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Scientist Made Key Cancer Advance

Professor Ian Frazer

Jian Zhou will be remembered as a scientist who made important contributions to the study
of viruses, but especially for his work on developing vaccines to prevent cervical cancer.

He was also a skilful bridge builder who saw it as part of his task in life to bring people
together and allow them to make full use of their potential. None who met him was
untouched by his enthusiasm or science, his warm smile or gentle sense of humour.

The only son of a surgeon, Jain was brought up in Hangzhou, in Zhejiang Province, China,
and trained at Wenzhou Medical College, where he completed his basic training and met
his spouse Dr. Xian Yi Sun.

He studied further at Zhejiang Medical University, where he graduated with a Master’s


degree; at Henan University, where he obtained his PhD; and at Beijing Medical University,
where he first pursued his research career and acquired an interest in virology.

In 1998, he left China for England. Under the able tutelage of Dr. Lionel Crawford at the
Imperial Cancer Research Institute laboratories in Cambridge, Jian applied his skills in
molecular biology and virology to the study of papillomaviruses (wart viruses).

This infection – often a subject of day humour – was increasingly being recognised for its
more sinister potential as an antecedent of cervical cancer, one of the commonest cancers
among woman throughout the world.

Jian and his wife soon acquired a reputation for “green fingers” – everything seemed to
work in their hands. Jian’s skills had impressed many and, when he was ready to move, he
was much in demand. At Princess Alexandra Hospital, Brisbane, the Lions Immunology
Research Laboratories had developed an interest in papillomaviruses and Jian decided to
join them.

It was to be an extremely productive time. In his first four years, he authored 11 scientific
papers – a prodigious achievement for any biomedical research scientist – including the
discovery for which he will most be remembered: the virus-like particles.

It was clear from the mid-1980s that a vaccine to prevent papillomaviruses infection could
prevent thousands of deaths each year from cervical cancer, but research was hitting a snag.
The standard method of producing a vaccine uses viruses grown in the lab and then
rendered safe. Papillomaviruses, however, could not be grown in the lab.
Jian was experimenting with different ways of making the external structural proteins of the
virus to study immune responses to infection. It crossed his mind that these proteins might
fold up into virus-like structures that did not contain the papillomavirus DNA but which
could be produced in the lab.

So it turned out. The empty viruses, christened virus-like particles, proved to behave, as far
as the body’s defences were concerned, much like the real thing, including immunity to
prevent infection.

Vaccines for cervical cancer, based on papillomavirus-like particles, are now on trial in
several countries, following encouraging animal studies. Jian also envisaged that existing
wart infections may be treatable with the particles and conducted a clinical trial in
collaboration with colleagues at his old medical school. Again, the results are promising.

Driven from Australia in 1995 by the unpredictably of funding for career scientists, Jian
took up a professorship at Loyola University in Chicago and continued work on the
papillomavirus. In a series of carefully planned experiments in Brisbane and Chicago, he
mapped out much of what is known about the virus’s assembly and function.

He returned to Brisbane in 1997, encouraged by the offer of a position at the newly formed
Centre for Immunology and Cancer Research at the University of Queensland, and turned
his mind to gene therapy.

He came up with a novel hypothesis about how cells infected with a virus are controlled by
the viral genes, the mechanism that causes disease. In the case of papillomavirus, although
it is present throughout the body, it acts only on the skin cells. Jian’s hypothesis suggests a
method of targeting an anti-viral vaccine so that it acts only on cells susceptible to the virus.

During the next two years, he gathered enough data, using experiments of considerable
technical difficulty, to convince his peers of his hypothesis.

His observations have led to exciting new prospects for human gene therapy, as they
suggest a method for avoiding some of the commonest side effects of such treatment.

In 1994, the University of Queensland recognised his viral research through the conferral of
a doctor of medicine degree signifying a substantial contribution to a single topic over
many years. This year, Jian’s work attracted no less than three grants through the
Australian National Health and Medical Research Council.

Although Jian was a citizen of the world, he understood the importance of cultural roots.
He established and worked in the Miao-Miao school in Brisbane, which teaches Mandarin
and Chinese culture to Australian-Chinese children. The school grew rapidly from 20
students to more than 200 and represents just one of the many contributions Jian made to
the Chinese community in Brisbane and overseas.

To his Chinese friends and colleagues, Jian was a model for success. He had integrated
into the international scientific community and made friends throughout his local
community in Brisbane. While retaining his birthright and achieving considerable
scientific success.
To scientists, he epitomised a rare breed of researcher; a clinician as much at home in the
laboratory as with patients, but also a laboratory scientist who could imagine new uses for
molecular genetics and who had the technical skills to make them benefits.

Jian is survived by his mother, his wife, a teenage son, and a vast group of former students
and colleagues who will be forever in his debt.

Professor Ian Frazer is director of the Centre for Immunology and Cancer Research, The
Queensland University.

Reprinted from The Australian April-21, 1999


癌症疫苗的开拓者
伊恩·
伊恩·弗雷泽教授

周健将永远为人们所怀念。作为一名科学家,他在病毒学领域,尤其是在疫苗研发方面所做之用
以预防子宫颈癌的工作,有着重大的贡献,令世人嘱目。
周健也是一位技能高超的搭桥者。他在科研上把相关的人才聚拢在一起,让他们完全发挥潜能和
专长。凡是认识他的人,无不被他对科学的高度热忱、温和的笑容和亲切的幽默感所感动。
周健的父亲是位外科医生,他是家中的独子,在中国浙江杭州出生长大。他毕业于浙江温州医学
院,在那儿接受了基础医学教育,同时结识了他的太太孙小依医生。之后,周健获浙江医科大学病理
系硕士学位,接着考入河南医科大学获博士学位。然后,他到北京医科大学(现称北京大学医学部)
从事博士后研究,对分子生物学和病毒学产生了极大的兴趣。
1988 年,周健离开中国去英国,加入由医学权威雷奥尼尔·高福德博士(Dr Lionel Crowford)
主持的剑桥大学帝国癌症研究中心实验室(Imperial Cancer Research Institute Laboratories)做研究
员。在这里,周健把他在分子生物的才华施展到人乳头瘤病毒(PHV)研究方面。
人们已经日益意识到子宫颈癌是全世界妇女最普遍的一种癌症,而人乳头瘤病毒则是导致子宫颈
癌的罪魁祸首。在剑桥,周健和他的太太潜心于人乳头瘤病毒研究。不久周健和他太太就荣获“神奇
的手指”的美誉,换言之,就是没有任何实验能难倒他们,任何实验只要经他们之手,都能做成。
周健在分子生物学上的高超技能及他的杰出的科研创新能力获得国际上广泛的认可,当他有足够
能力更上一层楼时,他已经是炙手可热的人物了。布里斯本亚历山大公主医院的狮子会疫苗研究实验
室有意开展 HPV 研究时,周健就决定加入。
从此开始了他超高产成果的四年。在此期间,他发表了 11 篇高质量的科学论文,这对任何生物
医学研究科学家来说,都称得上是惊人的巨大成就。其中包括他最令世人瞩目的发明:乳头瘤病毒的
病毒样颗粒,即宫颈癌疫苗的基础。
自八十年代中期,科学家们就试图发明一种疫苗以预防乳头状瘤病毒感染,从而将可避免每年数
以千万计的妇女因子宫颈癌而死亡。但这项研究碰到了极大的障碍:用实验室里标准方法,无法培养
及得到病毒,也无法对病毒进一步地研究,更谈不上制作疫苗了。
周健试着用不同的方法,即用病毒外壳结构蛋白质去研究病毒感染的免疫反应。他发明了用这种
病毒外壳蛋白人工合成了乳头瘤病毒的病毒样颗粒。这种颗粒不含病毒 DNA 的结构,但具有免疫
性。
实验结果表明:这些空壳病毒进入人体后会像真的病毒一样,刺激肌体产生免疫力来抵抗疾病。
用人工合成的“病毒样颗粒”制成宫颈癌疫苗,继动物试验成功之后,目前正在几个国家中进行人体
临床试验,也已获得了可喜的进展。
同时,周健也将研究拓展到尖锐湿疣病毒感染方面,提出或许可使用此“病毒样颗粒”疫苗予以
治疗。为此,他与他中国的母校温州医学院开展合作,进行临床试验,其结果又一次显示,这种治疗
卓有成效。
1995 年,为了开拓视野,周健离开了澳大利亚,去美国芝加哥 Loyola 大学任教授,仍继续 HPV
研究。经过在芝加哥和布里斯本一系列计划周密的详细试验后,周健绘制出了详图,标明已知病毒的
排序和功能。
1997 年在新成立的昆士兰大学医学系免疫癌症研究中心的鼓励和聘请下,周健回到布里斯本,把
全部心思放到基因治疗上。
周健提出了一个崭新的理论,是关于病毒感染细胞是受基因调控并治病的机理方面的。人乳头状
瘤病毒虽遍布于整个身体,但它只限于在皮肤细胞里活动。周健提出创新的假设:以一种方法将抗病
毒疫苗锁定在特定部位如皮肤细胞,使此疫苗仅对容易被病毒感染的细胞产生作用。
接下去的两年,周健操作技术相当高难度的实验,收集了足够的数据以说服他的同行确信他的新
理论。他开创了令人鼓舞的人类基因治疗的新途径,因为他发明的方法可以避免一些基因治疗最常见
的副作用。
1994 年昆士兰大学推崇周健的病毒研究,授予他医学博士学位,标志着他多年对医学科研的重大
贡献受到承认和重视。1998 年一年内,周健就获得三项澳大利亚国家健康与医疗研究会(NHMRC)
的研究经费。
虽然周健是一位世界村的公民,他也十分了解文化根源的重要。他是布里斯本苗苗中文学校的创
始人之一,这个学校教授汉语和中国文化,发展得很快,由最初 20 个学生增加到 200 人,这是周健
在布里斯本对海外华人社区的贡献之一。
在周健的同事和朋友眼中,他是成功的典范,多年以来他已经融入国际杰出科学家的圈子里,同
时在布里斯本社区结交良朋益友,不忘中国人的根。
以科学家来说,周健是个罕见的研究专家,值得留名科研史。无论在临床诊所面对病人,或是在
实验室,他总是会想出使用新方法。这是周健掌握了相关的技术和能力使其成功所在。
周健身后留下他始终孝顺的母亲、爱妻和一个少年儿子,以及为数众多的学生和同事。我们将永
远受惠于他的研究。

1997 年访问温州医学院,左一,吕杰强;左二,周健,左三,伊恩·弗雷泽;右一,瞿佳
————————————————————————
原载《澳大利亚人》(The Australian)1999 年 4 月 21 日,澳大利亚布里斯本王逸华翻译
Memories of Jian as a Friend and Colleague
Prof. Ian Frazeri

Jian and I met for the first time in the department of pathology in Cambridge, England in 1989. He was
visiting from China, and working on human papillomavirus immunotherapy in Dr Lionel Crawford’s ICRF
lab. I was also a visitor, in Professor Margaret Stanley’s lab next door, and working on production of
transgenic mice expressing papillomavirus proteins. As visitors with a common interest in HPV
immunotherapy, it was natural that we should get together to talk science. My work required frequent (short)
visits to the laboratory out of hours, and I was impressed by the fact that whatever time of day or night I came
to the lab, Jian and his wife Xiao-Yi were always there. I came to the conclusion that the lived in the lab,
though I was assured that this was not so. Clearly, they were hard working and dedicated to their work –
equally, it was clear that Jian was an original thinker, always coming up with ideas for moving his research
work forward. I wanted to make target cells for human immunotherapy studies and Jian’s expertise in
producing recombinant vaccinia viruses seemed very likely to enable us to jointly achieve this. Before I left
Cambridge, I therefore offered him a job in my lab in Brisbane, probably the best recruitment decision I ever
made.

