the watson

33
THE WATSON-CRICK MODEL BASE-PAIRING IN DNA Experiments have shown that DNA samples taken from different cells of the same species have the same proportions of the four bases. For example, human DNA contains about 30% each of adenine and thymine, and 20% each of guanine and cytosine. The figure is different for other organisms, but the amounts of A and T are always the same, as are the amounts of C and G! Why is this the case? In 1953, James Watson and Francis Crick proposed a structure for DNA that not only accounts for this pairing of bases but also explains how relatively simply the system of storing and transferring genetic information is. According to the Watson-Crick model , a DNA molecule consists of two polynucleotide strands coiled around each other in a helical "twisted ladder" structure. As mentioned earlier in the tutorial, the sugar-phosphate backbone is on the outside of the double helix, and the bases are on the inside, so that a base on one strand points directly toward a base on the second strand. When using the twisted ladder analogy, think of the sugar-phosphate backbones as the two sides of the ladder and the bases in the middle as the rungs of the ladder. In effect, each strand of DNA is one-half of the double helix. The two halves come together to form the double helix structure. The two strands of the DNA double helix run in opposite directions, one in the 5' to 3' direction, the other in the 3' to 5' direction. The term that describes how the two strands relate to each other is known as antiparallel . So what holds the two strands together at the bases? The strands are held together by hydrogen bonds between the nitrogenous bases. In the double helix, adenine and thymine form two hydrogen bonds to each other but not to cytosine or guanine. Similarly, cytosine and guanine form three hydrogen bonds to each other in the double helix, but not to adenine or thymine. If you clicked on the links above, you may have noticed the exact nature of the hydrogen bonds. Hydrogen bonds occur only between a Hydrogen atom on one base and either an oxygen or nitrogen atom on the other base. This explains why only two hydrogen bonds can form between A's and T's and three can form between G's and C's, because a hydrogen bond can only form where a H atom comes in close proximity to an Oxygen or Nitrogen atom of a base on the opposite strand. You may also have noticed that every base pair contains one purine and one pyrimidine ALWAYS. Again, this is related to the structure of each base and how a proper "fit" (both in base size and chemical makeup) allows the DNA helix to exist in a physically and chemically stable structure. This type of base pairing is called complementary rather than identical. Identical base pairing would mean that A's bond with A's, G's with G's, and so on, which (of course) isn't the case. The figure below shows a generalized structure of the DNA helix with all its components and hydrogen bonds. This complementary base pairing in the two strands explains why A/T and G/C always occur in equal amounts. A helpful way to remember the base pairing in DNA is to memorize the phrase "Pure silver taxi."

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Page 1: The Watson

THE WATSON-CRICK MODEL BASE-PAIRING IN DNA

Experiments have shown that DNA samples taken from different cells of the same species have the same proportions of the four bases. For example, human DNA contains about 30% each of adenine and thymine, and 20% each of guanine and cytosine. The figure is different for other organisms, but the amounts of A and T are always the same, as are the amounts of C and G!

Why is this the case?

In 1953, James Watson and Francis Crick proposed a structure for DNA that not only accounts for this pairing of bases but also explains how relatively simply the system of storing and transferring genetic information is. According to the Watson-Crick model, a DNA molecule consists of two polynucleotide strands coiled around each other in a helical "twisted ladder" structure. As mentioned earlier in the tutorial, the sugar-phosphate backbone is on the outside of the double helix, and the bases are on the inside, so that a base on one strand points directly toward a base on the second strand. When using the twisted ladder analogy, think of the sugar-phosphate backbones as the two sides of the ladder and the bases in the middle as the rungs of the ladder. In effect, each strand of DNA is one-half of the double helix. The two halves come together to form the double helix structure.

The two strands of the DNA double helix run in opposite directions, one in the 5' to 3' direction, the other in the 3' to 5' direction. The term that describes how the two strands relate to each other is known as antiparallel.

So what holds the two strands together at the bases?

The strands are held together by hydrogen bonds between the nitrogenous bases. In the double helix, adenine and thymine form two hydrogen bonds to each other but not to cytosine or guanine. Similarly, cytosine and guanine form three hydrogen bonds to each other in the double helix, but not to adenine or thymine.

If you clicked on the links above, you may have noticed the exact nature of the hydrogen bonds. Hydrogen bonds occur only between a Hydrogen atom on one base and either an oxygen or nitrogen atom on the other base. This explains why only two hydrogen bonds can form between A's and T's and three can form between G's and C's, because a hydrogen bond can only form where a H atom comes in close proximity to an Oxygen or Nitrogen atom of a base on the opposite strand.

You may also have noticed that every base pair contains one purine and one pyrimidine ALWAYS. Again, this is related to the structure of each base and how a proper "fit" (both in base size and chemical makeup) allows the DNA helix to exist in a physically and chemically stable structure. This type of base pairing is called complementary rather than identical. Identical base pairing would mean that A's bond with A's, G's with G's, and so on, which (of course) isn't the case. The figure below shows a generalized structure of the DNA helix with all its components and hydrogen bonds.

This complementary base pairing in the two strands explains why A/T and G/C always occur in equal amounts. A helpful way to remember the base pairing in DNA is to memorize the phrase "Pure silver taxi."

James D. WatsonFrom Wikipedia, the free encyclopediaJump to: navigation, search For other people named James Watson, see James Watson (disambiguation).

