It's not like giving your name and your position.
My name? Name's Andrew Pollard. I'm the director of the Oxford Vaccine Group and I'm a paediatrician here in Oxford.
Thanks very much. So that's what can you just tell me a little bit about yourself without giving me your entire life
history from how you first decided medicine was going to be a career to how you got to where you are now?
Well, I decided to to do medicine.
Yes. So I guess I decided that I would go into medicine only when I was already had started my A-levels.
And when I looked at the admission criteria, I discovered that you needed to have a physics A-level equivalent of a GCSE in order to do that.
So I then had to a great rush at the age of 17 to do an extra physics exam whilst studying
with my uncles and then applied to various medical schools and set off to do medicine.
But what was it that made you decide that medicine is going to be it? I think I always entertained the possibility and I don't know what it was.
The sudden it suddenly clicked as a 17 year old, but maybe I could do it.
I think before that I thought I just wouldn't have been up to it, but that perhaps it was actually the teachers giving me the encouragement.
You didn't have medics in the family. My parents are both dentists, but I didn't have a particular connection.
20 minutes. And so how did you get from doing a medical degree to where you are now?
Well, when I finished my medical degree, I mean, I enjoyed everything in medicine, so I didn't really know which area I wanted to specialise in.
So where did you study? So I studied at St Bartholomew's Hospital Medical School in London, and I so I did a job in A&E after I qualified.
And of course you see the whole spectrum of medicine there.
And I had always been quite interested in paediatrics and this was partly why did I need to
see whether I because in medical school you don't do a huge block of studying children.
And I thought there was a lot to offer and I really enjoyed communicating with children and their parents.
And so I then started training in paediatrics. And over the years I guess the large proportion of what you see in paediatrics are infectious diseases.
And that's I think the greatest number of people who come through the front door, snotty children.
And during the course of that early training, I was always doing some research,
interested in academic development and decided I wanted to do a PhD and looked at possibilities of doing
PhD in the tropics and discussed with the head of the Medical Research Council unit in the Gambia.
And we decided that I would go to the Gambia and and do my PhD there as a junior doctor,
but the funding fell through and so I ended up going to St Mary's and studying meningitis for my PhD.
That's in London. In London. And at that experience was just completely eye opening in terms both of the medicine,
because I was moonlighting as an intensive care doctor and children's intensive care dealing with these desperately sick children.
And during the very large increase in meningococcal disease, one form of meningitis during the 1990s, why was there a big increase when it goes?
It always goes in cycles. There's this particular disease and we were in an upsurge of a new strain, I guess in today's parlance,
a new variant emerging in in fact initially in the UK, but across the whole world, which caused a large increase in disease.
So over the the few years I was there at St Mary's, maybe saw 400 children in intensive care with this dreadful condition.
And my Ph.D. was studying the immunity to to this bacterium.
And the obvious step from there is into vaccines. And so I decided after I got my Ph.D. to finish my training in infectious diseases in Canada.
And so I spent two years in Vancouver and was offered a post to come back to Oxford after when I was in in Canada and decided that I
really wanted to continue this theme of studying immunity to infectious diseases and realised that the best tool to do that was vaccines.
Because you can study children's immune systems by vaccinating them and seeing how they respond.
And so 20 years ago I came to Oxford and started work on here at the Office of Vaccine
Group on trying to get a better understanding of immunity and very quickly realised
that you can actually save lots of lives by booking all vaccine development in
parallel with studying the immune response and the science behind how vaccines work.
So in terms of your own particular contribution in this field,
would it be true to say that you've been looking at the immune response and trialling vaccines in designing vaccines as somebody else's job?
Is that right to have you know,
I'm a bit of a not very good at anything but does everything and so we some what what might I do in my team is that we both design vaccines.
We try to understand which bits of bacteria or viruses are needed to make immune responses and test those out in the lab.
And then some of those vaccines we've taken into the clinic, we have phase one studies of vaccines for meningitis.
Currently, we work on a vaccine for plague. The that the biggest pandemic ever affected humans that we know of.
I mean, the 1300s where half of the population of Europe was wiped out.
The black death, the black that. So we have a number of those.
But but also because vaccine development normally takes a long period of time,
we have studies with other collaborators where we look at vaccines they've developed and evaluate them, help move them along more quickly.
And a particular area of interest for me has also been to look at the the vaccination program we already have and try to
understand whether it is optimal and to to do studies to see whether we can tweak it to improve immunity in children,
to make sure it persists better.
And so I think the contributions really from my team over the last 20 years, some of it's new vaccine development, some is evaluation of vaccines.
It helps get them licensed. And another part is understanding the population immunity so that we can treat vaccine,
tweak vaccine programs so that huge populations, particularly children, can be better protected.
So a lot of your work, apart from looking at the UK vaccine programme, you've done quite a lot of work in in tropical in developing countries.
Why? Why is that important?
Well, the biggest burden of infectious diseases in terms of both mortality and the severe disease is actually seen in low income settings.
And so in some ways, in a high income setting like ours,
we've dealt with most of the diseases that cause the infectious diseases that cause severe problems in children,
not all of them, but but a large proportion. And in low income settings.
There are lots of diseases that we don't have here at all that need addressing. But in addition to those diseases that that we don't have here,
even the diseases we do have here are at a much greater burden and children are under-vaccinated.
So focusing a lot of our work in those settings has a much bigger impact on those populations than it would do here.
So these are things like measles and meningococcal meningitis.
So the leading cause of death in childhood is pneumonia.
So a large programme, for example, in Nepal has been on pneumonia.
But my biggest program in terms of studies over the last decade was actually on typhoid.
And we came into that because working on pneumonia in Nepal,
I discovered that the bacterium that causes typhoid was the commonest cause of bloodstream infections in children.
And astonishingly, when we looked at children who came to the hospital and the paediatricians there thought that these were probably viral infections,
and we took blood samples. They had these bacteria growing in their blood.
And that's the reason why they were on. Well, fortunately, they they were all treated with antibiotics,
but it was a realisation that there's this disease which is causing a huge burden affecting children's health and their education in that setting.
