陈化兰

12 月 19 日出版的《自然（Nature）》杂志评选出 2013 年年度十大科学人物。中国农业科学院哈尔滨兽医研究所、国家禽流感参考实验室主任陈化兰研究员因 H7N9 禽流感病毒研究方面的卓越成绩而榜上有名。

陈化兰现任国家暨世界动物卫生组织（OIE）禽流感参考实验室主任，是我国第一位 OIE 专家， OIE 最高技术决策机构——生物标准委员会6名委员之一。

今年 4 月，陈化兰和她的科研团队发现在我国导致人感染的新型 H7N9 流感病毒与同一时期存在于活禽市场上的 H7N9 禽流感病毒高度同源，在国际上首次从病原学角度揭示了新型 H7N9 流感病毒的来源，为我国科学防控 H7N9 禽流感提供了重要依据。5 月，他们又发现 H5N1 病毒确有可能通过与人流感病毒的基因重配，获得在哺乳动物之间高效空气传播的能力，从而具备引起人间大流行的潜力，从全新的角度揭示了 H5N1 病毒对全球公共卫生构成的现实威胁。7月，陈化兰和科研人员研究发现， H7N9 病毒对禽类无致病力，但该病毒侵入人体发生突变后，对哺乳动物的致病力与水平传播能力得到明显增强，从而揭示了 H7N9 病毒存在较大人间大流行的风险。这些成果先后发表在《科学通报》英文版及《科学（SCIENCE）》杂志上。

“也曾有过许许多多温馨浪漫的梦想，也曾有过做一个贤妻良母的人生设计，但是陈化兰最后选择了在外人看来枯燥、单调的兽医科研工作。 ”没有最好，只有更好。“这是她用于不断自勉的箴言，也是她的团队的集体座右铭。”

在祖国找到自己的舞台

1999 年陈化兰前往美国疾病控制中心（CDC）进行博士后研究，并显露出卓越的才华，学习结束后，回到了祖国。

“当时考虑的原因，一是国内流感防治研究方面迫切需要人才，回国发展更能学有所用；二是哈尔滨兽医研究所也为我提供了广阔的发展空间。”陈化兰说，“更重要的是，在国外尽管条件优厚，但是从事的是职业；在自己的祖国，我感受这是一份事业。”

2002 年底，陈化兰告别了在美国做博士后的丈夫，带着两岁的儿子回到哈尔滨，把孩子托付给师妹提前代她雇好的保姆，便一头扎进了禽流感实验室。

在她主持下，国家禽流感参考实验室加强了我国禽流感流行病学监测和研究的力度，建立了系统、完整的中国大陆禽流感病毒种毒株资源库及其流行病学信息数据库，阐明了我国禽流感病毒的分子遗传演化和抗原变异规律，为禽流感疫情的预警预报、诊断试剂及疫苗研制与使用等，提供了科学依据。

同时，针对我国禽流感疫情防控的需要，陈化兰开展了全方位的禽流感疫苗研究，获得多项重大突破。

她主持研制的新型 H5N1 禽流感灭活疫苗是国际上首次研制成功并推向大规模应用的流感病毒反向基因操作疫苗，代表流感疫苗研制的国际先进水平和发展趋势，各项技术性能指标较 H5N2 灭活疫苗大幅提高，并在国内外首次证明可对水禽形成有效的免疫保护。

“人类有能力控制流感病毒”

2009 年 5 月 1 日，国家禽流感参考实验室宣布研制出一种新型人用禽流感冷适应致弱活疫苗，有望对人类感染 H5N1 亚型禽流感病毒实现完全保护。当时，正值墨西哥和美国暴发新型 HIN1 亚型流感病毒，因其较强的人与人之间水平传播能力，引起了新的公共卫生恐慌和对相关防控手段的关注。

主持这项研究的陈化兰在接受媒体采访时表示，在 H5N1 活疫苗研究的基础上，由国际相关领域专家共同建立的平台，有能力针对其他新出现的流感疫情快速研发出新的疫苗。

“禽流感可以控制，可以预防，人类具备这个能力。”陈化兰说。

近年来，陈化兰主持承担了 20 多项国家和国际合作项目。除在禽流感疫苗研制方面的突出成就外，在禽流感病毒的基础研究方面也取得了非常好的业绩，研究结果先后在美国国家科学院院刊（PNAS）、病毒学杂志（Journal of Virology）等重要国际学术刊物上发表了 60 余篇论文 .

