TORIma Academy Logo TORIma Academy
Francis Crick
Science

Francis Crick

TORIma Academy — Biologist / Geneticist

Francis Crick

Francis Crick

Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind…

Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. Alongside James Watson, Rosalind Franklin, and Maurice Wilkins, he was instrumental in elucidating the helical structure of the DNA molecule.

Francis Harry Compton Crick (8 June 1916 – 28 July 2004) was an English molecular biologist, biophysicist, and neuroscientist. He, James Watson, Rosalind Franklin, and Maurice Wilkins played crucial roles in deciphering the helical structure of the DNA molecule.

The 1953 publication by Crick and Watson in Nature established the foundational understanding of DNA's structure and functions. In collaboration with Maurice Wilkins, they received the 1962 Nobel Prize in Physiology or Medicine for "their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material."

Crick distinguished himself as a significant theoretical molecular biologist, contributing critically to the research that unveiled the helical architecture of DNA. He is widely recognized for coining the term "central dogma," which encapsulates the principle that genetic information, once transferred from nucleic acids (DNA or RNA) to proteins, cannot subsequently revert to nucleic acids. This implies that the ultimate stage in the informational transfer from nucleic acids to proteins is an irreversible process.

For the remainder of his professional life, Crick served as the J.W. Kieckhefer Distinguished Research Professor at the Salk Institute for Biological Studies in La Jolla, California. His subsequent research endeavors focused on theoretical neurobiology and efforts to advance the scientific investigation of human consciousness. Crick maintained this position until his passing in 2004; Christof Koch noted that "he was editing a manuscript on his death bed, a scientist until the bitter end."

Early Life and Education

Born on 8 June 1916, Crick was the eldest son of Harry and Annie Elizabeth Crick (née Wilkins). He grew up in Weston Favell, then a small village adjacent to Northampton, England, where his father and uncle operated the family's boot and shoe manufacturing business. His paternal grandfather, Walter Drawbridge Crick, an amateur naturalist, authored a study on local foraminifera (shelled single-celled protists), exchanged correspondence with Charles Darwin, and had two gastropod species (snails or slugs) named in his honor.

From a young age, Francis demonstrated an affinity for science, often seeking knowledge through books. Although his parents took him to church during his childhood, by approximately age 12, he expressed a preference for scientific inquiry over religious doctrine, ceasing his attendance.

His uncle, Walter Crick, resided in a modest dwelling on the south side of Abington Avenue, possessing a garden shed where he instructed Crick in glassblowing, chemical experimentation, and photographic printing. At the age of eight or nine, Crick enrolled in the most junior class at Northampton Grammar School, located on Billing Road. This institution was approximately 1.25 miles (2 km) from his residence, a distance he could traverse on foot via Park Avenue South and Abington Park Crescent, though he frequently utilized bus transport or, subsequently, a bicycle. While the instruction in the senior forms was adequate, it lacked significant intellectual stimulation. Following his fourteenth birthday, he attended Mill Hill School in London on a scholarship, where he pursued studies in mathematics, physics, and chemistry alongside his close friend, John Shilston. On Friday, 7 July 1933, Mill Hill School's Foundation Day, he was a co-recipient of the Walter Knox Prize for Chemistry. He attributed his academic achievements to the high standard of teaching he experienced during his time at Mill Hill.

Crick pursued his undergraduate studies at University College London (UCL), a constituent college of the University of London, obtaining a Bachelor of Science degree from the University of London in 1937. His doctoral research at UCL was initiated but subsequently interrupted by World War II. He later became a PhD student and an Honorary Fellow at Gonville and Caius College, Cambridge, primarily conducting his work at the Cavendish Laboratory and the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge. Additionally, he held honorary fellowships at Churchill College, Cambridge, and University College London.

Francis Crick commenced a doctoral research project focused on determining the viscosity of water at elevated temperatures, a task he subsequently characterized as "the dullest problem imaginable." This work was conducted in the laboratory of physicist Edward Neville da Costa Andrade at University College London. However, the onset of World War II, specifically an incident during the Battle of Britain where a bomb destroyed his experimental equipment, diverted Crick from a potential career in physics. Nevertheless, during his second year as a PhD candidate, he received the prestigious Carey Foster Research Prize. Subsequently, he undertook postdoctoral research at the Brooklyn Collegiate and Polytechnic Institute, which is now integrated into the New York University Tandon School of Engineering.

During World War II, Crick was employed by the Admiralty Research Laboratory, an institution that fostered the careers of numerous distinguished scientists, including David Bates, Robert Boyd, Thomas Gaskell, George Deacon, John Gunn, Harrie Massey, and Nevill Mott. His contributions involved the development of magnetic and acoustic mines, and he played a pivotal role in engineering an innovative mine design that proved effective against German minesweepers.

Post-World War II Life and Work

In 1947, at the age of 31, Crick transitioned into the study of biology, joining a significant movement of physical scientists entering biological research. This shift was facilitated by the burgeoning influence of physicists like Sir John Randall, whose wartime innovations, such as radar, had been crucial to Allied victory. Crick faced the challenge of adapting from the "elegance and deep simplicity" inherent in physics to the "elaborate chemical mechanisms that natural selection had evolved over billions of years." He characterized this transition as "almost as if one had to be born again." Crick asserted that his background in physics instilled in him a crucial lesson—hubris—and the conviction that, given physics' established success, comparable breakthroughs were attainable in other scientific disciplines, including biology. This perspective, Crick believed, emboldened him to adopt a more audacious approach compared to conventional biologists, who often focused solely on biology's formidable challenges rather than drawing inspiration from physics' historical achievements.

