Section 4：Double Helix
We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.). This structure has novel features which are of considerable biological interest… It has not escaped our notice that the specific paring we have postulated immediately suggests a possible copying mechanism for the genetic material.
Watson and Crick，1953
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Erwin Chargaff (1905-2002)
Erwin Chargaff (11 August 1905 – 20 June 2002) was an Austro-Hungarian-born American biochemist. From 1924 to 1928, Chargaff studied chemistry in Vienna, and earned a doctorate working. From 1925 to 1930, Chargaff served as the Milton Campbell Research Fellow in organic chemistry at Yale University. Chargaff returned to Europe, where he lived from 1930 to 1934, serving first as the assistant in charge of chemistry for the department of bacteriology and public health at the University of Berlin (1930–1933) and then served as a research associate at the Pasteur Institute in Paris (1933–1934). Chargaff immigrated to Manhattan, New York City in 1935. Then in 1938 he became an assistant professor and a professor in 1952.
Key conclusions from Erwin Chargaff's work are now known as Chargaff's rules. The first and best known achievement was to show that in natural DNA the number of guanine units equals the number of cytosine units and the number of adenine units equals the number of thymine units. This strongly hinted towards the base pair makeup of the DNA, although Chargaff did not explicitly state this connection himself. For this research, Chargaff is credited with disproving the tetranucleotide hypothesis (DNA was composed of a large number of repeats of GACT). Most researchers had previously assumed that deviations from equimolar base ratios (G = A = C = T) were due to experimental error, but Chargaff documented that the variation was real. He did his experiments with the newly developed paper chromatography and ultraviolet spectrophotometer. Chargaff's research later helped the Watson and Crick laboratory team to deduce the double helical structure of DNA.
The second of Chargaff's rules is that the composition of DNA varies from one species to another, in particular in the relative amounts of A, G, T, and C bases. It provided an evidence of molecular diversity which had been presumed absent from DNA, contributing to DNA as a more credible candidate for the genetic material than protein.
Maurice Hugh Frederick Wilkins (1916-2004)
Maurice Hugh Frederick Wilkins was born in New Zealand on December 15, 1916, and went to England with his parents for education at the age of 6. He died on October 5, 2004 in London, England. Maurice Wilkins is a British molecular biologist who graduated from Cambridge University and worked as an assistant to Professor Randall at the University of Birmingham after graduation. He was selected to participate in the "Manhattan Project" in the United States afterwards. After returning to the United Kingdom from the United States, he was engaged in X-ray analysis of DNA at King's College London.
He solved the molecular structure of DNA by X-ray diffraction during his time at King's College London. His main contribution was to obtain the first X-ray diffraction image of DNA in 1950, which provide the basis for Francis Crick and James Watson’s molecular modeling. Molecular modeling methods unraveled the double helix structure of DNA molecules. In the end, Morris won the 1962 Nobel Prize in Physiology or Medicine with his students Francis Crick and James Watson. His colleague Rosalyn Franklin at King's College London, who was also one of the main contributors to the study, died of illness and missed the award.
Rosalind Elsie Franklin (1920-1958)
Rosalind Elsie Franklin (25 July 1920 – 16 April 1958) was an English chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA. Although her works on coal and viruses were appreciated in her lifetime, her contributions to the discovery of the structure of DNA were largely unrecognized during her life.
She graduated in 1941 with a degree in natural sciences from Newnham College, Cambridge, and then enrolled for a PhD in physical chemistry at the University of Cambridge. But the advance of World War II changed her course of action: she took up a research position under the British Coal Utilization Research Association (BCURA) in 1942. The research on coal helped her earn a PhD from Cambridge in 1945. From 1947 to 1950 she worked at the Laboratoire Central des Services Chimiques de l'État in Paris, studying X-ray diffraction technology.
