So can you start by saying your name and what your position is?
My name is Catherine Green, but everybody calls me Kath and I am head of the Clinical Biomanufacturing facility at the University of Oxford.
And you've got another hat as well from you.
I also am an associate professor in the Wellcome Centre for Human Genetics and I'm a senior research fellow at Exeter College, Oxford.
We always have multiple hats set up, so tell me a little bit about yourself.
Obviously we don't have time for your entire life history,
but if you start from your earliest interest in science, how did you get to be where you are now?
Yeah, that's a good question. And I don't know if I know the answer because I think I always just was interested in science as a child.
And so to go and do science at university was an obvious thing for me.
I don't think I knew it was a job at that point. It was just something that I thought was interesting.
So I did Natural Sciences at Cambridge and then a PhD in London and then a post-doc in Paris.
And throughout all that time, I was interested in human genetics and how human genomes change over the course of your lifetime.
So where cancers come from effectively.
I continued that when I came back to the UK and the University of Sussex and my very first group leader position back in Cambridge,
funded by Cancer Research UK. So Student Cancer Research.
When I moved to Oxford in 2012, I was still doing cancer research, thinking about what chromosomes are like and how chromosomes change.
And in doing that, I grow a lot of human cells in culture, manipulate human cells,
and do the kind of lab techniques that you actually need to do to be able to grow vaccines.
I also did quite a lot of science management, managing other people's teams and running some aspects of my team as a business inside the university.
So when the clinical Biomanufacturing facility needed a new head,
the head of department asked if I would step in for a bit just to guide it through six months
while they looked for somebody else to just tell me about the clinical BIOMANUFACTURING facility,
what it was. So it's a fairly unique part of the University of Oxford.
Not all universities have one. It's a GMP manufacturing facility and GMP stands for good manufacturing practise.
So that is the set of rules that you have to follow if you want to make a medicine that can be used in a person.
So really strict set of regulations and requirements set by law in the UK coming from European legislation.
So any medicine that you use, whether that's a paracetamol that you buy in Tescos or a cancer drug that you're given as an
experimental medicine treatment has to be manufactured under these really strict regulations.
So pharmaceutical companies, drug manufacturing companies follow these rules.
And we in our little facility,
there were 25 of us in the team also follow these rules in a little building that you won't have ever noticed around the back of the church,
your hospital site. And so we as a university are able to make batches of medicines to use in clinical trials in people for the first time.
So that's great. As a university, the idea is that we can take innovations that are created in the university research labs,
transition them into a product that can be then tested in people for the first time to show that they work, and then that can then go on.
And seed innovation in health care. We mostly have been making vaccines over the last the team over the last 20 years.
And I'm sorry, did you give me a date for when you started?
So I started there in 2018, initially as an interim six month cover just to help out, but discovered that I loved it.
I love the people. I like the mission that will translational the idea of taking ideas that come from the university
and converting them into something real and a real treatment that's really meaningful.
But still, in a scientific background, it's still an experiment. It's an experiment that is in people, but it's still an experiment.
We don't know what the outcome is going to be at the beginning of starting a clinical trial.
So after the six months I went to the head of department, say, can I stay a bit longer?
And we were doing okay. So I said Yes, and I've been there ever since.
I do it only half time I run my research team in the welcome centre half time and I run the clinical Biomanufacturing facility half time.
And you're your research team. Are they still working on cancer? Yeah.
Cancer genetics, chromosome instability and mechanisms by which your genome changes during your lifetime.
So let's just. Switched off talking about it.
Oh, that's all I talk about. I know. I'm afraid. Can you remember where you were when you first heard about it?
So I thought about this a lot because Sarah had heard about it very early, because she is an infectious disease.
This is Sarah. Sarah Gilbert. Sarah Gilbert realised very early that this was an outbreak in Wuhan province
in China because it's part of her job to pay attention to outbreak pathogens.
But I don't do that for a living. My job is to manufacture things at a much later stage normally of the development pipeline.
So I would have heard about it at the same time as most of the population of UK did, which would have been on a TV news broadcast.
But I don't think they happened till the third, the fourth, the 5th of January as we were coming back and it didn't seem very serious at the time.
It was a novel pneumonia outbreak in China.
It made a few bulletins and then every day the bulletins got more serious, didn't they?
And the first meeting I had with Sarah about it was, I think the 22nd of January,
when she called me to her office and said, Cath, I've got I've designed the vaccine, we're going to start making it.
There's a possibility your team will need to be involved soon.
What are your feelings about that? And I had worked with Sarah before.
Yes. So as I said, one of the things that we do is kind of science as a business.
So manufacturing medicines to this extremely stringent regulation that you need to be allowed to put them in people is an expensive thing to do.
I need to buy very high quality ingredients.
We need to monitor everything that we're doing.
There's a lot of paperwork, there's a lot of checking, there's a lot of additional people needed, and we have to do it in a sterile environment.
So I need a specialised facility with a plant. And so the way that that works within the university is I eventually have customers.
So they the academic scientists that have the ideas for the new medicines, all my customers, they get funding from ground funders.
So that might be the Wellcome Trust, that might be Cancer Research UK,
that might be the government via the UK Research and Innovation Network, and they will then contract me to manufacture something for them.
So my team, prior to I started in 2018 and since, have made many vaccines in the past for Sarah.
And the probably the one of most interest to the Kovac project is that we had previously manufactured for, say,
a vaccine against Middle East Respiratory Syndrome MOAS, which is another coronaviruses in the same family.
And that was the basis by which they could move very quickly how to make a vaccine against a new coronavirus,
because she already had manufactured and tested a vaccine against a previously existing one.
So how did you react when she came to you?
