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Sebastian Lucas

Professor of Clinical Histopathology, St Thomas’, King’s and Guy’s Hospitals, London

Sebastian Lucas grew up in a non-medical family in the south of England, and was persuaded to do medicine rather than animal physiology at Oxford University because it would give him more choices in life. The decision to specialise in pathology came soon after he began work as a medical student. ‘I realised that the patients I was looking at on the wards were chronically sick and I just thought: “Can one face working with chronically ill people day after day? Is there a bit of medicine which is problem-solving, and where you can solve one case and move on to the next?” That’s pathology.’

Lucas made his name in the early 1990s with his pioneering autopsy work on AIDS in Africa, where he investigated and underscored the powerful link between HIV and tuberculosis. The extent of TB surprised some doctors in the Western world, who believed TB was no longer a threat in the age of antibiotics, and had let down their guard. Having performed autopsies on more than 1,000 people who died of AIDS in Africa and England, Lucas knows as much as anyone about the multiple manifestations of the disease in different environments, and his findings have had a critical influence on the management and treatment of people with HIV. However, as he freely admits, much of the vital research he carried out in the 1990s would be impossible in today’s legislative climate. He got caught up in infectious diseases almost by accident, he says.

I’ll tell you about what got me into infectious diseases, and incidentally led me to where I am today. It was the drought summer of 1976 and I was at University College Hospital [UCH]. I was looking at a bowel biopsy late on a Friday afternoon when the rest of the department had gone home, and the case history said: 30 weeks pregnant, severe diarrhoea, query proctitis [inflammation of the rectum], query cause. It was a white woman, aged about 30. The usual diagnosis would be: nothing, or ulcerative colitis, or one of the standard diseases, but I looked at this biopsy and it wasn’t any of these. It was inflamed, but it actually had amoebae in it. I’d never seen amoebae before, but I knew what they should look like because I was vaguely interested in infectious diseases even then. So I looked at a book and there was a picture of amoebae; I looked down the microscope and there they were, and I said to myself, ‘This has to be amoebic colitis.’ So I rang the houseman and said, ‘This is amoebiasis.’ What she answered was unprintable! Because, she said, the woman was in theatre at that moment having her colon taken out because it was perforated. ‘She’s got peritonitis, and she’s probably not going to live.’ And she didn’t.

This was a Friday afternoon and the biopsy had probably been taken on Wednesday, because processing these things takes time. I was thinking, ‘If we’d had the answer yesterday, might her life have been saved?’ Well, you can conjecture till Kingdom come, I don’t know. But the point is they thought she had ulcerative colitis and put her on steroids. That’s what you do if it’s ulcerative colitis or Crohn’s disease, but if you’ve got amoebiasis it’s the worst thing you can do: the disease just lets rip, perforates the bowel and you die. This is perfectly well known, but you have to think of amoebiasis first. And what on earth is a pregnant 30-year-old who’s never left North London doing having amoebiasis, a tropical disease?

Not many people had ever seen a case of amoebiasis in this country. Certainly I never had. And certainly the main surgeon involved in this process never had. I remember presenting the case at the next gut meeting we had, and saying, ‘Actually, this is amoebiasis,’ and watching the physicians sink their heads in their hands and whisper, ‘Oh, God.’ Because this was a treatable disease …

So I did a bit of further investigation … As I say, this is what got me into infectious diseases: this actually changed my life. I found out, probably from the widower, that what had happened was that his wife hadn’t felt like cooking and so the neighbours cooked something for her and passed it over the fence. Very nice of them. This is in north-west London, and they had just come in from Bombay. So basically the infection was on their hands. A goodwill gesture, sadly carrying rather unfortunate consequences. Because there is no endemic amoebiasis in that part of London.

And it went further, the bizarreness of this story. In those days there was an amoebiasis research unit in the Hospital for Tropical Diseases, which was run by an extraordinary guy – he was an air vice-marshall, one of the older Air Force medics. I gave him a potted version of this story, and said, ‘There’s no question about the cause of death: it was amoebiasis. As far as I can see, the infection came from the neighbours who had recently arrived from India,’ where amoebiasis is endemic, and they were obviously symptomless carriers. I’ll never forget his retort: ‘This doesn’t happen in the United Kingdom!’ and he put the phone down. So the second message of this story – and I tell all the medical students – is: ‘Don’t always believe what old experts say!’

