Highlights of Jian Zhou’s Life

Jing Zhou

Jian Zhou (1957-1999), a famous molecular biologist and virologist, has become a legend for his invention to the first cancer vaccine in the medical history. Jian was born in Hangzhou, China, in 1957. After finishing his secondary education, he was sent to work in a factory. In 1977 when China resumed the tertiary entrance examination, he was admitted to study medicine at Wenzhou Medical College where he obtained his MBBS degree. He then continued to study his Master’s degree at Zhejiang Medical University where he became interested in pathology. In 1985, he studied to pursue his Ph D degree at Henan Medical University where he became very interested in molecular biology and virology for human papillomavirus (HPV) and cancer research. In 1994, Jian was awarded with a degree of Doctor of Medicine by the University of Queensland. From 1987 to 1999, the year in which Jian’s own life was shortened by sudden illness, he held numerous research positions, from Postdoctoral Training Fellow, at Beijing Medical University, Beijing, China; Research Fellow of ICRF Tumour Virus Laboratory, Department of Pathology, University of Cambridge, UK; NHMRC Senior Research Officer, Centre for Immunology and Cancer Research, Department of Medicine, University of Queensland, Brisbane, Australia; Assistant Professor, Head of Papillomavirus Structure Protein Laboratory, Loyola University Medical School, Chicago, USA; Lions Principal Research Fellow & Head of the Papillomavirus Structure Protein Laboratory, Centre for Immunology and Cancer Research, Department of Medicine, Princess Alexandra Hospital, University of Queensland. From 1992 to 1999, Jian was granted with approximately twenty (20) research projects and eleven (11) patents. It is clear now that 99.8% of cervical cancer is caused by infection of HPVs, which are small DNA viruses. For decades, scientists, among whom are Jian and his wife Xiaoyi Sun, were working on this virus, but could not succeed in culture the virus in the laboratory. It was not until 1991 that Jian and his wife finally expressed the first HPV virus-like particle in their laboratory! This was a vital contribution to the success of today’s cervical cancer vaccine, the application of which has been suggested capable of wiping out the cervical cancer within a generation. However, in real life, Jian was more than just a biologist. In his honour, this collection of memoirs has recorded Jian as a dedicated scientist, a devoted son, a loving husband, a caring father and a faithful friend.

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Jing Zhou, Brisbane, Australia

周健生平
孙小依

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1957 年,出生于浙江杭州。 1982 年,毕业于浙江温州医学院获医学学士学位。 1984 年,毕业于浙江医科大学(现浙江大学)获病理硕士学位。 1985 年,考入河南医科大学病理系读博士, 致力于人乳头瘤病毒(简称 HPV)的研究。1987 年获理学博士学位。博士生期间得到北京病毒所的支持,开始在国际权威性学术刊物上发表 论文。科研成果获国家科技进步二等奖。 1988 年,进入北京医科大学(现北京大学)生化系博士后流动站做研究。其间赴位于剑桥大 学的帝国癌症研究基金会(ICRF)肿瘤与病毒实验室做研究工作。 1990 年,移民澳大利亚定居布里斯本。加入 Ian Frazer 领导的位于亚历山大公主医院的昆 士兰大学癌症研究中心继续 HPV 研究。 1991 年,率先用 DNA 重组技术人工体外合成了 HPV 病毒样颗粒。该颗粒就是癌症疫苗的基 础。1991 年 6 月,昆士兰大学为这项发明成果申请了专利。CSL、Merck 公司得到专利授权。

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1994 年,获昆士兰大学医学博士学位。同年到芝加哥 Loyola 医科大学任助理教授,仍继续 HPV 研究,任博士研究生导师。

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1996 年,回昆士兰大学医学系癌症免疫研究中心,任 Lions 主任研究员和 HPV 病毒学研究 室,担任博士研究生导师。至 1998 年,周健已经有近十项发明专利。同年,他获得 3 项澳大 利亚国家健康与医疗委员会(NHMRC)的研究经费,加上其他经费,成为当时昆士兰大学历史 上在一年内申请到经费最多的一位研究人员。周健还积极推动中国和澳大利亚两国之间学术 交流。

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1999 年 3 月,因长期超负荷的工作,过度疲劳,突发疾病去世,年仅 42 岁。追悼会挽联 “一世伟业真真切切科研巨擘 毕生勤奋坦坦荡荡学者楷模”是他的真实写照。

学士学位证书

硕士学位证书

中国博士学位证书

澳大利亚医学博士学位证书

A Brief Account of Dr. Jian Zhou’s Life
Xiaoyi Sun

In 1982, he graduated from Wenzhou Medical College with a degree of MBBS. In 1984, he was awarded with a Master Degree of Medical Pathology at Zhejiang Medical University (Currently Zhejiang University). He published two papers in an authoritative international scientific journal during that time.
In 1985, he commenced his PhD study at the Pathology Department of Henan Medical University and his major research interest was to study human papillomavirus (HPV), of which the infection is thought to be the major cause of the cervical cancer in women. He was awarded with a PhD Degree in Medicine in 1987. With the support from National Preventive Medicine Institute of Virology in China, he published a number of good papers in famous international Journals. His landmark work and achievements were reported by People’s Daily and Central People’s Broadcasting Station in China in February of 1987. He was granted with the second scientific advancement award of Chinese Government in that year.

In 1988, he joined in the Biochemistry Department of Beijing Medical University (currently Beijing University) as a post-doctoral fellow to carry out research in HPV field. His research papers written in English brought him to the prestigious Imperial Cancer Research Institute in Cambridge, England to continue his HPV study as a research fellow. In 1989, Jian’s creativity, broad and profound knowledge on HPV research attracted Professor Ian Frazer’s attention, who came from the University of Queensland in Australia on his sabbatical leave. Because of the common interest in the papillomavirus, Ian warmly invited Zhou to join his Centre for Immunology and Cancer Research at the University of Queensland and Jian moved to Australia in 1990. In 1991, he firstly generated HPV virus like particles (VLP) using DNA recombination technology, and made a remarkable achievement in the development of HPV vaccine. The landmark work was described in detail in the paper by Zhou and his wife and Ian Frazer published in Virology in that year. The University of Queensland applied a patent on the invention of HPV vaccine in June of 1991. This invention has been recognised as a significant achievement of human medical history. In 1994, he was awarded with the highest degree – Medical Doctorate by the University of Queensland. He took up an assistant professorship at Loyola Medical University in Chicago at the same year, and continued his HPV research while supervising PhD students there. In 1996, he returned to Brisbane to take the position of Lion Principle Research Fellow to chair HPV Structure Protein Laboratory at the Centre for Immunology and Cancer Research of the University of Queensland and supervised several PhD students. Up to 1998, he had around10 patents filed. He had three research projects funded by Australian Health and Medical Research Committee (NHMRC) in 1998. With the other seven funds – he was awarded as the highest fund researcher in the history of the University of Queensland in that year.

Meanwhile, he established close links to Wenzhou Medical University in China to improve the academic climate there, and acted as a bridge for academic exchange between Australia and China. It was the March of 1999 when the third-stage clinic trials were being undertaken, Jian went to China for a scientific visit. Jian tragically cut short his life at the age of 42 probably due to his tireless hard research work. It is very sadly he had not lived to reap the recognition and rewarded by the development of the vaccine for cervical cancer. To always remember Jian’s great contribution on medical research and human health, the Centre for Immunology and Cancer Research (Diamantina Institute) of the University of Queensland has had the annually Jian Zhou Lecture since he passed away. The world famous scientists are invited to give this named lecture. The lecture theatre in the Institute is named as Jian Zhou Forum. In the end of 2005, US Merck pharmaceutical company earnestly declared that the clinical trial of the cervical cancer vaccine was successful. This vaccine was put on market in 2006. More than 80 countries including USA, UK, Canada and Australia have approved to publically use the vaccine since then.

Since 2005, Professor Ian Frazer obtained many national and international awards because of co-invention of the cervical cancer vaccine, which included Australian of the Year, Florey Medal, shared prestigious William B Coley Awards with Germany scientist Prof. Harald zur Hausen, who first linked human papillomavirus to cervical cancer in the 1970s.

In 2007, Queensland government set up Dr Jian Zhou Smart State Fellowship for Immunology and Cancer Research to acknowledge and honour his landmark work and significant commitment to Queensland and Australian science.

In 2008, Queensland State Government, the Australian Chinese Foundation (ACF) and Chinese community organize the memorial service to commemorate Dr Jian Zhou at Queensland State Government Parliament House on 3rd of May, 2008 and publish a memorial book - Dr. Jian Zhou’s brilliant mind.

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Translator: Dr. Ruixuan Rong (PhD), Senior Research Fellow, Julius Kruttschnitt Mineral Research Centre, The University of Queensland, Australia

周健科研成就概述
孙小依

周健是世界著名的病毒学家和分子生物学家。他发明了世界首例预防癌症的疫苗——宫颈癌疫苗。该 疫苗由乳头瘤病毒样颗粒组成,能成功地预防宫颈癌的发生。2006 年,美国《时代杂志》将宫颈癌 疫苗的上市列为该年度世界十大医学成就之一。世界上包括美国、英国、加拿大和澳大利亚等在内的 80 多个国家批准使用该疫苗。 1977 年,周健考入温州医学院医学系学习并获得医学学士学位。大学毕业后,考入浙江医科大学攻 读硕士学位,开始研究人乳头瘤病毒并产生极大兴趣。1985 年,考入河南医科大学攻读病理学博士 学位,继续从事人乳头瘤病毒研究,期间到中国预防医学科学院病毒研究所学习分子病毒学、分子克 隆技术。在攻读硕士、博士阶段,周健研究人乳头瘤病毒感染和食道癌发生的关系获得了国家级奖 励。 1988 年博士毕业后,周健去北京医科大学做博士后研究。期间,他掌握了用痘苗病毒作载体,在体 外表达特定蛋白的技术,为其后来的重要发明打下了技术基础。周健在国际杂志上连续发表了他在攻 读硕士、博士期间的研究结果,引起了国际学术界的重视,同年他应邀去著名的英国剑桥大学帝国癌 症研究所肿瘤病毒实验室,在世界知名学者 Crawford 教授指导下继续从事乳头瘤病毒的分子生物学研 究。周健学习勤奋,工作努力,思维活跃,很快在普通病毒学、病毒学等国际著名杂志上发表了有影 响的论文,并对乳头瘤病毒的国际研究现状和发展方向有清晰的认识和了解。在剑桥,周健遇到了从 澳大利亚昆士兰大学去那里做学术休假的免疫学家 Ian Frazer。周健的勤奋、创造性的科研思路以及 他们对人乳头瘤病毒研究的共同兴趣,Ian Frazer 力邀周健来澳大利亚工作,共同进行该领域的科研 探索。1990 年,周健来到位于澳大利亚昆士兰首府布里斯本的昆士兰大学,翻开了他科研生涯中的 最重要的一页。 1991 年,在经历了多次实验后,周健利用重组 DNA 技术,以痘苗病毒作载体,成功地在体外表达了 乳头瘤病毒 L1 和 L2 衣壳蛋白。表达的衣壳蛋白能自行组装成病毒样颗粒。同年,周健和 Ian Frazer 将这一成果发表在 1991 年第 185 期的《病毒学》期刊上。1991 年 6 月,昆士兰大学为这项发明成果 申请了专利。当年 7 月,两人在美国西雅图举行的人乳头瘤病毒国际会议上报告了他们的实验结果。 这项成果被称为人类医学史上的一项重大突破。澳大利亚 CSL 生物制药公司、美国 Merck 生物制药公 司在得到专利授权后,进行了大规模的动物和人体临床实验,以验证人乳头瘤病毒样颗粒对预防宫颈 癌的临床效果。 此外,周健对乳头瘤病毒进行了多方面卓有成效的研究。他发现次要乳头瘤病毒衣壳蛋白 L2 在 DNA 结合和衣壳化方面的作用,表明其在 HPV 生命周期中的重要性。周健还发现,L1 蛋白的 C 末端不作 用于衣壳的形成。这个发现使得他利用由 C 末端截短型 L1 蛋白、和其它病毒早期蛋白的 T 细胞抗原 决定基构成的嵌合衣壳,制造出了兼具预防性和治疗性的疫苗。 周健于 1994 年获得昆士兰大学医学博士学位,其后去美国芝加哥 Loyola 大学医学院任助理教授,组 建了他自己的研究小组,并指导博士研究生。1996 年,周健返回昆士兰大学,被聘为 Lions 主任研 究员,在肿瘤和免疫学研究中心的乳头瘤病毒结构蛋白实验室任主任。在上世纪九十年代, 周健共 申请了十余项发明专利,并获得大量的研究经费。1998 年,周健获得了三项澳大利亚国家医学和健 康研究会科研项目的资助、一项美国医学卫生研究院科研项目、一项美国癌症基金会科研项目的资 助,加上其他科研项目的经费和专利费,他是那一年昆士兰大学有史以来获得经费资助最多的研究 员。 周健的另一项全新的研究是密码优化研究。他在这个研究中发现:HPV 衣壳基因不能在大多数哺乳动 物细胞中表达,但可以在酵母中表达,原因是哺乳动物细胞中的转移核糖核酸 (tRNA) 限制了衣壳蛋 白基因的表达。周健观察到,衣壳蛋白基因用了哺乳动物的稀有密码子,与它在受感染的终端分化皮

层可以有效地表达衣壳蛋白有着潜在的联系。这项技术可以用于提高蛋白质的表达效率,提高疫苗的 免疫原性,为基因治疗开辟新的途径。这是周健逝世前最后有划时代意义的一项研究。 一直以来,周健关心他的母校的发展,在母校温州医学院和澳大利亚大学之间的科研交流起到了桥梁 作用。1999 年 3 月,周健去中国进行学术访问,不幸得病,英年早逝,终年 42 岁,未能看到他发明 的疫苗可以成功地预防宫颈癌,给人类带来福祉。 为纪念周健对医学研究和人类健康的重大贡献,自他逝世后,昆士兰大学在周健生前工作的癌症和免 疫学研究中心,现在的 Diamantina 癌症免疫和代谢性疾病研究所设立每年一次的周健讲座,邀请世界 一流科学家来作演讲。该研究所还将其会议厅命名为周健会议厅。2000 年以来,在国际乳头瘤病毒 学大会上多次悼念周健。2005 年底,默克公司郑重地正式宣布,子宫颈癌疫苗临床试验成功。2006 年亚洲——大洋洲生殖感染和瘤形成研究组织(Asian-Oceania Research Organization on Genital Infection and Neoplasia, 简称 AOGIN) 的委员们一致同意在这两年一度的医学会议上设立以周健博士命名的最佳 演讲奖。2006 年昆士兰州政府设立一项以周健命名的“《智慧州》周健学者基金”,澳大利亚昆士 兰州政府及澳大利亚华人社团、澳大利亚-中国友好协会定于二 00 八年五月三日在昆士兰州议会大厅 联合举办 “周健博士纪念会”并出版《英才济苍生》周健博士纪念文集。 同时,Ian Frazer 教授因为共同发明宫颈癌疫苗获得了众多国际和国内大奖。这些奖项包括分享 2005 年美国癌症研究院杰出肿瘤免疫研究奖、2006 年美国癌症研究院 William Coley 金奖、2006 年度澳 大利亚杰出人物称号、2006 年度昆士兰杰出人物称号、2007 年国际生命科学奖、2007 年 Clunies Ross 金奖和 2007 年 Florey 金奖等。

Dr. Jian Zhou’s Major Patents
(not including the small one)

Xiaosong Liu
1. PAPILLOMA VIRUS VACCINE (WO 1993/002184). The University of Queensland. A method of providing papilloma virus like particles which may be used for diagnostic purposes or for incorporation in a vaccine for use in relation to infections caused by papilloma virus. The method includes an initial step of constructing one or more recombinant DNA molecules which each encode papilloma virus L1 protein or a combination of papilloma virus L1 protein and papilloma virus L2 protein followed by a further step of transecting a suitable host cell with one or more of the recombinant DNA molecules so that virus like particles (VLPs) are produced within the cell after expression of the L1 or combination of L1 and L2 proteins. The VLPs are also claimed per se as well as vaccines incorporating the VLPs. 2. METHOD AND POLYNUCLEOTIDES FOR DETERMINING TRANSLATIONAL EFFICIENCY OF A CODON (WO 2000/042215). The University of Queensland. A method is disclosed for determining the translational efficiency of an individual codon in a cell. The method comprises introducing into the cell a synthetic construct comprising a reporter polynucleotide fused in frame with a tandem repeat of said individual codon, wherein said reporter polynucleotide encodes a reporter protein, and wherein said synthetic construct is operably linked to a regulatory polynucleotide and measuring expression of said reporter protein in said cell to determine the translational efficiency of said codon. 3. POLYNUCLEOTIDE AND METHOD FOR SELECTIVELY EXPRESSING A PROTEIN IN A TARGET CELL OR TISSUE OF A PLANT (WO 2000/042190). The University of Queensland. A method is disclosed for constructing a synthetic polynucleotide from which a protein is selectively expressible in a target cell of a plant, relative to another cell of the plant. The method comprises selecting a first codon of a parent polynucleotide for replacement with a synonymous codon which has a higher translational efficiency in the target cell than in said other cell, and replacing said first codon with said synonymous codon to form said synthetic polynucleotide. 4. TREATMENT OF PAPILLOMAVIRUS INFECTIONS (WO 2000/035478). The University of Queensland. This invention relates to treatment of papillomavirus infections. Primarily there is provided a method of treatment of an existing papillomavirus (PV) infection which includes the step of administration of PV VLPs selected from the group consisting of PV L1 VLPs and PV L1/L2 VLPs to a patient suffering from the PV infection. Suitably the PV infection is characterised by the presence of epithelial lesions. The major infection which is treated are genital warts caused by HPV 6 and HPV 11. 5. PAPILLOMA VIRUS-LIKE PARTICLES, FUSION PROTEINS AND PROCESS FOR PRODUCING THE SAME (WO 1996/011272). Medigene Gesellschaft Fur Molekularbiologische Diagnostik, Thepaphie Und Technologie MBH

Recombinant papilloma virus-like particles result from the expression of viral structural proteins L1 and/or L2 in which one or several sections of the L1 and/or L2 protein are deleted. The ability to form virus-like particles is at least the same as, preferably higher than, that of native reproduction and/or in vitro production processes. 6. RECOMBINANT PAPILLOMA VIRUS L1 (WO 1995/031476). The University of Queensland. This invention relates to a recombinant papilloma virus L1 protein which can elicit an immune response which recognises papilloma virus VLP including L1 protein and can form extracellularly a multimeric structure or VLP wherein the multimeric structure comprises a plurality of recombinant papilloma virus L1 proteins. This invention also includes the use of the recombinant papilloma virus L1 protein to detect the presence of papilloma virus and can form the basis of a vaccine for prophylactic and therapeutic use. 7. MODIFIED PAPILLOMA VIRUS L2 PROTEIN AND VLPs FORMED THEREFROM (WO 1995/020659). The University of Queensland. The invention, in one aspect, is directed to a modified papilloma virus L2 protein which does not bind DNA or binds a substantially minimal amount of DNA. The invention is also directed to a method of producing one or more virus-like particles which incorporates a substantially minimal amount of DNA and the virus-like particles produced therefrom. 8. NEW AND USEFUL IMPROVEMENT IN THE CONSTRUCTION OF PAPILLOMAVIRUS HYBRID PARTICLES. September 28, 1994 and December 16, 1996 ,The Loyola Medical University of Chicago (i) the C.terminal deletion of HPV 16 as efficient for production of VLPs in insect cells (basis for GSK’s manufacturing process) and (ii) claiming the use of chimeric particles as combinatory (prophylactic and therapeutic) vaccine. 9. POLYNULEOTID AND METHOD. The University of Queensland.

10. CODON UTILIZATION. The University of Queensland. 11. NUCLEIC ACID SEQUENCE AND METHOD FOR SELECTIVELY EXPRESSING A PROTEIN IN A TARGET CEEL OR TISSUE. The University of Queensland 12. Jian has published more than forty articles in the authorised international Journal including two most significant articles as below: Zhou J., Sun XY., Stenzel DJ., and Frazer I: Expression of vaccinia recombinant HPV 16L1 and L2 in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology. 1991, 185:251-257. Zhou J., Liu W., Peng S., Sun X., and Frazer I.: Papillomavirus capsid protein expression level depends on the match cordon usage and tRNA availability. Journal of Virology, 1999.

周健的主要发明专利
刘晓松 赵孔南

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乳头瘤病毒疫苗( 乳头瘤病毒疫苗(WO1993/08)澳大利亚,昆士兰大学 )

提供乳头瘤病毒样颗粒的制备方法。乳头瘤病毒样颗粒可用于诊断,或用做预防乳头瘤病毒感染的疫 苗。发明包括购建表达乳头瘤病毒 L1 蛋白;L1 和 L2 蛋白的一个或多种重组 DNA 的方法;以及随后 用重组 DNA 转染宿主细胞;体外表达 L1 蛋白;L1 和 L2 蛋白;进而产生病毒样颗粒的方法。

2、 决定一个密码子翻译效率的多聚核苷酸和方法 、 决定一个密码子翻译效率的多聚核苷酸和方法(WO2000/042215)澳大利 亚,昆士兰大学
提供决定细胞内一单独密码子翻译效率的方法。发明包括将人工合成的多聚核苷酸倒入细胞内。该多 聚核苷酸由一报告多聚核苷酸和重复的单个密码子融合而成。通过测定报告多聚核苷酸的蛋白表达水 平可以得知某一个密码子的翻译效率。

3、 在植物细胞或组织选择性表达某一蛋白质的多聚核苷酸和方法 、 在植物细胞或组织选择性表达某一蛋白质的多聚核苷酸和方法(WO 2000/042190)澳大利亚,昆士兰大学
提供决定在植物特定细胞中表达蛋白质的多聚核苷酸构建的方法。通过优化密码子提高该蛋白质的表 达水平。

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乳头瘤病毒感染的治疗 (WO2000/035478)澳大利亚,昆士兰大学

本发明与乳头瘤病毒感染的治疗有关。用 L1 蛋白;L1 和 L2 蛋白形成的病毒样颗粒治疗已经感染乳 头瘤病毒的病人。

5、乳头瘤病毒样颗粒,融合蛋白和其合成过程。(WO1996/011272)Medigene 、乳头瘤病毒样颗粒,融合蛋白和其合成过程。 Gesellschaft Fur Molekularbiologische Diagnostik, Thepaphie Und Technologie MBH,德 国
由一个或几个部分被切除掉的 L1 蛋白,L1 和 L2 蛋白形成病毒样颗粒。这些一个或几个部分被切除 掉的 L1 蛋白,L1 和 L2 蛋白具有与野生型 L1 或/和 L2 形成病毒样颗粒相同或更高的效率。

6、 、

重组乳头瘤病毒 L1(WO1995/031476)澳大利亚,昆士兰大学

发明与重组乳头瘤病毒 L1 蛋白有关。L1 蛋白可产生识别乳头瘤病毒样颗粒的免疫反应,并可形成病 毒样颗粒。发明同时包括使用重组乳头瘤病毒 L1 检测乳头瘤病毒并且是组成预防和治疗乳头瘤病毒 感染的基础。

7、 改变的乳头瘤病毒 L2 蛋白和就此形成的病毒样颗粒 、 蛋白和就此形成的病毒样颗粒(WO1995/020659)澳大 利亚,昆士兰大学
发明一方面改变乳头瘤病毒 L2 蛋白,使其不或及少与 DNA 结合。另一方面提供形成不或及少与 DNA 结合的一种或多种病毒样颗粒。

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构建嵌合型乳头瘤病毒样颗粒 芝加哥 Loyola 大学医学院

C 端切除的乳头瘤病毒 16 型 L1 蛋白仍可在体外昆虫细胞中形成病毒样颗粒。使用嵌合型病毒样颗粒 作为预防和治疗性疫苗

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多聚核苷酸和方法 澳大利亚,昆士兰大学

10、密码子使用。澳大利亚,昆士兰大学 、密码子使用 11、核苷酸和在特定靶细胞或组织中表达蛋白质。澳大利亚,昆士兰大学 、核苷酸和在特定靶细胞或组织中表达蛋白质
周健博士在国际学术权威刊物上共发表四十余篇论文,其中两篇极具重要意义: 1. Zhou J., Sun XY., Stenzel DJ., and Frazer I: Expression of vaccinia recombinant HPV 16L1 and L2 in epithelial cells is sufficient for assembly of HPV virion-like particles. Virology. 1991, 185:251-257. 周健、孙小依、大维·斯蒂泽尔、伊恩弗雷泽:用痘苗病毒重组的人乳头瘤病毒 16 L1 和L2蛋

白在上皮细胞内表达足以形成乳头瘤病毒样颗粒。《病毒学杂志》
2. Zhou J., Liu W., Peng S., Sun X., and Frazer I.: Papillomavirus capsid protein expression level depends on the match cordon usage and tRNA availability. Journal of Virology, 1999.

周健、刘文军、彭世文、孙小依、伊恩·弗雷泽:乳头瘤病毒衣壳基因使用的密码子配合细胞 内可利用的 tRNA 以决定其蛋白的体外表达水平。 《病毒学杂志》

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刘晓松、赵孔南,澳大利亚昆士兰大学 Diamantina 癌症、免疫和代谢医学研究所 Diamantina Institute for Cancer, Immunology and Metabolic Medicine, the University of Queensland , at the Princess Alexandra Hospital, Australia

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UQ Researchers Develop New Gene Expression Technique
Published: 18 June 1999, UQ News

University of Queensland researchers have patented a simple yet elegant way to control gene expression with exciting possibilities for use in plant technology and in treating human disease. The method has the potential to work across all organisms, according to researchers in the Centre for Immunology and Cancer Research (CICR) in the Medicine Department at Princess Alexandra Hospital. "The technique could result in scientists being able to target the treatment of cancer cells without causing damage to normal cells," CICR director Professor Ian Frazer said. "It could also allow for pesticides to be expressed only in the parts of plants which are not eaten by humans." Gene expression is the expression of information in organisms to determine such physical characteristics as hair or eye colour, or resistance to disease. Professor Frazer said the new method, reported in the Journal of Virology, was a simpler alternative to the most popular techniques used today, which had largely been patented by multinational companies. "Each cell type has its own genetic code. It's always puzzled me that the current methods of regulating genes are sophisticated, work simultaneously and don't look as though they have evolved easily," he said. "This method doesn't require plants or animals to evolve early a complex mechanism for regulation of gene expression. It relies on the fact that genes are put together using some genetic codes which are redundant. It seems different cell types have preferences for using redundant code and assemble genes using preferred codes." The work results from a practical observation by CICR researcher the late Dr Jian Zhou three years ago while researching papillomaviruses. "Jian and I found that each cell contains particular molecules know as tRNAs, and if you matched genes to the different tRNAs you would achieve gene expression where you wanted it," Professor Frazer said. "The observation was serendipitous. It resulted in a set of data, which took some years of hard work, heated discussion and a set of experiments to expand into a theory and a method of putting it into practice." The technique has been further developed by Professor Frazer and more recently Dr Wen Jun Liu at the CICR. This method has been patented via UniQuest Pty Ltd, the University's technology transfer company. Professor Frazer discussed the technology with a number of interested biotechnology companies at the recent Bio99 meeting in Seattle.
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For further information, contact Professor Ian Frazer, telephone 07 3240 5315.

