with permission from Nature magazine
Structure for Deoxyribose Nucleic Acid
D. Watson and F. H. C. Crick
April 25, 1953 (2),
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 (4)
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.
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.
wish to put forward a radically different structure
for the salt of deoxyribose nucleic acid (5).
This structure has two helical chains each coiled round the same axis
(see diagram). We have made the usual chemical assumptions, namely, that
each chain consists of phosphate diester groups joining beta-D-deoxyribofuranose
residues with 3',5' linkages. The two chains (but not their bases) are
related by a dyad perpendicular to the fibre axis. Both chains follow
right-handed helices, but owing to the dyad the sequences of the atoms
in the two chains run in opposite directions
(6) . Each chain loosely resembles Furberg's2
model No. 1 (7); that is, the bases are on the inside of the
helix and the phosphates on the outside. The configuration of the sugar
and the atoms near it is close to Furberg's "standard configuration,"
the sugar being roughly perpendicular to the attached base. There is a
residue on each every 3.4 A. in the z-direction. We have assumed
an angle of 36° between adjacent residues in the same chain, so that
the structure repeats after 10 residues on each chain, that is, after
34 A. The distance of a phosphorus atom from the fibre axis is 10 A. As
the phosphates are on the outside, cations have easy access to them.
figure is purely diagrammatic
The two ribbons symbolize the two phophate-sugar chains, and the horizonal
rods the pairs of bases holding the chains together. The vertical
line marks the fibre 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 hydroden-bonded to a single
base from the other chain, so that the two lie side by side with identical
z-coordinates. 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
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) (9).
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 (10)3,4
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
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 data5,6
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 (11). We were not
aware of the details of the results presented there when we devised our
structure (12), which rests mainly though not entirely on published
experimental data and stereochemical arguments.
has not escaped our notice (13)
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 coordinates for the atoms, will
be published elsewhere (14).
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 (15).
One of us (J. D. W.) has been aided by a fellowship from the National
Foundation for Infantile Paralysis.
Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc.
U.S. Nat. Acad. Sci., 39, 84 (1953).
Furberg, S., Acta Chem. Scand., 6, 634 (1952).
Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff,
E., Biochim. et Biophys. Acta, 9, 402 (1952).
Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).
Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ.
Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta,
10, 192 (1953).
(1) It’s no surprise that James D. Watson and Francis H. C.
Crick spoke of finding the structure of DNA within minutes of their first
meeting at the Cavendish Laboratory in Cambridge, England, in 1951. Watson,
a 23-year-old geneticist, and Crick, a 35-year-old former physicist studying
protein structure for his doctorate in biophysics, both saw DNA’s
architecture as the biggest question in biology. Knowing the structure
of this molecule would be the key to understanding how genetic information
is copied. In turn, this would lead to finding cures for human diseases.
Aware of these profound implications, Watson and Crick were obsessed with
the problem—and, perhaps more than any other scientists, they were
determined to find the answer first. Their competitive spirit drove them
to work quickly, and it undoubtedly helped them succeed in their quest.
Watson and Crick’s rapport led them to speedy insights as well.
They incessantly discussed the problem, bouncing ideas off one another.
This was especially helpful because each one was inspired by different
evidence. When the visually sensitive Watson, for example, saw a cross-shaped
pattern of spots in an X-ray photograph of DNA, he knew DNA had to be
a double helix. From data on the symmetry of DNA crystals, Crick, an expert
in crystal structure, saw that DNA’s two chains run in opposite
Since the groundbreaking double helix discovery in 1953, Watson has used
the same fast, competitive approach to propel a revolution in molecular
biology. As a professor at Harvard in the 1950s and 1960s, and as past
director and current president of Cold Spring Harbor Laboratory, he tirelessly
built intellectual arenas—groups of scientists and laboratories—to
apply the knowledge gained from the double helix discovery to protein
synthesis, the genetic code, and other fields of biological research.
By relentlessly pushing these fields forward, he also advanced the view
among biologists that solving major health problems requires research
at the most fundamental level of life.