There was competition to employ Jian from CSIRO in Sydney, but they could not give him the chance to
work on his favourite topic, papillomavirus, and fortunately for our lab and the world at large, Jian chose to
come to Brisbane. There was a struggle to get him a visa, but after 6 months this was achieved and he and
Xiao-Yi arrived in the lab in 1990. Jian was a natural scientist, collaborating with all who wished to work
with him. He was also a determined research manager: he never let “minor” obstacles like access to resources
get in his way. His long working hours, intense devotion to his work, and infectious enthusiasm served as a
role model for the other scientists in the lab and these traits and his willingness to learn from others enabled
rapid progress on our project for producing infectious papillomavirus. This project produced, almost as a by-
product, the technology which has become the basis of the vaccines now available to prevent cervical cancer.
However, his creativity was not limited to the HPV vaccine project. As attested to by his many research
publications, the next 3 years produced a steady stream of papers on HPV virology, and on use of
recombinant virus particles to understand papillomavirus virology and immunology, and set the scene for
subsequent clinical trials of HPV prophylactic and therapeutic vaccines based on virus like particles.
Throughout this period, Jian and I had regular and stimulating discussions about his science – we both found
these something to look forward to. The synthesis of immunology and molecular virology enabled rapid
progress in our collective research.
In 1994, Jian’s desire to further his career led him to accept a position at Loyola University with Professor
Lutz Gissmann, where he spent a further productive period on papillomavirus research. Jian returned to
Brisbane in 1996 to set up his own research laboratory in the Centre. He brought with him a desire to find out
why papillomavirus capsid proteins were so difficult to express from the natural gene, particularly in skin
cells and he also wanted to understand how the papillomavirus packaged its genetic information within the
self assembling virus shell. He quickly recruited a number of students and postdocs to work with him on
these projects. He came up with the idea that codon usage, the way that the genetic code is used to instruct
cells to synthesise protein, might determine the efficiency of expression of the virus capsid proteins. This
followed from work he undertook which rigorously excluded the then dominant paradigm that there was a
suppressor sequence within the capsid gene that prevented capsid protein production and was active in all
cells except mature skin cells, where the virus normally assembled. He went on to show that expression
limited to mature skin cells was attributable to a difference between immature and mature skin cells in the
availability of tRNA building blocks necessary for protein assembly, thus discovering a new mechanism of
regulation of gene expression. This discovery on its own would have been sufficient to ensure Jian a place in
the textbooks equal to that due to him for his work on the cervical cancer vaccine.

Jian’s untimely death occurred just after he had achieved funding for his research program from the
Australian NHMRC, which would have enabled further expansion of his research efforts. Given that he had
achieved so much of significance in the short time he had to do research in the developing world, who knows
what he might have achieved in his lifetime! The lasting legacy from Jian’s research is by no means limited
to the HPV vaccine, though it is likely that the vaccine will be his major claim to fame. The work on gene
expression that he initiated lives on in a Biotech Company (Coridon), in the research careers of the many
students and scientists that he mentored over the years, and in the example of creativity combined with
selfless dedication to science that he has demonstrated to all who came in touch with him. Jian will be
remembered forever.

Feb 18 2008

HPV international Conference in SeattleJuly 1991, From left Ian Frazer and Jian Zhou

i
Prof. Ian Frazer, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, The University of Queensland,
Australia

i
这篇文章是昆士兰大学“免疫和癌症研究中心”主任暨获颁《2006 年度澳大利亚杰出人物》奖的伊恩·弗雷泽
教授写于 2008 年一月。
中文翻译:杨蝉,昆士兰大学,翻译系硕士
健的英名永留千古
——深切怀念友人及同事周健
i
伊恩·
伊恩·弗雷泽

1989 年,我在英国剑桥大学的病理学系第一次遇见了来自中国的周健,他在 Lionel Crawford 教


授的 ICRF 实验室研究人乳头瘤病毒(HPV)免疫疗法。我当时作为访问学者,在与之毗邻的 Margaret
Stanley 教授的实验室从事转基因鼠表达乳头瘤病毒蛋白的研究。自然而然地,作为共同关注 HPV 免
疫疗法的科研人员,我们常聚在一起,谈论相关科学。我的工作需要频繁地借用 Crawford 教授的实
验室几个小时,令我印象很深刻的是,无论白天黑夜,凡我去实验室,周健和他的助手孙小依总会在
那里。由此我得出个结论:他们是住在实验室的,尽管我确信事实并不是这样。很明显,周健和孙小
依在努力地工作,并专心致力于他们的研究。同样显而易见的是,周健是个很有独创性的人,他经常
会有一些想法来推动进一步的研究。我想培养研究人类免疫疗法的靶细胞,加上周健在培养重组疫苗
病毒方面的专长,通过合作,似乎很可能使我们达到这个目标。因此,在我离开剑桥之前,我力邀周
健和孙小依到我在布里斯班的实验室工作。这是我一生做出的最佳的聘请决定。
悉尼的澳大利亚联邦科学和产业研究组织(简称 CSIRO)也争着聘请周健,但是他们的科研题目
稍有不同,周健更喜欢乳头瘤病毒的研究课题。总的来说,周健选择了来布里斯班,对于我们实验室
和整个世界,都是很幸运的。为周健申请签证花了点时间,但六个月之后,他获得了签证。1990 年,
周健和孙小依来到了布里斯班。周健是个天生的科学家,与所有愿意与他一起工作的人合作愉快。他
也是个坚韧不拔、认真执着、要求严格的研究员,从不允许如怎样获得资料这一类的“小”障碍出现
在工作中。周健把大量的时间用在工作上,对工作的专心致志和极具感染力的热情,都成为了实验室
里其他科学家的榜样。周健的这些品质以及他乐于向别人学习的态度,使得我们在研究乳头瘤病毒的
项目上取得了迅速的进展。他发明的乳头瘤病毒样颗粒,几乎仅是他的研究中的一个副产品,但这个
项目现已成为预防子宫颈癌疫苗的基础。而且,周健的创造性并不局限于 HPV 疫苗项目,从他的许
多已出版的科研论文可以证实这一点。在接下来的三年里,他持续不断地发表了许多世界领先的论
文,其内容涉及 HPV 病毒学、使用合成病毒颗粒进一步理解乳头瘤病毒学和免疫学,并为随后的以
病毒样颗粒为基础的 HPV 预防和治疗性疫苗的临床试验提供了坚实的保障。在这整个期间,我和周
健经常一起兴奋地讨论关于他的科学研究——我们为此发现了许多可进一步研究的课题和项目。免疫
学和分子病毒学的结合使得我们的共同研究取得了飞速进展。
1994 年,周健想要进一步发展他的事业,他接受了 Loyola 大学 Lutz Gissmann 教授的聘用,在
那里做了一段时间颇有成效的乳头瘤病毒研究。1996 年,周健回到了布里斯班,在研究中心建立了
他自己的研究实验室。周健渴望找出为什么乳头瘤病毒衣壳蛋白这么难从自然基因表达,特别是在表
皮细胞。他还想弄明白在其自身融合的病毒壳中,乳头瘤病毒是怎样组装基因信息的。他迅速招收了
一批学生和博士后,与他一起研究这些项目。周健想到了应用优化密码子,使用基因代码来指示细胞
合成蛋白的方法,有可能会决定病毒衣壳蛋白表达的效率。随着他的研究,当时占主导地位的范例被
严密地排除了——在衣壳基因中有一个抑制序列,它阻碍衣壳蛋白的生产,并活跃于所有的细胞中,
除了病毒一般融合所在的成熟表皮细胞。周健发现,限制在成熟表皮细胞的表达,是由于不成熟和成
熟表皮细胞上可获得的蛋白质融合所需的转移核糖核酸(tRNA)结构单元的不同。从而,他发现了一种
新的基因表达调节机制。这一发现本身就足以保证周健的理论在教科书中,占有一席与他对子宫颈癌
疫苗的贡献同样重要之地。
周健在从澳大利亚国家健康与医疗委员会(NHMRC)获得了一大笔足以使他的研究工作进一步
深入的经费后,却不幸过早地谢世了。在短短的时间中,周健在人类医学科学的研究领域里就已经取
得了辉煌的成就。试想如用他一生的时间来做科研的话,将对人类战胜疾病和癌症有多少贡献?哀
哉。周健的科研遗产,决不仅限于 HPV 疫苗,尽管这个疫苗使他一举成名。但周健发明的并从事的
关于基因表达的密码子优化的研究, 九年后的今天仍在生物科技公司(Coridon)继续进行着,他指导了
多年的学生们和科学家们的研究工作还在继续进行着,他为我们所有的人树立了极具创造性和对科学
无私奉献的榜样。 他的英名永留千古。
附件
————————————————————————————————————

联邦国会议员的呼吁
2006 年 3 月 26 日

联邦国会议员迈克尔约翰逊今天致函给国家的国庆日委员会及昆士兰大学,要求给
已故的周健教授授予正式的 “2006 年的澳大利亚人” 荣誉称号。(注:澳大利亚不
授此奖于已故的人员)

在弗雷泽教授所取得的举世属目的医学成果中,周健教授发挥了关健性的作用。迈
克尔约翰逊议员呼吁国家应排除任何人为障碍,表彰周健教授在给人类带来福祉
的、世界上第一个癌症疫苗 - 宫颈癌疫苗发明中的突出贡献。追认周健教授为“2006
年的澳大利亚人”。
Michael Johnson MP
Federal Member for Ryan
Ryan

**MEDIA RELEASE**
6 March 2006

JOHNSON CALLS FOR OFFICIAL


POSTHUMOUS RECOGNITION OF
AUSTRALIAN OF THE YEAR’S LATE
COLLEAGUE

Michael Johnson MP, Federal Member for Ryan, today called on the National
Australia Day Council and the University of Queensland to formally honour the
memory and contribution of the late Professor Jian Zhou, alongside this year’s
Australian of the Year, Professor Ian Frazer.

“Given the critical role played by Professor Zhou in the success of Professor
Frazer’s medical research and its potential global impact, it is only fitting that our
nation acknowledges the late Professor Zhou. I am sure that Professor Frazer
would also want his friend and colleague to not only be remembered temporarily,
but indeed to be honoured in a lasting manner for his pioneering work,” Mr Johnson
said.

“Clearly Professor Frazer’s current success and achievements are the result of a
team effort which included Professor Zhou from the beginning. Any artificial
barriers that might prevent Professor Zhou receiving his due accolades can surely
be overcome.”

“I will be writing to the National Australia Day Council to have Professor Zhou’s
contribution posthumously recognised.”

“I also hope that the University of Queensland, which stands to benefit greatly from
Professor Frazer’s success and worldwide coverage, will also honour Professor
Zhou by establishing an enduring legacy.”

