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So could you just start by giving your name and your title affiliation, etc.?

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Oh, yes. My name's Peter Horby. I'm professor of Emerging Infectious Diseases in the Department of Tropical Medicine at the University of Oxford.

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Thanks very much. So could you just start by telling me a little bit about yourself?

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So we probably don't have time for your entire life story, but just in general,

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if you could go from how you first got interested in medical science and up to up to where you are now.

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Right. Well, that is a long story, isn't it? Well, you know, I trained trained in medicine in London.

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And what and what made you choose that as a subject for your first, which was I always found, you know, biology to be my favourite subject.

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I found it quite fascinating biology and evolution and the complexity of human systems and biological systems.

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So it was really the most appealing area of further education and I thought doing medicine would be the,

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the most valuable way of following that interest.

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So. So I trained in London. And I think quite early on got an interest in infectious diseases.

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I actually did an intercalated Bachelor of Science degree in History of Medicine and was particularly

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interested in at that time in the history of epidemics and expand the history of infectious diseases.

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So I think really quite early on I was interested in infections for lots of reasons, both because.

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You've got multiple facets. You've got the the biology of of the human disease, which you have for all all of medicine.

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But you also, in addition, have the potency of the virus,

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and you have this sort of the evolutionary competition between the viruses and individuals at the individual level and the population level.

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And also, you know, there's a lot of.

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Social behaviour and political elements as well.

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You know, if you've got heart disease and I'm sitting next to you, it doesn't affect my risk of having a heart disease.

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But if you've got Ebola, it does, you know, so there's a whole sort of social and societal construct to it, too.

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So it's a really fascinating area. And so that's why I went into infectious diseases.

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And where did you go after your first after you qualified?

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Well, I actually my my very first job was on an HIV ward in the very early days of the HIV epidemic at the Middlesex,

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where the patients were incredibly sick. This is before any effective antivirals were available.

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And that really, I think, sealed the deal. And my interest in doing infectious diseases,

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seeing these young people with these devastating infections and also cancers which were arising because of a lack of, you know, immune tolerance.

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You know, so those very early days were very formative.

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And very soon my interest in infectious diseases, I then went on, you know, to various medical specialities but with particular interest.

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Infectious diseases worked to the hospital for Tropical Diseases in London,

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then took decision to specialise actually in public health of infectious diseases rather than clinical infectious diseases.

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And so did higher training then was public health laboratory service and has now gone through various metamorphoses in different agencies.

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And, you know, actually, when I first qualified a consultant,

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my very first job was head of the variant CJD unit, the mad cow disease infection in humans.

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So right early on, it was really working on sort of epidemic prone infectious diseases.

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I then went to Vietnam for the SA's outbreak, silenced one outbreak in 2003.

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I originally went for six months and ended up staying eight years there.

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So had the the Oxford University unit in Vietnam already opened by that time or did it?

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Was it set up as a result of that epidemic?

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There was an Oxford University clinical research unit in in the South in Ho Chi Minh City that was working on infectious diseases.

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And I actually went to Vietnam, to Hanoi in the north, working for the World Health Organisation.

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I worked for that for three years. And then I was asked by Jeremy Farrell, who is director of the City Unit, if I would open assist to you in Hanoi,

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which I did, which opened the the the National Hospital for Tropical Diseases in Hanoi.

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And that was that was that was great. That was my first foray into academia.

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So I guess, I guess for a lot of people based in the UK,

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the idea of the the threat of global pandemics until the last couple of years had been relatively theoretical.

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But for you, it you were, you were seeing it firsthand in a developing country.

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What were the main threats that that were faced in Vietnam?

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Well, you know, we saw the sales outbreak, which was a real warning shot of what's possible.

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And, you know, I went in there for the for the outbreak and was involved in in the response to the outbreak.

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I then stayed on with W.H.O. And, you know, I remember I got a call from the director of the paediatric hospital, Penicillium,

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who said he had some children who were very sick and he was worried that it was solved.

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So I immediately stopped what I was doing, which was actually teaching some people about infectious disease epidemiology,

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travelled back to Hanoi and went to that hospital and with Professor Williams saw the children and was suspicious that it wasn't SaaS,

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SaaS company to not call severe disease in children and these were some very sick children.

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So we arranged to take some biological samples, some swabs and blood from these children and send them off to a laboratory in Hong Kong,

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because we suspected that they might have a severe influenza. And it turned out they did.

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So these were the first cases detected of the resurgence of bird flu, H5N1 bird flu in Vietnam.

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So and that was just at the end. It was just around Christmas, 22,003, 24.

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So all of these things happened around Christmas for some reason.

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So then we saw that, you know, these severe zoonotic influenza influenzas from animals, really quite scary, 50, 60% fatality in hospitalised cases.

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So, you know, yeah, I was very much aware from my direct your hands on experience of patients and populations,

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missiles and bird flu that these things are really serious, you know, present real threat.

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I was I brought under control in a relatively short space of time and didn't become a global global pandemics.

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Well, Charles Wang did. It did travel to many, many countries and caused quite a lot of deaths and disruption in Singapore, Hong Kong, Canada.

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But actually it was. There were two elements of the reason of that was control.

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One is it's not as infectious as COVID 19.

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And secondly, the peak infectiousness is much later in disease.

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So people were less infectious in the community, but were more infectious by the time they got to hospital.

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And so what you mostly saw was transmission within hospitals, which is different with Sars-Cov-1 virus to COVID 19,

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where actually your, you know, your peak infectiousness is early in disease when in the community.

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So that makes it harder to to to detect and control and then bird flu.

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But actually, these viruses, there is very limited capability for person to person transmission.

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But so far they've been well adapted mostly to birds and they transmit very efficiently between wild birds and domestic poultry,

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etc., but don't efficiently transmit between humans.

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So for that reason, they've only ever caused you to mostly survive slight cases or small clusters.

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But clearly, you know, influenza has the capability to become very transmissible between people.

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And the real worry is that you get at a highly pathogenic, you know, a virus that causes a lot of deaths from birds,

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but then it adapts in humans and becomes readily transmissible and causes a pandemic.

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So, you know, when people say that we were in one sense lucky with COVID 19, because the case fatality rate is is a lot less than 1%.

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They're right.

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You know, their advice is out there with with case fatality rates above 10%, which would be an absolute catastrophe if they were to spread.

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So back to your personal story. You ended up staying in Vietnam for within nine years.

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Eight years? Yes. So I was three years with W.H.O.

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Then I set up the research unit in Hanoi, which is still running and very successful, and I'm very pleased with that.

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I then went to Singapore for three years where I was still doing work in Vietnam,

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but I was also running an infectious disease programme in Singapore and then I returned.

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Well, in return, actually, I've never actually lived in Oxford.

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I came to Oxford in 2014 where I set up the Epidemic Disease Research Group in Oxford because it just a small group of us.

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And that very year, the West Africa Ebola outbreak happened.

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And so we just come to Oxford, just set up quite a small group and immediately thrown into the West Africa Ebola outbreak,

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which we you know, I think we did quite a lot of work in that area.

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And what what what sort of answers did you come to with Ebola?

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Oh, well. In the 2009 influenza pandemic.

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And it showed us that we had a real problem with clinical research in epidemic infections.

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We did a bit in sales one, we did a bit in bird flu, but then we had a pandemic 2009 influenza pandemic.

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And what was striking was actually the poor quality of clinical research we did at that

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time did not have any licenced antiviral drugs or treatments for severe influenza.

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There were treatments for mild influenza in the community, but they were not licenced to the hospitalised cases.

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And following the 2009 pandemic, which we kind of knew was coming, everyone's been doing pandemic flu preparedness, so it wasn't a surprise.

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We still didn't have any licenced antivirals for severe influenza because nobody was able to do the trials that were needed.

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And now, more than ten years later, we still don't have any licenced antivirals for severe influenza.

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And so it was a real. No real message, really, that, you know, if you're wanting to improve care for epidemic infections,

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you need to treat people with those infections, which you can only do during the epidemic.

