David Levison - Full Transcript

David LevisonProfessor of Pathology at Dundee University (retired 2009)

Interview location: Ninewells Hospital, Dundee.
Interview date: 5th September, 2007


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SA:  Not many children dream of becoming a pathologist – what did you want to do when you were a little boy – what were your first ideas about what you wanted to be in the world?

I didn’t really like pathologyDL:  I suppose the usual thing – I wanted to be a football player, or a rugby player, or a pilot.  These were the things I thought about.  I was never sort of outstanding at anything, but I was quite good at most things.  I think that was probably reflected in my Highers.  I did a mixture of Highers, both arts and science, so I could have done either at University.  And when I applied to university I applied to do economics and medicine at Edinburgh and St. Andrews.  I got acceptances for them all, in about the same two weeks, and I put them to one side.  And I remember, I was going out one Saturday evening and my mother just stood in the doorway and said, “You’re not going out until you make up your mind about what you’re going to do!”  I thought, “I want to get to that dance, there’s a nice girl there…Ok, medicine!" And she still stood in the doorway and said, “You’re not going out till you write the letter saying so.”  

I sat down and wrote the letter and I’ve never regretted it. But I think I went into medicine totally ignorant about what it involved -- nobody in the family was connected to medicine.  So really, very ignorant.  I don’t know whether I’d heard the word “pathology” when I started off, and I didn’t really like pathology as a medical student…

SA:  Why not?

DL:  I was a medical student in St. Andrews, and at that time we came across to Dundee to do our clinical work.  We did our big Second MB exam in March, and we came across to Dundee for the summer.  My attendance in that first term in Dundee was not good as there were competing attractions in St Andrews like sailing and bridge, and in the first pathology exam…I don’t know if I should tell you this, but I got 4%!   And an invitation to come and see the professor – which I didn’t enjoy.

I didn’t really like the way pathology was taught.  It was just straight lectures, long boring practical classes looking down monocular microscopes, and I couldn’t see anything down them or recognise anything.  I didn’t enjoy it at all until we had some revision tutorials near the end. I actually quite enjoyed the tutorials, and felt I was beginning to start to understand some disease processes. I never thought about pathology beyond that.

SA:   When was the moment you saw the light with pathology and thought, "This could be interesting"?

DL:  It was when I was doing my house jobs, and attempting to treat people with mixed success, and thinking, “Well, if I knew better what was going on in there and understood the pathological processes better, I’m sure I’d be better at this.”

SA:  So you felt wanting, did you, as a diagnostician, and you wanted a better insight?

DL:  Yes, yes.  I’d been coming round to thinking that I’d like to be a physician and go into general hospital medicine.  And then a job came up in pathology.  We were back in Dundee by that time (I’d done my house jobs in Leeds).  We had a small boy and there was another child expected, and I thought, “I don’t want to move again”.  A pathology job came up and I thought, “Well, that would be good. I’d get the chance to learn more about disease processes and that would be a great basis for going back to general medicine.”  Then when I started doing pathology, again I didn’t like it for the first few months.  But as I got to know a bit and became a little more useful, I got very interested.

Of pet birds and pathology

SA:  So was there a moment when you suddenly realised, "Okay, this is what I want to do, this really is where it’s interesting"?

He kept exotic tropical birdsDL.  Yes!   It was in my second year in pathology and I remember precisely when it was, because the GP’s practice in Carradale on the Mull of Kintyre came up.  That’s a place I like, on the West Coast of Scotland, I’d been there and thought, “Now if that GP practice ever comes up, I’d quite like that”.  And it came up and I thought, “Am I going to apply for that?…No, I’m actually really enjoying what I’m doing now.”

I’d got interested in…Well, it was a postmortem case, actually. We’d seen this lady, who’d died of endocarditis, infection of the heart valves, and it looked a bit unusual, the vegetations on the valves, so we’d taken imprints and sent stuff off for bacteriology and done detailed microscopy looking for organisms.  And it turned out to be due to psittacosis which is a disease you catch from birds.  We discovered that this woman's husband was a bird fancier -- he kept exotic tropical birds, and she used to go in and sweep out the cages.
This is what I want to doBut this case also brought to mind another case from three years earlier.  The senior pathologist at the time, Bill Guthrie, had done a postmortem and I’d remembered it.  I was a medical student at the time, and we’d seen this chap on the ward. The doctors thought he had psittacosis, and they thought there was something wrong with his heart.  Then he died.  A couple of us had been interested in the case, so we went along to see if we could watch the postmortem, but we were shooed away, “No, you can’t come in – danger of infection”.  I remembered that case well, and the consultant supervising me on his second psittacosis case was again Bill Guthrie.  We put our two cases together and wrote a paper for the Lancet.  And that was my first introduction to research and writing a paper.

SA:  And did you get quite a thrill from it?  

DL:  Yes, and I was involved in that at the time the GP practice came up in Carradale, and I thought, "Well, there’s a big difference between being a GP in Carradale and being an academic pathologist!  But gosh this is interesting; yes, this is what I want to do”.  And so I made the decision.

SA:  And once you’d decided that, how did you get your first job, and how did you pick the areas you wanted to do research into?  Because you’ve got quite a research record now…

DL:  I’ll answer that in a moment.  Can I tell you just a bit more about the psittacosis case first?

SA: Yes please do.

DL: I learnt quite a lot about life from this piece of work.  We were writing the case up – there was myself, the consultant pathologist, the microbiologist and the clinician – and we were having discussions about it.  (At that time also we saw quite a lot of people who had chronic heart valve disease, and we knew you could get congenital heart valve disease, but the only really recognised cause otherwise was rheumatic fever.)  And I just said at one of these discussions, “I wonder in some of the people who don’t have a history of rheumatic fever, if the chronic heart valve disease could be due to psittacosis?  Maybe they keep pet birds.”  And I said to the clinician, “It would be quite a good idea, in your clinics, if you asked the people you’re seeing with valvular heart disease who don’t have a history of rheumatic fever if they keep pet birds or anything.”

I thought no more about that and then two months later I was reading the Lancet and there was a letter, written by this guy.  He’d done exactly what I’d suggested, and he’d found that a lot of the people who hadn’t got a history of rheumatic fever actually kept pet birds.  

SA:  But still, from the learning point of view, were you then able to go back through historical examples and find out whether valvular problems caused by psittacosis were more common than was understood at that stage?

It taught me a lot about lifeDL: Well, that did sort of open up the area.  But at that time we didn’t have molecular techniques; we didn’t have Immunohistochemistry A technique that uses antibodies labelled with fluorescent or pigmented dyes to identify, or indicate the presence of, specific proteins in tissues when looked at under the microscope..  All you could do was, with the fresh tissue, try and grow the organism.  So I didn’t have the facilities or the tools to take it forward.  Nor the opportunity – it’s a pretty rare disease.  No, I got on to other things after that.  But it taught me a lot about life, a lot about people, a lot about how exciting and interesting things could be.  And also how doing your job properly – just being careful about doing it and thinking about it – you get a lot more out of it than you expect to.

SA:  This thing about doing your job properly -- is keeping an open mind hugely important?  Because I should imagine it might be quite easy to miss things if you have preconceptions.

A diagnostic coup

Having an open mind is tremendously importantDL:  Yes. I think doing things properly and having an open mind is tremendously important.  That again…Can I brag about another diagnostic coup?  [Laughs]

SA:  Do please!

DL:  It was my first medical house job and I was in Leeds General Infirmary.  A lady came in for coronary artery angiography.  She was a youngish lady, in her mid thirties I think, and she’d had a number of attacks of heart failure, so she’d come in to have  angiography to see what was wrong with her coronary arteries.  I just talked to her,  clerked her in and examined her.  Everything was normal: blood pressure normal, and everything else.  And I just took the time afterwards (I probably had nothing better to do!) -- I sat down and read through her notes.  And I noticed that each time she’d been into hospital ill, when they’d taken her blood pressure it had been high, but when she was seen as an out-patient, and when I’d clerked her in this time, her blood pressure was quite normal.  And having been reasonably well taught in pathology, I thought, "I wonder if she’s got a pheochromocytoma," which is a tumour of the adrenal medulla that produces adrenaline and noradrenaline.  So I thought, "Well, I’ll just send off urine to see if the relevant hormone level is raised."  It came back in the clouds.  

