Watson and Crick Announce the Double-Helix Model for DNA

Date April 2, 1953

James D. Watson and Francis Crick produced a model for the chemical structure of DNA that explained its self-replicating properties. Most subsequent advances in genetics, notably genetic engineering, depend on this discovery, which earned for them the Nobel Prize in Physiology or Medicine.

Also known as “The Structure of DNA”

Locale Cambridge, England

Key Figures

• James D. Watson (b. 1928), American molecular biologist and codiscoverer of the structure of DNA
• Francis Crick (1916-2004), English geneticist and codiscoverer of the structure of DNA
• Rosalind Franklin (1920-1958), English organic chemist and crystallographer who provided critical experimental data that led to the discovery of DNA’s structure
• Maurice Wilkins (1916-2004), English crystallographer and organic chemist who collaborated with Crick and Watson
• Linus Pauling (1901-1994), American chemist and Nobel laureate who discovered the helical structure of proteins

Summary of Event

The April 2, 1953, issue of the journal Nature contained two landmark articles on the structure of deoxyribonucleic acid (DNA), the molecules that store coded genetic information. “The Structure of DNA,” by James D. Watson and Francis Crick, described the ladderlike double-helical configuration of the molecule, with external ribose-phosphate chains connected by rungs composed of pairs of amino acids. In “Molecular Configuration Is Sodium Thymonucleate,” Rosalind Franklin and Raymond Gosling described the same helical structure and provided x-ray diffraction images of crystallized DNA that confirmed it.

Watson and Crick’s article contained additional insights crucial to understanding how DNA transmits genetic information. Its basic chemical composition, consisting of a sugar, deoxyribose, a phosphate group, and four amino acids—adenine, cytosine, guanine, and thymine—was established a decade earlier. It had also been demonstrated that the ratio of adenine to thymine, and that of guanine to cytosine, was always close to unity. They concluded that each rung of the ladder must consist of one of these two pairs, and they showed how these amino acids linked together via hydrogen bonds to form structurally equivalent elements.

Because of the unique amino acid pairing, each half of a DNA molecule contains a template for the other half. Thus, unraveling the molecular structure of DNA led directly to deducing how the molecule transmitted genetic information. During cell division, the DNA ladder splits down the middle along the hydrogen bonds, and each half reconstitutes itself. In 1961, Crick, along with Sydney Brenner, added another piece to the picture of the molecular mechanisms of inheritance by showing that base pair triplets encoded for a specific amino acid. A sequence of such triplets, in turn, contains instructions for producing a specific protein.

The discovery of DNA’s structure in 1953 was the most important link in a chain of genetic discoveries beginning with cytological investigations of the nucleus in the 1830’s. Geneticists have since produced a complete sequence for the human genome and are using this information to understand human pathologies at the molecular level. By the first decade of the twentieth century, biologists knew that the mechanisms of inheritance were located on chromosomes that replicated in a regular manner during cell division. In 1944, Oswald T. Avery demonstrated that DNA, and not protein, was the active chemical constituent of chromosomes. In the meantime, Linus Pauling discovered shared-electron hydrogen bonding as a force holding together molecules that have strong electrical polarity. In 1951, Pauling showed that hydrogen bonding between amino acids produced a helical configuration in proteins.

In the spring of 1951, Maurice Wilkins of King’s College London presented a paper on DNA crystallography at a conference attended by Watson. Watson, who had just earned his doctorate researching bacteriophages, arranged for a fellowship to study with Crick at the Cavendish Laboratory at Cambridge University. About the same time Franklin, an established crystallographer, joined the King’s College laboratory and began the painstaking process of preparing DNA for x-ray diffraction analysis. At the California Institute of Technology (Caltech) in Pasadena, California, Pauling was approaching the problem of DNA structure from a theoretical perspective. There was a certain rivalry between the groups, and at King’s College, where Franklin—justifiably, as it turned out—was reluctant to share data with Wilkins.

The central question was, How did the constituents of DNA fit together? Most models postulated a long helical chain, but whether single, double, or even treble, with the bases or the ribose-phosphate backbone outermost, nobody knew. Franklin pursued the problem experimentally, using x-ray diffraction to measure the width and pitch of the helix. This demonstrated empirically the double nature of the helix, with paired bases in its center. Watson, Crick, and Pauling all took a more theoretical approach. Watson made scale models of the constituent parts and attempted to fit them together like a three-dimensional jigsaw puzzle. He succeeded only after a colleague pointed out that he was using improbable isomeric forms of the amino acids. Once he moved certain hydrogen atoms to their usual position in biological compounds, the amino acid pairs fit together neatly to form rungs of identical width. The crucial insight linking unique pairing to the replication of DNA followed naturally from the modeling approach.

