James Watson & Francis Crick
 

It took an ex-physicist and a former ornithology student — along with some unwitting help from a competitor — to crack the secret of life

By ROBERT WRIGHT for Time Magazine
 

On Feb. 28, 1953, Francis Crick walked into the Eagle pub in Cambridge, England, and, as James Watson later recalled, announced that "we had found the secret of life." Actually, they had. That morning, Watson and Crick had figured out the structure of deoxyribonucleic acid, DNA. And that structure — a "double helix" that can "unzip" to make copies of itself — confirmed suspicions that DNA carries life's hereditary information.

Not until decades later, in the age of genetic engineering, would the Promethean power unleashed that day become vivid. But from the beginning, the Watson and Crick story had traces of hubris. As told in Watson's classic memoir, "The Double Helix," it was a tale of boundless ambition, impatience with authority and disdain, if not contempt, for received opinion. ("A goodly number of scientists," Watson explained, "are not only narrow-minded and dull but also just stupid.") Yet the Watson and Crick story is also one of sublime harmony, an example, as a colleague put it, of "that marvelous resonance between two minds — that high state in which 1 plus 1 does not equal 2 but more like 10."

The men were in some ways an odd pair. The British Crick, at 35, still had no Ph.D. The American Watson, 12 years Crick's junior, had graduated from the University of Chicago at 19 and nabbed his doctorate at 22. But they shared a certain wanderlust, an indifference to boundaries. Crick had migrated from physics into chemistry and biology, fascinated by the line "between the living and the nonliving." Watson had studied ornithology, then forsook birds for viruses, and then, doing postdoctoral work in Europe, took another sharp career turn.

At a conference in Naples, Watson saw a vague, ghostly image of a DNA molecule rendered by X-ray crystallography. DNA, he had heard, might be the stuff genes are made of. "A potential key to the secret of life was impossible to push out of my mind," he later wrote. "It was certainly better to imagine myself becoming famous than maturing into a stifled academic who had never risked a thought."

This theme of Watson's book — the hot pursuit of glory, the race against the chemist Linus Pauling for the Nobel Prize that DNA would surely bring--got bad reviews from the (relatively) genteel Crick. He didn't recall anyone mentioning a Nobel Prize. "My impression was that we were just, you know, mad keen to solve the problem," he later said. But whatever their aims, Watson and Crick shared an attraction to DNA, and when they wound up in the same University of Cambridge lab, they bonded.

Fatefully, such amity did not prevail at a laboratory over at King's College, London, where a woman named Rosalind Franklin was creating the world's best X-ray diffraction pictures of DNA. Maurice Wilkins, a colleague who was also working on DNA, disliked the precociously feminist Franklin, and the feeling was mutual. By Watson's account, this estrangement led Wilkins to show Watson one of Franklin's best pictures yet, which hadn't been published. "The instant I saw the picture my mouth fell open," Watson recalled. The sneak preview "gave several of the vital helical parameters."

Franklin died of cancer in 1958, at 37. In 1962 the Nobel Prize, which isn't given posthumously, went to Watson, Crick and Wilkins. In Crick's view, if Franklin had lived, "it would have been impossible to give the prize to Maurice and not to her" because "she did the key experimental work." And her role didn't end there. Her critique of an early Watson and Crick theory had sent them back to the drawing board, and her notebooks show her working toward the solution until they found it; she had narrowed the structure down to some sort of double helix. But she never employed a key tool — the big 3-D molecular models that Watson and Crick were fiddling with at Cambridge.

It was Watson who fit the final piece into place. He was in the lab, pondering cardboard replicas of the four bases that, we now know, constitute DNA's alphabet: adenine, thymine, guanine and cytosine, or A, T, G and C. He realized that "an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair." These pairs of bases could thus serve as the rungs on the twisting ladder of DNA.

Here — in the "complementarity" between A and T, between C and G — lay the key to replication. In the double helix, a single strand of genetic alphabet — say, CAT--is paired, rung by rung, with its complementary strand, GTA. When the helix unzips, the complementary strand becomes a template; its G, T and A bases naturally attract bases that amount to a carbon copy of the original strand, CAT. A new double helix has been built.

