Podcast 3 - transcript

TRANSCRIPT

[Theme music]

Suzie: This is Made at UCL, the podcast, bringing you closer to the UCL research answering life’s big questions. From engineering to art, healthcare to space exploration, ancient artifacts to the technology of the future. 
Episode 3: Re-purposing

Hello! I’m Suzie, welcome to episode three. 

[music stops]

It’s getting to the end of the year, which definitely gets me thinking about new starts, but also looking back over 2019. Fittingly, this episode is about giving things a new life. Taking something that’s served one use and giving it another. 

***

Our first repurposing story is about finding a new use for a drug named Exenatide. 

Tom: My name is Tom Foltynie. I'm a professor of Neurology at the National Hospital for Neurology and Neurosurgery in Queens square. I do clinical research looking at the development of new drug treatments for patients with Parkinson's disease and other movement disorders.

Suzie: Parkinson’s disease is the second most common neuro-degenerative disease after Alzheimer’s. Neurodegeneration is the decline of the nervous system, which runs throughout our bodies, and such diseases can particularly damage neurons in the brain.

The symptoms of Parkinson’s are:

Tom: It's a constellation of slowness of movement together with stiffness, and tremor, and over time, it's a progressive deterioration in these motor features

Suzie: Motor meaning movement

Tom: but also accompanied by a number of non-motor features, which include: difficulty with sense of smell, constipation, bladder and bowel upsets, and dizzy spells, fainting speech problems and this type of thing. 

Suzie: Sadly, Parkinson’s is a progressive disease, meaning it gets worse over time.

Currently, there is medication that can help reduce some of these symptoms, but no treatment that stops the disease from progressing.
Tom: Ideally, you want something to reverse the process and for people to feel better, not just less worse. But any of these effects will be disease modifying, and the more effective it is slowing stopping or reversing the process the better.

Suzie: In his attempt to find such a disease-modifying drug, Tom has been exploring Exenatide, a drug that is currently used to treat diabetes, which is a metabolic disorder. So how did it come to be seen as a potential treatment for a neurological condition such as Parkinson’s? To answer this question, we need to introduce the true hero of this story. The Gila Monster! 

[monster sounds, screams, dramatic music]

Tom: [interrupting music] And I think the correct pronunciation is 'healer' monster

Suzie: Sorry, healer monster!

Tom: But it’s spelled G-I-L-A so many people talk about the Gila monster. Because it lives in the Arizona desert, I think it comes from a Spanish derivation. And so, you know, for a Parkinson's patient, talking about a healer monster is very highly appealing. 

[Cheerful Latin music]

Tom: This is a small lizard. The not uncommon and you wouldn't like to get bitten by one it's very painful. So these animals grow to about 18 inches long. They tend to be striped or spotted in varying colours, browns and some pinks. And so it is quite a lurid looking creature. And they're found throughout the southern United States in the desert areas.

Suzie: I have to say, I got a bit excited when I heard that this little creature was the source of the medication Tom is researching. I knew that some medicines come from plants, like Aspirin being found in willow bark, but I had no idea that animals often hold the secrets to treating human diseases.

Tom: It's not a new thing. Venoms have been looked at over many decades. And heparin, which is a blood thinning medication, was found in the venom of the Malayan pit viper. And so it’s a very commonly used very helpful drug 

Suzie: However, is not venom, but the Gila Monster’s saliva that is interesting to us for this story and that’s because….  

Tom: This is a creature that that only eats twice a year.

Suzie: Wait, what?! That sounds like a pretty sad existence to me, but I suppose if you live in the Arizona desert you have to make the most of what you’ve got, which is why this little lizard could help out people with type 2 diabetes.

Tom: it has to have a very close control of its own metabolism. 

Suzie: And it keeps that control with a protein called Exendin 4, which is found in its saliva.

