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6 Biotechnology Literature Survey The following section summarizes the analysis of 160 articles published in Chinese scientific journals. Conducting a literature survey to In insights into Me 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 Hat Be survey would provide access ~ research perfonned at institutes in remote locations Rat were not visited during He evaluation trip. Third, it was possible to have outside experts review articles on science 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 He reviewers had some familiarity with science in China, He assessments of reach originality and accuracy are reasonably uniform for different disciplines. SOURCES The journals and number of articles reviewed in He survey are listed in Table 4. The selection of articles was from three major sources. Chinese Journal of Biotechnology. This is a ppecialt, jomnal Hat publishes scientific articles and reviews on applied biotechnology and closely related basic research. Because of the relevance of Ads journal to this report, every research article published between Volume 1-1 (1985) and Volume 3~ (1987) was surveyed. Scientia Suuca. This journal, which is published by CAS in English, is generally considered to be China~s most prestigious scientific journal. Similar to 22

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BIOTECHNOLOGY LITERATURE SURVEY TABLE 4 Sources for Literature Survey 23 Number of Papers lomnal Language Renewed Chinch Jo~al ~fBiotechn~ogy Chinese 71 Scat a Silica English 41 Acta Gcnetica Sinica Chinese 10 Acta Bu~c)dmica ct. Biophysica Chinese 10 Knee Tonghao (Science Reports) E;ngJ'ish 5 J - rnolofXiamenU~versity Chinese 5 Acta Microbidogica Swca these 4 Acta Biologicac Ex~crunen~lis Smica (`nese 4 Acta Physiologica Struck Chinese 3 Acta Zoolog~ca Sow These 2 Jaunt of Fudan Uni~crs;ty Chinese 2 Acta A~hropo~ogica Silica Chinese 1 Jackal of China Unn~ers;ty of Science Chinese 1 and Technology ActaScientiaru~mNaturalu~m Chinese 1 Um~ersitatis Pekinens~s Total 160 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 ~ either basic or applied b; - chnology. 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 relying to biotechnology were surveyed for Be period 1986 to 1987, and relevant articles were selected and obtained from ~e 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 Be arbitrary inclusion of all articles from the C - ese Journal of Biotechnology, the survey was strongly biased toward the most interesting articles in what are considered to be the best journals in China Id 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 Be survey, about 200 additional manuscripts were examined briefly. While including these articles in Be survey might have better met standards for

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24 TABLE 5 Geographical Distribudon of Articles Cited CS~ or Price Number of Attides Shank Bei3mg ~- mamen Wake Hangzhou ~ . 11~ - Hef" Guy Cha~gdu Jisnggu Pmvince Jilin Q~ou Sbiji~uang Wuxi Dot Fuzhou HI Hewn Province Nanjing Suzhou anyaDg Total 68 59 5 4 2 160 BIOTECHNOLOGY IN CHINA statistical analysis, it seems unlikely that it would have affected the qualitative conclusions. GEOGRAPHICAL DISTRIBUTION Despite a desire to have the survey compensate for He necessity of confining the evaluation Hip to major cities in eastern China, it did not, in the end, reveal much infonnation about He research being conducted in remote areas. As shown in Table 5, He 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 Tom other geographical areas suggests that the increased funding of CAS institutes and universities in provincial areas has not yet had a substantial effect on Heir scientific productivity. TECHNIQUES The use of various techniques reported in He articles surveyed is summarized in Table 6. Several interesting points emerge. First, techniques for cloning and analyzing DNA molecules were noted in more On half of He articles, which

