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
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)
- Discovery of nuclein
Found in cell nucleus, acidic, rich in PO4,
Lacks S (characteristic of protein)
Now know this as nucleic acid
- 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
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
Are there "other laws of physics?"
Wilkins' X-ray crystallography
DNA is a helix: two or three strands?
Two or three strands, bases inside or outside
For further reading:
[Biographical essays on the early days by the founders of molecular genetics.]
F. H. C. Crick
(1988). What Mad Pursuit? Basic
[Crick's version of the 'double helix' history, and lots more.]
Wheelis (1991). The
Guide to Genetics, 2nd ed. Harper Collins.
[A well-illustrated, entertaining primer of basic Mendelian and molecular genetics for non-biologists.]
H. F. Judson (1979). The
Eighth Day of Creation. Simon
[A general history of molecular biology.]
A. Sayre (1975). Rosalind
Franklin and DNA. Norton.
[A re-appraisal of the role of
J. D. Watson (1968). The
Double Helix. Athenaeum.
[An entertaining, irreverent, sexist, account of the discovery of the structure of DNA.
See the accounts of Crick and Sayre for another view]
Watson (2003). DNA:
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.]
All text material © 2011 by Steven M. Carr