40% of the investment in American biological science projects involves experimental animals; 60% of biological research projects need experimental animals. The US Department of Health spends $400 million annually to train 65.438 million people and support 20,000 projects. Of these two tasks, 50% can only be accomplished with experimental animals. The Cancer Research Center of the U.S. Department of Health spends 220 million yuan on research every year, and the research projects that need to use experimental animals account for 654.38+0.4 billion dollars, accounting for more than 63% of the total funds. There are more than 30 specialized animal companies that produce experiments, including 250 kinds of mice, 30 kinds of guinea pigs, 30 kinds of hamsters, 60 kinds of rats, 0/4 kinds of rabbits, 50 kinds of monkeys, dogs, cats and birds. The United States 198 1 year used 80 million mice of various strains; There are 70 million mice, 600,000-700,000 guinea pigs, 600,000-700,000 rabbits and 34,000 non-human primates. According to the number of relevant scientists in the United States, the average usage per person per year is not less than 1000. There are more than 50 senior laboratory animal experts and more than 6,000 intermediate laboratory animal science experts in the United States. They not only produce general experimental animals, but also mass-produce special animals such as SPF, GF and GN. The annual output reaches several million heads, which not only meets the needs of various research, but also meets the annual output needs of nearly ten thousand kinds of chemical drugs. A series of advanced achievements have been made in cardiovascular, endocrine, organ transplantation, tumor, senile diseases and immunity.
Experimental animal science has also been greatly developed in Japan. From 195 1, the modernization movement of experimental animals began, which experienced the enlightenment period of 1953- 1958, the popularization period of scientific modernization of experimental animals and the modernization development period of scientific industry of experimental animals. At present, Japan has international advantages in the facilities and technology of experimental animals. Inbred animals, sterile animals, learned animals and animals without special pathogens have been socialized and commercialized. The number of mice used each year is120,000, including 4 million SPF mice and 3.6 million rats, of which SPF accounts for half.
In these economically developed countries, there are not only a series of scientific organizations of experimental animals, but also clear division of labor and regulations in the research, production, application and development of experimental animals, as well as related facilities, buildings, cages, feeds, bedding and various instruments, until personnel training, degree evaluation, assessment and promotion. At the same time, there are laws and regulations on the work of experimental animals approved by experts and Congress. This relatively complete scientific management system ensures and promotes the rapid development of experimental animal science.
The first edition of the Regulations on the Administration of Laboratory Animals in the United States was passed by Congress after 1966. With the continuous enrichment of the management and application knowledge of experimental animals, it has been revised four times. Its main contents are: not abusing animals, ensuring the quality of experimental animals, ensuring all the conditions needed for the growth and development of experimental animals, and clearly stipulating the disease treatment of experimental animals, the surrounding environment and the quality of staff. Animals that fail to meet the specified requirements are not allowed to be kept, and the experiments done are not recognized. Therefore, after the promulgation of the regulations, almost all experimental animal production companies, scientific research units, pharmaceutical factories and related laboratories in colleges and universities have been rebuilt or renovated. The Ministry of Agriculture will check the implementation of the regulations every two months, and units that do not meet the regulations have the right to impose sanctions. Those who do not meet the requirements will be fined 65,438 yuan+0,000 yuan per day. If it fails to change within the time limit, the research funding shall be revoked or ordered to suspend business. The technical requirements of the Regulations are also very specific. For example, the safety test of chemicals, food additives and some cosmetics must be carried out with two or more animal experiments. One is large animals, such as monkeys or domestic dogs, and the other is small animals, such as rats and mice. Before putting new products on the market, it is necessary to report the strain quality of the animals used and the test results done in two or three years to the US Food and Drug Administration for approval. This not only ensures the quality of new products in laws and regulations, but also promotes the continuous development of this discipline.
In these economically developed countries, there are also independent research institutions dedicated to the development of experimental animal science and the improvement of animal quality. In many comprehensive universities, medical colleges, veterinary colleges, research institutes and many units engaged in animal experimental research, there are experimental animal centers with considerable scale, high level and modern facilities and environmental conditions. There are all kinds of experimental animals and scientific research work on animal experiments. According to different research needs and genetic engineering principles, they cultivated 2607 kinds of experimental animals. Among them, there are 772 species (540 species of mice) of various animal inbred lines; Some inbred lines 132 species (46 species in mice); 79 species of random inbred lines (45 species of mice); 45 kinds of recombinant inbred lines (18 kinds of mice); 506 mutant strains (60 mice); 372 inbred lines (135 mice); 528 species of homologous lines (390 species of mice); F 180 hybrids (60 mice); Other 129 species (93 species in mice).
