弗朗西斯·克里克对遗传密码研究的历史贡献
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摘要
弗朗西斯·克里克（F.H.C.Crick，1916-2004）是科学史上的杰出人物之一。他的科研兴趣经历了从物理学转向生物学的重大转变。即使在生物学领域，克里克的科学研究也是多方面的，涉及细胞质、蛋白质、DNA、遗传密码和人类意识等多个方向。
本文在研读克里克在遗传密码领域发表的原始论文和相关学术研究文献的基础上，利用文献研究和概念分析等方法，揭示克里克在密码研究中的理论观点的本质内容，力求构建克里克从事遗传密码研究的历史图景。
具体地讲，文章以克里克的原始论文和相关学术研究文献等第一手资料为依托，再现克里克密码研究的理论成果。梳理了克里克在密码研究中提出的概念和假说的历史演变；初步探索克里克的密码研究的影响，说明了当今密码研究领域的焦点问题，且采用案例研究法揭示突变危险性理论的本质内容和深受克里克密码研究之重要观点：摆动假说和冻结偶然性理论影响的痕迹。
本篇论文包括六章内容。第一章全面解析克里克的科研人生，综合分析了克里克的个人学术选择及主要科学成就，概要地总结了克里克在所研究领域的重大贡献；揭示克里克审慎、执着和智慧的科研人生，认为在克里克诸多的探索领域中，遗传密码研究是一个重要的组成部分。克里克的此项研究建构在物理学思维与生物学研究对象有机结合的基础之上，这个结合是克里克实现其初衷（涉入生物物理学领域）的一个富有成效的尝试。
第二章梳理了遗传密码研究的早期发展。介绍了“遗传物质”概念的历史演变，澄清了遗传密码研究的发端问题，并重点提出四种早期的密码研究雏形：认为胚胎学家布拉舍（J.Brachet）首先发起了从DNA到蛋白质信息流向问题的研究，生物学家杜恩斯（A.L.Dounce）第一个提出了编码设想，物理学家伽莫夫（G.Gamow）最先从细节上重视编码问题，克里克在此基础上开始走上遗传密码的研究之路，提出多种编码方案，初期探索步履维艰，显示其坚定执着，开拓创新的科学精神。
第三章基于对其科研论文、论著及个人通讯资料的研读，探究克里克密码思想形成的心路历程。提出有三点原因促使克里克走向密码研究之路，其一是自然选择思想，其二是洞察新问题的能力和物理学思想的影响，其三则是对科学研究全身心的投入。
第四、五章是克里克密码研究思想的主体部分。论文首次将克里克的密码研究分成基础性研究和综合性研究两部分。第四章探索了克里克对遗传密码的基础性研究，包括编码问题、论蛋白质的合成和三联体三部分内容。编码问题是密码研究中的一个基本问题，基于对克里克在编码问题中史实上的梳理和概念上的分析，认为克里克虽然不是第一个提出编码方案的人，但是是他首先意识到了编码问题的重要性，并为此付诸大量的思考和理论分析；在编码问题的研究处于“低谷”期间，克里克构建了蛋白质合成问题的理论框架，提出了序列假说和中心法则，彰显了假说的重要价值及经验出于错误的历史教训；克里克的密码研究突显循序渐进，追求实证的科研逻辑。随后他开创性地设计了遗传学实验，证实了密码子为“三联体”的本质。这一研究成果在全部密码子发现的历史过程中起到了决定性的作用，是克里克密码研究中一项承前启后的工作，首次阐明了密码的本质特征，并促使他进一步成为根植于实验的理论家。
第五章是从内史角度揭示克里克对遗传密码的综合性研究。本章分析了克里克对遗传密码的性质、摆动假说、终止密码子、密码表的建立和密码起源与进化方面的研究；探讨了克里克密码研究的五次综合，从实证方面展示其对密码研究发展到一定程度的理论综合及完善的过程，体现了密码表建立过程中多国科学家的集体智慧以及理论和实验两方面的共同协作。基于对克里克两个层次的密码研究充分显示了其密码研究的主体特征：一般性、系统性、逻辑性和根本性；框架式的研究风格；大胆假设和开拓创新；根植于历史和实验。这一切又体现了克里克深厚的物理学知识基础和物理学思想的影响。
第六章初步探讨了克里克密码研究的影响。分析了密码研究的一些焦点问题：密码的简并性和反常码、无义密码子的再编码、遗传密码的扩展和密码的起源与进化。然后，通过案例研究梳理了中国学者在遗传密码研究方面的成果——突变危险性理论，揭示其理论形成的历史背景和本质内容。突变危险性理论起源于上世纪80年代，在诸多关于密码起源与进化的理论观点中，突变危险性极小化理论从其基本假设的合理性、逻辑结构的明晰性和完整性以及解释实验资料的广泛性来看，是特别成功的。论文也从细节上首次研究了克里克的密码观对突变危险性理论的直接影响。
F.H.C.Crick (1916-2004) is one of the most distinguished scientists inthe history of science. He changed his major from physics to biology. Hisresearch interests arranged many fields of biology such as cytoplasm, protein,DNA, genetic code and human consciousness, etc..
Based on a careful examination of Crick’s original academic papers ongenetic code and related study literature, the present dissertation deals withthe essential contents of his theories by means of the methods of literature andconcept analysis.The ultimate goal of the dissertation is to give a historicalimage of his scientific work.
