Francis Crick life and biography

Francis Harry Compton Crick was a British molecular biologist, physicist, and neuroscientist, and most noted for being one of two co-discoverers of the structure of the DNA molecule in 1953, together with James D. Watson. He, Watson and Maurice Wilkins were jointly awarded the 1962 Nobel Prize for Physiology or Medicine "for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material".

Francis Crick was one half of the famous pair of molecular biologists who unraveled the mystery of the structure of deoxyribonucleic acid (DNA), carrier of genetic information, thus ushering in the modern era of molecular biology. Since this fundamental discovery, Crick made significant contributions to the understanding of the genetic code and gene action, as well as of molecular neurobiology. In Horace Judson's book The Eighth Day of Creation, the 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.

Before the Double Helix

The eldest of two sons, Francis Harry Compton Crick was born to Harry Crick and Anne Elizabeth Wilkins on June 8, 1916, in Northampton, England. His father and uncle ran a shoe and boot factory. He 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. He 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. He feels 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. Nonetheless, it is clear that Crick read widely and grasped the essence of the argument and logic of what he read.

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. Surprisingly, he found himself fascinated with two areas of biology, particularly, as he describes it in his autobiography, by "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.

The Double Helix

In 1947, Crick divorced Doreen, and in 1949 married Odile Speed, an art student whom he had met during the war, when she was a naval officer and Crick was working for the admiralty. 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.

The Genetic Code

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 overestimated. 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, to use the language of the molecular biologists, the genetic message is "transcribed" to a messenger, and that message is eventually "translated" into action in the synthesis of a protein.

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.

The Salk Institute

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 remained at the Salk Institute for the rest of his life, including a stint as its director. 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."

An interesting footnote to Crick's career at the Salk Institute was his proposal of the idea of "directed panspermia." Along with Leslie Orgel, he published a book, Life Itself, which suggested that microbes drifted through space, eventually reaching Earth and "seeding" it, and that this dispersal event has been caused by the action of "someone." Crick himself was ambivalent about the theory, but he and Orgel proposed it as an example of how a speculative theory might be presented.

During his career as an energetic theorist of modern biology, Francis Crick accumulated, refined, and synthesized the experimental work of others, and brought his unusual insights to fundamental problems in science. His extraordinary efforts brought him myriad honors in addition to the Nobel. Those included the Lasker Award, the Charles Meyer Prize of the French Academy of Sciences, and the Copley Medal of the Royal Society. The Royal Society also established a prize lecture in Crick’s honor. In 1991, he was appointed a member of the Order of Merit. There is probably no better description of Crick's intellectual gifts than that of François Jacob, who, in his book The Statue Within, describes Crick's famous paper "On Protein Synthesis" by noting, "On this difficult subject, Crick was dazzling. He had the gift of going straight to the crux of the matter and ignoring the rest. Of extracting from the hodge-podge of the literature, the solid and the relevant, while rejecting the soft and the vague."

Crick passed away on July 28, 2004 in San Diego. He was 88 years old.

WORKS

* Of Molecules and Men, University of Washington Press, 1966.

* Life Itself, Simon & Schuster, 1981.

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

* The Astonishing Hypothesis: The Scientific Search for the Soul, Scribner, 1994.

* Nature, A Structure for Deoxyribonucleic Acid, Volume 171, 1953, pp. 737-738.

* Nature, Genetical Implications of the Structure of Deoxyribonucleic Acid, Volume 171, 1953, pp. 964-967.

* Symposium of the Society for Experimental Biology, On Protein Synthesis, Volume 12, 1957, pp. 138-163.

* Cold Spring Harbor Symposium of Quantitative Biology, The Genetic Code---Yesterday, Today, and Tomorrow, Volume 31, 1966, pp. 3-9.

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