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Genome Giants: Kay Davies – Human Geneticist and Professor of Genetics, University of Oxford

Dame Kay Davies is a human geneticist and Professor of Genetics at the University of Oxford. Davies has spent her career exploring Duchenne Muscular Dystrophy and finding an effective treatment. Outside of her research career, Davies set up the MRC functional Genomics Unit which aims to exploit genome information for the analysis of the function of genes in the nervous system. Davies also launched the journal Human Molecular Genetics in 1992 and has just stepped down as after 30 years as a co-editor. In 2019, she was invited to co-chair an important commission on heritable human genome editing.

Please note the transcript has been edited for brevity and clarity.

FLG: Hello, everyone, and hello, Kay, thank you so much for joining me today for the latest Genome Giants as we take a look at the motivations and careers of some of the most influential people within the genomic space. Today, we are joined by British geneticist Kay Davies. So, Kay, if you could, just introduce yourself and tell everyone a little bit about what you do as well.

Kay: Thank you. I’m Kay Davies. I am a human geneticist working at the University of Oxford. Until very recently, I was a Dr. Lee’s Professor of Anatomy and Head of Department and I’ve now stepped down as Head of Department. So, I’m just Professor of Genetics. But the most important point is that I’ve dedicated most of my career to trying to find a cure or effective treatment for a muscle wasting disease caused Duchenne muscular dystrophy (DMD).

FLG: Before we get straight into your career, if we just take a step back and go back to the beginning. You were born in Stourbridge in England, what are some of your fondest memories growing up? And what were you like as a child as well?

Kay: No one will believe this, but I was a very shy little girl. And I grew up in the Black Country, which is the industrial part of the central part of England. And what I remember about my childhood is always driving off with my parents and my two brothers on Saturday mornings to go out into the country and climb the mountains in Wales. And the traffic was such that it didn’t take us long to get there in those days. So yeah, those are the happiest moments of being able to cycle around in the countryside, which very young children don’t seem to be able to do anymore and being able to go to what are now crowded places in the Welsh mountains.

FLG: When did you start taking an interest in science and see it as a career for yourself?

Kay: I was very good at maths in school. So even at primary school, I was very good at maths. And my parents don’t know where that came from. But I think it probably came from my father, actually, but never mind. And my mother was a very keen gardener. So, because of that, she was always interested in looking at the frogs and the frog spawn in the pond and telling us about the flowers and growing vegetables and that sort of thing. So, I guess that background was helpful. But again, I loved solving problems in maths in primary school and I inherited that as I went to an all-girls high school in Stourbridge, which has now been demolished, actually. It is now a multi-academy trust. So mixed gender as opposed to a single girl school. But I mean, that obviously didn’t do me any harm.

FLG: You went on to do your undergraduate degree at Oxford. What made you want to do your undergraduate degree there? And what did you study when you were there as well?

Kay: I was very much inspired by my chemistry teacher at school, who was very keen on me to aim high. And only one person had been to Oxford from that school before. No one in my family had been to university before. So, she really supported me in taking on that mission. And because you have to do Latin – in those days, you had to do Latin in order to get into either Oxford or Cambridge – I had never done biology. So, the only way I could think about getting in was to do a subject like chemistry because I didn’t really want to do maths as a primary subject. It was too abstract for me. I wanted to do something where I could sort of make a difference experimentally, as opposed to theoretically.

FLG: What was that application process like for you?

Kay: Very intimidating. Yes, the application process. First of all, you have to set a proper entrance exam, and then they interview a shortlist of people that pass that exam entrance exam. And what is the interesting thing is that we have a system called A-Levels, which is the exams you pass at the end of when you’re 18. And if you take the entrance exams before you’re 18, you haven’t done a lot of the syllabus, so they have to wing it a bit and see how you answer the questions rather than look at the absolute answer. And so, I was very lucky that they invited me up for interview in chemistry. And my parents took me up and I was scared to death. But the people that interviewed me were very sympathetic. So, it worked out alright. So, you go up, you take the exam in September, you go up for the interview in December, and they give you the answer in January.

