Andrew Rice, MD FRCP, FRCA is a Professor of Pain Research at Imperial College and Honorary Consultant in Pain Medicine at Chelsea and Westminster Hospital. He is a clinical academic active in translational research and clinical practice in the field of neuropathic pain. After completing his medical training at St. Mary’s Hospital School in 1982, Rice completed his research doctorate under the supervision of Professor Steve McMahon at St. Thomas’ Hospital Medical School (Sherrington School of Physiology) in 1991. Rice is an international keynote speaker at the upcoming 42nd Annual Scientific Meeting (ASM) of the Australian Pain Society, to be held in Hobart from April 10-13, 2022. In the lead-up to the ASM, Rice spoke with Lincoln Tracy, a research fellow from Monash University, Australia, about his path to working with neuropathic pain patients, the benefits of being part of research consortia, and his love of military history. Below is an edited transcript of their conversation.
What was your path to pain medicine and research?
A few years after graduating from medical school in London I knew I wanted to be in hospital medicine, but I wasn’t quite sure what to do. It could have been anaesthetics, intensive care, general medicine… But I was training in general medicine and met one patient who changed my career. He had a Pancoast tumour—a tumour in the apex of the lung, growing into the brachial plexus—which is a horrible and painful way to die. What fascinated me [about this patient] was the behaviour of my boss, who was a good and caring doctor, but who tended to avoid this patient because he was powerless to help him. He felt frustrated.
Similarly, the nurses could not avoid contact and they too became quite frustrated at being unable to relieve the patient’s suffering. They were giving the usual doses of morphine, but it was not touching his pain. I became fascinated by this patient and the reactions of my colleagues. At the same time, I met Pat Wall, one of the doyens of pain research. There was a group at St Thomas’ called PANG—the Pain and Nociception Group. The whole idea was to get London based scientists and clinicians together, and Pat would always talk to the younger people. I was just chatting to him—with no idea who he was at the time—and he suggested I go to St Thomas’, which I duly did.
Everything seemed to fall into place after that—not only was there a new [to me] fascinating, unexplored area of medicine, but there was some top-level neuroscience going on here. So, I changed course. I went to St Thomas’ and came under the influence of Douglas Justins, who’s an Australian expat living here. He really introduced me to pain medicine. But the most important thing he did was introduce me to Steve McMahon, who was my doctoral supervisor and remained my closest confidant, mentor, and friend for the rest of his life. Unfortunately, Mac died just before Christmas—you can see the obituary we wrote for him in the current edition of PAIN.
Mac was just one of those scientists that has an absolute joy for science. I didn’t intend to go on and do research, but he infected me with his energetic sense of curiosity and enthusiasm for research. He also appreciated the importance of debate and iconoclasm to scientific progress, probably something he inherited from Wall, and hopefully I in turn from Mac. From there to be a clinical academic I decided I needed clinical training in some area of pain medicine, but pain medicine didn’t exist as a specialty then. So, it was anaesthetics, neurology, or perhaps palliative medicine. I’m not clever enough to be a neurologist—I went to Oxford to study anaesthetics in the end, mainly because it was already an established centre for pain management. It was here that I came under the influence of two giants in pain research: Henry McQuay and Andrew Moore—the fathers of evidence-based pain medicine. I moved to Imperial [College London] in 1995, set up the first pain research group, and we’ve been going ever since. But the biggest influence on me, without any doubt was Steve McMahon.
Your research has focused on neuropathic pain in infectious diseases such as HIV and leprosy; how prevalent is neuropathic pain in these patients and how does it affect them?
Like pretty much everything else in my career, serendipity and unexpected chance played a role. I had been studying in Canada in 1981 when we saw one of the country’s first case of HIV. By the time I returned to London my teaching hospital St Mary’s, which has a strong tradition in infection- notably in Sir Alexander Fleming, was emerging as the key centre for HIV care and research in London. Then at a much later stage in my career, I moved campuses within Imperial to Chelsea and Westminster, which is one of Europe’s largest HIV centres. Soon after I arrived, one of the physicians—Sarah Cox—said, “Could [you] look after the patients with painful neuropathy?” And I said, “Sure, but I don’t know anything about HIV.” Sarah suggested we run the clinic together, and we did that for over 20 years. It was a huge learning experience, and those Friday afternoons were often the highlight of my week. But it also stimulated my research interest.
