guidance. Her energy, enthusiasm, and collaborative skills have greatly enriched the work of Agency and international scientific and risk assessment groups.

Toshio Narahashi

Toshio Narahashi, D.V.M., Ph.D., is the John Evans Professor of Pharmacology in the Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University. Since the 1950s his discoveries have elucidated the mode-of-action of important toxicants that impact human lives across the globe. Dr. Narahashi has been considered as the person responsible for driving the field of the effects of chemicals on excitable cell membrane function. Some of his publications are listed as Citation Classics. His studies have added immeasurably to our understanding of basic neuronal physiology and the action of a variety of neurotoxicants and drugs on axonal and junctional physiology. He is respected around the world and has received numerous scientific honors.

Steven Cohen

Steven D. Cohen, M.S., D.Sc., ATS, has contributed to the field of toxicology in education by developing new scientists and leaders in toxicology, providing professional leadership, and fostering the scientific growth of toxicology. He has received international recognition for his scientific contributions to understanding the mechanisms of acetaminophen-induced hepatotoxicity.

Dr. Cohen joined the University of Connecticut Storrs in 1972. In the early 1980s he founded the Center for Biochemical Toxicology and the Interdepartmental Graduate and Postdoctoral Research Training Program in Environmental Toxicology at the University of Connecticut at Storrs. He directed both for nearly 20 years until leaving the University in 2000 as Emeritus Professor of Toxicology. The Center was supported by the State of Connecticut as a “Center for Excellence” and became a statewide resource for toxicology expertise and training. The Toxicology Program was supported by funds from the University, the State, the chemical and pharmaceutical industry and importantly, by an Environmental Toxicology Research Training Grant from the National Institute of Environmental Health Sciences. Over 50 alumni of the Connecticut program are making important contributions to toxicology through their professional positions in academia, industry and government. His career contributions in toxicology education were recognized with the establishment in 2004 of an endowed graduate fellowship at the University of Connecticut (Rosenberg/Cohen Graduate Fellowship in Pharmacology and Toxicology) in his honor. In 2007 the School of Pharmacy Alumni Association further honored him with the Distinguished Emeritus Professor Award.

In 2000 Dr. Cohen joined the Leadership Team for establishment of the Massachusetts College of Pharmacy and Health Sciences School of Pharmacy –Worcester where he is Professor of Pharmacology and Toxicology and Chair of the Department of Pharmaceutical Sciences. For his dynamic leadership in toxicology education, his guidance of toxicology programs for over 30 years, and his outstanding example as a scientist-educator, the Society of Toxicology honors Dr. Steven D. Cohen with the 2008 Education Award.

John Doull

John Doull, M.D., Ph.D., ATS, is the recipient of the first Founders Award for his illustrious career in toxicology with more than 50 years of productive contributions to teaching, research, and the application of toxicological principles to safety evaluation in the support and enhancement of public health. Dr. Doull is trained and experienced both as a physician and as a scientist. He obtained his Ph.D. in pharmacology and his M.D. from the University of Chicago, spent several years at the Univeristy of Chicago, then more than 40 years at the University of Kansas where he is currently Professor Emeritus of Pharmacology and Toxicology.

Dr. Doull has had the experience of diagnosing and treating individuals who have been poisoned and has counseled many individuals who were concerned that they may have been poisoned. He has had far-reaching influence on the development and application of the safety evaluation of chemicals through his extensive research (with particular emphasis on modes of action) as evidenced by his numerous high quality publications. Particularly noteworthy has been his leadership in promulgating a most authoritative source of toxicology principles presented in the serial publication of Casarett and Doull’s Toxicology: The Basic Science of Poisons. Furthermore, he has advanced the safety evaluation of chemicals through his formal participation in numerous national and international authoritative groups including the National Academy of Sciences, the International Life Sciences Institute, and the National Institute of Environmental Health Sciences.

Dr. Doull has served on numerous governmental and non-governmental committees, and has been a leader in promoting use of the best science to understand problems and how to deal with them. In the face of emotionally-charged issues, Dr. Doull has been a source of reason in objectively approaching the issues and using common sense in decision-making, typically resulting in a report that is highly regarded and respected. His contributions to the use of sound science in safety evaluations have led to major improvements in governmental and non-governmental initiatives aimed at protecting and enhancing public health.

One of Dr. Doull’s outstanding contributions in toxicology is the training and guidance that he has provided to many productive scientists. At the University of Chicago and the University of Kansas, Dr. Doull helped train many young and aspiring toxicologists in the sound, fundamental principles of toxicology and the application of these principles to real-world toxicological problems in both medicine and the environment. In addition, Dr. Doull has served as a role model, mentor, colleague, and friend to many scientists in the field of toxicology. Those fortunate to have learned from his scientific creativity and insights have greatly expanded the field, and have helped to provide toxicology with a high degree of respect and recognition.