And yeah, so when she came to me, my first question is because I run a business, I'm doing science as a business.
So my first question was, yeah, fine. Of course we could help you with a new manufacturing project.
Who's paying for me? Where's the money coming from? And obviously, at this stage, there was no money.
There was no government task force, there was nothing set up. And we did that on the 22nd of January.
Now, how serious it was going to be. So I would say, to be honest, my first response is, yeah, we could assist you,
but I don't know if we're going to because I have funded projects, I have things that I'm making.
We were in the middle of making an Ebola vaccine. It was fine to do. It was rolling.
Commitments were made to that project. So I think we sat down and she said, Could you do it?
And I said, Yeah, well, what we do is we'll draw your plan will draw a plan, how fast could we go?
But on a theoretical basis,
I did not immediately commit to a manufacturing slot because that didn't feel like the right business decision at that time.
And then we kept on talking and every day the situation deteriorated and every day it got to be a
bit more easy to make the decision to stop making the vaccine and start on a coronavirus vaccine.
But it was something that grew. It transitioned over time to that decision.
And so once you got to making that decision, what did you then have to do?
How did you get started? So it's it's something that we know how to do.
So this is one of the ways. So Sarah had worked with coronaviruses before and making vaccines against outbreak
pathogens is what she knows how to do and manufacture manufacturing them.
We know how to do it. We've done it. My team, I mean, not me. My team are fantastic at making these adenovirus vector vaccines.
So Sarah has to give us a piece of DNA.
It's a piece of data which is synthetic in that it's been ordered by Sarah and Theresa LAMB.
They've designed it and they've set. For synthesis, and then that gets shipped to servers, research labs and what's happening today.
And I got in it. So it's got the coding sequence for the spike for the Corona virus, for the spike protein, the now famous spike protein.
And the reason that they chose the spike protein to use is because it's on the surface
of the SARS-CoV-2 virus and also because that was what they had used for years.
So they knew that was likely to be the thing that made a good vaccine. But not no virus vaccine is it's stuck onto the app.
So no. So this is an adenovirus vector vaccine because our delivery package isn't adding a virus, but it doesn't have the spike on that adenovirus.
It has the code for Spike inside it. So it's just the FedEx package, the adenovirus and inside are the instructions.
So the adenovirus vaccine works that it attaches itself to one of your cells.
When we inject the vaccine into you and it inserts the instructions to make spike into your cell,
your cell then makes Spike and puts it on its surface and the immune system
detects that as something new and unusual and unwanted and springs into action.
Protecting you against future recognition.
Not protecting you against future resolution. That's not right. So I've got to get to that again, because that's all right.
So they protecting you against future infection because.
Yes, because they've seen it before. We have already seen it before. So your immune system is mobilised to be able to detect it.
So the adenovirus is just a delivery system? Yes.
In the same way as the Pfizer biontech ammo in a lipid particle is the delivery system to get the code in.
So once the code is into the cells, they work in the same way.
Those two delivery systems. Yes. So we know how to make that delivery system.
We do it all the time. We've done it for Mars. We've done it for plague, for babies.
You've done it for Zika, malaria, influenza, TB.
So that's good. That's a platform. We can do this. We've done it before.
So we just have to get the DNA from Sam's team that codes for the entire genome of the adenovirus, including the code for the spike.
And then we have to put it into our controlled laboratory conditions and turn it into vaccine.
And you do that by allowing the virus to copy itself inside special human cells that are modified to enable the ads.
And they've allowed us to copy itself because they have the virus is designed such that it can't copy itself in the sense of you or I,
when it's used as a vaccine, it can only help yourself in the laboratory environment in these specialised modified human cells.
So you say that it gives you a piece of DNA? Yes.
I mean, that must be one piece of DNA.
But anyway, you start with something very small and then you have to scale it up until you've got enough used in the trials.
So she gives me a few nanograms of DNA, which should be billions and billions and billions of molecules of DNA, all of the same sequence.
And the sequence is 40,000 or so letters, long double stranded,
but it is just a chemical string of DNA letters, and we have to get that into cells for the first time,
because when you put that code into a human cell,
it can it contains the instructions for a virus particle to self-assemble, because that's how viruses work.
And that code encodes all the instructions to make a virus particle as particle self-assemble.
So the first thing you have to do is get it inside cells. So that's a process called Transfection.
It's a routine process in research laboratories. And we do exactly the same process as you would do in a research laboratory,
but just with a lot more care and with a lot more expensive reagents and with a lot more paperwork.
And then those first cells into which the code is put, stop making virus particles,
and then that pops those cells and the virus particles are released so we can collect them.
And then we've got a few tens of thousands of virus particles from that first infected cell,
and we can collect those and put them onto more cells to infect,
and each one of those will receive some virus and then replicate copy some more virus.
So that's made more vaccine and then we can put it in a single cell where people are listening.
This virus is the adenovirus. It's not the COVID virus. Yes.
It's the handlebars with a little bit of. That's right. So the vaccine is the adeno virus.
And we don't need ever to see the real SARS-CoV-2 virus for us to be able to make a vaccine against it.
We don't need to receive a swab from an infected person.
We don't need to be able to grow that dangerous pathogen in our research labs.
We just need an email from a clinician scientist who has had a patient with the disease who can
swab the nasal passage secrets of the genome and send us literally a text file that contains.
So he's nice. Jason TS So that's really good because it means that we don't need to work in a regulated environment to handle dangerous pathogens.
We don't need to learn a lot about the pathogen to be able to grow it, to make it into a vaccine.
We can just take the code and put that into the adenovirus so it makes the the design process and the manufacturing process very, very much easier.
And the same is true for the other type of vaccine that obviously is in the news a lot, the RNA vaccines.