James D. Watson

James D. Watson

Page 2: The Watson

BornApril 6, 1928 (age 82)Chicago

Nationality AmericanFields Genetics

InstitutionsCold Spring Harbor Laboratory; Harvard University; University of Cambridge; National Institutes of Health

Alma mater University of Chicago, Indiana University

Known for DNA structure, Molecular biology,

Notable awards

Nobel Prize for Physiology or Medicine (1962); Copley

Medal (1993)[1]

James Dewey Watson (born April 6, 1928) is an American molecular biologist, geneticist, and zoologist, best known as one of the co-discoverers of the structure of DNA with Francis

Crick, in 1953. Watson, Francis Crick, and Maurice Wilkins were awarded the 1962 Nobel

Prize in Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".[2] He studied at the University of Chicago and Indiana University and subsequently worked at the University of

Cambridge's Cavendish Laboratory in England, where he first met his future collaborator and personal friend Francis Crick.

In 1956, Watson became a junior member of Harvard University's Biological Laboratories, holding this position until 1976, promoting research in molecular biology. Between 1988 and 1992, Watson was associated with the National Institutes of Health, helping to establish the Human Genome Project. Watson has written many science books, including the seminal textbook The Molecular Biology of the Gene (1965) and his bestselling book The Double

Helix (1968) about the DNA structure discovery.

From 1968 he served as director of Cold Spring Harbor Laboratory (CSHL) on Long Island,

New York, greatly expanding its level of funding and research. At CSHL, he shifted his research emphasis to the study of cancer. In 1994, he became its president for ten years, and then subsequently he served as its chancellor until 2007, when he resigned, due to a controversy over comments he made claiming black Africans were on average less intelligent than whites during an interview.[3]

Contents

[hide] 1 Early life and education 2 Career in molecular biology

o 2.1 Double helix 3 Book: The Double Helix 4 Human genome project 5 Political activism 6 Controversies

Page 3: The Watson

o 6.1 Comments o 6.2 Use of King's College results o 6.3 Avoid Boring People, UK book tour

7 Personal life 8 Awards and decorations 9 Honorary degrees received 10 Professional and honorary affiliations 11 Selected books 12 See also 13 References 14 Further reading 15 External links

o 15.1 Multimedia

Early life and education

James Watson was born in Chicago, Ill., on April 6, 1928, as the only son of James D. Watson, a tax collector, and Jean Mitchell. His father was of Scottish descent (both Dewey and Watson being Scottish surnames).[4] His mother's father Lauchlin Mitchell, a tailor, was from Glasgow, Scotland, and her mother, Lizzie Gleason, was the child of Irish parents from Tipperary.[5] Watson was raised Catholic, describing himself as "an escapee from the Catholic religion."[6] Watson said, "The luckiest thing that ever happened to me was that my father didn't believe in God."[7]

He was fascinated with bird watching, a hobby he shared with his father.[8] Watson appeared on Quiz Kids, a popular radio show that challenged precocious youngsters to answer questions.[9] Thanks to the liberal policy of University president Robert Hutchins, he enrolled at the University of Chicago at the age of 15.[10]

After reading Erwin Schrödinger's book What Is Life? in 1946, Watson changed his professional ambitions from the study of ornithology to genetics.[11] Watson earned his B.S. degree in Zoology from the University of Chicago in 1947. In his autobiography, Avoid Boring People, Watson describes the University of Chicago as an idyllic academic institution where he was instilled with the capacity for critical thought and an ethical compulsion not to suffer fools who impeded his search for truth, in contrast to his description of later experiences. Watson attended Indiana University from 1947 to 1950 as a graduate student. He received his PhD degree from Indiana University in 1950.

Career in molecular biology

Originally, Watson was drawn into molecular biology by the work of Salvador Luria. Luria eventually shared a Nobel Prize for his work on the Luria-Delbrück experiment, which concerned the nature of genetic mutations. Luria was part of a distributed group of researchers who were making use of the viruses that infect bacteria, called bacteriophages.

Page 4: The Watson

Luria and Max Delbrück were among the leaders of this new "Phage Group", an important movement of geneticists from experimental systems such as Drosophila towards microbial genetics. Early 1948, Watson began his PhD research in Luria's laboratory at Indiana

University. That spring he met Delbrück first in Luria's apartment and again that summer during Watson's first trip to the Cold Spring Harbor Laboratory (CSHL).[12]

The Phage Group was the intellectual medium where Watson became a working scientist. Importantly, the members of the Phage Group sensed that they were on the path to discovering the physical nature of the gene. In 1949 Watson took a course with Felix Haurowitz that included the conventional view of that time: that genes were proteins and able to replicate themselves.[13] The other major molecular component of chromosomes, DNA, was thought by many to be a "stupid tetranucleotide", serving only a structural role to support the proteins. However, even at this early time, Watson, under the influence of the Phage Group, was aware of the Avery-MacLeod-McCarty experiment, which suggested that DNA was the genetic molecule. Watson's research project involved using X-rays to inactivate bacterial viruses.[14] He gained his PhD in Zoology at Indiana University in 1950 (at age 22).

Watson then went to Copenhagen University in September 1950 for a year of postdoctoral research, first heading to the laboratory of biochemist Herman Kalckar.[8] Kalckar was interested in the enzymatic synthesis of nucleic acids, and he wanted to use phages as an experimental system. Watson, however, wanted to explore the structure of DNA, and his interests did not coincide with Kalckar's.[15] After working part of the year with Kalcker, Watson spent the remainder of his time in Copenhagen conducting experiments with microbial physiologist Ole Maaloe, then a member of the Phage Group.[16]

The experiments, which Watson had learned of during the previous summer's Cold Spring Harbor phage conference, included the use of radioactive phosphate as a tracer to determine which molecular components of phage particles actually infect the target bacteria during viral infection.[15] The intention was to determine whether protein or DNA was the genetic material, but upon consultation with Max Delbrück,[15] they determined that their results were inconclusive and could not specifically identify the newly labeled molecules as DNA.[17] Watson never developed a constructive interaction with Kalckar, but he did accompany Kalckar to a meeting in Italy where Watson saw Maurice Wilkins talk about his X-ray diffraction data for DNA.[8] Watson was now certain that DNA had a definite molecular structure that could be elucidated.[18]