And infectious diseases are intellectually very teasing and exciting, are they?

Absolutely, yes. One of the things I do today, apart from looking at challenging autopsy cases, is a lot of infectious disease consultation work. People send me slides and say, ‘What is this? I think it might be this,’ or ‘I haven’t the faintest idea what it is.’ Every week will bring in one or two real gems.

Two days ago someone sent me a liver biopsy, saying, ‘What on earth is this?’ I looked at it and thought, ‘I can’t believe this! I’ve never seen it before, but I know what it is.’ It turned out to be someone who had had some abdominal trauma which had obviously ruptured a hydatid cyst, which is a parasitic cyst, and bits of that had gone into the liver circulation, blocked it off and damaged the liver. I didn’t know that could happen, actually. I’d written about hydatid cysts in the standard textbook of liver pathology, but I’d never seen this version of it.

That’s the thrill of this work: I’m looking at things which are either new versions of diseases I know, or genuinely really rare things, or even things that no one else has ever seen before. You’re kind of working on the edge all the time.

Tell me about your involvement with HIV and AIDS.

To my slight shame, I didn’t pick up on AIDS at the very beginning. It started nominally in 1981 when gay men in America started presenting with diseases no one had ever seen with any frequency before, if at all – that is, Kaposi’s sarcoma and Pneumocystis pneumonia [PCP]. In the AIDS calendar, 7 and 14 July 1981 are big days. That’s when Jim Curran of the US Centers for Disease Control [CDC] said, ‘I think we have a problem.’ He became the great man who drove the response to AIDS in the beginning. This is all in retrospect – I didn’t pick up on that at all at the time.

In 1982, I was here at St Thomas’ as a research fellow working on tropical infections with a charismatic pathologist, Michael Hutt, and we had a frozen section from a patient who had a lung problem, and no one knew what it was. Frozen sections are done during operations when surgeons want answers now so they can decide what to do. ‘Is it cancer? Do we chop out the rest of the lung? Is there something else?’ They’re sitting there waiting for answers and it usually takes five or ten minutes. The patient was called Terrence Higgins [one of the first people known to die of an AIDS-related illness in the UK]. Yes, him … Quite!

And he was under the knife?

He was. Maybe they thought he had cancer, I don’t know. Anyway, we looked at this and we just did not know what it was. But we knew it wasn’t cancer, so they closed him up; no more procedures were done. We looked it up in the textbooks and realised it was Pneumocystis pneumonia, which was the first case most of us had seen.

At that point the penny dropped: this was what we were then calling GRIDS – Gay Related Immune Deficiency Syndrome. AIDS hadn’t been officially labelled as that at that point. I remember that patient, Terrence Higgins, was looked after in a ward more or less to himself; he was treated like the proverbial leper. That’s one reason why the Terrence Higgins Trust was set up – to say that people shouldn’t be treated like this, and quite right. He died later of PCP and cerebral toxoplasmosis, a parasitic infection.

I left St Thomas’ shortly after that to go to UCH, so I wasn’t part of what happened here. But the name changed to AIDS, and then a group of people interested in AIDS grew up here at St Thomas’. Anyway, I forgot about it.

I was at UCH from 1983 until 1995, minus a year in Côte d’Ivoire in 1991/2. I got interested in AIDS not through anything going on at UCH, but actually because of Michael Hutt. He’s the grand old man, the main person in my professional life. Back in 1977, when I first realised that infectious diseases were interesting, I said, ‘Who knows about infectious diseases in Britain?’ and everyone said, ‘Michael Hutt.’ He was the professor of geographical pathology here – a unit set up to promulgate the importance of tropical pathology.

Michael Hutt had been at St Thomas’ in the 1950s as a junior doctor and a trainee pathologist, and then as a consultant pathologist. Then he decided to do something different, and he went to Makerere Medical School in Uganda as the pathologist. He was there through the 1960s. Mike and people like him – and there were a lot, all very famous clinicians, epidemiologists – made Makerere a jewel. There were loads of exciting things happening; it was virgin territory for describing diseases.

