Francis Crick and the Discovery of DNA

Francis Crick

• A Nobel Prize-winning British biophysicist who is celebrated for his joint discovery of the structure of DNA in 1953
• Studied physics at University College London, then began graduate work there on the viscosity of water
• Recruited by the Royal Navy during World War II to help develop magnetic and acoustic mines
• Retrained in biology and joined the Cavendish Laboratory in Cambridge in 1949
• Started a new PhD on the X-ray diffraction of proteins
• Met James Watson in 1951 with whom he tried to unlock science's greatest mysteries
• Collaborated to discover the molecular structure of DNA
• Completed PhD in 1954 and contributed to the study of the genetic code
• Moved to California in 1976 and studied developmental neurobiology and human consciousness
• Key milestones in his work and career:
  • Started PhD at the Cavendish Laboratory in 1949
  • Met Watson in 1951 and started investigating DNA
  • Co-published a landmark paper in Nature on April 25, 1953, revealing the structure of DNA
  • Received awards, including the Nobel Prize in 1962, and medals from the Royal Society in 1972 and 1975
  • Became Distinguished Research Professor at Salk Institute for Biological Studies, California, in 1977
• Said "The genetic code is... the key to molecular biology" in 1966

James Watson

• A US geneticist and biophysicist who launched a new era in biological research with his co-discovery of the double helix structure of DNA
• Enrolled at the University of Chicago at 15, gained a degree in zoology in 1947, and completed his PhD in virus research in 1950
• Moved to the Cavendish Laboratory in Cambridge in 1951 and formed a partnership with Francis Crick
• After publishing a paper on DNA structure, he lectured at Harvard and became professor of biology in 1960
• Led the Human Genome Project in 1989, aiming to identify and map all the genes of a human chromosome
• Key milestones in his work and career:
  • Conducted virus research at Indiana University in 1950 and gained knowledge to aid DNA investigation
  • Built a successful model with Crick to demonstrate the molecular structure of DNA in 1953
  • Was a Senior Research Fellow at Caltech from 1953 to 1955
  • Moved to Harvard in 1956 and taught biology
  • Directed the leading center of molecular research in 1968
  • Led the Human Genome Project in 1989
• Said "In science there is only one answer and that has to be correct" in 1987

DNA Discovery

• Crick and Watson's discovery revealed that DNA is composed of a double helix structure
• This proved to be one of the greatest scientific discoveries of the 20th century
• DNA (deoxyribonucleic acid) is the chemical substance within cells that determines hereditary patterns in all living things
• Working out its structure helped scientists learn how it can replicate and pass on genetic information and provided insight into how genes work
• US immunologist Oswald Avery discovered that DNA carries genetic information in 1944
• Discovering the double helix structure enabled new scientific techniques like gene sequencing and genetic engineering and opened up research into inherited medical conditions
• The study of heredity could not advance without knowing DNA's structure
• Key players in the race to describe it included US chemist Linus Pauling, Rosalind Franklin, and Maurice Wilkins at King's College London by the 1950s
• Scientists knew that DNA could pass on genetic information and make copies of itself
• They knew that the molecule was made up of a backbone composed of phosphoric acid and sugar, and four chemical "bases" (adenine (A), thymine (T), guanine (G), and cytosine (C))
• Crick and Watson applied themselves to the investigation with focus
• They built large 3D models to replicate DNA's structure according to its known chemical properties instead of conducting exhaustive experiments
• Their success was made possible after obtaining data belonging to Rosalind Franklin
• Made the DNA Discovery after only 18 months of research
• Built their final DNA model in 3 days
• Published their groundbreaking work in a paper just 1 page long
• Said "We have discovered the secret of life" - Francis Crick, 1953

Double Helix and Photograph 51

• "This structure has features which are of considerable biological interest" - Crick and Watson, 1953
• Franklin produced a clear image of DNA (Photograph 51) showing its double helix structure and was working alongside Maurice Wilkins
• Wilkins showed Photograph 51 to Crick and Watson without her knowledge
• Franklin's image helped them confirm the double helix and complete their model
• The double helix structure of DNA resembles a twisted ladder, with the phosphoric acid and sugar strands acting as the ladder's uprights and the paired "bases" forming the rungs
• Austrian scientist Erwin Chargaff previously noted that the A and T bases always appeared in equal ratios, as did the G and C bases
• Watson and Crick realized that each rung of the ladder must be composed of two bases (either A and T or C and G) bonded together
• The order of the bases formed the code for genetic information
• The molecule "unzips" and each "half ladder” bonds with newly formed DNA components to form two new genetically identical double helixes
• Crick and Watson completed the double helix model of DNA in March 1953, and published their discovery in a landmark paper in April
• Franklin's contribution to their work received little acknowledgment
• The work marked a turning point in genetics and advanced molecular biology
• Watson, Crick, and Wilkins were awarded the Nobel Prize in Physiology or Medicine in 1962
• Franklin having died in 1958
• Photograph 51 took 60 hours to produce in an X-ray

