Okay, So could you just start by saying your name and what your current position is and what your previous association with the university was?
So my name is Annie Oakley, Dr. Annie OPA,
and my current position is a group leader at a biotech company at Abyssinian just down the road in Milton Park.
And I used to work at the university as a senior postdoc, as senior immunologist with Frater Lab, Professor John Fritz's lab.
And yeah, I was with the university for about seven years before I left.
Mm hmm. Okay. And I'm going back to the very beginning.
Tell me about your your career to date. How did you first get interested in science and decide you are going to be a researcher?
So I thought about this question, and it's not it wasn't something that because I know that for some people here,
they've always wanted to be a scientist, they've always wanted to be a researcher.
But as you can probably tell from my accent, I did not grow up here.
I'm not from here. And so my I'm Nigerian by origin and I had my first degree there.
I did all of my primary education there. And it's not something we research and science isn't really a third world thing, if I can say it that way.
It's not something that developing countries really think about this issue, but it's not just our priority at the minute.
So even though I had a lot of real world examples of diseases and I was interested in them,
I didn't really think I was going to end up as a scientist or as a researcher.
I think you might be a doctor. Exactly. Exactly.
That's what I was just about. So you it sort of got you took what you were given.
And we had this entrance examination where you sort of state what you want to study at university.
And then that goes out and you write an exam and depending on your if you made the points for it.
But the points were also complicated by what parts of the country you came from.
So if you were considered to be from a part of the country that was highly educated,
your points were much higher and then it depended on what university you picked as well.
If it was within your catchment area, it meant that your points might not be so high.
But if it was outside your catchment area, you know, it just made it quite difficult to get into.
So I wanted to study medicine and be a doctor because those are the things you do.
Engineering, doctor, accountant, pharmacy. But I didn't make the points and so I got, I got given biomedical sciences or biological sciences,
as we called it, and I remember thinking, Oh, what am I going to do with it?
I'm just going to be a teacher afterwards.
And first year was a bit rough and then second year, third year, I think I strapped up my boots and said, Yeah, okay, let's do it.
And then I finished. And I think at that point we were starting to hear a bit more about cancers.
So growing up it was a whole lot of HIV and a whole lot of malaria.
Up towards the time I had I finished,
I started to hear a bit about cancers and I began with my fascination with infectious diseases or just diseases in general.
I wanted to know, you know, what was happening and there wasn't any chance to do that.
So I started out in the bank.
I worked in the bank for about a year, a year and a half, and then I was fortunate, privileged to be able to afford an education here.
And so I moved here for my master's degree, and I started out by doing a master's in molecular medicine with cancer research because I thought,
well, after my master's degree, if I went back home, I can sort of set up a diagnostic lab in Nigeria because we didn't have a lot of that.
I could, you know, do something along those lines to educate the public about how to identify this cancers,
what sort of test, you know, how do you screen for breast cancer and things like that.
And then I'm glad. Did you do it at Brunel University in London?
And then after my master's and the lab, I did my master's in, they had this really interesting project.
It was looking at this pair of jeans.
So they are called the Adequate response jeans. And then I went into a bit more of trying to understand what was going on.
So some more mechanistic studies. And we found out that the genes that we were interested in actually controls
one of the signature transcription factors for a very important T cell subset.
They are called the follicular helper T cells. So they help the B cells make this, you know, the gold standard of antibodies, you know,
the high affinity antibodies that have been semantically hyper mutated and you know, with different sort of response.
So let's, let's just go into that a little bit just so that we've got a good background on.
So what are the the main arms of the immune system and what's the difference between what the T cells do and what the B cells do?
So the main arms of the immune system would be the innate immune arm, which is like your immediate, your first responders is the way I'll put it.
They are very non specialised, but they are on the scene quite quickly and these are the T cells of the T cells.
Yeah, not the T cells. These would be your macrophages, your neutrophils would be the very first ones to arrive on the scene.
And I always use the analogy of a crime scene or an accident scene where you very
quickly you get the emergency responders and they come and they sort of take the,
you know, vital information, write down things on the notepad.
This is exactly what the response does to neutrophils with common or what's going on here.
They survive the place. They start to send out signals.
So like the sirens you get and the like, they start to send all of that out.
Then the macrophages would come in and they start to pick up the pieces,
sort of trying to form a pattern of this invader, of this crime scene, and then they then go away with the macrophages.
And there's another cell as well called the dendritic cell, that they do this quite well.
They engulf the particles that chomp it down into tiny pieces and then present it like a profile and say, look, this is who you're going for.
And then the specialised then come in. This is where we have the T cells and the B cells.
So that would now that that's the transition from the innate immune system to the adaptive immune
system where you have the T cells and the B cells and then they come in and they are so specialised,
they are like your top level snipers or whatever it is, they have the profile, they are going for the profile.
You don't have a lot of collateral damage with them because they know exactly what they are going for whilst with the other ones,
the non specialised guys, you get a whole lot of collateral damage.
So you've got the T cells that sort of targets cellular immune response.
So they target the cells that are infected and then you've got the B cells that are more humoral,
so they secrete this antibodies to shoot them up like 2000 molecules per second.
I think for some of them this antibodies then go through the bloodstream and then able to target pathogens the way the antibodies do it.
Again, kind of like a crime scene where you have, you know,
some of those veins that tell you if you try to steal from it, you get sprayed by something.
Yes. So this B cells, just the antibodies just sort of dot the patogeno, the antigen.
And then that means that all the cells can then come and say, oh, that's you and then engulf it.
So those are the two main things. That's a really good explanation.
Sorry I interrupted you in your story. No, no, that's fine.
I, I like to do this public engagement and I was doing one for a group of schoolchildren and I thought, what's the easiest way to.
Message the immune system to. I thought, oh, first responders.
That was. Yeah.
Pretty good. Yeah. So sorry. I think I interrupted you in mid-flight when you were talking about your PhD, right?
Okay. Yes. So we're talking about the T of hate cells Within the T cells.
You have different types. You have, I think the most common that people would know are the CD4+ T cells,
which we call the help of T cells and the CD8 T cells which are called the cytotoxic T cells.
