History of DNA

A brief history of the hereditary molecule

In principle:
taught for 50 years
   without knowledge of hereditary molecule or its structure

Search for the hereditary molecule & its function includes
     superb examples of experimental method in biology
     Multiple Nobel Prizes as milestones

Two candidates: protein versus nucleic acid

Cells contain H20, lipids, carbohydrates, and ...

GJ Mulder (1838) - Discovery of protein
        Abundant, water-soluble, nitrogenous
                "... complex... regulates cell metabolism...
                 most important component of living matter...
                 without it, life would not be possible"
        Hydrolysis of protein amino acids (~20 kinds)

F Miescher (1868) - Discovery of nuclein
        Found in cell nucleus, acidic, rich in PO4,
        Lacks S (characteristic of protein)
        Now known as nucleic acid

P Levene (1910) - Tetranucleotide hypothesis
        nucleic acid repetitive polymer of four bases
             A:C:G:T in approximate ratio 1:1:1:1
        Structure too simple to carry information

F Griffith (1928) - transforming principle
        Killed virulent viruses 'transform' live avirulent viruses (HOMEWORK):
              avirulent viruses become virulent,
              Transformation is inherited
        Hereditary makeup of organisms can be altered

O Avery, CM MacLeod, & M McCarty (1944) -
        Chemical isolation of  'transforming principle' from cells
                Transformation survives protease treatment,
                 destroyed by nuclease treatment (Homework)
        It's chemically pure deoxyribonucleic acid (DNA?!?!

A Hershey & M Chase (1952) - 'Blender Experiment'
       Bacteriophages grown in radioactive medium
             Proteins labeled with 35S
             DNA labeled with 32P
       During infection of E. coli by bacteriophage,
       32P goes in,  35S stays out
        DNA is transforming principle

JD Watson & FHC Crick (1953) "The Double Helix"

       E Schrödinger (1945) "What is Life?":
              Are there "Other laws of physics?"

       R Franklin, R Gosling, & M Wilkins' X-ray crystallography
              DNA is a helix: two or three strands? Bases inside or outside?

E Chargaff: Chargaff's Rules: Bases occur in specific ratios
              [A] = [T]  &  [C] = [G]   (Table)

       Model building:
              Two or three strands, bases inside or outside
              Key recognition : A+T pair looks like C+G pair

       The Watson - Crick structure for DNA (Nobel, 1962, w/ M Wilkins)
           double-stranded helix
                Two sugar-phosphate backbones outside
                Nitrogenous bases inside
                H-bonds hold strands held together

For further reading:

J Cairns, G Stent, & JD Watson (1966). Phage and the Origins of Molecular Biology. Freeman.
        [Biographical essays on the early days by the founders of molecular genetics.
         See also Stent (1963) Molecular Biology of the Bacterial Viruses. Freeman].

FHC Crick (1988). What Mad Pursuit? Basic Books.
        [Crick's version of the 'double helix' history, and his subsequent scientific work].

HF Judson (1996). The Eighth Day of Creation (25th Anniversary Ed). Simon & Schuster.
        [A general history of molecular biology. See especially material on sharing of Photo 51].

B Maddox (2003). Rosalind Franklin: The Dark Lady of DNA. London: Harper Collins.
        [cf. Sayre: Contrasting consideration of Franklin's career and sexism at King's]

A Sayre (1975). Rosalind Franklin and DNA. Norton.
        [A re-appraisal of the role of Franklin, with commentary on the role of women in science].

JD Watson (1968). The Double Helix. Athenaeum.
        [An entertaining, irreverent, sexist, personal account of the discovery of the structure of DNA.
         See also JD Watson (2012) The Annotated and Illustrated Double Helix. Simon & Schuster].

JD Watson (2003). DNA: The Secret of Life. Knopf
         [A narrative history of genetics and molecular biology in the 20th century,
           written for the 50th anniversary of the discovery of the DNA structure].

MHF Wilkins (2003). The Third Man of the Double Helix. Oxford.
        [See especially Wilkins' account of x-ray crystallography experiments on DNA and 'Photo 51'].

S Mukherjee (2016). The Gene: An Intimate History. Scribner
        [An extension of Judson into the 21st Century].

EA Carlson (2018). How Scientific Progress Occurs: Incrementalism and the Life Science. Cold Spring Harbor Press.   
        [A discussion of T Kuhn's theory of Scientific Revolutions with respect to life sciences].

All text material © 2022 by Steven M. Carr