FLG: How did you get on in your course? Why did you decide to then go on and do your thesis at Oxford as well?

Kay: Well, the first thing is that there were 20 chemists that were female in a class of 200 altogether. So, there weren’t many females in that class. And, you know, I was a little bit daunted by the sheer competitiveness of people at Oxford, but then you realise you can find your place, and because of the tutorial system – that is where you get taught by a tutor with one other person in the room – it is quite a lot of challenge, and also quite a lot of support. So that really improved my confidence. And then one of those tutors realised that, actually, I was more interested in biology than chemistry. I mean, I could do the chemistry. I’m not sure I excelled, but I could do the chemistry. I got a decent degree. But the fourth part of the degree course was a year’s research, and I chose to do that in the biochemistry department. That was really a turning point for me, because I thought, you know, biology definitely, even though I hadn’t got a background in biology, this is something you could learn fairly quickly. And I really enjoyed it. So that’s why I stayed on in Oxford, because my supervisor for that final year of my chemistry degree then encouraged me to stay on to do a PhD, which I did.

FLG: You did your PhD in slime moulds – what was that experience like?

Kay: Well, it’s these horrible yellow things that grow on filter paper. But the great thing about them is they divide synchronously. Physarum polycephalum divide synchronously, which means that you can put them into synchronous cycle and if you’re looking at chromatin structure in relation to when cells divide et cetera, you have the opportunity of keeping them all in the same phase and being able to get meaningful data out. So, I spent three years doing that, and learning about general concepts of biology really.

FLG: A PhD can obviously be very demanding. What challenges did you face during that time?

Kay: Well, again, it’s great support from one’s supervisor. But the other interesting thing was that I didn’t think I was good enough to do a PhD. So, I applied for teacher’s training. And I went to the teachers training interview in Oxford, and the man who interviewed me said, ‘Why don’t you do a PhD, because you won’t be able to do a PhD later in your life, and you’ll really enjoy it.’ And of course, you do really enjoy science, because science is discovery. It’s different every day. And so, I really found my feet when I started that PhD. And he held the place open to do teaching. Knowing that I actually had that as a safety net, I suppose might have helped. But of course, the experiments are always challenging, because, you know, two thirds of them don’t work! But that’s normal, you realise, in life, that’s normal. So, I think a PhD is really good training for responding to challenge and having enough confidence and also collaborating with colleagues.

FLG: You did your degree and then your thesis at Oxford. You have also had various roles at Oxford, including Professor of Anatomy and now Professor of Genetics. Why Oxford? What has attracted you to this institution for all these years?

Kay: Yeah, that’s an interesting question. So, when I was doing my PhD, my husband went to Paris, because he had an opportunity to work with a Nobel Prize winner, Barton (Sir Derek Harold Richard Barton). And at that stage, I decided that, maybe, I better go to Paris because I was commuting back and forth. And I really enjoyed the time in France too. And that’s where I met Bob Williamson, who was doing a sabbatical in the Pasteur. And he was going back to St. Mary’s Hospital in London, which is where he was professor, and he invited me to take up a postdoc there to do genetics. That stage I didn’t really know, I mean, I knew what a chromosome was, but I didn’t really understand the implications of genetics. And it was just as people were beginning to think about mapping the human genome at the very early stages. So, there was an opportunity there to come into the field – not that I realised at the time – at the very beginning and work with others to try and make an impact.

So, I didn’t want to go back to Oxford at that stage, because it was so sexist in those days. I mean, I think every place was, but because I just left there, I just felt it was perhaps more sexist than others and it probably wasn’t. And my husband had a lectureship in Oxford. So that was a bit of a pull. But so, I didn’t want to go back. I commuted from Oxford to London on a daily basis instead. And that worked out really well, because with Bob Williamson, it was very exciting. He knew who to collaborate with, whatever technique you needed. So, if you wanted to make a chromosome library to find the first diagnostic markers for Duchenne muscular dystrophy, the disease that I’ve been working on, then he knew the people in Glasgow to go and collaborate with, and that was really enabling. And so, it was great fun. And we all worked together. And we had a very good clinician who could collect the families in which we could do all the linkage analysis. And the late Peter Harper worked in Cardiff. And again, that was another extremely good collaboration.

