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Could you just start by saying your name and what your current job title is?

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Yes, I am Nicole Suzman.

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I am principal investigator here at the biochemistry department in Oxford, and I am leading an antiviral drug discovery group.

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And I'm also the associate, one of the associate heads of the biochemistry department at the moment.

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So I'm the head of the Infection and Disease Processes group ITP.

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Great. Thanks very much.

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And so going back to the very beginning, how did you first decide that scientific research was what you were going to want to do?

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Well, it was not my decision, really. It was made for me when I was still at school, in secondary school in Germany.

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I specialised very much in art, art history, ancient Greek and Latin, and that's what I wanted to do with my life.

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But I was quite good in all the subject matters. And when I finished school, my father was convinced that I should do something proper with my life.

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And in his mind that was science. I don't know where he got that from because he himself wasn't a scientist.

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But I think he must have admired science. And given that I had never concentrated on science before, I thought I go for the easiest option.

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That was biology at the time. And I started studying biology in Bonn for three years, and I did not enjoy that too much.

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So I in evening class, I started to learn English because I wanted to learn another language.

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And at that point it became possible to go abroad.

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And I thought, okay, I better immerse myself in the language, learn the language.

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And that wasn't possible as an English student because everybody wanted to go abroad.

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But I was still enrolled as a biology student.

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And at the time there was something called a European Social Fund that enabled me to go abroad to Scotland at the time.

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And of course I had this this vision of Scotland that you have as a young German girl of Highland, Romantic and all the rest of it.

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And I ended up as a biochemistry student in Dundee.

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And little did I know at the time that that was one of the best biochemistry departments in Britain, because I wasn't well prepared.

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I went there to learn the language. Of course, it wasn't English, it was proper Scottish, I learned.

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And but while I was there I started my master's and later the Ph.D. and there I absolutely fell in love with biochemistry.

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And that was mainly, I want to say, due to my then supervisor, Professor Mike Ferguson,

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who was also the first person to describe my uncle's Glycosylated Phosphatidylinositol,

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and because he had discovered them and analysed them and I ended up in his lab and the way this Anglo-Saxon way of teaching,

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I remember first walking into the lab and he was fiddling around with a mass spectrometer,

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which in Germany he would never as a student be able to come near.

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And he basically just said, Sit down, I'm doing this, you put this button over there, you will see these ions going up.

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So this kind of narrative teaching, I was absolutely, absolutely hooked by this.

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And yeah, I fell in love with biochemistry and in in Scotland.

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And from there on I never thought I would do a Ph.D., obviously, but encouraged me to do so.

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And what was the subject of sleeping sickness?

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So he worked on CPI and because that carried the surface proteins of trypanosoma, which are the causative agents of sleeping sickness.

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And so I did my first, my Master's and then my Ph.D. on the sugars that are attached to these proteins is that these

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little blood parasites carry to protect themselves from the immune system attacking them.

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Yes. So it's really thanks to Mike Ferguson that I am in science and state in science, and he had also been in Oxford for a while.

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So when it came when I finished my Ph.D., there are three ways of attaching sugars to proteins.

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One, I had just learned GPI anchors and the other ones are only glycans.

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And so there was this like a biology institute down here in Oxford, founded by Professor Raymond Dweck.

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And I thought, okay, you know, I know one. I can analyse one way of attaching sugars to proteins.

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If I now will just learn the other two, I will make myself very employable.

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I thought so down here. I came to Oxford in 1997 and.

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And it all linked comparable easy to understand after two and because I picked it up reasonably fast and at the time.

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So yes, I just went, oh, it just went a little bit more explanation why?

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What happens when targets get attached to proteins? Why do the proteins need to have sugars attached?

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There are many different reasons why I would want to do that. They're are very generic reasons.

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When proteins are being made and synthesised into the into the organelles called the endoplasmic reticulum,

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the ones that I'm interested in, I should say the proteins that I'm interested in are usually secreted proteins are made into the air.

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And so it's a super dense soup of proteins that are trying to fold.

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And so if they would be hydrophobic, they would just all clump.

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Together as one big glue and they couldn't fold properly.

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So one very generic reasons why then each of us at that point is just to put a lot of sugars around them.

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So that makes them soluble in water in a watery environment and to repel each other, you know, that makes them water soluble.

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So that's one generic reason. And but they are also extremely specific reasons why proteins need sugar.

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So sugars are attacks that tell a protein where to go inside a cell, where to go when they leave the cell,

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where if they are part of, say, multi organ body like all human body, tell them which organ to go to, what job to do.

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They know that they determine the half life of of glycoprotein hormones.

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For example sugars have a whole variety of of jobs and why proteins might need and in the context of viruses,

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of course, it becomes even more interesting. And that's important to know that these sugars are supplied by us, the human host.

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And so viruses can't bring them in with them. So they need they desperately need to steal them from us and they use them for their purposes.

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So when I arrived first here in the Oxford Like Biology Institute,

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I wasn't a virologist at all, but there were visiting professors from America at the time.

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A Professor Tim Logan had brought also some other American, Tim BLOCK LLC,

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and he was a he is a hepatitis B scientist and he had brought his American colleagues with some who did PhDs here.

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And so obviously I was working in the same physical labs and I heard them talking about viruses every day, and it was exciting.

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I could feel the vibration in the room and it was so important and I just was immediately hooked.

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Honestly, I just thought, Oh my goodness. And Barry Blumberg came a lot to the institute.

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And he obviously, you know, they're able to make the Nobel Prize for the prize for Epstein-Barr virus.

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No, Hepatitis B virus. Yeah, I guess it was. Yeah, exactly.

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And he was there and he kind of just took an interest in me and became my mentor and which was incredibly exciting for a young new post-doc.

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And he was a wonderful gentleman and, and, and talked just talked a lot about things of, of, of interest.

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And so because I was like a are trained like a biologist and I had met these virologists

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and what I then very quickly learned is that viruses steal these sugars from us.

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They need them to fold their envelope like proteins properly.

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Not all viruses, just those envelope viruses, but there are enough of them and many of them are human pathogens and killer viruses, really.

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And I thought, okay, if they need this so desperately, we should interfere with this glycosylation process.

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And as I explained, it's a wholesale process. It's something they can't do much about because they need these sugars.

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If I interfere with a wholesale produce process that the viruses need,

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they can't very easily mutate around this because we as a human host and mutate incredibly slowly.

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Hopefully if you mutate, you might get cancer. So so we have hundreds of ways to prevent us from mutating, you know, all these checkpoints, you know,

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And so viruses will have a problem if they need these sugars, they will have a problem to mutate around the need for these sugars.

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And that has actually held true over the last 20 years since I started working with viruses.

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We have yet to find a virus that is actually able to mutate around the drugs.

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And then we proceeded to develop over the last 20 years that are actually targeting the whole cell process of adding and modifying this in Glycans.

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It's one of these subsections of glycans to proteins that are synthesised into the and the plasmid reticulum.

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Is there a problem developing a Trump drug that does that given that it is a host,

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the process that so presumably the host needs it and you don't want to stop it doing what it normally does?

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That's absolutely true.

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It is a very justified question and is also often the question I first get on conferences and starting at the end of what you just said,

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we do not intend to entirely stop the host cell process.

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So we never set out to 100% inhibit the enzymes, our enzymes that put these sugars on and modify them in a way that the virus needs them.

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That is never the intended effect. Even if we wanted to, we never managed to, you know, the drugs that we developed, they need to get into the cell.

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They need to cross the cellular membrane. They need to cross a second membrane that gets them into that organelle.

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They never get to that organelle at a at an amount that can inhibit these enzymes to a large extent.

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We have a way of of gauging how much we are actually inhibiting these enzymes.

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And we have a way of estimating roughly by how much we need to inhibit to send them to get an antiviral effect.

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We for some and for every virus that will be different, but for the ones we did look at it,

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we possibly only need to take all these enzymes and possible.

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You inhibit them by around 10%, we reckon, to get a quite pronounced antiviral effect.

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So that is number one. So we never set out to do that to actually inhibited entirely.

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Plus, of course, by now these drugs have been in lots of different animal models as they have

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been in humans for a long time because they are also used for other diseases,

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I should say. Trying to develop them in antivirals wasn't the first idea.

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There are other processes in the body that can go wrong and that these drugs might help with, and they do.

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So some of these immunotherapies there are, they call them immuno sugar sugar analogues,

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and they inhibit some of these enzymes that modify the sugars.

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They have been in the clinic already and they are used clinically against things

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like all shades go shade disease and Tay-Sachs fabric diseases like this,

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almost like a story, like a lipid storage diseases.

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These drugs have been developed alternate like Biology Institute under the leadership of Professor Dweck by Fran Plotz,

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who's now the head of pharmacology, and Terry Terry Butters. This was instrumental people together with Monsanto, I believe.

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Yes. So what? What other viruses did you work on?

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So when I started, I obviously, you know, you get excited by this.

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You want it make a difference in the world. You want to work on viruses that actually kill people and that are a big problem.

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And at the time, the viruses that the virus had, everybody tried to do something about was hepatitis C virus.

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And the problem with that was you could not grow hepatitis C viruses outside of the human body at the time.

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And and that only became possible in 2005, I want to say, with three groups internationally at the same time,

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kind of managed to get everything in place to have a very complicated system up

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and running where you could grow hepatitis C virus outside as a human body.

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But before then, one of these people, a life like he had in Heidelberg in Germany, had been aware of our work that we tried to do.

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You just say his name a bit more. Sorry. Ralph Barton Talaga Okay.

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And and he had actually contacted me.