In 1951, the chemist Linus Pauling in California published his model of the amino acid alpha

helix, a result that grew out of Pauling's efforts in X-ray crystallography and molecular model building. Watson found out about Pauling's model quickly because it was communicated to him via Pauling's son, Peter Pauling, who had a copy of the manuscript. Watson claimed that such a model (with three central phosphate chains held together by hydrogen bonds) was easily recognized as incorrect because in an aqueous environment the phosphate groups would be ionized thus would not display hydrogen bonding and would repel each other.[19] After obtaining some results from his phage and other experimental research conducted at Indiana University, Statens seruminstitute (Denmark),

Page 5: The Watson

Cold Spring Harbor Laboratory, and the California Institute of Technology, Watson now had the desire to learn to perform X-ray diffraction experiments so that he could work to determine the structure of DNA. That summer, Luria met John Kendrew, and he arranged for a new postdoctoral research project for Watson in England.[8]

Double helix

Watson and Crick deduced the double helix structure of DNA. Sir Lawrence Bragg, the director of the Cavendish Laboratory (where Watson and Crick worked), made the original announcement of the discovery at a Solvay conference on proteins in Belgium on April 8, 1953; it went unreported by the press. Watson and Crick submitted a paper to the scientific journal Nature, which was published on April 25, 1953. This has been described by some other biologists and Nobel laureates as the most important scientific discovery of the 20th century. Bragg gave a talk at the Guys Hospital Medical School in London on Thursday, May 14, 1953, which resulted in an article by Ritchie Calder in the newspaper The News Chronicle of London, on May 15, 1953, entitled "Why You Are You. Nearer Secret of Life." The news reached readers of The New York Times the next day. Victor K. McElheny, in researching his biography, "Watson and DNA: Making a Scientific Revolution", found a clipping of a six-paragraph New York Times article written from London and dated May 16, 1953, with the headline "Form of 'Life Unit' in Cell Is Scanned." The article ran in an early edition and was then pulled to make space for news deemed more important. (The New York Times subsequently ran a longer article on June 12, 1953). The Cambridge University undergraduate newspaper Varsity also ran its own short article on the discovery on Saturday, May 30, 1953. Watson subsequently presented a paper on the double helical structure of DNA at the 18th Cold Spring Harbor Symposium on Viruses in early June 1953, six weeks after the publication of the Watson & Crick paper in Nature. Many at the meeting had not yet heard of the discovery. The 1953 Cold Harbor Symposium was the first opportunity for many to see the model of the DNA Double Helix. Watson claimed that he was refused a $1,000 raise in salary after winning the Nobel Prize.[20] Watson, Crick, and Wilkins were awarded the Nobel Prize in Physiology or Medicine in 1962 for their research on the structure of nucleic acids.[2][21][22]

[23][24]

Watson's accomplishment displayed on the monument at the American Museum of Natural

History in New York City. Because the monument memorializes only American Laureates, Crick is not mentioned.

At Harvard University, starting in 1956, Watson achieved a series of academic promotions from Assistant Professor, to Associate Professor to full Professor of Biology.

Page 6: The Watson

He championed a switch in focus for the school from classical biology to molecular biology, stating that disciplines such as ecology, developmental biology, taxonomy, physiology, etc. had stagnated and could only progress once the underlying disciplines of molecular biology and biochemistry had elucidated their underpinnings, going so far as to discourage their study by students. He left the school in 1976.

In 1968, Watson became the Director of the Cold Spring Harbor Laboratory. Between 1970 and 1972, the Watsons' two sons were born, and by 1974 the young family made Cold Springs Harbor their permanent residence. Watson served as the Laboratory's Director and president for about 35 years, and later he assumed the role of Chancellor. In October 2007, Watson resigned as a result of controversial remark about race made to the press. Watson has one son who has schizophrenia.[25] In a retrospective summary of his accomplishments there, Bruce Stillman, the laboratory's president said, "Jim Watson created a research environment that is unparalleled in the world of science." It was "under his direction [that the Lab has] made major contributions to understanding the genetic basis of cancer."

Generally in his roles as Director, President, and Chancellor, Watson led CSHL to its present day mission, which is "dedicat[ion] to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering." In October 2007, Watson was suspended following criticism of views on race and intelligence attributed to him, and a week later, on the 25th, he retired at the age of 79 from Cold Spring Harbor Laboratory from what the lab called "nearly 40 years of distinguished service",[26] In a statement, Watson attributed his retirement to his age, and circumstances that he could never have anticipated or desired.[27][28][29]

In January 2007, Watson accepted the invitation of Leonor Beleza, president of the Champalimaud Foundation, to become the head of the foundation's scientific council, an advisory organ. He will be in charge of selecting the remaining council members.[30]

Watson was also a former adviser for the Allen Institute for Brain Science.[31] The Allen Institute, located in Seattle, Washington, was founded in 2003 by Philanthropists Paul G.

Allen and Jody Allen as a 501(c)(3) nonprofit corporation medical research organization. A multidisciplinary group of neuroscientists, molecular biologists, informaticists, engineers, mathematicians, statisticians, and computational biologists were brought together to form the scientific core of the Allen Institute. Utilizing the mouse model system, these fields have joined together to investigate expression of 20,000 genes in the adult mouse brain and to map gene expression to a cellular level beyond neuroanatomic boundaries. The data generated from this joint effort is contained in the publicly available Allen Mouse Brain Atlas

application located at www.brain-map.org. Upon completion of the Allen Mouse Brain Atlas, this consortium of scientists will pursue additional questions to further our understanding of neuronal circuitry and the neuroanatomic framework that defines the functionality of the brain.

Book: The Double Helix

Page 7: The Watson

DNA model built by Crick and Watson in 1953, on display in the Science Museum (London).

