作者：李杰教授
翻译：同写意团队
杰克说药是著名药史专家Jie Jack Li（李杰）教授专为同写意打造的药林外史精品专栏，将讲述一个个药物发现背后的故事。李杰教授现为上海睿智的副总裁，先后出版了30本有机和药物化学方面的书籍以及药物发现史，其中10本与诺奖得主E. J. Corey合作完成。其《Blockbuster Drugs》一书获 2015 Alpha Sigma Nu Science Book 奖，并被翻译成中文出版，深受欢迎。
开设写意专栏，请联系同写意秘书处（微信号tongxieyimishuchu）
拉斯克奖被称为美国的“诺贝尔奖”。2021年9月24日，大卫·巴尔的摩被授予2021年拉斯克·克什兰医学科学特别成就奖。巴尔的摩1975年获得诺贝尔奖，是世界上最著名的生物学家之一。他最近获得的拉斯克奖一事提醒我：巴尔的摩教授在30多年前被不公平地卷入了一场名为“巴尔的摩案”的争议中........
这是美国科学界最不光彩的篇章之一。
David Baltimore（大卫·巴尔的摩）
01
一个科学家的诞生（钢铁是怎样炼成的）
大卫·巴尔的摩1938年出生于纽约市，父亲是一位从事服装生意的信正统犹太教的人，母亲是一名大学实验心理学教授。1954年，在母亲的鼓励下，巴尔的摩在缅因州巴港的杰克逊实验室度过了一个夏天，参加一个为有天赋的高中生开设的科学项目。
在那里，他遇到了斯沃斯莫尔学院的大四学生Howard Termin，对他广博的知识和对科学的坚定承诺表示钦佩。正如命运安排的那样，巴尔的摩和Termin因发现逆转录酶，共享了1975年的诺贝尔奖。
1956年，当在哈佛和斯沃斯莫尔学院之间做出选择时，巴尔的摩选择了斯沃斯莫尔，这是一所由费城附近的贵格会教徒创办的小型文理学院。在众多因素中，部分原因是他觉得哈佛对学术不够认真！斯沃斯莫尔是美国最左派的学院，巴尔的摩的母亲在那里有许多教员朋友。后来到了大学四年级，巴尔的摩自学了很多分子生物学知识，他自己教了这门课。
1960年，巴尔的摩进入麻省理工学院读研究生，一年后他转到洛克菲勒大学，开始研究一种叫做门戈病毒的小鼠病毒。这是一种小RNA病毒，是脊髓灰质炎病毒的近亲。他在被门戈病毒感染的细胞中发现了第一个RNA复制酶。对于一个年轻的研究生来说，这是一个独特且令人印象深刻的发现。值得注意的是，巴尔的摩在洛克菲勒大学求学的18个月中发表了10篇论文。除其中一篇之外，他是所有文章的主要作者。
1963年，完成博士学位后，巴尔的摩在麻省理工学院和阿尔伯特·爱因斯坦研究所攻读博士后，从事脊髓灰质炎病毒的研究。1965年，他搬到位于加州拉霍亚新成立的索尔克研究所，建立自己的独立实验室。在索尔克研究所，巴尔的摩和著名的雷纳托·杜尔贝科继续研究脊髓灰质炎病毒。约翰霍普金斯大学的博士黄爱丽以博士后身份加入了他的团队。黄女士出生于中国江西南昌，后来成为了他的妻子。黄女士最终升任纽约大学的院长。
1968年，巴尔的摩回到麻省理工学院，在那里他开始研究另一种RNA病毒——水疱性口炎病毒。
02
逆转录酶的发现
20世纪50年代末，弗朗西斯·克里克的分子生物学中心法则指出，遗传信息通过转录从DAN流向RNA，然后通过翻译从RNA流向蛋白质。
但Howard Termin对这一中心法则表示怀疑。Termin在加州理工学院的Dulbecco小组进行研究生研究时，怀疑劳氏肉瘤病毒的RNA可以直接将遗传信息提供给细胞，使其成为肿瘤细胞。
1959年成为Wisconsin大学教授后，Termin提出了“前病毒假说”。他认为，RNA肿瘤病毒的单链RNA在病毒粒子进入细胞后转化为双链DNA。这是与中心法则背道而驰的。随后，他进行了许多实验来证明该假说。但初步研究结果还不足以说服许多科学家。即使在他自己的研究小组中，也只有一半的学生相信他是正确的。
1969年夏天，Termin在戈登研究会上展示了他的一个实验。他提供了当时最令人信服的证据，证明病毒的遗传信息是从RNA复制到DNA的。当时的观众之一——巴尔的摩认为这个结果很有说服力！
在麻省理工学院，巴尔的摩被认为是才华横溢、傲慢自大、专心致志的形象。他将自己的研究方向扩展到水疱性口炎病毒，这也是黄爱丽研究生时期工作的重点。