They also can just take the code. They don't need the actual pathogen.
So you started with a few nanograms? Yeah. How much did you need to get going?
Yes. So we need a few nanograms to do that first transaction.
You've got to and then we we amplify the culture.
So we start in a very tiny culture which would be about the size.
So at first the cells grow in in layers like patio light your patio lights all side by side next to each other in a monolayer.
And the first piece of DNA will go into one cell. And when that bursts, it releases virus particles to infect the cells around it.
And that's in a a vessel that's about the size of the end of a pencil already, really small vessel.
And from there we then go into a larger vessel, eventually to a rest of the size of a postcard,
eventually to a vessel that's the size of ten postcards stacked on top of each other, like a book.
And at that point, we've. Not enough to start to do some real testing on it, to make sure it's correct, to make sure it's sterile,
and to start to get some idea of what the yield and the productivity will be.
So that's to produce the thing that we call the starting material and that we use an
analogy that is like the it's like the mother of a widow's daughter or something.
So from that, all the rest of the vaccine will be born. And so we made that in the lab round the corner from here by the end of March.
So that was was that false? Yeah.
I mean, we worked very hard because by the time the DNA came to us about the middle of February, it was clear this is no longer a research exercise.
This is no longer. Hey, let's just prove for fun how fast we could make a vaccine against a new disease that by the end of January,
confirmed cases in France, by early February,
confirmed cases in the UK, all over Southeast Asia, cases and death rates start information start to come out about how serious this might be.
So by the time the data came to us beginning middle of February, we had already started to tell the owner of the about approach,
it looks like we're going to have to stop Ebola before we get to the end. We froze it all.
We didn't waste that project and we reinvigorated it later in the year. So we do also have the Ebola vaccine that was scheduled.
Didn't go to waste, but it just got delayed a lot because COVID took priority.
So yeah,
so the starting material that initial about Coca-Cola cans was a full that will go on to be the feedstock for the entire global vaccine supply.
And that's crazy. That's 2 billion doses now all came from that Coke comes with that we had in my team in March.
And then we do a lot of tests on that sort of material to make sure it's absolutely perfectly good.
And that's then what we use to seed the GMP manufacturing,
the manufacture of the stuff that's going to be the first batches used in trials and also the stuff that we will use to make larger packs using other,
you know, the manufacturing sites. And eventually that we then shipped AstraZeneca to make the global supply.
Right. I've written Private Jet.
There is a story about a private jet. So what? Yes.
One of the people we ship the material to. So we normally make my team would make normally up to a thousand doses because we're
talking about making medicines that are going to be tested in people for the first time.
And so those are phase one. They're called clinical trials that just to normally assess that there's no extreme adverse reactions to those in people.
So that normally done in healthy volunteer individuals, participants that come in at closely monitored.
And we do a few people and then maybe a few more and then maybe a female.
But you'd be looking at a maximum of, say, 100 people in a phase one clinical trial normally.
So if we make a thousand doses, that's plenty to get us across that stage.
But already, by the time we were considering doing the manufacture for the COVID vaccine.
Andy Pollard and the clinical trials team were starting to think big because this is March and you know,
lockdowns, the 23rd, this can really see it spun out.
So as we're just starting to ramp up our initial very small scale manufacturing and they're what we're going to need to trial with 20,000 people,
we're going to need to trial with 30,000 people. And we know we can't make enough vaccine here in Oxford, in my tiny facility to do that.
So we had arrangement set up with another manufacturing site in Italy called Adjuvant,
and they've made adenovirus vector vaccines before for us and for other people, and they can just do it on a slightly larger scale.
You pay them a lot of money and they make you a product. So so I wanted to set that up right at the beginning that they would be able to do that.
Manufacturing in parallel to us maximise the amount we could get.
We could probably go slightly faster, but they could get more maybe with a three week delay.
So I perfect would use all that up and then we can use this. But it turns out obviously Europe, it was shut down.
Yeah. So we started our trial the 23rd of April using doses that we had manufactured.
And by I mean by the end of April, Andy Pollard's team, who were remarkable throughout the clinical trials team,
had, you know, they recruited so many people to the trials so fast that the doses were going to be all gone.
So we needed to get doses in from the advent batch, which is just about ready.
But there's no flights and no commercial flights available from Italy to London because everything was shut.
We were trying to figure out how to get it. Can FedEx drive trucks for the border to shut?
Can we drive a truck and then change trucks and then change it?
We're trying to figure out.
And one of the joys of this whole project was working with a team that really came together and a lot of diversity in the team,
people from different backgrounds with different ideas. And we were just stuck having to get this vaccine from Italy.
It's not possible because it has to be temperature controlled, has to be mapped.
It has to be under, you know, because it's a medicine.
One of our team said, you do know you could charter a plane and obviously we didn't know you could talk to a flight.
I mean, even theoretically, we knew you could charge to apply.
But we are you can actually do that, can you?
And it turns out you can if you have funding behind you, you can call some company at the airport to have small private jets with pilots in.
And you can say, will you please fly me a package from Rome to London tomorrow?
And yeah, there's a five figure fee attached to that.
But when you're testing a vaccine that might be of global importance, you can find private cafés.
You can't usually spend that kind of money on transport in a clinical trial.
But under these circumstances, you can you can find the money and you can justify spending it.
Mm hmm. Yeah. Yeah. So having.
What's once you got that far? You've done your bit.
Could you sit back? Yeah, well. To some extent, yes. So it is true that we were in some ways lucky.
So we were involved so intensely from end of January to the end of June, getting that batch,
that first clinical trial batch done, and then liaising with Advent and getting the the vials,
the logistics of getting the files labelled because that's the manufacturing stepped has also quite tightly regulated shipped across so 18
sites in the UK how we would need all of it so our process is extremely manual and it's all done on frozen vials at minus ISO on dry ice.
