Small Town Northern Ireland
E Magnus Ohman, MD: Hello. I'm Magnus Ohman. Welcome to the Life and Times of Leading Cardiologists. We are very fortunate to have Dr John McMurray here today, who is going to talk a little bit about his life.
But before we get into that, I want to acknowledge the prior host of this program, Dr Califf, who ran this series for 5 years. It is a great honor for me to follow in his footsteps and continue the tradition of finding out a little bit more about people's lives.
So John, welcome to this program.
John JV McMurray, MB ChB (Hons), MD: Thank you.
Dr Ohman: So tell me, you are currently in Scotland, professor of cardiology at Glasgow, but where did it all start? Where were you born?
Dr McMurray: I was born in a little town in the Northwest of Ireland called Enniskillen because my father came from there. In fact, he came from a small farm nearby, but he had left the farm at that time and was working in the town of Enniskillen, and that is where I was born.
Dr Ohman: Great. And this is in Fermanagh, so we are talking Northern Ireland, close to the border to the Republic of Ireland, I presume?
Dr McMurray: That is correct. I was born in the north of Ireland, yes.
Dr Ohman: How many in your family, mother, father, and?
Dr McMurray: There were four of us, four children. I am the oldest and my youngest brother is also a doctor. He is an obstetrician and gynecologist and he is working in Kilkenny in the Republic of Ireland.
Dr Ohman: And are you, one has to ask this if you're from Northern Ireland, you are Catholic or Protestant? That is a very common question.
Dr McMurray: I am Catholic.
Dr Ohman: What did your mother and father do?
Dr McMurray: When my father left the farm, he joined the civil service in Northern Ireland, so he worked for the government. My mother didn't work when we were small children but as we grew a bit older she decided to train as a nurse. I remember during my days as a schoolboy, at the same time as I was doing my biology exam, she was learning her nursing course and it was interesting because there was a lot of similarities with what we were both doing at the time.
Dr Ohman: So in a way this sort of medical domain that you ended up in was really driven a little bit by your mother's interest?
Dr McMurray: Well, it is always difficult to think when you are small to know what the influences on you were. I mean I was very interested in science and biology, though I think we called it nature in those days. But I suppose my mother's interest was parallel and, of course, every Irish mother wants her sons to become doctors or priests. Two of her sons became doctors and one almost became a priest, so there was probably some parental influence in that way, as well.
Dr Ohman: That's great. And so, now, as the saying goes in Ireland, if you have four children that is a small Irish family.
Dr McMurray: That's right.
Dr Ohman: And so good health in the family when you grew up?
Dr McMurray: The reason we had a small family was that my mother had a rhesus incompatibility problem, so my youngest brother was actually very ill as a newborn baby. He had multiple exchange transfusions, and I think my mother didn't have any more children after that because of that reason. But you are right, that was a small family. Her sister, for example, has nine children.
Dr Ohman: How old were you when that happened with your mother? Do you remember much of it?
Dr McMurray: I remember it very vaguely. I am 10 years older than my brother, so I would have been about 10 at the time.
Dr Ohman: And so you lived on a farm?
Dr McMurray: We lived in a town, but as a schoolboy I would go and work and live on the family farm every summer. We had long school holidays in Ireland, so a great time—until I was a teenager. By that stage my father had been transferred to Belfast and I went to primary and secondary school in Belfast.
Dr Ohman: I always wondered if farming and science are somewhat related. Do you feel that this early farming experience had anything to do with what came later in life?
Dr McMurray: Not really, though I did understand about reproduction probably earlier than many of my fellow school pupils, because on a farm you get to understand the birds and the bees and other things very quickly.
Dr Ohman: And you went to Catholic school, where education of that particular subject was somewhat limited?
Dr McMurray: Correct. I went to an all-boys primary school, St Joseph's, and an all-boys secondary school, St Patrick's, so there were no girls.
The "Troubles" in Belfast
Dr Ohman: So how did you move from Northern Ireland and Belfast to the rest of your career? What happened here?
Dr McMurray: Well, that is a difficult story because at the time that I was growing up it was the height of the so-called troubles, which was effectively a civil war in Northern Ireland and in Belfast, in particular. At the time I lived there, Belfast was a very segregated city. People of different religious and political persuasions tended to live in separate areas. I was on the wrong side in the wrong area, so it was a very traumatic period when I was at school.
Dr Ohman: Roughly which years were these? This would have been in the 1970s?
Dr McMurray: Well, the civil rights movement started in 1969 when I was at primary school and all the way through. I left Northern Ireland in 1977. By that stage Belfast as a city was a completely locked-down dead place. It was surrounded by a steel fence. You could only get into the city through British Army checkpoints, and there were rioting, bombs, and murders all the time. It was really very bad and affected us indirectly. Friends and even a priest in our church was shot. Some of my school friends got involved in the things that were happening. Some of their parents were killed.
