河北医科大学药学院 X-ray Crystallography Introduction to X-ray Crystallography estresoltetioaadrlebin Complementarity of Methods X-ray Crystallography “X-射线”的发现(1895年) The Father of Diagnostic Radiography 伦琴(Wilhelm Konrad Rontgen) 沙断射学之父 天然药物化学教研室史清文教授 1
河北医科大学药学院 天然药物化学教研室 史清文教授 1 X-ray Crystallography 361 有的化合物不溶于一般的溶剂---河豚毒素—一般NMR找不到合适的溶剂--- 本身有能得到结晶，X-衍射是比较好的办法 NMR is about 25 years younger than X-ray crystallography-青霉素的结构 Introduction to X-ray Crystallography 362 X-ray crystallography - highest resolution and reliability structures NMR - enables widely varying solution conditions; characterisation of motions and dynamic, weakly interacting systems, molecules with no ordered structure Complementarity of Methods 363 “X-射线” 的发现（1895年） 364 Wilhelm Roentgen (1845-1923，1901年诺贝尔物理学奖)革命性地推 动了物理学和医学的发展并创立了新的学科，为人类利用X射线诊断与 治疗疾病开拓了新途径。X-rays (Roentgen rays) 365 The Father of Diagnostic Radiography William Conrad Röntgen 1895年10月德国实验物理学家 Röntgen用一种未知的射线拍摄了他夫 人的手的照片，显示出手的骨骼结构引起巨大反响。因为当时无法确定这一 新射线的本质，Röntgen把这一新射线称为X-射线。并被应用到医学领域， 为人类利用X-射线诊断与治疗疾病开拓了新途径。"X-rays have radically changed the way we see and understand our world - our bodies in particular." X-射线把视觉的灵敏度 提高了1万倍 1901年首届诺贝尔物理奖 授予了发现X-射线的伦琴 诊断放射学之父 伦琴 (Wilhelm Konrad Rontgen) 366 In 2004 the International Union of Pure and Applied Chemistry named element 111, Rg, a radioactive element with multiple unstable isotopes, after him. X-射线直接影响了20世纪许多重大科学发现。 《100 most influential people in the world》 伦琴列第71位（旧版72） 伦琴(1845－1923)德国
河北医科大学药学院 “X射线”与诺贝尔奖 9 X-射线的散射 X-ray scattering.X-ray spectroscop X-ray Energy (keV) 质发装 对的种尚极 X射线在晶体中的衍射 Light Is A Messenger 913年1月第一会飞，粉腰光0收 明了X线是一种，对村的汉识曲了的一步。 失2 天然药物化学教研室史清文教授
河北医科大学药学院 天然药物化学教研室 史清文教授 2 “X-射线”与诺贝尔奖 367 X-射线的发现是19世纪末20世纪初物理学的三大发现(X-射线1896年、 放射线1896年、电子1897年)之一，这一发现标志着现代物理学的产生，为 诸多科学领域提供了一种行之有效的研究手段。X-射线的发现和研究，对 20世纪以来的物理学以至整个科学技术的发展产生了巨大而深远的影响。 一个多世纪以来，因研究X-射线技术、以及使用X射线进行研究、与X- 射线有关的研究而获得诺贝尔奖的已有几十人： 13人因在X-射线研究中有突破性进展而获得了诺贝尔物理学奖； 12人借助X-射线分析手段获得了诺贝尔化学奖； 4人借助X-射线分析获得了诺贝尔生理学奖及医学奖。 1. 1901年，伦琴就由于发现X-射线而获得了首届诺贝尔物理学奖。 2. 1914年，劳厄由于利用X-射线通过晶体时的衍射，证明了晶体的原子点阵 结构而获得诺贝尔物理学奖。 3. 1915年，布拉格父子因在用X-射线研究晶体结构分享了诺贝尔物理学奖。 4. 1917年，巴克拉由于发现标识X-射线获得诺贝尔物理学奖。 5. 1924年，西格班因在X-射线光谱学方面的贡献获得了诺贝尔物理学奖。 6. 1927年，康普顿与威尔逊因发现X-射线的粒子特性同获诺贝尔物理学奖。 7. 1936年，德拜因利用偶极矩、X-射线衍射法测定分子结构获诺贝尔化学奖 8. 1946年，缪勒因发现X-射线能人为地诱发遗传突变而获诺贝尔生理医学奖 9. 1954年，鲍林由于在化学键的研究以及用化学键的理论阐明复杂的物质结 构而获得诺贝尔化学奖（X-射线衍射研究密不可分）。 10.1962年，沃森、克里克、威尔金斯因发现DNA的结构分享了诺贝尔生理学. 医学奖(以X-射线衍射实验为基础) 11.1962年，佩鲁茨和肯德鲁用X-射线衍射分析法首次精确地测定了血红蛋白 和肌红蛋白的晶体结构而分享了诺贝尔化学奖。 12.1964年，霍奇金因在运用X-射线衍射技术测定青霉素和维生素B12的结构 获得诺贝尔化学奖。 368 13. 1969年，哈塞尔与巴顿因用X-射线衍射分析提出“构象分析”的原理同获诺贝尔化学奖。 14. 1973年，威尔金森与费歇尔因对有机金属化学的研究卓有成效而共获诺贝尔化学奖。 15. 1976年，利普斯科姆因用低温X-射线衍射和核磁共振等方法研究硼化合物的结构及成键规律 的重大贡献获得诺贝尔化学奖。 16. 1979年，诺贝尔生理.医学奖破例地授给了对X-射线断层成像仪（CT）作出特殊贡献的豪斯 菲尔德和科马克这两位没有专门医学经历的科学家。 17. 1980年，桑格借助于X-射线分析法与吉尔伯特、·伯格因确定了胰岛素分子结构和DNA核苷 酸顺序以及基因结构而共获诺贝尔化学奖。 18. 1981年，凯.西格班由于在电子能谱学方面的开创性工作获得了诺贝尔物理学奖。 19. 1982年，克卢格因在测定生物物质的结构方面的突出贡献而获诺贝尔化学奖。 20. 1985年，豪普特曼与卡尔勒因发明晶体结构直接计算法，分享了诺贝尔化学奖。 21. 