So that's just a lot of logistics and complexity of dealing with that.
But then after the kind of phase two was started, the advent material was finished with and the material was gone.
I mean, it was gone really rapidly. So yeah, I mean, our team didn't then have much more involvement.
Our job was to get that first stuff done as quickly as possible without sacrificing any quality, because you also need to just be as fast as possible.
The faster you can immunise your first volunteer, the faster you have the data that is telling you whether they're making antibodies,
whether they're making T cells, and eventually whether that vaccine is effective.
So we were the first line, the Rapid Response Unit,
and other people then came behind us doing the rest of the project, which is scale up, can you make a lot of it?
And then when AstraZeneca came on board, really a lot of it and how do you make it globally?
But that's not that's not our job.
So we then have to go back to doing the other things that we do, which is the Ebola vaccine and now Nipah virus and other emerging threats.
And that's yeah. How do you spell NEPA and IPH?
So one of the ones that so I I'm not an infectious disease expert but I have friends
who are and they tell me that Nipah is the one that we should be most worried about.
We do not want a Delta variant of Nipah, something which can spread rapidly in human populations because it's a devastating lethal virus.
So so on our watch list and we're currently making we've Sara Gilbert a vaccine against it so hopefully we'll
have a stockpile soon to give us some reassurance that pandemic preparedness is is going forward for that.
So how is all this for you personally is weird is it because there was a bit of a blur so it's hard to kind of
sometimes think you look back at your notes or you look back your diary or you look back on your whatsapps and say,
know, what was I? Because people ask me. I was just working.
I was working all the time. My daughter was at Key or school.
How old is she? She was nine, ten now.
So Kate ASCO, obviously a child at the beginning and then the school figured out how to arrange key workers go.
And that was quite a stressful thing to decide to go into because although I needed to go to work,
of course what you are doing because we didn't really have any public health, nobody really knew anything.
So the school was open for Keyworkers. First of all, we had to figure out whether we would qualify as key workers because we're academic scientists.
So we had to get put on the list because there was less doctors and nurses, but not scientists.
But soon, scientists working on COVID projects were added to the list.
And but obviously what you are doing is so so I'm sending Ellie into school, into a group of people whose parents are key workers.
So we were likely to be nurses and doctors. And so what you're doing is actually sending your child into a relatively high risk situation.
If there's going to be any COVID anywhere, it's likely to be in health care workers at the beginning of a pandemic.
And obviously, she has to come home with me every night. So by putting her in key workers.
So I definitely was increasing my risk of catching it and increasing my staff of taking into the team,
which would have been the worst thing to do, because we were the only people in the world that knew how to make a COVID vaccine at that point.
So it was a hard decision to make that. But as many of us at those early stages of the pandemic, there weren't many choices available to us.
I don't have my mum and dad locally, and even if I did,
I couldn't possibly have asked elderly parents to look after a child who was going into Keyworkers, so it was hard.
So there's a lot of juggling to do that. I'm separate from my husband at the time, ex-husband now, so he was doing half the day, so that was good.
So in half the days I had, we have freedom to work. But then I'm very glad that I had Ellie because she was the only person I could see,
because as a single person living alone, I didn't have anybody in my household.
So she was my only like non-work human contact.
And at work we were masked and distant because we knew we couldn't afford if one of us got COVID to spread it.
So we were rigorous about social distancing and masking from the very beginning.
And so it was a weird time because I was completely isolated from social contacts and working really hard with no outlet, but.
Then the other. So that should be really awful and stressful.
But we had a mission and it's surprising, I think, how far that dry, you know, having a good thing to do can get you through some really tough times.
So some of my friends who worked in hospitality had very tough time because they had nothing to do.
And so we were really busy. So that helps you, I think, get through some difficult times having a mission.
Mm hmm. And did you find that amongst all your colleagues?
I mean, did you have to set up any kind of systems to take care of the well-being of the group?
It was so hard because we were all trying to keep away from each other so as to minimise risk of transmission.
But obviously, in the University of Iowa, you know, people are very well paid.
People lived in shared people live in shared houses. A lot of my staff are very junior.
Some people have caring responsibilities, elderly parents at risk people.
And so some people were very nervous about coming to work. Some people would travel long distances on public transport.
And yet balancing the needs of everybody while trying to deliver the project of your life in a time scale that has never been done before.
Yeah, it was really challenging and some people really struggled and we lost.
So some team members left the team after COVID. And I think it was it was sometimes too much of an ask.
It was it was a big challenge.
I have a very strong friendship group in Oxford.
And so some, you know, I could call people and teams people and they would leave me little presence, you know,
if they knew I was feeling down my best, my Sally or Stephanie would, but just put a bunch of daffodils in my porch or a bottle of wine.
Yeah. And a lot of people, if you don't have that, when times get tough and you're alone, I think it can be very challenging.
And it's something we need to think of, you know, because if there's going to be another pandemic, nobody had thought about any of that before.
What? Die. How do we keep social structures intact? It's hard.
I don't have solutions to it, but I don't think it went always very well.
And certainly different people struggled more than others. Did you actually have any infections in the team?
We had I think so.
We had a few people that obviously there wasn't very much testing at the beginning.
So we if people had was symptomatic, they just look colds and cough, persistent cough.
So we had people that were off, but I think we had a couple of cases, but no confirmed transmission events at work.
So people then self-isolated and stayed off and we didn't then have them having passed it on at work, which is all you can ask.
Effectively, that means what we're doing at work is going okay.
And when we lost downtime for people,
often because they had to self-isolate because household members had tested positive, then the whole house had to isolate.