For nearly two years, Crick investigated the physical properties of cytoplasm at Cambridge's Strangeways Research Laboratory, led by Honor Bridget Fell, supported by a Medical Research Council studentship. Subsequently, he joined Max Perutz and John Kendrew at the Cavendish Laboratory. The Cavendish Laboratory, under the overall direction of Sir Lawrence Bragg—a Nobel laureate in 1915 at age 25—was actively engaged in the race to elucidate DNA's structure, aiming to preempt the renowned American chemist Linus Pauling. This endeavor followed Pauling's prior success in determining the alpha helix structure of proteins. Concurrently, Bragg's Cavendish Laboratory was in effective competition with the Biophysics department at King's College London, directed by Randall, who had previously rejected Crick's application for a position there. Francis Crick and Maurice Wilkins of King's College maintained a personal friendship, a relationship that significantly influenced subsequent scientific developments, akin to the close association between Crick and James Watson. Contrary to erroneous accounts by two authors, Crick and Wilkins initially met at King's College, not at the Admiralty during World War II.

In 1995, Francis Crick endorsed the Ashley Montagu Resolution, a petition submitted to the International Court of Justice (formerly known as the World Court) advocating for the cessation of non-therapeutic genital modification of children, encompassing female genital mutilation, circumcision, and penile subincision.

Personal Life

Crick was married twice and had three children. His brother, Anthony (born in 1918), predeceased him in 1966.

Spouses:

Children:

Francis Crick succumbed to colon cancer on the morning of July 28, 2004, at the University of California, San Diego (UCSD) Thornton Hospital in La Jolla. Following cremation, his ashes were dispersed into the Pacific Ocean. A public commemorative service took place on September 27, 2004, at the Salk Institute in La Jolla, California, adjacent to San Diego. Notable speakers at the event included James Watson, Sydney Brenner, Alex Rich, Seymour Benzer, Aaron Klug, Christof Koch, Pat Churchland, Vilayanur Ramachandran, Tomaso Poggio, Leslie Orgel, Terry Sejnowski, his son Michael Crick, and his younger daughter Jacqueline Nichols. Earlier, on August 3, 2004, a private memorial gathering was conducted for his family and professional associates.

Crick's Nobel Prize medal and accompanying diploma were auctioned by Heritage Auctions in June 2013, fetching $2,270,000. The purchaser was Jack Wang, Chief Executive Officer of the Chinese medical firm Biomobie. Twenty percent of the proceeds from the medal's sale were subsequently contributed to the Francis Crick Institute in London.

Research

Francis Crick's intellectual pursuits centered on two fundamental, unresolved biological questions: namely, the molecular transition from non-living to living matter, and the neural mechanisms underlying conscious thought. He recognized that his academic background better prepared him for investigations into the former, particularly within the domain of biophysics. In 1946, Crick's reading of Erwin Schrödinger's book, What Is Life?, alongside the influence of Linus Pauling, prompted his transition from physics to biology. The theoretical understanding at the time suggested that covalent bonds within biological macromolecules could confer the requisite structural stability for cellular genetic information storage. The precise identification of the genetic molecule then became a critical objective for experimental biology. Crick posited that the convergence of Charles Darwin's theory of evolution by natural selection, Gregor Mendel's principles of genetics, and insights into the molecular underpinnings of heredity would collectively unveil the fundamental nature of life. He held a highly optimistic perspective, anticipating the imminent laboratory synthesis of life. Nevertheless, some contemporaries, including fellow researcher Esther Lederberg, considered Crick's optimism excessive.

Initially, it was widely assumed that a macromolecule, such as a protein, constituted the genetic material. However, proteins were also recognized as versatile structural and functional macromolecules, many of which catalyze essential cellular enzymatic reactions. By the 1940s, however, emerging evidence began to implicate deoxyribonucleic acid (DNA), the other primary constituent of chromosomes, as a potential genetic molecule. Specifically, the 1944 Avery-MacLeod-McCarty experiment, conducted by Oswald Avery and his team, demonstrated that introducing a specific DNA molecule into bacteria could induce a heritable phenotypic alteration.

Conversely, some interpretations of existing data suggested that DNA possessed limited structural complexity, potentially serving merely as a molecular scaffold for the seemingly more dynamic protein molecules. In 1949, Crick's opportune circumstances—his location, intellectual disposition, and the prevailing scientific climate—led him to join Max Perutz's research initiative at the University of Cambridge, where he commenced work on the X-ray crystallography of proteins. While X-ray crystallography theoretically presented a pathway to elucidating the molecular architecture of large biomolecules such as proteins and DNA, significant technical hurdles at the time precluded its effective application to these complex structures.

1949–1950

Crick independently mastered the mathematical principles underlying X-ray crystallography. Concurrently with Crick's investigations into X-ray diffraction, colleagues at the Cambridge laboratory were endeavoring to ascertain the most stable helical configuration of amino acid chains within proteins, known as the alpha helix. Linus Pauling had previously established the alpha helix's characteristic ratio of 3.6 amino acids per helical turn. Crick observed the methodological inaccuracies encountered by his collaborators during their unsuccessful efforts to construct an accurate molecular model of the alpha helix; these observations provided crucial insights that would later prove instrumental in understanding the helical architecture of DNA. Specifically, he recognized the significance of structural rigidity imparted by double bonds to molecular configurations, a principle pertinent to both peptide bonds in proteins and the nucleotide structure of DNA.

1951–1953: DNA structure

Crick, alongside William Cochran and Vladimir Vand, contributed to the formulation of a mathematical theory concerning X-ray diffraction by helical molecules during 1951 and 1952. This theoretical framework demonstrated strong concordance with X-ray data obtained from proteins exhibiting alpha helix conformations of amino acid sequences. Furthermore, helical diffraction theory proved instrumental in elucidating the structural characteristics of DNA.

In late 1951, Crick commenced collaboration with James Watson at the Cavendish Laboratory, University of Cambridge, England. Utilizing "Photo 51," which comprised X-ray diffraction data generated by Rosalind Franklin and her graduate student Raymond Gosling from King's College London—data provided to them by Gosling and Franklin's colleague Wilkins—Watson and Crick collaboratively devised a helical model for DNA structure, publishing their findings in 1953. This seminal work, along with subsequent contributions, led to their joint conferral of the Nobel Prize in Physiology or Medicine in 1962, shared with Wilkins.

