Welcome to the Genome. Michael Yudell

Figure 1.7 This eugenic map shows an estimate, state by state, of the number of individuals sterilized in the United States through January 1935.

       Credit: DNA Learning Center, Cold Spring Harbor Laboratory

After World War II outward support for eugenics became unacceptable to most biologists. The eugenic horrors of the Holocaust all but guaranteed that. And work by prominent geneticists “countered the eugenicists’ simplistic assertions that complex behavioral traits are governed by simple genes.” (62) But even though eugenics as an organized movement ended, eugenic ideas and enactments did not. States and territories like North Carolina and Puerto Rico saw continued sterilizations in the post‐World War II era, (63) and globally, in countries from Mexico to Japan to Iran. (64) Throughout the twentieth century ideas about heredity, social behavior, and human breeding have come in various guises, creating a fear among some that the Human Genome Project could open the door to eugenics once again.

“A VERITABLE ‘AVALANCHE’ OF NUCLEIC‐ACID RESEARCH”

      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)

Working with pneumococcal bacteria, the cause of pneumonia, Avery, McCarty, and MacLeod showed that a benign or harmless strain of pneumococci could be made virulent if mixed with dead bacteria from the same species of pneumococci that were of the virulent type. The benign strain somehow picked up the characteristics of the virulent strain and itself became a deadly form of the bacteria. Just how did this happen? How did the bacterium transform itself? Somehow, a substance in the dead virulent strain was picked up by the active strain. This “transforming principle,” as it became known, altered the bacteria. To show this, the scientists isolated proteins from the virulent strain and mixed them in a laboratory culture with the benign strain. No effect was measured—the bacteria were unchanged. However, when nucleotides from the virulent strain were isolated and mixed with the benign strain, the bacterial culture turned virulent. There it was. They had purified the bacterium’s proteins from its nucleic acids. DNA was the transforming material and the chemical component of genes. One biologist called the findings “electrifying” and became “convinced that it was now conclusively demonstrated that DNA was the genetic material.” (69)

      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)