Rosalind Franklin

• A British chemist whose work was vital to the discovery of the structure of DNA, but was largely overlooked in her lifetime
• Born in London in 1920, and graduated from the University of Cambridge in 1941 with a degree in physical chemistry
• Took a research post studying the chemical structure of coal and graphite before gaining her doctorate from Cambridge in 1945
• Studied X-ray crystallography in Paris in 1947 that made her expert in the field and enabled her to make a crucial contribution to one of the biggest scientific conundrums of the 20th century
• Engaged to discover the molecular structure of DNA
• Franklin began photographing strands of DNA at King's College, London, in 1951
• Key milestones in her work and career:
  • Became a researcher for BCURA, the British Coal Utilization Research Association, in 1942
  • Trained under French engineer Jacques Mering in 1947 and became an X-ray crystallographer
  • Asked to head X-ray research at King's College, London in 1951
  • Produced the first sharp image of crystalline DNA in 1952, which reveals its double helix shape
  • Moved to Birkbeck College, London, in 1953 and led studies into major crop viruses
• Said "Science and everyday life cannot and should not be separated"

Photograph 51

• "The most beautiful X-ray photographs ... ever taken" - J. D. Bernal, 1958
• Produced the first clear image of the crystalline structure of DNA
• Franklin was recruited to take over DNA research using X-ray techniques and caused friction between the leader of the research team, Maurice Wilkins
• The “X” shape that her image revealed showed that the structure of DNA was a helix (spiral) and that it was formed of two strands
• Franklin also proposed the “backbone” of DNA lay on the outside of the molecule
• Wilkins showed Photograph 51 to Crick and Watson, as well as Franklin's unpublished thoughts about the shape of DNA
• This data helped the pair confirm DNA's double helix structure and they completed their model
• The first image of its crystalline structure that has been considered one of science’s important photographs
• Franklin moved to Birkbeck College, London, in 1953 to study the crystalline structure of viruses
• She proposed a model for the molecular structure of the tobacco mosaic virus (TMV) which was proven correct
• Her work on polio was recognized when its crystalline structure was confirmed in 1959
• Watson, Crick, and Wilkins won a Nobel Prize for their work on the structure of DNA in 1962
• Today, Franklin is credited with having advanced the field of virology
• Received a $13,000 grant to study the Polio Virus
• Bequeathed $4,000 to support a fellow scientist, Aaron Klug, in his work

Maurice Wilkins

• Born in New Zealand but raised in the UK and was a Nobel Prize-winning biophysicist known for his X-ray studies that helped determine the structure of DNA
• Worked on the Manhattan Project during World War II before joining the biophysics unit at King's College, London, in 1946
• He used X-ray imaging to study and data on DNA fibers, also working with Rosalind Franklin
• Shared a Nobel Prize in Physiology or Medicine with Francis Crick and James Watson for his work
• His contribution is not well known, and Wilkins called his autobiography The Third Man of the Double Helix
• Became director of the biophysics unit in 1970, and later emeritus professor of King's College

Frederick Sanger

• A two-time Nobel laureate and experimental biochemist who sequenced the three fundamental polymers of life: proteins, RNA, and DNA
• Revolutionary technique for sequencing DNA revolutionized molecular biology and heralding a new era in medicine, gene therapy, and genetic manipulation.
• Sanger was born in Gloucestershire, UK, in 1918 and went to Cambridge in 1936 to study natural sciences
• He began a self-funded PhD on the metabolism of amino acids in 1940 and received his PhD in 1943
• He joined a group of scientists in Cambridge who were studying proteins and spent the next decade deciphering the complete amino acid sequence of insulin
• Key milestones in his work and career:
  • Awarded PhD in 1943 for studies into amino acids, the building blocks of the body's proteins
  • Received the 1958 Nobel Prize in Chemistry for his work on the chemical sequencing of insulin
  • Published his dideoxy method of DNA sequencing in 1977, which would become known as "Sanger Sequencing"
  • Shared the 1980 Nobel Prize in Chemistry with Walter Gilbert and Paul Berg for DNA sequencing
  • Opened the Wellcome Sanger Institute in Cambridge, UK, in 1993
• He also revealed that each protein possesses a unique set of amino acids and distinct 3D structure
• "An ingenious experimentalist, Sanger developed novel day-to-day laboratory techniques."

Genetic Research of Sanger

• Sanger developed a sequencing method using radioactive isotopes to "label" individual fragments and build up the sequence by looking at the areas of overlap between them
• By 1967, he had a complete sequence of RNA from E. coli bacteria
• The sequencing breakthrough came in 1977, Sanger pioneered a method of isolating DNA fragments via dideoxy chain-termination-using a molecular inhibitor to prevent DNA
• Strands could then be ordered from the shortest to the longest so the base sequence could be read
• This rapid way let Sanger map the first human genome, the DNA of cell mitochondria, in 1981, and sequencing all 3 billion base pairs of the entire human genome
• Sanger's sequencing method enabled fragments of DNA to be isolated, cloned, and reattached to create modified genes to treat-or be resistant to-genetic disorders
• "I had 20 years when I could just do what I wanted" - Frederick Sanger, 200120120120111