Watson's famous "Aha!" was but the last in a long chain. It was Crick who had fastened onto a chemist friend's theoretical hunch of a natural attraction between A and T, C and G. He had then championed the complementarity scenario — sometimes against Watson's resistance — as a possible explanation of "Chargaff's rules," the fact that DNA contains like amounts of adenine and thymine and of guanine and cytosine. But it was Watson who had first learned of these rules.

As Horace Freeland Judson observed in "The Eighth Day of Creation," this sort of synergy is, above all, what Rosalind Franklin lacked. Working in a largely male field in an age when women weren't allowed in the faculty coffee room, she had no one to bond with — no supportive critic whose knowledge matched her gaps, whose gaps her knowledge matched.

Writing up their findings for the journal Nature, the famously brash Watson and Crick donned a British reserve. They capped a dry account of DNA's structure with one of the most famous understatements in the history of science: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." They faced the question of byline: Watson and Crick, or Crick and Watson? They flipped a coin.

The double helix — both the book and the molecule — did nothing to slow this century's erosion of innocence. Watson's account, depicting researchers as competitive and spiteful — as human — helped de-deify scientists and bring cynicism to science writing. And DNA, once unveiled, left little room for the ethereal, vitalistic accounts of life that so many people had found comforting. Indeed, Crick, a confirmed agnostic, rather liked deflating vitalism — a mission he pursued with zeal, spearheading decades of work on how exactly DNA builds things before he moved on to do brain research at the Salk Institute for Biological Studies in La Jolla, Calif.

Watson drifted from pure science into administration. As director of the molecular-biology lab at Cold Spring Harbor, N.Y., he turned it into a scientific powerhouse. He also served as head of the Human Genome Project, absorbing some fallout from the high-energy ethical debates whose fuse he and Crick had lighted nearly four decades earlier.

As the practical and philosophical issues opened by the double helix continue to unfold, policy, philosophy and even religion will evolve in response. But one truth seems likely to endure, universal and immutable. It emerges with equal clarity whether you examine the DNA molecule or the way it was revealed. The secret of life is complementarity.
 

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Francis Crick
British Biophysicist
1916 -

Francis Crick is the co-discoverer, with James Watson, of the structure of DNA. He has remained a significant contributor to theoretical biology since that discovery.


Education and Training

Crick was born in Northampton, England, in 1916. He studied physics at University College in London until the outbreak of the Second World War. He then joined the British Admiralty Research Laboratory, where he contributed to the development of radar for tracking enemy planes, and magnetic mines used in naval warfare.

During this time, Crick read What is Life?, a book by the physicist Erwin Schrödinger. Schrödinger's book popularized the work of physicist Max Delbrück, who had begun to apply the analytical tools of physics to inquire what a gene was and how it might behave. Like many other physicists at that time, Crick was excited by Delbrück's approach, and turned his attention to biochemistry and biological physics. While he knew a great deal of physics, he knew very little chemistry or biology at that time. In 1949 he began research at the Cavendish Laboratory in Cambridge, England, using X-ray crystallography to study the three-dimensional structures of proteins. At that time, Crick wrote that he was interested in "the borderline between the living and the nonliving, as typified by, say, proteins, viruses, bacteria and the structure of chromosomes. The eventual goal, which is somewhat remote, is the description of these activities in terms of their structure, i.e., the spatial distribution of their constituent atoms" (Judson, 88).


The Structure of DNA

Almost ten years earlier, it had been shown that genes encode proteins, but the chemical nature of the gene remained unknown. Genes were presumed to be composed of DNA (deoxyribonucleic acid), at least in part, but how DNA might encode hereditary information, and whether it acted alone or in partnership with proteins, was a complete mystery. Crick saw that the solution to the mystery lay in discovering the structure of DNA, whose linearity he guessed corresponded to the linear amino acid chains of which proteins are made.

In 1951 a 23-year-old American named James Watson joined the Cavendish Laboratory. Watson and Crick got along well, and they decided to work together on the structure of DNA. DNA was known to be composed of nucleotide subunits, each of which had a sugar (deoxyribose), a phosphate, and a nitrogenous base. The sugars were known to alternate with phosphates to make long strands, off of which the bases projected. The bases came in four types: adenine, thymine, cytosine, and guanine (A, T, C, and G). Shortly before Crick and Watson began to collaborate, American biochemist Erwin Chargaff had discovered that across a wide range of species, the amount of adenine in an organism's DNA always equaled the amount of thymine, and the amount of cytosine always equaled the amount of guanine.