1988年，戴森霍弗、胡伯尔、米歇尔因用X-射线晶体分析法确定了光合成中能量转换反应的 反应中心复合物的立体结构，共享了诺贝尔化学奖。 22. 1997年，斯科与博耶和沃克因籍助同步辐射装置的X-射线，在人体细胞内离子传输酶方面的 研究成就而共获诺贝尔化学奖。 23. 2002年，贾科尼因发现宇宙X-射线源，与戴维斯、小柴昌俊共同分享了诺贝尔物理学奖。 24. 2003年，阿格雷和麦金农因发现细胞膜水通道，以及对细胞膜离子通道结构和机理研究作出 的开创性贡献被授予诺贝尔化学奖（他们的成果用X-射线晶体成像技术获得）。 25. 2006年，科恩伯格被授予诺贝尔化学奖，以奖励他在“真核转录的分子基础”研究领域作出 的贡献（他将X-射线衍射技术结合放射自显影技术开展研究）。 369 X-射线的散射 Charles Glover Barkla (1877－1944) 1906年因发现X-射线散射现象 而获得1917年诺贝尔物理学奖 X-ray scattering, X-ray spectroscopy 元素的特征谱线(标识谱线) 对建立原子结构理论极为重要 X-射线在晶体中的衍射 371 Max Theodor Felix Von Laue (1879~1960) 劳厄: 1912年发现X-光衍射，证明了Ｘ-光具有波的性质 X光 X-光衍射由M. von Laue于1912年发现，1914年诺贝尔物 理奖。为从实验上观测晶体结构奠定了基础。《自然》杂志 把这一发现称为“我们时代最伟大、意义最深远的发现”。 表明了Ｘ-射线是一种波，对X射线的认识迈出了关键的一步 。 索末菲(1868-1951) Arnold Sommerfeld 372 Light Is A Messenger Bragg, W. H. The X-ray spectra given by crystals of sulphur and quartz. Proc. R. Soc. Lond. A 1914, 89, 575-580. 反映了衍射方向与晶体结构之间的关系。 1913年1月第一台X-射线光谱仪 A X-ray spectroscopy
河北医科大学药学院 X-射线和晶体结构rg's law:2n nw A Father,A Son,A Law and A Nobel Prize Nobel Prize in Physicsin 1915 8。 X-ray crystallography and Structure K-Ray 1924年的诺贝尔物理学奖 X-ray crystallography and Structure 天然药物化学教研室史清文教授 3
河北医科大学药学院 天然药物化学教研室 史清文教授 3 X-射线和晶体结构 373 利用X-光衍射确定结晶体结构的是W. H. Bragg爵士以及他的儿子L. W. Bragg爵士，显示了X射线衍射用于分析晶体结构的有效性(1912-13年), 解释 了劳厄的实验事实。证明了能够用X-射线来获取关于晶体结构的信息。 Sir William Lawrence Bragg (1890 – 1971) 1915 NP Sir William Henry Bragg (1862 –1942) 1913年第一台 X-射线光谱仪 Bragg's law: 2dsin Ø=kl A Father, A Son, A Law and A Nobel Prize Lawrence Bragg's work in crystallography changed the way we see the world 374 "For their services in the analysis of crystal structure by means of X-ray ", an important step in the development of X-ray crystallography. Bragg was the director of the Cavendish Laboratory, Cambridge, when the discovery of the structure of DNA was reported by Watson and Crick in February 1953. 从1874年至1989年一共产生了29位诺贝尔奖得主. Nobel Prize in Physics in 1915 金刚石结构：完美地说明了碳原子的四个键按正四面体形状排列的结论 375 William Lawrence Bragg: The Pioneer of X‐ray Crystallography W. Lawrence Bragg 1890–1971 The begin of X‐ray Crystallograph 1912 "Standing on the shoulders of giants" 376 X-ray crystallography and Structure X-Ray Diffraction Photograph X-Ray Crystallography: crystals scatter X-rays and spots reflect arrangement of atoms X-ray crystallography is an imaging technique first described in 1913 by the father-and-son duo of William Henry B ragg ( 1862–1942) a nd Willia m Lawrence Bragg (1890–1971), in which xrays are projected onto a crystalline solid to determine atomic positioning and molecular structure. 1924年的诺贝尔物理学奖 377 Karl Manne Georg Siegbahn 1886-1978, 1924 NP 西格班获得了1924年的诺贝尔物理学奖,成为继巴克拉之后 ，又一次因X-射线学的贡献而获诺贝尔物理学奖的物理学家。 X-ray crystallography and Structure 378 “通过对偶极矩以及气体中的X-射线和电子的衍射的研究来了解分子结构” 于1936 年获诺贝尔化学奖。为了纪念他，把偶极矩的单位称为“德拜”。 Peter Joseph William Debye 1884-1966 Linus Carl Pauling 1901－1994 P. J. W. Dedye 是第一个因运用X-光衍射而获得诺贝尔化学奖的科学家。 荷兰第2位获得诺贝尔化学奖的科学家 1936 NP, 为衍射仪的制造奠定了基础 得意门生1954 NP Lars Onsager 1903－1976 得意门生1968 NP 物理化学的奇才、饱受争议的人物：德拜，间谍？