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He had read about these immuno sugars and because we could not grow hepatitis C outside the human body, we had,

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we had looked at the viral family trees and we had picked the virus that is closest to hepatitis C, but it could grow.

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And that was to say that solely BTV Bovine Viral Diarrhoea Virus.

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And so we worked on Baby to be a pest virus. In the same family.

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It's a flooded river like hepatitis C and had done all our work on pesky viruses.

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And this immunity has worked. And so he he just briefly, before they actually published that they could grow hepatitis C,

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they had contacted us and asked whether we could try the immediate on hepatitis C,

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And of course, we were beyond excited at the time until we could show and we published studies and that it works against hepatitis C as well.

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At that point, they all just started. This is we're still talking about in vitro or in vitro.

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Yes. And then at that point, we started a clinical trial. But that that which did not work.

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But it was also not an it was also not I didn't go into so much detail.

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It was also not a folding inhibitor, the one that actually made it into the clinic.

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And there are other reasons why that clinical trial didn't work,

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because we couldn't take at the time blood samples of patients and then test outside of the human body,

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you know, because they had none of these wonderful artificially made viruses so you could grow.

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They have the real virus and we could not grow it outside the human body.

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So we couldn't really test for the infectivity of these viral particles because that's a big problem.

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This is host targeting is our approach of host targeting the other approaches.

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On the whole, we do not because we we do not directly target the virus.

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We are not these direct acting drugs, direct acting drugs which say, for example, inhibit the polymerases of viruses, the proteases of viruses.

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When they work, you get a massive drop of measurable viral RNA or DNA inside a human body.

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What we commonly refer to a block drop, you know, like, you know,

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thousands of tons of particles disappear quite quickly in over a few days or weeks window.

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And because everybody's used to this, everybody looks for this. And that is a clinical readout for for most regulatory bodies.

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They always compared to what's already out there and say, oh, do you have a two locked drop in two weeks?

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And no, we will never have that with a host targeting because these viruses often can still form.

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They just must fall their outside shell, you know, and they still are in your blood.

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So if you take a blood sample and look at the RNA, it's still there, but it is sitting inside a non-infectious particle.

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So that part cannot go to the liver and cause liver cancer later on.

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It can't go wherever which virus we talk about, but we can't have a clinical readout because the RNA or DNA is actually still there.

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And that makes it incredibly difficult for us to plan clinical trials to convince people that it's a worthwhile attempt to do this.

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And in any case, you should, I think, never just want to go for a monotherapy with a host targeting or and you know,

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that that might have been a very naive thought at the very beginning, 20 years ago when you first thought about this.

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But the idea would obviously always to be to put this together with, say, a direct acting drug.

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And the beauty there is that could, you know, a direct acting drug could cause a massive quick drop, the one that everybody wants to see.

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But the problem is that this direct action drugs is very often these viruses can

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mutate around them very quickly because they are directly against the viruses.

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And if you're dealing with a fast mutating virus and the viruses that we worked with at the time,

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hepatitis C, hepatitis A, HIV, hepatitis B, these are some of the fastest mutating viruses we know.

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So these direct acting drugs usually give rise to viral escape movements very, very quickly.

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And so the dream at that point, the idea was to at one of our immune as one of our host targeting,

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just to kind of put it into that cocktail is a very non-toxic drug.

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I didn't ever finish that one. I was wondering what I didn't finish earlier.

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It's very non-toxic. These a targeting GLYCOSYLATION inhibitors we are working on to add on to or say a drug cocktail to hoover up

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all these potential escape mutants of the direct action drug giving the direct acting drug a longer lease,

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a longer life to work, and maybe get totally rid of any viral reservoirs in your bodies.

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Maybe so. That's currently the idea.

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What we really would like to do with ways to use that is that was true until very recently

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and until we very recently stumbled across yet another way of giving this immuno sugar.

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So everything I've discussed so far is when you give me initial this, you know,

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I want to say in a normal way three times daily at quite low doses as a pill, as a pill orally available.

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That's one of the beauties of these amino sugars. After all, they are sugar analogue.

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They don't taste sweet, all of them there. Some of them are quite bitter tasting, but you can just obviously coat them in something nice.

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And and that's how how all our trials went.

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And so we are not the only group working on, on immune sugars and other groups who have looked at other sugars and done clinical trials.

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The toxicity that usually comes up with this kind of immunity to this in humans tends to be gut related because these are sugar analogues or drugs,

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so they are recognised by almost everything in the body that recognises, in our case glucose, glucose and our target sugar.

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And so there are, for example, in our guts we have these disaccharides,

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and if we inhibited by taking this drug that often leads to osmotic diarrhoea and

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in the very first immunosorbent trial and nobody actually knew how they worked,

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it was. And then and in the eighties they added this to an AIDS drug, AZT, the first and only one at the time they, they, they tried.

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Um the did decide the effect was osmotic diarrhoea.

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So there are some side effects when you do this and you give this for a longer time.

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And so together with other colleagues, with our industrial partners EBS at the time in America.

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Emergent Biosolutions. We discovered that if you give a very high dose of ammunition to us, but only once, that that was enough to to save,

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say, in this case and this paper be published, either dengue or influence infected mice from virally induced death.

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So normally this poor mice, they die after usually somewhere between day six and ten.

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And we could save most, if not all of them with a high dose.

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And we still don't know how that works. We are working very actively at finding out.

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But the thing is, it does work. And so at some point, at some point we will do more toxicity testing.

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That's the dream. Now, to do that in humans, to see how high up we can go with this immunity of this.

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And at the time we went up, I think to three. And again, it wasn't the toxicity that that was preventative.

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So we hope that we can go up. Actually maybe up to six gram in humans and then have a single pill or maybe six gram is a big,

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big might be actually three pills that you take and then people tell about that

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might be preventative and but you have to think back to say the early days of HIV,

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for example, people took 20 or 30 pills a day to survive.

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And then you make it better and better. And these days you have a single pill for HIV treatment.

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You know, you have to start somewhere and you could think of more maybe potent amino

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sugars or what We believe we have now identified the target enzyme for this,

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what we call a single high dose approach, which is one of these glycosylation enzymes that was always our target.

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We just never thought we could actually inhibited inside a cell, inside a living cell, but we found out we can.

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And so now this is the target enzyme that we could try to make other kinds of drugs again so it doesn't have to be an immune or sugar.

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But to be honest, I do like him initially to say that actually as a drug, not bad at all.

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People always say that. But it's also talking isn't a dangerous.

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I'm thinking just because I tell you it's always targeting doesn't make it dangerous because

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most drugs out there in this world are actually horse targeting and nobody bats with an eyelid.

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You know, it's like your aspirin. You anything you take as host targeting, you know, not anything.

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I mean, famously antibiotics are not. But, you know, many, many things you take for other diseases or pathologies.

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And you talked about this. You were talking about side effects and then you talked about the single high dose.

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Yes. So do you get the side effects, but not for very long. Is that is that the advantage?

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So I would imagine that that that to be the case. I would imagine that could possibly.

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We don't know. So quick answer. We have the toxicity.

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We have human tox data, and there doesn't appear to be any related toxicity with this.

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And the hope would obviously be if you only have to take it once.

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Just by not eating anything at the same time. Well, that drug is in your body.

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You will not get that side effect because these enzymes in your guts have nothing to do.

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You know that You wouldn't get an osmotic diarrhoea. You know, you could probably possibly not eat for a few hours if it's that or, you know.

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And also sometimes, I mean, of course side effects are a dealbreaker and can be a dealbreaker sometimes.

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I personally think if I'm faced with a potentially lethal virus and a short term osmotic diarrhoea,

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if that really was the worst side effect that will come out, which I can't predict, then I know what I personally would do.

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But I understand that this is a concern. But just because it's a host targeting, I don't think our side effects are any less.

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We observe as these drugs are any worse. And you see this purposefully day drugs, you know, the protease inhibitors,

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polymerase inhibitors come with quite considerable side effects and everybody seems to be it.

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I find it's almost a psychological problem.

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Everybody seems to be okay with that, you know, But just because I say I go on purpose for the host, then somehow it doesn't seem to be okay anymore,

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you know, so but I understand and we have to obviously toxicity breaks most drugs and whether that's DEA or HDI, it doesn't matter.

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You know, the toxicity has to be good, especially if, say, we're now dreaming this, our dreams of of giving this almost prophylactically.

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Or maybe if you think you've encountered somebody who was coughing or you had a COVID case or whatever influenza case,

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and if you ever even consider giving drugs like that,

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like almost prophylactic, the safety profile of these drugs have to be even more even more convincing than if you already know you have a disease.

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So, yes, safety will be the be all and end all across all drugs.

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So just one more general question. All this effort, all your effort, efforts going into finding drugs against viruses.

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But the other strategy for dealing with viruses is vaccines.

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What are the relative roles of vaccines and drugs? And I think especially when it comes to preventing outbreaks, preventing pandemics,

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certainly from preventing pandemics or turning into or epidemics turning into pandemics, I should say.

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I think vaccines are by far the most important by far the most important tool in the toolbox.

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There's no question about that. And I never see one against the other.

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You know, we need everything in the toolbox to fight these diseases.

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And of course, once you already have a disease, then the vaccine tends to not be that helpful anymore.

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So you will always you will end up in situations where lots of people carry viruses before a vaccine gets developed,

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whether that's a chronic virus like hepatitis B or, say, a new, acute and emerging virus, some possibly potentially pandemic causing virus.

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Very sadly, you will always have many, many more people infected by that time.

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You may or may not have a vaccine this time through the work of incredible people would be so unbelievably fast, have these vaccines available.

