Oswald Avery and His Coworkers (Avery, Et Al
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1984 marks the fortieth anniversary of the publica- tion of the classic work of Oswald Avery and his coworkers (Avery, et al. 1944) proving that DNA is the hereditary molecule. Few biological discoveries rival that of Avery's. He paved the way for the many molecular biologists who followed. Indeed, 1944 is often cited as the beginning of molecular Oswald Avery biology. Having been briefed on the experiments a year before their publication, Sir MacFarlane Burnet and DNA wrote home to his wife that Avery "has just made an extremely exciting discovery which, put rather crudely, is nothing less than the isolation of a pure Charles L. Vigue gene in the form of desoxyribonucleic acid" (Olby 1974). Recalling Avery's discovery, Ernst Mayr said "the impact of Avery's finding was electrifying. I Downloaded from http://online.ucpress.edu/abt/article-pdf/46/4/207/41261/4447817.pdf by guest on 23 September 2021 can confirm this on the basis of my own personal experience . My friends and I were all convinced that it was now conclusively demonstrated that DNA was the genetic material" (Mayr 1982). Scientific dogma is established in many ways. Dis- coveries such as that of the planet Uranus are quickly accepted because the evidence for them is so compel- ling. Some scientific pronouncements are immedi- ately accepted but later found to be erroneous. For example, it was widely accepted in the 1930s, 1940s, and early 1950s that humans had 48 chromosomes; in 1956 it was proven that we have only 46. Some find- ings are not accepted even though, in retrospect, the evidence was compelling. Such is the case with Avery's discovery. Although Avery convinced many, including Burnet, Mayr, and his friends, he did not convince the majority of scientists. Even fif- teen years after the discovery, some were still unwill- ing to accept DNA as the universal hereditary mole- cule. Avery was interested in the phenomenon of bac- terial transformation first described by Frederick Griffith in the 1920s. Griffith succeeded in transform- ing a nonvirulent, non-encapsulated, Type II variant of Streptococcus pneumoniae (formally Pneumococcus) into a virulent form with a Type III capsule. Since the capsule protects the bacterium from the pha- gocytic cells of the host's immune system, it cannot be easily destroyed. Thus, the encapsulated bacteria are virulent. Griffith found that if he injected the non-virulent Type II form into mice along with a large number of heat-killed, Type III, virulent bac- teria, the mice frequently succumbed to pneumonia. Upon autopsy the mice's blood revealed the pres- Charles L. Vigue is associate professor of biology at the University ence of living, encapsulated Type III bacteria. Thus, of New Haven, West Haven, CT 06516. He is also coordinator of the non-virulent, non-encapsulated form had been the Program in Environmental Science and chairman of the fac- ulty. He holds a B.A. and an M.S. in zoology from the University transformed into the Type III capsulated and there- of Maine and a Ph.D. in genetics from North Carolina State Uni- fore virulent form of Streptococcus. versity. He has published several articles on the functional and Avery and his coworkers, Colin MacLeod and evolutional significance of isoenzymes (in BiochemicalGenetics and GeneticalResearch) and articles in ABT, The Biologist, and The Jour- Maclyn McCarty, were interested in isolating the nal of College Science Teaching. transforming factor and characterizing it chemically. OSWALD AVERY 207 To this end, they partially purified the transforming claimed a role for protein (Olby 1974) are cases in principle from heat-killed Type III bacteria. DNA point. The large majority of the scientific commu- tests on the partially purified factor were positive. nity, however, was blind to Avery's discovery. RNA tests were only weakly positive. More impor- Severalreasons may be cited for this blindness. tantly, however, protein tests were negative. Avery, Humanity, and scientists are no exception, resists et al. (1944)concluded that "if the results of the pres- change. Scientists often resist new discoveries if they ent study on the chemical nature of the transform- do not conform to their preconceived notions. New ing principle are confirmed, then nucleic acids must ideas resulting from scientific discoveries that break be regardedas possessing biological specificity...." existing paradigms are difficult to establish. Pollock Thomas Kuhn said that "until the scientist has (1970)said that great discoveries are often "hated" learned to see nature in a new way-the new fact is because they require an "immense emotional (and not quite a scientific fact at all" (Brannigan1981). If therefore intellectual) effort of abandoning precon- Avery's work did convince scientists to look at ceived dogmata." Beadle and Stent believe that new Nature in a new way, it is not as obvious as many ideas will be accepted provided they can be fitted have said. Wyatt (1972)was