Now the CAC 40 cells, just as the name implies, they help the cytotoxic T cells.
There are different flavours of those. So you have, depending on the antigen, they c depending on the site of infection.
You have different ones. You could have the th1 CD4 cells which would be more geared to help the CD8 cells with viral infections.
Then you have the to hit 17 that sort of line your mucosal.
So your cells just epithelial surfaces that interact with the bloodstream.
Then you've got that. You've got the th2 as well that performs some important functions.
But at the moment they seem to be they get a bad rep for their role in allergies.
And then you've got the follicular helper T cells, which is the one that I was working on.
Then the states which are the are the types of T cells you have, as the name suggests, the sort of mediate this healing function of the T cells.
So they have this debt packages where they would shut it out,
they come into close proximity with their target and then they shoot up these death packages.
That's one way they would do it. Sometimes they would also engage with the cell they want to kill and then send those signals.
That then means that the cell gets killed. But all of this killing is done in a controlled manner so that you don't have
inflammation and then it's mopped up by other cells in the immune system.
So yeah, that was my pitch. So that sounds as if it was quite exciting because it was discovered something new and demonstrated it both ways, right?
Yeah, yeah, yeah, exactly. Exactly. And that's what you want to do in a season to get something novel and advance the field ever so slightly.
Then I moved to Oxford after my Ph.D.
I started in a lab just down the road in the Indian.
The Indian army. And we were interested in HIV.
And I was so pleased to be there because like I said, growing up, I saw a lot of first hand real world examples of the disease taking hold in Nigeria.
And I, I never really had the facts, but I was just so fascinated about it.
And so to be able to do it at this level, I was really, really pleased.
And what we wanted to do was I had completely left my Ph.D. I had taken those cells that I knew helped to make this really,
you know, gold standard antibody. And we were asking the question if those cells played a role in HIV.
And the reason was because we had found a group of HIV infected people, a very tiny proportion of HIV infected people,
depending on how broadly you look at your antibodies, they're an elite group of infected people that would make this broadly neutralising antibody.
So part of the problem with HIV is that it has a very high mutation rate.
So the diversity in one person alone,
the viral diversity of one person alone is so much that the immune system is always trying to play catch up with the virus.
The virus is evolving, the immune system is trying to catch up, and it just not because the immune system,
but in a group of group of people, we found that the myth is broadly neutralising antibodies that could neutralise a wide strain up to.
I think the figures at the time I left was up to 90% of circulating strains.
But the problem was it had no clinical benefit to them because they are a virus had mutated.
Yes, yes. So it had no clinical benefit. So what we wanted to do was how can we make this broadly neutralising antibodies.
All right, arise earlier in people or how can we even make it into a prophylactic vaccine
so that at risk populations or maybe even the general population can have.
That's just the same way we have our vaccination strategy.
So we thought, well, maybe this cells that play a role in driving this antibody response might be important in this people.
And what we found was that, yeah, they were the same.
It looked like they played a role because in this group of people they seemed to have a higher number of these cells in their circulation.
So we're trying to really get into how they were playing that role.
It was a very big it was it was with a very big consortium funded by the NIH and some collaborators at Duke University in the US.
But we it's quite it was quite a difficult question to ask because in order for this people,
this infected people to make this broadly neutralising antibodies,
it meant that it didn't go on the standard of care, which was antiretroviral therapy.
Yes. And at the moment, as soon as a person gets infected, they get put on ARDS.
So you don't really get to develop this broadly neutralising antibodies anymore.
And the reason why art limits the development of this is that you need the antigenic diversity.
You need the arms race to push the immune system to broaden its response, but as you would imagine, keeps the viral load down.
So there isn't really any evolution of the virus, so very minimal evolution of the virus.
And so the samples we had where from way back before I came in, so they were very precious.
And then because we're looking at subjects that did not go on antiretroviral therapy,
it meant that the immune system had been battered by the virus for years.
And as we know, with HIV, one of its canonical ways of battering the immune system is depleting the city for cells.
So the city fossils, which I was interested in, we're almost completely gone.
And I was looking for 5% of the almost completely gone cells.
Those were the cells I was interested in. So what while I didn't I didn't quite come out of that project with a publication,
I came out of it with a lot of learning because I had to optimise a lot of things.
I had to develop a lot of assays, I had to make my own sort of trying to find a needle in the haystack.
So I had to make my own ways of finding things.
And I think a lot of what I'm doing now is credit to that because it really put the resilience of the.
In the 95% of science is failure. Absolutely.
Yeah, yeah, yeah. And some of the methods that we developed while trying to find that, you know,
elusive or answer the elusive question we had were then used with other projects I was involved in.
For instance, I got involved in the malaria vaccine projects. Some of the the t cell assays I had set up was then used for that.
And I think we might touch on that later with when we talk about the COVID vaccines.
And then I left that lab and then moved to Johns lab again, still keeping within the the theme of HIV and antibodies.
He he had a very interesting project where he was looking at he had moved from we had moved from prophylactic vaccines now to therapeutic modalities.
And Johns Lab is very focussed on HIV cure.
And, you know, while I think for most people in the field, we have accepted that we're never going to have a sterilising cure,
at least not anytime soon, we wouldn't have a sterilising cure for HIV because the virus forms this reservoir.
And as soon as you take people off and through retroviral therapy just replicates very quickly, it rebounds.
What we want to get is some kind of functional cure where people can be off antiretroviral
therapy for a long time because there are issues with antiretroviral therapy like this,
the toxicity issue, there's the resistance and there's also compliance.
And as you can imagine, logistics as well. If you're thinking about remote villages in Africa or South East Asia,
there's also the fact that HIV is still a disease that people discriminate against.
So for some people going to get the antiviral viral therapy is it's it's quite risky for them, you know,
So if we can take that off them and make it in such a way that you don't need to take a pill every day anymore,
you can now take a pill once a year or once in six months.
Even once in two months would be much better than every single day.
And so that's what a lot of the HIV cure studies are focussed on, and that's what Jong's lab is focussed on.