Tom: This is very close in its structure to a hormone that we produce called GLP one or glucagon like peptide one. And after we eat a meal GLP one is released from the cells of the small bowel, it circulates around the bloodstream, and it stimulates the pancreas to produce insulin. And the good thing about it is it makes high blood sugar normal, but it doesn't make normal blood sugar low. But GLP one only circulates for a few minutes. It gets metabolized in the bloodstream. Whereas Exendin 4, or the synthetic version of this, Exenatide, will stimulate GLP one receptors, and it can continue working for many, many hours. And so this is a way of keeping blood sugar well controlled for many hours. And so it's become a licensed treatment for type two diabetes.

Suzie: So the Gila Monster’s adaptation to the scarce resources of the Arizona dessert have turn out to be useful for people with diabetes. But it was soon to become clear that the lizards story wasn’t going to end there!

Tom: It was, it was perhaps serendipity more than by design that the neuroprotective properties of Exenatide were found. I suppose it's the whole the background to repurposing drugs.

Suzie: Researchers often carry out scans of drugs that are already licenced to see if they might have other purposes. It’s much quicker and more cost effective than dreaming up and manufacturing a new drug and then later finding out it is too toxic to be used in the human body. 

A researcher called Nigel Gregg, from the National Institute for Health in the US, was doing this sort of screening on drugs to see if they had neuroprotective effects.  By chance, Exendin 4 was one of the compounds he was testing. He grew nerves cells in a culture and exposed them to toxins, and he found that exendin 4 protects them from those toxins.

Tom: So this is where we've got involved in doing clinical research, knowing that the drug is safe for the treatment of diabetes patients, knowing that it's got very strong neuroprotective properties in the laboratory, we wanted to try giving it to patients. So we recruited people back in 2010, to the first small open label trial of using this this drug. We wanted to press on and see if we could help some Parkinson's patients. 
And they had good results! They found patients taking Exenatide had less motor problems and less cognitive problems than those who didn’t take the drug. This led to a second trial, funded by the drug manufacturer and the Michael J Fox foundation.

Tom: And we found that, as in the first trial at the end of the year, patients on Exenatide had less progression in their motor disability. And what was just as Interesting and perhaps more important was that even 12 weeks later, when the drug completely washed out of their system, wasn't detectable anymore in the blood or in the spinal fluid, there was still an advantage in their motor disability. And this distinguishes it from some extent from any of the symptomatic drugs that we already have for Parkinson's disease, and suggested that this this is something that appears to be slowing down the rate of disease progression.

Suzie: If the conclusions drawn from these trials are correct, the effect of Exenatide could be life changing for Parkinson’s sufferers.

But while it may have been serendipity that brought scientists to this point, it might be that the Gila monster held a clue to this double usage all along.

[cheerful marimba music]

Tom: So why this creature only eats twice a year perhaps is due to the scarcity of food supplies in the Arizona desert. And when it eats, it eats a large meal and it wants to be able to control this blood sugar based on this very scarce feeding behavior. But I think the truth is more than just that Exendin 4 has this role on its metabolism, when the Gila monster produces Exendin 4 in its saliva, it appears to have a direct role on the brain. And by stimulating GLP one receptors in the brain, then this has an important role in learning and memory about where it is stored food or where it is previously found food and returns to them when it becomes hungry months and months later. There appears to be a dual role in this so that there's a link between strict control and metabolism, but also feeding behaviour learning and memory. So this is something that, you know, perhaps I'm not the expert on, but the links between metabolism and neuro degeneration are intriguing and multiple.

[music fades]

Suzie: This is just one of many examples where doctors and researchers are looking to repurpose drugs of all types. 

Tom: I think it's very important that we do learn from other specialties. And so I go to a meeting once a year, where cardiologists, neurologists, endocrinologists, hepatologists, and bone osteoporosis doctors will all discuss a set of proteins that include Exenatide, because these drugs appear to have relevant properties that cross specialties. And it may be that we should be thinking more and more about solutions to tissue specific diseases that may be found by looking at things that have been helpful in other conditions.