The National Institutes of Health (NIH) has 45 animal resources development centers, 37 of which are located in the Department of Comparative Medicine of university hospitals, the Department of Experimental Animal Science of Veterinary College and specialized research institutes. Japan Central Laboratory Animal Research has three departments, four centers and one research institute. Three of them are Laboratory Animal Science Department, Biomedical Science Department and R&D Department. There are 10 laboratories in these three departments: breeding laboratory, reproductive laboratory, nutrition laboratory, animal medicine laboratory, environmental impact laboratory, breeding technology development laboratory, genetic laboratory, immunology laboratory, endocrinology laboratory and tumor laboratory. These four centers are: disease inspection center, academic information center, animal management center and primate experiment center. One is the Institute of Basic Medicine. The institute consists of five departments, namely, management department, pharmacology department, pathological toxicology department, blood chemistry department and neuropharmacology department.
In the United States, there are 65,438+0,300 production and research units engaged in experimental animals. There are more than 50 companies specializing in the production of experimental animals in Japan. Laboratory animal work has become a professional, standardized, commercialized and socialized scientific research and economic system.
NIH Laboratory Animal Resource Center and Jackson Lab are the largest gene protection and research centers in the world. Only the NIH Laboratory Animal Resource Center maintains 250 kinds of inbred mice and rats, and there are more than 20 kinds of nude mice with different backgrounds. The successful breeding of recombinant inbred lines is an important progress in mammalian genetics, which has been widely used in the identification of new polymorphic gene loci and new histocompatibility loci, and the study of pleiotropic loci and their linkage relationships. At the same time, it is also widely used in the research of infectious, spontaneous and induced diseases as well as biology, pharmacology, morphology and behavior.
At present, all countries use the principle of gene regulation to study chimeras and single-parent homozygous and polyploid animals. Chimeric animals, also known as allotypic animals or tetraploid animals, can be used in cell lineage, experimental embryology, genetics and immunology. Breeding technology of single parent homozygous diploid animals, also known as gynogenesis technology, is a technology developed in recent years. The success of this new technology can greatly accelerate the cultivation of new varieties. It takes 100 years to breed experimental animals, and it can be completed in only one year, and the problem of embryo death caused by lethal genes can be solved in the homozygous process. Another trend of experimental animal research in various countries is to cultivate various pathological model animals. Immunodeficient animals with multiple gene mutations have been successfully bred. Japan has set up a research institute for "incurable diseases" disease models. According to the preliminary investigation, there are more than 40 kinds of "difficult diseases", and each kind of "difficult diseases" has a special disease model research group. Taking mice as an example, 893 mutation gene loci have been found, and 4 17 pathological models similar to human diseases have been cultivated. Three veterinary colleges in the United States (Cornell, Pennsylvania, Ohio) are conducting research in this field. Newfoundland dogs in Canada were screened by the College of Veterinary Medicine, University of Pennsylvania, USA, which can have almost the same heart disease as human congenital heart disease. Histopathology, cytogenetics and molecular biology methods were used to study the gene map. In order to know the secret of gene mutation clearly, they are exploring the technology of direct determination of DNA. At the same time, the metabolic laboratory of this university also used biochemical methods to screen cats with congenital carbohydrate disorder and domestic dogs with amino acid metabolism disorder. They are similar to many children's metabolic diseases. The US Department of Health allocated special funds for their research. In addition, they are cultivating animal models with various characteristics and effects for the elderly. Successfully cultivated are: animal models without thymus and spleen; Animal models of hypertension, diabetes and obesity; Animal model without B cell function; Animal model without K cell function; Animal models without macrophage function, etc. (A) the development of experimental animal science in China.
The development of experimental animal science in China is relatively slow. Before liberation, only a few universities and medical departments carried out some experimental animal work, mainly breeding a certain number of various experimental animals.
After liberation, with the attention and care of the party and the government and the joint efforts of Chinese medical, veterinary and experimental animal scientists, we have done a lot of work in the research and production of experimental animals and achieved many achievements. A professional team of about 500-600 experimental animals has been formed in China. Valuable inbred mice such as low-cancer strain Jinbai 1, high-cancer strain Jinbai-2 and leukemia experimental mouse 6 15 have been successfully cultivated, and 20 strains such as C3H, C57BL, DBA/2, BALB/c and nude mice have been widely preserved, propagated and applied from abroad. There are more than eight kinds of microbial monitoring techniques for SPF chickens, pigs and nude mice (statistics 8 1 year); Preliminary progress has also been made in monitoring technologies such as protection, breeding, feeding, management, reproduction, disease prevention and environmental control of experimental animals; In the application of medicine, veterinary medicine and other related biological sciences, some world-class achievements have been made, which have created conditions for the development of scientific research and industrial and agricultural production and made contributions to protecting people's health and developing the national economy.
