I first met Barry quite by Divine providence. I had just completed my medical training after many years first at Oxford and then at King’s College Hospital School of Medicine in Camberwell (this was before it was part of the GKT behemoth). I had no idea what I wanted to do with my life except that it had to involve basic, scientific medical research. I had met some very clever and eminent scientists while in Oxford who inspired me with this goal. I flicked though the BMJ appointments supplement (in those days there was no internet) and came across, quite by chance, an advertisement for a Clinical Research Fellow in Asthma at the Cardiothoracic Institute at the Royal Brompton Hospital in the Allergy & Clinical Immunology Department (hence the infamous ACID bunch). Owing to Barry’s insight and generosity this was as far as I needed to go.
I sent in my CV and to my delight and intrigue was summoned for an interview. Surely it wasn’t this easy! I was living in Chislehurst at the time and came up to Charing Cross railway station, walked up to Embankment tube then took the District/Circle to South Kensington. After that, a walk across the road (where they always hold the street market around Christmas), right along the Old Brompton Road, left down Sumner Place to the Fulham Road, and then right again to the Cardiothoracic Institute (Figure 1) which was adjacent to the old Brompton Hospital, originally the “Brompton Hospital for Consumption” (Figure 2) in the Fulham Road opposite what is still called the “South Block” of the hospital: this, as well as the original hospital have now gone and been replaced by super-exclusive blocks of flats called “The Bromptons”, some of which have been converted from the original hospital buildings. Later on I was to extend my journey left off the Fulham Road down Dovehouse Street to the National Heart & Lung Institute, but it did not exist then. This journey will remain emblazoned on my memory for life, since I travelled it every day for the more than 10 year period in which I worked with Barry (although I later moved back to my birthplace in Grays with my family and came up by train to Tower Hill via Fenchurch Street instead).
I met Barry for the first time in his office (top arrow in Figure 1) which was a floor up from the corridor in which his laboratories were situated (bottom arrow in Figure 1). I was met by a lady called Jennifer Mitchell, his amazing secretary, and escorted to his office. Barry was very polite and chatted to me a like colleague. I was mildly surprised that it was he alone doing the interviewing. I had to admit to him that, despite my first class degree from Oxford and my theoretical expertise in immunology, I barely knew one end of a test tube from the other. He didn’t seem daunted. I can’t really remember what we discussed. In fact, the question I remember him asking me most clearly is whether I knew Mary Carroll, evidently a colleague of his. He had noticed what he thought was her name in the author list in my extensive list of one scientific publication at that time (I had undertaken some research with Prof Alan Bennett at King’s where I trained looking at the role of prostacyclins in cancer metastasis: one of my colleagues there was named Mareid Carroll, not the person Barry had in mind). I was afforded this unique research opportunity because Alan Bennett was a keen saxophonist as well as a Professor of Pharmacology and played in our student rock band.
Anyway, Barry gave me the job. I believe that my lifelong friends and colleagues Andy Wardlaw and Robyn O’Hehir had a similar experience. Robyn told me that she had met Barry at an AAAAI meeting and accepted his offer of a PhD position following a visit to his office in Figure 2, relinquishing other possibilities in the US. Another lifelong friend and colleague who started as a clinical research fellow with Barry about this time (1985) was Tony Frew. It was the start of a unique and invaluable, mutually stimulating collaboration which has never ended. He told me that he thought T cells and eosinophils were likely important in asthma, which was revolutionary since asthma was seen in those days as episodic spasm of bronchial smooth muscle caused by the release or mediators from IgE-sensitised mast cells (and ignoring the fact that clinical atopy is neither necessary not sufficient for the development of asthma). He believed that allergen-activated T cells secreted factors which attracted eosinophils to the bronchial mucosa in asthma. Our tasks were assigned. My first task was to see whether helper T cells are activated in the blood of patients with asthma using this new-fangled flow cytometry. Andy was given the task of seeing how eosinophils ticked, and especially what made them migrate. Tony was tasked with taking biopsies of skin late-phase allergic reactions to look for evidence of T cell activation and eosinophil recruitment. Robyn was to generate allergen-specific T cell clones. What a vision! How could we have known then what a revolutionary vision this would prove to be!
Tony, Andy and Robyn were my constant companions in the laboratory in those days, as were two overseas visiting clinical research fellows, Jaw-Ji Tsai (a consultant physician in his native Taiwan) and Piero Maestrelli, a consultant specialising in occupational lung disease from Padua in Italy (if you go there, be sure to see the Giottos in the chapel and the ancient anatomy demonstration lecture theatre in the University). These two characters are still my friends: in fact, Jaw-Ji’s daughter is now training in medicine over here and it has been a pleasure to help her: one particularly memorable incident was helping her cope with a patient’s Geordie accent!
