CRICK, FRANCIS HARRY COMPTON

(b. Weston Favell, Northampton, United Kingdom, 8 June 1916;

d. La Jolla, California, 28 July 2004), molecular biology, the genetic code, the neuroscience of consciousness.

Crick was one of the central figures, one might say the central figure, in the molecular revolution that swept through biology in the latter half of the twentieth century. Having with James Watson discovered the structure of deoxyribonucleic acid (DNA), Crick went on to play a central role in the elucidation of the genetic code and the mechanism of protein synthesis. These achievements won him a share in the Nobel Prize in Physiology or Medicine in 1962. Much sought after as a lecturer, he became the “molecular evangelist,” seeking to convert biochemists and biologists to the new science. He traveled extensively, broadcast on radio, and frequently wrote for Scientific American. His later years were spent in California, where he plunged into the complex world of neuroscience. Crick was vivacious, party-loving, gregarious, hospitable, and a gentleman. But he could react in a forthright manner to pomposity, pretentiousness, and stupidity. Those who knew him well did not find him arrogant or immodest.

Crick was the firstborn of Harry Crick, boot and shoe manufacturer, and Annie Elizabeth Wilkins, the elder daughter of F. W. Wilkins, a gentlemen’s outfitter. Educated to the age of fourteen at Northampton Grammar School for Boys, he then entered Mill Hill School as a scholar and boarder. By the age of sixteen he had passed the Higher Certificate exams, gaining a distinction in physics, but stayed on a further two years. Failing to win a scholarship at either Cambridge or Oxford, he was accepted into the physics course at University College London. There he graduated with a second-class degree and began research on the viscosity of water. When World War II broke out in 1939, his physics department was evacuated to Wales, but he stayed behind.

Naval Research . Crick was among the six thousand scientists selected to support the armed forces as civilian scientists, and in 1940, he began work at the Admiralty Research Laboratory on the outskirts of London. In the winter of 1942, he was one of a five-man team of physicists and mathematicians sent to Havant, close to Portsmouth. There this team set to work to revitalize the Royal Navy’s mine design program. Put in charge of the design of mine-firing mechanisms, Crick displayed imagination and skillful planning in challenging the enemy’s use of mines as offensive weapons. Crick’s performance in this work won him the respect of his seniors. Although at war’s end Crick returned to London as a civil servant in the Admiralty, he felt dissatisfied with military research and decided to make a change.

Casting around for suggestions, he reflected on the principal subject matter of his scientific chats with colleagues. Instead of being physics it was biology: How do chromosomes perform their amazing “dance” in cell division? What is it that distinguishes a crystalline virus capable of reproduction from other organic crystals incapable of reproduction? What can neurophysiology reveal about the mystery of consciousness? Behind these concerns lay his ambition to show that “detailed scientific knowledge” that has already made many religious beliefs untenable, can banish the mystery of life and of consciousness too. While these mysteries “remain unexplained,” he judged, “they can serve as an easy refuge for religious superstition.” Removing these “unfortunate vestiges of earlier beliefs” would enable us to “find our true place in the universe.” “Obviously,” he confessed, “a disbelief in religious dogma was a very deep part of my nature” (Crick, 1988, p. 11).

A New Career: Crystallography . Cricks ambition was to learn the art of x-ray crystallography in order to study the structure of proteins, for in them surely lay the secret of life itself. The Medical Research Council (MRC) agreed to support him, however, only if he would first immerse himself in biology. That meant studying the whole cell, not just extracted material. After he spent two years at the Strangeways Laboratory fulfilling this requirement, his wish to study the structure of proteins was granted, and in 1949, he moved to the MRC Unit for the Study of the Molecular Structure of Biological Systems in Cambridge Universitys Cavendish Laboratory. There his first achievement was to administer a frontal attack on the methods of interpretation of x-ray data being used by his bosses, Sir Lawrence Bragg and Max Perutz, in their brave attempt to find the structure of hemoglobin. Teaching himself, Crick had mastered the application of Fourier theory to the data of x-ray diffraction patterns. Now he possessed an unrivaled insight into the strengths and limitations of these

techniques and a remarkable ability to visualize molecular structures and their symmetry relations in space. This was manifested in his success simultaneously with William Cochran in deriving the main features of the x-ray diffraction pattern that a helical molecule should yield. Next he introduced the idea of supercoiling of helices to account for anomalous diffraction data from the αkeratin of wool that had proved so difficult to accommodate in helical models.

Armed with this knowledge, Crick realized that conventional approaches to the structural interpretation of diffraction patterns have limited value when dealing with DNA fibers, for these consist of long chain molecules packed in a regular order only in the fiber direction. Therefore they lack the three-dimensional lattice of a single crystal. That said, there are strict limitations on the different conformations that long chain molecules can take because they are oriented and packed tightly together in the fiber direction. So it is possible to guess a plausible structure, predict its diffraction pattern and check this against the diffraction data without carrying out the traditional, lengthy calculations, and without knowing the phases of the reflections. Linus Pauling’s success with his alpha helix in 1951 was the classic example of this “stochastic method,” as Pauling called it.

The Structure of DNA . In the fall of 1951, Crick was diverted somewhat from his protein research by the arrival of a young American, James D. Watson. Now Crick had found a collaborator, who like him recognized DNA as the chief if not the sole hereditary material, and after two attempts at building a model by the stochastic method, they arrived at the essentially correct structure in the spring of 1953. Their first attempt in 1951 had proved a fiasco and had caused the ire of Professor Bragg. Not until Pauling was about to publish his own structure for DNA had Bragg in February 1953 permitted Watson and Crick to make a second attempt. Now they opted for a two-chain cylindrical molecule, the helical chains on the outside of the cylinder held together by hydrogen bonds between the bases on the inside. This pairing of bases was specific, always adenine paired with thymine and guanine with cytosine, thus accounting for the strange 1:1 ratios between these pairs of bases described by the biochemist Erwin Chargaff.