UQ Team Defeats Cervical Cancer
Jamie Walker
A revolutionary vaccine developed in Queensland has stunned the scientific world by proving almost totally effective in preventing cervical cancer. Professor Ian Frazer’s break-through vaccine is 100 per cent effective against the most common form of the virus that causes cervical cancer, according to final-stage trial results released yesterday. The University of Queensland researcher and his team are the toast of medical science amid predictions that the drug will pave the way for eradication of the disease. About 70 per cent of sexually active women in Australia are believed to have been exposed to the human papilloma virus, but the hope is that inoculation of prepubescent girls will deliver life-long protection. As well as making cervical cancer a scourge of the past, Professor Frazer’s vaccine could mean that women will need to undergo fewer invasive pap smear tests. Cervical cancer will kill at least 270 Australian women this year – 36 of them in Queensland. Speaking from New York, a delighted Professor Frazer, 52, said last night: “It is very rare, almost unheard of, to achieve a 100 per cent efficacy rate in any treatment, so these results are truly wonderful.” “It is the first time in the world that a vaccine designed to prevent cancer has been developed.” The Courier-Mail’s Qweekend magazine today traces Professor Frazer’s 20-year effort to develop the vaccine. He started work in a broom closet opening off a men’s toilet at Princess Alexandra Hospital and at one point mortgaged the family home to support his research. Shares in CSL Ltd, the Australian blood products and vaccine maker which holds the local marketing rights, surged yesterday on the announcement in New York of the phase III clinical trial results by pharmaceutical giant Merck & Co. Merck announced it would immediately apply for licensing to bring the drug to market under the name Gardasil. If approved, the vaccine could be on pharmacy shelves in the US, and subsequently Australia, next year.

The proving trial involved 25,000 women in 33 countries, half of whom were given Professor Frazer’s vaccine in three doses over six months. The rest received a dummy jab. Scientists say the vaccine was 100 per cent effective against the two types of the sexuallytransmitted HPV which cause 70 per cent of cervical cancers. Importantly, no significant side effects were reported among women who used the vaccine. Exports greeted the findings with scarcely concealed astonishment. “The results is absolutely fantastic, it will have enormous implications for women’s health around the world.” Queensland Cancer Fund Research Centre director Associate Professor Joanne Aitken said. Sydney-based Gynaecological oncologist Dr Gerry Wain described the breakthrough as monumental and “Nobel-prize-winning stuff.” Premier Peter Beattle said Professor Frazer was brilliant, adding: “Everyone should be very proud of him.” Professor Frazer and his PA Hospital-based team are now working with researchers in China to develop a version of the vaccine to treat existing disease. Yesterday he paid tribute to his late research collaborator, Dr. Jian Zhou, who died in 1999 before the project could come to fruition. “It is sad that he passed away before the work was publicly recognised.” Professor Frazer said.
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Reprinted from The Courier Mail on 8-9 October 2005

UQ Australian of the Year Will Continue Fight for Women’s Health
Fiona Kennedy Published: 25 January 2006, UQ News

Professor Ian Frazer and Dr Jian Zhou Professor Ian Frazer will use his profile as Australian of the Year to help ensure his cancer vaccine reaches those who need it most – women and girls living in poverty. Professor Frazer, of The University of Queensland, is a humble recipient of the nation's top honour. “It's a marvellous honour, especially as I follow in the footsteps of distinguished medical scientists who are recent Australians of the Year, including Professor Peter Doherty, Sir Gus Nossal and Professor Fiona Wood,” Professor Frazer said. “Gus, Fiona and I all chose to be Australians and to make this country the cradle of research that aims to improve the lives of millions of people. "My late co-inventor, Dr Jian Zhou, also chose to be an Australian citizen and it saddens me that I cannot share this award with him. “It's a great privilege to be recognised by Australia as the 2006 Australian of the Year. “But it's an even greater privilege to be able to do something tangible for the health of Australian women, and for women throughout the world,” Professor Frazer said. Professor Frazer and Dr Jian Zhou made a discovery at UQ more than 15 years ago that has led to the development of a vaccine for cervical cancer. The vaccine, known as Gardasil™ and Cervarix™, is expected to become available in the developed world in mid-2006. Dr Jian Zhou's life was tragically cut short at the age of 42 in 1999, before he could share in the joy of seeing the vaccine brought to market. He was a principal research fellow at UQ's Centre for Immunology and Cancer Research. "We will remember Jian's propensity for tireless hard work and his engaging sense of humour," said Professor Frazer. He was also named a 2005 Australian of the Year by The Australian on January 21, 2006. Professor Frazer said Australia and other developed nations had effective Pap smear programs to reduce the incidence of cervical cancer. “Despite this, cervical cancer continues to be a shocking disease for women in the developed world. “Women living in poverty in the developing world, where Pap smears are not widely available, account for most of the 250,000 deaths from cervical cancer each year. “So this vaccine has the potential to do most good in the developing world, where it could help lift women out of poverty by relieving the burden of disease.

“Women in China, Jian's birthplace, will be some of the greatest beneficiaries of the vaccine. “I feel I have a responsibility to ensure that they and other women in developing countries have affordable access to the vaccine that he helped develop.” Professor Frazer is working with the Gates Foundation and is a consultant to the World Health Organisation's Expanded Vaccine Initiative, with the aim of delivering the drug as cheaply as possible in the developing world. He welcomed the fact that both companies producing the vaccine had indicated that they would introduce a differential pricing structure so developing countries could get the vaccine at a cheaper price. “However ‘cheaper' does not necessarily mean it will be affordable in poor nations,” Professor Frazer said. “I intend to keep a close eye on the global distribution of the vaccine, with the aim of it being available to the women and girls who most need it.” UQ's Acting Vice-Chancellor Professor Paul Greenfield congratulated Professor Frazer on his award and praised his intention to apply it for the good of women worldwide. “UQ is honoured to have Ian Frazer working with us as Director of the Centre for Immunology and Cancer Research. “He demonstrates beautifully how long-term, meticulous research can lead to remarkable developments for human health. “Ian has never lost the focus of his work's potential to help others. “Throughout his outstanding career he has put his personal interests on the backburner – and that quality alone makes him worthy of the title ‘Australian of the Year',” Professor Greenfield said.

Legacy of Quiet Achievement
Newspaper reporter: Jamie Walker
THE name Jian Zhou isn't one you'd probably recognise. Chances are, Ian Frazer's is. The Brisbane immunologist was made 2006 Australian of the Year for developing a break-through vaccine for cervical cancer and this week, he unveiled a new treatment that could one day eradicate the killer disease. What's tended to be overlooked, though, is Dr Zhou's role in this saga of scientific achievement. The jovial, Chinese-born researcher was Professor Frazer's right hand in the laboratory, the co-inventor of the cancer vaccine, his friend and confidante. Yet he would not live to reap the recognition and rewards that have been heaped on Professor Frazer. Dr Zhou died in the saddest of circumstances in 1999, aged just 42, just as all that work they had done together was about to pay off in a way that was bigger than almost anyone could have imagined. Only now has Dr Zhou's family spoken out about his contribution - one that has always been fully acknowledged by his research partner, but which nevertheless slipped beneath the radar of public awareness as the limelight glimmered on Professor Frazer. In doing so, Dr Zhou's widow, Xiao Yi Sun, 49, says she is delighted for the success Frazer is enjoying. He proved a kind friend and “good boss” to her husband. The two families remain close. ``We share in his happiness''. Dr Sun says, with her son, Andreas, 19, at her side. But as she points out - and as Professor Frazer agrees - there would be no cervical cancer vaccine without Dr Zhou. ``We want people to remember Jian, also,'' says Sun, a well-credentialed medical researcher in her own right. ``He didn't win the award, but as Ian himself says, Jian was absolutely critical to the development of the vaccine. We would like people to know that.'' Andreas tells The Courier-Mail: “Ian has always mentioned my father as much as he possibly can ... but because my father has passed away, and obviously he can't be here with Ian, his work has not been recognised as much.'' It was Dr Zhou, after all, who made the key discovery that opened the way for the world-first cancer vaccine. At the time he and Frazer teamed up in the late 1980s, there was growing awareness of the potential to use immunotherapy against the human papilloma virus (HPV), which causes cervical and some other forms of cancer, as well as sexually-transmitted genital warts. The race was on. The problem for researchers was that HPV could not be grown in the lab, and it was impractical to collect sufficient quantities of live tissue to produce a vaccine by conventional means. So Zhou came up with the concept of the synthetic virus-like particle. Like the best ideas, it was breathtakingly simple: he would replicate the protein shell of the virus, minus its harmful core, to stir up the body's defenses and neutralise the infection. In practice, the task turned out to be mind-numbingly complicated. Dr Sun assisted her husband as he experimented with the molecular sequencing and various protein combinations. But in 1991, they finally got the mix right. A delighted Professor Frazer would later say they had ``green fingers'' - everything seemed to work in their hands. Still, it would take another 14 years of clinical trials, corporate wheeling and dealing and court cases to get the vaccine to where it is now, on the verge of being licensed in the US and subsequently Australia. Frazer drove the process with relentless energy. As Zhou put in 80-hour weeks in the lab, he ran from meeting to meeting, simultaneously managing the research effort and the increasingly complex business side with

Australia's CSL Ltd and US pharmaceutical giant Merke and Co, which had collaborated to bring the vaccine to market. US investment house Citigroup Smith Barney estimates that it will generate revenues of up to $5.8 billion over the next five years. ``Ian and Jian were a team ... they both had the same view, they had the same passion,'' Sun said. She had met her husband at Wenzhou Medical College in southern China. Both were children of the Cultural Revolution and had had their schooling disrupted by that decade of chaos between 1966 and 1976. After enduring a year of labouring on farms and factories, Dr Zhou emerged with a degree in medicine. His masters and PhD followed. But unlike many Chinese academics of the day, he published in English, which brought him to the attention of the prestigious Imperial Cancer research Institute in Cambridge, England. Frazer pitched up there on sabbatical in 1989. Scottish-born, he had been in Brisbane since 1985 and had identified HPV as a promising area of research, mainly because so little was known about the virus. He and Dr Zhou hit it off immediately. Professor Frazer would appropriate lab space and chemicals from his new friend's lab - ``he recognised in me an entrepreneurial streak with which he empathised''. It would take another year, but Frazer eventually prevailed on the University of Queensland to sponsor Dr Zhou out to Brisbane. The rest is scientific history. In four years, he wrote 11 scientific papers, including the landmark one with his wife and Professor Frazer detailing the break-through with virus-like particles. Dr Zhou took up an associate professorship at Chicago's Loyola University in 1995, but was lured back to Brisbane by Professor Frazer within two years. By then, he was reforging links with his old school in China, Wenzhou. On February 7, as Sun looked on, Frazer announced a joint clinical trial between his research staff in Brisbane and those in Wenzhou of a spin-off application to treat genital warts. The cancer drug expected to be licensed in Australia later this year is prophylactic, meaning it will protect only those women who have not already been exposed to HPV, which is thought to be just 30 per cent of sexually active women in Australia. But if the genital warts application works, there's every reason to think the vaccine could be further tweaked to treat existing cases of cervical cancer. While incidence of the disease is declining in developed countries such as Australia - thanks largely to preventative screening - it remains a leading killer of women in the developing world. Professor Frazer said a vaccine which both prevented and treated HPV-related infections could save millions of lives. In March 1999, as Dr Zhou was travelling in China, something he loved to do, his health suddenly deteriorated. He had been complaining of tiredness, but had otherwise been his usual cheerful self, putting in too many hours at the laboratory, of course, as he signed off on a round of research grant proposals. The cause of death was found to be septic shock. Sun says it has taken all these years for her to bear to speak publicly of his death. But she and Andreas want people to know what he achieved, to understand how much others will benefit from his work. And they draw pride and comfort in equal measure from Frazer's tribute to his late friend and colleague: Zhou packed more into the 10 years they had known one another than most scientists achieve in a lifetime, the Australian of the Year said.

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Jamie Walker and Andreas Zhou

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Reprinted from The Courier Mail. Feb 18-19 2006

无名英雄造福千秋 名英雄造福千秋
Jamie Walker

您可能没听说过周健这个名字,但一定知道依恩佛瑞瑟是谁。这位居住在澳大利亚布理斯班市的 免疫学专家,因子宫颈癌疫苗这个医学史上突破性的发明,荣获 2006 年度澳大利亚杰出人物的光荣称 号。本星期他公布了一种新的治疗方法,有望最终彻底根除这种致命的疾病。 然而,常常被人忽略了的,是周健博士在这个科学传奇中的重要作用。这位在中国出生的热情爽 朗的科学家,是佛瑞瑟教授科学实验中的左膀右臂,癌症疫苗的共同发明者,是他推心置腹的好友。但 周博士没有活到亲眼看见佛瑞瑟教授今天受到的公认和奖励。1999 年,正当他们多年的辛勤努力即将 获得无法想像的巨大回报之前夕,42 岁英年的周博士突然病逝,令人震惊伤痛。 他们俩一起发明了宫颈癌疫苗,此举将布里斯班作为世界医学研究中心之一载入世界版图。本星 期,佛瑞瑟教授宣布:子宫颈癌疫苗的研究进一步推广至临床试验治疗传染的猖獗性病尖锐湿疣。紧接 着,布里斯班的其他科学家也详细说明了他们正在研究预防前列腺癌症和疟疾的疫苗。 时至今日,他的家人才第一次向世人公开谈论他的贡献。尽管周博士的研究合作者始终充分肯定 他的贡献,然而当公众的目光如巨大的光环紧紧围绕着佛瑞瑟教授的时候,周博士渐渐被人们淡忘了. 谈起周博士时,他的遗孀,今年 49 岁的孙小依医生说,她为佛瑞瑟教授的成功而高兴。佛瑞瑟教授 是一个善良的朋友,她丈夫的“好老板”,“我们分享依恩的快乐,”她对记者说,她和周博士的儿子周 子晞也在一旁。 她同时指出:正如佛瑞瑟教授始终强调的——没有周健奇迹般的工作,就不会有子宫颈癌疫苗。 “我们希望人们也记得周健,”孙医生说,她自己也是一位出色的医学研究人员。 “他没有得到奖励。但正如依恩所说,周健在此疫苗的发明中,发挥了绝对关键的作用。我们希望 大家了解这一点。” 坐在她身边的儿子周子晞告诉记者,“尽管佛瑞瑟教授随时都尽可能提到我父亲,但因为爸爸不 在了,教授的身边再看不见他,他的贡献因而没有得到应有的公认。” 事实上,正是周健博士的关键发明,打开了通向这个有史以来世界上第一个癌症疫苗的大门。 上世纪八十年代末,当周博士和佛瑞瑟教授开始携手合作时,医学界已有越来越多的人开始注意到 运用免疫学来对付人乳头瘤病毒(HPV)的可能性。HPV 病毒引发子宫颈癌和一些其他癌症,以及由性行 为传染的尖锐湿疣。 为探索这个可能性,科研的攻关开始了。这项科研最大的问题是 HPV 病毒无法在实验室里得到培 养,而要按照传统方法收集足够的活组织来进一步研究和制造疫苗又不可能。 这时周健博士提出了人工合成类病毒微粒的设想。这个绝妙设想的原理很简单:他用病毒的晚期 蛋白质在体外人工合成病毒样颗粒。除去它有害的核心只有病毒的外壳,以此来激发体内的防疫功能 并中和感染。但实行起来, 却是异常复杂。在孙医生的协助下,周博士做了无数次实验。终于在 1991 年,他们成功了。兴高采烈的佛瑞瑟教授称赞他们夫妇俩有“神奇的手指”,这两双手似乎什么都能培 育出来。 打那以后,又过了漫长的十四年,经历了临床试验、商业谈判、法庭裁决等等,才走到今天,疫苗 终于即将在美国和澳大利亚先后上市了。 佛瑞瑟教授为推动这个进程作了不遗余力的努力。那段时期,周博士每星期在实验室工作超过八 十个小时,而佛瑞瑟教授则同时掌管研究和越来越复杂的商业谈判。他马不停蹄地从一个会议赶到另 一个会议,同澳大利亚的 CSL 公司和美国的药物巨头默克公司谈判,协力将疫苗推上市场。 美国的花旗斯密思巴尼投资公司预期:在未来五年内,该疫苗将产生 58 亿美金的收益。 “依恩和周健是一个团队。他俩有一样的观点,一样的工作激情,”孙医生说。 她和她丈夫当年是中国南方的温州医学院的同学,同属中国文化大革命中成长的那一代人。他们 的正常学校教育在 1966 年到 1976 年的那场大动乱中被中断了。在被送到农场和工厂劳动二年以后,

周健考入大学,先后在中国取得了医学学士、硕士和博士学位,并获澳洲昆士兰大学的医学博士学 位。但和当时大多数的中国学者不同,他用英语发表论文。而这些论文很快就引起了英国着名的剑桥 大学帝国癌症研究所的重视。1988 年,周健到剑桥大学帝国癌症研究所做研究员。 1989 年,佛瑞瑟教授利用他的大学休假年也到了那儿。在苏格兰出生的他,从 1985 年起就在布理 斯班工作,并确定 HPV 病毒作为他的研究方向,原因是当时医学界对此知之甚少。他和周博士一见如 故。他常到这位新朋友那儿,使用他的实验室和试剂。“他说从我身上看到了一些企业家的特质,这 是他十分看重的。” 佛瑞瑟教授花了一年的时间,说服昆士兰大学赞助周博士全家来到布理斯班。以后的事便是众所 周知的了。在四年的时间里,周健发表了十一篇科研论文, 包括那篇由他、他太太和佛瑞瑟教授共同 署名的详细论述类病毒微粒这个突破性发明的界标性的论文。1995 年,周博士接受了芝加哥鲁由拉大 学助教授的职位. 但两年后又受佛瑞瑟教授的邀请重返布理斯班。这时,他已同他在中国温州的母校 建立了联系。 今年二月七日, 在孙医生也出席的一个会议上,佛瑞瑟教授宣布了将由布里斯班和温州的研究人 员共同展开的一项临床试验:将子宫颈癌疫苗扩展用于尖锐湿疣的治疗。今年内,子宫颈癌疫苗将作为 预防性药品在澳大利亚上市。就是说,它仅为那些从未与 HPV 病毒有过接触的妇女提供预防,然而这些 人在有经常性性行为的妇女中只占了 30%。 如果临床试验证明用该疫苗治疗尖锐湿疣有效,那么则完全有理由相信该疫苗也可用于治疗已罹 患的子宫颈癌症。在发达国家,由于广泛采取了预防性检查,子宫颈癌的发病率正在降低。然而在发展 中国家,它依然是妇女的一个主要杀手。佛瑞瑟教授说,一个既能预防又能治疗子宫颈癌的疫苗, 将能 挽救几百万条生命。 周博士经常回中国访问。1999 年 3 月,他像往常一样踏上了回国之路。但是他的健康突然崩溃。 在那之前一段时间,他就常常感觉疲劳。但他依然兴致勃勃地每天在实验室工作到深夜,走之前还赶完 了研究基金的申请报告。 他辞世的病因确诊为因感染性休克。孙医生说, 这么多年后她才能面对公众谈起他的去世。她说, 她和儿子希望人们了解周健的成就,知道多少人会因他的工作而得救。 佛瑞瑟教授对他昔日好友兼同事的评价也让孙医生母子深感骄傲和欣慰。这位澳大利亚杰出人物 荣誉的获得者说:周博士在他们认识的十年当中所作的贡献,超过了大多数科学家一辈子的成就。 原载 2006 年 2 月 18 日“The Courier Mail”日报
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翻译:蓝湘,澳大利亚布里斯本

A Simple Idea
Louise Williams

Flying back into Australia recently, it suddenly hit Professor Ian Frazer that his life really had changed. Here, perhaps, was a chance to bask in a moment of hard-earned glory after decades of solid backroom work. So he put his characteristic humility to one side. And instead of filling in “medical researcher” under profession on his landing card, he carefully wrote out “Australian of the Year”. “No-one even noticed,” he laughs, recalling how an immigration clerk processed his documents and nodded him through without a second glance. Such is the modest public profile of a man now standing on the brink of medical history. Frazer’s cervical cancer vaccine was approved in June for use in Australia and the US. Other countries are expected to follow suit and, as a result, the next generation of women around the world may well dismiss the human papillomavirus (HPV) as a scourge from a bygone age, just as we take for granted the end of polio. Until now, this common sexually transmitted virus – which can go on to cause cervical cancer – has killed some 250,000 women a year. Cervical cancer is the only human cancer yet proven to be caused entirely by a virus. And Frazer’s vaccine, developed with his late research partner, Dr Jian Zhou, makes it possible for us to wipe it out. Professor Peter Doherty, an Australian Nobel laureate who made one of last century’s most significant medical discoveries in physiology and immunology, says that in a world of daily headline claims and hype, Frazer’s work truly can be called a breakthrough – one that surprised even the scientific community, because it works so well. “Ian has made an incredible contribution to human wellbeing,” he says. Growing up in the cold, smoggy cities of Edinburgh and Aberdeen, Scotland, in the late 1950s, Ian Frazer plus a chemistry set equalled an explosive combination. His father was a professor of medicine; his mother had a PhD in science. Little wonder that by early primary school, Frazer had decided he wanted to be a physicist. Then, when he was about nine, he remembers lining up with schoolmates for their polio vaccinations. “The needle got my attention,” he says – which is where most kids are happy to leave it. “Then, I realised there were [crippled] kids around who had had polio. That got me interested in how the body fights infection … how the body repairs itself.” Frazer studied medicine at university, graduating in 1977. From there, the young Scot with a brilliant eye for detail could have walked into a research job at Cambridge University. Instead, he had figured that much of the best work in immunology was coming out of the Walter and Eliza Hall Institute of Medical Research in Melbourne. He’d spent several months as an intern there in 1974 and liked the laid-back Aussie lifestyle, so he emigrated. “In retrospect, it was a risky strategy,” says the immunologist, now 53. But he also had a deliberate plan. A strange new illness was brewing. Frazer began working on liver diseases linked to hepatitis B in gay men. And when an US researcher dropped by the institute and mentioned a mysterious immunity problem among gay men in the US, Frazer realised his patients had a similar problem, later recognised as HIV-AIDS. Frazer also noticed his patients were commonly afflicted with genital warts caused by the human papillomavirus. HPV wasn’t just a nuisance; the warts seemed to be associated with abnormal cells that were on their way to becoming cancer. To link a virus to cancer was contentious. At that time, only one other scientist, German virologist Harald zur Hausen, had linked HPV in women to cervical cancer. But Frazer was convinced this needed further

investigation. Research grants were easier to find in Queensland, and with his wife Caroline, whom he had met while at university in Scotland, and their two children (with a third on the way), he moved to Brisbane and was soon running his own lab at the Princess Alexandra Hospital, the University of Queensland’s teaching hospital. The relaxed, friendly environment was some compensation for the long hours Frazer spent on his medical research. Then, in 1989, he was offered the chance to go and spend some time in Cambridge on a sabbatical. It was an academic’s dream, and once more Frazer and his family were unpacking suitcases in a new location. It wasn’t long, however, before the Frazers realised their Australian dollar savings converted to too few British pounds. In just such a precarious financial situation were a Chinese couple, Dr Jian Zhou and his wife and assistant Dr Xiao-Yi Sun, toiling long hours in the lab next door. And as they talked, they connected – a Scottish immigrant and a young Chinese molecular biologist who’d survived the proletariat farm and factory labour of the Cultural Revolution. “We just traded off each other. I could see what he was trying to do, and what I was trying to do was very similar,” says Frazer of their common interest in the papillomavirus. But for Zhou, a talented virologist, the interest was in the behaviour and characteristics of the virus itself. As an immunologist, Frazer was working on how the human body responded to it. It was a perfect scientific match. Zhou and Sun explained to Frazer that they were looking for the opportunity to advance our careers and work with leading international scientists, whether that be in the UK, US, Germany or Australia. “I encouraged Jian to think about Australia. And everyone else at Cambridge egged him on,” Frazer says. In the end, it took a few months for Frazer to get the papers necessary to get the two researchers to Brisbane and to clear some space in Frazer’s lab. It would be many more long months before the couple’s son, Andreas and mother finally came to Australia to join the family. The lab partnership, meanwhile, thrived. In March 1991, six months after they began working together in Brisbane, the team was stunned by the results of an experiment. Unlike most other viruses, the papillomavirus cannot be grown in a test tube; it grows only on intact, living skin. But to create a vaccine, they needed something that so closely resembled the real virus that the body would be tricked into recognising it and – as with all vaccines – trigger a mild immune response that it could quickly draw on if it ever had to deal with a serious attack. When the group examined the electron microscope photographs of their tests to combine two proteins, they spotted virus-like particles and they realised they’d managed to mimic the “coat” of the real virus; it was the building block they needed to create their revolutionary vaccine. “We’d cracked it. I don’t think any of us doubted for a moment that we had done it. We got very excited, but then we weren’t sure we should tell other people,” says Frazer. It wasn’t, he explains, “exactly a champagne moment”. They realised there was so much work still to be done. As it turned out, it was two more years before the vaccine was turned over to the Melbourne-based biopharmaceutical company CSL Limited, and another 13 years before the general public would see the benefit of the team’s work. The biggest regret Frazer has now is that Zhou’s sudden death in 1999, from a septic shock during a trip to China, means he can’t share the success with his partner of so many years. But the work is continuing. With a carbon copy of the papillomavirus in a test tube, Frazer has been able to conduct previously impossible tests on how it works. And now his lab is chasing down the next vaccine: one that can be used to treat someone who already has the virus in her system. What advice does Frazer have to other medical researchers to keep believing in what they’re doing? “The art in science is to make sure you are trying to answer answerable questions,” he says. “I tell my students, don’t go into science if you want to be famous.”

