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From the plague of Athens to the Spanish flu and from the Black Death to the Ebola outbreak, we've taken a journey through a litany of human misery.

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And as you listen now, we're experiencing another devastating pandemic, Kovik, 19, caused by the source code to virus, but could be worse yet to come.

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In 2015,

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the World Health Organisation asked a group of global experts to draught a shortlist of serious emerging infectious diseases around the world.

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The idea was to focus research and development on them to try to stop future outbreaks from turning into a public health emergency.

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The list contained some diseases. We discussed Ebola and songs and many we happened, including Zika, Lassa fever and Marburg virus in 2018.

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After meeting in Geneva, the team added one more name to the list Disease X,

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a place holder for an unknown hypothetical pathogen that might pose a future epidemic.

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Welcome back to the present day and welldone the making it through all of the diseases, not history of pandemics.

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In today's bonus episode, I interview the Oxford scientists working at the forefront of research into Disease X

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and discuss what we may or may not have learnt from experience of Koven along the way.

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I'll include a few discussions which couldn't quite get into the main series,

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including a conversation I had about whether a focus on pandemic masks the real problem.

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Humanity faces ongoing endemic diseases on the way.

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I'm Professor Sarah Gilbert, now world famous for her work on Oxford's Coronado's and Professor Peter 4B,

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co chief investigator of the trial, discovered that dexamethasone could be a lifesaving drug.

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First up, though, it's a John Bell Regis professor of medicine at Oxford.

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I began by asking John where he was when he first heard about Kovik.

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I was going about my daily routine in that principle, first over and then over Christmas.

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Twenty nineteen. I had a communication from Jeremy Ferrer, who is director of the Wellcome Trust and who is pretty in tune with emerging infections.

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Of course, he ran our unit in Vietnam at the time of the H5N1 avian flu epidemic.

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So he's pretty much linked in to all the epidemiologists and clinical scientists who do this in Asia.

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And the message I got from him is there's trouble brewing in central China.

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And it looks like there's quite a serious epidemic brewing there.

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Lots of sick people not care of the data. We're on it.

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Be careful because this may find its way into a pandemic. So that was pretty interesting.

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And George goWe, who worked in my lab for many years and went back and is assigned to the director of the CDC in China, was also in touch.

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And that was clear that they were really under pressure in China because they learnt rather too late about the epidemic.

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So they moved in to try and work out how to contain it. But it was clearly very, very serious.

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And it was really about that time that things started to leak into the press about there being a serious problem in central China.

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And then that sort of blew up in early January. The sequence was published the end of the first week of January, and then it all went from there.

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But it happened pretty quickly, you know, really literally over a three or four week period.

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It was pretty clear to me from they were almost from the initial descriptions that this was going to be bad.

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And I'm not a doomsayer, but I had been watching out for pandemic threats for a number of years.

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And the H5 N1 epidemic was pretty worrying.

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And we were really only saved by the fact the pathogen didn't transmit from human to human.

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It was only from birds to humans, but it carried a really high mortality.

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I think the numbers were between 30 and 50 percent. Scar's one adult, 35 percent mortality.

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And since the year 2000, we've had eight of those close calls.

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We've had two Saar's outbreaks, each self-contained.

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The murres outbreak, self contained, avian flu constrained by its inability to transmit between humans.

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Another avian flu in China since then, which again has been limited.

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And then, of course, the 2014 flu epidemic, which actually is global but wasn't as severe as we expected.

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And then we had Ebola and then we had Zika. So, you know, look, there's a whole set of these pathogens that are coming in to the world and appearing.

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And we've just been. Really lucky that none of them had blown up.

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So when I heard about this, I thought, you know, this may be the big one and it may become pandemic pretty quickly.

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And to be clear, at that stage, we knew nothing about the pathogen. We didn't know how many people were symptomatic.

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Coming to give or asymptomatic. We didn't know how it was spread.

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We didn't know what the case fatality rate was likely to be.

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We didn't know anything. And so it didn't need to be a quite a lot of work to work out what was going on.

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So I thought of this as being a problem. Very early by the end of December, I am pretty sure this is going to be a massive issue.

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And it was also pretty clear to me from the end of December that Oxford probably had quite a lot to contribute to this because first of all,

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our units globally will be in a good position to provide surveillance data.

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We had terrific contacts in China. We had terrific contacts elsewhere in Asia and of course, elsewhere in the global health space.

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And we had very, very powerful capabilities in vaccines, but also in testing and also in drug trials in all the areas which Oxford came to dominate.

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It was clear to me that we could actually make a big play. And now, nearly a year into tackling this disease.

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I wondered what lessons John thought we've already learnt. You could write a book on the lessons learnt.

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The real risk is that people will forget the lessons learnt and we'll go back to business as usual from next year.

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But the first big lesson is don't be complacent about the threat of a pandemic.

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The speed at which it can occur and the need to have real preparedness in place and to move quickly when you start to see it coming.

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You can't afford to say, oh, it'll burn itself out. It'll all be fine.

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Don't need to worry. And worst of all, the NHS is prepared because none of those things are true.

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And I think the failure in this country not to move quicker is a deep national embarrassment.

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Frankly, wasn't as if we didn't know about these things. And it wasn't as if people weren't told.

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They just chose not to do anything. I'll tell you, our problem, though, is we only know what we know.

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And of course, we know what we know from history. And you guys just bit over the history.

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The scary thing is what we don't know, and that may prove to be very tricky.

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And I mean, it's fair to say we knew a bit about this, but we didn't know much about this when it arrived.

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I think that's one of the big challenges. But I also have to say that the incredible efforts of the science community to interrogate this pathogen,

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understand how it worked, what it looked like,

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every bit of its genome and all its aspects of pathogenicity and and its infectiousness has been done in an unbelievably short period of time.

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And now we're sitting here with three good vaccines, the best of which is undoubtedly the Oxford vaccine.

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And we're ready to go and fight back in a pretty serious way.

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So, you know, the fight back has begun. But in that story, there's dexamethasone which came from the recovery trial.

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There's the mass testing programme with lots of flow tests, which has been led by Derek Warkentin Pito.

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There are any number of great stories that are hugely led by Oxford scientists.

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Moving on to future risks. Our main focus in today's episode.

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I was interested to ask John whether there are notan diseases we should be wary of or whether

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the pathogens that lead to major outbreaks are often entirely unknown until they strike.

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In reality, we do occasionally get a new outbreak of a pathogen that we haven't previously identified and characterise.

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So a good example of that is Lyme disease, which is spread by ticks in the east coast of the U.S. Legionnaires disease,

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which is an aerosol spread, pneumonia, which we didn't know and understand.

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There haven't been big outbreaks. They can start small. We tend to understand them better, and then we get a read on the pathogens.

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So we're in better position to know what's going on. So most of the things that blow up on a global scale we've seen before now quite a

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bit of documentation about the list of respiratory viral pathogens in particular,

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which I think are probably the biggest single risk that might potentially cause trouble.

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So, for example, when Ebola blew up in West Africa, we knew about it had been discovered ten, fifteen years before Nipah virus.

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There's been a few small outbreaks of Nipah. We know about that. Saar's Kobe one appeared in Hong Kong and then was transported to Canada.

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That was a class virus that we didn't know very much about. But we now know quite a lot about that class.

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And there's a whole family of Sabor virus. It's obviously better corona that potentially cause trouble.

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So there's steady progress and knowing what's out there.

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Now, each of the individual pathogens that cause disease will probably be different than the previous one.

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But we know a lot about the family, as it were. So we didn't go into this epidemic with no knowledge of Saar's.

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We just didn't have specific insights into Saras be to which we now do.

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So, yeah, so it's not as if we don't know what to prepare for.

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We do know what to prepare for and we know how to get the various assets in place to deal with an epidemic more efficiently than this one.

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I think the two or three big ones are still flu.

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Flu is still the biggest single threat in my view. It varies pretty substantially from year to year.

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There is a lot of avian disease out there that could, with a few mutations, become spread from humans and humans.

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At its worst, it carries a really high mortality. And of course, the great flu epidemic of 1917 1918 carried away, you know,

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somewhere between 50 and under a million people, depending on how you're counting it up.

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I think, in my view, that's still top of the list,

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that Corona viruses were probably always second on my list partment because the Saras and the murres outbreaks,

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there was always question about what it would take to produce one that actually had real pandemic capabilities.

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But we now know that that can happen. So I think that's the second big class.

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And then class of viruses that sit around Ebola are probably also still a risk.

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They're spread very, very effectively. They're infectivity is very high from human to human.

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That is another family of viruses I would worry about a lot.

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But there are only three of a long list. So we do need to be thinking about what that list looks like.

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John's list didn't include anti-microbial resistance, which came up during a number of my discussions with guests for the series.

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So I asked him why he left it out. Thing is, there is a little bit of antimicrobial resistance, but it's very little.

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Some pathogens, TB, it's a serious problem in TB and gram negative organisms.

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You're seeing more of it.

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But, you know, it hasn't swept the world and you don't have thousands of people dying and they will get their total hips down.

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Do you I mean, it's just basically isn't there. And to be clear.

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We've been talking about it for 10 years. So I think there is a bit of a problem about hyping these things up too early.

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I would say that's probably an example of one. And it also doesn't help to beat up the pharmaceutical industry because,

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you know, there's been lots of bleeding to say that pharma industry is at fault.

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The truth is, it's a massive example of market failure, because if you make an antibiotic to gram negative pathogens,

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you are resistant to the usual antibiotics that you use it.

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For those infections, you could easily spend a billion dollars making the product.

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And what are you going to do, sell it to 400 people a year? How is that going to work?

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So, you know, government really wanted to have this happen.

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They would have put pre-orders in for these things so that a company knew if they made one, they could get a return on investment.

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But nobody has done that. So I think it's not.

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I wouldn't put antimicrobial resistance in my top list of things I wake up at night worrying about.

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I mean, I had some experience on this because I have been on the board of Roesch for many years and the course had Tamiflu and is now gone.

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So she's had since got the only two really good anti flu medicines and they spent a lot of money developing Tamiflu and then they couldn't sell it.

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I mean, really, literally, they could not sell any.

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And it was a real problem until avian flu came along and everyone went, oh, anybody got an anti flu drug?

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And then suddenly they sold two billion dollars worth in a year.

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Right. And then the following year, everybody said, well, there's no flu epidemic this year.

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We're going to stop buying it. So it went from two billion in sales back down to nothing again.

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So, you know, if you're running a company that's not very out there, it creates its own problems.

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These infected medicines, it's a it's a real issue.