In 1951 Franklin joined the Biophysical Laboratory at King’s College, London, as a research fellow. There she applied X-ray diffraction methods to the study of DNA. When she first began her research at King’s College, very little was known about the chemical makeup or structure of DNA. Franklin soon discovered the two different conformations of the DNA molecule (A-form and B-form) and, more importantly, she established that the molecule existed in a helical conformation. Through the work of her and her graduate student Raymond Gosling, Franklin was able to obtain clear X-ray diffraction photos of DNA molecules (most notably “Photo 51”), which laid the foundation for James Watson and Francis Crick to suggest in 1953 that the structure of DNA is a double-helix.
After 1953, Franklin left Cambridge to work in the crystallography laboratory at Birkbeck College, London, where she led pioneering work on the molecular structures of viruses. On the day before she was to unveil the structure of tobacco mosaic virus at an international fair in Brussels, she died of ovarian cancer at the age of 37 in 1958. Watson suggested that Franklin would have ideally been awarded a Nobel Prize in Chemistry, along with her colleague Maurice Wilkins, but the Nobel Committee generally did not make posthumous nominations. Crick, Watson, and Wilkins shared the Nobel Prize in Physiology or Medicine in 1962 for their discovery of the double-helix structure of DNA.
James Watson (1928- ) and Francis Crick (1916-2004)
James Dewey Watson (born April 6, 1928) is an American molecular biologist and geneticist. Watson earned degrees at the University of Chicago (BS, 1947) and Indiana University (PhD, 1950). Following a post-doctoral year at the University of Copenhagen, Watson joined the University of Cambridge's Cavendish Laboratory in England, where he first met his future collaborator Francis Crick.
Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. Crick studied at University College London (UCL), earned a Bachelor of Science degree in 1937, and initially began a PhD research project on measuring the viscosity of water at high temperatures at UCL. But he was deflected from a possible career in physics by World War II, during which time he worked for the Admiralty Research Laboratory. In 1947, aged 31, Crick began studying biology and became part of an important migration of physical scientists into biology research. By 1949, he moved to the Medical Research Council (MRC) Unit for the Study of the Molecular Structure of Biological Systems in Cambridge University’s Cavendish Laboratory.
In mid-March 1953, Watson and Crick deduced the double helix structure of DNA. They submitted their academic paper “Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid” to Nature, which was published on April 25, 1953. The Watson-Crick structure was a proposal, based upon — and therefore supported by — the data of Rosalind Franklin, Raymond Gosling, and Maurice Wilkins published alongside it. Definitive proof of the structure, however, took almost another quarter of a century, owing to the difficulty of synthesizing small stretches of DNA in the form of single crystals. Watson, Crick and Wilkins were awarded the 1962 Nobel Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".
From 1956 to 1976, Watson was on the faculty of the Harvard University Biology Department, promoting research in molecular biology. From 1968 Watson served as director of Cold Spring Harbor Laboratory (CSHL), greatly expanding its level of funding and research. At CSHL, he shifted his research emphasis to the study of cancer, along with making it a world-leading research center in molecular biology. Watson has written many science books, including the textbook Molecular Biology of the Gene (1965) and his bestselling book The Double Helix (1968).
After the discovery of the double-helix structure, Crick went on to play a central role in the elucidation of the genetic code and the mechanism of protein synthesis. He is widely known for the use of the term "central dogma" to summarize the idea that once information is transferred from nucleic acids (DNA or RNA) to proteins, it cannot flow back to nucleic acids. During the remainder of his career, he held the post of J.W. Kieckhefer Distinguished Research Professor at the Salk Institute for Biological Studies in La Jolla, California. His later research centered on theoretical neurobiology and attempts to advance the scientific study of human consciousness.
Linus Carl Pauling (1901-1994)
Linus Carl Pauling, who was born on February 28th, 1901,in Portland, Oregon, and was died on August 19th, 1994. was an American chemist, biochemist, chemical engineer, peace activist, author, and educator. He published more than 1,200 papers and books, of which about 850 dealt with scientific topics. For his scientific work, Pauling was awarded the Nobel Prize in Chemistry in 1954.For his peace activism. he was awarded the Nobel Peace Prize in 1962. He is one of four people to have won more than one Nobel Prize. Of these, he is the only person to have been awarded two unshared Nobel Prizes.