And so when I made those observations in the early 2000, one of the thought was, well, we actually know how to make vaccines for typhoid.
What's holding it up? And we started working with an Indian vaccine company to try and support that
programme and to convince people that actually that could be a huge impact.
And what we did here in Oxford was that we vaccinated volunteers who were from a wide range of backgrounds,
but people particularly from science backgrounds, and then deliberately infected them with typhoid.
So we got to drink these bacteria as would happen if you went travelling and you got typhoid as a traveller.
And they what we found was that the vaccine was highly effective in preventing typhoid and that then led to the World
Health Organisation making global recommendations for the use of the vaccine and the Global Alliance for Vaccine,
releasing money so that countries could apply for funds to implement programmes there.
For us in our research, the next question really was for typhoid is how do you implement a typhoid vaccine now that we know that they work?
And so we did two things. The first, we went to countries in Africa and in Asia and set up a surveillance program to document the
burden so that we can help countries understand just what could be prevented if you had a vaccine.
And that was really hard work. We had 100,000 people in each of three countries, so 300,000 people in total.
And we just followed them to see if they'd develop typhoid, what the risk factors were and found this enormous burden of disease.
And with those sites now set up and we understood the epidemiology of typhoid we're funding.
From the Bill and Linda Gates Foundation. We went into those populations and vaccinated 100,000 children.
And that allowed us to show the massive impact there is of a vaccine program.
And now today, programs are rolling out in multiple countries that the most impressive so far this year was Pakistan,
that in February vaccinated a million children per day for typhoid in the middle of a pandemic of COVID.
My goodness, that is impressive.
So by the time COVID came along, you had enormous amount of experience in running vaccine trials on a global, global scale.
So just thinking back to the very beginning of the pandemic,
what when did you first become aware that something pretty bad was in the offing and that you might get involved?
Well, in January, I mean, we knew that there was this virus in and we had in China.
Did you hear about that just in internal just from the media?
I think probably from the media. I mean, it was on never with BBC stories as early as the 11th of January that I remember very, very distinctly.
In fact, the on the 14th of January, the first case outside of China was documented.
The headline on the 11th of January was New Virus in China, but it doesn't spread between humans.
So, I mean, I think we were aware of it.
I didn't I'm not much less interested in viruses because I always consider them not terribly important in the world.
Bacteria is so much more interesting. They've got much bigger genomes and so there's much more to them.
And they're tougher than viruses. But.
So I think during January, I don't think anyone was very aware of just what's a risk to the world this was going to be.
Not least because knowing that it was a coronavirus,
there have been two previous coronavirus outbreaks over the last 20 years which didn't turn into a pandemic.
And fortunately, my colleagues here in Oxford were already thinking about, well, if there was an outbreak in China, maybe we could help them.
And so it started as an academic interest project, putting together the vaccine in February,
obviously things became very obvious that there was there was going to be a major problem.
And so as it became very clear that this was a pandemic, the various vaccine teams in Oxford got together to discuss how we could help.
And I think it's important to understand that usually in universities you work on your research programme,
another people might have other research programmes in the same area, and you might work together on some programmes,
but to do to respond in a pandemic you have to do something unusual,
which is bring all of the teams together that would normally work in their own silos to develop their products or to do their own research.
Have to find a different way of working where everyone says, Actually, this is not about me, this is about a much bigger effort.
And so what we did in structuring that was put people in charge at different bits of the operation.
And so my colleague Sara Gilbert was was on the design side.
And to get the manufacturing started optimising manufacturing was Sandy Douglas and test lab was about initial
design but then took over coordinating the laboratory infrastructure and I took over the clinical trials.
And the great thing was that I then had access to multiple teams across Oxford who do clinical trials of vaccines,
but they had all reported to me that some live for Test lam in the laboratory.
She took my laboratory staff and they reported to her that capacity and capability that there is in the system here meant that we can
really stand up something which has competed with Big Pharma in being able to develop a vaccine and get it licensed in less than a year.
And how easy is up to do, as you say? I mean, were people out of their comfort zones or did everybody just not do it?
And I think the definitely the starting point of how do you work together and who's my boss was it had some teething troubles,
but I think it was very rapidly apparent as time went on that the virus that
arrived in the UK and the urgency of focus really brought everyone together in,
I think in a very strong team to do that.
Now there's clearly lots of different ways of thinking and discussions that you have to have as you build a team to work on it.
But because people were working as a single unit rather than split by departments or research groups, it really did mean that we could,
I think, bring the necessary focus and that that got beyond any of the sort of the personal interests that you normally have in an academic.
You make it cool, you get your paper published.
This was much more about can we make a vaccine that can contribute to saving the world in the pandemic?
And I think we did that know that was you pre-empt the question I was going to ask that that's that's great and.
I think just I think it would be helpful at this stage just to talk me through the clinical trials.
How did you start? How did the scale of your ambition grow?
As as time went on and they put further questions to you as we go.
Well, I mean, it all, of course, starts before the trial.
The first thing that was was happening was getting the the initial designed vaccine through the the early
stage processes that allows it then to go into a manufacturing facility that makes things for humans.
I should say that I've already interviewed Kathe Green. Okay. And I'm hoping to interview Sarah.
Yes. Put me off for the time being, but I'm working. So you don't need to tell me all the things they did because you get that from them.
But there's an important bit of context, though, that was lost. That work of getting into the manufacturing facility was happening.
Yeah, the that gave us the sort of timelines of what we needed in order to get everything stood up to the trials.
Yeah. And so we had to work very closely together to understand that.
And there's the, once the manufacturing has started, as long as nothing goes wrong,
you have a fairly clear idea of when things should actually be in a vial.
And then when the released testing, which is the quality testing of the product, can be completed.
So the, you know, the date on which the first dose can be given and we had a few weeks of uncertainty when that exactly would be.
And there are also animal studies going on in the US which were interestingly
the regulators didn't require to have those data in order to start the trial.
But internally, in discussion with the university,
we'd agreed that we would wait for those data before actually giving the first dose on your vaccine,
on our vaccine,
so that there are lots of the vaccine made in the US because there's some very good collaborators who had the best animal models already set up.