I was terribly popular with my consultant there, the cardiologist, because this lady had been under another cardiological team that he wasn’t involved in and they’d not picked it up; then she’d come to him and his houseman had picked it up!  And it was very important because it meant…She had radiology of the abdomen, and there was the tumour.  It’s usually a benign tumour or a pretty benign tumour.  She had that removed and was totally cured -- and didn’t have to have the risky coronary artery angiography.

I tell that story to the students.  I’ve incorporated it into a talk I’ve given regularly to them just as they’re graduating, just to remind them to take the time to do the job properly.  I tell them, "It’s not being intellectually brilliant that will make you effective all of the time, but just doing the job properly, and taking time to look at the background and so on."  You can sometimes get these amazing things out of it.


Solving the mystery of menstruation

SA:  Okay so how did you decide on the areas of research that you did go into?

DL:  It’s all been serendipitous, I think.  The first real good bit of research I did was on the endometrium, the lining of the womb.  The reason I got into that was because of one of the other senior pathologists in Dundee whom I trained under, Wallace Park, who was a very good gynaecological pathologist.  He had said to generations of trainees, “Look, in the premenstrual endometrium we see these little black dots in the glandular cells.  Why don’t you investigate these?”  Nobody had done it.  He said the same to me, and I thought, “Well, how could we do this?”  Again, we had limited tools available, but the department had just got an electron microscope and I thought, “I wonder if we could use electron microscopy to see what these little black dots are?”  

SA:  What was his feeling about them?  Were they pathological?

DL:  He didn’t know what they were, but he had recognised them as a very good marker of late secretory phase endometrium.

SA:  Which is what?

DL:  Well, when the endometrium cycles every month, it grows thicker and then is shed at menstruation -- at least that’s what the story was – and then goes back to normal.  So there are cyclical changes.  And as pathologists we get sent endometrium from the gynaecologists.  Irregular menstrual bleeding, painful menstrual bleeding, any symptoms to do with menstruation, they’re investigated by D&C [dilatation and curettage] and we’re sent the pieces of endometrium.  And if we’re told, “The last period was on such and such a date, so we’re eight days into the cycle”, we would expect to see proliferative changes, and if it was 18 days into the cycle we’d expect to see secretory changes.  If there was a discrepancy between what we actually saw and what we were expecting to see, then that was significant.  So we were always dating endometrium.  And one of the things that Wallace Park had picked up on was that these little black dots were very useful for telling you were dealing with the late secretory phase endometrium…

SA:…But he didn’t know what they were?

You’ve really got to do everything yourselfDL:  He didn’t know what they were.  So we’d got the electron microscope and I thought, “I don’t know anything about electron microscopy.”  But a chap had just joined the department, a chap called David Hopwood who’d been an anatomist (a very good anatomist) before he came into the department, and an electron microscopist.  He joined the department not knowing any pathology; I was an 'expert' because I’d been doing it for two years! We became friendly, and he has always kindly said that I taught him a lot of basic pathology.  I said, “David can you teach me some electron microscopy? Why don’t we look at these little black dots, and while we’re doing that you can teach me what we’re looking at in terms of general electron microscopy?”  So he thought that was a good idea.  

I would never have been able to do this project nowThis also taught me that if you’re doing a project, you’ve really got to do everything yourself.  What David and I did, for about six months, was that one of us would go every Monday morning to the gynae theatre and just stand there. And instead of putting the specimen straight into formalin, as they usually would for diagnosis, the gynaecologists would give it to us and we’d have a look at it and decide “No, this is too small, it all has to go into formalin”, or else “There’s plenty stuff here: we’ll put that much into formalin for diagnosis and take a couple of tiny bits for electron microscopy.”   If I didn’t think there was enough, and I’d taken a bit for electron microscopy, I could go and fish it back out.  Now I must say, I didn’t think there was anything ethically wrong with that.  I didn’t have the permission of the patient; it didn’t strike me that I needed it at that time.  And we didn’t have to go and ask for ethical permission to do it.  But I would never have been able to do this project now…Nowadays to do such a project, I would need to fill in a 64-page ethics form.

SA:  Really and truly? To get the products of a D&C (dilation and curettage) and have a look at them?

DL:  Yes.  Yes. To be able to use for research a bit of material that had been taken for diagnostic purposes -- even though I could still have used it for diagnostic purposes as well.  Nowadays I would have to fill in a 64-page ethics form, and it would have to be considered by the ethics committee – and they could well say, “Oh, this is just a bit of speculation.”  And you could have someone on there, even a conservative pathologist, who might say, “Well, often we have to say there’s inadequate material to make a diagnosis and here’s somebody wanting to take away some of that precious material beforehand.”  But I must say, at the time I thought, “Well I’m the chap who has to make the diagnosis, so why shouldn’t I try and get a bit more out of it at the same time?”

“Cell suicide”

SA:  So that was in the ‘70s was it?

This is apoptosis!DL:  Yes.  We got a lot of good material for both light and electron microscopy because we collected it all ourselves.  We first established that the black dots were pieces of nuclei, by corroborative electron microscopic observation and light microscopic stains for DNA stands for deoxyribonucleic acid.  This is the material inside the nucleus of the cells of living organisms that carries genetic information (see also RNA). , so we knew they were bits of breaking-down cells, but we were still baffled as to what was going on.  Then – and this was totally serendipitous – David and I went to one of the regular lunchtime post-graduate lectures, and it happened to be given by Professor Alistair Currie, who was at the time working in Aberdeen.  This was the first time I heard the word “apoptosis”.  (It was John Kerr, Andrew Wylie and Currie – who ‘invented’, or discovered, apoptosis.)  Prof Currie was talking about it and showing pictures of the very stuff we were looking at, and David and I just looked at each other, "This is apoptosis!"  

SA:  So you’d never heard of apoptosis by then?

DL:  No.  No.  

SA:  And did he explain what it was?

Programmed cell deathDL:  Yes.  He said it was individual cell death…They thought it was a distinct form of cell death -- they called it “programmed cell death” – which didn’t invoke an inflammatory response. They’d seen it in developing fetal tissue, and they’d looked at it in the adrenal glands, but they were just feeling their way, too.  I thought, “Okay, so the cells are dying.  But what’s the point of that, if they’re going to be shed during menstruation anyway?”  And then, at the same time, I was working for my MRCPath final exam, and I was reading Symmers’ textbook of pathology.  I was very bored by the gynae section, and then suddenly I came to this bit which referred to an obscure bit of work done by a chap called [George William] Bartelmez in 1936.  He’d been looking at the products of menstruation in rhesus monkeys, and he’d tried to measure what was actually passed out of the body, and he’d looked too at the staining of the wall of the endometrium before menstruation and after menstruation.

The penny droppedThe story was then, in all the books, that the top two-thirds of the endometrium was shed, and everything then regenerated.  This is conceptually a very straight-forward idea -- of course it had to be right!  But what Bartelmez had shown was that virtually no tissue was passed with the menstrual products, it was all blood.  And when he looked carefully at the endometrium before and after menstruation – using stains to show up the connective tissue framework – he could see that the top two thirds didn’t get shed, it just shrank down.  The penny dropped when I read that.  I realised that the epithelial cells of the large tortuous endometrial glands were dying by apoptosis and being recycled by being mopped up by other cells, and not being wastefully shed with the menstrual products.  All that is shed during menstruation is blood, fluid, and very few cells.

And I remember sitting in the library working for this bloody exam and suddenly that penny dropping, and rushing out of the library to talk to David about this.  We’d already submitted the paper, and it had been accepted for the Journal of Pathology by that time.  But I said, “Look we need to add this in.”  So I phoned up the editor and said, “We want to add just a paragraph.  I know it’s not the done thing at this stage in the publication process.”  But when I explained it to him, he said, “Yes, we’ve got to include that”.  So it was able to be included in that paper.

SA:  So is that now the accepted wisdom?  Is that now how people understand what menstruation is?

