Rockefeller University Digital Commons @ RU The Rockefeller Institute Quarterly The Rockefeller University Newsletters Spring 1958 The Rockefeller Institute Quarterly 1958, vol.2, no.1 The Rockefeller University Follow this and additional works at: http://digitalcommons.rockefeller.edu/ rockefeller_institute_quarterly Recommended Citation The Rockefeller University, "The Rockefeller Institute Quarterly 1958, vol.2, no.1" (1958). The Rockefeller Institute Quarterly. Book 5. http://digitalcommons.rockefeller.edu/rockefeller_institute_quarterly/5 This Book is brought to you for free and open access by the The Rockefeller University Newsletters at Digital Commons @ RU. It has been accepted for inclusion in The Rockefeller Institute Quarterly by an authorized administrator of Digital Commons @ RU. For more information, please contact [email protected]. VOLUME 2 NUMBER 1 BACTERIOLOGY, GENETICS, AND DNA- Strangely enough, a bacteriologist at the Rockefeller Institute who was absorbed in studying pneumonia made the most signi- A FRONTIER IN RESEARCH ficant step in discovering the key role of DNA in the regulation of living organisms. MOST BIOCHEMISTS and geneticists in the case of the human ovum, for ex- The late Dr. 0. T. Avery found that DNA today agree that deoxyribonucleic acid, or ample) contain all the information neces- extracted from the cells of one strain of DNA,is an essential part of the mechanism sary to enable it to elaborate itself into a pneumococci can transform another strain of heredity. Outstanding contributions to mature organism capable of carrying on into the first. But most important-the our understanding of the importance of the species. A central problem in genetics change is passed from generation to gen- DNA have been made by scientists of the research today is the attempt to discover eration. Avery was assisted by Dr. Colin Rockefeller Institute during the past 50 how this information is contained within MacLeod, who later left the Institute, and years, which we will describe briefly here. the cell nucleus, how it is passed from one Dr. Maclyn McCarty, then a National Before much can be said about the generation to the next, and how it is able Research Council Fellow, now studying significance of DNA,however, we must to control the character of the subsequent the relationship of streptococci to rheu- go back about go years in the history of development of the individual cell and the matic fever. biological science to the time of the monk, organism of which it may be a part. DNA is Dr. Avery had become interested in this Gregor Mendel, and the dawn of the believed to play the key role in this process. question after a British pathologist, F. science of genetics. Mendel, an extraor- More than 50 years ago Dr. P. A. Griffith, reported in I 928 that when he dinarily perceptive gardener, concluded Levene at the Rockefeller Institute took up inoculated mice with a mixture of a harm- from experiments with pea plants in his the task of determining the chemical less strain of pneumococci and the dead cloister garden that whatever carries the nature of the nucleic acids, one of which, remains of a harmful strain, the mice died traits of the parent plants to their offspring DNA, exists in the nucleus of cells. Thanks from live pneumococci of the harmful must be composed of discrete units that do to Dr. Levene's work and what has fol- strain! Either the dead bacteria were not lose their identity in the mating proc- lowed from it we now know DNA to be brought to life or something in them was ess. Tall plants mated with dwarf plants an immensely large and elaborate molecule able to transform a harmless strain into a do not produce middle-sized plants, but composed of only a few relatively simple virulent one. It was I 8 years later that some tall ones and some dwarfs, the traits sub-structures called nucleotides. These Avery, MacLeod and McCarty published being distributed among the offspring in a are arranged on a backbone of a sugar-like their classic paper which concluded that statistically predictable way. character strewn with phosphate groups. the agent causing the transformation is When more of the process was under- DNA is believed to be a double molecule DNA. Somehow molecules of this nucleic stood, the discrete units controlling indi- in which the phosphate-sugar backbones acid are able to transfer genetic informa- vidual traits were called genes and they of the two halves are coiled around each tion from one kind of cell to another kind were found to be arranged in a specific other in a long helix. Dr. Levene estab- and cause the revision to be inherited in- order along rod-like bodies that can be lished many years ago that the sugar-like definitely. seen in the nucleus of cells at certain stages backbone of DNA consists of deoxyribose. Mendel's genetic studies