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With all of these potential threats in mind, I was really keen to hear John's view on how we should prepare for future pandemics.

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This is a really interesting story, and I've been a bit involved in the national planning for pandemic preparedness,

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which is largely being led out of number 10, but also the Cabinet Office, as you know.

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Boris Johnson gave a speech, a U.N. speech about this a month or six weeks ago and indeed cited those eight examples of close calls that have occurred

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since the year 2000 as a warning harbinger that there's likely to be more trouble in the not too distant future.

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So the way I think about this is there's several boxes of activity that we probably need to establish is ongoing,

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sustainable functions of the global community to deal with pandemics.

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And the first one really relates to the ability to have better surveillance and a better heads up as to what's happening.

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Quick pathogen identification, global surveillance for outbreaks of severe disease have put people in intensive care units around the world,

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rapid identification, probably by genomic sequencing, which is the quickest way to do that.

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And we need a network of centres that do that so we can see what's coming and what isn't coming.

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So that's probably the first and most important initial capability.

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It's probably also worth thinking about whether we have a sort of nine one one team that can drop into these sites,

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which is a sort of rapid response group. I mean, Peter Harvey does some of this and of course, a huge advocate of quick response to pandemics.

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And he's probably as experienced as anybody in dealing with these emerging infections.

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So I think you use our words very serious consideration.

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So that surveillance piece is a crucial piece. We need good data.

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Global data, whether we see through lots of ZEW, not organisms, organisms that are found in the animal species, I think is a debateable issue.

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I mean, some people have argued, well, why don't we have a massive programme on animal pathogens that might pass from animals to humans?

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I mean, it's a great thing. It's great. That's a great soundbite. But, boy, is that a hard job.

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Because there are there are literally millions of those potential pathogens out there.

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I mean, just take bats alone. They're full of all kinds of pathogens.

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And if you go across multiple animal species, you can find lots and lots.

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And I'm not entirely sure what you do with that information because you'll end up with a great long list.

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But how you pick potential threats from ones that are not is quite challenging.

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So that's the surveillance box that the second box is.

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What do you do about having their reagents available to respond to a new epidemic with,

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for example, a new virus, a new member of a viral family, a new flu, new corona virus, whatever?

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And the answer is that there's quite a lot you can do now to get yourself ready for that.

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And these were all areas where we were clearly failing,

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at least in the UK and actually globally in terms of being prepared for this event, for example, with vaccines.

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There are now at least two vaccine platforms, RNA and adenovirus, both of which have shown that they can produce vaccines pretty quickly.

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And so there is an interesting question about can you pre-empt some of that activity that needs to be done early by creating model vaccines,

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checking their immunogenicity and normal people, making sure they generate strong neutralising immune responses,

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all that kind of stuff, even if you don't know the precise pathogen.

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You know, as Sara Gilbert's great success was migrating quickly from a Meurs programme,

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which she'd run very successfully into a Saras Kobe to programme, and being on the front foot for this is really important.

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And when you look at the Jenner portfolio, they're working on twelve emerging pathogens.

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So there are sort of already all over this. It would be good also to have an RNA programme that could be pretty interesting as a potential play.

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You can imagine getting range of vaccine platforms ready to go.

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That could move quickly in the face of a new family member that perhaps didn't have

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crossed reacting immunogenicity with previous infections as it was for COGAT 19.

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The second one is drugs. So it's an interesting question whether we could do a better job with drugs.

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This is not commercially very viable because you can make an antiviral against a Saras pathogen.

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You're not going to sell it to anybody. So it's got to be subsidised by government.

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But would it have been better if we'd had more model drugs targeted at, for example, the RNA dependent RNA polymerase, which is.

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Sweet spot in these Corona viruses or to the protease, which, again, is a potential sweet spot for this.

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And could we have a set of small molecule libraries that have been tuned and honed to target those particular targets across a range of emerging

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pathogens so that we had a better chance of moving quickly to find a molecule

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that you could use in patients now that when you look back at the epidemic,

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that's quite a hard sell. And the reason is, let's say in January, you said, let's get the library out.

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We know what this pathogen looks like. We've got the crystal structure, the protease.

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Let's make a protease inhibitor. Well, you could have got to a protease inhibitor probably pretty quickly by the summer.

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I would've thought. But then you got it in safe to study and you got to do trials.

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You got to do all that. So, I mean, Pfizer's going to protease inhibitor, as you know, to cope with 19.

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They're probably going to get licence just about the time the pandemic goes away.

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So you'd have to be pretty clever to get those things in place in a timely way.

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I think a better option, of course, is repurposing drugs in their recovery.

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You spoke to Peter Hornby. It's a good example of how repurposing has very substantial benefits in this setting.

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But then the other big play is antibody therapies.

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So monoclonal antibodies for this disease are going to prove to be very important role.

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I think they're very potent than virals. And again,

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we only started making those antibodies when the first convalesced serum started coming in

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and we started to clone the B cells that produce the antibodies and then characterise them.

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And of course, as soon as you've got a lot of sick people, it's quite easy to make a lot of monoclonal antibodies to these diseases.

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And I think we need to be prepared to do that and think about how we would set that up.

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But a final bit of that story is I become very intrigued by broadly neutralising

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antibodies so that basically antibodies that react to Saras Kohji to that they are

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equally effective against Saras coli one and they're equally effective against all

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the members of that family because they've designed a protein epitopes in Spike,

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which are shared between all those viruses and people been working on broadly energising antibodies for HIV for a long time.

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And there's been some beautiful work done, but in respiratory viruses, nobody's really focussed on that.

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And I think that's possibly the idea. So I've seen three broadly neutralising antibodies that seem to neutralise all the members of that Saras family.

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And there's about 10 members that we know about now.

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And so you think to yourself, well, Hammet, if you actually had those antibodies, those antibodies that would neutralise anything in the family,

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then I think you could make a very good argument of growing those up, lie off, slicing them,

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sticking them on the shelves, literally sticking a billion in them on the shelves so that you've got a buffer,

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because if they've been appropriately modified by modifying the F.C. receptor, they last, you know, four to six months after an infusion.

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So you could give yourself a buffer against just another Sari's virus infection by simply having a massive supply of those things.

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So, you know, that's another bit of a therapeutic vaccine piece that we need to develop.

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And then, of course, there's diagnostics. So we've had a huge amount of diagnostics, innovation in this epidemic.

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And I think we've got to continue to do that because it turns out that knowing who's

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got the disease is the first and most fundamental piece of knowing what's going on.

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Mostly, this has been PCR driven in most countries in the West, but there probably are better ways to do these diagnostics.

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And I think we do need a bit of innovation in this space to get better diagnostics,

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which you would probably have to conceive of in the early weeks of the epidemic.

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But you could probably move down the road very quickly. So that's the second.

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Boxton third box is really about data and clinical trials.

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We need an international standard for data. We've got to have groups that are ready to go to launch clinical trials as an international consortium.

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Almost immediately. You've got to have data sharing agreements that allows you to put data from the trials into a cloud that everybody can access.

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And you've got to have standards of data that allows different countries to know that

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their data is basically on the same standards as the French data and the German data,

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American data and the Australian data, because it did at the moment in this pandemic, all the data's everywhere.

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So you'd have no idea what he's doing, what to whom, which is a real problem.

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So that's a box of clinical trials. And data is another very important piece of the puzzle.

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And then there is a piece around manufacturing, which I think is also crucial.

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And that is we got caught without any substantial manufacturing capabilities in the UK, least none that we knew about.

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And V-neck Centre, which had been funded through the life sciences industrial strategy three years ago, three and a half years ago.

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They're having cleared a bit of ground it was supposed to sit on. So they were able to hasten the speed of that.

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But it's still not going to be ready till after the pandemic. So we need vaccine manufacturing capability.

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We need antibody manufacturing capability, and we need diagnostics, manufacturing capability.

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That's the other big box. And then the final big box is regulation.

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One of those things slow this down in this endemic is that we use the usual routes to approve or not approve individual medicines,

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diagnostics, antibody, selex. And I think there's an argument in the presence of a pandemic to change those

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rules so that you don't get tied down by the constraints of the regulatory system,

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which basically means you can't move fast enough. Now, I say that incomplete knowledge at the MHRA has been terrific in this pandemic.

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But they too have been caught by the rules where they have to do certain things, which I think if they had thought about it,

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they would have preferred not to ask for those kind of those kind of results or derogations because just should have been waved through.

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So I'm pretty sure that that will be a crucial bit of the puzzle is to try and get the regulatory right and the communications thing right.

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So that's another box. But those are the five or six things that I think are crucial.

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Next is Peter Hopea, professor of Emerging Infectious Diseases and global health at Oxford.

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As with John, I began by asking Peter where he was when he first heard about convened by the executive director of an organisation called a Sorich,

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which is the International Severe Acute Respiratory and Emerging Infections Consortium, which has got partners all over the world.

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And so I have very strong links, longstanding collaborations with colleagues in China.

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So I knew immediately that we would be involved somehow.

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And actually, the first contact with colleagues in China was on the 2nd of January, just a few days after the outbreak was announced.

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And it turns out that one of our close collaborators was nominated by the Beijing government

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to be the lead on clinical research for this new virus and was sent to him to investigate.

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And he rang up and we had on 2nd of January, it was serious.

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I've seen no outbreaks of soslan and bird flu in the past year.

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I'm from the clinical descriptions and from my conversations with my colleague in China,

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which we were having every night at about midnight and 2nd of January,

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it became clear that it was a serious illness, that it was transmissible from person to person.

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So it was clear pretty early that this was a serious virus and a serious outbreak.

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I don't think it became clear that it would be a pandemic, as in that it would spread around the world until quite a bit later.

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Initially, we saw some cases outside of China, but it didn't really seem to cause much onward transmission.

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They were taking control. So early spikes in Thailand and elsewhere.

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But I think what we then saw was continued spread outside of China and then it became pretty apparent some sort of sometime in February.

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This could be very difficult to contain. Peter and his colleagues immediately went about organising a new clinical trial to test the

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effects of numerous already known treatments on patients admitted to hospital with Kobe,

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19. This was called the randomised evaluation of Kuvin 19.

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Therapy, trial or recovery for short. They knew they'd have to act quickly.

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What we've learnt in the past is that business as usual doesn't work for epidemics or pandemics.

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They're very challenging for lots of reasons. They're very quick.

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They're hard to predict where they're going to occur. The health care system and individuals are under great pressure,

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both in terms of running the day to day jobs skills and in terms of political and other pressures.

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So you really have to have a different mindset.