FLG: What has it been like for you watching the field of genetics evolve?

Kay: Very exciting! Because every day was different and there were lots of different personalities. There’s an awful lot of competition, but an awful lot of collegiality. So, there was an awful lot of drinking in the bar at the American Society of Human Genetics, for example, and exchanging ideas. So yeah, it was great fun. It still is, actually, in human genetics, because it’s changing so rapidly.

FLG: Would you say that you’re a competitive person yourself?

Kay: Yeah, sorry, but that’s innate, I can’t help it. I’m very driven. I get that from my mother. I remember telling a radio interview that and she said, ‘No, no, no, no, I’m not competitive’. She is!

FLG: What was your early career like after your thesis? What challenges, if any, did you face?

Kay: I think the most important step for me was when I moved back to London. I was working on a disease called cystic fibrosis (CF), which is a common single gene disorder, except we didn’t know which chromosome it was on. So, we knew we had a difficult problem. And we met with the chief executive of the Duchenne muscular dystrophy charity, as was then. And Paul Walker said, ‘Well, why don’t you use DMD as a model for CF and prove the technology on that’, which is what we did.  So, the CF Foundation were funding me to do a DMD project. But I think the key point I’d like to make there though, is he then introduced me to the families and the patients and the clinicians. And that’s what makes a difference. It is that collaboration, all the way from the people working on the bench, all the way through to the bedside. Even in those early days, it was a really refreshing collaboration.

FLG: For those who don’t know, would you be able to discuss what Duchenne muscular dystrophy is?

Kay: Yeah, this is a disease that affects boys only because it’s on the X chromosome, and females have the compensation gene on their other X chromosome. And boys go into a wheelchair, generally about the age of 12. They now live into their 30s or 40s. It has got nothing to do with genetic therapy, it is better management. But nevertheless, they have hard lives because they end up going into wheelchairs. It’s progressive muscle weakness; a lot of them die of cardiac defects or respiratory failure. So, what we need to do is to try and find an effective treatment to stop these boys from going into a wheelchair and even if they do go into a wheelchair, can we keep them using their arms so they still have independence, in the sort of wizzy wheelchairs that they can design these days, and then live a good quality life.

FLG: What made you interested in studying this condition and still remain interested now?

Kay: I think it’s motivation. You’re driven by the patients and their families. Indeed, families continue to support the research, even when their children have died. And there’s enormous spirit and collaboration of several groups around the world who work together to try and achieve this goal. And so, knowing that you could make a difference collectively was a huge incentive.

FLG: Patient voice is so important. How can organisations and researchers ensure that they   incorporate patient voice a bit more?

Kay: I think almost in every case, they need to involve a parent of a patient. So, for example, I used to chair an exon skipping consortium. I don’t do exon skipping anymore (exon skipping is one of the strategies for treatment in DMD) and the first committees that were set up by Muscular Dystrophy UK had on it a parent of a Duchenne muscular dystrophy boy. And that was very important, because he could tell us exactly what it was like, what are the most important symptoms that you have to think about treating.It is valuable to get a treatment that may not be completely effective, in the sense that it will cure the disease, but it will make a difference to the quality of life of his son.

FLG: Would you be able to discuss some of the prominent research you were involved in in the early days?

