The Trieste Next Science Festival

Chris and James take on the Trieste Next science festival, and find out about some of the research going on.
04 October 2022
Presented by Chris Smith


Trieste Marina


This week the Naked Scientists have been in the City of Science - Trieste - to take part in their annual science festival and speak to some of the researchers pushing back the frontiers of knowledge in this beautiful part of northeastern Italy...

In this episode

Piazza Unita d'Italia

01:10 - Welcome to Trieste!

Suzanne Kerbavcic introduces James Tytko to the city of science...

Welcome to Trieste!
Suzanne Kerbavcic, ICGEB

The coastal city of Trieste is about an hour and a half north of Venice; it’s a short drive from the Croatian and Slovenian borders, and it overlooks the Adriatic Sea. It’s dubbed the “City of Science” because the place is dominated by research institutes and facilities including even a synchrotron particle accelerator. And where you’ve got a lot of scientists in one place, just like Cambridge, inevitably you also need a science festival. Eager to see the sights, James Tytko hit the streets…

James - Welcome to Trieste. You're joining me from the Piazza Unita d'Italia, Italy's largest town square here on the seafront of this historic seaport. It 's Thursday evening, we've just arrived and I'm taking a stroll past some majestic Austro-Hungarian architecture. You might just be able to hear some people enjoying their evening, much like me, in the busy bars which spill out onto the cobbles. I mentioned that this is one massive town square, but its vastness is somewhat compromised this weekend, thanks to an assortment of marquees and tents, all of which will be bustling with activity by tomorrow morning. This week, The Naked Scientists have been invited to be a part of Trieste Next, an annual festival dedicated to public engagement in science. We'll be attending and participating in some panels and discussions, and also get the chance to speak with some of the hardworking researchers here in one of Europe's most sciencey cities. But for now, I think I fancy one of those icy fruity drinks. Everyone else seems to be enjoying.

Suzanne - I'm Suzanne Kerbavcic and I'm responsible for communications and outreach at the International Center for Genetic Engineering and Biotechnology. So we're in Trieste where each year we organize a science festival called Trieste Next, which is the festival for scientific research. This is the 11th edition, and it brings together about 30 institutes that are all located within Trieste, working in different fields of science. So it's a fantastic opportunity for public engagement and citizen science.

James - What a setting for it. I mean, I'm looking out now on the Trieste seafront. Beautiful. So tell me a bit more about Trieste Next, it's all about public engagement in science. How's that facilitated?

Suzanne - So essentially, all of the institutes sponsor this festival and their researchers on a voluntary basis call guest speakers from all over the world and organize events that are held free for the public. There's also an international academy, so students from all European universities receive grants to travel to Treiste and attend events and meet with the researchers. So it's very exciting. It's a great opportunity and really promotes what Trieste is all about. There's about one scientist for every 38 citizens in Trieste and yet there are a lot of people who don't know what the institutes do, and they're very curious and always willing to come to these events.

James - Absolutely. We might have picked up some of the clapping going on from in the conference hall right behind me. How many locations across Trieste is this currently going on in?

Suzanne - Okay, so across the way you can see Piazza Unita d'Italia and in there we have the main stage where there are conferences. And in the surrounding area, there are stands that represent every institute. On the way along the seafront from here we are in Molo IV, which is a new conference area all the way through to the Piazza. There are about two other theaters, the Historical Giuseppe Verde Theater.

James - Is that the stunning one? It looks like an ancient place.

Suzanne - That's the one. It's a very historic theater. So all the authorities put the city at the disposal, if you like, of science and for its citizens. So it's an exciting time.

James - Wonderful. And Suzanne, to finish, is there any event in particular you're most looking forward to this weekend, or are they all equally as high on your priority list?

Suzanne - No, seriously. The biggest one for me is the event where we'll have Chris Smith speaking because we have our director, General Lawrence Banks, who's a tumor virologist, our former director general, Mauro Giacca, who's a cardiologist now at King's College, and yourselves here with us. And it's taken a long time to get you here, but we've just really excited about it. It's been sold out, but fully booked in. Looking forward to it, you have no idea.

A stylised blue explosion.

06:09 - Can AI help us understand dark energy better?

Does machine learning hold the key to unravelling the mysteries of dark energy?

Can AI help us understand dark energy better?
Roberto Trotta, SISSA

Explaining the origins and evolution of the Universe has taxed the brightest brains the world has produced, like Cambridge’s Stephen Hawking. But what we’re rapidly realising - and Stephen Hawking himself alluded to  over the course of his career and his writings - is that the human brain may just not be capable of comprehending the multidimensional relationships that drive the cosmos. So scientists are increasingly turning to computers and machine learning to look for the patterns that might steer us along the right path. Roberto Trotta is one of them. He’s at the International School for Advanced Studies (SISSA). They occupy what was once a hospital high in the hills overlooking Trieste, so anyone who works there gets the brain-stimulating bonus of an incredible vista…

Chris - You are in theory a cosmologist, but you probably should have a degree in real estate because if you got this office with a view like that, you should be selling apartments.

Roberto - Well, in fact, they sold this office to me and in fact I was a very happy buyer every time I come in.

Chris - For listeners at home, we are sitting in Roberto's office and I'm staring over a balcony at the most beautiful seascape bay dotted with boats. What are we, a few miles up the hills here from the sea?

