Biotechnology in China (1989)

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6Biotechnology Literature Survey The following section summarizes the analysis of 160 articles published in Chinese scientific journals. Conducting a literature survey to gain insights into the content and quality of China's biotechnology research was justified for several reasons. First, essentially all research performed in China is published in Chinese journals, in part because scientists receive a bonus for each article. Second, it was hoped that the survey would provide access to research performed at institutes in remote locations that were not visited during the evaluation trip. Third, it was possible to have outside experts review articles on scientific topics with which the authors were not familiar. All articles were read by at least one and, in many cases, by two or more expert reviewers. As all of the reviewers had some familiarity with science in China, the assessments of research originality and accuracy are reasonably uniform for different disciplines. SOURCES The journals and number of articles reviewed in the survey are listed in Table 4. The selection of articles was from three major sources. Chinese Journal of Biotechnology. This is a specialty journal that publishes scientific articles and reviews on applied biotechnology and closely related basic research. Because of the relevance of this journal to this report, every research article published between Volume 1-1 (1985) and Volume 3-4 (1987) was surveyed. Scientia Sinica. This journal, which is published by CAS in English, is generally considered to be China's most prestigious scientific journal. Similar to BIOTECHNOLOGY LITERATURE SURVEY 22

the Proceedings of the National Academy of Sciences in the United States, it publishes articles considered to be of broad interest in several areas of the natural sciences, physical sciences, and mathematics. The survey included every article published between January 1987 and February 1988 relevant to either basic or applied biotechnology. TABLE 4 Sources for Literature Survey Journal Language Number of Papers Reviewed Chinese Journal of Biotechnology Chinese 71 Scientia Sinica English 41 Acta Genetica Sinica Chinese 10 Acta Biochimica et Biophysica Chinese 10 Kexue Tongbao (Science Reports) English 5 Journal of Xiamen University Chinese 5 Acta Microbiologica Sinica Chinese 4 Acta Biologicae Experimentalis Sinica Chinese 4 Acta Physiologica Sinica Chinese 3 Acta Zoologica Sinica Chinese 2 Journal of Fudan University Chinese 2 Acta Anthropological Sinica Chinese 1 Journal of China University of Science and Technology Chinese 1 Acta Scientiarium Naturalium Universitatis Pekinensis Chinese 1 Total 160 Chinese Science Abstracts (Life Sciences). This publication contains English translations of abstracts of all articles published in 61 Chinese journals on the life sciences. All abstracts relating to biotechnology were surveyed for the period 1986 to 1987, and relevant articles were selected and obtained from the National Library of Medicine or the Library of Congress. Journals in China, as elsewhere, vary in prestige, quality, and the rigor of the peer review process. Except for the arbitrary inclusion of all articles from the Chinese Journal of Biotechnology, the survey was strongly biased toward the most interesting articles in what are considered to be the best journals in China. In addition, a serious endeavor was made to include articles on basic research, in particular in biochemistry (e.g., protein structure) and genetics (e.g., gene regulation). Besides the final 160 articles that were thoroughly reviewed and included in the survey, about 200 additional manuscripts were examined briefly. While including these articles in the survey might have better met standards for BIOTECHNOLOGY LITERATURE SURVEY 23

statistical analysis, it seems unlikely that it would have affected the qualitative conclusions. TABLE 5 Geographical Distribution of Articles Cited City or Province Number of Articles Shanghai 68 Beijing 59 Xiamen 5 Wuhan 4 Hangzhou 3 Tianjin 3 Hefei 3 Guangzhou 2 Chengdu 1 Jiangsu Province 1 Jilin 1 Quanzhou 1 Shijiazhuang 1 Wuxi 1 Dalian 1 Fuzhou 1 Harbin 1 Hunan Province 1 Nanjing 1 Suzhou 1 Xianyang 1 Total 160 GEOGRAPHICAL DISTRIBUTION Despite a desire to have the survey compensate for the necessity of confining the evaluation trip to major cities in eastern China, it did not, in the end, reveal much information about the research being conducted in remote areas. As shown in Table 5, the majority (80 percent) of the articles were from institutes in Shanghai and Beijing, reflecting the concentration of research centers in these two cities. The relative paucity of articles from other geographical areas suggests that the increased funding of CAS institutes and universities in provincial areas has not yet had a substantial effect on their scientific productivity. TECHNIQUES The use of various techniques reported in the articles surveyed is summarized in Table 6. Several interesting points emerge. First, techniques for cloning and analyzing DNA molecules were noted in more than half of the articles, which BIOTECHNOLOGY LITERATURE SURVEY 24

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indicates their widespread use. In contrast, techniques for analyzing RNA molecules were strikingly underrepresented. Thus, although there is good capability for isolating genes, there is weakness in understanding how they are expressed and regulated. Second, the use of sophisticated techniques for protein analysis was surprisingly well represented. Third, as might be expected from the emphasis on agriculture in China, there was widespread use of plant tissue culture and regeneration techniques. In general, this analysis suggests that the various techniques composing modern biotechnology have become widely available in China. EXPERIMENTAL ORGANISMS The organisms used in each article were classified under two categories: (1) The "organism studied" refers to the species whose biology is being investigated, and (2) the "organism used" refers to the species actually used in the experiments. For example, for an article describing the production of human interferon in Escherichia coli, the organism studied is human and the organism used is E. coli. A summary of the data on experimental organisms is presented in Table 7. The most important organism used was E. coli, the routine host for DNA- cloning experiments. Also popular were the yeast Saccharomyces cerevisiae, used for protein expression work, and economically important strains of antibiotic-producing fungi. The organisms studied reflected the emphasis of China's biotechnology research. There was a relatively strong emphasis on agricultural research, whereas animal research was predominantly directed toward humans. An interesting sidelight was the substantial number of articles on species of special interest to China, namely, fish (mostly species used for aquaculture), the silkworm, the panda bear, and the Peking duck. A noteworthy point of this analysis was the complete lack of research using certain species widely used in Western countries. In particular, there were no articles on Drosophila melanogaster or Caenorhabditis elegans, the two most useful organisms for studying animal genetics and developmental biology. There was only one article (of low quality) on Xenopus species, and none on sea urchins, despite the wealth of embryological data on these organisms. RESEARCH TOPICS AND GOALS Because of the multidisciplinary nature of biotechnology research, it was not always simple to assign a single research topic to any given article. Taking this into account, each article was categorized according to two systems: scientific discipline (Table 8) and research goal (Table 9). For instance, an article on computer modeling of the hepatitis B surface antigen protein would be classified as "biochemistry, protein structure" under scientific discipline and "applied, human vaccine" under research goal. BIOTECHNOLOGY LITERATURE SURVEY 26