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So you need to have systems that can operate in epidemics and pandemics.

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Otherwise, you're never going to improve care. And the 2009 the influenza pandemic is a map to the exemplar of that,

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where because everyone was too busy and they didn't really hadn't really thought through how we were going to do a clinical trial in the pandemic.

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We didn't manage to get any new answers, and so we didn't improve Cam and we haven't been able to sense that.

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You know, you have to take the opportunity when there's an outbreak, when there's an epidemic, you have to act.

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You have that one window of opportunity to get the data you need.

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And so you've just got to get on to it and to do the best you can and do it as quickly as you can.

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So we're going to get onto COVID very soon. But first of all,

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I just wanted to get you to tell me a little bit about the international Severe Acute Respiratory and and Emerging Infections Consortium is Eric,

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if that's how you normally pronounce it? I don't know. It's a bit of a terribly long acronym, need to be thinking about changing it.

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But it's it's kind of got a bit of a brand name.

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Yes. And it does what it says on the tin, doesn't it. So yeah,

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you so it was was was actually set up after the 2009 pandemic specifically to to try and bring

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together clinical research networks to try and improve the response to epidemic infections.

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So to do day to day research that has day to day utility for patients that people are seeing every day.

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But it also has the capacity to respond quickly to epidemics.

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And so that's what we've been working on since 2009 is to do that.

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And I think we've made steady progress. You know, we did manage to start trials,

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clinical trials in Ebola and actually then the next big outbreak after the West Africa outbreak which occurred,

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the second outbreak was in eastern Democratic Republic of Congo and a clinical trial

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was done and it was completed and said there were new treatments now for Ebola,

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seven now approved treatments without it because of that. And then, you know, that was the position we were in as COVID 19 emerged.

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And actually, we'd been working for, you know,

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a decade really in sort of preparing to be able to do clinical research in this kind of context and how does that network work?

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But from what I've looked at, it's extremely multidisciplinary, it's extremely international and involves people at all levels coordinating.

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That must be quite, quite a challenge. WORK Did you have a model to follow or did you have to make it up from scratch?

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Well, I'm. You know,

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having worked for the World Health Organisation and and for National Public Health Agency and

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in research it's clear that all of those different systems have their different strengths.

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They're all equally important and they all got something to offer.

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But you know, peer to peer research networks have a real advantage in that they're not politicised generally.

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You know, they're much hard to politicise and you have the ability to sort of build up a longer term trusted relationship.

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And so for me, that was the essential ingredient to things really is getting together people who have a common interest,

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which is basically improving the care of patients who've got, you know,

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severe infections from epidemics, and secondly, building that trust over a decade.

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So you're in a situation that you can just find someone up and they know you and they trust you and that

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they're happy to talk to you about potentially sensitive issues and to collaborate with you and with others,

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with your sense I.T. about whether their research ideas will be stolen or whether they'll get the recognition they need, etc., etc.

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And so really that that's the two forms of currency, really common interest and trust.

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It's not heavily financed. It's not heavily regulated.

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It's it's it's a you know, it's a special interest group of people who want to make a difference.

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Hmm. It's really interesting. Um. So.

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Yeah. I think we finally got to it. Can you remember how you first became aware that COVID was a thing and that it might become a serious pandemic?

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Yeah, well, you know, there was the there was obviously the The Pyramid Report, which is a sort of online disease,

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sort of, I guess almost like it might have been a precursor to a sort of social network.

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It's basically an interest group where, you know, people can tell the primate group of about suspicious outbreaks or clusters of

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diseases and the primate group kind of screen newspapers and news streams.

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And then they put out, you know, very regular emails to to people who are on what's called a list survey in the old days.

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And they said a primate report came out 30th of December about this cluster of infections in China.

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And obviously, there's this you know, you've been around the block a bit, you know, could see some red flags in that,

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you know, cluster severe acute respiratory pneumonia potentially linked to a wild animal market.

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You know, many of these viruses come via in animal sources originally.

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In fact, the majority of emerging infections from animal sources originally.

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So that was the first signal. And at the same time, you know, the chatter started amongst, you know, the sort of special interest group,

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you know, amongst the snake and between people like Jeremy Fowler and other colleagues about, well, what's this?

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And so, you know, right from, you know, first to January,

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we we were having discussions by SMS and an email telephone about, you know, what's going on in China.

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But I mean, I've been saying to everybody else, how did you decide to pivot your research to this new thing?

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But in fact, it didn't take much pivoting really for you because you're already right in the middle of that in that.

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Oh, yeah. You know, we've kind of been I guess I'm in a sort of slightly luxurious position of epidemic.

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Clinical research response is my raison d'etre, you know, so it's core business for us.

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So there was no question about not responding because.

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If we didn't what we here for with the you know around the epidemic diseases research group.

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So and there's an epidemic within research and you had colleagues in China that you were already in touch with, presumably?

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Well, yeah. So, you know, having worked in Southeast Asia for a long time and worked on Sars-Cov-1 and avian influenza,

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both of which have been issues in China and worked on influenza in general with colleagues in China.

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Obviously, I had had very close links with, you know, quite a few Chinese colleagues who I've known for a very long time, for ten years or more.

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So we were able to reach out very quickly and and have a discussion about what was happening there and what might be possible in terms of

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clinical research to improve our understanding of this virus to disease causes and how we might prevent spread and treat patients better.

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I would I mean, one important thing to say is. I've taken a very deliberate decision to focus on patients points because you

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can focus on virology or you could focus on epidemiology and public health.

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But I've taken a very conscious decision to focus on patients with these infections for a number of reasons.

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One is they tend to have been neglected, and it's a bit more challenging really than sometimes to say, virology,

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because you have all the issues of consent and privacy and all these other, you know, very important issues that you need to consider.

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But also, you know, actually studying patients is central to all of that activity.

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You know, where do you get the viruses from? You get them from patients who are infected and taking swabs from them.

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How do you understand about the immune response that you need to develop vaccines or vaccines if possible?

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Again, you get it from looking at antibody responses in patients.

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How do you understand what kind of infection control or public health measures are necessary to do that?

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You need to understand, you know, when people are infectious and how long they're infectious for and whether it's,

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you know, which body tissues are infectious, etc., again, you get that from patients.

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So when you're studying patients helps you understand the clinical presentation and improve the care.

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But it also really informs basic policy and public health responses.

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So. Were you able to actually in a hands on way approach patients in the early days?

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Or presumably travel was a bit of an issue?

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Not myself, no. But 390. Yes, we did.

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We co-wrote with George GAO, the senior person in China, with the very first sort of commentary on what was going on.

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Our colleagues in China that I knew very well wrote the very first clinical description,

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and we were able to support our Chinese colleagues to set up two clinical trials in the mine.

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And that was a great example of how it worked, because we had colleagues in China who were wishing to do clinical therapeutic trials.

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We also had colleagues in in the Middle East who had been doing clinical trials in type since with Middle East respiratory corona virus.

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This is known as coronavirus, which comes out of camels causes.

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It can cause severe disease in humans. It has been around for a while, but it hasn't really caused it hasn't haven't spread internationally very much.

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But he was running trials of Qualidade Yassine Arabe was doing clinical trials in those patients.

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And so we were able to, you know,

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call up and get a call together with myself and Yazdi and colleagues in China and adapt the protocols that were being used for Murres for SARS-CoV-2.

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So it really was showing you how the network. Can function really well.

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You know, we knew each other well enough. We were prepared enough to get on the phone chat protocols and get trials up and running very quickly.

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And what were you trialling at that stage? So early on,

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we started with a drug called Lopinavir Ritonavir because there was some preliminary data in other coronaviruses in

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Sars-Cov-1 and emerged which suggested it might have an antiviral effect against the new cells going about to virus.

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And it's a readily available drug. It's it's been used HIV for a long time.

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And we knew the safety profile. It's available in pharmacies.

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So it was something we could start very quickly. So we we started initially with the Lopinavir Ritonavir and we were able to start

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that really quickly thanks to the fantastic work of our colleagues within 20 days.