On this date, Nature published the paper you
According to science historian Victor McElheny of the Massachusetts Institute
of Technology, the publication of this paper helped change how scientists
approached biology. Increasingly in the 1950s, biologists were working
out the fundamental mechanisms of life—an undertaking that involved
figuring out how genetic information is stored and transmitted. The discovery
of the double-helix structure of DNA gave momentum to this kind of work.
Historians wonder how the timing of the DNA race affected its outcome.
After years of being diverted by the war effort, scientists were able
to focus more on problems such as those affecting human health. Yet, in
the United States, many research fields were threatened by a curb on the
free exchange of ideas. During the McCarthy era in the early 1950s, the
U.S. State Department denied American researcher Linus Pauling a passport
to travel internationally. Some think Pauling might have beaten Watson
and Crick to the punch if Paulings ability to travel had not been
(founded in 1869)—and hundreds of other scientific journalshelp
push science forward by providing a venue for researchers to publish and
debate findings. Today, journals also validate the quality of this research
through a rigorous evaluation called peer review. Generally at least two
scientists, selected by the journal’s editors, judge the quality
and originality of each paper, recommending whether or not it should be
Science publishing was a different game when Watson and Crick submitted
this paper to Nature. With no formal review process at most journals,
editors usually reached their own decisions on submissions, seeking advice
informally only when they were unfamiliar with a subject.
(4) The effort
to discover the structure of DNA was a race among several players: world-renowned
chemist Linus Pauling at the California Institute of Technology, X-ray
crystallographers Maurice Wilkins and Rosalind Franklin at Kings
College London, and Watson and Crick at the Cavendish Laboratory, Cambridge
The competitive juices
were flowing well before the DNA sprint was in high gear. In 1951, Pauling
narrowly beat scientists at the Cavendish Lab, a top center for probing
protein structure, to the discovery that proteins are arranged in structures
called alpha-helices. The defeat stung. When Pauling sent a paper to be
published in early 1953 that proposed a three-stranded DNA structure,
Sir Lawrence Bragg—the head of Cavendish—gave Watson and Crick
permission to work full-time on DNAs structure. Cavendish was not
about to lose to Pauling twice.
three-stranded helix had the bases facing out. While the model was wrong,
Watson and Crick were sure Pauling would soon learn his error. They estimated
that he was six weeks away from the right answer. Electrified by the urgency—and
by the prospect of beating a science superstar—Watson and Crick
spent four weeks obsessing about DNA in endless conversations and bouts
of model-building to arrive at the correct structure.
In 1952, Wilkins
and the head of the Kings laboratory denied Pauling's request to
view their X-ray photos of DNA—crucial evidence that inspired Watson's
vision of the double helix. Pauling had to settle for inferior older photographs.
In the same year, he was planning to attend a science meeting in London,
where he most likely would have renewed his request in person. But it
was the McCarthy era, and the U.S. State Department denied Pauling's request
for a passport because of his "un-American" antiwar activism.
It was fitting, then, that Pauling, who won the Nobel Prize in Chemistry
in 1954, also won the Nobel Peace Prize in 1962, the same year Watson,
Crick, and Maurice Wilkins won their Nobel Prize for discovering the double
the young scientists Watson and Crick call their model “radically
different” to strongly set it apart from the model proposed by science
powerhouse Linus Pauling. This claim was justified. While Pauling’s
model was a triple helix with the bases sticking out, the Watson-Crick
model was a double helix with the bases pointing in and forming pairs
of adenine (A) with thymine (T), and cytosine (C) with guanine (G).
(6) This central
description of the double-helix model still stands today—a monumental
feat considering that the vast majority of research findings are changed
According to science
historian Victor McElheny of the Massachusetts Institute of Technology,
the staying power of the double-helix theory puts it in a class with Newtons
laws of motion. Just as Newtonian physics survived centuries of scientific
scrutiny to become the foundation for todays space programs, the
double-helix model has provided the bedrock for several research fields
since 1953, including the biochemistry of DNA replication, the cracking
of the genetic code, genetic engineering, and the sequencing of the human
scientist Sven Furberg’s DNA model—which correctly put the
bases on the inside of a helix—was one of many ideas about DNA that
helped Watson and Crick to infer the molecule’s structure. To some
extent, they were synthesizers of these ideas. Doing little laboratory
work, they gathered clues and advice from other experts to find the answer.