And indeed it’s been a very long, uncertain road, 20 years at least since the first germ of an idea to a vaccine. But now Frazer’s discovery is the stuff of history, not mere celebrity. And that’s far more durable than a brief glance of recognition at the immigration counter. How the vaccine will change our lives In the not-too-distant future, girls are likely to be vaccinated against cervical cancer as infants, and the HPV vaccine will be just another of the cocktails protecting our children from previously common and very often devastating diseases. The virus There are about 30 types of sexually transmitted HPVs, but most are harmless. About 30% of women will get a high-risk HPV during their lifetime, usually between the ages of 18 and 25. In most women, their immune system kicks in to fight it and it disappears. That means a positive test for HPV does not necessarily put a woman at future cancer risk. Only about one in 50 women remain chronically infected and it is this group that may progress to cancer. The cancer Once a woman is infected, the papillomavirus gets inside a cell and triggers it to multiply, usually causing harmless warts. However, the cell multiplication can go wrong, says Frazer, causing a cancerous growth that ultimately overwhelms the virus because it kills its host. The jab It is best if girls get the vaccine before they are sexually active. At this stage, health experts are recommending vaccination between the ages of 9 and 12. This is when the immune response is strongest, making the vaccine most effective. The costs Gardasil (CSL’s trade name for the vaccine) costs around $460 for a course of three injections on private prescription. Health authorities are currently assessing it for inclusion on the national immunisation programme, which means it could be available free of charge to Australian girls as early as the end of this year. Adult women For those already exposed to HPV, the best defence is still regular Pap smears to pick up abnormal cells while they can still be treated. This screening test has proved itself to be very effective at saving lives in developed countries. Regular testing can prevent the most common form of cervical cancer in up to 90% of cases. Where the vaccine promises to save hundreds of thousands of women is in nations that don’t have the infrastructure for screening and where cervical cancer is usually well advanced by the time it is diagnosed. Frazer says vaccine manufacturers have promised to provide differential pricing; that is to supply the drug at lower, affordable prices to developing markets. Should everyone vaccinate their daughters? Yes, he says, but he also believes it shouldn’t be compulsory. The winding road to success 1983: Harald zur Hausen publishes a paper that links HPV and cervical cancer. 1984: Ian Frazer and Gabrielle Medley at the Walter and Eliza Hall Institute discover that anal HPV infection can become cancerous in immune-suppressed men. Findings published in The Lancet in 1987. 1989: Frazer meets Jian Zhou at Cambridge and they begin work on an HPV vaccine.

1991: Jian Zhou and Xiao-Yi Sun combine two virus proteins, forming the virus-like particles (VLPs) needed for an HPV vaccine. Zhou and Frazer show their VLPs boost immunity to HPV. 1994: Uniquest licenses the Frazer/Zhou VLP vaccine patents to CSL and Merck. 1995: Publication of the first tests of VLP vaccine on dogs and rabbits. 1997-1998: Frazer and Zhou successfully perform one of the first human HPV vaccine trials. 2001-2005: 12,000 women across 13 countries are tested in a pivotal (HPV VLP) vaccine trial. All vaccinated women show immunity to four types of HPV, including the two strains (16 and 18) responsible for 70% of cervical cancers. June 2006: US and Australian authorities approve the first HPV vaccine. The future: Frazer’s technology will be used to develop second-generation vaccines likely to protect against 8-10 types of HPV, preventing 95% of cervical cancers and removing the need for Pap smears.

Last Updated: 2006-08-27
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Reprinted from Reader’s Digest (Health Smart) August 2006

一个简单的设想开辟了一个新天地
路易丝・威廉斯 (Louise Williams)

子宫颈癌疫苗发明者之一 子宫颈癌疫苗发明者之一 发明者之 最近, 伊恩·弗雷泽教授飞回到澳大利亚,他突然意识到,他的生活真的发生了变化。此刻也许是该 享受一下因数十年艰辛的实验室工作所赢得来之不易的荣誉之时。因此,他放下了天生的谦虚。而没 有在他的登陆卡片上的行业一栏填写"医学研究员", 他认真地填上了“年度澳大利亚杰出人物”的称 号。“没人注意此事,”他笑着说, 回忆移民官怎么处理了他的文件, 点头示意他通过, 并没有多看他 一眼。 这就是一个现在正站在医学研究历史前沿的人的经历。六月份,宫颈癌疫苗在澳大利亚和美国被 批准使用。其它国家予料将对此作出同样的反应。结果,全世界的下一代妇女在未来可以免除人乳头 状瘤病毒(HPV)的痛苦,正如我们消灭小儿麻痹症一样。 直到现在, 这种过去通常被认为经性行为而传播的病毒能导致宫颈癌,一年导致大约 250,000 名 妇女死亡。现代研究证明,宫颈癌是由病毒造成的。弗雷泽和已故的周健博士共同研制的疫苗, 有可 能彻底消灭宫颈癌。 澳大利亚诺贝尔奖获得者彼得・道贺提(Peter Doherty)教授, 曾在上个世纪的生理和免疫学方面 做出了极为突出的贡献。他说,在全世界每日新闻的标题中, 弗雷泽和周健的工作可真正地称为突破性 的研究,甚至使科学界震惊, 因为这个疫苗的成效卓著。“伊恩和周健做了对人类健康难以估量的贡 献,”他赞赏道。 伊恩・弗雷泽在五十年代晚期,生长在苏格兰的爱丁堡(Edinburgh)和阿伯丁(Aberdeen)冷雾 蒙蒙的城市。少年时他曾设计了一个相当于爆破组合的化学装置。他的父亲是医学教授; 母亲获得过 科学博士学位。在刚上小学时, 弗雷泽想成为物理学家。 大约九岁时,他记得有一次与同学一起排队接种小儿麻痹症疫苗。“针头引起了我的注意,”他说,“这 是多数孩子想远离的东西。然而,我发觉在我们周围有患小儿麻痹症的残疾孩子,从而使我对身体如 何与传染病毒博斗以及身体又如何自我修复感到兴趣。” 弗雷泽在大学里攻读医学,一九七七年毕业。这位年轻的苏格兰人具有一双聪慧的眼睛, 对事物观 察入微,有机会进入剑桥大学这座科学圣殿做研究工作。然而,他考虑到,在免疫学方面许多最领先的工 作是由在墨尔本的沃尔特和伊莱扎·霍尔(Walter and Eliza Hall)医学研究所做出来的。一九七四年他 作为实习生在那里度过了几个月,他喜欢澳大利亚轻松的生活方式,因此他移居到了澳大利亚。“回想起 来,这是一个冒险的决定,”五十三岁的免疫学家说。 当时,一种奇怪的新病症正在传播。弗雷泽开始从事有关同性恋者肝脏病与乙型肝炎的研究。当 一个美国研究人员提出同性恋者的奇怪免疫问题,弗雷泽觉得他的患者具有一个相似的问题,这种病以 后被确认为是爱兹病。 弗雷泽注意到他的一些患者深受人乳头状瘤病毒引起的尖锐湿疣困扰。这种疣似乎也与演变成为 癌症的异常细胞密切相关。 病毒与癌症的联系引起学术界的争论。那时, 只有一位科学家,即德国病毒学家 Harald zur Hausen, 将宫颈癌与妇女人乳头状瘤病毒联系在一起。但弗雷泽确信这有必要作进一步深入的调查研究。 弗雷泽和在苏格兰上大学时结识了妻子卡罗琳(Caroline),二人生有两个孩子。由于在昆士兰较 容易获得研究经费,全家就搬到了布里斯班。他在亚历山德拉(Alexandra)公主医院, 也就是昆士兰大 学的教学医院从事研究, 并很快地建立了自己的实验室。轻松、友好的工作环境促进了弗雷泽的医学 研究。然后, 一九八九年他又获得机会去剑桥大学做学术休假。

这个机会是每个研究人员所梦寐以求的。在剑桥,他遇到了一对中国夫妇——周健博士和他的妻 子兼助理孙小依医生,他们在隔壁实验室里努力工作,经常起早摸黑,弗雷泽说。通过相互间的交 流,把一位苏格兰移民和一位年轻的中国分子生物学家联系在了一起。周健经历了中国无产阶级文化 大革命,并在工厂从事过体力工作。 “我发现他的研究目标和我的非常相似。”弗雷泽说他们都对人乳头状瘤病毒感兴趣。周健, 一 位才华出众的病毒学家, 其兴趣是在病毒的行为和特征。而作为免疫学者, 弗雷泽则关心人体对它的反 应。他们的结合是一种完美的科学匹配。 周博士和孙医生正在寻找发展研究工作的机会。“无论是在英国、美国、德国或澳大利亚,争取 和处于国际领先地位的科学家一起工作。”孙女士说。 “我力邀周健去澳大利亚,”弗雷泽回忆着。最后,花费几个月的时间, 弗雷泽备齐到必要的文件, 使两位研究人员来到布里斯班, 并在弗雷泽的实验室为他们提供相应的研究空间。晚些时候,周健的 妈妈带着这对夫妇的儿子 Andreas 到澳洲和他的父母相聚。 与此同时,实验室的合作初见成效。一九九一年三月, 也就是周健到达布里斯班六个月之后, 在他 们共同努力下, 研究小组被一组实验结果震惊了。 不同于多数其它病毒,人乳头状瘤病毒无法在试管里生存; 不能单独进行繁殖,必须寄生在活细胞 内。从理论上讲,既然某种疾病是由病毒感染导致的,那么就可能发明一种针对这种疾病的疫苗。通 常情况下,疫苗都是按这样的思路制作的——通过改造或弱化某种病毒,让它丧失引发疾病的能力但 却能激发身体的免疫系统并产生抗体。这样,当真正的病毒侵犯时,免疫系统就可以用已有的抗体来 对付这种病毒。 这是周建和孙小依散步时,周健的一个简单的主意。将二种蛋白质混合在一起,让它们在体外合 成病毒样颗粒。在电子显微镜下检查时, 他们发现了病毒样颗粒。他们惊喜万分。他们制造了真正病 毒的“外壳”。也就是说,他们在体外合成了空壳病毒。这就是他们为制造疫苗所跨出的革命性的一 步。 “我们制成了疫苗。我不认为任何人会怀疑我们成功地制作了疫苗。我们确实非常激动, 但另一 方面我们需要更多的试验。”弗雷泽说。那时,他确切地解释道,“还不是庆功的时候”。他们知道仍 然有非常多的工作要做。 结果是,用了两年时间将疫苗移交给位于墨尔本的 CSL 生物制药公司,又过了十三年, 公众才看到 这个小组的研究成果。 弗雷泽最大的遗憾是,一九九九年,周健在去中国访问时不幸去世。因此,他无法与多年的工作伙 伴分享成功。 但是工作还要继续。拥有了合成的病毒样颗粒,弗雷泽可以做从前无法实现的实验,做病毒的功 能测试。现在,他的实验室正在研制下一个疫苗:一个用来治疗已经罹患宫颈癌病症妇女的疫苗。 弗雷泽是如何使其他医学研究人员相信他们所做的一切呢?“科学的艺术就是在设法解答一个又 一个问题。”他说:“我告诉我的学生,如果你要想出名,就不要从事科学。” 的确,这是漫长的岁月,不确定的道路,从疫苗的最初设想到成功用了至少二十年时间。弗雷泽 的研究发现已经成为历史的里程碑,还不仅仅是出名而已。 这项研究对我们的生活的将产生怎样的影响? 这项研究对我们的生活的将产生怎样的影响? 在不远的将来,少女可接种宫颈癌疫苗,这种疫苗将保护我们的孩子免患这种致命的疾病。 走向成功的 走向成功的曲折道路 1983:Harald zur Hausen 发表了一篇论文,将人乳头状瘤病毒与子宫颈癌连系起来。 1984:伊恩·弗雷泽和加布利·梅德利(Gabrielle Medley)在 Walter and Eliza Hall 医学研究所发现,在 免疫系统受到抑制的男人身上,人乳头状瘤病毒在肛门的传染有可能变为癌症。这个发现发表在 1987 年的 Lancet 杂志上。 1989:弗雷泽在剑桥遇到周健,并开始人乳头状瘤病毒疫苗的研究工作。 1991:周健和孙小依发明了用二种人乳头状瘤病毒的外壳蛋白在体外合成病毒样颗粒(VLPs)。用 VLP 制作成宫颈癌疫苗。学术界有人称“周颗粒”。周健和弗雷泽证明了这种疫苗对人乳头状瘤病毒 的感染有免疫力。

1994:昆士兰大学的 Uniquest 公司将弗雷泽和周健的 VLPs 疫苗专利部分出售给了 CSL 和 Merck 医药 公司。 1995:发表了 VLP 疫苗对狗和兔子的首次实验结果。 1997-1998:弗雷泽和周健成功地进行了首次人乳头状瘤病毒疫苗的试验。 2001-2005:对遍布十三个国家的一万两千名妇女进行了关键性的人乳头状瘤病毒疫苗临床试验。所 有被接种疫苗的妇女都显示了对四种人乳头状瘤病毒的免疫性,其中包括导致百分之七十子宫颈癌的 两个型别(HPV16 和 HPV18 型)的病毒。 2006 年 6 月:美国和澳大利亚的药管部门批准了子宫颈癌疫苗的使用。 将来:弗雷泽的技术将被用来进一步开发第二代疫苗,它有可能抑制八到十个型别的人乳头状瘤病 毒,从而可以预防百分之九十五的子宫颈癌,并有可能屏弃现在通用的宫颈涂片检查。 原载 Reader’s Digest, August 2006

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中文翻译:谭斌, 澳大利亚布里斯本

Job Against Cancer
The Courier Mail August 29, 2006

Newspaper Health reporter: Jeff Sommerfeld

Medical breakthrough…Prof. Ian Frazer delivers first dose of Gardsail to Rachel McMillan, 15.

“Today we are making medical history. It is a great moment for science in this country” Anna Bligh said. (The current Premier of Queensland) Teenagers Rachel and Emma McMillan put on brave smiles yesterday as Australian of the Year Professor Ian Frazer prepared to make them the first Australians vaccinated against cervical cancer. Rachel's eyes gave away her discomfort, turning skyward as the 15 year-old gritted her teeth and tried to smile through the vaccination. A nervous Emma, 13, followed her older sister, but seemed to cope better maintaining a polite smile as she got jabbed in the shoulder. The history-making Gardasil vaccinations were the end of a 16-year journey for Professor Frazer and his team to bring the world's first and only cervical cancer vaccine on to the market. Professor Frazer yesterday acknowledged the breakthrough would not have been possible without his former colleague, Dr Jian Zhou, who died six years ago, aged 42. State Development Minister Anna Bligh also acknowledged the groundbreaking work of Dr Zhou, announcing a $450,000, three-year medical fellowship to commemorate his work. The State Government will contribute $100,000 a year for three years, matched by a $50,000-a-year commitment from Gardasil's manufacturer, CSL Ltd. "It is designed to encourage the brightest and best to stay here in Queensland and hopefully work on the next Gardasil," she said.

Ms Bligh said the world-first vaccine was "the result of a very strong team effort". "Today we are making medical history. It is a great moment for science in this country." Professor Frazer said nearly 100 per cent of cervical cancers are caused by the human papillomavirus (HPV) and clinical trials of Gardasil have found it 100 per cent effective. The vaccine prevents four of dozens of strains of the HPV which causes genital warts and cervical cancer. Professor Frazer said the development of the vaccine would not have been possible without more than 25,000 women world-wide who helped in the trials "to make sure this vaccine works". "I look forward to a world where cervical cancer will no longer kill," he said. Professor Frazer said:"This is not a substitute for pap smears – it is an adjunct."

人类抗癌的辉煌成就
邮报健康部记者:捷夫· 邮报健康部记者:捷夫·苏墨费德i

在见证人类历史上第一支抗癌疫苗注射的激动人心的那一刻,昆士兰州发展局局长(现昆州州 长)安娜。布莱说 “今天我们正在书写医学历史的新篇章。这是我国科学界的一个伟大的时刻。” 今天我们正在书写医学历史的新篇章。这是我国科学界的一个伟大的时刻。 澳大利亚年度杰出人物伊恩.弗雷泽教授给瑞頙·麦克密兰和她的妹妹艾玛·麦克密兰注射go宫 颈癌疫苗(HPV疫苗),她们笑脸相迎,非常勇敢。她们是第一批接受HPV疫苗接种的澳大利亚人。 15岁的瑞頙咬着牙接受注射,其仰视的目光 或许流露出一点儿不适,但一脸笑容。 她的妹妹艾 玛有些紧张,但没有显示出注射时有什么不适,一直笑得很自然。 HPV疫苗嘎德赛(Gardasil)是世界历史上第一个,也是唯一的一个抗子宫颈癌疫苗。它是 Frazer教授和他的团队16年努力探索的结晶。 弗雷泽教授昨日表示,如果没有周健博士的贡献这项历史性突破是无法完成的。周健博士于7年 前去世,享年 42岁。 昆士兰州发展局局长(现昆州州长)安娜。布莱宣布了一项三年45万澳元的已周健命名的医学研 究基金以纪念周健博士的杰出贡献。昆州政府将每年拨款 10万澳元连续三年。而嘎德赛的生产商CSL 公司也将每年赞助 5万澳元。“这是为了鼓励那些有才华之士在昆州创造出下一个嘎德赛”,她说。 布莱女士说抗宫颈癌疫苗的问世是团队努力的结果。 “今天我们正在书写医学历史的新篇章。这是我国科学界的一个伟大的时刻。” 弗雷泽教授说几乎100%的子宫颈癌由人乳头瘤病毒(HPV)所致,而临床试验实验显示嘎德赛的 有效率为100%。 该疫苗能预防十多种导致生殖道疣和子宫颈癌的HPV病毒中的4种。 弗雷泽教授说全球共有 2万5千多名女性参与了临床试验以验证该疫苗的效果。没有她们的帮 助,疫苗的研制成功是不可能的。 “我期待一个没有致命的子宫颈癌的世界,”他说。 弗雷泽教授说:“疫苗不是来替代帕氏宫颈涂片 ,其是作为一种佐剂来预防宫颈癌的。”

载于昆士兰邮报 2006 年八月二十九日

i

中文翻译:景全胜,澳大利亚布里斯本玛塔医院小儿科医师

Winner Hails Late Partner
Graham Lloyd

Australian of the Year Ian Frazer has paid tribute to his partner in the discovery of the cervical cancer vaccine for which has been recognised, Chinese Australian Jian Zhou. Professor Frazer said Dr. Zhou was “an equal partner” in the research and was responsible for discovery of the virus-like particle which led to the medical breakthrough. Dr. Zhou passed away in March 1999 on a visit to China. His wife Xiao Yi and son Andreas joined Professor Frazer at an official lunch yesterday to celebrate the Australian of the Year award. After the lunch, Professor Frazer said it was appropriate that Dr. Zhou’s contribution be properly recognised.

The Courier Mail on 28-29 January, 2006

God’s Gift to Women
Newspaper reporter: Mark Whittaker

Australian of the Year Ian Frazer wouldn’t even have been in this country but for a telegram landing on his Edinburgh doormat in 1980. It was from Ian Mackay, head of the clinical research unit at the Walter and Eliza Hall Institute in Melbourne. “We were expecting you last week,” the missive read. “Why aren’t you here?” This was something of a surprise to the Scotsman, who had done a couple of months’ work experience at the institute six years earlier. As he had left, Mackay said to him: ”When you’re finished your clinician training, we’ll expect to see you back here.” Frazer thought it was a nice thing to say, but didn’t think much about it as the next six years of his medical studies unfolded back in Scotland. “I was highly impressed with him,” recalls Mackay. He was very personable and very likeable; he just had that feeling of potential you’re always looking for, so I wrote him the letter. Turns out Mackay was a good judge. A quarter of a century later, his protégé stands on the brink of making medical history. In fact, he’s already made a fair chunk of it. Thanks to a vaccine discovered by the 53-year-old immunologist and his team, young women are about to have their risk of cervical cancer reduced by 70 percent and, ultimately 90 percent. Frazer’s efforts have already taken him to Australian of the Year status. Next stop, a Nobel Prize? The Mackay letter wasn’t the only twist of fate in Frazer’s glittering career. Perhaps even more crucial was his chance meeting with a pair of Chinese researchers at Cambridge University in 1989. The couple was effectively stateless, having had their travel documents revoked during the turmoil of Tiananmen Square. They needed a home and to be reunited with their four-year-old son, who was still in China. Frazer intervened on their behalf, an action that would lead to an enduring friendship and a collaboration that proved crucial to cracking the mysteries of cervical cancer. Tragically, it ended with the premature death of one of his research partners, Jian Zhou. Whatever plaudits and riches – expected to be in the billions – that eventually flow from Frazer’s vaccine, Ian won’t be forgotten. Says the award-winning medico of his late collaborator and friend: “He lives on in many areas.” There are about 30 types of sexually transmitted human papillomavirus (wart virus). Most of them are harmless, but some types can lead to cancer. About 30 percent of women will get a high-risk HPV some time in their life, usually between the ages of 18 and 25. On average they have it for about a year and a half. But some can’t shake it.

“If you are still got it after five years, chances are you won’t get rid of it,” says Frazer, “and if you’ve still got it then, you’ve got a significant chance of getting cervical cancer.” That is no certainty – a lot of people are chronically infected for life and don’t develop cancer – but about 20 percent of the people still infected after five years will go on to get a cancer. “That may take up to 30 years to happen,” says Frazer. Of course, none of this was figuring in Frazer’s thinking when he received the fateful telegram from Mackay in 1980. Back then he was planning to head off to Cambridge University to start a PhD. Suddenly, he had a decision to make. He opted for Melbourne. Why? “Because all that was good in immunology in those days was coming out of the Hall Institute,” he says. “If you look back at the papers on immunology in the ‘70s and early ‘80s, all the classic stuff was coming out of the Hall Institute. It was breaking off in chunks’, as they used to say in those days. I thought it would be a good place to learn.” Back then, the institute was run by another future Australian of the Year (2000), Sir Gustav Nossal. He recalls Frazer as “a delightful person who was almost incomprehensible because of his broad Scottish accent. He was a first-class clinician, a very astute person and, though his position at that time was relatively junior, we all admired and liked him very much.” If Frazer’s move from Edinburgh to Melbourne was a fateful fork in the road, another was to follow soon after he arrived. In 1981, an American immunologist whose name now escapes him dropped in for tea and a chat at his Melbourne lab and mentioned that a mystery illness in Boston and San Francisco was afflicting males who had sex with men. Frazer had been working with a cohort of gay men, looking at liver diseases in hepatitis B sufferers, so he thought he’d check his patients for this mysterious immunity problem. “Lo and behold, they had the same problem being described in Boston,” recalls Frazer. It was an epiphany for Frazer, who realised he was playing on the world stage, and that he had to think about the whole field and not just his specific job with his patients, or his mice in a lab. When the mysterious virus was eventually isolated and a diagnostic test developed in 1984, Frazer was part of the team that was able to confirm that a lot of his Melbourne cohort had what we now call HIV/AIDS. What these immune-suppressed men also had were a lot of anogenital warts. As a budding immunologist, Frazer wanted to find out about these warts and the human papillomavirus that caused them. So when he and his colleagues discovered that these men’s anal warts were associated with a lot of abnormal cells on their way to becoming cancer cells, it was published in the premier medical journal, The Lancet, and created quite a stir. At that time, the only link between wart virus and cancer was that a German immunologist, Harold zur Hausen, had just isolated wart virus in cervical cancer lesions. ‘It was still very contentious as to whether the virus had anything to do with cancer or not,” says Frazer. “There was a smoking gun in that rabbit papillomavirus had been associated with skin cancers in rabbits 50 or 60 years earlier. But that was pretty much it until then.

The concept that any virus caused cancer was still very much disputed.” So Frazer started thinking about how the immune system dealt with this virus. And why was it that his immune-suppressed men were getting cancer when others mostly did not? But there were more road forks before he would get to attack that question. The first took him to Queensland in 1985 after 5 years at the Walter and Elisa Hall Institute. The move prompted jokes over tea and scones in Melbourne that it was improving the IQ of both states. Mackay, the man who’d brought Frazer to Melbourne, was more pensive. “I was wondering what would become of him and I think he was wondering the same thing. Some people have big parties and then they’re gone. But this wasn’t like that.” It was not just that Frazer was going to the research backwaters of Queensland. He wasn’t even going to the main research centre there, the Queensland Institute of Medical Research. He was setting up a whole new unit at the Princess Alexandra Hospital, Brisbane. Mackay thought Frazer would get bogged down fighting for equipment and space. Sure, his lab was a broom closet, but in Queensland in 1985 there was less competition for grants and that was important for a young researcher having to catch and kill his own funding for the first time. AIDS was the apocalypse of the moment, but he couldn’t take his AIDS work with him. It was too competitive a field and the disease wasn’t big enough up north. The papillomavirus, however, was a relatively unexplored niche. The usual method of creating a vaccine is to grow large amounts of virus, render it harmless, and then give it to a person so their immune system can learn to recognise the foreign intruder. The reason no one had been able to do this for wart viruses was that they couldn’t be grown in test tubes. Frazer started to look at other approaches, but was always hindered by the fact that he couldn’t grow the virus and therefore couldn’t test his ideas to see if they worked. In 1989, he went on sabbatical to Cambridge University and the lab of the world leader in papillomavirus, Professor Margaret Stanley. He spent six months there and got to know a post-doc from China who was working in the lab next door, Jian Zhou. No matter what time of day or night Frazer turned up at the lab, it seemed that Jian and his wife Dr Xiao-Yi Sun were in there working. Being on sabbatical, Frazer had time to drink tea and chat the gregarious Jian about his work. And despite the Chinese man’s poor English, he was able to tell Frazer about a genetic engineering technique he was using – inserting virus genes into cells and using them to grow viral proteins. Frazer immediately saw the potential for working with Jian, using human skin cells to engineer an entire synthetic papillomavirus, but there was a problem: Jian’s lack of a passport. The Chinese man’s journey to Cambridge had been a difficult one. He hadn’t started university until he was 21 because of the Cultural Revolution – during which he had been packed off to labour on farms and in a factory. It was as if he were now trying to squeeze as much as he could into his life. His wife Xiao-Yi Sun, had few years in countryside. “Ian went to huge efforts and he got them visas to Australia,” recall Stanley. “It says a lot about Ian. If anything should come over in your article it’s that Ian is an extremely kind man.”

