The period of classical genetics focused on refining and improving the structural understanding of DNA. In contrast, modern genetics seeks to understand the processes of heredity and how genes work.
Many historians consider 1953—the year that American geneticist James Watson (1928–) and British biophysicist Francis Crick (1916–2004) famously described the structure of DNA—as the birth of modern genetics. It is important, however, to remember that the historic accomplishment of Watson and Crick was not the discovery of DNA—Miescher had identified nucleic acid in cells nearly a century earlier. Similarly, while Watson and Crick earned recognition and public acclaim for their landmark research, it would not have
FIGURE 1.8 Chargaff's rules. Argosy Publishing, Thomson Gale.
been possible without the efforts of their predecessors and colleagues such as Maurice Wilkins (1916–2004) and Rosalind Franklin (1920–58). Wilkins and Franklin were the molecular biologists who in 1951 obtained sharp X-ray diffraction photographs of DNA crystals, revealing a regular, repeating pattern of molecular building blocks that correspond to the components of DNA. (Wilkins shared the Nobel Prize with Watson and Crick, but Franklin was ineligible to share the prize because she died in 1958, four years before it was awarded.)
Another pioneer in biochemistry, Austrian-American Erwin Chargaff (1905–2002), also provided information about DNA that paved the way for Watson and Crick. Chargaff suggested that DNA contained equal amounts of the four nucleotides: the nitrogenous (containing nitrogen, a nonmetallic element that constitutes almost four-fifths of the air by volume) bases adenine (A) and thymine (T), and guanine (G) and cytosine (C). In DNA there is always one A for each T, and one G for each C. This relationship became known as base pairing or Chargaff's rules, which also includes the observation that the ratio of AT to GC varies from species to species but remains consistent across different cell types within each species. (See Figure 1.8.)
The Players—Watson and Crick
James Watson is an American geneticist known for his willingness to grapple with big scientific challenges and his expansive view of science. In The Double Helix: A Personal Account of the Discovery of the Structure of DNA, he chronicles his collaboration with Francis Crick to create an accurate model of DNA. He credits his inclination to take intellectual risks and venture into uncharted territory as his motivation for this ambitious undertaking.
Watson was just twenty-five years old when he announced the triumph that was hailed as one of the greatest scientific achievements of the twentieth century. Following this remarkable accomplishment, Watson served on the faculty of Harvard University for nearly two decades and assumed the directorship and then the presidency of the Cold Spring Harbor Laboratory in Long Island, New York. From 1988 to
FIGURE 1.9 James Watson and Francis Crick examine a DNA model. Public domain.
1992 he headed the Human Genome Project of the National Institutes of Health (NIH), the effort to sequence (or discover the order of) the entire human genome.
Francis Crick was an English scientist who had studied physics before turning his attention to biochemistry and biophysics. Crick became interested in discovering the structure of DNA, and when in 1951 Watson came to work at the Cavendish Laboratory in Cambridge, England, the two scientists decided to work together to unravel the structure of DNA. Figure 1.9 is a photograph of the young scientists in their laboratory using a model to display the double helical (spiral) structure of DNA.
After his landmark accomplishment with Watson, Crick continued to study the relationship between DNA and genetic coding. He is credited with predicting the ways in which proteins are created and formed, a process
FIGURE 1.10 Canonical B-DNA double helix models SOURCE: "Canonical B–DNA Double Helix," in Genetics, vol. 1, A–D, Macmillan Reference USA, Gale Group, 2002
known as protein synthesis. During the mid-1970s Crick turned his attention to the study of brain functions, including vision and consciousness, and assumed a professorship at the Salk Institute for Biological Studies in La Jolla, California. Like Watson, he received many professional awards and accolades for his work and, along with the scientific papers he and Watson coauthored, published four books. Published a decade before his death in 2004, Crick's last book, The Astonishing Hypothesis: Scientific Search for the Soul (New York: Scribner, 1994), detailed his ideas and insights about human consciousness.
THE WATSON-CRICK MODEL OF DNA.
Using the X-ray images of DNA created by Franklin and Wilkins, who also worked in the Cavendish Laboratory, Watson and Crick worked out and then began to build models of DNA. Crick contributed his understanding of X-ray diffraction techniques and imaging, and relied on Watson's expertise in genetics. In 1953 Watson and Crick published the paper "A Structure of Deoxyribonucleic Acid" (Nature, vol. 171, April 25, 1953), which contained the famously understated first lines, "We wish to suggest a structure for the salt of deoxyribonucleic acid (D.N.A.). The structure has novel features, which are of considerable biological interest." Watson and Crick then described the shape of a double helix, an elegant structure that resembles a latticework spiral staircase. (See Figure 1.10.)
Their model enabled scientists to better understand functions such as carrying hereditary information to direct protein synthesis, replication, and mutation at the molecular level. The three-dimensional Watson and Crick model consists of two strings of nucleotides connected across like a ladder. Each rung of the ladder contains an A-T pair or a G-C pair, consistent with Chargaff's rule that there is an A for every T and a G for every C in DNA. (See Figure 1.10.) Watson and Crick posited that changes in the sequence of nucleotide pairs in the double helix would produce mutations.
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