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8 Current Research at Selecmd Institutes The following section describes current biotechnology-related research at 19 institutions that were visited during a 1-mon~ evaluation trip to China The purposes of this somewhat anecdotal recounting are threefold: to support, in a concrete way, the general conclusions of Chapter 3 on how research funding is pnon~d and alla; to elaborate on research Mends and quality examined in Chapters 6 and 7; and to provide a road map for American scientists interested in cooperation and collaboration with Chinese colleagues. A list of contacts at these institutions is included in Appendix C. BELONG Beijing Agricultural University Beijing Agricultural University, formed in 1952 from the agricultural deparanents of Beijing and Qinghua Universities, is China's largest agricultural university with a staff of 1,050, including 100 professors, 235 associate professors, and 350 lecturers. The large campus on the outskirts of Beijing includes an experunental farm, and He university also operates experunental stations in Hubei and Hdrbin. Of the 21 departments, five actively pursue research involving biotechnology. The amount and type of equipment in He research laboratories have recently been improved by using funds from a World Bank loan. The university opt a national key laboratory for agricultural biology and plans to establish an open laboratory for agncul~1 biotechnology in the near future. The generation of uansgenic plants is of interest to several groups at the 40
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CUR~RE5;EARCHATSE~ED INSIlTUrES 41 university. Yun Longfei's group leas cloned a soybean 7S storage protein gene artful shown, in agreement win results of odes groups, Mat it is expressed in a dssue-,pecific fashion in Ti plasmid-genera~ bansgen~c tomato, potato, and tobacco plants. They are also attempting to generate CMV-resistant plants by using He strategy employed at the Beijing Institute of Microbiology. Attempts to clone plant photosynthetic and high nutritional value protein genes, by using probes from over groups, are skill at the genomic library construction stage. Work on transgenic animals at the Beijing Agricultural University focuses on Me use of grown hormone and grown hormone-releasing factor genes to improve the growth characteristics of pigs and rabbits. Although the relevant genes have already been cloned by Westem biotechnology companies, they are Lying to get Weir own genes and are still in the process of maying genomic libraries. Chinese Academy of Agricultural Sciences The Chinese Academy of Agncultuta1 Sciences was established in 1957 to coordinate agricultural rest activities at Me national level. Currently, it has 33 research institutes, a graduate school, an agricultural library, an agriculture and technology publishing company, a center for computer sciences, and the Center for Biotechnology. There are a total of 10,575 staff members, including 5,063 scientists, 812 a~minisbadve personnel, and 4,700 support staff. The Center for Biotechnology was established in 1986 with a mission that includes research and training. According to the original plan, the center will have 40 new positions. At the present time, there are Tree major laboratories: molecular biology and genetic engineering, plant cell technology, and tumors and monoclonal antibodies. Research subjects carried out at the center include vaccine and genetic engineering, plant genetic engineering, biological control and viral genetic engineenng, protoplast culture and fusion, and plant virus and monoclonal antibody studies. The Molecular Biology and Genetic Engineering Laboratory is led by Yak. Fang, director of Me center. Currently, there are about 20 people: one associate professor, two instructors, one postdoctoral fellow, Tree Ph.D. students, eight M.S. students, and five msearch associates. This laboratory is well funded win approximately 400~000 yuan from the Chinese government and $20,000 from the Rockefeller Foundadon. They are carrying out four major projects. In the isolation and identification of plant gems project, the genes that have been cloned are leghemoglobin and llS seed storage protein from soybean. In the nutritional improvement of crop species project, they are at the stage of constructing genomic libraries from alfalfa In the insect-resistant plants project, they are transferring plants with Bacillus th~ingiensis toxin gene by using §-glucuronidase as We reporter gene. The isolation of toxin genes from insecm project has just been started. The Plant Cell Technology Laboratory is led by S.C. Chia, who is currently
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42 BIOTEClINOLOGY IN CHINA taking sab;hadcal leave in Singapore. He As ~ group of nearly 10 people consisting of one associate professor, two research emaciates, and several M.S. students. This lab~ory has been credit win making contributions in fusing cucumber protoplasm and subsequently regenerating Rem into plants. It receives good support at 200,000 yuan per year. The Tumor ~ Monoclonal Andbody Laboratory conducts research on potato Viruses. It is Be newest among the Tree labc~ratones. Currently, there are about 10 people receiving about 200,000 yuan per year for research. Institute of Biophysics (CAS) The Beijing pastime of Biophysics, founded in 1959, currency houses some 800 wooers, including400 scientists. The institute is divided into 12 deparunents Hat include, in biotechnology-rela~d fields, bioengine~nng, enzymology, x-ray crys~llo~aphy, protein engineering, and cell biology. An interview conducted win Lei Kejian concentrated on scientific topics rawer than research support. However, it was obvious from the sophistical ins~entation in the l~iboratones Hat He institute is well funded The research highlight at the institute is their in~mationally recognized work on struct~e-function relationships in insulin. These studies ~nvolvehigh-resoludon x-ray crystallography to determine the precise structure of He molecule, chemical and enzymatic modifications to detennine the roles of venous residues in molecule function, and genetic engineering to produce novel derivatives. The structure of native insulin (~2hexamer founts has now been completed at a 1.2 A resolution, He highest yet reps. At this resolution, it is possible to visualize three hydrogen bonds and ~ detect asymmetry at two disulf~de bonds. The structure of chemically prepay despentapeptide insulin' which lacks five residues and has lost 8 percent of its biological activity, has been solved at a 1.5 A resolution and appears identical to the native form except for the position of the carboxy- ~mir~ residue. Narrowing in on the active site, attempts are now under way to solve He structure of deshexapeptide insulin, which lacks one additional residue and has lost all biological and receptor-binding activities. Struc~re-function relationships of insulin are also being studied by a comparative approach, and the structure of a fish liver insulin has been solved at a 2.S A resolution. Building on this basic research, the protein engineering group is attempting to engineer long-acting fonns of insulin. Insulin is stored and secreted as ~ Zn- coordinated hexamer, whereas Be active form is either a monomer or dimer (a point of dispute among He Beijing Institute of Biophysics and other groups). Therefore, if the association constant for the hexamer could be increased, administered insulin might have a longer action time. Using computer graphics, it was shown mat Here is an empty area between adjacent dimers in He hexamer sure, and that a valine and a glutamic acid residue reside on opposing forces of this region Molecular orbital calculations suggested Hat changing the valine
