Lives of the fellows

Robert Gwyn Macfarlane

b.26 June 1907 d.26 March 1987
CBE(1964) MRCS LRCP(1933) MB BS Lond(1933) MD(1938) MA Oxon(1948) FRS(1956) FRCP(1960) FRCPS Glas(1986)

Gwyn Macfarlane, the only child of Robert Gray Macfarlane and his wife Eileen, née Sanderson, was born at Worthing in Sussex. Sadly his father, Bangkok manager of the Eastern Trades Corporation, had succumbed to a bite from a rabid dog earlier in the year. After private school and Cheltenham College, Macfarlane entered St Bartholomew’s Hospital in 1926 but did not qualify until 1933. Not that he was lazy or stupid but there were so many other interests - sailing, ice skating at which he was an expert, music and ballet, and the pleasure of fast motorcycles and later motor cars - all of which he continued to enjoy throughout his life.

As a medical student he had two emotional experiences that affected his career and achievements. As a pathology clerk to the Horder firm he had a ‘brush’ with Sir Thomas, later Lord Horder, [Munk's Roll, Vol.V, p.198] over the accuracy of haemoglobinometry, which resulted in a decision to become a pathologist. Then, as a dresser he looked after a small boy with a cut on his chin which would not stop bleeding. He was known to be from a family of ‘bleeders’, two of his brothers having died from biting their tongues, and in spite of every effort the cut continued to bleed. Finally, as the boy had lost so much blood he was given a blood transfusion and almost immediately the bleeding stopped. Macfarlane was both fascinated and horrified and in 1931 this 24-year old student wrote ‘Haemophilia - a short survey’, a remarkable, critical and comprehensive study of this condition, of which little was then known. He concluded that the only effective treatment for stopping the haemorrhage was a fresh transfusion of human blood or plasma, something not generally appreciated at that time.

Shortly after qualification Gwyn received a legacy of 25 pounds and approached Edgar Kettle [Munk's Roll, Vol.V, p.229], in the hope that he might work on a cure for haemophilia in the department of pathology at Bart’s. Kettle, a shrewd judge of character, felt that this young man deserved encouragement and agreed to his joining the department.

After some initial experiments which came to nothing, Macfarlane learned from Hartridge that it was believed that some snake venoms affected blood clotting. Macfarlane immediately consulted the Zoo’s curator of reptiles, Burgess Barnett. They tested the coagulating powers of a large number of snake venoms and found that they did affect blood clotting, and that the Russell viper was far the most effective. The venom was purified and tested for the first time on a haemophilic patient on 19 July 1934 with entire success; it was later introduced commercially as ‘Stypen’.

By now Macfarlane was a junior demonstrator of pathology at Bart’s, and also a Sir Hailey Stuart research fellow, trying to find a cure for the disease. In 1936 he became clinical assistant pathologist at the new British postgraduate medical school, Hammersmith, under Janet Vaughan. Here he learned the full scope of haematology and the patterning of scientific experiments. He was also preparing a London MD thesis on ‘The normal haemostatic mechanism and its failure in the haemorrhagic state’, which was awarded the university gold medal in 1938; it was offered as a review in The Quarterly Journal of Medicine and revealed a completely new approach to the problem of haemostasis and its defects.

Macfarlane then spent a little over a year as assistant bacteriologist at the Wellcome Physiological Research Laboratories learning about the biological significance of enzymes, which was going to be important to him throughout his scientific career, but the oppressive commercialism was not to his taste and in December 1940 he was appointed clinical pathologist to the Radcliffe Infirmary, Oxford, a post in which he remained until his retirement a little over 25 years later.

At the Radcliffe he had to organize a department of haematology to meet the needs of the new Nuffield postgraduate scheme for research, as well as the training of pathologists and undergraduate teaching both in the clinical school and in the university department of pathology in particular.

In 1941 the Medical Research Council asked Macfarlane to organize a team to look into the discrepancies that appeared to exist between the normal haemoglobin levels in Britain and the United States. This was found to be due to an irregularity in the national Haldane standard but it also became apparent that there were very considerable observer errors in haemoglobinometry and a new, and more satisfactory, instrument - the MRC Grey-Wedge photometer - was introduced in 1948.