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And what we've seen in the past is the usual sort of clinical research or other types of research that are done,

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just not done at the pace and the way they need to be done in epidemics.

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As an example, clinical trials testing new drugs in patients often take 18 months to set up.

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News don't have that time. You don't have eight months. In fact, many epidemic waves are about six weeks so that the pandemic may last a long time.

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And then any one individual area, you get a wave. So you need to be ready for that.

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So what we we learnt with our experiences with songs, the bird flu and the 2009 influenza pandemic is you must have a great sense of urgency.

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You have to move very, very quickly. And that's what we did.

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And it was the right thing to do because it meant that we could capture the patients in the first wave of

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the illness and really make some progress in understanding this disease and finding new treatments for it.

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One of the key issues is that we need to have pretty big Charles detective, modest aflex of drugs and most benefits.

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The drugs are fairly modest and so we need to have thousands of patients now.

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Enrolling thousands of patients during an epidemic is challenging because you only have limited time,

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but also the health care staff are under a great deal of stress and pressure.

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So the first thing is it needs to be very simple.

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So we designed it to be a very, very simple trial that could be used at the front line by doctors and nurses under pressure during the epidemic.

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And because of that simplicity, we were able to roll it out very quickly.

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So I think we broke some records, retime from when we had the first draught of the protocol to the first patient enrolled was just nine days,

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which I think that's a record that will never be beaten.

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And then within two weeks, we enrolled nearly a thousand patients and within eight weeks, ten thousand patients.

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So it was really highly successful and we built it so it could be adaptable.

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So we built it so that we could and can move drugs and no evidence became available.

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And that's what's happened today. At the time that we're recording this, we called the result on three drugs,

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one of which takes measures that were successful, two of which were not successful.

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And we've still got five drugs in the trial and we keep updating them.

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So we've recently added an example.

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I want to call an antibody and then we know that, again, aspirin, and then we will be introducing more drugs as time goes on.

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So as we learn more about this virus in which drugs might be effective, we can slot them into the platform trying to recover.

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The speed of the recovery investigation, as well as what it's already achieved, was hugely impressive.

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And I asked Peter for his reflections on that. I reflect on it almost daily.

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It's it's an incredible achievement, I think.

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And I'm not saying to bolster my own, the achievement is really a fabulous clinical trials team that have been setting this up.

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And also the huge support we've had some chest than the national health mostue research infrastructure and support from government,

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from the chief medical officer and the doctor, chief medical officer has made this possible.

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And I think about this. I think, you know, this is the best thing that I've been involved in in my career.

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And this really made a difference.

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And it's something we can all be very, very proud of as a country and which we need to make sure we replicate in the future,

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not just in the UK, but elsewhere, because it really has been very effective.

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And we need to make this asset available globally in the light of this experience.

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I asked Peter what key lessons can be learnt about preparing for future pandemics.

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There are many things we need, but the top three probably are the will to do it.

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That's political will and will from universities, research, sexual research, condos, et cetera, to really make this happen.

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It's very hard to make an argument that will second it comes the investment because you do need resources to make this work.

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And what you need is resources that are there in peacetime as well as in times of crisis,

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because you can't suddenly create that infrastructure when there's a crisis, you need to have it in place.

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And that was one of the successes of options. We had a lot of the work done, a lot of the experience in the bank, and we had the technology is there.

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So you need that investment during peacetime. So it's your insurance policy for when things go wrong.

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And thirdly, you really need sort of the technological innovation, because as we've seen child designs with diagnostics and with vaccines.

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If you put in place those technologies that are broadly applicable across a whole range of threats,

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then you're already ahead of the game where you threat arises.

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I think the UK has done an extremely good job in terms of research and research, the impacts in the cockpit 19 pandemic, and that is recognised.

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I think that's recognised at all levels, both within the research community,

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within the leaders of Oxford University and other universities and within government.

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And so I do believe we're very well-placed and I'm hoping that we will see in the next few years a real

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consolidation and will all of what we've learnt to put us in a much better place to make to a safer world.

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However, Peter was very keen to emphasise that there are serious obstacles to our preparing for the next pandemic, whatever that may be.

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One of the dangers is always fighting the last war.

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And that's something I've observed over the years, is that the planning around response to Bursley was based on what happened in Salz and then

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the planning and response to the next flu pandemic was based on the experience with bird flu.

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And then the planning for Cobbett, 19, was based on the 2009 flu pandemic.

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So you have to be very wary about thinking that you know what's coming.

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It's very likely that we'll have some knowledge about an emerging virus to be

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from a class of viruses that we probably know about and we'll know a little bit.

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But it's very likely it will be a new variant of that virus, which will behave in a different way.

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Covered 19 is a good example. It's a corona virus and there are seasonal corona viruses that have been around and known about for many years.

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And then there's the Middle East Respiratory Corona virus, which has been around for some time, is much more severe and comes from animals.

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And we know about that. Now, this is in that same class, but it behaves differently.

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It's much more transmissible than most corona virus and it's more severe than seasonal corona viruses.

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And it has a different pattern of disease in terms of when the peak infectivity is different from sovs.

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When the patients develop an inflammatory syndrome, it's like other coronaviruses.

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So it'll be something we know something about, but there'll be many different aspects of it.

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And we have to be very careful not to make assumptions because it's from a class of viruses we've seen before that we've got to know how behaves and

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corona viruses had already been identified as a serious risk prior to our current pandemic converter boxes were on the WHL list of priority pathogens.

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So they were identified as a risk. So we got that right.

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What is new about the viruses that just have a slightly different genetic makeup in slightly different biology,

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which means that you have to rethink your suite of interventions, so you have to rethink your diagnostics.

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You have to rethink your drugs and vaccines cetera. The vaccines failed.

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As we've seen with clearly recent results of success in the cloning of our state, things was reasonably well advanced.

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And there had been work ongoing to develop vaccine constructs for the Middle East Respiratory corona virus and to the source coronavirus.

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So in that sense, that worked. We have the platform technologies up to be able to switch to a new corona virus.

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I think we did less well on drugs. What we didn't have was a suite of products that we thought were active against corona viruses.

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And we're ready to go into clinical trials. There were some very preliminary data from experience of trying medicines during the first

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signs outbreak that really there was nothing in that suite of drugs that was very spectacular.

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So we were left with starting out the clinical trials with rather unpromising drugs to end our conversation.

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I mentioned my discussion with Professor Brian Angus comparing Kovik, 19,

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to other diseases like Ebola and asked Peter which diseases concerns him most.

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The answer very much depends on what perspective you're taking.

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If you're taking a personal perspective about whether you would pick about a virus or corona virus if you had to.

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One of the two, I think the answer's pretty clear. But in terms of the global health impact, then I'm much more scared of things like corona viruses.

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But many other categories of viruses are common or garden, but have the potential to become more serious.

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Examples are much more serious strains of influenza, but there are also other viruses like enteroviruses, which are very common.

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What viruses that cause polio accentuate a new strain of something like that?

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Those viruses really could have a huge impact and we've seen that with this pandemic.

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And so it's not just about the severity of a single infection.

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It's about a whole package of how that virus transmits itself and the impact it has beyond the individual health.

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Our next guest has, like Peter, played a huge role in the global fight back against the Kovik 19 pandemic.

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It was a real privilege to talk to Sara Gilbert, professor of vaccinology at Oxford, particularly at such a busy time for her.

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Sarah has been rightly hailed as a pioneer of Oxford's Chad Ox, one in KOF 19 Corona virus vaccine, but her work in this area started a long time ago.

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I began by asking her when she first got involved. I started working on vaccines because Adrian Hale wanted to make a vaccine against malaria.

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That in particular that works for inducing strong t cell responses.

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And we've heard quite a bit this year about T cell responses as well as antibody responses.

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But remember that most of the vaccines that we use that are licenced today, we only think about the antibody responses that they induce.

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They usually work through antibody responses and to find out if they all work and we measure antibody responses.

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And so responses are important, but they're not at the forefront of what people were thinking about at the time when making a vaccine.

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But there's a particular stage in the malaria lifecycle where shortly after somebody has been bitten by an infected mosquito,

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the parasites that go into their bloodstream, which called, oh, it's at that stage very, very quickly get inside the liver in small numbers.

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There's only maybe 10 infected cells if if even that.

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So it's not a particular problem for the liver,

380
00:39:01,090 --> 00:39:06,320
but there will be a few infected liver cells as far as the whites turn into factories to make lots more

381
00:39:06,320 --> 00:39:11,600
of themselves in a similar way to a virus is taken over cells in our body and turn them into factories.

382
00:39:11,600 --> 00:39:15,070
That's what the malaria parasite does at that stage of the lifecycle in the liver.

383
00:39:15,070 --> 00:39:21,350
And because they're hidden away inside a liver cell and they stay there for about a week, antibodies can't reach them.

384
00:39:21,350 --> 00:39:25,340
So antibodies, if you have a very high level of antibodies in your blood,

385
00:39:25,340 --> 00:39:31,340
when the mosquito bites you and the antibodies can recognise as far as away and destroy it, then you won't get malaria.

386
00:39:31,340 --> 00:39:34,580
But there's a very short time. That's only about an hour.

387
00:39:34,580 --> 00:39:39,920
And so there's not really very much chance of that working, whereas the parasites then inside the liver,

388
00:39:39,920 --> 00:39:43,910
sitting inside a cell, making more itself for about a week.

389
00:39:43,910 --> 00:39:47,030
And T cells can recognise those infected liver cells and destroy them.

390
00:39:47,030 --> 00:39:54,590
And that does happen in people who live in malaria endemic areas and have done all their lives and they have some natural immunity to malaria.

391
00:39:54,590 --> 00:40:00,050
Then there is quite a bit of evidence that sometimes the parasite can be attacked at that stage of the lifecycle.

392
00:40:00,050 --> 00:40:07,610
So the idea would be to develop a vaccine that would induce cell responses that would kill these infected liver cells.

393
00:40:07,610 --> 00:40:10,730
Again, small number. So it's not going to cause a lot of liver damage.

394
00:40:10,730 --> 00:40:14,900
And then the person who'd been infected wouldn't become ill at all because you don't become ill

395
00:40:14,900 --> 00:40:19,400
until some days after the parasite comes out of the liver and starts infecting red blood cells.

396
00:40:19,400 --> 00:40:23,060
And then it starts to really multiply to high numbers in the blood level.

397
00:40:23,060 --> 00:40:30,380
And that's when you see people getting fevers. So all of that could be prevented if we could have a TSL inducing vaccine.

398
00:40:30,380 --> 00:40:37,220
And adenoviruses are really effective ways of making a good Tiso response when you vaccinate somebody.