Suzie: And the research into Exenatide is ongoing, including in cardiovascular (or heart and blood related) problems, in hepatitis patients and for people with the skin condition psoriasis.

As for its effect on Parkinson’s, Tom is just starting a third, larger trial, over 2 years, 

Tom: So what we are now looking to do, is to definitively prove that this drug is doing more than just masking symptoms. And we are hoping that we first off show that there's the same effect size in one year. But then that effect size continues to grow. And therefore there's a cumulative advantage of staying on this drug, not just a small benefit, which remains fixed with ongoing exposure. And so if we can demonstrate that we have a cumulative advantage year on year, then this will definitively be the first disease modifying drug for Parkinson's disease.

[cheerful, relaxed Latin music]

Suzie: I think it is really exciting that the natural world provided the inspiration to create a drug that can have such significant effects, even if the source was rather unexpected!

[music fades]

***

Suzie: I also met this month with artist Onya McCausland, a senior research fellow at UCL’s Slade School of Fine Art, to talk about a paint that she has made from another unexpected material.

[music featuring bell chimes and shimmering effect]

Suzie: Onya’s interest in pigments began during an artist’s residency at Gloucester Cathedral. She noticed little traces of red or ochre colour embedded into the cracks of its walls, which led her to seek out the sources of pigments in paint. From Gloucester, she began looking at the UK from above, and soon started work with the Coal Authority, local mining communities and paint manufacturer, Windsor and Newton.

Ochre

Onya: As a painter, I've been using pigment in paint for a long time. So I'm not so interested in colour for its own sake. I am interested in the material content of colour and its history with human culture, it's always been the materials that are involved in industry that end up being the materials that make paint.  The pigments that make paint have never been particularly special. They're derived from materials that are very much part of our everyday world. So carbon and iron, and chalk. And these are these are ubiquitous materials. 

What I discovered really was that a lot of this material had been mined out and that it didn't exist anymore. Part of the journey of finding these colours involved using Google Earth, and Google Earth was a means to find places. It became also a way of seeing or scanning the ground from a different perspective. I started to see these orange lakes of colour from above, and that opened up a question of well, what, what's going on in these lakes of colour?

[music restarts, with sounds of water and wind]

These were clearly kind of working industrial sites, run by the coal authority. So I contacted them and asked permission to be given access and also to ask them what the processes were, that were forming there. 

[music fades]

In order for mining to take place, they have to be kept dry and workable, and so the water is constantly being pumped out. When the mines close, the pumps stop, and the water levels start to rise. The water that floods the mines gradually began to seep into rivers, and groundwater drinking supplies. So it started to create problems in particular places where they'd be they call it an outbreak, and vast quantities of iron oxide would hit the river. The pumps have to be switched back on again now. By building these sites, they contain the pollution, but they need to keep the pumps switched on. And it's a legacy if you like that will go on for decades. 

[percussion, slow music]

The mine water that's pumped to the surface carries minerals that have been released as the geology has been worked by mining, those minerals get leached into the water and travel and get pumped up to the surface. So that polluted mine water, when it hits the surface, oxidizes, and the oxidization process means that iron particles turn into ochre sludge. And that is the orange colour that you can see from Google Earth. 

[music fades]

I visited about 40 sites over a period of about two and a half years. I collected buckets of sludge, which was pretty messy and I had to refine it a little bit. I had to dry it and grind it, sometimes wash it in my studio to get it into a condition that could then be mixed into a paint medium and then turned into paint. But during my PhD, my doctorate had a collaborative partner with Windsor Newton. And Windsor Newton. They gave me some lab space and we tested systematically tested each of these 40 colours or whatever. 

I began to spend more and more time with five colours in particular. And I began also to work with them in my studio, in paintings, in making paintings. And there was a sense that the landscape was being carried in the colour. Particular qualities of each of these landscapes became evident in the hue and the optical qualities of the colour but also in the sort of material and physical behaviour. So its thickness or density or its brightness or its lightness. It always pointed back to the place that it came from.