Frazer says his efforts were equal parts humanitarian and scientific. “The thing that impressed me and really motivated me to do something was that he and his wife were outside China but his son was inside China. There was no way they were going to meet up again unless we could get them somewhere to stay where they’d be allowed to have their son…but also Jian was a friend. He needed help. He was a good colleague scientifically and we could do good things together. He had the talent and the interest to do things that would work well with us. “It’s often the way when you choose people. You want people who will fit in scientifically and also be friends. It’s easier to work with friends. He was very outgoing, larger than life.” Frazer says he never doubted his new colleague would be successful, adding: “He had a very broad vision of where he was going with his work and what the future had in store for him.” Frazer had the same sense of density and purpose growing up as one of three sons of a medical professor father in Aberdeen. He says he had wanted to be an immunologist from the time he was at high school. He was part of the first generation to be given polio shots. He knew kids who had contracted polio and suffered partial paralysis as a result. “I was just interested in how the body dealt with infection. I don’t know, a curious mind, I guess.” His mother Marion, a PhD in electron microscopy, came out to join their son in Australia in the 1990s and is now retired with Frazer’s father, Sam, in Noosa. She remembers young Ian as an inquisitive child, always fiddling with locks and keys, who was later dux of his school. “We knew he was bright, we knew he was interested in a whole lot of things, but immunology? Well, I am not sure about that.” Frazer met his wife Caroline, at university. He was the “bus convener’ on the ski club bus and she was a first-year student on her first ski club trip to Aviemore in the mountains west of Aberdeen. “I think he did every job in the ski club,” says Caroline. “A very keen skier, we both are. The bus convener was in charge for the weekend and he liked being in charge.” From the outset, Frazer made clear to Caroline the difficulties of being married to a doctor. When he came to Australia for his two months of work experience in 1974, she worked as an unqualified nurse to get a feel for what a hospital was like. “He wanted me to understand the long hours and I had to be accepting of that because that’s what it needed. Whether it was medicine or now science, it’s never really changed. He’s always worked long hours, weekends, and nights. Something needs to be done at two in the morning, you go in and tweak your cells or whatever you have to do.” Caroline, who teaches children, with learning difficulties in state schools, says there is nothing of the absent-minded professor about her husband. “He’d like to give the impression occasionally, but he’s very businesslike. He makes lots of lists. He’s very organised, uses time very efficiently. He doesn’t care much for formalities. Likes nothing better than being in shorts and T-shirt, or his swimming togs or on his bike.” Like Caroline Frazer, Xiao-Yi Sun knew what it was like to be married to a committed scientist. Jian Zhou had been late for their wedding because he was in his lab tending his experiments.

It took nine months for Frazer to get the couple to Australia, but they were corresponding the whole time about their research plans, so they hit the ground running. The idea was to insert the DNA for the papillomavirus’s outer coating into another virus – the vaccinia virus, used to immunise against smallpox – which could infect skin cells. It was hoped that once in a skin cell, it would produce the wart virus coating. With a meticulous eye for detail, Xiao-Yi could grow anything in the lab. And indeed, she managed to grow something, but when they looked at it through the electron microscope, they found themselves starting at amorphous blobs of protein. After months they were increasingly despondent. They’d heard on the grapevine that some international competitors were getting similarly disappointing results. It would have been easy to give up, but they decided to keep trying for another six months. At the time, Frazer had been forced to go to farms and syringe out huge warts on cows as the only way of getting hold of large amounts of wart virus to work with. Xiao-Yi remembers taking a walk with her husband one night after putting their son, Andreas, to bed. Jian suggested they should just combine two virus proteins in a test tube. Xiao-Yi thought it sounded too simple. If it could be done that way, surely someone would have figured it out by now. As his assistant, she was meant to write down his ideas and carry them out in the lab, but two weeks later when he asked her how it had gone, she had to tell him she hadn’t done it. He insisted they try. Then she, her husband and Frazer trotted off to the University of Queensland to look at the results under an electron microscope. And there it was, protein forming into the shape of the virus’s outer shell. It was as close to a eureka moment as they got. “It was quite amazing,” recalls Frazer. “Because we’d seen so many negative ones, we were getting kind of used to seeing blank pictures and then just chucking them in the bucket.” After so many failures, they could now get on to building a whole virus. And they also knew that if the human immune system could recognise these empty virus shells, it might be enough to create an immunity. No vaccine had ever been made this way before, although there was a hepatitis B vaccine at a similarly experimental stage. But it seemed like a good chance. They put out a scientific paper in a few days, rushed it to a journal and used it as a provisional patent. “We didn’t go into the papilloma work with a view to making money,” says Frazer. “We took out a provisional patent because something I learnt was that you couldn’t get a commercial company interested unless you could protect the intellectual property. Like it or lump it, if you’re going to get a product out there in the market to be useful to anybody, you will need a commercial partner prepared to invest that billion dollars up front. “When I started, I thought the hard part was to make the vaccine, the actual material, but the hard part is to get the commercial process for making the vaccine and the harder thing still will be to educate the general public and the medical profession about this vaccine. Because it’s not intuitively something that people think about – a virus that causes cancer.

People know about Pap smears and cervical cancer but they don’t associate that with an infection.” After the vaccine had jumped through the initial safety and efficacy hoops, 12,000 women from 13 countries were tested in the final study that began in 2001. The US regulators needed to see evidence that this vaccine not only prevented infection by the wart virus but also prevented pre-cancerous changes to the cells, because the infection alone is not a disease. Most people catch it and get rid of it and never know. Half the 12,000 women were on a placebo. After two years, 21 had developed precancerous cells, a much higher rate than anticipated. The previous thinking had been that it took considerably longer for the virus to cause these changes. None of the 6000 women on the vaccine developed any pre-cancerous changes. In Australia, there are more than 1000 cases of cervical cancer a year, about 300 of which are fatal. Frazer’s vaccine protects against the two HPVs that cause 70 percent of them. More strains of HPV will be added as the vaccine, Gardasil, is updated, so that it will eventually protect against 90 per cent of cancers. Gardasil’s manufacturer, Australia’s CSL, hopes it will be passed by Therapeutic Goods Administration mid-year and be available by July. The company hopes to put it to the Pharmaceutical Benefits Advisory Committee in November. Without listing on the Pharmaceutical Benefits Scheme it would cost $300 to $400. CSL is looking at a school-based program to immunise girls. Tragically, Jian Zhou wasn’t there to see all this. In 1999, he had gone to China on business feeling unwell, thinking he might pick up some Chinese herbal medicines while he was there. He spoke to Xiao-Yi one night on the phone and said he felt sick. Next day she got a call from a hospital saying he was sick and about to die. The official verdict was sepsis – poisoning from a bacterial invasion of the body or tissues. But it’s a diagnosis Xiao-Yi isn’t happy with. “I still don’t know for sure what he died of,’ she says. Frazer has continued his work solo and most recently developed a “therapeutic vaccine” to help women who already have papillomavirus. The drug, which is about to begin human trials in Australia and China – at Jane’s old university – is designed to stimulate the immune system to produce “killer cells” that identify and hunt down cells infected with papillomavirus. Before the therapeutic vaccine trials were announced, Frazer said there had been a lot of spectacular failures in that area. “But if we can crack it for papillomavirus as a seed for other potential therapeutic vaccines for melanoma or hepatitis C, then we’ll be 80 per cent of the way to cracking it for them all. Cancer is different but the chronic infections should all crumble together.” Indeed, it may again start breaking off in chunks. In the meantime, despite the accolades and the wealth, Frazer continues to cycle to work each day, 14 km along the Brisbane River. He started using the bike when he was 40 and realised that if he was going to keep up on the ski field with his three kids – now all in their early twenties – he had to work for it. He didn’t have time to exercise otherwise. And although he’s gone, Frazer regularly reflects on his research partner Jian Zhou. Their families remain close. “In fact,” says Jian’s widow Xiao-Yi, “we are one family.” She confides that after Jian’s death, Frazer helped her financially. And while her husband never

lived to see his work come to commercial fruition, she and Frazer split the royalties. But more than that, they will be remembered as a ground-breaking partnership. Says Xiao-Yi: “They were the best team ever.”

The Weekend Australian Magazine on 4-5 March 2006

UQ Vice-Chancellor Welcomes Vaccine Funding For Australian Girls
Fiona Kennedy
Published: 29 November 2006, UQ News

Vice-Chancellor Professor Hay University of Queensland Vice-Chancellor, Professor John Hay, AC, has welcomed the Australian Government's decision to fund the delivery of a UQ-invented cancer vaccine to Australian school girls. Professor Hay congratulated the Prime Minister, John Howard, and the Health Minister, Tony Abbott, for committing $436 million to begin funding the vaccine's distribution next year. “This is an invaluable investment by the government in the health of Australian women,” Professor Hay said. “The vaccine is proven to prevent cervical cancer, so it will deliver enormous benefits in terms of the health and welfare of Australian women and families, as well as savings to the economy.” Professor Ian Frazer, the Director of UQ's Centre for Immunology and Cancer Research, and his late colleague Dr Jian Zhou, invented the vaccine, Gardasil®, in a UQ laboratory more than 15 years ago. Professor Frazer's role in the vaccine's development earned him the title of 2006 Australian of the Year. The government announced today that Gardasil® will be delivered to school girls aged 12 and 13 as part of the National Immunisation Programme from 2007. The spending of $436 million over three years will also fund a two-year school-based catch-up programme for girls and young women aged between 13 and 18 years. The vaccine will be available through GPs to women aged 18 to 26. Phase III clinical trials involving more than 25,000 women in 33 countries proved the vaccine's efficacy, and it has been approved in the United States.

Second Cancer Vaccine Welcomed
Fiona Kennedy
Published: 14 August 2007, UQ News

The co-inventor of the world's first cervical cancer vaccine and 2006 Australian of the Year, Professor Ian Frazer, has welcomed the availability of a second cervical cancer vaccine. Professor Ian Frazer, who is Director of UQ's Diamantina Institute for Cancer, Immunology and Metabolic Medicine, said: “I am pleased that a further vaccine has become available in Australia to help in the battle against cervical cancer, based on the virus-like particle technology the late Dr Jian Zhou and I developed in Australia in the 1990s. "Vaccination, together with regular pap smears, will be a woman's best defence against cervical cancer in the future. “Both vaccines now available are based on the same virus like particle technology, and both protect against the two HPV types most commonly associated with cervical cancer. Each vaccine has been proven safe and effective in clinical trials."

Fiona Kennedy and Andreas Zhou

食道癌病毒的首次发现,是当今医学界的一则重大新闻,发现者是谁?是一位浙江籍博士研究 生,人们赞他是————

“无名高峰”的征服者 无名高峰”
原载《浙江日报》1987 年 3 月 23 日 王道坤

今年 2 月 2 日清晨,中央人民广播电台在新闻联播里播出一条引起人们关注的新闻:正在河南医 学院攻读博士研究生的周健,首次发现食道癌病毒——人类乳头状病毒瘤是致癌原因。消息引起轰 动。专家们认为:这一发现为食道癌病因研究提供了一个新方向,对于进一步研究食道癌的防治具有 重要意义。 周健是杭州人,今年刚到而立之年。四年前,他从温州医学院毕业后,考取浙江医科大学硕士研 究生,1985 年又考取博士研究生。这一年,他的《铅对肺泡巨噬细胞影响》的研究成果,曾引起国 内外医学界的瞩目;今年,他成果再出。当人们纷纷向他祝贺时,他慷慨地说:“我是幸运的!” 对此,有人感到不解。可周健说的是由衷之言。他庆幸我们国家有安定团结的局面,庆幸自己受 党的培养,能有机会为振兴中华贡献自己的力量! 周健出身在杭州一个干部家庭。十年动乱,家庭遭难,学业受阻。这段岁月,在他心灵留下很深 的印痕,使得他格外珍惜党和人民给自己创造的学习机会。考上浙江医科大学硕士研究生后,他跟随 徐英含教授着手“病理学”铅污染专业的研究。周健搞研究有一股韧劲,实验室 8 点上班,6 点半他 必定出现在实验室;器皿的擦洗规定,每天 30 遍,他就一遍不少地擦洗 30 遍。他是在攻读硕士研究 生的第二年结婚的。结婚那天,亲友早早地等着喝他的喜酒,可他像往常一样,在实验室里呆到很晚 才回家,第二天清晨又早早地出现在实验室。他不能中断他的实验,细菌的培养换代比什么都重要。 刻苦的钻研终于结出丰硕的果实。

在食管癌组织中检出乳头状瘤病毒 在食管癌组织中检出乳头状瘤病毒
这一发现对食管癌的病因研究及防治有重要意义 这一发现对食管癌的病因研究及防治有重要意义
原载《健康报》 1987 年 2 月 19 日
本报讯(驻地记者 时仲省)河南医科大学病理学教授沈琼的博士研究生周健、陈全录,采用目前最 本报讯 灵敏的检测技术,于年前在食管癌组织中首次测出人类乳头状瘤病毒。 人类乳头状瘤病毒(HPV)是一种 DNA 病毒,能造成肌体许多部位如皮肤、喉、气管、膀胱、生 殖器等的感染,但多系良性病变,如皮肤的疣或粘膜的湿疣。近年来,人们发现这种病毒的某些类型 在体外和体内试验中具有致癌性,而且在人类的皮肤癌和宫颈癌研究中已得到证实。但多年来人们在 食管癌标本中尚未找到可靠的病毒颗粒。 周健、陈全录在沈琼导师指导下,收集检测了大量的食管癌活体标本。在中国预防医学科学院病 毒研究所谷淑燕和曾毅教授帮助下,对 90 例标本进行食管癌组织的 DNA 提取、分离和纯化检测。在 其中 25 例标本中发现了人类乳头状瘤病毒。这 25 例中,除一例为食管癌下段腺癌外,其余 24 例全 为鳞癌。 专家们认为,在食管癌组织中检测出人类乳头状瘤病毒基因,为食管癌病因研究提供了一个新的 方向,对于进一步研究食管癌的防治癌具有重要意义。

我国两青年首次发现食道癌病毒 人类乳头状瘤病毒是致癌原因
原载《人民日报》 1987 年 2 月 2 日

新华社郑州电 河南医科大学博士研究生周健、陈全录,最近在食道癌组织中首次测出人类乳头状瘤 病毒,证实是引起食道癌的主要原因。 周健、陈全录于 1986 年 1 月考取了著名病理学专家沈琼教授的博士研究生,在导师指导下从事 食道癌病因研究。他们收集并检测了大量的食道癌活检标本。去年 12 月进行实验研究,在其中二十 五例活检标本中发现了人类乳头状瘤病毒,占送检标本的 27%,其中一例为食道下段腺癌,其余二十 四例为鳞癌。有关专家认为,这一发现为食道癌病因研究提出了一个新的方向,对于进一步研究预防 食道癌具有重要意义。

周健在浙江医科大学读硕期间与同学合影

Virus Said Linked to Cancer
China Daily on 2 February, 1987

Two postgraduates at a medical college in Central China’s Henan Province have found a virus believed to be the main agent of cancer of esophagus. The virus, called HPV, can cause pathological changes in many parts of the human body including the skin, throat, windpipe, bladder, and sex organs. The discovery was made by Jian Zhou and Guanlu Chen, two Doctoral students studying the causes of esophageal cancer under Professor Qiong Shen, who has been doing research in the field for more than two decades in high-incidence areas and wrote “The Early Diagnosis of Esophageal Cancers.” The book is used as a textbook in many countries. Zhou and Chen examined a great number of esophageal cancer specimens collected in Henan Province, and found the HPV in about 27 per cent of their collection. Meanwhile, Chinese doctors called for support of the production of anti-cancer drugs to meet the growing need. Saturday’s Economic Daily reported that the incidence of cancer in China has gone up in recent years. By rough estimates, one million new cancer patients appear in the country each year, and 1.5 million patients wait to be treated. Although there was an increase of 30 per cent in the production of anti-cancer drugs in 1986, still a dozen kinds of drugs were in short supply. Yamei Hu, noted paediatrician and director of the Beijing Children’s Hospital, suggested that effective measures be taken to boost the production of anti-cancer drugs, according to the paper. She told a national forum that dozens of anti-cancer drugs can be manufactured at home at a much lower cost, and the government should give more support to domestic pharmaceutical houses in the form of funds and technology.

医学科学家周健:永远的温医情怀 医学科学家周健:永远的温医情怀
作者:在在 来源:新闻中心 编辑: 叶少芳 更新日期:2007年12月03日
http://www.wzmc.net/article1/ArticleShow.asp?ArticleID=4801

周健博士生前与瞿佳院长的合影 11 月初,在北京召开的第 24 届国际人乳头瘤病毒会议闭幕式期间,再次特别提到了我校七七级 杰出校友周健博士在乳头瘤病毒研究领域作出的卓越贡献,来自世界各地的 1500 余名专家代表向周 健表示了深深的敬意。中国《科学时报》、《财经日报》等多家国家级媒体连篇报道了他的相关事 迹。周健和他的宫颈癌疫苗再次在他的祖国引起瞩目。 1991 年,澳大利亚昆士兰大学免疫和代谢研究所的伊恩·弗雷泽教授和华人科学家周健合作, 利用重组 DNA 技术制造出一种外形与 HPV 极为相似的“HPV 病毒样颗粒”,这种颗粒不含病毒感染成 分却能刺激身体产生免疫反应,这是人类医学史上的一项突破,它奠定了人类历史上第一个癌症疫 苗——宫颈癌疫苗的生产基础。然而,周健却未能亲眼看到这项研究成果造福人类。1999 年,他在 回国访问时突发疾病去世,年仅 42 岁。 2006 年,在世界第一支宫颈癌疫苗被注射的当天,昆士兰州副州长宣布:为庆祝宫颈癌疫苗的 启用,州政府决定以周健的名义设立一项智慧之州奖助金,该奖助金在 3 年的时间里为获奖者提供 45 万澳元的经费,从事免疫学和癌症领域的研究。2007 年 2 月 20 日,昆士兰州长彼特·比提宣布, 智慧之州周健奖助金增加为 3 年 75 万澳元,他说:“周健奖助金的设立是政府对周健博士在世界上 第一个癌症疫苗研发中重大贡献的首次正式承认。” 此外,国际免疫学界还筹集建立“周健科学基 金”。在澳洲,每年 9 月份都会有来自世界各地的癌症研究专家聚集于此,参加纪念周健的学术活 动,缅怀他为人类医学做出的重大贡献。 “母校温医的发展总是给我力量和信心。其实学校大小没关系,主要看培养的人在社会上的适应 能力。作为文革结束恢复高考后温医招收的第一届学生,那时的学校真的很小,可现在我们一点也不 比别人差。”杰出校友周健生前总是这样自豪地说。 “他就像一棵树一样,他的成长与温医是同步的。他从那里汲取养分、思想,锻炼毅力,培养高 尚的人格,那里还给予了支撑他扎扎实实不断地往前走的希望,他与那里血脉相连。”周健夫人、温 医七七年级校友孙小依博士说。

特殊年代里的那些人,那些事,那些经历,在周健的生命里打上了深深的烙印。在他的身上, 彰显着一代温医人的气质和精神。 “珍惜”的重量 珍惜” 1977 年,文革结束,全国恢复高考,对于当年同时考入温医的周健和孙小依来说,能读书了, 那真是生命里的一段突然掉进蜜缸里的幸福岁月。 出生于杭城的周健,高中毕业后上山下乡,到农村劳动锻炼,深刻体验了农村劳作的艰辛。一 年后回城,在六一针织厂做起了临时工,干起了 8 毛钱一天的血汗活儿,每天拉大板车,背 100 来斤 重的大麻包,尽管经常累得满头大汗,但他还是马不停蹄地干活。后来,他又转到当时一家无线电通 讯工厂当起了焊接工人。“开始的时候厂里谁都不要他,因为看他年纪轻,人也瘦,但后来有一个班 长发现他焊接得又快又好,手脚很灵活,就如伯乐识千里马般地重用他。在那里,他一干就是两年, 临走时大家都舍不得。”孙小依转述。这段岁月,锻炼了周健吃苦耐劳的精神,也让他深刻明白了学 习机会的来之不易。 “在我的印象里,周健每天捧着一个收音机在学英语,走哪儿都看他在听英语广播,他的英语非 常好。”周健的同窗陈波蓓说。读大学时,周健的念头就是好好读书,有机会去外面看看。当时学校 里如钱礼、缪天荣等老一辈教师对周健的人生目标确立产生了深远影响,也为他的英语学习打下了扎 实的基础。他们广博的学识,深厚的文化底蕴,向同学介绍的国内外文化的差异和先进的知识理念, 以及兢兢业业的教学态度赢得了同学们的敬佩和尊重,也催发了同学们奋发读书的斗志。同时,大学 期间,身边有同学半途出国留学了,写回来的书信中描绘了外面的丰富世界和广阔天地,更进一步坚 定了周健放眼世界的想法和决心。 刚入校时,周健这一届共四个班 200 人,班级里同学年龄参差不齐。“最大的老大哥小孩子都 已经上小学了,年龄比我们大出十几岁,中间年龄层的就是跟我们一般上过山下过乡的,也是为数最 多的,但也有高中毕业直接考上大学的。”孙小依回忆说。当时学校周围都是农田,没有大教室,学 校里正在实施各项基建工程。尽管学习条件很艰苦,但每个人都是学习热情高涨。当时在食堂吃饭排 队时,很多同学手上都会拿着各种各样知识摘要的小卡片争分夺秒地背,周健也不例外。很多同学看 书还看到凌晨两三点钟,似乎要把损失的时间都补回来。许多人年纪大了,学外语非常困难,但也都 一点点啃下来了。“要知道,当我们在插队时,没有可翻阅的书籍,都是拿些手抄本在偷偷地看,精 神饥渴已经持续了很长的时间,现在能有机会这样坦坦荡荡地读书,真是如浴甘泉啊”。孙小依开玩 笑说,“要是没有考大学这个机会,也许周健还在做电焊工呢。” 周健的经历折射着一代温医人的影子。温医 77 级的很多学生,现在都是省内外一些医院的院 长、科室主任,或者成为了某个领域的专家、领头羊。这和他们当年培养的刻苦精神、追求上进的劲 头不无关系。那一代的大学生,是中国新一代人的代名词,不管是在哪一个领域,现在都是一个受到 普遍赞誉的群体。 平凡的天才 “在温医学习的五年,我与他同班同组,他是最优秀的学生。他机敏好学,他超然的智慧至今在 温州医学院传为美谈。”现任温医院长瞿佳说。 “我们都认为,周健取得的成绩和为社会所做出的贡献主要归功于他的勤奋和聪明。”陈波蓓 说。 “周健很朴实也很平凡,一直都是做着自己喜欢的事情。”孙小依说。 几十年过去,让当年的同窗回忆对大学时光里的周健的印象,有人会说:“他智慧超群,成绩优 秀”;也有人会说:“他特别爱观察、爱琢磨、爱钻研”。周健“爱琢磨”的性格在同学里也是人尽 皆知的,他总是什么事情什么事物都想弄个明白,所以他很自然地成为了寝室楼里的“修理工”,同 学们只要一有什么东西坏了就会想到找周健修理,甚至连当时极少有的手表坏了也会跑来找周健。 “所以结婚后,家里的电冰箱、电视机、洗衣机、油烟机等坏了,都是周健一手包修”。孙小依回忆 说, “可能正是他这种爱钻研爱挑战的精神,为他科研上各项成绩的取得奠定了基石。” 周健的成功除聪明外,勤奋和毅力是一份厚重的筹码。孙小依说:“他想做一件事情就会朝着 那个目标不懈地努力。读大学时,他一心想学好英语和专业,就花很少的时间在娱乐活动上,把听英 语广播变成自己生活最大的乐趣。在浙医大读研参加托福考试时,他凭着刻苦的精神考了全校第一 名。当时要在国外的杂志上发表论文是件非常困难的事情,而做为研究生的周健突破语言关在国外杂

