A brief history of the hereditary
molecule
In
principle:
Genetics 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
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 ()
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 :
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
[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
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].
[A discussion of
T
Kuhn's theory of Scientific
Revolutions with respect to life sciences].
All text material © 2022 by Steven M. Carr