[gentle guitar music]

One of the colours is from the northeast coast, just south of Middlesbrough. It's an old iron stone mine that closed quite early, in the early part of the last century. The outbreak happened very recently, essentially the beach at Saltburn, Saltburn-by-sea was stained with this iron oxide material. So there's a big community led campaign to get something done about the about the pollution. I'm hoping that some of those same people will be involved in, in seeing this colour come into being as a paint. 

But what's interesting about this colour is that it's the brightest of all of the pigments. But it comes from a part of the country that is where the deepest mines are. The landscape there is lit by the sort of reflection of the North Sea, off the light of the North Sea, so that the whole landscape feels very bright and the colour kind of has some of that kind of brightness in it. And yet it emerges from a very dark part of the landscape. So there's this lovely sort of contrast between the darkness and the lightness.

[music fades]

The mine water treatment sites are a culturally significant mark in the landscape. They are the only visible reminder of the hundreds of miles of networks of tunnels, of coal mines, that exist under the ground. That industrial wasteland that we don't see anymore, there is a very much a changing discourse around the history of, of mining. And, yes, you know, the history of the miners’ strike is a distant memory and most young people's or most people's minds and, and yet there are communities within [which] this very much uppermost in their memory. And so in a sense, this material is a conduit to talk about that, but to talk about it with a different set of framings. And rather than it being sort of historical look back to the particularities of, and the difficulties of mining history, to look back at it from a sort of angle of regeneration, partly, I mean, sort of an emotional regeneration it on one level; but also an environmental regeneration. And yet to not overlook or oversee the value of a historical industry, for the communities that worked in it. 

[gentle chiming music]

It's a colour that connects with the imagination. Because it's a colour that comes from something unexpected. It's the carrier of what is the underpinnings of a, of a particular kind of moment, which has an important resonance in terms of where we are environmentally, how we are thinking differently about the environment and about the ecology and about sustainability. This is a genuinely sustainable colour. It's not going to be mined out, it will be produced as a waste material for decades for even hundreds of years. The site is there is a… a record of that place and time and process.

[music fades]

Suzie: Onya is working with the coal authority, local communities and paint manufacturers on events  throughout 2020 that will see the paints made and the sites opened to the public. To keep up to date with when they take place, visit our website for Onya’s details. We’ve also got some wonderful pictures of the ochre and the sites themselves for you to see. 

[gentle acoustic guitar music]

One of the things I really enjoy about making this series is finding connections across all the many departments at the university. I find that themes come out or words get repeated in ways I couldn’t predict. Tom’s work on Exenatide seems to me a great example of how the natural world can help us understand how our own bodies work and how we can use that knowledge to stop some of the world’s most damaging diseases. And Onya’s work clearly has the earth, landscapes, cultural history and sustainability at its heart. 

***

Our final story follows this thread, but this time, in the engineering department, where researchers are exploring ways of reducing our impact on the planet. 

[upbeat, electric guitar music]

Paul: Hi, I'm Paul Hellier. I'm a lecturer here in the mechanical engineering department at University College London. 

Paul is a specialist in engines and fuels

Paul: I get to try out unusual things that we haven't thought about before. Basically burning unusual things that people haven't tried burning before. I really love burning things! [laughs]

Suzie: I went to visit his lab to find out about his research with a company called Biobean.

It was the idea of a guy called Arthur Kay and a colleague here at UCL. They saw that there is this great opportunity, they saw that people drink their coffee, and then they chuck the coffee grounds in the bin and it goes to landfill where it's slowly decomposes. And it produces methane, which is really bad greenhouse gas. So they thought, Well, if there's useful energy content in there, what if we went around and collected it up and then we try and turn it into something useful? 

Suzie: That was the birth of Biobean, which turns waste coffee grounds into two different types of fuel: biofuel for engines, and solid fuel for wood burners and heating. And Paul is making and testing the biofuel here at UCL to make sure it is as efficient and safe as possible.