399
00:40:37,220 --> 00:40:40,220
And so are some other viruses called pox viruses.

400
00:40:40,220 --> 00:40:46,430
So pox viruses are relatives of smallpox and vaccine, a virus that Edward Jenner used against smallpox.

401
00:40:46,430 --> 00:40:50,720
And there's a safer version of the vaccine, your virus.

402
00:40:50,720 --> 00:40:55,740
So the vaccine is a virus that is derived from the vaccine that Edward Gennie used.

403
00:40:55,740 --> 00:41:00,290
And there are some important differences that we don't really need to go into. But they're not the same.

404
00:41:00,290 --> 00:41:04,880
But that vaccine does actually spread through the body when you use it to vaccinate somebody with.

405
00:41:04,880 --> 00:41:08,300
And if somebody has a very weak immune system, it can actually be dangerous.

406
00:41:08,300 --> 00:41:14,480
But we use a replication deficient version of a pox virus like our replication deficient adenovirus.

407
00:41:14,480 --> 00:41:23,540
We have a replication deficient pox virus is called MBA, a modified vaccine virus, Ankara, and that is not able to spread through the body.

408
00:41:23,540 --> 00:41:31,580
When you vaccinate somebody in a very similar way to the adenovirus, you can add genes into it from different pathogens.

409
00:41:31,580 --> 00:41:34,010
And those genes are expressed at high levels.

410
00:41:34,010 --> 00:41:40,910
When you vaccinate somebody and you get a good immune response and the strongest TSA response is that could be generated,

411
00:41:40,910 --> 00:41:49,670
we found were from giving somebody an adenovirus carrying a malaria antigen and then following it four to eight weeks later with a pox virus,

412
00:41:49,670 --> 00:41:51,710
the MBA carrying malaria antigen.

413
00:41:51,710 --> 00:41:58,400
So they're both very safe to use because they can't spread through the body, both expressing the same malaria antigen.

414
00:41:58,400 --> 00:42:04,070
And if you use them in that sequence or actually you can reverse the order, it's not too important, which comes first.

415
00:42:04,070 --> 00:42:10,490
You get a really strong T cell response. The TSA response is actually stronger with the adenovirus than with the NBA.

416
00:42:10,490 --> 00:42:15,780
But it doesn't matter which way round you give them, you come to the same very high t cell response in the end.

417
00:42:15,780 --> 00:42:21,470
I worked on that technology and that's when we started being interested in using simian adenoviruses rather

418
00:42:21,470 --> 00:42:27,230
than human adenoviruses because of the problem of pre-existing immunity to human and viruses in humans.

419
00:42:27,230 --> 00:42:28,910
We knew that was going to be a problem.

420
00:42:28,910 --> 00:42:35,900
And although in the lab the human adenoviruses make great vaccines, it wasn't something we want to take into clinical trials.

421
00:42:35,900 --> 00:42:42,350
So we had to wait until we got a collaboration with somebody else who'd got a simian adenoviruses that we could use.

422
00:42:42,350 --> 00:42:47,630
And that's when we started doing clinical trials for the malaria vaccine. But these are very adaptable, technical.

423
00:42:47,630 --> 00:42:51,660
These other people were using them to make therapeutic of vaccines.

424
00:42:51,660 --> 00:43:01,170
It's possible to put antigens into them. Take him from lots of different pathogens, bacteria as well as viruses, and use them alone or in combination.

425
00:43:01,170 --> 00:43:05,520
And it was designed to be very adaptable technology.

426
00:43:05,520 --> 00:43:10,780
And they do induce good antibody responses as well as the strong T cell responses.

427
00:43:10,780 --> 00:43:15,420
And I then started working on influenza vaccines again, thinking about the T cell response,

428
00:43:15,420 --> 00:43:23,670
because the antigens that we make is our response to from the flu virus unless variable than the ones that we make an antibody response to.

429
00:43:23,670 --> 00:43:28,950
So there's a better chance of having broader protection. And that's a project that I worked on for a while.

430
00:43:28,950 --> 00:43:33,090
Haven't really brought that to a conclusion yet. I still have a flu project running at the moment.

431
00:43:33,090 --> 00:43:38,340
And with that, we're now exploring different routes of administering the vaccines because

432
00:43:38,340 --> 00:43:42,570
it may be more effective not to give the vaccines I intramuscular injection,

433
00:43:42,570 --> 00:43:45,780
but to get them into the respiratory tract directly.

434
00:43:45,780 --> 00:43:54,750
And that's particularly important for flu because the disease onset is very rapid for flu virus 48 hours after you've been exposed to the virus.

435
00:43:54,750 --> 00:43:58,100
That's when symptoms peak. And that's a really short space of time.

436
00:43:58,100 --> 00:44:06,060
Whereas for corona viruses of many other viruses, it takes longer for the symptoms to really onset after a person has been exposed to the virus.

437
00:44:06,060 --> 00:44:12,090
So if the T cells and the antibodies have to move to a different part of the body, that's a bit more time in most cases.

438
00:44:12,090 --> 00:44:17,870
But that's not true in flu. It needs a really rapid response to the incoming infection.

439
00:44:17,870 --> 00:44:23,300
Sarah has also done a huge amount of work on the subject of this episode, Disease X.

440
00:44:23,300 --> 00:44:31,430
And I asked her to tell me more about what kind of pathogen this might turn out to be and what we should perhaps fear most.

441
00:44:31,430 --> 00:44:34,490
So for people think about disease X, it's just the unknown.

442
00:44:34,490 --> 00:44:38,480
We don't know where it's going to come from or what it's going to be, but there will be something.

443
00:44:38,480 --> 00:44:42,350
The world had been halfheartedly preparing for a flu pandemic for quite a long time.

444
00:44:42,350 --> 00:44:45,770
And then we got a corona virus pandemic. So we weren't expecting that.

445
00:44:45,770 --> 00:44:49,430
But actually, the people who study these things would have said that we should have been expecting

446
00:44:49,430 --> 00:44:53,930
that because we've seen corona virus outbreaks before and we know what they can do.

447
00:44:53,930 --> 00:44:57,950
So we shouldn't have been surprised. What else is going to surprise us?

448
00:44:57,950 --> 00:45:03,470
We don't know. That's why we call it disease X. But the one that I'm most worried about, it's still flu because flu is still out there.

449
00:45:03,470 --> 00:45:09,140
There are so many different versions of flu in bird populations. We have no idea what they are, where they are.

450
00:45:09,140 --> 00:45:16,040
Maybe it mutates really rapidly. And when people get infected, the onset of the disease is very, very rapid.

451
00:45:16,040 --> 00:45:20,390
So there's not much time to do anything before the symptoms take hold.

452
00:45:20,390 --> 00:45:26,990
So a flu pandemic like the 1918 flu could still be absolutely devastating today.

453
00:45:26,990 --> 00:45:33,650
Studying and preparing for a coming disease X has been central to much of Sarah's recent work.

454
00:45:33,650 --> 00:45:42,280
So I was interested to hear what she was working on when this was added to the World Health Organisation's list of blueprint priority diseases.

455
00:45:42,280 --> 00:45:46,960
At the time that Disease X was added to the WTO list of priority pathogens,

456
00:45:46,960 --> 00:45:52,430
I was already working on vaccines for a number of other priority pathogens which are on the list.

457
00:45:52,430 --> 00:46:00,700
Meurs, NIPA and Lassa, three very different viruses, but all capable of causing outbreaks in different parts of the world with different outcomes.

458
00:46:00,700 --> 00:46:07,540
But we need a vaccine against all of them. Another one coming in Congo haemorrhagic fever and colleagues of mine were also

459
00:46:07,540 --> 00:46:11,680
working on vaccines against Rift Valley fever virus and chikungunya virus.

460
00:46:11,680 --> 00:46:15,970
Also outbreak pathogens which cause outbreaks in different parts of the world.

461
00:46:15,970 --> 00:46:23,620
And so we have settled on using the Cherrix one platform technology for all of these different outbreak diseases,

462
00:46:23,620 --> 00:46:29,500
because it's a technology that's very adaptable. We can use it to make vaccines in lots of different ways.

463
00:46:29,500 --> 00:46:32,800
And we know how to manufacture it. We know that it's safe to use.

464
00:46:32,800 --> 00:46:40,870
We know that it induces the kind of immune response that we want to see in a vaccine and doesn't need very low temperature situation and is therefore,

465
00:46:40,870 --> 00:46:47,170
in theory, suitable for use in many different parts of the world. So a lot of those different programmes were going on.

466
00:46:47,170 --> 00:46:51,610
But the early parts of each of those programmes took several years to get started.

467
00:46:51,610 --> 00:46:55,720
And when Doli Recto introduce a concept of disease X,

468
00:46:55,720 --> 00:47:02,290
we have to start thinking about how could we get from the knowledge of a new disease to having a vaccine

469
00:47:02,290 --> 00:47:07,210
that we could vaccinate people with in a clinical trial much more quickly than we have been doing.

470
00:47:07,210 --> 00:47:13,570
And to be honest, there weren't really any particular technical hurdles that we were going to need to overcome.

471
00:47:13,570 --> 00:47:17,080
It was more a question of rethinking the way that we did things.

472
00:47:17,080 --> 00:47:24,010
The order that we did things in doing more things in parallel, which is a concept that lots of people have become familiar with this year,

473
00:47:24,010 --> 00:47:27,880
instead of just thinking that we had a small amount of money.

474
00:47:27,880 --> 00:47:32,890
And so we make a vaccine and just test it in the lab and then think about moving on later.

475
00:47:32,890 --> 00:47:41,770
We started thinking about the prospect that we might be finding out about a new virus and would need to get into clinical testing really quickly.

476
00:47:41,770 --> 00:47:44,140
So what would be our approach to that?

477
00:47:44,140 --> 00:47:50,920
For some of the grant applications that I'd applied for, there was the opportunity to include what's called a demonstration project.

478
00:47:50,920 --> 00:47:55,810
So part of the process will be to demonstrate that the technologies works as a vaccine.

479
00:47:55,810 --> 00:48:01,870
But then you would have a demonstration project where you would ask somebody else to nominate a sequence that you didn't know what it is

480
00:48:01,870 --> 00:48:09,250
going to be and then see how quickly you could go through making a vaccine and get it to a particular point in vaccine manufacturing,

481
00:48:09,250 --> 00:48:15,100
for example. And so we thought about how we would go through that and what would be a good disease to do it with.

482
00:48:15,100 --> 00:48:19,720
And I've been thinking of influenza antigens because there are new ones occurring all the time.

