100 101 And then what happened? I vividly remember when developmentalists, studying Drosophila, found these interesting fruit flies genes which caused remarkable developmental anomalies, once genes were mutated. And when those genes were molecularly identified, a few young molecular geneticists interested in development said: «Let’s take these fruit flies genes at the DNA level, and see if we can find similar pieces of DNA in other animals». That seemed a very dubious prospect, but they quickly came up with these: «Wow, these genes, we can find similar pieces of DNA in mammals!». And so when our lab, and Rosbash’s lab, and Mike Young’s lab identified this first so called clock-genes, then very quickly several labs - once more including Rosbash’s and Young’s - thought «Let’s do the same thing that developmentalists did a little bit before, let’s see if we can find similar DNA to the fruit fly clock-gene in a mammal». That’s when your enterprise began to be more significant, or there have been other key moments? The two possible breakthroughs, with regard to the fruit flies alone, were the first back in ’84 when our lab, two labs in the Boston area and Young’s lab almost simultaneously identified the fruit fly clock-gene at a molecular level. The second breakthrough was in the late 1980s, when we found in our labs in Boston, Massachusetts, that the activity of this key clock-gene - the first stage product and the second stage product - went up and down in concentration every day, and so the next day and the next. In other words: when you mutate the gene, you dramatically change biological rhythms, but also the normal form of the gene makes its products according to its daily rhythm. And our idea was: this can’t be a coincidence. The normal gene form is defining a daily molecular rhythm. But, for example, if we think to other living species in the universe, then do they have a similar circadian gene? If there’s life on planets elsewhere in the universe it will depend on the planet day cycle duration, but almost certainly their inhabitants have evolved their rhythm-regulation biological clocks according to that. Just like circadian rhythms showed by us... Yes. But you have to notice the adjective means ‘circa diem’, that is ‘approximately a day’, in Latin. That is a built-in cycle duration, manifest by organisms including fruit flies, humans and everything else in constant environmental conditions, in lab experiments. Our cycle duration when we are in those conditions [meaning in no regular light-dark cycles], is 24 hours and 15 minutes, ok? So our cycle duration is circa diem, is approximately a day, it’s not exactly one day. And how does this affect our lives? The inescapable conclusion is that we must reset our clock 15 minutes every day. And we do. If we didn’t, for instance, we would wake up 15 minutes later every day, and pretty soon we’ll be waking up in the middle of the afternoon. About it, it’s quite famous the jet-lag disorder. What happens with it? ‘Jet-lag’ term means: if I go from East Coast, US, to where you live, that’s what? A six hours difference? Dawn is six or seven hours earlier, so if I want to flight from New York to Rome, then I would arrive after a rapid plane flight at six/seven hours or so in the morning, like dawn or after dawn - local situation - while I would be around two or three in the morning, body time. I am not saying that you should understand or care; is that when you quickly arrive at a new location, flying East or West, you should have to reset your clock in the new environment, in this case in Italy, about one hour per day. You can’t reset your clock six hours on the first day. There’s way too much lag. Professor Hall, I guess you travelled a lot in the world too. Have you ever been in Italy? Yes, I have, in 1960s, with a couple of friends. We went to Genoa, Pisa, Rome, then Siena, Florence, Venice and Garda’s Lake. I was enchanted, I was fascinated. It was very different from America. One thing I’ll never forget: when we were in Rome we walked all over, but one thing I wanted to see was a Caravaggio painting, The calling of Saint Matthew, which has always been in San Luigi dei Francesi, a small church in Rome. We went there several times and it was always closed, because of siesta or something. So we kept going back and forth but finally got that when it was open, and I saw this great painting for real. It was worth the effort. Now travelling is very difficult for me, not only because of my age, but also because of position from rural Maine to everywhere. The nearest airport is barely functional. It’s a nightmare. Did you enjoy at least your travel to Sweden, for the Nobel ceremony? I sort of enjoyed being in Sweden, where I had been before. Stockholm is a wonderful city, and the host, my handler, soon realized I was not very professorial. So we spent a whole day to Abba Museum. He took me there because he discerned that I’ve always enjoyed pop music. He said: «Do you like Abba?». I said: «Well, I don’t know. I have liked some of their songs». Then he: «There’s a museum here, do you want to go there?». And me: «For sure, I’d rather go there than to another reception. Let’s go there». So my host said: «Are you really willing to do that?». I answered: «I WANNA do it». I assume you didn’t like receptions that much… Nine or ten days of ceremonies and gatherings and formalities. I hated them, because all of these people came up to me to say: «Congratulations», and I said: «Thank you», and then, instead of just walking away, they started to describe to me the reasons why we won the prize. And every time they did that, I was realizing: «You don’t know what you’re talking about, actually. We didn’t do what you just said we did! Maybe we should have…». Why not just say «Nice to meet you, little winner. Congratulations», and leave it at that. Like Tuco. Tuco, Professor? Tuco in The Good, the bad and the ugly, when a person came in and he was in a bath tub. This slovenly cowboy was yelling out at Tuco like «I’m gonna kill you! You hurt me badly before, and now I’m gonna kill you», when Tuco pulled out a gun from underneath the water and shot him, saying right after: «When you have to shoot, shoot. Don’t talk». Gotcha. But let’s go back to rhythms. People could assume from your research about circadian rhythm you wake up at seven and go to bed at eleven, is it true? How old are you now, 30-something? I’m 37. When you’ll be 67 or 77 you’ll be about what I am now, and what happens as mammal age is that our inherent built-in cycle duration becomes shorter. This is a natural feature of aging. Nobody understands why, or how. It’s just a known phenomenon, although it is not universal. So, as I’m aging, I realize I get sleepy at nine o’ clock at night. And I don’t like it. When I was younger, I used to get sleepy at midnight ‘coz I wanted to stay up and do things, maybe just watch movies, who knows… Anything. Now I get tired and go to bed at nine, and automatically - with no alarm clock - I get up at three or four in the morning. And I don’t either like that. My clock wakes me up much earlier than it used to. O di Ólos O for Ólos
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