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.
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.
In 2015,
the World Health Organisation asked a group of global experts to draught a shortlist of serious emerging infectious diseases around the world.
The idea was to focus research and development on them to try to stop future outbreaks from turning into a public health emergency.
The list contained some diseases. We discussed Ebola and songs and many we happened, including Zika, Lassa fever and Marburg virus in 2018.
After meeting in Geneva, the team added one more name to the list Disease X,
a place holder for an unknown hypothetical pathogen that might pose a future epidemic.
Welcome back to the present day and welldone the making it through all of the diseases, not history of pandemics.
In today's bonus episode, I interview the Oxford scientists working at the forefront of research into Disease X
and discuss what we may or may not have learnt from experience of Koven along the way.
I'll include a few discussions which couldn't quite get into the main series,
including a conversation I had about whether a focus on pandemic masks the real problem.
Humanity faces ongoing endemic diseases on the way.
I'm Professor Sarah Gilbert, now world famous for her work on Oxford's Coronado's and Professor Peter 4B,
co chief investigator of the trial, discovered that dexamethasone could be a lifesaving drug.
First up, though, it's a John Bell Regis professor of medicine at Oxford.
I began by asking John where he was when he first heard about Kovik.
I was going about my daily routine in that principle, first over and then over Christmas.
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.
Of course, he ran our unit in Vietnam at the time of the H5N1 avian flu epidemic.
So he's pretty much linked in to all the epidemiologists and clinical scientists who do this in Asia.
And the message I got from him is there's trouble brewing in central China.
And it looks like there's quite a serious epidemic brewing there.
Lots of sick people not care of the data. We're on it.
Be careful because this may find its way into a pandemic. So that was pretty interesting.
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.
And that was clear that they were really under pressure in China because they learnt rather too late about the epidemic.
So they moved in to try and work out how to contain it. But it was clearly very, very serious.
And it was really about that time that things started to leak into the press about there being a serious problem in central China.
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.
But it happened pretty quickly, you know, really literally over a three or four week period.
It was pretty clear to me from they were almost from the initial descriptions that this was going to be bad.
And I'm not a doomsayer, but I had been watching out for pandemic threats for a number of years.
And the H5 N1 epidemic was pretty worrying.
And we were really only saved by the fact the pathogen didn't transmit from human to human.
It was only from birds to humans, but it carried a really high mortality.
I think the numbers were between 30 and 50 percent. Scar's one adult, 35 percent mortality.
And since the year 2000, we've had eight of those close calls.
We've had two Saar's outbreaks, each self-contained.
The murres outbreak, self contained, avian flu constrained by its inability to transmit between humans.
Another avian flu in China since then, which again has been limited.
And then, of course, the 2014 flu epidemic, which actually is global but wasn't as severe as we expected.
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.
And we've just been. Really lucky that none of them had blown up.
So when I heard about this, I thought, you know, this may be the big one and it may become pandemic pretty quickly.
And to be clear, at that stage, we knew nothing about the pathogen. We didn't know how many people were symptomatic.
Coming to give or asymptomatic. We didn't know how it was spread.
We didn't know what the case fatality rate was likely to be.
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.
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.
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,
our units globally will be in a good position to provide surveillance data.
We had terrific contacts in China. We had terrific contacts elsewhere in Asia and of course, elsewhere in the global health space.
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.
It was clear to me that we could actually make a big play. And now, nearly a year into tackling this disease.
I wondered what lessons John thought we've already learnt. You could write a book on the lessons learnt.
The real risk is that people will forget the lessons learnt and we'll go back to business as usual from next year.
But the first big lesson is don't be complacent about the threat of a pandemic.
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.
You can't afford to say, oh, it'll burn itself out. It'll all be fine.
Don't need to worry. And worst of all, the NHS is prepared because none of those things are true.
And I think the failure in this country not to move quicker is a deep national embarrassment.
Frankly, wasn't as if we didn't know about these things. And it wasn't as if people weren't told.
They just chose not to do anything. I'll tell you, our problem, though, is we only know what we know.
And of course, we know what we know from history. And you guys just bit over the history.
The scary thing is what we don't know, and that may prove to be very tricky.
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.
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,
understand how it worked, what it looked like,
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.
And now we're sitting here with three good vaccines, the best of which is undoubtedly the Oxford vaccine.
And we're ready to go and fight back in a pretty serious way.
So, you know, the fight back has begun. But in that story, there's dexamethasone which came from the recovery trial.
There's the mass testing programme with lots of flow tests, which has been led by Derek Warkentin Pito.
There are any number of great stories that are hugely led by Oxford scientists.
Moving on to future risks. Our main focus in today's episode.
I was interested to ask John whether there are notan diseases we should be wary of or whether
the pathogens that lead to major outbreaks are often entirely unknown until they strike.
In reality, we do occasionally get a new outbreak of a pathogen that we haven't previously identified and characterise.
So a good example of that is Lyme disease, which is spread by ticks in the east coast of the U.S. Legionnaires disease,
which is an aerosol spread, pneumonia, which we didn't know and understand.
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.
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
bit of documentation about the list of respiratory viral pathogens in particular,
which I think are probably the biggest single risk that might potentially cause trouble.
So, for example, when Ebola blew up in West Africa, we knew about it had been discovered ten, fifteen years before Nipah virus.
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.
That was a class virus that we didn't know very much about. But we now know quite a lot about that class.
And there's a whole family of Sabor virus. It's obviously better corona that potentially cause trouble.
So there's steady progress and knowing what's out there.
Now, each of the individual pathogens that cause disease will probably be different than the previous one.
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.
We just didn't have specific insights into Saras be to which we now do.
So, yeah, so it's not as if we don't know what to prepare for.
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.
I think the two or three big ones are still flu.
Flu is still the biggest single threat in my view. It varies pretty substantially from year to year.
There is a lot of avian disease out there that could, with a few mutations, become spread from humans and humans.
At its worst, it carries a really high mortality. And of course, the great flu epidemic of 1917 1918 carried away, you know,
somewhere between 50 and under a million people, depending on how you're counting it up.
I think, in my view, that's still top of the list,
that Corona viruses were probably always second on my list partment because the Saras and the murres outbreaks,
there was always question about what it would take to produce one that actually had real pandemic capabilities.
But we now know that that can happen. So I think that's the second big class.