were based on in their lives. These objects in the nucleus It was not until 1954, however, that J. D. observations of differences in plants such were called "chromosomes" because they Watson at the California Institute of as their size or the color of their flowers. become colored when the cell is stained Technology and F. H. C. Crick, his British The change produced in pneumococci by with certain dyes. It is astounding to re- colleague at the Cavendish Laboratory in transformation is less obvious, but it is flect that the chromosomes within one Cambridge, recognized its double helical observable. The original strain of pneumo- single cell (barely visible to the naked eye structure. cocci in the transformation experiment grew in small, irregular colonies, but when there was "nothing left but the grin" and assuming that DNA and not a protein con- transformed they formed large, smooth, the grin was the nucleic acid, DNA. taminant is responsible for the transform- glistening colonies. We have included Some doubted this however. They ing effect in pneumococci. Relatively pure here a photograph of colonies of the two argued that Avery could not be certain DNA-destroyingenzyme, termed DNA-ase, kinds of cell, magnified 3.5 times. This is, that his DNA extracts really were free of was prepared, and it completely destroyed in fact, the photograph with which Avery, protein contaminants that might be the the transforming power of the cell extracts. MacLeod, and McCarty illustrated their true transforming agent. It was revolution- McCarty's DNA-asewas extremely pure, paper in 1944. ary enough to conclude that any specific, thus making it very unlikely that trans- During these I 8 years some of Dr. identifiable, chemical compound could formation was stopped by DNA-ase only Avery's younger colleagues provided essen- produce inheritable changes in bacteria. because protein-destroying impurities in tial clues to the subsequent identification It was still more revolutionary to propose the enzyme were inactivating traces of of DNA's role in the transformation of that the compound was not even a protein, protein that were really the effective com- pneumococci. In 1930 Dr. Martin H. as are all the enzymes that play so funda- ponent of the transforming extracts. Ulti- Dawson, also a National Research Council mental a role in the regulation of bia- mately Dr. Moses Kunitz, now Member Fellow, who had begun to study this prob- chemical processes. DNA, as Levene had Emeritus at the Institute, long renowned lem while at the Institute, and Dr. Richard shown, is a kind of complicated sugar-like for his work in crystallizing biologically P. Sia, on a leave of absence from the molecule! Avery and McCarty continued active proteins, after long and difficult Peiping Union Medical College, succeeded to study this question, particularly that of attempts, succeeded in preparing extreme- in causing dead pneumococci to transform possible protein contamination of their ly pure crystalline DNA-ase. McCarty live cells just as in Griffith's experiment, transforming DNA extracts. They pushed found this to be even more effective than but in laboratory glassware instead of in a their estimates of the maximum possible his own. Pure DNA-asehas proved to be mouse. In the following year Dr. J. Lionel contamination closer and closer to zero one of the most significant research tools Alloway, another NRC Fellow at the Insti- and the transformation continued un- available for the study of DNA and re- tute, reported his success in discarding not affected. Yet until the level of zero was lated problems. only the mouse but even the intact dead reached doubt remained. Taking a dif- It is one thing, however, to show that cells themselves. Instead, Alloway used ferent approach Avery and McCarty de- DNA can cause heritable changes to occur; only cell-free extracts of the dead cells to cided to try to prepare an enzyme that it is something else again to show that DNA carry out the transformation. Avery, would destroy DNA, but leave proteins is part of the germinal material in which MacLeod, and McCarty continued this untouched. They reasoned that if the these changes occur. But Dr. Alfred process of eliminating components from activity of transforming extracts was de- Mirsky, working with Dr. Hans Ris, found the transforming systems until like the stroyed by such a selectively DNA-~~S~~OY-much to suggest that DNA is actually part Cheshire cat in Through the Looking Glass ing enzyme, they would be justified in of the chromosome material, perhaps even its sole constituent. They showed, for ex- ample, that the amount of DNA in all the different cells in an organism is the same, even though the cells vary enormously in other respects. This was suggestive be- cause all of the cells in a given organism also contain the same number of chromo- somes.