With the rapid advances in life science and biotechnology in China in recent years, much has been achieved by scientists, including super hybrid rice and cloned rat. Some of these findings have been published in international peer-reviewed journals and have been the subject of domestic and international patent applications. In the meantime, China is facing with unprecedented issues and challenges arising from new biotechnologies, such as biosafety, bioethics and intellectual property rights protection. However, with government support there has been much progress in the development of life science and biotechnology.
In the last 20 years, the rapid advances in life science and biotechnology have opened up new areas for human health, pharmaceutics, agriculture, natural resources, environment, food processing and aquaculture all over the world. Biotechnology, as a group of useful, enabling technologies with wide and diverse applications in a broad range of sectors, will change pattern of industry and economics.
Currently, China is facing huge challenges in fields such as human healthcare, medicine, industry, commerce and agriculture. Therefore, the development of life science and biotechnology is of great importance to the modernisation and sustainable development of the country.
Since the mid-1980s, the Chinese Government has been giving increasing attention to life science and biotechnology. Increasing amounts of funding from both central and provincial governments have been used to support basic research and development (R&D). Life science and biotechnology have been major components in the two biggest and most important programmes: the 863 Programme and the 973 Programme1. In the 863 Programme, total expenditure and biotechnology spending increased year on year between 1996 and 2002, and especially since 2001, with total spending in the biotechnology sector greatly increased (Figure 1). 2-4
Figure 1: Expenditure in the 863 Programme (1996–2002)
In the early days, almost all funding came from the central governments, but over time they have also come from other channels, such as the Rockefeller Foundation, the McKnight Foundation, the International Foundation for Science, and the European Union-China Collaboration Programmes. 1 The availability of financial support has helped to improve China’s research capacity, enabling it to increase its visibility in the global bioscience arena.
Life sciences in China
In China, the priority areas in the life sciences are genomics, functional genomics, proteomics, gene recognition related to severe diseases, stem cell research, cancers and bioinformatics.
In 2001, even though Chinese scientists joined the Human Genome Project (‘HGP’) late as the sixth participant after the United States, Britain, France, Japan and Germany, they sequenced 1 per cent of the human genome with an accuracy rate of 99 per cent, two years ahead of schedule. 5 Rice, as the major staple, is widely cultivated in China and Southeast Asia, so it became the next sequencing target. The genome sequence of Oryza sativa subsp. indica (9311) rice, with a 98 per cent coverage of genes and a chromosomal location of 95 per cent of sequences, and that of chromosome 4 of Oryza sativa subsp. japonica rice, have been completed, representing the first complete genome sequencing of cereal plants. 4 In addition, China participated in the International HapMap Project and undertook 10 per cent of the work.4 China was also the main participant in the microorganism genome project and sequenced six microorganism species genomes, such as Leptospira which could cause leptospirosis, one of the most common natural-immunogenic acute infectious diseases, which is particularly prevalent in China.
Chinese scientists have identified and cloned over 20 functional genes from major agricultural products such as rice, wheat, cotton and soybean, some of which were important for rice stalk application, product and vegetable quality improvement, and genetic improvement of crop nutrition and heterosis. 4 More than ten functional genes of animals like pig, chicken and fish relating to muscle growth, fat quality and developmental processes have been cloned, 4 with some of them the subject of domestic and international patent applications.
The R&D of proteomic-related technologies will play an important role in drug discovery, molecular diagnostics and medical practice in the first part of the 21st century. In 1998, the Chinese National Natural Science Foundation initiated a major project to study proteins, and protein dynamic structural changes and biofunctions.
In 2001, the Chinese Academy of Military Medical Sciences and Fudan University initiated a series of research projects with funding from the 973 Programme, including one studying the proteomes that may cause major human diseases. In December 2003, more than 200 ($24) million RMB was invested in the Human Liver Proteome Project (HLPP) 6. In this large project, scientists in China were given 30 per cent of the workload. 7 After the startup period of 2003–2005, the HLPP will enter a fully fledged implementation phase from 2006 to 2010, during which expression charts, decoration charts, positioning charts, chain charts, structure charts, sample bank, antibody bank and database will be completed. 7
So far over 60 research institutes from 16 countries have joined the HLPP, making it the largest project headed by China in its history of international co-operation, and the first proteome project in the world focusing on human tissues and organs. The outcome of the HLPP might be helpful for the better understanding of liver diseases pathogenesis and in proposing new diagnostic and treatment technologies.