Roberto - Yeah, we're just about 300 meters high up on the beginning of the Karst plateau overlooking Trieste and we can see, on one side, the eastern peninsula. On the other side, on a good day, you can almost imagine seeing Venice shimmering in the distance.

Chris - Was this always an institute where big brained physicists probe the origins of the universe, this building?

Roberto - Well it actually used to be a hospital for a patient with tuberculosis. So they needed the air, the fresh air of the Karst plateau, and they needed the terrace, which is a relic of that epoch. So our offices enjoy the view and the fresh air on the terrace as well.

Chris - You're devoted to trying to understand the evolution of the universe. Can you try to capture for us about 13.8 billion years, how it all fits together and where the interesting bits are?

Roberto - So the universe starts in a big bang, a big hot energetic state where the universe starts expanding at that accelerated rate. And then all of this disappears, and light, matter, neutrinos, dark matter, all the stuff the university has made of, emerges.

Chris - What would be the timeline on that?

Roberto - Probably something around 10 to the minus 32 seconds, something like that. Very, very short amount of time. A fraction of a fraction of a second. After that, it's another three minutes before all the atoms actually come into existence in a way that we recognized today, mostly hydrogen and helium. And after that it's 380,000 years of opaqueness. The universe is filled with a plasma, which means it's a very hot radiation and hydrogen bath that is so dense that light itself cannot propagate. So it's literally a moment in the life of the universe where it's like looking through a fog. You can't see anything. But then the magic happens. The universe cools off sufficiently so that electrons get captured by protons. The universe becomes neutral. Now light can propagate and a beautiful map of the early universe emerges and that map we can pick up with our telescopes. So we can look all the way back to this moment in time, 380,000 years after the Big Bang.

Chris - And that was when the first stars that we can see were shining?

Roberto - Not quite. At that moment in time, stars haven't had time to form yet. We need to wait another 500 million years before the first stars and galaxies begin to form. And then gravity starts doing its job. Galaxies form and so on and so forth. And things continue pretty smoothly for about 6 billion years until something else happens.

Chris - How do you know it's that time point? How do you know that things were pretty business as usual until 6 billion years?

Roberto - The most important marker of that point in time is the fact that we can look back at the expansion of the universe. And we see the universe expanding but decelerating, slowing down as it expands. This is what we expect from gravity because gravity tends to bring things together. But 6 billion years ago, something strange happens and the expansion of the universe starts picking up speed again, powered by something mysterious that we're trying to find out.

Chris - And that's dark energy, that's pushing things apart.

Roberto - Dark energy, we don't know exactly what it is, but it's one of the biggest mysteries in physics today. We know or we think we know that 70% of the universe is made of dark energy, yet we don't know what it is.

Chris - Do we have a clue as to why it took 6 billion years before dark energy begins to dominate and starts making things grow faster? Was there just a sort of balancing act going on with gravity, the matter we could identify, and some dark energy, but then it reaches a sort of tipping point where there's enough there to enter almost like a positive feedback loop where the faster it goes, the faster it grows.

Roberto - That's right. The fundamental property of dark energy, if it is indeed the property of empty space itself, is that as the universe expands, we create more empty space and form more dark energy. By contrast, matter of any kind, whether normal matter or dark matter, as the universe expands, gets diluted, there is the same amount of matter, but more volume, more space, therefore the relative importance goes down. So there is a tipping point like you rightly said, where dark energy takes over because there is more space, there is more dark energy. But the deeper question is - why at that point? Why not at an earlier time or a later time in the history universe? That's the deeper question, which we really don't know how to answer yet.

Chris - Are we not in a position though where we are into a realm of science now, where what we're trying to consider, the amount of information we're trying to relate, is so vast that it is beyond the comprehension even of big brained cosmologists?

Roberto - Cosmology has been undergoing a revolution. In the sixties, cosmology was not considered a real science because it was a playground for theorists because there were hardly any observations, constraining any crazy idea. Nowadays we're almost at the opposite end. We have so many observations, so much data, understanding is the bottleneck now and how to go from data to understanding and from understanding to theoretical models and the four deeper insights into the nature of reality and the nature of the universe. That is what we are really banging our head against. The usual tools or the sort of classical tools that we've been using for data analysis and statistics, are not up to the task. And so we are now turning towards artificial intelligence and machine learning and modern tools that will hopefully be able to extract meaning, extract patterns, extract structure from a large amount of data that no astronomer or no cosmologist, no human being can ever hope to be able to analyze, let alone look at. So it's really a question of having the machines understand what's relevant for us and sort of summarize it in a way that we can then interpret in a physically hopefully meaningful way.

Chris - Everyone I talk to about AI and machine learning says to me, 'this is great. It can spot patterns between one piece of information and another'. But when you ask it, 'how did you win that game of Go'? The machine can't tell you. It's not explainable. So is this not a difficulty? Because you'll get answers out, but you won't necessarily get the why?

