Molecular structure of Nucleic Acids
Encyclopedia
The "Molecular structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid" was an article published by James D. Watson
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...

 and Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...

 in the scientific journal
Scientific journal
In academic publishing, a scientific journal is a periodical publication intended to further the progress of science, usually by reporting new research. There are thousands of scientific journals in publication, and many more have been published at various points in the past...

 Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...

in its 171st volume on pages 737–738 (dated April 25, 1953). It was the first publication
Publication
To publish is to make content available to the public. While specific use of the term may vary among countries, it is usually applied to text, images, or other audio-visual content on any medium, including paper or electronic publishing forms such as websites, e-books, Compact Discs and MP3s...

 which described the discovery of the double helix structure of DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

. This discovery had a major impact on biology
Biology
Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

, particularly in the field of genetics
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

.

This article is often termed a "pearl" of science because it is brief and contains the answer to a fundamental mystery about living
Life
Life is a characteristic that distinguishes objects that have signaling and self-sustaining processes from those that do not, either because such functions have ceased , or else because they lack such functions and are classified as inanimate...

 organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...

s. This mystery was the question of how it was possible that genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 instructions were held inside organisms and how they were passed from generation to generation. The article presents a simple and elegant solution, which surprised many biologists at the time who believed that DNA transmission was going to be more difficult to detail and understand.

The nature of the discovery

Watson and Crick's 1953 article contains the answer to a fundamental mystery about living organisms
Life on Earth
Life on Earth: A Natural History by David Attenborough is a television natural history series made by the BBC in association with Warner Bros. and Reiner Moritz Productions...

. The nature of their discovery was distinctive and in some ways unsurprising. What is hidden in the technical jargon of the title is that Watson and Crick's discovery of the chemical structure of DNA finally revealed how genetic instructions are stored inside organisms and passed from generation to generation.

Origins of molecular biology

The application of physics and chemistry to biological problems led to the development of molecular biology. Not all biology that concerns molecules falls into the category that is labelled "molecular biology". Molecular biology is particularly concerned with the flow and consequences of biological information at the level of gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

s and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. The discovery of the DNA double helix made clear that genes are functionally defined parts of DNA molecules and that there must be a way for cells to make use of their DNA genes in order to make proteins.

Linus Pauling
Linus Pauling
Linus Carl Pauling was an American chemist, biochemist, peace activist, author, and educator. He was one of the most influential chemists in history and ranks among the most important scientists of the 20th century...

 was a chemist who was very influential in developing an understanding of the structure of biological molecules. In 1951, Pauling published the structure of the alpha helix
Alpha helix
A common motif in the secondary structure of proteins, the alpha helix is a right-handed coiled or spiral conformation, in which every backbone N-H group donates a hydrogen bond to the backbone C=O group of the amino acid four residues earlier...

, a fundamentally important structural component of proteins. Early in 1953 Pauling published an incorrect triple helix model of DNA. Both Crick, and particularly Watson, thought that they were racing against Pauling to discover the structure of DNA.

Max Delbrück
Max Delbrück
Max Ludwig Henning Delbrück was a German-American biophysicist and Nobel laureate.-Biography:Delbrück was born in Berlin, German Empire...

 was a physicist who recognized some of the biological implications of quantum physics. Delbruck's thinking about the physical basis of life stimulated Erwin Schrödinger
Erwin Schrödinger
Erwin Rudolf Josef Alexander Schrödinger was an Austrian physicist and theoretical biologist who was one of the fathers of quantum mechanics, and is famed for a number of important contributions to physics, especially the Schrödinger equation, for which he received the Nobel Prize in Physics in 1933...

 to write the highly influential book, What Is Life?
What is Life? (Schrödinger)
What Is Life? is a 1944 non-fiction science book written for the lay reader by physicist Erwin Schrödinger. The book was based on a course of public lectures delivered by Schrödinger in February 1943, under the auspices of the Dublin Institute for Advanced Studies at Trinity College, Dublin...

Schrödinger's book was an important influence on Francis Crick
Francis Crick
Francis Harry Compton Crick OM FRS was an English molecular biologist, biophysicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson...