However, due to the long-term "Left" interference, especially the serious damage of the Gang of Four, and many comrades' insufficient understanding of the importance of experimental animals, there is no modern scientific research center for experimental animals in China, and most of them are in a natural state of self-cultivation, self-reproduction, self-support and self-utilization under the condition of poor equipment, weak technical strength and few personnel. For example, there are 250 strains of inbred mice and 146 strains of mutant mice in the world, while there are more than 30 inbred mice of different strains in China (statistical data of 8 1 year), including imported mice, many of which have not been genetically monitored and identified. Mutant lines are still blank, and there is still a big gap compared with the international level. Many experimental animals are unqualified, which makes some scientific research projects impossible. In order to obtain more reliable data, many research topics have to repeat experiments many times, resulting in a serious waste of manpower, material resources, financial resources and time. Some achievements have been allowed to be exchanged internationally, attracting international attention. Many drugs and biological products cannot be put into production and sold to the international market due to the lack of experimental animals that meet the international verification standards. Some biological drugs are mixed with virulent viruses (bacteria), and there is a lack of qualified experimental animals for verification. For example, because there were no pigs without specific pathogens in the production and verification of classical swine fever vaccine, a large area of classical swine fever was caused, and one-time death1650,000 pigs caused great losses to the country, and the country paid more than 3 million yuan, which also brought great losses to farmers. Because the experimental animals are impure, the experimental results are unreliable, and even wrong conclusions are drawn, which brings serious harm. Therefore, experimental animal science has become an urgent problem to be paid attention to, studied and solved in China's scientific research, biopharmaceutical production, people's health and industrial and agricultural modernization.
After the Third Plenary Session of the Eleventh Central Committee of the Communist Party of China, under the guidance of the economic policy of opening to the outside world and invigorating the country, in order to meet the requirements of the four modernizations, China's experimental animal science has made new development and achieved remarkable results.
From 65438 to 0982, the State Science and Technology Commission held the first national conference on experimental animals in Xishuangbanna, Yunnan Province, and various regions and departments also held conferences on experimental animals in this industry. 1984, the State Council approved the establishment of China Laboratory Animal Science and Technology Development Center. Under the guidance of the general policy of national science and technology development, the principles, policies, regulations and plans for the development of experimental animal science and technology in China were studied and put forward. To coordinate and manage the development, research and personnel training of laboratory animal science and technology; Arrange and implement the development, construction and business of relevant conditions of experimental animal science and technology; Organize and implement international cooperation and academic exchanges in the field of experimental animal science and technology; Doing a good job in scientific and technological information, academic activities and scientific and technological consultation of experimental animals plays an important role in promoting the development of scientific and technological work of experimental animals in China. From 65438 to 0985, the State Science and Technology Commission held the second national conference on experimental animal science and technology in Beijing, and formulated the development plan and regulations for experimental animals, which effectively promoted the development of experimental animal science in China.
From 65438 to 0982, China successively established four national experimental animal centers: Tianjin Experimental Animal Research Center, Beijing Experimental Animal Research Center, Shanghai Experimental Animal Research Center and Yunnan Primate Experimental Animal Center. The experimental animal institutions affiliated to the industry system include: Animal Center of Life Science Research Department of China Academy of Sciences, Animal Center of China Medical and Health System, Experimental Animal Research Center of Agriculture, Animal Husbandry and Fishery System, and Animal Center of Chemical System. In these industrial systems, there are medical experimental animal centers of health system with a certain scale. Under the leadership of the Ministry of Health, there are seven animal centers. For example, the Institute of Experimental Animals of China Academy of Medical Sciences is a large-scale experimental animal research unit that pays equal attention to scientific research, production and teaching; Laboratory Animal Monitoring Center, Institute of Biological Products and Drugs, Ministry of Health. In addition, there are seven experimental animal breeding grounds. Among local units, provincial animal centers have been established in various provinces (autonomous regions) to meet the needs of relevant departments in various provinces (autonomous regions) for experimental animals. Many universities, hospitals and research institutes have departments and departments of experimental animals. All these constitute a multi-level experimental animal network system.
Since the Third Plenary Session of the Eleventh Central Committee, the development of experimental animal science in China has made remarkable achievements. Due to the attention of organizations at all levels and the vast number of life science workers, the leadership has been strengthened, the relations between various aspects have been coordinated, corresponding institutions and professional units have been established, a multi-level network system of experimental animal science has been initially formed, and a scientific and technological team of experimental animals has been initially formed.
