INTRODUCTIVE LECTURES

    John STEGEMAN

John Stegeman is Sr. Scientist and former Chair of the Biology Department at the Woods Hole Oceanographic Institution in Woods Hole, on Cape Cod in Massachusetts. He also is Director of the Woods Hole Center for Oceans and Human Health. His background is in biochemistry and he has been doing research on xenobiotic metabolism and cytochrome P450, mostly in marine animals, for more than 30 years, and he has authored or co-authored about 280 publications.
John Stegeman pioneered development of biomarkers and studies on alterations of biochemical systems as sensitive indicators of environmental contamination. His research on evolution and regulation of cytochrome P-450 isozymes from diverse species is outstanding. The studies on structure-function relationships involved in metabolism and effects of chemicals in relation to the susceptibility of different animal groups also represent a large body of pioneering work. His whole research is more than a significant contribution to the understanding of mechanisms of pollutant action.
John will give us a current view of “Diversity and evolution of cytochrome P450 genes in animals” in his invited lecture of the inaugural session that will open ISTA14.

Understanding the susceptibility of individuals and species to toxicity of xenobiotics can depend on knowing the diversity, regulation and function of cytochrome P450s. Genome searching is uncovering the total complement of CYP genes in animals from early metazoans to mammals. The numbers range widely, from 40 to more than 200 genes/species. Phylogenetic analysis is disclosing the relationships among CYP gene families, yet homologous relationships between particular genes can be obscured by evolutionary distance, and by gene conversion and birth-death evolution. These processes have confounded relationships among vertebrate CYP1s (including CYP1As) and led to different numbers of genes in fish (5) and mammals (3). However, gene structure and shared synteny do indicate orthologous relationships. Induction of the multiple CYP1s via AH receptors, is well known in vertebrates, but cell specific expression, critical to toxicity, is still poorly known. Identifiable CYP1 homologues occur in early Deuterostomes, but there is much uncertainty about CYP1 homologues in Protostomes, and we know little about CYP regulation by AH receptors in either group. In the CYP2 family, relationships in different taxa are even more clouded by extensive birth-death evolution. Synteny analysis has identified co-orthologs in some vertebrates, for example in the CYP2J subfamily, but functional implications of multiple co-orthologs are quite unclear. To obtain a comprehensive view of CYPs in one species, we are profiling transcript expression of all 89 zebrafish CYP genes, identifying genes with possible physiological and/or toxicological roles, particularly during development. This is coupled with expression and modeling-docking approaches to discern functional properties, including how species differences in structure of orthologous CYP, even of the CYP1As, can influence their participation in mechanisms of toxicity. Growing information on CYP and other gene families will continue to generate mechanistic insights pertinent to toxicity assessment. (NIH grants 1R01ES015912 and 5P42ES007381 – SRP).

     Eric VINDIMIAN

Eric Vindimian has spent most of his career on the edge between research and policy making. As a scientist he worked in the field of ecotoxicology and developed biomarkers of toxicity for aquatic ecosystems. He has been head of the unit biology of freshwater ecosystems at Cemagref, a research institute for environmental and agricultural public policies, he has also been director of chronic risks at Ineris a research and expertise public institute for industrial risks. He has been the representative of the ministry for research in the region Rhône-Alpes. He also spent six years leading the research department of the French ministry for ecology and sustainable development. He has been president of the subcommittee “Biological methods” of the technical committee 147 “Water quality” of the International standardization organisation (ISO). He is now regional director of Cemagref in Montpellier, region Languedoc-Roussillon in the south of France. He was recently elected President of the French Society of Ecotoxicology (SEFA).

The adoption of the new chemicals regulation : REACH, by the European parliament late 2006 has been considered by many observers as the end of a long story. After a decade long debating and discussing the ecological, health and economical issues, after serious revisions of the ambition of the initial text, a final draft was adopted that will change the way we regulate chemicals for the next century. The initial focus of the discussions was the cost of coping with REACH for chemical industry. A minority of stakeholders have tried to shift the googles to inspect the benefits for human health and ecosystem services. Such benefits are probably considerable but, unfortunately, not calculable. Nowadays, most of the discussions deal with the needs for a proper expertise and on the necessity of new tools for an optimum implementation of the regulation. Furthermore European chemical industry now communicates on the role that innovation might have to develop a green chemistry i.e. a chemistry that would provide goods and services to humanity, jobs for people and medicines for ill people while having not or at least negligible impact on the environment and unrenewable resources. This is where research can take the lead. From a regulator perspective the ideal situation would be the following : • A series of low cost tests to assess toxicity of chemicals with a good precision, especially no false negative, • A set of models to infer the effects in the real world from laboratory studies : sensitive human populations, populations, communities and ecosystem level, induced resistance and other genetic and epigenetic effects; Among those models, models that are based on chemical properties only are very welcome since they are very cheap and do not raise any ethical problem. • A panoply of chemical, biological and sensor-based tools to monitor the toxic substances and their effects in the environment. It is easy to understand that we are far from that ideal situation. It is our responsibility in the scientific community to find solutions to those issues. Many research questions, being raised from a solution minded orientation of from a pure knowledge perspective are currently developed that will provide the policy makers with relevant options for their action. ISTA2009 will certainly reveal new findings that contribute to policy making. This lecture is an attempt to put together some of these questions and recent tracks to answer them. It will focus on modelling, integrated management and monitoring.