河北医科大学药学院 “世界物理学全明星梦之队 X射线诱发遗传突变 1946年诺贝你生学-医学关 活设资使四*清二一 X-ray crystallography Knowing what you do not Know X-ray Crystallography ds.can he d 伊藤博文与“拼死吃河豚 河豚毒素(Tetrodotoxin,TTX) 天然药物化学教研室史清文教授
河北医科大学药学院 天然药物化学教研室 史清文教授 4 “世界物理学全明星梦之队” 379 第五次索尔维会议照片（1927）,二十世纪物理学和物理学史上最珍贵的一张 历史照片，史上最强大脑：二排左1为德拜(1936 NP)，Niels Bohr中排右一。 X-射线诱发遗传突变 380 缪勒(1890-1967) Hermann Josepn Muller 缪勒因发现X-射线能人为地诱发遗传突变而被授予1946 年诺贝尔生理学.医学奖。缪勒最早指出放射线对人类的遗传有 危害作用。 1946年诺贝尔生理学-医学奖 381 X-ray crystallographyKnowing what you do not Know This works a little like trying to figure out how tall a person is by looking at his shadow. 382 X-ray Crystallography By measuring the angles and intensities of diffracted beams, produced as the X-ray beams contact a single crystal, a 3-D picture of the density of electrons within the crystal is produced and and from this the positions of the atoms within the crystals, their chemical bonds, can be determined. 伊藤博文与“拼死吃河豚” 伊藤博文（1841-1909） 日本第一个内阁总理大臣 明治宪法之父 1975年自己百毒不侵日本 传奇歌舞伎演员三代目坂东三 津五郎吃了四份河豚的肝脏， 因而中毒身亡。 N N HO OH HO H O H O O- OH H OH NH - 河豚毒素（Tetrodotoxin，TTX） Yoshimasa Hirata It is about 1200 times more toxic to humans than cyanide and it has no known antidote. 局部麻醉作用是普鲁卡因的4000倍 眼镜蛇毒100倍KCN毒性的1250倍 R. Woodword
河北医科大学药学院 Dorothy Crowfoot Hodgkin Dorothy Crowfoot Hodgkin Using X-ray crystallography to "see"atom -Penicillin,1945 C。 These achievements had an immense impact on che chemistry. Even More Important She. Early Interests of a"Gentle Genius".. Dorothy's remarkable personality Dorothy Hodgkin:Structure as Art From black art Worked to improve relations between East She liked to "think with her hands" Going bevond the limits... 热科研得诺，热学出相 Oxford graduation,1932 5 X-ray studies at Cambridg Ow Labat Oxford rheumatoid arthritis 天然药物化学教研室史清文教授 5
河北医科大学药学院 天然药物化学教研室 史清文教授 5 385 Dorothy Crowfoot Hodgkin 晶体王国之花 霍奇金(1910-1994) Went beyond “feasible limits” Figured out something organic chemists could not! Vitamin B12 Penicillin G Cholesterol Using X-ray crystallography to “see” atoms Dorothy Hodgkin，one of the outstanding scientists of the 20th century，solved the structures of ——Penicillin, 1945 ——Vitamin B12, 1954 ——Nobel Priz, 1964 ——Insulin, 1969 These achievements had an immense impact on chemistry, biochemistry and medical science, establishing the power of X-ray crystallography, and changing the practice of synthetic chemistry. Dorothy Crowfoot Hodgkin Even More Important She… • Reinvented crystallography – From black art scientific tool • Established use of molecular structure to explain biological function • Worked to improve relations between East and West • Interested in World Peace: • Is the “Cleverest woman in England” • Has been called “Gentle Genius” Dorothy’s remarkable personality Early Interests of a “Gentle Genius”… • Chemistry, especially crystals • Crystals – atoms arranged in regular and repeated pattern • “A diamond is a girl’s best friend!” • 16th Birthday Party: – Received X-ray crystallography