Crick and Watson proceeded to build models of the nucleotides, which they attempted to fit together in accordance with what was known from experimental data. The most important data came from X-ray images of DNA that had been generated by Rosalind Franklin, who also worked at the Cavendish. Using this information, they constructed a model in which the two sugar-phosphate strands wind around each other to form a double helix, their bases projecting inward, like the stair treads of a broad spiral staircase. The two strands are held together and stabilized by the hydrogen bonding between the bases across the interior. These weak chemical attractions, they discovered, are strongest when adenine projects across to meet a thymine, and guanine a cytosine, explaining the ratios discovered by Chargaff. They published their model in 1953. Watson and Crick received the Nobel Prize in physiology or medicine in 1962 for this work, along with Maurice Wilkins of the Cavendish Lab.

After the publication of DNA's structure, Crick turned his attention to understanding the coding function of DNA. He and Watson proposed that the order of bases in a gene encoded the order of amino acids in a protein. Over the next decade, the details of this insight were worked out by a large group of scientists, including Crick, Watson, Sydney Brenner, George Gamow, Seymour Benzer, Marshall Nirnberg, and Har Gobind Khorana. As part of this work, Crick hypothesized the existence of an "adaptor" that intervened between DNA and amino acids. This led to the discovery of messenger RNA and transfer RNA, which serve this function.


Later Work

Crick received his Ph.D. in 1954. He remained with the Medical Research Council at the Cavendish Laboratory, and became head of the Division of Molecular Genetics in 1962, continuing to work closely with Sydney Brenner. He turned his attention to embryology in the mid-1960s, and in 1975 he moved to the Salk Institute in La Jolla, California, to pursue neurobiology, an interest that had vied with molecular biology from the very beginning of his career. At the Salk Institute, in collaboration with Christof Koch, he studies the neural correlates of conscious visual experience, seeking to understand how neuron firing patterns correspond to the conscious experience of seeing.
 

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Francis Harry Crompton Crick

The English molecular biologist Francis Harry Compton Crick (born 1916) contributed to the establishment of the double-helical model of the DNA molecule.

Francis Crick was born June 8, 1916, in Northampton, England. At University College, London, he studied physics and mathematics and obtained his degree in 1937. Work on an advanced degree was halted by the coming of World War II, when Crick had to shift his interest from pure science to the design and production of magnetic mines. By the time the war ended, he had decided to pursue a career in biology, not physics. His decision was influenced by a reading of the book What Is Life? by physicist Erwin Schrödinger, with its message that an intensive investigation of the gene was likely to reveal the nature of life.

Crick began his study of biology at Strangeways Laboratory, Cambridge, in 1947, but within 2 years he left to join the Medical Research Council Unit for Molecular Biology at Cavendish Laboratory and to enroll as a doctoral student at Caius College, Cambridge. While at Cavendish he met (1951) the young American biologist James D. Watson, who shared his interest in the gene and the genetic material, deoxyribonucleic acid (DNA). In 1953 Crick and Watson jointly proposed their doublehelical model of the DNA molecule, which brought them the Nobel Prize in 1962, an honor they shared with English biophysicist Maurice Wilkins. In addition to the prize, Crick received distinguished lectureships, awards from scientific organizations, and membership in honorary societies, including the Royal Society of London (1959).

The discovery of the structure of DNA is considered to be one of the greatest events in 20th-century biology. Genes are responsible for transferring hereditary information from one generation to the next, and since they are DNA molecules, or segments of them, the structure of DNA provides the key to understanding the physical basis of heredity. The giant DNA molecule is a complex one, and Crick and Watson faced the difficult task of determining the exact arrangement of its molecular subunits. While Wilkins and others attempted to discover this arrangement by concentrating exclusively upon x-ray diffraction techniques, Crick and Watson approached the problem by conceiving and building large-scale models that would account for all the known physical and chemical properties of DNA. Watson first suggested the double helix as the basic feature of DNA, but it was Crick, with his background in physics, who supplied the theoretical and mathematical knowledge so important to the team's success.

Upon completion of the work on the structure of DNA, Crick began an investigation of the genetic code, that is, the precise manner in which the gene controls the synthesis of proteins.
 