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But in one year, as you know, I mean, millions and millions and millions of people were suffering.

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If we had if we had a very generic drug site in my in my mind,

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that can by definition only be a host targeting antiviral because we never know what the next virus will look like.

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Like in this case, we had a rough idea. In fact,

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the direct acting drugs that were specifically developed against SARS-CoV-2 were so fast or in the

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pipeline because they already knew what the protease of that virus very quickly in the outbreak.

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They knew what the protease looked like. They could as they could do the FBI.

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These screens, I believe you talk to Anita from Delft. And yeah, so they were doing the moonshot and we were my group was heavily involved in this.

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And but again, even the fastest possible specific drug development will never be fast enough.

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It just can't be. So in this dream world of mine, there would be a drug on the shelf, a long live drug, a very cheap drug,

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something orally available that people, governments, countries could stockpile if they so decided.

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And that way you don't have to know the exact structure of that incoming virus.

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Maybe all you want to know, and even that you can find out very quickly is does a virus need sugars to survive or not?

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Oh, I never finished that question. Why do viruses need it? Obviously, one one reason is twofold.

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The envelope like proteins, and that's where we attack it. The other reason is they cover themselves in this code of sugars because that.

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Is there little code that makes them evade the immune system so they can hide themselves in a code of sugars?

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Because the sugars for us look like cells because we, after all, put them onto these viruses, that this is a big reason why viruses need sugars.

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So camouflage as a camouflage. So they need it for two reasons.

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They need to fold properly.

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And if you prevent them from folding properly, they are often non-infectious or less infectious and they can't mutate around it.

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Yeah, so I lost my well, I think you've brought us because we've now mentioned COVID several times.

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I think I'm going to take yeah, vaccines the most important but we should not neglect.

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Yeah. Also trying to find a drug and the dream would be to have something already there that no matter what virus comes around the corner,

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you could give it safely because you would have done all the toxicity studies before and with all the time in the world there is.

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So you don't have to have this panic and this rush at the time and it's too late.

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So we've got to the point where I ask you, as I've asked everybody,

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can you remember when you first heard about SARS-CoV-2 and if there was something happening in China?

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Yeah. And that it might be quite serious.

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I remember that very well because my birthday happens to be on the 31st of December and I love Venice and I had a bit of a birthday party in Venice.

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And of course, Venice turned out to be the epicentre of the European first cases coming over.

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And yeah, so I was in Venice when I heard that I think on the 21st of December when there was,

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you know, chatter on the radio about this, we didn't take it seriously at that time.

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I didn't, I would not expected it to be like this and yeah, and we flew home, went back to work.

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When did I really start thinking that was serious? Maybe. Yeah, first half of January.

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And. And when did you and your colleagues decide that it was time to drop everything and focus your attention on?

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I think immediately at that point, I remember when there was a first talk about all the department would have to close down.

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I thought, surely not to virologist, that's a long time. We can maybe do something useful for a trying.

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And I remember thinking about all the practical issues,

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but because we were also supposed to move from like a biology institute which had been our home for, in my case over 20 years to this new building.

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So all of this was going on, the plan move.

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And I said to my group, I remember that. I said, You know, guys, if they close this down, this will be many, many, many, many months.

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And my group didn't believe it, you know, and we made this little bet, you know, it's on on a few weeks we'll back on the council, sat down and said,

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no, I said, we will never be back before I think I guessed September or something, which at the time sounded absolutely outrageous.

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But I thought if this is for real, then yes, we will be closed for a long, long time.

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But I didn't know how bad it would get. So at that point we were thinking about what we could do if we were allowed to work.

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And I have to say that our head of department, Professor Francis Barr, was incredible when it came to making it possible for us to continue working.

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You know, we got letters from him saying these are the essential workers.

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They have to continue work or they should be allowed to continue working.

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The thing is that the biochemistry department isn't that well set up for doing these kind of experiments.

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We don't have these viral hoods or this containment level up that we need for something like SARS Cov two.

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And so what I normally do in my normal life are main viruses at the time dengue virus.

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So these are bloodborne viruses. They are also containment level three viruses.

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And in fact, dengue also happens to be a schedule five virus, one of these terrorist list viruses.

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But our rooms where we work routinely are more and so are in the middle of our building just across the road.

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And again, the director there, Professor Paul Kleinerman, incredibly helpful and would do anything to help anybody who's also a clinician.

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So he was already, I think, knowing what was coming their way and he knew that it would be very busy,

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but he immediately said he would help and make sure that you can work, which was just fabulous.

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And then it was actually the done school to have a containment level three.

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And that was very much as far as I know, started by Professor William James.

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And of course, we know each other. We all know each other.

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So he contacted me quite early on in March, I want to say, and said, look, you know, we have these we try to turn this into code up.

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He try to get the virus from colleagues. I live in Glasgow and eventually I think you got it from South Africa.

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And he wasn't he.

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I hope I say this correctly, but he wasn't that much interested in the drug development part,

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but he was more interested in screening antibodies because obviously people try to get biologics going on,

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antibodies going, and we knew very quickly that we would be absolutely overwhelmed by the demand for this.

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And so early on, he said. Nicole, would you like to take care of anything to do with drug screening?

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And we do anything to do with antibodies and antibody screening and maybe get involved in the vaccine trials and so on.

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And of course, that is where naturally our interests fall. It makes total sense.

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And so I was incredibly glad that you allowed us in because what was a problem was a scarcity of resources.

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And by that I mean hoods. I think for the first months, a few months, we had only two tools in all of Oxford.

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We could do this kind of high tide to SARS-CoV-2 work in.

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You can work on it when it comes from patients because it's actually quite low.

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And but for our kind of work, we need to grow these viruses up to really high titres and then because then we need to screen the drugs against it.

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So it is a slightly different safety issues here.

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And so we were allowed to do this and I was incredibly lucky yet again that one of my longest standing workers,

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Michel Hill, almost missed me at that time. Over ten years.

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She's she actually after this left work in the in the down school, she was trained to very high levels,

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not only at blood borne viruses, but also airborne viruses, which is slightly different training.

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You have to learn different things, nothing which is unsurmountable.

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So she very quickly trained up my group, the people who were virologists in my group and trained them up to do this.

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And yeah, they started screening for four drugs in the Dunn School and later on Pokeno and made available a room

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out in the middle of all so we then could move our antiviral drug screening into the Medawar building.

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We got internal COVID grants within as well. Took it out that that lab was wonderful.

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I've got to I've got to. You go ahead. I've got to. QUEST Because otherwise I think it was well, first of all, it's.

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So what was your what was your plan? What what what was it that you absolutely do?

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So as you know, normally so the plan was there is no drug against this virus.

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What do we do normally to develop a new drug takes between 10 to 15 years.

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We don't have this time. So all we could do was to start screening already approved drugs, so so-called repurposed drugs.

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And if none of them were to work, then slowly work our way down to drugs that were in phase three, somewhere in phase two,

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somewhere, you know, drugs that could possibly be approved much faster than little early beginners drugs,

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you know, And because we had so we wanted to start Exactly that was an algorithm you know whatever people so getting

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excited yet again because that was obviously our lifeblood and we were all talking the whole time.

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It was very intense. What do we do? What can we do? What can we meaningfully contribute to this worldwide effort given that we had only two hoods?

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We are we were the opposite of a high throughput screen.

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We hoped we knew that the people in the world who could do this, that's like, for example, in Riga, that,

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you know, Johan nights the, you know, in life and the highest throughput institutes of this world,

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the big ones at Scripps in America,

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we knew that they would kick into action and scream but they screen no but but they screamed on, on, on, on Vero Cell.

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So these are African green monkey kidney cells. And that is fine because they grow very quickly.

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You can do these high throughput screens. But then we want to add something that is useful to the world, right?

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So if you can't be fast anyway, if we are slower than all the rest, let's let's add quality rather than quantity.

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And so we knew that host cells are incredibly important, you know, determines what cell type you put a virus in and put the drug on.

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That makes all the difference. And so we thought, okay, if it can't be fast, we should at least use a lung epithelial cell, human cell type.

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So we work with these coloured cells that were given made available to us by let's see more here in oncology.

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Very kindly, you just say the name of Glenn C o Khalil three cells.

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Carlos. Three slices of human lung epithelial cells. From?

355
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Yeah. Yeah. How do you spell Kelsey et al?

356
00:35:44,500 --> 00:35:52,409
You? Oh, just like it. Yes, yes, yes. I'm trying to remember whether I ever knew what that stood for, but I don't think usually they.

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They tend to. Sometimes. Yeah. I don't know. Yes, I don't know.

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Um. And so we got these cells, end of March already.

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We had all the paper work again. Michelle Hill was incredibly essential for that.

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Together with William James and his group in the Dunn School, they made all of this possible.

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Just starting a lab, proving that you are proving that you can work in it and that level.

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I spoken to Becky. Oh, good. Yeah, that was. Yes, they seemed like Becky, but she was incredibly instrumental in this.

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And from my side of was Michelle Hill. So these two work together.

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Did all the soaps, all the protocols, make sure we were obviously safe and adhering to all the rules,

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which sometimes struck us as a little bit odd, I have to say, because we obviously were surrounded by COVID.

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When you just go outside and then in this lab we were, you know, but, you know, that's life and that's how it should be.

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So I losing my track.

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So yeah, me too. Just talk about. Yeah, So we wanted to have quality, so we wanted to have more physiologically relevant cell types.

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Then we asked all our colleagues in Oxford, I got in touch with Helen McShane,

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with, uh, Duncan Richards, with some people, with Peter Horby, who did the trial.