DL:  Let’s see.  That paper was published in 1975.  It’s taken about 30 years to become mainstream…  Apoptosis kind of went out of fashion for a bit after it was discovered.  It wasn’t until we got better molecular understanding of carcinogenic processes, and the balance between proliferation and cell death, that people began to realise that apoptosis was important -- that lack of apoptosis in some cases, and increased apoptosis in others, was important in the development of cancer, and we started to get the molecular tools to be able to work on these mechanisms. Then apoptosis came back into the forefront of biology again.  

SA:  This is really fascinating.  What exactly is apoptosis?  And what’s the difference between cell death by apoptosis and cell death by necrosis, for example?  What other dying processes are we used to seeing in tissues?  And what’s so special about apoptosis?

DL:  Necrosis is always a pathological process, and it happens because something goes wrong.  Apoptosis can be physiological [that is, a normal healthy process], and it can be pathological.  For example, when fetuses are developing there’s a stage when the fingers are fused together, webbed together, and the webs are removed by the process of apoptosis – ‘programmed cell death’.

SA:  And then what happens?  It sloughs off, or the macrophages [scavenger cells] take the tissue back into the blood stream?

DL:  Yes, the macrophages take it back into the blood.

SA:  With all the nutrients?

DL:  Yes, yes.  So it’s re-used, it’s not wasted.

SA:  So it’s not sloughed off, it’s absorbed by something in the body?

DL:  Yes.  So that was a totally serendipitous bit of research that we’d got into.  I think probably all of my interests have been serendipitous.  But I think that’s the way you enjoy life – you have to make use of the opportunities as they come along.


A kidney 'expert' by default

You bloody well report it thenAnother thing that happened during my training in Dundee, I remember.  This was on the diagnostic side.  We got a professor of medicine who started doing renal biopsies, which we’d never had before in the pathology department.  One of the consultants was dealing with them, and he was using the usual sort of stains we used in the department, and he was showing the renal biopsies to me as he went along.  I read up a bit about how you did renal biopsies, and I found that everyone else was using a different silver stain from the one we were using.  So I said, “Look, we should be doing this other stain because you can see these little spikes that help you to diagnose particular types of renal disease.”  And he said, “No, I’m used to this stain”, and he persisted with the silver stain we were used to in the lab.  But you couldn’t see the things he was trying to see.  

I must have been a really irritating person to have around, because I said to him,  “Look Bill, I don’t think we’re doing a very good job here.”  He just looked at me, glowered at me, and he picked up the form and all the slides and brought them across and dumped them by my microscope, and he said, “You bloody well report it then.”  So I did! [We both laugh]

SA: So what did you do?  You stained it with a different stain, did you?

DL:  Yes.  I went and talked to the people in the lab and said, “Look can you do this particular type of silver stain?”  And they said, “Well, we’ll just follow the recipe.  We’ve got the reagents.”  And they did.  So then, even though I was a junior person with no qualifications, I became the 'expert' renal pathologist in the department!  I had to do all the renal work.  But that was good, because it meant that I had a niche.

I felt quite insecure -- here was I becoming the renal expert, completely self taught!  But after I’d been doing it for about 18 months I went across to Edinburgh where Mary MacDonald was the renal expert, a very nice lady with a big reputation.  I just went for a couple of weeks and she’d pulled out a whole lot of stuff for me to look at  -- and it was very reassuring to find that I was coming to the same sort of conclusions she was wanting me to come to.

SA:  So renal pathology, kidneys, became your thing?

I had a really good nicheDL:  Yes.  And that was very useful when I moved to Barts to my first senior lecture job, because I knew I could do kidneys and they didn’t have anyone there at the time.  The chap who’d left had done all the kidneys, so I had a really good niche, and was able to build from that.  I suppose I got interested in renal disease through that, and we did a bit of renal research – just case reports and so on, we didn’t do any major studies. 

New tools, new insights in GI pathology

Another great opportunity I got when training in Dundee was to learn gastrointestinal (GI) pathology.  We had a new professor of medicine, who was a gastroenterologist, and so we started getting endoscopic biopsies.  This was just the time, the late 70s, when GI endoscopic biopsies were coming in, and David Hopwood picked up that and he took the lead. I saw a lot of it with him…I was very much not the front man there, but I learned a lot from him.  And that again was very useful when I went to Barts, because there was nobody picking up the GI stuff.  So even though I’d been number two in Dundee, I was number one in Barts.  And I learnt it very quickly because I had to.

SA:  But weren’t these major areas for diagnosis already?  Weren’t these some of the most common diseases – gastrointestinal problems and kidney problems, and that sort of thing?  Who was doing it otherwise?

DL:  They weren’t being diagnosed by biopsies.  Our understanding of gastrointestinal pathology was based on surgery and what came out of that.  I mean that’s one of the reasons why Helicobacter pylori [the main cause of ulcers and various other stomach diseases] wasn’t discovered – because, if you remove a stomach (and we’d been looking at stomachs for years) it autolyses (degrades) a little bit when it comes out and you just don’t, in surgical specimens, see the Helicobacter bacteria.  You only see them if you get a biopsy and it’s put straight into fixative.  I’ll say more about Helicobacter later.

SA:  So up until then, the understanding of what went on gastrointestinally came from these big things that surgeons removed?  

DL:   Yes, and animal work.

SA:  Okay, so when did it become possible to do biopsies, when was that?  

DL:  They hadn’t done renal biopsies in Dundee before; they started doing them when I was in the department.  You could do rectal biopsies through rigid sigmoidoscopes, but there weren’t colonoscopies at that time.  And there wasn’t upper GI endoscopy until the 70s.

SA:  So really you’ve been around during some major advances, or opportunities in pathology?

DL:  Yes, major opportunities.  I was around before Immunohistochemistry A technique that uses antibodies labelled with fluorescent or pigmented dyes to identify, or indicate the presence of, specific proteins in tissues when looked at under the microscope., and I can tell you some stories about that coming in at Barts – that was very interesting.

SA:  You were saying that up until the 70s most of what you knew about the GI tract came from surgeons, and what surgeons removed.  Can you describe for me the difference, once you started to get biopsies, and what you were able to discover then?  

It was almost like a virgin fieldDL:  [Considers] It was almost like a virgin field, because we’d really only seen stomachs that had been removed because they had cancer in them or because they had an established ulcer.  We never got to see any of the lead-up pathology, or the pathology from people who had lesser symptoms, or who had pre-cancerous disease, or pre-ulcer disease.  So really one had to learn it from scratch.

SA:  Was it exciting?

One had to learn it from scratchDL:  It was.  I mean, one felt a bit at sea, but we were all learning together … I enjoyed my time in London very much indeed, professionally and socially.  It was great working with fantastic people.  I got to know Basil Morson, who worked in St Mark’s Hospital just up the road from Barts.  He was on his own, and if he went on holiday I would go and do his work for him while he was away.  I got to know him and became very friendly with him. He wrote [turns to reach for a book on his shelf]…Well that’s the latest edition of it: Morson and Dawson’s Gastrointestinal Pathology.   It was really the first decent text book of GI pathology, and it was based on very careful studies of surgically removed specimens, and then into the biopsy specimens also.  It was fantastic to have the opportunity to work with somebody like him, and learn from him at that time.

The great ulcer breakthrough

SA:  Going back to what you were saying about being in virgin territory – what were you trying to do?  When you first saw these biopsies, how easy was it to see the pathology…to understand what you were seeing?

The pathologist who wouldn’t let goDL:  At first it was very difficult trying to understand or work out what might be the significance, if any, of what one was looking at.  And I know that I -- along with virtually every other pathologist -- dismissed the little things that turned out to be Helicobacter pylori.  I mean, Robin Warren [who won the Nobel Prize for medicine] was the pathologist who wouldn’t let go, and just kept on at his physicians about what he was seeing, saying, “Look, I’m sure these are bacteria.”  And everyone said, “Pah, you don’t get bacteria in the stomach…Acid!  How could you possibly have bacteria in the stomach?!”  And he said, “No, I’m sure these must be bacteria…”  And then you know the story -- Barry Marshall [joint winner of the Nobel], with nothing better to do, went and talked to him and got persuaded, and then they worked together, and the whole story goes from there...