And then class of viruses that sit around Ebola are probably also still a risk.
They're spread very, very effectively. They're infectivity is very high from human to human.
That is another family of viruses I would worry about a lot.
But there are only three of a long list. So we do need to be thinking about what that list looks like.
John's list didn't include anti-microbial resistance, which came up during a number of my discussions with guests for the series.
So I asked him why he left it out. Thing is, there is a little bit of antimicrobial resistance, but it's very little.
Some pathogens, TB, it's a serious problem in TB and gram negative organisms.
You're seeing more of it.
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.
Do you I mean, it's just basically isn't there. And to be clear.
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.
I would say that's probably an example of one. And it also doesn't help to beat up the pharmaceutical industry because,
you know, there's been lots of bleeding to say that pharma industry is at fault.
The truth is, it's a massive example of market failure, because if you make an antibiotic to gram negative pathogens,
you are resistant to the usual antibiotics that you use it.
For those infections, you could easily spend a billion dollars making the product.
And what are you going to do, sell it to 400 people a year? How is that going to work?
So, you know, government really wanted to have this happen.
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.
But nobody has done that. So I think it's not.
I wouldn't put antimicrobial resistance in my top list of things I wake up at night worrying about.
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.
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.
I mean, really, literally, they could not sell any.
And it was a real problem until avian flu came along and everyone went, oh, anybody got an anti flu drug?
And then suddenly they sold two billion dollars worth in a year.
Right. And then the following year, everybody said, well, there's no flu epidemic this year.
We're going to stop buying it. So it went from two billion in sales back down to nothing again.
So, you know, if you're running a company that's not very out there, it creates its own problems.
These infected medicines, it's a it's a real issue.
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.
This is a really interesting story, and I've been a bit involved in the national planning for pandemic preparedness,
which is largely being led out of number 10, but also the Cabinet Office, as you know.
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
since the year 2000 as a warning harbinger that there's likely to be more trouble in the not too distant future.
So the way I think about this is there's several boxes of activity that we probably need to establish is ongoing,
sustainable functions of the global community to deal with pandemics.
And the first one really relates to the ability to have better surveillance and a better heads up as to what's happening.
Quick pathogen identification, global surveillance for outbreaks of severe disease have put people in intensive care units around the world,
rapid identification, probably by genomic sequencing, which is the quickest way to do that.
And we need a network of centres that do that so we can see what's coming and what isn't coming.
So that's probably the first and most important initial capability.
It's probably also worth thinking about whether we have a sort of nine one one team that can drop into these sites,
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.
And he's probably as experienced as anybody in dealing with these emerging infections.
So I think you use our words very serious consideration.
So that surveillance piece is a crucial piece. We need good data.
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.
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?
I mean, it's a great thing. It's great. That's a great soundbite. But, boy, is that a hard job.
Because there are there are literally millions of those potential pathogens out there.
I mean, just take bats alone. They're full of all kinds of pathogens.
And if you go across multiple animal species, you can find lots and lots.
And I'm not entirely sure what you do with that information because you'll end up with a great long list.
But how you pick potential threats from ones that are not is quite challenging.
So that's the surveillance box that the second box is.
What do you do about having their reagents available to respond to a new epidemic with,
for example, a new virus, a new member of a viral family, a new flu, new corona virus, whatever?
And the answer is that there's quite a lot you can do now to get yourself ready for that.
And these were all areas where we were clearly failing,
at least in the UK and actually globally in terms of being prepared for this event, for example, with vaccines.
There are now at least two vaccine platforms, RNA and adenovirus, both of which have shown that they can produce vaccines pretty quickly.
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,
checking their immunogenicity and normal people, making sure they generate strong neutralising immune responses,
all that kind of stuff, even if you don't know the precise pathogen.
You know, as Sara Gilbert's great success was migrating quickly from a Meurs programme,
which she'd run very successfully into a Saras Kobe to programme, and being on the front foot for this is really important.
And when you look at the Jenner portfolio, they're working on twelve emerging pathogens.
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.
You can imagine getting range of vaccine platforms ready to go.
That could move quickly in the face of a new family member that perhaps didn't have
crossed reacting immunogenicity with previous infections as it was for COGAT 19.
The second one is drugs. So it's an interesting question whether we could do a better job with drugs.
This is not commercially very viable because you can make an antiviral against a Saras pathogen.
You're not going to sell it to anybody. So it's got to be subsidised by government.
But would it have been better if we'd had more model drugs targeted at, for example, the RNA dependent RNA polymerase, which is.
Sweet spot in these Corona viruses or to the protease, which, again, is a potential sweet spot for this.
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
pathogens so that we had a better chance of moving quickly to find a molecule
that you could use in patients now that when you look back at the epidemic,
that's quite a hard sell. And the reason is, let's say in January, you said, let's get the library out.
We know what this pathogen looks like. We've got the crystal structure, the protease.
Let's make a protease inhibitor. Well, you could have got to a protease inhibitor probably pretty quickly by the summer.
I would've thought. But then you got it in safe to study and you got to do trials.
You got to do all that. So, I mean, Pfizer's going to protease inhibitor, as you know, to cope with 19.
They're probably going to get licence just about the time the pandemic goes away.
So you'd have to be pretty clever to get those things in place in a timely way.
I think a better option, of course, is repurposing drugs in their recovery.
You spoke to Peter Hornby. It's a good example of how repurposing has very substantial benefits in this setting.
But then the other big play is antibody therapies.
So monoclonal antibodies for this disease are going to prove to be very important role.
I think they're very potent than virals. And again,
we only started making those antibodies when the first convalesced serum started coming in
and we started to clone the B cells that produce the antibodies and then characterise them.
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.
And I think we need to be prepared to do that and think about how we would set that up.
But a final bit of that story is I become very intrigued by broadly neutralising
antibodies so that basically antibodies that react to Saras Kohji to that they are
equally effective against Saras coli one and they're equally effective against all
the members of that family because they've designed a protein epitopes in Spike,
which are shared between all those viruses and people been working on broadly energising antibodies for HIV for a long time.
And there's been some beautiful work done, but in respiratory viruses, nobody's really focussed on that.
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.
And there's about 10 members that we know about now.
And so you think to yourself, well, Hammet, if you actually had those antibodies, those antibodies that would neutralise anything in the family,
then I think you could make a very good argument of growing those up, lie off, slicing them,
sticking them on the shelves, literally sticking a billion in them on the shelves so that you've got a buffer,
because if they've been appropriately modified by modifying the F.C. receptor, they last, you know, four to six months after an infusion.