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And we said, Look, if you have anything that you think you want to screen and you want to have a quick look and see in the cells,

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whether it does anything against this virus, let us help you. And the other way round, we wanted to inform them if we had something interesting,

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but at the end of the day, more often than not, we ruled out drugs rather than in.

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But if you ask me, like was any other scientific result, the ones that don't work are just as important.

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Because if you waste all your time screening hydroxychloroquine, say, you know, far fetched example, right?

376
00:37:40,350 --> 00:37:44,190
Then you have wasted the time for drugs that could have had a better chance.

377
00:37:44,190 --> 00:37:45,540
So yeah,

378
00:37:45,540 --> 00:37:53,180
So I was in touch with these clinical committees and we would chat and we had a lot of ideas and I don't know whether they were ever followed up on.

379
00:37:53,190 --> 00:37:59,400
I had an McShane set that there was a GP and again, her name escapes me just now sadly.

380
00:38:00,030 --> 00:38:05,280
Who was interrogating GP databases? Are there other drugs that people anyway take for something else?

381
00:38:05,970 --> 00:38:09,030
And then statistically they just happened to get caught?

382
00:38:09,420 --> 00:38:13,020
Not that often or maybe worse, you know, the worst case scenario.

383
00:38:13,920 --> 00:38:18,480
And so we would we would report back to them. That was. Julia Hipsley Was it?

384
00:38:19,350 --> 00:38:22,830
Yes. Yeah, it was. Talked to her, yes. Wonderful.

385
00:38:23,580 --> 00:38:31,120
So yes, exactly. Yeah. But in the end, long story short, by now I just checked the web page disastrous.

386
00:38:31,140 --> 00:38:39,390
So then the other added value was we didn't want in the whole world, the resources was a bottleneck for screening.

387
00:38:39,390 --> 00:38:42,870
We didn't want other labs to have to redo screens as they already were done.

388
00:38:43,260 --> 00:38:48,270
So if you do this just in your little locked away lab, you know,

389
00:38:48,270 --> 00:38:55,919
you waste a lot of resources worldwide at the same time on that from Delft and her group with to undergo and

390
00:38:55,920 --> 00:39:01,260
least become ill they all helped us setting up the SA structure web page because we were busy screening,

391
00:39:01,260 --> 00:39:05,610
you know, and they were fantastic. It was a web pages and on that it's just that way inclined.

392
00:39:05,610 --> 00:39:12,209
It's amazing. You know, she's she wants to share. She wants to make sure it's out there that people don't waste their own resources.

393
00:39:12,210 --> 00:39:15,060
We're doing something we already disproved or maybe said it was good.

394
00:39:16,500 --> 00:39:22,740
So we started the SA strike as all their group would mine the literature for everything that was published,

395
00:39:22,950 --> 00:39:25,290
so we would know what other people already screened.

396
00:39:25,290 --> 00:39:30,690
So we, we basically our decision tree, what we would screen was is it already approved that would be screened first.

397
00:39:31,290 --> 00:39:33,120
It could be immediately repurposed if it worked.

398
00:39:33,810 --> 00:39:38,610
Ideally, it would be generically available off patent because we wanted something that could be very quickly,

399
00:39:38,610 --> 00:39:42,360
very cheaply produced to help maybe the whole world, not just, you know,

400
00:39:42,360 --> 00:39:47,370
the ones who could afford it and then down the, you know, clinical development path.

401
00:39:47,820 --> 00:39:51,930
And so they scoured the literature and they would update the source tracker,

402
00:39:52,170 --> 00:39:55,979
I think at the time, at least weekly, if not daily, and we would do the same.

403
00:39:55,980 --> 00:40:01,620
We would actually physically screen the drugs and our all our results would be out on the SA strike.

404
00:40:01,830 --> 00:40:11,340
So the kinds of things I neta were looking for, they'd been screened possibly just through some kind of computational process or at that at that time.

405
00:40:11,700 --> 00:40:15,809
So at that time, at that time we're now talking March April that you actually started this.

406
00:40:15,810 --> 00:40:23,880
At that time the Moonshot Program consortium hadn't arrived yet at their first,

407
00:40:24,090 --> 00:40:33,719
so they started having their fragment based screens in March and the first compounds that they had available for us to screen was around June time.

408
00:40:33,720 --> 00:40:39,990
Oh, right. Okay. So we were ready and we had screened, so we thought we were really very I'm.

409
00:40:40,040 --> 00:40:50,359
Biased and very fair. Even our own drugs, which we were dying to test, we d prioritised because they were not yet approved.

410
00:40:50,360 --> 00:40:53,659
Right. So they all were in a queue and I checked on that.

411
00:40:53,660 --> 00:40:56,450
Of course we will help the moon. That's what we want to do.

412
00:40:56,690 --> 00:41:04,339
But the moonshots have to be in the queue and for them that was the lowest of the low because this was a totally unknown and you know,

413
00:41:04,340 --> 00:41:09,979
the very early starting point. But I also said, you know, if we are getting faster and better,

414
00:41:09,980 --> 00:41:15,620
by the time you have those treatments ready, maybe you anyway won't have to wait in the event.

415
00:41:15,620 --> 00:41:16,670
That's exactly how it would happen.

416
00:41:16,680 --> 00:41:22,879
We were through with everything we could have screened By the time the moonshot on the Moonshot Consortium had their first things,

417
00:41:22,880 --> 00:41:28,850
they wanted to ship to us. And so we and the other algorithm we had is like, Can we get to these drugs?

418
00:41:29,090 --> 00:41:32,470
Honestly, that was a very pragmatic point. Like, can we get distracted?

419
00:41:32,600 --> 00:41:35,330
And we got an internal COVID 19 grant.

420
00:41:35,360 --> 00:41:43,490
I think in the first round I just asked for money to buy all the drugs I could buy to screen, and I got that money of university fund.

421
00:41:43,520 --> 00:41:46,610
That's right. That's like from donors. That's right.

422
00:41:46,760 --> 00:41:51,380
Exactly. So from that first money I bought all at the time there was a paper published.

423
00:41:52,420 --> 00:41:56,360
Krogan was a senior researcher and they had already done a screen and said,

424
00:41:56,720 --> 00:42:00,380
These are all I was so interested because they also looked for host targeting as well.

425
00:42:00,590 --> 00:42:07,250
And he said, These are all the proteins that somehow change when there's a SARS-CoV-2 infection and all these drugs,

426
00:42:07,970 --> 00:42:11,990
all the ones that were available to buy on the open market, we bought in and screened.

427
00:42:12,440 --> 00:42:16,270
But yeah, even our own I mean, it sort of had to wait until it was a ton and,

428
00:42:16,410 --> 00:42:22,700
and it is two of the moonshot companies had to wait but we could screen them all eventually.

429
00:42:23,510 --> 00:42:28,100
We have never stopped screening moonshots and Moonshot, as you may or may not know, has continued very well,

430
00:42:28,100 --> 00:42:36,530
and we're ever closer to our clinical trial, I hope, and ours, when it was our turn to screen the initial us.

431
00:42:37,340 --> 00:42:43,430
By that time we had also all the variants of concerns which we also had all gotten into the screening lab.

432
00:42:43,440 --> 00:42:54,080
So we had the original strains altered, Delta and Micron and all the other ones, the Brazil strain and so on and the immune issue,

433
00:42:54,090 --> 00:42:58,040
this work against all of them, you know, not just against the original, against all of them.

434
00:42:58,040 --> 00:43:01,040
So exactly what we would have hoped is true.

435
00:43:01,610 --> 00:43:09,259
And that came out about. Yeah. And I also like the timing of this, this so-called single high dose paper that we published.

436
00:43:09,260 --> 00:43:13,280
You know, I had submitted that in January 2020.

437
00:43:13,520 --> 00:43:20,030
It came out in March. So we didn't know about COVID, but we submitted, wrote the paper, we didn't know.

438
00:43:20,330 --> 00:43:29,470
And I wrote in the discussion, this is what you need when whenever there's a pandemic, you know, and I just can't believe it, you know that.

439
00:43:29,480 --> 00:43:31,040
And then there was certainly a pandemic.

440
00:43:31,280 --> 00:43:41,330
But yeah, we were to be honest, at the beginning, I thought, okay, if not now, when, you know, when will they allow us to try a host targeting?

441
00:43:41,570 --> 00:43:45,080
But I didn't happen. It didn't happen.

442
00:43:46,310 --> 00:43:53,180
Of course, the world had had, you know, in a panic or in an emergency, you don't try out new things.

443
00:43:53,180 --> 00:43:59,540
You know, everybody does what they do best, understandably. And that's not when you try out a new strategy, I guess.

444
00:44:00,110 --> 00:44:04,399
But I just don't want to miss, you know, even when I lecture virology,

445
00:44:04,400 --> 00:44:08,650
like for the last 15 years, you know, I always said, oh, we need a host targeting percent.

446
00:44:08,810 --> 00:44:13,250
But my first slide always would say, because that's what you need to be prepared if there's a pandemic.

447
00:44:13,250 --> 00:44:17,750
And of course, nobody takes that serious in all honesty, including myself.

448
00:44:17,750 --> 00:44:22,040
You know, you say these words and you say, yes, look at it. The intervals get smaller and smaller.

449
00:44:22,820 --> 00:44:28,130
You know, it is not a question only sentence. It's not a question of if, but when it comes.

450
00:44:28,640 --> 00:44:32,450
But do we really believe it the second we say it? I don't think we ever did.

451
00:44:32,900 --> 00:44:35,050
And now I look at this licensing, of course.