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James Watson
Geneticist
1928-

James Dewey Watson was the codiscoverer of the structure of DNA. He has also made major contributions to research in genetics and molecular biology as an administrator, and has written widely read and influential books for both academic and nonscience audiences.


Early Life and Training

Watson was born April 6, 1928, in Chicago, Illinois. He showed his brilliance early, finishing high school in two years and appearing as one of the original "Quiz Kids," on a popular 1940s radio show of the same name. He was graduated from the University of Chicago in 1947 with a B.S. in zoology, reflecting an early love of birds. He did his doctoral work at Indiana University in genetics, and earned a Ph.D. in 1950. He was drawn to Indiana by the chance to work with Hermann Joseph Muller, who had been one of Thomas Hunt Morgan's associates in the famous "fly room" at Columbia University, and who had received a Nobel Prize for his discoveries in genetics. Watson's thesis adviser and principal mentor was Salvador Luria, who, along with Max Delbrück, had established bacterial genetics as the experimental system in which most of the major discoveries in molecular biology were to be made. Watson's thesis was on the effect of X rays on the multiplication of a bacterial virus, called phage.

Watson continued to study phage as a postdoctoral student in Copenhagen, Denmark where he worked from 1950 to 1951. While there, he met Maurice Wilkins, and for the first time saw the X-ray diffraction images generated in Wilkins's lab by Rosalind Franklin. Watson quickly decided to turn his attention to discovering the structure of important biological molecules, including DNA and proteins. By that time, DNA had been shown to be the genetic molecule, and it was believed that it somehow carried the instructions for making proteins, which actually perform most of the work in a cell.


The Structure of DNA

Luria arranged for Watson to continue his work at the Cavendish Laboratory in Cambridge, England, which was a center for the study of biomolecular structure, and Watson arrived there in late 1951. At the Cavendish, he met Francis Crick, who, after training in physics, had turned his attention to similar structural questions. The two hit it off, and began collaborating on the structure of DNA.

Watson and Crick approached the problem by building models of the four nucleotides known to make up DNA. Each was composed of a sugar called deoxyribose, a phosphate group, and one of four bases, called ade-nine, thymine, cytosine, and guanine. They knew the sugars and phosphates alternated to form a chain, with the bases projecting off to the side. The X-ray images they had seen suggested the structure was a helix, and offered more information about dimensions as well. They also knew that the biochemist Erwin Chargaff had discovered that the amounts of adenine and thymine in a cell's DNA were equal, as were the amounts of cytosine and guanine.

After several failed attempts, more analysis of the X-ray images, and a fortuitous conversation with a biochemist who corrected one of their hypothesized base structures, they developed the correct model. The helix is formed from two opposing strands of sugar phosphates, while the bases project into the center. Weak bonding (called hydrogen bonding) between bases holds them together. The key, as Watson and Crick discovered, was that the hydrogen bonds work best when adenine pairs with thymine, and guanine with cytosine, thus explaining Chargaff's ratios. The structure immediately suggested a replication mechanism, in which each side serves as the template for the formation of a new copy of the opposing side, and they speculated, correctly, that the sequence of the bases was a code for the sequence of amino acids in proteins. They published their results in 1953, and received the Nobel Prize for physiology and medicine for it 1962, along with Wilkins (Franklin by then had died, and was therefore ineligible for the prize).


Later Accomplishments

Watson remained active in the study of DNA and RNA for a number of years after the publication of the DNA structure. He joined the faculty of Harvard University in 1955, and remained there until 1976. During this time, he wrote an influential textbook, Molecular Biology of the Gene, and an enormously popular (and colorful) account of his and Crick's discovery, called The Double Helix.

In 1968 Watson became the director of the Cold Spring Harbor Laboratory on Long Island, New York, and he became president of the laboratory in 1994, a position he continues to hold. Watson revitalized this laboratory, helping it become one of the premier genetics research institutions in the world. His organizational drive was also called upon in 1988, when he spearheaded the launch of the U.S. Human Genome Project, dedicated to determining the sequence of the entire three billion bases in the genome. He headed the project from 1988 to 1992.

Throughout his career, Watson has invariably been described as "brash," reflecting his capacity to take on big projects and big ideas, and his enthusiasm for making daring, occasionally outrageous predictions about the causes of an unexplained phenomenon or the direction science will take. Explaining this tendency in relation to his work on DNA, Watson wrote, "A potential key to the secret of life was impossible to push out of my mind. It was certainly better to imagine myself becoming famous than maturing into a stifled academic who had never risked a thought."
 

