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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
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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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Representative terms from entire chapter:
million yuan
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.