So he got funding from the Gates and the Gates Foundation, and we set up this clinical trial that was just brilliant.
So they had this broadly neutralising antibodies, the ones that can neutralise more than 90% of circulating strains,
but they had tweaked them, they had engineered them so that they were now long lasting.
But also if you infused them on already infected people in the already infected people,
you could get a suppression of viremia even in the absence of art.
So the questions we're asking were twofold. Can we replicate this with the long acting b nabs?
And also, if we could, what?
How were they keeping viral load at B?
And what they had done in that study was try to sort of see what cells were controlling it.
So, you know, you would always want to start with something big and keep narrowing it.
So they started with the cells and then they depleted some of the cells that depleted the natural killer cells and the CD8 cells.
And they found when they depleted the cells, they had a spike in viral loads.
So that sort of gave an indication that something with the cells was helping to control it.
But it didn't quite make sense that, you know, how, you know, antibodies don't really interact with CD8 cells.
And antibodies could interact with the NK cells because part of the effect of functional antibodies would recruit the NK cells,
but not quite the seeds. So how were they doing that?
And this was where I came in as an immunologist on the trial.
I was the lead immuno immunologist on the trial. We wanted to first of all characterise what happened after we fused this.
People with this B nabs what happened to their immune response to the dyes and classify what kind of responses were they making.
And so we wanted to sort of. And this did this vaccinale effect that we thought was happening.
Yeah. And how did that go? Well, so we had COVID.
Julius Caesar came along. Yeah. Just. Okay.
Just when we were about to start the clinical trial, I think we had our first patient and we're ready to dose in March, and then COVID happened.
So we had to pause it and then it didn't get we didn't start until a year and a half later for the trials going really far and really well.
And I'm not allowed to share yet, but I think it's looking quite promising.
And I expect that there would be something a publication coming up quite soon.
Yeah. Mm hmm. Isn't. But you got us to open it so that my question that I'm asking everybody is,
can you remember when you first heard that there was some respiratory illness going on in
China and how you came to realise it might be serious and then how you became engaged?
Yeah, in a response.
So I think I heard about it in December because it was in the news towards, you know, the first week, second week of the set about that time.
And then it became more serious as we got to Christmas. And I think I saw it and I was like, Oh, okay, something else on the news.
You know, I didn't really pay a lot of attention to it.
And then I remember going away, it starts to get more and more serious and it was like the only thing on the news.
And I was like, Oh, this disease from China, you know? And then I went to I went on a holiday to Malta, and I remember just having a slight bit of.
Should I be going on this holiday? This was in January. But then we I think they had one or two cases in.
I don't I do remember if it was the UK or somewhere in Europe, but I went there and I had this cold before I went,
Oh, no, I came back with a cold and I couldn't shake off the cold.
And I think like everybody in the UK, when you speak to them, they're like, Oh, I had something in January, I think I go.
So even I was thinking, Oh yeah, I think I had COVID, but I don't think so.
It wasn't COVID.
And then I came back from Malta at the end of January, and I think that was when I really thought, okay, this is getting quite serious.
And also, you have really. At least for me,
I never really thought about it until we had the first case in the UK and then
the scaremongering started and we didn't know anything about this disease.
All we knew was the SARS cov one, which we knew was very deadly.
So I think we started to have a bit of panic.
And I remember thinking this was around February, March time when they were having the debate about the Cheltenham races,
and I think I had gone into full a full blown panic at that point.
I was like, No, the races shouldn't be going on. This is an airborne virus, it should not be going on.
And then everything just sort of happened very quickly and almost like a dream, because, you know,
one day the universe is like we're going to carry on with our work and blah, blah, blah.
And then the next day this talks about a press conference from number ten.
And I think just before the press conference,
which then got the news that everything is to CS in the university and we're all supposed to go work from hormones.
And it just it just felt it just felt like the end of days in a way.
So we were at home for two weeks while we tried to sort out our ethics and stuff, but we always knew that we would be involved in COVID somehow.
So for most of us, I think as soon as we started to hear that the the numbers were going up,
I think almost quite a number of us from here volunteered to work at the hospital and take our skills to the hospital.
All the doctors, all the medics had gone back to the hospital already.
And the scientists like myself, you know, we could do Q PCRs, we could do the PCR, and we had to wait.
Overwhelmed. We could do whatever it was.
You know, we were all trained. So just tell us what you needed.
And a few of us sort of started.
I think personally, I spent like a day or two, two nights in the hospitals doing the some of the assays for detection,
and then we had to be called back in the lab and it was just go, go, go from then on.
So what was the question that the lab set out to address specifically?
So I think at that time we just wanted to know what the immunology of this disease was.
So it was very much observational and that's what you can do on the stands, you know, observational studies.
What was the disease doing to the body? What was the body doing to COVID?
How long was it taken to clear COVID? Why were some people asymptomatic?
Why were some people asymptomatic, and why did some people even die?
And, you know, why did it impact children?
But they did not Why did it impact adults? So we didn't impact children so much.
Why was it more severe in certain ethnicities versus others?
Why was it why were males more impacted than females in terms of disease severity?
So it was all those questions.
So we set up an observational study where we started by just simply it sounds quite simple, but we didn't even know what tools to use.
So it's like you've got all this arsenal you're, you know, and you're like, Right now what do I do?
So what we did was we then took all our arsenal and just hit it with it and said, Which one answers the question?
But then where were you getting your samples from? From the hospital.
The health care worker. We set up a healthcare worker cohort and I mean, it was just fantastic collaboration because this people,
despite the fact that they were so busy, they were worn out, they were coming for regular bleeds.
It was just a beautiful collaboration to see everyone work together like that.
And it was so selfless. So we had the health care workers study.
We got our. Samples. Then from our end, we had the intellectual input as to how we're going to conduct our study.
So first of all, we wanted to know how do we characterise the immune response in this people?
We had the standard T cell acids that we would use, the earliest bullets we had the.
So elispot basically it looks at the functionality of a cell by you get the cells and then you get an antigen or a part of the virus.
You can either make that synthetically in the lab as protein shock peptides or you can get the
virus Lysate But at that time we weren't allowed to go anywhere near COVID because we didn't know.
