DNA discovery
The discovery of DNA as the carrier of genetic information marked a pivotal moment in the field of biology. The journey began in 1928 when Frederick Griffith observed a phenomenon known as transformation in pneumococcus bacteria, where nonvirulent strains could become virulent. This led to further investigations by Oswald Avery and his colleagues in the early 1930s, who sought to identify the "transforming principle" that facilitated this genetic change. Their rigorous experiments ultimately concluded that DNA was responsible for heredity, as it was the only substance that remained active in transformation after the elimination of proteins and RNA.
By 1944, Avery, along with Colin MacLeod and Maclyn McCarty, published their findings, establishing a biochemical basis for heredity and paving the way for molecular biology. This breakthrough inspired a wave of scientific inquiry into the molecular nature of life, culminating in the elucidation of DNA's double helix structure by Francis Crick and James Watson in 1953. The recognition of DNA's role in encoding genetic information has fundamentally transformed our understanding of biology, genetics, and heredity, impacting numerous fields such as medicine, biotechnology, and evolutionary studies.
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DNA discovery
The Event Three molecular biologists demonstrated that the genetic transformation of bacteria is caused by deoxyribonucleic acid (DNA), providing direct evidence about the chemical nature of hereditary information. Their discovery, doubted at first, eventually led geneticists to understand that DNA carried life’s genetic blueprints.
Until the Avery-MacLeod-McCarty experiment demonstrated that DNA is the hereditary chemical of life, most biologists believed that the substance responsible for heredity was protein because of its extensive diversity and variability. The Avery-MacLeod-McCarty discovery revolutionized the study of the biological sciences by focusing the study of living systems on molecular mechanisms and by changing the focus of the chemical nature of heredity from proteins to DNA.
Pneumococcus bacteria are categorized into various types (I, II, III, IV) based on the antigenic properties of their polysaccharide capsules. Under certain conditions, virulent, polysaccharide-encapsulated pneumococcus bacteria can grow into nonvirulent, unencapsulated bacteria. Colonies of encapsulated bacteria have a smooth surface (designated as S), while colonies of unencapsulated bacteria have a rough (R) surface. In 1928, geneticist Frederick Griffith discovered that although R bacteria are usually nonvirulent in mice, injection of R often caused death. Upon autopsy, S bacteria could be recovered. Griffith later demonstrated that heat-killed S bacteria could “transform” live R into live S bacteria.
Oswald Avery, a bacteriologist-immunologist at the Rockefeller Institute for Medical Research (now Rockefeller University), became interested in Griffith’s results, which were confirmed by Henry Dawson in Avery’s laboratory; later, at Columbia University, he and Richard Sia demonstrated transformation in vitro. In Avery’s laboratory in the early 1930’s, Lionel Alloway demonstrated transformation in vitro using cell-free bacterial extracts. Alloway introduced the use of ethanol to precipitate the active transforming principle from cell-free extracts.
Geneticist Colin MacLeod came to Avery’s laboratory in 1934 and transformed type II R to type III S in vitro using the Alloway procedure. MacLeod used chloroform to precipitate and remove protein from the transformation preparation. By 1937, MacLeod had partially purified the transforming chemical and found that it was inactivated by ultraviolet (UV) light, the first indication that the transforming principle might be a nucleic acid. By 1941, MacLeod and Avery had refined the isolation and purification protocol by heat-killing the pneumococcus before using it to prepare a cell-free extract and by using ribonuclease to eliminate ribonucleic acid (RNA).
In 1941, geneticist Maclyn McCarty extended MacLeod’s experiments by using an enzyme to digest the type III polysaccharide to remove it from the preparation. By early 1942, upon addition of alcohol to the preparation, a stringy, fibrous material precipitated. McCarty showed that all enzymes that degraded DNA destroyed the transforming principle, but inactivating these enzymes by heat eliminated their ability to destroy the transforming principle. By this time, the laboratory was convinced that the transforming and hereditary chemical was DNA. The manuscript describing the experiments and conclusions was published on February 1, 1944.
Impact
The Avery-MacLeod-McCarty experiment demonstrated that heredity could be explained in terms of chemistry. Many biologists, chemists, and physicists were inspired by the findings of the experiment and turned their attention to studying the molecular nature of living systems. Their work eventually led to the discovery of the structure of DNA and the mechanism by which it encodes the structure of polypeptides. The year 1944 is often cited as the birth of molecular biology.
Bibliography
Avery, Oswald T., Colin M. MacLeod, and Maclyn McCarty. “Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types: Induction of Transformation by a Desoxyribonucleic Acid Fraction Isolated from Pneumococcus Type III.” Journal of Experimental Medicine 79, no. 2 (February, 1944): 137-158.
McCarty, Maclyn. The Transforming Principle: Discovering That Genes Are Made of DNA. New York: W. W. Norton, 1985.
Tudge, Colin. In Mendel’s Footnotes: An Introduction to the Science and Technologies of Genes and Genetics from the Nineteenth Century to the Twenty-Second. London: Jonathan Cape, 2000.
Watson, James D. A Passion for DNA: Genes, Genomes, and Society. Cold Spring Harbor, N.Y.: Cold Spring Harbor Laboratory Press, 2000.