452
00:44:35,270 --> 00:44:42,049
So but of course, I'm not saying why did nobody listen, because that is in human nature, including my own.

453
00:44:42,050 --> 00:44:52,010
You know, you before the pandemic, you write this as like your unique selling point when you're trying to attract maybe grant funding or new strategy,

454
00:44:52,340 --> 00:44:58,610
but now just feels just so much more real. You know, you look at you said you just looked at the numbers.

455
00:44:58,610 --> 00:45:09,620
So how many How many? Yes. So why now? We have screens and things that I remember that, uh, 1834 entries in the South America.

456
00:45:09,680 --> 00:45:16,129
Yes. Yes. So we are now we have obviously stopped all but the moonshot ones now.

457
00:45:16,130 --> 00:45:18,890
So we're only screening moonshots compounds now.

458
00:45:19,520 --> 00:45:24,499
And this is all around the clinical needs that we have just too, because they are constantly trying to improve.

459
00:45:24,500 --> 00:45:35,210
And so we're constantly screening them. And how many of them have turned out to be a promise to to pursue further of the moonshots or just generally?

460
00:45:37,340 --> 00:45:42,389
Well, I think all the ones that actually made it into the. They didn't possibly, in all honesty,

461
00:45:42,390 --> 00:45:48,450
made it into the clinic because of this all strike at a cost to the the ones that were really needed, like remdesivir and so on.

462
00:45:49,530 --> 00:45:57,270
And and thanks, Senator. Thank you. Peter Hall We had already done Inhumans, so basically he had done the much more relevant study first.

463
00:45:57,430 --> 00:46:03,060
Right. So I can't I can't tell you whether anybody took this serious apart from us,

464
00:46:03,270 --> 00:46:06,990
you know, whether anybody said, oh, you know, maybe that's the one we will use.

465
00:46:07,000 --> 00:46:15,510
I don't know. I hope you prevented lots of people to waste a lot of resources, energy, what, as you say, excluding you, Excluding to.

466
00:46:15,640 --> 00:46:22,800
Exactly. Yes, yes, yes. And you never know. I mean, we didn't know whether we would find that one thing that, you know, you always hoped, you know.

467
00:46:23,460 --> 00:46:32,120
But. Yeah. And you say, but you did get a that although it hasn't gone on to be used in the clinic, you did get a positive result from the illness.

468
00:46:32,420 --> 00:46:36,380
Yes. So were you also pursuing that as a research?

469
00:46:36,560 --> 00:46:43,820
Very actively, Yeah. That's I mean, that has been my research before the pandemic and even more so now.

470
00:46:43,820 --> 00:46:51,490
And I really do not want to sound glib, but I did exactly what I thought I would do against the original virus, against all the variants of concern.

471
00:46:51,500 --> 00:46:55,310
That is the beauty of a host targeting and the initial approach.

472
00:46:56,040 --> 00:47:02,870
And once one variant, once I knew would work against the original strain, I knew it would work against all the escape.

473
00:47:03,080 --> 00:47:09,559
But it's not escape. These variants of concern, obviously, that try to get around, say, the rolling out vaccines, you know,

474
00:47:09,560 --> 00:47:17,720
and vaccines, even the the newer platforms, as they have RNA vaccines, they can switch very fast.

475
00:47:17,730 --> 00:47:21,620
That can make a new vaccine very, very quickly that just, you know, switch.

476
00:47:22,490 --> 00:47:28,910
And but even though, you know, it takes a few months, you know, the new virus arrives, you have to look at this even that.

477
00:47:28,910 --> 00:47:31,430
You have to make a new M RNA vaccine, blah, blah, blah there.

478
00:47:31,430 --> 00:47:39,170
Whereas this is there, the drugs that to say on day one will work against it until the last viruses got hopefully gone, you know.

479
00:47:39,740 --> 00:47:47,570
And so I just think it is such a worthwhile strategy to pursue and I and we suppose you would and we will continue to pursue it.

480
00:47:47,720 --> 00:47:57,200
So at the moment we are trying to get funding for a phase one clinical trial for what we call the single high dose approach against what.

481
00:47:57,230 --> 00:48:05,270
And so we decided as the most likely because of the patient availability, more often than not, it's very difficult to power a dengue trial.

482
00:48:05,840 --> 00:48:14,870
So we will go for influenza and or against a COVID human challenge in a cold human child study,

483
00:48:15,500 --> 00:48:21,260
because then we know exactly that's when when they get COVID and we give it, you know, 8 hours later, 10 hours later,

484
00:48:21,270 --> 00:48:25,849
whatever, and we see whether we can prevent symptoms again,

485
00:48:25,850 --> 00:48:35,450
clinical endpoints is is is difficult because obviously you you don't let these poor people die in the clinical and Human Challenge study.

486
00:48:35,870 --> 00:48:44,000
So, yes, I think it will be most like in influenza trial because we know we have tens of thousands of people dying of influenza every year and.

487
00:48:46,690 --> 00:48:51,110
Nobody talks about it. And what are the obstacles?

488
00:48:51,360 --> 00:49:01,010
Because the lab work looks so encouraging. And obviously all the you know, the the philosophical theoretical approach seems absolutely bang on.

489
00:49:01,020 --> 00:49:05,510
So what about the obstacles? What? Who are they? Yeah, that's how you do it.

490
00:49:05,520 --> 00:49:11,729
I don't know. I know it's funny. I often say do I portrayed wrongly because you say it's all bang on.

491
00:49:11,730 --> 00:49:15,060
But obviously that's not what the regulatory people think.

492
00:49:15,630 --> 00:49:21,270
Obviously, that's not what most companies think, what most drug developers think.

493
00:49:21,600 --> 00:49:25,049
And I never know. Is it is it a groupthink?

494
00:49:25,050 --> 00:49:35,310
Is it because it all came through the direct acting? Is it is it that we only tried not as personally the company we work together

495
00:49:35,310 --> 00:49:40,230
was at the time emergent biosolutions they they failed And I and the FDA,

496
00:49:41,280 --> 00:49:48,780
they I don't know all the ins and outs but they were asked to come back with more results.

497
00:49:49,440 --> 00:49:51,990
They did a phase one for the three times daily.

498
00:49:52,140 --> 00:49:56,400
They were allowed to proceed to phase two, but they stopped it at the time because the pattern was running out for them.

499
00:49:56,400 --> 00:49:57,300
It wasn't as wild.

500
00:49:57,990 --> 00:50:05,550
And so we don't care for the patents, you know, together with Professor Dweck, I would be helpful if we can get a generic, very cheap drug out there.

501
00:50:05,880 --> 00:50:08,190
For me, it's quite nice that the patents are running out, you know,

502
00:50:08,190 --> 00:50:14,549
so and we could make it in large quantities and it's and I believe it is very safe.

503
00:50:14,550 --> 00:50:20,370
We just need to need to know now because we really don't how high we can go and should go and humans.

504
00:50:26,870 --> 00:50:29,299
So we're trying to get that money. Who are they who prevent us?

505
00:50:29,300 --> 00:50:34,480
Well, at the moment we're trying to find the money to make GMP material, not have a commercial partner at the moment.

506
00:50:34,550 --> 00:50:39,470
At the moment we don't. And we are in discussion with several potential partners.

507
00:50:40,400 --> 00:50:46,610
But at the moment we don't know. As I said to you, we haven't run out of options yet.

508
00:50:47,480 --> 00:50:50,240
So there's the funders and then there's the regulatory bodies. Yes.

509
00:50:50,240 --> 00:50:58,540
And my problem, honestly, I think one of the problems is I am not a translational clinician, so I'm here to binge.

510
00:50:58,550 --> 00:51:02,600
I'm pushing it further towards translation than most Spanish based scientists do.

511
00:51:03,080 --> 00:51:06,310
And then there are people like Annette, and that's why this is so fantastic.

512
00:51:06,370 --> 00:51:07,219
If you happen to know what you know,

513
00:51:07,220 --> 00:51:14,720
then friends who kind of are exactly in that gap because she is a medic and she knows how to get something from here to then into the clinic.

514
00:51:15,140 --> 00:51:20,810
And this is this not very densely populated area where very few experts are.

515
00:51:21,080 --> 00:51:29,330
And the ones that exist, like the clinical developers, they tend to be all on the ace.

516
00:51:29,660 --> 00:51:37,549
And I said, you know, Annette, we need to find somebody who just gives us a very unbiased idea what a clinical study has to look like.

517
00:51:37,550 --> 00:51:37,760
You know,

518
00:51:37,760 --> 00:51:45,680
surely you have to tell us how an experiment has to look like or a clinical trial has to look like all the pre-clinical trials have to look like that.

519
00:51:45,680 --> 00:51:49,040
You feel comfortable enough as a clinician to take this further.

520
00:51:50,000 --> 00:51:53,329
And we have sent us to various, I think,

521
00:51:53,330 --> 00:52:05,510
two or three of such consultants who where we explained and the answers we are getting back ranged from why do you bother?

522
00:52:05,510 --> 00:52:10,030
We have oseltamivir you to 2 to 2.

523
00:52:10,580 --> 00:52:16,700
This is dangerous, this is horse targeting. And yeah, I think the fold is on our side.

524
00:52:16,880 --> 00:52:26,310
The education, the explanation. I have to just become much more patient and explain much better why I think

525
00:52:26,310 --> 00:52:31,730
this is a good idea rather than assuming that everybody thinks they get it.

526
00:52:31,730 --> 00:52:36,629
So maybe I'm saying it wrongly, you know? Yeah, I think I need to possibly go out there more.