And that's difficult when you've got a small team with really specialist expertise.
Losing one team member sometimes was really problematic for us.
Mm hm. So did you yourself ever feel personally threatened by the possibility of catching it?
I, I think I'm young enough. I'm 46.
I think I'm young enough that I always thought if I caught it, I'd be fine.
But my parents are in the mid to late seventies and so I did experience through them that we all fear.
But I think it's it's not wrong to say do I know what you think is also they were they were frightened because it is an extremely I mean,
I know that the case fatality rate is 0.1%, but that's a lot and more than 5 million people now have died globally.
And so the fear is, is a justified fear, particularly at the beginning when we knew very little about transmission routes.
And so taking precautions really did impact on your life.
And so you felt fearful. You didn't know if you needed to wash your groceries, you didn't know.
And there wasn't good information out there because nobody knew. So it's reasonable to take extreme precautions, I think.
And so I think myself, I wasn't concerned because I feel myself to be robust.
But I would say that I have experienced that the people that I love and it is a real true thing, and rightly, rightly so.
It was a fearful time. What did you do to stay sane when you weren't working?
So, I mean, for from end of January to June, we were working.
But you can't work all the time. We had families baking.
So it's weird. So my mom and dad live in Kent and my sister's in London and I wouldn't have classified us as a close family.
We don't see each other frequently. We would get on fine, but probably we get on fine because you don't see each other frequently.
But because mom and dad were really self-isolating, so they weren't seeing anybody and I was watching all the time go slightly mad.
When you say politeness that stage mom dad to your zoom,
unless at least once a week all the family together so Francis doesn't have to worry about them.
I get some, you know, outside influence and mom, I get to see the grandkids.
So we did a few Zoom chats and then we thought, what?
We can't just do Zoom chat me to do something. So baking mom loves to cook.
I like to cook, but not very good at it. My sister's probably two, too.
So we were following the Bake Off a bit or finding a recipe that we could all do together.
So simple things like we do a jam task, like, you know, like you should do with your mom.
Just some pastry and some jam. I mean, we can even mess that up, to be honest.
But so we'd find something to cook together and then obviously eat it together afterwards or file together.
The gnocchi. We might. Italian gnocchi. No potato balls.
No, I don't.
I I'm a good scientist, but I'm clearly not a chef because I thought you might these little dumplings and you spend all this time rolling them out,
and then you drop them in the boiling water and it just turns into potato soup.
It's just. I don't know.
We all failed spectacularly in sync. You can see us drop these gnocchi into the boiling water and go.
That's a pie. Yeah.
So we did that, and that was nice. And weirdly, once a week we did that.
We would never speak to each other once a week. It was much closer together, being enforced.
Apart. Tweets that they sent back to other things that have never happened before.
Let's take this in this order, as it were, you personally involved in interacting with national bodies like the Jcg?
I mean, I don't have to do that.
I sat on a few calls at the beginning if I needed something specific of the vaccine task force.
But I am lucky enough not to be senior enough to have to be called in to those kind of decision making things.
I just get on with doing my little job, making the vaccine and getting it into the trial.
That's fine. That's fine. So, yes, so we're talking less than a week after a new variant called Omega.
We are. There have been other variants that have come up with some is going on.
Did you have to get involved with thinking about possibly having to tinker with the vaccine?
Yes. So we had. So obviously, the first one was made against the original strain.
And like I said, because the design is done just by text file, if a new variant is detected,
it's easy to know how to change the vaccine to match the new variant.
So knowing how to do it is is routine. So I can just send off the new code to get synthesised.
We just do it all over again. Same process as we did for the first one.
So for some of the new variants, we have started that process that prove that we can just to see how far we can go.
And then for one of the variants, we then did make a starting material.
We made a few starting materials for the for the early variants.
And one of them we shipped to AstraZeneca and they manufactured it to GMP, and that went into clinical trials and that clinical trial is running.
So that gives us information about what happens if you've had, say, two doses of the original and then you get a booster with a different one.
Do you make different antibodies? Do you then start targeting? We need to know this stuff.
So those are important for clinical trials. And so we have the capacity to make new variants that we might have few.
And then what we did was we taught AstraZeneca how to do it.
So the process of taking the DNA and going through that small vessel, bigger vessel, bigger vessel,
bigger vessel starting material, and then obviously they have the process for making lots.
So we spent the latter part.
No, the first part of this year, the first part of 2021, teaching AstraZeneca how to do it so that hopefully we now don't have to say,
I has already ordered the sequence for the Omega and we don't know if we're going to proceed with that, but you might as well order it.
So that if in a week's time it looks like we need to either we will make it or AstraZeneca will.
And that depends on lots of data that we have yet to see.
And the other thing that came out happened, well, several things that happened.
But one of them was that you found yourself doing press interviews.
Is that something you'd ever had to do before? I had never had to do it.
So I so I didn't communicate. So I was a lot. But we tend to do it, I think, in probably two contexts for most scientists.
So we talk to other scientists at conferences and we lecture.
So we,
we give lectures to undergraduates and we quite often do some school outreach or some public engagement at a science festival or at a primary school.
So, you know, so is cool. This is what DNA looks like. We can extract it from a banana.
Yeah. So we've done a bit of that. And so university staff have some ability to communicate science to some diverse groups.
But yeah, what we found was we were we were a press story.
We were of interest, you know, the Daily Mirror, The Daily Express,
as well as The Guardian and the and the Times want to interview us and do in-depth pieces not only about the science, but also about us selves.
And we as a news article not. And we struggled a bit.
It was hard to do because it's a completely different kind of communication
and it has a different aim because it is to try sometimes and get sometimes.