book • Accepted to Oxford University in 1928 • On vacation, studied patterns of mosaic floors • “You’re finding what’s there and then trying to make sense of what you find.” Synagogue mosaic floor in Jerusalem. Dorothy Hodgkin: Structure as Art Rheumatoid arthritis never slowed her determined pursuit of science She liked to “think with her hands”… • Oxford graduation, 1932 • X-ray studies at Cambridge • PhD with J.D. Bernal 1934 • Own Lab at Oxford in 1934 Good News: Complex proteins could be analyzed Bad News: Diagnosed with rheumatoid arthritis 类风湿导致了手指严重扭曲 Going beyond the limits… • Took teaching job at Oxford. • Primitive lab in basement • Investigated sterols • Went beyond “feasible limits” • Figured out something organic chemists could not! • Victory Dance! Structure of Cholesterol 搞科研得诺奖，搞教学教出首相
河北医科大学药学院 Questions of a“Gentle Genius”. Even Geniuses Fall In Love... 1937 married Themas 1.Hedgkin ializs in nsw field of ree childre erothy in l "Combining two careers and three Her Project During WW II... children proved“reasonably easy” 1940 Britain at war Structure looked hopele Started from scratch Thomas also tauehtat oxfor Proved she was"master me for deep ealculations to kid talk Dorothy Hodgkin Determined the Penicillin Chemical Formula Chemical Structure of Penicillin B-lactam 人2 1946 :息 天然药物化学教研室史清文教授 6
河北医科大学药学院 天然药物化学教研室 史清文教授 6 Questions of a “Gentle Genius”… • Wondered if chemists were right • Wanted to “see” molecules for herself • Decided to specialize in new field of X-ray crystallography • X-Ray Crystallography: crystals scatter X-rays and spots reflect arrangement of atoms X-Ray Diffraction Photograph Even Geniuses Fall In Love… • 1937 married Thomas L. Hodgkin • “They really adored each other” – Max Perutz • He decided she was more creative • Three children • (1938, 1941, 1946) “Dorothy in love” Thomas L.Hodgkin (1910-1982), historian Hodgkin disease “Combining two careers and three children proved “reasonably easy”… • Thomas also taught at Oxford • Her arthritis improved w/each pregnancy • She made time for her kids • She could switch easily from deep calculations to kid talk! A devoted couple with 3 children 9 grandchildren, 3 great-grandchildren Her Project During WW II… • 1940 Britain at war • Penicillin – “high security secret” • Structure looked hopeless • Started from scratch 1942 • 1946 Mission Accomplished • Proved she was “master crystallographer” Structure of Penicillin G Dorothy Hodgkin Determined the Chemical Structure of Penicillin 牛津大学科学史博物馆中摆 放着霍奇金发现青霉素分子 结构的示意模型，黑色线圈 表示电子云，从线圈的密度 能推断出是什么原子 Molecular model of penicillin by Dorothy Hodgkin, c. 1945 Penicillin Chemical Formula 1946 b-lactam oxazolone “A magnificent start to a new era of crystallography
河北医科大学药学院 海LE Life after WW II got complicated... oved in Third World leade -Scientists -Children'sfriends Christmas parties On to Bigger and Going Beyond the Limits... Better Things... 2-raypho s and Linson Stri Vitamin B2 Structure(1948-1957) Winning the Nobel Prize... o Wom 天然药物化学教研室史清文教授 7
