Spotlight on China Supplement to Immunity 2013 : fm-2

EAS T MEETS WE ST: Enhancing the Global Influence of Immunology Research in China By Dr. Xuetao Cao , President of the Chinese Academy of Medical Sciences T he concept of “Yin and Yang,” now well known in Western culture and its medical field, has been a staple of f Chinese philosophy and traditional medicine for centuries. Interestingly, the concept of f immunity may have existed in traditional Chinese medicine more than 1700 years ago, as Ge Hong, a famous doctor, first proposed the idea of f “prophylactic immunization” to prevent the recurrence of f rabies by “covering the people with the sick k dog’s brain” around 303 AD. Children were also instructed to inhale powders made from patients’ crusty skin lesions to prevent smallpox in ancient China. The practice then spread along the “Old Silk k Road” connecting China with the West and inspired the discovery of f a vaccine against smallpox in 1798 by Edward Jenner (1749–1823), often considered the Founder of f Immunology. The birth of f modern immunology research in China can be traced back k to the 1930s, when Drs. Sizhi Liu (1904–1983) and Shaowen Xie (1903–1995), both from the Peking Union Medical College, first purified and quantified antibodies—and successfully prepared the inactivated vaccine for the prevention of f rickettsiosis, respectively. The research community, albeit small at the time, quickly recognized the critical importance of evidence-based medicine and the need to carry out translation-oriented research in order to improve patient care and the general population’s well-being. In the 1960s, Dr. Fangzhou Gu of f the Chinese Academy of f Medical Sciences (CAMS) spearheaded China’s polio vaccination program by developing an orally available polio vaccine. In the 1970s, Dr. Zongtang Sun of f CAMS launched a study using the hepatitis B virus (HBV) vaccine to immunize children and succeeded in reducing primary hepatocellular carcinoma (HCC) incidence inthe Qidong area that once had the highest incidence rate of f the disease in China. In the 1980s, Dr. Yunde Hou was the first to put recombinant human interferon-␣ on the market for the treatment of f chronic hepatitis B, engendering the biotech era of f China. Dr. Denian Ba of Harerbin Medical University meanwhile conducted the first clinical trial of adoptive cellular therapy for cancer patients, and Dr. Weifeng Chen from Peking University pioneered basic immunological research in China by studying T cell development in the thymus. These remarkable works provided a strong basis for the accelerated pace of f immunological research around the 1990s. However, it was not until the turn of f the new century, following the rapid expansion of f the national economy and the increasing trend in globalization, when science and technology development in China began to truly embrace its renaissance. During the past decade, much like other scientific disciplines, discoveries made in all areas of immunology and the research communities grew exponentially in China. Between 2001 and 2011, 119,529 immunology papers were SCI indexed and citations totaled 2,489,214 times in the world; among those papers, 3846 were from China with 33,205 total citations. Furthermore, the number of f publications from China in the field of f immunology rose from 856 in 2001– 2005 (ranked fifteenth in the world) to 2990 in 2006–2010 (ranked sixth in the world). At the meantime, numbers from the top five nations in the category (the U.S., U.K., Japan, Germany, and France) remained largely unchanged. Total citations of immunology papers from China ranked tenth among the nations. This being said, overall paper quality needs to be further (Continued on page iii)

