SEPTEMBER 2008 VOLUME 21, NUMBER 9 Copyright 2008 by the American Chemical Society
Guest Editorial The Developments and Challenges of Toxicology Education, Research, and Funding in China In most popular opinion, China is a country full of inconsistencies and inexplicability; however, this concept may already be growing old and becoming a part of ancient history. The blooming development of the Chinese economy gives courage to the nation to rapidly modernize. Our firm, long-established, and deeply rooted cultural deposits do not block the pace of absorbing and learning modern science and technology. This once mysterious, conservative, and closed oriental country with an ancient civilization now communicates with other countries all over the world, with a comprehensive and open attitude, just as all rivers run into the sea. China covers an area of about 9.6 million square kilometers. With approximately 1.3 billion inhabitants, the Chinese population accounts for one-fifth of humanity and is consequently the largest country by population. Science and culture in China have experienced vicissitudes of inheritance from over thousands of years of civilization, but now, China also exhibits renascent power and hope as an opening cocoon, and so it is with toxicology in China.
A Glance: The Silhouette of Chinese Toxicology over Thousands of Years Toxicology arose primarily from a combination of the sum of practical experience and naïve methodology, both of which were formed in the battle between humans and poisons and have been explored, identified, and researched throughout human history. In China, the idea of toxicology can be traced back to the antediluvian legend of ShenNong (Patron of Agriculture), the mythical herbal medicine master of ancient China who tasted hundreds of herbs (1). From the Warring States time (B.C. 475-B.C. 221), the aristocrats indulged themselves in making pills for immortal life. Even Emperor Chin (the first emperor of China, B.C. 259-B.C. 210) and Emperor Wu (B.C. 157-B.C. 87) in the Han Dynasty, the dominators of the country, abandoned themselves in these activities hoping to find
the elixir of life. Limited by the levels of science and technology at that time, many errors existed in the cognition of adverse effects of chemicals. People falsely believed that lead and mercury could maintain life indefinitely, so that they became the materials for “elixir” (1). Many historians believe that the most well-known and unfortunate victim in ancient China may have been Emperor YongZheng (A.D. 1678-A.D. 1735) in the Qing Dynasty, who took pills for immortality that contained excessive amounts of lead and died suddenly at 57 years old. At that time, the Western world had already recognized lead as a poison. A book named ShenNong’s Herbal (publishing period unknown), the first ancient pharmacology reference in China, classified medicines into high, middle, and low grades, representing the thinking regarding the classification of toxicity at that time (1). In the South Song Dynasty, The Collection of Being GiVen Back Innocence (A.D. 1247) written by SongCi registered that taking poison was the cause of suicide or homicide and also presented some methods for detoxification and identification of poisons. SongCi is considered to be the originator of forensic toxicology in China. Finally, in both the Sui Dynasty (A.D. 581-A.D. 618) and the Ming Dynasty (A.D. 1368-A.D. 1644), many references described and explored where poisons came from and how to validate their toxicity. Since the 1920s, with the introduction of Western medicine into China, Chinese scholars have started to apply pathology and chemistry analytical procedures to detect poisons. Medical staffs employ field surveys and animal experiments to deal with poisoning events. These practices indicate that modern toxicology has been established in China. During this time, toxicology in China has experienced a long time of transition from traditional to modern during the process of civilization. By the 1980s, the development of toxicology in education and research had entered the stage of modern toxicology.
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Toxicology Education in China Toxicology education in China has experienced several developmental stages over the past 50 years. In the 1950s and 1960s, as a subdiscipline of pharmacology, toxicology played an important role in pharmacological research and development. Few people received systematic education and training in toxicology, and there was not even a systematic toxicological textbook in China at that time. Scholars collected Russian or English reference books and literatures and translated them into Chinese to form the preliminary teaching materials. The toxicological training course was open as a lecture to graduates only. In the mid-1970s, Chinese scholars compiled Industrial Toxicology, which was the first specialized reference book of toxicology in China, and following this book issue, Food Toxicology was published. These books introduced the basic principles and methods of toxicology and played crucial roles in spreading the knowledge of toxicology. In the early 1980s, Dr. Frank C. Lu, a famous Chinese-American pharmacotoxicologist, held the first training program in toxicology education and research to provide the scientists who would form the backbone of the field throughout the nation. Subsequently, he edited Basic Toxicology, which was a systematic and comprehensive textbook in China at that time, and donated a series of toxicology reference books to promote the development of modern toxicology in China. After that, various versions of toxicology textbooks were introduced and translated into Chinese, for example, Casarett and Doull’s Toxicology (Klaassen, C., Amdur, M., and Doull, J., Eds.) and Principles and Methods of Toxicology (Hayes, A. W., Ed.). Thus, toxicology education in China entered a speedy developmental and golden stage. Toxicology is a compulsory course for undergraduates and graduates who major in preventive medicine in the School of Public Health or major in pharmacology in the School of Pharmacology. In addition, some students in medicine, life science, biology, and molecular science often attend toxicology courses as elective courses. The basic theory, knowledge, and experimental techniques of toxicology are highlighted in the course teaching and training, particularly in descriptive, mechanistic, and regulatory toxicology. In China, more than 70 universities have a School of Public Health and/or Pharmacology, and every year, each School of Public Health recruits about 100 students. Moreover, toxicology is also listed as an indispensable course in the continuing education of talents for the national and local Center for Disease Control and Prevention (CDC). So, the amount of trainees who have received toxicology education is not small in China. In recent years, overseas Chinese toxicologists who went abroad after 1978 further elevated and amplified the development of toxicology in China by international communication, short-term visiting, and cooperation.
