A Structure for Deoxyribose Nucleic Acid
A Structure for Deoxyribose Nucleic Acid
Journal article
By: Frances Harry Compton Crick
Date: April 2, 1953
Source: J. D. Watson and F. H. C. Crick. "A Structure for Deoxyribose Nucleic Acid." Nature (1953): 171, 737-738.
About the Author: James Dewey Watson (1928–) was born in Chicago, Illinois, on April 6, 1928. Watson's early days were spent in Chicago, where he attended Horace Mann Grammar School for eight years and South Shore High School for two years. Immediately after that, he received a tuition scholarship to the University of Chicago and, in the summer of 1943, entered their experimental four-year college. In 1947, he received a B.Sc. degree in zoology. During these years his boyhood interest in bird-watching had matured into a serious desire to learn genetics. Francis Harry Compton Crick (1916–2004) was born on June 8, 1916, at Northampton, England. Crick was educated at Northampton Grammar School and Mill Hill School, London. He studied physics at the University College, London, obtained a B.Sc. in 1937, and started research for a Ph.D., but, in 1939, this academic work was interrupted by World War II. During the war he worked as a scientist for the British Admiralty, where he designed acoustic and magnetic mines for naval warfare. He left the Admiralty in 1947 to study biology. Watson met Crick at the Cavendish Laboratory, Cambridge, England, in 1951, where they discovered their common interest in solving the DNA structure. They thought it should be possible to correctly deduce its structure, given both the experimental evidence generated by Rosalind Franklin (1920–1958) and the careful examination of all possible stereochemical configurations of polynucleotide chains.
INTRODUCTION
Watson and Crick staked their claim for scientific immortality with the introductory sentence: "We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.)." This could have seemed an audacious sentence, but when put into context it was, indeed, a quite modest way to start a milestone article entitled "Molecular Structure of Nucleic Acids," published in the British journal Nature on April 2, 1953.
In the less-than-two-page article, the secret of life was unraveled, revolutionizing many fields of biology, especially genetics, evolution, and medicine. The DNA structure discovery also garnered Watson and Crick, together with their co-worker Maurice H. F. Wilkins (1916–2004), the Nobel Prize in Physiology or Medicine in 1962. But why is such accomplishment so striking? And how did it change our lives?
All living organisms are assembled by a set of commands carried as a linear information string, the DNA molecule. This molecule shares a common line of descent with the first cell that arose on this planet. DNA carries the information of how life is made. DNA's recipe is written in nucleotide (nitrogenous base) sequences, so that amino acids are correctly put together to make proteins. This recipe is uninterruptedly used throughout the lifespan of all organisms.
The DNA molecule is a double-stranded helix that resembles a twisted ladder. Each strand of the helix includes only four different deoxyribonucleotides, adenine (A), thymine (T), cytosine (C), and guanine (G). Nucleotides in the double helix are complementary to each other, so if in one strand there is an A at a particular position, a T is found at the same position in the other strand. The same situation occurs with C and G. The main forces that stabilize the double helix are: hydrophobic interactions, base stacking, and hydrogen bonds. Because the nucleotide interior is hydrophobic, it is pushed away from the aqueous environment and grouped together in order to establish a water-free core. After this first structural decision, the hydrophobic parts of consecutive nucleotides are stacked on the top of each other making a very strong, but somewhat flexible structure. Finally, complementary nucleotides on opposing strands are aligned correctly by hydrogen bonds. Proteins are synthesized by reading the DNA string in nucleotide triplets, or codons, and translating each triplex into the amino acid it codes for. Several amino acids are linked together to form proteins, which are the molecules necessary for most known functions performed by a living cell.
Furthermore, DNA is a heritable molecule, passed through linear generations. The complementarity of nucleotides provides a means for the transmission of hereditary traits from one generation to the next. Because DNA harbors the code of life and because it also holds information concerning the evolution of all living organisms, the discovery of its structure is one of the most important accomplishments of science.
As envisioned by Ritchie Calder, a British journalist, discovering how these chemical "cards" are shuffled and paired kept scientists busy for fifty years after the golden year of 1953.
PRIMARY SOURCE
A STRUCTURE FOR DEOXYRIBOSE NUCLEIC ACID
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.
A structure for nucleic acid has already been proposed by Pauling and Corey. They kindly made their manuscript available to us in advance of publication. Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside. In our opinion, this structure is unsatisfactory for two reasons: (1) We believe that the material which gives the X-ray diagrams is the salt, not the free acid. Without the acidic hydrogen atoms it is not clear what forces would hold the structure together, especially as the negatively charged phosphates near the axis will repel each other. (2) Some of the van der Waals distances appear to be too small.
Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.
We wish to put forward a radically different structure for the salt of deoxyribose nucleic acid. This structure has two helical chains each coiled round the same axis….
… The structure is an open one, and its water content is rather high. At lower water contents we would expect the bases to tilt so that the structure could become more compact.