如今，陈化兰在国际禽流感研究领域已是一个“重量级”专家。2008 年 5 月，世界动物卫生组织（OIE）国际委员会在法国巴黎召开第76届大会，认可我国禽流感参考实验室为 OIE 禽流感参考实验室，标志着陈化兰所带领的动物流感研究团队及我国兽医工作得到国际社会的高度认可。

“只要禽流感警报还没解除，我们就不能掉以轻心。作为科研人员，我们职责就是保护人类生存和安全！”陈化兰说。

简介：

陈化兰，女，1969年出生，博士，研究员，博士生导师，中国农业科学院兽医兽药学科“一级岗位杰出人才”。任世界动物卫生组织（OIE）生物标准委员会委员，OIE/国际粮农组织（FAO）禽流感专业委员会执行委员，OIE禽流感专家。中国农业科学院哈尔滨兽医研究所农业部动物流感重点开放实验室主任，国家禽流感参考实验室主任，OIE禽流感参考实验室主任。

1994年以来，一直从事禽流感及猪流感相关基础研究和应用研究。国家杰出青年基金获得者，“973”项目首席科学家。先后主持国家“攻关”、“863”、“973”、国家自然科学基金等科研项目20多项；在国际重要学术杂志发表禽流感研究相关SCI论文50多篇；已获得6个禽流感疫苗新兽药证书，其中3个为基因工程疫苗；获得7项国家发明专利。主持完成成果“H5亚型禽流感灭活疫苗研制及其应用”获得2005年国家科技进步一等奖；主持完成成果“重组禽流感、新城疫二联活疫苗”获得2007年国家技术发明二等奖。主持研发的各种禽流感疫苗在国内外推广应用700多亿羽份。

学习和培训经历：

1987－1991年，就读于甘肃农业大学兽医系，获学士学位；

1991－1994年，就读于甘肃农业大学兽医系兽医病理专业，获硕士学位；

1994－1997年，就读于中国农业科学院研究生院传染病与预防兽医学专业，获博士学位；

1999－2002年，美国疾病控制中心（CDC）流感分中心，博士后。

主要科研工作经历：

1997－1999，中国农业科学院哈尔滨兽医研究所助理研究员；

2002－今，中国农业科学院哈尔滨兽医研究所研究员，农业部动物流感重点开放实验室主任，国家禽流感参考实验室主任。

2008－今，OIE禽流感参考实验室主任

主要奖励和荣誉：

1. 2005年获国家科技进步一等奖，成果名称“禽流感灭活疫苗的研制和应用”

2. 2007年获国家技术发明二等奖，成果名称“重组禽流感、新城疫二联活疫苗”

3. 2009年获黑龙江省自然科学一等奖，成果名称“H5N1亚型禽流感病毒进化、跨宿主感染及致病力分子机制研究”

4. 2010年获黑龙江省科学进步一等奖，成果名称“禽流感（H5+H9）二价灭活疫苗”

5. 2005年获“中国青年女科学家奖”

6. 2005年获“中华农业英才奖”

7. 2006年获“何梁何利青年科技创新奖”

8. 2006年获“全国五一劳动奖章”

9. 2006年获“中国青年五四奖章”

10. 2007年获“中国青年科技奖”

11. 2008年获“国家杰出青年基金”

