"Molecular Structure of Nucleic Acids: A Structure for Deoxyribose Nucleic Acid" was the first article

published Publishing is the activity of making information, literature, music, software and other content available to the public for sale or for free. Traditionally, the term refers to the creation and distribution of printed works, such as books, news ...

to describe the discovery of the

double helix A double is a look-alike or doppelgänger; one person or being that resembles another. Double, The Double or Dubble may also refer to: Film and television * Double (filmmaking), someone who substitutes for the credited actor of a character * ...

structure of DNA, using

X-ray diffraction X-ray crystallography is the experimental science determining the atomic and molecular structure of a crystal, in which the crystalline structure causes a beam of incident X-rays to diffract into many specific directions. By measuring the angles ...

and the mathematics of a

helix A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helic ...

transform. It was published by

Francis Crick Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical stru ...

and James D. Watson in the

scientific journal In academic publishing, a scientific journal is a periodical publication intended to further the progress of science, usually by reporting new research. Content Articles in scientific journals are mostly written by active scientists such ...

Nature Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...

'' on pages 737–738 of its 171st volume (dated 25 April 1953). DNA-structure-and-bases

This article is often termed a "pearl" of science because it is brief and contains the answer to a fundamental mystery about

living Living or The Living may refer to: Common meanings *Life, a condition that distinguishes organisms from inorganic objects and dead organisms ** Living species, one that is not extinct *Personal life, the course of an individual human's life * H ...

organism In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells ( cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and fu ...

s. This mystery was the question of how it is possible that genetic instructions are held inside organisms and how they are 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 deduce and understand. The discovery had a major impact on

biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary ...

, particularly in the field of

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar work ...

, enabling later researchers to understand the

genetic code The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...

Evolution of molecular biology

The application of physics and chemistry to biological problems led to the development of molecular biology, which is particularly concerned with the flow and consequences of biological information from DNA to

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

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 translate the information in DNA to specific amino acids, which are used in order to make proteins.

Linus Pauling Linus Carl Pauling (; February 28, 1901August 19, 1994) was an American chemist, biochemist, chemical engineer, peace activist, author, and educator. He published more than 1,200 papers and books, of which about 850 dealt with scientific topi ...

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 The alpha helix (α-helix) is a common motif in the secondary structure of proteins and is a right hand- helix conformation in which every backbone N−H group hydrogen bonds to the backbone C=O group of the amino acid located four residues ...

, a fundamentally important structural component of proteins. In early 1953, Pauling published a triple helix model of DNA, which subsequently turned out to be incorrect. Both Crick, and particularly Watson, thought that they were racing against Pauling to discover the structure of DNA.

Max Delbrück Max Ludwig Henning Delbrück (; September 4, 1906 – March 9, 1981) was a German–American biophysicist who participated in launching the molecular biology research program in the late 1930s. He stimulated physical scientists' interest int ...

was a physicist who recognized some of the biological implications of

quantum physics Quantum mechanics is a fundamental theory in physics that provides a description of the physical properties of nature at the scale of atoms and subatomic particles. It is the foundation of all quantum physics including quantum chemistry, qua ...

. Delbruck's thinking about the physical basis of life stimulated

Erwin Schrödinger Erwin Rudolf Josef Alexander Schrödinger (, ; ; 12 August 1887 – 4 January 1961), sometimes written as or , was a Nobel Prize-winning Austrian physicist with Irish citizenship who developed a number of fundamental results in quantum theo ...

to write, ''

What Is Life? ''What Is Life? The Physical Aspect of the Living Cell'' is a 1944 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 ...

'' Schrödinger's book was an important influence on Crick and Watson. Delbruck's efforts to promote the "

Phage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacter ...

Group" (exploring genetics by way of the viruses that infect bacteria) was important in the early development of

molecular biology Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and phys ...

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

Maurice Wilkins Maurice Hugh Frederick Wilkins (15 December 1916 – 5 October 2004) was a New Zealand-born British biophysicist and Nobel laureate whose research spanned multiple areas of physics and biophysics, contributing to the scientific understanding ...

who won the

Nobel Prize for Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, according ...

in recognition of their discovery of the DNA double helix.

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". Dna-split

The "specific pairing" is a key feature of the Watson and Crick model of DNA, the pairing of

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecu ...

subunits. In DNA, the amount of

guanine Guanine () ( symbol G or Gua) is one of the four main nucleobases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside is ...

is equal to

cytosine Cytosine () ( symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine ( uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached ( ...

and the amount of

adenine Adenine () ( symbol A or Ade) is a nucleobase (a purine derivative). It is one of the four nucleobases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The three others are guanine, cytosine and thymine. Its deriv ...

is equal to

thymine Thymine () ( symbol T or Thy) 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 pyrimidin ...

. 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 sugar-phosphate backbones. The

base pair A base pair (bp) is a fundamental unit of double-stranded nucleic acids consisting of two nucleobases bound to each other by hydrogen bonds. They form the building blocks of the DNA double helix and contribute to the folded structure of both D ...

s are held together by

hydrogen bond In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...

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

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: 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 sugar-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

s. Structurally, proteins are long chains of

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

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

Consequences

Other advances in molecular biology stemming from the discovery of the DNA double helix eventually led to ways to

sequence In mathematics, a sequence is an enumerated collection of objects in which repetitions are allowed and order matters. Like a set, it contains members (also called ''elements'', or ''terms''). The number of elements (possibly infinite) is called ...

genes. James Watson directed the

Human Genome Project The Human Genome Project (HGP) was an international scientific research project with the goal of determining the base pairs that make up human DNA, and of identifying, mapping and sequencing all of the genes of the human genome from both ...

at the

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the lat ...