Upon Watson's arrival in Cambridge, Crick was a 35-year-old graduate student, a status influenced by his World War II contributions, while the 23-year-old Watson had already completed his doctorate. Both researchers shared a profound interest in the fundamental question of how genetic information is encoded at a molecular level. Watson and Crick engaged in extensive discussions regarding DNA, particularly the feasibility of hypothesizing an accurate molecular model for its structure. Crucial experimental data emerged from X-ray diffraction images acquired by Franklin and Gosling. In November 1951, Wilkins visited Cambridge and disseminated this data to Watson and Crick. Both Alexander Stokes, an authority on helical diffraction theory, and Wilkins, both affiliated with King's College, had independently concluded that the X-ray diffraction data for DNA suggested a helical molecular structure; however, Franklin strongly contested this interpretation. Motivated by their conversations with Wilkins and insights gained by Watson from attending Franklin's presentation on her DNA research, Crick and Watson subsequently developed and presented an initial, albeit erroneous, model of DNA. Their urgency in constructing a DNA structure model was partly fueled by their awareness of competition from Linus Pauling. Given Pauling's recent achievement in elucidating the alpha helix, they apprehended that he might similarly be the first to determine the structure of DNA.

Speculation abounds regarding the potential implications had Pauling been permitted to travel to Britain in May 1952 as originally intended. However, his political engagements led to travel restrictions imposed by the United States government, preventing his Regardless, Pauling's primary research focus at that juncture was proteins, not DNA. Concurrently, Watson and Crick were not officially assigned to DNA research. Crick was engaged in completing his doctoral thesis, while Watson pursued other projects, including attempts to crystallize myoglobin for X-ray diffraction studies. In 1952, Watson conducted X-ray diffraction experiments on the tobacco mosaic virus, yielding results indicative of a helical structure. Following their initial unsuccessful attempt, Watson and Crick exhibited some hesitation in resuming their efforts, and for a period, they were prohibited from undertaking further endeavors to construct a molecular model of DNA.

A critical contribution to Watson and Crick's model-building endeavors stemmed from Rosalind Franklin's fundamental chemical insights. Her understanding posited that the hydrophilic, phosphate-containing backbones of DNA's nucleotide chains ought to be situated externally to facilitate interaction with water molecules, whereas the hydrophobic bases should be sequestered within the molecule's core. Franklin conveyed this crucial chemical principle to Watson and Crick by highlighting the evident flaws in their initial 1951 model, which incorrectly placed the phosphates internally.

Crick articulated that the perceived lack of collaborative effort between Wilkins and Franklin in pursuing a molecular model of DNA constituted a primary impetus for his and Watson's eventual second attempt. They successfully sought and obtained authorization for this renewed effort from both William Lawrence Bragg and Wilkins. In developing their DNA model, Watson and Crick leveraged data derived from Franklin's unpublished X-ray diffraction images, which had been presented at meetings and openly disseminated by Wilkins. This information also encompassed preliminary descriptions of Franklin's findings and photographic representations of the X-ray images, which were documented in a late 1952 progress report for Sir John Randall's King's College laboratory.

The propriety of Watson and Crick accessing Franklin's research findings, specifically her detailed analysis of X-ray diffraction data contained in a progress report, without her consent or prior to her formal publication, remains a subject of academic contention. Nevertheless, Watson and Crick challenged Franklin's firm stance that her data did not exclusively support a helical configuration for DNA, presenting them with a significant challenge. To address this controversy, Max Ferdinand Perutz subsequently disseminated the contents of the progress report, asserting that it contained no information beyond what Franklin had presented in her lecture (which Watson attended) in late 1951. Perutz clarified that the report was intended for a Medical Research Council (MRC) committee, established to "establish contact between the different groups of people working for the Council." Both Randall's and Perutz's laboratories received funding from the MRC.

The precise significance of Franklin's unpublished findings from the progress report to Watson and Crick's model construction efforts also remains ambiguous. Following the acquisition of initial rudimentary X-ray diffraction images of DNA in the 1930s, William Astbury had proposed that DNA consisted of nucleotide stacks separated by 3.4 angström (0.34 nanometre) intervals. Astbury's prior X-ray diffraction research was among the limited eight references included in Franklin's inaugural publication concerning DNA. Subsequent analysis of Astbury's published DNA data, combined with the superior X-ray diffraction images obtained by Wilkins and Franklin, elucidated the helical characteristic of DNA. This enabled the prediction of the number of bases stacked per single turn of the DNA helix (10 per turn), with a complete helical turn measuring 27 angströms [2.7 nm] in the compact A form and 34 angströms [3.4 nm] in the more hydrated B form. Wilkins communicated this specific information regarding the B form of DNA to Crick and Watson. Notably, Crick did not view Franklin's B-form X-ray images (Photo 51) until subsequent to the publication of the DNA double helix model.

Among the limited references cited by Watson and Crick upon the publication of their DNA model was a scholarly article featuring Sven Furberg's DNA model, which positioned the bases internally. Consequently, the Watson and Crick model did not represent the inaugural "bases-in" structural proposal for DNA. Furthermore, Furberg's research had accurately established the orientation of DNA sugars relative to the bases. In the course of their model construction, Crick and Watson ascertained that an antiparallel arrangement of the two nucleotide chain backbones was optimal for positioning the base pairs within the central axis of a double helix. While Crick's review of Franklin's late 1952 progress report bolstered his conviction that DNA possessed a double-helical structure with antiparallel chains, other lines of reasoning and informational sources also contributed to these conclusions.