河北医科大学药学院 天然药物化学教研室 史清文教授 7 Google commemorated Hodgkin's 104th birthday，May 12, 2014 Sir Robert Robinson did not like the b-lactam structure because this would be unstable, unlike penicillin. All they were taken aback when a young woman solved... John W. Cornforth said “If penicillin turns out to have the b-lactam structure I shall give up chemistry and grow mushrooms.” He did not keep his threat but later received a Nobel prize for his enzyme work 30 years later, in 1975. Life after WW II got complicated… • Commuter spouses • Dorothy’s sister and family moved in • Always had guests: – Third World leaders – Scientists – Children’s friends • Christmas parties Dorothy with husband and daughter A teacher, mother, friend, and guide all rolled into one-"warm, simple, affectionate, and caring" Hodgkin et al., Nature 1955, 176, 325 On to Bigger and Better Things… 8 years, 2500 X-ray photographs Beevers and Lipson Strips Going Beyond the Limits… Developed unbeatable repertoire of skills 10,000 calculations by hand took months/years Beevers and Lipson Strips – the early computer system Vitamin B12, published in Nature in 1954 Fellow of the Royal Society in1947 harder to achieve than the Nobel Vitamin B12 Synthesis (1960-1976) 钴啉胺酸 Total synthesized by Woodward & A. Eschenmoser Vitamin B12 Structure (1948-1957) Winning the Nobel Prize… • 1964 Nobel Prize in Chemistry • Did not share prize • 5th Woman • 1st British Woman • Did not stop research • Next project: Insulin (777 atoms) 'Grandmother wins Nobel Prize' “牛津主妇获得了诺贝尔奖” “一项完全不属于家庭主妇的技能
河北医科大学药学院 "Late Night News from Dorothy... Insulin-A Storytelling Molecule The three-dime ture ofinsulin 1934-1969 lin Is Solved Crisis in Organic Chemistry" 1 918n5i A Woman as Clear as A Crystal Dorothy C.Hodgkin 民林料李家、春来、妻子三个角色 金“中国人氏的老期友 八次来访我国的“中国人民的老朋友” 化学家唐有棋院士 会在中国 98年，唐有棋在英国科学家常奇金家中作客 天然药物化学教研室史清文教授 8
河北医科大学药学院 天然药物化学教研室 史清文教授 8 “Late Night News from Dorothy… • Computers now available • Structure is “so complicated and irregular” • 1969 “…Insulin Is Solved • 70,000 X-ray spots • “Crisis in Organic Chemistry” Atomic Structure of 6 insulin molecules Dorothy's greatest scientific achievement The three-dimensional structure of insulin 1934-1969 Insulin-A Storytelling Molecule Frederick Banting and Charles Best with one of the first diabetic dogs to receive insulin, 1923 NP Frederick Sanger 1918-2013,1958 NP Dorothy C. Hodgkin 1910-1994, 1964 NP The human insulin protein is composed of 51 amino acids 玩转科学家、母亲、妻子三个角色 分别与其曾孙子、丈夫、 三个孩子、实验室成员 A Woman as Clear as A Crystal Dorothy C. Hodgkin—— 霍奇金“中国人民的老朋友” 唐有祺院士 廖鸿英 （1905-1998） 八次来访我国的“中国人民的老朋友” 原文網址：ht 1977 年观看牛胰岛素晶体结构 霍奇金在中国 梁栋材等陪霍 奇金登长城 1978年，唐有祺在英国科学家霍奇金家中作客 1947年，唐有祺 在加州理工学院 Linus Pauling 化学家唐有祺院士
河北医科大学药学院 “Cleverest Woman in England”. President of Pugwash Royal Society at the youthful age of 37 A devoted protagonist of world peac sn1976 in the Cople Affairs Faith In the Socialist 撒切尔夫人和霍奇金 Social and political activism 190 The End of A Beautiful Life... The Life ofA“Gentle Genius”. from arthritis broken pelvi 29.1994the Hodgkin.19-9 天然药物化学教研室史清文教授 9