Roberto - Very much so, and that's one that we as physicists really are struggling with. For us we really want to understand what those structures, what those patterns mean and how the algorithms actually come to the conclusions that they come to. We've been really, really successful as a community in coming up with new ways of doing machine learning and AI that are slightly different from the Googles of this world, who have slightly different problems than us. They want to spot patterns in a mass of data for which there is no theory. We don't know why and how human beings behave, we just want to see what those patterns are. In our case, when we see galaxy distributions in the sky or whatnot, we have a theoretical understanding up to a point where those patterns come from and we can give some of this knowledge to the machine so that the machine can add on top things that we don't know about. So it's really a question of finding a sweet spot where we provide the machine with our human understanding and hopefully the machine can provide something else that we are missing at the moment. And so it's really finding that new equilibrium between machine and human intelligence that might solve the problems. If machine learning will discover a new property of dark energy or new patterns that we cannot explain where they come from, will we be able to trust it? Will we be able to say this is the true theory of the universe, if no human can ever explain where it comes from? That's very unsatisfactory. So we're working on making it more explainable, more understandable.

A large astronomical telescope against a dark starry sky.

15:03 - Can we measure radiation from the big bang?

The Cosmic Microwave Background Radiation from the big bang may allow us to see further back than with light

Can we measure radiation from the big bang?
Nicoletta Krachmalnicoff, SISSA

Also at the International School for Advanced Studies is Nicoletta Krachmalnicoff. She’s part of a team trying to see further back in time than we have ever managed previously. This is into that “opaque” period that Roberto Trotta mentioned in the very young Universe. She’s planning to do it by looking at tiny fluctuations in an entity called the Cosmic Microwave Background Radiation - CMBR. This is also referred to as the afterglow of the Big bang. It’s radiation produced as the Universe was first unfurling. And imprinted into that radiation is a footprint of the structure of the Universe as things were at the time. The key is how to read it…

Nicoletta - So the cosmic microwave background radiation, CMB, is the first light emitted by our universe 380,000 years after the Big Bang. So it's the first radiation that we can see. So wherever you look in the universe, you will be able to observe this radiation. And this radiation can tell us a lot of things about how our universe was created and how it evolved.

Chris - And how does looking at light tell you anything about its history?

Nicoletta - So the point here is that this radiation has tiny fluctuations in the signal. So I told you that you can observe it in whatever direction you look, but it has tiny fluctuations in the signal. The temperature of this radiation is slightly different in every direction of the universe. And these differences are due to fluctuations present in the primordial universe. So hotter points in the universe are where we had under densities in the primordial universe, while colder spots are where there were over densities in the universe. So by studying these little fluctuations, we can learn something about the distribution of the matter in the primordial universe and then understand how these tiny fluctuations that were present in the primordial universe evolved into the structures that we can observe today.

Chris - You're working on a new experiment that's going to go live in about a year's time. What's that going to do and what will it add that we haven't already learned?

Nicoletta - CMB radiation has been observed. We have been able to observe CMB for the past 50 years. So we have studied a lot and we have learned a lot of things, but now we are trying to observe the polarization of the CMB. Part of the CMB has a preferential direction, and we can observe this polarization. And thanks to this polarization, we can understand things about what happened in the very early phase of the evolution of our universe. And with the very early phase, I mean the fraction of seconds after the big bang, what we call inflation. So inflation is a theory that the universe, in the very first instant after the big bang, went through an exponential expansion that allowed the universe to go from microscopic scales to macroscopic scales. And this theory was introduced to explain some of the observations that we have in our universe, which were not explained by the standard Big Bang theory.

Chris - Because we talk about the very early universe as being this sort of dark period. It's opaque. We can't see there because light, as we see it, could not escape. Therefore, it's literally a black box. We don't have an insight into that. But your fluctuations, polarizations, in the microwave radiation give us potentially a window into that world if they're there and you can read them.

Nicoletta - Yeah, exactly. It's not like a direct window. So we cannot observe directly this dark phase of the universe, but we can observe the imprint of this phase into the cosmic background. So if we are able to detect this very tiny signal, then we can say something about inflation.

Chris - What's the experiment you're doing? Where are you doing it? How would it work?

Nicoletta - It's going to be a network of telescopes located in Chile in the Atacama Desert. So it's a ground based experiment for telescopes with two different kind of telescopes. One smaller, like a meter diameter. And the other type of telescope will be much bigger, like six meters diameter. And thanks to the complementary of these two experiments, we hope we will be able to observe for the first time this particular polarized signal of the CMB and to prove that inflation really happened.

Chris - And when will it go live? When will the first light flow into this telescope?

Nicoletta - In the current schedule, it could be in about one year. Then we will have a phase of a few months where we like to do commissioning. So we will try to understand whether our instruments are working well and then we start to do scientific observations and we will collect a lot of data and then we will start to analyze these data. So the first results will probably come in three years from now. Something like that.

Chris - Very exciting to be sitting on what's going to give us one of potentially our earliest looks at our universe.

Nicoletta - Yeah, that's super exciting. I must say that I'm lucky to have joined this collaboration since the beginning and to be able to really now see the telescope going live.

a body in front of a clock on pink background

20:26 - How does the brain measure time?

How do our senses and rhythm affect the way we perceive time?

How does the brain measure time?
Domenica Bueti, SISSA

How do we actually have a notion of time? What makes the brain tick? And why does something exciting seem to take no time at all, yet boring things seem to drag. And why does time seem to go into slow motion when something frightening happens? That’s what SISSA scientist Domenica Bueti works on. Her work suggests that the brain uses how much information we have stored about an event to decide how long something took to happen…

Domenica - Your perception of time depends on the amount of input, of sensory input, that your senses get. So the brighter, for example, a visual image is, the longer you perceive or the faster something moves, the longer is your perception of time.