Upon Franklin's departure from King's College to Birkbeck College, John Randall requested that she discontinue her research on DNA. Recognizing Franklin's impending transition to a new position and Linus Pauling's concurrent efforts on DNA structure, Wilkins and the supervisors of Watson and Crick opted to share Franklin's data with them, anticipating that they might develop a viable DNA model before Pauling. Franklin's X-ray diffraction data for DNA, coupled with her systematic analysis of its structural characteristics, proved instrumental in guiding Watson and Crick toward an accurate molecular model. The primary challenge for Watson and Crick, which the King's College data could not resolve, involved determining the precise packing arrangement of nucleotide bases within the core of the DNA double helix.

The elucidation of DNA's structure was significantly aided by Chargaff's ratios, which empirically demonstrated that the quantity of guanine consistently equals cytosine, and adenine equals thymine, within DNA's nucleotide subunits. Erwin Chargaff's 1952 The structural implications of these ratios for DNA remained unappreciated until Watson, through persistent structural modeling, recognized the inherent structural similarity between A:T and C:G pairs, specifically noting their identical base pair lengths. Furthermore, Chargaff informed Watson that, within the aqueous, saline cellular environment, the predominant tautomeric forms of pyrimidine bases (cytosine and thymine) were the amine and keto configurations, respectively, rather than the imino and enol forms previously hypothesized by Crick and Watson. Consultation with Jerry Donohue subsequently validated the most probable structures of these nucleotide bases. The stability of these base pairs is maintained by hydrogen bonds, a non-covalent interaction also responsible for stabilizing the protein α-helix. Accurate structural representations were crucial for correctly positioning these hydrogen bonds. These collective insights enabled Watson to infer the precise biological relationships governing A:T and C:G pairing. Following the identification of hydrogen-bonded A:T and C:G pairs, Watson and Crick rapidly developed their anti-parallel, double helical DNA model. This model posited hydrogen bonds at the helix's core, facilitating the "unzipping" of complementary strands for replication—a final, essential criterion for a plausible genetic molecule model. Despite the profound significance of Crick's contributions to the double helical DNA model, he acknowledged that he would not have independently discovered the structure without the opportunity to collaborate with Watson.

Although Crick made tentative attempts at experiments concerning nucleotide base pairing, his primary orientation was theoretical rather than experimental biology. A separate near-discovery of the base pairing rules occurred in early 1952 when Crick began contemplating inter-base interactions. He enlisted John Griffith to compute attractive forces between DNA bases using chemical principles and quantum mechanics. Griffith's preliminary assessment suggested A:T and G:C as attractive pairs. However, Crick, then unaware of Chargaff's rules, initially undervalued Griffith's calculations, though they did prompt his consideration of complementary replication. The definitive identification of the correct base-pairing rules (A-T, G-C) was ultimately achieved by Watson, who manipulated cardboard cut-out models of nucleotide bases, a methodology reminiscent of Linus Pauling's discovery of the protein alpha helix years prior. The successful elucidation of the DNA double helix structure by Watson and Crick stemmed from their readiness to integrate theoretical frameworks, physical modeling, and experimental data (much of which was generated by others) to achieve their scientific objective.

The double helix structure of DNA, as proposed by Watson and Crick, was predicated on "Watson-Crick" bonds formed between the four primary bases prevalent in DNA (adenine, cytosine, thymine, guanine) and RNA (adenine, cytosine, uracil, guanine). Subsequent investigations, however, revealed that more intricate DNA molecular architectures, such as triple-stranded and quadruple-stranded forms, necessitate Hoogsteen base pairing.

Within the domain of synthetic biology, researchers employ non-canonical bases in the construction of synthetic DNA, diverging from the standard adenine, cytosine, thymine, and guanine. Beyond synthetic DNA, efforts are also underway to engineer synthetic codons, endonucleases, proteins, and zinc fingers. Utilizing synthetic DNA, the potential number of codons could significantly increase; for instance, if there are n novel bases, the number of possible codons could expand to n§67§, compared to the conventional 43 codons. Current research explores the feasibility of expanding codons beyond three bases. These emergent codons possess the capacity to encode novel amino acids, and such synthetic molecules hold promise for applications not only in medicine but also in the development of new materials.

The discovery was made on February 28, 1953, with the initial Watson-Crick paper appearing in Nature on April 25, 1953. Sir Lawrence Bragg, director of the Cavendish Laboratory where Watson and Crick conducted their research, delivered a lecture at Guy's Hospital Medical School in London on May 14, 1953. This lecture led to an article by Ritchie Calder, published in the News Chronicle of London on May 15, 1953, titled "Why You Are You. Nearer Secret of Life." Readers of The New York Times received the news the following day. Victor K. McElheny, during his research for the biography "Watson and DNA: Making a Scientific Revolution," located a six-paragraph New York Times article, datelined London, May 16, 1953, with the headline "Form of 'Life Unit' in Cell Is Scanned." This article was included in an early edition but was subsequently removed to accommodate more pressing news. The New York Times later published a more extensive article on June 12, 1953. The university's undergraduate newspaper, Varsity, also featured a brief article on the discovery on May 30, 1953. Notably, Bragg's initial announcement of the discovery at a Solvay conference on proteins in Belgium on April 8, 1953, received no coverage from the British press.

In a seven-page, handwritten letter dated March 19, 1953, Crick informed his son, then attending a British boarding school, of his discovery, commencing the correspondence with, "My Dear Michael, Jim Watson and I have probably made a most important discovery." This letter was subsequently offered at auction at Christie's New York on April 10, 2013, with an estimated value of $1 million to $2 million, ultimately selling for $6,059,750, setting a record for the highest price ever paid for a letter at auction.

In April 1953, Sydney Brenner, Jack Dunitz, Dorothy Hodgkin, Leslie Orgel, and Beryl M. Oughton were among the first individuals to observe the DNA structure model constructed by Crick and Watson. At that time, they were affiliated with Oxford University's Chemistry Department. All were profoundly impressed by the novel DNA model, particularly Brenner, who later collaborated with Crick at Cambridge's Cavendish Laboratory and the newly established Laboratory of Molecular Biology. According to the late Dr. Beryl Oughton (later Rimmer), the group traveled together in two vehicles after Dorothy Hodgkin announced their trip to Cambridge to view the DNA structure model. Orgel also subsequently worked with Crick at the Salk Institute for Biological Studies.