, James D. Watson
James D. Watson
James Dewey Watson is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA in 1953 with Francis Crick...

, and Maurice Wilkins
Maurice Wilkins
Maurice Hugh Frederick Wilkins CBE FRS was a New Zealand-born English physicist and molecular biologist, and Nobel Laureate whose research contributed to the scientific understanding of phosphorescence, isotope separation, optical microscopy and X-ray diffraction, and to the development of radar...

 who won a Nobel prize in Medicine for the discovery of the DNA double helix. Delbruck's efforts to promote the "Phage Group" (exploring genetics by way of the viruses that infect bacteria) was important in the early development of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...

 in general and the development of Watson's scientific interests in particular.

DNA structure and function

It is not always the case that the structure of a molecule is easy to relate to its function. What makes the structure of DNA so obviously related to its function was described modestly at the end of the article: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material".

The "specific pairing" is a key feature of the Watson and Crick model of DNA, the pairing of nucleotide
Nucleotide
Nucleotides are molecules that, when joined together, make up the structural units of RNA and DNA. In addition, nucleotides participate in cellular signaling , and are incorporated into important cofactors of enzymatic reactions...

 subunits. In DNA, the amount of guanine
Guanine
Guanine is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine . In DNA, guanine is paired with cytosine. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with...

 is equal to cytosine
Cytosine
Cytosine is one of the four main bases found in DNA and RNA, along with adenine, guanine, and thymine . It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached . The nucleoside of cytosine is cytidine...

 and the amount of adenine
Adenine
Adenine is a nucleobase with a variety of roles in biochemistry including cellular respiration, in the form of both the energy-rich adenosine triphosphate and the cofactors nicotinamide adenine dinucleotide and flavin adenine dinucleotide , and protein synthesis, as a chemical component of DNA...

 is equal to thymine
Thymine
Thymine is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine nucleobase. As the name suggests, thymine may be derived by methylation of uracil at...

. The A:T and C:G pairs are structurally similar. In particular, the length of each base pair is the same and they fit equally between the two phosphate backbones (Figure 2). The base pair
Base pair
In molecular biology and genetics, the linking between two nitrogenous bases on opposite complementary DNA or certain types of RNA strands that are connected via hydrogen bonds is called a base pair...

s are held together by hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...

s, a type of chemical attraction that is easy to break and easy to reform. After realizing the structural similarity of the A:T and C:G pairs, Watson and Crick soon produced their double helix model of DNA with the hydrogen bonds at the core of the helix providing a way to unzip the two complementary strands for easy replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

: the last key requirement for a likely model of the genetic molecule.

Indeed, the base-pairing did suggest a way to copy a DNA molecule. Just pull apart the two phosphate backbones, each with its hydrogen bonded A, T, G, and C components. Each strand could then be used as a template for assembly of a new base-pair complementary strand.

Future considerations

When Watson and Crick produced their double helix model of DNA, it was known that most of the specialized features of the many different life forms on Earth are made possible by protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. Structurally, proteins are long chains of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 subunits. In some way, the genetic molecule, DNA, had to contain instructions for how to make the thousands of proteins found in cells. From the DNA double helix model, it was clear that there must be some correspondence between the linear sequences of nucleotides in DNA molecules to the linear sequences of amino acids in proteins. The details of how sequences of DNA instruct cells to make specific proteins was worked out by molecular biologists during the period from 1953 to 1965. Francis Crick played an integral role in both the theory and analysis of the experiments that led to an improved understanding of the genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....

.

Consequences

Other advances in molecular biology stemming from the discovery of the DNA double helix eventually led to ways to sequence
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....

 genes. James Watson played an important role in getting government funding for the Human Genome Project
Human Genome Project
The Human Genome Project is an international scientific research project with a primary goal of determining the sequence of chemical base pairs which make up DNA, and of identifying and mapping the approximately 20,000–25,000 genes of the human genome from both a physical and functional...

