From the Suitcase: Avery Discovers Genes Are Made of DNA

Few questions stump biologists of all shapes and sizes, from grad students to department heads, like “who discovered DNA?” In part, because it’s usually the wrong question. What most people actually want to know is who demonstrated that genes (the abstract carrier of heritable properties, the “yellow” or “wrinkled”-ness of Mendel’s peas) were made of deoxyribonucleic acid. The answer to the first question is Friedrich Miescher discovered DNA (“nuclein” in his words) while studying, for lack of a better word, pus in the 19th century. The wrong answer to the second question is “Watson & Crick” (the slightly more sophisticated wrong answer to the second question is “Hershey & Chase”).

Behind Door #3 we have Oswald Avery, accompanied by Maclyn McCarty and Colin MacLeod (it’s a big door):

“Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters. Among microorganisms the most striking example of inheritable and specific alterations in cell structure and function that can be experimentally induced and are reproducible under well defined and adequately controlled conditions is the transformation of specific types of Pneumococcus. This phenomenon was first described by Griffith who succeeded in transforming an attenuated and non-encapsulated (R) variant derived from one specific type into fully encapsulated and virulent (S) cells of a heterologous specific type.”

That’s how they introduce the problem tackled in their landmark 1944 JEM paper “STUDIES ON THE CHEMICAL NATURE OF THE SUBSTANCE INDUCING TRANSFORMATION OF PNEUMOCOCCAL TYPES”.  The stated goal is straightforward: to determine which chemical component of bacteria is responsible for conferring the encapsulated, virulent property. I’ve read summaries of this over the years, and seen many textbook illustrations. But here is what the experimental readout actually looked like, on the left are the attenuated, and on the right, the virulent (transformed) bacterial colonies (click on picture to enlarge):

Presentation2

The conclusion, after an epic series of biochemical purification experiments was clear:

“A desoxyribonucleic acid fraction has been isolated from Type III pneumoeocci which is capable of transforming unencapsulated R variants derived from Pneumococcus Type II into fully encapsulated Type III cells.”

Avery and his collaborators could also see that their results posed an important new question: which chemical properties conferred on DNA the ability to transmit information?

“If it is ultimately proved beyond reasonable doubt that the transforming activity of the material described is actually an inherent property of the nucleic acid, one must still account on a chemical basis for the biological specificity of its action.”

The need to answer this question was the starting shot in the race to understand the structure of DNA- the race that Watson and Crick did win, in 1953. In fact Avery et al‘s problem very neatly sets up the double helix paper’s famously coy conclusion:

“It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material.”

Alfred Hershey and Martha Chase? They did beautiful work in 1952. But it was an atomic age confirmation of Avery, MacLeod, and McCarty’s 1944 classic.

Bibliography:

Avery, O.T., MacLeod, C.M., and McCarty, M. 1944. Studies on the chemical nature of the substance inducing transformation of Pneumococcal types. J. Exp. Med., 79:137. 

Hershey, A.D and Chase, M. 1952. Independent functions of viral protein and nucleic acid in growth of bacteriophage. J. Gen. Physiol. 36:39.

Watson, J.D. and Crick, F.H.C. 1953. A structure for deoxyribose nucleic acid. Nature. 171:737. 

2 thoughts on “From the Suitcase: Avery Discovers Genes Are Made of DNA

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