Milestones in European Thyroidology (MET)

Rosalind Venetia Pitt-Rivers (1907-1990)

Rosalind (Ros) Pitt-Rivers was the second President of the European Thyroid Association. She succeeded our first President Jean Roche in 1971 and was followed in this position by Jack Gross. The names of all our first three presidents are inextricably linked with the discovery of triiodothyronine.

Ros was born into an aristocratic English family. Her father, the Honourable Anthony Ernest Henley, was a younger son of the fourth Baron Henley and a career soldier who rose to the rank of Brigadier during the First World War. He succeeded to the title on the death of his half brother and was in turn succeeded by his brother Francis who was a chemist and a Fellow of the Royal Society. Her mother, the Honourable Sylvia Stanley, was the daughter of the fourth Baron Stanley. The Stanleys were one of a group of intellectually distinguished families (which also included the Huxleys, Haldanes, Darwins and Mitchisons) who contributed substantially to the cultural, political and scientific life of Britain during the twentieth century. On her mother's side Ros was related to Clementine Churchill, Bertrand Russell, Venetia Stanley, the Mitfords and other members of the intellectual elite of the first half of the last century.

In common with many of her class, Ros was initially educated at home by governesses. At the age of 13 she was enrolled in one of the premier London schools of the time, Notting Hill High School (now Notting Hill and Ealing High School). She then proceeded to Bedford College to read for a Bachelor of Science degree graduating with first class honours.

The decade leading to the outbreak of the Second World War was a period in which Ros laid the foundations of her future scientific career, but it was also a time of considerable turbulence in her personal life. Ros married George Pitt-Rivers in 1931. He was the scion of a wealthy, aristocratic family and the grandson of Augustus Pitt-Rivers who founded the archaeological museum of that name in Oxford. The Pitt-Rivers were related to the Stanleys by marriage but relationships between the two families, which had never been close, became considerably more distant following the marriage. George Pitt-Rivers was intelligent, opinionated and seriously eccentric (like a number of his forebears). In particular he held extreme right wing and anti-semitic views which he published in a series of documents and in letters to The Times. Their son Anthony was born in 1932 and Ros lived for a number of years at the Pitt-Rivers family estate in Hinton St Mary in Dorset. The marriage, however, was not a happy one and ended in divorce.

At a professional level Ros' career developed. She completed her Masters in 1931 and following a period in Hinton after her marriage she returned to London and resumed her career as a postgraduate student at University College in the Department headed by Sir Charles Harington. The structure of thyroxine was first determined by Kendall at the Mayo Clinic during the 1920s. Harington built on this achievement and in 1927 achieved its total chemical synthesis. This was the first occasion on which a hormone had been synthesized and this success laid the foundation for later work on the biosynthesis of the thyroid hormones. Ros obtained her Ph D in 1939 and then joined Harington's own group to work on the biosynthesis of thyroid hormones. Shortly afterwards Harington moved to the National Institute for Medical Research (NIMR), the largest institute of the UK Medical Research Council, and Ros followed as a member of the Council's staff. Ros left NIMR for a period during the Second World War and worked in the Blood Transfusion Service but later returned to Harington's laboratory to work on iodoproteins, this being part of a project to enhance the milk yield of cows. She had a further spell away from Harington's laboratory at the end of the war as a member of a high level team carrying out nutritional studies on concentration camp prisoners. During this period she spent some time at Belsen, an experience which was to have a profound and lasting impact on her.

Following her return to NIMR, Ros carried out a number of studies on iodinated peptides in collaboration with Harington and, amongst others, Raymond Michel who was visiting from Paris. Raymond was also a founder member of the ETA and an early member of the Executive Committee (1971 - 1976). Ros made further important observations in the post-war period. These included the separation of optical isomers of thyroxine, the demonstration that d-thyroxine had no biological activity and the isolation of moniodotyrosine (MIT) in thyroglobulin. Earlier studies in Harington's laboratory had shown the presence of diiodotyrosine (DIT) in thyroglobulin and that thyroxine was formed from the coupling of two molecules of DIT. The laboratory of Jean Roche had shown that this reaction took place in the thyroglobulin molecule.

The Mill Hill laboratory was strengthened by the arrival of Jack Gross from Canada in 1950 who had worked in Charles Leblond's laboratory on thyroid function using radionuclides of iodine. He and Leblond had already identified a further iodinated compound which in chromatographic studies migrated close to thyroxine. At much the same time as these observations were made, Roche's group, which included Raymond Michel and Serge Lissitzky (also a founder member of our Association and a member of the first Executive Committee), described deiodinating activity in the thyroid.

