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And. Welcome to the Centre of Personalised Medicine podcast hosted by John Lee, president of the Oxford Personalised Medicine Society, and me,

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Dr. Monica Cooper, junior research fellow at the centre, the Centre for Personalised Medicine KPM is a partnership between University of Oxford.

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Welcome Centre for Human Genetics and Suntans College, Oxford.

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The KPM provides opportunities for students, academics, clinicians and the public to explore the benefits and challenges personalised medicine.

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In the second episode of our Meet the Advisory Board series, we have the honour to talk today Mary,

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after she started her career as a chemist with a focus on sustainable energy production and solar energy conversion,

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and taught and research at both Oxford and Cambridge University when she left academia.

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She had a number of appointments amongst them, chairing Cambridge University Hospitals,

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NHS Foundation Trust and currently chairing the Science Museum Group.

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In 2012, she was appointed Dame Commander of the British Empire for Services to the NHS.

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We had the pleasure to talk to her about her experience of working in academia and industry,

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her views on personalised medicine and clinical practise, and much more.

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Thank you so much. Then Mary Hart joining us today. It is our honour to have you with us.

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You've had a really interesting and exciting career path. What would you say is the most notable moment in your career?

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I have had an interesting and diverse career, and I think one of the things I would say is that when I've changed course, I haven't always.

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At once thought I've done the right thing, but I think the most.

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Notable thing did do was to be offered and accept the chairmanship of Cambridge

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University hospitals because that really set me off in a new direction of chairing,

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being in charge in some ways of a large and complex organisation.

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And I found that an enormously interesting thing to do.

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I was very privileged position to be in a position of considerable influence to do good, and I really enjoyed that.

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So I think probably that move, that career move was the most notable thing I've done.

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I've switched to a bit of a different part of your career first.

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You've done a lot of work as a chair of the Board of trustees of the Science Museum Group.

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This is a hugely important part of public engagement in the historical aspects of science.

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But as a scientist yourself, how do you think science can also increase public engagement with the modern scientific development?

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It's a good question because, of course,

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the very nature museum tells you that the Science Museum and other museums are going to be partly about the past.

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And the one a wonderful collection of objects that we have in the five museums, in fact,

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in the Science Museum Group are the world's most major collection of scientific technical engineering artefacts,

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dating mostly back to the 18th century and beyond more recently.

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But on the other hand, a strategic document and our mission statement is about inspiring futures,

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by which we mean inspiring the futures of young people to be literate in and sympathetic to STEM subjects.

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We can't all we shouldn't all be scientists, but we should all be sympathetic and literate in science,

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just as we should all be literate in English and mathematics,

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because the extent to which our culture is underpinned by STEM and digitally underpinned is ever increasing.

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And it's a huge part of one's life, I think, to have these tools at one's disposal.

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So in the museum, we aim to inspire people about the future and to build what we call science capital in individuals and society and in our visitors,

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both our physical visitors and our virtual visitors, of which there are over 11 million.

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By igniting curiosity about the wonderful inventions that we show, the wonderful bits of kit,

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the wonderful people who have made these discoveries created these improved devices and machines and equipment to make people appreciative of science.

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Now nobody is forced to go into a museum, not like you're forced to go to school when you're a youngster.

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And so we have to do all this in an informal and engaging way.

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And so going back to your question about engaging people, we put on a lot of events at the moment, virtual webinars about things.

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We've had a very interesting series of blogs from the science director of the Science Museum, Roger Highfield, on covid.

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As the pandemic has unfolded and museums have to, as it were,

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refresh their appearance and not seem at all cobwebby because the first rule of running

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a museum is you've got to get them in through the door or through the virtual door,

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and then you can engage the museum, which still feels a bit like something as gate captive and way.

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Yes. So we are the most family friendly of all the national museums in a normal year.

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And let's hope we get back to one of those soon. In a normal year in book school groups with their school teachers ready for a learning experience,

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we have through the doors of our five museums, over 600000 schoolchildren every year.

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So we do operate at scale and have a duty and a responsibility to those youngsters to ignite their curiosity.