So we had the synthetic peptides and then you put that on the cells and if a cell is specific,
if a T cell is specific for that particular antigen, it will start to make the molecules.
So so that's a signal.
And what we then do is we then trap that signalling in a plate on the membrane and then we can quantify how big the response is.
So you're asking the cell, do you recognise do you recognise this? Exactly.
Exactly. Kind of like an interrogation device. Yeah. So what they call it, you know, a line up.
Yeah, I know exactly right. That's what it's called.
Yeah. Yeah. And we were the ones behind the screen and we're saying, Yeah, which one of them is the criminal?
But yeah, we, we did that. And then it secretes this cytokines we call them and it's, it's all of our t cell, as is our own spectrums of sensitivity.
So there's, you know, it's a balance between sensitivity, specificity and,
you know, a number of different things that you may have to compromise with.
In some cases you're able to sort of take the take us the cell, you know, do you recognise this?
But then say, well, if you recognise this, I want to know exactly how you are, what's your own profile?
And so if we're using the analogy of a line up, it's a two way blinded thing where you can say, Oh,
someone here recognises it, but you don't quite know who the person is versus taking that blinds off.
You're like, Well, this person, this female, this male, you know, recognises this culprit.
So you can, you know, it depends on what you want.
So we took all the approach because we wanted to be able to, we wanted to be agnostic about it and come up with the best possible way of detecting it.
And we found that depending on the assay you had, you got different readouts.
So without any spots we're able to pick cross-reactivity but not a whole lot of cross-reactivity.
So cross-reactivity basically is the ability of one particular cell to be able to recognise multiple
antigens and which is advantageous in if you think about diseases that are closely related.
But it can also be disadvantageous because it can also lead to non-specific responses.
So again, that's this is a nuance of the immune system.
So we found that we were able to see some level of this cross-reactivity with the early spots.
We didn't see very much with the ISIS as the ISIS is another assay that's less sensitive than the early spot.
But with the ISIS, you can go into the fine details of what the cells are essentially intracellular, cytokine staining.
And so this would use it, just an in vitro ASR as well.
You stick the same peptide, but rather than letting the cytokines get secreted out of the cell and you trap it on the membrane,
you actually hold it in the cell and then you can come with the probes,
the antibody probes that we make,
and then you can stick all of these probes on them and then pass it through a machine that beams this lasers on it and then tells you,
Oh, it's got this, it's got that. Depending on what you put, what probes you put in there.
But it has it's a much more reduced sensitivity.
But sometimes you want to know exactly what it is.
So you would be willing to take that compromise of a bit less sensitivity.
But I get to know exactly what the cell is. And then there are other aces as well, where especially when the population is really low,
where the number of cells that recognise a particular pathogen is really low, you want to expand them out for a bit.
And what that happened, what that does is that, you know, you increase the sensitivity,
but it means that you don't know what you start, you don't know who started it, it started out who started to make it so.
Basically just say take this and pass it on to people and then a lot of people end up getting it.
But a lot of yeah, if you imagine sharing candy and you've just said pass this on, but you don't quite remember who started the passing on.
Yeah. So you don't get that information from the, the, the proliferation assays.
So we took all of that approach and then we found out depending on what you took,
you were able to answer different questions and that paper went out quite quickly.
And I think that paper is quite well cited now because it showed that, you know, different T sources,
we already knew it in the field, but it sort of solidified that that, you know,
different assays and especially with COVID, you want to be able to either use all all of the assays,
all everything you've got in your arsenal or at least pick the best one that answers your question.
Um, and then we then moved on to, I think quite quickly the vaccine started to come out, thankfully.
So we then moved into a lot of characterising the vaccine immune responses,
you know, knowing what sort of immune responses this vaccine is were making.
How long did it last? We did that in healthcare workers.
We also did comparative studies where we compared the RNA vaccines to the to the adenoviral vector vaccines that were made in Oxford.
Then as part of our work here at Oxford,
we made we had all the the vaccine and part of vaccine and the the trials that you would
have with a vaccine before it's rolled out is also looking in certain groups of people.
So sometimes it would start out in adults and move to kids and then move to other populations.
But because we had a group of HIV infected people that we had been working with for years, they were included in the study.
And so we did some of the things that they regarded as what the phrase is more vulnerable, and then they were regarded as more vulnerable.
Yes. So yeah, exactly. The where we got it is more vulnerable.
So we did a lot of the HIV, the preliminary work on the HIV vaccines for the child because we had a substudy and you know,
we published that in a paper as well. That's also heavily cited.
And I think I'm quite proud of the fact that some of the work we did with that vulnerable population did inform some
of the and the other policies on the management for COVID in HIV infected people and also the vaccination for them.
So what was the what was the outcome?
We found that it was safe in then, because the worry is that for certain vaccines we found that in HIV, when HIV infected people receive it,
it triggers it could potentially reactivate their immune system and then trigger increased replication in the virus.
So we found that, you know, we where we'd seen that we found that it was safe, they didn't have any adverse effect.
And also, when you consider that these are people whose immune systems are still in a way compromised because even though they go on us quite quickly,
artisan's retroviral therapy, they go on that quite quickly. The immune system never fully recovers.
So you have to make sure that whatever you are given to this population, it's well-characterized and is safe for them.
And that was what we did. And were they protected from COVID?
They were protected from COVID, yeah. When they received the vaccine, yes, they were protected to the same level as healthy or uninfected people.
We shouldn't use the word healthy because they are healthy as well. But uninfected people.
Yeah. Mm hmm. Yeah. And I don't want to rush.
You want but you it. I mean, I was just reading a study you've done on volunteers who are taking part in challenge studies.
Is that right? In the challenge? Um.
Oh, no, I'm not.
I'm not familiar. Oh, right. Sorry. I must have. Well, that's okay.
That's all right. That's all right. And but so.
Yes. So I think the paper I'm thinking of was a was about cross-reactivity and whether previous infection with.
I think it was the review that we wrote because we were quite interested in this cross-reactivity.