水疱性口炎病毒是一种负链RNA病毒，因此不能与细胞核糖体结合以启动蛋白质合成。巴尔的摩推测，病毒必须携带一种酶，可以将负链RNA转化为正链RNA，作为信使RNA。1970年初，巴尔的摩与黄教授和一名研究生一起，在水疱性口炎病毒的病毒粒子中，毫不费力地发现了一种复制酶。
按照逻辑，下一步做法是在RNA肿瘤病毒中寻找酶。巴尔的摩在国家癌症研究所工作的一位朋友向他提供了Rauscher小鼠白血病病毒。因为他知道自己在寻找什么，所以实验很容易进行：只需要一种洗涤剂、一些缓冲溶液和一些放射性标记的脱氧核苷酸三磷酸盐。
他还意识到这种酶只会在病毒粒子进入宿主细胞后才会出现。一旦有了这个想法，巴尔的摩亲自动手做了这个实验。他成功地检测出将RNA转化为DNA的酶：一种以RNA为模版的DNA聚合酶，后来改称为逆转录酶。这种酶可以将RNA肿瘤病毒的RNA基因组复制到DNA中，不是复制到宿主细胞中，而是复制到肿瘤病毒本身中！它一直存在于病毒颗粒中，等待被发现。如果知道去哪里找，这个实验极其简单，完成实验只需要几个小时。
实验成功后，巴尔的摩立即打电话给Termin，因为Termin是十多年就前提出这个想法的人。有趣的是，Termin回答说，他也发现了劳氏肉瘤病毒粒子中的酶。现实生活中的事件往往比小说更具有戏剧性。巴尔的摩的手稿在1970年6月2日寄到英国著名杂志《自然》，Termin的手稿则在6月15日寄到。该杂志在6月27日的期刊上连续发表了他们的论文。论文发表的速度充分说明了他们发现的重要性。
Termin和巴尔的摩在1975年获得了诺贝尔奖，那是在他们被发现短短5年后。巴尔的摩只有37岁！他是生理学和医学领域最年轻的诺贝尔奖得主之一。
逆转录酶的发现令人震惊，这是现代生物学史上最戏剧性的事件之一。它颠覆了中心法则的含义。随着逆转录酶的发现，遗传信息从RNA到DNA的"反向"流动显然是可能发生的，尤其是在RNA肿瘤病毒感染细胞时。因此，RNA肿瘤病毒开始被称为"逆转录病毒"。
他们的发现彻底改变了分子生物学，并为逆转录病毒学和癌症生物学奠定了基础。逆转录酶在1982年人类免疫缺陷病毒的发现中起了决定性作用。这也是基础科学研究对现实生活产生深远影响的一个很好的例子。
犹太人的数量如此之少，竟有这么多犹太科学家获得了诺贝尔奖。我认为这在很大程度上是因为有很多犹太人在科学领域工作，无论是出于个人选择还是历史原因。现在有这么多中国科学家在科学前沿领域工作，很多中国科学家开始获得诺贝尔奖的那一天将会很快到来。
03
世界上研究最多的科学论文
获得诺贝尔奖后，巴尔的摩于1981年用Jack Whitehead捐赠的1.35亿美元在麻省理工学院建立Whitehead生物医学研究所。
图注：Imanishi-Kari and Baltimore
1984年，巴尔的摩开始与免疫学家Thereza Imanishi-Kari合作。Imanishi-Kari于1981年加入麻省理工学院癌症研究中心，担任助理教授。1986年4月，他们共同发表了一篇题为《在含重排MU重链基因的转基因小鼠中内源免疫球蛋白基因表达模式的改变》的论文，他们不知道，该论文将成为"世界上调查最多的科学论文"。
Imanishi-Kari实验室的爱尔兰博士后Margot O'Toole被要求扩展《细胞》论文的结果。虽然她最初成功了，但她很快就很难重复自己和另一位科学家的成果。O’Toole感到沮丧和尴尬，她抱怨结果肯定是错的，因为她无法复制。她特别抱怨说，Bet-1试剂并不像《细胞》杂志上的论文声称的那样有选择性，这实际上是一个合理的观点。
O’Toole找到了一个盟友——一名心怀不满的研究生，曾与Imanishi-Kari发生过严重冲突，并发誓要进行报复。随着时间的推移，他们加深了彼此对Imanishi-Kari的敌意，对她的不满也不断升级。
为了回应O’Toole的投诉，麻省理工学院和Tufts组建了一个由三名免疫学教授组成的团队，其中包括O’Toole在Tufts的博士导师。他们同意O’Toole的观点，即论文中关于Bet-1有一个错误，但是个小错误。在科学上，错误不是欺诈。因为只有一句话不完全正确，整篇论文调理清晰、令人印象深刻，所以没有必要进行修改。
两个女人之间的严重性格冲突和仇恨升级了。事情一件接着一件，因为O’Toole在实验室的时间不够长，Imanishi-Kari对她大吼。后来，O’Toole成了一个“吹哨人”，开始指控Imanishi-Kari“故意歪曲数据”，这相当于科学欺诈。