Chris - So if I was suddenly galvanized into paying attention to something, I would be storing huge amounts of information. My brain would say, Well, there's lots of information corresponding to that event, therefore it must have happened over a long period of time. But equally we know it didn't. So therefore I'm going to assume time slowed down.

Domenica - Yeah, this is it. So it's just that your brain interprets this amount of information as if there are multiple events happening in that time lapse basically. And this is what we hypothesize based on these experiments that we run.

Chris - Tell us about those.

Domenica - Okay. For example, in this case, we ask this healthy individuals to put their hands in a water tank and the water tank could be filled of ice or of water at room temperature. And we measure actually the perceptual capacity. So how good they were in perceiving a simple visual image. And also we asked them to judge for how long this visual image was presented on screen. And what we saw is that their visual acuity was higher, so was much better. So they really were better under the stress. So when the hand was in ice compared to when the hand was in warm water. This was interpreted as okay, the fact that your visual system incorporates more information and this corresponds to your expansion of time, because of course the judgment was that the visual image was displayed for longer than it physically was.

Chris - It's really interesting that it transfers across senses then. So you put in a sensory stimulus, but it affects your perception of a visual one.

Domenica - Yeah, indeed. What we hypothesized was to change the physiological state of the subject. Indeed we measure some physiological illnesses like cortisol reactivity or some neuro-adrenaline

Chris - So these are little stress signals then.

Domenica - Exactly. We were stressing those people. So your physiological, your general, we call it arousal. So your physiological state was aroused compared to having your hands in warm water and this has caused this better visual perception and time expansion.

Chris - How does my brain know what happened last year versus the year before that? How is time coded for memories? How do we attach a timeline or a calendar to memory? Because it's one thing for me to have a concept of how long something took, but to then store when it occurred relative to everything else that's happened in my life, which we all do really well. How on earth do we do that?

Domenica - This has to do with the capacity of putting things in sequence, right? And again has been associated with the neural circuitry that deals with your memory capacity. So this hippocampus structure in the temporal lobes. It looks like that really it depends on the memory, and this memory is not just the memory of the past, it's your capacity of putting yourself into this timeline and imagining yourself in the future. There is a debate whether this is something that exclusively is a capacity that belongs to humans or also other animals have.

Chris - Do we know in the brain where that sort of metronome is? Do we know how the brain generates a clock sequence or a clock signature that gives us our concept of time?

Domenica - We don't know. Actually, this is the easy and quick answer. We don't know yet if there is a single clock or multiple clocks. Actually now based on our experiments, we seem more inclined to believe that there is no single clock, no single metronome in the brain. But actually there are multiple brain areas, multiple circuits that enable you to keep track of time. And most of those circuits are circuits that deal with movement.

Chris - I was just going to say, because I could see you tapping your foot. So am I as you are talking and that motor movement can happen just like a pendulum on a clock, can't it? So it is our brain generating a movement, even in the imaginary, one to then superimpose a sensation of time.

Domenica - I think this has to do with how we learn about time. You can sense it, but you cannot touch it. You cannot see it or smell it. But time is everywhere. And the way you learn time is through change. And the most prominent way we experience change is through motion. Our own movement, body movements or the movement we see and indeed the neural circuits that are related to this capacity of keeping track of time are areas that deal with motion. With visual motion like this area, V5 we call MT or the areas that are responsible for our own movement. Body movements like the premotor areas or motor cortex.


27:36 - The Trieste climate demonstration

What do the public of Trieste think about the current climate policies?

The Trieste climate demonstration
Carlos, Giada, Francesca

With such a high concentration of scientists in the city, and on the weekend of the Italian general election, perhaps we should not have been surprised to see the people of Trieste expressing their views on some of the most pressing issues of the day. Team member James Tytko ended up in a demonstration on his way to the central piazza…

James - I've literally just left my hotel ready for a morning of interviews and to join the science festival. And as you can probably hear, it feels like the festival has come to me. I don't think this is related to the event that we've actually come to witness, but there's quite the commotion here on the streets of Trieste.

Carlos - My name is Carlos.

Giada - Giada.

Francesca - My name is Francesca.

James - What's going on here today? Why is there so many people? Why is there so much noise?

Carlos - Protesting for climate change.

James - So Trieste - City of Science, or so I've heard, that's why I'm here. Is this, would you say this is a good turnout or...?

Carlos - Personally, I expected more people to come.

Giada - Me too. Yeah.

Francesca - I would've expected more, to be honest. In two days time we have the political elections and it would've been a good occasion, a good chance for us to, somehow make our voice heard. Just one or two programs of the political parties somehow mention this problem. And we've had a big problem with flooding in one of our regions, and a lot of people have died. Two weeks ago. We had so much rain, like all of Trieste. It was just so much water, you couldn't even cross the street.

Carlos - There's an international strike to defend the climate. They ask us, the working people, the youth, to make sacrifices because there's not enough energy. We have to build a hub in the south. We have to build nuclear plants and so on while the industry of the energetic sector in Italy is in massive profits and they are asking us to cut our consumption. So the point is not that we don't have the means to overcome these problems. The problem is that this means our energy is privatized basically,

James - I know this is mainly a large contingent of young people doing the march, not so many old people.