Specifically, the achievements of Crick on the study of genetic codetheory are presented according to the first hand materials including CrickCrick’s original academic papers and some related study literature. Theevolution of concepts and hypotheses raised by him is investigated, so is histhinking effect on modern code field. All the concentrated problems areillustrated. By using the case study method, the essential contents ofMutational Deterioration theory are reviewed, and the truth is that Crick’simportant views of wobble hypothesis and frozen accident have greatinfluence on Mutational Deterioration theory.
The dissertation is divided into the six chapters. The first chapter is about the study of Crick’s lifetime. His personal academic options and the mainachievements have been analyzed completely. The important contributions inhis research fields have been summarized briefly. All of these prove that hislifetime is prudent, constant and intelligent. Among his academic activities,genetic code is recognized as the most important part. The study on geneticcode is on the basis of the integration of physics thinking with biology objects.The integration is an effective attempt of his original ideal involved inbiophysics.
The early development of genetic code is reviewed in the second chapter.The historical evolution of the concept "genetic material" is introduced，theorigin of the study of genetic code is made clear, and moreover, the point isthat four early code rudiments are proposed. Embryologists J.Brachet firstlaunched the research related to information flow from DNA to protein,biologists A.L.Dounce first put forward the coding assumption, and physicistsG.Gamow attached importance to the coding problem at first in detail.By theinspiriting of the work of Gamow, Crick stepped into the road of studyinggenetic code, bringing forth a series of coding schemes and struggling withdifficulty in the beginning of research. The hard work embodies his scientificspirit such as perseverance and innovation.
The third chapter is to trace back to the reasons why Crick could giverise to the thoughts about genetic code. The whole psychological process ofCrick is probed through referring to his papers, books and personal communication letters. The dissertation comes to the conclusion that threeimportant factors contribute to his interests in the study of genetic code. First,it is from Darwinism. Second, Crick has the ability to gain an insight into thenew things and benefits from his physics thinking. Third, he has committedhis full devotion to science.