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Perhaps one in 100 is influenced to become a scientist.

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Moving on to our next question.

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Having spent 10 years touring the campus, university hospitals, NHS trust and spending time directing the Addenbrooke's Charitable Trust,

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how does your perception of health care in the UK changed both before and after this release?

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Well, when I took up the chair of Cambridge University Hospitals, I had already been on the board for 10 years.

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So I had been associated with Addenbrooke's Hospital and the Rosie,

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which is the Associated Maternity Hospital since 1993, during which time the NHS itself changed a lot.

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So when I first became involved, it was when the whole notion of NHS trusts were new.

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That's to say organisations with boards that had a reasonable degree of self governance,

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whereas before there were regional health authorities and the hospitals were run very

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much as units within those bigger organisations by managers rather than boards.

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And then came along the so-called Foundation Trust Movement, which again gave trusts who got foundation status,

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more autonomy and the freedom to borrow money, for example, which is quite important if you want to develop your hospital.

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So I think it would be fair to say that when I went on the board back in the early nineties,

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I knew remarkably little about the structure of the NHS and I learnt as I went along and it evolved as I went along.

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So fast forwarding to now there have been.

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Well, a number of organisational changes over the years, the internal market,

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so-called internal market between so-called purchasers and so-called providers was introduced.

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The idea to introduce competition between different hospitals and organisations for the same patient, if you like.

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So you'd have to offer better terms. That idea has fallen out of favour and it was organisationally complex.

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And the idea of integrated care has come in, so I think what I would say of the NHS now,

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apart from the fact that I think it has coped remarkably well with the covid epidemic.

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Is that it would be good to have a period.

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Of organisational stability, because these huge reorganisations are very time consuming and quite expensive,

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and I think that has sometimes been a tendency when things don't seem right to

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change the organisation rather than change the way that organisation does things.

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But I am a big fan of the NHS.

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It is a noble ideal that is largely realised in practise that people are treated without charge to them at the point of need,

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not according to the ability to pay. That being said.

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There's quite a lot of work to be done on public health in the United Kingdom.

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We are the most obese nation, is it in Western Europe?

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And we saw that, I think, in the very bad mortality statistics in the first couple of covid waves where being obese or having diabetes,

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which often goes together, of course. And having hypertension is a big risk factor.

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So I think there is a lot of work to be done on public health.

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Maybe recovering from the pandemic will spur us on, but it's often been said that the NHS is not a national health service,

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it's a national sickness service, which is, of course, true.

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You don't go to hospital unless there's something wrong and preventative medicine and healthy lifestyles and so forth.

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I don't know, it's something we don't. Do very well.

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So if I was still involved with the NHS, which I am actually, but not in the way of,

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you know, having to influence or seeking to influence the direction of travel.

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In terms of what gets the money. It would be to.

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Work on on public health and public health improvement.

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What I hear is that your work has influenced you and things, and we noticed that you spent time in academia as well as the cross industry.

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How do you think these experiences compare? And would you recommend that to people to spend time in both sectors?

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Yes, I would. I think that most people nowadays, perhaps involuntarily, as much as voluntarily, will have several career changes of direction.

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The days when you sort of joined up ISSI fresh out of your chemistry finals in my case,

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and sort of stay there until they give you a gold watch on retirement that just gone.

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And so people need to prepare for a more diverse career, which I have had more by a series of accidents than by grand design, if I'm honest.

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But so I think that a grounding in academia, particularly in a scientific subject.

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Is a good base to go out into business and industry with,

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it doesn't equip you with the legal and accountancy skills that you will need to pick up a bit crazy legal skills,

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but a grounding in academia and more particularly in science, gives you accuracy, numeracy, respect for evidence rather than opinion.

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Less usefully, it makes you obsess about details until you've got everything right or at least right to own satisfaction.

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And typically in business and in industry or indeed as head of a hospital or a museum,

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a lot of things kind of float across your desk and you have to make a decision often based on what you would regard as a scientist,

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as imperfect evidence. So you have to slightly loosen up.