527
00:52:36,630 --> 00:52:44,220
And but I remember when I first talked about it, my first postdoctoral conference, I was a young postdoc in 1999.

528
00:52:44,270 --> 00:52:51,480
I was in Italy and they had almost the equivalent of pulled me off the stage when I dared to say,

529
00:52:52,260 --> 00:52:56,370
we are we are trying to take this and, you know, inhibit these enzymes.

530
00:52:57,990 --> 00:53:04,120
And this was an HPV audience, and it was possibly one of my worst conference experiences I had.

531
00:53:04,150 --> 00:53:07,350
And of course, I was also young and I was an easy target.

532
00:53:07,890 --> 00:53:12,030
Things have changed slightly. But that wasn't encouraging.

533
00:53:12,120 --> 00:53:19,440
Mm hmm. So you mentioned earlier that this kind of drug is already in use and licensed for girls to see.

534
00:53:19,470 --> 00:53:25,200
Yes. Just explain a bit more. What is this disease And and do the people who are taking it.

535
00:53:25,680 --> 00:53:30,750
Yes. And benefiting also suffer side effects and does because you've gotten a sample?

536
00:53:30,790 --> 00:53:31,750
Yeah. Yeah, of course.

537
00:53:31,990 --> 00:53:43,500
It's the problem is that example is not a is a fraud example is that the level of drug you need to be efficacious against that disease are much lower.

538
00:53:43,680 --> 00:53:46,979
And that's where we started with our antiviral drug is three times daily.

539
00:53:46,980 --> 00:53:53,580
I think they take 200 packet per day, these patients for many, many years at that level.

540
00:53:54,690 --> 00:53:59,969
Against some viruses you can be antiviral but not against the ones we really want to talk about.

541
00:53:59,970 --> 00:54:06,630
You need to go higher than that. And disease is a it's an inherited condition.

542
00:54:07,240 --> 00:54:12,210
Uh, yes, you've got your ex front.

543
00:54:12,330 --> 00:54:15,450
It's not, but it's a lysosomal storage disease.

544
00:54:15,840 --> 00:54:22,800
So the glycol lipids in the glycol pathway, there's an enzyme that also, uh, deals with glucose while ceramide.

545
00:54:23,010 --> 00:54:26,879
So it recognises glucose and binds to glucose was a bit of a fairytale.

546
00:54:26,880 --> 00:54:35,280
So exactly what alter binds to immuno sugars And it is a substrate reduction therapy whereby you meaning sugar,

547
00:54:35,610 --> 00:54:42,900
inhibits that enzyme, you just make less of the product that is building up in these patients and causes the storage disease.

548
00:54:43,380 --> 00:54:52,290
So it's a substrate reduction therapy and the own and, and it's very comparably quite cheap because the only other, uh,

549
00:54:52,320 --> 00:54:58,139
therapy for that disease is an enzyme replacement therapy whereby you give working

550
00:54:58,140 --> 00:55:02,840
copies of the enzyme that is faulty and it is an inherited disease in those patients.

551
00:55:03,600 --> 00:55:10,259
Yeah. So immune to sugars invading is out the middle start it's called and it's been in patients for a long,

552
00:55:10,260 --> 00:55:16,799
long time and there are no these kind of toxicity issues to to worry about.

553
00:55:16,800 --> 00:55:25,230
Of course this is also a patient population that already has a totally different kind of and yeah weaknesses to stop this.

554
00:55:28,090 --> 00:55:33,840
Hmm. Yeah. You can't use them as saying, Oh, look, it's safe because we would have to go higher.

555
00:55:34,110 --> 00:55:37,330
We need to prove it's it's safe at higher levels.

556
00:55:37,350 --> 00:55:41,969
Having said that, when I started work on viruses, I worked on these long chronic viruses, hepatitis C,

557
00:55:41,970 --> 00:55:48,000
But as we I gave that one up at some point working with dengue and all this acute virus,

558
00:55:48,000 --> 00:55:53,370
because I was thinking, everybody always tells me the side effects are the problem.

559
00:55:54,870 --> 00:55:58,229
Then the longer you have to be on that drug, the worse if you have an acute viral infection.

560
00:55:58,230 --> 00:56:04,920
Dengue. Five days done. If you only have to give a drug for five days, maybe.

561
00:56:04,920 --> 00:56:11,040
And it might sound very naive, but maybe you can get away with, you know, shorter tox studies.

562
00:56:11,040 --> 00:56:15,990
Everything is also cheaper. But also you don't put this onto an organism for that long.

563
00:56:32,480 --> 00:56:39,620
Just like the penicillin experiments. So I thought that surely if that doesn't convince people that I really don't know what,

564
00:56:40,340 --> 00:56:45,470
but I know I'm obviously biased, but maybe I'm allowed to be biased because I have input.

565
00:56:45,740 --> 00:56:49,840
Putting 20 years of my my life and energy and love into this.

566
00:56:50,190 --> 00:56:54,230
Yes. Yes. Yeah. Yes. So go going.

567
00:56:55,010 --> 00:56:58,850
Moving on to your personal experience of working through the virus.

568
00:57:00,110 --> 00:57:05,120
How threatened did you feel by the possibility of actually getting the infection yourself?

569
00:57:06,980 --> 00:57:12,970
I don't know why, but strangely, not at all. Because I got it almost immediately at the beginning of it.

570
00:57:13,040 --> 00:57:16,400
We were closing down the lab and everything. I believe I might have.

571
00:57:17,540 --> 00:57:23,510
I know that one of the posters I finished a paper with and his children apparently had it quite early on.

572
00:57:24,260 --> 00:57:30,379
And I think then he became evil. And then I will do so in in March, April 2020.

573
00:57:30,380 --> 00:57:34,100
I had it for the first time, but I was so busy.

574
00:57:34,100 --> 00:57:40,700
Seriously, I was so busy working. That was exactly when we tried to get the screening lab up and running.

575
00:57:41,960 --> 00:57:49,490
And, you know, if you don't feel at death's door, which I didn't and I didn't have enough time to really worry,

576
00:57:49,490 --> 00:57:56,030
but we were on teams with my group all day long, and some of my team members are medics and and they were worried.

577
00:57:56,030 --> 00:58:04,669
And I remember one of my students is also an infectious disease because she sent me by a by post one of these oxygen monitors.

578
00:58:04,670 --> 00:58:06,260
Yes. But I said, try this.

579
00:58:06,260 --> 00:58:13,280
You know, these people could have low oxygen and not really not realised with this oxygen that they ten and all the rest of it,

580
00:58:13,280 --> 00:58:21,859
you know, is important. So I wore this. It's I had COVID twice so that time and then again on July 22.

581
00:58:21,860 --> 00:58:25,249
So I had the original straight ahead Omicron in both case and of course,

582
00:58:25,250 --> 00:58:31,430
vaccinated by the time by that time I had lots of shots in me and totally different

583
00:58:31,970 --> 00:58:36,470
disease progression and both cases totally different and symptoms as well.

584
00:58:36,920 --> 00:58:45,469
So the first time I had it was a scare. I got a little bit scared when so my oxygen levels never were really low, but because obviously it might not.

585
00:58:45,470 --> 00:58:49,610
Obviously I'm living on my own. I'm alone in the house. I.

586
00:58:50,930 --> 00:58:58,190
There was a the lab came up with this incredible support network and I have a dog that needs to get walked.

587
00:58:58,490 --> 00:59:05,330
So I would put by, you know, lay food at the door, walk the dog, check up on me and that oxygen monitor, actually,

588
00:59:05,330 --> 00:59:11,570
that became to the oxygen monitor for the whole family, because they all got but they got really I mean, they got really ill.

589
00:59:12,380 --> 00:59:18,140
I mean, I think no, no, not not hospital ill, but, you know, really blue lips and all that kind of stuff, you know?

590
00:59:18,690 --> 00:59:21,739
Yeah. I can't remember being scared.

591
00:59:21,740 --> 00:59:28,069
I remember I was due to give a COVID conversation and I know I couldn't string two sentences together.

592
00:59:28,070 --> 00:59:31,250
I couldn't remember at the end of the sentence how I had started the sentence.

593
00:59:31,250 --> 00:59:34,400
So I said, I can't give this conversation. And this is the video.

594
00:59:34,520 --> 00:59:38,390
Yes, exactly. And so I gave mine a few weeks later.

595
00:59:39,140 --> 00:59:43,940
So I know that I wasn't quite right because I would not have otherwise cancelled that talk.

596
00:59:45,650 --> 00:59:50,390
And. Yeah, and how so how was your ability to work effective?

597
00:59:50,400 --> 00:59:55,250
So you were I mean, were you once you got over your infection, Where you coming into the lab?

598
00:59:55,580 --> 01:00:00,080
No, I wasn't useful in the lab. You know, I think I would have been a burden.

599
01:00:00,380 --> 01:00:05,570
The people who were at that point, because they had a certain number maximum allowed in the COVID lab,

600
01:00:05,900 --> 01:00:08,300
because I shared it with James and other groups.

601
01:00:09,380 --> 01:00:15,710
We had a time schedule, and you needed two people working at the same time, but I would have just been an extra body.

602
01:00:15,920 --> 01:00:24,319
It does. I don't need to be. I'm not the one pipetting, you know. So I stayed at home very much felt like the bridge of the Enterprise, right?

603
01:00:24,320 --> 01:00:32,510
So if you talk to everybody, you try to get all the the the strings somehow together, make sure that everything runs smoothly.

604
01:00:33,500 --> 01:00:39,100
Obviously, the moonshot kickstarted at the same time for knocking on my door one night and says, Nicole, we will try this.

