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Levi's lesson, Watson's theft


Work on 'temperature mutants' leads to a discovery
Renato Dulbecco Scientist
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If there are two types, there must also be two types of protein inside the cells, because the proteins are the expression of the gene, and in fact it was already known for some time that are specific virus proteins, that are grouped together under the general name 'T antigen', 'tumoral antigen', you see? And these... then it is seen, that there are several types and we managed to demonstrate precisely that one of these types was produced by transformed genes and we also saw that this protein connected to the cellular DNA, therefore the influence on cellular DNA also came in part from that. Therefore, with all this, the general context became fairly clear. Naturally, there were relatively small points to be resolved and so we made mutants for the transformation. And the mutants were variants that behaved differently under different conditions. The most common that were used then were those called 'temperature mutants', which are mutants that do not function at a particular temperature that is a little higher, but only function at lower temperatures, so that, if the mutant is isolated and the temperature is raised, its activity lessens. So therefore, we saw that with these, the ability of the cells themselves to respond to changes in temperature changed and thus the mutant was a temperature mutant because the protein that was produced was sensitive to temperature, thus the virus clearly acted on the cell with these proteins.

And then things progressed; there was a lot of other work. Thus, this was effectively the most important part, the reason why they gave me the Nobel Prize, because it was this interaction... as you say the modification, the justification of the virus... it was said for having discovered the reciprocal interaction between the virus genes and the genes of the cell. But in short, for me, the most fundamental thing was still to have demonstrated that a gene, or one or two virus genes are capable of transforming the cell, therefore it shifted the problem to what this gene does that transforms and then, naturally, on the basis of this, one can think of normal cancer perhaps happening in the same way, not because there is a virus gene, that normally isn't there, but because a gene itself of the cell changes and in fact after these things are demonstrated.

[Q] It was in fact, let's say, the commencement of trying to understand cancer.

Yes, of course. And thus, all this was very good.

Se ci sono due tipi, ci dovrebbero essere anche due tipi di proteine dentro le cellule, perché le proteine sono l'espressione del gene, e infatti già si sapeva da qualche tempo che ci sono delle proteine specifiche del virus, che vengono chiamate sotto il nome generale 'T anti-gen', 'antigene T', antigene tumorale, capisci? E questi... poi si è visto, che ce n'erano parecchi tipi e noi siamo riusciti a dimostrare appunto che, uno di questi tipi era prodotto dai geni trasformanti e abbiamo visto anche che questa proteina andava a legarsi al DNA cellulare, perciò l'influenza sul DNA cellulare veniva in parte anche da quello, insomma. Perciò, tutto lì, il quadro generale veniva abbastanza chiaro. Naturalmente, c'erano piccoli punti relativamente da solvere e così abbiamo fatto dei mutanti per la trasformazione. E i mutanti sono varianti che si comportano diversi in condizioni diverse. Il più comune che si usava allora erano quelli che venivano chiamati i 'temperature mutants', che sono mutanti che non funzionano a una certa temperatura un po' alta, ma funzionano solo a temperature più basse, per cui, se si... isola il mutante e si alza la temperatura, la sua attività sparisce. Dunque perciò allora, abbiamo visto che con questi, si ottenevano anche, si cambiava anche l'abilità delle cellule stesse a rispondere a cambiamenti di temperatura e per questo il mutante era un mutante di temperatura, perché la proteina che è fatta era sensibile alla temperatura, perciò il virus evidentemente agiva sulla cellula con queste proteine, insomma.

E poi le cose sono andate avanti; c'è stato un mucchio di altro lavoro. Dunque, questa era effettivamente la parte piu´importante, per la ragione per cui mi han dato il Premio Nobel, perché era questa interazione... come dice la modificazione, la giustificazione, del virus... dice per aver scoperto l'interazione reciproca tra i geni del virus e i geni della cellula. Ma insomma... per me, la cosa ancora più fondamentale era di aver dimostrato che un gene, o uno o due geni del virus sono capaci di trasformare la cellula, perciò spostava il problema a che cosa fa questo gene che trasforma e poi, naturalmente, sulla base di quello, si può pensare al cancro normale forse avviene nello stesso modo, non perché c'è un gene del virus, che normalmente non c'è, ma perché un gene stesso della cellula si altera e difatti dopo queste cose son dimostrate...

[Q] È stato proprio, diciamo, l'apertura a cercare di capire per il cancro.

Sì, certo. E perciò tutto questo è stato molto bello.

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: T antigen, tumoral antigen, cancer, virus proteins, genes, cells, mutants, temperature mutants, Nobel Prize

Duration: 3 minutes, 25 seconds

Date story recorded: May 2005

Date story went live: 24 January 2008