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Know by late January we had the first patients enrolled in that trial and so that was the very first randomised controlled trial ever done in,

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in COVID 19. It wasn't placebo controlled, I, you know it was just the drug first is standard of care and people knew what they'd been allocated to.

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But meanwhile we were setting that up. We were also working hard to try and get Remdesivir into the country,

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working very hard with the drug company Regeneron to try and get their normal channel.

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And so I get to try and get the the drug into the country.

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And we managed to do that. So we managed to get the drug and placebo in the country.

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And so by February, we were able to start the very first placebo controlled trial in COVID 19.

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And what what what had remdesivir been useful previously of Remdesivir was it was again,

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it was an antiviral drug that wasn't licenced for any indication, but it had a sort of fairly broad spectrum antiviral activity in the laboratory.

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And so there were suggestions that it would be effective against coronavirus, too.

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So that was a more attractive drug.

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So whilst we were starting to have a ton of it, we managed to secure the the remdesivir and placebo and get that started in China.

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So by what month are we in by now, by the time you arrive in February, yes.

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You know, by fairly early in February, we had two trials running.

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And by that time, the spread around the world was beginning to look quite significant.

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Yeah, that's right. So what happened in China is we got the trial started pretty quickly.

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And I remember giving a presentation at the time, around that time about what we what our response was.

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It was at the Royal Society of Tropical Medicine and Hygiene that the response,

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the clinical research response to COVID 19 and same with Chinese colleagues,

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we managed to get the first patient into this trial within 20 days of of the outbreak being recognised or reported,

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which really, you know, was a record I thought I could never beat.

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And I gave examples of how long it takes normally, takes years to get trials started and then how we did in in Ebola,

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where we managed to get things started in a couple of months.

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And then so to get the pilot up and running and the patient first patient involved in three weeks, I thought was a record we never beat.

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But unfortunately, unfortunately, fortunately, what happened was the the Chinese authorities, you know,

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recognise the risk put in place very stringent public health measures in Wuhan and very big city, complete lockdown.

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And so they managed to control transmission very effectively in Wuhan.

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So what happened was the trials, even though they opened very quickly and recruited,

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they eventually finished with insufficient patients for a clear answer.

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So both trials had roughly 200 patients in them each, which really wasn't enough to give a clear answer.

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So we, we started the clinical research activities on one, you know, treatments for COVID 19.

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But because the outbreak had been controlled, we weren't able to answer that question at that time.

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So it's a bit of an irony that in order to get these clear answers, you actually need more people to get ill.

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Yes, I know. It's a it's a strange dilemma. That's actually if you want clear answers, you need more patients.

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And that means you do, but you have a bigger outbreak.

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So, you know, we do try and get the best evidence we can with the patients we have.

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Yeah. And so, you know, by that time it was starting to spread internationally and actually I'd,

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I'd applied for a grant to extend this research programme with colleagues in China

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because up until that point the research had not required any external funding.

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It was being funded by just, you know, volunteer time or from the Chinese government.

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So I applied for a grant to expand that research programme, that clinical trial research programme in China on therapeutics for COVID 19.

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But by the time the the panel had sat and made a decision and decided to award us the grant,

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there was not much COVID 19 in in China anymore, and there was quite a lot in northern Italy and other parts of the world.

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So I actually got a phone call from the grant agency saying, we're going to give you the grant, but you're going to have to do it in in UK or Europe.

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Because that's where we think the cases will be. It's a witch hunt funding body was this.

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And this was the Medical Research Council. Oh, it was. So we got the money, but we had to move from China where we meant to do it to the UK.

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And is that what became the recovery trial? And that's right. That's what became the recovery trial.

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Yes. So tell me a little bit about how that was set up. So the recovery trial.

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Yeah, which has been phenomenal experience, really.

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So we were in a situation where we started two trials in China that had not reached sufficient patients to give us a clear answer we had.

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So we had a summit and we had secured funding to expand the programme and we need to set up the trial now in the UK.

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And at that time it was becoming clear that.

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It's a very transmissible virus and things would take off pretty quickly in the UK as we were seeing what was happening in Italy at the time.

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So we had to get this up and running really very quickly in the UK.

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And so I was thinking about how this is going to happen because I'm in the tropical medicine department and I work on sort of high,

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high threat pathogens, mostly in tropical countries, and never had a clinical trial in the in the U.K.,

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which is a very different context from where I've generally done my work.

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And at that time, Jeremy Farrar, who, you know, obviously was a is a close colleague and friend, said, oh, you should talk to Martin Landry.

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And Martin obviously has a lot of experience of Olympic trials in high income settings because he

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works in the group that runs many beat cardiovascular trials and other sorts of clinical trials.

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And so Martin and I got on the phone, and I think it was a sort of marriage made in heaven, really, because, you know,

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I had the infectious disease threat pathogens, epidemic experience,

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and he had the experience of setting up mega trials, basically, and very streamlined trials.

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And so we came together and that became the recovery trial.

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And how did you recruit patients into the trial? Well, that just just take me through the kind of nuts and bolts of how you set up a trial like that.

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Yeah. I mean, it was a it was a a fraught time, I think, because on the one hand, we were we were, you know,

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being you know, I had been working with W.H.O. on the clinical research response to COVID 19 since the early days.

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And I personally was frustrated at the pace of change and progress and felt that it was too slow.

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And so there came a point when we had to decide, were we going to wait to W.H.O. and do this with W.H.O., or were we going to just go it alone?

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And, you know, after a busy deliberation, a few conversations, we decided that really, you know.

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We couldn't wait. Much as I'm supportive of W.H.O. and the work they do,

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I really felt that we were the right decision was to go it alone and set up the recovery trials, which we did.

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So, you know, I think Martin and I had and also we interviewed, you know, he dug out an old protocol of a very simple trial,

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the very earliest chances of clot busting drugs back in the eighties,

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and took that together with the information we had about the trial designs that we were already using for COVID 19,

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and sketched out a highly simplified protocol that focussed on the important things around patient safety and

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welfare and getting clear answers but streamlined wherever we could streamline because we knew a lot of things.

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We knew the trial had to be big.

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You know, because there's not going to be a miracle cure.

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And a lot of people are designing their trials based on the idea that there's some miracle cure out there.

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It's going to reduce mortality for 50% and that ain't going to happen.

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So you're looking for modest benefits. And in a pandemic, a modest benefit is a huge value.

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And so. If you wanted to have a 20% reduction of a 20% case fatality rate, which is kind of what the estimates were in hospitalised patients,

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you need about 2000 patients per RCD, 2000 patients on the active treatment and 2000 not on the active treatment for comparison.

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So you need 4000 patients per drug and since so need to be big.

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And it needs to be quick because, you know, we were going to see we knew we were going to see a very rapid uptake and it needed

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to be practical in the situation where hospitals were going to be overwhelmed,

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which, you know, we'd seen had.

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And we saw in northern Italy that hospitals and health care staff were under extreme pressure, you know, and so if you need to try,

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this can be big and it has to be quick and it has to function in a very, very stretched health care system.

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And it's got to be simple. That's the only way it's going to work. Is it simple?

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You know? So it was stripped back to the bare necessities.

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And so. We had a very simple sort of what we call case liquid form, which is the baseline information about the patient.

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We had a very simple consent form and we had a very simple follow up form.

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And the beauty of the system currently in the NHS is that we could use data linkage and again Martin has a lot of experience

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in his team and that's area where instead of asking doctors and nurses and others to fill in forms on all patient outcomes,

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we could collect a lot of it from electronic sources like death registration and intensive care unit registries and things like that.

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So a huge amount of effort starting to date, data linkage and it's been a real triumph, a fantastic team led by Marion,

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not simply to put together all the data linkage, which means that we've managed to really decrease the burden on the frontline health care staff.

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And so we had a very simple protocol. We had a data linkage that would be set in place.

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So we knew we could use that to supplement the simple data collection.