[Paul and Suzie talking quietly in the lab]

Suzie (voiceover): I brought a rather sad looking cup of waste coffee grounds from the café on site into Paul’s lab, with the thought that maybe he could put it into some into his fancy machines and turn it into fuel.

Suzie (in lab): Yeah! Shall we take our?

Paul: Shall we take our stunt coffee?

Suzie: Yeah!

Paul: Let’s take our stunt coffee so it knows what fate awaits it.

[sound of door closing]

Suzie (voiceover): Of course, it’s not that simple! But Paul did take me on a tour of the lab, which is underground in UCL’s Roberts Building.

[sounds of footsteps and fans]

It’s a bit of a maze of offices, large hunks of metallic equipment and side rooms filled with test tubes and extraction fans, all connected by long blue corridors that all look very much identical. We bumped into the occasional student wearing the obligatory lab coat.  And as he showed me around, Paul explained each of the stages that the coffee grounds go through, before being tested in the engine.

Paul: Cool, yeah. So the first thing that would happen when we when we have a sample of the coffee grounds come to us is that we'd want to find out how much water was present in the coffee grounds. So the oven is just around here in the furnace room. [door closes]

Suzie: We showed our little expresso cup of waste grounds the oven that would be used to dry them out.

Paul: It's just a big industrial oven, much like you would cook at home. So we’d leave it in here for five or six hours and we’d come back always to see at what rate the water was disappearing. And we tested out different coffee grounds from different sources, some from cafes, some from industrial sources and then they have different particles sizes and they come with different amounts of water. And we characterise all of those so we knew what we were dealing with before we got to the point when we tried extracting some fuels.

Coincidentally, here is some coffee oil, following the extraction process so we can take this with us on our journey. 

Suzie (in lab): So it's like here's one I made earlier.

Paul: Exactly. This is the end. Well, one of the products that would get from that

Suzie (in lab): So it goes from like soil coffee looking soil, to soil, sludge

Paul: Soil sludge. Yeah.

Paul: The way in which you get the oils out, is quite a lot like making a cup of coffee.

Suzie (voice over): To get the oil out of the dry grounds, they use

Paul:  something called a soxhlet apparatus. 

Suzie: To make a dodgy cup of coffee with solvents like ethanol or hexane.

Paul: So you wouldn't want to drink what you make. But what it does though, is it takes away some more of these oils that held inside the coffee grounds that we're interested in turning to a biofuel. 

[twinkly noises and fans from lab]

Suzie: Paul has two main goals in his work with Biobean. The first, is to make the process as efficient as possible. The other key thing that they are working on, is reducing the impact that the biofuel has on human health. To do this, they need to know the quantities of particulates and harmful gases that each type of coffee is likely to produce.

[fan sounds from lab]

Suzie: Down another corridor, and through another door…

Paul: Ok, so in this lab…

Suzie: Paul showed us a pyrolysis furnace,

Paul: which we can heat up to about 1500oC, to replicate what goes on inside an engine.

Suzie: So they run the fuel, through the furnace, where, like in an engine…

Paul:  It's hot enough that the oxygen can attack the nitrogen and it can oxidize the nitrogen. And so you end up with NOX, which is NO or NO2. And then it gets emitted in the exhaust and it can have health effects. It can it can affect respiratory system, it can help form ozone at low levels and can cause acid rain. And so we might be cutting greenhouse gas emissions. But we, you know, we don't want to be inadvertently making air quality in places like London worse and you know, aggravating people's immediate health. It's a really tough question when you go to like, you know, to a meeting or a workshop and say, ‘Well, what should we prioritize? Should we prioritize global climate change and preventing that or should we focus on people's immediate public health?’ It's, it's tricky, you want to do both. And it's, it's difficult to prioritize one over the other.

That’s why, at each stage, Paul’s team are testing the different coffee oil solutions, so they can find the one that is the most efficient AND the cleanest in terms of harmful emissions. To do this, they need to know exactly what compounds are in the oils that they make.