Macfarlane was appointed Radcliffe lecturer in haematology in the University of Oxford in 1943 and the following year spent six months, at the request of the Medical Research Council, in the RAMC working in France with Major Maclennan on gas gangrene, in which they were able not only to elucidate the pathogenesis of this condition but also recognized a new enzyme toxin ‘collagenase’ which had played a significant part in the local lesion.

When Macfarlane returned to Oxford he began an extensive study of fibrinolysis which was proving significant in relation to a wide range of biological processes and to tissue injury in particular. This research work attracted Rosemary Biggs to haematology, who had been studying the crush syndrome in morbid anatomy, but she so much enjoyed the department that she stayed as Gwyn Macfarlane’s assistant and collaborator and, when he retired, she succeeded him as the director of the Blood Coagulation Research Unit.

By now the Radcliffe haematological department was becoming recognized as a power house of research and exciting new ideas. Young assistants from all over the world were anxious to work there and, although there were many who stayed just for a week or more, Macfarlane was never prepared to have more than three attached research workers at one time; otherwise the department would have become impersonal and no longer stimulating.

The recognition of errors in haemoglobinometry was the start of a general study of the reliability of all haematological methods; now called quality control. The methods of controlling anticoagulant therapy were next investigated as it was found that the Quick test was not always consistent, and this in turn revealed that the classical theory of coagulation was no longer tenable and that there were other factors previously unrecorded involved in the process. However, it was probably the revelations of the errors of red cell counting and similar tests which caused real alarm on the part of clinical pathologists throughout the world.

To overcome this, Macfarlance had the idea of producing an automatic electronic red cell counter and with a young technician, Heinz Wolff, he built the first equipment of this type, which proved to be entirely reliable and efficient. Unhappily, the Ministry of Health decided that there was no need for such a machine and that therefore it should not be developed commercially. A few years later the American Coulter electronic red cell counter, working on a different principle, was introduced and became essential equipment for all diagnostic laboratories.

The fields of interest in the Radcliffe department of haematology were broadening; bone marrow tissue culture initiated the study of cytogenetics of the marrow cells, and there was also a unit of immunohaematology concerned with haemolytic anaemias and, particularly, haemolytic disease in the new born.

In 1950 circumstances within the department caused Macfarlane to decide that he could no longer carry on with research work on fibrinolysis, although during the 15 years in which he had studied it he and his colleagues had made important contributions which are well recognized. On the other hand, there were indications that the blood factor lacking in haemophilics could be identified, so Macfarlane and his colleagues decided to study the clotting of whole blood, something which had not been undertaken since the days of Lord Lister. It was discovered that in addidon to the well known extrinsic coagulation system there was an intrinsic system, equally powerful, which was initiated when blood came in contact with a foreign surface. It also became apparent that it was possible to identify and quantify the various clotting factors, including that which was lacking in haemophilia. Further, it was discovered that there was a haemorrhagic disease clinically and genetically identical with haemophilia but due to the lack of a different clotting factor, and this became known as Christmas Disease - named after the surname of the first patient recognized to be suffering from this condition.

A skilled enzyme chemist, Dr Edith Bidwell, now joined the team and began work on the purification and concentration of the various blood clotting factors but in particular that which was lacking in haemophilia, variously known as antihaemophilic globulin or Factor VIII. It became possible to offer haemophilics replacement therapy and by 1953 it was not only emergency operations which could be performed with a reasonable degree or safety but also formal orthopaedic and other major operations. In that same year Human blood coagulation and its disorders, Oxford, Blackwell Scientific Publications, 1953, appeared and was immediately highly popular and rapidly went through a number of editions.

Macfarlane was now receiving the recognition that he richly deserved: he became a fellow of the Royal Society, professor of clinical pathology at Oxford, a fellow of All Souls College, and was awarded the CBE. He was elected a Fellow of the College in 1960. Despite these honours he remained the same delightful, witty, friendly person who took no particular pleasure in the banquets, speeches and prize giving at international congresses.

In 1959 the Medical Research Council established a blood coagulation research unit at Oxford and this facilitated the inter-relationship of investigation and treatment, but inevitably there were administrative difficulties and Macfarlane was happy to occupy himself at the Sir William Dunn School, studying the early stages of thrombosis as seen through the electron microscope.