The Watson-Crick structure was a proposal, based upon—and therefore supported by—the data of Rosalind Franklin, Raymond Gosling, and Maurice Wilkins published alongside it. Definitive proof of the structure, however, took almost another quarter of a century, owing to the difficulty of synthesizing small stretches of DNA in the form of single crystals.

Watson and Crick’s first communication was exceedingly brief and went over the heads of most biologists, unfamiliar as they were with x-ray crystallography. The second paper, written largely by Crick, brought their proposal down to earth because it explained the relevance of their unusual two-stranded model to biologists. There they explained’

the precise sequence of the bases [on one chain] is the code which carries the genetical information. If the actual order of the bases on one of the pair of chains were given, one could write down the exact order of the bases on the other one, because of the specific pairing. Thus one chain is, as it were, the complement of the other, and it is this feature which suggests how the deoxyribonucleic acid molecule might duplicate itself. . . . The hypothesis we are suggesting is that the template is the pattern of bases formed by one chain … and that the gene contains a complementary pair of such templates. (Watson and Crick, 1953b, p. 966, 967)’

But could DNA carry the enormous variety of genetic determinants involved? Providing the pairing rules were followed, any conceivable sequence was possible on one chain, the other carrying the complementary sequence. Here was speculation on a grand scale.

Despite all the excitement about DNA—the steady stream of visitors coming to see the model, among them Pauling from California and Gerald Pomerat from the Rockefeller Foundation—the impact of Watson and Cricks proposal within the Cavendish laboratory was mixed. Members of the university’s Subdepartment of Crystallography—quite distinct from the Medical Research Council Unit—were unimpressed. But Bragg became very excited. He had been looking forward to Crick’s departure from the lab once his doctoral thesis was completed. Now he began to appreciate Crick’s potential. But Crick was scheduled to spend the next academic year at the Protein Institute in Brooklyn, New York, to help the team there studying the structure of the protein ribonuclease. Then he had the option to work with Linus Pauling at the California Institute of Technology.

Fortunately Crick was able to complete his doctoral dissertation and defend it before leaving for Brooklyn. It was formally awarded to him in absentia in 1954. Meanwhile his future was uncertain. Not until the spring of that year did he receive a new seven-year contract from the Medical Research Council and decide to return to Cambridge.

Crick stayed with the MRC Unit in Cambridge when in 1957 it was moved out of the Cavendish into the hut close by then, in 1962, to the new Laboratory of Molecular Biology two miles from the center of Cambridge. Meanwhile his friends’ nomination of him for a fellowship at King’s College Cambridge in 1956 failed, as did his application for the chair of genetics at Cambridge University as Ronald Fisher’s successor in 1957. The fellowship he accepted at the projected Churchill College in 1960 turned sour when the decision was taken to build a college chapel. Crick resigned over the issue in 1961, but was persuaded to accept an honorary fellowship subsequently. He was a member of Gonville and Caius College, subsequently was given dining rights, and made an honorary fellow in 1976.

The Genetic Code and Protein Synthesis . Given that the gene’s specificity or “information” is encoded in a base sequence of DNA, how is that translated into the immediate gene product: a polypeptide chain composed of a specific sequence of amino acids? Stimulated by the physicist George Gamow, Crick joined in the effort to use cryptography to solve the problem, but all the schemes considered suffered from limitations on the variety of possible amino acid sequences. Nature’;s proteins showed no such limitations.

Cogitating on the coding problem, Crick began to ponder the relation between the nucleic acids and the proteins, and to make this the subject of his lecture, “On Protein Synthesis,” delivered to the Society for Experimental Biology in 1957. Here he laid out the framework that was to constitute the core principles of what became the classical period of molecular biology. First came the Sequence Hypothesis stating that “the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein” (1958, p. 152). Second came the Central Dogma: “the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible. Information means here the precise determination of sequence …” (p. 153).

Given these restrictions on information transfer, how can a match be achieved between a triplet of bases and the amino acid for which the triplet is the cipher? Crick had already discussed this problem earlier and had suggested the existence of “adaptor molecules,” small molecules with hydrogen-bonding sites attached to the appropriate amino acid by special enzymes. His prediction was fulfilled by the discovery of transfer RNA (tRNA).

This framework served its purpose admirably at the time. The extraordinarily complex picture that has since emerged has understandably introduced qualifications. But the discovery in 1970 of a type of RNA that can transfer sequence information back to DNA (reverse transcriptase) did not flout Crick’s definition of the Central Dogma. The great surprise came eight years later. This was the discovery that whole chunks of the RNA transcribed from the gene are often excised before translation of the message into protein begins. Crick commented on these discoveries, accepting that the early ideas were too simple. In this sense he admitted that some of his critics were proved right.

When Sydney Brenner joined the MRC Unit in 1957, their remarkable collaboration began. Also attracted to the unit as visitors that year were the world experts on the genetics of bacterial viruses (bacteriophages or “phages”) Seymour Benzer and George Streisinger. They attempted to discover the code by establishing the base sequence in a gene and the corresponding amino acid sequence in its protein product. But Crick and Brenner continued their own study of the genetics of phage mutations.