In 1968, Watson wrote The Double Helix, one of the Modern Library's 100 Best Nonfiction books. The account is the sometimes painful story of not only the discovery of the structure of DNA, but the personalities, conflicts and controversy surrounding their work. Watson's original title was to have been "Honest Jim", in that the book recounts the discovery of the double helix from his point of view and included many of his private emotional impressions at the time. The book changed the way the public viewed scientists and the way they work.[32]

Some controversy attended the publication of the book. Watson's book was originally to be published by the Harvard University Press, but after objections from both Francis Crick and Maurice Wilkins, among others, Watson's home university where he had been a member of the biology faculty since 1955, dropped the publication of the book, and it was instead published by a commercial publisher.[33]

In the same way, Watson's first textbook, The Molecular Biology of the Gene, set a new standard for textbooks, particularly through the use of concept heads—brief declarative subheadings. Its style has been emulated by almost all successive textbooks. His next great success was Molecular Biology of the Cell, although here his role was more that of coordinator of an outstanding group of scientist-writers. His third textbook was Recombinant DNA, which described the ways in which genetic engineering has brought much new information about how organisms function. The textbooks are still in print.

Human genome project

In 1990, Watson's achievement and the success led to his appointment as the Head of the Human Genome Project at the National Institutes of Health, a position he held until April 10, 1992.[34] Watson left the Genome Project after conflicts with the new NIH Director, Bernadine Healy. Watson was opposed to Healy's attempts to acquire patents on gene sequences, and any ownership of the "laws of nature." Two years before stepping down

Page 8: The Watson

from the Genome Project, he had stated his own opinion on this long and ongoing controversy which he saw as an illogical barrier to research; he said, "The nations of the world must see that the human genome belongs to the world's people, as opposed to its nations." He left within weeks of the 1992 announcement that the NIH would be applying for patents on brain-specific cDNAs.[35] (The issue of the patentability of genes is still not resolved in the US; see Association for Molecular Pathology, et al. v. United States Patent and

Trademark Office, et al.)

In 1994, Watson became President of CSHL. Francis Collins took over the role as Director of the Human Genome Project.

In 2007, James Watson became the second person[36] to publish his fully sequenced genome online,[37] after it was presented to him on May 31, 2007 by 454 Life Sciences Corporation[38] in collaboration with scientists at the Human Genome Sequencing Center, Baylor College of Medicine. "'I am putting my genome sequence on line to encourage the development of an era of personalized medicine, in which information contained in our genomes can be used to identify and prevent disease and to create individualized medical therapies,' said CSHL Chancellor Watson."[39][40][41]

Political activism

During his tenure as a professor at Harvard, Watson participated in several political protests:

Vietnam War : While a professor at Harvard University, Watson, along with "12 Faculty members of the department of Biochemistry and Molecular Biology" including one other Nobel prize winner, spearheaded a resolution for "the immediate withdrawal of U.S. forces' from Vietnam."[42]

Nuclear proliferation and environmentalism: In 1975, on the "thirtieth anniversary of the bombing of Hiroshima," Watson along with "over 2000 scientists and engineers" spoke out against nuclear proliferation to President Ford in part because of the "lack of a proven method for the ultimate disposal of radioactive waste" and because "The writers of the declaration see the proliferation of nuclear plants as a major threat to American liberties and international safety because they say safeguard procedures are inadequate to prevent terrorist theft of commercial reactor-produced plutonium."[43]

The DNA-Helix 

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The sugar-phosphate backbone is on the outside and the four different bases are on the inside of the DNA molecule.

 

The two strands of the double helix are anti-parallel, which means that they run in opposite directions.

The sugar-phosphate backbone is on the outside of the helix, and the bases are on the inside. The

backbone can be thought of as the sides of a ladder, whereas the bases in the middle form the rungs of the

ladder.

Each rung is composed of two base pairs. Either an adenine-thymine pair that form a two-hydrogen bond

together, or a cytosine-guanine pair that form a three-hydrogen bond. The base pairing is thus restricted.

This restriction is essential when the DNA is being copied: the DNA-helix is first "unzipped" in two long

stretches of sugar-phosphate backbone with a line of free bases sticking up from it, like the teeth of a comb.

Each half will then be the template for a new, complementary strand. Biological machines inside the cell put

the corresponding free bases onto the split molecule and also "proof-read" the result to find and correct any

mistakes. After the doubling, this gives rise to two exact copies of the original DNA molecule.

The coding regions in the DNA strand, the genes, make up only a fraction of the total amount of DNA. The

stretches that flank the coding regions are called introns, and consist of non-coding DNA. Introns were

looked upon as junk in the early days. Today, biologists and geneticists believe that this non-coding DNA

may be essential in order to expose the coding regions and to regulate how the genes are expressed.

REPLICATION OF DNA How is cellular DNA copied?

DNA replication begins with a partial unwinding of the double helix at an area known as the replication fork. This unwinding is accomplished by an enzyme known as DNA helicase. This unwound section appears under electron microscopes as a "bubble" and is thus known as a replication bubble.

As the two DNA strands separate ("unzip"), and the bases are exposed, the enzyme DNA polymerase moves into position at the point where synthesis will begin.

Page 10: The Watson

But where does the DNA polymerase enzyme know where to begin synthesis? Is there some sort of marker, a start point?

YES; the start point for DNA polymerase is a short segment of RNA known as an RNA primer. The very term "primer" is indicative of its role which is to "prime" or start DNA synthesis at certain points. The primer is "laid down" complementary to the DNA template by an enzyme known as RNA polymerase or Primase.

The DNA polymerase (once it has reached its starting point as indicated by the primer) then adds nucleotides one by one in an exactly complementary manner, A to T and G to C.

How does the polymerase "know" which base to add?