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CURRENT RESEARCH AT S~CI.ED IN517TU7~5 43 to arginine, a basic amino acid, would allow formation of a But bridge and substantially ~ ease He association constant This change has now been achieved by site~imcted mutagenesis, and mass production in E. cold is under way. Another useful alteration, which has been achieved by chemical methods, is the deletion of phenylalanine residue B1. This produces an insulin which is still 100 percent biologically active but Lacks immunological reacting, an important step in Baaing diabetics Mat mount an immune response to ~niniste~ insulin. The same change is now being made by genetic engineering methods to allow large- .~le p~ucdon. Two organizational aspects of the insulin work are noteworthy. First, although He bunk of funding is from High Technology Program grants, it is clear that there is a major nona~lied component ~ this work and Cat the researchers' hearts are really in basic research. Second, the work has proceeded In close collaboration win groups at the Beijing Institute of Physics, the Shanghai Institute of Biochemistry, and Peking Universitr. Such collabaradve research, especially between CAS and non
44 BIOTEClINOLOGY IN CHINA The instate houses 60 scientists, including 13 senior researchers and 15 research associates. Although it does not have a formal PhD. program, Here are several doctoral students in Niu's laboratory. Several of Be institute's students and scientists have studied abroad, where Hey have shown themselves to good advantage. The institute is divided into five research groups that are working on 21 individual projects. Cement support from the High Technology Program, the Sevens 5-Year Plan, and NSFC is 1.8 million yuan per year, plus an undisclosed amount from CAS Specifically for Niu's laboratory. The institute occupies a unique position among China's biology research organizations. Under Niu's leadership, He institute obtained $650,000 from He Rockefeller Foundation, $550,000 from the United Nations Fund for Population Activities, and several million yuan from the Chinese government in order to build and equip its research facility. The institute's laboratories are the most modern, well equipped, and best maintained of those He authors visited in China. Clearly, Niu has been influential in the establishment of this institute, a role that is reflected in his position and the amount of funding the institute has been able amact However, the following overview of Niu's research casts doubt on the extent to which his enquiries can be counted as contributions to He international scientific community. The focus of N;u's beseech is on the role of RNA in biological systems and during development. In 1975, he claimed Hat the fungus Neurospora crassa could be stably, genetically transformed by RN\* This is a remarkable claim since it is universally believed that in Neurospora, as in all other organisms, it is DNA suer than RNA Hat serves as the genetic material. Moreover, despite intense world on the genetic transformation of Neurospora, this observation has never been reproduced in the published literature. Because transformation e~enments on Neurospora are easy to perform, it is likely Hat these experiments have in fact been repeated but without positive results. Niu has also claimed tam RNA can be stably inherited in higher organisms and can cause He derepression of normally silent genes. Far example, in 1977 he reported that mouse uterus injected with RNA fin ms or chicken synthesized bow mouse and tile donor species albumin} in uterine epi~elial cells, suggesting that the mouse genes were depressed by He heterologous RNA. However, it is difficult to interpret these embedments because He memos used to detect albumin synthesis was not sufficiently documented. Moreover, similar experiments using cloned, purified genes and well established gene transfer methods have failed to reveal any derepression of the endogenous genes. Starting in 1981, Niu described experunents in which goldfish developing from eggs microinjected with rabbit globin mRNA were purported to express rabbit globin, as determined by an immunological assay. The results were again ~M;sh~a. N.C, ~~ M.C, ~ Tom, Em, Prwee~gs of the Nmio - Art Escapes USA (1975): 642 645.
CURR~ITRESEARCH AT SELECTED INST171~1= 45 ambiguous because tile globin was not punfied or adequately charactenzed. Subsequently, successful gene transfer has been reported in fish, but these experiments all used DNA rather than RNA as He nucleic avid and purified genes Other than a crude mixture of species. Judging from Be rate of transformation win purified genes, it is difficult to believe He results claimed by Niu using total, unhactionated RNA containing thousands of different messages. The most spectacular of Niu's claims is He ability of RNA to redirect the formation of whole organs in intact animals. Specifically, he claims to have cream golds at have balancer appendages or tail shapes derived from newts orchid, and that these new traits can be inhen~. Such fish, if Hey existed, would be of intense interest to many biologists. However, when the authors asked to see these animals, Niu claimed Bat they are all kept at another location even Cough Be Institute of Developmental Biology has extensive fit raising facilities on its own campus. If and when these fish are made available to over investigators, it should be straightforward to- check Rem for the presence of newt or carp genetic information using modern methods. Only when these tests have been conducted will it be possible to determine whether He fish represent a real phenomenon. Appendix D, provided by Eric Davidson, provides a further analysis of the experimental and ~eoredcal problems raised by Niu's work. She laboratory of Yan Shaoyi, Director of the Institute of Developmental Biology, studies nuclear-cytoplasmic interactions in fish As group has shown that it is possible to recover fertile adult fish from enuclea~ eggs injected with He diploid nucleus from early embryonic cells. In agreement with work by other labcmones on amphibians, they observe that He ability to recover viable progeny declines with the developmental stage of the donor cells. They have also made hybrids between different species of fish and claim that it is possible to obtain viable progeny from crosses between different genera and some different subfamilies, but not between different families. While most of the hybrid progeny appear to be identical to the nucleus donor species, they also make the surprising claim Tut some offspring display morphological Gaits similar to those of the recipient species or intermediate between those of the donor and recipient. Even more remarkably, they claim that the recipient traits can be passed on to offspring and that the pension of the recipient characteristics can be increased by serial transplantations. One ex~nple, which has been reported widely in the Chinese press, is the cross between nuclei of the common carp Cypnnus carpio L. and enucleated eggs of the cn~cian carp Carasszas auratus L. It is claimed that this hybrid has a higher grown rate, higher protein content, and lower fat content than the common carp and that it can be bred stably. Yan attempts ~ explain these results by a theory in which `'silent genes" in the donor nucleus undergo activation and rearrangement under the influence of the recipient cytoplasm. However, a major flaw of these experiments is the lack of distinct markers for the donor nucleus. Without such makers, Were is no way ~ be sure whether the "hybrid" Blsh He really derived from the nucleus of the donor or from residual material of
