Origins of Molecular Biology & Biotechnology

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In principle:

Genetics taught for 50 years [Nobel Prize 1933]

    What inferences can be made about heredity from crosses ?
without knowledge of hereditary molecule or its structure

'Elementen' follow Mendelian Laws

          No chromosomes, no chemical basis

Molecular Biology arises with recognition of DNA structure & function
& 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

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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 nucleic acid [nuclein]
Found in cell nucleus, acidic, rich in PO₄,
        Lacks S (characteristic of protein)

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

F Griffith (1928) - transforming principle
        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 characterization 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'
Bacteriophage 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 DNA structure (1953)

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 : A+T pair looks like C+G pair

       The Watson - Crick "Double Helix" 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 / in vitro "cloning" of genes               [Nobel Prize 1980]
analysis & expression of cloned genes
Restriction enzymes                                           [Nobel Prize 1978]
DNA sequencing [Nobel Prize 1980] 
Automated DNA sequencing
HuGO: the Human Genome Project
                "Next Generation Sequencing" (NGS)

Polymerase Chain Reaction (PCR)                   [Nobel Prize 1993]
qPCR - quantitative PCR                               

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 cures Vitamin A deficiency (2004)

CRISPR / Cas9 "genetic scissors" [Nobel Prize 2020]
               Therapy for Sickle-Cell Anemia

Resurrecting ancient DNA (aDNA)    [Nobel Prize 2022]
mRNA vaccine for COVID-19                                 [Nobel Prize 2023]

DNA Forensics
        Environmental DNA (eDNA)

       et sequelae

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For further reading:

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 & molecular biology in the 20^th century,
written for the 50^th anniversary of the discovery of the DNA structure].

JD Watson (2012) The Annotated and Illustrated Double Helix. Simon & Schuster].

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

EA Carlson (2018). How Scientific Progress Occurs: Incrementalism and the Life Science. Cold Spring Harbor Press.   
        [A discussion of T Kuhn's theory of Scientific Revolutions with respect to life sciences].

B Lewin (2024). Inside Science: Revolution in Biology and its Impact. Cold Spring Harbor Labs.
        [The transformation of molecular biology from individual labs to Big Science].

All text material © 2025 by Steven M. Carr