I believed the dogma of the timeSA:  And once Warren and Marshall started publishing did you go back to it and have another look…?

DL:  [Laughing] Oh yes, they’re easy to see!

M:  Why had you missed it?

They were pilloried!DL:  Because I believed the dogma of the time – that there weren’t bacteria there.  And the alternative explanation was that they were just bits and pieces of sloughed cells.  It’s very easy in retrospect…I mean, it’s very easy in retrospect when you look at the endometrium to see that these little black dots are apoptotic bodies!  And it’s interesting, once you’ve done a bit of research on something and used a bit of electron-microscopy, if you go back to light microscopy you can start to see things that you didn’t see before, because you know what the basis of it is, so it sort of tunes your eyes to seeing things that you hadn’t recognised, or noticed, before.  But I don’t know…I mean, Warren and Marshall, they were pilloried!  But they hung in there and it was the established view that was shown to be stupid and wrong in the end. [Laughs]


The patient behind the puzzle

SA:  Okay.  All that you’ve been talking about has been the fascination of diagnosis and seeing things under the microscope and so on – how conscious are you, in your work, of the patient at the other end?  Are you much more of a scientist than you are a physician?

DL: [Long pause for reflection] I’m both.  I’m both.  If you’re diagnosing, you know there’s ... I am always very conscious there’s a patient at the end of it.  I don’t like writing a report when I have to say, “I can’t make up my mind” – though I have to do that fairly often. And I don’t like writing a report that says, “To make this decision you’re going to have to go back and get more material”.  And I have to do that fairly often too.  And I don’t like doing it.  

But, no, I’m very conscious…I was phoned the day before yesterday by a GP from Forfar who said, “This patient who you did a report for …” She’d sent in something she thought was a lipoma, a simple fatty tumour.  But it wasn’t; it was a very odd lymphoid reaction.  So I’d made some suggestions, I’d said, “Could this be at a site you’d normally find lymph nodes, or could it possibly be a site where there’ve been injections or vaccinations?”  And she thanked me very much for making the suggestions and said she was going to be seeing the patient later in the day.  That was very satisfying -- to get a phone call like that.  And I was able to discuss the patient with her and make some other suggestions too.

SA:  But do you see patients much?

DL:  No, hardly at all.  And I don’t miss that fact at all.  I mean, I have to deal with my colleagues who are just as difficult as patients!  [Laughs] Easier in a way, I suppose, because most of them have an empathy with me.  But do I miss contact with patients?  I don’t know…Well I hope this book might show that pathology is relevant to patients.

The information that the pathologist provides that is the crucial thingSA:  I’ve been interested to hear from some people that there is a stigma attached to pathology even sometimes amongst clinicians and others in the medical profession.  Is this so?  What do you feel the status of pathology is?

DL:  I think it’s better than it was.  A lot better than it was, with the emphasis now being on multi-disciplinary teams and trying to collate all the evidence, and with the pathologist always being part of such teams.  And I mean you can’t get away from it, it’s often the information that the pathologist provides that is the crucial thing.  Not always.  Okay, with imaging techniques coming on as they are at the moment, getting better and better, they can often see the extent of a disease process even better than we can.  But they’re still only looking at grey and black and so on….

SA:  Well don't you still need an explanation of what you’re seeing?  And a process – how it’s happened?

You can actually start to understand the mechanisms of thingsDL:  That’s right.  I think it’s probably what excited me about pathology – the fact that you can actually start to see and understand the mechanisms of things.  And I think microscopes are terrific things for that.

SA:  D’you remember when you first looked down a microscope – because it is another world down there, isn’t it.

DL: Yes, as I told you, I didn’t like using the monocular microscopes as a medical student – I could never see things. I was slightly worried when I started doing pathology that when I looked down a binocular microscope I wouldn’t be able to fuse the images and see a single image, and I wouldn’t be able to recognise what a mitotic figure [dividing cell] was and so on.  But I got over that in a few days!  Once I’d learnt how to use the bit of kit and could actually start seeing the cells and recognising them, starting to think about mechanisms of disease and understanding them was a gradual process.

Microscopes are terrific thingsPeople are very different.  I’ve mentioned David Hopwood to you – David was very, very good at thinking about mechanisms. He never ever saw an image without thinking about mechanisms.  Lots of pathologists see an image and they think about a diagnosis, and that’s very important too.  I mean it’s probably much more important to that individual patient for that to be the first reaction.  But David would start thinking about mechanisms, and that was great.

SA:  What sort of person are you? Are you the sort of person for whom the image tells you the story very quickly, or…?

DL:  I think I’m a bit schizophrenic!  Sometimes I’m happy to operate in one mode and sometimes that’s not enough, I have to operate in the other mode.  And I don’t know if I have control over which mode I approach it in.


A son of the Manse

SA:  Okay.  Going back to the other side of your life – what sort of family did you grow up in?  You told me how you chose medicine with your mum standing at the door and saying, “You’ve got to make a decision”!  But what sort of household was it?

My dad’s one of my heroesDL:  My dad, he’s still alive, he was a parish minister.  I was born in Perth, grew up initially in Gorebridge just south of Edinburgh, then Edinburgh, then Glenrothes, then university.  I always remember my dad working very hard – my dad’s one of my heroes.  I remember my childhood being very happy.  The other thing I remember about my childhood is my mother’s asthma.  I remember summer days with her in bed and the windows all open and her gasping for breath, and adrenaline keeping her alive in several acute attacks.  But she was a chronic invalid until I was about 20 or 22, and then Becotide inhalers came along and [snaps his fingers]…

SA:  She was better?

DL:  Fantastic!  I mean, asthma comes and goes, as you know, so she could function in between, and she managed to run the house even from her bed.  She wasn’t in bed all the time, though my childhood memories have her there a lot.  When I think about it, and think about going on holidays up to the North West, she was always there, and able to come on walks with us and so on.  But no, I remember my childhood with fondness.

SA:  Why is your dad one of your heroes?

DL:  He was obviously very respected in his job, respected by his parishioners, and that was reflected just in going around the town or the village…

SA:  But was he approachable to you?  Was he someone you could talk to easily?

DL:  Yes, he was.  He always used to take four weeks holiday in the summer – that was the highlight of my year as a child.  We would usually go up to the North West of Scotland…

SA:  And do what?

Some of the not-very-safe things we did in boats!DL:  Well we used to take a house in places like Arisaig or Mull, and then he got into caravanning in 1951, so it was caravanning from then on.  We took the first caravan into Achmelvich, which is now a very popular caravan site.  He used to pull that caravan with a 1936 Austin 10, which wasn’t nearly strong enough, and I used to sit in the back of the car holding a brick.  We would get stuck on hills regularly and my job, when we stuck, was to jump out of the car, run round and stick the brick under the wheel so we didn’t run back down the hill! [We both laugh]
He had an old canoe from his university days that he used to bring on holiday; and he introduced me to sailing.  I mean, he taught himself sailing while he was teaching me sailing, and we kept going swimming together… Some of the not-very-safe things we did in boats!

SA:  How many brothers and sisters do you have?

DL:  I have one brother and one sister both quite close to me – my sister is 16 months younger, and my brother is three years younger than me.  It’s one of my earliest memories, going on my dad’s back in to see him the day he was born.  He was born in the house, and going in to the spare room and seeing him in his cot.  I remember being given a piggy back in to have a look at the new baby.

SA:  I notice in your CV that you say the church is one of your main outside interests.  What I’ve found interesting talking to other pathologists is that nearly all of them have come from backgrounds where you would expect some kind of religious belief – Jews or Catholics -- but none of them have been believers or church goers.  I’m interested in the fact that you are a church-goer…

DL:  Well I’ll stop you there – I’ve drifted away from it, very much so.  As I say, my dad is one of my heroes, and I spent several summers on Iona which I thoroughly enjoyed.  That’s one thing, if you ever look at a picture of Iona Abbey, and look at the west range, which you see right in the front -- I transported every single stone in the west range, from Mull to Iona, on a boat!  That was funny…I had a job…The summer before I went to medical school I went to be a guide at Iona Abbey, and enjoyed it very much.  They had an old rowing boat that nobody had used for years, but I did a bit of work on it and went out rowing and did a bit of fishing and so on.  And I remember George McLeod [the founder and first leader of the Iona Community] the day I was leaving, he called me in to see him, and he said, “You’re interested in boats.  How would you like a job next summer?  We’ve arranged to get a boat because we need to transport across a lot of stones – would you like to come and take charge of the boat next summer?”  To me this was paradise: Iona with a boat, and getting paid for it! [We both laugh]

SA:  And you did it?