Pauling used to perform well in high school, especially in chemistry. He conducted chemistry experiments by scavenging equipment and material from an abandoned steel plant, and aspired to be a chemist. Due to his family’s poor financial situation, Pauling held a number of jobs to earn money for his future college expenses. In September 1917, Pauling was finally admitted by Oregon State University, majoring in chemical engineering.
Pauling was one of the founders of the fields of quantum chemistry and molecular biology. His contributions to the theory of the chemical bond include the concept of orbital hybridisation and the first accurate scale of electronegativities of the elements. Pauling also worked on the structures of biological molecules, and showed the importance of the alpha helix and beta sheet in protein secondary structure. Pauling's approach combined methods and results from X-ray crystalloaraphy, molecular model building. and quantum chemistry. His discoveries inspired the work of James Watson Francis Crick, Maurice Wilkins and Rosalind Franklin on the structure of DNA which in turn made it possible for geneticists to crack the DNA code of all organisms.
In his later years he promoted nuclear disarmament, as well as orthomolecular medicine, megavitamin therapy and dietary supplements. None of his ideas concerning the medical usefulness of large doses of vitamins have gained much acceptance in the mainstream scientific community.
Barbara McClintock（1902-1992）
Barbara McClintock (June 16, 1902 – September 2, 1992) was an American cytogeneticist and the only woman who has received an unshared Nobel Prize for Physiology or Medicine. McClintock was born as the third of four children and grew up in Brooklyn, New York. She studied at Cornell University and received a B.A. in agriculture in 1923 and Ph.D. in botany in 1927, where she developed a keen interest in the cytology and genetics of maize. After graduation, McClintock received multiple fellowships and worked at Cornell and California Institute of Technology and in Berlin.
McClintock accepted an assistant professorship at the University of Missouri in Columbia in 1936 but left four years later feeling that she would not receive tenure, and worked at Cold Spring Harbor Laboratory on New York’s Long Island since 1941.
McClintock was already a rising star in cytology and genetics by 1929. When experimenting on maize in 1944, she discovered chromosome segments that can modify genetic action and transit from place to place on the chromosome. She then presented on the transposable segments – the “Dissociation-Activator (Ds-Ac) units – at the 1951 Cold Spring Harbor Symposium and published “Induction of Instability at Selected Loci in Maize” on Genetics in 1953. Though McClintock’s work was not fully appreciated until the 1970s, McClintock survived to witness her long deserved glory and was awarded the Noble Prize “for her discovery of mobile genetic elements” in 1983.
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George Gamow (1904-1968)
George Gamow (1904-1968), Russian-born American nuclear physicist and cosmologist who was one of the foremost advocates of the big-bang theory, according to which the universe was formed in a colossal explosion that took place billions of years ago. In addition, his work on deoxyribonucleic acid (DNA) made a basic contribution to modern genetic theory.
Gamow attended Leningrad (now St. Petersburg) University, where he studied briefly with A.A. Friedmann, a mathematician and cosmologist who suggested that the universe should be expanding. At that time Gamow did not pursue Friedmann’s suggestion, preferring instead to delve into quantum theory. After graduating in 1928, he traveled to Göttingen, where he developed his quantum theory of radioactivity, the first successful explanation of the behaviour of radioactive elements, some of which decay in seconds while others decay over thousands of years.
He discovered a theoretical explanation of alpha decay by quantum tunneling, invented the liquid drop model and the first mathematical model of the atomic nucleus, and worked on star formation, stellar nucleosynthesis and Big Bang nucleosynthesis (which he collectively called nucleocosmogenesis), and molecular genetics.
In his middle and late career, Gamow directed much of his attention to teaching and wrote popular books on science, including One Two Three... Infinity and the Mr .Tompkins series of books (1939–1967). Some of his books are still in print more than a half-century after their original publication.
Matthew Stanley Meselson (1930- )
Matthew Stanley Meselson (born May 24, 1930) is an American geneticist and molecular biologist who joined Harvard University since 1960, famous for demonstrating semi-conservative DNA replication with Franklin William Stahl (1929-). Meselson was born as the only child and developed a keen interest in chemistry since childhood. He went to the University of Chicago at a young age in 1946 and studied broadly about natural sciences as well as classical literature under the school’s requirements. In 1953 Meselson entered the California Institution of Technology as a graduate student and graduated with a Ph.D. in chemistry in 1957.