Carlos - This is a good point. What we saw in Italy, but I think all over the world, like in England, I think you know very well that the youth is the most active and political active layer of society that wants to change. And they want a change I think, in a revolutionary way.

A pyramidal neurone in the human cerebral cortex

30:28 - Marconi and motor neurones

How much can we treat motor neurone disease, and why is there a giant boat outside the building?

Marconi and motor neurones
Emanuele Buratti, ICGEB

Up in the hills above Trieste is the International Centre for Genetic Engineering and Biotechnology - the ICGEB. They work on a range of topics related to the life sciences, including in the case of Emanuele Buratti, motorneurone disease. So why,  I found myself wondering, is there the front end of a very large iron boat plonked in front of the building…

Chris - We're out in the car park and I couldn't help noticing you have the front end of a boat in the car park. It's huge! What is this doing here? What is this?

Emanuele - Exactly, Chris? So basically it is actually the boat that used to belong to Guglielmo Marconi, as you know, a very famous international scientist in the early 1900s, the one who basically developed the telegraph. He managed to buy this boat, he called it Elektra after his daughter and after the goddess of electricity. And basically this boat during the second World War was taken over by the Germans and it was turned into a gunboat in order to participate to the war effort.

Chris - But that was sometime after Marconi had died by the Second World War, presumably?

Emanuele - Yes. He had already died. He died quite a few years before. So the boat was requisitioned in 1943. When it was turned into a gunboat, the first thing that happened, as soon as it left the harbor for the first time was for a British plane to come along, bombed it and strafed it, and then it sunk in very shallow water <laugh>. And so after they basically managed to recover the boat, they didn't know what to do with it because it was still a famous boat. It had been owned by Guglielmo Marconi for many years. And so they decided to keep it basically in a junkyard in the harbor. And half of it, we never knew what happened. The other half ended up in a museum in Rome and then there was this front end of the boat and nobody knew what to do with it.

Emanuele - And in Trieste, when they decided to develop a synchrotron facility, they said 'Oh, but the synchrotron facility is actually going to be named "Elettra", the same name as the boat. So why don't we take the front end of the boat and we stick it right next to the synchrotron facility. And the scientists there, they all went crazy because they said, We have electrons spinning around at almost light speed right now, in our synchrotron facility, and now you're going to put 2000 tons of iron next to it. This is going to mess up all our experiments. And they had already decided to bring it up the mountain. As you said, they didn't know where to put it and they ended up replacing it here in the area Di Cerca, where everybody's working on molecular biology, neurodegeneration, that has nothing to do with it really.

Chris - I have to say though, I went on holiday to the west of England recently and I found myself in a shed at the seaside in the middle of nowhere, National Trust property. And I thought, what is this shed? And it turns out that was the building that Marconi constructed to do the initial ship-to-shore experiments to test that the concept of transmitting radio signals over water. Probably the ship that it was talking to would've been this one.

Emanuele - Yes. he must have been walking on the deck <laugh> just above us. Absolutely. Because this is from where he basically, he turned this ship into his lab.

Chris - He must have been pretty well off because this would've been a very big vessel. It's a huge great iron hole cut in half and you've got a chunk in your car park. The hole at the front end, there's a massive great dent in the front. When I saw that, I thought someone had been careless positioning it here. Is that the damage that our boys did then?

Emanuele - Exactly. That's the British bomb <laugh>. That sunk it! <laugh>.

Chris - So you ended up the beneficiary of this historical object in a molecular biology institute, doesn't really fit, bit incongruous.

Emanuele - Well, I mean, in a way, if you think about the kind of energy that is transmitted in motor neurons, it's all based on the electrons, right? So maybe there is some <laugh> sense out of this <laugh>

Chris - When it comes to motor neuron disease. What are you doing though?

Emanuele - I'm working on a protein called TDP-43, and that is the main protein that is aggregating in neurons of patients affected by ALS. And what we're doing in the lab is trying to understand why it aggregates and especially the consequences of its aggregation, trying to understand why these neurons are dying when this protein is aggregating.

Chris - Can you just describe when a person has motor neuron disease or ALS, what is happening and how do they know they've got it?

Emanuele - So normally the onset of ALS is very subtle. People realise that they have maybe some problem walking or maybe moving their arms. And what is happening is that your motor neurons are gradually dying. And so you initially start to lose all your voluntary movements, including walking, moving your arms, moving your head. Then eventually the paralysis spreads to the involuntary muscles so that most people eventually die of respiratory failure.

Chris - You talk about aggregations going on in the affected cells. What's building up?

Emanuele - Basically this is a protein that normally shuttles from the nucleus to the cytoplasm. And what it does is actually controlling the fate of many hundreds of mRNAs. So their life cycle, how long they stay in the cell, how they're translated, how they're processed in general.

Chris - These are the messages that are gonna tell the cell what to do?

Emanuele - Exactly. So what happens is that the cell gradually loses this ability to process the messengers. And once this damage becomes big enough, then of course the cell is going to die.

Chris - This stuff builds up inside the cell, robs the cell of its ability to handle these messages properly so it dies. Is the goal then to try and work out why that is happening and reverse it or to use it as an intervention? How are you trying to tackle this?