DNA polymerase is described as being "template dependent" in that it will "read" the sequence of bases on the template strand and then "synthesize" the complementary strand. The template strand is ALWAYS read in the 3' to 5' direction (that is, starting from the 3' end of the template and reading the nucleotides in order toward the 5' end of the template). The new DNA strand (since it is complementary) MUST BE SYNTHESIZED in the 5' to 3' direction (remember that both strands of a DNA molecule are described as being antiparallel). DNA polymerase catalyzes the formation of the hydrogen bonds between each arriving nucleotide and the nucleotides on the template strand.

In addition to catalyzing the formation of Hydrogen bonds between complementary bases on the template and newly synthesized strands, DNA polymerase also catalyzes the reaction between the 5' phosphate on an incoming nucleotide and the free 3' OH on the growing polynucleotide (what we know is called a phosphodiester bond!). As a result, the new DNA strands can grow only in the 5' to 3' direction, and strand growth must begin at the 3' end of the template, right? Again, note that a phosphodiester bond is formed between the 3' OH group of the sugar and the 5' phosphate group of the incoming nucleotide.

Because the original DNA strands are complementary and run antiparallel, only one new strand can begin at the 3' end of the template DNA and grow continuously as the point of replication (the replication fork) moves along the template DNA. The other strand must grow in the opposite direction because it is complementary, not identical to the template strand. The result of this side's discontiguous replication is the production of a series of short sections of new DNA called Okazaki fragments (after their discoverer, a Japanese researcher). To make sure that this new strand of short segments is made into a continuous strand, the sections are joined by the action of an enzyme called DNA ligase which LIGATES the pieces together by forming the missing phosphodiester bonds!

The last step is for an enzyme to come along and remove the existing RNA primers (you don't want RNA in your DNA now that the primers have served their purpose, do you?) and then fill in the gaps with DNA. This is the job of yet another type of DNA polymerase which has the ability to chew up the primers (dismantle them) and replace them with the deoxynucleotides that make up DNA. Here is a link with a diagram of the overall process of DNA replication of Okazaki Fragments.

Since each new strand is complementary to its old template strand, two identical new copies of the DNA double helix are produced during replication. In each new helix, one strand is the old template and the other is newly synthesized, a result described by saying that the replication is semi-conservative. This process is shown schematically below. Crick described the DNA replication process and the fitting together of two DNA strands as being like a hand in a glove. The hand and glove separate, a new hand forms inside the old glove, and a new glove forms around the old hand. As a result, two identical copies now exist.

THE WATSON-CRICK MODEL BASE-PAIRING IN DNA

Experiments have shown that DNA samples taken from different cells of the same species have the same proportions of the four bases. For example, human DNA contains about 30% each of adenine and thymine, and 20% each of guanine and cytosine. The figure is different for other organisms, but the amounts of A and T are always the same, as are the amounts of C and G!

Why is this the case?

In 1953, James Watson and Francis Crick proposed a structure for DNA that not only accounts for this pairing of bases but also explains how relatively simply the system of storing and

Page 11: The Watson

transferring genetic information is. According to the Watson-Crick model, a DNA molecule consists of two polynucleotide strands coiled around each other in a helical "twisted ladder" structure. As mentioned earlier in the tutorial, the sugar-phosphate backbone is on the outside of the double helix, and the bases are on the inside, so that a base on one strand points directly toward a base on the second strand. When using the twisted ladder analogy, think of the sugar-phosphate backbones as the two sides of the ladder and the bases in the middle as the rungs of the ladder. In effect, each strand of DNA is one-half of the double helix. The two halves come together to form the double helix structure.

The two strands of the DNA double helix run in opposite directions, one in the 5' to 3' direction, the other in the 3' to 5' direction. The term that describes how the two strands relate to each other is known as antiparallel.

So what holds the two strands together at the bases?

The strands are held together by hydrogen bonds between the nitrogenous bases. In the double helix, adenine and thymine form two hydrogen bonds to each other but not to cytosine or guanine. Similarly, cytosine and guanine form three hydrogen bonds to each other in the double helix, but not to adenine or thymine.

If you clicked on the links above, you may have noticed the exact nature of the hydrogen bonds. Hydrogen bonds occur only between a Hydrogen atom on one base and either an oxygen or nitrogen atom on the other base. This explains why only two hydrogen bonds can form between A's and T's and three can form between G's and C's, because a hydrogen bond can only form where a H atom comes in close proximity to an Oxygen or Nitrogen atom of a base on the opposite strand.

You may also have noticed that every base pair contains one purine and one pyrimidine ALWAYS. Again, this is related to the structure of each base and how a proper "fit" (both in base size and chemical makeup) allows the DNA helix to exist in a physically and chemically stable structure. This type of base pairing is called complementary rather than identical. Identical base pairing would mean that A's bond with A's, G's with G's, and so on, which (of course) isn't the case. The figure below shows a generalized structure of the DNA helix with all its components and hydrogen bonds.

This complementary base pairing in the two strands explains why A/T and G/C always occur in equal amounts. A helpful way to remember the base pairing in DNA is to memorize the phrase "Pure silver taxi."

J. D. WATSON and F. H. C. CRICKA Structure for Deoxyribose Nucleic Acid

Nature, 2 April 1953, VOL 171,737 1953

Commentary by Tom Zinnen

For best use of this case study, please download the original from the "Naturepast" web area of www.nature.com.

The paragon of elegance, this paper is renowned for its simplicity, clarity, durability and understatement. The four

key characteristics of this model of DNA endure: DNA is double-stranded, anti-parallel, complementary, and the double strands are in a double-helix.

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And because the authors were 25 and 35 years old, respectively, when the paper was published, it serves as an example to students that sometimes extraordinary discoveries are made by people within a few years of completing high school.