In February 1961, Crick began a series of experiments based on an idea he had about the manner in which a mutation can be “suppressed” by a further mutation. The results led him to support Brenner’s suggestion that such “suppressions” are due not to substitution of a different base in a sequence of bases on the DNA molecule, but to addition or deletion of a base. After conducting extensive experiments for some five months, Crick attended a meeting in the Alps. There he mentioned this idea, and the hypothesis “that the code is read in short groups, starting from one end of the gene. The exact starting point is supposed to determine which group is read” (Crick, 1961a, p. 188).

Back in Cambridge Crick carried out further experiments to clinch the case for the “short groups” being composed of three bases or a multiple thereof. In their classic paper summarizing this work, the Cambridge group claimed that the genetic code “is of the following general type”: three bases (or a multiple of three) codes for one amino acid. It is not an overlapping code, “probably ‘degenerate’; that is, in general, one particular amino-acid can be coded by one of several triplets of bases,” and “the sequence of the bases is read from a fixed starting point.… There are no special ‘commas’ to show how to select the right triplets” (Crick et al., 1961, 1227).

Meanwhile he had listened in Moscow to Marshall Nirenberg describe the stunning result of his work with Johann Matthaei on the synthesis of the polypeptide polyphenylalanine (polyPhe), using as template the synthetic RNA polyuridylic acid. PolyU, they concluded, codes for polyPhe. The Cambridge group had revealed the general nature of the code, and Nirenberg and Matthaei had identified the specific cipher for one of the twenty amino acids.

This discovery of the code was the last time Crick worked at the bench. After exploring embryological development with Peter Lawrence, he turned to the mysteries of the chromosome, excited by the discussions ongoing over the enormous amount of nongenetic DNA therein. Here was a chance to provide a model the structure of which might suggest why there is so much repetitive DNA in chromatin and how gene expression is regulated. Unfortunately his structure was proved to be entirely wrong, but it served as the stimulus to attract Roger Kornberg and Aaron Klug to the subject. Kornberg turned the field upside-down by situating the histone on the inside of the chromosome in the form of beads (nucleosomes) and around these beads the DNA is wound. Crick went on to collaborate with Klug on a model that could achieve the ten-thousand-fold compacting suffered by human chromosomes during nuclear division.

From 1959 he had helped Jacob Bronowski and Jonas Salk formulate the plans for the projected Salk Institute in La Jolla, California, and was a nonresident fellow to the institute from 1962 until 1974. The academic year 1976–1977 he spent on sabbatical there. In 1977, he accepted the position of Kieckhefer Distinguished Professor at the Salk, holding it for the rest of his life. Although he avoided whenever possible undertaking administrative work and sitting on committees, he was a powerful influence in deciding policy both in Cambridge and in La Jolla. He refused honorary degrees, the CBE, and a knighthood, but in 1991, he accepted the very exclusive Order of Merit from Queen Elizabeth II. However, he has frequently been referred to erroneously as Sir Francis and even as Lord Crick.

The Brain and Consciousness . For many years Crick had been following developments in neurophysiology from a distance. It was the move to California that helped him to extricate himself from old agendas and turn to new ones. His long-term goal was to tackle “the problem of consciousness,” concentrating on visual perception in primates. He had “rather little expectation of producing any radically new theoretical ideas at such an advanced age,” but he thought he “might interact fruitfully with younger scientists.” At this time in his life, he felt he “had a right to do things” for his own amusement, so long as he “could make an occasional useful contribution” (What Mad Pursuit, p. 152).

He approached the subject without prejudice, ready to consider mathematical-computational and physiological approaches. Having Tomaso Poggio, David Marr, and Graeme Mitchison visit and work with him at the Salk Institute, he immersed himself in the computational approach. But he became skeptical of some of the mathematical modeling of visual processing. His strongest criticisms were directed at those cognitive psychologists who showed no concern for the lack of biological realism in their schemes. Repeatedly he stressed how inappropriate was the analogy drawn between the standard digital computer and the brain. And when he joined the group in the Psychology Department of the University of California at San Diego studying parallel distributed processing—as distinct from the serial processing of standard computers—he repeatedly stressed the need to consider whether their schemes were applicable to the manner in which the brain is wired.

An example of a computational approach that led to an interesting hypothesis was Crick and Mitchison’s paper on the function of dreaming. They found that computer simulations of neural nets when subjected to heavy use become overloaded and unable to continue functioning normally. Cutting off any input, and permitting the nets to cycle over and over, mysteriously restored normal function. Might this not happen in the brain also? Is that what happens when people dream, sensory input being cut off, and rapid eye movements (REM sleep) occurring? Accordingly they suggested that the function of REM sleep is to “unlearn” unwanted “modes of excitation.” They called it “reverse learning.”’

Crick laid most emphasis upon physiological and anatomical approaches to the brain, for these involved opening the “black box.” He had been delighted at the way David Hubel and Torsten Wiesel used the technique of single-cell recording to reveal the “functional anatomy” in the visual centers of the brain. Looking ahead, he urged that greater effort be put into developing new techniques for unraveling the brain’s immensely intricate anatomy.

For the last fourteen years of his life, Crick collaborated with Christoff Koch, professor of cognitive and behavioral biology at Caltech, on the subject of consciousness. Putting aside the difficult problem of explaining how neural events can yield the subjective states of consciousness known as qualia, they looked for the neural correlates of consciousness (NCC). What particular neural activity is present during conscious activity, but absent from activity that is not conscious? Their ambition was to achieve a “framework” that would do for consciousness what the DNA double helix did for molecular biology.