And of course early in the pandemic, lots of people were setting up the other models to allow you to do the studies.
But you we were fortunate to have a partner who had it already worked with coronaviruses and was ready to go and got this set up very quickly.
And so as the the readouts came from the animal studies and then the final release testing arrived, which was the 22nd of April,
we were then able to have worked out roughly what that date was so that on the 23rd of April we were able to start the trials.
But by that time you would have had to recruit the people. So.
So the way that we did that was having knowing the timescales, we could go to the Ethics Committee and to the MHRA,
the UK regulator, and to get all of the protocols and our plans approved.
And of course the UK regulator doesn't usually approve a trial until they've got that release test and the quality.
And so we negotiated with them. I know very flexible about this.
They would approve everything apart from the final signature which came on the 22nd of April.
But we had that preliminary approval many weeks before that,
and the MHRA did their approval for the trial in one week, and suddenly they were normally after you.
Once you submit the documents, you should get a result in about 30 days,
assuming they accept everything from this questions and it takes longer than that with the Ethics Committee, they were able,
from the date of submission of our protocols and information for the trial participants,
they gave approval four days later and nobody got any corners cut with any of these processes.
They just they didn't have administrative time lines to say, well, we'll review to the next committee in three months time.
They just said, we'll set up a committee to meet as soon as you submit.
And that's exactly what they did. So I think both of those organisations met in March.
We actually had the provisional approvals to start the study so.
So that meant that by the end of March, beginning of April, we could start advertising and we were completely inundated.
We opened a website and I don't know what it was, 10,000 people responded within a matter of hours wanting to take part.
And so we knew that we would be able to get the trials moving.
And it just they needed the capacity in the in the team here in the office to to do some initial screening of people and start booking appointments.
And do you think people volunteered out of altruism or because they thought they would it's that best chance of getting protected against the virus.
When I think if you can think back to that time and although I have no experience of lockdown, apart from the fact when you come to work,
there's no one on the street, most people were locked down at home, desperately wanting to make some contribution and to help end it all.
And most of the people I've spoken to that at that moment, they were saying we just felt we needed to do something.
The scientist felt, I can't go to work and do my science, but I could contribute in some way to the science that's required.
And it was it was, I think, quite emotional in a way that people were so desperate to make some contribution.
And the altruism question is an interesting one, because I, I suspect that it largely was about we've got to help the world to improve.
Self-interest, I think, is may may have driven some people, but when they come through the door and we say to them,
we don't know if this vaccine is safe, we don't know if it'll work.
Can you take part in the trial? I think altruism goes out of the door that this sorry, the self-interest goes out of the door.
At that point, people really are there because they've decided that they can make a contribution.
Many of them turn around and leave at that. I mean, usually we screen people out on the phone in that moment.
But of course, some people when you go through things like detail, you tell them how many blood tests they're going to have.
That's just too scary for them and they don't want to take it. So that was the next thing I was going to ask.
Well, what did they have to commit themselves to?
So the people who took part in the studies really committed to to be with us for at least one year and
to have multiple blood samples taken over the course of that time to monitor their immune response.
Those who were in the initial trials had a much more intense sampling because that's required to demonstrate the safety of the product,
and the regulators needed to have as much information as possible in order to do that.
And for people who took part in the later phase trials, they had much less intense involvement.
Yeah. So it's it's a big burden certainly initially for people.
What's the difference to you what you're looking for in the phase one trials and then in the next?
Well, the Phase one trial is trying to essentially evaluate safety.
And so we we're measuring how people feel or any symptoms, any adverse events they sort they suffer from.
But we also take blood tests to see if the blood flow is altered in any way by being vaccinated.
Does it affect their kidneys or their liver or, you know, does it have any effect on their their ability to fight infections and so on?
So all of us documented we also measure their immune response to the vaccine in the later phase trials.
We did measure immune response to the vaccine, but we don't do all of the other detailed blood work.
But the main point of those is to find out, does the vaccine work? And so half the group get the new COVID vaccine.
The other half gets a controlled vaccine, which doesn't protect.
And we wait to see who gets COVID and hopefully those who've been vaccinated with the new vaccine and are protected.
And indeed, that's what we saw. But of course, at the time that was happening, we were we were all in lockdown.
So the virus was that the circulation of the virus was being prevented as far as possible by the non pharmaceutical interventions.
Did that make it more difficult for you to conduct a trial?
Well, one of the one of the aspects of the trials that that was for us was critical was our ability to adapt to the circumstances.
And so when we set out with the Phase one trial,
I was talking to the well-known modellers who were predicting what was going to happen in the pandemic.
And in March the predictions were terrifying, and we thought that with a single dose of the vaccine, we could have an impact.
And they felt with the numbers of cases coming through by then, but by late March, April would be enough that we'd actually get the answer.
Within the phase one trial of whether the vaccine worked and because of this sort
of terrible scenario of maybe 300 or 500,000 deaths very rapidly in the UK,
we felt that a single dose was the only option because two doses would take too long to actually save people's lives.
And so the initial plan was a single dose vaccine. What then happened with lockdown was that the cases evaporated and there were two results for that.
One was that realising that the non-pharmaceutical interventions would work better than anyone had predicted.
So to maximise immune responses, we'd go to two doses.
And the second thing was that in order to increase the chance of being able to capture infections and be able to get a result,
we needed much larger studies because of the non-pharmaceutical interventions and I remember thinking,
I have no idea what's going to happen with the next wave.
Will it appear in Sheffield and not in Oxford, and would it only appear in some other country and not here?
Will we have to wait six months? We can't afford to wait. We need to find a way of answering that.
So we immediately may fact to.
I did this a couple of days after the first dose went and realised that we were going to need to expand for the later phase trials.
Contacted colleagues all over the UK and asked them if they would take part in a much bigger phase three trial.
And every single person said yes. And they started working on setting up their their trial site to be able to do that.
Three weeks later, we started the trials with them.
So they did their own recruitment, did they. So so we had a centralised database.