Both the fourth and the fifth chapters are the main parts of the wholepaper. The research work of Crick on the genetic code is divided into twoparts. The first includes his fundamentals, and the second is made of thesyntheses. In the fourth chapter, his fundamentals including coding problem，protein synthesis and triplet are probed. Coding problem is the most essentialissue in his study. Based on the historical study and concept analyzing ofCrick on coding problem, it is believed that although the first person who putforward to coding problem was not Crick, he was aware of the importance ofthe issue firstly. With a lot of thinking and theory analyses, Crick appliedhimself to that problem. At a low ebb of the coding research, he built up thetheory frame, making proposition of "sequence synthesis" and "centraldogma". The performance shows the value of his hypothesis and historicallessons that experience comes from mistakes. The research of Crick in theaspect proves the scientific logic that the academic research should conformto the way from easy to difficult and seeking evidences. Sequentially, hedevised an original experiment that proved the essence of code is triplet. Thesuccessful experiment plays an important role in history of code discovery and also serves as a link between the past and the future. It is the first timethat the essence of genetic code was expanded and helped him further tobecome a theoretician rooted in experiments.
The fifth chapter is to do some synthesis research of Crick on geneticcode from the perspective of internal history. The research of Crick involvedin the properties of genetic code, wobble hypothesis, stop codons, theconstruction of the standard code table and the origin and evolution of code isintegrated completely in the chapter. Contributions of Crick and otherscientists to the syntheses process of the theory of genetic code andconstruction of the code table are shown by explaining his five timessyntheses. Based on two-level researches of Crick，the author thinks that themain characteristics of his researches in the aspect are as follows: generality,systematicness, logicality and essentiality; frame research style; boldassumptions and innovation; thinking rooted in history and experiments.These characteristics show the influence of the strong foundation of physicsknowledge and physics thinking to him in his scientific activities on geneticcode.
The impact of the research of Crick in the field of genetic code is studiedprimarily in the chapter6. Some concentrated problems, such as thedegeneracy of genetic code and deviant code, redefinition of nonsense codons,the expanding of code, the origin and evolution of code, etc, are analyzed atfirst. And then, through a case study on Mutation Deterioration theory proposed by Chinese scholar, the historical background and the essentialcontent of the theory of genetic code is examined. Mutation deteriorationtheory may date back to1980s. From the rationality of underlyingassumptions, the clarity of the logical structure, the completeness and theuniversality of interpretation of experimental data, the theory is particularlysuccessful among many other theories on the code origin and evolution. Thefact that the code study of Crick has direct effects on the MutationDeterioration theory is demonstrated in detail for the first time.
