History of the hereditary molecule (to 1953)
"Genetics" was taught for 50 years
without knowledge of the hereditary substance or its structure
(see Orientation to Bio2250)
The story of the search for
the hereditary substance includes
superb examples of the experimental method in biology.
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
Killed virulent viruses 'transform' live avirulent viruses:
avirulent viruses become virulent, and
Transformation is inherited
Hereditary makeup of organisms can be altered
MacLeod, & McCarty (1944) -
Chemical isolation of 'transforming principle' from cells
Transformation survives protease treatment,
destroyed by nuclease treatment ():
It's chemically pure deoxyribonucleic acid (DNA)
Chase (1952) -
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?"
& Wilkins' X-ray crystallography
DNA is a helix: two or three strands? [Photo 51]
Two or three strands, bases inside or outside
Key recognition :
For further reading:
[Biographical essays on the early days by the founders of molecular genetics.]
E Chargaff (1978). Heraclitean Fire. Paul & Co. [Reflections of an also-ran on classical biochemistry vs modern molecular biology].
FHC Crick (1988). What
Mad Pursuit? Basic Books.
[Crick's version of the 'double helix' history, and lots more.]
& M Wheelis (1991). The Cartoon Guide to Genetics, 2nd ed.
[A well-illustrated, entertaining primer of basic Mendelian and molecular genetics for non-biologists.]
HF Judson (1979). The Eighth Day of Creation (2nd ed.).
Simon & Schuster.
[A general history of the "classical" period of molecular biology. Valuable for its interviews with the principals.]
A Sayre (1975). Rosalind Franklin and DNA.
[A re-appraisal of the role of
JD Watson (1968). The Double Helix. Athenaeum.
[An entertaining, irreverent, and sexist account of the discovery of the structure of DNA.
See the accounts of Crick and Sayre for another view
Re-issued in 2003 in a heavily annotated and supplemented edition by Cold Spring Harbor Labs. Includes reactions to publication]
JD Watson (2003). DNA: The Secret of
[A narrative history of genetics and molecular biology in the 20th century,
written for the 50th anniversary of the discovery of the DNA structure].
Wilkins (2003). The Third Man of the Double Helix.
[See especially Chapter 8 on the exchange of crystallographic data in Photo 51].
All text material © 2015 by Steven M. Carr