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And the other thing, of course, that's hugely important in business and public life is the ability to be a good team player.

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That's not something you necessarily learn in academia. It's not what they're about, academia is primarily about scholarship scholars.

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I mean, they're not necessarily natural team players.

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They can be quite loners sometimes. But I've never I've always found my scientific background an advantage.

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Or maybe it's fair to say that whatever your background is, if you halfway smart, you turn to your advantage.

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But for example, when I was chair of Cambridge University Hospitals that has a medical school, it is a university hospital.

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It has a huge clinical and biomedical research penumbra around it.

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And I was equipped to understand what was going on and was sympathetic towards it.

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And of course, in the science museum.

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Well, the that the alarming thing about that is people somehow expect you to know all the sciences and you come from one specialist background.

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I do remember when I was made chair of the Science Museum Group, my eldest son said to me, said,

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well, mom, he said, I know you know a bit about chemistry, but what do you know about Railway's?

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And I had to admit I didn't know a whole lot.

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But as the National Railway Museum and Locomotion in County Durham in our group, I've learnt a good deal about railways now and very fond.

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I am of our great steam locomotives that we have. So now we'd like to ask you about your experience of Oxford.

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You've been closely involved with Oxford from your studies at Sundance and now current students at the college by the Busari.

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What do you think some of the biggest changes Fox-Pitt students have been since a time here when I suppose

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the most obvious and biggest change in terms of social impact was the college and the university going mixed.

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So when I was up at St Ann's, which was 1962 to 1966, all the colleges were still single sex.

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And it wasn't until the next decade that the first of the men's colleges went mixed.

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So the university had a different flavour, the colleges had a different flavour and there were fewer women about it.

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Striking actually that when the move to go mixed was mooted, the women's colleges were against it, largely because they feared.

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That with men's colleges taking women, they wouldn't get the kind of cream of the cream that they were able to get when there were so few places,

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relatively speaking, for women at Oxford and Cambridge. But anyway, that was a great social revolution that I didn't live through at Oxford.

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But then when I came to Cambridge in 76 to teach,

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that was just the beginning of what you might call an almost a stampede of the former men's colleges to admit women.

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And I was I think I was the second woman on the high table of Trinity College, Cambridge, which rather characteristically, when mixed in a very.

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Prudent way by, first of all, getting people like me as joint appointees,

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so I was a lecturer in chemistry at Trinity and a fellow at Newnham before they went completely mixed.

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So that was one change. Another, and it's not specific to the university, but I think it is hugely altered,

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the experience of being a university student is the ubiquity of electronic devices.

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So computers, smart phones, social media, none of that was around.

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I remember the first little computer I used in my work.

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It was in the early 1980s and it was an apple with about sort of 2k of RAM, I can't remember.

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But it was I just did the most simple little calculation. So I suppose, again,

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I'm talking from my own perspective as a scientist that has to actually change the

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experience of being a student and what you need to learn and be proficient at.

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And then the job market has changed. In my day, it was very easy.

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The major employers did what was called a milk round. They came and milked the universities of their graduates.

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It was very much a buyer's market for graduates.

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And now it's so different. Much harder, much harder.

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Obviously, some disciplines, engineering, computer science and so forth, as it were, produced more easily employable students.

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And the other thing was many things that have changed student fees in my day, you know, a grateful nation largely financed you through.

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I had a state scholarship and the college gave me a scholarship, too.

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So I didn't cost myself or my parents, you know, much money.

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And student debt is something I was never saddled with. So life has changed.

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But on the other hand, many more young people now have the opportunity to go to university, and that's good.

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We would like to move now to some questions around personalised medicine as we are the Centre for Medicine.

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What kind of projects are happening in personalised medicine right now that you're personally excited about?

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Well, so personalised medicine has been quite a long time coming, so I'm old enough to remember, though not very clearly.

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Watson and Crick and their great discovery and then the early hopes that the basis of disease would be unlocked by knowledge of genetics.

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But reading genome's was much too expensive and much too slow, I think, to make an impact for many years, but as that became cheaper.