So you could give yourself a buffer against just another Sari's virus infection by simply having a massive supply of those things.
So, you know, that's another bit of a therapeutic vaccine piece that we need to develop.
And then, of course, there's diagnostics. So we've had a huge amount of diagnostics, innovation in this epidemic.
And I think we've got to continue to do that because it turns out that knowing who's
got the disease is the first and most fundamental piece of knowing what's going on.
Mostly, this has been PCR driven in most countries in the West, but there probably are better ways to do these diagnostics.
And I think we do need a bit of innovation in this space to get better diagnostics,
which you would probably have to conceive of in the early weeks of the epidemic.
But you could probably move down the road very quickly. So that's the second.
Boxton third box is really about data and clinical trials.
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.
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.
And you've got to have standards of data that allows different countries to know that
their data is basically on the same standards as the French data and the German data,
American data and the Australian data, because it did at the moment in this pandemic, all the data's everywhere.
So you'd have no idea what he's doing, what to whom, which is a real problem.
So that's a box of clinical trials. And data is another very important piece of the puzzle.
And then there is a piece around manufacturing, which I think is also crucial.
And that is we got caught without any substantial manufacturing capabilities in the UK, least none that we knew about.
And V-neck Centre, which had been funded through the life sciences industrial strategy three years ago, three and a half years ago.
They're having cleared a bit of ground it was supposed to sit on. So they were able to hasten the speed of that.
But it's still not going to be ready till after the pandemic. So we need vaccine manufacturing capability.
We need antibody manufacturing capability, and we need diagnostics, manufacturing capability.
That's the other big box. And then the final big box is regulation.
One of those things slow this down in this endemic is that we use the usual routes to approve or not approve individual medicines,
diagnostics, antibody, selex. And I think there's an argument in the presence of a pandemic to change those
rules so that you don't get tied down by the constraints of the regulatory system,
which basically means you can't move fast enough. Now, I say that incomplete knowledge at the MHRA has been terrific in this pandemic.
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,
they would have preferred not to ask for those kind of those kind of results or derogations because just should have been waved through.
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.
So that's another box. But those are the five or six things that I think are crucial.
Next is Peter Hopea, professor of Emerging Infectious Diseases and global health at Oxford.
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,
which is the International Severe Acute Respiratory and Emerging Infections Consortium, which has got partners all over the world.
And so I have very strong links, longstanding collaborations with colleagues in China.
So I knew immediately that we would be involved somehow.
And actually, the first contact with colleagues in China was on the 2nd of January, just a few days after the outbreak was announced.
And it turns out that one of our close collaborators was nominated by the Beijing government
to be the lead on clinical research for this new virus and was sent to him to investigate.
And he rang up and we had on 2nd of January, it was serious.
I've seen no outbreaks of soslan and bird flu in the past year.
I'm from the clinical descriptions and from my conversations with my colleague in China,
which we were having every night at about midnight and 2nd of January,
it became clear that it was a serious illness, that it was transmissible from person to person.
So it was clear pretty early that this was a serious virus and a serious outbreak.
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.
Initially, we saw some cases outside of China, but it didn't really seem to cause much onward transmission.
They were taking control. So early spikes in Thailand and elsewhere.
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.
This could be very difficult to contain. Peter and his colleagues immediately went about organising a new clinical trial to test the
effects of numerous already known treatments on patients admitted to hospital with Kobe,
19. This was called the randomised evaluation of Kuvin 19.
Therapy, trial or recovery for short. They knew they'd have to act quickly.
What we've learnt in the past is that business as usual doesn't work for epidemics or pandemics.
They're very challenging for lots of reasons. They're very quick.
They're hard to predict where they're going to occur. The health care system and individuals are under great pressure,
both in terms of running the day to day jobs skills and in terms of political and other pressures.
So you really have to have a different mindset.
And what we've seen in the past is the usual sort of clinical research or other types of research that are done,
just not done at the pace and the way they need to be done in epidemics.
As an example, clinical trials testing new drugs in patients often take 18 months to set up.
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.
And then any one individual area, you get a wave. So you need to be ready for that.
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.
You have to move very, very quickly. And that's what we did.
And it was the right thing to do because it meant that we could capture the patients in the first wave of
the illness and really make some progress in understanding this disease and finding new treatments for it.
One of the key issues is that we need to have pretty big Charles detective, modest aflex of drugs and most benefits.
The drugs are fairly modest and so we need to have thousands of patients now.
Enrolling thousands of patients during an epidemic is challenging because you only have limited time,
but also the health care staff are under a great deal of stress and pressure.
So the first thing is it needs to be very simple.
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.
And because of that simplicity, we were able to roll it out very quickly.
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,
which I think that's a record that will never be beaten.
And then within two weeks, we enrolled nearly a thousand patients and within eight weeks, ten thousand patients.
So it was really highly successful and we built it so it could be adaptable.
So we built it so that we could and can move drugs and no evidence became available.
And that's what's happened today. At the time that we're recording this, we called the result on three drugs,
one of which takes measures that were successful, two of which were not successful.
And we've still got five drugs in the trial and we keep updating them.
So we've recently added an example.
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.
So as we learn more about this virus in which drugs might be effective, we can slot them into the platform trying to recover.
The speed of the recovery investigation, as well as what it's already achieved, was hugely impressive.
And I asked Peter for his reflections on that. I reflect on it almost daily.
It's it's an incredible achievement, I think.
And I'm not saying to bolster my own, the achievement is really a fabulous clinical trials team that have been setting this up.
And also the huge support we've had some chest than the national health mostue research infrastructure and support from government,
from the chief medical officer and the doctor, chief medical officer has made this possible.
And I think about this. I think, you know, this is the best thing that I've been involved in in my career.
And this really made a difference.
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,
not just in the UK, but elsewhere, because it really has been very effective.
And we need to make this asset available globally in the light of this experience.
I asked Peter what key lessons can be learnt about preparing for future pandemics.
There are many things we need, but the top three probably are the will to do it.
That's political will and will from universities, research, sexual research, condos, et cetera, to really make this happen.
It's very hard to make an argument that will second it comes the investment because you do need resources to make this work.