Meanwhile, in February, 1953, Pauling published a triple-helix model for DNA, which Watson recognized as wrong on theoretical grounds and Franklin knew to be incompatible with her diffraction results. Watson had the additional advantage of having seen Franklin’s photographs, given to him by Wilkins without Franklin’s permission (or knowledge). Seeing the photographs enabled Watson and Crick to present their results with greater confidence.

News of the discovery of the double helix benefited from Watson’s natural talents as a publicist. Elaborations of the initial article soon appeared in major journals, and Watson appeared at conferences carrying an enormous plexiglass model of DNA. The story of its discovery quickly made its way into popular compendia of scientific achievements.

Watson, Crick, and Wilkins shared the 1962 Nobel Prize in Physiology or Medicine for their work on DNA. Franklin’s untimely death in 1958 rendered her ineligible. Her death also allowed Watson to boost his own reputation by downplaying and misrepresenting her role in his popular book The Double Helix (1968), which was once required reading for most biology students in the United States.

Significance

The discovery of the structure of DNA is widely considered the most critical and significant advance in the biological sciences in the twentieth century. Not only did the discovery transform the entire theoretical basis for understanding heredity and the mechanisms by which hereditary information translates into the physical traits of organisms, but it also rapidly led to practical innovations of profound importance to the lives of billions of people.

Understanding how a gene functioned raised the possibility of chemically altering individual genes to produce heritable traits, rather than waiting for such traits to occur spontaneously, propagating them through selective breeding. In the early 1970’s researchers discovered that certain viruses transmitted segments of host DNA between bacterial species. This knowledge spawned a whole industry of genetically engineered crop plants (and, to a lesser extent, animals), as it enabled breeders to take a useful gene from one species, attach it to a virus-like carrier, and introduce it into a completely unrelated species as recombinant DNA. Such traits not only are heritable in the conventional sense but also contagious.

In the 1970’s work also began on documenting actual base sequences for genes and organisms. Complete gene sequences for a bacteriophage (virus, 1977), Haemophilus influenzae (bacterium, 1995), saccharomyces (yeast, 1996), and drosophila (fruit fly, 2000) followed. In 1989 the Human Genome Project commenced, with Watson at its head. The human-gene-sequencing effort was completed in 2003.

The actual function of most human DNA is still unknown. For many traits, however, it is now possible to identify base pair substitutions associated with pathologies and, thus, potentially to use recombinant DNA techniques to splice healthy segments of DNA into cells of individuals suffering genetic disorders. DNA sequences also provide a powerful tool for determining degrees of genetic relationship, whether relationships of identity—as blood found at a crime scene, familial relationships, human migration patterns—or relationships that construct probable evolutionary trees encompassing different species, genera, or “higher” orders of plants and animals.

This explosion in DNA-based research owes something to the discoverers’ talent for publicity as well as to their scientific acumen. Given the currents of research at the time, the discovery itself would have happened sooner or later, but its application might well have waited for decades.

Bibliography

Frank-Kamenetskii, Maxim D. Unraveling DNA: The Most Important Molecule of Life. Translated by Lev Liapin. Rev. ed. Reading, Mass.: Addison-Wesley, 1997. An excellent history of the discovery of DNA. Also describes the nature of DNA and discusses genetic engineering and the ethical issues surrounding its practice.

Inglis, John R., Joseph Sambrook, and Jan Witkowski. Inspiring Science: Jim Watson and the Age of DNA. Cold Spring Harbor, N.Y.: Cold Springs Laboratories, 2003. A collection of reminiscences and testimonials by colleagues. Good historical time line with post-1953 advances in DNA studies.

Lightman, Alan. The Discoveries: Great Breakthroughs in Twentieth Century Science. New York: Pantheon Books, 2005. Chapter 17 offers a reprint of the Watson and Crick and the Franklin articles of 1958, discusses their contributions, and traces the implications of the discovery over the course of half a century.

Maddox, Brenda. Rosalind Franklin: The Dark Lady of DNA. New York: HarperCollins, 2002. An excellent biography of Franklin, whose photographs of DNA’s shape were foundational to its discovery. Sets the record straight on Franklin’s profound contributions.

Olby, Robert. The Path to the Double Helix. Seattle: University of Washington Press, 1974. A detailed chronological account of the gradual unfolding of the DNA story, with thorough explanations of scientific principles. This work was endorsed by Crick, who objected to Watson’s controversial book The Double Helix.

Ridley, Matt. Francis Crick: Discoverer of the Genetic Code. New York: Atlas Books, 2006. Good coverage of Crick’s work with viruses and his discovery of the triplet code.

Watson, James D. The Double Helix. A Personal Account of the Discovery of the Structure of DNA. 1968. New ed. New York: Scribner, 1998. As much a dramatic account of how people liked to believe science was done in the 1950’s as an accurate historical narrative. The book downplays Rosalind Franklin’s role in the discovery.