. The ability to sequence and manipulate DNA is now central to the

biotechnology Biotechnology is the integration of natural sciences and engineering sciences in order to achieve the application of organisms, cells, parts thereof and molecular analogues for products and services. The term ''biotechnology'' was first used ...

industry and modern

medicine Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...

. 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.

Collaborators and controversy

Although Watson and Crick were first to put together all the scattered fragments of information that were required to produce a successful molecular model of DNA, their findings had been based on data collected by researchers in several other laboratories. For example, they drew on published research relating to the discovery of Hydrogen bonds in DNA by John Masson Gulland, Denis Jordan and their colleagues at

University College Nottingham , mottoeng = A city is built on wisdom , established = 1798 – teacher training college1881 – University College Nottingham1948 – university status , type = Public , chancellor ...

in 1947. However the discovery of the DNA double helix also used a considerable amount of material from the unpublished work of

Rosalind Franklin Rosalind Elsie Franklin (25 July 192016 April 1958) was a British chemist and X-ray crystallographer whose work was central to the understanding of the molecular structures of DNA (deoxyribonucleic acid), RNA (ribonucleic acid), viruses, ...

, A.R. Stokes,

, and H.R. Wilson at

King's College London King's College London (informally King's or KCL) is a public research university located in London, England. King's was established by royal charter in 1829 under the patronage of King George IV and the Duke of Wellington. In 1836, King's ...

. Key data from Wilkins, Stokes, and Wilson, and, separately, by Franklin and Gosling, 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 acknowledged that they had been "stimulated" by experimental results from the King's College researchers, and a similar acknowledgment was published by Wilkins, Stokes, and 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'', which was not publicly accepted either by Crick or Wilkins. Furthermore,

Erwin Chargaff Erwin Chargaff (11 August 1905 – 20 June 2002) was an Austro-Hungarian-born American biochemist, writer, Bucovinian Jew who emigrated to the United States during the Nazi era, and professor of biochemistry at Columbia University medical scho ...

also printed a rather "unsympathetic review" of Watson's book in the 29 March 1968 issue of ''Science''. In the book, 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, Franklin had submitted a progress report to the Medical Research Council, which was reviewed by

Max Perutz Max Ferdinand Perutz (19 May 1914 – 6 February 2002) 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 haemoglobin and myoglobin. He went ...

, then at the

Cavendish Laboratory The Cavendish Laboratory is the Department of Physics at the University of Cambridge, and is part of the School of Physical Sciences. The laboratory was opened in 1874 on the New Museums Site as a laboratory for experimental physics and is named ...

of the

University of Cambridge , mottoeng = Literal: From here, light and sacred draughts. Non literal: From this place, we gain enlightenment and precious knowledge. , established = , other_name = The Chancellor, Masters and Schola ...

. Watson and Crick also worked in the MRC-supported Cavendish Laboratory in Cambridge whereas 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 Franklin's research summary in early 1953. (first published in 1968) Perutz's justification for passing Franklin's report about the crystallographic unit of the B-DNA and A-DNA structures to both Crick and Watson was that the report contained information which Watson had heard before, in November 1951, when Franklin talked about her unpublished results with

Raymond Gosling Raymond George Gosling (15 July 1926 – 18 May 2015) was a British scientist. While a PhD student at King's College, London he worked under the supervision of Maurice Wilkins and Rosalind Franklin. The crystallographic experiments of Frankli ...

during a meeting arranged by M.H.F. Wilkins at King's College, following a request from Crick and Watson; Perutz said he had not acted unethically because the report had been part of an effort to promote wider contact between different MRC research groups and was not confidential. This justification would exclude Crick, who was not present at the November 1951 meeting, yet Perutz also gave him access to Franklin's MRC report data. Crick and Watson then sought permission from Cavendish Laboratory head

William Lawrence Bragg Sir William Lawrence Bragg, (31 March 1890 – 1 July 1971) was an Australian-born British physicist and X-ray crystallographer, discoverer (1912) of Bragg's law of X-ray diffraction, which is basic for the determination of crystal structu ...

, to publish their double-helix molecular model of DNA based on data from Franklin and Wilkins. By November 1951, Watson had acquired little training in X-ray crystallography, by his own admission, and thus had not fully understood what 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 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 formerly worked on the X-ray diffraction data for other large molecules that had helical symmetry similar to that of DNA. Franklin, on the other hand, rejected the first molecular model building approach proposed by Crick and Watson: the first DNA model, which in 1952 Watson presented to her and to Wilkins in London, had an obviously incorrect structure with hydrated charged groups on the inside of the model, rather than on the outside. Watson explicitly admitted this in his book '' The Double Helix''.

References

Bibliography

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

Life Story (TV film) ''Life Story'' (known as ''The Race for the Double Helix'' in the United States) is a 1987 television historical drama which depicts the progress toward, and the competition for, the discovery of the structure of DNA in the early 1950s. It was ...

a BBC dramatization about the scientific race to discover the DNA double-helix.

External links

Annotated copy of the article
from San Francisco's

Exploratorium The Exploratorium is a museum of science, technology, and arts in San Francisco, California. Characterized as "a mad scientist's penny arcade, a scientific funhouse, and an experimental laboratory all rolled into one", the participatory natu ...

Access Excellence Classic Collection article on DNA structure

Online versions

Online version (Original text) at nature.com
*National Library of Medicine'
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in th
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*Commemorativ
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Am J Psychiatry 160:623-624, April 2003. {{Authority control 1953 documents Biology papers Genetics in the United Kingdom History of biology History of genetics James Watson Nucleic acids Works originally published in Nature (journal) 1953 in biology