Abstract
Reasons for Revisiting the “Toxicologic Neuropathology” Theme Now
A regrettable tendency throughout recorded human history is that neurotoxicants have initially been discovered during human epidemics of neurotoxicity. Well-known agents illustrating this trend include ethanol, n-hexane, lead, mercury, polychlorinated biphenyls (PCBs), and tri-ortho cresyl phosphate (TOCP) (Costa et al. 2004; Inoue et al. 1988). During the late 20th and early 21st centuries, neural dysfunction has remained a key occupational hazard for adults (Connelly and Malkin 2007; Gobba 2003) and a devastating congenital event in children (Bearer 2001). Both of these age groups may be exposed to neurotoxicants via endogenous production of toxic metabolites during the course of certain diseases (ammonia, unconjugated bilirubin) or, more commonly, by contact with exogenous materials in the external habitat (e.g., agrochemicals, metals, pesticides, solvents) or deliberately introduced into the body (i.e., biopharmaceuticals, drugs, natural toxins [animals, microbes, plants]).
The potential scale of toxicant-induced neuropathology is enormous. Each year, about 85,000 chemicals are manufactured and another 2,000 to 3,000 new compounds are registered in the United States alone (Goldman 1998). At least 2,500 (3%) of these entities are thought to be neurotoxic to some extent (Claudio 1992), though many—including up to two-thirds of chemicals made annually in amounts exceeding one million pounds—have not received a detailed analysis to assess their neurotoxic potential (Environmental Defense Fund 1997). Thus, a main aim of neurotoxicologic research today is to prospectively identify the neurotoxic capacity of novel compounds rather than to discover it retrospectively after neurotoxicity epidemics appear in humans. Many toxicologic pathologists are outstanding contributors to this public health effort.
The collective interest by the toxicologic pathology community has resulted in the selection of “Toxicologic Neuropathology” as the focus of the Society of Toxicologic Pathology’s annual scientific symposium about every decade during the past 30 years, with the subsequent production of dedicated issues of Toxicologic Pathology that collate the then current, state-of-the-art concepts and practices in this field. (Prior STP symposium issues devoted to toxicologic neuropathology may be accessed in Toxicologic Pathology [1990]
The Main Course: A Banquet of “Toxicologic Neuropathology”
The general scientific program for the joint STP/IFSTP meeting in 2010 featured key reviews of many topics related to neurobiology and neurotoxicology but also provided updates on currently accepted and novel neuropathology and neurological methods to probe neural structure and function. The overall organization of the scientific sessions represented the best judgment of an international organizing committee of STP members with expertise or interest in toxicologic neuropathology (Table 1 ). These individuals are to be commended for their dedication and effort in assembling and moderating this fine program, and for their commitment to the writing and editing chores necessary to produce this symposium issue.
Scientific Program Planning Committee for the 2010 STP/IFSTP Scientific Symposium.
Abbreviations: CE, continuing education course; GS, general scientific session; INHAND, International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice.
1 Participated by providing advice and serving as a speaker rather than serving as a CE or GS co-chair.
The general scientific sessions were opened on Monday (June 21) with a keynote address by Dr. Peter Spencer (currently at the Center for Research on Occupational and Environmental Toxicology at the Oregon Health and Science University in Portland). He is an internationally known experimental neuropathologist who has authored or co-authored dozens of original research papers and book chapters and is the primary author/editor of several classic neurotoxicology texts. Dr. Spencer related his experiences during a decades-long academic career in toxicologic neuropathology research, emphasizing the tools and tricks for integrating anatomic, clinical, physiologic, biochemical, and molecular information to better understand neurodegenerative disease mechanisms. The keynote address was followed by two sessions on neurobiology fundamentals (gross and microscopic anatomy, electrophysiological and functional assays) and modern pathology methods (qualitative and quantitative techniques for evaluating the central and peripheral nervous systems). On Tuesday, a single general session discussed gene expression, biomarkers, and glial cells (astrocytes and microglia) and their correlation to conventional neuropathology end points. The two general sessions on Wednesday examined neurooncology (comparative pathology and classification, useful animal models, potential therapeutic targets, and drug development issues) and animal models of non-neoplastic diseases (emphasizing neurodegeneration). Finally, the single Thursday morning session presented several special neuropathology problems (pathologies of the blood–brain barrier, choroid plexus, and synapses, as well as mechanisms responsible for selective neuronal necrosis). As in past STP symposia on toxicologic neuropathology, many invited speakers for these six general sessions not only delivered a timely and well-targeted presentation but also provided a relevant review paper for publication in this issue, as a permanent and easily retrieved record of the current state of the art in their branch of toxicologic neuropathology.
Two distinctive features of this symposium issue should greatly enhance its value as a standard toxicologic neuropathology reference for the foreseeable future. For the first time, the general session co-chairs have contributed mini-reviews of their sessions stating the topics that were covered, the rationale for their selection, and the main points raised during the presentations and subsequent question periods. We hope that these overviews will provide (1) a valuable reference for those seeking to quickly gain an appreciation for the material presented in each session and (2) a useful avenue for consolidating the manuscripts from that session into a cohesive learning unit. Second, this symposium issue contains two other unique features that will further augment its utility as a toxicologic neuropathology reference: an up-to-date compilation of online, international regulatory guidelines for toxicologic neuropathology in the nonclinical setting, and a list of essential electronic and literature references in toxicologic neuropathology. These additional articles should substantially enhance the utility of this symposium issue as a resource for working neuropathologists and neurotoxicologists.