quite accuratewhen he into established dogma without too much difficulty said that the history of the discovery and its subse- (Wyatt 1972). Scientists, often because of a healthy quent acceptance "has been mellowed by skepticism, will not accept new ideas until they can Downloaded from http://online.ucpress.edu/abt/article-pdf/46/4/207/41261/4447817.pdf by guest on 23 September 2021 hindsight." A survey of general genetics textbooks be proved beyond a reasonable doubt by repeated published from 1945to 1950clearly demonstrates that investigationin a variety of systems. Many scientists geneticistswere not particularlytaken by Avery's dis- were reluctantto accept DNA as the hereditarymol- covery. Laurence Snyder (1946) in The Principlesof ecule because its function had not yet been clearly Hereditaryand Sinnott, et al. (1950) in Principlesof described. Geneticsnever mention Avery's work. Snyder, with- Wyatt (1972) has demonstrated that the title of out saying that the hereditary material is protein, Avery's paper ("Studies on the Chemical Nature of says that "all estimates agree that the gene is of sub- the Substance Inducing Transformation of Pneu- microscopic volume, probably within the range of mococcal Types: Induction of Transformation by a size of large protein molecules." He also suggests that DesoxyribonucleicAcid FractionIsolated from Pneu- genes are large complex molecules and that nucleic mococcusType III") contained no key words (gene, acids are such complex molecules. Sinnott, et al. state for example) that would tip off the geneticist as to that "it is interesting that computations of sensitive the genetical implications of the work. Since geneti- values for various genes in Drosophilahave given cists were not trained as chemists, the biochemical dimensions of the order of magnitude of large pro- nature of Avery's work was foreign to most of them. tein molecules. Genes would have sizes within Transformationwas a phenomenon studied in bac- the range of smaller viruses and medium-to-large- teria, an organism not commonly studied by geneti- sized protein molecules." cists and whose status as "living" was questioned. At the 1946 Cold Spring Harbor Symposium on Experimentsdescribing the phenomenon were pub- Heredity and Variation in Microorganisms there lished in medical science journals (The Journal of were 27 papers presented. Only eight, one of which ExperimentalMedicine, for example) not normally was by Avery himself, made reference to the classic read by geneticists. World War II certainlyrestricted work. At the 1951 Cold Spring Harbor Symposium the dissemination and flow of scientific knowledge. on Genes and Mutations only three papers made ref- And, the paper itself did not make clear the work's erence to Avery. The Cold Spring Harbor Sym- genetical implications. Although Avery knew the posium on Viruses held in 1953 saw 42 papers pre- genetical implications, he was "unreasonably cau- sented. Only three mentioned Avery. One cannot tious and too modest in his conclusions" (Pollock escape the conclusions that Avery's work was viewed 1970).In a 1943letter to his brother, however, Avery with some skepticism by the general scientific com- was not as cautious: "Nucleic acids are not merely munity. structurally important but functionally active sub- Certainly,scientists such as RollinHotchkiss, Andre stances in determining biological activities and spe- Boivin, and Harriett Taylor, who were working in cific characteristics of cells . Sounds like a virus- the DNA field, accepted Avery's finding. McCarty's maybe a gene" (Olby 1974). statement that "the accumulatedevidence has estab- What were the preconceived ideas that afflicted lished beyond a reasonable doubt that the active sub- the scientific community with myopia? Although stance responsible for transformation is a specific FrederickMeishner, the discoverer of DNA in 1869, nucleic acid of the desoxyribose type" (Mayr 1982) and many others prior to Avery suggested that DNA and Boivin's assertion that the burden of proof no would be a good candidate for the hereditary mole- longer lay with those who believed that DNA was cule, most scientists rejected the hypothesis after it the hereditary molecule, but with those who was erroneously demonstrated that DNA was a 208 THE AMERICAN BIOLOGY TEACHER, VOLUME 46, NO. 4, APRIL 1984 small, simple, uniform molecule-too small, too sim- a letter from Hershey, who was denied a visa, said ple, and too uniform to be the hereditary molecule. "almost no one in the audience of over four hun- Thus, the role of the hereditary molecule fell to pro- dred microbiologists seemed interested as I read long tein, a large, complex, and variable molecule which sections of Hershey's letter" describing the experi- also is a component of the chromosomes. When the ments (Wyatt 1972). Among the DNA skeptics was experiments of Avery et al. and the many who fol- Hershey himself who said "my own guess is that lowed began to implicate DNA, it was contrary to DNA will not prove to be a unique determiner of established dogma.