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Tackling polio

RELATED STORIES

Animal virology
Renato Dulbecco Scientist
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Dunque il Caltech, arrivo lì, penso di continuare a lavorare coi fagi, che avevo già appunto preso esperienza, conoscevo già abbastanza bene e così ho fatto un po' di lavoro, però non è stato un lavoro molto interessante. Ero un po' giù per questa ragione e Max si vede se ne è accorto, Max Delbrück, ed ha approfittato di un'occasione, che è capitata lì accidentalmente, per cercare di sollevarmi e l'occasione era questa che... Naturalmente Caltech aveva un presidente e aveva un consiglio di amministrazione dove c'erano molte personalità anche locali, e una di queste persone soffriva di herpes e perciò aveva dei momenti in cui si riacutizzava, dolori, ecc, insomma così. E parlando con il presidente, gli dice, 'Ma voi lavorate coi virus, perché non cercate di lavorare con questo virus?' E il presidente dice, 'Ma guardi, quelli che lavoriamo qui, non sono virus degli uomini, sono fagi, virus di batteri'. E lui dice, 'Ma perché non cercare di organizzare, di cominciare a lavorare anche con questi virus umani?' E lui ha messo a disposizione una somma che allora era molto forte, credo fosse qualcosa come 100 mila dollari, e a quell'epoca, sai, erano molti. Evidentemente, il presidente ha dato a Max l'incarico di vedere quello che si poteva fare, perché lui era quello che lavorava lì, e allora Max, mi ricordo un giorno, chiama me e un altro mio collega, Benzer, che supergiù probabilmente un po' più giovane di me. Ma lui, Benzer, era un fisico ed era un biologo molto bravo, e spiegando questa situazione dicendo, 'C'è qualcuno di voi che si vuole mettere in questo campo?' Benzer dice, 'Ah no', dice, 'Io sono un fisico'. Io, invece dico, 'Io sono un medico di partenza, per cui questo mi interessa molto' e così dico, 'Sì, io lo faccio'. E allora mi dicono, 'Bene, come facciamo, come vuole organizzare questo?' E io ci penso e poi dico, 'Io bisogna che veda quello che si sta facendo in questo campo, perciò io devo andare in giro nei laboratori che si conoscono, così, per vedere quello che fanno, per vedere se si può tirare fuori qualche idea interessante da quello'. Allora dice, 'Sì, benissimo' e mi danno il tempo che ci vuole.

E così mi metto in viaggio e sono stato in viaggio per circa tre mesi effettivamente, andando da un'università all'altra, da un ospedale all'altro, parlando coi virologi, coi professori, insomma con tutti quanti. E da questo è venuta fuori questa idea che, per fare progresso nel campo dei virus, umani o animali insomma, questi virus diversi dai fagi, ci voleva un sistema di poter misurare precisamente il numero dei virus attivi, come si faceva coi fagi dei virus attivi, come si faceva coi fagi. Ma questo non c'era questo metodo, perché i metodi usati erano metodi molto primitivi, che davano un'idea generale della quantità, ma non davano nessun indirizzo speciale, nessun numero speciale.

E allora ritorno al Caltech e spiego questa mia idea, scrivo la mia proposta e' questa di... e allora mi hanno approvato e mi metto a lavorare. Così mi sviluppo, metto un laboratorio in ordine per... appunto per questo scopo, tutto basato su colture di tessuti, che io avevo imparato da Levi, perciò questa era una cosa che mi è tornata molto utile, capisci? Specialmente a quell'epoca, perché, a quell'epoca, di colture dei tessuti se ne sapeva pochissimo. Così mi organizzo e parlando a parecchi degli altri ricercatori, avevo visto che c'erano dei metodi per cercare delle colture un po' come quelle dei batteri... erano molto complicate, perché bisognava prendere pezzi di tessuto, pezzi di embrione, per esempio, di topo e metterli in una specie di provetta... al fondo la provetta aveva una rete, non era del tutto vetro, era una rete, per cui c'erano dei buchi...

[Q] Perché, a cosa serviva la rete?

Appunto, per centrifugare, spingere che... tutti questi pezzetti si rompessero producendo o singole cellule o piccoli numeri di cellule. Poi quello si metteva sulla piastra di vetro per cercare di determinare...

[Q] E tu lavoravi su embrioni di topo allora, prendevi embrioni di topo?