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And as molecular biology made the amazing advances it has in understanding the molecular basis of disease.

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So these two things have come together to produce a real era of personalised medicine and I suppose right now.

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A major part of the excitement of that field.

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Is, as it has been for a few years in understanding the genetic basis of cancer and

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tumour development and the certainly more targeted treatments that are now offered,

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for example, to breast cancer patients, where I think there are, broadly speaking,

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sort of 10 main tumour types to be looked at and lung cancer, another one.

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But of course, it's not just cancer where genomic medicine is is coming.

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Good so-called rare diseases in children so often have genetic causation.

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And that's beginning to be uncovered, I think, by the power of big data allied with whole genome association studies.

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So I was absolutely delighted going back five or six years now, time flies.

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When Tim Gardam, who was then the principal of St. John's,

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asked if I would become involved creating the Centre for Personalised Medicine by chairing its external advisory board.

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And I've been very pleased to do that ever since and thrilled to see how it has

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developed with a whole range of carefully thought through and impactful events.

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Moving on, during your time as chairman of the Cambridge University Hospital's NHS Foundation Trust

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and now you've done lots of work in creating Patient Decision AIDS for cancer patients,

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how do you think personalised medicine will affect the way patients make decisions?

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It's a very interesting question.

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So, yes, I did do a lot of work on Patient Decision AIDS, which I got into an accident of history really years and years ago.

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I took part in a squash tournament and failed to drink the requisite litre of

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water afterwards and found myself in Addenbrooke's in agony with a kidney stone,

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which I had grown always as well. But anyway, that qualified me to be a urology patient.

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And years later, the head of urology at Addenbrooke's asked if I would become involved in helping make so-called

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decision AIDS for patients with prostate cancer or benign hypertrophy of the prostate.

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So male patients, which I did and became very interested in the role of patient empowerment.

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So a decision aid is simply an aid to help patients exercise responsible choice over their treatment options.

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So prostate cancer is a good example because depending a bit on the stage and grade, there could be three reasonable ways to go.

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One is active monitoring, sometimes called watchful waiting. One is radiotherapy, whether internal brachytherapy or external beam radiation.

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And one is, of course, radical prostatectomy surgery.

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And depending on the patient and as I say, the stage and the greater the cancer, the clinical evidence may not be clear cut.

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That one path is overwhelmingly better than the other. And typically patients don't really like to be told.

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There are several things we could do for you patients.

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I think on the whole like to be told this is what we're going to do for you and this will be the best for you.

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And here's the evidence.

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But where the evidence is not clear, then it does empower patients to understand the choices and exercise a personal preference.

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I mean, they can always do that. No patient, of course, can have treatment forced upon them.

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So how will personalised medicine change that?

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Well, I think it will add another dimension, because the clinician will be able to say to the patient,

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yes, you have prostate cancer and your tumour is of this nature.

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And I can tell you that with those particular genetic signatures, you're likely to have an aggressive cancer,

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you're likely to have an indolent cancer, and therefore there should be much more targeted therapies and alternative paths of action offered.

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So I think that personalised medicine will add very powerfully to patient decision making.

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I think there's a challenge for the clinician to be able to set this out, Cambridge and Oxford,

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and notable for the enquiring minds of their sick, but not everybody wants a mini thesis on personalised medicine before they make a decision.

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And it has to be OK to say it's up to you. Also, so personalised medicine is here to stay.

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It is a force for good, increasingly powerful,

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and it should be part of the clinicians and the patients armoury in all appropriate cases

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to weigh that information and evidence and the balance of what is the best way forward.

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For that individual patient. Have you recognised any barriers to implementation of personalised medicine, such as clinical translate ability?

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I don't know that I know enough about that really to comment. But my perception is there is a challenge, actually, in terms of time.

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Consultation time is at a premium. And what I have seen actually going back to Decision AIDS is that it can be very

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helpful for the clinician to explain whatever it is and then to be able to hand over.

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Maybe it's a link to a website that runs over everything again.

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Certainly we did. One was funny thing. Yes.