46 BIOTECHNOLOGYIN CHINA He recipient There are some simple biochemical and molecular biologic Averments Mat could clearly resolve this question, but Yan shows no inclination to perfonn these analyses. Another serious flaw is Be lack of quantitative analysis and controls to show that these fish Me not simply mutants induced by Me various experimental manipulations. Until these controls are performed, Yan's results must be viewed with skepticism. Xiso Shuxi studies DNA polymerase in Erlich ascites cells. She claims to have discovered a new polymerase win a different pH optimum and size than any of He polymerases in no`~'a1 cells and hopes to use it as a marker for cancer cells. However, the experiments are impossible to interpret because of a complete Lack of controls. Moreover, since the Erlich cell polymerase has not acmady been purified, He idea of malting diagnostic reagents is premature. The laboratory of Lu Deyu works on He genetic manipulation of mammalian embryos. They have spent several years developing an electroporation method to perform nuclear uansplantabon in rabbits. The idea is to test Niu's cytoplasmic activation of He nucleus theory in a mammal, but so fa} no progeny animals have been recovered. They are also working on He production of ~nsgenic farm animals by He more conventional ONA injection method and claim to have obtained one cow which expresses BsAg. Visits to the laboramnes of two associate professors, Wu Naihu and Wu Zhengan, demonstrated that the Institute of Developmental Biology does conduct some research at an international level. Wu Naihu studies the rice chloroplast genome. He is continuing his work, stared In Ray Wu's laboratory in the United States, on He structure and regulated expression of various chloroplast genes such as psbA and psbB. He has also made the interesting obsenadon Mat in certain crosses between different rice species, tile Fat plants display a new chloroplast DNA restriction band. As is quite surprising, since He chloropLdst genome is known ~ be maternally indented. Wu Zhengan studies highly repeated DNA sequences in amphibians and mammals. He has made He interesting observation Hat an extra C band in one chromosome of a Chinese ground squirrel is due to the transposition of a satellite DNA. He is also studying a senes of satellite DNAs from Chinese newts and has shown that one form is specific to Asian species. Wu's work demonstrates the use of modem molecular }piques to study the basic biology of uniquely Chinese species. He was proud ~ note Hat his recent work, which has been published in an international journal, was conducted exclusively in China ~ summary, the quality of He research conduced at He Beijing Institute of Developmental Biology is highly variable. The work in several of the Ldboratones, particularly that of Niu, is so poorly controlled and documented ~ the results will continue to be questioned in China and abroad. Continued support for such research will not advance developmental biology in C hina, sets a poor example for over Chinese scientists, and casts doubts on the efficacy of peer review
CURR~JT RESEARCH AT SEED INSTIIITIZS 47 pies. On the other hand, He institute does have some laboratories, such as those of Wu Naihu and Wu Zhengan, that are performing creditable research on worthwhile topics. Given China's general weakness in developmental biology (see Chapter 6), it is urgent that this institute focus its considerable resources on supporting Be best possible research. Institute of Genetics (CAS) The Bering Instate of Genetics employs 470 workers, including 80 senior scientists, 180 middle-level scientists, and 40 gra~iuate student. There are 40 research groups working in Be areas of molecular genetics, gene and chromosome en~eenng, plant breeding and tissue culture, animal developmental genetics, and human and medical genetics. Approximately 70 percent of Be research is on plants. Funding is obtained Trough CAS, NSFC, the Sevens 5-Year Plan, the National Key PmjectProg~, and He High Technology Program. Approximately half the research is classified as basic, half as applied Located in the new Datun Road complex, it maintains an experimental farm and animal facility, as well as a laboratory building. Plant regeneration is a key research area and a point of pride for the Beijing Astute of Genetics. Ouyang Junwen's laboratory was the first to achieve anther culture of wheat and has continued to work on this project for He past 10 years. By systematically varying the medium and temperatures used for anther cultivation and callus induction, they have achieved up to 10 percent plant propagation efficiencies. Hey have also shown that the efficiency of callus formation and the percentage of albino plantlets, a serious problem in anther culture, are both complex multigenic traits. A focus of current research is the use of anther culture to obtain mutant plants resistant to diseases, such as Be wheat scab fungus, Fusarium species, or to herbicides such as alkaline. Two sca~resis~nt lines have been isolated End are currently being field Used. Attempts are also in progress to obtain wheat with a high lysine content, by selection with a lysine analog, but the investigator did not seem convinced of Be physiological soundness of As approach. The laboratory is also beginning gene transfer attempt, using marker genes such as kanamycin resistance, but Here was no clear focus on what useful genes might be employed in the future. ~ testimony to He somewhat unique position of this laboratory in the anther culture field, Monsanto Company has contracted win Ouyang to cull and provide seeds from their germplasm. The laboratory is supposed by 140,000 yuan for 5 years from the Seventh 5-Year Plan and High Technology Program grants and $60,000 from Monsanto. Li Xianghu's laboratory concentrates on the culturing, fusion, and DNA uansfonnation of plant protoplasts. Over He past 10 years, this group has successfully regenerated plants from nce, tobacco, pemn=, and others and has had initially encouraging results with wheats Species so far resistant to this technique. They recendy made front-page headlines in the Chinese press by
48 BIOTECHNOLOGYIN ClIINA bansfemng an a-ineerferon gene into tobacco. The uansgenic plants produce low levels of interferon (1~000 wets per gram of leaf dssue) And are currently being ~ for resistance to TMV. Curiously, Li's group has not done the control e~erunent of Mining whether direct interferon treatment protects against this virus. Zhen Zhu, who recently obtained his Ph.D. Tom We University of Tennessee and who holds a Rockefeller Foundation fellowship to return to He United States for 3 months each year, is studying the more basic problem of Be relationship between methyL~tion and gene expression in plants. Another very interesting basic project is an attempt to create new plant species by protoplast fission. This group is handsomely supported by 700,000 yuan for S years from He High Technology Program and He Sevens S-Year Plan. Li Liangcai's group Ho works on DNA transformation of plants using a two- step protoplast preparation met worked out in his laboratory. They have bansfer~d two marker genes' those for kanamycin Vance and §-glucuronidase, in both stable and transient ~nsfecdon systems. The main emphasis Is on methodology lamer than potential applications. The laboratory is supported by 150,000 yuan for 5 years from He Seventh S-Year Plan and High Technology Program and by $15,000 from He Rockefeller Foundation. From the above review, it is clear Rat He Beijing Instate of Genetics conducts research in several areas of modern biotechnology and gene manipulation. Therefore, it was surprising to note that few if any~f the senior scientists have a background in classical genetics, and Rat the institute does little research in the traditional areas Hat provide the foundation for modem molecular biology. Institute of Microbiology (CAS) The Beijing Institute of Microbiology houses S8O workers, including 236 middle- and senior-level scientists and 20 Ph.D. students. There are eight divisions: mycology, bactenology, Urology, genetics, physiology, ecology, natural resources, and a fermentation facility. The institute is supped by 6 million yuan per year, of which 60 percent is derived from various project grants. The mycology and bacteriology divisions, which are concerned mostly with systematics, have recently been designate as a national key laboratory with two postdoctoral positions. Plant virology is a highlight of the inshtute's biotechnology research. Tien Po's labor studies CMV, which infects several important crops such as tomatoes, green peppers, and tobacco. Dunng propagation, small satellite RNAs that depend on He main genome for their replicative functions occasionally occur. Tien's laboratory and over laboratories showed that these satellite RNAs can interfere win the replication and disease~allsing properties of superinfecting viruses. Therefore, they prepared a miscue of CMV and excess satellite particles and showed, in greenhouse experiments, that it protected plants against CMV superinfection. This "plant vaccine" can be administered either by individual inoculation of plants or, in more recent experiments, by a convenient Spray gun