Yes, but they used it, it was locally so they had I mean,
the ethics means that the data about the personalised data needs to stay with the local trial sites so it all runs through those sites.
So that was just a few days after the first dose had gone and we already knew we had to do that.
And over that week, I then contacted colleagues in Latin America,
in Africa and in Asia with the same message that know we need to collaborate is we
need much larger scale studies in order to move on to the next the next stage,
because we don't know where the virus is going to appear next.
And we then set up trial sites seven in South Africa and six in Brazil, as well as the 19 in the UK.
And we started work on Asian sites.
But in the end with the Partnership AstraZeneca, they contracted with service use of India, who then ran the Asian trials.
So at portfolio studies was UK, Brazil and South Africa a major challenge at that point,
having decided that's where we needed to go to get the scale needed to get the answer quickly,
but also to meet the next wave of the virus that was was funding.
And so the government had funded the UK trials,
but it was difficult at that moment to persuade anyone that they should fund a trial in Brazil or South Africa.
I said, Well, why? Why would we do that? We don't need that.
And I don't think we managed to make the argument that you need big, big studies and we should they should follow all of them.
And so in the end, the Bill Melinda Gates Foundation funded South Africa and the Lemon Foundation, a charity funded the trial in Brazil.
And so we then were able to coordinate those three trials, unfortunately run separately because of that and those different arrangements,
which made it much more complicated to then bring the data together for our regulatory submissions later on.
But I think we still managed that without too much difficulty, but much harder than it should have been.
Good. So, yes, you mentioned the AstraZeneca coming.
Was that something that you were personally involved in at all? So there were some initial discussions with several companies because it's absolutely
clear that whereas we know how to do vaccine design and development and clinical trials,
the things that we don't do is regulatory submissions and global manufacturing and distribution.
That's not what universities do. So we knew we needed a farmer partner and there was discussions with a number of these.
AstraZeneca in some ways was more unlikely because they although they did have a flu vaccine business, it wasn't the major part of what they do.
They're a big oncology pharmaceutical company, particularly.
And but they were, I think, very keen to get involved.
They also share the same vision of a not for profit development that the university had.
And so those those initial discussions, I think, showed that there was a joint thought process about how they should move forwards.
And then Central University that dealt with the negotiations over that and very much led
by senior figures in the medical sciences division and the Vice Chancellor herself.
And I'm. Yeah. You talked about MHRA and there was also the vaccine taskforce.
So all these national bodies, one of which you actually chair the Joint Committee on Vaccination Immunisation and.
Tell me about how you managed that role, but at the same time as running a mexican truck.
Yeah. So there's this several components to your question as they make sure they're the regulator, they're independent.
They're tough with us, as they should be.
But they were one of the most flexible regulators in the world in immediately getting this rolling review idea,
both for the trials and then later for regulatory submissions, which shortens the timescale of the review processes.
And I think to move swiftly,
they also were prepared to be very engaged to give advice during the trials in a much more open way than the normally happens,
obviously vigorously defending their independence from us,
but allowing me to share data with them to help advise on the next stages of the trial so they can make rapid decisions as they went along.
The vaccine taskforce, which was chaired by now Dame Kate Bingham, were absolutely critical both in working out where to put the government's money,
but but then also making the decisions about spending and moving things quickly forward.
And I think Kate has done the most astonishing job in doing that.
And I had regular meetings with her on usually on Sunday mornings to talk about the latest crisis or or
to share the latest results that she could use to inform government about how things were going and.
As far as GBI is concerned. I have charged GBI for many years now.
And very early on in the pandemic, we agreed with the Department of Health that I should recuse myself from chairing
the Komen committee because of my involvement in the vaccine development.
And so one of the other members, Wayne Limb, has been chairing the COVID 19 committee.
And I haven't taken any part in it. I haven't attended any of the meetings or been involved in any decisions there,
which in some ways for me has been frustrating because I'm so interested in what's going on.
But I've not taken part. But the main GBI meetings for all of the vaccines I continue to chair and those have continued.
But it's a slow pace during the pandemic, as has been so hard for the rest of the committee.
You've been meeting every week on the other on the other diseases.
So it's not unlike Georgia is not a regulated is it an advisory body?
Is that so? So GBI is a is a an independent scientific advisory body of the Department of Health.
And what we we do is we advise ministers on on vaccine policy for the U.K. So we don't we don't approve vaccines.
That's up to the MHRA, but we look at how they might be used optimally for the UK population and in the absence of a pandemic,
very much also whether it's cost effective for the NHS using Treasury rules to help make that determination.
So they would have been involved in decisions like how long the interval between vaccines should be.
Yeah, so? So jcvi decide on who should be vaccinated first.
And they quite rightly went for older adults and people with health conditions
first and then will decide on when pregnant should roll out in children and so on.
Yes. So all of those decisions are made by JCI and we jumped ahead a bit because we're talking about rollout now.
But what what were some of the moments that stand out in your mind from during the period when the trials were going on?
And. Well, probably the first jab was the first dose being given was was a major day.
And of course, the media ruled here. And it was it was a very busy day.
You got lots of filming of what was happening, talking to various media on camera and on a radio.
But I had a sense on that day that this is a huge palaver for what is the very beginning of the most enormous journey that we that we've set out on.
And but I didn't expect just three days later to be facing fake news.
The first Trump volunteer had died, which, of course, she hadn't.
And I got the got the information when I was out for a run early on the Sunday morning.
And as the person responsible for all the participants in the trial,
my thought was obviously for this individual and how she must be feeling her family,
who some of whom wouldn't even know whether it was true, her colleagues at work.
But then, of course, the impact it has on the other people in the trial.
And of course, competence in vaccines in general. And so there's two things I did.
One was talk to the university comms department to make sure that we got information out quickly.
And then also, I talked directly to the BBC and said, no,
you just met this this lady a couple of days ago and I need some help because this
the implications of not dealing with this quickly are just awful for the world.
And they immediately contacted the participant.
They tweeted an interview of her. He went on the BBC news website and it was immediately all around the world that it was fake news.