Dr. Doull displayed great foresight in 1961 when he joined the group that founded the fledgling Society of Toxicology. Since that time, he has fostered the aims of the Society by engaging in major leadership roles including serving ably as its President. He has been a major force in molding the future of the Society and in having it recognized worldwide as the central organization in the field of toxicology and in the enhancement of public health. The Society of Toxicology is pleased to recognize Dr. John Doull as the recipient of the first Founders Award for his leadership and integrity as a premier scientist and physician.

Lee Hartwell

Lee Hartwell has made important contributions to our understanding of cell division and cancer through his study of genes that control cell division in yeast. For this work Hartwell has received many scientific awards, including the 2001 Nobel Prize in Physiology or Medicine. Other honors include the Albert Lasker Basic Medical Research Award, the Gairdner Foundation International Award and the Alfred P. Sloan Award in cancer research.

Many of the genes that control yeast division also control cell division in humans and often are the site of alteration in cancer. Hartwell discovered a new class of gene responsible for accurate cellular reproduction: the “checkpoint” gene. These genes halt cell division when mistakes are made during cellular reproduction so that repair can take place. His insights into cell-cycle control are being used to develop treatments for cancer and other diseases. In collaboration with Steve Friend, Hartwell explored the potential to identify cancer therapeutics using a panel of yeast mutants defective in DNA repair. He and Lee Hood have founded a company to use transcript profiles and yeast mutants to identify new therapeutic targets.

As part of his efforts to use the enormous knowledge that has accumulated over the last 50 years in genetics and biochemistry to benefit cancer patients, he strives to improve molecular diagnostics to identify individuals at high risk for disease, detect cancer and other diseases at an early stage when they can be cured, provide prognostic information, and monitor therapeutic response. Proteins will likely provide the best diagnostic information because of their greater diversity and because their state reflects biological function. The technology for protein diagnostics, however, is in its infancy. He is involved in national and international projects to increase the number of laboratories working in protein diagnostics, develop more team science, improve the availability of informatics for data sharing, provide standardized reagents, and stimulate new technology development. He and Michael Birt organized the first international Pacific Health Summit held in June 2005.

Hartwell earned a Ph.D. from the Massachusetts Institute of Technology under the mentorship of Boris Magasanik. He engaged in postdoctoral work at the Salk Institute for Biological Studies with Renato Dulbecco. He then joined the University of Washington faculty and has been a genetics professor there since 1973. In 1996 he joined the faculty of Seattle’s Fred Hutchinson Cancer Research Center and in 1997 became its president and director. He is a member of the National Academy of Sciences.

H. Robert Horvitz

Pioneering studies by H. Robert Horvitz have made him one of the central figures in research on programmed cell death (apoptosis). He discovered key genes that control cell death in C. elegans. For this work and for his studies concerning organ development in C. elegans, Horvitz won the 2002 Nobel Prize in Physiology or Medicine, an award he shared with Sydney Brenner and John Sulston.

Horvitz’s work with C. elegans began during a postdoctoral fellowship in Brenner’s laboratory in Britain in the 1970s. There, Horvitz teamed with Sulston to trace the ultimate fate of each cell as it developed from an embryo into an adult. Their work revealed that cell division in the worm produces many more cells than survive to make up the mature animal.

In the mid-1980s at the Massachusetts Institute of Technology, Horvitz identified the first "cell death" genes, called ced-3 and ced-4. "Discovering that programmed cell death is specified by particular genes established that programmed cell death is a basic biological process, much like cell division, cell migration, and cell differentiation," Horvitz explained. Later, Horvitz showed the gene ced-9 protects against cell death by regulating both ced-3 and ced-4.

Horvitz’s graduate studies at Harvard were under the guidance of James Watson and Walter Gilbert (who developed a method to determine the exact sequence of the nucleotides in DNA). Both men are also Nobel laureates.

"As a graduate student, I came away with two beliefs that have driven my research career," Horvitz said. "First, do the ‘doable.’ I recognized early on that working on an important but intractable problem would not suit me. Second, it is no harder to work on an important problem than one that is not important; this bit of advice, from Jim Watson, was engraved in me."

Horvitz has also identified many additional apoptosis genes. His studies may improve the understanding of neurological disorders such as amyotrophic lateral sclerosis (ALS), a disease that killed Horvitz’s father. Horvitz collaborated in identifying a gene involved in the inherited form of ALS, and he is pursuing other genes involved in the disease.

He has also worked to understand how genes control other aspects of development and behavior and has discovered genes that are involved, again using C. elegans. His work reveals specific pathways shared by both worms and humans that are involved in a variety of human diseases.

Dr. Horvitz is a David H. Koch Professor of Biology at the Massachusetts Institute of Technology and Neurobiologist and Geneticist at Massachusetts General Hospital, in Boston.