CURR=TR1ESEARCH ATSF~CTED INST7TU~ 49 technique. Subsequently, large amounts of He material have been prepared in the he's fermentation facility and have been used on tomato and hen pepper plants in several paws of China Tien claims that infections, in some cases, have been cut by 50 percent and yields increased by 30 percent. Current research focuses on incorpofa~ng he interfering gene sequence into the tobacco genome to provide permanent protection. Mung Keqiang, together ui~ young colleagues Qing Xiaofong and Yang Maozbou, work on TMV, a close relative of CMV that also infects tomatoes and tobacco. Building on world performed in the United States, hey are a~empdng to prevent TMV infection by persistent expression of the coat protein of he virus in Dansgenic plants. She idea is that the coat protein, which nonnally forms he viral envelope, will bind to cell surface receptors and therefore compete with virus particles for a binding site. This group cloned a Chinese stun of TMV, showed Bat it has a sequence very similar to Cat of a previously characterized American swain, and introduced the coat protein gene into tobacco by Ti plasmid transformation. The resulting uansgenic plants express coat protein, and although Ploy are still susceptible to TMV infection, he symptoms He delayed by 1 to 2 months under field conditions. Mang's Ebony has also canned out comparative studies of various isolates of CMV, TMV, barley stripe mosaic vines, wheat mosaic virus, cereal mosaic virus, and a gladiolus virus by using DNA sequencing, RNA sequencing, and antibody techniques. The Beijing Institute of Microbiology also has a long history in industrial fermentation. Between 1972 and 197S, they developed a simple two-step fennent~on technique for the production of vitamin C' and in 1985, this process was sold to Hoffmann-La Roche, Incorporate They are currently working on the production of endue inhibitors to increase the efficiency of various p-lactam antibiotics against resistant stems of bacteria, and on a kit for blood cholesterol analysis by using two enzymes produced by fermentation. Over fermentation studies involve protoplast fusion of useful penicillin producers and characterization of a new ~ in Aspergillus niger. Institute of Virology (CAPM) The Institute of Virology, which is part of the Chinese Academy of Preventive Medicine (CAPM; previously Chinese Academy of Basic Medical Sciences), is the major research center for animal virology in China. Although a substantial proportion of He insti~te's research is in classical medical virology, there are four projects involving molecular biology: bio~ngineered vaccines; basic studies of vaccinia virus replication; production of interferon, interleukin-2, and other lymphokines; and protein engineering. This institute, with 12 High Technology Program grants and 18 Sevens 5-Year Plan grants, is one of the Ho most richly supported research institutes in China. They are currently erecting a national key laboratory funded by 5 million yuan from the State Planning Commission.
so BIO~IECHWOLOGY IN CHINA Although the physics facilities appear dilapidated and are located in a hatong, or alley, district far from other instates in Beijing, a relatively high proportion of scientists and students were seen to be actively performing experiments during several visits. Groups under He supervision of the insti~te's director Hou Yunde and former director Cod. Chu are involved in several biotechnology projects. One major area of interest is He use of vaccin~a vines as a vector for vaccine production. They have construct a new vector with two important differences hum the vectors used by Bernard Moss's laboratory in He Unit States. First, Hey use the hemagglutinin gene miner Han the ~ymidine Gnaw gene as on insertion site because hemagglutinin mutants can be grown on normal cell lines, whereas the ~ymidine kind mutants must be propagated on a special cell line. Moreover, He virus yield is higher. Second, the Chinese vector is based on He Than Tan swain, which has been widely used for smallpox vacciNabon in China The construction of the new vector required a substantial amount of basic research on vaccinia virus gene expression, including the sequencing of 30,000 base pairs of He vacant virus genome. An unexpected result of this research was He discovery Hat He vaccine virus hemaggluhnin gene is a member of the immunoglobulin gene superfamily. Their results suggest that hemagglutinin binds to lymphocytes in a manner analogous ~ Hat of the CD2 surface protein with T lymphocytes. Much of He basic research has been published in Westem journals. Development of a vaccine agony HBV is another priority of the institute. Closely following work in He West, institute scientists cloned and sequenced the surface antigen gene of a Chinese REV swain, inserted it into a DH~ vector, and introduced it into CHO cells. After amplification by me~o~exate selection, the cells were found to secrete 5 to 7.5 mgl of HBsAg per liter that was appropriately glycosylated and assembled into subviral particles. It is possible to culture the cells, and collect Be media every 2 days, for up to 120 days. In animal tests and phase one human clinical Dials, He genetically engineered vaccine is four tones more potent as an antigen Han is the current human plasma vaccine. The vaccine, which meets World Heals Organization standards, is currently produced and purified in a small laboratory at the institute. The production process is similar to one developed by Genentech in He United Sums. Production and genetic engineering of interferon is a long-standing project. Using standard E. cold methods, they have produced interferon which appears to be clinically useful against chronic cervical condylomas caused by human papillomav~ruses. They have also produced hybrids between interferon and tumor necrosis factor, which they hope will target the interferon to tumor cells, and between interferon and He pre-S region of ~sAg, which they hope will direct it to liver cells. These experiments also address He basic question of which par s of He interferon molecule are responsible for its antiviral activity. The Institute of Virology's work on viral replication is one of Cbina's few examples of basic research that has garnered notice internationally. At the same
CURRENT RESEARCH ATSF~1~;o INSTmTlES 57 postdoctoral scholar, will be He use of the naturally high secretor swain Kluyverorr~ces lacks. Zheng Zhao~cin and associates work on genetic engineering in bacteria. They He particularly interested in He use of Corynebactenum gluta~ucum, an organism that is widely used for amino acid production and Hat possesses several advantages over E. cold for fermentation purposes' i.e., fast growth, safety, lack of proteases, and good secretion. They have constructed a Corynebactenum vector and established a t~ansfor~on system; attempts to ferment a useful product are now in progress. This work is sufficiently novel to have attracted the attention of several European groups. A second project is to produce He c~citonin gene- related peptide hormone which, in a collaboration win Peking Medical University, has been shown to reduce blood pressure within 90 minutes of administration. A major new effort revolves around Schistosoma japonicum, a liver parasite that is carried by rice paddy Nils and affects Free million people in China Following Australian scientists' wow on He Filipino parasite swain, two major antigen genes have been cloned and charac~ize~i Overproduction of these proteins, and of co~~ponding