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BIOTECHNOLOGY LITERATURE SURVEY TABLE 6 Techniques Used in He Articles Surveyed 25 Technique Number of Percentage of Octagons G.~. DNA analysis DNA clog 33 21 lion engine analysis 37 23 Soud~em blat 8 5 DNA sequencing 9 6 O]iganucle~de These 3 _ 57 RNA analysis cDNA clog 1 1 Nor~em blot 2 1 RNA sequencing 1 1 Id ~ ~nscnpuan, tIanslaiion 2 1 4 PI analysis Highs an separator: HPLC, PAGE 10 6 Airily purification 2 1 P=temsequenang 4 3 Pepude synthesis 2 1 X-ray crystallography, NMR 5 14 Immunological methods Monobl~1 and polyclonal antibody production 8 Assays: RIA, Ff ISA s 6 4 9 Animal technique, Call allure and hybrid cdl lines 7 4 Gene transfer into cultumd "us 6 4 Gene transfer mto animals 4 3 11 Plant and microbial technique" r-11 end tissue assure 18 11 Plant regenemnon 10 6 P~xLplast fusion 10 6 23 Bioprocessmg Controlled fermentation 12 8 linm~i~d enz~nt~es and cells 10 6 14 miner Electron niicmscc~py, Clay miaasnalysis 4 3 Computer modeling 3 2 5 aAb~iations: cDNA, complementary DNA; HPL(:, high performance liquid chromatography; PAGE,polyac~ylamide gel blemophc~sis; NOR nuclear magnetic mscnance; RIA, radiounmunoassay, ELISA, enyme-linked immunoso~ent assay. "Rounded to the neatest integer. Note Cat these percentages add up to greater Can 100 because some articles described the use of more than one teclmique.

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26 BIOTE{:HNOLOGYIN CHINA indicates their widespread use. On contrast, techniques for analyzing RNA molecules were smilingly unde~e~en~ Thus, although Here is good capability for isolating genes, Here is weakness in understanding how they are expressed and regaled. Second, tile use of sophistic techniques for protein analysis was s~pnsingly well represented Third, as might be expected from He emphasis on agriculture in China, there was widespread use of plant tissue culture and regeneration techniques. On general, this analysis suggests Hat the various techniques composing modern biotechnology have become widely available In China. EXPERIMENTAL ORGANISMS The organisms used in each article were coiffed under two categories: (1) The `'organism studied" refers to He species whose biology is being investigated, and (2) He 4'organisrn used" refers to He species actually used in the expenments. For example, for an micle describing He production of human interferon in Escherichia coli, He organism studied is human and He organism used is E. coli. A summary of the data on experimental organisms is presented in Table 7. I he most unponant organism used was E. coli, the routine host for DNA-cloning experiments. Also popular were He yeast Saccharomyces cerevisiae, used for protein expression wow, and economically important smains of andbiodc-pToducing fungi. The organisms studied reflected the emphasis of China's biotechnology research. There was areLatively strong emphasis on agncul~ral research, whereas animal research was predominancy directed toward humans An interesting sidelight was He substantial number of articles on species of special interest to China, namely, fish (mostly species used for aquaculture3, He siLkwonn, the panda bear, and the Peking duck. A noteworthy point of As analysis was He complete lack of research using certain species widely used in Westem countries. In particular, Here were no articles on Drosophila melanogaster or Caenorha~ds elegans, the two most useful organisms for studying animal genetics and developmental biology. There was only one article (of low qualify 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 ~ two systems: scientific discipline (Table 8) and research goal (Table 9~. For instance, an article on computer modeling of He hepatitis B surface antigen protein would be classified as "biochemistry, protein structure" under scientific discipline and "applied, human vaccine" under research goal.