Mike Hutt retired from St Thomas’ in early 1983, and he gave me his practice, which was looking after diagnostic histopathology for mission hospitals abroad, particularly in Africa. I simply took over that work en bloc and built it up. It was partly cancer, partly TB, partly infectious diseases, partly just general stuff. These cases would come in by post. Surgeons in mission hospitals all over the place – but particularly East and Central Africa – would send in these specimens. They’d do operations, put the specimens in formalin, let them fix, then pack them up – usually in the ends of surgical gloves, which are very good containers, water-tight, tie them off with a piece of cotton or simply tie a knot in them like a balloon – and put them in an envelope.

We’d look at the specimens, write our reports and then send them back by airmail. I built that up because it was seen to be useful, and it was great fun. I saw loads of things I had never seen before – wonderful things, pathologically, that don’t happen in Britain.

One of the series of materials we were getting from overseas came from the Makerere School of Medicine in Kampala, Uganda – as I have mentioned, the best medical school in East Africa then, as now really. Among the stuff was a set of intestinal biopsies taken from people in Mulago Hospital under the auspices of two very active and dedicated clinicians. One was Nelson Sewankambo, a great Ugandan friend who is now Dean of Medicine at Makerere, and the other was Rick Goodgame, an American Baptist missionary doctor, who was an enormous enthusiast. They sent me all these bowel biopsies from people with slim disease. ‘Slim’ was the name given to a condition being seen in the early 1980s, and which we now know was AIDS. At that time, of course, we didn’t have the virus; HIV wasn’t known about till 1983. This condition had started in the southwest of Uganda, and had moved up country. The patients had wasting, and they had terrible diarrhoea, like cholera, and they wanted to know why. So the doctors started doing biopsies but the local pathology lab couldn’t cope, so they sent them to us.

It was obvious that there were some very strange things going on. One of them was a huge amount of an infection called cryptosporidiosis, a gut parasite that you don’t see much of now, but it was big then. It became evident that slim disease was gut cryptosporidiosis. We had a series of about 23 cases and we wrote up our findings in a paper with the title: ‘Ugandan AIDS: wasting disease is cryptosporidiosis’ – something like that. It was the first article published in a new journal called AIDS. Volume one, page one was us! Goodgame, Sewankambo, and my name tucked on the end. And that got me into the AIDS scene.

Then, as that was brewing up, two things happened. One was that the First International Conference on AIDS in Africa was held, organised by another remarkable clinician called Nathan Clumeck, a Belgian, who was working in Rwanda, where AIDS was also big. At that time, 1983/4, the first accounts of AIDS in Africa being an issue came out from Projet SIDA, which was a US-sponsored project based in Kinshasa and run by great people like Jonathan Mann [who died in an air crash in 1998], Peter Piot, Marie Laga, Anne Nelson and Robert Ryder … All these names! All history now. They were in Kinshasa in 1983 and they published a big paper in the New England Journal of Medicine which said: ‘There is AIDS in Africa, and it’s the same disease as in America, it just looks different.’

At the same time, Nathan Clumeck published a very similar paper which said, ‘We’re seeing the same thing in Kigali as well, and in Burundi …’ So gradually these reports were coming in, and Nathan organised a two-day conference in Brussels in November 1985, which was attended by about 100 people. At the end there were two press conferences held, one organised by Nathan that said there was a big problem of AIDS in Africa, and the other by a few black African physicians that said, ‘There isn’t a problem’!

Anyway, I met several important people at that conference, including Kevin de Cock, who is the most important AIDS physician–epidemiologist around now and is my best medical friend, really. After the conference we wrote a document for the Dean of the London School of Hygiene, saying that the School should get into AIDS in Africa ‘because AIDS is going to be very, very big’. In fact it is much bigger than we ever thought it was going to be.

Kevin then went back to CDC in Atlanta, and we remained in touch. And then I got a phone call from an extraordinary surgeon working in Kampala called Wilson Carswell, who said, ‘Come out. We know you looked through all this gut stuff and we’ve got to document it properly – AIDS is ravaging this country, it’s dreadful; come and see the hospital, you won’t believe it. Come and stay for a fortnight.’ Wilson met me at the airport; took me home for a shower and then to the hospital and just said: ‘Look.’