DL:  I did it!  And we had some real adventures that summer, because I mean I was self taught -- I didn’t know anything about engines or boats, but we had to learn very quickly to stay alive and get the stones across.  We did some silly things with that boat!  But we survived and we got all the stones across, and every time I see a picture of Iona Abbey I can think, “All the stones in that bit of the building were transported across by me!”

SA:  I was saying that I was interested that quite a number of people’s religion didn’t seem to be big in their lives, and I got the feeling that the kind of work they were doing had made them drift away from it, and I wondered how, if at all, your work may have affected your religious beliefs?

DL:  As I say, my dad’s one of my heroes.  George McLeod was one of my heroes too.  And these guys -- I can’t believe they’ve based their lives on something that doesn’t matter.  But I mean [religion] is not an important part of my life any more.  I’ve certainly drifted away from it…I guess, partly, I sail at weekends -- I prefer that to sitting in a church.  I don’t go regularly to church any more.

SA:  Well how would you say that your work and your everyday familiarity with death and dying and disease has affected your philosophy of living and your feelings about the meaning of life?

DL:  Not at all.

SA:  Not at all?  You really think not?

But it is by no means a definite scienceDL:  I don’t think so. I don’t think that’s affected my attitude to these bigger questions, I really don’t.
I think perhaps one of the reasons I like pathology is it provides more answers than many other branches of medicine – or more definite answers.  But it is by no means a definite science.  I mean, it’s all judgement.  Why do you say that’s cancer, when you look at that slide?  Well, because my experience of looking at this sort of thing before has shown me that a patient who has this, if you don’t do anything, will be dead within a few weeks.  It’s experience-based rather than based on anything more solid than that. 


Immunohistochemistry: replacing educated guesswork with hard science

SA:  Okay, you were telling me earlier that you've seen the advent of some of the big advances in pathology like immunohistochemistry in the 1980s – what is it and how big has it been?

DL:  It’s been huge.  I mean what you can do with this technique is you can visualise where a particular protein is in a cell or in a section.  You use antibodies which are labelled in some way with something you can see down a microscope [as a stain] so that you know, if you have an AntibodyA protein produced by the body's immune system that recognises and attacks foreign substances. to protein A, wherever you see that stain you know that protein A is there.  It was the advent of Monoclonal antibodyAn antibody produced in the laboratory from a single clone of cells, which is therefore a single, pure, homogeneous type of antibody that recognises only a single, specific antigen, or protein.   that are absolutely specific to particular proteins – just one antibody to one protein – that has been very helpful. 

A huge differenceI told you how much I enjoyed working with Basil Morson, and how much I admire him.  But I do remember a mistake he made, and that was in relation to immunohistochemistry.  One of the first antibodies to cytokeratins was produced by a girl called Carol Makim, and she took along some of her preparations to Basil and said, “D’you think this might be any use in diagnostic pathology?”  And he looked at it and said, “Well it stains all different sorts of Epithelium  The layer of cells covering most of the body's structures and organs, internal and external.  It includes the skin. – I don’t think that’ll be any good at all.”  It’s actually one of the most useful antibodies that’s ever been invented!  [Laughs] But  I suspect I might have said the same thing if she’d shown it to me! 

But Immunohistochemistry A technique that uses antibodies labelled with fluorescent or pigmented dyes to identify, or indicate the presence of, specific proteins in tissues when looked at under the microscope. has made a huge difference.  Before we had this, if we saw a mass of malignant cells, we could tell it was a tumour, but not definitely if it was a LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers., which is treatable, curable; or if it was an undifferentiated CarcinomaA type of cancer that starts in epithelia, the tissues that line or cover most body organs.  At least 80% of cancers are carcinomas (see also sarcoma, leukaemia, lymphoma). in situ which virtually nothing will touch, will kill you in a few weeks or months; or if it was a sarcoma for which there might be some other specific treatment.  Now, with immunohistochemistry and the molecular techniques as well, we can tell in almost every case, "Yes that’s a lymphoma, it’s a B-cell lymphoma, usually curable.” The chances are that 90% of people who have this sort of tumour will be still alive in five years, if they are treated with this particular regime.  So…

SA:  How can you tell?  Because it shows you which proteins are there and where they will have come from in the body?

I could make an educated guess... ...technology has made diagnosis much more specificDL:  Yes.  If the malignant cells are expressing lymphoid AntigenAny foreign substance or organism that stimulates the body's immune system to produce antibodies and cells that react specifically with it. s, then you know it’s a lymphoma.  If you can tell they’re not producing lymphoid antigens but are producing proteins you usually find in epithelial cells, you can say, "That is a carcinoma."  And now with newer antibodies, you can say (prostate, for example, produces 'prostate specific antigen') you can say, “Right, that's carcinoma; it’s producing 'prostate specific antigen'; it’s a man, this is almost certainly prostatic carcinoma”.  Before this technology became available I could make an educated guess.  I could say, “Well, it’s undifferentiated.  Okay, it’s an elderly man; doesn’t look very lymphoid. I’ll guess it’s prostate.”  Because there was a high probability of it being prostate.  But no, this technology has made diagnosis much, much more specific.

SA:  David, tell me about the study group you have here?  What is it…?

The politics of pathology

I’m going to play very hard in these negotiationsDL:  I’m the chairman of the Tissue Bank Committee here and the principle grant holder for the Tissue Bank.  We’re funded by Cancer Research UK, and we collect tissue, fresh, that’s surplus to diagnostic requirements -- we have to have signed written consent from the patients to do that -- and I chair the committee that deals with requests to use that tissue.  So I’m getting quite involved with the political side of things, and am on a group that is advising the Scottish Government on exactly what the legislation should be for research tissue in Scotland. 

I must say, I’m going to play very hard in these negotiations for the “presumed consent for the use of surplus tissue for research” position.  (I hope the politicians might see what political capital they could make, because this is really something Scotland could do and take the lead in the UK).  And if I get batted back from that position, then I’ll go for the position that if somebody’s having an operation under the NHS they should always be asked, at the same time as they’re being asked for permission to have the operation, if the surplus tissue that the pathologist doesn’t require for diagnosis can be used for research.  If we can get to that position, we’ll be light years ahead of England, which doesn’t do that.  

SA:  How inhibiting is it at the moment?  You were saying that some of the research you did at the beginning – with apoptosis in the endometrium – you couldn’t…

DL:  I could never have done that now, no.
The legacy of Alder Hey

SA:  But is there a brake on medical progress?

It really does slow things upDL:  I think so.  I know of studies that have not been done because it’s just not worth the effort of going through the ethical hoops you have to go through to get permission to do it.  It’s hard enough to get money to do research, but when you’ve got to do this in addition… I’m sure I wouldn’t have done a lot of my research projects.  I might not even have gone into academic pathology at all had you to go through the rigmarole then that you’ve to go through now. It really does slow things up.
I know Lesley Christie who’s a clinical research fellow here – she's got the funding for herself for three years and all she needs is tissue to do the experiments to work on an unusual LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers.-related condition called Langerhan’s cell histiocytosis.  There’s plenty of the tissue around the country, but she’s got to get ethical permission from all sorts of places, and she’s pissing about, writing these ethical things instead of doing the bloody work!  It does make me very annoyed, this sort of thing.  She’s spent lots of time and effort on this when she could be getting on with actually working on the disease.  And it’s all in the interests of being ‘politically correct’. 

I’m at one extreme in this kind of thing… You’ll probably fall out with me over this, but I don’t think that Alder Hey and Bristol were scandals.  They’re only scandals because the media say they were scandals.  I don’t think it was good practice, but I don’t think that keeping tissue potentially to use it, when somebody was already dead, and not telling the relatives was actually wrong.  It was a bit of dead waste tissue that was being kept, not a piece of the dead person’s soul or personality.  I think it was being considerate to people not to tell them they were keeping a bit of postmortem  tissue.