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And in the in the UK, we had the National Institute of Health Research, which is this national health research infrastructure that parallels the NHS,

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which meant that there was an existing infrastructure across across the NHS to doing research.

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And in 2009 the from the pandemic, the principle had been set of priority public health research.

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So in the event of a health emergency, the NIH are we have a process to prioritising what research done so that they prioritise the important stuff.

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And that also was pretty unique in the UK.

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Not many countries were able to do that to have a system where you actually set across the whole health service.

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These are the priorities you need to stop doing this other stuff or we're not going to stop doing this other stuff.

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And so that was essential as well. So given those things, you know, I had a meeting with with Chris Whitty and Jonathan Van-Tam,

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the Chief Medical Officer and the Deputy Chief Medical Officer in in March where I was going there

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to present the the principles of what we wanted to do because we needed to get CMOs by them.

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I think it was a 10th of March that I met them and said, Yeah, in a very quick meeting, 15 minutes in the Department of Health.

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This is what we going to do is that's going to work. Response was, yeah, do it.

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Go ahead. Green light. And we enrolled the first patient in the John Radcliffe Oxford nine days later.

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So we beat our 20 days. We have halved it just nine days after that meeting, at which point we didn't even have a protocol in time in the first place.

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It was nine days. It's not an absolutely fantastic team effort from the clinical research team and the programmers

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and the clinical trials management team and research services and everyone in Oxford,

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plus the Ethics Committee that we used in Cambridge and the medicines, health regulators, our team are all the same, you know, and.

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Did a fantastic job in in reviewing the proposal made short time and signing off set to get the protocol written

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together with all the stuff set up by the the IT infrastructure and the RANDOMISATION procedures and materials,

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the consent forms, the website and to get approval,

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ethics approval and regulatory approval and it was the first patient in nine days was quite, quite phenomenal.

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I remember going over to the John Ratcliffe with them, Richard Haynes, who's the person that makes the whole thing, Ron Tindall, the first patient.

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And it was just it was an amazing to you know, we started so quickly with the mode of transportation.

334
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Mm hmm. So just to clarify for future listeners that the recovery programme is.

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Is. The recovery trial is for patients who are sick enough to have been admitted to hospital.

336
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Yes. So it's a clinical trial of treatments for hospitalised patients with with COVID 19.

337
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Yep. And then and so what, what was the first because you've trialled a number of different treatments.

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Run me through those quickly. Oh, well, I guess that's actually a long list.

339
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So we'll pick out the key ones because haven't drugs so far.

340
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All right. Okay. Well, we have results for nine of them.

341
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Hmm. It was a yeah it was interesting the in the very first patient enrolled I think was randomised to dexamethasone the low cost

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stellar drug and I believe you know something which you know since then there might be a contract that he was a little acid,

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he was allergic to medicine which nobody never is allergic to.

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Steroids really is very strange. And so you give people if they have allergies, that's what you do.

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If someone has an attractive response, you give them steroids.

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It it's very strange. So then you have to find the find the patient's GP and say, oh, what's this?

347
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You know, is that true? And the GP said, No, it's a mistake.

348
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He's not allergic to steroids. So and the patient was kept out of it could be randomised to dexamethasone or not.

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So the very first patient we had to sort of pick up the first patient become randomised.

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So we initially started with what we call repurposed drugs,

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which is drugs that were already available and licenced for other indications

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like dexamethasone as a standard use for lots of inflammatory conditions like,

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you know, skin diseases or asthma, etc. So that's licenced.

354
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There was also hydroxychloroquine, which is exactly an anti-malarial drug,

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but it's been used for many decades and was available and lopinavir ritonavir again,

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the one we didn't get an answer for in there in Milan was included.

357
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So we started with the repurposed drugs,

358
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knowing that later on we could bring in more experimental drugs that became available, which we have subsequently done now.

359
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Yeah. And so, yeah, 1111 drugs so far as we speak.

360
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Trial still ongoing. And we have we have nine answers, six negatives and three positives, which is great.

361
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Three new drugs that save lives in COVID 19.

362
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Yeah. So that's the next step. Obviously, what you've done has an immediate impact on policy and practise in the treatment of of patients.

363
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So how big a difference have those positive results made to the the the death rate in in hospitalised patients.

364
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Well I mean first I would say that, you know, three AB nine is a pretty good hit, right?

365
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Yeah, absolutely. A lot of drugs fail and we were starting with a brand new virus,

366
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which we didn't know anything about and we didn't have any specific drugs developed for it.

367
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And we were just using repurposed drugs to begin with. So three out of nine is pretty good.

368
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It's also important to know that, you know, showing things don't work is important.

369
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You know, lots of people were taking hydroxychloroquine. It's myosin.

370
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And, you know, we were talking about things and actually many, many national treatment guidelines were recommending these drugs based on their data.

371
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They were saying, you know, there is no doubt about it, we recommend you try it anyway.

372
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So a lot of people getting these drugs recommended, not treatment guidelines.

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You know, we were able to pretty conclusively well, very conclusively showed they were not effective.

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They were not effective and they were not to be used for treatment.

375
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And that's a good thing, because that means that you can stop giving drugs unnecessarily to patients.

376
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You can stop wasting the time of the prescribers and the pharmacist to prescribe this stuff,

377
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and you can focus on then evaluating drugs that are much more promising.

378
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So our very first result was I don't see chloroquine just doesn't work in hospitalised patients drew a lot of anger

379
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because a lot of people had been convinced by very poor quality observational data that it was very effective.

380
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When you say people, do you mean clinical, clinically qualified people?

381
00:43:12,540 --> 00:43:19,679
Yes. Surprisingly, some of members in non clinically qualified members of the public life is not quite the right word.

382
00:43:19,680 --> 00:43:30,870
But were convinced and many politicians were convinced that, you know, examples of Bolsonaro and Trump saying, we think this stuff works.

383
00:43:32,700 --> 00:43:41,220
Stepping outside their area of expertise, I might add. And a lot of people believe the hype around these drugs,

384
00:43:42,840 --> 00:43:48,060
which has been shown very clearly to be just that, just to be hype, and that they're not effective.

385
00:43:49,110 --> 00:43:55,140
But because I think we were the first trial to to say that Dr. Kevorkian was not affecting hospitalised patients,

386
00:43:55,310 --> 00:43:59,370
we were the very first to draw from a lot of the fire around that.

387
00:43:59,940 --> 00:44:07,610
You know, we used a high dose of hydroxychloroquine based on very careful modelling of what concentrations you need to have

388
00:44:07,620 --> 00:44:15,360
an antiviral activity and very careful modelling of the safety profile and then what doses it might be harmful.

389
00:44:16,530 --> 00:44:21,509
But that didn't stop people saying that the trial didn't work because we were poisoning people,

390
00:44:21,510 --> 00:44:28,320
etc., etc. But subsequently one of the other big randomised trials have been negative as well.

391
00:44:28,770 --> 00:44:35,340
In fact every result we've had this been looked at in other big trials, adequately powered trials have been confirmed.

392
00:44:35,520 --> 00:44:39,720
So we're very confident that our results are very reliable because we're the biggest trial.

393
00:44:41,310 --> 00:44:48,480
So that was our first result. Hydroxychloroquine doesn't work. I spent a lot of time dealing with hostility for that result.

394
00:44:49,440 --> 00:44:56,489
Second result was that dexamethasone does work, which is fantastic.

395
00:44:56,490 --> 00:45:02,850
If you were to use any of the drugs to work, you would win that one because it's extremely well understood.

396
00:45:03,300 --> 00:45:09,530
It's pretty safe. You know, you get some complications in a poor diabetic control and some secondary infections and things.

397
00:45:09,540 --> 00:45:17,050
But we really know how to use this drug and it costs virtually nothing, you know, and it's available everywhere in the world.

398
00:45:17,370 --> 00:45:21,060
You know, you can get steroids over the counter in many pharmacies around the world.

399
00:45:23,040 --> 00:45:30,299
And so we had a drug that costs very little and was available everywhere and in some patients had a good effect.