Kay: Well, besides the diagnosis, because the first DNA markers for DMD were developed very early on in the early 1980s, with colleagues mainly in Leiden, and Lou Kunkel’s group in Boston. Once the gene had been cloned, then we focused on using exon skipping, which is where you trick the machinery in the cell to skip over the mutation, which are mostly deletions in this disease, stitch the gene back together again so it’s still in-frame. You make a smaller protein, but it’s partly functional. So, we developed that technique. And then my postdocs left the lab and set that up themselves. We discovered a protein called utrophin, which is very similar to the gene that is mutated or missing in Duchenne Muscular Dystrophy patients. And we realised that if you could increase the levels of this very similar protein, you could compensate for the lack of dystrophin. And we proved – and it’s always easy to cure a mouse – that if you do this in the mouse, you do, essentially, cure the mouse. Not completely, but you do greatly improve the pathology. So, the idea is to find a drug that will increase those levels of this other related protein called utrophin to compensate for the lack of dystrophin in these patients.

FLG: What are the current therapeutic strategies?

Kay: Most of the agents that are used in the clinic at the moment, and I won’t go through them all because there are a lot of them, either deal with trying to decrease the amount of fibrosis, dampen down the inflammation in muscle, or stop the necrosis. Steroids like prednisolone, new steroids coming along, like deflazacort. So, there are oxidative stress and lots of aspects of the muscle degeneration that these other pharmacological agents aim to, at least, minimise. And of course, they will extend the time that these boys have before they go into a wheelchair. So that’s quite important. But what we want is a genetic therapy. So, several drugs have been approved for exon skipping, produced by Sarepta Therapeutics, which skip the most common exon, exon 51. And now some of the other exons that affect other groups of patients. PTC Therapeutics have got a drug which is in the clinic, which reads through stop codons. And there are 10% of patients that have stop codons in their gene, so that’s very helpful. But at the moment, they only marginally increase the lifetime, or the time in which they go into a wheelchair. What we want is an effective therapy, gene therapy, which is now being pioneered by three companies, Sarepta, Pfizer and Solid Biosciences, in the clinic. It’s not been approved yet, but they’re getting spectacular results.

And that’s where they take a smaller gene because it’s got to be smaller than dystrophin, which is too big to go into the conventional virus. And so, they’re using so-called microgenes delivered by a vector like AAV to replace the missing dystrophin in those patients. But it is interesting because in the early days, one of those collaborations with clinicians, Sarah Bundey from Birmingham sent us a sample of DNA from a patient who was very mildly affected. And she sent us lots of samples, she said, ‘This one will just have a small mutation, a small deletion, because he’s so mildly affected. He showed no symptoms until his 40s.’ And actually, he died in his 70s – he was in a wheelchair by then. But the amazing thing is, he had 50% of his gene missing. And we recapitulated his gene in the mouse, and it showed if you recapitulate this gene by stitching it together, you could show that it did actually prevent the pathology in the mouse. So that gene, because it works in vivo in humans, was the basis that many other investigators – Jeff Chamberlain, Sarepta, Pfizer – made microgenes from. They nibbled even further bits out of this guy’s minigene so they could eventually fit it in the AAV vector together with a promoter. So that just goes to show that that partnership between clinicians, and knowing how meaningful some of these observations are, made sharing that information so that others can build on it in their way has led to an effective gene therapy that we hope will be approved for DMD in the near future.

FLG: Apart from obviously, as you said, the size of the gene, what are some of the challenges that exist trying to find a genetic therapy for this condition?

Kay: Okay, of all of the diseases that needs a cure, this is it. Because first of all, the mutation comes up in the populations all the way around the world all the time; it’s got the highest mutation rate. But to answer your question more directly, it’s also one of the largest genes in the genome. Dystrophin is one of the largest proteins in muscle, not the largest. And if you want to cure muscular dystrophy, you’ve got to put that gene back in every single muscle in the body to be really effective. And as I mentioned earlier on, these boys have cardiomyopathy as well. So, it means you’ve got to deliver it to the heart. So big gene, big protein, and a lot of tissue, and try and do it without an immune response. That’s a huge challenge!

FLG: You helped to develop a test to screen for foetuses whose mothers were high risk of carrying DMD. What was this process like?

