Welcome to the Genome. Michael Yudell

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Welcome to the Genome - Michael Yudell


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he was acknowledged as “one of the most important pioneers in the field of racial hygiene” (59) and the visit to Berlin in 1935 by Clarence Campbell, head of the Eugenic Research Association. Campbell proclaimed that the Nazi approach to eugenics “sets a pattern which other nations and other racial groups must follow if they do not wish to fall behind in their racial quality, in the racial accomplishments, and in the prospects for survival.” (60) These types of relationships set the stage for the distribution, in the United States in 1937, by American eugenicists, of a Nazi eugenic propaganda film. (61)

Image described by caption.

       Credit: DNA Learning Center, Cold Spring Harbor Laboratory

      Despite the horrors of eugenics, by the 1930s the ideas of Charles Darwin were once again making headlines as the scientific search for the mechanisms of heredity continued. Darwin’s theory of evolution lacked the mechanism to explain heredity. His theory articulated a “big picture” of evolution. He was right when he explained the ways in which evolution worked, but his theory was incomplete without genetics. Darwin’s theory could not explain how evolutionary traits were passed through time. (65) Evolutionary biologists like R. A. Fisher, J. B. S. Haldane, and Sewell Wright successfully bridged the gap between evolution and genetics and spent their careers developing the mathematical framework for incorporating Mendelian genetics into evolutionary biology. This significant body of work led to what is known as the Modern Synthesis in biology, the merger of Darwinian and Mendelian science. This allowed scientists like Theodosius Dobzhansky, Ernst Mayr, and George Gaylord Simpson, who were based more in data collection than in theory, to develop an empirical approach to evolutionary biology and to open up evolutionary ideas for a broader interpretation in a genetic context. (66)

      While the Modern Synthesis provided a framework for understanding questions about heredity in the context of evolution, other scientists were still trying to determine the chemical components of the hereditary material. Some remained wedded to the belief that proteins transmitted traits between generations, among them Hermann Muller, who had originally worked in Thomas Hunt Morgan’s laboratory, whereas others argued that nucleic acids were the fundamental elements of life. (67) No one had been able to prove this either way until a series of ingenious experiments conducted in 1944 by Oswald Avery, Maclyn McCarty, and Colin MacLeod showed that nucleic acids constituted genes. (68)

      Every living thing on Earth—every plant and animal, every bacterium, and even viruses—shares one of the most fundamental structures of life, molecules called nucleic acids. When DNA came to be known as the stuff of heredity, focus immediately shifted from simply understanding its function to understanding its physical structure and chemical characteristics as well. Although work in this area had begun over 70 years earlier in Germany when Friedrich Miescher discovered nucleic acids in 1869, it was Avery, McCarty, and MacLeod’s discovery that unleashed what one observer called a “veritable ‘avalanche’ of nucleic‐acid research.” (70) Many scientists in related fields excitedly began studying DNA, including biochemist Erwin Chargaff, who remodeled himself as a molecular biologist and shifted his work to studying nucleic acids. This was a particularly common move among biochemists, who were well suited for DNA research because of their training in chemistry and biology.

      With DNA’s structure as yet unknown, Chargaff turned his attention to the chemical characteristics of nucleic acids. In DNA there were four known bases—adenine, guanine, cytosine, and thymine–which are commonly referred to by their first letters, A, G, C, and T. Each of these bases has different structures and characteristics. Analyzing the number of these bases with a chromatographic technique, Chargaff came to a startling conclusion—in all the organisms he studied the amount of A in any given cell was always equal to the amount of T in the same cell. The same went for G and C. The ratio of A to T and G to C was always 1. This 1:1 ratio became known as Chargaff’s rule and is still one of the cornerstones of molecular biology. (71)

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      Many wondered how Nature could be so exact across all species on Earth. The significance of Chargaff’s rule would not be entirely clear until the three‐dimensional structure of nucleic acids was determined. To do this, scientists had to take an actual look at the physical structure of DNA, which they began to do in the 1940s. Once they “saw DNA,” the pieces of the puzzle fell into place very quickly.

      Genetics in the twentieth century saw many milestones, including the work we have already described by scientists like Morgan, Avery, and Chargaff. This work and the work of their collaborators and colleagues propelled the revolution in genetics forward. Their discoveries alone are striking for the ways in which they advanced thinking in heredity. The discovery of the structure of DNA in 1953, however, has garnered all of the headlines. On both sides of the Atlantic scientists were working on cracking the structure of DNA. Solving this puzzle was important because it would expose the fundamental structure of heredity and show how the molecule at the center of life replicates itself and functions. Although chemists had already identified the molecular components of DNA—“that nucleic acids were very large molecules built up from smaller building blocks, the nucleotides”—James Watson remembers that in the years preceding the discovery of DNA’s structure “there was almost nothing chemical that the geneticist could grasp at.” (72) Three prominent groups worked on solving this problem: James Watson and Francis Crick at Cambridge University, Maurice Wilkins and Rosalind Franklin at King’s College, London, and Linus Pauling and Robert Corey at the California Institute of Technology.


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