400
00:45:30,300 --> 00:45:34,560
So it didn't have a benefit in everyone, but in patients who were more severe,

401
00:45:34,950 --> 00:45:41,430
so who required oxygen or high levels of respiratory support and there was a very clear mortality benefit.

402
00:45:41,730 --> 00:45:52,230
So it was a really fantastic result. I can remember looking at those results with Martin just thinking, Wow, yeah, this is great.

403
00:45:52,630 --> 00:45:55,920
But there was also a lot of resistance to putting dexamethasone into the trial.

404
00:45:57,060 --> 00:46:04,350
There were many clinicians who thought it was dangerous to give a steroid, to suppress your immune system in somebody who's got an infection.

405
00:46:04,740 --> 00:46:10,620
Kind of goes against the grain and you might end up making the infection worse and that the box will replicate.

406
00:46:11,280 --> 00:46:20,100
So we had quite a lot of people telling us that it was not ethical to put steroids into the trial because we would definitely make people worse.

407
00:46:21,720 --> 00:46:25,520
So there was a bit of nervousness about putting that in because, you know,

408
00:46:26,640 --> 00:46:32,850
we did get letters and those letters were copied to people in government saying it was unethical to put steroids into the trial.

409
00:46:33,900 --> 00:46:39,120
So it was remarkable to see that it was so effective.

410
00:46:39,360 --> 00:46:48,989
And that went into policy overnight. And the day we announced the results, we did a, you know, a press conference.

411
00:46:48,990 --> 00:47:01,350
And then, you know, I went to number ten when we announced it and that evening that the chief medical officers of the UK sent out a an alert

412
00:47:01,350 --> 00:47:07,049
to all clinicians to start using it in patients who are more severely ill and subsequently been adopted worldwide.

413
00:47:07,050 --> 00:47:10,150
Which is which is amazing. Hmm.

414
00:47:11,140 --> 00:47:18,010
So what were the other two worked? So you actually did what was a drug called an interleukin six inhibitor.

415
00:47:18,020 --> 00:47:24,160
So this particular one was tocilizumab. So this is a much more targeted anti-inflammatory.

416
00:47:24,170 --> 00:47:29,290
So you might think of steroids like dexamethasone is a bit of a blunderbuss sort of approach.

417
00:47:29,290 --> 00:47:32,860
It really dampens down the whole immune system in many in many different ways.

418
00:47:33,550 --> 00:47:44,590
Whereas Tocilizumab is a very highly targeted targets, just one specific part of the inflammatory pathway and that also had a mortality benefit,

419
00:47:44,590 --> 00:47:55,630
which is great again in a subset of patients and patients who have signs, inflammation and the need for oxygen therapy, then tocilizumab helps.

420
00:47:56,230 --> 00:47:59,280
And what's important is it helps on top of steroids.

421
00:47:59,290 --> 00:48:03,759
So. Steroids became standard practise.

422
00:48:03,760 --> 00:48:08,260
And so we were testing Tocilizumab on top of steroids being used as standard of care.

423
00:48:08,680 --> 00:48:18,250
When we show, we saw an additional incremental benefit with the use of Tocilizumab and again that entered into into practise in the UK and elsewhere.

424
00:48:18,820 --> 00:48:27,010
And I think it was a we'll be approved we believe fairly shortly by some of the regulators.

425
00:48:27,030 --> 00:48:30,970
So that would be two drugs, dexamethasone,

426
00:48:31,000 --> 00:48:41,860
tocilizumab where it's come right through from first in inpatient in these patients right through to full approval from regulators and changing of see

427
00:48:42,280 --> 00:48:49,780
of the product in setting the boxes to say you can now use this for kind of patient and recovery trials that's that's really fantastic to see that.

428
00:48:50,890 --> 00:48:57,530
Hmm. And if the drug was a monoclonal antibody preparation, which is an artificial antibody preparation.

429
00:48:59,210 --> 00:49:01,490
The particular one we tested was called one, two, three.

430
00:49:02,660 --> 00:49:09,830
And what we showed was that in patients who did not have their own antibodies in giving them artificial antibodies improved their survival.

431
00:49:10,520 --> 00:49:14,540
So again, in a subset of patients, this drug is effective.

432
00:49:14,840 --> 00:49:19,460
The difficulty with the monoclonal antibodies, though, is that the.

433
00:49:20,450 --> 00:49:26,029
Okay. Targets the virus. You can get resistance to the monoclonal antibodies.

434
00:49:26,030 --> 00:49:31,759
And with the American variant, there's just a reason we have seen that,

435
00:49:31,760 --> 00:49:37,069
that it looks like there will be some problems of resistance against some of these

436
00:49:37,070 --> 00:49:40,610
monoclonal antibodies so that we don't have the full results as we speak at the moment.

437
00:49:41,150 --> 00:49:46,400
But the monoclonal antibodies are great because you can design them for new viruses quite quickly.

438
00:49:46,760 --> 00:49:49,910
But there is a challenge that resistance can develop.

439
00:49:51,750 --> 00:49:57,270
Okay. So I've noted various other things that you are involved with as well as the recovery trial,

440
00:49:57,630 --> 00:50:05,490
and you were also interested in predicting how well patients were going to do from the.

441
00:50:06,950 --> 00:50:10,309
Yeah. So yeah, it's been a busy couple of years.

442
00:50:10,310 --> 00:50:13,850
So there was the there was trials in China, there was the recovery trial.

443
00:50:13,850 --> 00:50:20,810
And then through esoteric, um, we set up a clinical characterisation database again so that we could work ten years.

444
00:50:21,020 --> 00:50:24,320
So talk me through how, what, what is that and what does it do.

445
00:50:24,890 --> 00:50:30,980
So what it is, is, it's a form basically that, that, that gathers information about patients with a disease, about their character.

446
00:50:30,980 --> 00:50:34,040
It does this in an anonymous way. So we can't identify anyone.

447
00:50:34,040 --> 00:50:38,390
But what's their age bands, their gender, how they got diabetes,

448
00:50:38,690 --> 00:50:44,960
they overweight how long since symptom onset and then follows them through through their treatment and their outcomes.

449
00:50:46,220 --> 00:50:54,500
And it really helps you understand who's at risk of severe disease because this is a database of patients who've made it to hospital.

450
00:50:54,500 --> 00:51:00,809
So who's at risk of severe disease? And that helps you targets preventive measures.

451
00:51:00,810 --> 00:51:07,140
All right. Or early treatments. What's the clinical presentation?

452
00:51:07,150 --> 00:51:10,500
What do people present with? What sort of symptoms do they present with?

453
00:51:10,830 --> 00:51:12,810
And then what's their clinical progression?

454
00:51:13,920 --> 00:51:24,750
What factors lead you to end up needing higher levels of care, going to intensive care, being ventilated or even dying?

455
00:51:25,500 --> 00:51:30,130
And so we set up that database. Very early on again in January.

456
00:51:30,550 --> 00:51:34,540
And at the moment it's got about three quarters of a million patients.

457
00:51:34,540 --> 00:51:43,690
So I'd say it's a really big database and it's been really useful. So in the UK that data was used and looked at by the Sage Committee every week.

458
00:51:43,990 --> 00:51:49,270
They were looking at that technical data and we've now produced a lot of bigger reports,

459
00:51:49,270 --> 00:51:56,980
global reports, and we've got a lot of papers and insights published and a lot more planned as well.

460
00:51:58,060 --> 00:52:03,400
And we can look at many different things like the risks of needing support for kidney function,

461
00:52:04,420 --> 00:52:12,040
the risks in pregnant women, as you said, risk scores, who's predicting, who's likely to do badly.

462
00:52:12,040 --> 00:52:16,119
And so you can give some more intensive treatment earlier on and so many, many things.

463
00:52:16,120 --> 00:52:19,239
So that's been really another great success.

464
00:52:19,240 --> 00:52:28,470
And I think. Um, is another example of where preparation helps because we've been working on those forms and the procedures for many years.