483
00:48:19,720 --> 00:48:27,310
And it would be possible to ask somebody as a kind of test run to nominate a new influenza antigen that only just been identified.

484
00:48:27,310 --> 00:48:34,290
That exact sequence. And then we could put it into a vaccine and see how fast we could get through the manufacturing process.

485
00:48:34,290 --> 00:48:39,670
And we would have been able to demonstrate that we couldn't have started before, particularly like the sequence wasn't known.

486
00:48:39,670 --> 00:48:47,890
And so when a new pathogen like Sarkozy to arise is that SoftLayer brilliant demonstration project because nobody knew what it was before.

487
00:48:47,890 --> 00:48:54,130
So thinking about and wanting to test the technology, not knowing if we'd actually need to use the vaccine,

488
00:48:54,130 --> 00:48:59,200
but anyway wanting to see how quickly we could make a vaccine to start the process.

489
00:48:59,200 --> 00:49:04,900
This was an ideal candidate. The story of Sarah and the rest of the teams work on Coupet, 19,

490
00:49:04,900 --> 00:49:11,110
is definitely one for another podcast, which I hope we'll make in the not too distant future.

491
00:49:11,110 --> 00:49:16,620
For now, though, I was keen to find out whether Sarah was already reflecting on those efforts.

492
00:49:16,620 --> 00:49:19,300
There's quite a lot of things I think we could do better next time.

493
00:49:19,300 --> 00:49:26,050
One is that we've been advocating for better manufacturing facilities so that we can get the vaccines made into clinical trials.

494
00:49:26,050 --> 00:49:27,970
And that hasn't happened yet.

495
00:49:27,970 --> 00:49:34,690
The vaccines manufacturing, the innovation centre had been funded and the building had started to be built, but it wasn't ready to use.

496
00:49:34,690 --> 00:49:39,880
So it wasn't any use to us on our own manufacturing centre, the clinical bio manufacturing facility.

497
00:49:39,880 --> 00:49:44,440
We've been trying to get that extended and upgraded for years as well, and there's been no money to do that.

498
00:49:44,440 --> 00:49:49,540
We really want to be able to go much more quickly with more candidates as well.

499
00:49:49,540 --> 00:49:54,250
So one thing that we had to deal with this year is that we had one choice for the vaccine.

500
00:49:54,250 --> 00:49:59,320
There was no opportunity to try to make two or three different versions of the vaccine and then

501
00:49:59,320 --> 00:50:03,490
decide which one we wanted to take into clinical trials because we only have one clean room.

502
00:50:03,490 --> 00:50:08,800
So it had to be one shot from the beginning. That's why we only made one subsequently.

503
00:50:08,800 --> 00:50:13,870
We made some different versions in the lab and we've tested them and we're still happy with what we started out with.

504
00:50:13,870 --> 00:50:17,260
It would have been good and in some cases for different viruses,

505
00:50:17,260 --> 00:50:22,600
it would have been more important to be able to start off with making maybe up to five different versions

506
00:50:22,600 --> 00:50:27,940
of a vaccine at the early stages until we get some preliminary work done with it and then select.

507
00:50:27,940 --> 00:50:35,520
But we knew we couldn't do that this year. So bigger, better, more available manufacturing facilities is one thing.

508
00:50:35,520 --> 00:50:39,680
Then we have to think about the testing in animal models that we did.

509
00:50:39,680 --> 00:50:46,070
We were required to demonstrate that we weren't going to cause a phenomenon known as vaccine enhanced disease,

510
00:50:46,070 --> 00:50:49,790
which is something that's been seen in some vaccines in the last century.

511
00:50:49,790 --> 00:50:54,020
There was a respiratory Sin City ill vaccine that was tested in children,

512
00:50:54,020 --> 00:50:58,790
and it did actually make the disease worse when the children then got exposed to the virus.

513
00:50:58,790 --> 00:51:04,760
And understanding that that was not going to happen this year, that the vaccines that we were making was really important.

514
00:51:04,760 --> 00:51:10,640
And we think that we already understood it. And we know what kind of immune response was responsible for the enhanced disease.

515
00:51:10,640 --> 00:51:15,560
And that's not the kind of immune response we get with this technology. But we still had to demonstrate it.

516
00:51:15,560 --> 00:51:20,870
And that takes time because you can't demonstrate it with animal models until there is an animal model.

517
00:51:20,870 --> 00:51:28,310
And that will have to be done very quickly. And I think I would like to put a bit more effort into just really understanding the immune

518
00:51:28,310 --> 00:51:33,980
responses that we get from different vaccination technologies so that we are not having to cheque,

519
00:51:33,980 --> 00:51:37,670
that we're not going to get vaccine enhanced disease because we are absolutely certain

520
00:51:37,670 --> 00:51:41,570
that we won't with these technologies that would enable us to go faster as well.

521
00:51:41,570 --> 00:51:46,670
And then there's things that I think we learnt after Ebola on clinical trial design.

522
00:51:46,670 --> 00:51:51,620
So in the Ebola outbreak, there were vaccines that were ready to go into efficacy trials,

523
00:51:51,620 --> 00:51:57,770
but nobody could agree on how those efficacy trials should be set up and whether it should be a placebo controlled trial,

524
00:51:57,770 --> 00:52:04,250
because it was thought that wasn't going to be ethical. And in the end, after enormous amount of discussion and months and months, months of delay,

525
00:52:04,250 --> 00:52:08,150
we had a ring vaccination trial with either immediate or delayed vaccination.

526
00:52:08,150 --> 00:52:12,240
So some people in the delayed vaccination group who had to wait three weeks for that

527
00:52:12,240 --> 00:52:17,730
vaccine did contract Ebola during the time they were waiting for their Ebola vaccine.

528
00:52:17,730 --> 00:52:25,280
But it's necessary in any efficacy study that some people are going to get infected with the disease in order to know that the vaccine works.

529
00:52:25,280 --> 00:52:28,940
And when you think back to the idea of a placebo controlled trial,

530
00:52:28,940 --> 00:52:33,260
which horrified everybody because it wouldn't be ethical, because some people wouldn't be vaccinated,

531
00:52:33,260 --> 00:52:37,340
it's actually not really very different doing a delayed vaccination trial in which some

532
00:52:37,340 --> 00:52:42,200
people will be impacted because they haven't received the vaccine until later on.

533
00:52:42,200 --> 00:52:48,650
So thinking about child designs, particularly for viruses with a high fatality rate.

534
00:52:48,650 --> 00:52:54,350
So Kobe, it doesn't have a very high fatality rate. It spread so rapidly, it causes major disruption.

535
00:52:54,350 --> 00:53:00,500
But actually, the percentage of people who die from it is much lower than Ebola and many of the other outbreak pathogens.

536
00:53:00,500 --> 00:53:03,680
So we probably still haven't really addressed the point of how should we test

537
00:53:03,680 --> 00:53:07,460
the efficacy of a vaccine against a virus that does have a high fatality rate.

538
00:53:07,460 --> 00:53:10,880
And that's something that probably requires more discussion and modelling and

539
00:53:10,880 --> 00:53:14,850
better planning so that we would be ready in the future to do that kind of thing.

540
00:53:14,850 --> 00:53:16,670
Well, what's worked really well this year, I think,

541
00:53:16,670 --> 00:53:24,170
has been the collaboration's within the university with AstraZeneca between different companies, with lots of different academic collaborators.

542
00:53:24,170 --> 00:53:25,430
That's all been really good.

543
00:53:25,430 --> 00:53:31,340
And I hope that will continue in the future because without that kind of collaboration, nobody can make progress as quickly.

544
00:53:31,340 --> 00:53:35,770
So we need to see a lot more of that before our conversation ended.

545
00:53:35,770 --> 00:53:45,170
Sarah and I got onto the theme of this season, the broad history of pandemics and the role of one man in particular, Edward Jenner.

546
00:53:45,170 --> 00:53:53,320
I'm including it here because Sarah has a unique and fascinating perspective on his achievements and how it relates to her work today.

547
00:53:53,320 --> 00:54:01,250
A lot of similarities in what Janet did and what we do today. One of the things that he did on a very small scale was the challenge experiment.

548
00:54:01,250 --> 00:54:06,460
So he didn't just give somebody a vaccine and then say, well, they're fine, obviously.

549
00:54:06,460 --> 00:54:13,550
So I vaccinated them. They'll be protected. Now, he vaccinated his gardener's son with the cowpox, and then he did it,

550
00:54:13,550 --> 00:54:18,320
deliberately exposed the boy to smallpox and showed that he wasn't infected with smallpox.

551
00:54:18,320 --> 00:54:19,850
That sounds horrendous,

552
00:54:19,850 --> 00:54:28,160
but that was done because actually exposure to low amounts of smallpox was the way at the time that people were being protected against smallpox.

553
00:54:28,160 --> 00:54:35,690
So smallpox, if you had an outbreak coming through a particular area, one in three of the children would be killed by smallpox.

554
00:54:35,690 --> 00:54:42,470
And people were using let's called Barry relation, which is deliberate infection with a small amount of the smallpox virus,

555
00:54:42,470 --> 00:54:48,650
because that was known to protect people against smallpox infection. And apparently, Janet had this done to himself as a child.

556
00:54:48,650 --> 00:54:52,610
And it was pretty horrendous process, partly because they didn't really understand how it worked.

557
00:54:52,610 --> 00:54:56,420
So the children were kept in the dark on a very poor diet while this was happening.

558
00:54:56,420 --> 00:55:00,770
It was meant to be stopping the virus from having the power to take over the child.

559
00:55:00,770 --> 00:55:03,490
She probably just made the child more likely to be very ill.

560
00:55:03,490 --> 00:55:09,290
The death rate from vaccination was about one in 50, which sounds terrible, but it was much better than one in three.

561
00:55:09,290 --> 00:55:13,880
And then Jana wanted to replace very lation with something much safer.

562
00:55:13,880 --> 00:55:20,840
And the death rate from vaccination against smallpox with this live replication competent vaccine here is about one in a million.

563
00:55:20,840 --> 00:55:24,770
So, again, we wouldn't use a vaccine like that today. That's far too dangerous.

564
00:55:24,770 --> 00:55:29,660
But it was so much better than one in 50 with Barry elation or one in three with smallpox infection.

565
00:55:29,660 --> 00:55:34,010
So it was all about reducing the risk continually. And that's always something we're looking to do.

566
00:55:34,010 --> 00:55:39,350
However safe something is, we're always looking at any possibility to reduce the risk even further.

567
00:55:39,350 --> 00:55:49,040
So when he exposed his Goldman son, James Facts to smallpox, he was being put through the normal process of exposure to a small amount of smallpox.