monoclonal antibodies, should allow development of a reliable diagnosis method. Institute of Biochemistry (CAS) The Shanghai Institute of Biochemistry, established in 195B, is one of China~s best known research centers. It was one of the only research institutes to remain active throughout He Cul~1 Revolution, during which important work on the synthesis of insulin and alanine GINA was performed, and in the past 20 years, it has been at the forefront of bringing molecular biology to China The recent history of the institute provides insight into the effects of China's new scientific policies on how research is conducted and sub at a major center. ~ 1984, CAS provided for all research costs, whereas now it is responsible for only about 10 percent. At Fat time, He institute was organized into several large divisions, each win about 40 people, and the pathway for founding was from institute director to division head to individual researcher. Now the institute has been reorganized into 37 much smaller groups, each responsible for obtaining its own funding. While the new system allows greater autonomy for individual scientists, it lacks the cohesiveness that made major projects such as the synthesis of insulin possible. Previously, the institute took gem pride in its emphasis on basic research, but because of the new funding pnonties, this stance has been abandoned. The decentali=don and diversification of the instituters administration is evidenced by the opting, in 198S, of the Shanghai Molecular Biology Laboratory as a center for science Paining and international cooperation. Although this laboratory has its own director and publishes its own annual report, it is housed in
58 BlOTECHNOL4GYIN CHINA the same building as the Shanghai Ibstitute of Biochemistry and numbers among its member Lin Qishui, director of the institute. Plans are also afloat for two new national laboratories focusing on eukaryoiic gene region and neuropeptides. One clear benefit of the new policies is increased attention to international c~ation. In 19~7, the institute hosted over 300 foreign scientists and conduct numerous symposia, workshops, and minicourses (including two organized jointly by CSCPRC and CAS). The institute has a staff of 646, including 396 research and technical workers. It is lmamd in tile CAS Yueyang Road complex, in Be old French quarter, adjacent to the Shanghai Estates of Cell Biology' Physiology, and Materia Medical Oratories are local in a large, old, but well equipped main building arx1 a new wing devoted to molecular genetics. The group of Li Zaiping, who is well known in tile West for his pioncenng work on bnn~g molecular biology to China and promoting international cooperation, works on various basic and practical Acts of eukaTyotic gene regulation and ~anseripbon. They have isolated and sequenced the 5.8S nbosomal RNA gene of the silks, Altacus Scud, and shown Cat the chromosomal copy contains a DNase-hypersensitive site under active transcription conditions. Interestingly, this site corresponds to a nuclease S,-sensitive site in the cloned, supercoiled DNA, perhaps indicating an underlying irregularity in the structure of the DNA. More recently, Li and colleagues have been studying the transcription of the BV genome. They are using antisense RNA and antibodies to determine whether He "X-gene" id an autoregulator and are also searching for trans-acting factors encoded by the nuclear genome. A more applied project relating to BV is Be construction of vaccinia virus recombinants to be used as vaccines. This is similar to wow in Be United States and at the CAPM Institute of Virology. A vaccinia virus recombinant expressing BsAg has been constructed and turned over to the Beijing Institute of Biological Products for ~ale-up. Recombinants expressing the preps and pre-S2 antigens, which contain binding sites for serum albumin, have also been constructed and will be compared with the shorter S- antigen for effectiveness. Yeast and E. cold have been used to express S- and X- fi~sion proteins as potential immunological screening reagents. In addition, fusion genes between Be surface antigens of hepatitis B vims and hepatitis A virus are being constructed with Be idea of making a multivalent hepadds vaccine. [i's Coup is also pursuing several cancer-related projects. Several tumor growth factm fusion pervades have been expressed and shown, in agreement we; results from Be United Suates, to have inch antiviral activity. In collaboration win Japanese scientists, a study of andoncogenes has been initiated. Several different classes of those genes, each capable of suppressing transformation by a different set of oncogenes, have been cloned. The demiled characterization of these genes could yield important insights into the biochemical pathways of neoplastic transformation.
CURRENTRESEARCH AT SF7FiCIED INSIIT1~17IS 59 One of He newer and most active sow members at the Shanghai Institute of Biochemistry is Hong Guafan, whose research focuses on the molecular biology of nitrogen fixation. Nodule formation is an essential prerequisite for symbiotic nitrogen Anion. In collabaradon win workers at the John Ones Smite in England, Hong has identified a series of genes expressed by Rhizabium legununosarum in As. One of these, He nods gene, was sequenced and expressed in E. coli, =d it was shown Hat As protein specifically binds to the nod cluster in~genic region. While the initial phases of this wow were done in England, students In Hong's lab in Shanghai are now actively pursuing the question of how chin organic compounds switch nods from a repressor ~ an activator. In research initiated in Shanghai, Hong's group has also started to characterize the Owl genes of fast-growing Rhizobium shins isolated from nearby fields. Following ~ on work sad in Fred Sanger's laboratory at the Medical Research Council in Cambridge, England, Hong has also continued to improve DNA-sequencing methods by He use of a heat-stable DNA polymerase which can read Trough hairpin structures in the DNA at high temperatures. Several U.S. biotechnology reagent companies have expressed interest in this method. ~ order to entice Hong to reman to Shanghai, CAS offered several incentives: a full professorship, an independent research group, a good-sized laboratory, research support, and He oppo~ni~ ~ go abroad annually ~ perform collaborative research. These were wise invesunents because Hong's group is certainly one of the strongest in China Regular collaboration with Western scientists has been especially important, particularly during the early years when Hong was still seeing ~ his laboratory and training students. Now workers in this laboratory have the opportunity, rare in China, to do original research on a current topic Aver Can simply repeat experiments done in the West In a sense, the John Innes Institute provided He critical mass to establish an active research group in China. Structme-function relationships of insulin have been a major focus of the Shanghai Astute of Biochemistry since 1965. Using modified synthetic methods, several denvadves of insulin have been prepared and evaluated for biological activity and receptor binding. The results show Hat Phe26 plays a critical role in He structure of He hormone. The insulin A-chain has been expressed in E. cots, and several site directed mutants are being worked up. In addition, venous short peptide segments of insulin have been chemically synthesized and then tested for biological activities or Be ability to compete for insulin inhibitors (i.e., inhibitor- binding sites). The conformation of these fragments has been probed by nuclear magnetic resonance methods, including nuclear Overhauser effect, with spin- lattice relaxation time measurements. Many of the insulin experiments at the Shanghai mistime of Biochemistry overlap with those at Be Beijing Smite of Biophysics; perhaps more rapid progress could be made by combining the Shanghai inserters expertise in synthesis and nuclear magnetic resonance methods with the Beijing institute's expertise in crystallography.