志上连发两篇论文。就像人乳头状瘤病毒(HPV)的发现一样,也是在经历了无数次的实验之后,他还 是反复琢磨不断提出新的想法和实验手段,在不屈不挠、不言放弃的精神下才成功的。” 同窗情深 “在温医的那段岁月,生活是艰苦的,但也是最值得怀念的,同学之间的真诚纯朴让我一辈子 都难以忘怀。”周健在给陈波蓓的信中这样写道。 大学时,周健的真诚和乐于助人远近闻名。逢年过节,同学回家要途径杭州转车的,就经常受 到周健家的热情招待,吃住包办。读书时很多同学的家庭条件比较艰苦,周健寝室有位老大哥的饭票 菜票经常会不够用,周健总慷慨热心地说:“把我的拿去吧。”“在他的一生中,总是在别人需要帮 助的时候主动去帮助别人。”孙小依说。 大学时有一年考生物化学,周健生病了,有三、五个月时间请假在杭州治疗,没能来上课,大 家都担心周健要通不过考试而被留级了。那一年的生物化学考试试题难度很大,班里只有寥寥几人能 考优秀,还有十几人补考的。周健回校时已临近考试,很多同学纷纷帮他补习,并把自己的笔记本借 他复习。出人意料的是,周健参加考试竟然取得了九十几分的好成绩,同学们对他的自学能力、记忆 力、理解力佩服得五体投地。 孙小依说:“周健性格乐观,幽默风趣,哪儿只要他在,就一定会有笑声和快乐。他还很调 皮。记得当时碰上上大课的时候,大教室尚未建好,同学们就在大礼堂里一起上课,礼堂紧挨着学校 的食堂。因为文革刚结束不久,当时社会上很多肉类食品供应不足,学校的炊事班长就在食堂后面养 了很多猪来维持肉类食品的供应。结果常常是一边学生在上课,一边猪在叫,有时还会有几只爱遛达 的猪突然闯进礼堂,这给坐在后排如周健一般调皮的同学提供了恶作剧的可趁之机。他们合计好,一 起拿着自带的开水瓶实行烫猪行动,烫的那几只猪四处乱串哇哇叫,引得同学们抱腹大笑。” 当周健和孙小依与 1997 年的同学会擦肩而过时,他们遗憾不已。当年,正逢一位同学去澳大利 亚考察,特意带去了同学会的合影。周健夫妇得知,立马驱车赶到这位同学所在的地点会面,与同窗 叙旧情。连续几夜,周健和孙小依端详着照片里的合影,一个个认别那熟悉却又改变了的面容,激动 得没有合眼。 心系母校 在周健的事业取得举世瞩目的成就时,他虽然身在国外,却始终心系生他养他的祖国,时刻牢记 哺育他成长的母校。“无论我们走到哪里,从国内到国外的各个地方,周健总是最依恋温医,对那里 最有感情,他觉得虽然当时学校管理严格,但同学之间的感情来得特别纯朴。虽然你离开那里了,但 总有一种力量让你的心一直牵挂着那里,让你不舍得离去。虽然我们两个都不是温州人,但我们一致 都把那里当成我们的第二故乡”。孙小依说,“也许,这就是温医特有的人情味儿和凝聚力。” “周健总是想方设法为国内的高校、科研机构与国外的著名学术单位牵线搭桥。他不辞辛劳,自 己花钱、花时间接待来自国内的学者和教授,安排吃、住、行,安排学术访问和学习进修。一些曾经 在周健实验室学习和工作过的国内学者,现在都已在学术上有所建树。他也多次不远万里回国讲学, 帮助国内的单位开展科学研究。记得 1996 年我在美国波士顿学习,当周健从别人处得知后,立即给 我打电话,并给我寄来了往返的机票,让我到芝加哥讨论如何支持母校温州医学院开展医学科研。从 那时起,他就为温州医学院和他所在的单位建立了学术联系,双方互派留学生。等他到了澳洲,他又 帮助我校与澳洲布里斯本昆士兰大学医学院建立起联系。他多次在澳洲和中国之间往返,经他努力, 我校已建立了他所建议的免疫学科研方向和科研课题,并获得了世界卫生组织基金的支持。通过派遣 人员到周健单位进修、学习,使我们的老师增长了见识,学到了本领。”温医院长瞿佳说。 目前,我校分子病毒与免疫研究所研究团队取得了诸多可喜的成绩,与昆士兰大学合作开展的 HPV 相关疾病的免疫治疗研究目前仍在继续,这要归功于 1997 年开始的在周健的指导下,与澳大利 亚昆士兰大学癌症与免疫研究中心(CICR)合作进行的 HPV 感染及其预防的研究。经过多年研究,一 批研究成果已获得了广泛认可,其主持的研究项目获得了 WHO(UICC)、国家自然科学基金、浙江省自 然科学基金委的资助,研究成果获得了浙江省科学技术二等奖等多个奖项,并在国内外知名杂志上发 表了多篇论文,还带动和培养了一批年轻的科研人员。在周健去逝后,周健的合作伙伴、子宫颈癌疫 苗的共同发明人、被评为“2006 年度澳大利亚杰出人物”的昆士兰大学免疫和代谢研究所伊恩·弗 雷泽教授为了怀念周健,每年都会莅临温医访问交流。他认为:“回中国,回温医,就像回到了老 家。”

斯人已逝,但其精神和音容笑貌却留给后人无限的怀念。周健的事迹,他视科学为至高无上的事 业的态度,是温医精神的一个缩影,在他的身后,有许许多多敬业的老师和像他一样献身于医学事业 的温医学子,撑起了温医人奋发求实、敢于拼搏的蔚蓝天空。

1997 年周健和伊恩·弗雷泽在温州与温医管理层合影

让女性远离子宫颈癌
——访世界首例抗癌疫苗专家弗雷泽教授(上) 本报驻澳大利亚记者 李景卫
《人民日报》 ( 2006-07-10 第 07 版 ) 澳大利亚每年都会对获重大科研成果、经济成就和对社会有特殊贡献者进行表彰和奖励。在今年 受嘉奖的人员中,昆士兰大学免疫与癌症研究中心主任伊恩·弗雷泽教授的名字最响亮。霍华德总理 亲自为他颁奖,并授予他“2006年度澳大利亚模范公民”荣誉称号。 现年53岁的弗雷泽获此殊荣,是因为他领导的癌症研究中心研制出人类乳头状瘤病毒疫苗取得 突破性进展。这种疫苗的接种,可使妇女子宫颈癌发病率至少减少70%。在昆士兰大学免疫与癌症 研究中心高级研究员、弗雷泽教授的临床试验项目助手庞建宏博士的帮助下,记者通过电子邮件采访 了全球首例抗癌疫苗研制者弗雷泽教授,详细了解了人类乳头状瘤病毒疫苗的最新进展情况及其研制 过程。 弗雷泽说,由他研制的人类乳头状瘤病毒疫苗的药物名称叫“加德西”(Gardasil)。6月8 日,美国食品与药物管理局已正式向美国默克制药公司颁发投产许可。“加德西”很快将在美国上 市。在澳大利亚,“加德西”将由墨尔本CSL生物制药公司生产,定于8月28日正式上市。该产 品随后将逐步与欧洲、亚洲、非洲各地的妇女见面。 人类乳头状瘤病毒(也称疣病毒)多达30多种,但只有几种会致癌。约30%的女性在生活中会感 染高风险的乳头状瘤病毒。经过治疗或自身免疫系统的作用,部分女性可在12—18个月内痊愈, 但另一些女性却难以摆脱这种病毒的威胁。受感染达5年以上者基本上会终身受乳头状瘤病毒的折 磨,其中患子宫颈癌的几率为20%。据统计,全球每年至少有27万妇女被子宫颈癌夺去生命。 弗雷泽祖籍苏格兰。20多年前,一次偶然机会使他认识了墨尔本霍尔研究所临床医学研究室主任伊 恩·麦凯先生。年轻的弗雷泽在免疫学方面的兴趣受到麦凯的赏识。1980年,麦凯给弗雷泽发去 一纸电文,邀请他到霍尔研究所从事免疫学方面的研究。弗雷泽放弃了到英国剑桥大学攻读博士学位 的计划,毅然决定移居澳大利亚。在霍尔研究所里,弗雷泽参与了艾滋病病毒的研究。1985年, 正当艾滋病病毒研究受到全球普遍关注的时候,弗雷泽突然离开霍尔研究所前往昆士兰州亚历山德拉 公主医院,并在那里创建了昆士兰大学免疫与癌症研究中心。弗雷泽认为,全世界都在从事艾滋病病 毒研究,自己的研究空间极其有限。因此,他决定在昆士兰大学免疫与癌症研究中心独辟蹊径,从事 人类乳头状瘤病毒研究。 通常,研究人员在研究某种病毒时,首先要培养大量的病毒,并对所培养的病毒进行特殊处理, 使其失去致病性,然后用这些病毒做动物试验,观察这些病毒进入动物体后免疫系统对入侵者的识别 和反应。但由于乳头状瘤病毒无法在试管里培养,弗雷泽始终做不了这类试验。他尝试过其他的方 式,还是不成功。在这种情况下,他对乳头状瘤病毒研究的一些理论推测始终无法得到验证。 在研究乳头状瘤病毒过程中遇到的重重困难并没有使弗雷泽气馁。相反,他决心沿着自己选定的道路 走下去。1989年,他利用假期前往剑桥大学做病理学客座研究员。剑桥大学对乳头状瘤病毒的研 究处于世界领先地位。弗雷泽希望能在那里敲开该领域研究的大门。 (本报堪培拉电)

——访世界首例抗癌疫苗专家弗雷泽教授(下) 本报驻澳大利亚记者 李景卫
《人民日报》 ( 2006-07-11 第 07 版 )

如果说是伊恩·麦凯把弗雷泽引向医学研究的道路,那么,在弗雷泽步入辉煌科学殿堂的道路 上,又是谁给了他重要的启示呢? 在剑桥大学的实验室里,弗雷泽结识了从中国到剑桥大学从事博士后研究的周健和夫人。无论白 天还是夜晚,只要弗雷泽到实验室,都能看到周健夫妇在那里孜孜不倦地工作。在茶点时间,弗雷泽

经常与周健夫妇聚在一起,与他们探讨、交流乳头状瘤病毒研究情况和所遇到的难题。周健向弗雷泽 介绍他在采用基因工程技术培养滤过性毒菌蛋白——将病毒因子注入某种细胞,用其培养实验所需的 病毒。机敏的弗雷泽立即看到了乳头状瘤病毒研究取得突破的希望,于是力邀周健到澳大利亚与他一 道从事乳头状瘤病毒的研究。 尽管人类早已推测女性子宫颈癌和女性的许多性病都可能由这种病毒引起,但由于乳头状瘤病毒极其 微小,且难以在细胞里培养,科研人员在其致病机理的研究方面始终未能获得突破性进展,因而对这 种病毒致癌的推测也无法加以证实。 1990年,周健应弗雷泽的邀请来到昆士兰大学免疫与癌症研究中心。周健以他一贯的坚忍精 神,与弗雷泽通力合作。他们利用DNA重组技术,人工合成人类乳头状瘤病毒疫苗,并很快取得成 功。1991年,弗雷泽与周健联名申请了DNA重组技术人工合成人类乳头状瘤病毒疫苗的专利。 周健在乳头状瘤病毒方面的研究成果,引起了昆士兰大学和有关科研机构的高度关注。1994年, 昆士兰大学授予周健医学博士学位。1996年,周健被昆士兰大学聘为高级研究员,并于次年担任 人类乳头状瘤病毒学研究室主任。 1999年是一个令人难忘、又令人痛心和惋惜的一年。周健和弗雷泽共同研究合成的人类乳头 状瘤病毒疫苗即将进入全面临床试验。但人们万万没有想到,就在这关键而又重要的时候,年仅42 岁的周健因病不幸逝世。送别同事,深感悲痛的弗雷泽继续着他们的事业。他带领澳、美两国的医学 科学家对33个国家的2.5万名妇女先后进行了三期人类乳头状瘤病毒疫苗临床试验。2005年 10月7日,澳、美科学家在纽约宣布,人类乳头状瘤病毒疫苗预防子宫颈癌非常有效,试验取得圆 满成功。面对这一震惊世界的喜讯,弗雷泽深感陶醉。与此同时,他更难忘已故的中国同事周健。弗 雷泽在接受采访时说:“周健是一位亲密的朋友和同事,同时也是病毒样颗粒技术的共同发明者。这 一技术使得人类乳头状瘤病毒疫苗研制获得成功。在整个分子病毒学领域,周健做出许多重大贡献。 他1999年不幸早逝对世界、对科学都是一个巨大的损失。” 人类乳头状瘤病毒疫苗是世界第一例有效预防癌症的疫苗。它的研制成功无疑将为人类最终揭开 所有癌症之谜带来希望。 (本报堪培拉电)

1996 年周健和伊恩·弗雷泽访问温医。

追忆世界第一个癌症疫苗发明者之一周健博士:

生 伟 业 真 真 切 --周健夫人孙小依访谈 --周健夫人孙小依访谈
陈欢欢 王丹红
引言

2006 年,人类历史上第一个癌症疫苗——子宫颈癌疫苗问世,一年之内,包括美国、英国、加 拿大和澳大利亚等在内的 80 个国家先后批准了这种疫苗的使用。世界每年有 50 万女性被诊断出患上 子宫颈癌,有 25 万人死于这种疾病。专家指出,新疫苗的使用有可能在一代人中根除子宫颈癌。 99.8%的子宫颈癌是因人乳头瘤病毒(HPV)而发生的,但今天的子宫颈癌疫苗不是 HPV 本身的减 毒或灭活的抗病毒疫苗,而是使用了 1991 年伊恩·弗雷泽教授和周健博士合作发明的病毒样颗粒。 用基因工程手段生产的病毒样颗粒不含病毒感染成分、却能刺激人体产生免疫反应,能有效地控制 HPV 感染,这是人类医学史上的一项重大突破。2007 年 8 月伊恩·弗雷泽博士在北京举行的第四届中 国-澳大利亚科学合作论坛上,首次在中国介绍了子宫颈癌疫苗的发明和周健在其中的重要作用。然 而,周健却未能亲眼看到这项研究成果在临床上大规模应用和在人类抗肿瘤中的巨大作用,于 1999 年他在回国访问时突然病逝,年仅 42 岁。 周健夫人孙小依曾做过他 8 年的助手,1991 年,孙小依亲手参与合成了第一个病毒样颗粒。从 挪威到丹麦,几经周折,记者联系上了正在欧洲参加学术会议的她.在近 2 个小时的电话采访中,她 回顾了周健的生命历程,她说:“周健其实只是一名普通的研究人员,也是一个十分朴实的人,对我 来说是一个称职的丈夫,对儿子来说是一个好爸爸,对科学工作来说他是一个认认真真、 踏踏实 实、勇于进取、不知疲倦的研究人员。”

周健夫妇在 1998 年的圣诞节晚会上。孙小依/提供 “我真是站在巨人的肩膀上” 我真是站在巨人的肩膀上” 周健和孙小依都是杭州人,中学毕业后,他到工厂做工人,她到农村插队。1977 年,“文革” 结束后恢复高考制度的第一年,俩人考入温州医学院医学专业,大学五年,从相识、相知,直到相 恋。

“我们两人的性格完全不同,我比较好动,整天不是在操场上跑步就是在参加各种文娱活动,他 很安静,每天都拿着录音机专心学习英语,他很喜欢我活泼的个性,我也羡慕他能专心致志而取得优 秀成绩。”孙小依说:“大学毕业后就自然地走到了一起,这也是一种缘分。” 1982 年大学毕业后,周健考入浙江医科大学攻读硕士学位,师从病理学家徐英含教授做病理学 研究,天天在实验室做得很晚。这时,孙小依在浙江省人民医院任眼科临床医生,家就在医科大的街 对面,所以,常常晚上到实验室去,帮周健做些细胞培养方面的工作。 周健用两年的时间读完了硕士,又考入河南医科大学攻读病理学博士,导师沈琼教授是我国食管 细胞学创始人,长期从事食管癌的早期诊断、癌前病变和预防研究。在大量查阅了文献之后,周健提 出了从病毒病因学的角度,用分子生物学技术研究食管癌的设想。沈琼说:“你的想法非常好,我可 以送你到北京病毒所去学习。” 沈琼立即将周健介绍给了自己的同学,时任北京病毒所所长曾毅,曾毅又将他介绍给北京病毒所 副所长谷淑燕。当时谷淑燕刚从德国学习回来。正承担着国家“七五”攻关计划的几个项目,专门做 HPV 研究。孙小依说:“周健运气很好,谷老师非常喜欢他,手把手地教他,谷老师是真正把他带入 用分子生物学方法研究 HPV 的启蒙人。” 1986 年,博士毕业后的周健进入北京医科大学生物化学研究所博士后流动站,跟随病毒学家张 迺蘅教授继续做 HPV 研究。这时,儿子周子晞刚出生,孙小依借调到了北医三医院眼科工作。 1988 年,周健申请到位于剑桥大学的英国帝国癌症研究基金会(ICRF)的肿瘤和病毒实验室做研 究,并成为国际 HPV 研究的先驱 Lionel Crawford 教授接收的第一位中国研究员。孙小依说:“周健 极其幸运,Lionel 的实验室是国际 HIV 和分子生物学领域最顶尖的实验室之一;Lionel 也很喜欢 他,因为他是一个很有创造性的人。” 1998 年,当周健在事业发展比较顺利, 已经有了近十项发明专利时曾说:“我能取得一些成功 全靠这一个个的老师,我真的是站在巨人的肩膀上。” Crawford 教授的实验室资金多、设备条件非常好,只要有想法就能做,周健在剑桥做的实验很 有意义,但实在忙不过来了,他希望孙小依能到实验室助一臂之力。Lionel 给了孙小依一个访问学 者的职位,1989 年,在周健到剑桥后 10 个月,孙小依来到他身边,成为他的助手,但她没想到的 是,这一做就是 8 年,并共同经历两人生命中最激动人心的时刻。 剑 桥 偶 遇

1985 年,当周健在博士阶段专心研究 HPV 时,在地球的另一端,伊恩·弗雷泽获得澳大利亚墨 尔本大学博士学位后,他通过阅读文献得知:子宫颈癌是由 HPV 感染造成的,也在潜心专研 HPV。 1985 年,弗雷泽到昆士兰大学的教学医院亚历山大公主医院创办了自己的免疫和癌症研究实验 室,决定加入 HPV 和子宫颈癌疫苗的研究。这时的弗雷泽身兼数职:教学、临床医生和研究。1989 年,他决定利用学术休假年到剑桥大学病理系的实验室进修。他所在的 Margaret Stanley 教授的实 验室正好与 Lionel Crawford 的实验室毗邻,因此,“幸运地遇见了不久前来自中国的周健博士。” 他说。 “那时,周健和夫人孙小依是两位最为勤奋的研究人员,无论白天黑夜,凡我去实验室时,总会 看到他俩在那里努力工作,实际上,我是他们实验室的打扰者,由于我的实验室过于拥挤,没有空间 供我活动,加之经费紧张,缺乏购买药物试剂的资金,所以老是借用 Crawford 教授的实验室和试 剂。” 弗雷泽说,在剑桥,周健夫妇被称为“神奇的手指”,什么难事到他们手上总能行。孙小依说: “那时周健刚起步,我专心做他的助手,我们性格互补,他很有创造性,主意多,我比较有条理性, 手巧,做细胞培养从未污染过,给我的任务我都能细心完成,我们不但在生活中互相理解,而且在实 验室里也配合默契,他只要朝哪里看一眼,我就知道他需要什么东西,同事都说我们俩配合得可称天 衣无缝。” “伊恩与周健在很多方面很相像,他们都很努力,” 孙小依说,“每天早上一定是他们俩最早 到实验室,晚上一定是最晚走。他们很合得来。 弗雷泽说:“我们也常常在喝咖啡时间相遇,并谈论彼此间如何可以通过合作来创造实现并验证 一些新的设想。” 但由于种种原因,俩人没有条件在剑桥进行太多的合作。当弗雷泽准备返回澳大利亚时,他盛情 邀请周健夫妇到昆士兰大学他所在的实验室一起工作。他已经申请到了不少经费,有条件通过努力就 能继续深入研究。1990 年,周健带着家人来到了昆士兰。

孙小依说:“到昆大后我们还是接着做同样的题目,一点没有耽误时间,换实验室没有带来任何 影响,进展很顺利。伊恩也一直支持我们。不到一年,周健这一最重要的创造发明就有了眉目。” “我们真的合成了一个病毒!” 我们真的合成了一个病毒! HPV 是一个很小的病毒,直径 45~55 纳米,科学家们已经对这个病毒研究了几百年了,但对它 的认识一直很肤浅,从未在实验室中培养成功过,而且一旦寄存到宿主细胞后,它就会将自己的基因 与宿主细胞的基因融合,因此,无法在体外看到完整的病毒颗粒,对它的研究进展受到了限制。 以前,科学家们曾试了许多方法,希望在体外培养这种病毒,周健和孙小依也一直在想方设法, 但也都没有成功。孙小依说:“我们试了许多不同的方法,确实很难,做基础研究还是有些进展有文 章可发表,但是对怎么看到这个病毒颗粒真的是束手无策。”拿不到病毒,疫苗又从何谈起呢? 夫妻俩人习惯在孩子睡觉后出去散步,周健往往走几步会突然冒出一个想法,有时孙小依就拿笔 记在手心,回实验室后进行试验。1990 年年底的一天,他们像往常一样出去散步,周健忽然说: “我们现有的 L1、L2(HPV 晚期蛋白、病毒壳膜的主要构成成分)表达很好,纯化的也不错,何不把 这两个蛋白放到试管里加上一定条件,看有没有结果?”孙小依说:“我当时就嘲笑他,哪有这种可 能,将两个东西放在一起就成了事?能有这么简单?” 过了半个月,周健又问孙小依那个实验做了没有,孙小依说:“我当时是记下来了,但我觉得你 不会在开玩笑吧?”在丈夫的第二次催促下,她“抱着试一试的心态,按照他的思路,将两个现存的 HPV 晚期蛋白放在试管里,加一点这个,加一点那个,好像幼儿园小朋友做游戏一样,就这么简 单。” 大约过了两个星期后,两人将合成好的东西拿到电子显微镜下观察,“结果一看我们俩都傻眼 了,真的是一个病毒样颗粒合成了,我们实实在在的看到一个体外合成的病毒样颗粒了! 这真是惊 喜的一刻!”孙小依说,“这真是很幸运,我们赶紧将这个结果告诉伊恩,他高兴得嘴都合不拢。这 是我们一辈子难以忘怀的瞬间,在不经意间实现了梦寐以求的突破。” 病毒学家都知道这个病毒样颗粒的重要性:这个颗粒是个空壳,里面没有病毒 DNA 内核,所以没 有感染性但外壳上有很多抗原,进入身体后就会刺激免疫系统而产生抗体,因此它本身就是一个疫 苗。 我们就用这个 HPV 病毒样颗粒作动物试验,动物体内出现了免疫反应。弗雷泽和周健将这一成果 发表在 1991 年第 185 期的《病毒学》期刊上。1991 年 6 月,昆士兰大学为这项发明成果申请了专 利,当年 7 月,俩人在美国西雅图举行的乳头状病毒国际会议上报告了这项成果。 动物试验成功之后就开始转入临床试验。 英 年 早 逝

当临床试验做到某一阶段时,昆士兰大学已无力支付昂贵的科研费用成本,就将部分专利给澳大 利亚一家生物技术公司 (CSL),由这个公司接着做。但几年后又支撑不去了,因为这阶段在全世界很 多国家做临床试验需要更多的经费,然后又将部分专利卖给实力更雄厚的制药公司―美国默克公司。 孙小依说:“在每一次疫苗专利买卖过程中,这些公司都要给昆大一笔数目很大的基金来继续做 研究,我们实验室又拿到更多的经费,又能做更多的实验, 所以这是一个正向循环, 这是很激动人心 的事。” 在弗雷泽的鼓励下,周健在做研究的同时,也在攻读昆士兰大学的医学博士学位。1994 年,一 位德国教授在美国芝加哥 Loyola 医科大学成立了一个新的 HPV 研究室,周健又去挑战,他说:“人 要不断流动,学习新的知识,武装自己。”在芝加哥,周健有了自己的博士生和博士后,他鼓励孙小 依去参加考芝加哥眼科资格考试,孙小依因此回到眼科临床。 1996 年,昆士兰大学给周健提供了一个更高的职位,他带着全家人又回到了澳大利亚,建立了 自己的实验室。1998 年,他获得 3 项澳大利亚国家健康与医疗委员会(NHMRC)的经费,加上公司回 馈做疫苗研究的经费,成为当时昆士兰大学历史上在一年内申请到 NHMRC 经费最多的一位研究人员。 宫颈癌疫苗的临床试验还在世界各地进行。每年 3 月,周健都回到温州医学院看在那里进行的临 床试验。1999 年的 3 月也不例外,但没有人会想到,这竟成了一次没有归途的旅程。 “周健的身体一直很好,出国之后 10 来年没有请过病假,他的勤奋是有目共睹的,他经常一周 工作 7 天,日夜操劳。1999 年 2 月,他整天坐在那里写基金申请书,写完后说‘我怎么这么累 啊?’ ”孙小依说,“我就劝他休息,3 月份就不要去温州了。但他坚持要去。”