465
00:52:28,770 --> 00:52:33,989
So by January we had to step it up and we had to network the network where

466
00:52:33,990 --> 00:52:38,700
people trusted us that we weren't going to just steal the data and publish it.

467
00:52:39,420 --> 00:52:44,970
So they felt confident to contribute. Now more than half the data is from low and middle income countries,

468
00:52:45,840 --> 00:52:50,820
and we set up a very clear process of making sure that people are putting data

469
00:52:51,120 --> 00:52:55,020
and get the recognition that they deserve and are involved in the analysis.

470
00:52:56,190 --> 00:53:00,450
So again, it's the preparation in terms of the the technical side and the methodology,

471
00:53:00,450 --> 00:53:04,080
but also the preparation in terms of building up a network where people trust each other.

472
00:53:05,550 --> 00:53:08,550
This explains why some of your papers have an awful lot of authors on them.

473
00:53:09,300 --> 00:53:20,750
They do have a lot of balance. So, I mean, you've talked several times about things becoming policy and going to Downing Street.

474
00:53:20,760 --> 00:53:26,100
I mean, was that something you were already I mean, you must have been to a certain extent familiar with that from your previous work.

475
00:53:26,100 --> 00:53:34,049
But what observations would you like to make on the relationship between research and

476
00:53:34,050 --> 00:53:39,750
clinical medicine and how that interacts with policymaking at the government level?

477
00:53:40,170 --> 00:53:45,680
Yeah, I mean, I have experience because I have been on one of the Department of Health's

478
00:53:45,690 --> 00:53:50,399
committees called the New and Emerging Respiratory Viruses Threats Advisory Group,

479
00:53:50,400 --> 00:53:54,930
which was nervtag. Yes, yes, yes. And another terrible I still do.

480
00:53:54,950 --> 00:54:03,870
But it was, you know, looking at severe influenzas, most corona virus, avian influenza, etc.

481
00:54:03,870 --> 00:54:11,129
And I was a member of that and actually became the chair of that committee just before the pandemic started.

482
00:54:11,130 --> 00:54:15,480
So it was spaced out to two meetings a year at most.

483
00:54:15,480 --> 00:54:16,950
And, you know, it's a voluntary thing.

484
00:54:16,950 --> 00:54:26,370
It's it's independent experts who are volunteering their time so you can get paid anything to meetings a year and, you know, X number of hours a year.

485
00:54:26,370 --> 00:54:31,200
And I think we up to more than our 65th meeting last two years.

486
00:54:31,980 --> 00:54:35,460
So Nervtag is at the peaks was meeting every week.

487
00:54:36,600 --> 00:54:40,379
So that was keeping me busy as well because we were having to sort of prepare the papers for that and

488
00:54:40,380 --> 00:54:48,160
chair that and then do reports back to government about some the science and what it means and how.

489
00:54:48,280 --> 00:54:54,280
How does Nervtag relate to Sage? So is only set up during emergencies.

490
00:54:54,280 --> 00:54:56,349
And so nervtag was the standing committee. I see.

491
00:54:56,350 --> 00:55:05,410
Yes, actually, NERVTAG met before Sage was convened, so we had a couple of meetings about COVID 19 before Sage even started.

492
00:55:06,100 --> 00:55:12,010
Once Sage was stood up. Then really, Nervtag becomes a sort of committee sage.

493
00:55:13,240 --> 00:55:17,770
And in one way it's owned by the Department of Health and reports to the Department of Health.

494
00:55:17,770 --> 00:55:21,670
But in another way, it also has a sort of reporting functions for Sage.

495
00:55:23,240 --> 00:55:32,030
And then I was, you know, a member of the Sage Committee stopping on the Sage Committee for COVID 19 since the subsequent experience.

496
00:55:32,060 --> 00:55:35,610
Now, science and policy, you know,

497
00:55:35,660 --> 00:55:42,440
I think it's critically important that the independent scientists can give independent scientific advice to government.

498
00:55:44,000 --> 00:55:55,370
And I think the real trick is making sure that as scientists, we give scientific advice, but we don't tell the government policies to follow.

499
00:55:55,890 --> 00:56:04,040
You know what we tell them? Is it this is what we know. If you do this, this is what might happen if you do that, this is what might happen.

500
00:56:04,190 --> 00:56:07,270
It's up to them to decide if they do this or that. Not us.

501
00:56:07,280 --> 00:56:12,859
But we tell them what we think, the implications, what's the evidence base then for this or that,

502
00:56:12,860 --> 00:56:17,000
and what might happen if they do this or that and they take the decision?

503
00:56:22,460 --> 00:56:28,460
So there's doubt, I think, standing up now a pandemic sciences centre here in Oxford.

504
00:56:28,940 --> 00:56:32,000
Is that right? Tell me how that came about. Well.

505
00:56:33,540 --> 00:56:37,170
Very early on. Again, data was escaping very early on.

506
00:56:39,260 --> 00:56:42,800
I went to see which is the head of department here.

507
00:56:42,890 --> 00:56:47,060
He's head of the Nothing Department Medicine Oxford. So he's my my boss, in a sense.

508
00:56:47,480 --> 00:56:50,750
I went to see him and said it's early days.

509
00:56:50,750 --> 00:56:55,250
But I remember during the Ebola outbreak, the West Africa Ebola outbreak,

510
00:56:56,450 --> 00:57:01,430
the London School of Hygiene Tropical Medicine said it set up a school wide Ebola taskforce

511
00:57:02,300 --> 00:57:06,970
and they basically turned everything around to Ebola across all all of the departments.

512
00:57:07,730 --> 00:57:11,570
And it was extremely effective. And as a result, they did some really good work.

513
00:57:12,050 --> 00:57:13,910
And I think we should do this for COVID 19.

514
00:57:14,360 --> 00:57:21,589
We should set up almost like a taskforce across the department to bring everyone together, because there were so many people doing things.

515
00:57:21,590 --> 00:57:29,690
You had people doing wonderful structural biology, people working on the diagnostics, people at the G.A. working on vaccines.

516
00:57:29,690 --> 00:57:32,780
We were working on clinical characterisation of therapeutics.

517
00:57:34,790 --> 00:57:39,050
We need to sort of all be on the same page and collaborate and have a programme.

518
00:57:39,800 --> 00:57:49,490
And so Richard agreed and he convened a meeting of all of the key scientists in the medical sciences division,

519
00:57:50,360 --> 00:57:52,310
and that proved to be really successful.

520
00:57:52,850 --> 00:58:01,370
And I think that's one of the reasons that the university was so productive was because of the leadership of people like Richard,

521
00:58:01,370 --> 00:58:11,180
who saw that there was huge capability within the university, but it could be even greater if we put everyone together and supported them.

522
00:58:11,540 --> 00:58:17,270
So Richard was really central in making sure that we'll work together and when we needed support and,

523
00:58:17,420 --> 00:58:23,330
you know, if we needed financial backstopping or we needed to turn over some lab space urgently, he did that.

524
00:58:24,020 --> 00:58:30,889
And so, you know, he's he needs to take some credit for the successes of of of what's been done.

525
00:58:30,890 --> 00:58:35,610
And the same is true of other departments as well enough the department population elsewhere will be comments and yeah,

526
00:58:35,630 --> 00:58:40,760
it's turned over the whole machinery of clinical trials to the recovery trial.

527
00:58:41,420 --> 00:58:43,640
And so that kind of leadership has been really important.

528
00:58:44,090 --> 00:58:52,880
And so having seen what's possible in terms of coordination of scientific power across the university

529
00:58:53,390 --> 00:58:59,870
and seeing what's possible in terms of accelerating going from science through to actual impact,

530
00:58:59,870 --> 00:59:03,180
both in terms of the therapeutics but also the vaccine.

531
00:59:03,530 --> 00:59:11,179
I'm sure you'll talk to Sarah and others about the AstraZeneca Oxford vaccine and also diagnostics.

532
00:59:11,180 --> 00:59:17,060
You know, the university runs them, you know, the diagnostic platforms for some of the national studies in the UK.