And it's it's I can give you a bit of history on how we sort of stumbled on it.
So we had this. We're looking for healthy controls that have never been infected with COVID and we led.
I remember that there were 30 people and I played 30 people.
So you are involved in the sample collection? Yeah, yeah, yeah.
So I'm a trained phlebotomist as well, so I was the only one on site that day.
So there was a long queue of people and we thankfully at that time we had stopped doing the assays fresh.
We had started to freeze down the samples, so we had time to go back to it.
But I remember doing the first set of assays because I did them.
I was leading a team of scientists that were doing this assays and I did the first set and with the
proliferation assay you had to wait seven days to wait seven days and then get a result that you don't.
Well, at that time I thought this was a bad result, but to wait seven days and not get what you expect, that can be quite heartbreaking.
But I was looking at it and I was like, no, this doesn't this doesn't look right.
People. This people have all said they haven't been infected with COVID.
It's still very early days, so I'm quite certain they haven't.
But everyone, you know, when you look at almost everyone,
when you look at the part of the envelope protein that almost everyone had the response there.
So where is that coming from? And I remember thinking, I'm going to have to repeat this.
So I set the first set aside and then I did the second set of patients, another ten.
The first set was ten, I did the second set another ten, and it was the same results.
And then I got someone else to repeat the first set, the first set because I was like, okay, maybe I've gone crazy.
And then they got the same thing as I did. So we started to think and then and I think the first the first t cell paper came out around that time.
It was sometime in April or May, and we're like 22, 20, 20.
Yeah, 12, 20, 20, 2020. Yeah, yeah, I remember.
Which we're all waiting for the first papers to come out because we were not ready with any papers yet,
but because you're sort of digging in the dark and you're doing it under so much pressure and the eye of the world suddenly was on you.
Like, if every time a scientist was important, that was.
Yeah. I remember driving through on the motorway and being the only car there with my permit saying I was not important,
a key worker here, I thought, Oh, okay. So we did it.
And then the first few papers started to come out and then we signed from elsewhere.
From elsewhere, I think it was from La Hoya and the Scripps in La Hoya, the first ones.
And we started to decide to report this cross-reactivity by at really low levels.
And so we then started to align the sequence of the virus because I think the sequence we had the sequence for, there was just so much to do.
But we then aligned the sequences with the virus and we saw that, you know,
there were parts of the sequences that were very potent conserved across the coronaviruses,
particularly the beta coronaviruses, and that would include some of the seasonal colds.
So what we were picking up could have been a response to some of the seasonal colds.
But also those responses, as we've come to know with COVID, don't last very long.
But because we're coming out of the winter and people may have encountered those, it was quite strongly you had one put.
Yeah, exactly. And I was quite strongly Well, it was interesting because it was just the envelope.
And so we found out that if you want to look for COVID specific responses,
don't look for the envelope proteins, because that would be quite cross-reactive.
In fact, you would probably be better off looking for something using an AC that's less sensitive, because if it's less sensitive,
you're more likely to pick up more recent infections versus the highly sensitive ones that would pick up within minutes of signals.
And then we sort of started to ask the question, well, what's the role in this?
Cross-reactive response is what do they do? And I remember sitting on it for a really long time.
Like, I just I really I really got into it.
And I think I had written up a grant for funding.
I didn't get the funding, but I really wanted to go into those cross-reactive responses because what I was thinking was,
well, maybe if we can find something that is common to all of.
Then we can make a pun coronavirus vaccine and maybe we don't need to go all the way because we know Sars-cov-1 and Mers-cov are quite lethal.
If we can find something that we can, you know, we don't have a pandemic for those and the epidemics,
I think we're years previously, but maybe we can, you know, protect against future outbreaks.
And so we we're having the meeting and and this time I'm John and I were,
you know, just a meeting on something else which I think Alibaba's some worry.
John Frater we're talking about I think it was the one of the cohorts, I think it was the cancer cohorts.
And we just talked about, oh, you know, I said, I'm very interested in looking at this cross-reactive responses.
And I think no one really knows what's going on with them.
You know, we were one of the first people to report it, and I think we should go a bit deeper.
If nothing if we can't do the experiments,
let's let's put the literature together and see what it sees and then plan and experiment after we know what the literature says.
Yeah. So that went on for two years and the papers just kept coming out and coming out.
But what was quite interesting was that we got to the end of that exercise and we pitched the idea as to the reviewers at Nature.
They were happy with it and they were very, you know, they were very helpful in bouncing ideas.
And we kept talking for like the full two years.
But when we got to the end of it, we realised we may have put it on paper, but it's still not clear.
It's still just as nuanced as when we started.
But at least now you can read the nuance in an untangled.
Piece of work, you know, someone had done the job of bringing it altogether.
So we found that depending on whether it was T cells or B cells, it could be beneficial or non beneficial depending on where you looked at,
depending on who it was, depending on if it was children, depending on if you had natural infection or vaccination.
And it was it was a fantastic piece of work and that, you know.
Yeah. So it's just yeah, it's, it's, it's still very nuanced, I think.
Yeah. Okay, good.
So, um, yeah, I want to talk a bit more about collaboration because, I mean, sometimes science is seen as quite competitive, you know, within labs.
People want to kind of hold onto what they're doing and yeah, obligation.
But you've already talked about the, the extent of the collaboration.
Yeah. Did did that feel very different? It did.
It did. So I think you're right that science can be very competitive.
But I think one of the things I liked about where I was working at the time the
Med were this building was that they were already quite collaborative as a group.
So it was they already had that rapport.
But with COVID, I think I saw collaboration on a scale that I have never seen before.
And for that brief moment where we were allowed to dream of what science could be, I think it was it was just beautiful.
It was beautiful. People did not care about their publications.
I think science came back to what it should be, where the goal is, how can we help?
What good can we do for humanity? Now? It's not a case of how can I increase my publication record?
And everyone just pitched in. There were people with samples, there were people with no house,
there were people with I trained molecular biologist on cell assays and, you know, all the divisions that we would normally have.
Oh, no, I'm a molecular biologist. I don't do this stuff. You know, cells are just weird or, you know, that sort of things all gone.