END
For further informat ion, please contact Michael on (07) 3720 2599
Office of the Federal Member for Ryan, PO Box 704, Indooroopilly Q 4068
回忆和周健在一起工作的时光
齐英妹ii

记得在 1991 年的夏天,许多中国留学生参加澳大利亚-中国友好协会组织的 Redcliffe 海滩一日


游。当大家都在陪着孩子们戏水的时候,我们看到了一对青年夫妇相依着在远处的海滩散步。当他们
走近我们并看到孩子们的时候,他们那种难以形容的兴奋是无法用语言来表达的。经简单的自我介
绍,得知他们就是刚从英国来到澳大利亚不久的周健和孙小依。原来他们的儿子和我们的儿子同龄,
当时正在中国等待来澳的签证,可想而知他们那种思念儿子的心情。在随后的时间里,他们和孩子们
玩得非常开心,一起建沙山,一起戏水,同时和孩子们交谈了许多关于这里的幼儿园和学前班的情
况。不难看出这对夫妇是多么盼望自己的儿子能尽早来澳大利亚和他们团聚。
自从第一次相遇之后的一年多的时间里,我依然在昆士兰大学读学位,而周健和孙小依在昆士兰
大学医学系工作。直到一年多之后,我才再度和周健及孙小依重逢,那是因为我的第一个博士后工作
就是在 Ian Frazer 教授和周健博士的实验室里。记得当我看到那栏广告时,我只是觉得他们的课题
新颖,有些技术和我的专业有关,故带着很强的试试看的想法递交了申请信。当得到面试的通知时,
我才再次细读那栏广告。当我看到周健博士的名字时,我还在怀疑他是不是我在 Redcliffe 见到过的
周健啊?带着了解更多关于 Ian Frazer 教授和周健博士实验室情况的信念,我打通了周健的电话。
电话那端宏亮而又热情的声音让我马上想起了那位曾经相遇但又不真正相识的周健。通过简短的电话
交谈,我对周健的印象是,他非常珍惜时间,并试图用最简练的语言告诉对方尽可能多的信息。在那
次面试中,周健和 Ian Frazer 都问了什么问题我已记不清了,但我的印象是,这是一个严谨的科研
集体。我开始工作没多久,就亲眼目瞩了周健和小依对待科研事业的积极和认真态度。在 20 多人的
实验室里,他们总是最早来、最晚走的一对;周末来实验室观察试验结果,对他们来说这已是再正常
不过的事情了。他们这种兢兢业业的忘我精神,带动了整个实验室的科研竞争气氛。
在我到周健和 Ian Frazer 实验室工作不久,实验室里每月一次的科学杂志学术研讨会轮到我选
材并讲解。考虑到我工作时间太短,Ian Frazer 教授向我介绍了几篇前沿课题的文章,并极力支持
我把我的主要研究课题放在“乳头瘤病毒受体”方面。为此,我选了一篇有关其他病毒受体的研究论
文作为讲解和讨论的主要内容。但我反复阅读这篇论文时,无论从技术和方法学角度,还是从理论的
深度,我都遇到了很多难题。细心的周健,看出了我的困难,他在繁忙的工作中,抽出了时间约我坐
下来,并且为我详细解释这篇文章的背景、方法和结果。由于我是初涉这个研究领域,我当时提出的
一些问题,都是非常幼稚可笑的。但周健仍然非常耐心地为我解释,并鼓励我阅读一些其他的辅助文
章。通过这次研讨会,我深深地感受到了这两位严师对待科研事业的那种一丝不苟的态度及对未来研
究方向的预测。
Ian Frazer 教授总是极尽全力地支持自己的科研人员到国际会议上去开开眼界扩宽视野。我有幸
在 5 年中,参加了 4 次“国际乳头瘤病毒年会”。1997 年的“国际乳头瘤病毒年会”是在意大利的
西雅纳举行的,我与周健和孙小依及其他的博士生一起参加了这次会议。在 Ian Frazer 教授和周健
的鼓励支持下,我申请了在大会上宣讲我的论文并得到了大会组委会的准许。这种难得的机会对我来
说是第一次,所以即兴奋又紧张的心情是可以理解的。在离开布里斯本去意大利之前,我认为自己已
作了充分的准备,但富有多次国际会议上宣讲论文经验的周健,对我的要求更高了一层。他利用会议
期间有限的空余时间,听我给他预讲,并指出需要修改的部分。这样经过几次反复,我们最后终于得
到了满意的宣讲效果。
在历届“国际乳头瘤病毒年会”上,周健总是忙得不可开交,这与他在这一科研领域的国际知名
度的不断提高是分不开的。周健在乳头瘤病毒研究方面的作品,不但数量多,而且质量高。他的每一
篇作品都具有其独特性和原创性。他对科研的投入,以及他思维和反应的敏捷,让很多和他工作过的
同事惊叹!虽然他的努力已开花结果——乳头瘤病毒疫苗,但他的早逝乃是这一科研领域的重大损
失。
1994 年 4 月于布里斯本。左起:周健、孙小依、郭小月、陈洁、齐英妹和郑元志

i
齐英妹博士,澳大利亚昆士兰大学生化系
因为工作,
因为工作,我认识了周健
庞建宏i

布里斯本,是一个温暖、迷人的阳光之城。如果说因为布里斯本的阳光明媚和四季繁花盛开使这
座城市显得格外温暖,那么即将在这里举行的纪念已故科学家周健博士的活动将使生活在这里的我们
倍感温暖。
我工作生活在这座城市,虽然对昆士兰连年的干旱以及政府的限水措施感到无奈,甚至曾经考虑
去另一个城市发展,但最终我还是选择了留在这里,继续我所热爱的工作,我相信这是正确的选择。
作为昆士兰大学免疫与癌症研究中心国际多中心临床试验项目协调管理负责人,能够从事由该中心主
任 Ian Frazer 教授和周健博士共同研制的癌症疫苗的相关临床研究工作,我感到非常荣幸。正因为主
管国际多中心临床试验,特别是与中国的临床试验合作项目,我有机会认识了周健并了解他对宫颈癌
疫苗研究所做出的杰出贡献。我深深地为他的英年早逝而惋惜,为他对科学的献身精神而感动。虽
然,我从未见过他,也从未与其一起共过事,但在我的工作中,听到最多的是他的生平故事,影响我
最深的是他对科学研究的那份执着和追求。对我而言,他并不陌生,他依然和我们一起工作着。
2005 年底,美国默克公司郑重地宣布子宫颈癌预防疫苗临床试验成功。2006 年,基于“病毒样
颗粒”技术,子宫颈癌疫苗加德西终于面市。这是世界上第一个癌症预防性疫苗,是一项非常振奋人
心的突破,而创造这一突破的研究者之一——周健,却未能亲眼看到自己的研究造福人类。全世界每
年有 25 万名妇女深受宫颈癌的困扰,她们大多数生活在发展中国家,其中很多人被该病夺去了宝贵
的生命。中国也是一个发展中国家,拥有着全世界最多的人口。宫颈癌也是中国面临的一个严重问
题。期待宫颈癌疫苗能够早日在中国上市,使中国人能够早日受益,这也是周健生前的愿望。
在 1999 年周健追悼会的悼词中,Ian Frazer 教授将周健形容为“热情而崇高的架桥人”。是
啊,他架起了我们的祖国中国与澳大利亚昆士兰大学多方面合作之桥。正是有了周健生前所做的努
力,才有了我们现在和国内频繁的科研合作,周健的母校温州医学院也与本中心建立了长期的合作关
系。这几年来,我经常随同 Ian Frazer 教授访问温州医学院,在旅行途中我和教授无话不谈,教授
常会谈起他与周健的过去。在温州,现任医学院和附属医院的院长以及课题合作的项目负责人都是周
健生前的同窗好友,每次见面总会和我提起周健。他们至今仍然非常怀念周健,并经常在温州医学院
的网站上发表纪念专辑,让更多的温医学子了解这位杰出的校友。每当他们谈起与周健的往事时,也
让我不由地跟着一起走进了他们同学的情谊之中,深深地被他们的友谊感染着。就这样,让我认识了
周健并越来越清晰地熟悉着周健。所以,每次来到温州医学院,我仿佛回到了自己的母校。当陪伴或
者代表 Ian Frazer 教授出席一些会议的时候,我总是会和相关领域的科研人员以及国内政府部门领
导人谈起周健。曾经有位来澳访问的国内领导人问我:“莫非你和周健是同学,也毕业于温州医学
院?”我告诉他,虽然我毕业于国内别的医科大学,但因为这份特殊的工作,已经紧紧地将我与周健
及温州医学院联系在一起。我一直以能为 Ian Frazer 教授工作,能沿承周健博士的工作而感到自
豪。
我相信,我认识的周健是我们中国人的骄傲,是所有在澳华人的骄傲,他的精神将激励着每一位
从事医学研究的科学家们继续奋斗。而我也将沿着这位科学家的足迹,在癌症疫苗的临床研究工作中
继续贡献我微薄的力量。
2006 年于布里斯本亚力三大公主医院免疫癌症研究中心与温医多中心临床试验新闻发布会。 左为孙小依,右为
庞建宏。 Right: James Pang in the public announcement for multi-center clinic trial at PA Hospital, 2006

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庞建宏博士,澳大利亚布里斯本亚里山大公主医院昆士兰大学免疫与癌症研究中心国际多中心临床试验协调管
理负责人(Dr. James Jianhong Pang, PhD, MD, Diamantina Institute for Cancer, Immunology and Metabolic Medicine,
University of Queensland, Princess Alexandra Hospital, Australia)
缅怀良
缅怀良师益友-
师益友-周健
赵孔南i

我初知周健,只闻其名,不识其人。时间回溯 1995 年,我在美国明尼苏达大学做博士后研究,栖


居姐妹城。朋友陈宇光贺丽莎一家自芝加哥来,移居明州姐妹城。其时,周健在芝加哥一大学做助教
授,独立领导一个研究小组,从事宫颈癌疫苗研究。在芝城,宇光一家与周健一家相善,朋友常聚。
故而,我们在姐妹城相聚时,其总不忘提周健和孙小依他们一家。周健,杭州人,温州医学院学士,
浙江医科大学硕士,河南医科大学博士,英国剑桥大学博士后,澳大利亚昆士兰大学研究员,从事抗
癌研究,时间不长,成就斐然,影响巨大。对于这样一位乡贤,我着实心仪。

人生如是,有缘相聚。其后年月,周健乃成我的良师益友。1996 年,美国之仲秋,我举家南迁,回
来澳大利亚定居。其时,周健一家也回澳大利亚定居,在昆士兰大学重建实验室。经丽莎推荐,周健鼎
力相助,我得以开始了过去十多年的基础医学研究。今昆州政府举行周健逝世九周年的纪念活动,缅怀
其对人类抗癌疫苗研发所作的杰出贡献,我深受其恩,无以为报,吟一联,作一词,缅怀良师益友——周
健。

诔联悼周健 ——成功之时君却去, 硕果未享我伤心。

诔词悼周健

周健吾师,周健吾友。幼时顽皮,聪明无比。毕生好学,智慧超群。活力漾溢,朴实无华。风趣幽默,独
具魅力。好助乐施,坦诚相待。出国十年,拼博成名。拯救苍生,事半功倍。造福人类,奋不顾身。长
期劳累,憔悴身心。踌躇满志,一朝去矣。走得何急,丢下亲人。妻闻噩耗,痛不欲生。小儿悲切,彻夜
难寐。老母哀悼,朝青暮雪。英年早逝,我辈伤心。苍天在上,地府在下。幽冥水隔,旷世悲音。人生苦
短,长寿难寻。喜怒哀乐,无影无痕。富贵贫贱,亦幻亦真。来者有声,去者无音。一代科星,就此陨
落。山川为愁,草木皆悲。