Since my laboratory expertise was limited, to say the least, I was completely indebted to the technical scientists in Barry’s lab to help me, most notably Oliver Cromwell, who was in charge of all technical facilities, Redwan Moqbel, Gary Walsh, Adele Hartnell and Andrea Champion. These kind people smiled at my pathetic incompetence and showed me how to isolate blood lymphocytes by centrifugation on Ficoll (20 minutes, 20°C, no brake), while Adele very patiently showed me how to use our flow cytometer (which was an early, 2 channel only model driven by a bicycle light bulb) without breaking it. She was very patient, especially when I tried to use it on Friday afternoons after a lunchtime visit to the local pub (regrettably, Barry was not generally invited to these). I also had to venture onto the wards at the Brompton and ask asthmatic patients if they’d donate blood.
Barry was passionate about research, and passionate in his support for his team: I’m sure we will never forget the famous Friday Morning Meetings at which we all presented our latest advances: a struggle for our foreign visitors at times who couldn’t keep up with Barry’s “constructive criticism” (I remember Jaw-Ji bursting into tears one morning because he couldn’t make out what “caveat” meant). He was ecstatic when I started to produce evidence that T cells from asthmatics expressed CD25, one of the few T cell markers described at that time (nothing was known then about Th1 and Th2 T cells and cytokines). When Andy reported to Barry at one meeting that PAF attracted eosinophils, he was so astonished by this that he sneaked into the laboratory the following day and checked for himself….meanwhile Robyn was looking for these new-fangled cytokines in her clone supernatants and Tony was collecting biopsies of skin late-phase reactions from human volunteers which – surprise, surprise – showed a T cellular infiltrate. With his inspiration I was able to win an MRC Clinician Scientist award which was renewed following a 2 year probation period for a further 5 years. I remember Barry telling me about it in the car park at work. He approached, all stern and po-faced. “I suppose you want to know if you got your grant from the MRC?” (It was very harrowing, speaking to a panel of about 12 scientists and clinicians pestering me with questions: perhaps you have been there….). “Yes please”, I said. “Well you did, and that’s a great honour for the Department.” A friendly tap on the back and that was that.
I have many memories of those days. There was nowhere to relax or eat or drink in our department in the Cardiothoracic Institute, so we all tended to congregate (mostly standing up) in a little glass –walled office off the corridor which also served as Oliver and Redwan’s office: we called it The Bubble. It also housed the one and only departmental computer which ran a very primitive word processing programme: there was no internet, no computer graphics programmes, no Medline or PubMed and of course no E-mail. We used to sit for hours looking through journals for the latest publications in the library. I remember Oliver and Redwan flying off the handle every time somebody sneaked a go on the computer and almost inevitably put a spanner in its works. All of the illustrations for our scientific manuscripts were done by Barry’s wife Rosy: a tremendous task which she performed superbly.
You can see us all in a team photograph taken in the little space just outside the entrance to the Cardiothoracic Institute (Figure 3).
Working with Barry was inspiring in so many ways. His theories about the role of T cells in asthma were an amazing feat of insight and soon received attention in the big journals: in fact I could hardly believe that I was featured as first author, with Adele next and Barry senior, in the Lancet (no less) in 1988, just a few years after I’d learnt to distinguish one end of a test tube from the other. It also took us to some marvellous international meetings, which were a revelation to me, having never travelled out of the country at all (aside from a couple of brief school trips). My fifth international presentation was at an AAAAI meeting in Anaheim. Here I was with Barry and the Bubble folk in a plane over the Atlantic, looking at Iceland! These opportunities to interact with national and international colleagues have been for me one of the most invaluable aspects of scientific teamwork instilled into me by Barry. Indeed, for my own PhD thesis I collaborated with Stan Szefler at the National Jewish Hospital in Denver, Colorado, who was able to measure prednisolone concentrations for me in the serum of my clinically resistant asthmatics (again, an unique facility at that time).
Graham Crompton, a very old mate of Barry while he was previously in Edinburgh and a consultant respiratory physician up there, used to send me (with appropriate informed consent) blood samples from his acute, severe asthma patients: they inevitably arrived in the afternoon and often necessitated departure from the laboratory after dusk.
In those days there was no PowerPoint and all our slides had to be drawn and photographed by hand (the little team in the technical department in the basement of the Royal Marsden Hospital over the road used to make our slides for us: many’s the trip I’ve made over there). Of course there was no changing of photographed slides, so it was vitally important to get them right first time. I remember Barry telling me: if there is so much crammed on them that you can’t read them at arm’s length, then they are too busy………(also useful not to sit on them in the plane, as I noted one year). I met many, many excellent colleagues at these meetings who are still friends, such as Steve Holgate (Figure 4) and my other great colleague Tak Lee (Figure 5),
another of Barry’s alumni whom I went on later to join and with the inspiration and insight born of them both, discovered many more interesting things about asthma.
