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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.

Jing Zhou, Brisbane, Australia


- 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


- 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

- 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。

- 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。

- 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

- 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。

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.

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

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
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

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
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
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

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

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

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

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

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

- 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.


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.


A TARGET CELL OR TISSUE OF A PLANT (WO 2000/042190). The University of

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.



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


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.


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.


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.


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.
刘晓松 赵孔南

1、 乳头瘤病毒疫苗(

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(WO2000/042215)澳大利


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(WO


4、 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


5、 乳头瘤病毒样颗粒,融合蛋白和其合成过程。 融合蛋白和其合成过程。(WO1996/011272)Medigene
Gesellschaft Fur Molekularbiologische Diagnostik, Thepaphie Und Technologie MBH,德

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

7、 改变的乳头瘤病毒 L2 蛋白和就此形成的病毒样颗粒(WO1995/020659)澳大

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。

8、 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

9、 多聚核苷酸和方法 澳大利亚,昆士兰大学




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

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.
内可利用的 tRNA 以决定其蛋白的体外表达水平。 《病毒学杂志》

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
UQ Researchers Develop New Gene Expression

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

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.

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

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

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

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 sexually-
transmitted 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

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

"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

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

“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

``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,

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.

Jamie Walker and Andreas Zhou

Reprinted from The Courier Mail. Feb 18-19 2006
Jamie Walker

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
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。
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
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
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
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。
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,
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
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
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
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%。
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
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。
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,

原载 2006 年 2 月 18 日“The Courier Mail”日报

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

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

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

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

Reprinted from Reader’s Digest (Health Smart) August 2006
路易丝・威廉斯 (Louise Williams)

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
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
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
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
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。

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
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
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,
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。
“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
“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
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
“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
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



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

1987 年的 Lancet 杂志上。


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
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

1995:发表了 VLP 疫苗对狗和兔子的首次实验结果。


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。


原载 Reader’s Digest, August 2006

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."


长)安娜。布莱说 “今天我们正在书写医学历史的新篇章。
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
前去世,享年 42岁。
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。
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
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

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

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.

“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

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

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
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

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
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

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

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 pre-
cancerous 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

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

“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


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
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
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

原载《健康报》 1987 年 2 月 19 日

本报讯 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
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
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

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
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

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.
作者:在在 来源:新闻中心 编辑: 叶少芳


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
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
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


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,
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
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
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


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。”


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


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
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
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

1997 年周健和伊恩·弗雷泽在温州与温医管理层合影
本报驻澳大利亚记者 李景卫
《人民日报》 ( 2006-07-10 第 07 版 )


本报驻澳大利亚记者 李景卫
《人民日报》 ( 2006-07-11 第 07 版 )



1996 年周健和伊恩·弗雷泽访问温医。

一 生 伟 业 真 真 切 切
陈欢欢 王丹红


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。
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
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
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

周健夫妇在 1998 年的圣诞节晚会上。孙小依/提供


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”
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
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
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
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。”
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
“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
能继续深入研究。1990 年,周健带着家人来到了昆士兰。


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

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
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
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
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
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。

英 年 早 逝

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
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
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
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
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


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
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。
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
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
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,
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
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
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
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
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
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
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

科学时报》2007 年 10 月 22 日
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
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

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

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

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 break-
through 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


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.

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
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
“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
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
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,
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
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
80 个国家先后批准了这种疫苗的使用。


澳中科学家合作 发明世界上
本报记者 王丹红

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
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
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


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,

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

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
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
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)。
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
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


有 25%左右癌症是因病毒感染引发的
颈癌等 ,这就意味着至少 25%的癌症可以通过疫苗预防

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
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。
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
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

剑 桥 遇 周 健

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
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
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
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。
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
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
“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
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。


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
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
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
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
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


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,
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
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
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
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
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
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
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
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
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
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
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
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……

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

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

“……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 re-
organised 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 molecular-
virologist, 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

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 high-
level 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

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.

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



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
“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
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
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
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
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
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


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
“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
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。
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

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

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

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

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

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

Translator: Dr. Ruixuan Rong, Senior Research Fellow, Julius Kruttschnitt Mineral Research Centre, The University of
身后不寂寞 科苑留奇葩

原载于温州日报 2005 年 11 月 04 日

本报讯 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
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
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
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
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
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
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

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