我本农人,业无所就。承君提携,入转医门。二载春秋,相随以沫。搜寻信息,一幕荧屏。
集思广益,读书忘形。键锵声声, 二六字盘。规划项目,字字推敲。实施方案,三尺平台。手脚并用,雕
琢精心。辛勤耕耘,四方斗室。水到榘成,石破天惊。耳染目睹,言传身教。
教诲一日,受益终生。岁月流逝,八个寒暑。虽无大就,亦有小成。世卫组织,临时顾问。未负庶几,亦
慰英魂。呜呼周健,扬幡招魂。你我二人,素昧平生。短暂相与,却成契友。
追思懿德,念念在心。九周年祭,作此诔词。祭奠亡师,悼吊故友。斯人虽去,英名永存。
1998 年 12 月于黄金海岸。前排左起:刘晓松、赵孔南、卡丽;后排左起:马克·威廉和周健

i
赵孔南博士,澳大利亚昆士兰大学肿瘤免疫研究中心资深研究员
Dr Kongnan Zhao, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, the University of Queensland,
at the Princess Alexandra Hospital,Australia
Jian’s Great Contribution
John Doorbariii

It is difficult to recollect my first meeting with Jian, but it must have been soon after my move to the Lab of
Lionel Crawford at the start of 1989. The lab was situated on the roof of the Pathology Department in Tennis
Court Road, and had been recently refurbished by the Imperial Cancer Research Fund. Jian’s bench was next
to the door in from the roof and everyone would pass by his bench when walking in from the lift, which was
situated on the roof outside. My bench was in the bay opposite, and we were both enthusiastic young
scientists, who were making the most of the exciting research environment and enjoying the opportunity to
work in a dynamic lab environment in the heart of the city. During that time, we had many light hearted
discussions across the lab, and although pioneering work was beginning here, it was truly a fun place to be,
with Jian’s impish sense of humour contributing greatly to the wonderful atmosphere there. It was a hard
working lab though, and the mixture of personalities worked well together, with Tim Crook, Alan Storey and
Arian Parton contributing also to the lab banter.

From the start, I got on exceptionally well with Jian, and we developed a special relationship which endured
through his move to Brisbane, during his time at Loyola University, and following his return to Brisbane.
During my time in Cambridge, as an unmarried post-doc, Jian was an endless source of advice on matters
both in the lab and outside. It is difficult to pin point exactly why we got on so well, but I think a lot of this is
down to personalities. Jian never took himself too seriously, and his sense of humour was always fair and
generous. He never spoke badly of people, but he was an excellent judge of character. There was certainly a
spark about Jian, which always made him a great person to be with.

There are one or two key memories which stand out for me. One of these was a lab outing to Hunstanton on
the west Norfolk coast during a week when Lionel Crawford was away. It was a great day to visit the seaside,
with warm weather, and we set off in a convoy of cars, with a few lucky ones being driven by Margaret
Stanley, who I believe had air conditioning in her vehicle, which was not the norm in the UK. We played
games on the beach, visited the fair, and had a picnic, with Jian and Xiao-Yi contributing amongst other
things, boiled eggs soaked in tea. Another trip was to visit Lionel in his newly acquired farmhouse in Shotley
in Suffolk, and I remember also one of many parties in Cambridge, being held in the house that Jian shared
with other members of the Chinese community in Cambridge at that time. Eventually Jian’s status in
Cambridge rose, and he invested in a very old brown triumph dolomite, which was regarded as a bit of a
‘dodgey’ (to use one of Jian’s favourite words at the time) vehicle, but which is now listed on ebay as a
classic car!

Initially, Jian was on his own in Cambridge, having made the trip from China, but in time he was joined by
Xiao-Yi, and the two of them formed a determined team working on expressing the viral late proteins using
the vaccinia system. Although there was other work being done on L1 in the lab, Jian’s arrival marked a
change in gear for this project, although I think that few people in the lab truly appreciated the significance of
the work that was being carried out in their midst. I remember at one point during the very early 1990’s
Lionel Crawford appearing on UK TV to say that we would have a vaccine against HPV in under 5 years. It
was through Jian’s determination and his great technical skills as a researcher that this has now reached
fruition. Jian was certainly someone who could be depended on to ‘make it happen’ and there was never any
real doubt that he would achieve success in the project that he started. If you ever found yourself in a crisis,
then Jian would be the person you would want with you.

When Jian and Xiao-Yi left Cambridge for Brisbane, we kept in regular e.mail contact and we initiated many
collaborative projects with my e.mail communications continuing right up until 1999 when we were doing
collaborative work to look at nuclear import and export sequences with in the HPV E4 protein. We were sent
BPV preparations for preliminary structural analysis and in 1998 Jian visited our lab with his son Andy, who
played on the lab computers. This was one of several research visits that Jian made to Cambridge and to
London, and there is little doubt that a hugely productive career in science was cut short by his untimely death.
My last meeting with Jian was in January 1999 at the Papillomavirus meeting in Charleston. He was in good
spirits and full of fun, and we had many in depth discussions and enjoyed each others company greatly at that
meeting. On parting he bought a ladybird soft toy for our first son, who was just two at that time and I
remember him saying that he had bought a pair of shoes for Xiao-Yi. Although his untimely death soon after
that was an enormous loss for everyone that knew him, and for the scientific community, it is heartening to
see where his work, which started during his time as a post-doc in Cambridge, has lead. I’m not sure whether
Jian realized when he arrived in Lionel’s lab in the late 1980s just where his endeavours would lead, but it’s a
true testament to what can be achieved given determination and the qualities of a great individual.

27th February, 2008, Dullingham, Newmarket, Suffolk

Members of Lionel Crawford’s lab between 1989 - 1991

Jian Zhou post-doc


John Doorbar post-doc
Tim Crook post-doc
Alan Storey post-doc
Carol Pye research support
Kate Hartley research support
Ruth Atkinson research support
Lionel Crawford Lab Head
Nick Keen PhD student
Franco Carlotti PhD student

From left: John Doorbar, Heather Doorbar, Xiao Yi Sun and John Zhou in John's home, Newmart Suffolk, Uk
in Sep 1992
Jian’s farewell card-Carton drawn by Camilla Lauro, Cambridge, UK, 1990

Jian Zhou in ICRF, TVG lab, Cambridge University, 1989. From left: Jian Zhou, Camilla Lauron, John
Doorbar

Dr. John Doorbar, Group Leader, Division of Virology, National Institute for Medical Research, London, UK
周健无可估量的贡献
John Doorbari

已经记不清楚我第一次遇见周健时的情景了!那是 1989 年初我转入 Lionel Crawford 的实验室


工作后不久的事情。实验室位于 Tennis Court 路剑桥大学病理学系大楼顶层,不久前才由帝国癌症
研究基金资助装修过。电梯就在大楼顶层旁边,到达顶层一进门就是周健的实验台,每个从电梯出来
的人都得从他的实验台旁经过。我的实验台与健的实验台相接,位于另一端,中间隔着试剂架。我们
都是具有极高热情的青年科学家,用我们充满活力的研究激情,装点着也享受着这个位于城市中心的
充满活力的实验室的机遇和幸运!那段时间,实验室里经常都是兴高采烈的讨论。虽然我们的研究工
作处于初创阶段,但这里确实是一个令人愿意常呆的地方,而周健用他那充满顽童式调皮的幽默更使
得这里常常是欢声笑语,气氛温馨!这里的工作是很辛苦的,然而不同个性的同事们相处融洽。褆
姆·克鲁克、艾伦·斯道理和阿里·帕顿等人,也是善意玩笑和幽默风趣的制造大家。
从一开始,我就和周健处得相当好。在他搬到布里斯班,又到 Loyola 大学工作,然后又回到布
里斯班的这整个期间,我们的友谊一直特别友好地维系着。在剑桥的那段日子里,我是一个未婚的博
士后,不管是有关实验室的工作,还是其它的事情,周健都始终不渝地给我提供着宝贵的建议。很难
说得清楚为甚么我们能够那么好,但一个毋庸置疑的原因就是他的人品。他从不自恃,他幽默,他对
人一视同仁,他慷慨大度。他从不说他人的坏话, 但却洞察人的品行。他身上闪耀的光洁品行使得人
人愿与他为伍。
有几件事我仍记忆犹新:有一个礼拜 Lionel Crawford 外出了。我们到位于西诺福克海岸的
Hunstanton 游玩,那是一个看海的好日子。天很热,我们的车队出发了,几个幸运儿坐在马格丽
特·史丹利的车上,我相信她的车上有空调,在英国这是不多的。我们在海滩上玩游戏,逛集会,野
餐……而周健和小依做了包括煮茶叶蛋等的许多事情。另一件事是探访他们在萨克福 Shotley 的新
居。在剑桥我参加过许多聚会,而这一次至今我记得很清楚。当时那个房子是周健和其他海外学者合
租 的 , 聚 会 就 在 那 里 举 行 。 后 来 周 健 在 剑 桥 的 地 位 提 升 了 , 他 买 了 一 辆 褐 色 的 二 手 Triumph
Dolomite 车。按当时周健的“口头禅”,那是一辆道奇车,如今这种车在 eBay 网上已被列为老爷车
了!
开始,周健一个人从中国来到剑桥。后来小依来了,他们两人组成了一支颇为强势的团队,用痘
苗病毒系统表达乳头瘤病毒晚期蛋白(L1, L2)的研究。虽然当时实验室里其他人关于 L1 的研究工作
也在进行,但当时很少有人充分认识到这项进行中的工作之重要性,而周健的到来的确使得这个项目
面目一新。我记得在 90 年代早期的一个晚上,Lionel Crawford 出现在英国电视台上,宣告我们将
在五年的时间里研制出抗人类乳头状瘤病毒的疫苗。这项宣告是建立在研究者周健的决心和他出色的
技术技巧上的。而如今我们已是硕果累累!周健是这项成果的开创者和奠基人,而凡由他开创的项目
无疑地都会获得成功。毋庸置疑,任何时间当你的研究有了危机,周健就是你最想得到的合作者。
后来,周健和小依离开剑桥去了布里斯班,我们一直保持着频繁的电子书信联系。通过这种联
系,我们曾讨论了许多合作项目,直到 1999 年我们开始合作进行人乳头状瘤病毒 E4 蛋白质序列在细
胞核内的转入和转出研究,在这个合作中,人乳头状瘤病毒标本送到我们这里进行初步的结构分析。
1998 年周健访问了我们的实验室,他的儿子周子晞还在我们实验室的电脑上玩了一阵。在他多次对剑
桥和伦敦的访问中,这是其中的一次!不幸的是,英年早逝中断了他极为高产的科研学术生涯。我最
后一次遇见周健,是 1999 年 1 月份在查尔斯顿举行的乳头状瘤病毒学术会议上。那时他英气勃勃,
充满风趣。会议期间我们就许多事情进行了深入的讨论,彼此相惜相重。在聚会上,他给我们当时只
有两岁的长子带来了一只瓢虫软玩具。我记得他说,他给小依买了一双鞋。此后不久,他就走了!
他的早逝对于所有认识他的人,对于科学界,都是一个巨大的损失。令人欣慰的是,当年在剑桥他作
为一个博士后所开创的事业已经引领风潮!我不知道当 1980 年代周健到达 Lionel 的实验室时,是
否意识到他所做的是一个划时代的开创,但是他的成就无疑是一个杰出人物的决心和品质的最佳凭
证!