Genes related to severe diseases
China, which has more than 1.3 billion people and abundant and diverse genetic resources, has moved increasingly into functional genomics and the isolation of genes related to diseases. Samples of 850 families of diseases and the genetic resources of 2 million copies of DNA, tissues and cell lines have been collected. 4 More than 100 genes related to major human diseases have been identified. 4 In addition, six sets of research results on human genes related to dentinogenesis imperfecta 1, brachydactyly type A-1, autosomal dominant lamellar and Mar ner cataract, artifical fibrillation and familial nasopharyngeal carcinoma have been published in Science or Nature. 4 These achievements will be very helpful in understanding how to cure ultimately related severe diseases.
Other advanced life science aspects
In the field of bioinformatics, in 2002, a series of biological databases were completed and started to provide online information services, including genome information of Thermoanaerobacter tengcongensis, Leptospire interrogans and Shigella dysenteriae. 4 More than 130 international public databases have been set up in China. 4 In addition, the Shanghai Centre for Bioinformation Technology, the first R&D base in China aimed at promoting bio-data-sharing, was established, and has been engaged in constructing bioinformation databases and developing bioinformatics software. 4
Biotechnology in China
In China, the main R&D aspects of biotechnology are the genetic breeding of new varieties of high-quality and highyield crops, innovative drugs, tissue (organ) engineering, gene therapy, biochips, bioreactors, advanced technology and novel products for water-saving agriculture.
The focus of biotechnology R&D in the early stages was on cell engineering, tissue culture, and cell fusion, and emphasised the breeding of crops such as rice, wheat, cotton, and vegetables by traditional biotechnologies. However, the most significant progress in agricultural biotechnology came after the first transgenic plant was bred successfully in 1983. Since then, Bt (Bacillus thuringiensis) cotton has had the greatest success.
The release of Bt cotton initiated the first large-scale commercial application of a biotechnology product.8 In 2002, a new super hybrid rice line, with an average yield of over 12,000 kilograms per hektare, was bred successfully.4 As for other transgenic disease-resistant rice varieties, over 50 quality maintainers and sterile lines and eight new combinations of hybrid rice with certain disease-resistant properties have been obtained, of which six combinations have come into field demonstration and two have qualified for the First Class National Quality Standard, planted over a total area of 60,000 hectares. 4 In addition, new varieties of high-quality and highyield wheat and ‘Chaoyou 2’, a new cole cultivar for industrial use, which was bred by genetic engineering and contains rich oil (53 per cent) and erucic acid (66.6 per cent), have been planted across the country. 4
There has also been progress in plant biotechnology in recombinant microorganisms such as soybean nodule bacteria, nitrogen-fixing bacteria for rice and corn, and phytase from recombinant yeasts for feed additives. 8 Genetically modified (GM) nitrogen-fixing bacteria and phytase have been on the market since 1999. 8
The global debate over biotechnology’s potential benefits and risks still continues more than a decade after GM products first came into commercial use.
Proponents of GM technology claim higher yields, less pesticide usage or even increased nutrition, and point to the impending global food crisis to encourage support for GM crops. Indeed, the global GM crop area has grown at a sustained rate of over 10 per cent during the last seven years, and more than 5.5 million farmers are using biotechnology in 16 countries.9 Despite their apparent success, however, many countries are still hesitant about GM products primarily because of uncertainties regarding food safety and environmental damage.10 In addition to discussions on long-term health and environmental risks, the contentious issues also include world trade, product labelling, and public awareness concerns. China was the first country in the world to commercialise a GM product in 1992, and approved for commercial release over 31 cases covering four crops by 1999.11 More recently, however, there has been less commercialisation of GM crops. Despite increasing research, no new GM crops have been approved since 1997.
This turnaround can be attributed to government concerns, evidenced by the number of new regulations, including the ‘Safety Administration Regulation on Agricultural GMOs’ drawn up by the Chinese State Council in 2001 and the ‘Detailed regulations on biosafety management, trade, and labelling’ set out by the Ministry of Agriculture in 2002.12 Furthermore, these new rules include provisions on foreign investment and import safety regulations, so consequently also involve trade issues.
