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To listen to more of Renato Dulbecco’s stories, go to the playlist: • Renato Dulbecco (Biologist) The Italian biologist Renato Dulbecco (1914-2012) had early success isolating a mutant of the polio virus which was used to create a life-saving vaccine. Later in his career, he initiated the Human Genome Project and was jointly awarded the Nobel Prize in Physiology or Medicine in 1975 for furthering our understanding of cancer caused by viruses. [Listener: Paola De Paoli Marchetti; date recorded: 2005] TRANSCRIPT: My next point emerged from the fact and, again, accidental facts... as you'll see, accidental things continuously change, have an enormous significance... then naturally, they say, luck helps, but only those that can see it. And in fact this is the other stroke of luck. I had a student called Howard Temin, and another guy came to the laboratory also on a post-doc, who was a vet, called Harry Rubin. Harry Rubin worked with viruses which is why he came to me, because he was working with viruses and wanted to use these methods to measure... and these viruses that he was using were special, they were producing leukaemia in chickens and he studied this because such a system of cells that, if he introduced the virus in this layer of cells, the cells that became infected started to grow abnormally producing points and thus this was the means to measure the activity of these viruses. Therefore, while in the others, those that we were using before, it was the fact that the virus destroyed the cell when it multiplied, however in this case the virus was invading the cell and making it grow. It was doing the complete opposite but functioning the same, you see. And Temin started working with him... [PDPM] With Rubin? With Rubin, because he liked this system and then Temin wrote a thesis on this, because he... from his work, that I was supervising, you could see this, you could see that the cells, once they had become infected, stayed infected, changed characteristics and these characteristics then remained constant. Thus the idea was that this virus was introducing something that persisted in such a way as to give these changed, yet constant characteristics to the cells. And I remember that he wrote about this in his thesis... the degree was all based on this... Max Delbrück was on the thesis committee and he did not want to hear this, because he said, 'But there's no evidence, this is an idea, there's no evidence'. In short, these long discussions... at the end of the day, he was right, but he was also wrong, because if there is an idea, all you then need to do is pursue it, go and look for the method to verify it, but don't abandon it simply because it hasn't been verified. But this was very important for me, because this idea fascinated me... almost certainly this is true, so this could be the key to cancer, cancer as a gene disease, so I was thinking, how is it possible for this to happen with a virus like this, that as a virus it has genes made of RNA, not DNA and RNA is not a permanent carrier of genes like DNA. Therefore it seemed strange to me and then I thought why don't we take a virus that has the same effects but which is, which has DNA genes. During this period, it happened that researchers from Washington, from the NIH, had discovered a virus of this type, which they called the polyoma virus. They called it polyoma because it produced tumours in various organs when injected into mice. And it seemed to me that this virus, from the characteristics that it had, that perhaps it had DNA genes as do all viruses, so that I asked them to send me a sample. We grew it and extracted the nucleic acid and it was DNA, so I had the gene, the virus that I wanted, a virus that produced tumours, but which had DNA genes, so that I didn't need to worry about what happened in the RNA. What happened in the RNA was later resolved by Temin and Baltimore. So we started to work on this virus and, first of all, we developed the means for the test, for... for this virus we discovered that had an anomalous characteristic that is that on certain cells, it grows and multiplies killing the cells; on other cells, it infects them and does not grow and the cells become transformed, the cancerous cells... we called them transformed cells. For example, in the mouse, it grew, multiplied and killed the cells, in the hamster this transformation was formed. Therefore, this was interesting, it could be seen that this had something to do with the relationship between virus and cell and therefore this became the main objective of our work.