Foundation of Toxicology in China Funding applications in China have had multiple sources since 1982; either state and local governments or companies provide many opportunities for applicants. The National Natural Science Foundation of China (NSFC) is one of the major sources that mainly support the development of basic research and applied basic research. It is similar to the National Institutes of Health in the United States. Toxicology is listed in the Division of Preventive Medicine and Hygiene in the Department of Life Science, and every year, it supports 3-5% of the proposals out of all applications. Every 2 or 3 years, the NSFC launches 2-3
key research projects to support the national strategic development of necessary and possible breakthroughs in innovative academic thought, techniques, and approaches, especially those with original innovative ideas and those that have the capacity of prompting the development of toxicology-related disciplines. Multidisciplinary teams of investigators are particularly encouraged to respond to these kinds of projects. To encourage, support, and promote the charitable and academic activities of young scientists, on one hand, young investigators are encouraged to participate in the proposed collaborative and integrated research. On the other hand, NSFC sets up special grants for training young scientists as independent principal investigators. National Key Research Projects for toxicology from the Ministry of Science and Technology, Ministry of Education, and Ministry of Health have scarcely been launched in the past years, except in the case of nanotoxicology. However, the opportunity to be supported can be greatly increased by applications from many other projects involved in the field of toxicology. Investigators of toxicology also submit their proposals in interdisciplinary and cutting-edge subjects. In recent years, on the basis of development and regulations for safety assessment, more and more industrial enterprises are beginning to pay greater attention to the advancement of toxicology and cooperation with universities and institutions. The government encourages enterprises to strengthen cooperation with academic institutions. With the fast development of the economy, local governments would like to provide funding to support plans for the regional development of science and technology, which becomes an important source of financial support for research. In some developed provinces, the scale and strength of support has increased quickly in the past several years and is now close to NSFC’s level.
Research of Toxicology in China In the 1950s and 1960s, toxicological research was launched in China. In 1957, as a representative work, Chinese scholars reported that the oil extracted from cottonseed, when eaten, gave rise to male infertility (2). This was then shown to be caused by the effects of gossypol on the germ cells of the testis (3, 4). However, rapid development and significant progress for Chinese modern toxicology did not occur until the 1980s (5). In that period, the transition from a negative self-closed society to one actively opening up to the outside world began. This was the first time in thousands of years for this oriental country with an ancient civilization, with an open and sincere attitude, that communication was expanded with other countries and that the progress of merging into the mainstream world and joining in the global establishment and development was accelerated. A series of branch disciplines of modern toxicology such as genetic toxicology, food toxicology, occupational toxicology, pesticide toxicology, and environmental toxicology were founded. Standard test methods and procedures based on toxicity, target organs, various test end points, and safety assessment procedures for chemicals were established by absorbing foreign experience and using overseas models for reference (6–8). At the same time, the relevant departments of government and institutions of scientific research directly accepted, cited, or referred to Guidelines for Drinking Water Quality (WHO), National Primary or Secondary Drinking Water Regulations (U.S. EPA), and so on to enact China’s own standards, regulations, and laws. Through communication and cooperation with developed countries, Chinese toxicologists studied abroad and were supported by various communication, cooperation, or training programs. They learned advanced technology and thought directly and
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contacted elites and authorities in the same areas, and the whole team of Chinese toxicologists was keenly alive to the development and progress of toxicology all over the world. International frontier theory, advanced technologies, and models were continually introduced to China, founding the basis for the development of modern toxicology in China. Since 1985, China has begun to hold domestic and international academic conferences at different levels that provide a good stage for promoting the communication and cooperation between domestic and foreign toxicologists. Driven by this situation, the development of Chinese toxicology really merged into the progress of the global development of toxicology. Some visiting scholars have finished their training programs, returned to China to set up laboratories, and made a series of influential contributions in environmental toxicology and occupational toxicology. Their results provide a profile of modern Chinese toxicology research. For example, Wang et al. have investigated the combined action of arsenic and fluorine on human health (9). They have found that excessive quantities of arsenic and fluorine trace elements in blood might have a synergistic harmful effect on the nervous and circulatory systems. Peripheral neuritis and cardiovascular changes observed in the syndrome of endemic arsenism and fluorosis occurred more often than in simple arsenism or simple fluorosis. Dr. Jin’s group has found that the levels of plasma MT-Ab can be used as a biomarker of susceptibility to renal dysfunction in occupational cadmium exposure (10). Zheng’s laboratory has found that HLA-B*1301 could be used as a biomarker for genetic susceptibility to hypersensitivity dermatitis induced by trichloroethylene among workers in China (11).