(2) Progress of experimental animals
A monitoring system for experimental animals was established. Beijing, Shanghai, Harbin and other places have established relatively complete monitoring systems, and carried out monitoring of microbiology, genetics, nutrition, environmental sanitation, infectious diseases and other aspects of experimental animals such as rats, mice, chickens and dogs. In addition, Beijing, Shanghai and military units have also established quality monitoring systems for experimental animals, so that genetic pollution and infectious diseases of experimental animals can be found at any time and controlled in time.
In the prevention and treatment of laboratory animal diseases, the quarantine work and sanitary management of animal feed, bedding and cages have been strengthened, and the sanitary conditions such as disinfection and animal rooms have been improved, effectively controlling the occurrence and epidemic of laboratory animal diseases.
In recent years, China has established an experimental animal seed bank, which has attracted the attention of national and international counterparts. From 65438 to 0984, the United Nations World Health Organization, the NIH Laboratory Animal Department of the United States, the British Oila Breeding Center and the Japanese Central Research Institute of Laboratory Animals successively provided breeding mice to China in different ways. At present, there are 40 different strains of inbred animals preserved by the Institute of Experimental Animals of China Academy of Medical Sciences, among which there are 5 different strains of nude mice.
Research on information animals and information biology has been carried out. China has successfully bred sterile rabbits and guinea pigs with domestic plastic transparent film isolators, and can produce chickens and pigs without specific pathogens.
The research on the animalization of wildlife experiments has also made gratifying progress. There are more than 2000 species of terrestrial vertebrates in China, accounting for 10% of the world's species, including amphibians 196, reptiles15, birds 165438 and mammals14. Some of these species have high development value. For example, Lassa dogs, which were introduced to Europe and America very early, have already attracted worldwide attention. At the beginning of this century, China successfully cultivated some wild animals into model animal for life science research, some of which have been recognized as experimental animals by scientists at home and abroad, and have been widely used internationally. Such as black hamster, Mongolian gerbil, tree shrew, marmot and so on.
China has established a laboratory animal information consultation, book publishing and information network system. Information groups or information laboratories of different scales have been established in experimental animal centers around the country, which are responsible for collecting, sorting out and storing information on the scientific development of experimental animals, and conducting academic exchanges through relevant magazines to provide information to experimental animal scientists. The existing libraries in China have different quantities of experimental animals. Some monographs on experimental animals with good quality have been published in China. There are at least seven or eight specialized journals on experimental animals, including internal communication. China began to carry out audio-visual education through TV, video, photography, slides and other means to popularize the scientific knowledge of experimental animals.
China has strengthened scientific education and professional training of experimental animals. With the development of experimental animal science, people gradually realize the significance of experimental animals and experimental animal science in life science research. At present, many scientists have turned to the scientific research of experimental animals, and some experts and professors recruit master's and doctoral students of experimental animals. The country also sends overseas students to train senior researchers. Medical College, Agricultural College and Animal Husbandry College offer laboratory animal science courses, and Beijing Agricultural University also offers specialized courses and departments of experimental animals. Relevant research institutions and animal centers also train junior and middle-level professionals in various ways, such as further education and short-term training. All these have greatly improved the academic quality of laboratory animal scientists and technicians in China.
China has successively established academic groups for experimental animals and actively carried out academic exchanges with the international experimental animal community. The National Laboratory Animal Association was established. At present, provincial experimental animal associations have been established in all regions of China, which have played a positive role in uniting the vast number of experimental animal scientists, promoting the exchange of scholars at home and abroad, strengthening the horizontal ties at home and abroad, and developing experimental animal science in China. Shanghai 1984 and Beijing 1986 have successively established regional management committees for experimental animals. They are the executive bodies of experimental animal legislation composed of relevant administrative personnel and scientific workers. They inspect and supervise the quality of experimental materials and the effect of animal experiments, and issue experimental animal certificates to relevant units that have passed the appraisal, so as to ensure the quality of experimental animals, feed, padding and instruments and equipment.
China also actively carried out research on experimental animal equipment and engineering. We have been able to produce various types of aseptic isolators, vacuum autoclaves and cages for experimental animals that do not induce sodium, replacing the original animal production tools in one fell swoop. It shows that in the near future, the production and experiment of experimental animals in China will be modernized. China's animal breeding room will be produced in the control system, so that our experimental animals can basically meet the international unified standards. In terms of feed and filler, we can now produce granular feed for rats, mice, rabbits, chickens and guinea pigs and puffed feed for dogs, and we can design and build SPF animal houses by ourselves and develop diagnostic products for various diseases.