And what you need is resources that are there in peacetime as well as in times of crisis,
because you can't suddenly create that infrastructure when there's a crisis, you need to have it in place.
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.
So you need that investment during peacetime. So it's your insurance policy for when things go wrong.
And thirdly, you really need sort of the technological innovation, because as we've seen child designs with diagnostics and with vaccines.
If you put in place those technologies that are broadly applicable across a whole range of threats,
then you're already ahead of the game where you threat arises.
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.
I think that's recognised at all levels, both within the research community,
within the leaders of Oxford University and other universities and within government.
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
consolidation and will all of what we've learnt to put us in a much better place to make to a safer world.
However, Peter was very keen to emphasise that there are serious obstacles to our preparing for the next pandemic, whatever that may be.
One of the dangers is always fighting the last war.
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
the planning and response to the next flu pandemic was based on the experience with bird flu.
And then the planning for Cobbett, 19, was based on the 2009 flu pandemic.
So you have to be very wary about thinking that you know what's coming.
It's very likely that we'll have some knowledge about an emerging virus to be
from a class of viruses that we probably know about and we'll know a little bit.
But it's very likely it will be a new variant of that virus, which will behave in a different way.
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.
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.
And we know about that. Now, this is in that same class, but it behaves differently.
It's much more transmissible than most corona virus and it's more severe than seasonal corona viruses.
And it has a different pattern of disease in terms of when the peak infectivity is different from sovs.
When the patients develop an inflammatory syndrome, it's like other coronaviruses.
So it'll be something we know something about, but there'll be many different aspects of it.
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
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.
So they were identified as a risk. So we got that right.
What is new about the viruses that just have a slightly different genetic makeup in slightly different biology,
which means that you have to rethink your suite of interventions, so you have to rethink your diagnostics.
You have to rethink your drugs and vaccines cetera. The vaccines failed.
As we've seen with clearly recent results of success in the cloning of our state, things was reasonably well advanced.
And there had been work ongoing to develop vaccine constructs for the Middle East Respiratory corona virus and to the source coronavirus.
So in that sense, that worked. We have the platform technologies up to be able to switch to a new corona virus.
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.
And we're ready to go into clinical trials. There were some very preliminary data from experience of trying medicines during the first
signs outbreak that really there was nothing in that suite of drugs that was very spectacular.
So we were left with starting out the clinical trials with rather unpromising drugs to end our conversation.
I mentioned my discussion with Professor Brian Angus comparing Kovik, 19,
to other diseases like Ebola and asked Peter which diseases concerns him most.
The answer very much depends on what perspective you're taking.
If you're taking a personal perspective about whether you would pick about a virus or corona virus if you had to.
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.
But many other categories of viruses are common or garden, but have the potential to become more serious.
Examples are much more serious strains of influenza, but there are also other viruses like enteroviruses, which are very common.
What viruses that cause polio accentuate a new strain of something like that?
Those viruses really could have a huge impact and we've seen that with this pandemic.
And so it's not just about the severity of a single infection.
It's about a whole package of how that virus transmits itself and the impact it has beyond the individual health.
Our next guest has, like Peter, played a huge role in the global fight back against the Kovik 19 pandemic.
It was a real privilege to talk to Sara Gilbert, professor of vaccinology at Oxford, particularly at such a busy time for her.
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.
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.
That in particular that works for inducing strong t cell responses.
And we've heard quite a bit this year about T cell responses as well as antibody responses.
But remember that most of the vaccines that we use that are licenced today, we only think about the antibody responses that they induce.
They usually work through antibody responses and to find out if they all work and we measure antibody responses.
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.
But there's a particular stage in the malaria lifecycle where shortly after somebody has been bitten by an infected mosquito,
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.
There's only maybe 10 infected cells if if even that.
So it's not a particular problem for the liver,
but there will be a few infected liver cells as far as the whites turn into factories to make lots more
of themselves in a similar way to a virus is taken over cells in our body and turn them into factories.
That's what the malaria parasite does at that stage of the lifecycle in the liver.
And because they're hidden away inside a liver cell and they stay there for about a week, antibodies can't reach them.
So antibodies, if you have a very high level of antibodies in your blood,
when the mosquito bites you and the antibodies can recognise as far as away and destroy it, then you won't get malaria.
But there's a very short time. That's only about an hour.
And so there's not really very much chance of that working, whereas the parasites then inside the liver,
sitting inside a cell, making more itself for about a week.
And T cells can recognise those infected liver cells and destroy them.
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.
Then there is quite a bit of evidence that sometimes the parasite can be attacked at that stage of the lifecycle.
So the idea would be to develop a vaccine that would induce cell responses that would kill these infected liver cells.
Again, small number. So it's not going to cause a lot of liver damage.
And then the person who'd been infected wouldn't become ill at all because you don't become ill
until some days after the parasite comes out of the liver and starts infecting red blood cells.
And then it starts to really multiply to high numbers in the blood level.
And that's when you see people getting fevers. So all of that could be prevented if we could have a TSL inducing vaccine.
And adenoviruses are really effective ways of making a good Tiso response when you vaccinate somebody.
And so are some other viruses called pox viruses.
So pox viruses are relatives of smallpox and vaccine, a virus that Edward Jenner used against smallpox.
And there's a safer version of the vaccine, your virus.
So the vaccine is a virus that is derived from the vaccine that Edward Gennie used.
And there are some important differences that we don't really need to go into. But they're not the same.
But that vaccine does actually spread through the body when you use it to vaccinate somebody with.
And if somebody has a very weak immune system, it can actually be dangerous.
But we use a replication deficient version of a pox virus like our replication deficient adenovirus.
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.
When you vaccinate somebody in a very similar way to the adenovirus, you can add genes into it from different pathogens.
And those genes are expressed at high levels.
When you vaccinate somebody and you get a good immune response and the strongest TSA response is that could be generated,
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,
the MBA carrying malaria antigen.
So they're both very safe to use because they can't spread through the body, both expressing the same malaria antigen.
And if you use them in that sequence or actually you can reverse the order, it's not too important, which comes first.
You get a really strong T cell response. The TSA response is actually stronger with the adenovirus than with the NBA.
But it doesn't matter which way round you give them, you come to the same very high t cell response in the end.
I worked on that technology and that's when we started being interested in using simian adenoviruses rather
than human adenoviruses because of the problem of pre-existing immunity to human and viruses in humans.