And I think that was, for me, the first moment where I realised that we were not in the place that we normally are with vaccine development,
because every time we looked out the window from then on, the whole world was watching.
And that's very different. I mean, I you know, I have to confess, I didn't know about your typhoid study, which is clearly had enormous global impact.
Well, the typhoid study has been in the news. You obviously don't read the news. Certainly.
I mean, that kind of. No, but it but interestingly, it's had more media attention than almost any other of the programs that run.
But on vaccines, it's had huge media attention. But because the Chinese studies that we were doing went to infecting people was big news.
And the the the work that we did in Nepal showed the vaccine was reported all over the world.
But it but it doesn't chime with the public because it has for most of us, typhoid is a traveller's problem.
You go to the travel for they can get your vaccine. Um, but here we're dealing with COVID, which matters for all of us.
And I think in, in some ways it makes me feel a bit frustrated.
The impact of vaccines are having every day in the world is greater than COVID vaccines, and yet we don't celebrate them at all.
Maybe that will change. Maybe. At the moment.
Yes. So we've been talking about that with other events during the trial that really stand out in your mind?
Yes. I mean, I think during the trials, the other big events that were very difficult to handle were around safety.
And what what happened there was that the right way of managing safety in trials is
that you have a system where whenever there is an event which you can't explain,
that if it's serious and you think it might be related to the vaccines, you can't disprove that.
You then have to go through quite a process of deciding whether it's safe to
give further doses whilst you're trying to work out whether this is a problem.
And so on two occasions during the trials, I took the decision to stop the trial in order to have independent review of an event which had happened.
And that's done by our Data Safety Monitoring Committee, who are independent, the Americans mostly.
But there's also representation from Latin America and Africa and the UK and the MHRA.
And in fact we also had an independent neurologist who was also reviewed information.
So there's a very well set up review process that gives me the confidence that it's all been looked at by people who are not vested in the trial,
and that allows me to then restart. And so we went through that process on two occasions in the clinical trials,
and on the second occasion it was someone who developed a neurological condition called transverse myelitis,
which I think the view is that it's not associated with the vaccine,
that even if it had been with a single case when it was looked at at that time, there's no way that you could have told whether it was or not.
But as it turns out, those cases are not the size of the vaccine. You know, that there's 2 billion doses been given.
We know it isn't. But at the time, we I couldn't say for certain that this wasn't a very unusual, rare side effect.
So it needed independent review as to the processes were followed as they are in every clinical trial I've ever been involved with.
But the media side immediately got hold of this trial, stopped a serious neurological event caused by the vaccine,
and the difficulty of managing that because, you know, again, it's having this global impact on confidence.
But the message should have been this is normal safety processes.
Isn't it wonderful that the trials are running in that way to very carefully evaluate each case?
And what was surprising to me now in retrospect, and I know this happens with other developers, zero media noise about any of them,
but I just can't understand why we got so much attention damaging to the vaccine because of these events happening.
And I think probably it was because we were so far ahead of everyone and there
was nothing else to talk about it apart from what was happening in our trials.
But in a way, to me, it just shows good trial governance and it haunts many people who suffered through
the the and the difficulties of that and the huge media attention it generated.
And so then but eventually your positive result emerged, although in a slightly nuanced way, it wasn't just one number.
Well, it's interesting that you say that, because for all of the vaccines that have been out, there isn't just one number.
And I think one of the maximum was something like seven or 11 with one of one of the vaccines.
But again, we had three numbers and I'd explain why.
But but that generated an enormous amount of media attention as it being a problem.
From from our perspective, we didn't want to hide anything.
Absolutely. We wanted to put the information out publicly that was there.
We discussed that with a data safety monitoring board.
And it was the right thing to do to to.
And, of course, it's important to understand that what happens is that you do this initial analysis focusing on the high level numbers and those,
and that that was on a Saturday, which would have been the 21st of November.
And those I didn't know the results.
They don't put together by an independent statistician who then goes through them with the Data Safety Monitoring Board.
So this is all online. I was sitting here in my office at the computer when I was then invited into that meeting.
You know, I felt like I was in the headmaster's office, about to hear the results.
I had no idea what it would show. And I think that this was in the evening, I know, 630 or something in the evening.
And they they then went through the results are some of the results of the first time.
I was the only person who saw those apart from the statistician,
and there was no discussion with the Data Safety Committee that they had ended the call.
And then I had the results the next step. And I phoned Sara Gilbert and told her the results.
And then we had to start a process of sending all of the data to AstraZeneca so it could be verified during day,
and then we could work through Sunday to establish how we would then start sharing that publicly,
because for them, those the markets meant that when they had new data, they had to go to the markets.
So we just had this these high level three numbers that we had not had time to dig
into the data and fully understand why they were like they were and what they meant.
But to show just one of them would have been it would have been a commercially the right thing to do
before an integrity point of view was it would not have been right because we knew we had three numbers,
but in fact were quite good. They're they're all good. They're good. And so the next day we took it.
We should make this clear. The number we're talking about is the percent effectiveness.
Yeah, it's the efficacy of the vaccine.
And in fact, it's more than three numbers because it was 100% protective against severe disease and hospitalisation.
And then we had within the study two different dose intervals.
We had the shorter interval, which had a lower efficacy, the longer dose until and it gave an overall number of around 70% efficacy.
One of the things that's also very difficult to to for people to understand is
that the efficacy as you measure it very much depends on what you call a case.
And in our trials, we were looking largely at very mild disease because we were hoping people every week.
And so we had a lot of cases that were extremely mild.
And so as we now know, the efficacy of vaccines against mild disease or asymptomatic infection is much lower than it is against severe disease.
So if you put your study in a way that you're measuring much more severe disease, you'll have a higher number than if you look at milder disease.
So the comparisons made with the other vaccines that we that people were understanding that in the absence of head to head study, you can't say that.
And then the fact that we couldn't fully explain why we had three numbers made it look like it was messy.
But actually it wasn't. It was the study. And it was just just presenting things as they on the Monday morning.
You know, I then had to do lots of interviews by the evening.
I was in Downing Street announcing the results with the Prime Minister.