60 BIOTECHNOLOGY IN CHINA Institute of Cell Biology (CAS) The Shanghai Institute of Cell Biology, founded in 1950 as the Institute of Expenmenm1 Biology, employs 370 personnel, including 50 senior researchers, 60 research associate, and 50 senior technicians. The institute comes out biotechnology research in several areas such as chromosome and chromatin biology, production of immunotoxins, and vaccine development using transgenic tunings. This institute was one of the first to develop monoclonal andbody technology in China, and many of the basic and applied research projects use this misology. The institute is also responsible for maintaining China's mammalian cell line bank The chromosome biology grow, in collaboration with colleagues at Be Beijing Institute of Biophysics, is attempting to develop chromosome-like vectors for plants, especially rice. Using a novel andbody approach, they are trying to clone chromosomal DNA fragments containing centromere and telomere sequences. Few, Fey prepared a panel of monoclonal antibodies directed against nuclear structures. Second, Hey determined the specificity of Be antibodies by imm~mostaining nuclei; Hey also tested He function of these structures by inhibition studies. Lastly, in Heir current work, they by to pull out specific DNA figments associated with these antigens. While the ultimate aim of He world is applied, it also involves a healthy dose of basic research on the structure and function of important chromosome components. A group under the leadership of L.C. Sze Is attempting ~ use whole animals as bioreactors to produce valuable proteins such as BsAg~ In collaboration with Jiangsu Province Agricultural College, they injected a metallothionein-HBsAg hybrid gene into rabbit embryos and obtained 20 percent transgenic animals of which 10 percent produced debatable surface antigen in the blood. This work, support by 1 million yuan Tom the High Technology Program and 1 million yuan from He Seventh 5-Year Plan, is being turned over to a biological products institute for further development. Consistent with the instituters traditional emphasis on immunology, several groups are using anomies to defect end eventually fight cancer. An immunological kit for detecting a-fetoprotein, an early indicator for liver cancer, has been developed and marketed. Several monoclonal antibodies against hepatoma cell surface antigens have been isolated, and antlbody-ncin immunotoxins have been produced in collaboration with the Shanghai Institute of Biochemistry. While these appear somewhat specific in vitro, their potential applications in viva will require much funkier testing. Several members of He Shanghai Institute of Cell Biology attended He joint CSCPRC~AS minicourse on immunotoxins in 1988, which, hopefully, will help Hem to design the appropriate experiments. Institute of Materia Medica (CAS) The Shanghai Institute of Materia Medica, founded in 1932, searches for new, physiologically active compounds and studies Heir struc~re-function relationships.
CENT RESEARCH AT SEl~CIED INSITlU7ES 61 The institute has over 44)0 smut, including 64 at senior levels. While members of We institute's staff are best known for their research on traditional Chinese medicines, Hey have recently begun to use He techniques of genetic engineering and molecular biology to produce and characterize new drugs. Antibiotic production and improvement is Be main focus of a group led by Yang Shenti. They cloned, and overproduced in E. coli, penicillin G-acylase for use in the semisyn~etic production of penicillin. The immobilized enzyme is now used commercially by several pharmaceutical companies in China Attempts to improve the enzyme by genetic engineering are under way, but in the absence of basic information about He structure of He enzyme, it is unclear what residues to change. This group Ms also developed a microbial technique for producing threonine, a precursor for synthesis of He moxalac~n series of antibiotics. In related research, this group is carrying out structural Abominations on certain p- lac~na" inhibitors which could potentially allow the use of penicillin and other -lactams against nonnally resistant bacteria A second project combing classical and modern approaches is a search for new neuropeptides mom such sources as amphibian sldn and gut, human brain, and certain tumor cells. Several new peptides have been isolated, sequenced, synthesized, and tested for biological activities, including analgesic effects. Attempts to produce some of these pepudes by genetic engineering are just . · — negmmng. Several projects at He Shanghai Institute of M6terua Medica concern the mechanism of action of anticancer drugs denved from Chinese medicinal herbs such as Camptotheca acu7runata, a traditional Chinese treatment for leukemia. It was found Hat hydroxycamptothecin, the active ingredient, inhibits the expression of the ras and arc oncogenes while having little effect on fos or erb oncogenes. However, it is far from clear that the effect is either specific or the primary mode of action. The institute also produces the active components of several potential anticancer drugs by various methods including plant tissue culture; some of these are being tested in clinical trials in the United States in collaboration with the National Cancer Institute. Eventually, it is hoped that mutant cell lines Hat Overproduce these drugs will be isolate Institute of Plant Physiology (CAS) The Shanghai Institute of Plant Physiology is one of the best known institutes in CAS and }has made many significant con~ibudons in the field of plant physiology. Therefore, it was selected to house one of among a few plant molecular biology key laboratones. Designated as the Plant Biotechnology Laboratory, it was established in 1986 and occupies 2,500 square meters of space in the inshtute's new building. The Plant Biotechnology Laboratory was planned to have the capacity to house 60 scientists: 20 from Shanghai and the rest from elsewhere around the nation. Currently, Here are several research groups, although the number can vary as He number and interests of visiting scientists fluctuate. The disease resistance and genetic engineering group, like over groups working