533
00:59:18,500 --> 00:59:25,460
Having seen what's possible, what we can do if we really put our shoulders to the wheel and do things differently,

534
00:59:26,900 --> 00:59:30,710
we so we need to sort of formalise that.

535
00:59:31,130 --> 00:59:33,240
And that's the idea behind the Pandemic Sciences Centre,

536
00:59:33,240 --> 00:59:41,030
which is to bring together the expertise working on emerging infections, epidemic prone infections, pandemic infections,

537
00:59:42,410 --> 00:59:47,180
and get us all working together on a day to day basis, not just during a crisis,

538
00:59:47,660 --> 00:59:55,550
and try to ensure that we can work at the same pace on other diseases, not just on COVID 19.

539
00:59:56,090 --> 01:00:00,799
So that'll be a virtual centre, will it, rather than a physical space? It will be a physical space.

540
01:00:00,800 --> 01:00:07,400
We have a lot. So we're hoping that we will be able to raise enough funds to build that.

541
01:00:07,400 --> 01:00:14,990
So there will be a building. I probably take, you know, I think 3 to 5 years to finish the building.

542
01:00:16,190 --> 01:00:23,540
So it will be virtual for a couple of years and then it will start to consolidate and eventually we will have a new building.

543
01:00:24,710 --> 01:00:28,020
You're you're the director? Yes. I've been asked to be the director.

544
01:00:28,660 --> 01:00:38,570
So that's also something that's, you know, an active part of my work, my wife's finances, etc.

545
01:00:38,810 --> 01:00:39,490
Yeah. Yeah.

546
01:00:39,910 --> 01:00:47,719
So so that's is that that's actively operating at the moment as a virtual centre, but with a focus presumably on Corona for the time being.

547
01:00:47,720 --> 01:00:53,210
Corona virus is operating in the sense that we've even started looking beyond COVID 19 actually.

548
01:00:54,650 --> 01:00:59,450
But a lot of the activities at the moment of setting up the scientific, you know, so it is working, but we're still,

549
01:00:59,660 --> 01:01:06,050
you know, formulating the full scientific strategy and and also the sort of the operational governance strategy as well.

550
01:01:06,890 --> 01:01:13,520
So presumably this is something that you would have even before COVID 19, you would have thought this was something that was a good idea.

551
01:01:13,520 --> 01:01:21,470
But it took I suppose it took COVID 19 to bring home the necessity and the possibility of doing something like that.

552
01:01:22,340 --> 01:01:28,879
Absolutely. You know, I had in the past written funding applications, you know,

553
01:01:28,880 --> 01:01:35,810
to set up a sort of multi-disciplinary research centre, an academic sciences at Oxford, which had not been successful.

554
01:01:39,280 --> 01:01:44,589
I think because people didn't potentially see the value or the risks from pandemics.

555
01:01:44,590 --> 01:01:49,890
I think that's changed a bit now. So hopefully we'll be able to get the right investment we need.

556
01:01:52,290 --> 01:01:59,700
So I'm just going I've just got a few questions that are more about how you sort of personally affected by by the pandemic.

557
01:02:00,660 --> 01:02:10,790
So did did the lockdown and other provisions that were mitigating regulations that were brought in have an impact on on what you were able to do,

558
01:02:10,800 --> 01:02:18,840
change the way you worked? Well, like everyone I mean, I'm not I'm not a laboratory person, you know,

559
01:02:18,840 --> 01:02:23,970
so we so we work with clinicians and nurses and pharmacists working in hospitals.

560
01:02:25,320 --> 01:02:29,160
So you need access to that to our own laboratories.

561
01:02:29,170 --> 01:02:34,080
So subsequently we did do some about to work on some of the drugs we evaluating, but.

562
01:02:35,350 --> 01:02:39,260
It meant that a lot of it could be done from home and so from, you know,

563
01:02:39,940 --> 01:02:44,110
meetings virtually simply so very quickly I to make time pretty much home working.

564
01:02:45,640 --> 01:02:52,810
And because you know, our building, which is the port two cabins were closed down pretty,

565
01:02:52,960 --> 01:02:58,300
pretty early and pretty extensively and actually have only just reopened after being shut for almost 18 months.

566
01:02:58,300 --> 01:03:02,890
I think that that had to do it all from home working.

567
01:03:02,890 --> 01:03:08,770
So I've spent a very many long hours in this office, I mean, at the start of the pandemic in 2020.

568
01:03:09,280 --> 01:03:15,580
But I was having in telephone calls with colleagues every night at midnight.

569
01:03:17,220 --> 01:03:22,020
For many, many weeks. It's been I'm pretty sick of this, to be honest.

570
01:03:25,390 --> 01:03:30,370
And to what extent did you feel personally threatened by the infection, if at all?

571
01:03:31,570 --> 01:03:40,630
No, not really. I mean, I think having dealt face to face with patients with sores and bacteria and Ebola and Lassa fever,

572
01:03:42,700 --> 01:03:48,850
I felt less threatened by this because I knew that it was an individual level.

573
01:03:49,000 --> 01:03:52,900
You know, the risk of fatalities is not that high.

574
01:03:53,620 --> 01:03:57,760
The problem is, is that, you know, because it's so transmissible with so many, you know,

575
01:03:58,150 --> 01:04:01,060
hundreds of millions of infections that you do end up with a lot of sick people.

576
01:04:01,420 --> 01:04:08,110
But the individual person, individual risk of any one person ending up in hospital dying is relatively low,

577
01:04:09,460 --> 01:04:15,580
although I am only getting towards the old age spectrum where we may start to shoot up.

578
01:04:16,720 --> 01:04:18,910
So I didn't feel particularly affected at all really.

579
01:04:18,910 --> 01:04:27,430
And given the fact that we were having all the social measures in place, it really I don't think is a concern for me personally.

580
01:04:27,700 --> 01:04:32,110
Mm hmm. I mean, you mentioned that you're pretty sick of people at that space.

581
01:04:32,380 --> 01:04:37,330
And I think that was one of the major issues for most people in lockdown,

582
01:04:37,330 --> 01:04:41,350
was that the limited social contact and the fact that they were stuck in the same place.

583
01:04:41,710 --> 01:04:49,510
Did the fact that you were working on something that was clearly going to be helpful towards resolving the the the pandemic,

584
01:04:50,180 --> 01:04:54,540
do you think that helped your your own wellbeing? Oh, I'm sure.

585
01:04:54,570 --> 01:05:00,300
Yeah. You know, I think we're in a luxurious position of being able to do something.

586
01:05:00,840 --> 01:05:03,950
I mean, it must be terrible if, you know,

587
01:05:04,390 --> 01:05:12,270
you're you're seeing all this unfolding without the sort of the expert content knowledge that we have and

588
01:05:12,270 --> 01:05:18,060
without being able to sort of see your friends or work colleagues and not being able to do anything about it.

589
01:05:18,980 --> 01:05:22,170
You see an American that could be quite, quite distressing, really.

590
01:05:22,830 --> 01:05:30,450
You know, we were in the position where we understood the virus, kind of knew what the lab looks like,

591
01:05:30,990 --> 01:05:35,130
and we were doing something that was useful and it was working.

592
01:05:35,370 --> 01:05:41,820
And it could be frustrating if you were trying to do something and and it and it wasn't being effective for whatever reason that would that would,

593
01:05:41,970 --> 01:05:45,660
I'm sure not be a good place to be in.

594
01:05:45,660 --> 01:05:53,190
But it was also it was working when we saw that the for example, you know, the trials could get up and running and they they were doing that quickly.

595
01:05:53,190 --> 01:06:00,020
In that case, numbers were coming out from them and seeing a lot of patient information being uploaded on the databases.

596
01:06:00,030 --> 01:06:04,860
We could see that what we're doing is working. So, you know, that gave us a lot of succour.

