April 25, 2016

The secret of life revealed: Today in science history

by Bonnie Denmark

On April 25, 1953, the “secret of life” was revealed in a short article in Nature that began, “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.” Quite the understatement given that the double helix structure of DNA proposed by James D. Watson and Francis H. C. Crick is one of the greatest scientific discoveries of all time.

By then, DNA was widely recognized as the genetic material. However, it would be impossible to know how DNA worked without first understanding its structure. Little was known about DNA aside from the fact that it was a large molecule built from smaller molecules called nucleotides that have a phosphate group, a sugar group, and one of four nitrogen bases: adenine, thymine, cytosine, or guanine.

Maurice Wilkins (1916–2004). (National Institutes of Health)

It was at a 1951 scientific conference in Naples, Italy, that American research fellow David Watson was captivated by an X-ray diffraction picture of DNA displayed during a talk by London-based physicist Maurice Wilkins. This showed that DNA could crystallize, and thus must have a regular structure. The photo put Watson on the trail to seek out that structure. (For more on how the structure of crystals reflects a regular internal arrangement of component atoms, read our module Defining Minerals.)

At Cambridge University, Watson and British graduate student Francis Crick set themselves to building physical models of DNA, a technique made popular by American chemist Linus Pauling. Sixty miles south at King’s College in London, Maurice Wilkins continued investigating DNA with X-ray diffraction as did another major player in the story, chemist Rosalind Franklin, an expert at X-ray crystallography. With this technique, Xrays were passed through crystallized DNA. As the rays bounced off the crystals, the way they bent – or were diffracted – formed patterns that could be captured on film and gave clues to the molecular structure of the crystallized DNA. (Read more about X-ray crystallography in our module Properties of Solids.)

Rosalind Franklin (1920–1958). (Jewish Chronicle Archive/Heritage-Images)

In 1951, Watson and Crick came up with a three-stranded helix model of DNA with the nitrogen base rings on the outside and the phosphate groups on the inside. Franklin was not impressed, noting that the phosphate group backbone should be pointed outwards with the nitrogen bases on the inside. In addition, she was not quick to accept the tinker-toy approach of building physical models of molecules as a legitimate method of scientific inquiry. Prominent biochemist Erwin Chargaff was not taken with the young scientists’ work either, saying, “I never met two men who knew so little – and aspired to so much” (McElheny, p. 48).

A year later, to Watson and Crick’s dismay, Linus Pauling – who earlier determined that some protein molecules have a helix shape – proposed a model of DNA’s structure. It also was a three-stranded helix, much like the model that Watson and Crick had proposed and discarded the previous year. Watson noticed that the way hydrogen atoms were bonded in Pauling’s model meant that the DNA molecule had no net charge, yet a charge would be necessary to hold together the spirals. “By then I knew we were still in the game,” Watson wrote in The Double Helix (p. 161).

Watson and Crick’s 1953 double-helix DNA model on display at the National Science Museum in London. (Wikimedia Commons)

True, their first model was flawed, and Crick suspected that key to the solution were Chargaff’s rules about the quantities of nucleotide bases: Chargaff had discovered that the four nitrogen bases of nucleotides are found in predictable quantities, with the amount of adenine equal to the amount of thymine and the amount of cytosine equal to the amount of guanine. So Watson and Crick went back to the drawing board with a focus on why the two sets of nucleotide bases are found in matching quantities. They realized that if the nitrogen base adenine bonded with thymine while cytosine paired off with guanine, the bonded base pairs would fit beautifully into a double helix structure! That afternoon, Crick announced at a pub that they had discovered the secret of life.

This photo looking up through the middle of a double-helix staircase resembles the X-ray photograph of DNA taken by Rosalind Franklin that was crucial to the discovery of the molecule’s double-helix structure. (Wikimedia Commons)

A critical piece of the puzzle was an X-ray diffraction photograph of DNA taken by Franklin that Watson and Crick obtained without her knowledge. Known as Photograph 51, the clear image indicated DNA’s helical shape. Four decades later, Watson acknowledged that seeing this photograph was “the key event” in understanding the structure of DNA (Maddox, p. 316). That Franklin’s contribution wasn’t acknowledged at the time is a clear breach of scientific ethics, one that Watson has had to answer for many times over his career.

Franklin and Wilkins published separate papers in the same 1953 issue of Nature in which Watson and Crick announced their double helix DNA model. In 1962, James Watson, Francis Crick, and Maurice Wilkins shared the 1962 Nobel Prize in Physiology or Medicine for determining the structure of DNA. Sadly, Rosalind Franklin had passed away in 1958 at age 37 of ovarian cancer, likely related to her many years’ work with X-rays.

James D. Watson (b. 1928) in 2005. See younger Watson at bottom right and Francis Crick (1916–2004) in the upper left. (Steve Jurvetson)

In April 2003, 50 years after the discovery of the double helix, another milestone was reached in the study of DNA: The Human Genome Project was completed. The goal of the project, launched in 1990 by the US National Institutes of Health and Department of Energy, was to understand how DNA is used to build a human being. It took $3 billion and 13 years to identify the approximately 20,500 genes that make up the human genome (the complete genetic material of an organism) and determine the sequence of the over 3 billion chemical base pairs.

University of Leicester, UK, scientists printed out the entire human genome, filling 130 volumes with print that is almost too small to read. It would take an estimated 95 years to read this complete DNA code for one human. (Wikimedia Commons)

Knowledge of the human blueprint has served as a launchpad for major discoveries about human diseases, ushering in a new era in medical science. So today we celebrate National DNA Day to commemorate these advances in our understanding of the secret of life.

 

LEARN MORE

Find out more in our module DNA II: The Structure of DNA.

Read James Watson’s fascinating account of the discovery of the structure of DNA in The Double Helix, Simon & Schuster, 1968.

For more of the inside drama surrounding the discovery of the structure of DNA, see Victor K. McElheny’s Watson and DNA: Making a Scientific Revolution, Basic Books, 2004 (available on Google Books).

For a detailed look at Rosalind Franklin’s life and science, read Rosalind Franklin: The dark lady of DNA by Brenda Maddox, Harper Perennial, 2003.

Read more about the Human Genome Project.

Watch a televised DNA Day lecture, Harry Potter and the Genetics of Wizarding, on GenomeTVLive.

 

Written by

Bonnie Denmark holds an MA in linguistics and teacher certification in English, ESL, and Spanish. She has devoted her professional life to educational and accessibility issues as a computational linguist, multimedia curriculum developer, educator, and writer. She has also worked nationally and internationally as a language instructor, educational technology consultant, and teacher trainer. Bonnie joined the Visionlearning team as a literacy specialist in 2011, assisting the project by developing comprehension aids for science modules and creating other STEM learning materials.