Dr R P Stephenson (1925-2004)

Dr R P Stephenson, known universally as Steve, died on the 24 April 2004. Steve was best known for his commitment to receptor theory. His research took him in many directions, which pleased some and infuriated others. His ground breaking paper in 1956(1), published in the BJP, based on a study of the action of acetylcholine analogues on isolated tissues, introduced two novel concepts: spare receptors and efficacy. He proposed that the parameter, efficacy, determined the link between the “strength” of a single drug-receptor complex and the size of the response.

Slowly it was appreciated that this term allows the response of a tissue to a variety of compounds to be characterised in terms of the number of receptors and the nature of the coupling between the receptor and the response. Furthermore, across a range of tissues the coupling of the same receptor to the response could be served by a variety of transduction mechanisms, thus accounting for the changes in the relative potency seen over a range of agonists. For a simple account see Rang and Dale (1991)(2) who, in addition, highlight the physiological role of spare receptors, and Kenakin (2004)(3) who has continued to reinterpret the concept of efficacy to fit with advances in our understanding of transduction at a molecular level. Importantly, Steve’s work enhanced the credibility of the age-old use of parallel log-dose response curves and the terms agonist and partial agonist.

In 1997(4), the 1956 paper was republished in Landmarks in Pharmacology, a selection of the most distinguished papers to have been published in the BJP. In his retrospective introduction(5) Steve commented:

“I do not know how much impact the paper had, although I know that it has been widely read: in copies in several libraries, there is a visible vertical black line in volume 11 of the British Journal of Pharmacology where pages 379-393 have been much fingered. Jim Black [Sir James Black] tells me that he found it useful when developing ß-blockers, and Sir David Jack once told me that he instructed new recruits to Glaxo research that it was the most important paper published this century. But, for many years, there seemed to be few published discussions of drug action which took in the changes I had proposed”.

Steve was born on 17 September 1925 in Milnsbridge, Huddersfield where his father was a weaver in a local mill. He showed unusual intelligence, attended Royd’s Hall Grammar School, where Harold Wilson had been a star pupil, and went on to read Chemistry at the University of Birmingham during the war, after which he spent a year in the Department of Pharmacology in Oxford testing substitutes for coal tar as starting materials for the chemical industry. A research assistantship at Bristol followed, and in 1949 he was appointed to a Lectureship in Edinburgh, in one of the few departments of Pharmacology in Britain. He spent the rest of his career, as a Senior Lecturer and Reader, in Edinburgh until he took early retirement in 1987.

Steve joined the BPS in 1949 and was a member of the committee from 1966 to 1969, Treasurer from 1971 to 1975 and subsequently became a Trustee of the Society from 1983 to 1993. In 1994 he was elected to Honorary Membership (from 2004, Honorary Fellowship). In his later years, he suffered from a variety of minor ailments which together rendered him increasingly less physically active. He became positively frail in the last six months of his life and died peacefully, with his wife, Jill, at his side.

Earlier in the 1970s and 1980s Edinburgh was a good place to be a pharmacologist. One colleague explains: “What they seemed to do, as far as I could see, was drink coffee and think and get the PhD students to look at various preparations.” The important point is that there was time to think. More than that, as another colleague says, “You could argue in Edinburgh. It was good to be here…. It was very healthy. I found it different elsewhere. You might be thought aggressive if you dared to speak out. Here, you were regarded as stupid if you didn’t.” In that atmosphere Steve thrived, arguing animatedly and at length with colleagues whose intellect he respected. With others, as a former colleague has said, ‘Steve did not mince his words, and he made some powerful enemies in Pharmacology’. He did not tolerate gladly – or even at all – colleagues whose intellect was inferior to his own. To hear him take a presentation apart at a conference session was to be relieved that one was not on the receiving end. Yet there was no malice in it: simply, he was highly impatient of shoddy work and sloppy thinking. In this, as in so much else, he was no respecter of rank or status. For example, the Professor of Pharmacology at Oxford, Bill Paton, had posited an alternative theory of receptors, called rate theory, to that posited by Steve in the 1950s and elaborated by him thereafter. As Steve told it in the 1990s,

“I never took [rate] theory seriously…. One year, we had [in the honours students’ exam] a question about rate theory and one chap more or less started off his answer by saying ‘Judging by the way Stephenson and Ginsborg laugh about it, it can’t be taken very seriously’. This was in a paper for which [Bill] Paton was the external examiner. I don’t recall any comment being made in the examiners’ meeting.”

Undoubtedly Steve’s best testimony came from his wife Jill. “Steve was a wonderfully patient and supportive husband, and a true friend. He had few pretensions, no personal ambition and neither the ability nor the inclination to dissemble. He really did epitomise the old saying about computers, ‘what you see is what you get’.”

John Kelly
Jill Stephenson

Based on an address given at Steve’s funeral, quotations are from a book by David Healy (6).

References:

(1) Stephenson RP. Modification of Receptor Theory. British Journal of Pharmacology and Chemotherapy 1956; 11(4):379-393.
(2) Rang HP, Dale MM. Pharmacology. 2nd ed. Edinburgh: Churchill Livingstone, 1991.
(3) Kenakin T. Principles: Receptor theory in pharmacology. Trends in Pharmacological Sciences 2004; 25(4):186-192.
(4) Stephenson RP. A modification of receptor theory (Reprinted from Brit J Pharmacol, vol 11, pg 379, 1956). British Journal of Pharmacology 1997; 120(4):106-120.
(5) Stephenson RP. A modification of receptor theory - Commentary. British Journal of Pharmacology 1997; 120(4):103-105.
(6) Healy, D. (2000). Robert P.Stephenson (Edinburgh) Receptors and classical pharmacology. In The Psychopharmacologists III: Interviews, ed. Healy, D., pp. 175-188. Arnold, London.