And so that whirlwind of the huge amount of work to get the data ready to go to the statisticians the week before.
And I remember standing there at the podium in in Downing Street and thinking, I have no idea what I've just said.
I'm so tired. I'm exhausted. It was the most.
I mean, I remember every moment of it, but I just at that time, I was just in some ways, it was a blur.
It was just a blur. And how did you feel emotionally? I mean, did you did you feel triumphant or was it to with all this other stuff,
making it difficult for you to feel a sense of, yes, we've put this off?
I think there wasn't really much time for reflection because there was so much to do from the moment of getting the results.
There was thinking about Sarah, we need to get the data, upload it to AstraZeneca tomorrow.
We've got to start meeting with them with their statisticians and all the relevant parties
meet with government to show them the results so that they're not blindsided the next day.
It really wasn't time for a triumphant moment or a deflated moment or whatever.
And of course, the we were very aware that having some uncertainty be what the three numbers meant.
It looked like it was probably the dose interval, but we couldn't we hadn't had time to dig into the data to answer that.
And so we weren't in a position initially to say categorically, and that made us look like we didn't know what we were doing.
But of course, that really wasn't the case. And.
So, yes, I think there was a lot of time spent thinking about how best to manage all of these uncertainties.
And I don't know whether we got it right, but somehow, certainly from a UK perspective, there's been huge confidence in the vaccine.
And today when you know, when I look at the UK data, tens of thousands of lives have already been saved here already in November.
We're into the millions globally of lives saved, which is just astonishing.
We're in December now, actually. It's just an.
Yeah. So were you involved at all in the discussions about the rollout or was that the people's responsibility?
Um, so the yes and no.
I mean, the rollout really was something that the Department of Health and the NHS were putting together.
I did have some interactions with with scientists in government over this period,
but the details of how the rollout was going to work was really not in our hands.
I mean, the fact that we had a vaccine which could be used for average temperatures meant that it was much easier to roll it out,
particularly at that time, because the RNA vaccines didn't have the the data to show how they could be more widely distributed.
So that was really hubs that were dealing with those vaccines.
So there was some of those discussions, but really the details of the rollout was the NHS doing that and looking at it globally.
I mean, one of the things that I think people have been very proud of is that the university
agreement with AstraZeneca was that it should be provided on a not for profit,
not for profit basis to the two lower middle income countries.
Was that something you had any part in? So we had discussions about that.
And, you know, our views were sort of on that. And I think, yeah, I mean, all of the academics felt that was the right direction to go in.
You know, the vice chancellor was very strident on it about not profiteering in a pandemic.
And so I think it was it was the academic view.
It was the university's view.
And as I say, whenever there was discussion about it, but I don't think there was there needed to be much discussion, as everyone just agreed.
And so what proportion of the vaccines that have gone to the developing world?
Is it possible to say what proportion have been yesterday? Well, through COVAX, it's I believe today it's around 40%.
But but a bit critically, the vaccines that save lives are the ones that got out early.
And although supply was low for most of the first six months of this year,
over 90% of the doses were from from our programme because the other developers were focusing on high income markets.
And so I think it really this whole idea of not for profit means there's no commercial driver to to sell to, to a high income country.
The driver is to distribute the doses and to do the right thing, not to do things for commercial benefit.
And that to me was it was 24th of February.
The first dose went through COVAX. That was an incredibly exciting moment to see those planes landing in Africa.
So COVAX is so COVAX is a is a facility which has the funding to to purchase vaccines from the
developers and then connections into governments globally to to distribute them when they're ordered.
And who supports that? That's a collaboration.
Presumably it's governments who put money into that to to international governments to fund it.
And there's international organisations like GAVI, A.J., who and UNICEF, who are involved in all of those processes.
But of course, there's already a vaccine distribution system globally, normally anyway for vaccines.
And so it's tapped into the partners who work on both the the driving new vaccines into the into developing countries,
as well as the routine vaccines we all enjoy.
Mm hmm. And you talked a little bit about.
Oh, yes. The question I had, which I haven't seen, he answered in a straightforward way in the sort of general scheme of things.
Is it an expensive vaccine? I know how you put prices on these things is a bit of a mystery to most people.
But well, because it's not for profit, I it's around about $3 a dose.
I mean, that's that's not an expensive vaccine.
And if you it depends where you look at the perspective from, you know, some vaccines cost hundreds of dollars and to to buy in high income markets.
But usually for low income countries, there are systems in place to have a low price for that.
It doesn't need to be kept in a -80 degree fridge. Help to keep the price then.
Well, that isn't included in that price of the vaccine.
I mean, a big part of the the price of vaccines is, is the delivery, which is both the the storage facilities and they have the staff injected.
And but but the the not for profit relates to the costs of actually binding the materials and manufacturing it.
So. So you told me that it was it wasn't exactly a new experience for you to have to deal with the media, but the level of it was much higher.
Yeah, I do. I mean, I've I've done some media since since the mid-nineties,
and I felt like my first televised interview was with Fergus Walsh from the BBC in about 1996 or seven,
which a very odd experience because I was doing my Ph.D., I came into some Mary's hospital where the lab was I was working in,
and the CEO of the hospital grabbed me and said, Could you do a press conference?
What was on?
And they my supervisor had been up all night working on the intensive care unit and had gone home and he was supposed to do a press conference.
So they gave me the press release, which was about the genetics of meningitis.
And of course it was in my department.
So I knew roughly about I read the press release and then I went and did a press conference based on the press release,
and it was about 20 minutes of journalists napping and asking questions.
And then the last person to ask question was Fergus Walsh. And I answered his his question succinctly.
The first one, I was just thinking succinctly, and that was the one that was broadcast across all of the news outlets that evening.
And so I've been interviewed by him a number of times now, over over many years.
But that was the first experience.
So I'd say, well, you perhaps were displaced by the massive media scrutiny as some of your colleagues might have been.
No, I mean,
I've been surprised and sometimes shocked by the journalists and but also found many who genuinely do want to report the stories truthfully.
So, yes, I know a lot more about the game that that playing than I did before.