Kay: Well, we needed to get the markers that were close enough. These were the very early days, the DNA markers. Nobody knew whether they were really going to work very close to where the gene was, because we hadn’t then cloned the gene. And this was before Lou Kunkel identified the dystrophin gene. And so, with colleagues in Leiden, we could get a marker on one side of the gene and a marker on the other. So, the chances of double crossovers were small. And we had a lot of families that really did want to know what their carrier status was because there wasn’t a carrier test. And also, some of these families had actually aborted all males because they didn’t want an affected male. And that was interesting, because the executive director of the muscular dystrophy campaign then was a Catholic, and he didn’t believe in prenatal screening. But he could see that this was saving 50% of the boys that would otherwise have been aborted. And so together again, we collected the families. Peter Harper in Cardiff collected the families with all the documentation so we could demonstrate that these particular two markers followed the disease 99% of the time, and therefore we were able to do carrier status, as well as prenatal diagnosis from very early on as soon as we’d identified markers that were close to the gene.

FLG: Aside from the amazing research that you do, you are also Executive Editor of the Human Molecular Genetics journal. What has this been like for you because it’s so different from the research side?

Kay: Yes, it is. It wasn’t to start with, and I don’t think I would have started the journal if I hadn’t had a colleague who was also working on the X chromosome at the time, Huntington Willard. He was in America. Because there was one person in America, and I was obviously a British person. And he was a driven person as well. And OUP (Oxford Academic Journals) were very supportive, because Nature Genetics was actually launched roughly at the same time. And if you start a journal from the beginning, it’s not much work. So, it gradually ramps up. And the field really needed a place to publish this new genetics – mapping genes and identifying new genes. And so, it’s gone on and on. And Hunt stepped down after the first 15 years, and Anthony Wynshaw-Boris took over as Editor and I’ve worked very well with Tony. But the journal is 30 years old this year and so we’re having a 30th anniversary issue.

But I’m stepping down as Editor and handing that over to Charis Eng who’s been an assistant editor for some time. So, the journal will go off in new directions. So why was it good to do? Because if you’re a journal editor that is a major publisher of papers, people come and talk to you at genetic conferences, because they want to know whether you’re going to publish their paper. So, I got to know a lot of people. I mean, some people I knew already, because I collaborated with them. But over the last 10 or 15 years, younger people come up and talk to me, so I get to know them as well. So that’s a huge bonus in spending a lot of time running a journal, because you’re contributing to the community. But the community is also keeping you up to date with what’s going on and what the most exciting thing is.

FLG: People must be trying to sell themselves to you!

Kay: Absolutely, and good for them!

FLG: What has made you want to step down?

Kay: Because I think it’s time for a younger person to take it on, and a more active person, because I’m involved in a lot of administration now, and hopefully contributing by mentoring and being on boards. And I think if someone’s at the coalface of human genetics, with all the latest technology, single cell biology et cetera, they’re in a better position to take the journal forward. And that’s why it’s great to have Charis take over from Tony and I.

FLG: What has it been like for you adopting that mentor role?

Kay: I think, because if you’re a woman in science, you’re in demand as a mentor. So that’s the first. So, you got to make sure you don’t get overwhelmed by the requests. But it’s obviously it’s a very pleasurable thing to do. And what is really good is that even your graduate students, not everyone, not everyone needs to, but you know, one or two of them still write to me, write to me on my birthday, say what they’re doing, some of them are not in science anymore. You know, the person that identified that minigene that I just referred to as the basis of gene therapy, now does environmental things in France, and her daughter is an Oxford student. I think she’s doing law; I’m not quite sure what she’s doing. So, I meet her again, we’ve never lost touch. And it’s wonderful to just watch all these different careers. And to watch those different careers enables me to say to other people, you don’t have to follow me in an academic career. You could join industry, you could go into the environment, you can do almost anything with a science degree, actually, because you have a very analytical scientific brain. You know how to meet challenges. With a bit of luck, because you’ve had to present your data, you’ve got some communication skills. I think I enjoy it anyway.

FLG: You were invited to co-chair on the commission on Heritable Human Genome Editing, the report which came out late last year. How were you approached? How did you feel about being involved?