In 1957 Meselson collaborated with Stahl on the Meselson-Stahl experiment at Caltech: The scientists first grew several generations of the bacteria Escherichia coli (E. coli) in an environment of nitrogen-15 (a stable nitrogen isotope that is heavier than the common form, nitrogen-14), switched the bacteria to a nitrogen-14 environment for several more generations, and used a centrifuge to separate the DNA by density. The results showed that some contained only nitrogen-14, some only nitrogen-15, and some contained equal amounts of the two isotopes. They then used heat to separate the double strands of DNAs that contained both isotopes and discovered that one strand contained only nitrogen-14 and its partner only nitrogen-15, which confirmed that one strand came from a parent and one was more recently replicated – the semi-conservatively replication of DNA. John Cairns (British molecular biologist, 1922-2018) praised the simple and strong evidence as “the most beautiful experiment in biology.”
Franklin William Stahl (1929- )
Franklin William Stahl (born October 8, 1929) is an American molecular biologist and geneticist, and currently an Emeritus Professor of Biology at the University of Oregon's Institute of Molecular Biology. Stahl used “serendipity” when looking back on his career in 2015: Born as the youngest of three children, Stahl studied biology at Harvard College from 1947 to 1951. He then pursued a Ph.D. in biology at the University of Rochester. When taking a course by Daniel Mazia (1912-1996), Stahl met Matthew Meselson (1930-) during one lab section, with whom he carried out the Meselson-Stahl experiment that proved semi-conservative replication of DNA in October 1957.
It should be mentioned that Stahl has developed a keen interest in bacteriophage since 1952. Stahl and Meselson first tried to experiment on the T4 bacteriophage, but failed and switched to the bacteria Escherichia coli (E. coli) eventually. After the Meselson-Stahl experiment, Stahl studied the DNA structure of T4 bacteriophage, and his later work focused on the bacteriophage Lambda, which has a more complex structure than T4. Stahl joined the new Institute of Molecular Biology at the University of Oregon in Eugene in 1959. He retired to emeritus status in 2005 but retained his campus office and intended to remain active.
Beckman Model E Ultracentrifuge Rotor，1950s
Science History Institute. Beckman Model E Ultracentrifuge Rotor. Photograph, 2021.
Science History Institute. Philadelphia.
Beckman Instruments began producing centrifuges after their January 1, 1955 acquisition of industry leader, Specialized Instruments Corporation, or Spinco. With Spinco came the famous Model E Ultracentrifuge, which was developed in 1947 and was used for many important scientific discoveries of the 20th century, like the 1957 CalTech experiment that proved James Watson and Francis Crick’s theory on DNA replication.
The ultracentrifuge is a centrifuge optimized for spinning a rotor at very high speeds, capable of generating acceleration as high as 1,000,000 g (approx. 9 800 km/s²). There are two kinds of ultracentrifuges, the preparative and the analytical ultracentrifuge. Both classes of instruments find important uses in molecular biology, biochemistry, and polymer science. This analytical ultracentrifuge rotor is a black, oval-shaped device. The rotor has two holes, one to hold a sample cell and the other to hold a balance cell. The top of the rotor has a sharp needle, and the device is stabilized on a red plastic base.
“Beckman Centrifuge Rotor,” n.d. Beckman Historical Collection, Box 78.
Science History Institute. Philadelphia.
Cary Model 11MS Recording Spectrophotometer，1947
Science History Institute. Cary Model 11MS Recording Spectrophotometer. Photograph, 2017.
Science History Institute. Philadelphia.
Spinco Model 120B Amino Acid Analyzer
First marketed in 1960, the Beckman/Spinco Model 120 Amino Acid Analyzer used the Spackman-Stein-Moore technique of amino acid chromatography.
“Spinco Model 120B Amino Acid Analyzer,” 1960–1969. Beckman Historical Collection, Box 59, Folder 97.
Science History Institute. Philadelphia.