It still makes my blood pressure go up whenever people refer to the organ retention ‘scandal’.  That’s how it is referred to -- it’s called ‘the organ retention scandal’.  And I would argue with anybody that scandal is not the right word.

SA:  So the guy, Van Velzen, who was keeping the material, was he doing things that were basically unethical or not?

DL:  Well, I believe the Alder Hey enquiry report concluded that he had lied, falsified research reports and didn’t store things properly – all of which are, of course, unethical.  But the basic fact that he kept postmortem tissue, which was what all the fuss was about, had been standard practice for ever and was generally thought to be ethically acceptable.  People who say that ethics don’t change with time are, I think, deluded.

SA:  What drives the changes in ethical standards, or ethical practices?

DL:  The media.

SA: You think so?

DL:  Yes.  I’m afraid I’m a bit cynical about this.  I don’t think people who run newspapers are in it to tell me the news; they’re in it to sell newspapers.  And you’re much more likely to sell a newspaper if you call keeping an organ without someone’s express permission ‘a scandal’ than if you present it in what I would call a more balanced fashion.

SA:  And how much damage has it done to you, the controversies over Alder Hey and Bristol?

DL: To me not at all.  To the profession quite a lot.  And to paediatric pathology a great deal.  I know of quite a few people who have given up being paediatric pathologists because of this -- because they couldn’t stand the kind of pressures they were being put under, the phone calls, and the abuse they were getting as they walked home, and this sort of thing.  It has done a lot of harm to some people, and I mean it has really kicked paediatric pathology in the teeth.  

I know several paediatric pathologists who have changed to being GPs, have given up altogether, have had nervous breakdowns and so on.  And even here… I mean, I was spared most of it here, but it was Frank Carey who had to deal, on behalf of the Trust, with irate relatives.  He’s a real good guy, Frank, a nice guy, easy going and ebullient, and a first rate diagnostician, and it took a great deal out of him doing this. He had to meet with… not a lot of families, because it was small scale here compared with many other places, but while some of them were perfectly reasonable, others were not.  They wouldn’t listen, and they ranted and raved, and he had to sit there and be polite and reasonable, and go through all this in the evenings when he should have been back home with his family.  It got me quite annoyed!
But personally, apart from it making research more difficult, and making it more difficult encouraging people to do research, it really hasn’t affected me directly.


Professional heroes

SA:  Okay, more personal things…Who, apart from your father, are your heroes?

DL:  Well I’ve mentioned Basil Morson to you.  I’ve mentioned Alfred Stansfield to you.  They’re professional heroes.

SA: Can you remember any specific thing you carry forward from someone like Morson?  Is there a lesson you were taught by either of those two that you remember?

DL:  It’s easier to answer with Alfred.  Alfred was the archetypal English gentleman, and he would always apologise to you about everything – even coming into your room!  But he was hugely respected in Barts, and he’s the only person I think I’ve ever met who, when telling you he’d made a mistake or got something badly wrong (which was very rare, I can tell you!), he’d go up in everyone’s estimation!  You could palpably feel people thinking, “Well if you got it wrong, nobody would have got it right!” [laughs]  But he was very nice.  And he was very good to me when I went to Barts at first, just making me welcome, giving me my space, and teaching me without being intrusive or anything.  No, from knowing nothing about LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers., I had to learn very quickly, because with only the two of us… He wasn’t there all the time and I had to do them if he wasn’t there.  So I learnt very quickly and it became one of my main diagnostic interests – and also a research interest. 

A new classification of gut lymphomasThat links in with Basil as well.  Because he got all sorts of weird things sent to him, he built up at St. Mark's a huge collection of gut lymphomas.  One of the registrars in Barts, Tony Blackshaw, had written a little bit about them, but sort of given up.  But then I was asked to write a chapter on gut lymphomas for a book, so I said, “Look Tony, can I base what I’m going to write on your draft?  You be a co-author with me of the chapter, and we’ll get Peter [Hall] as well to write the clever molecular and immunohistochemical stuff.” 

So I wrote this chapter with Peter putting in his bit, and I remember, when I’d written it, Peter came and said, “You know David, you’ve written a new classification of gut lymphomas.  We should put this into the Lancet in letter form.”  So we got together with Basil and a famous American pathologist and Alfred and Jeremy Jass, and we wrote this letter for the Lancet clearly showing for the first time that gut lymphomas are biologically distinct from lymphomas elsewhere.  (It’s partly due to the fact that a lot of them are dependent on Helicobacter pylori [laughs], though we didn’t know that at the time.)

SA:  How are they so different? 

DL:  When somebody presents with a low-grade LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers., at the time of diagnosis it’s usually pretty widespread.  But gut lymphomas remain localised.  And usually when they present they’re still localised as well.  And stomach is the commonest site and Helicobacter is the cause.  That’s why the tumours stay localised ? for a long time in their biology they remain dependent on the driving force of Helicobacter.  They eventually break away from that, as they develop other further mutations and so on.  But that’s a fundamental difference between gut lymphomas and other lymphomas, and that was really what fell out of my chapter.

We had about 220 cases and I grouped them all together and wrote about them.  We were talking about them, and I think it was Peter (he was sharp, very sharp), he said, “You know, this is new.”  I had written it as a chapter, and put it in a book. We got a very nice review from a very hard reviewer called Henry Appelman too, who said, “This is the first sensible account of gut lymphomas I have ever read.” [Laughs]  So I thought, “That’s pretty good!”

Of bladder stones and bezoars

SA:  Give me one of your most exciting cases that you’ve dealt with….an example of your most exciting cases.

DL:  Well, I can think of the amusing ones, the ones that tickled me.

SA:  Yes, give me a tickling one!

DL:  Okay.  This is another serendipitous thing I got into in Barts, and what I eventually did my MD on, which is up there [he waves his hand towards a thick tome on his shelves] – on micro-analysis in histopathology.  I used to get frustrated looking at sections, because we could often see bits of particulate foreign matter in the tissues, and there's only a limited number you can stain for. You can stain for iron, you can stain for copper, you can stain for glycogen, but there are millions of other substances in the world that you can’t stain for. 

And I got interested because there was a chap running the electron microscopy unit at Barts called Peter Crocker, who’d done some work on crystals in joints – gout and pyrophosphate arthropathy and other types of arthropathy.  He’d worked with the electron microscopes and done micro-analysis through various types of spectroscopy.  Being frustrated seeing these particles, I’d given him some paraffin sections to look at, and we’d started doing some basic analytical work and started to find all sorts of bits and pieces of metal and other things that shouldn’t be there.  And we'd started writing papers.

[One day] a guy came from the biochemistry department and said, “David, we’ve been sent this stone.  It’s been passed from this guy’s bladder, we’ve tried to analyse it and it won’t do anything.  It’s not oxalate, it’s not urate; it’s not triple phosphate (which is what bladder stones are usually made of), can you help us?”  I said, “We’ll have a go.”  So we stuck it in our machine and it said: silicon.  Silicon in the bladder?  I thought, "That’s ridiculous".  And I said to Peter, “I don’t believe it.  The machine’s playing up again!”

Peter had more faith in the machine and said, “Oh, I’ll do an infrared analysis as well.” And it told us it was silicon dioxide.  So I thought, "This is crazy; bladder stones made of silicon?  I’ve never heard of that".

SA:  What is silicon?  Where would you find it normally?

DL:  In rocks!  But, I said (and being a pathologist probably helped here),   "The only medicine I know with silicon in it is magnesium trisilicate, which you can buy over the counter in chemists as a remedy for indigestion".  And I thought, "I wonder if this guy has ever taken magnesium trisilicate?"  So I phoned the ward, and of course the chap had gone home ages ago, so I got the notes out and read through.  The houseman had recorded ‘suffers from indigestion’, so I thought "We might be on to something here".  I rang the patient’s GP and I said to him, “Sorry to bother you, but do you think this chap might take anything for indigestion?”  And he answered, “Young man, I have been this man’s GP for the last 35 years; he has never ever complained to me of indigestion.  I’m quite sure that he doesn’t take anything at all.”  So I was very down, and I was just about to put the phone down, then I said, “Would you mind if I wrote to him, just to ask?”  And he said, “Of course I wouldn’t mind”. 

