[MUSIC] Now we're reaching the discussion part, the end of the paper by Avery, McLeod and McCarty. And it's written in a very, very careful way. I mean, those of you who read today's science will notice that the style of the time was quite different. It was more I would say more literary, more, also more precise and the details were included, that today would maybe find a way to supplement their material. The first thing is that they stated their two findings. There's DNA in bacteria. And remember, bacteria were not considered to be proper organisms. They didn't have a nucleus, and they were supposed to not to have DNA. And the second is that the transforming principle is DNA, a chemically defined substance. And the criticism about the single example is a little bit unfair because they state right away, although the observations are limited to a single example they acquire broader significance from the work of earlier investigators. So, at the end they claim and I think it's quite important that for them, the substance evoking the reaction and the capsular substance produced in response of it are chemically distinct. One is a sugar, and the other one is a nucleic acid. Basically what they say by this is that the. What today we would call an instructive hypothesis. That a piece of something is directing the folding of another piece. Homologous, a mold and then the mold can direct the synthesis of the, or the folding of another piece of something. These are called instructive theories. All these instructive theories disappeared. And they believe it's not an instructive theory because the chemical nature is not the same. They are aware that the mechanism by which the reaction occurs is not clear. And how, they say the substance evoking the reaction. So, the reaction is a presence of a capsule and the substance is the DNA. They don't have yet the notion of transfer of information DNA, RNA [INAUDIBLE]. That will come several years later. Now, there's one hypothesis that had been proposed at some times was that actually what they were doing was mutagenizing the R cells into S cells, and that DNA could have a mutagen. That is not compatible with a fact that they only get type three when they use DNA from a type three strain. And none provided use type one, than when you get type one itself. That the specific change is not compatible with the general mutagenic effect, that would act and should ideally provoke many, many kind of changes. So, they don't believe in that. And the sentence by which they state their ignorance as to the mechanism of gene expression is, there is an inherent property of the nucleic acid, but one must still account on a chemical basis for the biological specificity of its action. Biological specificity means transcription and translation into protein that will make a capsule. You have to realize that for many, many years, people believed that RNA was present in plants and DNA was present in animals, like in kind of thymus DNA. Yeast RNA, yeast was considered to be a plant, it has a cell wall. And so that, there was this today absurd notion that there's an animal nucleic acid and a vegetable nucleic acid. That's not the case. They are aware of the problem of DNA and what they call otolithic ferment. They are clearly aware of it, they struggle against this. And it's amusing to think that what led to this paper is an experiment by Avery, where he did something that is of general interest for anybody who's going to do experimental science. Before they were extracting the cells, they were extracting the cells and killing them by heat. Basically what Avery did, he inverted the two steps, the first two steps of the purification and that worked. So, don't believe that if you have an experimental protocol it's the Bible and you have to follow it letter by letter. Be prepared to be flexible because sometimes it's useful. Their discussion of genes is completely influenced by Jablonski, who was a major figure in both animal and natural genetics. If this transformation is described as a genetic mutation and it is difficult to avoid, so describing it. We are dealing with authentic cases of induction of specific mutations by specific treatment. The specific mutation has been a holy grail for the geneticist. Now, because people can do recombination in embryonic cells, you can actually do site directed mutation. At specific points in mammals and mice, etc., and do in plants. This was a dream for geneticists. Geneticists were plagued until the event of what's now called reverse genetics. Geneticists were plagued by this, the fact that the mutation were induced by mutagenic agents. But you had to go and pick the one particular mutant that you were interested in. The phenomenon of transformation. Now, transformation is a difficult word because transformation is used in many different contexts. Transformation by meaning introduction of a DNA into its bacterial cell is still one of the main use of this work. But there are others. When you take a normal cell and you make it into a cancer cell, you transforms it. That's also a transformation. So, transformation is a useful word that can be used in different contexts. And you have to be aware of that. So at the end, basically, their conclusion is that the evidence presented supports the belief that a nucleic acid of the type, is the fundamental unit of the transforming principle of type three. They don't say is the transforming principle, it is a fundamental unit of the transforming principle. This is overly cautious and that's every style. And basically, the paper was accepted with not a single word change because the editor of the journal, Payton Rouse, the guy who discovered RNA tumor viruses knew that Avery was a very, very careful and precise mind and that he wouldn't say a word that would go beyond what he had said. And this style is a style that is completely gone today. I mean, today if you don't claim that you have made a major contribution to science, you sound that you should go to a mental institution. You have to be flamboyant. The second example of precision and modesty in writing is, or the second best comes from a paper by Hershel and Chez. The paper that is considered by everybody, and was considered at the time, and is considered now by everybody as being the evidence, the ultimate evidence that DNA is a genetic material. That paper, which we won't read in this class but we've had it some years, ends with a sentence that DNA has some function. That's very, very low key. So this is the end of our discussion of Avery's paper on the transforming principle.