568
00:55:49,040 --> 00:55:55,370
But it didn't take he didn't get any kind of infection at all, whereas other children would have had an infection, been quite ill and then recovered.

569
00:55:55,370 --> 00:55:58,460
Hopefully at least 49 out of 50 of them did.

570
00:55:58,460 --> 00:56:05,420
And then they would have been immune to smallpox and not satisfied by doing this once he did it a second time and the violation still didn't take.

571
00:56:05,420 --> 00:56:08,960
So James Phipps is known to be immune to smallpox.

572
00:56:08,960 --> 00:56:18,170
So the idea of vaccinating and then testing efficacy, which in the time of Kobrick we're doing with very large phase three trials,

573
00:56:18,170 --> 00:56:25,130
waiting to see if people who got the vaccine or got a control vaccine get infected with COPD is still the same concept.

574
00:56:25,130 --> 00:56:32,450
You have to test to see if the vaccine works and not just give the vaccine and say that it must work because you vaccinated somebody.

575
00:56:32,450 --> 00:56:38,930
And then the other thing that Janet did that was absolutely huge. And that does, I think, have a lot of bearing on what we do now.

576
00:56:38,930 --> 00:56:44,840
Is he communicated his findings. He wasn't the first person to use cowpox to protect against smallpox.

577
00:56:44,840 --> 00:56:50,690
Other people have done it before. They are quite a few records of it happening. But what he did was having done his experiments.

578
00:56:50,690 --> 00:56:54,110
He went to the world society and gave a presentation.

579
00:56:54,110 --> 00:57:02,780
And then he continued to talk about it and he continued to vaccinate large numbers of people and promoted the cause of vaccination,

580
00:57:02,780 --> 00:57:07,100
eventually managed to get very chelation. The exposure to smallpox. He got that outlawed.

581
00:57:07,100 --> 00:57:11,910
So he was very vocal about what he was doing and why it was important.

582
00:57:11,910 --> 00:57:15,260
And I think that's something that scientists often don't really want to do.

583
00:57:15,260 --> 00:57:20,120
We want to get on with the science that we have to follow in Dennis footsteps in that way as well,

584
00:57:20,120 --> 00:57:24,230
and communicate the findings and be clear about what it is that we've done.

585
00:57:24,230 --> 00:57:30,470
But make sure that everybody knows about it and understands it, because if they don't understand it, then there won't be any impact.

586
00:57:30,470 --> 00:57:40,830
This if we come up with a fantastic discovery in a lab and don't really tell anybody, it's not going to make any difference.

587
00:57:40,830 --> 00:57:46,230
The next voice is your. Here are two you may recognise from earlier in the series.

588
00:57:46,230 --> 00:57:54,860
The first of these is Professor Jemmy Whitworth from the London School of Hygiene and Tropical Medicine, whom we met in Episode nine.

589
00:57:54,860 --> 00:58:04,890
You're about to join us midway through a conversation about plague and the potential threat of anti-microbial resistance.

590
00:58:04,890 --> 00:58:08,640
Now, it's a bacterial infection, as I've mentioned.

591
00:58:08,640 --> 00:58:18,870
And so it is treatable with antibiotics and in fact, it's it's pretty sensitive to some standard antibiotics.

592
00:58:18,870 --> 00:58:30,000
So as long as you have a level of suspicion that you identify cases of plague and that people present early enough in the course of their infection,

593
00:58:30,000 --> 00:58:31,860
they should be eminently treatable.

594
00:58:31,860 --> 00:58:39,420
It's not like the situation historically where vast numbers of people died and there was nothing that could be done about these days.

595
00:58:39,420 --> 00:58:43,770
Once you know that there is plague in an area and you're alert to it,

596
00:58:43,770 --> 00:58:49,980
then as long as you can see those cases quickly and get them onto treatment, then they should do very well.

597
00:58:49,980 --> 00:58:54,870
The vast majority will recover from plague with antibiotics.

598
00:58:54,870 --> 00:59:00,840
Anti-Microbial resistance is a problem for plague, as it is for many other conditions.

599
00:59:00,840 --> 00:59:06,630
There is some suggestion from the Madagascar outbreak that there might have been some development

600
00:59:06,630 --> 00:59:13,200
of anti-microbial resistance that made the antibiotics not as successful as we've seen previously.

601
00:59:13,200 --> 00:59:16,710
That's certainly something that needs to be kept an eye on.

602
00:59:16,710 --> 00:59:26,990
And all around the world, there are problems with the development of antibiotic resistance, which makes diseases much harder to treat,

603
00:59:26,990 --> 00:59:35,550
and that we are reaching a situation where for some conditions, they are becoming close to untreatable.

604
00:59:35,550 --> 00:59:40,290
I don't think we've reached that really for any diseases yet.

605
00:59:40,290 --> 00:59:44,490
What for? Conditions even such as gonorrhoea, for example.

606
00:59:44,490 --> 00:59:52,440
High level of antibiotic resistance means that there is a looming possibility that some infections

607
00:59:52,440 --> 00:59:58,290
which have been treatable in the past might become essentially untreatable in the future.

608
00:59:58,290 --> 01:00:04,260
Having said that, that's thinking to the future. And I think we do need to keep that in mind.

609
01:00:04,260 --> 01:00:10,410
But at present, the major problem with antibiotics is lack of access to.

610
01:00:10,410 --> 01:00:20,100
So there are currently many more deaths that occur because of lack of access to antibiotics and because of antibiotic resistance, particularly,

611
01:00:20,100 --> 01:00:31,050
of course, that is in low resource settings in poor countries, particularly those which have limited access to health services and so on.

612
01:00:31,050 --> 01:00:39,210
So I think it's important that the message is that we need to reduce inappropriate antibiotic use.

613
01:00:39,210 --> 01:00:50,940
It's not that we should reduce all antibiotic use because we're in a situation, a global situation where we don't have adequate access to antibiotics.

614
01:00:50,940 --> 01:00:59,430
So it's important that the message is appreciated as reducing inappropriate antibiotic use later on in our conversation.

615
01:00:59,430 --> 01:01:08,760
Jemmy also had a warning about the ways in which one of the other major threats facing humanity, climate change could impact on the spread of disease.

616
01:01:08,760 --> 01:01:23,190
One of the issues, recent trends that we've seen is that with climate change, the endemic range of a number of infectious diseases has increased.

617
01:01:23,190 --> 01:01:33,750
And this is because as temperatures rise, that means that insect vectors, particularly mosquitoes, are able to expand their range.

618
01:01:33,750 --> 01:01:44,070
We've seen this in recent times in Europe, where conditions such as Denki, but also Chicken Gunya,

619
01:01:44,070 --> 01:01:51,030
even Zika, have started to transmit during summer months within southern Europe.

620
01:01:51,030 --> 01:02:00,000
And you can see the march of the range of the mosquitoes steadily moving north over time.

621
01:02:00,000 --> 01:02:09,660
And this starts to threaten major centres of population, places like Paris or Amsterdam or even London and so on,

622
01:02:09,660 --> 01:02:13,680
in the future that these diseases will start to spread.

623
01:02:13,680 --> 01:02:22,800
We're already seeing that EDI's mosquitoes, particularly Aedes albopictus, so-called Asian tiger mosquito,

624
01:02:22,800 --> 01:02:29,550
is a fact of life in Spain and Italy in a way that it was not seen before.

625
01:02:29,550 --> 01:02:35,130
So these mosquitoes have established themselves in places where they were not before,

626
01:02:35,130 --> 01:02:39,810
and that means that epidemic diseases are occurring more frequently.

627
01:02:39,810 --> 01:02:46,410
So we are seeing outbreaks of West Nile fever, diseases like Crimea,

628
01:02:46,410 --> 01:02:55,140
Congo haemorrhagic fever occurring in Europe in larger numbers and over wider areas than we have seen before.

629
01:02:55,140 --> 01:03:04,370
And that means that public health authorities need to be aware that these diseases are on the march and they need to have.

630
01:03:04,370 --> 01:03:09,800
Control measures in place to be able to deal with them when they occur.

631
01:03:09,800 --> 01:03:15,770
And for countries like the UK where they have not yet arrived, but they are threatened,

632
01:03:15,770 --> 01:03:21,710
then we need to have very good surveillance systems in place so that we can identify when they occur.

633
01:03:21,710 --> 01:03:28,430
Because if you have just a few of the mosquitoes that are relevant for this,

634
01:03:28,430 --> 01:03:36,890
that's a much easier situation to be able to control and eliminate that focus than if you wait until it is well established.

635
01:03:36,890 --> 01:03:46,190
We do need to think about novel infections and particularly zoonotic infections, those that affect largely animals,

636
01:03:46,190 --> 01:03:58,580
but that could pass on into the human population with global warming, with population increase moving into forested areas and so on.

637
01:03:58,580 --> 01:04:04,520
We do come into contact more with zoonotic diseases than we do in the past.

638
01:04:04,520 --> 01:04:13,400
So we're always going to be vulnerable as a human population to epidemics from novel viruses that we've not seen before.

639
01:04:13,400 --> 01:04:19,990
We've seen this with Corona virus and I'm sure we will see this again in the future.

640
01:04:19,990 --> 01:04:27,940
Having just talked about novel pathogens, we then moved on to discuss a disease that we already know a great deal about.

641
01:04:27,940 --> 01:04:35,830
I think cholera is a very interesting problem and one that should probably have more attention.

642
01:04:35,830 --> 01:04:46,630
This probably causes more large scale epidemics around the world every year than other epidemic diseases.

643
01:04:46,630 --> 01:04:53,560
And yet we know an awful lot about cholera, how it is spread, how it can be controlled.

644
01:04:53,560 --> 01:05:02,980
We have treatments. We have a vaccine. And yet it occurs every year, predictably, in various parts of the world.

645
01:05:02,980 --> 01:05:10,450
And it shows that we really do need to have a holistic approach to dealing with epidemics.

646
01:05:10,450 --> 01:05:19,300
And the idea that, oh, if we have a vaccine or if we have an effective treatment, then all our problems are solved.

647
01:05:19,300 --> 01:05:26,590
It just shows that that's not the case, that even when we do have those, we need to be able to apply those.

648
01:05:26,590 --> 01:05:34,540
And we need to be thinking about improving sanitation and improving the health of populations,

649
01:05:34,540 --> 01:05:40,060
the risk and so on if we want to be able to control these diseases.

650
01:05:40,060 --> 01:05:44,290
With so many potential threats on the horizon. I asked Jemmy.