Kay: So, these are the two academies, the National Academy in the States, and the Royal Society, following the experiment from China with these babies born and the uproar. Even following the report that had been written from the National Academy of Sciences previously, there was a real urgency to examine the science to see whether it was safe enough, or ready enough, to go into the clinic. And then perhaps to just give a little bit of a steer as to, because progress is so fast, if we did reach the point where it was safe, what would be the mechanisms to try and get into the clinic. So, I was approached to head that group, with Rick Lifton as co-chair, by the biological secretary of the Royal Society, John Skehel, who knew me. And you know, they needed a human geneticist, and indeed, Rick Lifton is an excellent, top flying human geneticist. So, it was fun to work with him. And we had some say in who was on the committee, but obviously, it was a lot of steer from the academies. And we included a lot of academies – as many academies as we could – from around the world.

FLG: How long did this process take? And what was involved?

Kay: At the very beginning, we said, ‘Okay, there are going to be three meetings. A public consultation will be the first meeting, followed by a meeting of the commission, and then we would write a draft of the report, meet again, and then we’d almost finalise a draft, and then meet again.’ So that was three meetings, and it would be all over. We’d start in August 2019 and then finish in the following March. But of course, COVID intervened, so there was no chance of that happening. But the huge advantage was, if you had these Zoom meetings, everybody could turn up to Zoom meetings. And we didn’t have to confine ourselves to the three meetings we’d originally envisaged. We had the second one, but not the third. And trying to get consensus was hard, you know, where do you draw the line between what diseases should be treated first, and so on.

But we got together on Zoom, and if we disagreed, we agreed to disagree. And we came back a week later and went round the circle again. And it was such a good team. And I think with Zoom because, of course, there are language and cultural differences too across the commission, that allowed everyone to have their say, and everyone really got to know each other. So, it was an incredibly rewarding experience because everyone piled in with their views and debated their views. And so, I think we ended up with a really internationally representative set of views with those recommendations. And let’s hope now that that will stop other rogue scientists coming out with inappropriate applications of this, and will provide some guidance in an international sense, because you can’t tell other countries what to do, but perhaps will encourage the development of a framework that will allow more ethical debate and science debate as we move forward. Maybe society doesn’t really need this technology! And I think we’ve started the debate now. And I look forward to continuing to participate in it.

FLG: Overall, are you happy with the outcome?

Kay: Yes, I was. I mean, I think I’m somewhat disappointed now because it’s sort of buried by COVID. But in the sense, you know, when the world becomes a better place, she says, hopefully, post-COVID, then people can look at this. And the WHO report, which is looking at somatic cell editing, as well as germline editing, is going to come out soon. And that, of course, has been delayed by COVID. And I think the two reports together will form a basis to move forward and that’s really important.

FLG: In your opinion, what will the future of human heritable genome editing look like? How do we ensure that there is good communication with the public and that we get them involved in these discussions as well?

Kay: We did involve the public, but we didn’t have a patient group on the committee. And I think going forward, we need to involve those groups as much as possible. The difficulty, as we say in the report, it’s only applicable in those cases where parents can’t have a genetically related child by any other means. So, for example, for an awful lot of the genetic diseases, if you want prenatal diagnosis, you can do that by IVF. Now, sometimes IVF doesn’t work, well often in some couples, and therefore, they may have to result in heritable genome editing. But our recommendation is that, in the first instance, it should only be used for serious, monogenic disorders if the science is right. And we’re a long way from being able to monitor off-target effects, or even on target effects, which don’t just change that one sequence you want to change but very often change other things inadvertently. So, there’s a lot of basic science that has to be done. We have to do that in human embryos, because what happens in a human embryo is different from what happens in a mouse embryo. So, it’s a long road to get somewhere that safe. But, you know, somatic cell therapy, where you’re not doing the germline problem, is already showing great promise for beta-thalassemia and sickle cell anaemia, and there will be more.

FLG: What challenges do you think remain in this field? Because these rogue scientists tend to have a negative effect on the field and public perception. What do you think needs to be done in this sense?

