Honorary Member, Dafydd Walters, on how chance has affected the path of his career in physiology.

https://doi.org/10.36866/pn.90.42

Since 1974, I have been employed as a clinical academic; my primary post was at London University with an honorary position in a hospital in order to practice clinical medicine, in my case paediatrics. I have just retired and what strikes me, in retrospect, is how chance has affected my career.

I studied medicine at University College London (UCL) in the late 1960s. Initially I found physiology difficult but I warmed to its ability to explain biological functions in a quantitative way and I was persuaded to undertake an intercalated degree in the subject by two people. The first was J Z Young, Professor of Anatomy whose advice in the final Second MB BS oral examination when he was obviously sorting out the sheep (the anatomists) from the goats (physiologists) was that “if you like tissues, do anatomy, if you like tissues and machines, do physiology”. The second was my fellow student John Smaje (Laurence’s brother) who thought it was madness to consider doing any other subject. My teachers included Andrew Huxley, Bernard Katz, David Colquhoun, Jack Diamond, Ricardo Miledi, Jim Pascoe, Otto Schild, Laurence Smaje and Doug Wilkie – but I took all this for granted (such is youthful naivety) and thought this was how physiology departments were everywhere else! But it was Alan Ness, an eccentric rather unappreciated dentist-physiologist who inhabited some intriguingly decorated rooms in the attic of the physiology department at UCL, who altered my thinking most. He taught us how to read scientific papers properly, a skill which I have found invaluable ever since.

I qualified in medicine in 1971 and did some busy junior hospital jobs and intended to train as a chest physician. However out of the blue I was offered a clinical lectureship in paediatrics by Leonard Strang at UCL in 1974. The research work in progress, when I joined him and Richard Olver, was on the development of the fetal lung and its preparation for air breathing at birth (a major paediatric clinical problem at that time, if not still, was the management of premature babies’ respiratory problems). My first two years were almost totally fruitless as far as results were concerned. The main reasons were that firstly the hypothesis we were testing was wrong and secondly we were not able to realise this for some time because the results were not be available for months after performing the experiments. We did three experiments per week each producing 10 samples containing several molecular sized tracers which had to be separated by size on a sephadex gel column. Each sample produced 200 fractions and each had to be counted once if not twice for radioactivity. Counting time was 10.65 minutes per sample. You can do the sums but I can tell you that each week of samples took over six weeks just to measure before they could analysed. Nevertheless, that period was useful as I learnt many practical techniques in animal physiology and taught myself Fortran 77 (for those of you who can remember that) in order to process our data on Imperial College’s main frame computer down a telex dial up line (note to the young: desktop computers did not exist then!)

The next intervention of chance came in 1977 when the professor went to France for a six month sabbatical. Within that period Richard Olver and I, fed up with no definite results, revisited an intriguing chance result from an experiment we had performed over a year before and had ignored because we could not understand it and assumed it was due to a technical hitch. The background to this is that the lungs of all mammalian fetuses are filled with liquid which is secreted by the lung epithelium at considerable rates (3-4 ml.kg-1.h-1) throughout gestation. In the few months of Leonard’s absence we discovered that fetal adrenaline, released by the stress of labour, induced the absorption of liquid at birth. This was a novel finding which kept us in research work for a further decade, discovering the mechanism of absorption (activation of sodium channels) and the hormonal control (by thyroid hormone and cortisol) of its expression in the fetal lung at the end of gestation. It is worth noting that this finding was made well before the identification of ENaC (epithelial sodium channel). Some twenty years later, ENaC knockout mice showed its vital importance to lung adaptation at birth (Hummler et al 1996). In the late 1980s Andy Ramsden and I extended this work by examining what mechanisms existed after birth to maintain postnatal lungs relatively free of liquid and our results pointed to the appearance of a non-ENaC absorptive mechanism in adult lungs.

I was appointed to the Chair of Paediatrics at St George’s Hospital Medical School in April 1994. Chance intervened again through a challenge by Sandra Guggino (Baltimore) at an ENaC meeting; asking for an explanation of what some relatively recently discovered non-selective cation channels were doing in the lung. This gave Rod Junor, a medical student just starting an intercalating PhD with me, his project: he made short shrift of it. The subsequent collaboration with Sandra Guggino demonstrated that, at least in some species, CNG1 channels (first described in the retina) appeared in the lung epithelium some months after birth. This fulfilled the prediction that Ramsden and I had made some years earlier.

In the late 1990s unexpectedly (chance once more?), I was approached to stand, I believe as the token clinician representative, for the “Committee” which then managed The Society. A few years later I became Chairman of the Executive Committee – a “doddle” they said as The Society was in future going to be run by a team of professional managers rather than the secretaries scattered around the country. Well, the reality was rather different. It was a time of enormous change for The Society. Its constitution and structure had just been altered to be fit for the new century, so that the Committee was to become the Council from which a small executive group would be elected with its own Chairman, and a President would be appointed to lead The Society and to chair the Council. Chris Fry, my predecessor, was the last Committee secretary and first chairman of the Executive; Colin Blakemore was our first President. All this coincided with a tendering for a new contract to publish The Society’s journals, a move of office in London (from Dilke House to Caroline House) to accommodate increased centralisation of staff and major changes of very senior staff in the London office. It was stressful, but I was particularly grateful to the calming influence of Colin Blakemore, the practical support of Jeremy Ward (then Treasurer) and of the other Executive Committee members which at that time included Bridget Lumb, Stuart Sage, Rob Clarke, David Brown and later Gio Mann. The rocky times (and anxious ones particularly for the staff in the London and Cambridge offices) were weathered and The Society ended up with a new publisher, Blackwells, and a lucrative contract, sadly ending an association with Cambridge University Press of over 125 years. I was chairman from 2002 to 2004. It was a time of great change for The Society’s way of working and apart from the structural changes mentioned above it included a reduction in the number of large meetings, the abandonment of voting on abstracts and the advent of electronic publishing. The changes were not unanimously supported!

Research is not an isolated activity and I recognise the invaluable contribution of colleagues and collaborators. Chance provided me with two individuals who have been central to the research. My assistant of 22 years (Audra Benjamin) was always a totally dependable rock; she has obtained her PhD, gained a husband and borne two children and, to coincide with my retirement, has changed career to teaching. My other stalwart Research Fellow and PhD student, Richard Stephens, moved on to pastures new some years ago.

Physiology has been central to my life and I consider myself so very fortunate in the colleagues I have worked with, to have contributed to uncovering some some interesting physiological mechanisms and also had the experience of being at the centre of some major changes to The Society’s working. I have been equally lucky in having had a parallel but overlapping busy and fulfilling career as a clinician. The influence of chance on my clinical career and life are separate stories!