This framework, they claimed, was the first “coherent scheme for the NCC.” Underlying it was the idea of competing coalitions of neurons, some at the back of the brain, others at the front. The mechanisms of attention “bias the competition among these nascent coalitions.” Crick had the conviction that most of what people assume is conscious activity is in fact zombie-like activity. People have the sense of consciously coming to decisions, but they are really the product of unconscious computation. What they are conscious of is only the end result of that computation. As for the function of consciousness, Crick and Koch suggested it serves “to produce the best current interpretation” of the sensory data. Like an “executive summary” it overcomes the problem of data overload thus making possible a swift response.

Crick as Author . From the earliest of his scientific papers, Crick showed good organization and clarity of expression. Not surprisingly, he was the one asked to write the first draft of so many of the jointly authored papers. In writing for general audiences, he knew how to explain the science at their level without being condescending. He started several book projects, but traveling so frequently to meetings and being on the international lecture circuit he was rarely sufficiently settled to carry them through. His first book Of Molecules and Men contained his John Danz lectures. They were devoted to critiquing vitalism by marshaling the successes of molecular biology. The lectures ended with a denunciation of religious education, denial of the existence of an immortal soul, and a prevision of “a time when vitalism will not seriously be considered by educated men” (p. 99).

Very different in tone was Life Itself: Its Origin and Nature. This was distilled from his many discussions with Leslie Orgel, his colleague at the Salk Institute, and enlarges on an idea they had in 1973 and called “directed panspermia.” They suggested that life did not originate on this Earth, but was brought to it in the form of microorganisms carried in an unmanned spaceship from a “higher civilization” elsewhere. This would account for the fact that the genetic code on this Earth is universal, barring a few trivial variants. It assumes that the primitive environment of the Earth was too hostile for the emergence of life here. As an exercise in imagination it was intended to provoke the reader. Crick doubted whether it was likely to be true.

Asked by the Sloan Foundation to write about his life, Crick decided to use his experiences “to teach some general lessons about how research is done, and what mistakes to avoid.” Hence, the book begins with a quotation from Oscar Wilde: “Experience is the name everyone gives to their mistakes.” The book’s title he took from his first public talk on the structure of the proteins: What Mad Pursuit. Crick described the experience early in his career at Cambridge of witnessing Bragg’s failure to discover the alpha helix that made such a deep impression on him. The most striking error he identified was that of assuming that the nucleoprotein particles in the cytoplasm, later called ribosomes, contain the genetic message. Here, fortunately, aided by their colleague Francois Jacob from the Pasteur Institute, Crick and Brenner were among the first to realize there must be a separate RNA messenger (mRNA).

His last book, The Astonishing Hypothesis, was the product of his long-felt need to reconstitute the moral and legal framework of society on a scientific basis. Hence the need to understand human nature, but to achieve this, he claimed, requires a scientific understanding of the nature of consciousness. Only then can people hope to understand humanity’s place in nature. Continuing with outmoded concepts will only lead, he foresaw, to a world so overpopulated as to spell disaster. After explaining with consummate skill many of the complex features of the brain, he ended with “Dr. Crick’s Sunday Morning Service.” Here he expressed his hope that scientific research will make it possible to argue that “the idea that man has a disembodied soul is as unnecessary as the old idea that there was a Life Force” (p. 261).

Crick died in 2004 after a courageous fight against colon cancer. Following a private family memorial, a public memorial was held at the Salk Institute to honor his remarkable contributions to twentieth-century science. Crick’s marriage to Ruth Doreen Dobbs in 1940 was dissolved seven years later. In 1949, he married Odile Speed. He was survived by his wife, his son Michael from his first marriage, and Gabrielle and Jacqueline from his second, plus six grandchildren.

BIBLIOGRAPHY

For a complete list of Crick’s published papers see: http://www.pitt.edu/rpsdept/people/primary_faculty.html#Olby.For manuscript sources see: The Wellcome Library for the History and Understanding of Medicine. Online catalogue of Western Manuscripts and Modern Papers. Reference PP/CRI/A to M. A copy of these papers is at the Mandeville Special Collections Library 0175-S, University of California at San Diego, MSS 600. The Crick Family Papers are only available at UCSD, MSS 660.

WORKS BY CRICK

With W. Cochran. “Evidence for the Pauling-Corey _-Helix in Synthetic Polypeptides.” Nature169 (1952): 234–235.

“Is αKeratin a Coiled Coil?” Nature170 (1952): 882–883.

With W. Cochran and V. Vand. “The Structure of Synthetic Polypeptides: I. The Transform of Atoms on a Helix.” Acta Crystallographica 5 (1952): 581–586.

With James D. Watson. “The Molecular Structure of Nucleic Acids: A Structure for Deoxyribonucleic Acid.” Nature171 (1953a): 737–738.

With James D. Watson. “Genetical Implications of the Structure of Deoxyribonucleic Acid.” Nature171 (1953b): 964–967.

With James D. Watson. “The Complementary Structure of Deoxyribonucleic Acid.” Proceedings of the Royal Society, Series B, 223 (1954): 80–96.

“The Structure of the Synthetic αPolypeptides.” Science Progress 42 (1954): 205–219.

“The Structure of the Hereditary Material.” Scientific American 191 (1954): 54–61.

With B. S. Magdoff and V. Luzzati. “The Three-Dimensional Patterson Function of Ribonuclease II.” Acta Crystallographica 9 (1956): 156–162.

With James D. Watson. “The Structure of Small Viruses.”Nature 177 (1956): 473–476.

“On Degenerate Templates and the Adaptor Hypothesis: A Note for the RNA Tie Club.” Unpublished paper distributed to members of the RNA Tie Club, 1956. Crick Papers, Wellcome Library. Online catalogue of Western Manuscripts and Modern Papers. Reference PP/CRI/H/1/38.

With J. C. Griffith and L. E. Orgel. “Codes without Commas.” Proceedings of the National Academy of Sciences of the United States of America43 (1957): 416–421.