Sì, al principio erano proprio embrioni di topo. Il virus che ho usato è il virus dell'encefalomielite acuta dei cavalli, equina, perché ho dovuto scegliere un virus che uccidesse le cellule in maniera definitiva, perché volevo sviluppare delle placche come quelle dei fagi, capisci? Insomma, alla fine, tanti tentativi, le cose in principio non andavano bene, poi pian pianino sono migliorate e un bel giorno faccio lì, vado a vedere una di queste piastre, la guardo sotto una luce diversa e vedo tutte le placche. Allora mi ricordo che vado da Delbrück e gli dico, 'Vieni qui, Max', lo porto giù e lui dice, 'Ah, qualcosa funziona. Gli faccio... Guarda questa qui, guarda questa qui'. E lui mi dice, 'Che giorno è?' Non lo so, me lo son dimenticato.

[Q] Ah, che peccato!

So, well then Caltech, I arrived there, I continued working with the phage, as I'd already had experience of this and knew it fairly well, so I did a bit of work, but it wasn't very interesting work. I was a little down on account of this and Max noticed, Max Delbrück, and he took advantage of an occasion, which happened accidentally, to try and lift my spirits and the occasion was that... Naturally, Caltech had a president and a board of directors where there were many people including locals, and one of these people suffered with herpes and there were times when it became acute again, pain, etc. And speaking with the president, he said, 'So, you're working on viruses, why not try to work with this virus?' And the president said, 'Look, what we are working on here are not human viruses, they are phages, bacteria viruses'. And he said, 'But why not try to organise, to start working with these human viruses too?' And he gave us a grant of something like $100,000, which was a lot of money at that time, you know, it was a lot. Obviously, the president gave Max the task of seeing what he could do, because he was the one involved with viruses, and then Max, I remember one day, he called me and another of my colleagues, Benzer, who was probably a little younger than me. But he, Benzer, was a physicist and an excellent biologist and explaining this situation saying, 'Do either of you want to get involved in this field?' Benzer said, 'Oh no, I'm a physicist'. I, on the other hand, said, 'I began as a doctor so this interests me a lot' and so I said, 'Yes, I'll do it'. And then they said to me, 'Good, how shall we do this, how do you want to organise this?' And I thought about it and then said, 'I need to see what is being done in this field, so I should go and visit the various laboratories where they work with these viruses, in order to see what people are doing now, to see if any interesting ideas can be taken from this'. So he said, 'Yes, great', and gave me the time that I needed.

So I started to travel and I travelled around for about three months altogether, going from one university to another, from one hospital to another, speaking with virologists, with professors, in fact with everyone. And from this the idea emerged that in order to progress in the field of viruses, human or animal whatever, these different viruses from phages, a good system for accurately measuring the number of active viruses was needed, how to acquire active viruses with phages. But this... there was no method, because the methods used were very primitive ones, which gave a general idea of the quantity, but did not give any special indication, any particular number.

And then I returned to Caltech and I explained my idea to them, I wrote my proposal and then it was approved and I started to work. So, I developed, I arranged a laboratory for... precisely for this reason, all based on tissue cultures, which I learned from Levi, therefore this was something that turned out to be very useful for me, you see. Particularly at this time, because, at this time, very little was known about tissue cultures. So I organised myself and speaking to several other researchers, I saw that there were methods for looking for cultures a little like those of the bacteria. They were very complex, because they needed to take pieces of tissue, pieces of mouse embryos, for example, and to put them in a type of test tube... at the bottom of which there was a fine net, not all glass, a net, so that there were holes.

[Q] Why, what was the purpose of the net?

For centrifuging, pushing... all these little pieces would break producing either individual cells or small numbers of cells. Then this was placed on the glass plate to try to determine...

[Q] And you worked on mouse embryos then, did you take embryos from mice?

Yes, at the start mouse embryos. The virus that I used was the acute equine encephalitis virus, because I had to choose a virus that killed the cells definitively, because I wanted to develop plaques like those of the phages, you see. In fact, in the end, after many attempts, things in principle were not going well, then gradually things improved and one fine day I was there, going to look at one of these plates, I looked underneath a different light and I saw all the plaques. Then I remember that I went to Delbrück and said to him, 'Come here, Max'. I took him down and said to him, 'Something is working. Look at this here, look at this here'. And he said to me, 'What day is it?' But I don't remember.

[Q] What a shame!

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: Caltech, Max Delbrück

Duration: 6 minutes, 39 seconds

Date story recorded: May 2005

Date story went live: 24 January 2008