本文在研读克里克在遗传密码领域发表的原始论文和相关学术研究文献的基础上，利用文献研究和概念分析等方法，揭示克里克在密码研究中的理论观点的本质内容，力求构建克里克从事遗传密码研究的历史图景。
具体地讲，文章以克里克的原始论文和相关学术研究文献等第一手资料为依托，再现克里克密码研究的理论成果。梳理了克里克在密码研究中提出的概念和假说的历史演变；初步探索克里克的密码研究的影响，说明了当今密码研究领域的焦点问题，且采用案例研究法揭示突变危险性理论的本质内容和深受克里克密码研究之重要观点：摆动假说和冻结偶然性理论影响的痕迹。
本篇论文包括六章内容。第一章全面解析克里克的科研人生，综合分析了克里克的个人学术选择及主要科学成就，概要地总结了克里克在所研究领域的重大贡献；揭示克里克审慎、执着和智慧的科研人生，认为在克里克诸多的探索领域中，遗传密码研究是一个重要的组成部分。克里克的此项研究建构在物理学思维与生物学研究对象有机结合的基础之上，这个结合是克里克实现其初衷（涉入生物物理学领域）的一个富有成效的尝试。
第二章梳理了遗传密码研究的早期发展。介绍了“遗传物质”概念的历史演变，澄清了遗传密码研究的发端问题，并重点提出四种早期的密码研究雏形：认为胚胎学家布拉舍（J.Brachet）首先发起了从DNA到蛋白质信息流向问题的研究，生物学家杜恩斯（A.L.Dounce）第一个提出了编码设想，物理学家伽莫夫（G.Gamow）最先从细节上重视编码问题，克里克在此基础上开始走上遗传密码的研究之路，提出多种编码方案，初期探索步履维艰，显示其坚定执着，开拓创新的科学精神。
第三章基于对其科研论文、论著及个人通讯资料的研读，探究克里克密码思想形成的心路历程。提出有三点原因促使克里克走向密码研究之路，其一是自然选择思想，其二是洞察新问题的能力和物理学思想的影响，其三则是对科学研究全身心的投入。
第四、五章是克里克密码研究思想的主体部分。论文首次将克里克的密码研究分成基础性研究和综合性研究两部分。第四章探索了克里克对遗传密码的基础性研究，包括编码问题、论蛋白质的合成和三联体三部分内容。编码问题是密码研究中的一个基本问题，基于对克里克在编码问题中史实上的梳理和概念上的分析，认为克里克虽然不是第一个提出编码方案的人，但是是他首先意识到了编码问题的重要性，并为此付诸大量的思考和理论分析；在编码问题的研究处于“低谷”期间，克里克构建了蛋白质合成问题的理论框架，提出了序列假说和中心法则，彰显了假说的重要价值及经验出于错误的历史教训；克里克的密码研究突显循序渐进，追求实证的科研逻辑。随后他开创性地设计了遗传学实验，证实了密码子为“三联体”的本质。这一研究成果在全部密码子发现的历史过程中起到了决定性的作用，是克里克密码研究中一项承前启后的工作，首次阐明了密码的本质特征，并促使他进一步成为根植于实验的理论家。
第五章是从内史角度揭示克里克对遗传密码的综合性研究。本章分析了克里克对遗传密码的性质、摆动假说、终止密码子、密码表的建立和密码起源与进化方面的研究；探讨了克里克密码研究的五次综合，从实证方面展示其对密码研究发展到一定程度的理论综合及完善的过程，体现了密码表建立过程中多国科学家的集体智慧以及理论和实验两方面的共同协作。基于对克里克两个层次的密码研究充分显示了其密码研究的主体特征：一般性、系统性、逻辑性和根本性；框架式的研究风格；大胆假设和开拓创新；根植于历史和实验。这一切又体现了克里克深厚的物理学知识基础和物理学思想的影响。
第六章初步探讨了克里克密码研究的影响。分析了密码研究的一些焦点问题：密码的简并性和反常码、无义密码子的再编码、遗传密码的扩展和密码的起源与进化。然后，通过案例研究梳理了中国学者在遗传密码研究方面的成果——突变危险性理论，揭示其理论形成的历史背景和本质内容。突变危险性理论起源于上世纪80年代，在诸多关于密码起源与进化的理论观点中，突变危险性极小化理论从其基本假设的合理性、逻辑结构的明晰性和完整性以及解释实验资料的广泛性来看，是特别成功的。论文也从细节上首次研究了克里克的密码观对突变危险性理论的直接影响。
F.H.C.Crick (1916-2004) is one of the most distinguished scientists inthe history of science. He changed his major from physics to biology. Hisresearch interests arranged many fields of biology such as cytoplasm, protein,DNA, genetic code and human consciousness, etc..
Based on a careful examination of Crick’s original academic papers ongenetic code and related study literature, the present dissertation deals withthe essential contents of his theories by means of the methods of literature andconcept analysis.The ultimate goal of the dissertation is to give a historicalimage of his scientific work.
Specifically, the achievements of Crick on the study of genetic codetheory are presented according to the first hand materials including CrickCrick’s original academic papers and some related study literature. Theevolution of concepts and hypotheses raised by him is investigated, so is histhinking effect on modern code field. All the concentrated problems areillustrated. By using the case study method, the essential contents ofMutational Deterioration theory are reviewed, and the truth is that Crick’simportant views of wobble hypothesis and frozen accident have greatinfluence on Mutational Deterioration theory.