62 BIOTECHNOLOGY IN CHINA on genetic engineering for plant disease resistance, focuses on plant viruses. However, this group is attempting to use a different coat protein gene from TMV alla different experimental strategy than the other groups. The results are not yet available for evaluation. However, they anticipate Hat deletion of the bases coding for polymerase can suppress He synthesis of Be TMV coat protein subgenomic RNA. If this is successful, TMV infection can be prevented instead of delayed ~ addidon, this group also inidateda project toaaack diseases caused by fungi They plan to isolate He components from a rice cultivar sensitive Pyricularia oryzae. Cu~endy, Hey have molmed a protein Tom Gastrodia elata Cat may contribute to He resistance of such fungal disease. Ike leMer of this gropp is C. Wang, who joined He institute very recently. He has received substantial financial support, but He lack of mined and experienced workers is proving to be a major obstacle. The primary goal of the regulation of gene expression group, led by the well- known professor, ~M. Hong, is to study the orgar~ion, expression, and reguladon of the waxy gene from rice. In rice (Oryza saliva), Me waxy gene is loam on He number one chromosome. The starch granule-bound undine diphosphate-glucose starch ~ansferase is the catalyst for the synthesis of a- arnylase in the pollen grain and endosperm. Since a-arnylase is synthesized only in these tissues, He expression of He waxy gene is tissue and developmental stage specific. Therefore, this group is working on the cloning, isolation, and sequence of this gene. It is intended to study the coding as well as the regulatory regions of this gene. It is hoped that the cis-acting elements as well as He trans-acting factors can be identified. This is a very important step in He attempt to improve He quality of nce. At the same time, this group is also interested in studying the cause of differences in a-amylase content between Japonica and Indica stains of nce. This may be related to the regulation of expression of He waxy gene. Furthermore, He lack of a-arnylase in some cultivars of rice may reflect the lack of expression of the waxy gene. This group has constructed four rice genomic libraries since 1987. Using the waxy gene probe provided by Nina Fedoroff at Johns Hopkins University, they have proceeded expeditiously in identifying the waxy genes. The cell and tissue culture group reflects the institute's uadidonal strength in this area Currently, there are four areas of investigation under He leadership of Cad Xu, He deputy director of the institute: 1. In vitro cloned propagation: Using in vitro ~hn~ques, Xu's group has regenerated over 70 plant species. Many of them are important crop sties including rice, wheat, maw, sorghum, soybean, cabbage, and rape. It should be noted Hat the orchid derived from He in vitro clonal method flowers in a few months compared with 5 years for orchids derived from stings. 2. Protoplastfusion and cell hybndizatzon: They have obtained over 10 plant
CURRENT RESEARCH AT SF~CTED INSTITUTE 63 species derived from fused pratoplasts. Among Hem are some important crop species such as rice, soybean, and tobacco. 3. Mutation induction: They have focused on the selection of mutants with a high concentration of essences amino acids Swim new sass resistances. Tobacco plants which can tolerate 2 percent sodium chloride and soybean cells resistant to glyphosate (~e active ingredient in Roundup, an herbicide made by Monsanto3 have been selected and regenerator into plants. 4. Cell tran~form~on: Using Ti plasmid and reporter genes, Hey have obtained a series of transformed plants, but no novel contnbunons are forthcoming. The cotton disease resistance group, which is led by G.Y. Zhou of to Shanghai Institute of Biochemistry, will be administratively, if not physically, transferred to be part of this open laboratory. For many years, Zhou's group has wowed on a technique for He introduction of foreign DNA from disea=-resistant cotton species into disease-sensi~ve corn species. They tom advantage of He pollen tube pathway and inject foreign DNA into the embryonic sac to transform the zygote. This approach has encounter technological difficulties as well as collegial cndcisms. In collaboration Ada He Jiangsu Province pastime of Industrial Crops, they have obtained some cotton hybrids expressing disease-resistant traits. In addition, Here is a group working on B. th~ngiensis toxin and a group working on storage proteins. GUANGZHOIJ Guangdong Agricultural Academy of Sciences In 1987, the Center for A~cultum1 Biotechnology was established in the Guangdong Agncul~al Academy of Sciences. It is mainly an oration Hat coordinates existing activities loosely related to the broad definition of biotechnology. Currendy, there are 54 staff members, 34 of whom are scientists at different levels; 1 senior, 6 associate, and 13 assistant staff scientists; and 14 technicians. According to their plan, the cent will have four divisions: gene, cell, enzyme, and fermentadon biotechnology. To do ~is, additional scientists have to be recnuted, which will not be easy. Most research activities at He present time are centered around tissue culture work for He purpose of propagation, e.g., banana and pineapple. SuIprisingly, great effort has been directed to He breeding of seedless watermelon, which was successfully achieved almost 30 years ago in Taiwan. Obviously, this center is in its infancy, and it will be a long time before it can move into molecular aspects of agricultural research. However, this center is an excellent resource for improving rice crops: they are studying a unique swain of
64 BIOTEGNNOLOGYIll CHINA black rice Hat is claimed to be more nutritious than the ordinary strain and to possess other values. South Chma Agricultural University Soup China Agncul~ral University attained its university stems in 1984. Currently, there are 10 academic deparunents including most of the classical agricultural disciplines such as agronomy, horticulture, animal husbandry, veterinary medicine, agricultural engineering, and forestry. Among the 820 faculty members, there are 240 professors and associate professors, 480 instructors, and 100 teaching assistants. The undergraduate population is 3,000. The university also offers graduate degrees at bow M.S. and Ph.D. levels in highly selected areas. In addition, there are 36 foreign students, mosey from over developing countries. The current a~ninis~on is interested in promoting and s~eng~ening research activities within He university. Under He present organization, there are 20 research units, one of which is genetic engineering. The others include crop genetics and postharvest physiology. 1 he university has a very large collection of germplasm, including over 7,000 cultivars of nce. Currently, there are six faculty members in the research unit of genetic engineering: two associate professors, one senior research staff, and three research associates who focus on two areas. In animal sciences, the emphasis is on growth hormone and antibacterial peptides. In the plant sciences, rice and rape diseases are the major interest. This unit is currently supported by grants from the Seventh S-Year Plan, NSFC, and donations from various sources in Hong Kong (~$500,000; HK$7.8 = USED. South China Institute of Botany (CAS) The South China Institute of Botany, established in 1929, was originally known as the Instate of Agnculture and Forestry and was affiliated win Sun Yatsen University. It was reorganized in 1954 and transferred to CAS, where it was expanded from one taxonomy department to include over botanical disciplines. Currendy, it has six departments and a botanic garden and is staffed with 568 workers at different levels. Among them are 334 scientists or technicians, 10 professors, 65 associate professors, 3 senior scientists, 10 senior engineers, and 25 M.S. graduate students. The six deparanents and Heir respective focuses are listed below: 1. Ta~conorrry: classification and phylogenetic studies of many plant families aided by chemotaxonomy, cytology, anatomy, and polynology are actively canned out 2. Phytomorphology: includes anatomical studies on weed structure, embryology, and pollen morphology.