We knew that was going to be a problem.
And although in the lab the human adenoviruses make great vaccines, it wasn't something we want to take into clinical trials.
So we had to wait until we got a collaboration with somebody else who'd got a simian adenoviruses that we could use.
And that's when we started doing clinical trials for the malaria vaccine. But these are very adaptable, technical.
These other people were using them to make therapeutic of vaccines.
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.
And it was designed to be very adaptable technology.
And they do induce good antibody responses as well as the strong T cell responses.
And I then started working on influenza vaccines again, thinking about the T cell response,
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.
So there's a better chance of having broader protection. And that's a project that I worked on for a while.
Haven't really brought that to a conclusion yet. I still have a flu project running at the moment.
And with that, we're now exploring different routes of administering the vaccines because
it may be more effective not to give the vaccines I intramuscular injection,
but to get them into the respiratory tract directly.
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.
That's when symptoms peak. And that's a really short space of time.
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.
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.
But that's not true in flu. It needs a really rapid response to the incoming infection.
Sarah has also done a huge amount of work on the subject of this episode, Disease X.
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.
So for people think about disease X, it's just the unknown.
We don't know where it's going to come from or what it's going to be, but there will be something.
The world had been halfheartedly preparing for a flu pandemic for quite a long time.
And then we got a corona virus pandemic. So we weren't expecting that.
But actually, the people who study these things would have said that we should have been expecting
that because we've seen corona virus outbreaks before and we know what they can do.
So we shouldn't have been surprised. What else is going to surprise us?
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.
There are so many different versions of flu in bird populations. We have no idea what they are, where they are.
Maybe it mutates really rapidly. And when people get infected, the onset of the disease is very, very rapid.
So there's not much time to do anything before the symptoms take hold.
So a flu pandemic like the 1918 flu could still be absolutely devastating today.
Studying and preparing for a coming disease X has been central to much of Sarah's recent work.
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.
At the time that Disease X was added to the WTO list of priority pathogens,
I was already working on vaccines for a number of other priority pathogens which are on the list.
Meurs, NIPA and Lassa, three very different viruses, but all capable of causing outbreaks in different parts of the world with different outcomes.
But we need a vaccine against all of them. Another one coming in Congo haemorrhagic fever and colleagues of mine were also
working on vaccines against Rift Valley fever virus and chikungunya virus.
Also outbreak pathogens which cause outbreaks in different parts of the world.
And so we have settled on using the Cherrix one platform technology for all of these different outbreak diseases,
because it's a technology that's very adaptable. We can use it to make vaccines in lots of different ways.
And we know how to manufacture it. We know that it's safe to use.
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,
in theory, suitable for use in many different parts of the world. So a lot of those different programmes were going on.
But the early parts of each of those programmes took several years to get started.
And when Doli Recto introduce a concept of disease X,
we have to start thinking about how could we get from the knowledge of a new disease to having a vaccine
that we could vaccinate people with in a clinical trial much more quickly than we have been doing.
And to be honest, there weren't really any particular technical hurdles that we were going to need to overcome.
It was more a question of rethinking the way that we did things.
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,
instead of just thinking that we had a small amount of money.
And so we make a vaccine and just test it in the lab and then think about moving on later.
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.
So what would be our approach to that?
For some of the grant applications that I'd applied for, there was the opportunity to include what's called a demonstration project.
So part of the process will be to demonstrate that the technologies works as a vaccine.
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
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,
for example. And so we thought about how we would go through that and what would be a good disease to do it with.
And I've been thinking of influenza antigens because there are new ones occurring all the time.
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.
That exact sequence. And then we could put it into a vaccine and see how fast we could get through the manufacturing process.
And we would have been able to demonstrate that we couldn't have started before, particularly like the sequence wasn't known.
And so when a new pathogen like Sarkozy to arise is that SoftLayer brilliant demonstration project because nobody knew what it was before.
So thinking about and wanting to test the technology, not knowing if we'd actually need to use the vaccine,
but anyway wanting to see how quickly we could make a vaccine to start the process.
This was an ideal candidate. The story of Sarah and the rest of the teams work on Coupet, 19,
is definitely one for another podcast, which I hope we'll make in the not too distant future.
For now, though, I was keen to find out whether Sarah was already reflecting on those efforts.
There's quite a lot of things I think we could do better next time.
One is that we've been advocating for better manufacturing facilities so that we can get the vaccines made into clinical trials.
And that hasn't happened yet.
The vaccines manufacturing, the innovation centre had been funded and the building had started to be built, but it wasn't ready to use.
So it wasn't any use to us on our own manufacturing centre, the clinical bio manufacturing facility.
We've been trying to get that extended and upgraded for years as well, and there's been no money to do that.
We really want to be able to go much more quickly with more candidates as well.
So one thing that we had to deal with this year is that we had one choice for the vaccine.
There was no opportunity to try to make two or three different versions of the vaccine and then
decide which one we wanted to take into clinical trials because we only have one clean room.
So it had to be one shot from the beginning. That's why we only made one subsequently.
We made some different versions in the lab and we've tested them and we're still happy with what we started out with.
It would have been good and in some cases for different viruses,
it would have been more important to be able to start off with making maybe up to five different versions
of a vaccine at the early stages until we get some preliminary work done with it and then select.
But we knew we couldn't do that this year. So bigger, better, more available manufacturing facilities is one thing.
Then we have to think about the testing in animal models that we did.
We were required to demonstrate that we weren't going to cause a phenomenon known as vaccine enhanced disease,
which is something that's been seen in some vaccines in the last century.
There was a respiratory Sin City ill vaccine that was tested in children,
and it did actually make the disease worse when the children then got exposed to the virus.
And understanding that that was not going to happen this year, that the vaccines that we were making was really important.
And we think that we already understood it. And we know what kind of immune response was responsible for the enhanced disease.
And that's not the kind of immune response we get with this technology. But we still had to demonstrate it.
And that takes time because you can't demonstrate it with animal models until there is an animal model.
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
responses that we get from different vaccination technologies so that we are not having to cheque,
that we're not going to get vaccine enhanced disease because we are absolutely certain
that we won't with these technologies that would enable us to go faster as well.
And then there's things that I think we learnt after Ebola on clinical trial design.