That was another original paperSo I wrote, and by return I got this letter from the patient and it said something like, “Since February 26th 1945, after every meal I have taken a tablespoon full of magnesium trisilicate”. [Laughs heartily] I was able to work out how many kilograms he’d taken in and I looked into the metabolism and estimated how much he would have passed out in his urine. I was able to work all that out and we wrote it up.  So that was another original paper in The Lancet on a new type of urinary tract stone!

And again just from doing the basic…Just from writing and asking the patient, having not been put off by the GP who’d said, “Young man...”  (If he hadn’t said, “Young man,” I’d probably have given up anyway!)  But I thought, "Well I’ll write to him," and I got this letter. 

SA:  And did you write back to the GP and tell him?

DL:  Oh yes! [We both laugh]

We had another nice one too…You know what a bezoar is?

SA: No.

DL:  It’s a lump of foreign material removed from the stomach, and often from women who chew long hair…

SA:  Oh God!  Like a cat gets a fur ball?

This bezoar was in fact coconut mattingDL:  Yes, exactly.  Or people who chew string sometimes get them.  Anyway we got this bezoar removed from this young man’s stomach.  He was asked, “What have you been chewing?” and he said, “Well, as a young man I used to chew the sleeve of my duffle coat.”  It didn’t look very like a duffle coat, but I still had my old university duffle coat, so I brought it in and we took fibres from the toggles and from the coat and everything and tried to match them up to the bezoar fibres in the scanning microscope.  Nothing matched up. 

Then Peter Crocker said, “You know David, that looks to me just like a coconut mat.”  You know, the sort of doormat?  And I said, “It does a bit.” So we got a floor mat and took fibres out and matched them up to the fibres in the specimen…Exactly the same!  And then the analysis… We couldn’t do the usual inorganic analysis because this was obviously organic material, but we did infrared analysis and we got exactly the same spectrum on the two.  So we’d proven that this bezoar was in fact coconut matting.  We told the surgeon, and he went back to the patient and said, “Look, we think it’s not your duffle coat, it’s coconut matting.”  And the patient said, “Well… I used to chew coconut mats as well”!  [We both laugh]

More medical mysteries

SA: So people can't hide their funny habits from you lot!  That's a wonderful story.  I don't expect many people will tell me funny stories – have you got any others?  Or any other just big stories from your pathology case book?

DL:  This was another one from while we were at Barts.  Tony Dawson was a very well known Gastroenterology  The branch of medicine that deals with the digestive system and its disorders. physician and he used to get patients referred to him from all over.  He got one chap referred to him who was emaciated. This was in the early 1980s.  The chap had been a POW in Burma in the war, and he dated back his emaciation to this.  He was being assessed for compensation and Tony was asked to review the case and, being a good physician, he got hold of the patient's notes.  He noted that the chap had been admitted in other hospitals in different parts of the country between 1950 and 1980 and had bits of bowel removed, so he thought he'd get these [tissue samples] in and send them to me to be reviewed. 

SA: Historical samples?

He got no compensation, but he got betterDL:  Yes. Yes.  We got them sent from the other hospitals, and they'd been reported non-specifically, just showing ulceration and a bit of inflammation.  They were from the duodenum and the upper jujunum and I looked at these and I thought, "These look like peptic ulcers".  And I thought, "Peptic ulcers that far round the small bowel?"  You only get that in one thing, and that's the Zollinger-Ellison syndrome, which is a syndrome due to excess gastrin production usually from a benign tumour in the pancreas.  So I thought, "These look like peptic ulcers", and I said so to Tony Dawson, and said, "It'd be worth checking his serum gastrin". It came back very high.  So he put him on ranitidine which was the proton pump inhibitor available at the time, and the chap, within two weeks, put on two stone or something like that.  He was completely cured… And didn't get any compensation, so he was probably most displeased with us!  He got no compensation, but he got better, so at least he would feel well after that!

SA:  Poorer, but well.

DL:  There was another case…This was a lymph node biopsy, and I think Alfred must have been away at the time because I had to wrestle with it -- I didn't know what it was.  Because it had big foamy macrophages in it, I thought it was benign and I tried a PAS (periodic acid-Schiff) stain, which you use for fungi and various bacteria (it's a bit non-specific), and they stained up a bit. So one of the differential diagnoses I suggested was something called Whipple's disease, which is caused by bacteria.  It usually affects middle aged men and predominantly affects the gut, but it can affect the lymph nodes and the central nervous system, and even the heart sometimes.  So they did a biopsy of the gut, where you usually see a lot more macrophages, and it confirmed it was Whipple's disease.  So the physician put him on tetracycline and he got better.  We got a biopsy of his gut a year later – completely back to normal. 

I didn't think anything more about the patient, but then he turned up again at the physician's and he was obviously demented.  And the physician thought at the time, "Well now, what did I treat this patient with?  I treated him with tetracycline.  That doesn't cross the blood-brain barrier.  Could the dementia be due to Whipple's disease affecting the CNS?"  So he put him on trimethoprim, which does cross the blood-brain barrier.  Dementia vanished. 

We never actually published that case, though I've written about it as a case study in the latest Muir's Textbook of Pathology which I'm now the senior editor of.


Personal tragedy

SA:  Now a nasty question… What about bad moments that you're prepared to admit to?  Real low moments.

The worst moment ever in my lifeDL: [Long pause].  Some of my nicest moments are with family.  Some of my highs that I can still remember in detail are sailing races that we've done well in, and always with family.  I suppose the worst… The worst moment ever in my life was when my first wife Jill died. That was three years after we'd moved to London, and she just died suddenly and without any warning from a Subarachnoid haemorrhageBleeding between the brain and one of the covering membranes, often due to a ruptured aneurysm, a weak spot in the wall of a blood vessel..  I went off to work in the morning, she was absolutely fine, and I just got a phone call late in the afternoon to say she'd been admitted to hospital.  I had to ring up the hospital and was told she was dead.

SA:  What age was she?

DL:  We moved to London when I was 33, and she was a year older than me, so she must have been 37.  That was certainly the worst moment in my life.  I've been extremely lucky in that I married Rosie about three years later, and the nicest thing that anyone has ever said to me was said by my oldest boy Simon after I'd been married to Rosie, I think, for about two years.  She was fantastic with the four older children…

SA:  So how old were they?  They were still quite little, were they?

The nicest thing anyone's ever said to meDL:  Now, I have to think. Well Simon was the oldest, he was 13 at the time, and Scott would have been about 8 and the other two in between.  But after I'd been married to Rosie for about two years – as I say, Rosie has been fantastic with the older children – I remember Simon coming up to me and he said, "Dad, you choose your women well."  That's the nicest thing anyone's ever said to me!

So I've told you the worst thing that ever happened to me, and the nicest thing anyone's ever said to me in that sentence.

SA:  How did you look after the little ones?  How did you pull your life together at that stage?

DL:  Well again I was very lucky.  Five ladies who lived near us – we knew some of them actually through the church, and some were just neighbours we knew across the fence – they organised themselves into a rota and produced an evening meal for the kids for a period of about four or five months, which was fantastic.  And then my dad and mum, who lived in Haddington – my father was just coming up to retirement – they moved down and moved in with us.  So it enabled me to sort of keep functioning.  And then I was lucky enough to meet Rosie.

SA:  That kind of experience is absolutely seminal, isn't it? 

DL:  It is.  It is.

SA:…Because up until then you still do believe awful things happen to other people, they don't happen to you.  Does it stay with you, that sense of human frailty, that we simply don't know from moment to moment what's going to happen?

I felt tremendously reassured by the postmortemDL:  Yes it does. And I mean, bringing it back to pathology, …I mean, I felt tremendously reassured by the postmortem that was done on Jill to be told what the cause of death was.

SA:  It wasn't clear at that stage?