In the early 1950's, the structure of DNA had become a crucial puzzle, following the discovery that DNA and not protein was the "transforming" principle.

The puzzle was more intriguing because of the challenge of figuring out how a polymer composed of only 4 different "letters" could encode for a polymer such as proteins that are composed of 20 different letters.

The date: 2 April 1953. (Note: Also the year of the Hershey-Chase experiment that tested whether DNA or protein was the informational molecule.)

The title: A Structure for Deoxyribose Nucleic Acid

Note the use of "deoxyribose nucleic acid" rather than "deoxyribonucleic acid" that is more commonly used today.

Note that this is "a" structure and not "the" structure. Other possible configurations were not excluded. And in fact, known configurations of DNA include single-stranded and triple-stranded, and even the double-stranded type occurs in three forms (A, B and Z; they describe the B form).

Lead sentence: "We wish to suggest a structure for the salt of deoxyribose nucleic acid (D.N.A.)."

DNA is an acid, owing to the phosphate groups between each deoxyribose. The "salt" of DNA is the form in which some of the hydrogen ions have disassociated from the phosphate group. The salt then has a net negative charge, specifically at the oxygens of the phosphates. This net negative charge is a key characteristic to keep in mind when reflecting on the function of histones or on the movement of DNA in electrophoresis.

The Pauling-Corey model: "Their model consists of three intertwined chains, with the phosphates near the fibre axis, and the bases on the outside."

Note that about the only characteristic in common with the Watson-Crick model is "twining." The differences include three strands instead of two, the sugar-phosphate backbone is in the center rather than on the outside, and there is no mention of base-pairing. Without base-pairing, there is no explanation for "Chargaff's Rules": in DNA the moles of A and T are about the same, as are the moles of G and C. Note that in 1952 "Chargaff's Rules" referred only to the amounts of A and T, and of G and C. The idea that A binds to T and T to A, and G binds to C and C to G, is first presented in this paper.

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Yet note that the two specific criticisms that Watson and Crick list about the Pauling-Corey model center on net charge and on distances between atoms. Perhaps these were sufficient to show the model was unsatisfactory.

The Watson-Crick Model

"This structure has two helical chains each coiled round the same axis (see diagram)."

See diagram, indeed. Further evidence that 1 picture = 1kilowords.

Characteristics 1 and 2: DNA is double-stranded in a double-helix. Note that two helical chains can share a common axis without necessarily being linked the way DNA is. The rung-and-ladder scheme is so commonplace now that we may not realize that other double-helix arrangements are plausible.

Biochemistry review time: "We have made the usual chemical assumptions, namely, that each chain consists of phosphate diester groups joining ß-D-deoxyribofuranose residues with 3',5' linkages."

Phosphate diester: This refers to a single phosphate that is linked by ester-type bonds to two nucleosides. It is a diester because there are two ester linkages, one to each nucleoside.

ß-D-deoxyribofuranose: organic chemistry or biochemistry.

1. ribo refers to ribose, a sugar with 5 carbons.

2. deoxyribo refers to deoxyribose, a ribose that's missing an oxygen at the Number 2 carbon.

3. deoxyribofuranose means a particular five-carbon sugar that's in a circle with five members (Carbons 1 through 4 and an oxygen), rather than in a linear arrangement. Carbon 5 sticks up above the five-member circle.

4. ß means that of the two possible arrangements of the deoxyribofuranose, this molecule is in the version in which both the hydroxyl group of the Number 1 carbon and the Number 5 carbon are both above the plane of the circular furanose. The alternative is the alpha arrangement, in which the hydroxyl group would be below the plane of the circular furanose, while the Number 5 carbon would be above it.

5. D means this five-carbon sugar has the same stereochemical configuration at the Number 4 and 5 carbons as the Number 2 and 3 Carbons of D-glyceraldehyde.

6. "3',5' linkages" means that two deoxyribose sugars are connected to a phosphate in the middle by the Number 3 carbon on one sugar and by the Number 5 carbon on the other sugar.

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Characteristic 3: the two strands in DNA are anti-parallel. "Both chains follow right- handed helices, but owing to the dyad the sequences of the atoms in the two chains run in opposite directions."

Dyad means the pairing of opposite bases. This is analogous to two teams shaking hands in two passing lines after a championship game. The two teams are in two lines moving in opposite directions. This allows people to shake each other's right hands. If the two lines were parallel instead of anti-parallel, would they be able to shake hands easily?

"Right-handed helices" refers to the orientation of the helices. Compare to the threads on a screw. Standard threads are "right-handed." The alternative of course is "left-handed." I'd suggest using a nut and bolt to show how the handedness works. Occasionally you can even get "reverse-threaded" or "left-handed" hardware, but it's rare. "Right-handed" means a helix or screw that will move away from you if you turn a screwdriver clockwise.

Some Calculations. "We have assumed an angle of 36 degrees 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."

Compare this to a circular staircase. In this analogy, you start out on stair 1; you look directly above you, and see a stair. To get to the stair directly above stair 1, you have to go up 10 stairsteps.

"As the phosphates are on the outside, cations have easy access to them." The phosphates are negatively charged, and attract cations (net positive charge). The phosphates, being charged, are also hydrophilic.

Characteristic 4: DNA is complementary. "The novel feature of the structure is the manner in which the two chains are held together by the purine and pyrimidine bases.... 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."

Hydrogen bonding between the keto forms of A and T and between G and C explains complementarity and Chargaff's rules. To know one strand is to know the opposite strand. Note that this base-pairing model makes sense only if one assumes the bases are in the "keto" form. The "enol" form does not provide an opportunity for hydrogen bonding.

"Keto" and "enol" are two possible tautomeric forms of a carbon in the bases. A carbon in the "keto" form is a carbon with a double bond to oxygen (as in "ketone"), and two single bonds to adjacent members of the ring. A carbon in the "enol" form has a single bond to an alcohol group (-OH) and a double-bond to a nitrogen and a single bond to an adjacent carbon.