Kay: I think if there are many national committees that look at this, they can create more transparency within the field. So, people working in this field are continually exchanging ideas, and so mostly people will know who’s doing what around the world. And up to 2018, when those children were born, there was not much exchange of information, because no one knew that those experiments were going on. I think that has completely changed. Ethics committees will publish an awful lot, as much as they can at least, not the bits that are not confidential, about what trials are proceeding, so everyone will know. It’s up to the individual country about what they approve, but hopefully, there will be these international guidelines and there will be international discussions about what we think is good for society and what is not, taking into account that there will be cultural differences around the world.  

FLG: Throughout your career, your contributions to the field have been noticed with various   awards. What has been your favourite achievement?

Kay: My favourite achievement was discovering the utrophin gene with the postdoc, Don Love, in the lab. I can still remember him coming in on a Sunday morning and he said, ‘Look, this doesn’t map to the X chromosome, it’s something different’. That was a really exciting day, a eureka moment, if you like. And then I was given the Muscular Dystrophy Association award that year for the most significant progress in muscular dystrophy. So that meant a lot.

FLG: How do you think our understanding of DMD has evolved? Do you think that it has rapidly evolved since we first discovered the gene?

Kay: Yes, and it’s still evolving! I don’t think we understand everything about muscular dystrophy. And there’s a lot of focus on skeletal muscle. But there will be smooth muscle connotations. And 30% of patients have some sort of mental impairment. Now, that’s not so important when you’re trying to develop the first treatment. But in the end, what we want is a treatment that will early enough prevent any of those other symptoms, whether it be in smooth muscle, cardiac muscle, skeletal muscle, and so on.

FLG: How did you feel finding out you were becoming a Dame?

Kay: That came as a big surprise, as I’m sure it does to everybody. I was in my kitchen. I had an envelope which had got ER on it. And I thought, ‘What is this?’ So, I was completely amazed to read, where it said, ‘Your name will be put forward to the Queen for approval, so don’t reply to this letter.’ And it’s confidential until the birthday lists are announced. So, you go through this period where you don’t know whether anyone registered to the fact that you’d like to accept this because you’re not allowed to reply to the letter. And so, until your name finally appears, and you’re not allowed to discuss it with anyone else except your nearest of kin. So, I was in Australia when the list came out. I was staying with friends in Margaret River as part of a conference, so I will never forget that moment.

FLG: What was the day itself like?

Kay: Yeah. So that’s when you realise, you wonder what the Honours list is for, except it’s obvious it’s to reward people for doing good work. But the fact that you got lots of people, from the post office lady and the paper boy, all the way through to people that have done great things in the armed forces, or whatever. It really encapsulates a lot of society. And so, it’s very impressive. And so, you go to Buckingham Palace, amazing loos in Buckingham Palace! It’s just a great historical event. And it’s extremely well managed. And I was fortunate to have the Queen herself. And she asks, you know, ‘How did you get into this field?’, the usual questions. And then you have to stand up because you’ve curtsied and hopefully go backwards without falling over in front of a few 100 people. So, it was a bit nerve wracking, but I really enjoyed it.

FLG: Yeah. I’ve been watching The Crown recently. I feel like I’m all clued up on the royal family.

Kay: It’s very ceremonial, absolutely.

FLG: Are there any notable people throughout your career that you felt inspired you or helped you   get to where you where you are today?

Kay: I think watching Dorothy Hodgkin in Somerville College, because I was a student of Somerville. And I mean, she had arthritis towards the end, but she was always inspiring young women, in particular, to aim high and do what they were passionate about. I think that’s the important thing. Don’t do things just because you think it might give you a reward. Are you really interested in it? Are you motivated and driven by it? And she certainly was driven, right to the end. So, she was an inspiration. Bob Williamson for his energy. You would say, I need this by this afternoon as a joke. And he would try and find it by this afternoon by ringing up his network and finding out who you could collaborate with to go on that extra step. And David Weatherall, I was fortunate to work with the late David Weatherall, who was in Oxford, and set up the Weatherall Institute of Molecular Medicine. And it wasn’t just David, it was the collegiality of clinicians working in that Institute applying basic science to the clinic. And you know, people like Doug Higgs that work on thalassemia, that don’t work in the same field as me, but use similar technology and exchange ideas. I was very fortunate to work there.