DL:  No!  I mean, she was well when I left; and then she was dead.  And I think…Well I know in the hospital they assumed she'd taken an overdose.  She was the last person in the world who would ever have taken an overdose, and that annoyed me, that people could even think that about her.

SA:  And it must have hurt at the time?

DL:  It did.  And I  could understand that.  But the postmortem told me unequivocally that it was a Subarachnoid haemorrhageBleeding between the brain and one of the covering membranes, often due to a ruptured aneurysm, a weak spot in the wall of a blood vessel..  I knew that there was absolutely no doubt at all, and that was tremendously helpful to me to know that.  So  postmortems can be very, very helpful to individuals – to the living.

SA:  That's interesting.  Irene Scheimberg, who does paediatric and Perinatal Pertaining to the period shortly before and shortly after birth, variously defined as beginning between the 20th and 28th week of gestation and ending the 7th to 28th day after birth. postmortems, this is what she says too – that they are just so important to families. 

Puzzling postmortems

DL:  Have you got time for two other stories related to postmortems?  We used to always teach on the postmortems at lunchtime at Barts, and just two quick stories.

The student audience just fell about!One of the students – well he's a famous cardiologist now – told me that the highlight of his medical career was during one of these postmortem demonstrations.  One of the medical professors, a chap called Michael Besser -- a fantastic guy, ran an endocrine unit which was terrific -- he gave the history, and he said, " This patient came in and we did all these investigations, and then the patient just turned his face to the wall and died.”  I was standing there, I had all the organs displayed and there was this massive pulmonary Embolism The obstruction of a blood vessel by a foreign substance or a blood clot., and I said, "Well, I think we can do slightly better than that for a cause of death."  And the student audience just fell about!  There was uproar in the room.  And I'd said it quite innocently -- "I think we can do slightly better than that for a cause of death"! [We both laugh]

I think he resented me a little bit for that…

SA:…A laugh at his expense!

DL:… No, we get on well; we always had a joust.  And then a postmortem on another of his patients who'd died -- he'd come in to be investigated and they couldn't find anything, and the patient just got sicker and sicker and sicker and died.  I was supervising the postmortem and presenting it, and I didn't know what the cause of death was – the organs were just a little bit swollen: the kidneys were swollen; the heart was a bit swollen; the brain was, but nothing definite to find.  I said, "To be perfectly honest, I don't know what the cause of death was here."  And he just stood there and said, "That's no help at all, David.  That's absolutely useless; I don't know why we bothered to get a postmortem."  And I said, "Now wait a minute Michael, we've still got to do the histology.  You never know what you might find when we do the Histologythe study of cells and tissues, usually carried out with the aid of a microscope.."  Usually in these circumstances you don't find anything conclusive, because I've been in that position before.  But anyway, I put the tissues through quickly…

SA:  The histology would be the tissues?

Every single capillary stuffed with tumour cellsDL:  The tissues studied by the microscopy in other words.  I couldn't tell just by looking at the organs what the cause of death was, so I said, "There's still the microscopy to come."  And I remember putting the first slide under the microscope -- it was a slide of brain, and I just looked at it, and every single blood vessel was stuffed with tumour cells.  Then I put the lung section under the microscope, and every single capillary stuffed with tumour cells.  There was no tumour, just tumour cells in the blood vessels.  I put the kidney under… Every single capillary stuffed with tumour cells. 

What this is is a very rare form of LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers. called angiotropic lymphoma.  Well that's what it's called now, it wasn't known what it was then.  It wasn't known whether it was a tumour of the blood vessel endothelial cells [lining cells] or not – but we were able to do Immunohistochemistry A technique that uses antibodies labelled with fluorescent or pigmented dyes to identify, or indicate the presence of, specific proteins in tissues when looked at under the microscope..  I'd been sensible enough to keep some of the tissue from that case frozen so we could do molecular studies on it as well, and we were able to prove that these were lymphoid cells, and B-lymphocytes.  So we wrote a paper on angiotropic lymphoma, which was the first time it had been described with immunohistochemical and molecular proof that it was a lymphoid malignancy without any tumour mass anywhere, just circulating around in the blood. 

That was my reputation made in Johns Hopkins!This patient… All his capillaries had been blocked up by these damned tumour cells, so it was very easy to see why he had died!  We got a very good paper out of it, with Michael Besser as a co-author as well. Then three years later I was doing a sabbatical in Johns Hopkins in Baltimore.  It was in Gastroenterology  The branch of medicine that deals with the digestive system and its disorders., and one day there was a bit of a commotion.  People came in and said, "You're Prof Levison, aren't you? You know about angiotropic lymphoma.  What's this?"  They shoved a slide under my microscope – it was a renal biopsy from one of their patients -- and I said, "Yup, that's what I think it is.  I think it's angiotropic lymphoma."  So that was my reputation made in Johns Hopkins!  They'd done a literature search and found this paper, and thought, "There's someone here who knows about it.  We'll get him to see if we're right about the diagnosis."  So that was a nice story too!

SA:  So how much of your time is taken up with autopsy?

DL:  None now.  I don't do any now.  I did right up until I became Dean of the Medical School and that was 10 years ago.  I did a little bit of autopsy work, but the department is much better organised – Frank Carey has revitalised it – so we're now able to specialise.  I really do GI and LymphomaCancer originating in lymphoid tissue, a key component of the body’s immune system.  Cancers of lymphocytes (lymphomas) and other white cells in the blood (leukaemia) together account for about 6.5% of all cancers. work.  I have to share the odd little bit of prostate and bladder work, but I don't have to do breast and gynae work and so on – that is done by people who specialise in that, which is better.  We have a group of four consultants who look after the autopsy service – and they're interested in it, so much better.

SA:  What did you feel about autopsies?

I'm squeamish – I don't like blood!DL:  Um…It took me about two years of doing them till I stopped feeling squeamish with the first cut.  But always after the first cut it became a technical exercise – trying to find what had been going on. I don't think I could ever say I enjoyed doing postmortems, but I learnt a huge amount from them, and we got an awful lot of useful information from doing them.  So that made it, if not enjoyable, very satisfying to do them.

SA:  What was the significance of the first cut – why were you squeamish till you'd done that?

DL:  You may think it's funny, I'm squeamish – I don't like blood!  [We both laugh]

SA:  Now he says!

DL:  [Still laughing]  I know.  I don't know why I went into medicine!

I think until you've made the first cut you think of the body as a person; once you've made the first cut, as I say, one's focus is on finding out what went on.  It's usually quite easy to stay detached from the person because we've never seen them alive, and I think that is useful.  I wouldn't say it makes me or others who do this any less respectful of the person, but if you keep thinking of the body as a person then it will inhibit your ability to be clear minded about what you're supposed to be doing.

SA:  So you've never seen a person on the ward before they died and then had to do an autopsy?

I would not do an autopsy on anyone I'd knownDL:  Yes I have.  But not very often. 

SA:  And was it difficult?

DL:  Um…I'd been at it for quite a long time before I did that, so it didn't really make that much difference.  But I think it was very helpful, when I was learning to do autopsies, not to have known the person as an individual.  And even now I would not do an autopsy on anyone I'd known, unless there were real extenuating circumstances – unless I was the only pathologist who could possibly do it and it was vital to find out what had happened.

Matters of life and death

SA:  So is death as much of a mystery to you as it ever was?  Because I think a lot of people wonder whether those of you who have to see it, have to confront it, have a more intimate understanding of death, or relationship with it, or whether it remains just as much of a mystery.

DL: [Long pause]… I think if I take the trouble to think about it then it does remain a mystery.  I don't dwell on it though. 

SA:  D'you fear it yourself?

DL:  Do I fear death?  No I don't think I fear it.  I don't look forward to it!  I want to do quite a lot more of enjoying myself.  I mean I know everyone says they want to travel, but there are places in this world that I'm very keen to see that I haven't seen.  I want to see New Zealand.  I want to see more of Australia.  I want to go to China.  I've never been to India.  Never been to Africa.  There are loads of places…

SA:  You haven't started!

DL:  I know, I know.  Lots of places I want to go.  And I've enjoyed wherever I have been.

SA:  What's interesting about this interview is that you seem to get a lot of fun out of life – would you say that's true?

DL:  Yes, I do.  I do.


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