A total of 18 biopharmaceutical products have been commercialised, including recombinant medicines and vaccines, 21 are in clinical trials and 35 are in pre-clinical trials. The new biopharmaceutical products have been capturing more and more of the medical market; for example, the recombinant human interferon -1b (rhuIFN-1b) commands 60 per cent of the domestic market.
The recombinant hepatitis B vaccine (yeast) for prevention came into production in 1995, while that for treatment will come onto the market soon. The hepatitis antigen-antibody complex from serum has been granted a licence for special clinical trials, the genetic engineering antigen-antibody complex will undergo clinical trials and has obtained domestic and international patents. Recently, the biopharmaceutical industry has undergone a period of change, from ‘me too’ pharmaceuticals to R&D pharmaceuticals. Nowadays, there are over 60 biopharmaceutical companies that have considerable abilities in research, development and production. Moreover, the growth rate in the China pharmaceutical sector is expected to remain at around 10 to 12 percent over the next five years and the development of new drugs, including genetic engineering drugs, is on the increase. 13
Other advanced biotechnology R&D
In terms of animal biotechnology, transgenic pig, cow, sheep, rat, and carp have been produced since 1997.8 One of the most significant achievements is the first cloned rat in the world carried out by Professor Qi Zhou, a researcher at the Institute of Zoology Chinese Academy of Sciences. This was published in Science in 2003, the first innovative Science paper by scientists in China in the field of animal cloning. Owing to the significant contribution to animal transgenic technology Professor Qi Zhou was awarded the 2004 GENOWAY Prize for Transgenic Technologies at 5th Trans- Tech-Meeting, because the rat is one of the most widely used animal models in scientific research, this cloning will contribute to the development of innovative therapeutics for major pathologies such as cardiovascular diseases, cancers, obesity, diabetes and neurological disorders.
By contrast, the bioscientific patents granted to China in the United States Patent and Trademark Office (USPTO, Washington, DC) have increased only slowly.5 This suggests that, with the rapid development of health biotechnology in China, there is room for increasing related international patents in the future.
Challenges for life sciences and biotechnology in China
The rapid development of life sciences and biotechnology provides us with advanced technologies in many fields. However, it also presents us with unprecedented issues and challenges, such as biosafety, bioethics, intellectual property rights protection, and so on.
The biosafety issue is one of the key issues of transgenic technology and has been vigorously debated in recent years. Many measures have been taken in order to deal with this intractable problem. Biosafety-related laws and regulations on transgenic products have also been drawn up. In 1993, the Safety Administration Regulation on Genetic Engineering was issued by former State Science and Technology Commission, and recently the National Biosafety Law was drafted and is being debated. At the same time, scientific guidelines for evaluating long-term biosafety were also established, and a special programme has been set up to carry out further research on related biosafety issues.14 In addition, biosafetyrelated information is available to the public.14 People need to know not only the human benefits of GM products and also the facts about them. Therefore the profits of any new biotechnologies are assured, while minimising their potential risks for human beings and the environment.
Currently bioethics is attracting worldwide attention, in particular in the area of human cloning technology. When Dolly the sheep was born in 1997, the cloning technology sent shock waves through the scientific community. Since then, the possibility of human cloning has become the subject of heated debate as to its benefits, risks and impacts on society and ethics. Nowadays, there are two distinct attitudes towards the cloning technology: some countries, such as the United States, Costa Rica and the Vatican, ban all cloning research, while others like China, Britain, France and Japan hold that cloning research for reproduction and medical treatment should be treated differently. On 15 January 2004, China’s Ministry of Science and Technology and Ministry of Health issued the ‘Guidelines for Research on Human Embryonic Stem Cells’, which was the first time the Chinese Government published policies officially forbidding research on human cloning for purposes of procreation while allowing research on embryonic stem cells and remedial cloning. 15 In this relatively free environment, research on human embryonic stem cells and cloning in China has the potential to develop rapidly.