And but not just that people were just willing to work.
We it was just all hands on deck and it really felt like a frontline.
And everybody just wanted to protect and everyone was doing their part.
I, I love that model of science and I don't know if I think since then I've been in a lot of papers.
We've become such as a huge auteur list.
So I'm hoping that that means that something about COVID has stayed with the scientific community.
But I left shortly after COVID, so I don't know what's what's been happening.
Yeah, so have we got to that moment?
I think we may have got to that moment, yes. So.
Yes. So you left in April 2022?
Yes. Right. Yeah. And why was that? I think like a lot of people, I, I was feeling burnt out by the whole thing.
It just it didn't stop. I was feeling a bit.
So while my community, the scientific community, banded together and got stronger,
I was feeling a bit disillusioned by the outside community and the, you know, it didn't matter what we did.
The anti-vaxxers had something to say. You know, we put a paper out there and they took the paper and twisted it.
I think there was some twisting about the cross-reactive immune, you know, And I just and I don't know,
maybe people higher up had like the kind of support to deal with all of that, but certainly not at our level.
We didn't have that support. There was no support for burnout.
There was no support for. So, for instance, some people went on furlough and the they were at home not by choice, but they were at home.
And it meant that their expenses had in a way reduced for me.
My expenses had multiplied because I used to take the train to work.
I could no longer take the train. I had to drive in to work every day.
I you know, and it was just it.
I was just burnt out. I think physically, mentally I was burnt out.
But also it's sort of highlighted another problem for me, which was, um.
I may have reached a glass ceiling for myself and I could stay and keep hammering up that ceiling.
But I think it took a bit more than my local environment to change.
For me to see a change, or at least a change that I wanted it needed, they needed to be structural changes like proper frameworks put into place.
Because, you know, I did a lot of work with COVID and I did that with a lot of my colleagues that did not necessarily look like me.
And I saw the benefits were different. How they came out of it was very different from how I was coming out of it.
And sometimes that stage was just for them, and my stage constantly had to be shed and on and on.
I see it and it wasn't because there was any it wasn't conscious.
It was unconscious the way it happened, because people could see a medic having a group and leading a group in academia.
People could see a white man or a white woman leading a group.
In academia in Oxford, no one could really see a black girl doing that.
And so it just meant that unconsciously you weren't being prepared for that or you weren't being guided along that part.
And I think I just I was just punked out.
Did you? I mean, the university does have diversity people in in the central administration.
Hello? I said, I assume that job is to address that kind of issue.
Yeah. Did you. Did you get so? I don't know how. So I got into this mentorship program with the BSA and the British Society for Immunology.
Right. Yes. And because I felt like I needed I had gone this far on my own.
I needed a mentor. Right now, it's I had gone as far as I can go on my own.
And around about the same time I was writing the paper and my experience as a black woman in academia
and they were talking about their diversity initiatives and some of the things they were doing.
And then I decided to research into it and I saw that.
Do you know the. Athena Swan Mm hmm. Okay.
So most people have heard of Athena Swan, which is the gender equality initiative,
and not a lot of people have heard about the Race Equality initiative,
and I didn't even know that our university was or had pledged to the charter just the same way as they had done with the.
Athena Swan So Athena Swan is very visible.
The race equality initiative is not, it's not, it's not that visible.
I think it's just it's there, but it's sometimes it's felt like it's just a veneer, it's not really being used.
Um, yeah. So.
Mm hmm. So you, did you start looking around for other opportunities?
I did. I did. So I started looking around. I had started to write my own while I was in academia.
I was I was still hoping that I could move on to the next level.
I had postdocs for this long. I wanted to get a fellowship, get, you know, start to start as a junior.
PI get the kind of support I had written grants.
I had some ideas that I wanted to push along,
but I because I didn't quite have the sort of support that I wanted to that I thought I needed at that time.
I started to look around, so I put a linked in that was open to opportunities.
And then I got a recruiter approached me and said, Oh, we've got this opportunity in biotech and are you ready to move?
And I think at that point I was a bit frustrated.
Sounds like, Yeah, sure, why not?
You know, and I went through with the first stage and almost immediately she came back and she said, Oh, they want to meet for the second set.
I was like, Oh, really? Okay, yeah, sure, let's do it.
I think I remember on one of the interviews I was actually analysing some data and because I didn't think it was going to,
I didn't think it was serious. I didn't think it was going to get far. And then we got to the point where, Oh, now you have to meet with the VP's.
And I was like, Oh, it's got quite serious.
I think that's when I started to struggle a bit because I had reached this glass ceiling.
I didn't want to be a quitter. And I kept thinking, you know, you think about certain things.
You think about and not to be dramatic or anything.
Well, you think about the civil rights movement. And I think, well, if they quit some of the rights we've got, we wouldn't have had it, you know, and.
I thought maybe stay, maybe push a bit more.
And then the other part was like, well, you can't sacrifice yourself, right?
But the other thing I struggled with was my identity, as far as I knew was as a scientist,
as a researcher, and not just a researcher because I could I was still going to maintain that.
But I was an academic.
I thought like an academic, I you know, everything had to be broken down into logical arguments and stuff, to the annoyance of my friends.
So that was my identity. What are you doing on the weekend?
Oh, yeah. I've got this paper to read. I've got that. And in a way, it was a bondage ball.
At the same time. It was our identity and I didn't know whether I could be anything other than that.
And so I was struggling with that. If I lost that, if I.
If I was no longer any who worked at the University of Oxford on HIV and other viral diseases, what would I be?
You know, and there's this thing about biotech as well. It's like, Oh, this is where field academics go to.
And, you know, that's that's that's what people say, you know, the ones that couldn't make it.
So I was like, Oh, does that mean I've accepted to female? Oh, just silly mindset.
But then I had the interview and then I thought about it.
I've got a job. It's a group leader position.
So exactly the next step that I was wanting in academia, I still get to do a lot of research.
It's a very important focus that the company I was working with had AIDS cancer.
I met with the team and they seem to have this clear career path.
They had a structure, so I knew from a group leader what was next.