通常，这种争议很容易解决，因为科学是自我纠正的，这就是科学的美和力量：科学过程中的验证，包括其他科学家的复制和扩展。如果存在欺诈，那么其他科学家就不能进行重复，从而使其名誉扫地。
但对于诺贝尔奖得主巴尔的摩来说，作为《细胞》杂志论文的合著者，风险是很高的。两名来自美国国立卫生研究院的普通科学家，自封为“欺诈终结者”的Ned Feder和Walter Stewart，也加入了这场争论。Feder和Stewart都不是免疫学家。巴尔的摩说，他们“绝对没有资格评价这篇论文的科学性”，并抱怨说他们从事“……一场诋毁我和我的工作的运动，并获取证据来支持他们错误的结论。”
图注：O’Toole,Fede和Stewart
政客们最喜欢的一件事就是宣传。来自密歇根州的国会议员、众议院能源和商务小组委员会主席John Dingell认为，这是一个机会，可以让他被视为打击科学欺诈的典型。这是他被视为打击科学欺诈的一个机会。
当然，Dingell对免疫学一无所知，并明确表示他无意学习。国会听证会成了一位有权势的国会议员和一位傲慢的诺贝尔奖得主之间摊牌的舞台。巴尔的摩如此努力公开斗争的一个原因是为了科学，因为他不相信政府应该监管科学。巴尔的摩强烈反对政府干预科学研究。Dingell小组委员会对ImanishiKari(一个外国人，缺乏人脉且英语不流利，无法有效地为自己辩护)的攻击，深深冒犯了巴尔的摩。
Dingell似乎拥有无限的资源，他要求特勤局检查ImanishiKari的实验室笔记本。1991年，因为特勤局不知道科学如何运作，所以特勤局错误地断定她伪造数据，并声称她犯有“严重的科学不端行为”。
“科学骗局”迅速爆发，成为轰动一时的全国性新闻，很快被称为“巴尔的摩事件”，一个科学“水门事件”。“巴尔的摩事件”似乎分裂了整个国家。许多人把Dingell的调查比作伽利略的起诉，包括他的家乡报纸《底特律新闻》，一些人把它比作科学“麦卡锡主义”，而还有一些人为看到诺贝尔奖得主受辱而窃窃自喜。
1992年的某个时间，巴尔的摩因公众舆论对他不利，不得不辞去他在洛克菲勒研究所仅任职18个月的主席一职。Dingell的政治迫害不仅威胁到了巴尔的摩，也威胁到了科学。
但这并不是故事的结局。1992年，一位专家成功证明了特勤局是错误的。归根结底，这件事成了所有参与者指责、程序失败和彻头彻尾固执的悲剧。有段时间，O’Toole对ImanishiKari提出了18项指控！最具讽刺意味的是，一些所谓的“欺诈性数据”否定了《细胞》杂志论文的结论。
几位哈佛大学的生物学教授以攻击和诋毁巴尔的摩为己任。发现DNA双螺旋结构的詹姆斯·沃森恶意攻击巴尔的摩，甚至宣称应该撤销巴尔的摩的诺贝尔奖。唉，沃森是如此的种族主义者、性别歧视者、恐同者和反犹主义者，今天，许多人认为沃森的诺贝尔奖应该被撤销。
尽管动荡不安，巴尔的摩仍然是当时被引用次数最多的科学家之一。
1993年，Imanishi-Kari在复制了她1986年《细胞》论文中的数据，并分别被斯坦福大学和哥伦比亚大学的两个免疫学小组证实。
1994年，美国国立卫生研究院研究诚信办公室认定Imanishi-Kari犯有19项科学欺诈罪，并禁止她在10年内接受研究资助。
但在科学领域，真相终将胜利。在Imanishi-Kari提出上诉后，美国政府介入了。美国卫生与公众服务部聘请了一个由免疫学专家组成的上诉小组来查清这件事的真相。经过数年的详尽调查，在法律顾问的帮助下，Imanishi-Kari终于在1996年被免除了所有对她的指控。
1997年，Tufts大学终身教职委员会一致推荐她为终身教职副教授。她今天仍在那里教书。令我惊讶的是，O’Toole有很多支持者。她曾在波士顿的生物技术公司遗传学研究所(Genetics Institute)有一份工作，现已退休。
巴尔的摩案可能是美国科学史上最令人遗憾的一章，许多人欠巴尔的摩一个诚恳的道歉。巴尔的摩从1997年到2005年在加州理工学院担任校长。他为蛋白核因子κB(NF-κB)和重组激活基因(RAG)重组酶蛋白方面的研究做出开创性贡献。
巴尔的摩可能是当代最杰出的生物医学科学家。他对现代生物学的几乎每个领域都产生了持久的影响。今年，他被授予拉斯克·克什兰医学科学特别成就奖，这再合适不过了。
真金不怕火炼！
英文原文及参考文献