We eventually moved over the road into our brand new laboratories in the brand new National Heart and Lung Institute. Again, Barry remained right on the ball about where to go next. He recruited Qutayba Hamid, one of the early exponents of the new-fangled (again) technique of in situ hybridisation. With this we were eventually able to show, directly and for the first time, that Th2-type cytokines are present in asthmatic tissues and, with Douglas Robinson, that Th2-type cytokine mRNA expression is elevated in BAL T cells following allergen bronchial challenge. Later, my special and lifelong friend Sun Ying, now a Professor in Beijing, and his wife Qiu Meng came along and added to this expertise. Lajos Nagy, sadly now deceased, worked with me on identifying neutrophil chemotactic agents. I was able, with several excellent helpers, notably Paddy Kimmitt, to develop the other new-fangled technique of PCR and show that corticosteroids inhibit Th2-type cytokine transcription. Steve Till, then a science graduate, joined and completed his PhD with us again looking at cytokine production by T cell clones, and was so enthused that he went away and became a doctor himself. He is now a permanent and close friend and colleague: indeed he is a Professor at King’s, just as I am, and works just round the corner.
Mimi Haselden and Mark Larché helped us demonstrate, for the first time, that there are T cells specific for allergen-derived peptides in the bronchial mucosa of asthmatics. There have been many other visitors to Barry’s lab, many of whom have excelled in highly successful international careers as clinicians and scientists: Phillipe Collard, Lajos Nagy, Brian Bradley, May Azzawi, Mina Gaga, Anne Tsicopoulos, Vasso Gemou-Engesaeth, Francesca Levi-Schaffer, Patrick Kimmitt, Luis Taborda-Barata, Basil Assoufi, Nick Powell, Marc Humbert and Angela Haczku to name but a few. I worked with Andy Alexander, then a clinical research fellow as I had been, for three years undertaking a trial of cyclosporin A therapy, the only other inhibitor of T cells apart from corticosteroids available at that time which Barry confidently predicted would improve asthma, even in corticosteroid resistant patients. This again was an unique Barry-type initiative and, looked at retrospectively, an astonishing undertaking at that time. It also facilitated the unforgettable Corrigan/Alexander portrayal of the Blues Brothers singing “Everybody Needs Somebody” at the Departmental Christmas show (video available on application). Steve Durham was of course always a large force in the background, his interactions with Barry no doubt inspiring his tremendous work on the development and mechanisms of allergen immunotherapy.
Outside the laboratory, Barry was also a personal friend who was very kind to me. On many, many occasions I was invited over to Stamford Brook House for drinks, dinner, chats and music practice! I met Rosy and his lovely daughters Emma, Becky and Beth who were at school then. Emma was a talented artist: I have several of her pictures at home. It was the time when those new-fangled CDs were replacing LP records, and we had many discussions about the relative merits of each (I have always been a bit of a hi-fi fanatic). Barry was particularly indignant when I pointed out to him one day while sitting in front of his own hi-fi and harpsichord that only CDs marked DDD were direct digital recordings. “Why didn’t I know that?” he said. On some occasions, particularly when I had early starts at Kingston Hospital where Geoff Knowles, Barry’s mate and a consultant there, was teaching me fibreoptic bronchoscopy so that I could take my own bronchial biopsies, I was invited to stay overnight. I will always be grateful to Barry, Rosy and the girls for their kindness.
I also travelled with Barry on many occasions to “Baroque Week”, a week in summer, often in Oxford but once in Chichester, when we joined a bunch of like-minded individuals to play (?hack) through Baroque music, Barry on his bassoon and me on the harpsichord. One memory we loved to share was my attempt at playing the harpsichord in the 5th Brandenburg at one of these meetings. Really made my eyes water: I don’t know what happened to Barry…. Barry was always a very keen and able bassoonist and played regularly with many orchestras over the years. He was forever nagging me for playing too quickly. Sadly, our last session playing together was for the memorial service of Tony Frew, one of the original “Bubblers” who, like all the rest, had been a lifelong friend and colleague, and who tragically took his own life recently. It was an honour to perform this last little tribute to our Tony, and even then Barry had to remind me not to play too quickly…..
Barry had a great life with his ever-expanding family of grandchildren. Maddeningly I missed his 80th birthday celebration (Figure 6) because I had already booked a holiday which I couldn’t cancel. It was great, and a fitting tribute to Barry to see nearly all of the original Bubblers there, as well as the greatly expanded group of scientists and clinicians that his insight inspired, save Tony of course and Redwan who died of cancer. I continued to visit him in Barnes, where he had then moved, and we toddled off to the local bird sanctuary there. He told me that he had developed bladder cancer which had progressed despite chemotherapy. He was very philosophical about dying and discussed it with many people, including my wife Annie who is a theologian. He truly believed that he was on his way to heaven and that he would meet all the Bubblers again. He had a chance to have private conversations with Rosy and all of his daughters before he died, and so departed in peace. God rest his soul. Until the next Friday morning meeting……