By now it was beginning to be recognized that there were a large number of blood clotting factors, with a confusing nomenclature until a committee was set up - in which Macfarlane played a considerable part - which suggested that they should be clearly defined and allotted roman numerals for identification, thus making communication much easier. It was also thought that many of these factors were either enzymes or substrates and, in 1965, Macfarlane put forward ‘The basis of the cascade hypothesis of blood coagulation’, Thromb. Diath. Haemorrh., 15:591-602,15 May 1966, in which he suggested that there was a sequence of enzyme reactions from the initial contact with a foreign surface, step by step accelerating and amplifying until the great energy release required in the transformation of fibrinogen into fibrin. His idea of a trigger mechanism was quite novel in biology and has been shown to extend to quite a number of other physiological systems.

Macfarlane had always intended to retire at the age of 60, and the administrative difficulties which the Ministry of Health were introducing in relation to the haemophilia unit gave him no reason to change his mind, for he already had a delightful house in Wester Ross. On the occasion of his retirement in 1967, a special number of the British Journal of Haematology appeared, with papers by many of his pupils, and a bibliography of his writings, as well as an acknowledgement of a delightful talk which he had given: ‘Russell Viper’s venom’.

Hilary and Gwyn Macfarlane found great contentment in Malla’s Cottage, a converted croft in the small West Highlands village of Opinan which at that time had very few incomers. Macfarlane found the opportunity to write, something that he had always wished to do for he had a natural ability and elegance of style. He first wrote a philosophical fantasy in the form of a novel, which has not yet been published, but then he wrote a life of Howard Florey, (Lord Florey), [Munk's Roll, Vol.VI, p.178], Howard Florey: the making of a great scientist, Oxford, OUP, 1979, for whom he had a great admiration. It is a marvellous account of the develoment of a great scientist, with an ability to coordinate others, and the problems he had to face and the success he was to have. But Macfarlane was disappointed that the public did not see it like this; from their point of view Fleming and penicillin were synonymous and Florey did not exist. Macfarlane always felt that there was some sort of newpaper plot against Florey; so he wrote a life of Fleming, Alexander Fleming: the man and the myth, London, Chatto and Windus, 1984, and found that there was no plot, it was just that Florey was not very gracious to the media and Fleming thoroughly enjoyed publicity. Somewhat to Macfarlane’s chagrin, his Fleming biography - which is the only accurate account of his life - was a great success, in contrast to the one on Florey which was much the better book. Macfarlane gave a brilliant ‘Horizon’ television programme,‘The Mould, the Man and the Myth’, and he was writing his own autobiography, but this was not completed.

In 1981, Sir Weldon Dalrymple-Champneys [Munk’s Roll, Vol.VII, p.133] a former deputy chief medical officer of health, who had taken a great interest in the care of haemophilics and had been president of the Haemophilia Society for many years, died and Macfarlane - who had been vice-president for some time - was asked to succeed Sir Weldon. He agreed to do so provided he was not required to make any speeches, but he was most assiduous in his work for the Society and needless to say was bitterly disappointed that the Ministry had ignored the accurate estimates which he had made as to the amount of Factor VIII which would be required for the treatment of haemophilics, and instead had purchased from America virus contaminated material; at first with hepatitis virus - which was bad enough - but then with AIDS which was really serious. Macfarlane was much saddened to know that the work that he and his colleagues had done to relieve haemophilics had, through no fault of theirs, become a vehicle of death and disease. Somewhat bitterly, he would quote Andrew Mellon’s ‘No good deed goes unpunished.’

Although he had one or two illnesses, Macfarlane enjoyed his retirement and celebrated his golden wedding anniversary quietly with his family. On the evening of 25 March he developed severe myocardial ischaemia and died peacefully, in his sleep, in the early hours of the following day.

Gwyn Macfarlane had married Hilary Carson, then a medical student, on 25 January 1936, and it was a perfect marriage. They had five children who, in their different ways, reflected the interests and skills of their parents. One son, a doctor working in the field of blood disorders; another in the world of motors, two sons who combine engineering and boat building, and a daughter who is a skilled photographer as well as being a wonderful mother with the charm of both her parents.

AHT Robb-Smith

[Lancet, 1987,1,932; The Times, 30 Mar 1987; Wellcome Inst.Hist.Med.,,RGM'S Working Paper]

(Volume VIII, page 303)

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