So in the Ebola outbreak, there were vaccines that were ready to go into efficacy trials,
but nobody could agree on how those efficacy trials should be set up and whether it should be a placebo controlled trial,
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,
we had a ring vaccination trial with either immediate or delayed vaccination.
So some people in the delayed vaccination group who had to wait three weeks for that
vaccine did contract Ebola during the time they were waiting for their Ebola vaccine.
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.
And when you think back to the idea of a placebo controlled trial,
which horrified everybody because it wouldn't be ethical, because some people wouldn't be vaccinated,
it's actually not really very different doing a delayed vaccination trial in which some
people will be impacted because they haven't received the vaccine until later on.
So thinking about child designs, particularly for viruses with a high fatality rate.
So Kobe, it doesn't have a very high fatality rate. It spread so rapidly, it causes major disruption.
But actually, the percentage of people who die from it is much lower than Ebola and many of the other outbreak pathogens.
So we probably still haven't really addressed the point of how should we test
the efficacy of a vaccine against a virus that does have a high fatality rate.
And that's something that probably requires more discussion and modelling and
better planning so that we would be ready in the future to do that kind of thing.
Well, what's worked really well this year, I think,
has been the collaboration's within the university with AstraZeneca between different companies, with lots of different academic collaborators.
That's all been really good.
And I hope that will continue in the future because without that kind of collaboration, nobody can make progress as quickly.
So we need to see a lot more of that before our conversation ended.
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.
I'm including it here because Sarah has a unique and fascinating perspective on his achievements and how it relates to her work today.
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.
So he didn't just give somebody a vaccine and then say, well, they're fine, obviously.
So I vaccinated them. They'll be protected. Now, he vaccinated his gardener's son with the cowpox, and then he did it,
deliberately exposed the boy to smallpox and showed that he wasn't infected with smallpox.
That sounds horrendous,
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.
So smallpox, if you had an outbreak coming through a particular area, one in three of the children would be killed by smallpox.
And people were using let's called Barry relation, which is deliberate infection with a small amount of the smallpox virus,
because that was known to protect people against smallpox infection. And apparently, Janet had this done to himself as a child.
And it was pretty horrendous process, partly because they didn't really understand how it worked.
So the children were kept in the dark on a very poor diet while this was happening.
It was meant to be stopping the virus from having the power to take over the child.
She probably just made the child more likely to be very ill.
The death rate from vaccination was about one in 50, which sounds terrible, but it was much better than one in three.
And then Jana wanted to replace very lation with something much safer.
And the death rate from vaccination against smallpox with this live replication competent vaccine here is about one in a million.
So, again, we wouldn't use a vaccine like that today. That's far too dangerous.
But it was so much better than one in 50 with Barry elation or one in three with smallpox infection.
So it was all about reducing the risk continually. And that's always something we're looking to do.
However safe something is, we're always looking at any possibility to reduce the risk even further.
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.
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.
Hopefully at least 49 out of 50 of them did.
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.
So James Phipps is known to be immune to smallpox.
So the idea of vaccinating and then testing efficacy, which in the time of Kobrick we're doing with very large phase three trials,
waiting to see if people who got the vaccine or got a control vaccine get infected with COPD is still the same concept.
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.
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.
Is he communicated his findings. He wasn't the first person to use cowpox to protect against smallpox.
Other people have done it before. They are quite a few records of it happening. But what he did was having done his experiments.
He went to the world society and gave a presentation.
And then he continued to talk about it and he continued to vaccinate large numbers of people and promoted the cause of vaccination,
eventually managed to get very chelation. The exposure to smallpox. He got that outlawed.
So he was very vocal about what he was doing and why it was important.
And I think that's something that scientists often don't really want to do.
We want to get on with the science that we have to follow in Dennis footsteps in that way as well,
and communicate the findings and be clear about what it is that we've done.
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.
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.
The next voice is your. Here are two you may recognise from earlier in the series.
The first of these is Professor Jemmy Whitworth from the London School of Hygiene and Tropical Medicine, whom we met in Episode nine.
You're about to join us midway through a conversation about plague and the potential threat of anti-microbial resistance.
Now, it's a bacterial infection, as I've mentioned.
And so it is treatable with antibiotics and in fact, it's it's pretty sensitive to some standard antibiotics.
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,
they should be eminently treatable.
It's not like the situation historically where vast numbers of people died and there was nothing that could be done about these days.
Once you know that there is plague in an area and you're alert to it,
then as long as you can see those cases quickly and get them onto treatment, then they should do very well.
The vast majority will recover from plague with antibiotics.
Anti-Microbial resistance is a problem for plague, as it is for many other conditions.
There is some suggestion from the Madagascar outbreak that there might have been some development
of anti-microbial resistance that made the antibiotics not as successful as we've seen previously.
That's certainly something that needs to be kept an eye on.
And all around the world, there are problems with the development of antibiotic resistance, which makes diseases much harder to treat,
and that we are reaching a situation where for some conditions, they are becoming close to untreatable.
I don't think we've reached that really for any diseases yet.
What for? Conditions even such as gonorrhoea, for example.
High level of antibiotic resistance means that there is a looming possibility that some infections
which have been treatable in the past might become essentially untreatable in the future.
Having said that, that's thinking to the future. And I think we do need to keep that in mind.
But at present, the major problem with antibiotics is lack of access to.
So there are currently many more deaths that occur because of lack of access to antibiotics and because of antibiotic resistance, particularly,
of course, that is in low resource settings in poor countries, particularly those which have limited access to health services and so on.
So I think it's important that the message is that we need to reduce inappropriate antibiotic use.
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.
So it's important that the message is appreciated as reducing inappropriate antibiotic use later on in our conversation.
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.
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.
And this is because as temperatures rise, that means that insect vectors, particularly mosquitoes, are able to expand their range.
We've seen this in recent times in Europe, where conditions such as Denki, but also Chicken Gunya,
even Zika, have started to transmit during summer months within southern Europe.
And you can see the march of the range of the mosquitoes steadily moving north over time.
And this starts to threaten major centres of population, places like Paris or Amsterdam or even London and so on,
in the future that these diseases will start to spread.
We're already seeing that EDI's mosquitoes, particularly Aedes albopictus, so-called Asian tiger mosquito,
is a fact of life in Spain and Italy in a way that it was not seen before.
So these mosquitoes have established themselves in places where they were not before,
and that means that epidemic diseases are occurring more frequently.