主要发表文章：1. Yanbing Li, Liling Liu, Yi Zhang, Zhenhua Duan, Guobin Tian, Xianying Zeng, Jianzhong Shi, Licheng Zhang, Hualan Chen*. New lineage of H5N1 influenza virus detected in wild birds in Qinghai, western China. Emerging Infectious Disease, 2010, in press.2. Ying Chen, Gongxun Zhong, Guojun Wang, Guohua Deng, Yanbing Li, Jianzhong Shi, Zhuo Zhang, Yuntao Guan, Yongping Jiang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen*. Dogs are highly susceptible to H5N1 avian influenza virus. Virology. 2010, 405, 15-19, on-line, June 25.3. Lihong Tao, Jinying Ge, Xijun Wang, Hongyue Zhai, Tao Hua, Bolin Zhao, Dongni Kong, Chinglai Yang, Hualan Chen*, and Zhigao Bu*. Molecular Basis of Neurovirulence of Flury Rabies Virus Vaccine Strains: Importance of the Polymerase and the Glycoprotein R333Q Mutation. Journal of Virology. 2010, 84 (17), 8926-8936. on-line, June 104. Yanbing Li, Jianzhong Shi, Gongxun Zhong, Guohua Deng, Guobin Tian, Jinying Ge, Xianying Zeng, Jiasheng Song, Dongming Zhao, Liling Liu, Yongping Jiang, Yuntao Guan, Zhigao Bu, Hualan Chen*. Continued evolution of H5N1 influenza viruses in wild birds, domestic poultry and humans in China from 2004 to 2009. Journal of Virology. 2010, 84(17), 8389-8379. On-line, June 10.5. Yujie Tang, Gongxun Zhong, Lianhui Zhu, Xing Liu, Yufei Shan, Huapeng Feng, Zhigao Bu, Hualan Chen*, and Chen Wang. Herc5 Attenuates Influenza A Virus by Catalyzing ISGylation of Viral NS1 Protein. Journal of Immunology, 2010, 184, 5777-57906. Bo Wah Leung, Hualan Chen, George G. Brownlee. Correlation between polymerase activity and pathogenicity in two duck H5N1 influenza viruses suggests that the polymerase contributes to pathogenicity. Virology, 2010, 401：96-106.7. Yuwei Gao, Ying Zhang, Kyoko Shinya, Guohua Deng, Yongping Jiang, Zejun Li, Yutao Guan, Guobin Tian, Yanbing Li, Jianzhong Shi, Liling Liu, Xianying Zeng, Zhigao Bu, Xianzhu Xia, Yoshihiro Kawaoka, Hualan Chen*. Identification of Amino Acids in HA and PB2 Critical for the Transmission of H5N1 Avian Influenza Viruses in a Mammalian Host. PLoS Pathogens, 2009, 5(12): e1000709.8. Yongping Jiang, Hongbo Zhang, Guojun Wang, Pingjing Zhang, Guobin Tian, Zhigao Bu, and Hualan Chen*. Protective Efficacy of H7 Subtype Avian Influenza DNA Vaccine. Avian Disease, 2010, 54(S1), 294-296.9. Jinying Ge, Guobin Tian, Xianying Zeng, Yongping Jiang, Hualan Chen and Zhigao Bu*. Generation and Evaluation of a Newcastle Disease Virus-Based H9 Avian Influenza Live Vaccine. Avian Disease, 2010, 54(S1), 290-293.10. Guobin Tian, Xianying Zeng, Yanbing Li, Jianzhong Shi, Hualan Chen*. Protective Efficacy of the H5 Inactivated Vaccine against Different Highly Pathogenic H5N1 Avian Influenza Viruses Isolated in China and Vietnam. Avian Disease, 2010, 54(S1), 287-289.11. Neumann G, Chen H, Gao GF, Shu Y, Kawaoka Y. H5N1 influenza viruses: outbreaks and biological properties. Cell Research, 2010, 20(1):51-6112. Qimeng Tao , Xiurong Wang, Hongmei Bao, Jianan Wu , Lin Shi, Yanbing Li, Chuanling Qiao , Yakovlevich SA, Mikhaylovna PN, Hualan Chen. Detection and differentiation of four poultry diseases using asymmetric reverse transcription polymerase chain reaction in combination with oligonucleotide microarrays. J Vet Diagn Invest. 2009;21(5):623-63213. Chuantian Xu, Qiyun Zhu, Huanliang Yang, Xiumei Zhang, Chuanling Qiao, Yan Chen, Xiaoguang Xin, Hualan Chen*. Two genotypes of H1N2 influenza viruses appeared among pigs in China. Journal of Clinical Virology. 2009, 46: 192-195.14. Hualan Chen, Zhigao Bu. Development and application of avian influenza vaccines in China. Current Topics in Microbiology and Immunology. 2009;333:153-62 (Review)15. Hualan Chen. Avian influenza vaccination: the experience in China. Rev Sci Tech. 2009, 28(1): 267-74 (Review)16. Jiyong Zhou, Wenbo Sun, Junhua Wang, Junqing Guo, Wei Yin, Nanping Wu, Lanjuan Li, Yan Yan, Ming Liao, Yu Huang, Kaijian Luo, Xuetao Jiang, Hualan Chen. Characterization of the H5N1 Highly Pathogenic Avian Influenza Virus derived from Wild Pikas in China. J Virol. 