1999 年 3 月 8 日晚,刚到杭州没几天的周健还给家里打电话,儿子在电话说:“爸爸,这次回 来你给我买什么礼物? 给我买一个最新的 lego(垒高拼装玩具)吧!”周健说:“没问题,我肯定给 你买回来。”孙小依对儿子说:“爸爸太累了,让他早点休息。” 3 月 9 日,周健因为感染性休克病重。3 月 10 日,当孙小依带着周健的母亲和儿子从澳大利亚赶 到杭州时,他却永远闭上了眼睛。8 年后,孙小依还是难以抑制悲痛地说:“太突然了,至今都很难 相信他真的离开我走了,很难接受。” “四海之水难书痛情” 四海之水难书痛情” 1983 年,当周健准备结婚时,他给孙小依提过唯一条件是和父母住在一起。孙小依说:“他很 孝顺。我这个人比较容易相处,谈恋爱的时候就跟他妈妈相处很好,所以说行啊。” 周健在家中排行第二,上有一位姐姐。 1988 年,周健父亲去世,母亲就一直跟周健在一起。 “从美国到澳大利亚,走到哪里都把妈妈带上。”孙小依说,“妈妈对我们也无私地关怀和帮助,我 们俩就像母女一样,我跟她开玩笑说,妈妈你是一个带工资的保姆,军功章有您的一半啊。” 周健非常宠爱儿子,每次出差都会给儿子带礼物,反而是孙小依来为儿子制定规矩。孙小依性格 柔和,婚后基本上都顺从周健。然而,周健的骤然离去改变了这一切。 “我从周健身上学到的最大的东西就是坚强和毅力,擎天柱突然倒了之后我觉得我必须站起 来,不能让儿子因为没有父亲就倒下了,”孙小依说,“当时儿子只有 13 岁,刚上初中,我对儿子 说,‘没关系,妈妈现在又是妈妈又是爸爸’。但这一突然的打击还是缩短了儿子的童年,他一下成 熟懂事了。他在周健的追悼会上说,‘我将追随父亲的脚步,做一个对社会有用的人。’” 母亲为儿子题写的挽联书: 尊师重友敬业忠诚有加 为事业呕心沥血殚精竭虑 垒五岳之石不齐丰碑 孝亲爱妻诲子无微不至 对生活淡泊自甘嫉恶如仇 罄四海之水难书痛情 岳父为女婿写的挽联: 老天无情夺吾周郞 哀啼白发送黑发 宏业有成泽惠神州 忍听涛声慰悲声 “一世伟业真真切切科研巨擘 毕生勤奋坦坦荡荡学者楷模”,这是岳父为追悼会写的灵堂挽联, 孙小依说:“这很好地概括了周健的一生,他就是这样一个人。” 周健大学时代的同学、温州医学院院长瞿佳回忆,周健曾同他彻夜长谈,自信地表示自己虽然在 本专业领域占有一席之地,但决不满足,要在《科学》、《自然》这样的顶尖刊物上也发表论文。然 而,“出师未捷身先死,长使英雄泪满襟。一个为征服人类疾病而日夜奋斗的科学家,却因当代医学 的无能而丧失了宝贵的生命。” 弗雷泽在给孙小依的信中说:“健是一位非常优秀的科学家,他在分子病毒学领域 10 年中所取 得的成就是许多科学家在 30 年中也无法企及的。他在研究领域中的杰出贡献之一是:使我们能首先 在世界利用人乳头瘤病毒疫苗预防子宫颈癌成为可能,他在该领域的研究成果将使世界受益。” 1999 年 3 月,昆士兰大学癌症、免疫学和代谢医学研究所决定:每年举办以周健名字命名的学 术活动以及新建立的报告厅以周健名字命名, 永久地纪念他的研究工作。 愿 更 多 的 人 受 益 2005 年底的一天,制药公司郑重地正式宣布:子宫颈癌疫苗临床试验成功了,疫苗可以正式上 市。这时,弗雷泽在纽约开会,当记者打电话去采访时他才知道这个消息,他表示异常惊喜,但提到 周健对疫苗的贡献时,马上哽咽地说不出话来:“可惜周健没能看见这一天!” 2006 年 8 月 28 日,在澳大利亚昆士兰亚历山大公主医院,弗雷泽为一对少年昆士兰姐妹注射了 世界第一例子宫颈癌疫苗,孙小依和儿子周子晞见证了这一历史时刻。20 岁的周子晞已是一名工业 设计专业的的大学生,他在周健演讲厅演讲时说:“我父亲的创造性和弗雷泽教授的管理经验结合在 一起,他们形成一个完美的团队。没有弗雷泽,我父亲就没有资源或很难将专利变成产品;反之亦 然,没有我父亲的研究,弗雷泽教授也很难在对这种疾病的预防和认识上有重大的进展。” 当天,昆士兰财政部长宣布:为了庆祝子宫颈癌疫苗的启用,州政府决定以周健的名义设立一项 智慧之州奖助金,该奖助金将在三年的时间里为获奖者提供 45 万澳元的经费,从事免疫和癌症领域 的研究。2007 年 2 月 20 日,昆士兰州长彼特·比提宣布,智慧之州周健奖助金增加为三年 75 万澳 元,他说:“周健奖助金的设立是政府对周健博士在世界第一个癌疫苗研发中的重大贡献首次正式表 彰。”

由于对子宫颈癌疫苗研制做出的非凡贡献,弗雷泽被评为“2006 年度澳大利亚杰出人物”和 “2006 年度昆士兰杰出人物”。他在接受媒体采访时说:“周健的贡献和我一样多,他不能活着看 见疫苗的梦想成为现实,这是一个悲剧。” 2006 年 3 月,澳大利亚的音乐家创作了一首题为“伊恩·弗雷泽教授”的乐曲,庆祝他荣获 “2006 年度澳大利亚杰出人物”和“2006 年度昆士兰杰出人物”殊荣。这首乐曲的第二乐章以东方 风格的形式纪念弗雷泽教授的合作者周健博士和彰扬周健的夫人孙小依,表彰他们在子宫颈癌疫苗的 研制中做出的贡献。 这首曲子让孙小依热泪盈眶,心中充满骄傲、荣誉、悲伤和喜悦。她说:“周健对我最大的影响 就是让我懂得怎么去爱别人,让我懂得什么是真正的爱。虽然他已经走了,还是希望更多的人能受益 于这种疫苗。” 在子宫颈疫苗成功后,孙小依在此以前基本没有发表过谈话或写文章。她说:“我这个人比较低 调,这个疫苗的成功是千千万万科学家的结晶,周健在里面起到了重要的作用,他在关键环节上的突 破有必然性也有偶然性。我想,他如果活着的话也不会有意过分宣扬,他肯定会说我就是一个科学 家,这就是我应该做的,能做出来只是自己勤奋努力加上运气,世界上还有那么多人没有做出来,但 人家也一直在努力。这个事情没有那么伟大,只是正好被我们做出来了。” 如今,孙小依计划做两件,一是协同昆士兰政府和澳大利亚华人基金会(ACF)在明年 5 月举办 “周健纪念日”活动;二是计划和儿子一道成立“周健基金会”,奖励最优秀的科学家,让更多人来 继续从事医学研究,给人类带来更多的福祉。她说:“我的另外一个想法是希望这些活动能激励我儿 子,做人就是要踏踏实实地去做,让儿子从这些社会活动中学会关爱别人,回馈社会。”(完) 原载于《科学时报》2007 年 10 月 22 日 原载于《科学时报》

A Brilliant Life, an Honest Person
– An interview with Jian Zhou’s wife, Dr. Xiaoyi Sun Huanhuan Chen & Danhong Wangi

In 2006, the world first cancer vaccine in human history, the cervical cancer vaccine, became available. Within a year, 80 countries including the USA, UK, Canada and Australia have successfully approved this vaccine for use. In the World, over 500,000 women are diagnosed annually suffering from cervical cancer, and about 50% of those women die from this disease. Experts have suggested that the application of this vaccine may completely wipe out cervical cancer in a generation. It has been identified that 99.8% of cervical cancer cases are caused by human papillomavirus (HPV). However, the current cervical cancer vaccine is not an antiviral vaccine that either attenuates or inactivates virus from HPV itself. This vaccine has been based on the virus-like particle (VLP) that was co-invented by Professor Ian Frazer & Dr. Jian Zhou in 1991. The virus-like particle produced by genetic engineering does not contain viral infection ingredients, but can stimulate the body to produce immune responses that effectively control HPV infection. This invention is a significant breakthrough in human medical history. In August 2007, in the Fourth China – Australia Scientific Cooperation Forum held in Beijing, Prof. Frazer for the first time in China introduced the invention of cervical cancer vaccine and Dr. Zhou’s significant role in the invention. Sadly, Dr. Zhou was not able to see for himself the research achievements – large-scale clinical application and its enormous effects in human’s effort against tumour. Dr. Zhou passed away by sudden illness during a research visit in China in 1999, at the age of 42. Zhou’s wife, Dr. Xiaoyi Sun, was used to be Dr. Zhou’s research assistant for 8 years. She made great contribution in the synthesis of the first VLP in 1991. Searching from Denmark to Norway, passing through many difficulties, the reporter was eventually able to contact Dr. Sun while she was just attending an academic conference in Europe. In a nearly 2-hour telephone interview, she recalled about Zhou’s life. She commented: “Jian actually was an ordinary researcher and a very simple person. While he was a competent husband for me, a good father for our son, he was an earnest, honest, enterprising and tireless hardworking research fellow for science.” “I’m standing on giants’ shoulders” Both Jian Zhou and his wife come from Hangzhou in China. After finishing from high school, Jian worked in a factory and Xiaoyi was sent to work and live in the countryside. In 1977 when China resumed the tertiary entrance examination after the “cultural revolution”, they were both admitted to study the medicine in Wenzhou Medical College where they were acquainted, appreciated each other and fell in love. Xiaoyi said: “We had totally different personalities. I was active, always involved in sport such as running and other recreational activities while he was rather quiet, always seen learning English with a portable recorder in hand. He liked my active personality whereas I admired his dedication to achieve a goal.” Xiaoyi continued, “After graduation, we were married. I guess that was natural.” When Jian completed his first degree in 1982, he continued to study his Master’s degree at Zhejiang Medical University under the supervision of Professor Yinghan Xu, a pathologist. Xiaoyi was then working as an ophthalmologist at Zhejiang People’s Hospital and their home was just opposite Zhejiang Medical University. As Jian worked until very late in his laboratory, Xiaoyi often went to the laboratory in the evening to help him with the cell culture. Two years later, Jian completed his Masters’ degree. He then continued to study his PhD degree at Henan Medical University with Professor Qiong Shen, the founder in oesophageus cytology in China who specially studies oesophageal cancer of early diagnosis, prevent and the pathological change prior in situ of oesophageal cancer. Two or three months later, after Jian had reviewed a lot of reference articles, he had

proposed a different angle to study the oesophageal cancer of pathogens with a molecular biology technique. Professor Qiong Shen fully supported him and sent him to study in Beijing Virus Research Institute.” Shen Qiong immediately introduced Zhou Jian to his classmate Yi Zeng who was the Director of Beijing Virus Research Institute. Zeng then put Jian under the supervision of Zhuyan Gu, the deputy of this Research Institute. At that time, Gu had just returned from Germany, was in charge of several projects for China’s Seventh Five-Year Science and Technology Program and specialised in HPV. Xiaoyi commented, “Jian was very lucky. Professor Gu liked him very much and taught him how to do HPV research with great patience. She was the person who took him to the HPV research via molecular biology.” In 1986, Jian completed his PhD study and entered into the Biochemistry Research Institute in Beijing Medical University as a Postdoctoral Training Fellow. He continued his research in HPV with Professor Naiheng Zhang, a virologist. His son Zixi Zhou was just born at that time, so Xiaoyi was transferred to work in the department of ophthalmology of a hospital in Beijing Medical University. In 1988, Jian received a fellowship from Imperial Cancer Research Fund (ICRF) to do the research in the Tumour Virus Laboratory at Cambridge University, UK. He was the first Chinese researcher accepted by Professor Lionel Crawford, an international HPV research pioneer. Xiaoyi recalled “Jian was extremely lucky. Lionel’s laboratory was one of the world’s best for HIV and molecular biology research. Also Lionel liked him very much because he was a person with a great deal of initiative and creativity.” When Zhou had achieved nearly 10 invention patents in 1998, he said: “I owed all my success to my teachers. I am really standing on these giants’ shoulders.” As the funding and equipment in Professor Crawford’s laboratory was excellent, Jian’s research progressed so well that he felt he would need help from Xiaoyi’s hand. In 1989, Professor Crawford invited Xiaoyi to the Laboratory as a visiting scholar. Soon Xiaoyi arrived at Cambridge and ended Jian’s ten months at Cambridge alone. For the following eight years, Xiaoyi was Jian’s assistant and they spent their most exciting years of their lives together. Meeting at Cambridge In 1985 when Zhou Jian was studying HPV for his PhD, on the southern hemisphere, Ian Frazer was awarded his PhD degree by Melbourne University, Australia. Frazer learned from published research literatures that cervical cancer is caused by the HPV infection, and he was also concentrating on the HPV research. In the same year, Dr. Frazer established his own immunology and cancer research laboratory at the Princess Alexandra Hospital, a teaching hospital of University of Queensland. At that time, Dr. Frazer had several responsibilities – lecturing, clinic diagnosis and research. In 1989, Frazer decided to do some research in the laboratory of the Department of Pathology at Cambridge during his sabbatical leave. He worked at Prof. Margaret Stanley’s laboratory which was adjacent to Prof. Lionel Crawford’s laboratory. So, ‘lucky to meet Dr. Jian Zhou who came from China not long before.” Frazer said. Frazer recalled, at Cambridge, the Zhou couple were the most diligent researchers, and regarded as ‘green fingers’, nothing was ever too difficult for them. Xiaoyi said: “At that time, Zhou Jian had just started; I concentrated on being his assistant. Our different personality was complimentary, he was creative and had full of ideas and I was more organised and deft. I had completed all the designated tasks and had never failed one culture of cells. We understood each other well not just in daily life, but also in our cooperation in the laboratory. He only needed to look in a direction and I knew what he would need. Everyone was saying that we were one person in two bodies.” “Ian and Jian were alike in many aspects, they both worked very hard,” continued Xiaoyi, “They were the first to go to the laboratory every morning and the last to leave at night. They got on well with each other.” Frazer said: “we often met during coffee break and discussed how to cooperate to realise and test some new hypothesis.”

Unfortunately, they weren’t able to cooperate much due to many different reasons at Cambridge. When Frazer was leaving for Australia, he warmly invited the Zhou couple to work with him in his laboratory at University of Queensland. He said he had received quite a sum of funding for further research. In 1990, the Zhou family arrived in Brisbane, Queensland. Xiaoyi said: “We didn’t waste any time, continuing with the same project when we arrived at University of Queensland. The change of laboratory didn’t have any negative impact. Everything continued as planned. Ian was always supportive to us. As a result, in less than a year, Jian Zhou’s most important invention started to take shape.” “We did succeed in constructing a virus!” HPV is a very small virus, only 45-55 nanometres in diameter. Scientists have been working on this virus for a very long time, but have never succeeded in constructing it in the laboratory. This is because the virus fuses its gene with host gene, resulting in incomplete virus particle, and this has limited further progress of the research. Scientists had attempted numerous methods, hoping to cultivate the virus outside the human body, so had Jian and Xiaoyi, but without success. Xiaoyi said: “We tried many different methods and it was really hard. We made some progress on the basic research and then published some articles, but helpless when it came to develop this virus particle.” Without the virus, where would vaccine come from? Jian and Xiaoyi had a habit of going for a walk after their son had gone to sleep. Jian would often suddenly come up with an idea, and sometime Xiaoyi would note it down in her hand at the time and then experiment in the laboratory later. One day at the end of 1990, they went for a walk as usual. Jian suddenly said to Xiaoyi: “We have now L1 & L2 (the major ingredients that constitute the HPV late protein and virus coat) well presented and purified, why don’t we put them in a test-tube under certain conditions and see if anything happens?” Xiaoyi said: “I laughed at him at the moment, how could that be possible, just simply put two things together? If so, we wouldn’t be doing this here now because people would have seen the virus particle already.” Two weeks later, Jian asked Xiaoyi if she had done the experiment. Xiaoyi replied: “I noted it down at the time, but thought you were only joking.” Jian again asked her to do the experiment. Following his idea, Xiaoyi “put the two existing HPV late proteins into a test tube, adding a little bit of this and then a little bit of that, as if children in the kindergarten were playing games, it was that simple”. Approximately two weeks later, they observed their experiment under the electron microscope. Both of them were shocked as soon as they saw the result. A virus particle had been constructed! They did see a virus produced outside human body! That was a really exciting moment! Xiaoyi said: “It was very lucky indeed. We immediately told Ian about it and he couldn’t stop smiling at the news. It was an exciting moment we could not forget for a lifetime, a break through with least expectation.” Pathologists understand the importance of this virus-like particle: this particle is hollow without a viral DNA core inside, therefore it is not infectious. Yet it has many antigens on the coat, which will stimulate immunity system to produce antibody once in the human body. Therefore, the virus-like particle is a vaccine in itself. Jian and Frazer tried this HPV virus-like particle on animals and observed antibody reaction in these animals. They published this result in the Journal Virology, Volume 185, 1991. In June 1991, the University of Queensland applied for a patent for this invention. In July of the same year, Jian and Frazer made a presentation at the International Papillomavirus Conference in Seatle, USA. The clinical trials on humans started after the animal trials were successful. Early Departure When the clinical trials reached certain level, University of Queensland could no longer bare the expenses for this research. The University sold a partial patent to an Australian pharmaceutical company CSL for sponsorship, which lasted a few years. By this time, many countries in the world were participating in the

clinic trials and more funding was required. As a result, a further partial patent was sold to a US company Merck Pharmaceuticals to meet the demand for increased funding. Xiaoyi said: “Each sale of the patent provided University of Queensland and us with a large sum of funding for further research. So this was a positive cycle and was very exciting.” Encouraged by Frazer, Jian completed his Doctor degree in medicine at the University of Queensland while continuing his research. In 1994, a German professor established a new HPV research laboratory at Loyola Medical University in Chicago, USA, Jian joined to Chicago to meet the challenge, saying: “one should move around and learn new knowledge to enrich oneself.” In Chicago, Jian had his own PhD students and Postdoctoral students. He encouraged Xiaoyi to sit the Chicago ophthalmological examination and thus Sun returned to her eye clinic work. In 1996, the University of Queensland offered Jian a higher position. Jian returned to Australia with his family and established his own laboratory. In 1998, he became the researcher to obtain most amount of funding in the same year in the history of the University of Queensland, succeeding in obtaining funding for 3 areas from National Health and Medical Council (NHMRC) grants and other funds from pharmaceutical companies. The clinic trials on the vaccine continued around the world. Each March, Jian would go back to Wenzhou Medical College for an inspection and supervising the trials. It was the same in 1999. No one would expect that it was a trip of no return for Jian. “Jian had been robust in his health, and he was healthy person in ten years. Everyone knew he had worked very hard, often working 7 days a week, day and night. One day in February 1999, he had been sitting all day to write applications for funding. After finishing writing, he turned to Xiaoyo: “Why am I so tired?” Xiaoyi then asked him to have a rest and not to go to Wenzhou in March that year. But he insisted on going. In the evening of the 8th March 1999, Jian phoned home in Australia when he arrived in Hangzhou. His son asked him on the phone: “Dad, what present are you going to bring me this time? Will you buy me the latest Lego?” Jian replied: “Yes, not a problem.” Xiaoyi then said to her son: “Your dad is too tired, let him have a rest earlier.” Next day, Zhou’s health conditions deteriorated into coma caused by septic shock. On 10th March, Xiaoyi rushed to Hangzhou with Jian’s mother and son, but it was too late. Jian had closed his eyes forever. Today, eight years later, Xiaoyi still finds it very difficult to accept Jian’s passing “It happened too suddenly, I still cannot believe that he has left me, it is hard to accept this reality.” “A heart-breaking pain” In 1983 when Jian was preparing his wedding, the only request from him was that they should live with his parents. Xiao said: “He was a dutiful son and I’m an easy-going person. I got on with his mother well when we were dating. So I said to him, that’s OK”. Jian was the second child in his family, and he had an older sister. His mother had been with him since his father passed away in 1988. “From USA to Australia, wherever we went, so did his mother,” said Xiaoyi. “His mother has been of great assistance to us. She and I are like mother and daughter. I was joking with her and said mum you are our unpaid housekeeper, and you deserve half of the award” Jian spoilt their son – bringing him presents every time on his return from his trip. It was Xiaoyi who set up rules for their son. Xiaoyi has a gentle and soft character and had generally been following Jian’s pattern after the marriage. However, all this has changed after Jian’s unexpected departure. “The most important things I have learned from Jian are strength and determination. After his death, I felt I must be strong to bring up our son,” Xiaoyi said. “Our son was only 13 years old at the time, in Year 8. I said to him, ‘Everything will be fine. I am now both your mum and your dad.’ Nevertheless, this unexpected tragedy cut short his childhood by a few years; he became more mature for his age. He said at Jian’s memorial service: “I will follow in my father’s foot-steps and be a useful person to society.”

Jian’s mother wrote an elegiac couplet “Jian Zhou showed great respect and loyalty to his teachers, friends and career. He worked his heart in his career, this should always be remembered. He loved and took care of his family in every possible way. He was tranquil and satisfied with his life, and had an abhorrence of sin. His leave is an enormous heart-breaking pain to all of us.” Jian’s father-in-law also wrote in the memorial service: “Jian was an honest person with a brilliant life, and he played pillar role in science research. Jian was diligent and hardworking all his life, and he was a fine model for researcher.” Sun commented: “This summarised him well. He was that kind of person. ” Qu Jia, Jian’s classmate at the university and the now president of Wenzhou Medical College recalled that once Jian had talked with him all night, saying that he would never be satisfied although he had achieved something in his field, he would also like to publish articles in other reputable magazines such as Science and Nature. Unfortunately, before he could realise his dream, he was taken away. A scientist who had been working all his life for others’ better health lost his precious life because of today’s medical limitation. In the letter to Xiaoyi, Frazer wrote: “Jian was an outstanding scientist and a great colleague who has contributed more to his chosen field of molecular virology in ten years than most scientists can achieve in thirty years. His pivotal contributions to the development of papillomavirus vaccines now allow us to be the first to prevent cervical cancer, and his achievement in this area will bring great benefits to the world.” In March 1999, University of Queensland Centre for Immunology and Cancer Research decided to hold academic activities annually named after Jian Zhou, and also named the newly established auditorium after him in memory of his contribution. Jian’s research work will be always commemorated. Hope more people to benefit One day at the end of 2005, Merck Pharmaceuticals announced the success in cervical cancer vaccine clinical trials and the vaccine could be on the market. Frazer was in New York for a conference at the time and only learned the news when a journalist interviewed him through the phone. He immediately phoned Sun, telling her this exciting news, and then choked with tears: “It’s a pity that Jian cannot share this joy today!” On 28th August 2006, at Princess Alexandra Hospital, Frazer injected the world’s first cervical cancer vaccine for two sisters in Queensland, and Xiaoyi and her son have been the witnesses to this historical moment. Her son Zixi was 20 years old and a university student in industrial design. He said this at Jian Zhou Auditorium: “My father’s diligence and creativity combined with Professor Frazer’s experience management made them the perfect team. Without Ian, my father would not have the resources or the understanding of patents to transform his idea into a product, and vice versa, without my father’s research, Professor Frazer would not have had the major advances in understanding of the disease and its treatment to work with. On August 28, 2006, the Minister of Queensland Treasury announced that in order to celebrate the cervical cancer vaccine being ready to use, the State government decided to establish a special Smart State senior research fellowship in honour of Jian Zhou. The fellowship would provide the winner with AU$450,000 over 3 years for research in the fields of immunology and cancer. On February 20, 2007, Queensland Premier Peter Beattie announced that the Dr, Jian Zhou Smart State Fellowship Grant was increased to AU$750,000 over 3 years. “The Dr. Zhou Fellowship is the first recognition by the Government to Dr. Zhou’s significant contribution for the development of the world’s first cancer vaccine.” Mr. Beattie said. Because of the outstanding contribution to the cervical cancer research, Ian Frazer has been awarded as the “Australian Year 2006” and “Queensland Year 2006. Frazer said in an interview: “Jian made the contribution as much as I did, but tragically, he did not live to see the dream of the vaccine fulfilled.” In March 2006, an Australian musician composed a music entitled Professor Ian Frazer to celebrate the two awards he received. The composer used oriental style in the second movement to commemorate Professor Frazer’s co-researcher Dr. Jian Zhou, recognising the contribution of Jian Zhou and his wife to the success of cervical cancer vaccine.

The music moved Sun Xiaoyi to tears, feeling the pride, the honour, the sadness and the joy. She said: “Jian’s biggest influence on me is that he let me know how to love people, and what the true love is. Although he has left us, he would have loved to see more people benefit from the vaccine.” Sun Xiaoyi has not spoken or written articles since the success of the vaccine. She said: “I’m rather quiet. Hundreds and thousands of scientists have contributed to the success of the vaccine. Jian’s critical breakthrough had its inevitability and contingency. I think if he was still here, he wouldn’t be happy with excessive publicity. I don’t think I would want to be against his wish.” Currently, Sun Xiaoyi is planning to do two things, one being to prepare with Queensland government and Australia Chinese Foundation for “Dr. Jian Zhou Memorial Day” event in May 2008; the other being to establish, with her son, “Jian Zhou Foundation to award the most outstanding scientists so as to encourage more people to contribute to medical research for the benefit of mankind. She said, “My other idea is to inspire my son, via these activities, to learn to love other people, to learn to be useful in the society in which we are living.” Reprinted from Science Times on 22 Oct 2007

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Translator: ChanYang (杨婵), MA in Translation and Interpreting (English and Chinese), The University of Queensland, Australia and Jing Zhou, Brisbane, Australia. Edited by Keith Jenvey, Chairman of the Australian Chinese Foundation and Dr. James Pang, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, Princess Alexandra Hospital, The University of Queensland, Australia.