John Sulston

• John Sulston was an English biologist and the first director of the Wellcome Sanger Institute genome research center
• Shared the 2002 Nobel Prize for work on programmed cell death
• Sulston's most important research centered on Caenorhabditis elegans, a 0.03-in worm with an exact number of cells
• Sulston pushed for the genetic sequencing of C. elegans, which in 1988 became the first animal to have its entire genome sequenced

Richard Feynman

• An exceptional physicist and teacher
• Made the most esoteric of subjects (quantum theory) seem engaging
• Subatomic ideas marked the beginning of a new era for physics and technology
• Did not learn to talk until he was 3 years old but showed a prodigious capacity for mathematics
• Refused admission to Columbia University, he instead attended the Massachusetts Institute of Technology (MIT), studying first mathematics, then physics
• Completed his PhD in quantum mechanics in 1942
• Concerned about a Nazi victory in the war he participated in the Manhattan Project
• Was appointed professor of theoretical physics at Cornell University in 1945
• QED described the interactions of electromagnetically charged particles in terms of an exchange of photons which had mathematical flaws
• Key milestones:
  • Appointed junior physicist in the Manhattan Project at Los Alamos, New Mexico, in 1943
  • Became professor of theoretical physics in 1950 at Caltech
  • Received the Albert Einstein Award, a physics honor instituted while Einstein was still alive, in 1954
  • His lectures were published in 1964 as "The Feynman Lectures on Physics"
  • Awarded the Nobel Prize in Physics in 1965

Feynman's Quantum Probabilities

• Formulated a version of the theory that produced meaningful results, with the aid of what became known as Feynman diagrams
• Useful graphics illustrated the concepts of electrons and photons moving in both time and space
• The particles in his diagrams could move not only forward but also backward in time
• Feynman diagrams were in fact a mathematical model in which the probabilities of all possible events could be added up
• In Feynman diagrams, electrons are depicted by straight lines, while photon exchange between electrons is shown by wavy lines
• QED became one of the most successful theories in physics and was adopted as the model for theories of other basic forces
• He proposed a theory of "partons"; helped to introduce nanotechnology; theorized about the future existence of quantum computing; and explained why, when cooled to absolute zero, helium flows without viscosity
• He was part of a team investigating the Challenger disaster

Murray Gell-Mann

• With talents, including languages, abstract thinking, and particle physics, Gell-Mann was able to conceive the modern system for classifying subatomic particles
• In 1964, he proposed a model for classifying the different types of subatomic particles
• He distinguished two main groups of particles: fermions, the building blocks of matter; and bosons, which are force-carriers
• Used a hypothetical fundamental unit he called the “quark.” Quarks group together to form hadrons
• model became what is now known as the "standard model" and he won the 1969 Nobel Prize in Physics

Henry Stommel

• Combined his intellect with his passion for the sea
• Transformed his discipline into a scientific field and helped explain the power of ocean currents
• Stommel studied astronomy at Yale and joined Woods Hole Oceanographic Institute (WHOI) in 1944
• Stommel published a groundbreaking paper showing that the Coriolis effect causes stronger currents to be found on the western boundaries of ocean basins in 1948
• Developed a theory of global ocean circulation with work on temperature and salinity effects
• Sea gets saltier and denser and sinks to depths, pulling in warmer water to create a conveyor belt of moving water
• Surface currents are predominantly wind-driven
• Key Milestones
  • Key paper, “The westward intensification of wind-driven ocean currents," was published in 1948
  • PANULIRUS research station was set up in Bermuda in 1954, to gather data
  • "The Gulf Stream" was published in 1958,
  • Became oceanography professor at Harvard in 1959

Yang Chen-Ning

• Studied subatomic decay and helped revolutionize the field of particle physics
• Moved to Princeton and studied subatomic decay in 1949
• The conservation of parity stated that is not possible to distinguish between different directions in particle interactions
• Worked with Tsung-Dao Lee, the pair proposed the law was invalid for certain so-called “weak" interactions
• An experiment later occurred that proved their proposition was correct.
• Key Milestones:
  • US scholarship in physics was awarded in 1946 at the University of Chicago
  • Yang-Mills theory on elementary particles proposed
  • a paper was published in 1956 to prove conservation is fallible and a Nobel Prize followed in 1957

Benoît Mandelbrot

• A French mathematician
• Founded fractal geometry, and created ways to collecting and analyzing data
• Emigrated to France in 1936, and gained a mathematics PhD
• Took a role at IBM in New York in 1958 and devised fractal geometry
• Key Milestones
  • Took a position in IBM to analysis noise pollution in 1958
  • Coined term "fractal" and proposed theory of fractal geometry in 1975
  • Received honors and awards that include a Nobel Prize for Physics in 1993

Learn about Francis Crick, the Nobel Prize-winning biophysicist. He is known for co-discovering the structure of DNA in 1953 with James Watson. This lesson explores his early life, education, research, and contributions to molecular biology and neuroscience.