Dr Ohman: It is interesting you talk about this because in the media and later in films, there has been a lot of discussion about this. It is rare for physicians to grow through this sort of war zone, but that is really how it was.
How did you shield yourself from this, was it getting down to books and being a really good student? Is that how it was?
Dr McMurray: Looking back on it, it seems like a bad dream. It seems like it couldn't be true that it really was like that, but it was. I suppose as a child and a teenager you accept that the way things are is the way things are. You don't really have another experience. We hadn't traveled very much, you don't really know that it could be otherwise. So looking back, it seems appalling that it could have been like that, but that was the way it was.
I think you are right about education. Education was seen as a way to get on in life. I come from a rural background, nobody in our family had ever been to university before. I was determined to leave Belfast as soon as I could, and exam success was a way of getting out of Belfast and getting out of the country.
A Move to Manchester
Dr Ohman: So where did you go from there?
Dr McMurray: I went to the University of Manchester in the north of England. I went there because at that time it was very innovative in its medical training. It introduced a new style of course where students were introduced to patients and medical problems from day 1.
Dr Ohman: So the McMaster style.
Dr McMurray: A McMaster-type approach, and that was very attractive, and in addition they gave me a scholarship, which was very nice.
Dr Ohman: So how did you find Manchester? It is a war zone of a different type.
Dr McMurray: It was interesting. I have to say, in those days people with an Irish accent weren't particularly popular.
Dr Ohman: But probably better there than anywhere else in the UK, right?
Dr McMurray: I had a great time. It was a great course. I thoroughly enjoyed it, and to this day, I look back fondly on my time as a student in Manchester. And I met my wife there, of course, so that was very important.
Dr Ohman: And what is her background?
Dr McMurray: Well, I am afraid we are very traditional. My wife was a staff nurse on the ward where I was a newly qualified doctor, so she made sure I didn't make too many mistakes, and we ended up getting on well and getting married.
Dr Ohman: That's great. Did you get married in medical school or shortly after?
Dr McMurray: Shortly afterward. As was the way in those days when you did what we called house jobs, I did 6 months of medicine and 6 months of surgery, and you apply for another job. I decided to do medicine and general medical training, it was at that stage, so I applied for all the jobs that came up that were advertised. The first place I interviewed was Edinburgh in Scotland, and I got appointed so that is how I ended up in Scotland. Christine, wasn't my wife then, but she decided to come with me to Scotland, and we got married in Scotland.
Dr Ohman: That's great. So medical school, different curriculum at Manchester, very close to Liverpool, a lot of Irish influences there, any people who stand out in medical school as ones who made you go into medicine as opposed to surgery? I believe you told me your brother is an obstetrician?
Dr McMurray: Correct. Truthfully, in Manchester we had so many role models and mentors it is hard to single anybody out. I know that sounds crazy today, but in those days people were a lot less homogenous. They were, what I would call, characters, individuals, who had very special attributes and qualities. Some of them might not be regarded quite so highly today, but it was a place with lots of big people with big personalities, and they were fantastically stimulating and motivating.
My professor of medicine was Prof Stanbury when I was a house officer, and he was very good. Derek Rowlands, a cardiologist I worked for when I did my medical house job, was probably the person who motivated me most to do cardiology, which is what I ultimately did, but there were lots of other people. The professor of orthopedic surgery was a South African gentleman called Charles Galasko who was fantastic. There were so many good people. It was fabulous.
Dr Ohman: So then you went to Edinburgh and, talking about illustrious individuals, I believe Michael Oliver was there then?
Dr McMurray: That's correct, yes.
Dr Ohman: This is a different system. It is very different. It is hard for many of us who listen to this to understand that Manchester and Edinburgh are fairly far apart in terms of how the structure is set up.
Dr McMurray: A million miles.
Dr Ohman: How was it? Was it a shock to you to get to Edinburgh?
Dr McMurray: It was quite a shock, and I don't think anybody from outside Edinburgh had ever got this particular job before, so I was fondly reminded of that almost every day. But again, I worked with great people. You are right, Michael Oliver was there, David de Bono was there, Hugh Miller was a cardiologist I worked for. Edinburgh was a beautiful city with a very strong and famous tradition of medicine in Europe. I enjoyed it immensely.
Intrigued by BNP and Heart Failure
Dr Ohman: You start your house-officer years, that would be resident's year in US parlance, and then you have to apply for registrar, which is chief resident, almost, but a little bit different. Tell us a little bit about how you went about getting a registrar post, because now you really have to decide what you are going to do.
Dr McMurray: I had done two years in Edinburgh and got what we call the membership of the Royal College of Physicians, an exam you have to pass to progress in your hospital medical career. I decided to do some research, because I thought that would position me well to get a registrar specialty training job.