2008 年 2 月 27 日写于英国萨福克郡(Suffolk)纽马克特市(Newmarket)的都灵汗(Dullingham)
1989 至 1991 年间 Lionel Crawford 实验室的成员

Jian Zhou 周健 博士后


John Doorbar 约翰.杜巴 博士后
Tim Crook 题姆.克鲁克 博士后
Alan Storey 艾伦.斯道理 博士后
Carol Pye 技术员
Kate Hartley 技术员
Ruth Atkinson 技术员
Lionel Crawford 实验室主任
Nick Keen 博士生
Franco Carlotti 博士生

i
约翰.杜巴(John Doorbar)博士,英国伦敦国家医学研究院病毒学系实验室主任。
翻译:刘广斌博士,澳大利亚南昆士兰大学讲师
Aldo Venuti’s Tribute to Jian

Jian represents for me a morning, as in this marvellous poem

Mattina
1917 – by Giuseppe Ungaretti

M'illumino
d'immenso.

Note:

English Translation.

Morning

Lighting myself
of immense

Giuseppe Ungaretti (February 10, 1888 - June 2, 1970)was one of the foremost Italian poets of the 20th
century. Ungaretti is considered the founder of the "hermetic" school of poetry.

________________________
Aldo Venuti MD PhD, Laboratory of Virology, Regina Elena Cancer Institute, Italy
Denise A. Galloway Ph.D.
Member and Head, Program in Cancer Biology
Fred Hutchinson Cancer Research Center
1100 Fairview Avenue North C1-105
P.O. Box 19024, Seattle, WA 98109-1024

206 667-4500 Phone 206 667-5815 Fax


dgallowa @ fhcrc.org

February 6, 2008

Dear Xiao Yi, Andy and other family and friends of Jian Zhou,

It was hard not to think of Jian at this year’s International Papillomavirus Conference in Beijing. I often saw
young, tall Chinese men, and just for a second thought “Oh, it’s Jian”, but just as quickly remembered “Oh no,
it isn’t”. And then of course, seeing their faces, none of them had Jian’s ebullient smile.

I thought of how proud Jian would be that a vaccine to prevent HPV infection and cervical cancer is now a
reality. In fact, the HPV meetings have been transformed by the influence of companies that manufacture
prophylactic HPV vaccines, HPV diagnostics and hopefully therapeutic vaccines and anti-virals. How far the
HPV community has come from the first work of Jian and colleagues, who presented in Seattle their first
efforts to make virus-like particles, expressing the L1 and L2 genes of HPV 16 in vaccinia virus vectors.

For me, the 1991 Papillomavirus meeting in Seattle was a blur – too busy with organizational details to focus
on the science. Of all the meetings where I met with Jian, and there were many, my favorite memory is of the
1997 meeting in Siena, Italy. I can picture meeting Jian in front of the conference center, with his big smile
and great enthusiasm, hands waving. He seemed typically Italian. Maybe that was part of his success and
charm, that wherever he went, he seemed totally in step with the culture. I remember having long discussions
in Siena about Jian’s new research on codon usage. It was a novel mechanism of gene regulation, to me at
least, and though not all aspects have been proven (I think because Jian did not have long enough to pursue it),
it has also revolutionized the HPV field, facilitating the development of pseudovirions. So while Jian is most
remembered for his contributions to VLP technology, he scored another major hit with codon usage.

Jian’s untimely death has robbed us all of someone special – a son, brother, husband, father, friend and
colleague. The HPV community was lucky to have him for a short time, as his contributions were great.
When I go to Malmo for the 2009 HPV meeting, I will try to imagine a Swedish version of Jian. I can’t quite
picture it, except for his endearing smile.

With all my best wishes,


Denise Galloway 给孙小依等人的信

亲爱的小依、安迪、及周健的亲朋好友们:

在今年北京国际乳头状瘤病毒学会上,我不由得想起了周健。每当我看到一个高个子的中国青
年,马上就会想到这是周健,然而随即又醒悟到,这不可能是他。当然,再细看他们的面庞时,就发
现他们谁也没有周健那热情奔放的笑容。
我觉得如果周健能得知他所发明研究的预防 HPV 感染和宫颈癌的疫苗,如今已经推广实施,他
将会多么地自豪。事实上,在各方厂家的影响下,HPV 研讨会的内容已经转化到生产预防 HPV 疫
苗、HPV 诊断技术、以及进一步研制治疗性疫苗和抗病毒制剂等问题上来。自从周健和他的合作研究
者首次在美国西雅图的会议上报告他们用 HPV 16 的 L1 和 L2 晚期蛋白合成 HPV 病毒样颗粒,宣告
HPV 研究领域中的重大突破以来,HPV 研究已经在此基础上取得了很大的成就。
我对 1991 年西雅图乳头状瘤病毒会议已记忆模糊,因为当时太忙于大会的组织安排工作。但我
曾在国际会议中多次与周健相见,记忆最深的是 1997 年在意大利 Siena 的会议上。我至今还清晰地记
得与周健在会议中心相遇,他笑容灿烂,极其热情地向我挥手致意。他看上去完全是个意大利人。这
也许正是他成功及吸引人的魅力所在,因为他走到哪里,他总是能地地道道地与那里的文化相融合。
我记得,对周健在那次会议上提出的应用密码子优化的新研究,我们进行了长时间的讨论。至少对我
来说,这是一个可以编在教科书里的尚未予以完全证实的新的基因调控理论(也许是时间的缘故,周
健未能阐述完全),这显然是 HPV 领域的一次革新,为以后发展类病毒颗粒提供了前提。 因此,在
纪念周健在 VLP 技术上做出的巨大贡献时,不要忘了周健在应用密码子技术上的另一个重大贡献。
周健的早逝使我们大家失去了一个难得的特殊人物:他曾为人之子,为人之兄,为人之夫,为
人之父,为人之友,和为人之同事。我们 HPV 学会有幸有了周健,尽管很短暂,但他的贡献却是重
大的。我将要出席 2009 年在 Malmo 举行的 HPV 会议,我想我会设想周健的瑞典绅士风度,尽管不
能确定,但周健那可敬可爱的笑容会永远留在我的脑海中。

谨致以
最美好的祝愿

伽罗威 教授
弗雷德·金生肿瘤研究中心肿瘤生物学研究室主任
于美国西雅图

————————————————————
中文翻译:张四力医生,澳大利亚昆士兰黄金海岸眼科医院
Jian Zhou: My Colleague and My Friend
Germain Fernandoi

I still remember the day when Jian and Xiao-Yi first came to the lab. I was photocopying something near the
entrance to the old Lion’s building. They were at the door, this nice and friendly couple. I opened the door
and asked Jian who he wanted to meet. He introduced himself as Jian and I took them to Ian’s office.
Usually I do not remember trivial things like this but this instance was an exception. I think it is because of
Jian’s extremely friendliness even to a stranger. Jian’s friendliness extended to everybody. He always greets
us with a smile. He was never nasty to anyone, and never tried to run down anyone. Always willing to help.
It was a great pleasure to work with him. He treated the Janitor of the department as he would treat the Dean
of the Faculty or the Vice Chancellor. Even though he is very intelligent, he was very humble. In this day
and age where people look solely after their own interest and do not care what happens to the others; Jian was
not like that. He cared very much about the well being of his colleagues, students and people around him. A
quality I very much admire of him. It was very sad for me to see Jian was taken away from this world at the
prime of his life. He was one of my best friends and I miss him very much.

HPV conference,Perth Australia in December 1991, from left Ian Frazer, Xiao Yi Sun, Jian Zhou and Germain Fernando.
1991 年 12 月 HPV 会议于澳大利亚珀斯,左起,伊恩弗雷泽、孙小依、周健、杰美法南杜。

i
Dr. Germain Fernando, Research Fellow, Australian Institute for Bioengineering and Nanotechnology, University of
Queensland
My First NHMRC Grant
Graham Leggatti

I first met Jian Zhou in 1997 when I returned to Australia after a postdoctoral period at the National Institutes
of Health (NIH) in the USA. At the time, Ian Frazer was looking to recruit an immunologist to his research
group and I was keen to apply my knowledge of “killer” T cells to developing treatments for cervical cancer
and viral infection. Jian was already well established in Brisbane and I remember his excitement about the
potential his HPV VLP technology had for vaccine development. He was particularly interested in the idea
that small peptides incorporated into the VLP backbone might efficiently stimulate “killer” T cells which
would then destroy established cancer or virally infected cells. After several roundtable discussions involving
Xiaosong Liu and Ian Frazer, we decided that this vaccine approach could be tested in HIV infection models
and began writing an NHMRC grant to support the project.

Jian’s energy, enthusiasm and ability to focus always impressed me – and everyone else. He also knew how
difficult it could be for young scientists returning from overseas to establish themselves in Australia. With
this in mind, he included me as a chief investigator on the NHMRC grant that was submitted in 1998. He
lived to see the grant successfully funded in early 1999, but never had the chance to participate in the
productive research which followed. Although the problem of developing a therapeutic vaccine was more
difficult than first thought, Jian’s idea of using hybrid HPV VLPs continues to be investigated in our
laboratory almost ten years later.

In my own case that first grant success established my career at the University of Queensland, where I have
since obtained many more grants, fellowships and national recognition of my science. I thank Jian for always
taking a personal interest in my career during the short time I knew him. Whenever I shared my worries, he
gave support, encouragement and sound advice. To this day I am always reminded of Jian by his final words
to me, after yet another conversation about careers, when he simply said : “You’ll be OK”.

i
Dr. Graham Leggatt PhD, Senior Research Fellow, Diamantina Institute for Cancer, Immunology and Metabolic
Medicine, the University of Queensland , at the Princess Alexandra Hospital, Australia
Jian’s Brilliant Mind
-Remembering Jian
Jeanette A Paintsili

Whenever I think of Jian, the phrase: “You do this experiment and I guarantee you a paper” comes to mind.
What a great teacher and what a loss. I owe my success in part to Dr. Jian Zhou who was in my life for a short
period but the mark he left was extraordinary and unforgettable. As one of the inventors on an HPV patent
with Dr. Zhou I will forever be grateful for his guidance during my doctoral research.
I first met Jian Zhou in the fall of 1994 and immediately took a liking to him because of his openness,
extraordinary sense of humor and keen intellect.
I was a graduate student in the Microbiology & Immunology Department at Loyola University of Chicago
(Medical Center).
I had joined Dr. Lutz Gissmann’s research group to complete my doctoral dissertation and Jian was
selected to be my research supervisor. Jian already had a number of research projects lined up for me to tackle
and he wasted no time in getting me to work. As a mentor and a supervisor he was really tough but fun.
Always smiling and joking around.
Dr. Zhou took me seriously and treated me like a colleague. I was a doctoral candidate, a woman and a
native of Ghana but he was full of encouragement and was highly motivating. He had a passion for research
and that rubbed off on me. He taught me to think critically and analytically and above all to be creative in
research analysis.
Anybody who had the privilege of working with Jian can attest to his dedication to research and the zeal
with which he approached the subject of HPV research.
Thank You Jian!

January 30, 2008

From left: Jian Zhou, Jeannete Paintsil & Xiaoyi Sun in Chicago, 1996.吉奈·潘淑与周健夫妇 1996 年于芝
加哥
i
Jeanette A Paintsil, PhD, Health Care Manager, EMPACARE, 230 Devon Dr., Burr Ridge
Thoughts on Jian Zhou
John Schilleri

Jian Zhou always struck me as man who enjoyed his work. His enthusiasm for his science invariably showed
through and he overflowed with ideas for new experiments. I always looked forward to seeing Jian at the
annual Papillomavirus meetings and sought him out for extended conversions. In part this was because our
research interests overlapped so extensively. In part, it was because he was always good natured in defending
his point of view with enthusiasm and determination. It was really a joy to get into a friendly argument with
him. I vividly remember the smile on his face as he presented his counter argument to some point I was
trying to make. For example, I recall animated discussions about whether codon modification of
papillomavirus late genes increased levels of protein expression primarily by changing the codon usage or
primarily by removing negative regulator elements. I don’t recall that we ever resolved one of these
“disputes”, but it didn’t really matter because it was the playing of the game that was the main point of the
exercise.

