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最激动人心的科学是现在

——为Tim Hunt学术报告的引言  
 
当我的年龄接近于在座的多数时,我有个和你们一样的担心:最好的科学都已经做掉了,我们没有赶上过去的好时代。  
 
确实,很多进入科学不久的人,在经历最初的激动后,常常发现科学研究的日常有很多重复工作:克隆基因、纯化蛋白质、培养细胞、筛选突变…。一般来说,手头的工作好像远远不如听老师讲的科学发现故事那么精彩、那么美妙。  
 
不少学生会失望,可能还会转而埋怨:现代科学已经变质了,都是骗我们进来做苦力。  
 
这不是新的现象,不仅你们现在,我们二三十年前,也有学生经常聚在一起说同样的话。比如我在中国是1983年开始念研究生,我的同学里就有很多这样的议论。  
 
但是,事实上,我们今天的学术报告人,Tim Hunt博士,就是在1982年,做出他最重要的工作(发现cyclin分子, 1983年发表)。也就是说,象我一样愚蠢和不敏感的人正在发表自以为是的高论的时候,正是Tim这样的科学家,他们有洞察力、有敏感性、或者有运气,正在做突破性的发现。  
 
等我1985年到UCSF读研究生后,不长的几年内,我们看到,在美国、英国、加拿大、日本等地的科学家推动下,细胞周期的分子机理随着一个一个实验结果的发表,非常美妙地呈现大家面前。对于Tim Hunt发现的cyclin,其功能的重要证明,正是我当时学校Marc Kirschner实验室的Andrew Murray提供,当他们在校内介绍工作的时候,我们旁观者如何激动,我今天还记忆犹新。  
 
所以,我们如果抱怨,千万不要搞错了:不是科学不激动,不是科学没有进展,而是科学的重大进展不来源于只会抱怨、只看到自己鼻尖的人。  
 
我希望,今天来听讲座的年轻学子,今后不是重要工作的旁观者,而努力成为重要工作的贡献者。  
 
因为,至少在生命科学领域:  
 
最激动人心的研究正在进行,我们希望这种实验是正由你进行;  
 
最重要的研究在将来,而不是过去。  
 
今天晚上,Tim还有一个一般性讲座,他给的开玩笑的题目是“如何获得诺贝尔奖”。我还建议你们读他的学生Tom Evans回顾发现过程,特别是怎么觉得做实验好像在度假。  
 
下面,请Tim Hunt开讲他最近的研究进展。  
 
2011年4月28日下午1点  
 

Evans T, Rosenthal ET, Youngblom J, Distel D and Hunt T (1983). Cyclin: a
protein specified by maternal mRNA in sea urchin eggs that is destroyed at
each cleavage division. Cell 33:389-396.
 
Murray AW and Kirschner MW (1989) Cyclin synthesis drives the early
embryonic cell cycle. Nature 339:275-280.
Murray AW, Solomon MJ and Kirschner MW (1989). The role of cyclin synthesis
and degradation in the control of maturating promoting factor activity.
Nature 339: 280-286.
 
Hunt T (2004) The discovery of cyclin (I) Cell S116:S63-S64.
 
Tom Evans (2004). The discovery of cyclin (II) Cell 116:65.
 
以下转载Evans文章:
 
“I was fortunate to do my final year degree project with Tim Hunt in
Cambridge looking at the control of protein synthesis in sea urchin
extracts. I think the project barely achieved a result, but I was fascinated
by the subject and caught Tim's infectious enthusiasm. He very kindly asked
me to come to Woods Hole as his "bag carrier" for the summer after I had
graduated.
 
The problem we were to address was how the quiescent sea urchin egg kept its
maternal mRNA inactive until fertilization, at which point it was able to
direct new protein synthesis and many rounds of cell division. Some sort of
(deeply unfashionable) mechanism of translational control of mRNA must
exist. Instead of dull Eppendorf tubes of egg extracts, Woods Hole had the
real beasts, kept on sea-tables within the labs. I was amazed that a simple
12V shock (from a device nicknamed the orgasmotron) would induce a massive
outpouring of gametes, which could be fertilized, and the subsequent
dividing cells analyzed at leisure. Previous studies in urchins had
suggested that fertilization resulted in virtually no change in the
qualitative pattern of proteins synthesized, just a large increase in
synthetic rate. Probably because we hoped for some fancy control of mRNA
translation, Tim thought it would be a good idea to look again at the
pattern of protein synthesis following fertilization of sea urchin eggs. He
decided we should use continual labeling of the cells with [3sS]-methionine
and analyze the accumulating radioactive proteins with onedimensional SDS
acrylamide gels.
 
As it happened, both these choices were highly significant. I remember
looking at the autorad of our first experiment. Even to a neophyte such as
myself, it was obvious that something rather interesting was going on after
fertilization. Not only were brand new proteins synthesized after
fertilization, but the most abundant protein virtually disappeared and then
reappeared periodically. We photographed the developing eggs and it became
apparent that the protein was being degraded around the time of cell
division. Whether removal of this protein was the cause or effect of cell
division was not clear at that point. Tim saw straight away that this
protein must be related in some way to the rather mysterious MPF and came up
with the excellent name of cyclin. We thought that this could be part of a
larger family of proteins named after leisure pursuits--huntin, shootin, and
flshin were clearly the next to be uncovered; a better joke in North
America, because nobody got it, and probably reinforcing the view that the
English were essentially mad.
 
Tim, who knew more embryology than he admitted, got one of the course
students to repeat the experiment in clam oocytes. Two proteins showed the
same periodic destruction following fertilization. Tim knew that mollusks
and echinoderms were very distant relatives indeed (all shellfish to me...),
and thus the likely significance of cyclin might be quite high. I don't
think any of us thought that this would be a fundamental protein in all
cells. We presented the results at the end of summer Woods Hole meeting. The
paper was politely received, but a few caught our excitement; I remember
Gary Borisy telling me that it was absolutely essential that this result was
followed up.
 
Back in Cambridge, Tim wrote up the results which still looked amazing
although already rather far away. I also had the overwhelming thought that
it could not be that important as it was myself who had been involved in the
experiments. Tim did not waver, however, in his understanding that this was
a very important piece of work. The initial review did rather wound him, as
although Cell agreed to publish, the caveat was "...in nothing like its
present form." I also remember going to hear Tim speak about the work in
seminars in the Biochemistry department at Cambridge. Several of those who
attended would roll their eyes and shake their heads when Tim expanded on
his ideas about the possible role of cyclins. But when the paper appeared in
Cell, it acquired a much greater respectability, although the exact
significance and role of cyclins in cell division was still a long way off.
 
It was a very heady summer in Woods Hole. Tim was a marvelous mentor and
enormously generous in his appreciation of the contributions of others
(including novices such as me), as well as in buying countless beers and
meals for students on the course. He had a real feel for the nuts and bolts
of doing the experiments and thought long and hard about the results. It was
a fantastic introduction to science for me, and the peculiar atmosphere at
Woods Hole made you work incredibly long hours and yet still feel as if you
were on holiday.”
 



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