So we are seeing outbreaks of West Nile fever, diseases like Crimea,
Congo haemorrhagic fever occurring in Europe in larger numbers and over wider areas than we have seen before.
And that means that public health authorities need to be aware that these diseases are on the march and they need to have.
Control measures in place to be able to deal with them when they occur.
And for countries like the UK where they have not yet arrived, but they are threatened,
then we need to have very good surveillance systems in place so that we can identify when they occur.
Because if you have just a few of the mosquitoes that are relevant for this,
that's a much easier situation to be able to control and eliminate that focus than if you wait until it is well established.
We do need to think about novel infections and particularly zoonotic infections, those that affect largely animals,
but that could pass on into the human population with global warming, with population increase moving into forested areas and so on.
We do come into contact more with zoonotic diseases than we do in the past.
So we're always going to be vulnerable as a human population to epidemics from novel viruses that we've not seen before.
We've seen this with Corona virus and I'm sure we will see this again in the future.
Having just talked about novel pathogens, we then moved on to discuss a disease that we already know a great deal about.
I think cholera is a very interesting problem and one that should probably have more attention.
This probably causes more large scale epidemics around the world every year than other epidemic diseases.
And yet we know an awful lot about cholera, how it is spread, how it can be controlled.
We have treatments. We have a vaccine. And yet it occurs every year, predictably, in various parts of the world.
And it shows that we really do need to have a holistic approach to dealing with epidemics.
And the idea that, oh, if we have a vaccine or if we have an effective treatment, then all our problems are solved.
It just shows that that's not the case, that even when we do have those, we need to be able to apply those.
And we need to be thinking about improving sanitation and improving the health of populations,
the risk and so on if we want to be able to control these diseases.
With so many potential threats on the horizon. I asked Jemmy.
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.
Midges are all over the UK.
We have no control measures for dealing with them at all.
Just think about people who go on holiday in Scotland in the summer and the mej population that we have there.
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.
We've been quite lucky. There have been two outbreaks of mej infections in the UK in recent years.
One has been bluetongue virus and the other was Schmallenberg.
Both of these affect animals, livestock in particular.
But luckily for us, they don't cross into the human population.
And the veterinary profession has been able to develop vaccines very rapidly.
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.
And those epidemics have been controlled.
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,
given the wide variety of outbreaks that any country could, in theory, have to plan for.
I'd put to Jemmy that pandemic preparation is an almost impossible task.
He had an interesting perspective on whether we should be optimistic or
pessimistic about a country's ability to plan for the emergence of a new disease,
previously pandemic flu was right up there at the top of the UK is National Risk Register.
But that didn't translate into robust plans really to be able to control it.
I really do feel that this current pandemic has galvanised policymakers and will make changes to the future on how we deal with this.
So I'm optimistic that things will be done.
I'm slightly pessimistic in that the history of dealing with epidemics is that we always put plans in place for the last epidemic,
not for the future epidemic, but for what happened last time.
And of course, that is very much shutting the stable door after the horse has bolted, which is difficult.
I mean, what should we put in place?
I'm in a position where I can be confident that there will be another pandemic or certainly major, extensive epidemic that occurs.
But what I can't tell you is when or where or what it will be caused by.
And that means that we need to have put in place systems that are frameworks that are adaptable
and flexible enough to deal with epidemics of whatever sort may come about for the future.
And it means that we have to learn on the hoof and apply what we know from first principles
or from other diseases that we've dealt with to be able to control these epidemics.
But it means that we do have to be prepared and we must not allow the resources to be run down so
that we're not in a position and that it takes a long time to be able to deal with with an epidemic.
The best time to deal with it is when it first occurs and to control it.
Then if you allow it to get out of control, then it is much harder.
With diseases like Corona virus, we're seeing doubling times with four days, 10 days,
that kind development, that means that you get exponential rise very rapidly indeed.
And you can quadruple your number of cases in a week or two.
And that's very serious. So you need to be prepared to act very rapidly when epidemics occur.
My final guest for today poses a more fundamental challenge to the whole way we've been thinking about epidemics.
Erica Charters, associate professor in the history of medicine in Oxford's faculty of history, who we met in Episode five,
cautions that concentrating too much on specific periodic outbreaks risks ignoring the constant threat of endemic disease.
One of the really interesting things about an epidemic is that we tend to think
about non periods of epidemics as periods when there's not disease and the past.
That's just not true. There's always disease lurking around in the world.
So the difference between normal periods, what we make health care is a pandemic disease and epidemic disease is when disease becomes a problem.
There is no magical number when disease something becomes an epidemic.
It's actually when we either feel that it's unacceptable levels or, for example,
when policy officials deem that this disease is now a danger to the population or present some kind of risk.
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.
And it's something that we often don't think about when we talk about epidemics,
that actually epidemics only make sense if we also think about how it needs the context of acceptable that is endemic levels of disease.
I'm a historian of endemic disease, probably more so than epidemic disease.
But you can see how if you take a long term approach, if you're looking at the history of disease,
you're going to be looking at fluctuations when something is at one point epidemic.
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,
as you can see, how there might be a cycle when influenza becomes an epidemic disease, but it's also about spatial differences.
So plague is a great example where we see that it recedes from some locations
in the world and then is maintained as a constant in other parts of the world.
And so actually, what you're calling an epidemic disease probably depends on which position in the world you happen to be placed.
The other way of thinking about.
This is, of course, some diseases are deemed acceptable and endemics or something like malaria is obviously endemic in some parts of the world.
If we were to see an outbreak of malaria, say, in England, we would consider it an epidemic.
Even that would be much. Lower rate simply because we think of that as being a foreign and somewhat unacceptable disease.
You can see how it's as much about geography as it actually is about space and time.
This seemed a fascinating idea. But I was curious why Erica fought epidemic diseases appear to be so much more prominent, you know,
cultural memory than the endemic diseases that many people around the world live alongside every day.
This is where probably it's because I'm a historian of endemic disease and I feel like we forget about endemic disease.
Right. And it makes sense why we remember epidemics, because they are dramatic.
They're exciting. They seem to have this storyline. People have a chance to be heroes.
It's much harder to to write or to tell.
Even today, I think people who are trying to raise money for fighting against endemic diseases will tell you it's much
harder to have an exciting narrative to sell to the public about your battles against infant diarrhoea.