651
01:05:44,290 --> 01:05:56,170
Which diseases concern him the most? What I'd worry about from a UK perspective is an epidemic of a disease that's caused by midges.

652
01:05:56,170 --> 01:06:00,040
Midges are all over the UK.

653
01:06:00,040 --> 01:06:04,210
We have no control measures for dealing with them at all.

654
01:06:04,210 --> 01:06:11,560
Just think about people who go on holiday in Scotland in the summer and the mej population that we have there.

655
01:06:11,560 --> 01:06:24,580
If we were to get a infection that was spread by midges coming into the UK and affecting humans, then I think we would be in a very serious problem.

656
01:06:24,580 --> 01:06:33,820
We've been quite lucky. There have been two outbreaks of mej infections in the UK in recent years.

657
01:06:33,820 --> 01:06:38,230
One has been bluetongue virus and the other was Schmallenberg.

658
01:06:38,230 --> 01:06:43,300
Both of these affect animals, livestock in particular.

659
01:06:43,300 --> 01:06:48,970
But luckily for us, they don't cross into the human population.

660
01:06:48,970 --> 01:06:55,150
And the veterinary profession has been able to develop vaccines very rapidly.

661
01:06:55,150 --> 01:07:02,560
It's much easier to make a vaccine against animal diseases than it is for the human ones in terms of regulation and so on.

662
01:07:02,560 --> 01:07:05,980
And those epidemics have been controlled.

663
01:07:05,980 --> 01:07:16,600
But if either of those had spread into human populations or had an effect on humans, then I think we would have been in a very serious way,

664
01:07:16,600 --> 01:07:21,790
given the wide variety of outbreaks that any country could, in theory, have to plan for.

665
01:07:21,790 --> 01:07:27,470
I'd put to Jemmy that pandemic preparation is an almost impossible task.

666
01:07:27,470 --> 01:07:31,220
He had an interesting perspective on whether we should be optimistic or

667
01:07:31,220 --> 01:07:36,680
pessimistic about a country's ability to plan for the emergence of a new disease,

668
01:07:36,680 --> 01:07:46,310
previously pandemic flu was right up there at the top of the UK is National Risk Register.

669
01:07:46,310 --> 01:07:53,120
But that didn't translate into robust plans really to be able to control it.

670
01:07:53,120 --> 01:08:05,730
I really do feel that this current pandemic has galvanised policymakers and will make changes to the future on how we deal with this.

671
01:08:05,730 --> 01:08:08,630
So I'm optimistic that things will be done.

672
01:08:08,630 --> 01:08:19,670
I'm slightly pessimistic in that the history of dealing with epidemics is that we always put plans in place for the last epidemic,

673
01:08:19,670 --> 01:08:24,140
not for the future epidemic, but for what happened last time.

674
01:08:24,140 --> 01:08:31,940
And of course, that is very much shutting the stable door after the horse has bolted, which is difficult.

675
01:08:31,940 --> 01:08:34,220
I mean, what should we put in place?

676
01:08:34,220 --> 01:08:44,600
I'm in a position where I can be confident that there will be another pandemic or certainly major, extensive epidemic that occurs.

677
01:08:44,600 --> 01:08:50,720
But what I can't tell you is when or where or what it will be caused by.

678
01:08:50,720 --> 01:08:59,900
And that means that we need to have put in place systems that are frameworks that are adaptable

679
01:08:59,900 --> 01:09:06,260
and flexible enough to deal with epidemics of whatever sort may come about for the future.

680
01:09:06,260 --> 01:09:13,160
And it means that we have to learn on the hoof and apply what we know from first principles

681
01:09:13,160 --> 01:09:19,070
or from other diseases that we've dealt with to be able to control these epidemics.

682
01:09:19,070 --> 01:09:25,850
But it means that we do have to be prepared and we must not allow the resources to be run down so

683
01:09:25,850 --> 01:09:31,700
that we're not in a position and that it takes a long time to be able to deal with with an epidemic.

684
01:09:31,700 --> 01:09:36,050
The best time to deal with it is when it first occurs and to control it.

685
01:09:36,050 --> 01:09:40,700
Then if you allow it to get out of control, then it is much harder.

686
01:09:40,700 --> 01:09:47,630
With diseases like Corona virus, we're seeing doubling times with four days, 10 days,

687
01:09:47,630 --> 01:09:53,390
that kind development, that means that you get exponential rise very rapidly indeed.

688
01:09:53,390 --> 01:09:58,340
And you can quadruple your number of cases in a week or two.

689
01:09:58,340 --> 01:10:05,360
And that's very serious. So you need to be prepared to act very rapidly when epidemics occur.

690
01:10:05,360 --> 01:10:12,650
My final guest for today poses a more fundamental challenge to the whole way we've been thinking about epidemics.

691
01:10:12,650 --> 01:10:20,000
Erica Charters, associate professor in the history of medicine in Oxford's faculty of history, who we met in Episode five,

692
01:10:20,000 --> 01:10:29,390
cautions that concentrating too much on specific periodic outbreaks risks ignoring the constant threat of endemic disease.

693
01:10:29,390 --> 01:10:34,310
One of the really interesting things about an epidemic is that we tend to think

694
01:10:34,310 --> 01:10:38,100
about non periods of epidemics as periods when there's not disease and the past.

695
01:10:38,100 --> 01:10:41,120
That's just not true. There's always disease lurking around in the world.

696
01:10:41,120 --> 01:10:49,300
So the difference between normal periods, what we make health care is a pandemic disease and epidemic disease is when disease becomes a problem.

697
01:10:49,300 --> 01:10:54,260
There is no magical number when disease something becomes an epidemic.

698
01:10:54,260 --> 01:10:59,450
It's actually when we either feel that it's unacceptable levels or, for example,

699
01:10:59,450 --> 01:11:08,090
when policy officials deem that this disease is now a danger to the population or present some kind of risk.

700
01:11:08,090 --> 01:11:16,430
So I think the very interesting point to make here is that this means that we have to start from a baseline of acceptable levels of disease.

701
01:11:16,430 --> 01:11:19,280
And it's something that we often don't think about when we talk about epidemics,

702
01:11:19,280 --> 01:11:27,890
that actually epidemics only make sense if we also think about how it needs the context of acceptable that is endemic levels of disease.

703
01:11:27,890 --> 01:11:31,520
I'm a historian of endemic disease, probably more so than epidemic disease.

704
01:11:31,520 --> 01:11:36,110
But you can see how if you take a long term approach, if you're looking at the history of disease,

705
01:11:36,110 --> 01:11:40,580
you're going to be looking at fluctuations when something is at one point epidemic.

706
01:11:40,580 --> 01:11:46,220
And then when it's considered endemic and it's not just about as we said, it's there's probably this kind of cyclical nature,

707
01:11:46,220 --> 01:11:53,510
as you can see, how there might be a cycle when influenza becomes an epidemic disease, but it's also about spatial differences.

708
01:11:53,510 --> 01:11:58,670
So plague is a great example where we see that it recedes from some locations

709
01:11:58,670 --> 01:12:03,140
in the world and then is maintained as a constant in other parts of the world.

710
01:12:03,140 --> 01:12:10,790
And so actually, what you're calling an epidemic disease probably depends on which position in the world you happen to be placed.

711
01:12:10,790 --> 01:12:11,660
The other way of thinking about.

712
01:12:11,660 --> 01:12:20,360
This is, of course, some diseases are deemed acceptable and endemics or something like malaria is obviously endemic in some parts of the world.

713
01:12:20,360 --> 01:12:25,820
If we were to see an outbreak of malaria, say, in England, we would consider it an epidemic.

714
01:12:25,820 --> 01:12:32,550
Even that would be much. Lower rate simply because we think of that as being a foreign and somewhat unacceptable disease.

715
01:12:32,550 --> 01:12:37,980
You can see how it's as much about geography as it actually is about space and time.

716
01:12:37,980 --> 01:12:46,570
This seemed a fascinating idea. But I was curious why Erica fought epidemic diseases appear to be so much more prominent, you know,

717
01:12:46,570 --> 01:12:53,560
cultural memory than the endemic diseases that many people around the world live alongside every day.

718
01:12:53,560 --> 01:12:58,660
This is where probably it's because I'm a historian of endemic disease and I feel like we forget about endemic disease.

719
01:12:58,660 --> 01:13:03,970
Right. And it makes sense why we remember epidemics, because they are dramatic.

720
01:13:03,970 --> 01:13:09,550
They're exciting. They seem to have this storyline. People have a chance to be heroes.

721
01:13:09,550 --> 01:13:13,360
It's much harder to to write or to tell.

722
01:13:13,360 --> 01:13:18,700
Even today, I think people who are trying to raise money for fighting against endemic diseases will tell you it's much

723
01:13:18,700 --> 01:13:24,760
harder to have an exciting narrative to sell to the public about your battles against infant diarrhoea.

724
01:13:24,760 --> 01:13:29,350
Right. What is the great drama at hold there? And I think that's what's fascinating is, of course,

725
01:13:29,350 --> 01:13:37,150
endemic disease is probably much more significant in terms of mortality or even in terms of

726
01:13:37,150 --> 01:13:42,760
numbers of people who are constantly ill and therefore more susceptible to other diseases.

727
01:13:42,760 --> 01:13:48,580
But those things are much harder. So I'm always a champion of remembering endemic disease.

728
01:13:48,580 --> 01:13:53,650
One of the things that I'm working on right now is a project on how epidemics end.

729
01:13:53,650 --> 01:14:00,580
And, of course, usually how epidemics and for the most part is by turning into endemic disease, by becoming acceptable.

730
01:14:00,580 --> 01:14:04,930
There's very few stories of disease simply disappearing.

731
01:14:04,930 --> 01:14:08,140
And so I do think if we were to take into a broader context,

732
01:14:08,140 --> 01:14:14,800
that would help us to remember that actually epidemics also need to be seen within the context of endemic disease.

733
01:14:14,800 --> 01:14:22,030
I was really struck that kind of image that was going around early on in the pandemic by this website called the Visual Capoulas,

734
01:14:22,030 --> 01:14:27,400
which is about epidemics in the past. And they had these little coloured bubbles that were supposed to be representing

735
01:14:27,400 --> 01:14:30,910
numbers of people who died according to different epidemics in the past,

736
01:14:30,910 --> 01:14:38,890
stretching all the way back to show Cubitt in context. But what struck me so much as is these empty spaces between each bubble and of course,

737
01:14:38,890 --> 01:14:45,230
those empty spaces are full of endemic disease, but they just don't they don't get captured in that kind of model.