“On Protein Synthesis.” In “The Biological Replication of Macromolecules.” Symposia of the Society of Experimental Biology12 (1958): 138–163.

With Leslie Barnett, S. Brenner, and R. J. Watts-Tobin. “General Nature of the Genetic Code for Proteins.” Nature 192 (1961): 1227–1232.

“The Genetic Code.” Scientific American207 (1962): 66–74.

“Discussion.” Deoxyribonucleic Acid. Structure, Synthesis and Function, Proceedings of the 11th Annual Reunion of the Société de Chimie Physique, June 1961, p. 188.

Of Molecules and Men. Seattle: University of Washington Press,1966.

“Central Dogma of Molecular Biology.” Nature227 (1970):561–563.

“General Model for the Chromosomes of Higher Organisms.” Nature234 (1971): 25–27.

With P. A. Lawrence. “Compartments and Polyclones in Insect Development.” Science189 (1975): 340–347.

“Split Genes and RNA Splicing.” Science204 (1979): 264–271.

“Thinking about the Brain.” Scientific American241, no. 3(1970): 219–232.

Life Itself: Its Origin and Nature. New York: Simon and Schuster,1981.

With G. Mitchison. “The Function of Dream Sleep.” Nature304 (1983): 111–114.

What Mad Pursuit: A Personal View of Scientific Discovery. New York: Basic Books, 1988.

With C. Koch. “The Problem of Consciousness.” Scientific American267 (1992): 152–159.

The Astonishing Hypothesis: The Scientific Search for the Soul. New York: Simon and Schuster, 1994.

With C. Koch. “A Framework for Consciousness.” Nature Neuroscience6 (2003): 119–126.

OTHER SOURCES

Ashe Lincoln, F. Secret Naval Investigator. London: William Kimber, 1961.

Blackmore, Susan. Conversations on Consciousness. Oxford:Oxford University Press, 2006.

Brenner, Sydney. My Life in Science. London: BioMed Central, 2001.

Chadarevian, Soraya de. Designs for Life: Molecular Biology after World War II. Cambridge, U.K.: Cambridge University Press, 2002.

Cowie, Captain J. S. Mines, Minelayers, and Minelaying. London:Oxford University Press, 1949.

Judson, Horace F. The Eighth Day of Creation: Makers of the Revolution in Biology. Expanded edition. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory, 1996.

Olby, Robert. “Francis Crick, DNA, and the Central Dogma.” Daedalus 99 (1970): 938–987. Reprinted with a postscript and comments from Dr. Crick and his aunt, Mrs. Arnold Dickens. In The Twentieth-Century Sciences: Studies in the Biographies of Ideas, edited by Gerald Holton. New York: Norton, 1972.

Ridley, Matthew. Francis Crick: Discoverer of the Genetic Code.London: Harper Collins, 2006.

Watson, James D. The Double Helix: A Personal Account of the Discovery of the Structure of DNA. Norton Critical Edition. New York: Norton, 1980.

Robert C. Olby

Crick, Francis (1916- )

English molecular biologist

Francis Crick is one half of the famous pair of molecular biologists who unraveled the mystery of the structure of DNA (deoxyribonucleic acid ), the carrier of genetic information, thus ushering in the modern era of molecular biology . Since this fundamental discovery, Crick has made significant contributions to the understanding of the genetic code and gene action, as well as the understanding of molecular neurobiology. In Horace Judson's book The Eighth Day of Creation, Nobel laureate Jacques Lucien Monod is quoted as saying, "No one man created molecular biology. But Francis Crick dominates intellectually the whole field. He knows the most and understands the most." Crick shared the Nobel Prize in medicine in 1962 with James Watson and Maurice Wilkins for the elucidation of the structure of DNA.

The eldest of two sons, Francis Harry Compton Crick was born to Harry Crick and Anne Elizabeth Wilkins in Northampton, England. His father and uncle ran a shoe and boot factory. Crick attended grammar school in Northampton, and was an enthusiastic experimental scientist at an early age, producing the customary number of youthful chemical explosions. As a schoolboy, he won a prize for collecting wildflowers. In his autobiography, What Mad Pursuit, Crick describes how, along with his brother, he "was mad about tennis," but not much interested in other sports and games. At the age of fourteen, he obtained a scholarship to Mill Hill School in North London. Four years later, at eighteen, he entered University College, London. At the time of his matriculation, his parents had moved from Northampton to Mill Hill, and this allowed Crick to live at home while attending university. Crick obtained a second-class honors degree in physics, with additional work in mathematics, in three years. In his autobiography, Crick writes of his education in a rather light-hearted way. Crick states that his background in physics and mathematics was sound, but quite classical, while he says that he learned and understood very little in the field of chemistry. Like many of the physicists who became the first molecular biologists and who began their careers around the end of World War II, Crick read and was impressed by Erwin Schrödinger's book What Is Life?, but later recognized its limitations in its neglect of chemistry.

Following his undergraduate studies, Crick conducted research on the viscosity of water under pressure at high temperatures, under the direction of Edward Neville da Costa Andrade, at University College. It was during this period that he was helped financially by his uncle, Arthur Crick. In 1940, Crick was given a civilian job at the Admiralty, eventually working on the design of mines used to destroy shipping. Early in the year, Crick married Ruth Doreen Dodd. Their son Michael was born during an air raid on London on November 25, 1940. By the end of the war, Crick was assigned to scientific intelligence at the British Admiralty Headquarters in Whitehall to design weapons.