Emanuele - For a very long time it was thought that the best strategy would've been to prevent this aggregation. But now there is some evidence basically considering this aggregation as initially protective. So the cells has an excess of this protein tries to put it into the aggregate because it doesn't do any harm. But once the aggregates become very big, then of course they become toxic and the cell dies. So now most strategies mostly aim at making the cell work better.

Chris - Are you able to do that? I mean, can you see any avenues through which you might be able to intervene meaningfully to either stop these things growing any bigger or stop them having a toxic effect on the cell?

Emanuele - Some people are trying to find small molecules to stabilise the cell metabolism. In our case, what we're doing in the lab is to look for modifier genes that can allow the cell to cope much better in the presence of these aggregates. And so we're trying to find these genes. Also, there are gene therapy approaches where basically people are trying to get rid of the mutant protein to replace it with a normal gene.

Chris - Of course, one of the problems that very often happens with these sorts of diseases is that by the time you know you've got it, you've lost the vast majority of the cells that you started with and you can't put them back. And so people are saying we'd need to diagnose people early, intervene with preventative treatments early and that should stop it happening. But that means we need to be able to test people and have a meaningful test but we also need to put a whole bunch of people on treatment for many, many years potentially. Which may not be ideal.

Emanuele - Yes, exactly. So the idea is that of identifying biomarkers that will be able to tell when the disease is starting and so start the therapy long before the symptoms can arise.

Chris - Have you got any?

Emanuele - So there are several under study. We will soon hopefully be starting a project on looking at this protein in blood platelets to see if we can actually see some signs of the disease in people who are still asymptomatic.

Chris - And by looking at the blood, it's a proxy marker for what's going on in the spinal cord.

Emanuele - Yes. So basically what happens is that this protein is present in all cells of our body. And so what we think could be going on is that the same kind of insult that are occurring in the brain cells will also be present in the platelets identified there. That is a much easier source of material.

An underwater view of the ocean surface.

39:37 - Working from home with an underwater drone

How oceanographers have been mapping salinity changes from the comfort of their living rooms

Working from home with an underwater drone
Nunzia Pirro, OGS

And now we head out to sea, but not in person, because Nunzia Pirro, from the National Institute of Oceanography and Applied Geophysics, told me how marine scientists like her can now productively “work from home” and still be out on the ocean, by using shark-sized remote control vehicles to explore the depths and report on the effects of climate change. She’s studying how ocean currents, driven by the sinking of denser, heavier water and the elevation of more buoyant, lighter water might be changing…

Nunzia - Denser water is more heavy, so it stays at the bottom and less dense water stays at the surface. In order to move the ocean, this water has to mix so the dense water has to sink and the light water has to rise. So there is a changing of the current and we are trying to understand how this change occurs

Chris - Is it not just as simple as that in summer more ice melts and puts fresh water in the sea and that's less dense? Is that one of the mechanisms?

Nunzia - Yeah. Yeah. I mean this is a bad mechanism because look at the Arctic. If you have the ice melting, you don't have salty water. You have light water. So you have this light water on the top of the layer and then you cannot have the dense water formation. That's one of the mechanisms that stops the dense water formation.

Chris - I see. So if you put lots of light melted, icy water at the top, it stops that overturning, that sort of mixing and that could have consequences for ocean currents then?

Nunzia - Yes. Not only for the ocean current, but for us. For example, if you look at the Arctic, if all ice of the arctic melts, you don't have this mixing, this overturning. You don't have the current forming. And the current is important for the climate, so it means that we will get, for example, a colder Europe, because the current moves the heat through the globe.

Chris - This is the Gulf stream, isn't it? When you get hot water forming in the Gulf of Mexico, that comes traditionally up past the west of the UK and it's bringing enormous amounts of heat along and making Europe much warmer than it should otherwise be. If we melt the Arctic and push that back, because we stop that circulation, we will actually paradoxically get colder through global warming.

Nunzia - Yes, that's correct. So if this occurs, the Gulf Stream will not work anymore. So we will not have this water coming from the Arctic that usually the normal pattern is from the Arctic, it goes through the Gulf stream and goes to the Antarctic. Then from the Antarctic it rises to the equator, so in India for example. And if you don't have this dense water forming, you don't have this circulation. And so as you can see it's very bad for us, for all the globe for the climate.

Chris - Apart from just moving heat around, are those currents also moving nutrients? So are there knock on effects in that respect?

Nunzia - Yeah. Yeah, that's a good question. Of course they move nutrients. Nutrients usually stay at the bottom of the ocean and we don't have this mixing with this dense water formation. Nutrient stays at the bottom and this means that at the surface, we don't have food for the fish. Not having food for the fish means we will not eat fish.

Chris - I was gonna say no food for the fish ultimately ends up meaning no food for us doesn't it? How do you actually study this then? How do you register what these currents and these densities are doing and where they are?

Nunzia - We have several instruments. One of those is the glider. It's an autonomous vehicle, like a fish. It's around one meter long and 50 kilos. It's a small shark.

Chris - And how do you launch it, control it, and then get the data off of it?

Nunzia - Yeah, we actually have technicians that go to the sea and deploy it for a boat. You just throw away this small shark in the sea and then you pilot from your bedroom from here.

Chris - What?