738
01:14:45,230 --> 01:14:50,080
And so we really do run the danger of just looking at the bubbles than the bubbles don't make any sense

739
01:14:50,080 --> 01:14:55,450
because we don't understand what's actually in between each of those those bubbles of epidemics.

740
01:14:55,450 --> 01:15:04,000
And Erica suggested that the most useful way of thinking about disease is something that's just part of our day to day experience.

741
01:15:04,000 --> 01:15:08,800
The really important thing to think about is that disease is something that's part of society.

742
01:15:08,800 --> 01:15:14,050
I think we tend to think about disease as something that's outside of it and maybe occasionally comes in.

743
01:15:14,050 --> 01:15:19,730
But actually, if you're taking a long term perspective, disease only makes sense within a social context.

744
01:15:19,730 --> 01:15:28,280
Right. So we can think about how there's obviously the biological phenomenon. But in terms of how it's transmitted, that depends on human activity.

745
01:15:28,280 --> 01:15:33,170
Right. So take cover at 19. It's about shaking hands or kissing cheeks or whatnot.

746
01:15:33,170 --> 01:15:38,530
So it's about human interaction. And the same way that the actual rates, the rates of mortality, for example,

747
01:15:38,530 --> 01:15:43,240
are shaped by human intervention, whether it be political or whether a medical.

748
01:15:43,240 --> 01:15:47,830
So I think actually the category of epidemic can be very helpful because it reminds us

749
01:15:47,830 --> 01:15:53,770
that disease is as much a social and political phenomenon as it is a biological one.

750
01:15:53,770 --> 01:15:59,170
But I think it's therefore very important because we tend to assume that epidemic is this kind of obvious,

751
01:15:59,170 --> 01:16:04,900
self-contained category when actually, as I've been saying, it probably depends on who's defining it.

752
01:16:04,900 --> 01:16:12,550
Who says that it is a problem? Why it's a problem. To whom it's a problem and where you're placed when you're saying that is an epidemic

753
01:16:12,550 --> 01:16:18,100
or actually that's just a normal rate of disease that we should simply accept.

754
01:16:18,100 --> 01:16:21,970
You could talk about how epidemics are very traumatic. Right.

755
01:16:21,970 --> 01:16:28,570
So these are the things that we pay lots of attention to, things like chronic diseases or infant diseases we tend not to notice.

756
01:16:28,570 --> 01:16:33,120
And so one way of thinking about this is how epidemics groups that are like the tips of icebergs.

757
01:16:33,120 --> 01:16:35,200
Right. So they are the things that are very visible.

758
01:16:35,200 --> 01:16:41,620
It's when you have a lot of government intervention, that's when people are very upset about rates of disease and deem that they're unacceptable.

759
01:16:41,620 --> 01:16:49,390
But those rates of disease actually usually depend on substantial mass of the iceberg that's underwater that often you can't see.

760
01:16:49,390 --> 01:16:54,310
One way you can think about this is comorbidities. And again, I think Covered 19 has really brought this home.

761
01:16:54,310 --> 01:17:01,600
That disease is complex, right? It interacts with other diseases, but it also interacts with different kinds of health structures,

762
01:17:01,600 --> 01:17:06,220
including things that are tied into social structures, socio economic conditions.

763
01:17:06,220 --> 01:17:11,650
Living conditions. Right. Population density. So those are the types of things that disease.

764
01:17:11,650 --> 01:17:15,910
It doesn't just strike everyone in the same way. Actually, it uncovers all of these differences.

765
01:17:15,910 --> 01:17:23,890
I think that's one way to think about this kind of broader social context for thinking about how epidemics interact within a society.

766
01:17:23,890 --> 01:17:31,630
But therefore, also how they reveal these different social structures, political differences within a society.

767
01:17:31,630 --> 01:17:33,550
We've been coming to the end of our conversation,

768
01:17:33,550 --> 01:17:40,770
but I was still keen to explore this idea of our natural bias towards remembering certain types of outbreak.

769
01:17:40,770 --> 01:17:48,510
I asked Erica, why was she thought that some diseases live on in history while others are largely forgotten?

770
01:17:48,510 --> 01:17:52,470
It's a great question because I think there's two parts to this, right.

771
01:17:52,470 --> 01:17:59,910
One is what shapes our response as to whether we think a disease is important and we can think about how some diseases

772
01:17:59,910 --> 01:18:06,000
are feared and others probably maybe because of symptoms that we can think about how Ebola has very striking,

773
01:18:06,000 --> 01:18:10,590
dramatic symptoms. Cholera, too, was very noted for having these dramatic symptoms.

774
01:18:10,590 --> 01:18:15,420
Death was very fast. So that's something that people often pick up on yellow fever,

775
01:18:15,420 --> 01:18:19,590
which kind of the term people used to describe it in the 18th century as the black vomit.

776
01:18:19,590 --> 01:18:26,670
So you can again imagine that has these very striking symptoms. So part of it has to do with the type of disease itself.

777
01:18:26,670 --> 01:18:31,410
But the other thing we can think about is, again, who is it affecting and in what ways?

778
01:18:31,410 --> 01:18:35,220
And I think this is always this debate that we have over. Is it?

779
01:18:35,220 --> 01:18:39,510
Say those in power who are affected most by this disease.

780
01:18:39,510 --> 01:18:46,470
And so therefore have reason to kind of energise political structure or invest in therapeutics towards it?

781
01:18:46,470 --> 01:18:50,400
Or is it those who are say perhaps have less political power?

782
01:18:50,400 --> 01:18:54,090
The other thing, which I think is really important is that there is a long history,

783
01:18:54,090 --> 01:18:58,770
actually, of using disease to mobilise what we might call public opinion.

784
01:18:58,770 --> 01:19:04,980
So the period that I look at in the seventeen hundreds people might be surprised to hear that even then,

785
01:19:04,980 --> 01:19:10,020
in their early days of newspapers in the 18th century in England, disease was used as a partisan criticism.

786
01:19:10,020 --> 01:19:14,040
So it was especially during wartime, because I look at soldiers and sailors,

787
01:19:14,040 --> 01:19:19,620
what you see is that it's OK for your soldiers and sailors to die from combat,

788
01:19:19,620 --> 01:19:24,600
but it's deemed very problematic if they're dying from diarrhoea or from yellow fever.

789
01:19:24,600 --> 01:19:28,290
Those are just not glorious ways or expected ways to die.

790
01:19:28,290 --> 01:19:34,230
And so reports of disease get used in the press by, you know,

791
01:19:34,230 --> 01:19:42,300
the other political party to say there's something wrong with leadership or leadership is corrupt or our foreign policy needs a rethink because

792
01:19:42,300 --> 01:19:53,520
this is far too expensive an investment to be losing our precious national manpower to yellow fever or to disease rather than to combat.

793
01:19:53,520 --> 01:20:03,630
So disease. Also has this very long history of being part of political arguments, even diplomatic arguments about who can care for their troops.

794
01:20:03,630 --> 01:20:14,550
And the best way before we finished. I had a warning to Postle about the implicit moral framework which can accompany the way we talk about disease.

795
01:20:14,550 --> 01:20:22,380
There's always a moral framework. Right. And and another way of saying that this is, although perhaps we don't always think and religious terms,

796
01:20:22,380 --> 01:20:26,070
we probably think in terms of responsibility, which is very similar.

797
01:20:26,070 --> 01:20:30,420
So I think very often when we talk about there's a sense in which disease often is,

798
01:20:30,420 --> 01:20:37,530
although we don't talk about sane people will often relate it to, well, that's because you acted inappropriately.

799
01:20:37,530 --> 01:20:45,090
You didn't take the proper cautions. I think the rhetoric about young people going out and partying obviously has very similar

800
01:20:45,090 --> 01:20:50,670
frameworks thinking about this as disease being the result of acting irresponsibly.

801
01:20:50,670 --> 01:21:00,180
So I think that's another thing to think about as look, a lot of us would know in a kind of theoretical way that disease acts somewhat randomly.

802
01:21:00,180 --> 01:21:05,940
And yet what very often happens, especially during the period of an epidemic, is that we want to make sense of it.

803
01:21:05,940 --> 01:21:10,950
So Charles Rosenberg, a wonderful is kind of medicine, but this classic piece about what is an epidemic.

804
01:21:10,950 --> 01:21:18,390
And he talks about how it's a kind of drama. It's a narrative that starts and has various stages, kind of moves to a climax.

805
01:21:18,390 --> 01:21:26,820
Has actors and characters. Part of this is this need that we have to try to make sense of what actually is in some ways a kind of random event.

806
01:21:26,820 --> 01:21:31,020
And very often it is by saying that there are good people and bad people.

807
01:21:31,020 --> 01:21:34,680
Bad things should happen to those bad people, including the outbreak of disease. And again,

808
01:21:34,680 --> 01:21:39,240
I think this is where our own argument about which countries are doing well and which countries are

809
01:21:39,240 --> 01:21:45,240
not doing well is partly our attempt to try to say we have some control over what's happening.

810
01:21:45,240 --> 01:21:51,120
And it's because if you act the right way, then you'll be able to avoid the bad outcome of disease.

811
01:21:51,120 --> 01:21:59,190
But as many people remind us, that's not a sure thing, especially when you're dealing with a new and rather unknown disease.

812
01:21:59,190 --> 01:22:04,950
Thank you for joining me. This bonus episode in our series on the history of pandemics.

813
01:22:04,950 --> 01:22:08,180
If you haven't listened to the whole series yet, please do.

814
01:22:08,180 --> 01:22:16,050
In it, I explore ten world events that may have had a significant impact on the way we think about and prepare for pandemics.

815
01:22:16,050 --> 01:22:23,400
We'd love to know what you thought of this season of future makers and to hear your recommendations for future themes.

816
01:22:23,400 --> 01:22:30,210
So please do leave a review or get in touch on social media. We'll be back soon with more episodes.

817
01:22:30,210 --> 01:22:49,330
In the meantime, I'm still Peter Milliken and you've been listening to Future Makers.

818
01:22:49,330 --> 01:22:53,640
Future Makers is created in-house at the University of Oxford.

819
01:22:53,640 --> 01:22:57,790
The school for the series was composed and recorded by Richard Watts.

820
01:22:57,790 --> 01:23:02,110
It's presented by me, Professor Peter Milliken from Hartford College.

821
01:23:02,110 --> 01:23:09,310
And the series is written and produced by Ben Harwood and Steve Pritchard, who've been a delight to work with.

822
01:23:09,310 --> 01:23:33,792
Thank you. On behalf of the whole team for listening to our history of Pandemic's.