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Origins of Molecular Biology & Biotechnology

Origins of Molecular Biology & Biotechnology


In principle: 

Genetics taught for 50 years [Nobel Prize ]

    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



Two candidates: protein versus nucleic acid

Cells contain H20, lipids, carbohydrates, and ...

(1838) - Discovery of protein
        Abundant, water-soluble, nitrogenous
        Hydrolysis of protein amino acids (~20 kinds)

(1868) - Discovery of nucleic acid [nuclein]
        Found in cell nucleus, acidic, rich in PO4,
        Lacks S (characteristic of protein)

(1910) - Tetranucleotide hypothesis
        nucleic acid repetitive polymer of four bases
             in approximate ratio 1:1:1:1
        Structure too simple to carry information

(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

, , & (1944) -
        Chemical characterization of  'transforming principle'
                Transformation survives protease treatment,
                 destroyed by nuclease treatment (HOMEWORK)
        It's chemically pure deoxyribonucleic acid (DNA?!?!

& (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

& DNA structure (1953)

       (1945) "What is Life?":
              Are there "Other laws of physics?"

       , , & ' X-ray crystallography
              DNA is a helix: two or three strands? Bases inside or outside?

      
: 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    [ 1962, w/ ]
           double-stranded helix
                Two sugar-phosphate backbones outside
                Nitrogenous bases inside
                H-bonds hold strands held together

Molecular Biology replaces Genetics   [Nobel Prizes in & ]

    Bacteriophage Genetics                                          [Nobel 1969]
    "Cracking" the Genetic Code                                  [Nobel ]
    Transposable elements - "Jumping Genes"            []
    Intron / Exon "split gene" structure                         [ ]

    Genetic Engineering: laboratory manipulation of DNA
          What does a particular region of DNA do?

          Isolation & manipulation of recombinant DNA  []

             in vivo / in vitro "cloning" of genes              
[]
             analysis & expression of cloned genes
                            
       Restriction enzymes                                           []
       DNA sequencing                                                
[
                Automated DNA sequencing
                HuGO: the
                "Next Generation Sequencing" (NGS)

       Polymerase Chain Reaction (PCR)                   []
            qPCR - quantitative PCR                               

Biotechnology - "The use of biological systems to produce goods & services"
         Genetically Modified Organisms ()
                    : bovine-sourced insulin replaced by cloned human insulin (1983)   
                    : first GMO food, engineered for longer shelf line (1994)  
                    : beta-carotene enhanced rice cures Vitamin A deficiency (2004)

        "genetic scissors"                        [ 2020]
               Therapy for Sickle-Cell Anemia

        Resurrecting ancient DNA (aDNA                        []
        mRNA vaccine for COVID-19                                 [ 2023]

        DNA Forensics
        Environmental DNA (eDNA)

        et sequelae




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 ].

JD Watson (2003). . Knopf
         [A narrative history of genetics & molecular biology in the 20th century,
           written for the 50th 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 's theory of 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