605
01:00:39,110 --> 01:00:40,759
We'll just ask for crowdsourcing.

606
01:00:40,760 --> 01:00:47,930
We'll do like if we get a compound, can you help us at that time aside from we're just trying to get the the screening up and running.

607
01:00:47,930 --> 01:00:50,990
Of course we will help. I don't know when, but of course we will help.

608
01:00:51,770 --> 01:00:59,960
That started then eventually the the project started the vaccine initiative, an evaluation led by Paul Newton.

609
01:01:01,070 --> 01:01:06,740
And we kept that very, very confidential for the longest time for obvious reasons,

610
01:01:08,000 --> 01:01:16,830
because as soon as there was a need for anything, criminals kick in and pollute and or who used to lead the allows.

611
01:01:17,510 --> 01:01:20,030
Oh, that's a trust saying. Paul Newton, right? Yes. Yes.

612
01:01:20,270 --> 01:01:27,889
So he's now an Oxford based in Oxford and he's leading a medicine quality control group and he had done a lot of work in in pills,

613
01:01:27,890 --> 01:01:32,240
in medicines that come in pill form, but never on liquids, never on something like a vaccine.

614
01:01:32,900 --> 01:01:40,220
And we had worked together. We had a shared dphil student, Amina Bharucha, that infectious disease doctor who sent me the oxygen monitor.

615
01:01:40,850 --> 01:01:45,800
And we had been trying because I came from LA and they knew the problems there, the public health problems, and said,

616
01:01:46,190 --> 01:01:52,069
We just need to find out who here has Japanese encephalitis and who has another fever,

617
01:01:52,070 --> 01:01:55,580
you know, just to inform the public health policies in that country.

618
01:01:55,580 --> 01:01:57,860
So we had started that. So we that's how we knew each other.

619
01:01:58,400 --> 01:02:04,820
We had started a mass spectrometry based biomarker discovery project for Japanese encephalitis.

620
01:02:04,820 --> 01:02:14,660
So when COVID then hit and then new me and he said, Look, criminals are already taking in the first vaccines.

621
01:02:14,660 --> 01:02:19,580
Fake vaccines were sold before the real ones were even available in South America.

622
01:02:20,150 --> 01:02:22,700
And so he said, you have to do something. Can you help?

623
01:02:22,700 --> 01:02:31,669
And he was this amazing ability he has of bringing the right people together and making everybody wanting to work started this consortium,

624
01:02:31,670 --> 01:02:39,620
which to this day the IEEE Vaccine Identity and Evaluation Consortium, a consent to links.

625
01:02:40,760 --> 01:02:49,370
And so that started this Parramatta's sick who is the inventor of um's sauce Ramen special offset Ramen spectroscopy,

626
01:02:49,370 --> 01:02:55,849
the kind of machines you see at any international airport, You know, the ones where you put your breast milk in and see whether it's explosive or not.

627
01:02:55,850 --> 01:03:00,049
He invented that. And so he does this also on Monday for vaccines,

628
01:03:00,050 --> 01:03:06,410
we made we started doing the mass back together with the mass spectrum from Professor James McCullough.

629
01:03:06,410 --> 01:03:15,229
It's a chemistry. So he's involved in this. And Paul offers obviously in this whole medicines quality control group, and he got us in touch.

630
01:03:15,230 --> 01:03:21,049
So we had weekly, several weekly. Teams calls trying to get this off the ground.

631
01:03:21,050 --> 01:03:27,110
And we did again with a philanthropic donations to families.

632
01:03:27,620 --> 01:03:30,860
I think they stayed anonymous and and also the Oak Foundation,

633
01:03:30,980 --> 01:03:36,200
I think a three philanthropic donors and they got us through to Now you're still working on this.

634
01:03:36,200 --> 01:03:47,210
We developed lots of techniques by which we can give hopefully, hopefully machines to inspectors and to those people somewhere out there.

635
01:03:47,480 --> 01:03:50,480
Let it be Africa, let it be, let it be anywhere in the world. It doesn't matter.

636
01:03:50,840 --> 01:03:54,260
How do you know that the thing you're about to inject into somebody is a real thing or not?

637
01:03:55,010 --> 01:03:58,819
And we were very concerned that not to talk about it,

638
01:03:58,820 --> 01:04:08,780
because obviously this is a is a very fine balance to strike between raising public worries and trying to help.

639
01:04:09,560 --> 01:04:15,290
And so all of this, we we kept confidential and we developed lots of techniques, also low cost techniques.

640
01:04:15,290 --> 01:04:22,129
So from the high end spec stuff we did here all the way to supply chain along the supply chain,

641
01:04:22,130 --> 01:04:25,430
things we could maybe techniques we could maybe use in the hops,

642
01:04:25,430 --> 01:04:32,180
in the harbours were shipments arrive all the way down to the nurse GP you might or the pharmacist

643
01:04:32,180 --> 01:04:37,850
who takes it off the shelf how to detect what may or may be a fake or a substandard vaccine.

644
01:04:37,850 --> 01:04:44,360
That's the other problem that can be fakes, a criminal fakes, but they can also be things that were standing on the runway.

645
01:04:44,650 --> 01:04:51,080
Yeah, exactly. Yeah, exactly, exactly. Yeah. So that if you tell them about fake malaria drugs, you to ago.

646
01:04:51,080 --> 01:04:52,220
Years ago. Yeah. Yeah.

647
01:04:52,340 --> 01:05:03,079
So yeah so that is what that that the consortium honestly a consortium of so many so well-meaning people that really got me through the pandemic.

648
01:05:03,080 --> 01:05:08,680
I think that and my own group who were just absolutely fabulous you know this whole screening, they worked 24 seven.

649
01:05:08,810 --> 01:05:13,530
Nothing was too much for them. You know, they would go out of the way. I think they including myself.

650
01:05:13,530 --> 01:05:17,089
You also felt very privileged that it could work because we had news, the other colleagues here,

651
01:05:17,090 --> 01:05:23,479
they couldn't you know, only only things that had to do with sales could continue projects.

652
01:05:23,480 --> 01:05:28,340
And so we were glad that we could work and do something because I think it really hurt.

653
01:05:28,340 --> 01:05:31,600
Mental health. Exactly. That's it. That's one of my questions.

654
01:05:31,850 --> 01:05:38,179
Yeah. Because some of the students in my group who were not on any of so were not trained virologists who are chemists doing something else.

655
01:05:38,180 --> 01:05:44,630
You know, they couldn't come in, you know, and they had a much tougher time of it than the people could just do something,

656
01:05:44,840 --> 01:05:47,240
you know, And even if it's a lot of work,

657
01:05:47,600 --> 01:05:52,700
because none of us could go home, you know, none of us could go home for Christmas or even my my group was quite international,

658
01:05:52,700 --> 01:05:56,170
so we couldn't fly home Christmas we spent here.

659
01:05:56,180 --> 01:05:59,240
You know, we were anyway in a bubble at that point because we were working together.

660
01:06:00,100 --> 01:06:03,150
Yeah, yeah, yeah.

661
01:06:03,890 --> 01:06:08,720
And yes, yes.

662
01:06:10,070 --> 01:06:13,500
Oh yes. They all your working hours. So you talked about working?

663
01:06:14,270 --> 01:06:17,719
Well, I think. Well, I think we all worked way too much.

664
01:06:17,720 --> 01:06:22,040
We worked honestly, it failed. Obviously it wasn't, but it felt like 24 seven.

665
01:06:22,100 --> 01:06:27,229
Yeah, because obviously it wasn't 24 seven, but we were always alert and you just never took a break.

666
01:06:27,230 --> 01:06:32,060
And we're constantly talking. Everybody was talking about what to do next, how to do it.

667
01:06:32,840 --> 01:06:36,080
The early days were more exciting because just how to do it, you know,

668
01:06:36,790 --> 01:06:44,389
I think everybody goes into science at heart as a problem solver and whether it's on the bench, a scientific problem or a very pragmatic problem,

669
01:06:44,390 --> 01:06:47,690
how do I get coloured cells from up there who don't have a nobody's allowed to travel,

670
01:06:47,690 --> 01:06:52,280
you know, everything like this or where are the stores if people send us a drug,

671
01:06:52,280 --> 01:06:58,370
nobody's even here to take these drugs, you know, all these kind of little, little problems to solve.

672
01:06:58,370 --> 01:07:04,520
And we solved all of them. And the group was amazing. My group, Michelle Hill, I mentioned Julie Ball and.

673
01:07:05,650 --> 01:07:09,700
JLP up as a chemist who did all this massive amount of drug dilutions.

674
01:07:09,700 --> 01:07:14,349
You know, Michel, she had a a repetitive stress disorder because they were just honestly,

675
01:07:14,350 --> 01:07:18,220
they were pipetting through and she had to have a frozen shoulder operation, you know?

676
01:07:20,470 --> 01:07:25,030
Yeah, it was. But the group we all, to be honest, we all loved it.

677
01:07:25,270 --> 01:07:32,700
We all were. We all worked together as never before because we all have like ten different projects going on normally and everybody does a little.

678
01:07:32,710 --> 01:07:38,890
Yeah, we all are very active, but this time we felt, Oh my goodness, if we all put our expertise together,

679
01:07:38,890 --> 01:07:41,410
that's what we can achieve, you know, And that's, that's what we did.

680
01:07:41,410 --> 01:07:47,910
And, and did you I mean, I saw from your group website it you, you know, in normal times you do fun things together.

681
01:07:47,910 --> 01:07:51,850
Yeah, sometimes, yeah. Were you able to do any fun things? Well, no, no, no.