I very much appreciate Jian’s interest and talent in both basic virology and applied vaccinology. He managed
to balance and integrate these two endeavors exceptionally well. My guess is that this is in part a reflection of
the breath of his own interests and in part due to influence of two primary mentors, Lionel Crawford and Ian
Frazer. In my opinion, Jian was and equal partner early on with both of these distinguished scientist,
particularly with regard to the focus on basic virion biology. It is interesting to speculate on what Jian might
have done with his research, had he not died prematurely. It is my guess that he would have had his largest
impact in studies of virion molecular biology, which seem to me to be his first love. However, I feel certain
that he would have also applied his insights into basic virion biology to advance translational research. Quite
frankly, I miss the challenge of competing with Jian in this area of research. He was equally a great
competitor and esteemed colleague.

January 28, 2008

i
Prof. John Schiller, Senior Investigator, National Cancer Institute, Bestheda, MD USA
怀念周健
约翰•斯希勒i

周健给我的最深刻印象是:他是一个相当热爱工作的人。他对科学的热情,体现在他的新的实验
想法层出不穷。每年的国际乳头瘤病毒会议上,我总是盼望能见到周健,与他交流科研信息和研究想
法。这一方面是由于我们有共同的研究兴趣;另一方面,是因为他在为自己的观点辩护时,总会自然
而然地流露出他的热情和决心。我真的很高兴能跟他进行这样一种友好的辩论。我还清晰地记得,当
周健在反驳我的一些观点时,脸上总是笑容洋溢。例如,我记得我们之间的一次讨论是关于乳头瘤病
毒晚期基因的密码子优化提高了蛋白表达水平的看法,这主要是通过改变密码子的应用、还是通过去
除消极调节元素。我不记得我们曾解决了这些“争论”当中的哪一个问题,但这真的没有关系,因为
这些“争论”就象士兵的操练,目的是为了不断提高。这才是操练的宗旨。
我非常欣赏周健在基础病毒学和应用免疫学方面的兴趣和天分,他能平衡这两个学科并很好地结
合应用。我猜想,这部分地反映了周健自己的兴趣,部分地是受到了其两位主要的良师益友利奥内尔
•克罗福德 (Lionel Crawford) 和伊恩•弗雷泽 (Ian Frazer) 的影响。在我看来,周健与这两位杰出的科学
家是平等的合作者,特别是在基础病毒生物学研究方面,周健尤为卓越。想象和推测一下,如果周健
没有过早地逝世,他又能为人类做出多少研究成果和贡献?我猜测他会对病毒分子生物学的研究产生
巨大的影响,因为在我看来,这是他最喜欢的研究领域。但是,我确定他还会将他的想法应用到基础
病毒生物学,推进研究转化为成果。坦率地说,我极其怀念周健以及他带给这个研究领域的竞争和挑
战。他既是一名了不起的竞争对手,也是一位受尊崇的同事。

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约翰•斯希勒教授(John Schiller),美国国家癌症研究院高级研究员
中文翻译:杨蝉,昆士兰大学翻译系硕士
Jian’s Brilliant Mind

Laimonis A. Laiminsi

It is both a pleasure and an honor to share my recollections of Jian Zhou as part of the memorial service that is
being held for him. Jian was a dear colleague and a talented scientist. To designate this memorial a “brilliant
mind” is truly fitting, as it characterizes Jian Zhou quite accurately. Jian’s work as a scientist was at the
cutting edge of innovation in the study of papillomaviruses. His initial studies provided the framework for
major advances in the treatment of HPV-associated disease. These studies eventually led to the development
of the HPV vaccine.

I first met Jian in the early 1990’s at an international papillomavirus workshop after he had just started
working in Australia with Ian Frazer. Jian had completed his postdoctoral work with Lionel Crawford in
Cambridge and had moved to Brisbane in 1990. One of his first areas of study was to investigate the
expression of HPV capsid proteins using vaccinia expression systems. His work resulted in the important
finding that expression of these viral proteins leads to the spontaneous assembly of viral like particles or
VLPs that resemble HPV virions. These findings formed the basis for the development of the vaccine for
HPV. Jian Zhou, together with Ian Frazer and investigators from the U.S., executed the pioneering work for
the development of this vaccine and deserve significant recognition for this achievement.

In 1994, Jian moved to Chicago to become Assistant Professor at Loyola Medical School in the Department
of Obstetrics and Gynecology. After Jian moved to Chicago, we held joint meetings with my group and that
of the HPV investigators at Loyola Medical School. The Loyola group included Jian Zhou, Lutz Gissman and
Martin Muller. We would hold these joint meetings every few months and alternate between Loyola and
Northwestern. These were always lively and fun interactions where, along with the science, we shared pizza
and beer. I also served on graduate student committees with Jian. This was a nice excuse to get together, as it
was always a pleasure to talk science with Jian and have a few laughs about the goings-on in the field.

I was quite saddened when Jian decided to leave Loyola and return to Australia. After he moved back to
Brisbane, I continued see Jian at papillomavirus workshops. I remember an occasion at a papillomavirus
workshop in Sienna when I ran into Jian and his family at the train station. He had decided to travel to Pisa,
which was over three hours away, because he wanted his son to see the world-renowned leaning tower. I was
shocked and saddened to hear that he had died not long afterwards, but heartened by the fact that his memory
lives on in his science and in those who had the pleasure to know him.

Jian Zhou was an outstanding scientist, colleague and family man. His enthusiasm for science was truly
infectious. While he is sincerely missed, he will always be remembered in the minds of others for whom his
life’s work has had a profound affect. He was the consummate professional and was a great role model for
young scientists. Jian Zhou was indeed a brilliant mind who is truly missed.

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Laimonis A. Laimins, Guy and Anne Youmans Professor and Chair, Department of Microbiology-Immunology,
Northwestern University, Chicago, USA
A tribute to Jian
Lutz Gissmann and Martin Muelleriv

We were a splendid crowd of people when we all gathered in Chicago-land, following the call of an
enthusiastic fellow from Latin America who had the vision of generating an HPV vaccine. As it turned out,
we did make very significant contributions in pursuit of this goal and are now proudly watching the
distribution of two drugs that are suspected to significantly reduce the burden of an important cancer in
women.

We originated from three distant parts of the world: Germany, China and West Africa. Whereas the Germans
had a rather boring history, the others had already travelled the world. In particular, Jian Zhou and his wife
Xiao-Yi Sun, together with their small son Andy, already looked back on a busy life, having moved from
China to Cambridge, UK and to Australia. We also experienced Jian's roving nature in our everyday lives. It
was he who organized the trips to remote areas of Michigan, just to pick cherries on a farm, but then to
become quickly distracted and ready to head for the next destination.

Jian was a special character: sparkling, provoking, charming and very likeable. He was able to drive you crazy
with a smiling face ready to discuss ideas you had never dreamed of before. He translated his unconventional
personal outlook into his daily life as a scientist and it is that which made him such an unusual and
outstanding researcher. We already missed him when he decided to return to Australia and we have been
missing him even more ever since his untimely departure from us for ever.

We never had a dull moment with Jian Zhou and remembering him brings back the feeling of adventure we

had had every day in his company

Front left: Martin Mueller (1), Lian Qiao(4), Lutz Gissmann (5), Second row: Jian Zhou (3)

i
Prof. Dr. Lutz Gissmann and Dr Martin Mueller, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
怀念周健

路斯·盖茨曼教授和马丁·穆拉博士v
路斯·盖茨曼教授和马丁·

当接到我们同事中一位充满激情的拉丁美洲的研究伙伴的电话,提出了要研制 HPV 疫苗的设想


后,我们这帮杰出的研究人员随即聚集在芝加哥开会予以探讨,周健就是其中一位猛将。。从那次会
议后,我们大家为了实现这个目标不懈努力,并做出了具有历史性意义的贡献。今天,我们很自豪地
看到已有两种可用的药物,其能如期有效地预防一种致命率很高的子宫颈癌。
我们这些创新者来自三个相距遥远的国家:德国、中国和西非。当时,我们这些德国人还是恪守
本分,而其他的同行们已经去过世界的许多地方。特别是周健和他的太太小依,还有他们当时还很小
的儿子安迪,他们已经从中国迁居到英国的剑桥,又从英国移居到澳大利亚。在我们日常的接触中,
我们也领略了周健那种好动的天性。有一次,周健计划组织我们大家一同去密西根的郊外农场摘樱
桃,可是没多久他就改变了主意,因他要去做一个重要的实验来证明他的新理论。
周健是一个特殊的人物:他充满了活力,具有挑战性,可爱又具魅力。他常常会笑容满面地与你
讨论那些你从来未想到过的研究课题,而这些新的设想往往会令你兴奋入迷。他把他那超俗的个性特
征融汇进了他的科学家的生涯,这使他成为一个非凡杰出的研究学者。当他离开我们去澳大利亚时,
我们都很恋恋不舍。当他过早和永远地离我们而去时,使得我们更加怀念他。在我们和周健共事的那
些日子里,总是充满了兴奋和新意。在纪念他的此时此刻,又把我们带回到了那种和周健一起创新和
探索的感觉之中。

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路斯·盖茨曼教授和马丁·穆拉博士,德国海德堡 DKFZ 研究中心
中文翻译:张四力博士、澳大利亚昆士兰黄金海岸眼科医院医生
Jian in Our Mind Forever
Nick Saundersvi
It was late spring 1993 that Prof Frazer invited me to return from the USA to establish a research group at
what was then, The Papillomavirus Research Unit. My wife, Marion and I had not lived in Brisbane before
and so, like most other scientists, we were both excited but also very anxious about the move to Brisbane.
Our first days here were occupied with finding housing and transport as well as keeping dry (it used to rain in
Brisbane back then). A day or two before starting work at the Princess Alexandra Hospital, Marion and I
attended a dinner with Jian and Xiao Yi as well as visiting dignitary from China at Prof Frazer’s house. This
was my first introduction to Jian and Xiao Yi and my first impression of that occasion has remained with me.
Jian and Xiao Yi never stopped smiling and were warm and friendly right from the outset. As I later realized,
this was not a superficial attitude but reflected a genuine fondness by Jian, for his colleagues as well as his
general happy disposition. Over the next few years I was to develop a great fondness and respect for Jian as a
person and as a scientist.

Back in 1993 the Papillomavirus Research Unit was quite dispersed with a group of researchers, including
Jian and Bob Tindle, working on the 3rd floor of the Lions Building in shared premises with the Clinical
Immunology staff. Another section of the Unit was located on the second floor (Germaine Fernando’s group
and many Technical Staff and students) of the Lions building and finally a third, small group which included
myself, Anne-Louise Bulloch and Linda Dunn, was located in the old “Nurses Quarters” or Diamantina
House as it was officially known. The notoriety of the “nurses quarters” in those days was well known
amongst the taxi drivers in Brisbane and if you asked to be taken to Diamantina House at the PAH they would
look at you blankly. Yet, if you were to ask to be taken to the old “nurses quarters” at the PAH they always
knew where you were going. Anyway, I digress. The dispersed nature of the Unit was a reflection of the
success of the Frazer / Zhou team. At that time, the success and reputation of Jian and Ian was developing
amongst the scientific community in Australia and this was reflected in their ability to attract funding to fund
their growing empire. Hence, upon my arrival there were already plans for expansion and the establishment
of new premises. This has not changed since 1993, and now in 2008 we are still planning to move to yet
another new building. The only difference being that back in 1993, we were talking in terms of $1 million
dollar premises whereas today we are talking of premises in excess of $300 million. Much of this ability to
expand has been based upon the success of the Gardasil vaccine and the increased profile of the makers (Zhou
and Frazer). With their success came influence and this has allowed the development of a large translational
research base at the current PAH campus. Thus, directly and indirectly, the discovery by Jian and Ian of the
HPV vaccine, is continuing to have influence over a great many other research projects and will likely lead to
improvements in patient outcomes for many years to come.

