The Search for DNA - The Birth of Molecular Biology 


   The Search for DNA - The Birth of Molecular Biology            

   Biotechnology Industry Organization (BIO). "Biotechnology in
   Perspective." Washington, DC: Biotechnology Industry Organization,
   1990.
   -----------------------------------------------------------------------

   The History of DNA Research

   The history of deoxyribonucleic acid (DNA) research begins with
   Friedrich Miescher, a Swiss biologist who in 1868 carried out the
   first carefully thought out chemical studies on the nuclei of cells.
   Using the nuclei of pus cells obtained from discarded surgical
   bandages, Miescher detected a phosphorus-containing substance that he
   named nuclein. He showed that nuclein consists of an acidic portion,
   which we know today as DNA, and a basic protein portion now recognized
   as histones, a class of proteins responsible for the packaging of DNA.
   Later he found a similar substance in the heads of salmon sperm cells.
   Although he separated the nucleic acid fraction and studied its
   properties, the covalent structure of DNA did not become known with
   certainty until the late 194Os.

   DNA Carries Genetic Information

   Even though Miescher and many others following him suspected that
   nuclein or nucleic acid might play a key role in cell inheritance,
   others argued that their lack of chemical diversity compared to, say,
   proteins ruled out such a possibility. It was not until 1943 that the
   first direct evidence emerged for DNA as the bearer of genetic
   information. In that year, Oswald Avery, Colin MacLeod, and Maclyn
   McCarty, working at the Rockefeller Institute, discovered that DNA
   taken from a virulent (disease-causing) strain of the bacterium
   Streptococcus pneumonae permanently transformed a non-virulent (or
   inactive) form of the organism into a virulent form.

   Avery and his colleagues concluded from these experiments that it was
   the DNA from the virulent strain which carried the genetic message for
   virulence and that it became permanently incorporated into the DNA of
   the recipient non-virulent cells. Although the scientific community
   was slow to adopt the idea that DNA was the carrier of genetic
   information, a subsequent experiment provided evidence that this was
   indeed the case. In 1952, Alfred Hershey and Martha Chase showed by
   means of radioactive isotope tracer experiments that when a bacterial
   virus (bacteriophage T2) infects its host cell (the bacterium
   Escherichia coli), it is the DNA of the T2 virus, and not its protein
   coat, which enters the host cell and provides the genetic information
   for replication of the virus.

   From these very important early experiments, and a wealth of other
   corroborating evidence, it is now certain that DNA is the carrier of
   genetic information in all living cells.

   Unraveling the DNA Double Helix

   Despite proof that DNA carries genetic information from one generation
   to the next, the structure of DNA and the mechanism by which genetic
   information is passed on to the next generation remained the single
   greatest unanswered question in biology until 1953. It was in that
   year that James Watson, an American geneticist, and Francis Crick, an
   English physicist, working at the University of Cambridge in England
   proposed a double helical structure for DNA. This was the culmination
   of a brilliant piece of detective work - and a discovery that has
   proven to be the key to molecular biology and modern biotechnology.
   Using information derived from a number of other scientists working on
   various aspects of the chemistry and structure of DNA, Watson and
   Crick were able to assemble the information like pieces of a jigsaw
   puzzle to produce their model of the structure of DNA.

   It had already been established by chemical studies that DNA was a
   polymer of nucleotide subunits, each nucleotide comprising a sugar
   (deoxyribose), phosphate and one of four different bases - the
   purines, adenine (A) and guanine (G) together with the pyrimidines,
   thymine (T) and cytosine (C). A most important clue was the discovery
   in the late 1940s by Erwin Chargaff and his colleagues at Columbia
   University that the four bases may occur in varying proportions in the
   DNAs of different organisms, but the number of A residues is always
   equal to the number of T residues; similarly equal numbers of G and C
   residues are present. These quantitative relationships are important,
   not only in establishing the three-dimensional structure of DNA, but
   also in providing clues on how genetic information is encoded in DNA
   and passed on from one generation to the next.

   X-ray Diffraction Reveals the Molecular Structure of DNA

   The elegant and comprehensive X-ray diffraction studies of Rosalind
   Franklin and Maurice Wilkins at King's College, (London, England)
   yielded a characteristic diffraction pattern from which it was deduced
   that DNA fibers have two periodicities along their long ans: a major
   one of 0.34 nm and a secondary one of 3.4 nm.

   The problem that Watson and Crick addressed was to formulate a model
   of the DNA molecule that could account not only for these
   periodicities, but also for the specific A - T and G - C base
   equivalences discovered by Chargaff. The manner in which they solved
   the problem involved building three-dimensional models incorporating
   all these elements. This resulted in their now famous model for the
   structure of DNA consisting of two helical chains of DNA coiled around
   the same axis to form a right-handed double helix.

   A Schematic Diagram of the Structure of DNA

   In the double helix the two strands of DNA run in opposite directions
   and are complementary, being matched by the hydrogen bonds of the A -
   T and G - C base pairs. This complementary pairing of the bases
   ensures that, when DNA replicates, an exact duplicate of the parental
   genetic information is made. The polymerization of a new complementary
   strand takes place using each of the old strands as a template. The
   elegant simplicity of molecular structure of DNA in relation to its
   role as the repository of all genetic information was not lost on
   those involved in its discovery.

   For their outstanding work in discovering the double helical structure
   of DNA, Watson and Crick shared the 1962 Nobel Prize for Physiology
   and Medicine with Maurice Wilkins. Sadly, Rosalind Franklin, whose
   work greatly contributed to this key discovery, died before this date,
   and the rules do not allow a Nobel Prize to be awarded posthumously.

   Table Of Key Dates

      * 1868: Friedrich Miescher isolates nucleic acid from pus cells
        obtained from discarded bandages

      * 1943: Avery, Macleod and McCarty use bacteria to provide the
        first evidence that DNA is the bearer of genetic information

      * 1952: Hershey and Chase show that it is the DNA part of the T2
        viral particle, not the protein part, that enters a host cell,
        furnishing the genetic information for the replication of the
        virus

      * 1953: Double helix structure of DNA is revealed by Watson, Crick,
        Franklin, and Wilkins

      * 1961-65: Genetic code is cracked

      * 1972: First successful DNA cloning experiments are carried out in
        California

      * 1975: Monoclonal antibodies are produced

      * 1975-77: Rapid methods of sequencing DNA are perfected

      * 1977: The first human gene is cloned

      * 1982: Genetically-engineered insulin is approved for use in
        diabetics in the USA and UK

      * 1987: First genetically-engineered microorganisms are used in
        field experiments

   -----------------------------------------------------------------------


----------------------------------------------------------------------------