I have never seen anything like it. These are enormous wards, and every bed was occupied by a dying skeleton. I was staggered. Again, it flicked a switch: this is interesting, this is worth doing, this is a disaster. Wilson said, ‘It wasn’t like this 10 years ago. Something’s happened, and you are going to tell us what.’ I said, ‘Well, it’s AIDS.’ And he said, ‘I know that, but what have they got that’s making them like this? We know some of them have Cryptosporidium, but what else?’ And I said, ‘How about TB?’

I looked at patients, spoke to the pathologist there, did a few autopsies myself, took photographs, and we began to feel that, actually, ‘an awful lot of what we think is HIV-related disease may well be tuberculosis – made worse by HIV’. Which turned out to be entirely true.

When you saw all those emaciated people in the wards, had they been diagnosed with TB?

No, they hadn’t. It was a concept that gradually built up and finally became completely solid in 1991. But that’s five years later. So, I grabbed material – with consent – and brought it back to the UK.

I’ll tell you a good story. On my last day in Kampala, the British Council gave me a Landrover. January/February 1986, Kampala; not a good time to be there. Museveni had only just conquered the capital, and was moving north to try to get rid of the rebels from Gulu and beyond. Getting around Kampala was bloody difficult – pot holes, shell holes and what have you. Nelson Sewankambo and his great buddy David Serwadda – another Ugandan public health physician who’s become very famous in AIDS – said, ‘We should do a quick study. Is the virus (because it was still not HIV, it was just ‘the virus’) transmitted horizontally?’ In other words, if you live in the same household as someone, but don’t sleep with them, do you get it? ‘How can we answer this? What we need is a lot of blood samples very quick. Let’s go down to Rakai District, where this is supposed to have started.’

Nelson said, ‘I know the district medical officer of health; I’ll ask which are the worst-affected villages and do we have his consent to bleed everyone and bring the samples back for analysis.’ The DMO said, ‘Yes.’ So we drove down there in the Landrover at dawn. The DMO had a map and he said, ‘Go to these villages here.’ So we went with our bundles of syringes and needles; we found the village head man and asked, ‘Do you approve?’ (This is what consent was in those days!) We bled about 100 people in two or three villages. At the end of a long day we came back with lots of little vials of blood, all labelled and coded and so on. My task was to get these to England, and to the public health laboratory in Porton Down – and in particular to Bob Downing or Graham Lloyd, two more famous names in HIV virology, who would do the analysis.

The next day I left Kampala, having spent two extraordinary weeks that changed my life. I had a Thermos flask packed with ice and containing 100 vials, and in my suitcase I had loads of tissue blocks of AIDS pathology. I kept thinking, as I passed through several airport departure stations, ‘If someone asks me what’s in this flask, what am I going to say?’ But no one ever asked! A different world now, isn’t it?

When I got home, a courier took them away to Porton Down. It became a paper: ‘The AIDS virus is not transmitted horizontally.’

As I say, we were also wondering about TB. While I was still in Uganda I thought, ‘HIV makes TB worse in many contexts, but how can we prove this? I wonder if the pathology looks different?’ We obtained tuberculous lymph node biopsies from patients with AIDS, analysed them and published our findings. It was the first description of tuberculosis pathology being very different from standard TB when you’ve got HIV disease. The bacterial loads in these people were just colossal. If you do the stain for tubercle bacilli, which we call a Ziehl–Neelsen test, the bacilli come out red. With these cases you didn’t need to look under the microscope – if you just held them up to the light the whole slide looked red! Phenomenal densities.

However, the sheer overwhelming importance of tuberculosis didn’t really sink in until the early nineties – another half decade. And that happened in part, I like to think, from work we did in Côte d’Ivoire.

How did you find yourself working in Côte d’Ivoire?

Kevin de Cock had started a project in West Africa. He was asked by CDC to investigate HIV-2, which had just become evident. CDC didn’t want to be caught with its pants down a second time, because they had kind of misfired with working out what HIV-1 was. (In fact, no one did very well – Heavens, this was a new disease!) So the CDC said, ‘We need an HIV-2 project; go and find the place to do it.’ It became evident that the only place he could possibly work was Abidjan, because the communications in alternative places didn’t work. And there was a big American Embassy there, so the Retrovirus Project, Côte d’Ivoire – a collaboration between the CDC and the Ministry of Health of Côte d’Ivoire – was set up with American money. A new building went up in the grounds of the huge hospital; Kevin set up his unit and they started doing basic HIV work, with HIV-2 as the added interest.