As expected, the predominant scientific disciplines represented in the articles were molecular biology and genetics, mostly because of the large number of articles on gene cloning. Next most popular was biochemistry, with a concentration of articles on protein structure. The fields of microbiology, virology, botany, and immunology were all reasonably well represented. (Note that the apparent paucity of articles on virology is because most of them were assigned to other disciplines; see Table 7.) The weakest areas noted were developmental and cell BIOTECHNOLOGY LITERATURE SURVEY 27

TABLE 8 Scientific Discipline Discipline Number of Citations Percentage of Citationsa Molecular biology and genetics Gene cloning and expression 20 13 Gene regulation 11 7 Population genetics 5 3 Gene mapping 4 3 Mutation and recombination 6 4 Other 3 2 — 32 Biochemistry Protein structure 14 9 Enzymology 5 3 Structure and metabolism of natural products 5 3 Immobilized catalysts 11 7 Other 3 7 — 29 Microbiologyb Strain isolation and characterization 11 7 Fermentation 9 6 — 13 Virologyb Structure 5 3 Detection and prevention 3 2 — 5 Botanyb Plant propagation 16 10 Physiology and anatomy 5 3 — 13 Immunology Diagnostic reagents 10 6 Other 2 1 — 7 Other Developmental biology 3 2 Cell biology 4 3 Neurobiology 5 3 — — 160 8 a Rounded to the nearest integer. Each citation was assigned to a single discipline. b Other than molecular biology and genetic citations. BIOTECHNOLOGY LITERATURE SURVEY 28

TABLE 9 Research Goal Goal Number of Citations Percentage of Citationsa Basic Genetics 15 9 Biochemistry 18 11 Other 17 11 31 Applied Foodstuffs and natural products 21 13 Antibiotics 14 9 Therapeutic proteins 11 7 Diagnostics 11 7 Improved animal species 6 4 Improved plant species 14 9 Human vaccines 10 6 Animal vaccines 9 6 Plant vaccines and herbicides 6 4 Other 8 5 160 70 a Rounded to the nearest integer. biology (seven articles for both fields combined) and protein-nucleic acid interactions (no articles). The research goals of the articles surveyed are summarized in Table 9. Applied research was favored over basic research by a more than two-to-one margin. The most important applied goal was the production of foodstuffs and other natural products, with antibiotic fermentation and the improvement of agricultural crops close behind. The most important conclusion from this analysis is that a close correlation exists between research funding priorities and the research that is actually performed. EVALUATION OF RESEARCH Reviewers were asked to evaluate the scientific originality and accuracy of each article according to the following criteria: Originality A. Very original. Describes a new phenomenon or technique or yields significant information on an important problem. B. Original. Describes new results in an area of basic or practical significance. BIOTECHNOLOGY LITERATURE SURVEY 29

C. Somewhat derivative. Repeats previous research but uses a different organism or a slightly different approach. D. Very derivative. An exact copy of already published research. Accuracy A. Very thorough. Proves the point conclusively. B. Good. The main point is not in doubt. C. Weak. Insufficient data. D. Unacceptable. Poor experimental design or interpretation—would not be published in a U.S. journal. A summary of these evaluations, broken down by type as basic or applied research, is provided in Table 10. In terms of originality, basic research articles far outstripped applied research articles. For example, 22 percent of the basic research articles were considered to be ''very original'' as compared with only 3 percent of the applied research articles. More striking was the fact that 81 percent of the applied research articles "repeat previous research," either completely or with only minor changes in methodology or experimental material. Many of these articles described either the isolation of genes already cloned in the West or the production of previously described materials. For example, more than half of the applied genetics articles described the cloning of genes already sequenced and published in international journals. Because virtually all such journals have the policy that published clones must be made available to all who ask for them, this represents an especially fruitless expenditure of time and resources. One Chinese colleague quipped, "Many of the experiments are like Xerox copies, only made with brush and ink." TABLE 10 Evaluation of Research Type of Research Number of Citations per Categorya Originality A B C D Basic (50 articles) 11 18 17 4 Applied (110 articles) 3 17 46 44 Accuracy A B C D Basic (50 articles) 10 21 16 3 Applied (110 articles) 31 47 23 9 a See text for definitions of the letters under the headings of originality and accuracy. BIOTECHNOLOGY LITERATURE SURVEY 30

The evaluations of scientific accuracy showed a greater equality between basic and applied research. More than half of both types of articles were considered to "prove the point." Those that failed this test did so more often because of a lack of completeness rather than genuine faults in experimental design or interpretation. Several reviewers commented on the tendency to split a single body of work into several articles. BIOTECHNOLOGY LITERATURE SURVEY 31