弗雷泽特稿
编者按: 编者按: “全世界每年有 25 万名妇女深受子宫颈癌的困扰,她们大多数生活在发展中国家,其中 很多人被子宫颈癌夺走了宝贵的生命。伊恩·弗雷泽教授和周健博士研制的子宫颈癌疫苗有望根除宫 颈癌,为全世界女性的健康做出了重大贡献。” 这是今年 8 月在北京举行的第四届中国—澳大利亚科学和技术研讨会上,澳大利亚驻华使馆为本 次会议做的“澳大利亚百年科学成果”展板上的一段介绍,文中还写道: “伊恩·弗雷泽教授和后来加入研究的周健博士勤奋工作了 20 载,致力于研究乳头状瘤病毒与 癌症之间的关联,寻找预防和治疗的方法以减少癌症的发病率。15 年前,他们完成的这项发现,推 动了子宫颈癌疫苗的研发工作。” “......周健博士是澳大利昆士兰大学亚免疫学和癌症研究中心的创始人之一,同时也是乳头状 瘤病毒类病毒微粒的发明者之一,他和弗雷泽教授的这一发现为子宫颈癌的预防提供了基础,1999 年,周健博士不幸逝世,年仅 42 岁。” 这无疑是一个震惊世界医坛的重大的科学发明!多么重要的科学新闻! 然而,出乎记者意料的 是,故事的主角弗雷泽教授就在我的面前。弗雷泽应邀做了本次会议的唯一专题报告,介绍子宫颈癌 疫苗发明的过程。报告结束后,他接受了《科学时报》记者近一个小时的采访,讲述他与中国分子病 毒学家周健博士在剑桥大学的“幸运相遇”、以及这次相遇后经过几年的努力给世界所带来一个石破 天惊的重大成果。 周健的夫人孙小依曾经做过周健 8 年的实验助手,她亲手参与合成了第一个类人乳头状瘤病毒, 为子宫颈癌疫苗的成功做出重要贡献。她目前是澳大利亚昆士兰亚历山大公主医院及布里斯本眼激光 中心的眼科医生。从挪威到丹麦,几经周折,记者终于联系上了正在欧洲参加学术会议的她,在近 2 个小时的电话采访中,她回顾了周健的科研生涯、以及那个“改变世界的想法”是怎样获得灵感并想 出来和做出来的……。 子宫颈癌疫苗是人类历史上第一个癌症疫苗,但它不是用真正的病毒而是用不含感染成分的人造 类病毒样颗粒制造出来的。2006 年,基于“类病毒样颗粒”技术,默克制药公司和葛兰素史克制药 公司生产的两种子宫颈癌疫苗终于面市。一年之内,包括美国、英国、加拿大和澳大利亚等在内的 80 个国家先后批准了这种疫苗的使用。 子宫颈癌疫苗的研制成功是医学史上一项重大的突破,里面还蕴涵着许多勤奋、执着、合作、机 会、发现、爱和悲伤……的美好故事。 澳大利亚科学家伊恩·弗雷泽博士: 澳大利亚科学家伊恩·弗雷泽博士:

澳中科学家合作

发明世界上 发明世界上第一个癌症疫苗
本报记者 王丹红

子宫颈癌是由病毒感染而引发的癌症,它是女性中一种常见癌症,发病率仅次于乳腺癌。每年, 世界约有 50 万女性被诊断为子宫颈癌,25 万多女性因此而死亡。 人乳头状瘤病毒(HPV)是导致子宫颈癌的罪魁祸首。1991 年,澳大利亚昆士兰大学免疫和代谢 研究所的伊恩·弗雷泽和中国科学家周健合作,利用重组 DNA 技术制造出一种外形与 HPV 极为相似的 “病毒样颗粒”。这种类病毒样颗粒内部不含导致疾病的 DNA,却能刺激身体产生针对这种病毒的免 疫反应。 2006 年,采用“病毒样颗粒”的合成技术,默克制药公司和葛兰素史克制药公司生产的两种子 宫颈癌疫苗终于面市。一年之内,包括美国、英国、加拿大和澳大利亚等在内的 80 个国家先后批准 了这种疫苗的使用。弗雷泽说,疫苗的使用有可能在一代人中根除宫颈癌。

这是一项振奋人心的重大突破,但在进行这项创造的历程中之主角之一的周健博士,为了攻克技 术关键而付出了自己全部的心血, 却未能亲眼看到自己的研究成果造福人类。1999 年,周健在回国 访问时积劳成疾而突发疾病逝世,年仅 42 岁。 2007 年 8 月,第四届中澳科学和技术研讨会在北京举行,弗雷泽应邀在大会上作学术报告,并 在会后接受了《科学时报》记者的采访,讲述了子宫颈癌疫苗发明和周健的往事。 从爱丁堡到墨尔本 个月的工作假期时, 1974 年,当弗雷泽从苏格兰启程到澳大利亚度过 3 个月的工作假期时,他从未想到这次的行程 将会改变他的人生以及世界上数以亿计的妇女得以摆脱子宫颈癌的困扰。 将会改变他的人生以及世界上数以亿计的妇女得以摆脱子宫颈癌的困扰。 的妇女得以摆脱子宫颈癌的困扰 1953 年,弗雷泽出生在苏格兰,是家中的长子,父亲是爱丁堡大学的生物化学教授,参与了第 一例病人肾脏透析治疗;母亲从事糖尿病医学研究。在父母的熏陶下,他热爱上了科学。孩提时代, 他喜欢将收录机、电视机等拆开又装上,想弄明白它们是怎么工作的,后来,他发现人体是最复杂的 机器,因此,也想弄清楚人体的各个器官是怎么工作的。 上大学时,弗雷泽主修物理,但后来认为学物理找职业前途渺茫,而医学则意味着既可以研究科 学又可以做自己喜欢的事。因此,决定做一名治病救人的医生。从爱丁堡大学毕业后,他专心致志地 做了几年的在职医生,觉得自己很喜欢这个职业。 1974 年,作为爱丁堡大学免疫学学生,21 岁的弗雷泽参加了一个名为“澳大利亚工作访问计 划”的小组。他选择了到墨尔本的沃尔特伊莱扎医学研究所从事免疫学研究,因为这里有当时世界最 先进免疫学研究,他说:“我在大学时阅读的论文一半以上是来自这个研究所的”。沃尔特伊莱扎医 学研究所创立于 1915 年,是澳大利亚第一个医学研究机构(免疫学诺贝尔奖获得者 Sir Macfarlane Burnet 所在的研究所)。 然而,弗雷泽从未想到这次的行程将会改变他的人生和世界上数以亿计的妇女得以摆脱宫颈癌的 困扰。1981 年,他和妻子移民澳大利亚,他在沃尔特伊莱扎医学研究所获得了一个职位,并在墨尔 本大学攻读博士学位。 在沃尔特伊莱扎研究所,弗雷泽研究了许多通过性交传播的传染病。当时,科学家已经发现,子 宫颈癌是因病毒 HPV 感染而引发的,他对 HPV 产生了特别的兴趣,他想知道这种病毒是如何导致子宫 颈癌的发生。如果是病毒感染而致的癌,那么可否用疫苗来预防这种癌症呢? 病毒与子宫颈癌 25%左右癌症是因病毒感染引发的 比如乙肝病毒所导致的肝癌, 左右癌症是因病毒感染引发的, 有 25%左右癌症是因病毒感染引发的,比如乙肝病毒所导致的肝癌,人类乳突病毒所导致的子宫 颈癌等, 颈癌等,这就意味着至少 25%的癌症可以通过疫苗预防。 25%的癌症可以通过疫苗预防。 的癌症可以通过疫苗预防 子宫颈癌是子宫颈处细胞的异常生长。最初,流行病学的研究发现子宫颈癌与性生活有关,19 世纪中叶的学者注意到,修女和妓女的子宫颈癌发生率有显著差异。之后,许多流行病学家指出,性 生活的某些特质,如早婚、多产及复杂的性关系都和子宫颈癌的发生有关,因而逐步形成子宫颈癌是 性传染病的观念。但直到 20 世纪 60 年代,子宫颈癌的病因研究仍围绕着淋病、梅毒、滴虫等病原体 打转,没有突破。 20 世纪 60 年代后期,对 HPV 的研究成为热门课题。这时,流行病学的研究发现,HPV 感染率在 一般妇女约为 10-15%,在子宫颈上皮内肿瘤患者则为 20-50%,在子宫颈癌患者则为 80-90%。科 学家们确信,HPV 在子宫颈癌发生过程中扮演了重要角色。 1980 年,科学家们证实,子宫颈癌是由 HPV 感染所导致,但并不是所有感染 HPV 的女性都会发 生这种癌症。在人的一生之中,80%以上的男性和女性会在某个阶段感染上 HPV,然而,在被感染的 女性中,98%的人会自动击退这种病毒,只有 2%的感染者会发展成癌症,但就是这 2%的发生率,也造 成了世界上每年有 50 多万名女性罹患此症,其中 20 多万人因此而丧生。 从理论上讲,既然某种疾病是病毒感染导致的,那么就有可能发明一种针对这种疾病的疫苗。通 常情况下,疫苗都是按这样的思路制作的:通过改造或弱化某种病毒,让它丧失引发疾病的能力但却 能激发身体的免疫系统产生相应的抗体,这样,当真正的病毒侵犯身体时,免疫系统都可以用已有的 抗体来对付这种病毒。

然而,HPV 是一种特殊的小 DNA 病毒,它不能单独进行繁殖,必须寄生在活细胞内才有可能。矛 盾的是,当这种病毒在活细胞中繁殖时,病毒的基因就与细胞的基因产生了融合。因此,迄今为止, 科学家们既没能在实验室中成功培育出这种病毒,也没有获得过这种病毒的纯基因组。 如果不能获得病毒,那么疫苗的研制就是空想。世界上至少有 2000 多位科学家在研究 HPV 与子 宫颈癌,他们冥思苦想、搜肠刮肚地希望能找到提取或制作这种病毒的方法。弗雷泽和周健就是其中 的两位。 剑 桥 遇 周 健 弗雷泽说, 我希望能生产出一种疫苗来预防这种癌症。 弗雷泽说,“我希望能生产出一种疫苗来预防这种癌症。” 生产出一种疫苗 20 世纪 80 年代初,在墨尔本学习和研究的弗雷泽通过阅读文献已经得知,子宫颈癌是由 HPV 感 染造成的。“这时我认为,做一名研究人员比做一名医生更有意义,因为作为一名医生,你只能一次 医治一个病人,但如果你是一名科学家,只要你做出了有价值的发明或发现,那么将会有更多的病人 受益。”弗雷泽说,“我希望能研制出一种疫苗来预防这种癌症。” 1985 年,在沃尔特伊莱扎医学研究所工作 4 年后,弗雷泽想建立自己的实验室。他说:“在科 学研究中,一个人应该成为团队中的一员,绝大多数优秀的科学来自于团队。但是,你也必须准备好 带领一个团队,这样你可以做自己想做的事。” 他开始四处寻找工作。这时,位于昆士兰州首府布里斯班的亚历山大公主医院正急于找人来建立 新的实验室,他们找到了弗雷泽。于是一拍即合。弗雷泽说:“那时,我已决定要从事 HPV 和子宫颈 癌疫苗的研究。” 初来乍到,弗雷泽身兼数职。在医院,他需要管理一个诊断实验室并提供临床服务;在昆士兰大 学,他有繁重的教学和管理任务,还要推进自己的研究发展计划。在几年的紧张忙碌中,他有过一些 小小的成就并为此颇感兴奋,但也觉得该自己充电了。 1989 年,弗雷泽决定到英国剑桥大学度学术休假。在那里,他“幸运地”遇见了不久前来自中 国的周健博士。“周健是一位分子病毒学家,对乳头瘤病毒有特别的兴趣,他在 Lionel Crawford 教 授的实验室工作,而我正好在隔壁实验室跟随 Margaret Stanley 教授工作。”弗雷泽说。 “那时,我发现周健和夫人孙小依是两位最为勤奋的研究人员,无论白天黑夜,凡我去实验室 时,总会看到他俩在那里努力工作。实际上,我是他们实验室的打扰者,由于我的实验室过于拥挤, 没有空间供我活动,加之经费紧张,所以老是借用 Cranford 教授的实验室和试剂。我们相处得很融 洽,周健承认我是他所强调的那种有经济头脑的科学家,我则意识到他是一位学识过人的好同事, 值 得信赖的好朋友。” 周健 1982 年毕业于中国温州医学院,1982 年-1984 年间,他在浙江医科大学攻读硕士时对病毒 的分子生物学产生了兴趣,1987 年在河南医科大学获得病理学博士学位,在北京医科大学做博士后 期间,赴英国剑桥大学英国帝国癌症研究基金会免疫学与癌症研究中心肿瘤病毒实验室从事研究工 作。 “我们也常常在喝咖啡时间相遇,并谈论彼此间如何可以通过合作来试验一些新的设想, 进行一 些新的创造”,弗雷泽说。 但那时,两人在剑桥没有办法做太多事情,当弗雷泽准备回国之前,他热情邀请周健夫妇全家去 澳工作。1990 年,周健和孙小依带着儿子来到澳大利亚,夫妇俩在昆士兰大学的免疫实验室,和弗 雷泽共同研究 HPV。 制做一个病毒的“稻草人” 制做一个病毒的“稻草人” “他具有非凡的技术,他能提取出这种病毒的基因并克隆它们。” 他具有非凡的技术,他能提取出这种病毒的基因并克隆它们。 研制子宫颈癌疫苗面临的最大问题是如何才能获得 HPV?既然这种病毒不能在体外组织液中培 育,而在活细胞中繁殖时与宿主的细胞基因融合,那么,有什么捷径能制造出这种病毒呢?那时周健 真是废寝忘食日夜思索。 分子生物学研究早已发现,HPV 有 70 多种类型,也就是说,这一病毒家族里有 70 多个相似而又 不同的病毒(亚型),其中至少有 10 个类型与尖锐湿疣有关(如 6,11,16,18 及 33 型,最常见 6、11 型),而第 11,16,18 型与生殖器癌有关。虽然 HPV 有 70 多种类型,但所有的 HPV 都具有相 似的颗粒状结构:内核是导致疾病的病毒 DNA,外表是一层有 20 个面的蛋白质“外壳”。

作为一名分子病毒学家,周健擅长克隆基因并在细胞中将它们表达出来,他试图通过重组 DNA 技 术做出这种病毒的外壳。他的想法是要制造出外表类似 HPV 但内核不含病毒 DNA 的病毒样颗粒,这样 的颗粒可以像“稻草人”一样让体内产生免疫反应但又绝对安全。 重组 DNA 技术是指利用载体人工修饰有机体遗传组成的技术,即在体外通过酶的作用将异源 DNA 与载体 DNA 重组,并将该重组 DNA 分子导入受体细胞内,以扩增异源 DNA,并实现其功能表达的技 术。但是,当他将这种技术用于 HPV 颗粒的制造时却遇到了极大的困难,这种病毒的基因很大,当时 提取和克隆大基因非常不易,他们曾在 6 个月时间里一无所获。 一天夜里,周健在和孙小依散步时突然想到一个主意:不是已经有表达和纯化了的 L1、L2(HPV 晚期蛋白、病毒壳膜的主要构成)蛋白,何不把这两个蛋白放在组织液里,看看它们能否合成病毒样 颗粒?孙小依笑着说:哪里有这么简单的事?但一个月后,她照着周健的想法做了,在电子显微镜 下,他们看到了难以置信的事实——与 HPV 病毒十分相似的颗粒!一个 HPV 的“稻草人”! 这就是奇迹发现的那一刻!弗雷泽说:“我清楚地记得 1991 年那个特别的日子,我们第一次看 见了这张病毒样颗粒的图片,当时我们就知道如果有某种东西可以制成疫苗,那么就应该是它!” 作为一名免疫学家,弗雷泽更关心的是疫苗和免疫学,他们想的是如何进一步纯化和更多地合成 病毒样颗粒以便做动物试验。经过多次的努力,他们终于证实了病毒样颗粒能够激发免疫反应。 他们的第一篇论文发表在 1991 年第 185 期的《病毒学》期刊上。 论文中详细介绍了制造病毒样 颗粒的实验细节:“通过设计,一个重组的牛痘病毒可以用来共同表达 HPV16 型晚期基因 L1 和 L2 的 表达......用重组牛痘病毒制造了 HPV。论文中详细介绍了制造病毒样颗粒可用于生物化学研究,并 为疫苗的开发提供了一个安全的来源......HPV16 型和 18 型对人体子宫颈的感染与宫颈癌发生密切 相关。” 弗雷泽高度评价周健具有的才能和精湛的技术,他能提取这种病毒的基因并克隆它们。他发明的 “病毒样颗粒”方法已成为今天“制造子宫颈癌疫苗的基础”。 当梦想成为现实时 “这是一个悲伤的时刻,因为我的父亲今天不能够和我们在一起” 这是一个悲伤的时刻,因为我的父亲今天不能够和我们在一起” 在第一眼看到“病毒样颗粒”后,弗雷泽和周健最担心的问题是:“病毒样颗粒”所产生的免疫 反应是否足以让它制成疫苗? 在最初的几年里,他们努力让这种“病毒样颗粒”表现出所期望的效果。当这一目标实现后,昆 士兰大学开始与投资公司和有疫苗研发能力的制药公司联系。在获得默克公司支持后,大规模的动物 试验和临床试验开始了。 但天有不测风云。1999 年,当疫苗的第三期临床研究还在进行时,周健回中国进行学术访问, 因过度疲劳意外去世。 2006 年,默克制药公司和葛兰素史克制药公司生产的两种子宫颈癌疫苗面市,一年之内,包括 美国、英国、加拿大和澳大利亚等在内的 80 个国家先后批准了这种疫苗的使用。澳大利亚是第一个 批准这种疫苗使用的国家。 2005 年底,由于在子宫颈癌疫苗发明中的杰出贡献,弗雷泽当选为“2006 年度澳大利亚杰出人 物”,这是一名澳大利亚公民所能获得的最高荣誉,媒体称他为“上帝给女人的礼物”。弗雷泽在接 受媒体采访时说:“我是如此的遗憾,此时此刻周健不能在这里我和分享这份荣誉,他非常应该获得 这一份殊荣,因为在这个疫苗的发明中,他的贡献和我一样多。” 2006 年 8 月 28 日下午,在澳大利亚昆士兰州的亚历山大公主医院,弗雷泽为一对昆士兰少年姐 妹接种了世界第一支子宫颈癌疫苗,孙小依和 20 岁的儿子周子晞见证了这一时刻。周子晞说:“我 们多么高兴,试验表明这种疫苗百分百地有效。这是一个幸福的时刻,人们终于可能接种这种疫苗。 但这也是一个悲伤的时刻,因为我的父亲今天已经永远不能够和我们在一起。” 在第一支疫苗接种的当天,昆士兰州副州长宣布:为了庆祝子宫颈癌疫苗的启用,将以周健的名 义设立一项智慧之州高级奖助金,该奖助金在三年的时间里为获奖者提供 45 万澳元的经费,供从事 免疫和癌症领域的研究之用。 2007 年 2 月 20 日,昆士兰州州长宣布,智慧之州周健奖助金增加为三年 75 万澳元,他说: “周健奖助金的设立是政府对周健博士在世界第一个癌症疫苗研发中的重大贡献首次正式的认可和表 彰。” 让世界知道周健 我认为自己 责任确保中国和其它发展中国家的女性能获得我和周健合作发明的这种疫苗。 “我认为自己有责任确保中国和其它发展中国家的女性能获得我和周健合作发明的这种疫苗。”

周健骤然去世的消息让弗雷泽悲伤不已。2006 年,在作为“年度澳大利亚杰出人物”接受采访 时,这段悲伤的回忆仍然让他眼里浸满泪水。他说,周健不能活着看见疫苗的梦想成为现实,这是一 个悲剧。 弗雷泽发誓要铭记周健。并让他的贡献为世人所知。他将和周健的夫人和儿子共享成果利益。 弗雷泽开始向世界介绍周健。2006 年 1 月 25 日,在昆士兰大学对“年度澳大利亚杰出人物”的 新闻报道中,他和周健的照片并排出现在文章中。 2006 年 3 月 7 日,在澳大利亚国家广播电视公司的专访中,弗雷泽详细介绍了自己在剑桥与周 健从相识到合作研究的过程,他说:“他擅长分子病毒学,他能提取基因并在细胞中表达出基因,我 的兴趣在疫苗和免疫学这方面,我想如何将这些用于疫苗制造。” 2007 年 3 月 15 日,在接受澳大利亚国家广播电视公司的电视专访中,弗雷泽说:“1989 年,我 到剑桥大学学术休假,我并没有学多少想学的干细胞知识,但却幸运地遇见了周健。我们开始合作研 究 HPV 并探讨研制疫苗的可能性,周健的贡献在病毒学,我的贡献在免疫学。” 2006 年 7 月 10 日-11 日,中国 《人民日报》连载了题为 “让女性远离子宫颈癌” 的报道, 还 刊登了弗雷泽和周健的照片。 2006 年 3 月,澳大利亚的音乐家创作了一首题为“伊恩·弗雷泽教授”的乐曲,庆祝他荣誉 · “2006 年度澳大利亚杰出人物”和“2006 年度昆士兰杰出人物”殊荣。这首乐曲的第二乐章以东方 风格的形式纪念周健博士和彰扬周健夫人孙小依,表彰他们在子宫颈癌疫苗的研制中所做出的贡献。 周健的早逝让弗雷泽认为自己还有一份特殊的责任:“中国是周健的祖国,子宫颈癌也是中国面 临一个严重问题,我认为自己有责任确保中国和其它发展中国家的女性能获得我和周健合作发明的这 种疫苗。” 2007 年 4 月 10 日,弗雷泽来到新疆石河子大学,作了题为《人类第一个癌症疫苗的诞生—— HPV 预防性疫苗的研究与应用》的演讲,并受聘为该校名誉教授;2007 年 8 月 11 日,弗雷泽应邀到 四川大学华西第二医院发表演讲,受聘为四川大学荣誉教授,双方洽谈有关宫颈癌疫苗临床及基础研 究方面的合作事宜;2007 年 11 月,弗雷泽还将到北京参加 HPV 病毒学国际学术会议…… 目前,弗雷泽正与盖茨基金会、世界卫生组织疫苗发展计划组合作,努力将疫苗以尽可能廉价的 方式送达发展中国家。但他认为“‘便宜’并不必然意味着贫穷的国家能够获得它们”。“我会特别 关注疫苗在全球的销售,目的是让最需要的女孩和妇女能够得到它们。” 结束语:做一名滑雪教练曾是弗雷泽孩提时代的梦想,他是在苏格兰大学的滑雪俱乐部里与夫人 结束语 卡罗琳相识的,他曾想过退休后要实现这个梦想。但子宫颈癌疫苗的成功激发了他永恒的信心和责 任,他说:“我再也没有机会成为一名滑雪教练了... ...,因为我老想当我 80 岁时,我也许还会呆 在实验室。” 原载《科学时报》 原载《科学时报》2007 年 10 月 22 日

Scientist Cooperation in Invention of the Cervical Cancer Vaccine in Australia – Interview Australian Award Scientist Prof. Ian Frazer
Newspaper reporter: Danhong Wang Science Times 22 October 2007

Editor’s Note: “About 250,000 women were suffered and puzzled by the cervical cancer every year round the world. Majority of them are living in developing countries, of which a lot of invaluable life was taken away by the disease. The cervical cancer vaccine developed by Professor Ian Frazer and Dr. Jian Zhou is able to eradicate the cervical cancer, and this is a great contribution to the women’s health in the world.” The above introduction was shown on the exhibition board “Australian 100-year scientific achievements” prepared by the Australian Embassy in Beijing for the 4th China – Australia Scientific and Technology Symposium held in Beijing in August 2007. The introduction also described: “Professor Ian Frazer and late Dr. Jian Zhou have worked hard for 20 years at studying the relation between the human papilloma virus (HPV) and cancers. They were searching an effective prevention and treatment methods to reduce the incidence of cancers. The discovery they obtained 15 years ago has advanced the development of the cervical cancer vaccine.” “……Dr Jizn Zhou was one of the founders of the University of Queensland’s Immunity and Cancer Research Centre in Australia, while he is also one of the inventors of the papillomavirus like particle. This discovery has provided the base for preventing the cervical cancer. Unfortunately, Dr. Jian Zhou untimely passed away in 1999, at the age of only 42.” No doubt, this is a significant medical invention and scientific news shocking the whole world! It was surprised to know that the leading person of the story Professor Ian Frazer did attend the Symposium and was invited to have a unique speech in this meeting. After the speech, he received one-hour interview from a reporter of the <Science Times>. He told the reporter that he was very lucky to meet Dr. Jian Zhou who was a research fellow in Cambridge University. Dr. Jian Zhou was an excellent molecular biologist and virologist who came from China originally. Their hard and diligent research works for many years leading to the great contribution to the world.

Jian Zhou’s wife Xiao Yi Sun was used to be an experimental assistant of Jian Zhou for 8 years. She has participated in producing the first papillomavirus like particle, and made remarkable contribution to the successful development of the cervical vaccine. At present she is working in the eye clinic at the Laser Sight Centre and the Alexander Princess Hospital in Brisbane Australia. After passing many setbacks in contact trials from Norway to Denmark, the reporters finally found her who was attending an academic conference (ESCRS) in Europe at that time. During nearly 2-hour telephone interview, she reviewed Jian Zhou’s research career, and how to envisage the inspiration of the “idea changing the world” and how to manufacture the HPV virus-like pellet etc. The cervical cancer vaccine is the first cancer vaccine in the mankind history. It does not come from the real virus but using virus-like particle which excludes infection component. In 2006, two types of cervical cancer vaccine produced by Merke and Glazosk pharmaceutical companies were on the market. Around 80 countries including USA, UK, Canada and Australia have approved the application of such a vaccine within just one year. The successful development of the cervical cancer vaccine has been a pivotal breakthrough in medical history which covers many beautiful stories in relation to diligence, persistence, cooperation, opportunity, discovery, love and sadness…… ******* The cervical cancer vaccine is a cancer initiated by the viral infection. It is one kind of common feminine cancer, and its incidence rate is only inferior to the breast cancer. Nearly 500,000 females every year in the world are diagnosed with cervical cancer, of which more than 250,000 do not survive. The human papilloma virus (HPV) is the chief responsibility causing the cervical cancer. In 1991, Ian Frazer and his colleague Jian Zhou, of Chinese origin, in the immunity and metabolism Research Centre of the University of Queensland in Australia cooperated to make “the HPV virus type pellet” which is extremely similar to HPV in contour using reorganised DNA technology. This kind of viral type pellet does not contain the DNA that causes the internal disease. It actually stimulates the body to produce immune response towards the virus. Frazer said that the vaccine use has the possibility to eradicate the cervical cancer in one human generation. This is an exciting breakthrough, but one of the major people for the invention – Dr. Jian Zhou has not been able to see the research to benefit the humanity by his own eyes. In 1999, when Zhou visited his homeland, he suddenly became ill and passed away because of septic shock influenced by overwork and tiredness, at the age of only 42 years old. In August 2007, The 4th Chinese and Australian Science and technology Symposium was held in Beijing, Frazer was invited to have a key speech in the Symposium. Meanwhile Frazer received “Scientific Times” reporter’s interview, which narrated the invention of the cervical cancer vaccine and Zhou’s past events. From Edinburgh to Melbourne When Frazer started on a three month-long work vacation in Australia from Scotland in 1974, he never thought that this journey would change his life, and let 100 million women in the world get rid of the puzzle of the cervical cancer.