These observations inevitably indicated the possibility that there might be a second biologically active thyroid hormone. The identification of 3:5:3' triiodothyronine was finally achieved by Ros and Jack late in 1951 and in a subsequent series of experiments they showed that it was anti-goitrogenic in mammals and, in collaboration with W R Trotter, that it was effective in the treatment of hypothyroidism in patients. Following a series of further studies they proposed that thyroxine was the precursor of triiodothyronine which was the active hormone at tissue level. Later work by Ros and others demonstrated that deiodinase activity is also present in a wide range of extra-thyroidal tissues. The debate has extended for many years as to whether thyroxine is solely a pro-hormone or whether it has intrinsic hormonal activity. It can be shown that it does have intrinsic hormonal activity but the experimental conditions required to demonstrate this are such that they preclude a definitive answer to the question. The discovery of triiodothyronine (T3) led to many honours for Ros. The most significant of these was her election as a Fellow of the Royal Society (Britain's premier scientific institution) two years later.

The discovery of triiodothyronine (T3) led to subsequent work elucidating its biosynthetic pathway and the study of the physiological actions of T3 at tissue and cellular level. These studies were initially carried forward by Ros' laboratory at NIMR and by that of Jean Roche in Paris and later by many others. The principle focus of Jean Roche and his colleagues was on the biosynthesis and secretion of the thyroid hormones and that of Ros on the physiological actions allied with studies on analogues of T3.

In 1953 Jack Gross left the laboratory and went to New York. In the same year Ros spent a sabbatical at the Massachusetts General Hospital (MGH) with John Stanbury. She was just one of many alumni of our Association who spent time in that distinguished institution. John, of course, was a Corresponding Member of the ETA and participant in many of our meetings. Ros was later (in the late 1950's and 1960's) to spend time at the National Institutes of Health in the laboratories Ed Rall and Harold Edelhoch. Her later research was focused on four specific areas - the elucidation of the physiological actions of the thyroid hormones (including studies on secretion, transport and turnover), the investigation of the possible physiological activity of thyroid hormone analogues, thyroglobulin and, in a different field, the development of immunochemical reagents. Her work on thyroid hormone analogues proved to be a disappointment but in the other areas her studies provided a valuable body of knowledge although none of her later activities had the same seminal impact as the discovery of T3. Nevertheless this single major success was a landmark in thyroid research and represents an achievement that exceeds those of the majority of the members of our Association.

Ros continued to work at NIMR until she reached retirement age. She had a major and important collaboration with Avrion Mitchison (who headed one of the Divisions at the NIMR and was a member of an intellectually and scientifically distinguished family - vs). This work was focused on the development and exploitation of the synthetic immunological determinant NIP (4-hydroxy-3-iodo-5-nitrophenylacetic acid). She moved to University College London following her retirement from NIMR in 1972 where she maintained a laboratory until her health forced her second and final retirement to her home in Dorset where she lived until her death in 1990.

Ros was a founder member of the ETA. The first steps towards the creation of our Association were taken during the 5th International Thyroid Conference in Rome on 24th May 1965. Ros was one of those present at a lunch at which the idea of establishing the Association was first floated. The others present included Donald Alexander, Mario Andreoli, Paul Bastenie, Christian Beckers, Michel de Visscher, Jacques Dumont, André Ermans, Paco Escobar del Rey, Raymond Greene, Demitri Koutras, Axel Lamberg, Serge Lissitzky, Raymond Michel, Jacques Nunez, Jean Roche and Nino Salvatore. This group included 5 future Presidents of the ETA, the two Vice-Presidents (when that position existed), the founding Secretary-Treasurer and two others who were to be Chairmen of local organising committees. Ros played an active role in the early days of the ETA and was our second President in succession to Jean Roche. She remained a committed member and continued to participate actively in meetings until the early 1980's. She was always ready to discuss issues relating to the development of the Association and was active in encouraging younger members. Her advice was always constructive and delivered with a degree of frankness which was refreshing.

She provided the inspiration for many young scientists and was always prepared to take time to share her knowledge and enthusiasm with her younger colleagues as well as with those whose interests overlapped with her own. She was one of the most approachable of the senior members of the Association and at least one of the younger members of the Association habitually referred to Ros as his scientific mother.

Dr David Evered
Padworth Common, Berkshire RG7 4JD (UK)

For a fuller account of Ros Pitt-Rivers life and work see JR Tata, Biographical Memoirs - Royal Society of London, 1994, 39, 325-348.

I am grateful to Dr Jamshed Tata FRS for kindly reading the manuscript and for making a number of helpful suggestions.