Whilst I may have been located in a separate building to Jian, the short walk from Diamantina to “the dark
side” was familiar to all of us and I spent considerable time chatting with Jian about various research ideas I
had. I found Jian to be a patient listener and always quick to offer constructive advice about my work. Jian
was also technically very capable and consequently I learnt a good deal about cloning and molecular biology
from him in my early years at the Unit. In those days we used to have seminars and group meetings in
various locations around the hospital until we settled on the Psychiatry building as our main venue. The use
of the lecture theatre there was necessitated by the rapid expansion of the Unit. These meetings were always
lively and Jian was often vocal and constructive in his comments. I can still remember the enthusiasm he
showed at these meetings and when he was interested in a topic his animation was boundless. I have always
admired Jian’s enthusiasm for science and have tried to emulate it in my own career.

Since Jian’s passing, the Unit has gone on to become the Centre for Immunology & Cancer Research and
more recently the Diamantina Institute for Cancer, Immunology and Metabolic Medicine and is staffed by
over 200 people and occupies at least 3.5 floors in a dedicated research building on the PAH campus. I think
we lost a spark when we lost Jian but his legacy will live through those of us lucky enough to have known
him as well as through the continued success of the researchers who are involved with the Diamantina
Institute.

I miss Jian and will continue to miss him.


i
Dr. Nick Saunders, Associate Professor, Head of Epithelial Pathobiology Group, Diamantina Institute for Cancer,
Immunology and Metabolic Medicine, the University of Queensland, at the Princess Alexandra Hospital, Australia
A Personal Tribute to Dr Jian Zhou
M Saveria Campovii

I do not remember when I first met Jian and the exact date is not important. What I remember though was his
scientific acumen, his warmth and his friendship.

His scientific abilities were always in full view at Congresses, Workshops, Meetings, in published papers and
other scientific media. These points will be elaborated by many colleagues; what I want to remember here is
the fantastic (in all meanings of the word) banquet he prepared for us during one of our visits to Brisbane.

My husband I had some work to do with our respective collaborators in Adelaide and Brisbane, so we
scooped up our little son and went to Australia. At the same time Jian’s parents were visiting Jian and his
family in Brisbane. This was the occasion for a memorable feast!

It is often said that Glasgow and Edinburgh have the best Chinese restaurants outside China. Maybe, maybe
not…. Surely nothing compares with what we had at Jian and Xiao Yi’s house!

Amazing dishes kept coming, and coming and coming…… We thought the dinner had come to an end; Jian
burst into laughter: those dishes were only the starters! And so it went on, with lots and lots of indescribably
delicious food, with lots and lots of laughter and delight, with Jian and Xiao Yi’s son Andy and our son
Thomas playing on the floor as if they had known each other from birth….

Why have I described this dinner and why do I remember it so vividly? This dinner was not “just” a dinner, it
was not “just” food: it was an expression of friendship, hospitality, generosity of spirit; it was a metaphor for
warmth, kindness, for all that is better in us humans, embodied that day, as all days, by Jian. Jian’s smile was
lighting the room and his laughter was the background music….

Alas, Jian’s no more but, like his scientific achievements, his smile and laughter remain, and that dinner in
Brisbane will remain with me forever.

i
Prof. M Saveria Campo, Professor of Viral Oncology, Institute of Comparative Medicine, University of Glasgow,
Scotland, UK
Professor Suzanne Garland
MB BS MD FRCPA, FAChSHM FRANZOG Ad Eundem
Department of Microbiology & Infectious Diseases,
Department of Obstetrics and Gynaecology,
University of Melbourne.
WHO HPV Regional Reference Laboratory

Memorial Day for Dr Zhou: “Jian’s Brilliant Mind”

I am honoured to be invited by Dr Xiao Yi, widow of the late Dr Jian Zhou, although saddened not to be
present to the Memorial Day, to deliver my thoughts and contribution. As a scientist and medical practitioner
myself who has worked in the field of human papillomavirus (HPV) since the mid-1980s, I first met Dr Zhou
at International Papillomavirus meetings. Not only do remember him as a gentle, approachable medical
scientist, but an outstanding virologist. We all admired Jian for his great discovery (with Professor Ian Frazer)
of the viral-like- particle (V LP), which has underpinned the vaccine development, and merely responsible for
where we are to date in rolling out the vaccine as a public health tool. We were all so proud when we read the
seminal paper in Virology in 1991, putting not only the Queensland group on the map, but Australia high into
the scientific arena, particularly in the world of HPV and cervical cancer.

Realising that more than 50% of cervical cancer cases in the developing world occur within the Asian-Pacific
region, a new society called AOGIN (Asian-Oceania Research Organization on Genital Infection and
Neoplasia) was established in 2005, my being the Inaugural President. AOGIN brings together clinicians and
scientists whose work is related to genital infections and neoplasia. The aims of the organisation are to
promote and develop, at an Asia-Oceania level, research, training, screening, prevention, and information
concerning genital infections, pre-cancers, and cancers in women. AOGIN has four main areas of activity:

1. Collaboration and Research


2. Scientific Exchanges, Education and Training
3. Information
4. Surveys and Audits

The inaugural meeting occurred in Malaysia in 2005, followed by Philippines 2006, Korea will be held late
May, 2008. The Board of AOGIN wished to honour the eminent works of an outstanding scientist by
awarding a prize in his name for the best oral proffered presentation for the biennial medical conference. We
agreed unanimously to choose the great medical virologist, Dr Jian Zhou. In the future we plan a sponsored
travelling speaker for AOGIN, the "Zhou Lecture."

At the conference in Cebu, Philippines we were honoured to have Dr Xiao-Yi Sun present this prize.

In our short time together in Cebu, I had the privilege of learning more about Dr Xiao Yi. She too was
instrumental in this HPV VLP work: explaining with great enthusiasm how she assisted her husband in his
works and in fact having been the first to see the viral like particles down the electron microscope!

She is the second author on the seminal paper published in Virology 1991. Subsequent to Jian’s untimely
death Dr Xiao-Yi has had her own cross to bear: A very brave woman, one with a great career herself as an
ophthalmologist. I learnt how amazingly stoic she has been and I am sure Jian would be extremely proud of
what she has achieved to date herself.

I myself have been intimately involved in running some of the key clinical trials for the HPV vaccine, seeing
the fantastic results, preventing disease. We can all say that the women of the world in the future owe so much
to Jian and Ian. This fantastic public health tool now needs to be delivered widely worldwide and particularly
countries which are resource poor and have the greatest burden of disease. Thank you Ian and Jian!

.
Kind regards,
Professor
Suzanne M. Garland

Director of Microbiological Research and


Head of Clinical Microbiology and Infectious Diseases
Royal Women’s Hospital,
Senior Consultant Microbiology, Royal Children’s Hospital,
WHO HPV regional reference laboratory, Western Pacific region for HPVLabnet.

Professor , Faculty of Medicine, Dentistry and Health


Department of Obstetrics and Gynaecology
University of Melbourne

President of AOGIN (Asia Oceania research organization on Genital Infections and Neoplasia)
周健纪念日:
周健纪念日:“英才济苍生”
英才济苍生”有感

苏赛因•M.
苏赛因 加兰德

尽管很遗憾因故不能出席周健纪念日活动,但我荣幸地接受周健夫人孙小依医生之邀,来表达
我对周健的怀念和我的一些想法。作为一名科学和医学工作者,从 1980 年代中期开始,我就从事人
乳头瘤病毒 (HPV)的研究。我第一次与周健博士相识,是在国际人乳头瘤病毒会议上。我记忆中的周
健,不仅是一位和蔼可亲的科学家,还是一位杰出的病毒学家。我们所有人都很钦佩周健(和伊恩•
弗雷泽)的重大发现——病毒样颗粒 (VLP),这个颗粒制成了宫颈癌疫苗,并为今天我们推行疫苗作
为一项公共健康措施奠定了基础。1991 年,当我们读到这篇意义重大的病毒学文章时,我们是多么地
自豪。这一成果不仅将昆士兰州的实验室放上了世界版图,还将澳大利亚推向了世界科学舞台,特别
是在 HPV 和子宫颈癌领域。
调查发现,发展中国家超过 50%的子宫颈癌病例发生在亚太地区。2005 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) 成立了,我是该组织的创会主席。AOGIN 组织临床医生和科学家一起合作,研究生殖感染和
瘤形成。这个组织的目标是在亚洲——大洋洲地区,促进和推动有关生殖感染、前期癌症和女性癌症
的研究、培训、检查、预防以及进行各相关领域中的合作和信息交流。AOGIN 的活动主要有四方
面:
1. 合作和研究
2. 科学交流、教育和培训
3. 信息交流
4. 调查和审计
2005 年,在马来西亚召开该组织的创立会议;2006 年,在菲律宾开了第二次会议;2008 年 5
月下旬,将在韩国召开第三次会议。AOGIN 委员会希望设立为两年一次的医学会议上的“最佳讲
座”颁奖仪式,并以一位杰出科学家名字命名的奖项来表彰该科学家的突出贡献。我们一致同意选择
优秀的医学病毒学家周健博士,以他的名字来命名之。将来,我们计划由主办方轮流派出 AOGIN 的
发言人主持的专业讲座,名之曰 “周健讲座”。
在菲律宾宿务举行的会议上,我们很荣幸地邀请到孙小依医生来颁发这个奖项。在宿务的短
聚中,我有幸对孙小依有了更深的了解。她也曾是 HPV 病毒样颗粒研究的成员之一,她充满热情地
给我讲述了周健发明 VLP 的经过以及她是怎样协助周健的研究的。事实上,她经历了在电子显微镜
下首次观察到病毒样颗粒这一激动人心的时刻!
1991 年发表在《病毒学》上的影响重大的文章,孙小依是其第二作者。周健逝世后,孙小依
承担起了重担:她不仅是一位坚强的女性,她本身还是一名优秀的眼科医生。她有着多么惊人的坚忍
和毅力,我相信,周健一定会为今天的孙小依倍感骄傲。
我亲身参与了 HPV 疫苗的一些关键临床实验,看到了预防疾病的卓有成效的、极其出色的结
果。可以说,将来世界上的女性都要感激周健和伊恩。现在,这项优异的公共健康措施需要向全世界
推广,尤其是那些资源贫乏、疾病发生率高的国家。伊恩、周健,谢谢你们!

