A brief history of the hereditary molecule

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In principle:
"Genetics" was taught for 50 years
without knowledge of the hereditary molecule or its structure

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

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Two candidates: protein versus nucleic acid

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

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)

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

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

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

Avery, MacLeod, & 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)  ?!?!

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

Watson & Crick (1953) "The Double Helix"

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

Franklin, Gosling, & Wilkins' X-ray crystallography
DNA is a helix: two or three strands?
HOMEWORK

Chargaff's Rules : Bases are not equimolar, but 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
double-stranded helix
Two sugar-phosphate backbones outside
                Nitrogenous bases inside
                H-bonds hold strands held together

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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].

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

HF Judson (1996). The Eighth Day of Creation (25th Anniversary Ed). Simon & Schuster.
[A general history of molecular biology].

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, 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 20^th century,
written for the 50^th 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 and 'Photo 51'].

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

All text material © 2017 by Steven M. Carr