作为环境兽医毒理学的 candidate Ph.D., 需要敏锐的洞察力和感觉能力。 学校一到年底或年初,总需要大批大批的打印与课题项目有关的材料,所以需要多次去印刷厂,以前去印刷厂鼻子总是嗅到一种怪怪的味道,而且感觉好难受,后来听师妹说说那是臭氧( OZONE )。我猛然醒悟,原来我已经多次暴露在 Ozone 下。于是,前几天我在印刷厂的行为改变历历在目: 1. 高高兴兴地哼着小齐的歌拿着师兄交给我的任务,去印刷厂。行为表明未进印刷厂前是心情愉悦的,是兴奋的; 2. 进入印刷厂,我就开始嗅到臭氧。表明呼吸接触,我整个人已经处在臭氧的暴露中; 3. 1min 后,高兴劲开始逐渐淡去,头脑开始晕,逐渐的有点不太清醒, 5min 后我开始抑郁( depression )了,所以找了个座坐下。以上表明,臭氧发挥效应还是很快的,头脑发昏,说明臭氧已经投过血脑屏障,根据文献,可能影响了多巴胺系统,出现了抑郁症状; 4. 20min 后,印刷厂的工人,让我去把需要复印的原件拆开,我说“有工具吗 ”? 她说 : “没有”!当时,看着那厚厚的材料和书钉,我恨不得吼他一顿,让我牙咬啊!看来,抑郁行为开始转化为暴力行为; 5. 1h 后,心跳没那么加速了,脸不红脖子也没那么粗了,什么都没了心情,只是不时的有点焦虑。照这样,我开始适应了臭氧的刺激,尽管偶尔有点焦虑行为。 6. 2h 后,我走出印刷厂,狠狠地吸了几口 fresh air ! 突然感觉到还是大自然的空气好,尽管山西空气也是那么的充满焦煤味! 亲身感受臭氧的威力,于是,我怀疑:臭氧是诱导社会情绪行为的风险因子,所以我 google scholar 关键词: ”Ozone exposure; behavior”, 在 medical hypotheses 发现一篇有意思的 paper : 原文中这样几句话: ” Biologically, ozone is able to influence the immune system, is a strong trigeminal irritant and might influence neurotransmitter systems such as serotonin, which are known to vary with season and play a major role in impulsivity, aggression, depression and thereby suicidality. Putative psychological explanations for the suicide peak in summer include the influence of a higher ambient temperature leading individuals to a more disinhibited, aggressive and violent behaviour possibly resulting in an increased proneness for suicidal acts that is influenced by ozone ” 。 研究证明:臭氧会造成抑郁、冲动、攻击和焦虑行为! 严重的甚至可能导致自杀! Oh , my god! 好可怕 ! 怪不得印刷厂的员工都那么的不和谐! 由此想到富士康的“跳楼事件”,不知道富士康的工厂(电子元件已焊接,是不是会有臭氧产生)里是不是臭氧浓度很高?当然跳楼的少数,不知道富士康的员工是不是很多很抑郁,甚至有暴力倾向! 臭氧影响神经行为,不容忽视!
他们为什么没有获得诺贝尔奖——谈科研创造力、洞察力与执行力 单克隆抗体技术的思路非常简单:把具有生产特异性抗体的浆细胞与具有无限增值能力的淋巴瘤细胞融合得到一个兼具二者特点的融合细胞。该融合细胞既可以无限增值,又可以产生特异性抗体。 1984 年,三位科学家因为该项发现而获得诺贝尔生理医学奖。 消息传来,某大学的 A 教授很激动,因为他在几年前就想到过同样的想法,还和实验室的成员探讨过呢。他于是逢人便宣布:其实我也可以获得诺贝尔奖的!我实验室的研究生和博士后可以给我作证! 可是,为什么获得诺贝尔奖的不是 A 教授呢? 其实与 A 教授有类似情况的科研人员还有很多。 B 教授十年前就想到了这个想法。可是,他的想法太多,这个想法只是他很多想法中的一个,在他看来没有什么特别的,于是很快就忘记了。 C 教授十年前也想到了这个想法,他还把这个灵感记了下来。他也觉得这个想法很好,可是,他还有其他更好的想法,于是决定先做他认为更重要的。那些想法确实不错,也发了很好的文章,可是最终没有导致科学的突破。 D 教授也是很久就有了这个想法。他不仅与实验室的成员讨论过,还做了实验希望实现这个想法。可是,实验过程中遇到很多问题,他最终放弃了。 E 教授不仅想到了这个想法,做了实验,而且他清楚的知道这个想法的重要意义,他完全明白这个想法是“诺贝尔奖”级别的想法。他投入了全部的时间和精力努力去实现这个想法。遗憾的是,别人在他之前做出来了。 (说明:本故事不纯属虚构。) 为什们他们都没能获得诺贝尔奖呢?因为根据创造力、洞察力和执行力,可以把科研人员分为以下几个层次: 第一级:根本没有好的想法。大部分科研人员属于这个级别,他们缺乏创造力。 第二级:有很多想法,其中极少数很好的想法,可是无法判断哪个重要,结果做了次要的想法。 ABC 教授都属于这一类,有一定创造力,但缺乏洞察力。 第三级:有很多想法,有些是很好的想法,并且能够判断哪个最重要,可是,无法实现自己的想法。 E 教授属于这一类,创造力和洞察力都不错,唯有执行力不够。 D 教授介于第二级与第三级之间。如果他事先知道一旦实现这个想法就可以获得诺贝尔奖,他还会轻易放弃吗? 第四级:有很多想法,有些是很好的想法,并且能够判断哪个最重要,并克服困难把它做出来。创造力、洞察力和执行力都很好。获得诺贝尔奖的 Georges Köhler , César Milstein 和 Niels Kaj Jerne 都属于这一类。 创造力是基础,没有好的想法就没有一切。洞察力指明方向,否则因为 idea 太多就不知道从哪一个做起。执行力不可或缺,否则一切都是空中楼阁。 大部分人缺乏创造力,具有创造力的人大部分又缺乏洞察力,兼具洞察力和创造力的人,大部分又不具备执行力。所以,做出突破性科研成果的每年就那么几个。 孔晓飞老师的博文 《对话 David Baltimore 》 提到的两个想法都非常简单,能够想到的人有多少?想到了觉得确实重要因而着手去做人的又有多少? 本文中的“诺贝尔奖”仅用以指代重大的科学发现,不代表我们做科研必须以追求获奖为目标,也不认为没有获得诺贝尔奖的科学成果就不重要。
—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 -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.”