Sometime around 1989 he said, ‘Come out to Côte d’Ivoire to see what we’re doing and see if it interests you.’ So I went out for two weeks in early 1990. I was appalled by the climate, and I was staggered by the amount of work going on. They had a wonderful lab. Most of the scientists were Ivorian – basically, they’d employed the best of the medical and paramedical Ivorians to work there, and paid them salaries which were somewhere between Ivorian and American. And they had very good infrastructure, with computers the like of which I’d never seen before. I met a lot of doctors. I met the pathologist, who was very nice. I looked at the mortuary, and thought, ‘God almighty, what a ghastly place.’ They all said, ‘Come and work here,’ and I said, ‘No, no, no!’

But then Kevin said, ‘Would you like to finish off a project for us?’ He gave me a whole lot of tissue blocks and slides. They turned out to be a set of autopsies, and as I worked through them I found that they were 50/50 HIV-positive and HIV-negative people. The HIV-positive people had TB and a bit of Pneumocyctis, and the HIV-negative people had boring things like lung cancer. And when I looked more closely I saw they were, in fact, consecutive deaths – every person over a period of, say, three months had been autopsied. I thought, ‘You can’t do that in England!’ I asked Kevin, ‘How on earth did you get consecutive deaths autopsied?’ And he said, ‘Ivorian Law, Napoleonic Code, it’s French. Anyone who dies in a teaching hospital can be autopsied without consent required.’ I said, ‘Kevin, I’m coming back!’ And he said, ‘I knew you’d say that. That’s why I got you out here.’

I still have nightmares just thinking about 1990 and the panic to get things going. We got a project that seemed okay but it would never pass muster now – ethically, no one would even contemplate doing this today. We drew up a project to autopsy as many people with HIV – and some HIV-negative controls, including children – as we could in a year. God, it was hard work! My own kids were doing O and A levels, so I went there by myself, and just worked flat out essentially for a year. But when people accuse me of being bad – which they do, very occasionally – I say, ‘They wanted it. The Côte d’Ivoire Ministry of Health supported this to the hilt, and more! And that’s what was done then.’

What manifestations of AIDS did you find in Africa that were different from in the West?

I was doing a lot of HIV work in London by then. UCH and Middlesex Hospital refurbished a mortuary dedicated to HIV for me in 1989, and we did loads of consented autopsy cases, and a few coronial ones. They all seemed to be the same then: all Pneumocystis. All the patients I was looking at were gay, white, middle-class men – that’s what AIDS was in London then. Africa was completely different.

The first thing that struck us in Côte d’Ivoire was, ‘Actually, it’s all TB.’ More than half of the cadavers I looked at had tuberculosis. I couldn’t believe it. This became evident after about the first two or three months, and Kevin and I said, ‘Well, even if the project comes to a stop now, we’ve proved what it is, it’s TB.’ So you’ll find, in the early nineties, loads of papers written by Kevin and me and others just banging the TB drum, and stressing the importance of diagnosis, prophylaxis, etc., because we knew TB was the major problem.

I should say that whilst we were doing this project, the clinicians in the hospital in Côte d’Ivoire rapidly got wind of it and every Saturday morning there was a clinico-pathological meeting of the cases we’d seen that week – with the professor of that particular ward, his senior doctors and all the junior doctors as well – and they all loved it. No one said, ‘Ethically you shouldn’t be doing this.’ They all said, ‘This is fantastic. We’ve never had feedback like this; this is hot feedback. The patient died on Monday; we now know why he died. This has never happened with us before.’ They gave me every possible help. This was real clinical pathology going hand-in-hand with management of cases. They gave me a huge party when I left, and said, ‘Please come back! This is what medicine’s meant to be all about.’

I came back to the UK in 1992. And the next two or three years were basically spent writing everything up. It doesn’t happen overnight; there’s a lot of analysis. Kevin was also back in Britain, which was wonderful. He was a professor at the London School of Hygiene, so we sat together and wrote papers. And that enabled me to get the chair here.