Watson and Crick’s extraordinary scientific preparation, passion,
and collaboration made them uniquely capable of this synthesis.
(8) A visual
representation of Watson and Crick’s model was crucial to show how
the components of DNA fit together in a double helix. In 1953, Crick’s
wife, Odile, drew the diagram used to represent DNA in this paper. Scientists
use many different kinds of visual representations of DNA.
(9) The last
hurdle for Watson and Crick was to figure out how to arrange DNAs
four bases (adenine, thymine, guanine, and cytosine) inside the double
helix without distorting the molecule. To visualize the answer, Watson
built cardboard cutouts of the bases. Early one morning, as Watson moved
the cutouts around on a tabletop, he found that the overall shape of an
adenine molecule paired with a thymine molecule was similar to the overall
shape of a guanine-cytosine pair. He immediately realized that arranging
the bases in these pairs made a DNA structure without bulges or strains.
Watson solved the puzzle "not by logic but serendipity," Crick
recalled in his book What Mad Pursuit.
Watson and Crick
picked up this model-building approach from eminent chemist Linus Pauling,
who had successfully used it to discover that some proteins have a helical
sentence refers to the work of Erwin Chargaff, a biochemist at Columbia
University. In the late 1940s, Chargaff analyzed the proportions of the
four different types of base molecules in DNA, and found that DNA always
contains equal amounts of guanine and cytosine, and equal amounts of adenine
of this discovery remained unclear until February 1953. Thats when
Watson figured out how DNAs four bases paired with one another.
By fiddling with cardboard cutout versions of the base molecules, he discovered
that adenine always pairs with thymine, and guanine always pairs with
cytosine. Now Chargaffs finding made perfect sense to Watson and
Crick: If every adenine and thymine are paired in DNA, there must be an
equal number of these two molecules. The same goes for guanine and cytosine.
the Watson-Crick paper in the April 25, 1953, issue of Nature
were separately published papers by scientists Maurice Wilkins and Rosalind
Franklin of King’s College, who worked independently of each other.
The Wilkins and Franklin papers described the X-ray crystallography evidence
that helped Watson and Crick devise their structure. The authors of the
three papers, their lab chiefs, and the editors of Nature agreed
that all three would be published in the same issue.
communications” that our authors are referring to are the papers
by Franklin and Wilkins, published on the journal pages immediately after
Watson and Crick’s paper. They (and other papers) can be downloaded
as PDF files (Adobe
Acrobat required) from Nature’s
50 Years of DNA Web site.
Here are the direct
Molecular Configuration in Sodium Thymonucleate
Franklin, R., and Gosling, R. G.
Nature 171, 740-741 (1953)
Molecular Structure of Deoxypentose Nucleic Acids
Wilkins, M. H. F., Stokes, A. R., & Wilson, H. R.
Nature 171, 738-740 (1953)
Watson and Crick say that they "were not aware of the details"
of the work of King’s College scientist Rosalind Franklin—a
statement that marks what many consider an inexcusable failure to give
Franklin proper credit.
According to Lynne Elkin, a science historian at California State University,
Hayward, it’s true that Watson and Crick were not aware of all the
details of Franklin’s work, but they were aware of enough of the
details to discover the structure of DNA. Yet this paper does not ever
formally acknowledge her, instead concealing her significant role by saying
they "were not aware" of her work.
What exactly was Franklin’s research, and how did Watson and Crick
gain access to it? While they were busy building their models, Franklin
was at work on the DNA puzzle using X-ray crystallography, which involved
taking X-ray photographs of DNA samples to infer their structure. By late
February 1953, her analysis of these photos brought her close to the correct
But Franklin stopped her work on DNA because she was frustrated with a
strained environment at King’s, one that pitted her against her
colleagues. In an institutional culture that barred women from the dining
room and other social venues, she was denied access to the informal discourse
that is essential to any scientist’s work. Seeing no chance for
a tolerable professional life at King’s, Franklin decided to take
another job. As she was preparing to leave, she turned her X-ray photographs
over to her colleague Maurice Wilkins.