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James Dewey Watson
 

The American biologist James Dewey Watson (born 1928) was a discoverer of the double-helical structure of the deoxyribonucleic acid molecule.

James D. Watson was born April 6, 1928, in Chicago, Illinois. At age 15 he entered the University of Chicago. He graduated in 1947 and went on to pursue graduate study in the biological sciences at Indiana University. There he came under the influence of some distinguished scientists, including Nobel laureate Hermann J. Muller, who were instrumental in shifting his interests from natural history toward genetics and biochemistry. In 1950 Watson successfully completed his doctoral research project on the effect of x-rays upon the multiplication of bacteriophages (viruses that attack bacterial cells).

Watson spent 1950-1951 as a National Research Council fellow in Copenhagen doing postdoctoral work with biochemist Herman Kalckar. He had hoped to learn more about the biochemistry of the genetic material deoxyribonucleic acid (DNA). These studies proved unproductive. It was not until the spring of 1951, when he heard the English biophysicist Maurice Wilkins speak in Naples on the structure of the DNA molecule, that Watson enthusiastically turned his full attention to the DNA problem.

Watson's next research post at Cavendish Laboratory, Cambridge, England, brought him into contact with the physicist turned biologist Francis Crick. Together they shared an interest in DNA while he was preparing for his doctorate. Thus began the partnership between Watson and Crick which resulted in their joint proposal of the double-helical model of the DNA in 1953. Watson, Crick, and Wilkins shared the 1962 Nobel Prize in physiology or medicine for their DNA studies.

The structure of the giant and complex DNA molecule reveals the physical and chemical basis of heredity. Watson and Crick were convinced that the molecular subunits which made up DNA were arranged in a relatively simple pattern that could be discovered by them. Their mode of operation stressed the conception and construction of large-scale models that would account for the known chemical and physical properties of DNA. To this model-building endeavor Watson contributed the double-helical structure, along with other fruitful, intuitive suggestions, while Crick provided the necessary mathematical and theoretical knowledge. After their work on DNA was completed, Watson and Crick collaborated again in 1957, this time in clarifying the structure of viruses.

After a two-year stay at the California Institute of Technology, Watson accepted a position as professor of biology at Harvard University in 1956 and remained on the faculty until 1976. In 1968 he became the director of the Cold Spring Biological Laboratories but retained his research and teaching position at Harvard. That same year he published The Double Helix, revealing the human story behind the discovery of the DNA structure, including the rivalries and deceits which were practiced by all.

While at Harvard Watson wrote The Molecular Biology of the Gene (1965), the first widely used university textbook on molecular biology. This text has gone through seven editions and exists in two large volumes as a comprehensive treatise of the field. He gave up his faculty appointment at the university in 1976, however, and assumed full-time leadership of Cold Spring Harbor. With John Tooze and David Kurtz, Watson wrote The Molecular Biology of the Cell, originally published in 1983.

In l989 Watson was appointed the director of the Human Genome Project of the National Institutes of Health. Less than two years later, in 1992, he resigned in protest over policy differences in the operation of this massive project. He continued to speak out on various issues concerning scientific research and upheld his strong presence concerning federal policies in supporting research. In addition to sharing the Nobel Prize, Watson received numerous honorary degrees from institutions, including one from the University of Chicago (1961) when Watson was still in his early thirties. He was also awarded the Presidential Medal of Freedom in 1977 by President Jimmy Carter.

Watson, as his book The Double Helix confirms, has never avoided controversy. His candor about his colleagues and his combativeness in public forums have been noted by critics. Nevertheless, his scientific brilliance is attested to by Crick, Delbruck, Luria, and others. The importance of his role in the DNA discovery has been well supported by Gunther Stent, a member of the Delbruck phage group, in an essay which discounts many of Watson's critics through well-reasoned arguments.

Most of Watson's professional life has been spent as a professor, research administrator, and public policy spokesman for research. More than any other location in Watson's professional life, Cold Spring Harbor (where he is still director) has been the most congenial in developing his abilities as a scientific catalyst for others. His work there has primarily been to facilitate and encourage the research of other scientists.

In 1968 Watson married Elizabeth Lewis. They had two children, Rufus Robert and Duncan James.

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