1、英文原文（向下滑动查看更多）
David Baltimore: Scientist Extraordinaire——The Nobel laureate was once embroiled ina sensational national controversy over a Cell paper
The Lasker Awards are known as the American “Nobel Prize”. On September 24, 2021, David Baltimore was bestowed its 2021 Lasker–Koshland Special Achievement Award in Medical Science. Baltimore, who won the Nobel Prize in 1975, is of course among the most well-known biologists in the world. But for me, his recent Lasker Award has reminded me that Prof. Baltimore was unfairly dragged into a notorious controversy known as the “Baltimore case” more than thirty years ago……..
It was one the most disgraceful chapters of American science.
1.The making of a scientist (钢铁是怎样炼成的？)
Born in 1938 in New York City, David Baltimore’s father was an orthodox Jew in the garment business and his liberal mother was a college professor of experimental psychology. In 1954, upon his mother’s encouragement, Baltimore spent a summer at the Jackson Laboratories in Bar Harbor, Maine in a science program for gifted high-school students. There, he met Howard Termin, a senior at the Swarthmore College and venerated him for his wide knowledge and deep commitment to science. As fate would have it, Baltimore would share the 1975 Nobel Prize with Termin for their discovery of reverse tranase.
In 1956, when it was time to choose a college between Harvard and Swarthmore, Baltimore picked Swarthmore, a small liberal arts school founded by Quakers near Philadelphia. Among many factors, it was partially because he felt Harvard was not serious enough with academics! Swarthmore was the most liberal colleges in America and Baltimore’s Mother had many friends there on faculty. Later on in his senior year, Baltimore learned so much Molecular Biology on his own that taught the class himself.