Hydrogen bonding is a key attribute of the Watson-Crick model. The opportunity for hydrogen bonding depends on whether the bases are in the "keto" or the "enol" form.

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Watson and Crick found that the AT and GC pairing make sense only if the bases are in the "keto" tautomeric form.

The keto/enol dilemma is particularly well illustrated in Chapter 26 of Watson's "The Double Helix." (see book citation below)

Sic semper dyslexia: in the web version, the following misspellings occur: "the ration (sic) of guanine to cytosine, are always bery (sic) close to unity for deoxyribose nucleic acid." The misspellings seem to be a function of the website and not a verbatim copy of the original.

Double-stranded RNA? What difference can an oxygen make? The authors write that "It is probably impossible to build this structure with a ribose sugar in place of the deoxyribose..."

This implies doubt about the possibility of dsRNA. Yet now we know that dsRNA does exist routinely in nature, especially in some viruses of plants and fungi.

Question: Is dsRNA comparable structure to dsDNA? It is known to be double-stranded, antiparallel and complementary. Is it also a double-helix?

The Great Understatement: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

The novel feature of the model--namely, complementarity---means that knowing one strand tells you what the opposite strand should be. This is a remarkable feature for a template. It also means that pulling the double-stranded DNA apart yields two single strands of DNA. And if you fill in the missing strand of each, merely following the Watson-Crick binding rules (A to T, T to A, G to C, C to G), you can get two copies of the original double-stranded DNA.

Imagining this idea and generating ways to test it are two different challenges. It took another 5 years for Miselson and Stahl to develop the experiments that tested whether DNA was copied by "semi-conservative" or "conservative" replication. Their results, published in 1958, supported the semi-conservative mechanism.

Acknowledgments

"We are much indebted to Dr. Jerry Donohue for constant advice and criticism, especially on interatomic distances..."

Wilkins, Watson and Crick were awarded the Nobel Prize for Physiology or Medicine in 1962 for their work on the structure of DNA. Rosalind Franklin had died in 1958, and Nobel Prizes are not awarded posthumously.

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For more insights, these books are great storytelling.

The Double Helix by James D. Watson. 1968. Penguin Books, New York. ISBN 0-451-62787-3

What Mad Pursuit by Francis Crick. 1988. Basic Books, New York. ISBN 0-465-09138-5

The story of the research is told in the books and in a docu-movie called based on Watson's book. In the UK the movie is called "Life Story" and in the US it's called "Double Helix". Ironically, Jeff Goldblum, who plays Watson in the movie, has played a range of significant science characters in movies: Watson in "Double Helix", The Fly in "The Fly," and Ian Malcom in "Jurassic Park" and in "The Lost World."

A Structure for Deoxyribose Nucleic AcidJ. D. Watson and F. H. C. Crick (1)

April 25, 1953 (2), Nature (3), 171, 737-738

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) and Corey1. 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 (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

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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.

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 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) (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 experimentally3,4 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 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 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 (10). We were not aware of the details of the results presented there when we devised our

Figure 1This figure is purely diagrammatic (8). 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.

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structure (11), which rests mainly though not entirely on published experimental data and stereochemical arguments.

It has not escaped our notice (12) 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 (13).

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.

1 Pauling, L., and Corey, R. B., Nature, 171, 346 (1953); Proc. U.S. Nat. Acad. Sci., 39, 84 (1953).2 Furberg, S., Acta Chem. Scand., 6, 634 (1952).3 Chargaff, E., for references see Zamenhof, S., Brawerman, G., and Chargaff, E., Biochim. et Biophys. Acta, 9, 402 (1952).4 Wyatt, G. R., J. Gen. Physiol., 36, 201 (1952).5 Astbury, W. T., Symp. Soc. Exp. Biol. 1, Nucleic Acid, 66 (Camb. Univ. Press, 1947).6 Wilkins, M. H. F., and Randall, J. T., Biochim. et Biophys. Acta, 10, 192 (1953).

Annotations(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 directions.

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.

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(2) On this date, Nature published the paper you are reading.

According to science historian Victor McElheny of the Massachusetts Institute of Technology, this date was a turning point in a longstanding struggle between two camps of biology, vitalism and reductionism. While vitalists studied whole organisms and viewed genetics as too complex to understand fully, reductionists saw deciphering fundamental life processes as entirely possible—and critical to curing human diseases. The discovery of DNA’s double-helix structure was a major blow to the vitalist approach and gave momentum to the reductionist field of molecular biology.

Historians wonder how the timing of the DNA race affected its outcome. Science, after years of being diverted to the war effort, was able to focus more on problems such as those affecting human health. Yet, in the United States, it was threatened by a curb on the free exchange of ideas. Some think that American researcher Linus Pauling would have beaten Watson and Crick to the punch if Pauling’s ability to travel had not been hampered in 1952 by the overzealous House Un-American Activities Committee.

(3) Nature (founded in 1869)——and hundreds of other scientific journals—help 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 published.

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. They were world-renowned chemist Linus Pauling at the California Institute of Technology, and X-ray crystallographers Maurice Wilkins and Rosalind Franklin at King’s College London, in addition to Watson and Crick at the Cavendish Laboratory, Cambridge University.

The competitive juices were flowing well before the DNA sprint was in full gear. In 1951, Pauling narrowly beat scientists at the Cavendish Lab, a top center for probing protein structure, to the discovery that certain proteins are helical. The defeat stung. When Pauling sent a paper to be published in early 1953 that proposed a three-stranded DNA structure, the head of the Cavendish gave Watson and Crick permission to work full-time on DNA’s structure. Cavendish was not about to lose twice to Pauling.

