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Bureaucracy and Italian citizenship


Relationship between a virus and the cell
Renato Dulbecco Scientist
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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...

[Q] 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.

Il mio punto successivo è venuto fuori dal fatto e, di nuovo, cose accidentali... come vedi, le cose accidentali capitano continuamente, hanno un significato enorme... pero' naturalmente, come dice lei, la fortuna aiuta, ma solo quelli che sanno vedere. E difatti questo è l'altro colpo di fortuna. Avevo uno studente che si chiamava Howard Temin, ed era venuto nel laboratorio anche un post-doc, che era un veterinario, che si chiamava Harry Rubin. Harry Rubin lavorava con virus per quello era venuto da me, perché lavorava con virus e voleva usare questi metodi per misurare... e questi virus che lui usava erano speciali, che producevano leucemie nei polli e lui ha studiato perciò un sistema di cellule tali che, se lui immetteva il virus in questo strato di cellule, le cellule che venivano infettate, cominciarano a crescere in modo anormale, facevano quello che chiamano i fuochi, dei punti e perciò questo era il mezzo per misurare l'attività di questi virus. Perciò, mentre negli altri, quelli che usavamo prima, era il fatto che il virus distruggesse la cellula quando si moltiplicava, invece in questo caso il virus invadeva la cellula e la faceva crescere. Faceva tutto l'opposto ma funzionava lo stesso, capisci? E Temin si è messo a lavorare con lui...

[Q] Con Rubin?

Con Rubin... perché gli piaceva questo sistema e poi Temin ha fatto la tesi sopra questo, perché lui... dal suo lavoro, che io sorvegliavo insomma, si vedeva questo, si vedeva che le cellule, una volta che venivano infettate, rimanevano infettate, cambiavano caratteristiche e queste caratteristiche poi rimanevano costanti. Perciò l'idea era che questo virus introduceva qualche cosa che persisteva in maniera da dare queste caratteristiche cambiate, ma costanti, alle cellule.

E mi ricordo che ha fatto sulla sua tesi... la laurea era tutto basato su questo... nel comitato per la tesi c'era Max Delbrück e Max Delbrück non voleva sentirlo quello, perché lui dice, 'Ma non c'è prova, questa è un'idea, ma non c'è prova'. Insomma, queste lunghe discussioni in fin dei conti, lui ha ragione, ma anche aveva torto, perché se c'era l'idea, bisogna perseguirla poi, andare a cercare il metodo per verificarla, ma non abbandonarla semplicemente perché non l'hai ancora verificata. Ma per me questo è stato molto importante, perché, per me, questa idea mi affascinava... quasi certamente questo è vero, perciò questo può essere la chiave del cancro, il cancro come malattia dei geni, però pensavo, come è possibile che questo succeda con un virus come quello, che e' un virus che come geni ci ha i geni fatti di RNA, non di DNA e l'RNA non è un portatore permanente di geni come il DNA. Perciò mi sembrava strano e allora ho pensato perché non prendiamo un virus che abbia le stesse effetti ma che sia, che abbia i geni di DNA. È capitato che, proprio in quel periodo, dei ricercatori di Washington, dell'NIH, avevano scoperto un virus di questo tipo, che avevano chiamato il virus del polioma. Lo chiamavano polioma perché, iniettato nei topi, produceva tumori in vari organi. E questo virus mi sembrava, dalle caratteristiche che aveva, che forse aveva i geni di DNA come tutti i virus, per cui ho chiesto che me ne mandassero un campione. L'abbiamo fatto crescere e abbiamo estratto l'acido nucleico ed era DNA, per cui avevo il gene, il virus che volevo, un virus che produceva tumori, ma che aveva i geni del DNA, per cui non dovevo preoccuparmi di quello che succede nell'RNA. In fondo, quello che succede nell'RNA è stato risolto più tardi da Temin e Baltimore.

Allora, così, abbiamo cominciato a lavorare sopra... sopra questo virus e, prima di tutto, abbiamo sviluppato i mezzi per il saggio, per... per questo virus abbiamo scoperto che ha una caratteristica anomala cioè che, su certe cellule, cresce moltiplicandosi e uccidendo le cellule; su altre cellule, le infetta e non cresce e le cellule diventano trasformate, cioe' cellule cancerose... le chiamiamo le cellule trasformate. Per esempio, nel topo, cresce, si moltiplica e uccide le cellule, nell'hamster forma questa trasformazione. Dunque, perciò lì la cosa era interessante, si vede che c'è qualche cosa che ha a che fare il rapporto tra virus e cellula e perciò questo è diventato l'obiettivo principale del nostro lavoro.

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.

Listeners: Paola De Paoli Marchetti

Paola De Paoli Marchetti is a science journalist who graduated with an honours degree in foreign languages and literature from the University Ca’Foscari, Venice. She has been a science journalist since the 1960s and has been on the staff of the newspaper Il Sole 24 Ore since 1970. She was elected president of UGIS (Italian Association of Science Journalists) in 1984. She has been a Member of the Board of EUSJA (European Union of Science Journalists’ Associations, Strasbourg), and was its president in 1987-1988 and 1998-2000. In May 2000 she was unanimously elected president emeritus. She was a member of the National Council of Italian Journalists (1992-1998). From 2002 to 2004 she was member of the working group for scientific communication of the National Committee for Biotechnology. She has also been a consultant at the Italian Ministry of Research and Technology and editor-in-chief of the publication MRST, policy of science and technology. She has co-authored many publications in the field of scientific information, including Le biotecnologie in Italia, Le piste della ricerca and Luna vent’anni dopo.

Tags: NIH, National Institutes of Health, Max Delbrück, Howard Temin, Harry Rubin

Duration: 5 minutes, 57 seconds

Date story recorded: May 2005

Date story went live: 24 January 2008