Challenges of Toxicology in China Toxicology in China has experienced rapid development and made great progress in education and research in conjunction with economic development in China over the past two decades. However, at present, the field of toxicology seems to be entering a plateau and meeting a bottleneck. We have noticed a similar situation with developed countries such as the United States and Japan, which face challenges associated with the reduced interest of students, less available funding, and insufficient support strength of funding. In China, the education system for graduates contains Masters Degree and Ph.D. programs. Usually, it takes 2.5 or 3 years to acquire a Masters Degree and another 3 or 4 years for a Ph.D. The number of students recruited for Masters Degree and Ph.D. programs increased almost 5- and 3-fold as compared to 20 years ago. Nowadays, with the blooming economy, students have more opportunities and choices for personal development, taking seriously their devotion and productivity, future jobs, and outcomes. Undergraduates tend to choose the disciplines free of complex and heavy experimental procedures such as epidemiology, statistics, health economics and management, and social medicine. Moreover, with the enlargement of international communication, undergraduates and graduates in China face more and more opportunities to study abroad, inducing a serious brain drain from the domestic toxicological infrastructure. This also affects the sustainable development of the team of toxicologists in China. On the other hand, toxicologists in China mainly come from preventive medicine and public health, whereas foreign toxicologists major in many different specialties such as medicine, chemistry, biology, and so on. Most toxicologists in China prefer to recruit students with a public health or medicine background who have a good basis in pathology and physiology. Similarly, students also would like to stay in their preliminary majors.
These conditions greatly inhibit interdisciplinary communication. Moreover, we have not established a qualification system for the certification of toxicologists, so that the team of toxicologists in our country lacks effective management and guidance. However, in both Japan and the Republic of Korea, two countries in East Asia like China, a certification system for toxicologists has been established (12). As for funding, although the proportion and strength of funding support gradually increase every year, the speed and the scale do not match the development of the economy. The general grants and young scientists’ grants from the NSFC are about 40000 dollars and 30000 dollars for 3 years, respectively. Even for key projects, funding is only 300000 dollars over 3 years. The cost of chemicals, materials, equipment, and instruments used in China is the same as in the developed countries or may be even more expensive. Therefore, funding support can not completely satisfy the development demand of toxicology in China. At present, there are no strategic projects that are similar to the United States’s toxicogenomic projects and environmental genomics projects, although they have been discussed for a long time. Thus, toxicology research in China may fail to keep abreast of the significant revolutionary changes that accompanied the arrival of the era of molecular toxicology and may be restricted to keeping a close relationship and communication with the mainstream field of toxicology. Furthermore, as other developing countries have commonly faced, Chinese toxicologists are ineluctably confronted with the issues of how to perform high-quality research, keep up with the footsteps of development in toxicology, publish their results in international journals, and participate in wider international research and cooperation. Chinese toxicologists have established the framework of toxicological research, hygienic standards, and safety assessment procedures through absorbing international thought and experimental technology. However, this referring and simulating pattern of development has produced the phenomenon of “Path Dependence”. Most of the standards or limit values of chemicals were enacted by copying or accepting foreign standards. There are few chemicals for which the standards were enacted through risk assessment on the basis of domestic toxicological research and epidemiologic data according to the actual situation in China. Some chemicals in drinking water detected with high frequency lack basic toxicological data. Therefore, it is impossible to establish their control standards or limit values. Some chemicals in drinking water with high detection frequency exceed foreign limit values, but they are not listed in the Standards for Drinking Water Quality in China, while some chemicals detected infrequently or not detected were put in the list of the standards. Although the number of Chinese toxicological papers published in international journals has significantly increased, high-quality research papers completed in the mainland of China have been published in the top grade journals infrequently. This indicates that quite a bit of toxicological research in China lacks innovation. So, it is not accepted by international journals. Taken together, these factors are the potential barriers against the further development of toxicology in China.
