About JSOT / President's Message
Sunao Manabe, President of the Japanese Society of Toxicology
As of January, 2014, I have been selected as the president of the Japanese Society of Toxicology (JSOT) for the next 2-year term. JSOT now has more than 2,600 members, and is the second largest toxicology society in the world (among IUTOX members) following the Society of Toxicology and still growing. As president I intend to reinforce the on-going activities and add indispensable new activities. I really appreciate all of your support in progressing the JSOT.
In the environment surrounding us, there are a huge number of chemicals including natural products. Toxicology is the science that investigates comprehensively the responses to any xenobiotics, natural products or synthetic chemicals, entering our body via various routes by scientific methods, and its final goal is prediction of hazards to people, animals, plants, and the environment and protection from such hazards. Therefore, toxicology is a multidisciplinary science consisting of basic, applied, and social sciences. JSOT has been promoting and expanding by cooperative efforts between researchers in industry, government, and academia. Under the background of this society described above, I was the first member from industry to be selected president following previous presidents who were from government and academia.
Paracelsus (1493-1541), a physician-alchemist in the late Middle Ages, noted "All substances are poisons; there is none which is not a poison. The right dose differentiates poison from a remedy." Chemicals have multiple targets in humans, exerting effective, beneficial, or hazardous actions. For pharmaceuticals, the "beneficial effects" on patients confer drug efficacy, while the "inappropriate effects" on patients are recognized as adverse or harmful effects, or toxicity. These adverse effects include carcinogenesis, tissue damage such as liver injury or nephrotoxicity, or functional disturbances such as circulatory failure. For environmental pollutants, human risk is evaluated based on the exposure level and incidence in humans derived from epidemiologic investigation or case studies. In the case of hazardous materials, measures aimed at reducing the amount of materials in the environment are required to reduce human exposure.
To ensure "human safety", it is necessary to evaluate and characterize the adverse effects of each chemical by dispassionate insight into research results obtained from prototype experiments including animal studies, experiments using cutting edge tools for research, etc. Biomarkers as research tools are one area where significant progress has been made in recent years. Appropriate biomarkers are required to be detected with precision, specificity and sensitivity. In addition to ordinary clinical pathology, DNA, RNA, proteins, and endogenous metabolites are utilized as biomarkers. From 2002 to 2012, transcriptome analysis with 150 chemicals in rat liver and kidney and human liver cells treated has been performed in the national industry-government-academia joint project centered around the National Institute of Health Sciences and National Institute of Biomedical Innovation, Japan. It has been revealed that non-coding short length RNA (micro RNA) plays an important role in function or differentiation of cells and organisms. This also suggests the possibility that several biomarkers capable of evaluating energy pathways, the cell cycle, etc. will be used for diagnosis and/or prediction of toxicity. It is expected that practicable biomarkers will be established from these above-mentioned activities in the near future.
In biotechnology-derived pharmaceuticals, monoclonal antibodies playing principal roles in the immune system have been developed and approved for clinical use. A mouse monoclonal antibody was approved by the FDA for the first time in 1986, and since then chimera antibodies and humanized antibodies were developed and marketed to reduce adverse effects seen with the murine antibody product. Research and development of gene therapy and nucleic acid medicine also continue worldwide. Initiation of the first clinical study of regeneration medicine using human iPS cells was announced in 2013. Although guidelines for preclinical safety evaluation of monoclonal antibodies have been issued and standard study methods have been established in Japan, U.S. and Europe, development of gene therapy, nucleic acid medicine, and regeneration medicine is managed on a case-by-case basis. It is important that toxicologists in industry-government-academia cooperate closely for standardization and establishment of clinical and preclinical safety evaluation studies of these biotechnology-derived pharmaceuticals.
One of the social demands for JSOT is to expand our coverage of our contribution to public health. As can be found in the document written by our former president Professor Hitoshi Endo titled "Mission and outline of JSOT" (http://www.jsot.jp/about/index.html in Japanese), the JSOT, which has grown as a result of the continuous merging of the academic, industrial, and governmental sectors of toxicology, now faces inevitable demands to collaborate with medical and social sectors. I believe that JSOT continues to integrate the scientific knowledge derived from each related discipline and to contribute further to the advancement of social life and welfare on the basis of the direction shown by previous presidents including our former president, Dr. Kanno.