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After I did the prostate cancer and the BPH decision AIDS, I became a urology patient much more seriously because I contracted bladder cancer,

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which was very successfully treated surgically at Addenbrooke's when I was chairman, which was interesting.

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And thereafter I helped the urology department make a decision aid for bladder cancer patients, because, again, there's several courses of action.

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So I think the challenges are, yes, finding the time for the clinician to explain, for the patient to absorb and consider the options.

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And so there, again, decision AIDS links to good websites.

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The bodying system is good, but raises difficulties about patient confidentiality sometimes.

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Could you quickly explain what the buddy system means in this case?

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Yes. So, well, again, taking the example of myself as a former bladder cancer patient,

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before my operation, I had what's called an illegal or subtopic bladder substitution operation,

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which in layman's terms is they take about half a metre of your small intestine, snip it down the tube so it makes a ribbon.

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So the ribbon up into a nice pouch, as they call it, and plummet in between your urethra and your reaches.

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And you've got a kind of new bladder. It's not a bladder because it isn't muscular, but anyway, it works really well.

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So before I had that operation, which is a big operation, takes some time to recover from.

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I was offered a buddy who'd been through it and was willing to talk about experience.

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And that was really hugely helpful as a woman of about my own age, had an active lifestyle as I do.

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And she continued to be a body, you know, during my period of recovery.

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And when I said, oh, you know, this and that happening, she said, yeah, that happened to me, too.

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So that's the buddy system. And it's great. But as I say, it can raise issues about patient confidentiality.

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So it has to be very carefully organised, as it were, a pair at a time.

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You see what I mean? That's that's definitely helpful.

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I think not exactly a barrier to the uptake of personalised medicine, but a risk that needs to be considered is that it may be the case.

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I think that some patients have rather unrealistic expectations of what personalised medicine may do for them.

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There's a lot of excitement about finding drugs that although they're not very good for a generalised population with a particular disease,

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may be brilliant for a small subset, for genetic reasons. And of course, that's a real phenomenon.

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But it may be harder. It's always hard for people to accept that they have a condition that is probably terminal.

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That doesn't mean to say it can't be treated, but it can't be cured.

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I think as medical knowledge advances and personalised medicine does offer more cures,

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it may be even more difficult for people who aren't able to be helped to accept that.

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So I think there's a bit of a risk, if you like, about personalised medicine being oversold, at least in the minds of some patients.

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It's been really interesting to hear that personalised medicine empowers the patient's autonomy as well as conscious decisions for treatments.

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And we are also interested in the interdisciplinary aspect of personalised medicine, so moving on to the next question we like to ask you,

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how do you think your background in the physical sciences and your work in

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sustainability have influenced your outlook towards personalised medicine research?

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Well, I think profoundly, having been trained as a chemist and then worked as an academic for 10 years with a small research group,

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I was never going to be a really big time researcher.

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But it has given me enormous respect for the advances that brilliant researchers with good equipment and good support can make.

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And this is really quite a golden age of discovery in terms of the molecular basis of disease.

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Hugely exciting. Going back to what I said rather earlier in the early years of, well,

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when the when the human genome was first read, people, I think, expected quicker advances than were made,

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partly because of the expense and the time involved in sequencing genomes and partly for the lack of a database,

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the correlated genetic abnormalities with disease and pathology.

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And now, of course, all that is tumbling out terabytes at a time from the information that is being clinically amassed.

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So I think it's probably never been a better time to be a scientist.

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And you mentioned interdisciplinarity. You know, you don't have to be a molecular biologist.

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You could be a device engineer needing to produce some new piece of kit to do some new thing more cheaply or more quickly.

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Look at actually at Oxford, of course, the great work of reading genomes is still the sort of Illumina technique.

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But look at minion. Very different technology came out of Oxford.

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We know a whole lot more about the basis of life and disease than we did, and that's exciting.

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If you want to find out more about the centre or are interested in joining us for one of our upcoming events, please visit our website.

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KPM dot w e l l dot dot dot UK or follow us on Twitter at KPM Oxford.

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Thank you for listening and we look forward to having you here in the next episode.