(3) Progress in animal experiments
Reproductive physiology and family planning were studied with rats, mice and rabbits. The process of oocyte maturation and cleavage embryo formation in rabbits and the distribution of estrogen receptors in endometrial nuclei were observed. It is found that microwave irradiation of testis can inhibit the reproductive function of testis. The application of flavonoid-—RHA peptide in rats can inhibit decidua formation and terminate pregnancy. The interstitial tissue of testis was also studied, which proved that germ cells might exist in it. In addition, the antifertility and racemization effects of gossypol on 15 methyl prostaglandin F2 mice were also studied.
In the study of cardiovascular system, the normal electrocardiogram of dogs and rats and the relationship between nerve nuclei and blood pressure were studied.
Immunology has made great progress in recent ten years, and humoral immunity and cellular immunity have been studied in mice and rats. Various hybridomas and monoclonal antibodies were developed with mice and rats.
To observe the distribution and function of hematopoietic cells in dogs (the thoracic vertebra is the most active, with a slight decrease from the center to the end) and the effect of radiation on the micronucleus of red blood cells in dogs.
It is very active to study tumors with experimental animals, including inducing tumor formation models with various carcinogens, studying tumor formation mechanism, and discussing tumor inhibition and drug treatment.
Since 1979, more than 50 experimental animal tumor models have been established, accounting for 45.5% of the total tumors formed in the 36 years since liberation. Tumors such as lung cancer, gastric cancer, liver cancer, breast cancer, lymphocytic leukemia, lymphoma, fibroma, brain tumor, testicular tumor, colorectal cancer, esophageal cancer, etc. The anticancer effect of Coriolus versicolor polysaccharide was studied. The mechanism of precancerous lesion of gastric cancer induced by white ore: Leprosy bacillus was cultured in nude mice and inoculated with human tumor to study the occurrence of tumor and the therapeutic effect of drugs.
Clonorchis sinensis in domestic dogs was studied in parasitology. Infection rate of different strains of mice to plasmodium; Effect of cobalt radiation on parasites.
In order to study the effect of hormones on neurotransmitters, rats can be used to study the inhibitory effect of lactoferrin and vitamin D on cadmium absorption by liver. In addition, the normal value, morphogenesis and function of experimental animals were studied, such as the dynamic changes of esophagus, forestomach, thymus and lung in 6 15 mice during development. It was found that the vein distribution on the surface of cat kidney had strain characteristics.
(D) The prospect of experimental animal science in China.
Talent is the primary condition for the scientific development of experimental animals, so it is necessary to put talent training in an important position, speed up talent training and mobilize the enthusiasm of experimental animal staff to meet the needs of developing experimental animal work.
Formulate and implement relevant regulations on the management of experimental animals to ensure the quality of experimental animals. The management of experimental animals must be scientific and conform to international unified standards and regulations. Starting from the actual situation in China and referring to the relevant foreign laws and regulations, starting from the quality standards, feeding facilities and operating procedures of experimental animals, this paper puts forward the national unified management regulations that are both in line with internationally recognized standards and feasible, and establishes monitoring institutions and implements them step by step.
Adhere to the simultaneous development of human, financial and material resources, encourage experimental animal scientists to carry forward the spirit of hard struggle and in-depth research, and also create necessary conditions for them, strive for the state to allocate special funds for key support every year, and give play to the enthusiasm of departments, localities and units to do a good job together. Organize and coordinate the trial production, appraisal, standard adoption and mass production of houses, instruments and materials and equipment needed for the scientific and technological work of experimental animals, so as to standardize, commercialize and socialize the series.
The State Science and Technology Commission promoted the establishment of the National Laboratory Animal Institute and the China Laboratory Animal Society, and founded the National Laboratory Animal Magazine.
In the standardization of experimental animals, formulate and supervise the implementation of unified national management regulations. Work in accordance with internationally recognized standards in the following work:
Center for the introduction, protection and reproduction of experimental animals; Experimental animal breeding and production base; Laboratory animal quality control center; Production base of experimental animal feed and padding; Production base of scientific and technological equipment and instruments for experimental animals; Laboratory animal science and technology management technology and information exchange center; Laboratory animal training center.
China joined the International Scientific Committee on Laboratory Animals. Strive to send more scholars to attend the international annual meeting of experimental animal science. Equip the computer network terminal of scientific and technological information of experimental animals as soon as possible. Expand international information academic exchanges and friendly personnel exchanges, and strive to make experimental animals, science and technology, instruments and equipment and experimental animal engineering produced in China more widely enter the international market, so as to find new ways of self-development and make contributions to the people of the world!