Nunzia - Yeah, from your bedroom, from your house.

Chris - There's a TV advert in the UK where they're trying to push an internet service provider. They show a family landing an airplane in their living room and they say, We landed a plane on this network because it's got really good data rates. And so are you telling me you are basically working from home then? You fly this underwater thing from your bedroom?

Nunzia - Yes, yes, yes. We really pilot from home and tell him where to go up and down, which way to go and when it has to come to the surface. And when they come at the surface through the satellite, they transmit this data.

Chris - I get it. So it surfaces and talks to the satellite and sends you back what it has learned from all the other instruments aboard when it's been down. How deep does it go?

Nunzia - It depends. Usually one kilometer, but now technology is going fast and so they're trying to make these instruments go up to two kilometers. I mean if we consider the ocean goes up to five or six kilometers, there is a lot to discover. So the deeper he goes, the more we know.

Chris - I'm still intrigued by the working from home concept behind this. What, have you got an app on your phone or something or does it work on your desktop? What do you see? How do you control it?

Nunzia - So far, we have a website where you log in and there are several files where you tell this instrument how deep to go, how fast he has to go, and when it has to come up to the surface. And basically every time he goes up to the surface it's really nice because you can change plans.

Chris - How long can it stay at sea for?

Nunzia - Usually four months.

Chris - It's a long time.

Nunzia - It's a long time. Yeah. For one instrument it's a long time, but this is an instrument that costs 250k. It's a lot, but is still cheaper than a ship.

Chris - Well that was gonna be my next point, which is that historically to do this kind of work, someone like you would've had to have been at sea for months on end. And that would've obviously had a huge carbon footprint, a huge economic impact. And it would've been your time. Now you deploy an army of these and you are getting all that data without having to leave your home. Literally.

Nunzia - Yeah, yeah, yeah. That's really nice, because also the ship, as you said, is much more expensive for the environment and for our pocket.

Chris - And what have you learned so far? Because we started this talking about the importance of understanding ocean currents, these changes in density, and so on. Is it beginning to bear fruit?

Nunzia - Actually this dense water formation is not increasing. The question is why? Because the water is getting warm and this is one of the side effects of climate change. Of course you won't see it in one or two years, we'll see the effect in 30 years, so on a climate scale. But so far it's been three, four years that the dense water formation is losing power. If we think about what will be in 10 years, the scenario is not really nice.

Legal paperwork

46:55 - The science behind policy making

How science is used to decide if policies really benefit the public

The science behind policy making
Ludovico Carrino, Univeristy of Trieste

Historically, governments have relied heavily on economic principles to guide policy-making and improve our societies. But are these interventions evidence based, and do they consider all of the knock-on consequences? James Tytko caught up with Ludovico Carrino, professor of Public Economics at the University of Trieste…

Ludovico - So public policies, many times intervene in order to push people to do things or force people to do things that they wouldn't do otherwise because the government thinks that this is good for them. And basically we study what is the impact of this government's interventions beyond what the government wants to do. For example, yesterday at Trieste Next, we discussed a pension reform in the UK that pushed women in the UK to work longer with the increase in the state pension age. The first result of this, the desired outcome of the government, was to increase their employment rate, they work more. But we have studied how this affects the health of these women around the age of 60. Their mental health actually worsens a lot depending on the job that they do. If they do heavy jobs, working more years because of their reform could be very detrimental.

James - What started out as a policy to boost the economy, to boost GDP ends up, in the long run, costing more because of health costs?

Ludovico - I am prudent to say things on the long run in this case because this happened in 2010. So we need to understand what happens. But for some groups in the population, working longer clearly increases the conflicts between family and work time. Working in heavy jobs might be detrimental. So this kind of outcome must be considered by policy makers when they evaluate their policies. There are also good examples, for example, giving the free bus pass in the UK to old people, actually, not just induced them to use the public bus, but also had a causal effect, positive effect on their mental health and cognition. So we try to broaden the traditional perspective of policy evaluation going beyond the direct and anticipated outcome, looking at indirect unanticipated outcomes.

James - I want to go back to something you were saying about building a causal link instead of just a correlational link.

Ludovico - One of the main important areas of research for me right now is long-term care policies. So social care in the UK, but typically our city calls it long-term care. And we are trying to focus on a crucial research question, which is we are spending some money on long-term care. Many people want to cut it, for example, and give more public provided formal care. Many people argue families should do it. Not just the government. So we want to measure somehow whether long-term care, public care, is effective? Do people who receive care feel better somehow? Now, if you just interview a lot of people, like you can do with micro data, you can know their health, their mental health, and also whether they use care or not. If you do this comparison, let's look at whether people who receive care have better or worse health than people who do not receive care. Well, you will always find that people who receive care are worse off than people who do not receive care. Now, this is the correlation, but can you conclude that they are worse off because they receive care? So this is the causal link. Of course, you can't, I hope it's clear they receive care because they are worse off. They are worse off therefore they receive care and you just observe this. So you need more sophisticated econometrics to actually capture, identify as we say, the causal link. By the way, we try to do it. We hope we are doing it right, and we find that receiving care is actually beneficial for health, when you look at the causal element.

James - The role of science in government, in policy making has never been as prominent as it has been over the past two years. I'm wondering, I see this growth in science as a tool that policy makers use. We're now used to scientific press briefings on TV and things like that. Has that helped your field of research gain a bit more prominence?

