Origins of Molecular Biology & Biotechnology

Origins of Molecular Biology & Biotechnology


In principle:
Genetics
taught for 50 years [Nobel Prize 1933]
    without knowledge of hereditary molecule or its structure
Molecular Biology arises with recognition of DNA
   
& elucidation of molecular mechanisms
Biotechnology applies mechanisms to manipulate Genes
    & to produce "Goods & Services"



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

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 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
       During infection of E. coli by bacteriophage,
      
       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 : A+T pair looks like C+G pair

       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 Cairns, G Stent, & JD Watson (1966). Phage and the Origins of Molecular Biology. Freeman.
        [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 the context of Photo 51].

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].

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 Franklin, with commentary on women in science].

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].

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].


All text material © 2024 by Steven M. Carr