In 1960, Baltimore went to graduate school at MIT, but he transferred to Rockefeller one year later and began studying a mouse virus called mengovirus, a small RNA virus and a close relative of poliovirus. He discovered the first RNA replicase in mengovirus-infected L-cells. For a young graduate student, that was a unique and impressive finding. Remarkably, Baltimore published ten papers during his 18-month stay at Rockefeller. More remarkably, he was the lead author on all but one of them!
After completing his doctorate around 1963, Baltimore did postdoctoral research on poliovirus at MIT and the Albert Einstein Institute. He then moved to the newly founded Salk Institute in La Jolla, California in 1965 to establish his independent laboratory. At Salk Institute, Baltimore continue his research of poliovirus, another RNA virus, along with the famous Renato Dulbecco. Alice Huang, a Ph.D. from the Johns Hopkins University, joined his group as a postdoctoral fellow. Born in Nanchang, Jiangxi, China, Huang would become his future wife. She eventually rose to be Dean of New York University later on.
Baltimore returned to MIT as an associate with Huang in 1968, where he began to study vesicular stomatitis virus, another RNA virus.
2.Discovery of reverse tranase
The Central Dogma of the molecular biology, established in the late 1950s by Francis Crick, states that the genetic information flows from DAN to RNA via tranion and then from RNA to proteins via translation.
But Howard Termin had doubts of the central dogma. Termin, while doing graduate work in Dulbecco’s group at Caltech, suspected that the RNA in Rous sarcoma virus could contribute genetic information directly to the cell to enable it to become tumorous.
After he became a professor at the University of Wisconsin in 1959, Termin proposed the “provirus hypothesis”. He argued that the single-stranded RNA of RNA tumor viruses was converted into double-stranded DNA after a virus particle entered a cell. This was contrary to the central dogma. He then carried out many experiments to prove his provirus hypothesis. But his initial results were not compelling enough to convince many scientists. Even among students in his own research group, only half of them was convinced that Termin was on the right track.
In the summer of 1969, Termin presented one of his experiments at a Gordon Research Conference. He offerred the most compelling evidence at the time that viral genetic information was copied into DNA from RNA. One person in the audience who found the result compelling was Baltimore.
At MIT, Baltimore was described as brilliant, arrogant, brash, and single-minded. He expanded his research interests to vesicular stomatitis virus, which was the focus of Alice Huang’s graduate work.
Vesicular stomatitis virus is a negative-strand RNA virus thus cannot associate in a functional way with cellular ribosome in order to initiate protein synthesis. Baltimore speculated that the virus MUST carried along an enzyme that could convert its negative RNA strand to its positive version to serve as the messenger RNA. In early 1970, Baltimore, along with Huang and a graduate student, discovered a replicase with little difficulty in the virions of vesicular stomatitis virus.
The logical next step was to look for an enzyme in an RNA tumor virus. A friend of Baltimore’s at the National Cancer Institute provided a supply of Rauscher mouse leukemia virus to him. Once he knew what he was looking for, the experiments were easy to carry out, which only required a detergent, some buffer solutions and some radiolabeled deoxynucleotide triphosphates. He also realized that the enzyme would only appear after the virions entered the host cells. Once Baltimore conceived the idea, he carried out the experiment himself with his own hands. He succeeded in detecting the enzyme that converted RNA to DNA: an RNA-dependent DNA polymerase, soon changed to reverse tranase. The enzyme that could copy the RNA genome of an RNA tumor virus into DNA, not in cells, but in the tumor virus itself! It was there all along in the virus particles, waiting to be found. The experiment was extremely trivial to do if you knew where to look. It would only take hours to complete the experiment.
With positive results in hands, Baltimore called Termin immediately because Termin was the one who conceived the idea more than a decade ago. Interesting enough, Termin replied that he also found the enzyme that already existed in the virions of Rous sarcoma virus. Real life events are often more dramatic than fiction. Baltimore′s manu arrived at the prestigious British journal Nature on June 2, 1970, Temin′s on June 15. The journal published their papers back to back on the June 27th issue. The speed with which their papers was published spoke volume of the importance of their discovery.
Temin and Baltimore won the Nobel Prize in 1975, a short five years after their discovery. Baltimore was only 37-years old! He was one of the youngest Nobel laureates in Physiology and Medicine.