The Rest of the Menu: Continuing Education, Career Development, and the IFSTP Comparison of Training Practices, Resources, and Needs around the World
Toxicologic neuropathology was by no means the only dish at the feast! Several other excellent options were available for personal and professional enrichment at the 2010 joint STP/ IFSTP symposium.
The most obvious opportunities were the several pre-meeting continuing education (CE) opportunities. The first offering, on Saturday, was the traditional full-day satellite session “Pathology Potpourri,” which is sponsored by the U.S. National Toxicology Program and coordinated by Dr. Susan Elmore. Several subjects were covered at this event, including similarities and differences between lesions in mice and rats, a series of unusual structural changes in several organs, and an introduction to the nomenclature recommendations for rodent neural lesions that are being developed as part of the International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice (INHAND) initiative; these cases are again reported within this issue. In addition, three traditional half-day CE courses were provided on Sunday (Table 1), so that participants could consider noninvasive imaging as a translational tool for evaluating toxicant-induced lesions over time, renew and expand their understanding of hemostasis pathways and the impact of exogenous agents on them, and explore conventional and innovative morphologic methods as well as “best practices” for developmental neurotoxicity testing. A new feature of this symposium issue is that the co-chairs of the CE courses have written their own session mini-reviews. We are especially pleased with this new section because in the past the content and names of participating speakers from CE courses have not been published and therefore have not been easily retrievable by those who did not attend the session but who might need to contact a subject-matter expert in that area at a future date.
Another opportunity for professional enhancement on Sunday was the half-day career development seminar, which was co-sponsored by the STP Career Outreach Committee and the Continuing Education Committee. The title of the session was “Managing Your Career in a Changing Environment.” It was designed to provide an interactive format by which attendees might (1) better understand the evolving role of toxicologic pathologists in the pharmaceutical industry and (2) discover new strategies and tactics for enhancing their career trajectory and satisfaction in a time of constant economic and scientific change. Participants also learned how to anticipate and positively react to such fluctuations in their work environment (especially where the change required a move to a new employer or temporary termination of employment). An exit poll of participants in this seminar indicated that a popular feature was the tendency of the speakers to illustrate their points using examples they had experienced in the course of their own careers.
Another Sunday innovation was the opportunity for all STP participants to attend the ACVP/STP Coalition Scientific Conference. The full-day session provided a unique forum in which students funded by the Coalition presented updates on their ongoing residency projects or PhD research to their sponsors and the broader toxicologic pathology community. Periodic intermissions allowed trainees, teachers, and sponsors to freely network over topics as diverse as specific student projects, current trends in toxicologic pathology, and interesting activities in Chicago.
Two lunchtime seminars added additional zest to the midday meal on Monday. The first was a career development lecture for trainees, entitled “The Value of a Research Degree to a Career as a Toxicologic Pathologist: The Debate Continues.” A panel of toxicologic pathologists (some with research degrees, and some without) employed by pharmaceutical firms discussed such questions as the benefits versus the cost of obtaining a graduate degree, the relevance of research in various toxicologic pathology careers, and the likelihood that some skills can be learned only in a graduate school setting. The second seminar was a Spanish-language CE session on laboratory animal neuropathology. The first presentation, “Lesiones inducidas en SNC y SNP de animales de laboratorio y posibles metodos de evaluacion (Toxicant-Induced CNS and PNS Lesions in Laboratory Animals and Their Possible Methods of Evaluation),” was delivered by Dr. Klaus Weber (Harlan Laboratories, Switzerland). A second talk, “Una tecnica para disectar y evaluar el SNC y SNP de primates no humanos para estudios generales de toxicidad (A Technique to Dissect and Evaluate the CNS and PNS in Nonhuman Primates for General Toxicity Studies),” was given by Dr. Ingrid Pardo (Pfizer, USA). These traditional noontime offerings at the annual STP symposium have become popular activities for learning and networking.
An additional opportunity for continuing education was provided by the IFSTP through its two venues for comparing educational practices, resources, and needs associated with the training of toxicologic pathologists among different nations. The first was a poster session, in which entries by six of ten IFSTP member societies illustrated the specific activities, resources, and needs within their nation or region. The second occasion was an interactive panel discussion between representatives from six of ten IFSTP member societies, in which brief presentations by societal representatives were followed by a question-and-answer forum that focused on potential mechanisms of integrating international efforts at training toxicologic pathologists. Such exchanges should help various national and regional toxicologic pathology societies to strengthen their teaching practices and bolster their available training resources (both domestic and foreign) to better meet their educational needs for preparing future toxicologic pathologists.
The final educational opportunity was the interactive Town Hall forum on Monday evening, which dealt with the topic “International Perspectives on Pathology Peer Review.” This session was hosted by Drs. Daniel Morton and Rani Sellers, the co-chairs of an STP working group (with international membership) that is updating the STP best practices paper on pathology peer review. In a series of five-minute presentations, toxicologic pathologists from the United States, Europe, and Japan provided their insights on the viewpoints of pathologists and regulatory agencies from their nations regarding current peer review practices. A spirited discussion then ensued between the presenters and the audience regarding potential alterations that might be sought by regulatory agencies in the future (such as locking the pathology dataset before peer review). Many of the comments collected during this debate will help refine the ultimate form of the revised “best practice” document on this topic.
We will let the efforts of the session co-chairs and their speakers tell the full tale of the 2010 joint STP/IFSTP scientific symposium through the manuscripts collected within this issue. That said, we must again acknowledge that the fabulous efforts by all of these individuals have helped a new generation of toxicologic pathologists to gain an appreciation for the complex beauty of the nervous system. We anticipate that the high quality of this symposium issue will nurture the skills of toxicologic neuropathologists and neurotoxicologists for years to come and will be a powerful aid in the worldwide effort to better protect mental health.