Crick was frequently characterized as highly loquacious, with Watson, in The Double Helix, suggesting a lack of modesty. His distinctive personality, coupled with his scientific achievements, often elicited reactions from individuals both within and outside the scientific community, which constituted the core of his intellectual and professional existence. Crick spoke rapidly and rather loudly, possessing an infectious, reverberating laugh and a vibrant sense of humor. A colleague from the Salk Institute described him as "a brainstorming intellectual powerhouse with a mischievous smile. ... Francis was never mean-spirited, just incisive. He detected microscopic flaws in logic. In a room full of smart scientists, Francis continually re-earned his position as the heavyweight champ."

Following Crick's passing, allegations emerged concerning his use of LSD when conceiving the helical structure of DNA. While his use of LSD is highly probable, it is improbable that this occurred as early as 1953. He reportedly received LSD from Henry Todd in the late 1960s; Todd had met Crick through his girlfriend, who had modeled for Crick's wife.

Molecular biology

In 1954, at the age of 37, Crick successfully defended his PhD thesis, titled "X-Ray Diffraction: Polypeptides and Proteins," and was awarded his degree. Subsequently, Crick joined David Harker's laboratory at the Brooklyn Polytechnic Institute, where he further refined his expertise in analyzing X-ray diffraction data for proteins, focusing primarily on ribonuclease and the mechanisms of protein synthesis. David Harker, an American X-ray crystallographer, was famously characterized as "the John Wayne of crystallography" by Vittorio Luzzati, a crystallographer at the Centre for Molecular Genetics in Gif-sur-Yvette near Paris, who had previously collaborated with Rosalind Franklin.

Following the elucidation of the DNA double helix model, Crick rapidly shifted his focus to the structural biological implications. In 1953, Watson and Crick co-authored an additional publication in Nature, asserting that: "it therefore seems likely that the precise sequence of the bases is the code that carries the genetical information".

In 1956, Crick and Watson hypothesized about the structural organization of small viruses. They proposed that spherical viruses, exemplified by Tomato bushy stunt virus, exhibited icosahedral symmetry and were composed of 60 identical subunits.

Following a brief period in New York, Crick relocated to Cambridge, where he remained professionally active until 1976, subsequently moving to California. Crick participated in multiple X-ray diffraction collaborations, including a project with Alexander Rich investigating collagen structure. Nevertheless, Crick progressively disengaged from ongoing research directly utilizing his expertise in interpreting protein X-ray diffraction patterns.

George Gamow founded a scientific collective, known as the RNA Tie Club, dedicated to exploring RNA's intermediary function between DNA, the cellular genetic storage molecule located in the nucleus, and protein synthesis occurring in the cytoplasm. Crick recognized the necessity of a code wherein a concise nucleotide sequence would dictate a specific amino acid within a nascent protein. In 1956, Crick authored an informal document addressing the genetic coding challenge for Gamow's RNA group. Within this paper, Crick analyzed evidence supporting the existence of a conserved set of approximately 20 amino acids utilized in protein synthesis. Crick posited the existence of a complementary set of diminutive "adaptor molecules" capable of hydrogen bonding to short nucleic acid sequences while simultaneously binding to a specific amino acid. He further investigated numerous theoretical frameworks through which short nucleic acid sequences could encode the 20 amino acids.

Throughout the mid-to-late 1950s, Crick was intensely intellectually involved in deciphering the mechanism of protein synthesis. By 1958, his conceptual framework had advanced, enabling him to systematically enumerate the fundamental characteristics of the protein synthesis process:

Subsequently, the adaptor molecules were identified as tRNAs, and the catalytic "ribonucleic-protein complexes" were designated as ribosomes. A pivotal insight emerged on April 15, 1960, when Crick and Brenner, during a discussion with François Jacob, recognized that messenger RNA was distinct from ribosomal RNA. Later that summer, Brenner, Jacob, and Matthew Meselson performed an experiment that provided the initial empirical evidence for messenger RNA's existence. Nevertheless, these discoveries did not resolve the fundamental theoretical inquiry into the precise nature of the genetic code. In his 1958 publication, Crick, alongside other researchers, hypothesized that a nucleotide triplet could encode an amino acid. Such a code might exhibit "degeneracy," given 4×4×4=64 potential triplets from the four nucleotide subunits, yet only 20 amino acids exist. Consequently, certain amino acids could be specified by multiple triplet codes. Crick also investigated alternative coding schemes where, for various reasons, only a subset of triplets was utilized, purportedly yielding precisely the 20 required combinations. Empirical data were essential, as theoretical considerations alone could not definitively establish the code's nature. Crick additionally coined the term "central dogma" to encapsulate the concept that genetic information flow among macromolecules is fundamentally unidirectional:

DNA → RNA → protein

Critics interpreted Crick's use of "dogma" as suggesting an unquestionable rule, though he intended it to signify a compelling concept lacking substantial empirical support. When conceptualizing the biological mechanisms connecting DNA genes to proteins, Crick explicitly differentiated between the requisite materials, energy, and information flow. This informational component became the foundational organizing principle of molecular biology, a field in which Crick's focus was central. By this period, Crick had established himself as a highly influential theoretical molecular biologist.

Definitive evidence for the genetic code's degenerate triplet nature emerged from genetic experiments, some of which were conducted by Crick. The specific characteristics of this code were primarily elucidated through the research of Marshall Nirenberg and his collaborators, who synthesized RNA molecules and employed them as templates for in vitro protein synthesis. Nirenberg initially presented his findings to a limited audience at a 1961 conference in Moscow. Crick subsequently extended an invitation to Nirenberg to present his research to a broader scientific community.