Realizing that he would need additional education to satisfy his desire to do fundamental research, Crick decided to work toward an advanced degree. Crick became fascinated with two areas of biology, particularly, as he describes it in his autobiography, "the borderline between the living and the nonliving, and the workings of the brain." He chose the former area as his field of study, despite the fact that he knew little about either subject. After preliminary inquiries at University College, Crick settled on a program at the Strangeways Laboratory in Cambridge under the direction of Arthur Hughes in 1947, to work on the physical properties of cytoplasm in cultured chick fibroblast cells. Two years later, he joined the Medical Research Council Unit at the Cavendish Laboratory, ostensibly to work on protein structure with British chemists Max Perutz and John Kendrew (both future Nobel Prize laureates), but eventually to work on the structure of DNA with Watson.

In 1947, Crick was divorced, and in 1949, married Odile Speed, an art student whom he had met during the war. Their marriage coincided with the start of Crick's Ph.D. thesis work on the x-ray diffraction of proteins. X-ray diffraction is a technique for studying the crystalline structure of molecules, permitting investigators to determine elements of three-dimensional structure. In this technique, x rays are directed at a compound, and the subsequent scattering of the x-ray beam reflects the molecule's configuration on a photographic plate.

In 1941 the Cavendish Laboratory where Crick worked was under the direction of physicist Sir William Lawrence Bragg, who had originated the x-ray diffraction technique forty years before. Perutz had come to the Cavendish to apply Bragg's methods to large molecules, particularly proteins. In 1951, Crick was joined at the Cavendish by James Watson, a visiting American who had been trained by Italian physician Salvador Edward Luria and was a member of the Phage Group, a group of physicists who studied bacterial viruses (known as bacteriophages, or simply phages). Like his phage colleagues, Watson was interested in discovering the fundamental substance of genes and thought that unraveling the structure of DNA was the most promising solution. The informal partnership between Crick and Watson developed, according to Crick, because of their similar "youthful arrogance" and similar thought processes. It was also clear that their experiences complemented one another. By the time of their first meeting, Crick had taught himself a great deal about x-ray diffraction and protein structure, while Watson had become well informed about phage and bacterial genetics.

Both Crick and Watson were aware of the work of biochemists Maurice Wilkins and Rosalind Franklin at King's College, London, who were using x-ray diffraction to study the structure of DNA. Crick, in particular, urged the London group to build models, much as American chemist Linus Pauling had done to solve the problem of the alpha helix of proteins. Pauling, the father of the concept of the chemical bond, had demonstrated that proteins had a three-dimensional structure and were not simply linear strings of amino acids. Wilkins and Franklin, working independently, preferred a more deliberate experimental approach over the theoretical, model-building scheme used by Pauling and advocated by Crick. Thus, finding the King's College group unresponsive to their suggestions, Crick and Watson devoted portions of a two-year period discussing and arguing about the problem. In early 1953, they began to build models of DNA.

Using Franklin's x-ray diffraction data and a great deal of trial and error, they produced a model of the DNA molecule that conformed both to the London group's findings and to the data of Austrian-born American biochemist Erwin Chargaff. In 1950, Chargaff had demonstrated that the relative amounts of the four nucleotides, or bases, that make up DNA conformed to certain rules, one of which was that the amount of adenine (A) was always equal to the amount of thymine (T), and the amount of guanine (G) was always equal to the amount of cytosine (C). Such a relationship suggests pairings of A and T, and G and C, and refutes the idea that DNA is nothing more than a tetranucleotide, that is, a simple molecule consisting of all four bases.

During the spring and summer of 1953, Crick and Watson wrote four papers about the structure and the supposed function of DNA, the first of which appeared in the journal Nature on April 25. This paper was accompanied by papers by Wilkins, Franklin, and their colleagues, presenting experimental evidence that supported the Watson-Crick model. Watson won the coin toss that placed his name first in the authorship, thus forever institutionalizing this fundamental scientific accomplishment as "Watson-Crick."

The first paper contains one of the most remarkable sentences in scientific writing: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." This conservative statement (it has been described as "coy" by some observers) was followed by a more speculative paper in Nature about a month later that more clearly argued for the fundamental biological importance of DNA. Both papers were discussed at the 1953 Cold Spring Harbor Symposium, and the reaction of the developing community of molecular biologists was enthusiastic. Within a year, the Watson-Crick model began to generate a broad spectrum of important research in genetics.

Over the next several years, Crick began to examine the relationship between DNA and the genetic code. One of his first efforts was a collaboration with Vernon Ingram, which led to Ingram's 1956 demonstration that sickle cell hemoglobin differed from normal hemoglobin by a single amino acid. Ingram's research presented evidence that a molecular genetic disease, caused by a Mendelian mutation, could be connected to a DNA-protein relationship. The importance of this work to Crick's thinking about the function of DNA cannot be underestimated. It established the first function of "the genetic substance" in determining the specificity of proteins.

About this time, South African-born English geneticist and molecular biologist Sydney Brenner joined Crick at the Cavendish Laboratory. They began to work on the coding problem, that is, how the sequence of DNA bases would specify the amino acid sequence in a protein. This work was first presented in 1957, in a paper given by Crick to the Symposium of the Society for Experimental Biology and entitled "On Protein Synthesis." Judson states in The Eighth Day of Creation that "the paper permanently altered the logic of biology." While the events of the transcription of DNA and the synthesis of protein were not clearly understood, this paper succinctly states "The Sequence Hypothesis... assumes that the specificity of a piece of nucleic acid is expressed solely by the sequence of its bases, and that this sequence is a (simple) code for the amino acid sequence of a particular protein." Further, Crick articulated what he termed "The Central Dogma" of molecular biology, "that once 'information' has passed into protein, it cannot get out again. In more detail, the transfer of information from nucleic acid to nucleic acid, or from nucleic acid to protein may be possible, but transfer from protein to protein, or from protein to nucleic acid is impossible." In this important theoretical paper, Crick establishes not only the basis of the genetic code but predicts the mechanism for protein synthesis . The first step, transcription, would be the transfer of information in DNA to ribonucleic acid (RNA ), and the second step, translation , would be the transfer of information from RNA to protein. Hence, the genetic message is transcribed to a messenger, and that message is eventually translated into action in the synthesis of a protein. Crick is credited with developing the term "codon" as it applies to the set of three bases that code for one specific amino acid. These codons are used as "signs" to guide protein synthesis within the cell.

