[MUSIC] Today we're going to talk about recombination in bacteria. The subject of this class could have been moved much, much earlier. Because in a way it follows directly the work of Beadle and Tatum that was the object of the first class. DNA is not yet in the picture. It could have followed the Luria and Delbruck paper on the occurrence of mutations in bacteria. Because it's also linked to that discovery. But, because recombination and conjugation, that's the way it's called today, are immediately important for the subject of next week. Namely the regulation of gene expression and the lac Operon, I've decided to have it now. But you know this history is not completely linear. And so we have to be aware of it, and use it the way we want. The way we can. So today, the first part of the class we'll deal with two characters, Tatum and Lederberg. Tatum, we have met already during the first class. Tatum was a bacteriologist or microbiologist who was interested, for all his life, in bacterial metabolism. Was born in 1909, published his first paper in 1932, on bacterial metabolism. And from 32 to 37, he published a lot of papers on, eight papers on bacterial metabolism, various aspects of bacterial metabolism. And then, in 37, he joined Stanford, where he stayed until 45. And in Stanford, he met Beadle. And their first collaboration was in the biochemical characterization of the pigment of the Drosophila eye. The pigment that was absent or altered in the eye color mutants, like vermilion and cinnabar, and white. That work was very painful, very tedious. Because it involved biochemistry by making extracts and purifying components out of Drosophila paste. Which required a lot of Drosophila embryos. And, In that adventure, they were beaten by a German chemist, who instead of purifying, tested the various chemical he had in his drawer. And found the one that was missing in the vermilion and cinnabar mutants. But Beadle and Tatum had a very good relationship. And it is during the class of Tatum that Beadle attended to, that Beadle had the idea of isolating nutritional mutants. So, all these years, 37 til 45, Tatum worked a lot on Neurospora. But very early on decided to use bacteria because he thought bacteria were easier to handle than molds like Neurospora. Of course bacteria had one disadvantage, bacteria had no sex. So you could not do mating, getting a zygote and meiosis the way you can with Neurospora, always other yeast. But this work on bacteria had a highlight in 1944. When Gray and Tatum found out that they could get nutritional mutant of E coli, the bacterium, with X-ray. And later on with UV mutagenesis. After that, Tatum got a job at Yale. And the paper we're going to read today comes from the Yale period of Tatum. 45, 48, went back to Stanford. And in 57 he moved to Rockefeller University where he stayed until his retirement. At Rockefeller he discovered the function and the role of two drugs that were believed to be very important in understanding how genes are expressed, namely mitomycin C and actinomycin D. He was very interested in what we would call today genetic medicine or molecular genetics and medicine. But throughout these years, his main love was bacterial metabolism. And in fact he died in 1975 and his last paper, published by his students in 1980, was on fructose transport by bacteria. So he stayed all his life faithful to his first love, bacterial metabolism. Now Tatum has two connections with the University of Geneva. Very indirect, granted, but two connections. The first connection is the fact that one young MD who wanted to do research, went to do his PhD with Tatum. And this young MD was given as a project, the synthesis of proteins by nonribosomal means. Which was quite a strange thing to do in the 60s when ribosomes, protein synthesis was the, Event of the time. And so this young student worked on synthesis of cyclic peptides, which are used as antibiotics for some of them. And he got his PhD with that and went on, came back to Geneva, and became professor of microbiology at the medical school. His name is Bernard Mach. That's a first connection. The second connection with Geneva is an indirect one, even more indirect one. Namely, the fact that one of Tatum's students, Ed Reich, became a professor at Rockefeller. And among the people who worked with him, he had Bernard who was later to become director of the university. The current director Jean who did his PhD with Ed Reich and myself was a post doc in that lab. So we have a debt, a moral debt, to Tatum, and to Tatum view of how you make science. The second character is completely different. Tatum was a gentleman. Tatum was relatively shy and one would say reserved, extremely polite and gentle. The second character was a wunderkind and one of the most abrasive scientists of that period. The second character is Josh Lederberg. Josh Lederberg started by getting his [FOREIGN], his baccalaureate, his the end of secondary school at the early age of 15. He studied medicine and got his medical degree at the early age of 19, just after four years. He basically combined every two years of medical school into one year. And since he was a bit slow, he finished in four years instead of three and a half. That was his plan. So that was a very, very, talented young man. And he went on to do a PhD, nominally under Ryan at Columbia, but in fact, with Tatum, at Yale. And his first paper was a paper published in nature at the tender age of 21, which is quite remarkable even, by all criteria. And Lederberg was awarded the Nobel prize together with Beadle and Tatum, when he was 33 years old. He worked on many things. First on recombination and sex in bacteria. Then on another way he discovered with Norton Zinder, another way of exchanging material between bacteria called transduction, which involves viruses. And he realized very early on that these were important discovery in the field of bacterial genetics, in the field of molecular biology. But also in the field of evolution, because it provided a way to exchange genetic material between distant species. And thus, it provided a way to have a much quicker evolutionary process than the one provided only by mutations. And he realized that very early on. In his, he spends several years at Wisconsin, Wisconsin University at Madison. And to give you an idea of how abrasive Lederberg was, he, At one point, Beadle and Tatum had proposed this one gene-one enzyme hypothesis. And at one point they discovered a mutant that required two growth factors, isoleucine and valine. And so Lederberg considered that this discovery was the burial of the one gene-one enzyme hypothesis. And to celebrate this burial, he made a fake picture of a cow with two heads. And he sent that with a, like a cross for, the thing you put on a grave, here lays the one gene-one enzyme hypothesis. And he sent that to Beadle and Tatum. Not very nice. Of course, he didn't realize at the time that isoleucine and valine are made from a common precursor. And it was a common precursor that was not synthesized with this double requirement mutant. After that in 78, he came back to New York, and he was President of Rockefeller University. And he was extremely influential in the science policy of the United States. And he had one interest at that time. And that was life on the planet Mars. Which is a bit far away from his previous work. He was convinced that the condition were such on the planet, on Mars, that life could exist. And he set up experiments designed to identify, The consequence of life on the planet. And some of these experiments have actually been integrated into the projects that led to the little jeep that is traveling around in Mars, on Mars surface. And is aimed to detect a number of things including possible bacteria and possible traces of bacterial life on the planet Mars. So that was quite a career. The third person which we will talk about a bit later is Madame Lederberg, Esther Lederberg. Esther Lederberg had three claim to fame. The first one was that she was capable of handling her husband and his mercurial character for several years. But she's remembered in the field of biology because, Lederberg went to the to do an experiment, Joshua, that could prove that mutants pre-exist their isolation. There can be mutants in the bacterial population that you will not see because they're one in a million or one in ten million. But if you could identify these mutants without ever selecting for them. And so they wanted to transfer colonies from one plate to another plate. And Madame Lederberg went to a store that was selling fabrics. And she's tested a very large number of fabrics until she came upon a particular kind of velvet that was suitable for transferring bacteria or yeast from one plate to another, keeping their position. And that was the basis of their experiments showing that antibiotic resistant mutant pre-exist their selection. That's a practical contribution, but probably her major contribution was the discovery of a phage, the phage lambda that we will see in the second part, in the second article.