[MUSIC] Today we are going to talk about extremely colorful characters, pioneers and giants in the world of molecular biology. The first of this character is Max Delbrooke. Max Delbrooke was born in Berlin. He was from a Prussian family, mostly civil servants and intellectuals. His mother was the grand daughter of Houston Sleevy, a very famous German chemist. And one of Max's sisters married one of the VonHoeffel brothers, and the VonHoeffel brothers were, one of them was intelligent, I think the other one was an MD, I'm not sure. They were both very active in the late 30s and early 40s in the anti-Nazi movement. Not the Communist movement, but the so-called liberal, or Christian and liberal movement. And the two VonHoeffels were actually shot in 1945, towards the end of the war, by the Nazis. They had been associated in one way or another with the von Stauffenberg attempt to kill Hitler in 44. So Max is a very bright student and he goes to the best place to study physics in 25, 26, and that's Goettingen. Goettingen is where Max Born was teaching quantum mechanics and modern physics. Max Bourne and Niels Bohr were the two big people in this time and to give you an idea about their environment, Born had two assistants. One was Pauli, who later discovered the exclusion principle, and the other one was Heisenberg, who discovered the uncertainty principle, named the principle of Heisenberg. Among the other students were Victor Weisskopf, who was later to become the first director of CERN, Teller, a Hungarian physicist who developed the H bomb, Vena, the informatician, and Oppenheimer. It's a pretty nice collection of people. So in that little group, Max is flourishing and very, very happy. He goes to England for a short Erasmus stay, you would say today, and then he was to take his final exam. And for the final exam at the time, the final exam was oral and you had three professors. One in solid state or statistics, one in theatrical physics, and one in astrophysics. And Max Delbruck was extremely arrogant already as a young man, and he didn't prepare. And he showed to this exam totally unprepared. And he went. The first guy was picked by lottery, and the first guy was the astrophysicist. And he trashed Delbruck. He trashed Delbruck so much that the other two declared him failed. So he failed his final exam. That's probably one of the very rare instance in German university where somebody would fail the final exam. That was quite a shock, and Delbruck had to wait an extra year to pass again the exam. I mean, he said I could come back next week, and the professor said, no, no, no, no, next year. So of course he passes brilliantly because he'd prepared. And he immediately takes off to go to the other giant of the time Niels Bohr in Copenhagen. And in Copenhagen he gets an offer to come back to Berlin and work in the Physics department with a very famous lady, Lise Meitner. Now it's very likely that you have not heard about Lisa Meitner, because Lise Meitner was working with Otto Hahn on fission, and she actually discovered fission experimentally. But because she was Jewish, she was not allowed to be proposed for the Nobel prize in Hangarten. So Delbruck worked with Meitner for a few years and he's honest enough to say that it was good luck that he left nuclear physics in Meitner's lab because he would have probably inhibited her from doing the right experiment to discover fission. Whether that's true or not is debatable of course. But in 1932, Delbruck goes back to Niels Bohr because Bohr had organized a conference on light and life, the complementarity between life and physics. And he felt this was a good time to start such a conference, such an interdisciplinary meeting, you would call it today, because a few years before that, Muller had discovered that x-ray could induce mutations. And so light, x-ray, photons, and biological event. So he's very excited about that, and when he comes back to Berlin he decides to start biophysics. And this is a typical way of Delbruck. Instead of starting on his own in his little corner, he first convinced his mother to organize a weekly seminar at their home. She would feed the 10 or 20 students, and post-docs and young scientists, and they would discuss about science for four, five, six, eight, ten hours. And Delbruck's mother would just feed them, and give them enough to drink. And one of the first person to arrive at this meeting is a guy named Timor, we're going to come back to Timor. And one of the second waves of people who arrived there is a Russian emigre called Timofeyev, and we'll come back to Timofeyev because his history is also quite interesting. And these people together were discussing about how to bring physical experimental design into biology. And Timofeyev was studying mutation in. So basically what he was doing was put embryo or larvae in front of an x-ray lamp for various amount of times, at various distances from the lamp, and score for mutation. That was very crude. And at that time, measuring the energy and the wavelength of x-ray photons was quite difficult. There were very few people who could do that. One of these people was Karl Zimmer. So Delbruck did his first experiment in biology by putting together Zimmer and Timofeyev. So Zimmer measured the X axis, the intensity of X rays, the energy. Timofeyev measured the yield, in mutations, and Delbruck devised a theory, it was sort of a nice combination, and their paper was published in of course in German at the time. In the [FOREIGN] in 1935. [FOREIGN] and at that point Max Delbruck calculated from the efficiency of the x-ray, he calculated a target size and this target size was the size of the