I knew what I had to do to get to the next level.
Whilst in academia, it felt like the goalposts kept changing.
You know, it's you need this paper, that paper. And then when you had that paper, well, it took you so long.
So now you need this paper. And then also the way of setting structural things like one of the major funding bodies,
I don't remember which one now has got this grant that a lot of people who make it often have had that grant.
I think it's either the Henry welcome or the Henry Doe one of them.
But for a long time, I think it's changing now.
You couldn't apply for that grant if you weren't a British or EU citizen.
I see. And I wasn't. So it didn't matter how much good work I was doing.
Grants like that were inaccessible to me.
And it's it's those sort of structural things that needed to change.
And, you know, how long were that? And by the time I got to seven years, they like, oh, certain grants.
You can only apply within your first five years post Ph.D. So it just felt like I it
was just better to leave and then try to establish something else outside of academia.
And I have to say that it's not a choice that I have regretted at all.
It's a much better work life balance. The questions are, you know, very focussed, very translational.
You can see how it's going to impact the patients.
And I still get to do a lot of science, you know, really, really important science and you get to publish.
So and I haven't, I haven't published there.
No, but I think the focus is slightly different.
And also because I was slightly more, I was slightly more downstream of the research.
So you, you have the team that does all of the researching.
So my company did TCR Engineering. So there's a team that does all of that and what's what kind of engineering?
TCR Engineering. So the T cell receptor. All right. The injuries I was more once that's done and it's come, then I characterise it.
Yeah, yeah. Before it goes to the clinic and after after it's gone into the patients and we get the patient sample.
So that was what I was doing. So it's kind of similar to what I have been doing here, characterising the immune response.
So I haven't, no, I haven't published yet, but yeah, but you look happy.
I do. I joke, I joke to my colleagues here that when, when next I come to visit them,
I'm going to come with a helicopter and arrive on the ceiling just so that I can pull the legs of how much better it is in industry.
Yeah. No, I think I'm surprised that I mean, I can I can hear what you say about people saying that it's that you failed academics.
You go doing stupid. There's a lot of to and fro. Some people go one way and then go back the other.
Yeah. I mean it's, it's even it's more to and fro e if there's a word like that these days now because people have accepted them,
industry is making a lot of connection with academia and academia is making a lot of connection with industry
because I think academia has come to a point where it can't sustain the number of people it's churning out.
So it needs to prepare the people. It's heading out for a career in industry and in your company.
It up to me and it was up to Spinner and Oxford University. Spinner I think so.
I think so, yeah, I think so. I think the original founders would have been affiliated with Oxford, but I think almost every biotech in the Oxford.
This is a spinoff from Oxford.
Yeah. Yeah. Um, great. So I'm just going to talk a little bit about your, your personal experience of living through the COVID pandemic.
So did first of all, how threatened did you feel by infection with the virus itself just moving around in the community or, or through your work?
Personally, I didn't. And I think it this is a bit of arrogance where as a person you feel immortal.
And I was like, Well, I've never been diagnosed with any sort of co-morbidities, so.
I'll probably be fine. But I think. And to this day, I still think the same way.
I think about people who are vulnerable and people who had to shield.
And that informed a lot of my actions during the pandemic and even till now,
because it almost feels like the world's moved on and forgotten that there's still a virus.
Maybe it's not a pandemic anymore, but there's still a virus that could potentially be lethal to some people.
And, you know, the world has just said, well, tough, get on with it.
And if I was in that position, how would I feel?
You know, it's their way of life, their work.
You know, they if they couldn't go to work because of it, if they went to work and they had a mask,
you know, people would maybe jokingly, but people would make fun and just yeah,
So personally, I didn't feel threatened, but I,
I took a lot of actions because of people who were vulnerable and because of people who needed to shield.
Yeah. So I didn't I eventually got COVID, but I got COVID quite late.
I got COVID. The summer of last year.
I went for a festival. I know that that's contradicting what I said.
But in my in my defence, I was doing the debate on the immune system at the festival.
And so I went myself and my partner came back with COVID and I remember doing my because I still didn't think it was COVID.
I thought I was just really tired and I felt feverish and stuff.
So maybe it's just the cold. And then then I decided, okay, I might as well just do the test.
So I did it and I had a really, really think positive band and it felt a bit surreal.
But at the same time I felt relieved. Oh, now I can tick the box, you know, it's happened.
And then I went into a slight panic. I was like, Oh, what if I get long COVID?
Because that was the other thing. You could get COVID and you could be fine, but what about long COVID?
And then I was like, Oh, what? What about what if I did it?
No, that had a heart condition and maybe this is it. This is how I died.
But I was fine. We were better in about two weeks, I think, like most people had reported, you get better,
but for like a few weeks after, you're still breathless and you're still tired.
Brain was foggy for a while, but we did get better. We did recover.
And yeah, and thankfully, none of my No one that I knew had had it really bad.
And so that's I think we were fortunate.
But then the the work pressures were a different thing again.
So what kind of hours were you working?
So that's interesting. So we would start it was just it almost didn't stop.
We're having meetings at 8 p.m., 9 p.m. and I say that's, I think we had a good compared to the other guys down the road,
the Jenna because don't quote me on this, but I heard at some point they were running shifts and they were having to pretty much not shut down.
But we were having meetings really neat. We went so we were getting samples from all over the world.
And I remember times when I'll coming to work, I live in Bunbury, I'll come in and then we will have a sample stock at.
I had driven to Birmingham before to pick up a sample.
I was about to drive to Luton to pick up another sample because the airport at Luton to pick up a sample.
So it was quite chaotic and sometimes the work would start early enough so that you could finish by like six, seven and head home.
And all the times the samples were arriving like 4:00.
So you knew that that was going to be a really late night.
You could be here till like 1112.
It wasn't unusual that we either were here till that Leeds or we were at home and we were working till like well past midnight.
I, I remember going home sometimes when they had the claps and I kind of felt judged because I would
be the only car on the road and there were people hitting their palms and clapping for the.
And he chose and they were probably thinking, and this one just gets in their car and just drives to places.
And I was like, If only you knew.