Right. What is the great drama at hold there? And I think that's what's fascinating is, of course,
endemic disease is probably much more significant in terms of mortality or even in terms of
numbers of people who are constantly ill and therefore more susceptible to other diseases.
But those things are much harder. So I'm always a champion of remembering endemic disease.
One of the things that I'm working on right now is a project on how epidemics end.
And, of course, usually how epidemics and for the most part is by turning into endemic disease, by becoming acceptable.
There's very few stories of disease simply disappearing.
And so I do think if we were to take into a broader context,
that would help us to remember that actually epidemics also need to be seen within the context of endemic disease.
I was really struck that kind of image that was going around early on in the pandemic by this website called the Visual Capoulas,
which is about epidemics in the past. And they had these little coloured bubbles that were supposed to be representing
numbers of people who died according to different epidemics in the past,
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,
those empty spaces are full of endemic disease, but they just don't they don't get captured in that kind of model.
And so we really do run the danger of just looking at the bubbles than the bubbles don't make any sense
because we don't understand what's actually in between each of those those bubbles of epidemics.
And Erica suggested that the most useful way of thinking about disease is something that's just part of our day to day experience.
The really important thing to think about is that disease is something that's part of society.
I think we tend to think about disease as something that's outside of it and maybe occasionally comes in.
But actually, if you're taking a long term perspective, disease only makes sense within a social context.
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.
Right. So take cover at 19. It's about shaking hands or kissing cheeks or whatnot.
So it's about human interaction. And the same way that the actual rates, the rates of mortality, for example,
are shaped by human intervention, whether it be political or whether a medical.
So I think actually the category of epidemic can be very helpful because it reminds us
that disease is as much a social and political phenomenon as it is a biological one.
But I think it's therefore very important because we tend to assume that epidemic is this kind of obvious,
self-contained category when actually, as I've been saying, it probably depends on who's defining it.
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
or actually that's just a normal rate of disease that we should simply accept.
You could talk about how epidemics are very traumatic. Right.
So these are the things that we pay lots of attention to, things like chronic diseases or infant diseases we tend not to notice.
And so one way of thinking about this is how epidemics groups that are like the tips of icebergs.
Right. So they are the things that are very visible.
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.
But those rates of disease actually usually depend on substantial mass of the iceberg that's underwater that often you can't see.
One way you can think about this is comorbidities. And again, I think Covered 19 has really brought this home.
That disease is complex, right? It interacts with other diseases, but it also interacts with different kinds of health structures,
including things that are tied into social structures, socio economic conditions.
Living conditions. Right. Population density. So those are the types of things that disease.
It doesn't just strike everyone in the same way. Actually, it uncovers all of these differences.
I think that's one way to think about this kind of broader social context for thinking about how epidemics interact within a society.
But therefore, also how they reveal these different social structures, political differences within a society.
We've been coming to the end of our conversation,
but I was still keen to explore this idea of our natural bias towards remembering certain types of outbreak.
I asked Erica, why was she thought that some diseases live on in history while others are largely forgotten?
It's a great question because I think there's two parts to this, right.
One is what shapes our response as to whether we think a disease is important and we can think about how some diseases
are feared and others probably maybe because of symptoms that we can think about how Ebola has very striking,
dramatic symptoms. Cholera, too, was very noted for having these dramatic symptoms.
Death was very fast. So that's something that people often pick up on yellow fever,
which kind of the term people used to describe it in the 18th century as the black vomit.
So you can again imagine that has these very striking symptoms. So part of it has to do with the type of disease itself.
But the other thing we can think about is, again, who is it affecting and in what ways?
And I think this is always this debate that we have over. Is it?
Say those in power who are affected most by this disease.
And so therefore have reason to kind of energise political structure or invest in therapeutics towards it?
Or is it those who are say perhaps have less political power?
The other thing, which I think is really important is that there is a long history,
actually, of using disease to mobilise what we might call public opinion.
So the period that I look at in the seventeen hundreds people might be surprised to hear that even then,
in their early days of newspapers in the 18th century in England, disease was used as a partisan criticism.
So it was especially during wartime, because I look at soldiers and sailors,
what you see is that it's OK for your soldiers and sailors to die from combat,
but it's deemed very problematic if they're dying from diarrhoea or from yellow fever.
Those are just not glorious ways or expected ways to die.
And so reports of disease get used in the press by, you know,
the other political party to say there's something wrong with leadership or leadership is corrupt or our foreign policy needs a rethink because
this is far too expensive an investment to be losing our precious national manpower to yellow fever or to disease rather than to combat.
So disease. Also has this very long history of being part of political arguments, even diplomatic arguments about who can care for their troops.
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.
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,
we probably think in terms of responsibility, which is very similar.
So I think very often when we talk about there's a sense in which disease often is,
although we don't talk about sane people will often relate it to, well, that's because you acted inappropriately.
You didn't take the proper cautions. I think the rhetoric about young people going out and partying obviously has very similar
frameworks thinking about this as disease being the result of acting irresponsibly.
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.
And yet what very often happens, especially during the period of an epidemic, is that we want to make sense of it.
So Charles Rosenberg, a wonderful is kind of medicine, but this classic piece about what is an epidemic.
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.
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.
And very often it is by saying that there are good people and bad people.
Bad things should happen to those bad people, including the outbreak of disease. And again,
I think this is where our own argument about which countries are doing well and which countries are
not doing well is partly our attempt to try to say we have some control over what's happening.
And it's because if you act the right way, then you'll be able to avoid the bad outcome of disease.
But as many people remind us, that's not a sure thing, especially when you're dealing with a new and rather unknown disease.
Thank you for joining me. This bonus episode in our series on the history of pandemics.
If you haven't listened to the whole series yet, please do.
In it, I explore ten world events that may have had a significant impact on the way we think about and prepare for pandemics.
We'd love to know what you thought of this season of future makers and to hear your recommendations for future themes.
So please do leave a review or get in touch on social media. We'll be back soon with more episodes.
In the meantime, I'm still Peter Milliken and you've been listening to Future Makers.
Future Makers is created in-house at the University of Oxford.
The school for the series was composed and recorded by Richard Watts.
It's presented by me, Professor Peter Milliken from Hartford College.
And the series is written and produced by Ben Harwood and Steve Pritchard, who've been a delight to work with.
Thank you. On behalf of the whole team for listening to our history of Pandemic's.