It felt like the journalists were trying to get us to say something contentious because it makes a good headline, of course.
But scientists, we like to say the truth. And if the truth is complicated, saying scientists don't know anything about COVID is not good.
And we did what we should say.
But the other point to that is that as scientists, we give a talk and then people put their hands up and ask questions.
Yeah. And, and it's part of our job to answer those questions.
So we are trying to listen to the questions, think about the question and then answer the question to the best of your ability.
And so when a journalist asked you a question, what do you think?
I think we have been quite proud that, no, we would tell them what we think. And it turns out that's not necessarily what you should do,
because what we think isn't necessarily what we would think if we thought about, you know, but actually, this is from a press interview.
I'm not just talking to my mates in the pub, so I'm not speaking to a scientific audience, so we have to settle into that.
Did you have any training? Not much, to be honest.
And. We have a lot of help. So this is the thing called the Science Media Centre, who are phenomenal, giving us, you know,
the confidence to try and speak the complicated truth, give the whole picture and not dumbed down.
And part of that so say when I wrote a book, partly because we felt that it was we wanted a longer format to try and explain some of the
nuance and complexity about things without having to condense everything into a 200 word piece.
Get on to the book. Yeah,
but one of the things I wanted to pick up was that one of the complexities you have to deal with was this business about the Italian trial material,
your trial, which. Yes. Being slightly different. Yes.
And how that affected the result of the clinical trials. It was again, so that was a very complicated scenario.
We had more than one efficacy outcome from the first set of clinical trial data.
And yeah, it was because the trial was complicated.
We didn't just do exactly the same thing with exactly the same vaccine batch in all of our participants.
And normally you would you would have one protocol. We're going to do just this thing.
So we got everybody the same, but we had to be making a vaccine in a pandemic.
And so the trial, the remit of the trial, the reason for doing the trial changed as we were doing it and we need to make more vaccine.
It became apparent as we were doing it. So we ended up with different batches of vaccine manufactured in completely different ways.
And so you're trying to we were trying to measure the two vaccines made in completely
different ways to see if they were likely to be equivalent to each other.
And we used a variety of tests to do that. And it turned out that one of them.
Doesn't accurately measure the concentration of the vaccine.
If you manufacture in a certain way because they have different they have
different physical properties depending on the way that you've purified them.
But the outcome of it was that effectively some trial participants didn't get the same dose.
So we had this data set that we couldn't make sense of.
We knew the vaccines were safe, but it turned out that one of them, we were giving it a lower dose than expected.
As soon as it became clear, very obvious, it became obvious quite early that that's what happened.
They were getting a lower dose than expected. And then we could correct it and give them some a dose as much.
But we had a small group of participants that had received a lower dose.
And so it meant that we obviously had to separate those in the in the reporting,
because you want to report on groups of people that have been treated the same.
So the trial, the first interim trial data when it came out,
was more complicated than other people's trial data had been because they'd only done one thing lots of times and we'd done multiple things.
And so that it was complicated. And so that's why when the journalists thought,
why have you got to try to explain that is a complicated story, and the judges don't want to hear that.
So it comes across as although Oxford scientists didn't know what they were doing, but that isn't right.
What it was, was we were having to respond to an evolving situation.
But nobody wanted to listen to us about. It was hard and it had consequences because it had consequences for people trust in what we have done.
Now, everything that we've done in those trials is completely published and transparent.
So it's all in there. Anybody can read it. It's quite technical documents, but if any of the journalists would have wanted to read it, it's there.
We didn't hide anything, but it was quite stressful time to know how to respond because.
We don't want to be seen to be like trying to justify ourselves.
We just want to explain this is what happened. This is what did we not tell you?
Ended up getting well knocked off effect. Yeah, we got knocked for a lot of things.
It felt like obviously, of course, that is part of journalism.
That is part of transparency. You have to answer for what you've done.
So you have to be questioned on what you've done and you have to be able to answer it.
It was it was. Yes, because but but that's okay.
You the fact that I'm disheartened because, you know, just because I've worked hard,
that's not good enough is what matters is the data and the outcome.
So the robust challenge is is reasonable and correct.
So you might ask as a team, feeling disheartened is of no consequence.
That's not what we should be worried about or we can't upset the scientists. Of course you can upset the scientists.
That is that's what scrutiny is. Yeah. So you mentioned that you and Sarah wrote a book that came out earlier this year.
Yes, 21. But you started thinking about it quite early on.
Was it June 20,
20 or so that you of think I am fortunate enough to be a fellow at Exeter College and when we were in lockdown over the summer of 2020,
all of those social things that you do so were cancelled.
So there's no dinners and there's no get togethers.
So the, the college was doing online zoom events like after dinner science to after dinner talks from the fellows who were experts in anything,
you know, modern Spanish history, macroeconomics, vaccine development.
So I gave a talk there on on the story of us having just started the clinical trials and one of the members of the Odesza
next an alumni is a is a publisher all in publishing and so it said cut this is a great story for a book Knock on the Door.
And he was quite persistent. Get those emails get saying when you write a book.
So eventually I sent an email to say I have a saying. We could write a book of of these offers that quite seriously would help us because
so and I don't know how to write a book on who knows how to do that with scientists.
So they gave us a lot of help. They found us a publishing house.
We had a great editor.
And it's just to write the story in long form, not only of the science, but also of placing the science in what was happening in the world.
Some of the politics, some of this, the stresses of funding,
hopefully giving credit to all of our teams and all of the phenomenal amounts of help we got from all kinds of diverse sources,
from philanthropists to volunteers. It was a pleasure to write isn't easy book to write because it is just writing down what happened to us.
It's not the whole story. It's a little part of the story.
And did you? So. But you did, right? You didn't. It wasn't a ghost written.