I'm so tired from work. Yeah.
So it was it was chaotic at work.
And was there anything you could do or that you managed to make time to do to support your, your wellbeing?
I think I had my partner was a real source of support for me.
We had formed a bubble, so that was really good.
It was difficult as well because most times you try to have a separation between work and home,
but with work moving home, there was no separation anymore.
I remember taking lots of walks. I used to do lots of walks when I could.
What else did I talk to? I tried painting. I wasn't very good at it, but I felt like we didn't have enough time to consider other things.
It was. There was just always something else and we needed to move really fast.
It's almost like you need to channel the data in real time with the eyes of the world watching.
So you need to make sure that there was no mistakes and it was just hard.
We never really switched off.
And did that outweigh the sense of achievement or the sense of the sense that you were doing something important in terms of giving you up,
you know, supporting your wellbeing? I don't think so. I don't think so because I was I was exhausted, but I was happy.
Oh, you were happy. I was. I was. I was happy. I didn't that I love.
Yeah, I it was it was manic but it was.
This sort of. Let's do it. Let's do it. And then I had a lot of I had a lot of responsibility during COVID as well.
So while it was scary, I knew that I needed that.
I needed that. That's that being thrown in that situation to develop.
So that really brought out skills that I needed for the next step of my career, leadership skills, you know, deciding what's perfect and what's good,
when to draw the line, you know, between perfection and good learning how to triage things and just yeah, I think I was really I was really happy.
It didn't outweigh it at all. I enjoyed it.
And I would always tell my partner that, oh, you know, walking on the front lines, I he's like, oh, you sound you make it sound like you went to war.
I think it was like I think I've heard one person I interviewed said that when monkeypox first arose and that for just a moment, it's only a few days.
I think there was a fear that it might become very big. He said the people in his group really were showing signs of PTSD.
Yeah, that they thought, Oh no, not to get going again.
Yeah, yeah.
I think a lot of us were bummed out in the end, but we didn't realise because we're driving on adrenaline, I think, and we just didn't realise.
You know,
when you're writing publications or you're writing papers for really high publications and in fact you write in the paper at all that goes out.
It's your name out there. You don't want to have to, Oh, I made a huge mistake and I have to redact.
It is it's within.
You had to be so focussed in what you're doing so that and you were the first name on some of those papers that have also lists half a page long.
Yes. Yours is the first. Yeah. That's how I found. Yeah.
So it wasn't pressure. Yeah. It was a whole lot of pressure because you're making shut out.
Yeah. Yeah. You're like, my name is on this.
It needs to be done. Well, I need to be able to defend it years from now and see, you know, things change.
You know, certain things will change.
And this is where I would always say that science cannot be. You can't be dogmatic about it.
You need to be able to change your stance with changing evidence, but you need to be able to see with the information we had then,
with what we had, with the materials, with the reagents, with everything we did.
We took the right decision. We made the right decision. And that's what's in this paper.
And, you know, you just want to be able to sleep at night. And it was that pressure.
Yeah, but I enjoyed every minute of it. Yes.
So final question. Has the I mean, you've probably partially answered this,
but has the experience of working through the pandemic changed your attitude or your approach to your work?
In a way, yes. What it showed me is as a scientist, I've always been quite engaged with the with the public about my work,
like I said, to the annoyance of my friends.
But I think what I realised was that we don't talk enough about things we do in the lab and we, we as scientists,
we're not the best with social skills, but, but we, we tend to just close ourselves in and then keep doing our work.
And we don't sometimes we don't think about the translational side of it, but all the times we don't think about letting the world know.
We publish it in this very, very scientific papers that only another scientist would read.
So for me it's meant that I am always open to opportunities to engage with the public now,
because I think the public needs to know if they knew that the vaccine did not just spring up after a few months,
You know, it was years and years of research that went into this.
Maybe we would have had less stick.
Maybe we would have had less vaccine hesitant people if they knew that we acknowledge and we empathise with some of the we some of their feelings,
you know, some of the mistakes that science had made in the past with certain communities that were vaccine hesitant if they knew that,
okay, we understand where you're coming from. But look, we're honestly, you know, it's not we're not we're not we're not playing the game here.
We're really trying to help. That could have we had to do a lot of emergency public health, public engagement.
But I think we need to build that into our work.
And that's what I try to do now. I try to talk to people about what's going on in science recently.
What I'm trying to do is set up a podcast where I take on different papers that have
been published and then just break it down for the layperson and get my partner.
Well, well, it might be a podcast, it might be a vlog.
Not sure yet, but get my partner who is a software developer, to ask me questions about the paper.
And then if I can't explain it well enough for him to understand, then I assume I have an extremely well enough for a layperson to understand.
So that's that's what I want to do. I want the public to know how science is moving.
It shouldn't science shouldn't be closed anymore.
And I think if we can bring the public in more, we can have a lot more collaboration and a lot more advancement with what we're doing,
you know, because, yeah, they can be missing just for us.
They can, you know, we could have had people who would have said, No, I know about this work.
You know, they've been working on this many vaccines for years.
Part of the one one interesting point that someone made during COVID was, oh, if making a vaccine was so easy, why don't we have a vaccine for.
HIV and why do we have a vaccine for cancer? And those are two things I was involved in.
I was like, That is such a simple answer.
If the public doesn't know that, then we failed in engaging with the public.
You know, with HIV, it's just a really difficult virus to make a vaccine for.
And although traditional methods have failed, in fact, the Moderna vaccine was to be trialled in HIV before it was very quickly pushed to COVID.
So a lot of what we know for COVID and a lot of other infectious diseases came from the work we've done with HIV,
and that's why we could really ramp it up so quickly.
And then we cancers, there isn't just one.
You know, we have a vaccine for HPV, but we can't get a vaccine for any of the others because it's so diverse.
So if simple things like that, the public are not, I'm like, why should they know if we haven't been told them, you know?
So for me, that's that was the biggest change that I got out of COVID.
I need to engage more with the public. What?
I think you'd be very good at it. I evidence this conversation because I just talk too much.
That's just what I want.
Okay. Thanks so much.