682
01:07:51,850 --> 01:07:54,999
We were not allowed to write we were not allowed to do any fun things.

683
01:07:55,000 --> 01:07:59,079
We could have thought maybe on teams. To be honest, I think I, for one, was too exhausted.

684
01:07:59,080 --> 01:08:07,060
I couldn't. I was very exhausted, I have to say. And also, there was a lot of stressful things going on at work as well.

685
01:08:08,560 --> 01:08:12,340
Yeah, it was a very stressful time. I don't think I came out of this very, very healthy.

686
01:08:12,340 --> 01:08:17,800
I have to say mentally, I think I'm very resilient, but that was some of it was too much things that happened with too much.

687
01:08:18,580 --> 01:08:24,250
And did I mean, do you think was there support available if you had access to it or do you think mental health?

688
01:08:24,280 --> 01:08:29,500
Yes. I mean, to be honest, I would typically. Right. I never thought about asking for help.

689
01:08:30,880 --> 01:08:38,650
My group is it's a family at that point anyway, you know, And they were all very supportive of me, of each other.

690
01:08:40,190 --> 01:08:43,340
The pope was good. I'm really, really proud of that.

691
01:08:44,270 --> 01:08:47,450
Are you proud of them? And you've mentioned lots of collaborations with.

692
01:08:47,450 --> 01:08:52,009
Yes. Other people. Yes. Was that a step change from how you would normally be working?

693
01:08:52,010 --> 01:08:57,860
Because I mean, one can see signs sometimes as being a bit more competitive than collaborative.

694
01:08:57,890 --> 01:09:03,530
I know there was our collaborations, but people's priorities to get to paper, written and published and be first.

695
01:09:04,280 --> 01:09:06,550
And didn't get the next grant and yeah, yeah.

696
01:09:06,800 --> 01:09:14,900
But for some people in COVID, it seemed that that went away to a certain extent, and it was very much a collaborative effort too.

697
01:09:14,930 --> 01:09:20,540
I think I want to agree that. I think I have to say that my own group and myself, we're always very open,

698
01:09:20,540 --> 01:09:24,529
very collaborative, and all our stuff was open Science and Moon Shop was open science,

699
01:09:24,530 --> 01:09:31,939
which is not regarded in the same positive light everywhere in the university and in what we did to South Africa.

700
01:09:31,940 --> 01:09:33,200
But it was open.

701
01:09:33,230 --> 01:09:39,889
None of us was in there for IP, and that's actually what we wrote out, you know, is that if you submit something to us, there's no IP.

702
01:09:39,890 --> 01:09:45,590
There's, you know, it's like, you know, you can't. We also didn't want to be used by industry as a cheap screening effort.

703
01:09:45,590 --> 01:09:52,880
Right. And that also caused some some some small rifts.

704
01:09:53,240 --> 01:09:57,590
That's not because not not all scientists were doing that, you know.

705
01:10:01,260 --> 01:10:04,499
But the people I interacted with, it was wonderful.

706
01:10:04,500 --> 01:10:08,290
It was fabulous to see, you know, But I knew them from before.

707
01:10:08,310 --> 01:10:13,920
You know, we all know each other here in this house Parks Road area anyway. And they were doing what they always do.

708
01:10:13,920 --> 01:10:15,370
They stepped up. Mm hmm.

709
01:10:16,110 --> 01:10:24,089
And I just wondered whether that increased level of openness and collaboration might be something that you foresee continuing in the future,

710
01:10:24,090 --> 01:10:27,620
or will it only come into being? Oh, that's a good question.

711
01:10:27,630 --> 01:10:37,230
I think personally, with the groups I work together with never had even before a competitive situation, you know, even before it was never a problem.

712
01:10:37,230 --> 01:10:44,700
So I think friendships were absolutely consolidated and will be even stronger than before.

713
01:10:45,240 --> 01:10:50,610
I would imagine in the same the same coin,

714
01:10:50,610 --> 01:10:58,530
different side is that people that you knew before you might not get along that well with that was also confirmed.

715
01:10:58,950 --> 01:11:06,720
And so. So I don't think I will have a chance to collaborate with some people in this university, and that's okay.

716
01:11:12,890 --> 01:11:18,090
Oh, I know it is. I mean, this old sentence is really true.

717
01:11:18,110 --> 01:11:23,650
I mean, if the going gets tough, the best and the worst comes out and people.

718
01:11:23,660 --> 01:11:29,180
Yeah. And, and and I think we have to all remember that that was a very stressful time for everybody, you know?

719
01:11:29,270 --> 01:11:33,710
For me, the positive definitely definitely one.

720
01:11:34,490 --> 01:11:37,750
And what about the constraints of having to work remotely?

721
01:11:38,150 --> 01:11:45,440
I mean, did that have some advantages? Um, the advantage for me was that I would never have tried it before, you know, this whole team stuff.

722
01:11:45,440 --> 01:11:50,990
And my group is very as you saw on the web page, we've been doing a lot of fun stuff, you know, and that, of course, can't happen.

723
01:11:51,500 --> 01:11:56,750
And I got so used to be at home because I'm certainly working too much anyway.

724
01:11:57,230 --> 01:12:02,090
If I then don't have to commute and my commute is not a long one, you know, it's 30 minutes max.

725
01:12:03,410 --> 01:12:07,879
I work those 30 minutes and I can get more done when I'm at home and not at home.

726
01:12:07,880 --> 01:12:10,940
People don't just pop in and just disturb you.

727
01:12:11,720 --> 01:12:18,620
So I had actually trouble to go back. But obviously here is exactly what I love about my work.

728
01:12:18,650 --> 01:12:26,200
It is that people pop just in that I talk to my group, that they come in with all the problems they want that they would not team me about at home.

729
01:12:26,210 --> 01:12:29,680
You know, I want to hear the big things and the small things, and I want to be part of the.

730
01:12:29,700 --> 01:12:35,269
So I, I can't remember when I started coming back three times a week.

731
01:12:35,270 --> 01:12:43,940
And, you know, I have changed a little bit in that one day a week, usually in Friday's I work from home and I do get much more.

732
01:12:44,620 --> 01:12:52,010
It sounds kind of much more done then, but by that I mean things that need continuous concentration of that long piece of writing.

733
01:12:52,070 --> 01:12:56,510
I have no chance, you know, and I love being here because I like to have people just popping in.

734
01:12:56,510 --> 01:12:59,120
But when I try to concentrate over there on my desk,

735
01:12:59,450 --> 01:13:04,069
I don't know how do have 5 minutes or 2 minutes to have 3 hours and then say, oh, but you had 3 hours.

736
01:13:04,070 --> 01:13:11,030
Yes, but I didn't know whether I would have, you know, So you you never get into this, you know, creative space.

737
01:13:11,250 --> 01:13:15,950
You can just get frozen, you know, just take off my list.

738
01:13:17,570 --> 01:13:22,049
Working from home, I know it's a big problem these days because too many people work from home.

739
01:13:22,050 --> 01:13:25,430
Then there is no community left here in the department.

740
01:13:26,180 --> 01:13:34,430
So there is a there is a people would like people to come back and understand that I'm a your group mostly here.

741
01:13:34,430 --> 01:13:45,400
500 yeah, yeah. Well, most of them never really left and they're all back five days a week, or six or six or seven.

742
01:13:45,710 --> 01:13:49,790
They are all working way too hard. And I try to tell them, Take your holidays and they never do.

743
01:13:49,790 --> 01:13:53,120
And yeah, they're all working way too hard.

744
01:13:53,990 --> 01:13:57,520
So I think we go to the end unless are I was Yeah.

745
01:13:57,590 --> 01:14:05,360
I'm trying to remember to ask this. Yeah. Are there any particular stories that stick in your mind during that time of.

746
01:14:06,460 --> 01:14:10,900
Things you had to do, things that were funny. Things were particularly difficult.

747
01:14:13,630 --> 01:14:16,660
Things you won't forget. There are things I won't forget.

748
01:14:16,660 --> 01:14:20,310
But the one I really won't forget. I don't think I want to talk about it.

749
01:14:20,530 --> 01:14:24,160
Okay. That has to wait for a bit longer.

750
01:14:27,280 --> 01:14:33,760
So has the experience of working through that period changed your attitude or your approach to your work in any way?

751
01:14:34,600 --> 01:14:39,490
You know, before it was often lip service, even by myself when I said that we are doing important work.

752
01:14:39,640 --> 01:14:47,140
You know, as I said, there was never a pandemic. And now it's it's very easy to be a virologist these days.

753
01:14:47,320 --> 01:14:52,480
You know, if you go and give a lecture, everybody knows what you're talking about and everybody has a vocabulary.

754
01:14:52,510 --> 01:14:57,180
All of a sudden, you know. Talk about our just before a pandemic, nobody would know.

755
01:14:57,820 --> 01:15:02,890
And now everybody tells you what's going on, which is really nice, actually.

756
01:15:03,190 --> 01:15:07,620
You know, for all the wrong reasons. Does it changed it?

757
01:15:08,680 --> 01:15:13,389
On one hand, it makes me think I always loved my work anyway, to be honest.

758
01:15:13,390 --> 01:15:20,709
But now it makes me think, yeah, I spent my life on something that was useful and hopefully will be more useful in the future if we

759
01:15:20,710 --> 01:15:25,990
get this post targeting drugs somewhere closer to where they should be or could maybe be tried.

760
01:15:27,280 --> 01:15:34,840
On the other hand, I think it has caused a lot of. I definitely feel much older than two years older.

761
01:15:36,850 --> 01:15:39,120
Definitely much more exhausted. Yeah.