The discovery of reverse tranase was stunning, among the most dramatic events in the history of modern biology. It clarified the meaning of the Central Dogma. With the discovery of reverse tranase, the “reverse” flow of genetic information, from RNA to DNA, was now clearly possible and seemed likely to happen when RNA tumor viruses infected cells. Therefore, RNA tumor viruses began to be called “retroviruses”.
Their discovery revolutionized molecular biology and laid the foundations for retrovirology and cancer biology. Reverse tranase played a decisive role in the discovery of human immunodeficiency virus (HIV) in 1982. This is also a good example where basic scientific research could have a profound impact on real life.
It remarkable that so many Jewish scientists have won the Nobel Prizes considering Jewish population is so small. I think it is largely because so many Jewish people are working in the science field, by choice or by historical reasons. Now with so many Chinese scientists working on cutting-edge sciences, the day will come when many Chinese scientists begin to win Nobel Prizes.
3.The world’s most extensively investigated scientific paper
After receiving the Nobel Prize, Baltimore went on to found the Whitehead Institute for Biomedical Research in 1981 at MIT with $135 million donated by Jack Whitehead.
In 1984, Baltimore began a collaboration with immunologist Thereza Imanishi-Kari who joined the Center for Cancer Research at MIT as an assistant professor in 1981. In April 1986, they published a paper together titled “Altered Repertoire of Endogenous Immunoglobulin Gene Expression in Transgenic Mice Containing a Rearranged Mu Heavy Chain Gene”. Little did they know, that paper would go on to become “The world’s most extensively investigated scientific paper”.
Margot O’Toole, an Irish postdoc in Imanishi-Kari’s lab was asked to extend the results of the Cell paper. Although she initially succeeded, she soon was having difficulty repeating her own and another scientist’s results. Frustrated and embarrassed, O’Toole complained that results must be wrong because she could not replicate them. She especially complained that a reagent called Bet-1 was not as specific as the Cell paper claimed, which was actually a legitimate point. O’Toole found an ally in a former disgruntled graduate student who had epically clashed with Imanishi-Kari and vowed to revenge. They fueled each other’s hostility toward Imanishi-Kari and their grievance against her escalated as time went on.
In response to O’Toole’s complaint, MIT and Tufts assembled a team of three immunology professors including O’Toole’s Ph.D. supervisor at Tufts to investigate. They agreed with O’Toole that there was an error in the paper with regard to Bet-1, but not a flagrant one. In science, an error was not a fraud. It did not even warrant a letter of correction because only one sentence was not completely correct and the entire paper was clear and impressive.
The severe personality conflict and animosity between the two women escalated. One thing led to another, Imanishi-Kari yelled at O’Toole because she was not spending enough time in the lab. Then O’Toole became a “whistleblower” and began to accuse Imanishi-Kari of “deliberate misrepresentation of data”, which amounted to a scientific fraud.
Normally such disputes are readily resolved because science is self-correcting, that is the beauty and power of science: validation by the scientific process including replication and extension done by other scientists. If there is a fraud, then other scientists cannot repeat them thus discredit it. But with Baltimore, a Nobel Laureate, as a co-author of the Cell paper, the stakes were high. Two self-appointed “fraud busters,” Ned Feder and Walter Stewart, two mediocre scientists from the NIH, invited themselves into the fray. Neither Feder nor Stewart were immunologist. They were “absolutely unqualified to evaluate the science of this paper” according to Baltimore, who complained that they waged “... a campaign to discredit me, my work and to obtain evidence to support their faulty conclusions.”
One thing that all politicians love more than anything else is publicity. John Dingell, Congressman from Michigan and Chairman of the House Energy and Commerce Subcommittee, saw this as a chance for him to be seen as cracking down of scientific fraud.
Of course, Dingell did not know any immunology and made it clear that he had no intention to learn. The congressional hearing became a theater of gigantic showdown between a powerful congressman and an arrogant Nobel laureate. One reason why Baltimore fought so hard publicly was for the sake of science because he did not believe that the government should be policing science. Baltimore was strongly against intrusion of government in the conduct of scientific research. The Dingell subcommittee’s attack on ImanishiKari, a foreigner who lacked the connections and the fluency in English to defend herself effectively, offended Baltimore deeply.