2009, 83: 8957-896417. Hualan Chen. H5N1 avian influenza in China. Sci China C Life Sci. 2009, 52(5):419-27. (Review)18. Szretter KJ, Gangappa S, Belser JA, Zeng H, Chen H, Matsuoka Y, Sambhara S, Swayne DE, Tumpey TM, Katz JM. Early Control of H5N1 Influenza Virus Replication by the Type I Interferon Response in Mice. J Virol. 2009 83(11): 5825-3419. Kashiwagi T, Leung BW, Deng T, Chen H, Brownlee GG.. The N-terminal region of the PA subunit of the RNA polymerase of influenza A/HongKong/156/97 (H5N1) influences promoter binding. PLoS ONE. 2009; 4(5):e5473.20. Shufang Fan, Yuwei Gao, Kyoko Shinya, Chris K-F. Li, Yanbing Li, Jianzhong Shi, Yongping Jiang, Yongbing Suo, Tiegang Tong, Gongxun Zhong, Jiasheng Song, Ying Zhang, Guobin Tian, Yuntao Guan, Xiaoning Xu, Zhigao Bu, Yoshihiro Kawaoka , Hualan Chen. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates. PLoS Pathogens, 2009, 5(5), e100040921. Chuanling Qiao, Yongping Jiang, Guobin Tian, Xiurong Wang, Chengjun Li, Xiaoguang Xin, Hualan Chen, Kangzhen Yu. Recombinant Fowlpox Virus Vector-based Vaccine Completely Protects Chickens from H5N1 Avian Influenza Virus. Antiviral Research, 2009, 81(3):234-822. Shufang Fan, Guohua Deng, Jiasheng Song, Guobin Tian, Yongbing Suo, Yongping Jiang, Yuntao Guan, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology, 2009, 384: 29-3223. Murakami S, Horimoto T, Mai le Q, Nidom CA, Chen H, Muramoto Y, Yamada S, Iwasa A, Iwatsuki-Horimoto K, Shimojima M, Iwata A, Kawaoka Y. Growth determinants for H5N1 influenza vaccine seed viruses in MDCK cells. Journal of Virology, 2008, 82: 10502-924. Beibei Jia, Jianzhong Shi, Yanbing Li, Kyoko Shinya, Yukiko Muramoto, Xianying Zeng, Guobin Tian, Yoshihiro Kawaoka, Hualan Chen. Pathogenicity of Chinese H5N1 Highly Pathogenic Avian Influenza Viruses in Pigeons. Archives of Virology, 2008, 153: 1821-182625. Chengjun Li, Jihui Ping, Bo Jing, Guohua Deng, Yongping Jiang, Yanbing Li, Guobin Tian, Kangzhen Yu, Zhigao Bu, Hualan Chen. H5N1 influenza marker vaccine for serological differentiation between vaccinated and infected chickens. Biochemical and Biophysical Research Communications, 2008, 372(2): 293-726. Kiyoko Iwatsuki-Horimoto, Yasuko Hatta, Masato Hatta, Yukiko Muramoto, Hualan Chen, Yoshihiro Kawaoka, Taisuke Horimoto. Limited compatibility between the RNA polymerase components of influenza virus type A and B. Virus Research, 2008, 135(1): 161-527. Jihui Ping, Chengjun Li, Guohua Deng, Yongping Jiang, Guobin Tian, Shuxia Zhang, Zhigao Bu and Hualan Chen. Single-amino-acid mutation in the HA alters the recognition of H9N2 influenza virus by a monoclonal antibody. Biochemical and Biophysical Research Communications, 2008, 371(1): 168-37128. Peirong Jiao, Guobin Tian, Yanbing Li, Guohua Deng, Yongping Jiang, Chang Liu, Weilong Liu, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A single amino acid substitution in the NS1 protein changes the pathogenicity of H5N1 avian influenza viruses in mice. Journal of Virology, 2008, 82 (3): 1146–1154.Comment in Journal of Virology: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses. Journal of Virology, 2008, 82 (3): 1065Comment in Microbe: Single-Amino-Acid Substitution Changes the Virulence of H5N1 Influenza Viruses.29. Qiyun Zhu, Huangliang Yang, Weiye Chen, Wenyan Cao, Gongxun Zhong, Peirong Jiao, Guohua Deng, Kangzhen Yu, Chinglai Yang, Zhigao Bu, Yoshihiro Kawaoka, Hualan Chen. A naturally occurring deletion in its NS gene contributes to attenuation of an H5N1 swine influenza virus in chickens. Journal of Virology, 2008, 82 (1):220–228.30. Hualan Chen, Rick Bright, Kanta Subbarao, Catherine Smith, Nancy Cox, Jacqueline M. Katz, and Yumiko Matsuoka. Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Research, 2007, 128(1-2):159-63.31. Yongping Jiang, Kangzhen Yu, Hongbo Zhang, Pingjing Zhang, Chenjun Li, Guobin Tian, Yanbing Li, Xijun Wang, Zhigao Bu, Hualan Chen. Enhanced protective efficacy of H5 subtype avian influenza DNA vaccine with codon optimized HA gene in a pCAGG plasmid vector. Antiviral Research, 2007, 75: 234-241.32. Jinying Ge, Guohua Deng, Zhiyuan Wen, Guobing Tian, Yong Wang, Jianzhong Shi, Xijun Wang, Yanbing Li, Sen Hu, Yongping Jiang, Chinglai Yang, Kangzhen Yu, Zhigao Bu, Hualan Chen. Newcastle disease virus-based live attenuated vaccine completely protects chickens and mice from lethal challenge of homologous and heterologous H5N1 avian influenza viruses. Journal of Virology, 2007, 81, 150－158.33. Chuanling Qiao, Guobin Tian, Yongping Jiang, Yanbing Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. Vaccines Developed for H5 Highly Pathogenic Avian Influenza in China. Ann. N.Y. Acad. Sci. 2006, 1081: 182–19234. Zejun Li, Yongping Jiang, Peirong Jiao, Aiqin Wang, Fengju Zhao, Guobin Tian, Xijun Wang, Kangzhen Yu, Zhigao Bu and Hualan Chen. The NS1 Gene Contributes to the Virulence of H5N1 Avian Influenza Viruses. Journal of Virology, 2006, 80：11115-11123.35. Taronna R. Maines, Li-Mei Chen, Yumiko Matsuoka, Hualan Chen, Thomas Rowe, Juan Ortin, Ana Falco’n, Nguyen Tran Hien, Le Quynh Mai, Endang R. Sedyaningsih, Syahrial Harun, Terrence M. Tumpey, Ruben O. Donis, Nancy J. Cox, Kanta Subbarao, and Jacqueline M. Katz. Lack of transmission of H5N1 avian–human reassortant influenza viruses in a ferret model. Proc. Natl. Acad. Sci. USA, 2006, 103(32): 12121-1212636. Hualan Chen, Yanbing Li, Zejun Li, Jianzhong Shi, Kyoko Shinya, Guohua Deng, Qiaoling Qi, Guobin Tian, Shufang Fan, Haidan Zhao, Yingxiang Sun, Yoshihiro Kawaoka. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. Journal of Virology, 2006, 80(12):5976-83.37. Yanbing Li, Chengjun Li, Liling Liu, Hongwei Wang, Chuanbin Wang, Guobing Tian, Robert. G. Webster, Kangzhen Yu, Hualan Chen. Characterization of an avian influenza virus of subtype H7N2 isolated from chickens in northern China. Virus Genes, 2006, 33:117-12238. Yanbing Li, Zhixiong Lin, Jianzhong Shi, Qiaoling Qi, Guohua Deng, Zejun Li, Xiurong Wang, Guobin Tian, Hualan Chen. Detection of Hong Kong 97-like H5N1 influenza viruses from eggs of Vietnamese waterfowl. Archives of Virology. 2006, 151: 1615-162439. Yu H, Shu Y, Hu S, Zhang H, Gao Z, Chen H, Dong J, Xu C, Zhang Y, Xiang N, Wang M, Guo Y, Cox N, Lim W, Li D, Wang Y, Yang W. The first confirmed human case of avian influenza A (H5N1) in Mainland China. Lancet. 2006, 7: 367(9504):84.40. Zejun Li, Hualan Chen, Peirong Jiao, Guohua Deng, Guobin Tian, Yanbing Li, Erich Hoffmann, Robert G. Webster, Yumiko Matsuoka, Kangzhen Yu. Molecular basis associated with replication of duck H5N1 influenza viruses in a mammalian mouse model. Journal of Virology, 2005, 79: 12058–1206441. Guobin Tian, Suhua Zhang, Yanbing Li, Zhigao Bu, Peihong Liu, Jinping Zhou, Chengjun Li, Jianzhong Shi, Kangzhen Yu, Hualan Chen. 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Murphy and Kanta Subbarao. Generation and characterization of a cold-adapted influenza A H9N2 reassortant as a live pandemic influenza vaccine candidate. Vaccine, 2003, 21(27-28): 4430-443649. Hualan Chen, Kanta Subbarao, David Swayne, Qi Chen, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka, Generation and evaluation of a high-growth reassortant H9N2 influenza A virus as a pandemic vaccine candidate. Vaccine 2003, 21(17): 1974-197950. Kanta Subbarao, Hualan Chen, David Swayne, Louise Mingay, Ervin Fodor, George Brownlee, Xiyan Xu, Xiuhua Lu, Jacqueline Katz, Nancy Cox and Yumiko Matsuoka. Evaluation of a genetically modified reassortant H5N1 influenza A virus vaccine candidate generated by plasmid-based reverse genetics. Virology, 2003, 1.Jan 5, 305(1): 192-200Book Chapters:1. Hualan Chen, Zhigao Bu, Jingfei Wang. Epidemiology and Control of H5N1 Avian Influenza in China. Klenk H-D, Matrosovich MN, Stech J (eds): Avian Influenza. Monogr Virol. 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