. The ability to sequence and manipulate DNA is now central to the biotechnology
Biotechnology
Biotechnology is a field of applied biology that involves the use of living organisms and bioprocesses in engineering, technology, medicine and other fields requiring bioproducts. Biotechnology also utilizes these products for manufacturing purpose...

 industry and modern medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....

. The austere beauty of the structure and the practical implications of the DNA double helix combined to make Molecular structure of Nucleic Acids; A Structure for Deoxyribose Nucleic Acid one of the most prominent biology articles of the twentieth century.

Controversy

Watson and Crick based their molecular model of the DNA double helix on data that had been collected by researchers in several other laboratories. Watson and Crick were the first to put together all of the scattered fragments of information that were required to produce a successful molecular model of DNA.

Much of the data that were used by Crick and Watson came from unpublished work by Maurice Wilkins
Maurice Wilkins
Maurice Hugh Frederick Wilkins CBE FRS was a New Zealand-born English physicist and molecular biologist, and Nobel Laureate whose research contributed to the scientific understanding of phosphorescence, isotope separation, optical microscopy and X-ray diffraction, and to the development of radar...

, Rosalind Franklin
Rosalind Franklin
Rosalind Elsie Franklin was a British biophysicist and X-ray crystallographer who made critical contributions to the understanding of the fine molecular structures of DNA, RNA, viruses, coal and graphite...

,
A.R. Stokes, and H.R. Wilson
Herbert Wilson
Professor Herbert R. Wilson, FRS was a physicist, who was one of the team who worked on the structure of DNA at King's College London, under the direction of Sir John Randall.-College education:...

 at King's College London
King's College London
King's College London is a public research university located in London, United Kingdom and a constituent college of the federal University of London. King's has a claim to being the third oldest university in England, having been founded by King George IV and the Duke of Wellington in 1829, and...

 in the University of London
University of London
-20th century:Shortly after 6 Burlington Gardens was vacated, the University went through a period of rapid expansion. Bedford College, Royal Holloway and the London School of Economics all joined in 1900, Regent's Park College, which had affiliated in 1841 became an official divinity school of the...

. Key data from Wilkins, Stokes, and Wilson, and, separately, by Franklin and Gosling
Raymond Gosling
Raymond Gosling is a distinguished scientist who worked with both Maurice Wilkins and Rosalind Franklin at King's College London in deducing the structure of DNA, under the direction of Sir John Randall. His other KCL colleagues included Alex Stokes and Herbert Wilson.-Early years:He was born in...

, were published in two separate additional articles in the same issue of Nature with the article by Watson and Crick. The article by Watson and Crick did acknowledge that they had been "stimulated" by experimental results from the King's College researchers, and a similar acknowledgment was published by M. H. F. Wilkins, A.R. Stokes, and H. R. Wilson in the following three-page article.

In 1968, Watson published a highly controversial autobiographical account of the discovery of the double-helical, molecular structure of DNA called The Double Helix
The Double Helix
The Double Helix: A Personal Account of the Discovery of the Structure of DNA is an autobiographical account of the discovery of the double helix structure of DNA written by James D. Watson and published in 1968. It was and remains a controversial account...

, and which was not accepted—at least publicly—either by Francis Crick or by M.H.F. Wilkins. Furthermore, Erwin Chargaff
Erwin Chargaff
Erwin Chargaff was an American biochemist who emigrated to the United States during the Nazi era. Through careful experimentation, Chargaff discovered two rules that helped lead to the discovery of the double helix structure of DNA...

 also printed a rather "unsympathetic review" of James D. Watson's booklet in the March 29, 1968 issue of Science. In his `autobiographical' booklet, Watson stated among other things that he and Crick had access to some of Franklin's data from a source that she was not aware of, and also that he had seen—without her permission—the B-DNA X-ray diffraction pattern obtained by Franklin and Gosling in May 1952 at King's in London. In particular, in late 1952, Dr. Franklin had submitted a progress report to the Medical Research Council
Medical Research Council (UK)
The Medical Research Council is a publicly-funded agency responsible for co-ordinating and funding medical research in the United Kingdom. It is one of seven Research Councils in the UK and is answerable to, although politically independent from, the Department for Business, Innovation and Skills...