No. So we had so we had real a lot of help from our lovely vertical Debra crew.
So Sarah and I decided that we dropped half H and Debra had suggested we could do alternating chapters on specific topics so we could tell.
So I would do the chapter on the manufacturing of the first batch because I know how to do that.
So we would run the chapter on how did you get money for it? Because she knows how to do that.
So we could then be quite focussed on lying about things we knew.
And so said when I just wrote content, whenever we had time in relatively rough draughts, I write long form prose.
Sarah wrote some. I think she dictated some. And then we sent that into Deborah individual chapters, and she did a really hard edit.
There's a lot of red pen, but that's okay. Scientists are used to writing collaboratively.
So we write we write scientific publications all the time, and they have multiple authors.
So you write your first draught and you send it to your collaborator, isn't they hack it to piece it.
So we're used to that critique, but we're not precious about our form, that sentence.
But they notice take out a piece of it. So a professional writer took our crude chapters, turned them into something better,
and did all that checking that we haven't repeated ourselves too much and that the narrative is there.
And then we had a lot of help with just fact checking, you know, the stuff that would be time consuming to do.
We were like, Oh, Emmanuel Macron definitely said some annoying quote in March.
Can you find it? And and Deborah, all the team holder would find it.
So they did the they did the hard work. We just had to write the content.
So I recommend that highly. I think we were very lucky to have such a great team behind us.
We really believed that this was a story people want to read. And what's the reception of the book?
That's been amazing. We were we were writing a full book.
Imagine that. My mum was actually writing for Book of the Week. We were even a Sunday Times best seller.
I mean, which is nice. It means people have gone out and bought it.
But I guess the real nice thing is that people have read it.
People sent us nice messages. I get emails from people saying, I read your book.
It taught me something and you know, I might be crying.
Apparently we're quite good at making people cry, I think just because some of it was quite emotional.
Yes, yeah. No, I told you, I read it and I was very impressed with how unfiltered it was.
I don't have a very strong feelings. Oh, yeah.
Yeah. And a few between you receive various kinds of honours.
Well, it's been a it's been met, it's totally mad. So first of all we will recognised in the some of the team,
not all of the team but some of the team are recognised in the Queen's Birthday Honours list.
So you get this weird email from this weird address saying Now don't tell anybody,
but you have been recommended by the Prime Minister or something to be on Twitter since July 20, 2102 2021.
Yes, you're right. Yes. Yeah, March is my march.
So that was after the vaccine trial. So, yes, after the rollout.
Yes, yes, yes. With Emma, I think they probably used to send you nice letters on thick paper, but obviously COVID wags.
So you gets weird emails from. The Birthday Honours Committee or something I think is a joke.
I really did things that one of my friends is Donna April Fool and you know, have to tell anybody.
So are you trying to figure out? I think I'm supposed to accept how everybody else is gonna want to play.
You know? Really had to ask if they had. I don't know. It was very weird.
And then obviously the day that's announced and there was press about that and that was before the book was out.
And then after the book was out, there was a lot of press out by the, by the publishers for that.
And then yeah. So then we started to have some recognition, the whole team for the enormous effort that had been put in.
Sarah was ten, got a standing ovation. And then we got we got awarded a GQ Man of the Year award, too.
And it's inscribed on it. It says GQ Man of the Year, Sarah Davis, Catherine Green and the vaccine team.
I'm I'm very proud of being the man of the year makes us very happy and other that's
that's just marvellous to be recognised by people outside of the scientific community.
And it's weird to have your name specified there because it's such a team effort.
Each of us individually, I mean not say, okay, we did everything and did everything, but most of us is tiny little bits in that story.
But to go and accept an award and then to say, look, I accept this on behalf of my team,
gave them a shoutout occasionally is I think a lovely thing to do and it's humbling to get recognised in that way.
It's a lovely thing to happen. Mm hm. And we're doing very well.
We're doing very well. Um, you answered that one.
Oh, yes. I'm not sure if this question will annoy you or not. I mean, it's very apparent from the book that you work in a largely female team.
Has that been your experience throughout your career? And if not, is it different?
I Yeah. I'm trying to think now about the numbers.
I. So biological sciences at the kind of entry level and medium level is certainly well represented by women scientists.
I would suspect that things like wet lap science, where at least 50% that is not true in physics or chemistry, even at low levels even now.
But representation is increasing all the time at the professorial level in the university.
Women are still massively underrepresented. That's very clear in the manufacturing team.
I think we probably are more women than men. I mean, it's a small number.
It's 25. So what's the. But also, it's not statistically significant collaborators like Sarah.
So the team is six pages that were on the initial team and that's three in three.
So that's Andy Sun, Adrian, May, Tess and Sarah,
who are the team of six that came together to cover all of the parts of the expertise that we needed to go from design to scale up.
And that's in three. So you don't get more equitable than that.
We are all white. There are other metrics of diversity which are missing in the table at least.
There are lots of lots of other types of people we would like to be represented who aren't at that level.
But you talked about your team being very diverse.
We have people from a lot of different countries and from a lot of different ethnic backgrounds and a team of 25.
But I mean, there are lots of groups that it is very clear who are underrepresented in science in general, and we're no exception to that.
I did. Okay. I think I think we can move to a conclusion.
So that's as far as you're concerned, the work that you did on COVID and the COVID vaccine raise questions that you'd like to explore in future.
So it's helped us a lot because we have used it to move towards more modern manufacturing processes.
We actually did it for that first batch that we made in a hurry.
We used our old fashioned process because we know how to do that and we needed it to work first time.
But the scale up that was not done by, by us, but we have seen that in action,
makes us realise that we need to modernise how we do things here, even at small scale.