I went to Dundee, which is in Scotland, and the reason I went there was that there was a young, newly appointed clinician scientist there call Allan Struthers who was doing work on a newly discovered substance called B-type natriuretic peptide and A-type natriuretic peptide. By that stage, I was already intrigued by heart failure and I was really intrigued by the idea that the heart was an endocrine organ and not just a pump.
Dr Ohman: Put this in perspective, was this a long time ago?
Dr McMurray: Yes, this was in the 1980s.
Dr Ohman: This process is now live for us 25 years later. Amazing, yes.
Dr McMurray: That is why I have had such an amazing time because in the mid-1980s, I was infusing people with natriuretic peptides trying to understand how they worked and what they did in human beings. That is what I did my thesis on and my early publications were in that field. Once I had done that I decided I wanted to specialize in heart failure. I knew one of the leading cardiologists with an interest in heart failure in Europe, at that time, was Henry Dargie in Glasgow, and I asked my bosses in Dundee would they contact him to see if there was any possibility of a job in Glasgow. They did, and I went down and I met Dr Dargie, as he was in those days to me, and he was kind enough to give me a job.
And one of the reasons I particularly wanted to go there was that he started working a drug called candoxatrilat, which was a neutral endopeptidase inhibitor or neprilysin inhibitor, and it had been discovered that this enzyme, neprilysin, breaks down natriuretic peptides. So here was an oral drug that theoretically could increase endogenous natriuretic-peptide levels, and that struck me as really interesting in heart failure.
Now, sadly, it didn't work out, but that is how I ended up in Glasgow.
Privileged Friendships and Paying It Forward
Dr Ohman: That is a great story. So after Struthers, was Henry your main mentor?
Dr McMurray: Yes, correct.
Dr Ohman: Tell us a little bit about that working relationship.
Dr McMurray: I was doing clinical training at the time so I worked with a lot of cardiologists. In the UK you have to train in everything, as you probably remember, and so I had to do angiography, pacemakers, intervention, all of that, but I kept a particular interest in heart failure. I continued to try to do research in heart failure working with Henry, so he was really important in helping me do that.
Subsequently, I got a staff appointment in Glasgow, though, actually, I did return to Edinburgh, briefly, for a year or two, and then came back to Glasgow. After that I began to develop international links and in many ways got fantastic mentorship from colleagues and friends in other countries and, indeed, in other parts of the UK. Philip Poole-Wilson, who was a professor of cardiology at Imperial College in London and, again, a leading UK and European expert in heart failure, was also incredibly good to me during my training in Glasgow. In many ways, you know, people could have seen Glasgow and London as rivals in the heart-failure sphere, but Philip was absolutely not like that.
Dr Ohman: How did you connect with him?
Dr McMurray: I met him at the British Cardiac Society meetings, as it was in those days. I was doing presentations, and he was interested, so I talked to him, and he always kept great interest in what I did and was always helpful in whatever way he could be. I have to say: my experience of academics whom I have worked with around the world has always been like that. I would say my greatest mentor in recent times is my colleague and now friend Marc Pfeffer in Boston. I would say I have had exactly the same experience with him and some of your colleagues at Duke, as well.
One of the great privileges of what we do in academia and research and clinical trials is that we form these lifelong friendships.
Dr Ohman: How do you foster young doctors? You have had terrific mentors, so how do you paying it forward to the next generation?
Dr McMurray: I try to do that, and I am at that stage in life where I have had a lot of people train under me who have now moved on to become full-fledged cardiologists. I realize that means I am getting old, but it is also immensely satisfying to see these people in their own positions.
How do I do it? I hope I motivate them. I hope I interest them. I certainly try to help them with their ideas, with their research, with their writing. All of my life I have been incredibly lucky. In many ways I don't feel I deserve what I have got and where I am. When I see all of these young people coming along below me, they are so much brighter, so much smarter, so much better than I was. But then, maybe that is just the way it is generation by generation.
It is a privilege for me to try to help them, and I feel like I am helping them. They have the inherent skills themselves, the qualities, all I am doing is helping bring them out.
PARADIGM HF Working With Industry
Dr Ohman: So you became the leader of the PARADIGM heart-failure trial,[1] one of the more fascinating trials that have come out in the past several years, with a new model for care in heart failure. How did you get into that, and how was the relationship working with industry and creating this very important trial?
Dr McMurray: There were two PIs in PARADIGM, myself and Milton Packer. And actually, strangely enough, our history goes back quite a while to a study with another drug called omapatrilat.[2] PARADIGM HF used a compound that is an angiotensin receptor-neprilysin inhibitor, or ARNI, as we call it now. There was also a drug that was somewhat similar called omapatrilat, which was a neprilysin ACE inhibitor. I worked with Milton on that drug a long time ago.