About 50% of people living with HIV have a neuropathy if you go and look for it, but the extent to which it is painful and that pain impacts on their quality of life is more variable. Originally it was thought that the neuropathy was a consequence of the early antiretrovirals, as they were undoubtedly neurotoxic. So, everyone expected it to go away when we stopped using those drugs. However, we showed that neuropathic pain is one of the manifestations of living with HIV that doesn’t go away with efficient antiretroviral therapy. But there hasn’t been a decent prevalence study of neuropathy and HIV for a few years now, so it’s certainly an area worth looking at if there’s an aspiring young researcher out there.
Leprosy was a rather different story. Like most people, I thought leprosy had gone away and didn’t cause pain, but it hasn’t, and it does. Diana Lockwood, who is the UK’s premier leprologist and ran the main clinic at the Hospital for Tropical Diseases in London, had observed a lot of patients who had been mycobacteriologically cured of leprosy but who were living with neuropathic pain. Leprosy is a largely a clinical diagnosis and you need to see signs of nerve damage in order to make a diagnosis – and that nerve damage is often not reversible with successful leprosy treatment. Diana had taken a sabbatical and asked, “Can I come to your lab and learn about neuropathic pain?” I agreed, of course, and for the first week or so was telling her what I knew about neuropathic pain, which isn’t very much. Then the next five months and three weeks were spent with me learning from her about leprosy [laughs].
[Leprosy] is an interesting teaching experience because most people think leprosy is a painless disease. But in fact, it’s a disease with neuropathic pain often characterised often by sensory loss phenotype (Anaesthesia Dolorosa). So, we started to run a clinical service managing pain for patients attending Diana’s clinic and had some fantastic collaborations in India, Ethiopia, and Indonesia, for example. I’ve been interacting happily with leprologists for quite some time now. [The patients] have interesting sensory profiles that are different to that we see other neuropathic pain conditions. That was a revelation to us, but some wise leprosy doctors who’ve worked for many years said, “Oh, yes. We’ve known that for quite some time [laughs].”
You’ve collaborated with historians and archivists to explore the history of neuropathic pain, how did this come about?
I’ve been interested in history since I was a kid. Then 11 years ago, I had a significant illness that required me to take a year off work to recover from surgery. My wife and the [university] departmental administrator knew I would go straight back to work and not recover properly because I love my job; it was clear that something needed to change. There were family diaries in the Imperial War Museum in London which I’d never read, so I read them. Then my wife gave me her grandfather’s diaries, who was a New Zealand ANZAC in the First World War. Around the same time, my neighbour—Mike Senior who is a prominent author on the Battle of Fromelles [considered one of the most tragic events in Australia’s military history], and which also had massive impact on the village where I live and doing his PhD—started teaching me about First World War history and we visited Fromelles together.
Since then, we’ve had several collaborations, mainly through the Imperial College’s Centre for Blast Injury Studies with people like Emily Mayhew, George Hay, and our joint PhD student Sarah Dixon-Smith. The main area of our work has focused on amputations in the First World War. We followed soldiers who underwent amputations using things like pension records, and we’re just beginning to publish on all this work. We are also engaged in a collaboration looking at the pain aspects of a large cohort of British service personnel injured during combat in the recent Afghanistan over a 30-year period. The parallels across 100 years are both fascinating and somewhat depressing.
We’ve also done some work on painful nutritional neuropathies in Far East Prisoners of War in the Second World War [Ber-Beri/Burning Feet Syndrome]. During this work I had the real privilege of working with a lot of wonderful people who have written about the medical history of those dreadful times like Meg Parkes, Geoff Gill, Paul Watkins, and especially Bill Frankland; a former prisoner of war in Singapore himself. Bill went on to become the founding father of British allergy medicine and indeed had taught me as a student. It was incredible to have someone with firsthand experience as a doctor treating these patients. Sadly, Bill died in the early stages of the COVID pandemic aged 108, but he was still publishing academic papers at that point and saw patients until he was well over 100! He had also worked with Fleming on Penicillin and was probably the last remaining person alive with firsthand memories of those times, which we often chatted about. Bill’s signed copy of his biography has pride of place in my history library alongside a signed copy of Weary Dunlop’s diaries; Bill knew Weary well and had plenty of anecdotes to tell.