Ludovico - The last years with the covid pandemic surely made people, and people in government, realize that we need a broader perspective in looking at our choices. Now, think about people that started working from home and then never went back to work because there was something invisible, but very valuable for them in changing their work environment. Yes, I think that's helping us.

James - We've discussed a couple of examples so far. Is there anything else particularly that you thought you mentioned that you're excited about working on or that you're looking into?

Ludovico - Yesterday, for example, we discussed the impact of urban regeneration policies on mental health with an example from Italy. The city of Torino has been through important urban regeneration policies in the 2000's. And this had an effect on the prescription for antidepressants, reducing them. So a positive effect. Then another example, which I think is very important, we now have estimated the causal effect of working conditions on mental health of workers. Working conditions, meaning can you choose the schedule of your work? Do you work during weekends or at nights? How heavy is your job? How much can you apply your skills in your job? And it's very difficult to check with empirical sophisticated econometrics, whether this affects mental health. In a recent research with two Italian colleagues, we looked at the UK and found that women at the early stage of their career, but also at the mature stage of their careers, really react to changes in working conditions much more than men. And this is something I really want to work on because this connects with a lot of dimensions of people in their lives. In your life, you do a lot of things and the nature of your job might affect the other aspects of your life. But not only of your life, also of your parents, your children, your grandchildren. So there are intergenerational effects. When you have a problem, it's not just yours. It's your partner's problem, your parents, your children, grandchildren. And the opposite, when you benefit from something, there are many spillovers, what economists call externalities.

Plastic packaging for some pills.

53:41 - Recreating drug formulas for poorer countries

How one laboratory is working out drug compositions, to allow poorer countries to make them cheaper

Recreating drug formulas for poorer countries
Natasa Skoka, ICGEB

When drug companies make medicines, they initially protect them with a 20 year patent. Once that expires, anyone can make and sell the agent, but only if they know how to make it. And there’s no obligation on anyone to reveal that. So the problem is that many modern drugs - while highly effective - are based on things like antibodies, so they’re very complicated to make and often beyond the reach of the poorest countries. So what Natasa Skoko’s lab does is work out how these drugs can be made from first principles, and then teaches people from poorer countries how to make them. She showed me around…

Natasa - We are sitting in the lab where we produce biological drugs. Biological drug is a drug produced in living organisms like bacteria, yeast or mammalian cells. We are talking about insulin antibodies, different growth factors.

Chris - Most of the time when we're talking about drugs though, we're talking about pharmaceutical companies - 'Big Pharma'. You are a research laboratory, so how do you fit into the equation then?

Natasa - So we are a research lab who is working on the technologies to produce biological drugs, the same drugs that pharma companies produce today. So we are basically mimicking all the process in our lab to find this technology and to develop this technology in our own hands.

Chris - But why are you taking on big pharma? Because presumably they've got deeper pockets and better international networks for manufacturing and distribution and sales, et cetera. So where do you come in?

Natasa - Biological drugs are very expensive. So yes, this big pharma can produce it, but they also protect it for 20 years. So we wait until the patent expires and then everyone is free to produce it. We are trying to mimic all the processes to produce something as similar as possible to those biological drugs.

Chris - In essence then, you are reinventing the pharmaceutical wheel. They've done the hard graft of working out what works and they've tested it, and proved it's safe, it's then got an expired patent. But what people can't do, even though they know what the stuff is, is make it because that's the hard bit and that's where you come in.

Natasa - Exactly. The hard bit is actual processes and knowledge. So we need really deep knowledge into the process and no pharma company will open their books and show you. So this is where we come and we put all our knowledge and then make the process from the beginning to the end in the lab. Today we are now in the new facility, in the new lab that is a lab where we are trying to develop the process for the production of antibodies, monoclonal antibodies, because we all heard now the antibodies against the breast cancer for example, they made a revolution in the treatment of cancer patients. What's most important is that we transfer this knowledge to the local producers in least and middle income countries. So that means that they can come here, we can teach them good manufacturing standards. So they can be trained here for between four or six weeks they spend in our lab and we can teach them how to produce it.

Chris - So in the process of working out how to make really otherwise hard to make and expensive to make agents, you've also got a sort of training pathway. So you bring the people in, as well as giving people the knowledge in other countries, you're also giving them the pairs of hands type knowledge as well. So people go away armed with the skills as well as the piece of paper that says that's how you make that insulin or that breast cancer drug.

Natasa - There is a need in the world to have this bio manufacturing training hub. We train more than hundred people from 22 different countries and now they're able to produce and to bring the product to the local market.

Chris - That was one of the things that emerged during the COVID pandemic, wasn't it? Lack of on-the-ground manufacturing facilities and skilled people in lower income countries. So when you've trained these people, is there, critically, an infrastructure for them to go back to? Is there adequate on the ground facilities and provision of equipment, materials, et cetera so that those highly trained people taking away the recipes you are cooking up here can actually put this into practice in their own country?

Natasa - So we help them to do that. So we help them and teach them how to build this facility. But you know, even if you build a huge and nice facility, even if the government invests money into the building, there's an actual lack of trained professionals. So we really need to have a critical mass of people in these countries to be able to receive technology and reproduce the process.


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