But I think you're right to say that it wasn't I wasn't totally fazed.
But I'm also somewhat wary about the intentions of some journalists, particularly some of the experiences in the U.S.
Yeah. Yeah. And then, of course, social media is another thing altogether, isn't it?
Yes. I mean, social media is complex because a lot of social media is really an echo chamber.
So if you've got a view about something, it's very easy to find that lots of other people agree with it.
And the I mean, certainly social media for me has had some downsides because I get targeted
by anti-vaccine people and I have some pretty horrible things said about me.
I also get lots of emails from people accusing me of genocide and appalling things like that.
But I think the most sinister bit from the social media side has been some evidence that we're aware of,
of state actors trying to deliberately amplify negative messages about our vaccine and of course,
other vaccines as well, which, of course, there's nothing we can do about it.
And as a group of academics, but it is all part of the additional burden that there is on us to communicate, to tell how serious the problem is.
Vaccine, misinformation, I think, is a terribly serious problem.
And it's the misinformation that is through this.
The more widely used social media platforms is clearly very problematic but should be regulated.
The misinformation from websites in other countries that that no one can control, there's nothing you can do about.
So the fake news about the person dying, that's a well known fake news website, but no one in the UK has any reach into that to, to stop it.
And the clearly the, the state actors, this is, is a sort of political issue which is again not for us to,
to deal with, but misinformation is a major, major problem.
And it gets amplified by, by social media.
One of the other problems that I've seen is communities who have their own interactions but may not interact much with the mainstream media.
And so I had dealings with a community who work in the hospital, and one of their members said to me, you know, you involved in the vaccine?
And I was talking to them about it.
And he had a list of multiple concerns that he had and it was his community and were communicating with each other using WhatsApp groups and so on,
and discussing the fact that vaccines were dangerous and they might affect their fertility and so on.
And there was no reference that he could get to the to the safe information about it as we talk through all of those issues earlier this year.
And there's sort of a couple of weeks later and he said, yes, 15 of us got vaccinated after I spoke to you.
And it just made me think that the problem is we can't reach into many of the communities.
We need to we need to get better at doing that because know that that's 15 people.
But there will be tens of thousands just in our country and who who are in those communities that they don't have access to the credible information.
So I'm hoping to interview some of the other people around Oxford who specifically look at this area.
So, yeah, the it's very interesting to hear that you've at least managed to have a positive impact on.
Well, I hope I've had some personal effects business. You can never be sure.
Yeah. I think one of the other things you've actually written about that in a sense the opinion articles rather than interviews is vaccine equity.
In terms of this question, do we go for boosters in this country or should we be getting doses overseas?
I mean, do you think your relatively high level of experience with the need to make you more confident that making those statements?
I felt I feel sort of a duty to to say these things,
particularly in the face of a of a system which is not really geared up to be thinking outwardly and maybe we've got worse.
And it's in the UK and it's absolutely clear when you look at the number of doses being produced in the first half of this year,
that there were enough doses to prevent almost all of the deaths in the world that have happened since.
And that is if we had focussed on older adults and people with health conditions everywhere as we did in the UK,
if we, if we could have done that first, most of the deaths would have been prevented.
The problem for domestic politicians is the most of the deaths because there would still have
been deaths in young people and those who weren't in those initial programmes in the UK.
And for our elected politicians we expect them to protect us.
And so there is this dilemma between what's right to do.
From a global equity point of view and the drive of domestic politicians.
And I think the problem is that until domestic politicians feel confident that that the things are okay for them,
that they've done all that they could have done, it's very difficult for them to take those global decisions to protect the rest of the world.
And I do think the news I was speaking just over a week after the new Micron variant was named,
do you think is going to make things worse because of the scale of the booster programme?
Yes and no.
I mean, I think that there's no doubt that boosters are going to be scaled up everywhere that can afford them and that will reduce the global supply.
However, we are at a moment where there is quite a lot of global supply and doses that could be widely distributed.
So I think it's an uncertain moment in time.
The the lifting of the blockade in India of distributing vaccines from India, which has the biggest centres for producing, including our vaccine,
really means that there is a moment where if countries have the capacity to receive and distribute the doses,
that things could change very rapidly over the next few months. But the only way that can happen is if the systems now start working for distribution.
But as far as boosters are concerned, they are a risk, but they're not as much of a risk as they were a few months ago,
simply because there's a lot more supply in the world that might. But they say the devil's in the detail of what happens next.
Yes. Yes. Which we don't know. Yes. Well, yes. You know, now we are in another very uncertain and sad moment,
uncertain about how countries will react, but not so uncertain about what we're seeing happening.
I mean, as you would still expect with all the remains to be proven, but you still expect the vaccine to prevent severe disease caused by it.
And probably from the data we're seeing in South Africa, it will spread readily.
But of course the centre of the population is a bit different from ours. They've had almost no vaccination and waves of following.
We've had of beta that delta. We're in a highly vaccinated population that has had alpha and delta.
So how does that play into it? We just don't know.
So the world is conducting a massive experiment all the time. Know.
But. But the knee jerk reactions are likely to be to be small because it probably that is a good idea.
But we have to that's ahead of the evidence to say that that's necessary.
So that the last few questions are more about your personal question.
Is that your personal response to things that went long but that how did the first lockdown impact on what you were able to do?
Did it change the way you work and where, in fact, any of those changes positive after the first lockdown?
And I mean, it didn't really change the the way that you conduct trials and to you know,
now we were all in work everyday doing the same jobs that we always do.
So it's it was a it's a strange thing that people, you know, giving accolades to us for having done something extraordinary.
We've actually done something pretty ordinary at an extraordinary moment.
And so from that perspective, you must have had provision for how you were able to work together and if you were coming into the into the building.
Yes. So so we had to put in place social distancing and so on to trial.
And we didn't have any outbreaks in the team over the last two years. And because of the attention to detail,
I asked one of the team to be responsible for infection control and to make sure we were keeping up with the latest guidance.
We actually had clinical social distancing and mask wearing and protocols before the NHS did.