For the last six years you’ve served as an IASP Councillor and acted as a liaison for the Association of South-East Asian Pain Societies—can you tell me about that work?
That’s probably one of the best parts of my job. It’s a long-term strategic role—I’m there to act as a liaison between ASEAPS and IASP Council, to oil the wheels, and provide bit of institutional memory as the original leadership of ASEAPS begins to retire and is replaced by new leadership. I’ve just added the South Asian Pain Societies to the portfolio as well, which is a new and rather different challenge. I’ve learned far, far, far more from my Asian colleagues them than they’ve learnt from me. In Europe we sometimes have more of a confrontational and competitive culture in our professional interactions. But these pain societies have a different way of doing things—there is much more working together to advance things for the common good.
These are countries with disparate economies, disparate religions, diverse geography, and diverse languages and ethnicities. Yet they’ve collaborated in the most elegant way to develop pain management and increase pain research in the region. One of ASEAPS founders Pongparadee Chaudakshetrin, from Thailand, gave a plenary last year at the World Congress, and there’s a great review in PAIN about what they’ve achieved. With IASP funding ASEAPS deliver very successful 12-month clinical training fellowships based at Siriraj hospital in Bangkok. And they have these pain management camps every two years that are heavily based on Essential Pain Management, which have been efficient at spreading clinical skills and knowledge. They have just completed the development and roll out of a fantastic ToolKit, led by Mary Cardosa from Malaysia, geared to help colleagues in Low- and Middle- Income Countries develop multidisciplinary pain management centres.
Throughout your career you have consistently worked in research consortia—why do you feel researchers and clinicians should be involved such initiatives?
These consortia are multidisciplinary—or more accurately—interdisciplinary work, where you learn from each other. [My involvement with consortia] started with the Wellcome Trust funded London Pain Consortium, for which I was administrative director, and which was led by Mac. But the consortia that changed my perspective are the European Union funded ones, like DOLORisk and EUROPAIN. These [consortia] are quite big and the administration is a headache. They force collaboration, which encourages interdisciplinary working, including in a mutually beneficial fashion with industry colleagues. It is a buffer against the sort of insular, ” my lab is competing with that lab” approach and which pools knowledge and resources. Competition in science can be good [and fun] but it can also sometimes be rather destructive. It’s perhaps one area in science where Europe somewhat “trumps” the United States—if you’ll pardon the pun.
But the real advantage is the scale of these things. There are things we just couldn’t do without them. For example, we’ve run to what is, to date, the only published multicentre animal study on pain. We couldn’t have done that in only a few months if it weren’t for the EUROPAIN consortium. In such a big collaborative structure you have the benefit of many eyes looking at a problem from different perspectives, there’s debate, there’s people with strong bullshit detectors—which is always useful. That’s something you don’t always get in the normal single lab or couple of labs collaborating with each other.
Is there something you have changed your mind about with respect to pain over the course of your career?
There are two things that come to mind. The first is that when you work in a lab, you start to believe in silver bullets and the one pharmacological solution [to chronic pain]. But I think we all know that’s unlikely to be the case to such a complex bio-psycho-social problem. So, over the years, despite the enthusiasm of laboratory discoveries, I’ve slowly realised that it is all about interdisciplinary pain management—medicines on their own are not going to be the cure. It’s likely to be a combination of approaches.
The other thing that has changed is how I read a paper. I spoke about the time when I was in Oxford and Henry McQuay and Andrew Moore were starting the evidence-based pain medicine movement. Before I met them, I would read the abstracts and results first to see if the paper was worth reading. Now I read the methods first. The methods are important because if it’s not a good paper, there’s no point in going on and reading the results. It frustrates me when big journals like Nature put the methods entirely in fine print and make them inaccessible. We have a reproducibility crisis and need to value rigour over novelty, so we need to continue to push for improving experimental design, conduct, analysis, and publication. The results of a rigorously designed, conducted, and reported study asking an important question are important, irrespective of whether they prove the hypothesis or not. I intensely dislike the concept of a “negative” study.