So we have learnt a lot scientifically about what to do.
The regulatory space is how we will go about doing vaccine trials in the future.
How we go about manufacturing in the future has definitely had a lot, lot we've learnt there.
Um, what was the question, uh, whether it's raised new questions that you're interested in exploring and then I mean is,
is, are there any plans to expand the, the, the manufacturing?
Yeah. So it is also the same thing in Hall of Fame.
So in terms of manufacturing, I really want to we are we are trying at the moment to negotiate capital investment, to expand my facility.
At the moment, I can only make one thing at a time. So when we had to do COVID in January 2020, we had to stop doing Ebola.
And that's that's a shame. I would like to be able to make more than one product at once.
Innovative medicines are going to be the future of healthcare if our mission is to.
Provide patient benefit. You know, the more trials we can run with new things, the better.
So I need to be intimate and faster. So I'm trying to pull all the levers that I can to get the capital investment in.
I need to expand the facility and the university being very supportive of that.
I'll need bigger, clean rooms. I need a bigger team.
You know, everything has to grow to do that. It's complicated. It's expensive.
And then across the UK, the government has realised that we needed capacity to manufacture vaccines in
country because during a pandemic it's clear that supply chains get complicated.
Protectionism gets complicated.
Of course, if you're making a medicine in a country, there is some imperative to use that facility to supply doses to that country.
Any politician is going to want to do that. It doesn't feel equitable on a global thing, but it's human nature.
So the Government realised we need good quality manufacturing capacity in the UK, which was perhaps missing.
But why was the private sector and the government are expanding?
The ability to manufacture complex biological medicines doesn't have to be vaccines.
Flexible manufacturing that will enable us to respond to future pandemics or other health issues is a requirement.
And yes, I said that needs a combination between private sector and government support.
And I think the right noises are coming out of government about that.
So we'll see how that pans out in the next couple of years.
But you mentioned theme. Does that sense I would be make is the Vaccines Manufacturing and Innovation Centre at Harwell which we see it was
was to be a purpose built manufacturing facility ready to make any vaccines that the government needed in a hurry.
But Oxford University had some at the beginning. Oxford was involved.
I don't think they really are now, and I don't know the long term future with that, but nothing to do with it.
No, it's not to do with us. And yes, this is the final one.
How has the experience of the whole experience changed your attitude or your approach to your work?
And are there things that you'd like to see change in the future that you haven't mentioned, whether it's.
It's been surprisingly hard to recover from it, I think,
particularly because we've been still on social distancing and masks and a lot of people working from home because as
facilities are very small and so our desks are too close together for the university to allow us to work at full capacity.
And so we've had this really interrupted year when we haven't been back as a cohesive unit.
We were this incredibly strong team that got this huge thing done in a six month period,
and then we were in limbo for a bit and we still haven't got that back.
And I think that's something we really have to work on as we now will try and move into this post pandemic.
There's a lot of healing to be done probably, and a lot of fixing to be done.
And I don't want us just to revert back to the old ways because some of the things that we learnt were very valuable.
So some of the, the collaboration that we did across teams was really effective remotely.
So Zoom calls and teams calls because obviously most of these were do not in this being in the same room,
these big decisions were being made very effectively in meetings of lots of people.
That can be a very good tool, but it has to be used well.
So I just want to find ways to take some of the good stuff that came from from the situation, some of the how to motivate a team,
how to get stuff done effectively,
but also lose some of the bad things about fragmentation and and loss of that social ness that keeps a team together.
I haven't quite figured out where we are.
Yeah, I think the whole thing feels a bit discombobulated. How long it's going to take us to get back to normal.
I don't know if we ever will, but it's not the same normal.
But your went back to working what you might regard as sensible hours.
Yes. Yes. Because you can't ask a person to be on mission mode.
All the time because it's too this too exhausting.
People need to have time off. Tired people and hungry people make bad decisions.
So the thing about when we were tired and hungry, we were making group decision.
It was hardly ever down to one person to make a decision during that period of intense working.
There was something very creative about the leadership that wasn't ever just from one person.
And so there was you always had somebody sent to check on you, I think, which I think was is a really good way to work.
Going forwards, some collective decision making was was really good, I think.
And how do you this is asking you to blow your trumpet, which you don't really do but.
How do you feel about the fact that that little vial that you started with and has
now turned into a vaccine that's vaccinated millions of people all over the world?
Yeah, yeah. We're really proud of it. I mean, we are very proud of it. I think it's okay just to say that we have a we have a picture of it.
So the very first I told you the patio is a patio of cells.
And you put that that piece of virus on for the first time, this DNA on for the first time.
And so pops and then it pops the ones around.
So you get a hole in the patio and we've got the first it's called date because the the wells are numbered.
So the down and eight, of course,
that's why it was in the grid and and we print it out on the door as we all as you walk into the clinical biomanufacturing facility date is there.
So that is the one that sale. That was the start of now more than 2 billion doses delivered by AstraZeneca globally.
That's I think 20% of the entire vaccine doses that have been shipped.
A large proportion of those going now to low income countries via the COVAX scheme and via
the fact that AstraZeneca is still supplying not for profit to to developing countries,
to developing countries. I think the idea is in perpetuity.
I think they are transitioning to a small amount of next year there'll be a transition to a a small profit on supply to high income countries,
which is the reality of the world we live in, that global pharmaceutical companies, they're not going to keep doing this for free forever.
It's reality, isn't it? I think. And that was always agreed upfront.
I don't think it's anything that was a surprise to any of us.
That's all the questions I have. Is there anything obvious, Lieutenant?
I have no idea. I don't know.
It's fine. I. No.
I mean, that's fine. It's lovely. Thank you very much indeed.