that it had solved the puzzle, proposing that DNA was a triple‐stranded helix. Pauling, who had already uncovered the structure of proteins, was perhaps overzealous in his pursuit of deciphering the structure of DNA, and as a result, one of the greatest chemists in the world made an error in his calculations. (73) Scientists in England quickly picked up on Pauling’s mistake. Watson and Crick recognized the error immediately as one they had almost made more than a year earlier. In the wake of this miscalculation they quickened the pace of their own research. (74)
Figure 1.8 James Watson and Francis Crick are seen here at Cambridge University around the time of their discovery of the structure of DNA.
Credit: DNA Learning Center, Cold Spring Harbor Laboratory
In the early 1950s the Cavendish Laboratory at Cambridge University housed an amazing faculty of physicists, biologists, and chemists who helped create an atmosphere in which Watson and Crick could conceive of and construct models of the structure of DNA. One of the important experimental tools that Watson and Crick utilized was “pictures” of molecules. This required special physical and chemical techniques because molecules are so small. Snapshots could be taken of these extremely small molecules by first making crystals of proteins and other small molecules like nucleic acids. To take a “snapshot” of DNA, small waves of X‐rays were passed through the crystals. The diffraction of these X‐rays by the atoms in the DNA crystal were in essence “pictures” of these extremely small molecules. This technique, known as X‐ray crystallography, allowed the scientists at Cavendish and other laboratories to interpret the three‐dimensional structure for any molecule that could be crystallized.
Rosalind Franklin, a physical chemist at King’s College, London, was also working on solving the structure of DNA and happened to be one of the world’s leading X‐ray crystallographers.
Figure 1.9 Once called the “dark lady” by her colleague Maurice Wilkins, Rosalind Franklin’s valuable scientific work and her important role in the discovery of the structure of DNA have often been overlooked.
Credit: DNA Learning Center, Cold Spring Harbor Laboratory
Her DNA photos were once described as “among the most beautiful X‐ray photographs of any substance ever taken.” (75) Just a few weeks into 1953, one of these snapshots was shown to James Watson without her knowledge or permission. Watson wrote in The Double Helix, his memoir of the discovery of the structure of DNA, that “the instant I saw the picture my mouth fell open and my pulse began to race.” (76) Franklin’s superior X‐ray crystallography enabled Watson and Crick to take the intellectual leap they had needed to complete their model of DNA.
Using X‐ray data, including the measurements of the shape of DNA shown in Franklin’s photo, Watson and Crick, piece by piece, figured out that DNA was shaped like a spiral staircase or a double helix. (77) The hereditary molecule was two chains of nucleic acids connected to one another like two snakes coiled together. The sugar backbones of the nucleotides are like supports under each step in a staircase. The nucleotide bases bond to form structures that are like steps, each one rotated slightly in relation to its neighbors in the stack. The steps that span from rail to rail of each side of the staircase are of equal length because of the specific way that two nucleotides pair. To develop their model of DNA, Watson and Crick followed Chargaff’s rules closely and discovered that the double helix was complementary. That is, to form the staircase an A on one strand is always directly across from and connected to a T on the other; likewise, a G on one strand is always directly across from and connected to a C on the other. The complementary nature of the double helix revealed how DNA replicated itself and passed genetic information between generations. This process occurs during cell division when the double helix splits apart and makes identical copies of itself.
Figure 1.10 Franklin’s X‐ray crystallography of DNA, shown to James Watson without her knowledge, helped Watson and Crick solve the puzzle of DNA. Franklin was renowned for her X‐ray crystallography talents.
Credit: Normal Collection for the History of Molecular Biology
Chargaff’s rules made Watson and Crick’s three‐dimensional model a reality. The great strength of Watson and Crick lay in their ability to reconcile their model with existing science. None of the other participants in this discovery put the pieces together quite as Watson and Crick had. And so they built their model.
There are three important chemical forces that hold together the DNA molecule. The first chemical bond, hydrogen bonds between a G and a C or an A and a T, connects the two strands of the helix. These bonds are relatively weak and can be broken apart by acids and/or heat. At approximately 90 °C the hydrogen bonds across a double helix can be broken, allowing the two strands of the double helix to separate.
The second kind of bond, the phosphodiester bond, keeps the Gs, As, Ts, and Cs together along a helix’s strand. These bonds can be made on both ends of a base and to any other base, resulting in long strands of Gs, As, Ts, and Cs. Phosphodiester bonds are the strongmen of the helix, withstanding high temperatures and even highly acidic conditions. It is the position of these bonds on the nucleotide carbon rings that gives DNA its helical twist, its third dimension. Molecular biology takes advantage of the characteristics of both hydrogen and phosphodiester bonds all the time. Because of the difference in relative strengths between these bonds, scientists would later figure out how to separate the two DNA strands. Why is this so important? Because to make copies of a double helix, you need to have both strands—let’s call them the Watson and Crick strands—as a template. If they are bonded in a double helix, they cannot be used to replicate themselves. By melting the weak hydrogen bonds between the two strands, the freed strands can now be copied.
Figure 1.11 This diagram shows the double helix structure of DNA. In the model you can see where hydrogen bonds bond the nucleic acids to one another and also the sugar‐phosphate backbone that holds the helix in place.
Credit: Wiley Publishers
The race to uncover the structure of DNA became the stuff of scientific legend after the publication in 1968 of James Watson’s The Double Helix. Watson’s telling of the DNA story drew ire from within the small community of scientists in which he himself worked. Facing strong objections from Francis Crick, Linus Pauling, Maurice Wilkins, and the family of Rosalind Franklin over the way in which Watson characterized all of the major players in the discovery, Harvard University Press dropped the book. (78) Of particular concern was Watson’s portrayal of Franklin, who was just 37 when she died in 1958 of ovarian cancer and whose role in the discovery was reduced in The Double Helix to that of an incompetent scientist and hot‐tempered woman. (79) Watson’s book, picked up by another publisher, went on to become a best‐seller, and for almost 30 years the story of the discovery of DNA was told by The Double Helix. It is only recently, with the publication of a new biography and with acknowledgments by Watson that Franklin’s work was “key” to their success, that Franklin’s image as a brilliant scientist was rehabilitated. Years after his own co‐discovery of the structure of the double helix, Francis Crick suggested that Franklin was just months away from solving the puzzle herself. (80)
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