What is the best piece of advice you have received throughout your career?
The best piece of advice I’ve received was given to me by Doug Justins, who said, “Go and talk to Steve McMahon.” I owe pretty much everything in my career to that event.
But I really like a quote from [former director of the London School of Hygiene and Tropical Medicine] Peter Piot’s autobiography No Time to Lose, where he relays the advice he received from a colleague while working in Africa. He described that you want to be like a chameleon. Although they are always moving forward, their eyes are continually moving independently to take in what is going on around them. Although it can change its colour to adapt to its current environment, it keeps moving in the same direction. But most importantly, it’s ready to catch that moment of serendipity when fly moves past ready for capture with its tongue. So, I commend his advice to you: be like a chameleon.
What is some advice you try to teach your students and trainees?
The first thing is to listen to patients—they tell you everything you need to know. One thing that frustrates me is how infrequently some scientists seize the opportunity go to the clinics and listen to the patients. Without that input they are dealing with something of an abstract problem. Pat Wall knew the importance of that and advocated the benefit of scientists interacting with clinicians and patients- hence the erstwhile London PANG group to which I referred earlier it. Of course, interdisciplinary interaction is at the core of IASP’s mission. We are now, at last, beginning to benefit from more and more lived experience input in designing, conducting, and disseminating our research. For example, IASP is doing a lot around lived experience representation. One of our expert patient advisors has a great expression -, which is, “Don’t talk about us without us.” A great example comes from the early days of my career, when I was told by a distinguished neurologist that “People with multiple sclerosis don’t get pain, it’s not an important problem in them.” So, I went and asked his patients and they said, “Well, it is, but he never asks us!”
Another thing I really learned from Steve McMahon is the drawback of becoming a researcher defined by an expertise in a technique or method. Of course, t this doesn’t mean that colleagues who are real technical experts in certain areas are not vital, as they form important parts of collaborations. Rather, it means that there is also room for scientists who identify the most important question and then deploy the relevant method, and collaborations, instead of doing it the other way around.
Finally, don’t invest too much emotion in the ownership of your hypothesis. I think it was an Australian colleague who once said, “There’s nothing quite so dangerous as a scientist who believes their own hypothesis.” And we see the dangers of that. I was a classmate at medical school of Andrew Wakefield’s—the original anti-vaxxer. He really believes his own hypothesis despite the data; I think he genuinely believes it. There was a good saying that came out in the early part of COVID: “A good scientist changes their mind because of the data, [but] a politician doesn’t change their mind despite the data.” So, develop a hypothesis, test it robustly, but don’t have such an emotional attachment to it that you feel that have to defend it at all costs.
What do you do when you’re not doing research? Any interesting hobbies or secret talents?
I don’t want to say they’re secret talents, but they’re certainly hobbies. I feel that I can describe myself as a military historian and have just published my first military book. I’m also a battlefield guide and have been so for about 10 years. I’m in the middle of doing my formal exams in battlefield guiding; I’ve passed four out of nine [exams]. My mother was Swedish and I’m proud of my Nordic heritage, so many of my hobbies relate around the sort of outdoor life which is central to Scandinavian culture, especially skiing and fishing. I love sailing, but my kids don’t particularly enjoy being aboard a sailing boat skippered by me—I’m a bit of a dictator when afloat, apparently [laughs].
I am the worst sort of cricket fan. But through my sons I now love watching it. Not sure how much I am going to enjoy my time at the APS as my Aussie friends will inevitably mention the humiliation of the England men’s and women’s teams in recent Ashes!
Lincoln Tracy is a postdoctoral research fellow in the School of Public Health and Preventive Medicine at Monash University and freelance writer from Melbourne, Australia. He is a member of the Australian Pain Society and enthusiastic conference attendee. You can follow him on Twitter (@lincolntracy) or check out some of his other writing on his website.