[MUSIC] Today we're going to talk about essentially two French scientists and Francois Jacob The problem that they were addressing is a very old problem. It's a problem of fermentation. Essentially, how do you make wine or vinegar out of grape. And in the 19th century, there was a controversy about the process. In this century the two big theories and the two big fighting teams were led one by a German Eustis Leiby who believed that fermentation was a purely chemical process and the other one led by Pasteur who believed that you need living cells for fermentation to occur. And this is in the context of the discussions about a vital force or a special force present in living organism or not present in living organism. Turns out that they were both right. It is a purely chemical process driven by enzymes. Which can be performed or achieved in the absence of cells and that was the work of Buchner. But for the yeast to be able to ferment the yeast has to be alive, if you kill the yeast it will not ferment. So, they were in fact both right. This work on fermentation and use of different carbon sources was also very helpful because it allowed the classification of bacteria. You could say that if a bacteria can ferment or use lactose or fructose or saccharose, you could classify a bacteria. So basically at the end of the 19th century, you had three ways of classifying bacteria. The shape, rods or coccus. And the gram staining, gram positive, gram negative, which is still used today. And the capacity to ferment various sugars. Now, around the beginning of the 20th century, scientists working at the Pasteur Institute, Frederick Jenner showed that, he did an experiment using two carbon sources with yeast. One was glucose and one was galactose. And what he observed was that the cell would use the glucose first and then only the galactose. This effect was called adaptation or accustomation. This effect was observed by many people, many different people, over and over. And this is basically where started his scientific career. Was an extremely brilliant personality. He spoke perfect English, which was unusual in France at the time, because his mother was American. After his studies, he went to Cal Tech to work with Morgan and his team on genetics. And he actually didn't really like working with Rosafala, he thought he was sort of messy. And he spent most of his time at Cal Tech by playing the Cello. He was an extremely good Chellist and by organizing chamber music concerts for the for Cal Tech. And so he was back in France at the beginning of the war, and he was a bit older than Jacob. He was born in 1910, so he was at the beginning of the war he was 30 years old, so he was too old to be drafted into the Army, and he stayed in Paris, and decided to work on bacteria growth, and essentially on using mixture of sugars. Most of the work was done with which is a. But some work was also done on E coli and he discovered, or rediscovered, adaptation. Namely, the fact that the will use one sugar, glucose, the most common sugar, before using less common sugar like galactose or the other one he was using. And so since he didn't really understand how to interpret this observation, he went to see Andre Lwoff who was already well known and was leading a microbial department at the Pasteur. And was working on lysogeny and he explained his results and say adaptation. And he gave in a reprint from a Finnish scientist, that had been published just before the war, and that had because he was well-connected and so he gave him this to read and This helped a lot. Monod, who essentially used a bunch of sugars, that were and still are the sugars most used for genetic and physiological purposes. Namely galactose, arabinose, mannose, maltose, lactose, Sacarose as well. And so, what Monod did, which was a very very cute experiment. What Munroe did, was he looked at the growth. So this is the number of bacteria or the mass of bacteria, versus time. And he used a mixture of two sugars. Like lactose and glucose. You have to use very low concentration of sugars, in order to see the effect. But if you find the proper concentration and you use a mixture which is one to one glucose, lactose, you will see that the cells will grow exponentially reach a plateau and then, start again and reach a final plateau. During this first phase, glucose is utilized almost exclusively, then there is this lack phase, a second base orders, no detectable growth over a little detectable growth. And then you start utilizing lactose until lactose is exhausted. If instead of using a 1 to 1 mixture you use, say 25% glucose 75% lactose, you will have exactly the same phenomenon, But the cur will stop earlier and will reach the plateau. So this was the main contribution of adaptation. Now, adaptation was not a very clear cut phenomenon. And it was not clear whether you actually had mutants that were new and would contribute to the growth, or whether you had a change in the physiology of normal cells.