FLG: What has it been like for you as a female in this industry? And what would you say to other young aspiring females?

Kay: That it’s improving all the time. It used to be very difficult. But the thing is, never be put off, and never feel bitter. If someone puts you down – I’m sure that happens to men as well as women, it probably happens more often to women – but you just need to move on and have the confidence to move on. And, if you’ve got a very supportive family – and I had a very supportive husband, who just threw me back in when those sorts of things happened and just said, ‘Forget about it, forget about them’. I used to go to scientific meetings where men used to say to me that I should be at home, either looking after my husband, or looking after my children. But of course, they don’t do that anymore, fortunately. And it’s not because they’re not allowed to. They don’t even feel that way, because men are more involved with every aspect of life. So, embrace it, don’t feel bitter, and believe you can do it, and ask other people how you might do it if you think you’ve got stuck. I think that’s the key. So different mentors at different stages of your life are very helpful in that regard.

FLG: What are some of the major life lessons that you have learnt along the way that you would want to tell your younger self?

Kay: I always tell myself, and actually, people have told me, I need to be more patient. I need to play the long game. And that’s true, I would say politically, but if you want to achieve something, you don’t always achieve it in the first two or three years – you need to have a longer view. So, it’s sort of ABCD. You don’t always have to go ABCD, sometimes you can go A to D, but that’s rare. So, I think a little patience, and find other ways of getting there. I would tell my younger self to try and be a bit calmer and think if you can’t get to A to D, try B and C, try the detour because you can still get there in the end. But I mean, the passion and the drive are always there. So, my younger self would never change from that, I don’t think.

FLG: Outside of your career, what do you like to do in your spare time?

Kay: A lot of walking and music, mainly, going to concerts. My second husband and I, you know, seven-mile hikes! Actually, one of the things that lockdown has taught us is how beautiful Oxford is. It always is beautiful, but there are no people in it at the moment. But even the canals and the rivers, I mean, there are places you discover. And we’ve got a flat somewhere in the south of England, where we can also do a lot of walking. So that’s a real passion, getting outside into the open air and walking. That gives us both a lot of pleasure. And you can of course Zoom from anywhere, so that means you can go and stay somewhere, do some new walks and still Zoom in the afternoon!

FLG: What type of music do you like? And are you missing concerts at the moment?

Kay: We are going to the opera for the first time tomorrow, a local opera called Garsington. We are guests of the Chairman and I’m really looking forward to that. Of course, it will not quite be the full experience, but music for me just makes me relax. And so, I always have to have my moment every week, where I am in my study with my headphones on and I’m playing something full blast. And, yeah, that could be Sting, or it could be opera. Sometimes it’s jazz, but rarely. It usually is opera; it just brings me out of myself. And if you’re in trouble or something is very difficult, in my case, you can unpick the stress by listening to the music, you just have to choose the right sort of music.

FLG: I am the same, I love music as well. This is a bit of a silly question. But if you could turn your  life and career into a book or a film, what would the title of that be called?

Kay: I thought a lot about this one! I don’t know. The hard journey from diagnosis to therapy, because I’m not quite there yet. And I don’t intend to stop until I’ve got to the therapy. But it is a long, hard slog, so never give up! And that’s what I would tell my younger self and a lot of young scientists out there. Things are advancing quickly, science is different every day and it’s fun, but you’ve got to be tenacious in order to get to the goal at the end.

FLG: Thank you so much for joining me today, Kay, it’s been really great talking to you, and keep up the great work that you’re doing. And don’t lose that determination!  

Kay: I won’t! Thank you so much, it’s been a pleasure.

FLG: Thank you so much!