Origins of Molecular Biology &
Biotechnology
In principle:
Genetics taught for 50 years [Nobel Prize 1933]
without
knowledge of hereditary molecule or its structure
'Elementen' follow Mendelian Laws
No chromosomes, no chemical basis
Molecular Biology arises with recognition of DNA
& elucidation of molecular
mechanisms
"Forward"
vs "Reverse" genetics
Biotechnology applies
mechanisms to manipulate Genes
to produce "Goods & Services"
Bioinformatics applies
computational science
to extract information from large data sets
Two
candidates: protein versus nucleic acid
Cells contain H20,
lipids, carbohydrates, and
...
GJ
Mulder (1838) - Discovery of protein
Abundant,
water-soluble, nitrogenous
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
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'
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
When bacteriophage infect E. coli,
32P
goes in, 35S stays out
DNA
is transforming principle
JD
Watson & FHC
Crick
structure (1953) "The Double Helix"
/ "The Base Pair" ?
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 strands, bases inside
Key recognition :
The
Watson -
Crick structure
for DNA
[Nobel
Prize
1962, w/ M
Wilkins]
double-stranded helix
Two sugar-phosphate backbones
outside
Nitrogenous
bases inside
H-bonds hold
strands held together
Molecular Biology
replaces Genetics
[Nobel Prizes in Physiology
& Medicine
& Chemistry]
Bacteriophage
Genetics
[Nobel Prize
1969]
"Cracking"
the Genetic Code
[Nobel Prize
1968]
Transposable elements - "Jumping
Genes"
[Nobel
Prize 1983]
Intron / Exon "split gene"
structure
[Nobel
Prize 1992]
Genetic
Engineering: laboratory
manipulation of DNA
What does a particular region
of DNA do?
Isolation & manipulation of recombinant
DNA [Nobel
Prize 1980]
in vivo or
in vitro "cloning" of genes
[Nobel Prize 1980]
analysis of the cloned gene
gel electrophoresis
DNA
sequencing
[Nobel Prize 1980]
mRNA expression
Restriction
enzymes
[Nobel
Prize 1978]
DNA
sequencing
Automated DNA sequencing
HuGO: the Human
Genome Project
"Next Generation Sequencing"
(NGS)
Polymerase Chain Reaction (PCR)
[Nobel Prize 1993]
Biotechnology
- "The use of biological systems to produce
goods & services."
Genetically
Modified Organisms (GMOs)
Humulin:
bovine-sourced insulin replaced by cloned human
insulin (1983)
FlavrSavr
Tomato : first GMO food, engineered for longer
shelf line (1994)
Golden
Rice: beta-carotene enhanced rice
offsets Vitamin A deficiency (2004)
CRISPR
/ Cas9 "genetic scissors"
[Nobel
Prize
2020]
Resurrecting ancient DNA
(aDNA)
[Nobel
Prize 2022]
mRNA vaccines
for COVID-19
[Nobel
Prize
2023]
DNA Forensics
Environmental DNA
(eDNA)
etc etc etc
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].
JD Watson (1968). The Double Helix. Athenaeum.
[A personal account of the discovery of
the structure of DNA., much criticized.
See also JD Watson (2012) The Annotated and Illustrated
Double Helix. Simon & Schuster].
A Sayre (1975). Rosalind Franklin and DNA.
Norton.
[A re-appraisal of the role of
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 the context of Photo 51].
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].
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]
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].
[The
transformation of molecular biology from individual labs
to Big Science].
All text material © 2025 by Steven M. Carr