Controversy

Utilization of Other Researchers' Data

The utilization of DNA X-ray diffraction data, acquired by Franklin and Wilkins, by Watson and Crick has precipitated a persistent controversy. This contention stems from Watson and Crick's incorporation of some of Franklin's unpublished data into their double helix model of DNA, reportedly without her awareness or authorization. Among the four principal DNA researchers, Franklin alone possessed a chemistry degree, while Wilkins and Crick specialized in physics, and Watson in biology.

Before the publication of the double helix structure, Watson and Crick maintained minimal direct communication with Franklin. Nevertheless, they possessed knowledge of her research, exceeding her own perception of their awareness. In November 1951, Watson attended a lecture where Franklin detailed the two molecular forms, A and B, and elucidated the external placement of phosphate units. Wilkins presented Watson with an X-ray photograph of B-DNA, designated Photograph 51, in January 1953. Raymond Gosling, Rosalind Franklin's PhD student, had provided Photograph 51 to Wilkins. Prior to Franklin's appointment by director John Randall to oversee both DNA diffraction research and Gosling's thesis supervision, Wilkins and Gosling had collaborated within the Medical Research Council's (MRC) Biophysics Unit. Randall's communication regarding Franklin's appointment seemingly lacked clarity, thereby fostering confusion and discord between Wilkins and Franklin. Mid-February 1953, Max Perutz, Crick's thesis advisor, furnished Crick with a report prepared for a December 1952 Medical Research Council biophysics committee Franklin remained uninformed that Photograph 51 and additional data had been disseminated to Crick and Watson. She authored three draft manuscripts, two of which posited a double helical DNA backbone. Her two manuscripts concerning form A DNA were received by Acta Crystallographica in Copenhagen on March 6, 1953, preceding the completion of Crick and Watson's model by one day.

The X-ray diffraction images obtained by Gosling and Franklin constituted the most compelling evidence for DNA's helical configuration. Previously, Linus Pauling, Watson, and Crick had independently proposed incorrect models featuring internal chains and externally oriented bases. Franklin's experimental data yielded estimations of DNA crystal water content, which strongly supported the placement of the three sugar-phosphate backbones on the molecule's exterior. Specifically, Franklin's X-ray photograph unequivocally indicated an external positioning for the backbones. Initially, she vehemently maintained that her data did not necessitate a helical DNA structure; however, her 1953 draft submissions presented arguments for a double helical DNA backbone. Further developing her manuscripts, she ascertained that form A DNA possessed antiparallel backbones, thereby reinforcing the double helical model of DNA. This determination was achieved by identifying the space group for DNA crystals. This insight subsequently influenced Watson and Crick's decision to investigate DNA models incorporating two antiparallel polynucleotide strands.

Watson and Crick accessed Franklin's unpublished data through three primary channels: her 1951 seminar, which Watson attended; discussions with Wilkins, a colleague in Franklin's laboratory; and a research progress report designed to foster collaboration among Medical Research Council-supported laboratories. All four scientists—Watson, Crick, Wilkins, and Franklin—were affiliated with MRC laboratories.

Crick and Watson acknowledged Wilkins' contributions, offering him co-authorship on their seminal article detailing the DNA double helix structure. Wilkins declined this offer, which may explain the concise acknowledgment of experimental work conducted at King's College in the final publication. Instead of including King's College DNA researchers as co-authors on the Watson and Crick paper, a decision was made to publish two supplementary papers from King's College concurrently with the helix article. Brenda Maddox posits that Franklin's experimental results were so crucial to Watson and Crick's model construction and theoretical analysis that she should have been credited as a co-author on their original Nature paper. Concurrently, Franklin and Gosling submitted their joint "second" paper to Nature, alongside the "third" paper on DNA submitted by Wilkins, Stokes, and Wilson.

In The Double Helix, Watson presented a negative depiction of Franklin, implying she was Wilkins' assistant and incapable of interpreting her own DNA data. Conversely, Nathaniel C. Comfort, a historian of medicine at Johns Hopkins University, notes that Franklin's colleague Aaron Klug asserted Franklin was "two steps away" from discovering the double helix. Following a thorough analysis of her laboratory notebooks, Klug concluded that she would undoubtedly have arrived at the structure.

Franklin's X-ray diffraction images constituted the most compelling evidence supporting the helical structure of DNA. Although her experimental contributions were pivotal to Crick and Watson's formulation of the accurate model, Franklin herself did not fully comprehend its implications at the time. Upon her departure from King's College, Director Sir John Randall asserted that all DNA-related research was proprietary to the institution and explicitly instructed Franklin to cease any further consideration of the topic. Consequently, the scientific community largely underestimated the profound scope of Franklin's contributions. Subsequently, Franklin conducted exceptional research on the tobacco mosaic virus in J. D. Bernal's laboratory at Birkbeck College, further advancing concepts related to helical construction.

Eugenics

Crick periodically articulated his perspectives on eugenics, primarily through private correspondence. For instance, he championed a form of positive eugenics, advocating for incentives to encourage affluent parents to procreate more. He once commented, "Ultimately, it is inevitable that society will begin to concern itself with the characteristics of future generations... This is not a topic we can readily address currently due to diverse religious convictions, and until a more unified self-perception emerges, I believe attempting any eugenic measures would be perilous... I would be astonished if, within the next one or two centuries, society did not adopt the perspective that it must endeavor to enhance the next generation to some degree or by some means."

Sexual harassment allegation

Biologist Nancy Hopkins reported an incident during the 1960s, when she was an undergraduate, alleging that Crick placed his hands on her breasts during a laboratory visit. She recounted the event: "Before I could rise and shake hands, he had zoomed across the room, stood behind me, put his hands on my breasts and said, 'What are you working on?'"