A few years later, American geneticist Marshall Warren Nirenberg and others discovered that the nucleic acid sequence U-U-U (polyuracil) encodes for the amino acid phenylalanine, and thus began the construction of the DNA/RNA dictionary. By 1966, the DNA triplet code for twenty amino acids had been worked out by Nirenberg and others, along with details of protein synthesis and an elegant example of the control of protein synthesis by French geneticist François Jacob , Arthur Pardée, and French biochemist Jacques Lucien Monod. Brenner and Crick themselves turned to problems in developmental biology in the 1960s, eventually studying the structure and possible function of histones, the class of proteins associated with chromosomes .

In 1976, while on sabbatical from the Cavendish, Crick was offered a permanent position at the Salk Institute for Biological Studies in La Jolla, California. He accepted an endowed chair as Kieckhefer Professor and has been at the Salk Institute ever since. At the Salk Institute, Crick began to study the workings of the brain, a subject that he had been interested in from the beginning of his scientific career. While his primary interest was consciousness, he attempted to approach this subject through the study of vision. He published several speculative papers on the mechanisms of dreams and of attention, but, as he stated in his autobiography, "I have yet to produce any theory that is both novel and also explains many disconnected experimental facts in a convincing way."

During his career as an energetic theorist of modern biology, Francis Crick has accumulated, refined, and synthesized the experimental work of others, and has brought his unusual insights to fundamental problems in science.

See also Cell cycle (eukaryotic), genetic regulation of; Cell cycle (prokaryotic), genetic regulation of; Genetic identification of microorganisms; Genetic mapping; Genetic regulation of eukaryotic cells; Genetic regulation of prokaryotic cells; Genotype and phenotype; Immunogenetics

Francis Crick

Born June 8, 1916, in Northampton, England; died of colon cancer, July 28, 2004, in San Diego, California. Scientist. Called "one of the most brilliant and influential scientists of all time," by Richard A. Murphy, the president of Salk Institute, in Patricia Sullivan's Washington Post article, Francis Crick discovered, along with James Watson, the double-helical structure of deoxyribonucleic acid (DNA). This one discovery has been called one of the most important in modern times. DNA, the blueprint of life, is the thing responsible for heredity. This discovery made it possible for the fields of genetic engineering and biotechnology and for most of the advances in medicine in the late 20th century and beyond.

Crick was born in Northampton, England, in 1916. The area was famous for its cobbling businesses, and Crick's father, Harry, ran a shoe factory. Crick was a curious boy and his parents bought him a children's encyclopedia when he was young that helped answer a lot of his questions. So many things were being discovered and so many questions answered as he grew up that Crick once admitted to his mother that he was afraid that by the time he grew up everything would have been discovered. He need not have worried. He attended Northampton Grammar School before going to a boarding school in London. After graduation Crick attended University College in London, earning a bachelor's degree in physics in 1937. He had just started work on a Ph.D. in physics at University College when World War II started. He joined the military and served as a scientist at the British Admiralty during the war, designing magnetic and acoustic underwater mines. When he returned to his studies he realized that he was more interested in molecular biology than physics, and he began his studies at the Cavendish Laboratory.

Crick went to Cambridge University in the early 1950s where he met James Watson. The two men discovered a shared interest in DNA and began researching together, with Crick often leading the quest. As a person, Crick was quite an individual. Mark S. Bretscher in the Independent said of Crick, "Francis Crick's greatest assets were his curiosity and ruthless intellect . He could be uncharacteristically mean to a pompous speaker; his presence at meetings made sure everyone was on their toes. He had a fine sense for aesthetic elegance, reflected in his scientific discoveries and writing. His wonderful humor, accompanied by a somewhat raucous laugh, was infectious. He was a great entertainer." It was often this verve and humor that helped along the strenuous research into the obscure nature of DNA.

Scientists at the time knew that cells had a nuclei that contained DNA, but no one knew what its function was. Crick and Watson were convinced that DNA contained the clue to heredity, but that no one had proved this yet. After much research, the pair discovered the spiral ladder shape of DNA and gleaned from this discovery the information about DNA that has become the prevalent and accepted belief. The spiral staircase, they discovered, is actually made up of four different chemicals that make up the "steps" of the ladder. These steps repeat and form a pattern or code. Areas of this code form genes, which carry the blueprints for proteins. Proteins do most of the work in the body and carry out most of its functions, so basically DNA controls everything that a body is and does. The report of the double-helix form of DNA was first reported in the May 23, 1953, edition of the British journal Nature. Crick's wife, Odile Speed, an artist who generally painted nudes, created the first model of the DNA double-helix for the men, and Watson's sister typed up the article.

It was an amazing, life-altering discovery that since that time has been used for just about everything medical. This one discovery gave rise to the biotechnology industry. According to Sullivan in the Washington Post, "The discovery helped scientists understand how humans inherit traits and how that system of inheritance further explains evolution." The discovery has also led to the ability to clone animals. Crick and Watson were awarded the Nobel Prize in Medicine in 1962 for their discovery.

