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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

Go to Graphics Gallery: The Structure of DNA, DNA Replicating Itself

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