谨致以
最美好的祝愿

苏赛因•M. 加兰德 (Suzanne M. Garland) 教授


亚洲–大洋洲生殖感染和瘤形成研究组织 (AOGIN) 主席
世界卫生组织 HPV 地方性参考实验室,西太平洋地区实验室网络
皇家妇女医院微生物学研究主任,临床微生物学和传染病主任
皇家儿童医院微生物学资深顾问,

医学、牙科和健康学院教授
墨尔本大学妇产科系
Prof Suzanne M. Garland at Cebu Conference, 2006.苏赛因•加兰德教授在 2006 年宿务会议上。

————————————————————————————
中文翻译:杨蝉,昆士兰大学翻译系硕士
Jian Zhou – A Personal Tribute

Professor Margaret Stanleyi

Jian Zhou was a remarkable scientist whose seminal work has resulted in the development of vaccines that
will almost certainly result in the eventual elimination of cervical cancer in women. Carcinoma of the cervix
is a disease caused by infection with a virus, the human papillomavirus (HPV). HPVs belong to a huge
family, a small subset of whose members, particularly HPV 16 and 18. can cause cancer in the cervix in
women and in some other sites in the ano-genital tract in both men and women. Vaccines against HPV
seemed a distant dream in the late 1980’s since the viruses could not be grown in tissue culture and preparing
pure native protein from the virus coat or capsid appeared to be an insuperable technical challenge. Jian
changed all that.

Jian Zhou came to work in 1989 as a postdoctoral fellow with Dr Lionel Crawford at the ICRF Tumour
Virology Laboratories in Cambridge. My laboratory and the Crawford laboratory were adjacent and our
groups collaborated very closely indeed. A former PhD student of mine, Helena Browne, had been the first
person to express an HPV protein using vaccinia virus as the expression system when she made an HPV 16
L1 recombinant vaccinia virus. These types of recombinant viruses were very useful for immunological
studies, particularly for trying to determine cytotoxic T cell responses to the recombinant viral protein. Jan’s
expertise was very much in the generation of recombinant vaccinia viruses and he set about determining
different sites in which one could insert the gene of interest into vaccinia. The objective was to improve
expression of the protein. He inserted the L1 gene into the vaccinia serpin gene site and then selected the
recombinant viruses with mycophenolic acid. This was a novel approach and resulted in very much improved
expression of the inserted gene and higher levels of protein.

Jan’s long term objective, as was all of ours, was immuno-prophylaxis, that is prevention of infection and the
aim was to use the vaccinia expression systems to generate full length L1 protein in the native or
conformational form since unless the protein could be generated in the native or conformational correct form
then neutralising antibodies would not be produced against the protein if and when it was used to immunise
animals or humans. We already knew that the L1 protein was the protein that the immune system recognised
and generated serum neutralising antibody against - this information had come from experiments in rabbits
and cows and, as it turned out, dogs. Jan’s serpin gene insertion recombinants were much better at generating
increased protein and he showed also in a paper in 1990, that immunisation with these reagents produced
much more antibody.

Jian left the Crawford laboratory together with his wife Xiao Yi Sun, in 1990 and joined Ian Fraser in
Brisbane. Xiao Yi had “green fingers” in the laboratory and was an essential helpmate to Jian in every aspect
of his science. In the Fraser lab Jian continued in his pursuit of producing full length L1 for the purposes of
immunoprophylaxis. The papillomaviruses are closely related to the small DNA papovaviruses - SV40 and
polyoma. It had been shown in 1986 in the Garcea laboratory that expression of the major coat protein, VP1
of polyomavirus via a bacterial expression system was enough to allow macromolecular assembly and
formation of empty capsid-like structures that consisted only of the VP1 protein. The papillomavirus capsid
structure shares many similarities with the papovavirus capsid and this did suggest that expression of the HPV
coat proteins L1 and L2 might result in the formation also of empty capsids. With typical determination and
adventurousness, because this was a very significant technical challenge and in unknown scientific country,
Jan set about performing the experiments to test this notion using vaccinia as his expression system.
He made a very important breakthrough. Up to this point the HPV 16 L1 gene had been cloned out of the
viral DNA in a manner that allowed expression of the gene from the first ATG. Jian cloned out HPV 16 L1
so that expression started at the second ATG, a procedure that has been followed ever since for the expression
of HPV 16 L1. He made a series of HPV 16 L1 and L2 vaccinia recombinants including a recombinant co-
expressing both L1 and L2. He used the mycophenolic acid selection system which had been developed in
the Crawford laboratory that allowed reasonably high level production of these proteins. All of these aspects
would become important in the outcome of the experiment. He and his colleagues infected monkey kidney
epithelial cells with these recombinants. He then used classical techniques for viral extraction and
purification from the cells and showed using electron microscopy that empty protein shells comprised of the
HPV 16 L1 protein had been formed. These structures morphologically were very similar to papillomavirus
particles and were the first HPV 16 virus like particles (VLPs). HPV vaccines for the prevention of infection
of HPV consist of VLPs and are the outcome of the landmark work from Jian Zhou and his colleagues in 1991.

Jian went on to make further important observations. He generated infectious bovine papillomavirus particles.
He dissected the L1 molecule of BPV to permit the formation of hybrid VLPs comprised of the L1 protein
and other HPV proteins suitable for both prophylactic and therapeutic intervention. He showed that
papillomaviruses tightly control how much protein they make by codon usage that is relatively inefficient in
mammalian cells.

Jian was a scientist of great insight and intuition. This, combined with his capacity for hard work, technical
skill and his huge drive, made him a major force in virology. Science is a matter of team work but someone
has to light the flame and energise the team and that was one of Jian’s gifts. His enthusiasm, sense of fun and
sheer enjoyment of life were infectious activating his more cautious colleagues to “give it a go”. His
premature death deprived us of a very fine and innovative scientist but his legacy is the HPV vaccine. The
benefits that these vaccines promise are immense, they will improve the health and well-being of women
worldwide.

Feb 2008

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Professor Margaret Stanley, Department of Pathology, University of Cambridge
颂周健
玛格丽特 • 斯坦利i

周健是一位杰出的科学家,他影响巨大的研究工作,使得疫苗的发展最终一定能在女性中根除子
宫颈癌。子宫颈癌是因一种病毒——人乳头瘤病毒 (HPV) 感染而发生的。HPVs 有一个大家族,有许
多型别,HPV16、18 型病毒感染、诱发女性的子宫颈、女性和男性生殖道的某些部位引起癌症。在
1980 年代晚期,防治 HPV 的疫苗似乎是一个遥远的梦想,因为这种病毒不能进行组织培养和体外生
产,并且,表达病毒 L1 衣壳抗原蛋白似乎是一个难以克服的挑战。周健挑战了所有这些难题。
1989 年,作为一名博士后研究员,周健在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,跟随 Lionel Crawford 教授做研究。我的实验室正好与 Crawford 教授的实验室毗邻,
我们两个小组确实也比较紧密地合作。我以前的一个博士生 Helena Browne 做出了 HPV 16 L1 重组疫
苗病毒,曾第一次用痘苗病毒作为表达系统表达了 HPV 蛋白。这些类型的重组病毒对免疫学研究非
常有用,特别是在确定细胞毒性 T 细胞对重组病毒蛋白的反应方面。周健非常擅长于培养重组痘苗病
毒,他着手确定不同的点位,可以将相关的基因加入到痘苗病毒基因组中,目标是提高蛋白的表达。
他将 L1 基因加入到痘苗蛋白酶抑制剂基因位点,然后用霉酚酸来挑选重组病毒。这是一种创新的方
法,提高了加入的基因的表达和蛋白的水平。
周健和我们所有人的长期目标,是免疫预防:即预防感染,其目标是用重组痘苗病毒表达系统来
表达出具有免疫原性并构象的完整 L1 衣壳蛋白,因为只有这种具有免疫原性和正确构象的 L1 衣壳蛋
白,用它来免疫动物或人,才能产生出对蛋白的中和抗体。我们已经知道,L1 蛋白是免疫系统,能
识别、并能产生血清中和抗体的蛋白——这一信息来自对兔子、牛和狗进行的实验。周健构建蛋白酶
抑制剂基因的重组质粒,能产出更多的 L1 蛋白。1990 年,他发表论文,阐明用重组 L1 蛋白免疫,
能产生出更多的抗体。
1990 年,周健和夫人孙小依一起离开了 Crawford 教授的实验室,加入到伊恩•弗雷泽 (Ian
Frazer) 在布里斯班的研究室。孙小依在实验室有“神奇的手指”之称,对于周健来说,在他研究的
各个方面,孙小依都是不可或缺的助手。在弗雷泽教授的实验室,周健继续进行以免疫预防为目标、
培养完整 L1 的研究。乳头瘤病毒与小 DNA 乳头多瘤空泡病毒——猿猴病毒 40 (SV40) 和多瘤病毒联
系紧密。 1986 年,Garcea 实验室发现了主要衣壳蛋白的表达,通过细菌表达系统,多瘤病毒 VP1 足
够允许大分子融合,并形成只由 VP1 蛋白构成的空衣壳样结构。乳头瘤病毒衣壳结构与乳头多瘤空泡
病毒衣壳有很多的相似性,由此可推断:HPV 衣壳蛋白 L1、L2 也可能形成空衣壳。因为这是一项非
常巨大的技术挑战,并且一切还是未知数,周健带着其典型的决心和创造性,着手进行实验,用痘苗
作为表达系统来测试这一想法。
周健取得了非常重大的突破。此时,HPV 16 L1 基因已被从病毒 DNA 克隆出来,这就允许了基因
从第一个启动子表达。周健克隆出了 HPV 16 L1,可以在第二个启动子开始表达。从那以后,这一步
骤被沿袭下来用于 HPV 16 L1 的表达。周健做了一系列的 HPV 16 L1、L2 痘苗重组质粒,其中包括了
一种能共同表达 L1、L2 的重组质粒。他使用了在 Crawford 实验室研究出的霉酚酸挑选系统,这在很
大程度上提高了这些蛋白的生产。所有的这些方面都对实验结果很重要。周健和他的同事用这些重组
质粒来感染猴子肾脏上皮细胞,然后用传统技术从细胞中提取及纯化病毒。结果用电子显微镜观察
到,由 HPV 16 L1 蛋白构成的病毒空壳形成了。这些结构与乳头瘤病毒颗粒在形态上非常相似,这就
是第一个 HPV 16 病毒样颗粒(VLPs)。预防 HPV 感染的疫苗是由病毒样颗粒构成的,这是周健和他
的同事在 1991 年的杰出研究成果。
周健继续做进一步的重要观察。他人工合成出了感染性牛乳头瘤病毒颗粒。周健解剖了牛乳头瘤
病毒(BPV)的 L1 分子,使得形成由 L1 蛋白和其它 HPV 蛋白构成的合成病毒样颗粒,以此来达到既
预防又治疗之目的。他发明了通过调控基因的密码子优化,大大提高了乳头瘤病毒 L1 和 L2 蛋白的表
达产量,而在哺乳动物细胞中,密码子的效能相对不明显。
周健是个有着非凡洞察力和敏锐性的科学家,再加上他的勤奋努力、专业技术和巨大的干劲,使
他成为了病毒学领域的领军人物。科学是一项团队工作,但是需要某个人来点燃对科学的激情和激励
这个团队——这是周健的贡献之一。他的热情、幽默感和对生活的热爱,感染了周围的每一个同事。
周健的早逝使我们失去了一位非常优秀和极具创造性的科学家,但他留给了我们 HPV 疫苗。这种疫苗
的益处是巨大的,它将造福于全世界女性的健康。

孙小依与玛格丽特 • 斯坦利教授 2006 年 9 月于菲律宾宿务。Xiao Yi Sun and Margaret Stanley in Cebu,


Philippines, Sep 2006

i
玛格丽特 • 斯坦利(Magaret Stanley) 教授,剑桥大学病理学系
中文翻译:杨蝉

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