After the DNA discovery Crick continued his research at Cambridge University's Medical Research Council into the mid-1970s, with a focus on the genetics of viruses, protein synthesis, and embryology. In 1976 he took a one-year sabbatical at the Salk Institute for Biological Studies, which he liked so much that in 1977 he moved to La Jolla, California, to work full-time, even holding the position of president of the Salk Institute for a while. At the institute, Crick transferred his focus to the study of the brain and the nature of consciousness. He held the title of J.W. Kieckhefer distinguished professor at the institute until his death. He was also an adjunct professor at the University of California at San Diego.

While he was involved in his research and teaching, Crick was also actively publishing books about his research. In 1981 he published the book Life Itself, which discusses the idea that life began on Earth when microorganisms wafted in from space. It was a shocking, controversial idea and he later came to regret the book. In 1994 he published The Astonishing Hypothesis: The Scientific Search for the Soul, a treatise on consciousness.

After a long bout of illness, Crick died on July 28, 2004, of colon cancer in San Diego, California; he was 88. Watson, Crick's one-time partner, looked back at his friendship with Crick on the CNN website, "I will always remember Francis for his extraordinarily focused intelligence and for the many ways he showed me kindness and developed my self-confidence . I always looked forward to being with him and speaking to him, up until the moment of his death. He will be sorely missed." During his lifetime Crick married Ruth Doreen Dodd, but the couple divorced after seven years. They had one son, Michael F. C. Crick. He married Odile Speed, a French artist, in 1949 and had two daughters, Gabrielle and Jacqueline. He is survived by his wife, three children, and four grandchildren.

Sources

CNN.com, http://www.cnn.com/2004/TECH/science/07/29/people.crick.reut/index.html (July 30, 2004).

Independent (London), August 3, 2004, p. 34.

Los Angeles Times, July 28, 2004, p. A1, p. A26.

New York Times, July 30, 2004, p. A1, p. A13.

Washington Post, July 30, 2004, p. A1, p. A4.

—Catherine Victoria Donaldson

Crick, Francis

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.

see also Delbrück, Max; DNA; DNA Structure and Function, History; RNA; Watson, James.

Richard Robinson

Bibliography

Crick, Francis. What Mad Pursuit: A Personal View of Scientific Discovery. New York: Basic Books, 1988.

Judson, Horace F. The Eighth Day of Creation, expanded ed. Cold Spring Harbor, NY: Cold Spring Harbor Press, 1996.

Crick, Francis

British biophysicist 1916–

Francis Harry Compton Crick, a British biophysicist, was co-winner of the Nobel Prize in physiology and medicine in 1962, for his work in genetics. This award was shared with American biologist James D. Watson and British biophysicist Maurice Wilkins.

Francis Crick, the son of a local shoe factory owner, was born on June 8, 1916, in Northampton England. He did his undergraduate work at University College, London, where he studied physics. Crick's science education was interrupted by World War II. After the war, in 1946, Crick's interest in chemical research was awakened after he attended a lecture given by American chemist Linus Pauling. Crick remained fascinated with organic molecules, and with quantum mechanics and the chemistry of genetics.

Crick went on to conduct research at the Cambridge Medical Research Council Unit at the famous Cavendish physics laboratory. He received his doctorate in 1953 from Cambridge University during the beginning of his collaboration with American biologist James Watson.

In 1952, at Cambridge, Crick and James Watson began to investigate the molecular structure, and significance to genetics, of nucleic acids. They began by looking specifically at earlier X-ray diffraction analyses of deoxyribonucleic acid (DNA), by Maurice Wilkins. DNA was already then considered to be the substance of which genes were made.

Watson and Crick used Wilkins's data, part of which came from coworker Rosalind Franklin, to create a three-dimensional model of the DNA molecule. The model included known facts, such as the chemical constituents (nitrogen bases, sugar, and phosphate), and took into account data from Wilkins's X-ray diffraction experiments.

Watson and Crick tried out various ways of arranging model molecules in space, finally settling on the aptly named double helix. Their model, afterwards referred to as the Watson-Crick model, showed DNA as a twostranded twisted "helix." The two strands contain complementary nitrogen bases. This model both matched chemical facts previously known about DNA, and provided a viable explanation for how DNA could replicate, and thus for how genetic information could pass from one generation to the next generation of living organisms.

Crick's discoveries revolutionized biology. After the acceptance of the Watson-Crick model, biologists could begin to understand living things at the molecular level. Living organisms could be related to one another according to their genetic similarities and dissimilarities.

Following the elucidation of the structure of DNA, Crick turned his attention to how genetic information is stored and used in a cell, and formulated the "central dogma" of molecular biology: that DNA dictates the sequence of ribonucleic acid (RNA), which dictates the sequence of amino acids in proteins , without the possibility of a reverse flow of information. He continued to make important theoretical contributions to genetics with a particular interest in development, until he turned his attention to neuroscience in the late 1970s. Crick's focus since then has been on the biology of consciousness and the nature of visual processing in the brain.

Among Crick's well-known publications are Of Molecules and Men (1996) and Life Itself (1982).

see also DNA; Gene; History of Biology: Inheritance; Nucleotides; Watson, James

Hanna Rose Shell

Bibliography

Crick, Francis. What Mad Pursuit? New York: Basic Books, 1988.

Sherborn, Victoria. James Watson and Francis Crick: Decoding the Secrets of DNA. Woodbridge, CT: Blackbirch Press, 1995.

Strathern, Paul. The Big Idea: Crick, Watson, and DNA. New York: Anchor, 1997.

Watson, James. The Double Helix. New York: Norton Press, 1968.