Then, in perhaps the most pivotal moment in the search for DNA’s
structure, Wilkins, a longtime friend of Crick, showed Watson one of Franklin’s
photographs without Franklin’s permission. Watson recalled, "The
instant I saw the picture my mouth fell open and my pulse began to race."
To Watson, the cross-shaped pattern of spots in the photo meant that DNA
had to have a helical structure. Franklin’s photograph was critical
in solving the problem, as Watson admitted in his 1968 book, The Double
Watson and Crick also had access to an internal report from the Medical
Research Council, a British agency for funding life sciences, summarizing
much of Franklin’s unpublished work on DNA, including precise measurements
of the molecule. As the Cavendish representative to the agency, scientist
Max Perutz had a copy of the report, and when Crick asked to see it, Perutz
obliged. While the report was not confidential, science historian Lynne
Elkin contends that "showing unpublished work to an unacknowledged
competitor was a questionable act which justifiably infuriated" John
Randall, the head of King’s.
Crick later said the data in the report enabled him to reach the significant
conclusion that DNA has two chains running in opposite directions. Although
Franklin was listed in the acknowledgements section with other scientists,
there was no specific mention of her contributions.
Was it unethical for Wilkins to reveal the photographs, or for Perutz
to hand over the King’s report? How should Watson and Crick have
recognized Franklin for her contribution to their paper? For decades,
scientists and historians have wrestled over these issues.
To read more about Rosalind Franklin and her history with Wilkins, Watson,
and Crick, see the following Web sites:
“Light on a Dark Lady” by Anne Piper, a lifelong friend of
“The Double Helix and the Wronged Heroine,” an essay on Nature’s
“Double Helix: 50 years of DNA” Web site
A review of Brenda Maddox’s recent book, Rosalind Franklin:
The Dark Lady of DNA, in The Guardian (UK)
phrase and the sentence it begins may be one of the biggest understatements
in biology. Watson and Crick realized at the time that their work had
important scientific implications beyond a “pretty structure.”
In this statement, the authors are saying that the base pairing in DNA
(adenine links to thymine and guanine to cytosine) provides the mechanism
by which genetic information carried in the double helix can be precisely
copied. Knowledge of this copying mechanism started a scientific revolution
that would lead to, among other advances in molecular biology, the ability
to manipulate DNA for genetic engineering and medical research, and to
decode the human genome, along with those of the mouse, yeast, fruit fly,
and other research organisms.
This paper is short because it was intended only to announce Watson
and Crick’s discovery, and because they were in a competitive situation.
In January 1954, they published the "full details" of their
work in Proceedings of the Royal Society. This "expound
later" approach was common in science in the 1950s. In fact, Rosalind
Franklin did the same thing, supplementing her short April 25 paper with
two longer articles.
Journals today offer scientists a greater variety of publishing formats
than journals in the 1950s. Nature now has more than five different
options, most of which are subjected to a rigorous evaluation known as
peer review. Since Watson and Crick largely presented a hypothesis instead
of new data in this paper, Nature would likely have published
it today as an "Analysis" paper—one of the journal’s
shorter peer-reviewed formats. This paper was not peer-reviewed—Nature
had no formal review process in the 1950s—but it would have been
peer-reviewed if submitted today.
For many decades, conferences have also been an important forum for researchers
to present their work. Watson reported his and Crick’s results at
the prestigious annual symposium at Cold Spring Harbor Laboratory in June
1953. Meetings continue to be a significant part of the culture of science
at Cold Spring Harbor.
historian Lynne Elkin calls this sentence an understatement. She argues
that Watson and Crick were "more than stimulated" by Franklin’s
work—and had "more than a general knowledge" of it—because
they relied on her X-ray photograph and her specific DNA measurements.
Interestingly, this sentence contained a stronger acknowledgment of Franklin’s
work in an early
draft of the paper: "We have also been stimulated by the very
beautiful experimental work of Dr. M. H. Wilkins and his co-workers at
Kings College, London." Elkin suggests that the phrase "very
beautiful" is most likely a nod to Franklin’s X-ray photograph.
The same draft also acknowledged Franklin’s work with the sentence:
"It is known that there is much unpublished experimental material."
When Maurice Wilkins read the draft, he advised Watson and Crick to delete
this sentence and the phrase "very beautiful." They agreed to