Paul: Because the composition of those oils, the type of oils, how large these molecules are, how saturated unsaturated they are, has a big impact on how they perform inside an engine, how efficiently they'll burn as a fuel.

Suzie: Now they know exactly what is inside their fuel, they are almost ready to put it into their engine for the final series of tests.
The only problem, is that often these oils are too thick. Which runs the risk of breaking the engine, or at the very least makes them wasteful. So there’s one final process that has a wonderful name that I’m still not sure I can pronounce. 

[twinkly test tube sounds[

Suzie (in lab): So like wait, trans trans... 

[Paul] Transesterification. So when you esterify anything, it's the act of turning an acid into an ester, so it makes it a smaller molecule that it has more oxygen in that molecule, so it can take something that's really thick and viscous like this and make it a lot less viscous. So a lot more runny, and so a lot easier for the engine to inject.

Suzie (voice over): So! After drying, extracting, pyrolysising, categorising and transesterifying (I’m not sure all of these are real words!) The waste coffee grounds become a nice flowing oil ready to be put into an engine.

Paul:  It's been used for many years in things like black cabs that's been using transit vans

[engine sounds]

Suzie: It’s been raised up from the ground and modified to allow the researchers to control exactly how much fuel is going in, and to measure how that fuel changes as it is passed through the engine. There’s electrical clamps, metal cylinders with bits of blue roll stuffed inside, pipes coated in foil, tanks and caps and dials. On one side of the room is a  window that overlooks the engine, and on the other side of that, there’s  a whole row of computer screens, where students and researchers sit and monitor everything that’s going on when the engine is running.

Paul: So we would fill up a coffee biodiesel in the system, seal it up. And so we could try out different by diesels... we could, we did try the coffee old before we done the trasnesterification to see how helpful that was in reducing things like particulates. And so then we get all of this data. We log data from it continuously. We have lots of emissions analyzers. So those are the kinds of things that we look at. When we when we test these fuels.

[engine slows and stops]

Suzie: And the good news is,, they’ve got a working biofuel! 

It's good it works! It's quite similar to other bio diesels. But what's really exciting about It is it's a waste stream that we're taking, we're getting a second use out of it. It's not something that's been cultivated directly to make a few something that people normally throw away. And we were covering some useful energy out of it.

This is really important. Using waste coffee grounds is very different to other biofuels, because they aren’t being grown specifically to be used as fuel, taking up land to be grown and using up energy to produce.
Instead, they are a waste product that exists already, and if they went to landfill like usual, they’d be letting off CO2 and methane as they decompose.

If we’re going to solve the global climate crisis, we will still need to reduce how much we burn fuels at all. But this is a step away from fossil fuels, which is a step in the right direction. 

[upbeat electric guitar music]

Paul: I think that's the only way we're going to tackle all these, you know, issues of sustainability, cutting fossil carbon emissions. We have to be inventive and take things that we wouldn't normally think of as being useful as a source of energy and saying, ‘Well, this isn't a waste, actually, it's a useful energy source,’ and you know, tying up all of those kind of different process streams. I think that's really exciting and really fun and really important.

Suzie: Do check out Biobean if you want to get your hands on some of their solid fuel for your fireplace this winter! As with our other stories, links are on our website.

[music stops]

And that brings us to a close for 2019 Thanks for joining me this episode as we go from old purposes to new. We’ll be back in the New Year with more research breakthroughs for your ears.

[theme music]

Made at UCL: The Podcast is produced by me, Suzie McCarthy. The executive producer is Nina Garthwaite. Additional reporting this episode from Isis Thompson.  Mixing support from Mike Wooley. We'd like to thank all our researchers for welcoming us into their labs and offices. #MadeatUCL is a campaign that brings to life disruptive thinking from UCL. Research presented in this episode was nominated and selected because of the impact it has made on everyday life and society. This episode is brought to you from UCL Minds, events, lectures and podcasts open to everyone.