Pauling's proposed structure of DNA was a three-stranded helix with the bases facing out. While the model was wrong, Watson and Crick were sure Pauling would soon learn his error, and 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 discovered the double helix after a four-week frenzy of model building.

Pauling was foiled in his attempts to see X-ray photos of DNA from King's College—crucial evidence that inspired Watson's vision of the double helix—and had to settle for inferior older photographs. In 1952, Wilkins and the head of the King's laboratory had denied Pauling's request to view their photos. Pauling was planning to attend a science meeting in London, where he most likely would have renewed his request in person, but the United States House Un-American Activities Committee halted Pauling’s trip, citing his 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 and Crick won their Nobel Prize for discovering the double helix.

(5) Here, 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.

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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 either rejected or changed over time.

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 Newton’s laws of motion. Just as Newtonian physics has survived centuries of scientific scrutiny to become the foundation for today’s 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 genome.

(7) Norwegian 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 DNA’s four bases paired without distorting the helix. 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 only one combination of base molecules made a DNA structure without bulges or strains. As Crick put it in his book What Mad Pursuit, Watson solved the puzzle “not by logic but serendipity.” 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 structure.

(10) Alongside 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.

The “following 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 website (http://www.nature.com/nature/dna50/archive.html).

Here are the direct links:

Molecular Configuration in Sodium ThymonucleateFranklin, R., and Gosling, R. G.Nature 171, 740-741 (1953) URL: http://www.nature.com/nature/dna50/franklingosling.pdf

Molecular Structure of Deoxypentose Nucleic AcidsWilkins, M. H. F., Stokes, A. R., & Wilson, H. R.

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Nature 171, 738-740 (1953)URL: http://www.nature.com/nature/dna50/wilkins.pdf

(11) This sentence marks what many consider to be an inexcusable failure to give proper credit to Rosalind Franklin, a King’s College scientist. Watson and Crick are saying here that they “were not aware of” Franklin’s unpublished data, yet Watson later admits in his book The Double Helix that these data were critical in solving the problem. Watson and Crick knew these data would be published in the same April 25 issue of Nature, but they did not formally acknowledge her in their paper.

What exactly were these data, and how did Watson and Crick gain access to them? 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 DNA model.

But Franklin was frustrated with an inhospitable environment at King’s, one that pitted her against her colleagues. And in an institution 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 (a longtime friend of Crick).

Then, in perhaps the most pivotal moment in the search for DNA’s structure, Wilkins showed Watson one of Franklin’s photographs without Franklin’s permission. As 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 be a double helix.

Was it unethical for Wilkins to reveal the photographs? Should Watson and Crick have recognized Franklin for her contribution to this paper? Why didn’t they? Would Watson and Crick have been able to make their discovery without Franklin’s data? 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:

“Light on a Dark Lady” by Anne Piper, a lifelong friend of Franklin’sURL: http://www.physics.ucla.edu/~cwp/articles/franklin/piper.html

“The Double Helix and the Wronged Heroine,” an essay on Nature’s “Double Helix: 50 years of DNA” Web siteURL: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v421/n6921/full/nature01399_fs.html

A review of Brenda Maddox’s recent book, Rosalind Franklin: The Dark Lady of DNA in The Guardian (UK)URL: http://books.guardian.co.uk/whitbread2002/story/0,12605,842764,00.html

(12) This 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.

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(13) 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 a longer paper (in Proceedings of the Royal Society). This “expound later” approach was usual in science in the 1950s as it continues to be. In fact, Rosalind Franklin did the same thing, supplementing her short April 25 paper with two longer articles.

Today, scientists publish their results in a variety of formats. They also present their work at conferences. Watson reported his and Crick’s results at the prestigious annual symposium at Cold Spring Harbor Laboratory in June 1953. As part of our recognition of the fiftieth anniversary of the double helix discovery, we will join scientists at Cold Spring Harbor as they present their papers at the “Biology of DNA” conference.

 

Watson-Crick modelA Dictionary of Zoology | 1999 MICHAEL ALLABY | 412 words | Hide copyright information

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Watson-Crick model The currently accepted model for the structure of DNA, as proposed by J. Watson and F. Crick in 1953. It is suggested that DNA is composed of two right-handed, antiparallel, polynucleotide chains coiled around a common axis to form a double helix. This structure is maintained by hydrogen bonds formed between the chains through the basepairing of adenine to thymine and cytosine to guanine.

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. Though it was originally slated to be published by Harvard University Press, Watson's home university dropped the arrangement after protestations from Francis Crick and Maurice

Wilkins,[1] co-discoverers of the structure of DNA, and it was published privately. It has been criticized as being excessively sexist towards Rosalind Franklin, another participant in the discovery, who was deceased by the time Watson's book was written. In 1998, the Modern Library placed The Double Helix at number 7 on its list of the 20th century's best works of non-fiction.

The intimate first-person account of scientific discovery was unusual for its time. The book has been hailed as a highly personal view of scientific work, with its author seemingly caring only about the glory of priority and willing to appropriate data from others surreptitiously in order to obtain it. A 1980 Norton Critical Edition of The Double Helix edited by Gunther Stent, analyzed the events surrounding its initial publication. It presents a selection of both positive and negative reviews of the book, by such figures as Philip Morrison, Richard Lewontin, Alex Comfort, Jacob Bronowski, and more in-depth analyses by Peter Medawar, Robert K. Merton, and Andre Lwoff. Erwin Chargaff declined permission to reprint his unsympathetic review from the March 29, 1968 issue of Science, but letters in response from Max Perutz, Maurice Wilkins, and Watson are printed. Also included are retrospectives from a 1974 edition of Nature written by Francis Crick and Linus Pauling,

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and an analysis of Franklin's work by her student Aaron Klug. The Norton edition concludes with the 1953 papers on DNA structure as published in Nature.