Views on religion

Crick identified himself as a humanist, defining this philosophy as the conviction "that human problems can and must be faced in terms of human moral and intellectual resources without invoking supernatural authority." He publicly advocated for humanism to supersede religion as a primary guiding principle for humanity, stating:

The fundamental human predicament is a perennial challenge. Individuals inhabit this slowly rotating planet, situated in a remote region of an expansive cosmos, without personal volition. Human inquisitive intellect precludes an unquestioning acceptance of this existence, fostering a profound imperative to comprehend one's purpose. Fundamental inquiries pertain to the composition of the world and, more critically, the essence of human identity. Historically, religion provided comprehensive responses to these questions. However, contemporary understanding suggests that many of these explanations are largely unsubstantiated, having originated from human ignorance and a significant propensity for self-deception. The simplistic narratives of global religions now resemble childlike fables. Even when interpreted symbolically, these accounts are frequently problematic, if not disagreeable. Consequently, humanists inhabit a mysterious, stimulating, and intellectually evolving world, which, upon apprehension, renders traditional religious frameworks appear artificially comforting and antiquated.

Crick expressed particular criticism regarding Christianity.

He expressed a lack of respect for Christian beliefs, deeming them untenable. Crick posited that dispelling these beliefs would facilitate a more direct engagement with the fundamental inquiry into the nature of existence.

Crick humorously remarked that while Christianity might be acceptable among consenting adults in private, it should not be disseminated to young children.

In his publication Of Molecules and Men, Crick articulated his perspective on the interrelationship between science and religion. He postulated the potential for a computer to be programmed with a soul, subsequently posing questions regarding the precise moment a soul emerged during biological evolution or at what stage an infant acquires one. Crick asserted his belief that the concept of a non-material soul, capable of entering a body and persisting post-mortem, is merely a conceptual construct. For Crick, the mind constitutes a product of physical brain activity, with the brain having evolved through natural processes over millions of years. He emphasized the importance of teaching evolution by natural selection in educational institutions and deemed it unfortunate that English schools mandated religious instruction. Furthermore, he observed the rapid emergence of a new scientific paradigm, forecasting that with the eventual elucidation of the brain's intricate workings, fallacious Christian notions concerning human nature and the world would become unsustainable. He predicted that conventional notions of the "soul" would yield to a novel comprehension of the mind's physical basis. Crick was skeptical regarding institutionalized religion, identifying as a skeptic and an agnostic with "a strong inclination towards atheism."

In 1960, Crick accepted an honorary fellowship at Churchill College, Cambridge, partially due to the absence of a chapel within the new institution. Subsequently, a substantial donation was offered for the establishment of a chapel, which the College Council voted to approve. In response, Crick relinquished his fellowship as an act of protest.

In October 1969, Crick contributed to the centennial commemoration of the journal Nature, offering prognostications regarding the trajectory of molecular biology over the ensuing three decades. These conjectures were subsequently published in Nature. Towards the conclusion of the article, Crick alluded to the search for extraterrestrial life, though he expressed limited optimism that such life would be discovered by the year 2000. He also discussed a potential novel research avenue, which he termed "biochemical theology." Crick remarked that "so many people pray that it is difficult to conceive that such practices yield no personal gratification." A discipline analogous to Crick's proposed "biochemical theology" has since emerged, known as neurotheology.

Crick posited the potential for identifying chemical changes in the brain that served as molecular correlates for the act of prayer. He hypothesized a discernible alteration in the levels of specific neurotransmitters or neurohormones during prayer. Crick's perspective on the relationship between science and religion remained influential in his endeavors as he transitioned from molecular biology research into theoretical neuroscience.

In 1998, Crick posed a rhetorical question: "If certain portions of the Bible are demonstrably erroneous, why should the remainder be unquestioningly accepted? Furthermore, what could be of greater significance than ascertaining our true position in the universe by systematically dismantling these detrimental remnants of antiquated doctrines?"

In 2003, he was among 22 Nobel laureates who endorsed the Humanist Manifesto.

Creationism

Crick was a staunch opponent of young Earth creationism. During the 1987 United States Supreme Court case, Edwards v. Aguillard, he collaborated with other Nobel laureates to assert, "'Creation-science' simply has no place in the public-school science classroom." Furthermore, Crick championed the recognition of Darwin Day as a British national holiday.

Directed Panspermia

During the 1960s, Crick developed a significant interest in the genesis of the genetic code. In 1966, he substituted for Leslie Orgel at a conference where Orgel was scheduled to discuss the origin of life. Crick theorized about the potential evolutionary stages through which an initially rudimentary code, comprising a limited number of amino acid types, could have progressed to the intricate code observed in contemporary organisms. At that juncture, proteins were exclusively considered enzymes, and ribozymes remained undiscovered. The challenge of elucidating the origin of a protein-replicating system, as complex as those found in extant terrestrial organisms, perplexed numerous molecular biologists. In the early 1970s, Crick and Orgel advanced a hypothesis suggesting that the emergence of living systems from molecules might be an exceedingly rare cosmic event; however, once established, such life could be disseminated by intelligent species employing space travel, a mechanism they termed "directed panspermia." Subsequently, in a retrospective publication, Crick and Orgel acknowledged their excessive pessimism regarding the likelihood of abiogenesis on Earth, which stemmed from their initial assumption that a self-replicating protein system constituted the molecular origin of life.

In 1976, Crick, alongside Sydney Brenner, Aaron Klug, and George Pieczenik, explored the origins of protein synthesis in a collaborative paper. They posited that specific code constraints within nucleotide sequences could facilitate protein synthesis independently of ribosomal involvement. This mechanism, however, necessitated a five-base interaction between mRNA and tRNA, involving an anticodon flip to establish triplet coding, despite the five-base physical engagement. Thomas H. Jukes subsequently highlighted that the requisite code constraints on the mRNA sequence for this translational process remain conserved.

Neuroscience and Other Interests

Crick's tenure at Cambridge represented the zenith of his extensive scientific career; however, he departed the institution in 1977 after three decades, having declined the Mastership of Gonville and Caius. In 2003, during a Cambridge conference commemorating the 50th anniversary of the DNA structure discovery, James Watson asserted:

Now perhaps it's a pretty well kept secret that one of the most uninspiring acts of the University of Cambridge over this past century was to turn down Francis Crick when he applied to be the Professor of Genetics, in 1958. Now there may have been a series of arguments, which led them to reject Francis. It was really saying, don't push us to the frontier.

