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Events and Exhibits

The Transforming Principle:

DNA - the molecule of heredity

February – November 2009

Discovering DNA

The story of DNA is one of the most fascinating of modern science. Contrary to popular belief, the discovery of the chemical structure and biological function of deoxyribonucleic acid (DNA) did not occur within several years in the twentieth century and was not accomplished by a small, select group of scientists. In fact DNA was discovered almost a century and half ago. Solving the problems of DNA was similar to the painstaking work in assembling the many isolated pieces of a large jigsaw puzzle. A great number of scientists working in a variety of fields contributed to the final outcome, but few ever received anything more significant than the personal satisfaction of having been a participant. Gregor Mendel, Austrian priest and scientist, played a very important role in the discovery of genes and heredity. He is considered to be “the father of genetics” with his famous experiment in 1865 about peapods that explained the patterns of inheritance. In 1869 Swiss physician Frederich Miescher isolated DNA from white blood cells and called them “nuclein,” later known as nucleic acid. At the beginning of the twentieth century Phoebus Aaron Theodore Levene, biochemist at The Rockefeller Institute, identified the components of DNA. In 1928, Frederick Griffith, a British geneticist, discovered what he called a transforming principle in which a nonvirulent bacteria was turned into a virulent one. It was not until sixteen years later that Griffith’s “transforming principle” was identified as DNA by Avery, MacLeod, and McCarty.






The Professor, the Institute, and DNA

Oswald Theodore Avery was born on October 21, 1877 in Halifax, Nova Scotia. The family moved to New York City in 1887 where Avery chose a career in medicine. He received his medical degree in 1904 and moved in 1907 to Hoagland Laboratory in Brooklyn where he developed an interest in tuberculosis. It was during this time that Avery established what his biographer René Dubos called the pattern of his career, the “systematic effort to understand the biological activities of pathogenic bacteria through knowledge of their chemical composition.” Avery’s work came to the attention of Rufus Cole, the director of The Rockefeller Institute Hospital, and he asked Avery to join the Hospital’s pneumonia research program. Avery moved to The Rockefeller Institute in 1913, where he focused most of his research for the next thirty-five years on a single species, the pneumococcus. There he worked with scientists who were widely recognized as being among the elite in their fields, including Alphonse R. Dochez, René Dubos, Michael Heidelberger, Rebecca Lancefield, Rollin Hotchkiss, Walther Goebel, Maclyn McCarty, and Colin MacLeod. His research career culminated in 1944, when, with McCarty and MacLeod, Avery published the seminal paper proving that the hereditary material was DNA and not protein as most scientists initially assumed.






The Transforming Principle

After Colin MacLeod moved to New York University in 1941, Maclyn McCarty joined the laboratory and aided Avery in his research. Avery and McCarty focused first on purifying the transforming substance. They soon determined that the substance was rich in nucleic acids, but ribonuclease, an enzyme discovered by René Dubos that destroys ribonucleic acid (RNA), did not inactivate the substance. Further, the transforming substance had a high molecular weight and gave a strong reaction to the Dische diphenylamine test, which detects for the presence of DNA. Consequently Avery and McCarty concluded that the transforming substance, which produced permanent, heritable change in an organism, was DNA. Avery, Macleod, and McCarty had accumulated all the basic experimental information and presented their discovery to The Rockefeller Institute's Board of Scientific Directors in April 1943. Their report that the transforming principle was DNA, "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," was published in the Journal of Experimental Medicine in February 1944.






When Avery, MacLeod, and McCarty identified DNA as the "transforming principle" in the early 1940s, they resolved a fundamental problem in biological science. At the same time their discovery launched the field of molecular biology and marked the start of the contemporary era in genetics.  After reading their paper, many scientists changed the focus of their research to further investigate nucleic acids. One of the most successful, Erwin Chargaff, examined DNA using the recently developed techniques of paper chromatography and ultraviolet spectroscopy and found the composition of DNA to be constant within a species but to differ widely between species. This led him to conclude that there must be as many different types of DNA as there are different species. This discovery, announced by Chargaff in 1950, was of crucial importance in constructing the Watson–Crick model of DNA. James Watson and Francis Crick, working together at Cambridge University in England, assimilated all this information along with the help of Maurice Wilkins and expert X-ray crystallography images prepared by Rosalind Franklin, both of King’s College in London. In 1953 Watson and Crick came up with their historic model of the shape of DNA: the double helix. Identifying the shape of DNA was a major breakthrough in genetic research, for which Watson, Crick, and Wilkins won the Nobel Prize in Physiology or Medicine in 1962.






The exhibit was opened in conjunction with Hospital Centennial celebrations of the 65th anniversary of the publication of the landmark genetic discovery of Drs. Oswald T. Avery, Colin M. MacLeod, and Maclyn MacCarty. Their discovery grew from their research on more than 1,000 patients who were treated for pneumococcal pneumonia in the Rockefeller University Hospital.





Idea, design, and text: Olga Nilova

Consultants: Carol Moberg, Margie McCarty

Archival Support: Meg Hogan


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Avery, O. Acute lobar pneumonia; prevention and serum treatment. New York, 1917

McCarty, M. The transforming principle. New York, c1985

Watson, J. DNA: the secret of life. New York, 2003

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Watson, J. Genes, girls, and Gamow: after the Double Helix. New York, c2001

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McElheny, V. Watson and DNA: making a scientific revolution. Cambridge, c2003

Chargaff, E. Heraclitean fire; sketches from a life before nature. New York, 1978 

Chargaff, E. Essays on nucleic acids. Amsterdam, New York, 1963


        MendelGregor Mendel

Mendall GardenMendel's garden in the monastery at Brno

Genetic variation in pea plantsGenetic variation in pea plants

Frederich MiescherFrederich Miescher

Griffith’s experimentGriffith’s experiment

OswaldOswald Theodore Avery
Courtesy of the Rockefeller Archive Center

Colin MacLeodColin MacLeod, 1940s
Courtesy of the Rockefeller Archive Center

Maclyn McCartyMaclyn McCarty
Courtesy of the Rockefeller Archive Center

PneumococcusPneumococcus, the bacterium that O. Avery began investigating in 1913

Colonies of pneumococciColonies of pneumococci on the surface of blood agar

Erwin ChargaffErwin Chargaff

James Watson and Francis CrickJames Watson and Francis Crick

Colin MacLeod and Maclyn McCarty

Colin MacLeod and Maclyn McCarty at the Avery Memorial Gateway dedication ceremony, 1965