597
01:06:06,580 --> 01:06:10,300
And do you think that amongst the people that you that you worked with your colleagues

598
01:06:10,570 --> 01:06:16,240
and was there any need to sort of be aware that you might need to put in place extra

599
01:06:16,240 --> 01:06:20,979
support for them for their mental and emotional well-being as a result of things like

600
01:06:20,980 --> 01:06:26,020
family members being sick or just very long hours or isolation or anything like that.

601
01:06:26,610 --> 01:06:32,650
Yeah, well, to be honest, I probably neglected that. We were so busy during the response that I actually worried that actually some of our

602
01:06:32,680 --> 01:06:36,790
team members who it and who were less involved probably had a more difficult time.

603
01:06:37,410 --> 01:06:49,970
And because of those issues. I've done that.

604
01:06:49,980 --> 01:06:53,880
I've done that. Okay. I think. I think we're moving towards a conclusion, though, actually.

605
01:06:56,030 --> 01:07:04,370
So this sort of sounds like a silly question. I read it, but has the work raised new questions that you're interested in exploring in the future?

606
01:07:07,740 --> 01:07:14,370
Well, it's really showing the power of these sort of these mega trials,

607
01:07:15,660 --> 01:07:20,010
which are platform trials where you can add in new treatments and just keep the platform going.

608
01:07:20,820 --> 01:07:24,420
It's really showing the power of that. And I think, you know,

609
01:07:24,420 --> 01:07:28,800
many people have said that the recovery trial is a transformation in the way that it's really simplified

610
01:07:28,860 --> 01:07:36,660
to become an extremely complex trials network and showing that you can you can make a real difference.

611
01:07:36,750 --> 01:07:42,570
And regulators have accepted the results of these trials and we've changed practise.

612
01:07:43,500 --> 01:07:52,830
So why can't we do this every day? So I'm really hoping that it will have a long term legacy from the trials in the way things are done,

613
01:07:53,370 --> 01:07:57,540
and simplifying trials and making sure that we get big numbers of patients in simple

614
01:07:57,540 --> 01:08:05,520
trials to give clear answers on a more sort of technical level that the the benefits of.

615
01:08:07,930 --> 01:08:17,319
Immuno modulation. So the anti-inflammatory drugs in COVID 19 have been a bit of an eye opener to see that steroids work and that the other drugs,

616
01:08:17,320 --> 01:08:20,680
tocilizumab and some other anti-inflammatories are beneficial.

617
01:08:20,950 --> 01:08:31,330
So I think it really has opened the door for looking at the more closely at the role of anti inflammatory approaches in infectious diseases.

618
01:08:31,360 --> 01:08:37,000
You know, there are some well, we know that anti-inflammatories can work like TB, meningitis, etc., but.

619
01:08:39,450 --> 01:08:44,430
Then I just kept optimising that and there may be scope for using immunomodulators in in other infectious diseases.

620
01:08:44,760 --> 01:08:50,219
So one of the things we'd like to look at is the use of steroids in severe influenza to patients

621
01:08:50,220 --> 01:08:55,470
hospitalised with influenza because again there is evidence of a severe inflammatory line that's going on.

622
01:08:55,950 --> 01:09:00,510
So I think that's, you know, an area of scientific endeavour, which is quite exciting.

623
01:09:00,840 --> 01:09:04,710
Mm hmm. And in terms of global health, generally,

624
01:09:05,460 --> 01:09:14,070
what lessons do you think there have been and what would you like to see change in the way global health research and practise is implemented?

625
01:09:16,130 --> 01:09:19,480
But that's another talk, isn't it?

626
01:09:21,090 --> 01:09:36,310
Uh, well, I think. Seeing, you know, serious investment in research and development for health threats is the key is is the key lesson.

627
01:09:36,790 --> 01:09:43,870
And we said this after the Sars-Cov-1 outbreak, and really there wasn't much investment and it was very short lived amendments and very short.

628
01:09:45,910 --> 01:09:53,320
And now we've seen, you know, the massive impact that is possible from these viruses.

629
01:09:53,620 --> 01:10:03,090
And this is with the virus is not even that severe. Can you imagine, as I said, you know, five or 10% mortality or even sort of, you know,

630
01:10:03,850 --> 01:10:09,520
mortality that isn't concentrated in the older age groups but is concentrated in younger age groups.

631
01:10:10,210 --> 01:10:14,410
You know, the fear, the disruption, the cost is astronomical.

632
01:10:15,850 --> 01:10:19,270
And, you know, others have said it, but I'll say it as well.

633
01:10:19,300 --> 01:10:27,700
You know, we spend billions and billions on defence spending for weapons,

634
01:10:27,820 --> 01:10:35,770
weaponry that really does not have quite this sort of global health value of research and development on pandemic infections.

635
01:10:36,560 --> 01:10:39,250
You know, this is our insurance policy. We need to take it seriously.

636
01:10:39,250 --> 01:10:45,549
We need to invest properly, heavily in it, in a sustained way in research and development for infectious diseases.

637
01:10:45,550 --> 01:10:49,410
And that can be focussed day to day on day to day infections.

638
01:10:49,420 --> 01:10:54,579
You know, we still have plenty of infectious diseases we need to tackle, like dengue.

639
01:10:54,580 --> 01:10:58,660
TB You know, still the HIV is not not curable.

640
01:11:00,580 --> 01:11:04,510
There's plenty of work to be done, dates down infections and we can invest heavily in that.

641
01:11:04,510 --> 01:11:08,080
And it will also be an insurance policy against pandemic infections.

642
01:11:08,530 --> 01:11:12,700
I think also there's a need to look at the ecology of emerging infections.

643
01:11:13,420 --> 01:11:23,559
Most of these viruses do come from animal sources. We need to think about how we are managing the ecology of these animals and how we're

644
01:11:23,560 --> 01:11:29,140
interacting with them and what risks we are generating and how we can mitigate them.

645
01:11:30,540 --> 01:11:34,109
Is that, do you think is a better way of organising internationally?

646
01:11:34,110 --> 01:11:42,960
I mean, you mentioned that W.H.O. was a bit slow early on and is Eric was able to be quite fleet footed because it was a peer to peer network.

647
01:11:43,200 --> 01:11:51,150
Is is does something need to be done about essentially the human resources and infrastructure globally to to improve things?

648
01:11:53,580 --> 01:12:02,600
I'm absolutely sure that there's a lot that could be done in that there's there's this whole areas that we haven't touched on like,

649
01:12:02,610 --> 01:12:15,989
you know, uh, you know, political decision making and interaction between governments financing an equitable access to vaccines and drugs,

650
01:12:15,990 --> 01:12:19,380
which, you know, really she was inequitable access to vaccines.

651
01:12:20,530 --> 01:12:24,870
Many of the drugs, for example, the monoclonal antibodies that we tested are very expensive.

652
01:12:26,550 --> 01:12:34,860
You know, that needs to change. There's some way of making them available, affordable prices to the whole world, not just selected parts of the world.

653
01:12:36,270 --> 01:12:42,290
And in terms of the research response, yeah, I think, you know, we have to look at what's worked and what hasn't worked.

654
01:12:42,300 --> 01:12:51,660
I think what has worked is. Having invested in infrastructure and people over a long time periods to work on infectious diseases,

655
01:12:53,130 --> 01:12:58,530
but also empowering them to be able to respond quickly to in 19 threats.

656
01:12:58,530 --> 01:13:02,730
I think that's the way forward and I think international agencies like W.H.O.

657
01:13:02,880 --> 01:13:07,650
have a really important role in sort of normative saying normative standards.

658
01:13:08,850 --> 01:13:15,840
How should we be doing this? How do we ensure equity of access and costing and pricing?

659
01:13:16,200 --> 01:13:19,410
How do we prioritise what we do? And then secondly,

660
01:13:20,100 --> 01:13:28,050
the implementation really needs to build up grassroots capabilities because this research needs to be done by people who are on the ground,

661
01:13:28,560 --> 01:13:33,270
know the patients and know the health care system and the public health system they're working in.

662
01:13:35,520 --> 01:13:36,750
Great. Thank you.