This ostensibly "pretty well kept secret" had, in fact, been previously documented in Soraya De Chadarevian's 2002 publication by Cambridge University Press, titled Designs For Life: Molecular Biology After World War II. Furthermore, Crick's substantial contributions to molecular biology at Cambridge are thoroughly detailed in The History of the University of Cambridge: Volume 4 (1870 to 1990), published by CUP in 1992.

As per the official website of the University of Cambridge's genetics department, the electoral committee for the professorship failed to achieve consensus, necessitating the involvement of the then University Vice-Chancellor, Lord Adrian. Lord Adrian initially extended the professorship offer to Guido Pontecorvo, a compromise candidate, who declined. Subsequently, the offer was reportedly made to Crick, who similarly refused.

In 1976, Crick undertook a sabbatical year at the Salk Institute for Biological Studies in La Jolla, California. Having served as a nonresident fellow of the Institute since 1960, he expressed a sense of belonging in Southern California, stating, "I felt at home in Southern California." Following this sabbatical, Crick departed from Cambridge to permanently join the Salk Institute. Concurrently, he held an adjunct professorship at the University of California, San Diego. He independently acquired expertise in neuroanatomy and explored numerous other domains of neuroscience research. His transition from molecular biology spanned several years, primarily due to the ongoing emergence of significant discoveries, such as alternative splicing and restriction enzymes, which were instrumental in advancing genetic engineering. Ultimately, by the 1980s, Crick successfully redirected his complete focus to his long-standing interest in consciousness. His autobiography, What Mad Pursuit: A Personal View of Scientific Discovery, elucidates his rationale for transitioning from molecular biology to neuroscience.

Upon commencing his work in theoretical neuroscience, Crick observed several notable aspects:

Crick aimed to advance neuroscience by fostering productive collaborations among specialists across the diverse subdisciplines engaged with consciousness. His collaborations extended to neurophilosophers, including Patricia Churchland. In 1983, based on their investigations into computer models of neural networks, Crick and Mitchison posited that the role of REM sleep and dreaming involves the elimination of specific interaction patterns within cellular networks of the mammalian cerebral cortex, terming this theoretical mechanism "reverse learning" or "unlearning." During the concluding phase of his career, Crick initiated a significant collaboration with Christof Koch, which resulted in a series of publications on consciousness between 1990 and 2005. Crick strategically narrowed his theoretical inquiry into consciousness, concentrating on the brain's generation of visual awareness within milliseconds of perceiving a scene. Crick and Koch hypothesized that the enigmatic nature of consciousness stems from its reliance on poorly understood very short-term memory processes. In his work The Astonishing Hypothesis, Crick articulated that neurobiology had attained a sufficient level of maturity to permit a concerted investigation of consciousness across molecular, cellular, and behavioral dimensions. Crick expressed skepticism regarding the utility of computational models of mental function that lacked foundational grounding in specific details of brain structure and operation.

Crick recognized the inherent challenges in consciousness research, as evidenced in his correspondence with Martynas Yčas in April 1996:

I do not anticipate a complete comprehension of consciousness by the close of this century; however, it is conceivable that we may achieve an initial insight by that time. Whether this understanding will coalesce organically, akin to the progression of molecular biology without recourse to a vital force, or if it necessitates a fundamentally new theoretical framework, remains to be determined. Best wishes, Yours, Francis. P.S. Incidentally, I have not received a knighthood.

Awards and Honors

Beyond his one-third share of the 1962 Nobel Prize in Physiology or Medicine, Crick garnered numerous accolades and distinctions. These included the Royal Medal (1972) and the Copley Medal (1975) from the Royal Society, as well as the Order of Merit (awarded on November 27, 1991). Despite declining an offer for a CBE in 1963, he was frequently, though erroneously, addressed as 'Sir Francis Crick' and occasionally as 'Lord Crick'. In 1964, he was elected as an EMBO Member.

The conferral of Nobel Prizes upon John Kendrew and Max Perutz, alongside Crick, Watson, and Wilkins, was satirized in a brief sketch on the BBC television program That Was The Week That Was, wherein the Nobel Prizes were facetiously termed 'The Alfred Nobel Peace Pools'.

Crick was elected as a member of several prestigious organizations, including the American Academy of Arts and Sciences (1962), the United States National Academy of Sciences (1969), and the American Philosophical Society (1972).

Francis Crick Medal and Lecture

The Francis Crick Medal and Lecture was instituted in 2003 through an endowment from his former colleague, Sydney Brenner, co-recipient of the 2002 Nobel Prize in Physiology and Medicine. This annual lecture is presented across the biological sciences, with a specific emphasis on the research domains pioneered by Francis Crick. Notably, the lectureship is designed for early-career scientists, typically those under 40 or at a comparable stage in their professional development. By 2019, notable lecturers included Julie Ahringer, Dario Alessi, Ewan Birney, Simon Boulton, Jason Chin, Simon Fisher, Matthew Hurles, Gilean McVean, Duncan Odom, Geraint Rees, Sarah Teichmann, M. Madan Babu, and Daniel Wolpert.

Francis Crick Institute

The Francis Crick Institute represents a £660 million biomedical research facility situated in central London, United Kingdom. It operates as a collaborative venture involving Cancer Research UK, Imperial College London, King's College London, the Medical Research Council, University College London (UCL), and the Wellcome Trust. Upon its completion in 2016, it became Europe's preeminent center for biomedical research and innovation.

Francis Crick Graduate Lectures

The University of Cambridge Graduate School of Biological, Medical and Veterinary Sciences serves as the venue for the Francis Crick Graduate Lectures. The inaugural two lectures were delivered by John Gurdon and Tim Hunt.

Other Honors

Books

The Crick, Brenner et al. experiment, which contributed to the discovery of DNA structure.

Sources