, which was reviewed by Dr. Max Perutz, then at The Cavendish Laboratory of the University of Cambridge
University of Cambridge
The University of Cambridge is a public research university located in Cambridge, United Kingdom. It is the second-oldest university in both the United Kingdom and the English-speaking world , and the seventh-oldest globally...

, UK. Watson and Crick also worked in the MRC-supported Cavendish Laboratory in Cambridge whereas Drs. Wilkins and Franklin were in the MRC supported laboratory at King's in London. Such MRC reports were not usually widely circulated, but Crick read a copy of Dr. Franklin's research summary in early 1953.

Max Perutz's justification for passing this information to both Crick and Watson was that the report contained information which Watson has previously heard in November 1951 when Dr. Franklin talked about her unpublished results with Raymond Gosling
Raymond Gosling
Raymond Gosling is a distinguished scientist who worked with both Maurice Wilkins and Rosalind Franklin at King's College London in deducing the structure of DNA, under the direction of Sir John Randall. His other KCL colleagues included Alex Stokes and Herbert Wilson.-Early years:He was born in...

 during a meeting arranged by Dr. M.H.F. Wilkins at King's College, following a request from Crick and Watson; this justification does not hold however for Crick who was not present at this November 1951 meeting, but who also was given access by Max Perutz to Franklin's MRC report data which prompted Crick and Watson to seek permission from Sir Lawrence Bragg--who was at the time the head of the Cavendish Laboratory
Cavendish Laboratory
The Cavendish Laboratory is the Department of Physics at the University of Cambridge, and is part of the university's School of Physical Sciences. It was opened in 1874 as a teaching laboratory....

 in Cambridge—to publish in Nature their double-helix molecular model of DNA based on Franklin's and also Wilkins's data. Moreover, in November 1951 Watson had acquired—by his own admission—little training in X-ray crystallography, and therefore had not fully understood (again, according to his own admission, in "The Double Helix") what Dr. Franklin was saying about the structural symmetry of the DNA molecule. Crick, however, knowing the Fourier transforms of Bessel functions that represent the X-ray diffraction patterns of helical structures of atoms, correctly interpreted further one of Dr.Franklin's experimental findings as indicating that DNA was most likely to be a double helix with the two polynucleotide chains running in opposite directions. Crick was thus in a unique position to make this interpretation because he had previously worked on the X-ray diffraction data for other large molecules that had similar, helical symmetry to that of DNA. Dr. Franklin, on the other hand, rejected at first the molecular model building approach proposed by Crick and Watson because their first DNA model presented by Watson to her and Dr. M.H.F. Wilkins in 1952 in London had an obviously incorrect structure with hydrated charged groups on the inside of the model, rather than on the outside, as explicitly admitted by James D. Watson in his "Double Helix" booklet.
It is therefore questioned whether Crick's colleague, Dr.Max Perutz
Max Perutz
Max Ferdinand Perutz, OM, CH, CBE, FRS was an Austrian-born British molecular biologist, who shared the 1962 Nobel Prize for Chemistry with John Kendrew, for their studies of the structures of hemoglobin and globular proteins...

, acted unethically by allowing Crick access to Dr. Franklin's MRC report about the crystallographic unit of the B-DNA and A-DNA structures. Dr. Perutz claimed, however, that he believed he had not because this report was not confidential, and had been designed as part of an effort to promote contact between different MRC research groups.

See also

  • DNA
    DNA
    Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

  • X-ray scattering
  • Paracrystal model and theory
    Paracrystalline
    Paracrystalline materials are defined as having short and medium range ordering in their lattice but lacking long-range ordering at least in one direction....

  • Crystallography
    Crystallography
    Crystallography is the experimental science of the arrangement of atoms in solids. The word "crystallography" derives from the Greek words crystallon = cold drop / frozen drop, with its meaning extending to all solids with some degree of transparency, and grapho = write.Before the development of...

  • Nucleic acid modeling

Books about the discovery of the double-helical structure of DNA

(with foreword by Francis Crick; revised in 1994, with a 9 page postscript.) (first published in 1968)

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