Feynman 的第一堂数学课 Feynman是物理学家中公认的大牛人。他还在满地乱爬的时候,家里有很多或蓝或白的塑料拼花地板。他老爸就让他把这些塑料块排成一行,一脚踹下去,就成了渐次倒下去的多米诺骨牌,非常好玩。但是,他老爸不让他乱摆,非的要一块白的,一块蓝的,摆成非常有规律的蓝白相间,否则就让他推倒重来。小孩子一开始自然不认这个理,乱摆一气,老爸就不让他玩多米诺骨牌,急得Feynman 直嚷嚷。老妈毕竟心肠软,就说:Richard,你就让他随便摆吧。 Feynman老爸说:不行,我要让他从小就养成对模式的直观感受。 Feynman后来感叹道,只是他一生中最早的一堂数学课(因为数学无外乎是某种抽象模式的认识),这让他以后对物理和数学中的各种模式,有超乎常人的洞察力。 扑克牌中的科学发现 我还在念博士的时候,英国政府有一个在高中生中间推广对科学兴趣的计划,叫作Researcher in Resident,就是鼓励博士生到各个中学展开一对一的科学课外活动。我去的是苏格兰的一家很有声望的公立中学,所有的博士们都要到爱丁堡参加一个培训,因为对中学生的科学训练需要有不同的思维和方法。一位非常有经验的中年女老师,在培训之前让我们玩一个游戏:每五个人一个小组,发一副扑克牌,一个人做庄并制定任意一个规则:比如偶数为红色,奇数为黑色;或者点数正好是张数的平方加一等等。其余四个人抽出一张牌,询问庄家,如果符合其规则就放在桌上,不符合就拿走。这四个人看着桌上的牌,来猜扑克牌后面隐藏的规则。私下里以为,这种对隐藏模式的猜测能力,对科学发现能力的训练可能比微积分更加重要。 发现双螺旋 最近读了分子生物学鼻祖之一 Waston 的一本自传--- The Double Helix 。这是一本真正值得每一位青年科学研究者一读的好书。关于DNA这一解释生命奥秘最重要的分子结构,问题是如何提出的,为何被当时的科研界主流所忽视,三个课题组之间的竞争与协作,关于发现双螺旋的进展是如何跌宕起伏,充满悬念。整个故事的主人公宛如舞台上莎士比亚的一幕戏剧,声望崇高而所向披靡的 Linus Pauling ,冷若冰霜、拒人千里之外的 Rosy ,成天念念不忘要打败 Pauling ,并与其竞争Nobel的 Waston 和 Crick ,他们之间的故事是如此吸引人,使你不得不一口气将起读完。Waston和Crick之所以能在这场竞争中胜出,发现双螺旋并由此名垂青史,最重要的不是复杂的数学演算,而是他们像小时候的Feynman一样,用过家家搭积木的方式来猜测正确的DNA结构,尤其是Waston以惊人的洞察力猜到了adenine 与thymine, guanine与 cytosine配对居中,sugar chain在外的这一异常漂亮的模式,完成了这一石破天惊的发现,当时Waston 年仅25岁。 Fig. 1 Watson and Crick with their hand-made DNA model Fig. 2 Watson speech to recall how he discovered DNA 因此,对模式的敏感和乐于猜测,是科学发现最重要的训练之一。而这一点,是科学与艺术最接近的地方。这里有个简单的测试,看看你对模式的敏感和猜测能力:假设我们有一个无穷长的符号序列,给出其中的头三个符号,看看你能不能猜测出其中的规则,并给出你的理由,并由此可以写出无穷多个的后继符号。 Fig. 3 一个无穷长的符号序列 The book The Double Helix in amazon: http://www.amazon.com/Double-Helix-Personal-Discovery-Structure/dp/074321630X END