The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases. The planes of the bases are perpendicular to the fibre axis. They are joined together in pairs, a single base from one chain being hydrogen-bonded to a single base from the other chain, so that the two lie side by side with identical z-co-ordinates. One of the pair must be a purine and the other a pyrimidine for bonding to occur. The hydrogen bonds are made as follows: purine position 1 to pyrimidine position 1; purine position 6 to pyrimidine position 6.
If it is assumed that the bases only occur in the structure in the most plausible tautomeric forms (that is, with the keto rather than the enol configurations) it is found that only specific pairs of bases can bond together. These pairs are: adenine (purine) with thymine (pyrimidine), and guanine (purine) with cytosine (pyrimidine).
In other words, if an adenine forms one member of a pair, on either chain, then on these assumptions the other member must be thymine; similarly for guanine and cytosine. The sequence of bases on a single chain does not appear to be restricted in any way. However, if only specific pairs of bases can be formed, it follows that if the sequence of bases on one chain is given, then the sequence on the other chain is automatically determined.
It has been found experimentally that the ratio of the amounts of adenine to thymine, and the ratio of guanine to cytosine, are always very close to unity for deoxyribose nucleic acid.
It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose, as the extra oxygen atom would make too close a van der Waals contact. The previously published X-ray data on deoxyribose nucleic acid are insufficient for a rigorous test of our structure. So far as we can tell, it is roughly compatible with the experimental data, but it must be regarded as unproved until it has been checked against more exact results. Some of these are given in the following communications. We were not aware of the details of the results presented there when we devised our structure, which rests mainly though not entirely on published experimental data and stereochemical arguments.
It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.
Full details of the structure, including the conditions assumed in building it, together with a set of co-ordinates for the atoms, will be published elsewhere.
We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances. We have also been stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King's College, London. One of us (J. D. W.) has been aided by a fellowship from the National Foundation for Infantile Paralysis.
J. D. WATSON F. H. C. CRICK
SIGNIFICANCE
The knowledge about DNA's molecule structure has shed light on the mystery of life and since then, has transformed the way humankind sees itself. In spite of its great significance, the DNA structure story also harbors one of the most famous cases of unsung heroes science has ever known. Her name is Rosalind Franklin, from whom Watson and Crick obtained the DNA X-ray photographs, as acknowledged by Watson. Franklin also was attempting to discover DNA's structure, and almost deciphered the images, when Watson and Crick published their manuscript in 1953. Rosalind Franklin died in 1958, at the age of 37, from ovarian cancer.
Molecular biology and modern genetics have grown dramatically in the past fifty-two years. After cracking the DNA molecule, many advances have been possible through a biotechnological revolution, such as: the sequencing of entire genomes; the laboratory production of many proteins (such as human insulin and growth hormone, which are now obtained from bacteria as a result of recombinant DNA techniques), and the promise of gene therapy for diseases such as cancer. Moreover, DNA information is now assembled in minuscule spaces, so that thousands of genes can be tested simultaneously and effortlessly, creating new promises for the next fifty years of research. Nonetheless, we must learn with this great discovery that science and development must be pursued under the highest principles of integrity, ethics, and respect for life.
FURTHER RESOURCES
Books
Maddox, Brenda. Rosalind Franklin: The Dark Lady of DNA. London: Harper Collins, 2002.
Watson, James. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. New York: Touchstone, 2001.
Watson, James, and Andrew Berry. DNA: The Secret of Life. New York: Knopf, 2003.
Periodicals
Dennis, Carina, and Philip Campbell. "The Eternal Molecule." Nature 421 (January 23, 2003): 396.
Gibbs, Nancy, Michael Lemonick, James Watson, et al. "Solving the Mysteries of DNA—The DNA Revolution." Time 161 (February 17, 2003).
Web sites
Cold Spring Harbor Laboratory. "James D. Watson: Chancellor." 〈http://www.cshl.edu/gradschool/jdw_.html〉 (accessed November 6, 2005).
DNA from the Beginning. "The DNA Molecule is Shaped like a Twisted Ladder." 〈http://www.dnaftb.org/dnaftb/19/concept/index.html〉 (accessed November 6, 2005).
Nobel Prize.org. "The Nobel Prize in Physiology or Medicine 1962." 〈http://nobelprize.org/medicine/laureates/1962/index.html〉 (accessed November 6, 2005).
Time. "Scientists & Thinkers: James Watson & Francis Crick." 〈http://www.time.com/time/time100/scientist/profile/watsoncrick.html〉 (accessed November 6, 2005).
Audio and visual media
DNA: The Amazing Double Helix, produced by Educational Video Network, Inc., 2000 (DVD).
DNA: The Secret of Life, created by the Moorehead Planetarium and Science Center. Windfall Films, 2003 (DVD).
Understanding DNA, produced by Educational Video Network, Inc., 2004 (DVD).
WGBH. Nova. "Cracking the Code of Life." Available from 〈http://www.pbs.org/wgbh/nova/genome/program.html〉 (with video link; accessed December 14, 2005).