河北医科大学药学院 天然药物化学教研室 史清文教授 9 “Cleverest Woman in England”… • 1965 Queen Elizabeth gave her the Order of Merit,second • 1960s and 70s worked for Peace organizations for 13 years • Elected chancellor of Bristol University in 1970-88 布里斯托大学 • Effect on Margaret Thatcher and Mikhail Gorbachev • The first woman to win the Copley Medal (RS) in 1976 Royal Society at the youthful age of 37 霍奇金 (1910-1994) President of Pugwash 帕格沃什科学和世界事务会 （Pugwash Conferences on Science and World Affairs） Nobel Peace Prize in 1995 Thinkers' Lodge, Pugwash, Nova Scotia, Canada, site of the first Pugwash conference in 1957 1975-1988 Bertrand Russell (1872-1970) A devoted protagonist of world peace Faith In the Socialist Lomonosov Gold Medal Russian Academy's highest accolade in 1982 Lenin Peace Prize in 1986 Russian Academy's highest accolade Linus Pauling in 1970 1950 Social and political activism 撒切尔夫人和霍奇金 和刚卸任的首相撒切 尔夫人交谈 1991年 Her list of students, colleagues and co-workers includes the names of over 110 men and women from over 20 countries. The End of A Beautiful Life… • 1977 retired to house near Oxford • Thomas died 1982 • Traveled to scientific and peace conferences • Wheelchair bound from arthritis and broken pelvis • Died at home July 29, 1994 at the age of 84 Dorothy Crowfoot Hodgkin, 1910-1994 The Life of A “Gentle Genius”…
河北医科大学药学院 米品 What are major works and disceveries by Dorothy? How did you become familiarwith thework of Dorothy Hodgkin do you think that Dorothy is considered a heroime of sciene odycrmta ing about Hodekin? Why is Dorothy Hodgkin our hereine of science? The Role of the X-ray in the Elucidation of 1962年的诺贝尔生理学奖或医学奖 the Structure of DNA Two unknown scienti 学 有价值的论文不千字Na1S3Ap Man Who Opened the Door to DNA 诺贝尔美饭的发现 N-H-- -N 种 Chargaff's Rules 天然药物化学教研室史清文教授
河北医科大学药学院 天然药物化学教研室 史清文教授 10 “晶体化学皇后” “晶体魔术师” What are major works and discoveries by Dorothy? How did you become familiar with the work of Dorothy Hodgkin? Why do you think that Dorothy is considered a heroine of science? What inspires you about Dorothy? What do you find the most fascinating about the work of Dorothy Hodgkin? Why is Dorothy Hodgkin our heroine of science? 417 DNA分子双螺旋结构的发现，让人类解开了自己的“遗 传密码”，同时催生了许多新药物开发、新疗法发现，“亲 子鉴定”的实现， 给人类带来巨大的福祉。 The Role of the X-ray in the Elucidation of the Structure of DNA 1962年的诺贝尔生理学奖或医学奖 沃森James Watson和克里克F. H. C. Crick 最有价值的论文-不足千字 Nature, 1953 April 25 Two unknown scientists Donohue and Chargaff 's Input Turned out to be Critical Jerry Donohue (1920 – 1985) Pauling Assistant "We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances" Donohue knew structural chemistry inside and out. The original DNA model Erwin Chargaff (1905–2002) Chargaff's rules 1950 A=T, G=C Man Who Opened the Door to DNA Erwin Chargaff (1905–2002) 腺嘌呤 胸腺嘧啶 鸟嘌呤 胞嘧啶 诺贝尔奖级的发现