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BI077~1NOLOGY Lrl~ERATURE SURVEY TABLE 7 Experimental Organisms 27 Orgamsm Studieda, Organism Used, O~arnsm Number of Percentage of Number of Percentage of Gt.au~ TIC amu~ amu~c Bad E. coti 9 6 47 30 Bacillus 9 6 5 3 Stleptamyces 6 4 4 3 Over 5 _ 4 3 19 39 Fungi S. cerc~isiac 5 3 16 10 Andbioi~c producers 14 7 14 9 Over 4 _ 4 3 13 22 Rice Maize Tobacco Fruits Other Art s 6 4 9 6 6 4 4 3 22 5 3 4 3 7 6 4 - 17 4 Human 16 10 5 3 Over mammals and rodents 6 4 3 2 Birds (mostly duck) 5 3 2 1 Amphibians ant fish 9 6 ~ 5 Silkworm 5 2 2 ~ 5 12 Vinlses HepaiibsB 9 6 4 3 Other anunal 4 3 2 1 Inset 5 3 9 6 Plam 8 5 5 3 17 13 See tan for OCR for page 22
28 TABLE ~ Sciatic D~ciplim BIOTECHNOLOGY IN CHINA Discipline Number of Crayons Percentage of C:itati a Mde~ biology and genetics Gene blanmg and Hessian 20 13 Gene region 11 7 Papulanon genetics 5 3 Gene mappmg 4 3 M~ionand~nbinanon 6 4 Other 3 2 32 Biochemistry Pin mumure 14 ~~gY S Snuct~c and metabolism of natural products S ldund~d <=talym 1 1 Other 3 9 3 3 7 7 29 Miachiology. Strain molanon and charactenzanon 11 7 Fennentaiion 9 6 13 Virology Shuck 5 3 Deteclic~n and p~enuot1 3 2 Botany Plant propaga~al 16 10 Physiology and anatomy 5 3 l~nunology Diagnostic reagents 10 6 Other 2 1 Other Developmental biology 3 2 Cell biology 4 3 Neurobiology _ _ 16(} 8 7 fRo~mded to do nean st integer. Each crayon was assigned to a single discipline. iOther Han molecular biology and genetic citations.

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BIOTECHNOLOGY LITERATURE SURVEY TABLE 9 Research Goal 29 Gal Number at ~itaca~s Percentage of Citadel a Bloc Genetics 15 9 Biochemistry 18 11 Other 17 1 1 31 Awlied Foodstuffs and natum1 products 21 13 Andbioucs 14 9 Therapeutic prows 11 7 Diagnostics 1 1 7 linpraved awns species 6 4 Proved plant species 14 9 Human vacanes 1() 6 Atonal Vaccines 9 6 Hant va~nes and he*,iades 6 4 Other 8 160 70 fRounded 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-tmone margin. The most impmant 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 Hat a close correlation exists between research funding priorates and the research that is actually performed. EVALUATION OF RESEARCH Reviewers were asked to evaluate He scientific oiginalin~r and accuracy of each article according to He following cnterua: 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.

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30 BIOTECHNOLOGY IN CHINA 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 Me point conclusively. B. Good. The ~ point is not in doubt. C. Weak. Insu~cientd~ D. Unacceptable. Poor experimental design or inerpretabo~would not be published in a U.S. Journal. A summary of these evaluations, broken doom by We as basic or applied research, is provided in Table 10. In terms of onginalin,r, basic research articles far outstripped applied research articles. For example, 22 percent of We basic research articles were considered to be '~very original" as compared win only 3 percent of the applied research articles. More striking was the fact that X1 percent of the applied research articles "repeat previous research," either completely or win only minor changes in methodology or experimental material. Many of these articles described either the isolation of genes already cloned in the West or Me production of previously descn~ mmenals. For example, more Man half of the applied genetics articles described the cloning of genes already sequenced and published in international journals. Because virtually all such journals have Me policy ~ published clones must be made available to all who ark for ~em, this represents an especially fruitless expenditure of time and resources. One Chinese colleague quipped, "Many of the experiments are like Xerox copies, only made win brash and ink." TABLE 10 E,raluabon of Research Type of Research Number af ~aiials per Category Basic (50 oracles) Applied (110 ambles) Basic (50 ambles) Applied (110 articles) A 11 ad B C 18 17 17 46 D 44 A 10 31 Accuracy B C 21 16 47 23 D 9 See tan for deElninons of me letters under Be headings of onginali~ and accuracy.

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B 1 0 7 7 = H N O L O G Y I d T E R A T U R E S U R V E Y 31 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 n Those Hat failed this test did so more often because of a lack of completeness lamer than genuine Cults in experimental design or interpretation. Several reviewers commented on Be tendency to split a single body of work into several articles.