Hanspeter Witschi

Hanspeter Witschi, M.D., is Professor Emeritus, University of California –Davis. Dr. Witschi was an enthusiastic proponent of the value of mechanistic toxicology in contributing to risk assessment. He represented the thinking man’s pathologist.ºan experimentalist, Dr. Witschi put much thought into the design of a study and what the outcomes could be. Consequently, his studies were precise, economical, and always produced results. His studies were a stimulus to himself and others to reveal a greater understanding of the phenomenon under investigation. He published seminal articles in pulmonary toxicology, adaptation to toxicant exposure, second-hand smoke, and lung carcinogenesis. He made an enormous contribution to teaching and education, and was the recipient of the SOT Education Award in 1991. His service to toxicology has been exceptional as he served on many local, regional, and national offices. He is considered a complete scientist—always interested in discussing the dilemmas of toxicology and never tempted to arrive at the quick and easy conclusion.

Jose Manautou

Jose Manautou, Ph.D., Associate Professor of Toxicology at the University of Connecticut, receives the 2008 AstraZeneca Traveling Lectureship Award. The award recognizes excellence in research and service in toxicology and enables a lecture tour of Europe to promote collaboration between European and North American toxicologists. Dr. Manautou’s research in the fields of hepatotoxicity and drug transporters has gained international recognition for excellence. In addition to an impressive publication record, he has been Associate Editor of Toxicology and Applied Pharmacology and a member of an NIH study section. Dr. Manautou has been a contributor to SOT programs since 1998, serving as a member of several committees, as principal investigator of the SOT’s NIH grant that supports its undergraduate educational program and as SOT Councilor. Dr. Manautou’s planned visits to Switzerland, Portugal, France, Hungary, and England will expand his collaborative network and bring new perspectives to his research efforts.

George Michalopoulos

George Michalopoulos, M.D., Ph.D., is the Professor and Head of the Department of Pathology, University of Pittsburgh School of Medicine. Dr. Michalopoulos isa eminent researcher and an authority on hepatocyte culture techniques and their use in research. His current areas of research focus are growth factors and receptors in hepatocytes, mechanisms of liver regeneration, growth regulation in human hepatocytes, and hepatic carcinogenesis. He will be hosted by the Toxicology program at University of Louisiana—Monroe College of Pharmacy where he will demonstrate the newest hepatocyte culture techniques, present liver toxicity and in vitro techniques lectures, and participate in hepatobiology and carcinogenesis discussion forums.

The Board of Publications has unanimously selected the paper entitled “Sequential Exposure to Cytokines Reflecting Embryogenesis: The key for In Vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-like Cells” as the best paper published in Toxicological Sciences in the past year (December 2006; 94:330–341). The authors of the paper, comprising an international research team, are Sarah Snykers, Tamara Vanhaecke, Peggy Papelue, Aernout Luttun, Yuehua Jiang, Yvan Vander Heyden, Catherine Verfaillie, and Vera Rogiers.

The plasticity of stem cells renders them capable of overcoming germ lineage restrictions to develop molecular characteristics of cells from a different tissue. It has previously been shown that adult bone marrow stem cells (BMSC) can differentiate into hepatocyte-like cells when exposed to a cocktail of cytokines and growth factors. However, in the recognized paper, Snykers and colleagues applied basic knowledge of liver embryogenesis and development to design an experimental paradigm in which BMSC were treated sequentially with liver-specific factors that regulate hepatocyte differentiation in a manner that reflected their temporal expression during in vivo hepatogenesis. They evaluated the morphological, molecular and functional characteristics of the resulting hepatocyte-like cells and compared these features to BMSCs treated simultaneously to the cocktail of differentiation factors.

Their innovative approach produced poylgonal cells that presented with many features of differentiated hepatocytes which included binucleated morphology, expression of ?-fetoprotein early in the course of the culture that then disappeared, expression of maximal levels of albumin and cytokeratin 18, markers of later stage differentiated hepatocytes, only after 18 days in culture, and evidence for constitutive and inducible cytochrome P450 1A1/2 and 2B1/2. These features comprise a profile that is consistent with the array of developmental stages that is comparable with liver development, whereas the simultaneous exposure paradigm induced an aberrant pattern of differentiation.

The use of stem cells in clinical and preclinical research is an important, timely and controversial topic. As such, the work by Snykers et al. is a major scientific achievement relative to the development of a method that yields hepatocyte-like cells from BMSC and represents a significant contribution to the field of stem cell research. The model provides important new methods for the purification and culture of pluripotent stem cells from nonembryonic origin. Furthermore, the work offers new opportunities to study fundamental biological processes involved in development and differentiation, and it yields an unlimited source of hepatocyte-like cells for pharmacology and toxicology research.