Were you able to get as much PPE is you needed? So we we had a problem with PPE.
Interestingly, we managed to get a large donation from China very early on, which helped.
But we had we did have some crunch points. And there was one day where Sara Gilbert and I were on a call with Matt Hancock and asked
him if he could provide help us get PPE because we needed to run a clinic that week.
And he picked up the phone to talk to the head of the Trust Hospital here at Oxford.
And we had PPE delivered the next morning from them to support the vaccine effort.
Well, the power.
And to what extent did did I mean, did you ever feel personally threatened by the infection itself?
By the infection? By the infection? I have looked at the data.
I'm fit. I'm just over the age of people worried about being in my mid-fifties.
And so my overall personal risk is relatively low and being being a healthy individual.
So I didn't personally feel very threatened. But I think I was take life as it comes.
So if I got sick, I would have to deal with that.
But, you know, we were all taking great care and precautions to to make sure we were protected from the virus.
But, you know, we just have to deal with whatever it is anybody tries to infect it all.
Well, there are there are people in the team who've been infected, you know, home from their kids or from their families.
So there's lots of people around that I know who have been infected, but we haven't had any of that spread within the team here.
Right. Mm hmm. And yet when I got a question about working out, as you said, you just kept on coming to work as normal, but it doesn't.
You did that. But you also mentioned that you were completely exhausted by the type of results.
Yeah. I mean, I think the thing that's different was I was I've always worked a lot, but it really didn't.
I made it very hard in the evenings to even get away from here, to go home.
And particularly with the international nature of the work.
There's definitely some time zone issues which meant that a lot of the communication was happening in during other hours of the day.
So it was it was much longer hours.
And I think everyone I say that all the senior people in the team worked seven days a week and many of the more junior people as well, um,
over the course of the two years and it that really hasn't stopped today that I was in a meeting
for an hour this morning and I had 100 emails that came in whilst I was in the meeting.
I just, it just shows the amount of activity that still lives and you seem remarkably well on it.
What is there that you're able to do to keep your your general state of wellbeing?
I think I think a lot of it is is where you where you sit mentally and it all it's,
um, I, I think to a large extent most of what I do I'm in control of.
And so I think if you from a resilience point of view where you feel in control, then it's quite easy.
The problem for most of us is when we're not in control. And so I think the stressful points were when external things were happening,
the the unpleasant things being said about the vaccine or about us, I think those things are much more stressful and troubling.
But the things you can control,
which and I tried to run high quality studies and to look after the team and that's I think that's fairly straightforward.
But you mentioned running earlier and I noticed from something I've read that when I was being a mountain climber.
Yes. Well, I mean, I cycle every day to work and I run on the weekend.
So that but that's about the only stuff that I do, I suppose.
I've watched a number of late night Netflix series,
usually between about 11 to midnight to try and get my head out of the the thinking about vaccines to help sleep.
But apart from that, there's not really been space for anything.
And and as far as the team as a whole is concerned, have you felt the need to institute any kind of support provision for the wellbeing of people?
Well, I think there's several aspects that one is trying to make sure we recognise the team and we've had a number of opportunities to do that.
And over the course, particularly of this last year, good communication.
So particularly during the most troubling moments to communicate with the whole team about what's going on and to to thank them and congratulate them.
We've also been able to help here with in my team in the Department of Paediatrics
with rewarding them for the work that they've done and by giving some extra time off,
things like that which to try and to support people, recognise them.
And we've, we've also done the best we could to make sure people get holidays and get breaks that I that's not true for all of us,
but it's been quite an important part of it. Of course the difficulty with that is that for everyone holidays have been very, very difficult.
So it's very hard to give people a proper break. And in the middle of a pandemic, I can't fix that.
But we've sent people away from wherever we could.
And yet in terms of talking rewarding people, you were knighted in the in the Queen's Birthday honours.
Yeah, I was. Was that a surprise or did you know it was coming?
Well, you always know it's coming because they you get a letter from the asking whether you accept it.
And but but in a way, the way that that is written, you don't have absolute certainty until the the the award appears in the London Gazette,
because the letter says, you know, if you accept the nomination, we'll ask the queen if she agrees.
And so until it appears that there's no communication at all about it.
But but I will say I'm delighted, but actually delighted for the team because it really,
you know, I'm just one of the cogs in this enormous operation.
And if you take any of the cooks out of the whole thing falls apart.
And so there are many other people who are just as deserving as me.
But so I sort of see this as something that I receive on behalf of a of a larger group.
Just two more questions. How has this work raised new questions that you're interested in exploring in the future?
Well, I think it raises a lot of questions. And coming back to where we started about understanding the immune response,
there's so much that we've started to scratch the surface of with COVID vaccines,
about dose intervals, about whether high doses or low doses are better.
And the studies now being started, which we're involved in, in different countries, looking at could you boost with much lower doses?
So all of all of these questions need addressing.
To me, it also raises the profile of being better prepared for pandemics.
What what do we need to do? So that when it's a virus that we've never heard of before, that we can react as rapidly as we did with Kobe.
Kobe, it was easy. It's a virus that we knew a lot about.
We knew that you had to use spike protein to make the vaccines.
We knew which platforms were likely to work, like the RNAs and the viral vectors, and we were fortunate that it only had a 1% mortality.
What would we do if it was a virus we'd never heard of before from an animal species?
We didn't know which part of it to make the vaccine from, and it killed 50% of the people it infected.
We need to be much more on the ball for that scenario than we are.
And I think to me, that's a critical part of the next steps.
Mm hmm. So has the experience of COVID changed your attitude to your approach to your work?
And how would you like things to change in the future? You've covered that.
I haven't had any time to reflect on on whether my attitudes have changed at all.
I mean, at the moment, we've just got too much to do in the in the day job to think much about the future.
I think it's I've always known the importance of what we do and seeing the impact, the work, what we have on people's lives and particularly children.
Because that's my main focus as a paediatrician. And every day the work that we've done here is saving lives and even before COVID.
So in many ways, that's, that's what I want us to continue to do, is to have an impact.
And that's the great thing about vaccines. They work. Thank you very much.