Frazer was born in 1953 in Scotland, was the family’s eldest son. His father is an Edinburgh University’s biochemistry professor. He participated in the first kidney dialysis treatment of a patient. His mother is engaged in the diabetes medical research. Under parents’ gradually influence, he developed his love of science. He liked to disassemble and assemble radio cassette and television at infancy time, with the intent of understanding how they worked. Later, he found that the human body was a most complex machine and he also wanted to know how each organ of the human body worked. Frazer majored in physics when he studied at university, but afterwards thought that the professional future was uncertain in studying physics. Considering that medicine is the science he most favoured he decided to be a doctor to treat disease and help to save patients. After graduating from Edinburgh University, he has been a doctor for many years, and enjoyed his career. As an immunology student of the Edinburgh University, 21 year-old Frazer participated in a group called as “work and visit plan in Australia” in 1974. He chose to do the immunology research in Walter Ellis Medical Research Institute in Melbourne, because this institute was conducting the most advanced immunology research in the world at that time. The Walter Ellis Medical Research Institute established in 1915, was the first medical research organization in Australia. Of the papers Frazer wrote during his university study, more than half papers came from his study in this research institute. Frazer and his wife immigrated to Australia in 1981, and he obtained a position in the Walter Ellis Medical Research Institute, while he studied for his PhD in Melbourne University. In this institute, Frazer has studied many sex-transmitted diseases. At that time, scientists have already discovered that the cervical cancer was initiated by the viral HPV infection. Frazer has had special interest in HPV, and wanted to know how this kind of virus causes the cervical cancer. If the cancer is really caused by the virus, is it possible to use a vaccine to prevent this cancer? HPV Virus and Cervical Cancer It is known that about 25% cancer was initiated by viral infection. For instance the hepatitis B virus causes the liver cancer; the person papilloma virus causes the cervical cancer and so on. That means at least 25% of cancer may be prevented by using vaccines. In the later period of 20th century, the HPV research became a popular topic. German scientist Zur Hausen confirmed in 1980 that the cervical cancer is the result of the HPV infection, but certainly not all women who were infected would suffer this cancer. In human being’s life, more than 80% men and women can be infected by HPV in some stages. Of the female who infects, 98% person can automatically repel this virus, and only some 2% infection can develop to the cancer. But even with the 2% formulation rate, more than 500,000 females suffer from this illness in the world every year, and over 200,000 females lose their life. Theoretically speaking, it is possible to invent a vaccine to treat a disease which is caused by viral infection. In the usual situation, the vaccine is developed by this method – transforming or weakening a kind of virus, and lets it lose the initiation ability of a disease while stimulating the bodily immunity system to produce the immune body. Thus, when a

virus infringes, the immunity system may use the already existed immune body to cope with this kind of virus. However, HPV is a particular small DNA virus, it cannot carry out reproduction locally and must parasitize in the living cell. Moreover, when HPV reproduces in the living cell, its gene and the cell gene are fused. Therefore, scientists have neither successfully cultivated this kind of virus in laboratories, nor obtained this virus’s pure gene group until now. If the virus can’t be obtained, the vaccine development is a fantasy. At least 2000 scientists are studying the HPV and cervical cancer in the world. They ponder diligently, and hope to find methods to withdraw and make the virus. Ian Frazer and Jian Zhou are two of them. Meet Zhou in Cambridge At the beginning of 1980s, Frazer already knew that the cervical cancer was caused by HPV infection through published literature. He was more inclined to be a researcher than a doctor, because a doctor only treats a patient at a time, but scientists would provide more benefits to patients if they can make valuable inventions or discoveries. Frazer was awarded a PhD degree in Melbourne University in 1985, and he intended to establish his own laboratory. At that time, the Alexander Princess Hospital in Brisbane was anxious to find a person to build a new laboratory. Thereupon, they fit easily. Frazer said:”I then decided to be engaged in the research of the HPV and cervical cancer vaccine”. Newly arrived Frazer held several positions at the same time. He managed a diagnosis laboratory, provided clinical services in the hospital, and undertook arduous teaching together with management duty in Queensland University. Meanwhile he also advanced his own development plan. During the several years of bustling life, he was excited by some small achievements, however he understood that he needed to acquire more new knowledge in this area. Frazer took an academic leave to go Cambridge University of England in 1989. He “luckily” met Dr. Jian Zhou who just came from China. Frazer said: “Zhou is a molecularvirologist, and has special interest in the papilloma virus. He worked in the laboratory of Professor Lionel Crawford while I worked in a next door laboratory under Professor Margaret Stanley”. Frazer also said: “I found Zhou and his wife Xiao Yi Sun were two most diligent researchers. Regardless the daytime or night, I always saw them to do hard work there. In fact, I was a disturber to their laboratory activity, because my laboratory was too crowded, there was no moving space for me. In addition, the research funds of my project were very tight, so that I usually borrowed Professor Crawford’s laboratory and reagent. The relationship between us was very harmonious. Zhou acknowledged that I was a scientist with commercial mind and I realized that he was a friend worth trusting and colleague with excellent knowledge. We usually met together at coffee time, and discussed how to experiment some tentative plan and carry out new creations through cooperation.” At that time, Frazer and Zhou did not have the means to do many things in Cambridge. When Frazer prepared to return to Australia, he invited Zhou and his wife to go Australia to

work. In 1990 the couple and their son arrived in Australia and conducted HPV research in the Queensland University’s immunity laboratory with Frazer. Manufactures of a Virus “the Scarecrow” The major problem of manufacturing a vaccine for cervical cancer is how to obtain HPV. This virus can’t be cultivated in out-body tissue fluid, but reproduces in the living cell fusing with host’s cell gene. What sort of methods can manufacture this kind of virus? The molecular biology research already discovered that HPV has more than 70 types, but they all have the similar granulated structure: the essence core is the viral DNA causing the disease, and the semblance is a protein “outer shell” possessing 20 surfaces. Frazer said that Zhou had extraordinary technical knowledge. He could develop the gene of this kind of virus and clone the gene. As a molecular virologist, Zhou was an expert in cloning the gene and expressing them in the cell. He attempted to produce the outer shell of the virus through reorganizing DNA technology. His idea was to produce this kind of viral pellet which had the similar HPV in its semblance, but did not contain the viral DNA in its essence. Such a pellet may be like “the scarecrow” which lets the body generate the immune response but is absolutely safe. Reorganising the DNA is the technology of artificially embellishing genetic composition of organic part using a carrier, namely in vitro reorganising different source DNA and the carrier DNA through the enzyme function, and inducting the reorganised DNA molecule into the acceptor cell so as to increase different source DNA and realize its function expression. But he encountered enormous difficulty when this technology was applied to manufacture the HPV pellets. This kind of virus’s gene is very big, and it is not easy to withdraw and clone the big gene. At one stage they had achieved nothing after 6 months of laboratory testing. One evening, Zhou suddenly generated an idea while walking with his wife Xiao Yi Sun. They already had expressed and purified L1, L2 protein (HPV later period protein and main constitution of the viral shell), why not put the two proteins into a tissue fluid and see if they could synthesize the viral type pellets. Zhou’s wife smiled and said how could this be such a simple solution? One month later, she tried Zhou’s idea, under an electron microscope; they found an unbelievable fact – an extremely HPV-like pellet and a HPV “scarecrow”. That was the moment when the miracle discovered. Frazer said that I clearly remembered the special date in 1991, and that we first time saw the picture of this viral type pellet, and we knew at that time, if any thing can be used to make the vaccine, this should be it. As an immunity scientist, Frazer was more interested in vaccine and the immunology. They finally confirmed that the viral type pellet can stimulate the immune response. The first paper from Zhou and Frazer were published in the 185th issue “Virology” in 1991. They described in detail the experimental process of manufacturing the viral type of pellet. Frazer said “a reorganized smallpox virus could be used to express HPV16 type of late period gene L1 and L2……. through such a design. That is to say that the HPV was made by reorganizing the smallpox virus”. In this paper, they indicated that the manufactured virus type pellet could be applied in biochemistry research, and has provided a safe source

for the vaccine development. The HPV16 and 18 have the close correlation to the infection of human body cervical cancer. When the dream became reality The question which Frazer and Zhou most worried was whether the immune response generated by the virus type of pellet was sufficiently strong enough to make the vaccine after first seeing the virus type of pellet. In the initial several years, they diligently let the virus type of pellet show the expected effect. When this goal was realized, the University of Queensland commenced to deal with investment companies and the pharmaceutical companies having the research and development ability. After receiving support from Merke and Co., large-scale animal experiments and clinical tests started. In 1999 when the 3rd stage clinical research was carried on, Zhou went to China for an academic visit, but suddenly died due to septic shock influenced by overwork and extreme tiredness. In 2006, two kind of cervical cancer vaccines produced by Merke and Glazosk pharmaceutical companies were on market. More than 80 countries including USA, UK, Canada and Australia have approved the application of such a vaccine within just one year. Australia was the first country to authorize this vaccine. In the end of 2005, Frazer was elected as “2006 Australian of the Year” because of his brilliant contribution on the invention of the cervical cancer vaccine. This is one of the highest honours that an Australian citizen can be awardwed. When Frazer was interviewed by media, he said “I feel very sorry that Jian Zhou can’t share this great honour with me. Zhou extremely deserves to have this honour, because his contribution is equal to mine in the invention of the vaccine”. On August 28, 2006 the afternoon, Frazer has vaccinated the world first cervical cancer vaccine for a pair of Queensland young sisters in the Alexander hospital of the Australian Queensland state. Zhou’s wife Xiao-Yi Sun and 20 year old son Zixi Zhou were witnesses to the exciting moment. Zixi said “We are now so happy; the clinic test indicated that this kind of vaccine is 100% effective. This is a happy time; people finally accept this vaccine; however this is also a sad time, because my father can’t be with us today”. On the same day of the first vaccination, the Queensland Deputy Premier announced that in order to celebrate application of the cervical cancer vaccine, the state set up a smart highlevel fund in the name of Jian Zhou. This fund provides AU$450,000 over 3 years for a prize-winner engaging in the immunity and cancer domain research. On February 20, 2007, the Queensland premier announced that the Jian Zhou smart fund was increased to AU$750,000 over 3 years. The premier said: “establishment of Jian Zhou fund is the first formal acknowledgement of Zhou’s significant contribution to the world first cancer vaccine research and development by the government”. Let the world know Jian Zhou

The news of Jian Zhou’s suddenly past away let Frazer feel very sad. In 2006, when “the year Australian” accepted an interview, such a sad recollection still let his eyes soak the full tears. He said that Zhou could not see the vaccine dream become reality, and this was a tragedy. Frazer pledged that Zhou and his contribution must always remembered by the people of the world. In a news report on ‘the year Australian” published by the University of Queensland on 25 January 2006, the pictures of Frazer and Zhou presented abreast in row in the article. In a special interview conducted by Australia Broadcasting Television Company on 7 March 2006, Frazer introduced in detail about the course that he met Zhou in Cambridge and further cooperation in research. He said: “Zhou excels at the molecular virology, and can withdraw the gene and express the gene in the cell. I am interested in the vaccine and immunology, and consider how to use this aspect to manufacture vaccine”. On 15 March 2007, Frazer accepted another special interview from Australia Broadcasting Television Company in which he said: “Within an academic leave in Cambridge in 1989, I have not learned much about the stem cell knowledge which I wanted to study, luckily I met Jian Zhou. We started cooperate study on HPV, and explored the possibility of developing vaccines. Zhou’s contribution was in virology, and my contribution is in immunology”. Australian musicians created a piece of music called “Professor Ian Frazer” to celebrate his honour in receiving the awards “2006 the Australian” and “2006 the Queenslander” in March 2006. The second movement of this music memorialized Dr. Jain Zhou and praised Zhou’s wife Xiao-Yi Sun by eastern style commending their contributions in development of the cervical cancer vaccine. Zhou’s early past away leaves Frazer a special responsibility: “China is Zhou’s motherland, and the cervical cancer is also a serious problem which China faces. I think I have the responsibility to ensure females in China and other developing countries to obtain the vaccine invented Zhou and myself”. On 10 April 2007, Frazer went to the Xinjiang Shihezi University to present a lecture with the topic “Establishment of the first human cancer vaccine – research and application of HPV preventive vaccine”. Frazer was invited to be a professor emeritus of this university. On 11 August 2007, with the invitation of the Sichuan University, Frazer made a lecture in the second Huaxi hospital. He was also invited to be a professor emeritus of Sichuan University. Frazer also arrived at Beijing to attend the HPV international academic conference in November 2007……. At present, Frazer is co-operating with Gates Foundation and the vaccine development plan group of the World Health Organization making effort to deliver the vaccine to developing countries by as far as possible the inexpensive way. He will pay attention to the global sales of this vaccine intending that the vaccine will be obtained by the women who most need it.

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Translator: Dr. Ruixuan Rong (PhD), Senior Research Fellow, Julius Kruttschnitt Mineral Research Centre, The University of Queensland, Australia

“这才是真正的男人” 这才是真正的男人”
记者 陈欢欢

1991 年 7 月,弗雷泽和周健在美国西雅图参加 HPV 国际研讨会。 宫颈癌疫苗发明者之一周健博士对科研事业的贡献是有目共睹的。而他对妻子、家庭、国家的爱 心也令他身边的人至今记忆犹新。 “从未忘记自己的根” 从未忘记自己的根” 自己的根 周健在英国时, 他的博士后导师张迺蘅给他的一封信对他影响非常大。张迺蘅在信中说:知识是 没有国界的,只要有条件能做好 HPV 研究工作,不管是在中国、英国还是在美国都一样。 1999 年,弗雷泽教授(Ian Frazer)在周健追悼会的悼词中, 曾把周健形容为“热情而崇高的 架桥人”,他说:“周健无疑是一位世界村的村民,而他从未忘记自己的根。” 周健一直是华人社团的活跃分子,并牵头和国内一些研究单位建立了合作关系。温州医学院院长 瞿佳回忆,周健经常自己花钱、花时间接待和培训来自国内的学者,安排吃、住、行、访问和进修。 “1994 年我在波士顿学习,周健知道后就给我寄来往返机票,让我到芝加哥讨论如何支持母校开展 医学科研。” 在芝加哥时,周健对美国的中文学校印象颇深,回到澳大利亚后,“为了不让我们的孩子忘记中 文,他和小依出钱、出力、出主意,热心地和朋友一起组建了一所苗苗中文学校。”在澳的华人科学 家魏明谦说。 1997 年,布里斯班能收看到卫星电视的还很少。周健特意赶在香港回归前把卫星电视装好,让 在他那里工作的中国人到家里来看。香港回归当天,十多个人来到周健家里,一起欢呼雀跃。 “当时很多人都不愿意说自己拿的是国内的学位。周健则不管到哪儿都骄傲地说,‘我是中国 人、是中国培养的土博士’,不管到哪儿发言都这么说。他就是这么实在的一个人。”妻子孙小依 说。 “蛋白分层、纯化的时候要用到氯化铯,这是非常贵的稀有金属化合物,在国内我们都是纯化之 后反复使用,但是剑桥用完都丢掉。周健觉得太浪费了,要把它们收集起来,自己纯化后寄回中国再 用。我当时觉得很不好意思,我说你去跟 Lionel 讲,人家还把你当成讨饭的。结果 Lionel 听完他的 想法,拍拍他的肩膀说:‘That’s the real man.(这才是真正的男人。)’后来还专门给我们一 个小储藏室。实验室里换下来的旧仪器、一次性的实验设备,我们都洗干净,收集了大约半个集装箱 寄回国内。” 刚到剑桥的时候,Lionel Crawford 邀请实验室里的人去他乡下的别墅聚会,Crawford 夫人做了 一个英国传统布丁,问大家好不好吃,结果周健说:“我不喜欢,从来没吃过。”孙小依回忆:“他 夫人的脸一下就红了,当时很尴尬。周健就是这样的个性,刚开始相处,人家可能接受不了,但是时 间长了都会发现他就是这样一个很耿直的人。后来 Lionel 和他的夫人特别喜欢周健。Lionel 说,我 手下这么多人,还从没遇到过一个这样敢讲真话的。” 1990 年,周健夫妇接受弗雷泽的邀请来到澳大利亚。弗雷泽后来回忆:“Crawford 教授很后悔 将周健放走。”1999 年周健去世时,Crawford 年事已高,没能亲自参加追悼会,他写了一篇唁文, 请求 Frazer“在追悼会合适的时候逐字宣读一下”。他说:“周健对我来说是个很重要又很特殊的 朋友……他的创造才能和精湛技艺都是异乎寻常的……从未在挫折面前退却过。我猜想,周健是经过

中国文化大革命的考验。因此,对于后来在剑桥和很多地方碰到的困难都不在话下……与他在一起工 作是一种享受,只是我们在一起工作的时间太短了。” 夫妻是捏在一起的泥巴 夫妻是捏在一起的泥巴 除了在工作上兢兢业业,周健还是个“居家男人”。 孙小依说:“周健不光实验勤奋,做家务更是好手,只要他在家,肯定是他下厨做饭,很多朋友 都不知道我也会做饭。家里电器有毛病都是他动手修,只要有空他就带孩子出去玩,常去图书馆、博 物馆和展览馆。在芝加哥的时候经常去滑雪。全家去过很多旅游胜地,世界名胜古迹,还专程带儿子 去美国的迪斯尼乐园和英国的 LEGO 世界。周健是个具有深厚生活情趣的人,他还爱好摄影,喜欢在 自己家的花园里养花种草,还喜欢钓鱼和游泳……所以现在我们有很多美好的家庭回忆。 “不管在实验室还是家里,只要有他在,我们常常开怀大笑。”孙小依说。有段时间, 周健的实 验室正好在孙小依的眼科隔壁,他的实验室硕果累累,但是工作环境却很轻松,实验室里笑声不断飘 出,眼科的护士经常不得不过去关门。 科研和生活中,周健和孙小依也都心灵相通配合默契。孙小依说:“我们俩是一对很恩爱的夫 妻,就像社会上其他家庭细胞一样。” “我们相互尊重并支持彼此的事业。”孙小依说:“出国之后我们说好他先发展,因为在国外想 站住脚很难,要科研上做出成绩来就更难,我们的想法都是两根绳拧在一起更有力量。后来儿子长大 了,周健的实验室也扩大了,经费充裕、有很多人帮他,我们商量也该我发展我的眼科专业了。” 1994 年到美国以后,孙小依参加了资格考试,重新回到眼科做临床工作。 周健经常请朋友到家里来聚会。孙小依认为周健的朋友就是自己的朋友,因此,花时间做准备给 他们创造交流的机会。周健也很支持孙小依,“我喜欢参加舞会,唱卡拉 OK, 他不太喜欢,他就负 责音响,配合默契,小家庭生活十分温馨。就像周健说的,夫妻就是两块泥巴捏在一起,你中有我, 我中有你,时间长了也分不清谁是谁了。” “我有时候觉得很宽慰,人的一生能有一次这么刻骨铭心真正的爱,虽然已经失去,但曾经拥有 过。”孙小依说。

原载《科学时报》2007 年 10 月 22 日

This Is a Real Man
Huanhuan Chen

The contribution to scientific research from one of inventors of the cervical cancer vaccine Dr. Jian Zhou is obvious to all. His deep love to family and his motherland has remained fresh in memory of those people who have been close to him. Never Forgot His Chinese Root When Jian Zhou was in UK, a letter he received from his post doctorate supervisor Naiheng Zhang has influenced him greatly. Naiheng Zhang said in his letter that there were no national boundaries for knowledge, and it should be the same for HPV research whether it is carried out in China, UK or the United States. Ian Frazer described Jian Zhou as a warm and lofty bridge builder in Jian Zhou’s memorial meeting. He said that although there is no doubt Jian Zhou was a member of a world village, he never forgot his Chinese roots. Jian Zhou has established close co-operation between Australia and some research institutes in China. The Chancellor of Wenzhou Medical University, which was Zhou’s old Institute, Jia Qu recalled that Jian Zhou warmly received scholars from China, and arranged their visit, advanced study and accommodation using his own money. Jia Qu also said: “When Jian Zhou knew I was studying in Bostom in 1994, he sent me return airline tickets to Chicago to discuss support for medical research in Wenzhou Medical University”. Jian Zhou was always an active member of overseas Chinese organisations. He was impressed deeply on the local Chinese school in Chicago. In order to prevent children from forgetting their Chinese language, Jian Zhou and his wife together with other friends had spent their own money and time, and made efforts to establish the Miao Miao Chinese language school in Brisbane on their return to Australia. In 1997, very few people could see satellite TV in Brisbane. To celebrate Hong Kong’s return to China, Jian Zhou specially set up a satellite TV at home before the ceremony. At the date of the Hong Kong’s return, a dozen Chinese people who were working and studying in Brisbane went to Zhou’s house to watch the ceremony and enjoy the historic time. It was different from those people who did not like to admit that their high degree was awarded in China, Jian Zhou always said proudly “I am Chinese and I obtained my PhD degree in China”. His wife Xiao Yi Sun said: “He was a real and honest person”. Stratification and purification of protein require cesium chloride which is a very expensive rare metal compound. A normal procedure in China is to recycle it after purifying by that time, however, it is usually disposed as waste in Cambridge. Jian Zhou did not like to waste this material, and suggested they purify it and send it to China. Xiao Yi worried if

Zhou talked this idea to his Supervisor Lionel Crawford, we would be thought as beggars. Surprisingly when Lionel listened to Zhou’s explanation, he patted Zhou’s shoulder and said: “This is a real man”. Afterwards, Lionel made available a small storage room where we stored unused old instruments and equipments, cleaned them and sent them to China voluntarily. When they had arrived at Cambridge, Lionel invited all the people working in his laboratory to a party in his country villa. Crawford’s wife made a traditional England pudding, and asked if the pudding was delicious. Jian Zhou said: “I have never eaten it before, and I don’t like it”. Xiao Yi Sun recalled that Crawford’s wife immediately became red faced with embarrassment. Jian‘s forward attitude was just like that. People initially dealing with Jian Zhou may not appreciate his frankness, however, they would later find that Zhou was different to their first impression. Lionel and his wife liked Jian Zhou a great deal and Lionel said that he had many staff members, but none who dared to speak truth like Jian Zhou. Jian Zhou & family accepted an invitation from Ian Frazer and came to Australia in 1990. Frazer recalled that Prof. Crawford regretted Jian Zhou’s leaving. When Zhou passed away in 1999, Crawford could not come to attend the memorial meeting due to his old age. Instead he wrote a message of condolence and asked Frazer to read it at an appropriate time in the meeting. In this message, Crawford said: “Jian Zhou was a very important and special friend to me, he had remarkable creative ability and skill with technology. He has never been setback despite meeting continuing difficulty. I enjoyed working with Zhou, but unfortunately the time for our co-operation was too short”.

Man and Wife Are a Moulded Mud Xiao Yi Sun said: “Jian Zhou was not only diligent in his research work but also a good family man. He enjoyed cooking food and repairing home appliances at home. When he had time, he usually carried our son to the library, museum and exhibitions he often went skiing in Chicago. Our whole family have visited many scenic spots and historical sites around the world, including the Disney Paradise in the United States and the LEGO world in UK. Jian Zhou was a man with deep temperament and interest in life. He liked photography, gardening, fishing and swimming, we have many beautiful memories of our family”. Xiao Yi said that whenever Jian Zhou was in, we were usually laughing with each other, no matter whether it was at our laboratory or home. The work environment was very happy and relaxed in Zhou’s laboratory despite the outstanding research achievements. Jian Zhou and his wife’s hearts were linked together and had a tacit mutual understanding. Xiao Yi said: “we loved each other like other family unit in society”. They respected and supported each other’s career. Xiao Yi said: “we determined to make joint efforts to support Zhou’s career first after we left China. When our son was growing up, Zhou’s laboratory was enlarged, plus he had more research funding and assistants, we thought I should return to my career – ophthalmologist”. After arriving at the United State

in 1994, Xiao Yi passed the qualification examination, and back to eye clinic in practice again. Jian Zhou usually invited his friends to parties at their home; Xiao Yi spent time with the preparation, this would always create a good opportunity for their friends to exchange ideas and for the social event. Similarly, Jian Zhou supported Xiao Yi’s interest and hobby. Xiao Yi said: “I like dancing and singing, Jian put his maintained our sound equipment despite not liking this form of entertainment”. Our family life was always filled with tender feelings. Jian Zhou has said: “Man and wife are a moulded mud, and it is difficult to differentiate one from the other”. Xiao Yi said with deep feeling: “I feel comforted sometimes, because I have had a true love which I will remember with gratitude to the end of my life, although I unfortunately lost him nine years ago”.

Reprinted from Science Times 22 October 2007

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Translator: Dr. Ruixuan Rong, Senior Research Fellow, Julius Kruttschnitt Mineral Research Centre, The University of Queensland

身后不寂寞 科苑留奇葩
温医校友周健参与的预防子宫颈癌疫苗研究获得重大突破

原载于温州日报 2005 年 11 月 04 日

本报讯(记者郑海华) 美国默克公司和澳洲科学家联合在 10 月 7 日在纽约举行的新闻发布会上 本报讯 宣布:预防子宫颈癌疫苗 Gardasil 研制成功,有望明年全球上市。该疫苗的研制者 Ian Frazer(傅理 沙)教授在宣布这一新闻时特别提到:这一疫苗是他和他的亲密战友周健博士一起研制的,周来自中 国,毕业于温州医学院。“令人悲伤的是,周健未能在他去世之前看到这项成功被全球承认。”傅理沙 教授说。昨前几天,澳洲主流媒体纷纷致电温医,预约来温采访。 周健 1957 年出生在杭州,1982 年毕业于温医。1984 年在浙医大读硕士时,开始人类乳头瘤状病毒 的研究。1987 年 2 月 2 日,《人民日报》头版报道周健在人类乳头状瘤病毒研究的重大突破。1988 年,周健赴剑桥大学免疫学和癌症研究中心从事研究。 澳大利亚昆士兰大学免疫与癌症研究中心主任傅理沙教授在剑桥结识周健并力邀赴澳。1990 年,周 健前往昆士兰,研究人工合成乳头状瘤病毒疫苗并获成功。1991 年,周健与傅理沙联名申请了 DNA 重组技术人工合成乳头瘤状病毒疫苗的专利,比美国早了一年。1995 年,周健应聘美国 Loyola 大学 任副教授,以惊人速度发表许多高质量的论文。澳美两国开始合作进行全球临床试验,1996 年,周健 回昆士兰担任乳头瘤状病毒研究室主任。 1999 年 3 月 9 日,当其研究成果 Gardasil 疫苗全面开始临床试验时,42 岁的周健积劳成疾突发肝病 英年早逝。国际免疫学界震惊于新星的陨落,筹集建立“周健科学基金”,每年在澳举行纪念周健的学 术活动,悼念他的杰出贡献。昆士兰大学把一个会议厅命名为“周健会议厅”。 Gardasil 疫苗经过 33 个国家 2.5 万名妇女的三期临床试验,证明了疫苗对预防由人类乳头瘤状病 毒 HPV16 和 18 引起的子宫颈癌 100%有效且无副作用,这意味着第二大女性杀手子宫颈癌将因此终 结。 作为同班同学,温医院长瞿佳昨天向记者深情回忆起周健:“我们是恢复高考后的首届大学生。 周健对母校充满热爱,1998 年他带着傅理沙和昆士兰大学领导来温,促成昆士兰和温医的合作,协助 建立基础免疫学科,并帮助温医获得世界卫生组织基金支持。周健是华人学者的光荣,是温医的骄 傲。”