Message From The President Of The Chinese Academy Of Medical Sciences

Dr. Xuetao Cao

EAST MEETS WEST:<br /> <br /> Enhancing the Global Influence of Immunology Research in China<br /> <br /> The concept of “Yin and Yang,” now well known in Western culture and its medical field, has been a staple of Chinese philosophy and traditional medicine for centuries. Interestingly, the concept of immunity may have existed in traditional Chinese medicine more than 1700 years ago, as Ge Hong, a famous doctor, first proposed the idea of “prophylactic immunization” to prevent the recurrence of rabies by “covering the people with the sick dog’s brain” around 303 AD. Children were also instructed to inhale powders made from patients’ crusty skin lesions to prevent smallpox in ancient China. The practice then spread along the “Old Silk Road” connecting China with the West and inspired the discovery of a vaccine against smallpox in 1798 by Edward Jenner (1749–1823), often considered the Founder of Immunology.<br /> <br /> Thebirthofmodernimmunology researchin China can be traced back to the 1930s, when Drs. Sizhi Liu (1904–1983) and Shaowen Xie (1903–1995), both from the Peking Union Medical College, first purified and quantified antibodies—and successfully prepared the inactivated vaccine for the prevention of rickettsiosis, respectively. The research community, albeit small at the time, quickly recognized the critical importance of evidence-based medicine and the need to carry out translation-oriented research in order to improve patient care and the general population’s well-being. In the 1960s, Dr. Fangzhou Gu of the Chinese Academy of Medical Sciences (CAMS) spearheaded China’s polio vaccination program by developing an orally available polio vaccine. In the 1970s, Dr. Zongtang Sun of CAMS launched a study using the hepatitis B virus (HBV) vaccine to immunize children and succeeded in reducing primary hepatocellular carcinoma (HCC) incidence in the Qidong area that once had the highest incidence rate of the disease in China. In the 1980s, Dr. Yunde Hou was the first to put recombinant human interferon- on the market for the treatment of chronic hepatitis B, engendering the biotech era of China. Dr. Denian Ba of Harerbin Medical University meanwhile conducted the first clinical trial of adoptive cellular therapy for cancer patients, and Dr. Weifeng Chen from Peking University pioneered basic immunological research in China by studying T cell development in the thymus. These remarkable works provided a strong basis for the accelerated pace of immunological research around the 1990s. However, it was not until the turn of the new century, following the rapid expansion of the national economy and the increasing trend in globalization, when science and technology development in China began to truly embrace its renaissance.<br /> <br /> During the past decade, much like other scientific disciplines, discoveries made in all areas of immunology and the research communities grew exponentially in China. Between 2001 and 2011, 119,529 immunology papers were SCI indexed and citations totaled 2,489,214 times in the world; among those papers, 3846 were from China with 33,205 total citations. Furthermore, the number of publications from China in the field of immunology rose from 856 in 2001– 2005 (ranked fifteenth in the world) to 2990 in 2006–2010 (ranked sixth in the world). At the meantime, numbers from the top five nations in the category (the U.S., U.K., Japan, Germany, and France) remained largely unchanged. Total citations of immunology papers from China ranked tenth among the nations. This being said, overall paper quality needs to be further Improved as few publications in China in the area of immunology ranked as top 1% papers with extraordinary global impact. In 2008, I summarized recent milestones and considered the future of immunological research in China (Cao, 2008). Since then, an increasing number of papers by Chinese immunologists have been published in top-tier journals such as Cell, Immunity, Cell Stem Cell, Molecular Cell, Nature Immunology, Nature Medicine, Nature Genetics, etc. Such high-impact publications from China are a welcoming sign of the shift of priority from quantity to quality of scientific research. In addition, more and more overseas Chinese scholars with strong education backgrounds in the West and experiences running their own labs are encouraged by special supporting policies of the central government to return to China and establish research labs and facilities in universities, research institutions, and even R&D centers of pharmaceutical companies. An increasing number of talented young scientists living abroad, with great passion and mission, are also being appointed as Principal Investigators with special financial support from the government to set up their own labs.<br /> <br /> Keeping with the tradition of focusing on medical care, newer generations of Chinese immunologists not only want to publish original papers but also stay close to translational research using multidisciplinary approaches and incorporating novel technologies and platforms so as to better understand, diagnose, and treat immunology-related disorders and develop immunotherapy for diseases. For example, more than 90 million people are currently infected with HBV, and many HCC patients with chronic HBV infection are diagnosed every year in China, placing heavy burdens on the public healthcare system. To circumvent this, many investigators are actively looking for HCC biomarkers and designing new preventative or treatment immunotherapeutic regimens such as HBV vaccines. Scientists in China also adopt practical approaches with the goal of making therapeutics more affordable to patients, especially those in rural areas. As a result, recombinant proteins and Therapeutic antibodies are now in the market or under clinical or preclinical studies.<br /> <br /> With the tremendous increase of funding from the National Natural Science Foundation of China, the Ministry of Science and Technology, the Ministry of Health, as well as regional governments in past years, Chinese immunologists are in a good position to address the most critical and difficult challenges facing the community. With great efforts on basic and translational immunological research and the emphasis on new technologies and innovations, Chinese immunologists have made strides in multiple topic areas (see the following articles). There are research groups actively focusing on the pathogen recognition receptor signaling in the innate response that have successfully identified new sensors for the invading pathogens as well as new regulators of the Toll-like receptor or retinoic acid-inducible gene I (RIG-I)-triggered inflammatory innate response against viral and bacterial infection. Several groups are investigating the development of immune cell subsets such as regulatory T cells, Th17, regulatory dendritic cells, regulatory monocytes, tumor-associated macrophages, etc. Furthermore, functional regulations of NK cells, NKT cells, T cells, mast cells in the immune response, and the pathogenesis of immunological disorders have been extensively studied by several labs. New mechanisms for the microRNA-mediated regulation of Th17 in the autoimmune diseases and a new working model for the molecular control of Th2 migration in allergic airway inflammation are being proposed, and inhibitory receptors on NK cells to regulate killing of NK cells and subsequently affect liver tissue damage are being identified. These original studies from China provided insights into the cellular and molecular mechanisms for the initiation or termination of innate response and the determination of attitude, duration of adaptive immune responses, and maintaining the balance of the immunological networks. Researchers are also encouraged to apply new, innovative immunological techniques and to integrate other approaches such as genomics, epigenomics, proteomics, and imaging to not only analyze Immune response systemically and quantitatively but also to investigate the pathogenesis of major diseases such as cancer and infectious and autoimmune diseases. Several groups have now uncovered critical genetic loci involved in the pathogenesis of autoimmune diseases by using genome-wide association studies and identified new factors important in chronic inflammation and cancer by deep sequencing. The application of these new technological advances will undoubtedly continue to create excitement in future studies of the immune system and immunological disorders.<br /> <br /> With a vision to highlight the research frontiers as well as facilitate and strengthen international collaborations, the Chinese Society for Immunology (CSI) is playing an increasingly important role in bringing the Chinese immunologists together to build a strong national immunology research network and promote scientific communications with immunologists around the world, and the outcomes have been very productive. With membership increased from 2500 in 2008 to more than 5000 now, CSI is rapidly expanding in recent years. CSI has successfully organized annual meetings, advanced courses in immunology, and hosted The First Joint Symposium on Immunology co-organized by CSI, the Japanese Society for Immunology, the Korean Association for Immunologists, the FIMSA Congress, as well as other international conferences on immunology. With joint efforts from all CSI members, the future will be bright and Chinese scientists will increasingly contribute to the global effort of immunology research and the eradication of public health threats.<br /> <br /> Xuetao Cao, M.D., Ph.D.<br /> <br /> President, Chinese Academy of Medical Sciences <br /> <br /> President, Chinese Society for Immunology <br /> <br /> President, Federation of Immunology Societies of Asia-Oceania<br /> <br /> REFERENCE<br /> <br /> Cao, X, (2008). Immunology in China: the past, present and future. Nat. Immunol. 9, 339–342.

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