Why did I get involved with PARADIGM HF? I have an interest in natriuretic peptides going back, as you correctly pointed out, a very long time, and then we have the candoxatrilat story and then we had omapatrilat, so this was like the third attempt.
Dr Ohman: And if it didn't work here you would have been done, right?
Dr McMurray: Somebody in Novartis had the ingenious idea of coupling a neprilysin inhibitor and angiotensin-receptor blocker, and that gave us another chance, and I was fortunate enough to get the opportunity to lead the development of the trial.
In regard to working with industry, I know that this is something that is often criticized, but I have been involved in many large trials working with industry, and we have had a free hand in developing the studies, the protocols. For example, when I was first asked about what became PARADIGM, Novartis had an idea of doing a phase 2 proof-of-concept study. Milton and I with the rest of the executive committee persuaded them to do this large, phase 3 outcomes study. So the design, the comparator, everything was determined by us. It was an extremely collaborative and, I believe, productive relationship that is beneficial to all involved and hopefully to many patients with heart failure.
My experiences of collaboration with industry in the clinical-trials sphere have been largely very positive. The reality of clinical research today is that there are not many governments that are going to fund trials of the size that we need to demonstrate the effectiveness of treatment. So while people may criticize industry involvement in trials, what is the alternative?
My own experience, as I have said, is that you can actually work with the industry in a very collaborative, productive, and, I believe, honest and upright fashion.
Dr Ohman: You have had staying power. You stay with a concept for many years—you are really a leading light in this way.
Family and Footie
Dr Ohman: We got talking about your career, but along the way you had family. Now, did you have a large family, like the standard Irish family? Probably not in the UK, right?
Dr McMurray: Well, I managed to marry a good, English, Catholic girl, so we have six children. We had five fairly close together: my oldest son is 29 and my second-youngest son is 21. And then we have what we call our surprise, who is 11. It shouldn't have been a surprise, I suppose, but he was, so he is a lot younger than his next-oldest brother. And our fourth grandchild is on the way very shortly.
Dr Ohman: That is great. Of your six children, any one of them decided on medicine as a career?
Dr McMurray: Sadly, no. I have got five boys and one girl. One of my sons did do medicine for a period of time but decided it wasn't for him. Another is doing a PhD in mathematics at Imperial College, one works in entertainment, and my second-youngest son, is at university studying modern languages.
Dr Ohman: So when you get together for Christmas there are some widespread interests.
Dr McMurray: Christmas was a big do at our house this year.
Glasgow Celtic
Dr Ohman: What do you do recreationally? You have been an extreme leader here in the heart-failure arena. You focused on an area that many of us didn't think would pan out, besides you, Struthers, and a few others. What have you done on the side to keep yourself occupied in other areas?
Dr McMurray: Probably worked too hard. My wife and family would certainly say that. But I suppose my main alternative passion is my favorite football team in Glasgow and, of course, that is Glasgow Celtic. Celtic is a team that was founded in Glasgow by Irish immigrants for the very large Irish immigrant population in the city that had arrived there after the famine. In Glasgow about one-third of the population are of Irish descent. They still feel very proudly that they are Irish as well as Scottish, and Glasgow Celtic is their football team. We have an intense rivalry in Glasgow between Celtic and Rangers, who are the indigenous Scottish team, and I have spent a lot of time watching those matches, even a few years ago following Celtic on European trips where they have been moderately successful, shall we say, in European football.
Next Steps
Dr Ohman: What is next, do you believe, in your career? What would you like to tackle next?
Dr McMurray: Personally I think my career has been about two things. One is being a practicing cardiologist, because I think there is still nothing better than seeing individual patients and trying to help them and their families, and nothing better than when you are successful at doing that. It is a very rewarding experience, so I want to continue to do that.
And then the beauty of my job is that in addition to that I have tried to do things that will change the way that we treat patients so that I can improve the outlook, not just of the individuals I personally look after, but many, many patients with the diseases that we all are concerned about.
I hope to continue to do both of those things. I hope to continue to work in clinical trials. I have learned an awful lot about clinical trials. I believe that you learn as you go along. You learn how to do them well. You learn by your mistakes, and there have been many of those. I have got better at that, and I hope to get better still, and I hope we will bring along more new treatments that will make a difference for patients.
Myself and Scott Solomon, who is another great friend of mine from Boston—I met him through Marc Pfeffer—we are leading a new trial with this angiotensin receptor–neprilysin inhibitor, LCZ696, in patients with heart failure and preserved ejection fraction. If we are successful in that trial it will be the first-ever treatment shown to improve outlook in that type of heart failure.
And it is a big if, and it is early days, but if we were able to do that, that would be something I would be very happy about.
Dr Ohman: That is a tremendous story from Fermanagh in Northern Ireland through Dundee, where some of this original work was done, to the present time. I want to thank you for sharing all this great information with us. Thank you.
Dr McMurray: Thank you very much.