With seemingly unlimited resources, Dingell asked the Secret Service to examine Imanishi-Kari’s lab notebook. The Secret Service erroneously concluded that she falsified data and claimed her guilty of “serious scientific misconduct” in 1991 because the Secret Service did not know how science worked. The “scientific fraud” exploded and became a sensational national news, soon dubbed as “the “Baltimore case”, a scientific Watergate. The “Baltimore case” seemed to have divided the country. Many compared Dingell’s inquiry to the Galileo prosecution including his hometown newspaper Detroit News, some likened it to scientific McCarthyism, while some derived some satisfaction to see a Nobel laureate humbled. Indeed, at one point in 1992, Baltimore had to resign his presidency of the Rockefeller Institute only eighteen months on the job because public opinions were not at his favor. Dingell’s witch hunt threatened not just Baltimore, but also science itself.
But that was not the end of the story. An expert resoundingly proved in 1992 the Secret Service was incorrect. At the end of the day, the affair became a tragicomedy of accusations, failed procedures, and outright stubbornness by everyone involved. There was a time when O’Toole made 18 counts of allegation against Imanishi-Kari! Most ironically, some so-called “fraudulent data” disapproved the Cell paper’s conclusions. Several Harvard biology professors made it their mission to attack and discredit Baltimore. James Watson, the discoverer of the DNA double helix, viciously attacked Baltimore, even declaring that Baltimore’s Nobel prize should be revoked. Alas, Watson has been such a racist, sexist, homophobic, and antisemitic, today many think that Watson’s Nobel prize should be revoked.
Despite the turmoil, Baltimore continued to be one of the most cited scientists of the time.
In 1993, Imanishi-Kari’s data in the 1986 Cell paper results were reproduced by herself and confirmed by two immunology groups at Stanford and Columbia, respectively.
In 1994, the Office of Research Integrity at NIH found Imanishi-Kari guilty of 19 counts of scientific fraud and recommended she be barred from receiving research grants for 10 years.
But in science, the truth will eventually triumph. After Imanishi-Kari’s appeal, the US government got involved. The Department of Health and Human Services hired an appeal panel of experts in immunology to get the bottom of the affair. After several years of exhaustive investigations and with helps of legal counsels, Imanishi-Kari was finally exonerated in 1996 of ALL charges leveled against her. In 1997, the Tenure Committee at Tufts University unanimously recommended for her promotion to associate professor with tenure. She still teaches there today. To my surprise, O’Toole had many fans and supporters. She was gainfully employed by the Genetics Institute, a biotech company in Boston, and has now retired.
The Baltimore case was probably the sorriest chapter in American science and a lot of people owed Baltimore a serious apology. Baltimore went on to serve the president of Caltech from 1997 to 2005. His research on the protein nuclear factor kappa B (NF-κB) and recombination-activating gene (RAG) recombinase proteins are ground-breaking.
Baltimore has been probably the most prominent biomedical scientist of the time. He has had a lasting impact on virtually every realm of modern biology. It is most fitting that now this year that he was bestowed the Lasker–Koshland Special Achievement Award in Medical Science.
True gold fears no fire!
2、参考文献（向下滑动查看更多）
1. Baltimore, D. Viral RNA-dependent DNA Polymerase: RNA-dependent DNA Polymerase in Virions of RNA Tumour Viruses. Nature 1970, 226, 1209–1211.
2. Temin, H. M.; Mizutani, S. RNA-dependent DNA Polymerase in Virions of Rous Sarcoma Virus. Nature 1970, 226, 1211–1213.
3. Weaver, D.; Reis, M. H.; Albanese, C.; Constantini, F.; Baltimore, D.; Imanishi-Kari, T. Altered repertoire of endogenous immunoglobulin gene expression in transgenic mice containing a rearranged mu heavy chain gene. Cell 1986, 45, 247–259.
4. Kevles, D. J. The Baltimore Case: A Trial of Politics, Science, and Character. W. W. Norton: New York: NY, 1998.
5. Crotty, S. Ahead of the Curve: David Baltimore’s Life in Science. University of California Press: Berkeley, CA, 2001.
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