The dissertation is divided into the six chapters. The first chapter is about the study of Crick’s lifetime. His personal academic options and the mainachievements have been analyzed completely. The important contributions inhis research fields have been summarized briefly. All of these prove that hislifetime is prudent, constant and intelligent. Among his academic activities,genetic code is recognized as the most important part. The study on geneticcode is on the basis of the integration of physics thinking with biology objects.The integration is an effective attempt of his original ideal involved inbiophysics.
The early development of genetic code is reviewed in the second chapter.The historical evolution of the concept "genetic material" is introduced，theorigin of the study of genetic code is made clear, and moreover, the point isthat four early code rudiments are proposed. Embryologists J.Brachet firstlaunched the research related to information flow from DNA to protein,biologists A.L.Dounce first put forward the coding assumption, and physicistsG.Gamow attached importance to the coding problem at first in detail.By theinspiriting of the work of Gamow, Crick stepped into the road of studyinggenetic code, bringing forth a series of coding schemes and struggling withdifficulty in the beginning of research. The hard work embodies his scientificspirit such as perseverance and innovation.
The third chapter is to trace back to the reasons why Crick could giverise to the thoughts about genetic code. The whole psychological process ofCrick is probed through referring to his papers, books and personal communication letters. The dissertation comes to the conclusion that threeimportant factors contribute to his interests in the study of genetic code. First,it is from Darwinism. Second, Crick has the ability to gain an insight into thenew things and benefits from his physics thinking. Third, he has committedhis full devotion to science.
Both the fourth and the fifth chapters are the main parts of the wholepaper. The research work of Crick on the genetic code is divided into twoparts. The first includes his fundamentals, and the second is made of thesyntheses. In the fourth chapter, his fundamentals including coding problem，protein synthesis and triplet are probed. Coding problem is the most essentialissue in his study. Based on the historical study and concept analyzing ofCrick on coding problem, it is believed that although the first person who putforward to coding problem was not Crick, he was aware of the importance ofthe issue firstly. With a lot of thinking and theory analyses, Crick appliedhimself to that problem. At a low ebb of the coding research, he built up thetheory frame, making proposition of "sequence synthesis" and "centraldogma". The performance shows the value of his hypothesis and historicallessons that experience comes from mistakes. The research of Crick in theaspect proves the scientific logic that the academic research should conformto the way from easy to difficult and seeking evidences. Sequentially, hedevised an original experiment that proved the essence of code is triplet. Thesuccessful experiment plays an important role in history of code discovery and also serves as a link between the past and the future. It is the first timethat the essence of genetic code was expanded and helped him further tobecome a theoretician rooted in experiments.
The fifth chapter is to do some synthesis research of Crick on geneticcode from the perspective of internal history. The research of Crick involvedin the properties of genetic code, wobble hypothesis, stop codons, theconstruction of the standard code table and the origin and evolution of code isintegrated completely in the chapter. Contributions of Crick and otherscientists to the syntheses process of the theory of genetic code andconstruction of the code table are shown by explaining his five timessyntheses. Based on two-level researches of Crick，the author thinks that themain characteristics of his researches in the aspect are as follows: generality,systematicness, logicality and essentiality; frame research style; boldassumptions and innovation; thinking rooted in history and experiments.These characteristics show the influence of the strong foundation of physicsknowledge and physics thinking to him in his scientific activities on geneticcode.
The impact of the research of Crick in the field of genetic code is studiedprimarily in the chapter6. Some concentrated problems, such as thedegeneracy of genetic code and deviant code, redefinition of nonsense codons,the expanding of code, the origin and evolution of code, etc, are analyzed atfirst. And then, through a case study on Mutation Deterioration theory proposed by Chinese scholar, the historical background and the essentialcontent of the theory of genetic code is examined. Mutation deteriorationtheory may date back to1980s. From the rationality of underlyingassumptions, the clarity of the logical structure, the completeness and theuniversality of interpretation of experimental data, the theory is particularlysuccessful among many other theories on the code origin and evolution. Thefact that the code study of Crick has direct effects on the MutationDeterioration theory is demonstrated in detail for the first time.
引文
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