[MUSIC] This result of Griffith was extremely interesting for many, many people and the experiment was repeated in several labs including Avery's lab. But the problem with Griffith's experiment is that the container the vessel in which the experiment was done was a mouse. Which is not exactly an easy biochemical simple system. And Avery was immediately aware that if one wants to go further, one has to get an in vitro system. And the in vitro system basically means you're going to incubate the S3 killed bacteria, with a type two R bacterial together in liquid, and you're going to see if anything happens and if you can recover what would be known later on or will be called later on, transformants. And it worked. 1931, Dawson and Siata, but Dawson mostly managed to get the system to work. And then, in order to go a little bit further, what somebody named Alloway, also in Avery's lab managed to made an extract of killed bacteria, add it to the R bacteria, and obtain S-transforms. So we've been from a mouse to a test tube with a mixture of two bacteria. To an extract from a bacteria and the other bacteria. Once you have an extract you can start thinking about purification. What is causing this event. So then basically nothing happened for several years. Because it was very hard to reproduce the effect. And Avery was working on something else. And so, basically, the lab was not really dropping, but putting aside the work on transformation. And then in, 1940, Avery decided to go again, to start again to work on transformation because he had two new collaborators. Colin Macleod and Maclyn McCarty. Colin Macleod had worked a lot on purification and as bacteriologist. Maclyn McCarty was a very innocent young pediatrician fresh out of med school, fresh out of internship and he wanted to do some research and he had no idea about what he was going to enter and McCarty would become a very, very active member of the scientific community. He would become the editor of one of the photo journals and he was the last survivor of the trio, Avery, McClouden, McCarthy. So, Avery, McClouden, McCarty were trying to purify the system. The substance which is causing, And as you will read the paper and we will discuss this next week. This was a quite difficult task. But at the end they had pretty good evidence that DNA was the transforming principle, at least for streptococcus. Now, that was a big surprise because at that time, very few people would have bet that DNA was a genetic material everybody believed it had to be proteins. Only proteins were complicated enough to be genes. For the geneticist, the geneticist didn't care. The classical genetics was all a very theoretical science. The gene was a practical abstract notion. The chemical basis for the gene was not that interesting for the classical geneticists. So few people believed that DNA would be the gene. One of the reasons was that DNA was believed to be too simple. You have to realize that information theory practically did not exist at the time. What you today are used to, binaries, zero, one, zero, one, zero, one, the thing that make our computer run didn't exist, people had some notion about information theory that were mostly based on books. How did you store information in books, with letters and words and so on and so forth. And that sounded like best applicable to proteins and not to DNA. Genes have to be enzymes. And then there was an experiment by a very good scientist, a virologist named Stanley who claimed that he could get virus production by using a protein-only extract of a virus preparation. What he didn't realize was that he had an RNA contamination in his acid, and what was really the transforming agent was the RNA. That took another ten years to count. So lots of reason not to believe that DNA could be genetic material, and on top of that there has been a theory propose by a guy named Phil LaFeine that DNA's in fact One A, one G, one C, one T linked together and that's it. That's a very boring structure. That's really, it's impossible to imagine that such a structure could be good carrier information. Okay, but there were some evidence in favor at that time, available in favor of DNA as a potential candidate for the genetic material. The first thing was that DNA was present in the chromosomes and in the nucleus. And people knew that the genes were in the nucleus. So that, and there were DNA in the chromosomes, there were also proteins, so you could bet, well, its 50% chance its a protein, 50% chance its a DNA. Okay. So there's another reason why the work of Avery was hard to accept. You have to realize that at that time, bacteria did not have genes. And so the simple notion that you would identify the gene from a living organism that doesn't have genes, just makes it impossible. So for all of these reasons people were not all that confident. And then came one aspect, the notion that Avery had done something very interesting, after all he's the first to have shown that it was DNA in bacteria. That was already a first. But it was limited. His work was limited to a single event, namely capsule. It was not a general observation. General observation when an observation is general, then you can extrapolate. But in this case, it was a single observation. And then, of course the last criticism was there must a protein contaminating his DNA. that criticism was laid by Swedish professor named Hammerstein, who was a very good bio chemist, who knew a lot about DNA, physical chemistry of DNA and he knew how hard it was to purify DNA. So Hammerstein was right in the sense that it's difficult to exclude the presence of a protein. Now, two years later Mechin Lecarty published a paper where he showed that a DNA, a crystal in DNA is pretty fine, could be used to destroy the transforming principle. And so, that was supposed to be the end. No way. Your DNA is contaminated with a protease that is destroying the protein that is the transforming principle. So up until 1950, people knew about Avery's result. But didn't believe that it was of significance. And in 1950 Alfred Mirsky was old colleague of Avery F. Rockefeller was willing to accept that DNA is part of the gene. But there has to be something else. Even 1950. And it took 1952 and 1953 was the structure of DNA proposed by Watson and Crick, to make it acceptable. And now the question which was, will be raised again in the case of Rosen and Franklin is why did Hershey not get, Avery not get a Nobel prize. Well, he was nominated since 1930. Now, 1953, everybody believed DNA was the gene. So why didn't he get a Nobel prize afterwards? Well, the problem that he died in 1955. Avery was an old man when he published his paper. He was 65 years old. And he died. And so the only two years in which he could have gotten a Noble Prize were 1953 and 1954. In 1953 the Prize went to Fritz Lipmann, who was also at Rockefeller, and Krebs from the Krebs Cycle, very important biochemist. And in 1924, it was given to somebody who had made a major contribution for medicine. Namely three three scientists were able to grow a polio virus in culture which was a beginning of making a vaccine against polio virus. Now, remember, we were in the 50's. The figure of Roosevelt, the President that was affected with polio was still very very well known, polio was consider to be a dreadful disease, it was a dreadful disease and so somebody who lay the little step forward to cure polio or vaccine against polio. Polio was very a important Scientist and more important than this obscure microbiologist. And so Avery died without what should have been the record mission that he deserved.