Looking back on your early research into AIDS and how easy it was to collect material, do you feel the Alder Hey debacle was waiting to happen, and that it was right that people should start challenging the practices of pathologists?

Only up to a point. And that’s because, when autopsies are done well, the public health benefits are so colossal that in my opinion they override, to some extent, personal objections. I’d be quoted saying that in public quite happily because it’s true, but it doesn’t look good. I had two complaints throughout the whole process. No parents of any of the kids in Abidjan complained, and we did about 150 children. So my point about overriding what we now regard as narrow consensual requirements is that it’s completely outweighed by the public good it does.

When Alder Hey happened I was here at St Thomas’, and we were more vulnerable than most other places in the country because we have the biggest collection of paediatric kidneys, hearts anywhere – much bigger than Bristol, because we’re a big cardiac surgery unit. We had a professional perinatal pathologist who was very interested in congenital heart disease, and she kept everything, because one did – no criticism of her. She took the whole Alder Hey and Bristol business very badly, and after some months she left. Now the last thing she’ll ever do is perinates – all that phase of life, all gone; she’s doing other things now.

I have to say the chief exec here, Sir Jonathan Michael, was brilliant. I have only praise for him. He realised that organ retention was a big issue, we were vulnerable and it had to be addressed openly. So very rapidly we had a team organised to work out what we’d got; that was the first consideration and there was a lot of work to do.

We have the biggest pathology museum in the country here, the Gordon Museum, in Guy’s. Not for a moment did we shut a door, remove an exhibit, close anything. Unlike Dublin, which closed its museum. Unlike the London Hospital, which cemented it in! I joke not. A whole lot of deans took fright, and actually shut the museums. We said, ‘We do not do this. We will keep our displays open.’ And particularly, we have a fantastic series of pots of malformed fetuses. Now this is not prurient stuff; this reminds the students that this is why we have prenatal scanning: so that we don’t have any more babies born with no heads, with spina bifida and things like this. It’s a brilliant display. You can be lectured like mad about the importance of antenatal screening; 10 minutes in the Gordon Museum and you can see why we do it.

One thing that didn’t happen here, and that did happen in Bristol, Alder Hey and other places, was that we didn’t have a whole lot of anguished relatives on our doorstep. I think the reason is that London is very different from Liverpool: patients coming to this hospital come from an enormous catchment area, so big that they never get together. So from that point of view the reaction was diluted. We talked to people, and we were not sued. We handed back some material, but most people were not interested.

But looking at Alder Hey, was what Van Velzen did standard practice for the time, or was he actually behaving unethically?

The major criticism of what Van Velzen was doing was that he took much more than anyone else did. Secondly, a very legitimate criticism is that he actually lied, in that there were reports coming out that said he’d done work on these materials which he obviously hadn’t done because they were still intact. That was professionally unforgivable. He took stuff intending to work on it but never actually did – and probably knew he would never be able to because he’d just got so much material, but he just kept on collecting.

But does that not go into an archive that other people can use?

Yes, they could do if it was properly documented. But it wasn’t properly documented, so that archive is effectively useless to anybody else. And he didn’t tell people he was doing it. Now there’s a lot of discussion as to whether he needed to have told, in all circumstances, what he was doing, but I’m not going to revisit all that, because it was a mess.

Actually, things haven’t got much better. They’ve got more bureaucratic, but there’s still a huge grey area in tissue retention. It’s very clear what to do if you want to be squeaky clean: you do nothing. That’s easy. But the point is, to be good and to be useful for public health you need to do a bit more than that, and that’s where the grey areas come in. I experience this day by day, and I know how to deal with it because I’ve rubbed along the raw edges; I’ve worked out how to do things that are ethically reasonable with appropriate consent built in, but so that you get what you want in order to advance knowledge and help people.

So are the rules now so constraining that you’re actually losing an awful lot of what might be beneficial?

Absolutely.

So has that in any way dimmed your enthusiasm for the work? What drives you to continue?

Curiosity! Even though I’m 60 I’m still very, very curious about things, and I haven’t yet seen it all. It’s a real important driver, actually, curiosity. It’s probably the biggest driver of all. I come into work every day early and leave later than my wife would like because there’s such an amazing amount of things to see, and some of it I’ve never seen before. In a way, every case is a challenge – you think: it’s me against the truth, and can I find it?