gene. That was the first time that somebody would talk about a physical measurement for something so abstract as a gene. For Mendel, for Morgan later, the gene was an abstract notion. They didn't give a damn about it's physical nature. They believed it had some physical nature, but that was not their problem. They were interested in how genes do what they're doing, how they can change, but they had no idea what a gene was. What Delbruck was saying is that the gene is something which has about x angstrom in diameter. That was a very, very innovative kind of reason. Now, Later on, basically a year later, Max Delbruck and Timofeev published a second table, this time in Nature, famous journal, Cosmic Rays and the Origin of Species. And in that very short note, they calculated the intensity of cosmic rays and integrated that intensity through x million years of evolution and say the cosmic ray cannot account for evolution. There's not enough mutation, mutagen power in the cosmic rays to account for evolution. There has to be something else. They didn't know what, but there has to be something else. Now, that paper was well read and well cited. The first paper was called the [FOREIGN] or the Three Men Paper and Max considered that the Three Men Paper got a funeral first class. He was published in this obscure journal which is read by absolutely nobody except when you send them a reprint. And, They considered it was enough to have the reprint system to send it around and they didn't have to publish it in a highly publicized journal. So they just had the reprints. Turns out that the reprint system was quite successful in this case, because two of the reprints ended up in good hands. One of the reprints was sent to another famous physicist, Erwin Schrodinger, from the wave equation and Schrodinger in the 40s was in Ireland. He was exiled from Austria and the Germany-occupied Austria and he was teaching, he had a lot of time to reflect and he basically got interested in biology. And he wrote a book, What is Life, that was extraordinarily instrumental in bringing physicists to study biology and in that book there's a chapter called the Delbruck Model. So that made certainly an impact on Schrodinger. The other person who got a reprint was an Italian physicist named Rossetti and Rossetti gave his reprints to a young fellow who had started working in the lab and this young fellow, we'll find later was Salvador Luria. So Luria heard about Delbruck already in 1935. They would not meet until 1941, but he heard about Delbruck. So 1933 was a very bad year for Europe and the world because that's the year when the Nazis took power. It was a good year for science because a very, very bright mathematician called Weaver became the Director of the Natural Science Division of the Rockefeller Foundation. And Weaver was very instrumental in helping a huge number of scientists to work abroad or to come to the States through the gift of fellowships. And Weaver should be also remembered because he's the guy who coined the word molecular biology. Molecular biology was an invention of Weaver in 1938, at the time where molecular biology did not exist. It was kind of a vision for the future. So when you hear about new terms in science like nanosurgery or neuroeconomics, some of them are probably fake, but some of them may just be visionary names. So Delbruck wanted to leave Germany. He was a strong opponent to Nazis because he considered Nazi to be stupid brutes. He was not political, but he was very much against the sheer violence that was in the streets in Germany at the time and he wanted to go away. And he was offered a fellowship at the Rockefeller Foundation and he choose to go to Caltech in 1937. So that's the first man. Now, the second man we're going to speak about a little bit, even though he's not an author of the paper we'll discuss later, is an important guy, is an interesting guy and that's Timofeev. Timofeev was born in 1900 in Russia, and he studied in Moscow. And then there was a revolution, and Timofeev belonged to a political group that is probably ignored today, but was quite prominent at the time, they were certainly more numerous than the Bolsheviks, they were the Anarchists. And the Anarchists were part of a political movement and an army against the pro-tzar Whites. So he fought in the Civil War and after that, he got back to Moscow and started to work in the lab, which he started right before the revolution started. He was a very bright and young student. He started university at 16. And so he worked under and he worked under in genetics for awhile, and then he was offered the possibility to go to Berlin, 1925. Now, 1925 was a time when Germany was very unaccepted, unliked by all the Allies. And so, it was very difficult for scientists in Germany to go to England or to France, and there was a lot of resistance. Relationship with Russia were much easier. They didn't have the same government, but they were both losers in the war. So they want a lot of relationship, economical, military, and scientific. And so 1925 this young guy and his wife go to Berlin to the Kaiser Wilhelm Institute for Brain Research. What does [INAUDIBLE] genetics have to do with brain research, you may ask? Well that is just a big institute and they had a, they were very generous in their thinking and they accept a lot of different scientists doing a lot of different things. So it's there, he is in a little town outside Berlin. And he gets support from the Rockefeller foundation and he meets Delbrook, and they worked together for the [INAUDIBLE] allied. And they become very close. He also meets with another Russian immigrated to France [INAUDIBLE] and basically, Timofeyev stays in the lab even after 1933. It may sound bizarre. Timofeyev's boss was purged and sent to Mauthausen, to a concentration camp, for being communist inclined. But Timofeyev was not touched. He was a scientist working the lab. There was some kind of respect for intellectual work. His son, who was a Communist activist, was in prison during the war, sent to Mauthausen, and shot during the war. But Timofeyev escaped with no problem. Now, which is sort of difficult to imagine this day now, Timofeyev worked in Berlin until 1945, throughout the war. And the first time I heard about Timofeyev, and this is something that you don't find on the web or in the history books, is that Timofeyev had this idea that he needed help. So he need young assistant to help him. So he went to the army, because he knew a few people there. And he went to the army and he told them, listen. You have these French, Belgium, British prisoners of war. Soldiers, they are held by the army. They're useless. They can't work. They are prisoner of war. They can't do anything. It's a waste of time, it's a waste of energy. It's a waste of brain. With our brain research. So he convinced these guys that the physicists among the prisoners of war who wanted could join his lab. So Timofeyev ended up working with a crew of about 15 French, there were one or two Belgian, physicists. Who wore their uniform in Berlin, or on the outskirts of Berlin, in an institute. They were not in a camp. They were sleeping some place in the institute. They were fed. It wasn't as cold as in the prison camp. And one of these French guys, actually the French people had asked their physics mentor in France. People like whether it was okay to go and work for the enemy. After all, they were the enemy. And, they got the okay. They were working on flight mutations. Of course, in 1937, the Stalinist regime wanted Timofeyev to go back, but he said he could not leave his equipment in Berlin, and he decides it was too important, so he didn't go back. But he was not considered to be an exiled. He was in kind of a limbo. So of course the Russian arrive in Berlin and imagine the surprise of Russian troops, arriving in a suburb of Berlin and being greeted by a guy in a lab coat speaking Russian. You know, you have to imagine that. So of course the first political officer who meets Timofeyev understands that this guy is doing something that can be interesting because he working on effect of radiation on living things. The second team is not that understanding. And the second team sends Timofeyev straight to Russia, and straight to the gulag. Now history has strange twist. While in the Butyrka Prison in Moscow, in transit for the Gulag, Timofeyev was put, so he was a 45 year old man, really a grown up adult. He was put up in a cell with many other people. These were crowded times for prisons. There were lots of people in little space. So there was something like 40 people in this cell and one of these people turned out to be somebody you probably have heard of, Aleksandr Solzhenitsyn. A young captain arrested for writing criticism of Stalin to his brother. Arrested, sent to the gulag. And in transit, in the same cell, Solzhenitsyn recalls Timofeyev, that Timofeyev when he was brought in the cell he started organizing side seminars for the inmates. So that they could occupy their time and do things useful. And so he's sent to one of the harsh camps. He's lucky he's not shot, and in 47, Frederic Joliot-Curie, the French nobel laureate in chemistry discovered artificial fission, artificial radioactivity, fission. Goes to Moscow, he's a Communist, he's a leader of the French Resistance, he's a hero, blah blah blah. And so he's welcomed to Moscow. And, he's smart enough not to talk to Stalin about Timofeyev. He talks to Berria. Why is that smart? Because Barria was head of the secret police, and Barria was in charge of the atomic bomb project. And [INAUDIBLE] knew that. He tells him, listen you have one guy whose a specialist on the effect of radiation on living things. You can't let him rot. I mean, he can be useful for your project. And Barria thought about it, and he decided, yes, we'll take him from his heavy duty camp and we'll bring him to one of these sweet, first circle camps. Like the first circle of where people are reasonably well treated. They're fed, it's heated, and they work inside. And so for all this time, and then he's freed finally, completely. Now there's a problem, because in order to give him a pension, he has to be a scientist. In order to be a scientist, he has to have a degree. He has to be a PhD. Timofeyev never did his PhD. You know, he didn't have time. He was busy doing interesting things. So he didn't do his PhD. So finally people convince him in 1963, at 63 years of age, to write down his thesis and become a real doctor in science. And he was never rehabilitated in his life. He died in 1981, the same year as Delbruck. Delbruck visited him in Moscow but he could never get him to travel outside the Soviet Union. But the story of this guy, I think is quite amazing, if you think of it. And I heard first about Timofeyev by one of the French physicists who was a friend of my family, and he told us about his stories of the war and how he met his wife, who was a Berliner. And he told us about this crazy Russian. And that was before I had the slightest intention of studying biology. But was a name present, and when I rediscovered it, I was quite impressed. I wish the paper could be read, the paper could be read but I don't think it's been, I haven't found a translation, it's only been published in German. So we have a second guy.