CURR~JT RESEARCH ATSEl~:CTED INSTITUTES 65 3. Phytocherrustry: surveys the chemical compounds exacted from a large number of plants for useful or valuable substances such as the effective antimmor compounds H~ringtonine and Homer Tingtonine. 4. Ecology: mayor studies include ecosystem, pollution ecology, and He use of artificial plant association for He regeneration of Chinese plant species. 5. Phy iology: investigates stress adoption, seed end postharvest physiology, and tissue culture and protoplast fusion. 6. Genetics: He primary emphasis of this deparunent is on biotechnology to study heterasis and cytoplasmic male senility. This department invested heavily in rice breeding for high~uality, high-yield, and disease resistant crops. The insd~te's biotechnology prog~n is carried out at the interdeparunenm1 level. The scientists involved are primarily from Free mats: genetics, physiology, and botanic garden. This biotechnology group is moderately supported by grants Mom the High Technology Program, Seventh 5-Year Plan, and NSFC at about 21)QOOO yuan per year, plus $10~000 from the Rockefeller Foundation to support research on rice. Like so many over groups in China, they stared in He early 1960s with cell and tissue culture methods. In fact, most activities related to biotechnology am centered around the production of planters by tissue cultivars for commercial purposes. The micropropagation group is large and consists of over 40 people, including two professors and six associate professors. In the protopL~st fusion groups, they have produced eggplant and potato hybrids that had already been achieved in the West. Obviously, there is need for more molecular biologists in this program. One scientists Huang Yuwen, just returned from Broad She is in He process of seeing up a molecular biology laboratory to work on rice cytopLasmic male sterility. Bat progress is extremely slow, a frustration faced by almost everyone who returns from overseas. Zhongshan (Sun Yatsen) University Zhongshan University was established in 1952 by combining certain academic deparunents in basic and social sciences from two well-established universities Ming Nan and Sun Yatsen). Currently, it has over 30 academic departments and institutes, including basic science departments in biology, chemistry, physics, mathematics, computer sciences, electronics, mechanics, geography, and geology. We student population has just reached the 9,000 mark. In addition, there are over 100 graduate students, 10 percent of whom are Ph.D. students. lithe faculty- to student ratio at Zhongshan University is roughly 1:7; there are about 120 professors, 350 associate professors, 700 instructors, and 200 Thing assistants. 1h 1986, the Center for Biotechnology was established at Zhongshan University by organizing into a separate adminis~auve unit existing faculty members whose research interests were Plated to biotechnology. It was initially funded by 1.2 million yuan from SEDC and 200,000 yuan from Guangdong Province. She
66 BIOTECHNOLOGY IN CHINA director of He center is Li Baojian, a plant molecular biologist who has recently Hurtled Tom Cornell Universitr. The plant genetic engineering group is the largest in He center. I.here are Ho professors, seven associate professors, five instructors, and 24 research associates at He M.S. level being supported by 120,000 yuan Tom the High Technology Program and He Sevens 5-Year Plan. Since this group has been actively working on rice, a $30,000 grant hum He Rockefeller Foundation has proved to be extremely helpful. The research subjects of this group are rather diffuse and include gene ~al3sfo~Tnation, cell fusion, artificial seed, and micropropaga£ion. Formation of a highly focused program should be He top pnonW. One area of considerable interest is Ale attempt to locate and to clone the gene Cat is believed to play an unpor~nt role in the wide compatibility of rice cul~vars. It was good news to learn that Hey were successful in developing artificial seeds, but disappointing to learn dial Hey failed to keep them. Another nomble group In the cent is Be microbial genetic engineering section. It is staffed by two full professors, Free instructors' three research associates, and seven graduals students. This grouses support is primarily provided by He Seventh 5-Year Pow, NSFC, and Guangdong Province at 120,000 yuan annually. Its main focus is on the cons~ucuon of vectors from Bacillus species, cloning of industrially useful genes, and Be isolation of heavy metal resistance plasmids. One unique project, which is jUSt under way, deserves special mention. They have isolated a plasmid from bacteria found In He gut of an insect that grows on rice. This plasmid may }Eve He potential ~ be used as a biological control agent because it kills some pathogens when it is transferred into E. coli. This center is a very well-coordinated, multidisciplinary organization that includes biologists, chemists, physicists, and engineers. The petrochemical engineering group is very active, and they apse immobilized enzymes for scaled up production. This is a new and energetic group Eat has the potential to advance rapidly. TIANJ~N Nankai University Nankal University, located in the major port city of Tianjin, is one of China's national key universities. Biotechnology research is earned out in the Department of Biology and Be Institute of Molecular Biology. The Deparunent of Biology, founded in 1971, is staffed by 170 people, including nine full professors and 42 associate professors. There are 450 undergraduate students, 66 M.S. candidates and four Ph.D. students. Total research funding is approximately 550,000 yuan per year, mostly Tom Seventh 5-Year Plan grants. SEDC pays staff salaries and 20,000 yuan for each Phi. student's research costs but provides no direct research grants. The DeF~runent of Biology is divided into seven groups focusing
CURR~TRE:~;EARCH AT SF' F3C7ED INSTIIU~IES 67 on molecular biology, biochemistry, microbiology, genetics, enzymology, plant physiology, and marine biology. The department publishes approximately 30 articles a year, all in Chinese. The university's l~itute of Molecular Biology was founded in 1983 ~ provide a cuter for advanced biotechnology research at Nankai. There are 50 staff members, including nine full professors, eagerer wig 75 M.S. students and 21 PAD. students. Me instate is supported by 400,000 yuan per year Mom thme High Technology Program grants, nine Sevens S-Year Plan grants, and several awards from industry and from Tianjin City. Fifteen of the institute's Ph.D. Tamales have been sent abroad for posaloct~ Gaining, and all of Gem apparently have reamed The institute is housed in its own well equipped 4,500-square- meter building. Much of ~e biotechnology research focuses on microbiology win potential industrial and a~cult~al applications. A gene for heat-stable a-amylase has been cloned from a ~ermophilic bacterium. A naph~alene~eg~ing plasmid Tom Pseudomonas aerug~sa has been transferee to E. colt. Toxins from Bacillus sphericus (s~i6~c for mosquitoes) Id B. th~uingiensis (specific for cabbage worms) have been characterized, and attempts at gene cloning and transfer are under way. While lacking Be vitalizer of Beijing or Fudan Universities, it is skill regarded as one of Cl~ina's best educational institutions and attracts topnotch students. (It has also built a strong repumion in mathematical sciences, largely Trough the efforts of Me famous Chinese-Amencan ma~emadcian, S.S. Chern.) The fact Rat biological research has gone from essentially no s~port ~ nearly 1 million yuan per year, all within 5 years, speaks to He influence of the new granting policies throughout China's educational system. However, judging from the sever projects reviewed during a brief visit, it does not appear Hat competition for this funding has lent any special urgency or in~ren~veness to He research process itself.
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