Intellectual property rights protection is another huge challenge. Innovation is the stimulus for a knowledge-based economy, while intellectual property rights protection will stimulate and accelerate technology transfer. In China there has been a good balance between the free exchange of information and the protection of inventors' interests. To take HGP as an example, as a part of the consortium, China insists that all he basic human DNA sequence information should be available to the public and used freely, alongside patent protection of advanced techniques and new products, especially in the field of functional genomics.14 In the meantime, policies to protect patents and intellectual property rights have been adopted, and various laws and regulations on patents, trademarks and copyrights have gradually been introduced, including the Patent Law of the
People’s Republic of China, the Trademark Law of the People’s Republic of China, and the Copyright Law of the People’s Republic of China. The international consensus on patent and intellectual property rights protection has been formally accepted by the government, thus protecting the interests of patent owners. As a result, the number of patent applications has increased significantly over the past few years.
It’s well known that China is the biggest developing country in the world currently, with particular advances in technology. Biotechnology, as a group of useful, enabling technologies with wide and diverse applications in a broad range of sectors, has received increasing attention and government support. This has resulted in bioscientific achievements such as super hybrid rice and cloned rat, some of which have been the subject of domestic and international patent applications. Faced with huge challenges in, for example, healthcare, medicine, industry, commerce and agriculture, the development of life science and biotechnology is of great importance in the country’s modernisation and sustainable development. On the other hand, although the rapid development of life science and biotechnology does provide us with advanced technologies in many fields, it also presents us with unprecedented issues and challenges like biosafety, bioethics and intellectual property rights protection. However, with the coming into force of relevant laws and regulations to deal with these problems, the signs are favourable for the continuing development of life science and biotechnology in China.
*) The author would like to thank Professor Zheng Chengsi and Professor Gao Youhe for their support and encouragement, and Professor Zhang Jianying and Dr Zhan Xiangjang for reviewing and revising the manuscript. Any errors or omissions in this article are the author’s own.
1) Qifa Zhang, ‘China: Agricultural Biotechnology Opportunities to Meet the Challenges of Food Production’, in G.J. Persley and M. M. Lantin, Agricultural Biotechnology and the Poor, section three, 45–50.
2) ‘Annual Report 2000 of The National High Technology Research and Development Programme of China (the 863 Programme)’.
3) ‘Annual Report 2001 of The National High Technology Research and Development Programme of China (the 863 Programme)’.
4) ‘Annual Report 2002 of The National High Technology Research and Development Programme of China (the 863 Programme)’.
5) Li Zhenzhen, Zhang Jiuchun and Wen Ke, ‘Health biotechnology in China – reawakening of a giant’, Nature Biotechnology 22, DC13 – DC18 (2004).
6) Hepeng Jia and Sabine Louët, ‘China pushes liver proteomics’, Nature Biotechnology 22, 136 (2004).
7) The Ministry of Science and Technology People's Republic of China, ‘China Leads Human Liver Proteome Project’ , China Science and Technology Newsletter, No. 383, 30 October 2004.
8) Jikun Huang and Qinfang Wang, ‘Agricultural Biotechnology Development and Policy in China’ AgBioForum, 5(4): 122–135.
9) Clive James, ‘Global Status of GM Crops in 2002’, ISAAA, 2003.
10) Lizette Alvarez, ‘Consumers in Europe Resist Gene-Altered Food’, New York Times, 11 February 2003.
11) Huang Jikun, Scott Rozelle, Carl Pray and Qinfang Wang, ‘Plant Biotechnology in the Developing World’, Science, Vol. 295 (25 January 2002), 674–677.
12) Kevin Teng and Jikun Huang, ‘The Commercial Environment and Product Development for Agricultural Biotechnology in China’, CCAP Working Paper 04-E3.
13) 2004 China Medical Market Report (pharmaceutical market report).
14) Speech by Mr Jin Ju, Head of Chinese Delegation, at the meeting of fifth Session of United Nations Commission on Science and Technology for Development (May 28–1 June 2001, Geneva) 2004.
15) ‘China issues document to ban human cloning’, People’s Daily, 15 January 2004.
Source: Life Science and Biotechnology in China, bIO-sCIENCE law Review, SONG ELI* Department of Pathophysiology, National Key Laboratory of Medical Molecular Biology, Proteomics Research Centre, Institute of Basic Medical Science, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005