Conclusion There are three aspects to the effort to improve the current situation of Chinese toxicology. First, it is important to absorb students with various backgrounds to join the study and research of toxicology and to elevate the educational quality of toxicology at all levels. Second, it is key to encourage participation in wider venues of international cooperation emphasizing China’s ad-
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vantages in population and diversity. Third, further amplifying international communication will become an effective way to reveal Chinese knowledge and advances in toxicology. The Chinese Society of Toxicology was founded in 1985. The number of registered members reached about 1600 last year. The annual meeting of the Society of Toxicology absorbs thousands of toxicologists from around the world to join this grand gathering of toxicology, but only several toxicologists are from China. Now, the availability of information and financial support combined with the ease of visa applications has greatly improved as compared with 10 years ago. Obviously, this will increase the possibility for Chinese toxicologists to join the international community. Weidong Qu* and Weiwei Zheng Key Laboratory of the Public Health Safety Ministry of Education Department of EnVironmental Health School of Public Health Fudan UniVersity Shanghai 200032, China Tel: 86-21-54237203 Fax: 86-21-64045165 E-mail:
[email protected] Yuxin Zheng National Institute for Occupational Health and Poison Control Chinese Center for Disease Control PreVentiVe Beijing 10005, China
Acknowledgment. The author’s laboratory is supported by grants from National Key Technology R&D Program in the 11th
Five-Year Plan (No. 2006BAI19B02) and National Science Fund (No. 03QD14011).
References (1) Fu, L. J. (2001) Modern Toxicology and Its Application, Shanghai Science and Technology Publication, Shanghai, China (in Chinese). (2) Qian, S., and Wang, Z. (1984) Gossypol: A potential antifertility agent for males. Annu. ReV. Pharmacol. Toxicol. 24, 329–360. (3) Dai, R. X., and Dong, R. H. (1978) Studies on antifertility effect of gossypol. I. An experimental analysis by epididymal ligature. Acta Biol. Exp. Sin. 8, 15–22 (in Chinese). (4) Dai, R. X., Pang, S. N., and Liu, Z. L. (1978) Studies on the antifertility effect of gossypol I. A morphological analysis of the antifertility effect of gossypol. Acta Biol. Exp. Sin. 11, 27–30 (in Chinese). (5) Jiang, Q. G. (2000) Looking back to the 50 years of toxicology in China. Chin. J. Ind. Med. 13, 107–108 (in Chinese). (6) Yin, M. Q., Yu, Y. N., and Zheng, Y. W. (1999) Retrospective review of the development of genetic toxicology in China. J. Health Toxicol. 13, 229–233 (in Chinese). (7) Zheng, D. X. (2006) Retrospective and perspective of food toxicology in China. Chin. Trop. Med. 6, 1880–1881 (in Chinese). (8) Wu, D. C. (2000) Status and perspective of environmental toxicology. Chin. J. Radiol. Med. Prot. 20, 145–148 (in Chinese). (9) Huang, Y. Z., Qian, X. C., Wang, G. Q., Xiao, B. Y., Ren, D. D., Feng, Z. Y., Wu, J. Y., Xu, R. J., and Zhang, F. E. (1985) Endemic chronic arsenism in XinJiang. Chin. Med. J. (Engl.) 98, 219–222. (10) Lu, J., Jin, T., Nordberg, G., and Nordberg, M. (2005) Metallothionein gene expression in peripheral lymphocytes and renal dysfunction in a population environmentally exposed to cadmium. Toxicol. Appl. Pharmacol. 206, 150–156. (11) Li, H., Dai, Y., Huang, H., Li, L., Leng, S., Cheng, J., Niu, Y., Duan, H., Liu, Q., Zhang, X., Huang, X., Xie, J., Feng, Z., Wang, J., He, J., and Zheng, Y. (2007) HLA-B* 1301 as a biomarker for genetic susceptibility to hypersensitivity dermatitis induced by trichloroethylene among workers in China. EnViron. Health Perspect. 115, 1553– 1556. (12) Satoh, T., Hayes, A. W., Tsuda, S., Wang, X. R., and Yu, I. J. (2006) Toxicology education roundtable. Chin. J. Pharmacol. Toxicol. 20, 186–189.
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