05 August 1919 – 20 December 2016
Professor Douglas B. Brewer, an important figure in the development of understanding of the kidney and one of the pioneers of renal biopsy pathology, died on 20 December 2016 aged 97.
Douglas Bertram Brewer was born on 5 August 1919 in South Wales, the son of a general practitioner. He studied medicine in the University of Cardiff but took the University of London examinations, and qualified MB BS in 1943 and MD in 1947. He served in the Royal Army Medical Corps from 1944 to 1946 in Europe and East Africa. From 1946 to 1948 he was a registrar in the Department of Pathology and Bacteriology in the Welsh National School of Medicine, under Professor J. B. Duguid, by whom he had been inspired as a student to become an academic pathologist. He began to be interested in two topics that later were to produce fruitful research findings. One, stimulated by the eminent lung pathologist, Jethro Gough, was to lead to work in the 1960s on the mechanism of pulmonary hypertension in chronic obstructive pulmonary disease. The other, which was to produce a larger research output and for which he is much better known, was pathology of the kidney.
While in Cardiff he studied autopsies in lipoid nephrosis, which was the name then for the nephrotic syndrome in the absence of an identifiable disease such as amyloid or intercapillary glomerulosclerosis (diabetic glomerulopathy). Like others, he was impressed by the apparent normality of glomeruli despite heavy proteinuria. A fortunate chance allowed him to expand his interest in the kidney. Professor John Squire was just beginning in 1948 to develop a Department of Experimental Pathology in the University of Birmingham. Douglas Brewer became a lecturer and was asked by Squire to study the renal clearance in rabbits of dextrans of different sizes. This arose from Squire’s work on the use of dextran solutions for resuscitation following accidents and burns. Douglas showed unambiguously that glomerular permeability to macromolecules was related to molecular size, which had not been clearly shown before.
In 1953 Douglas became Senior Lecturer in Pathology in the University of Birmingham and Honorary Consultant Pathologist in the United Birmingham Hospitals. He was promoted to Reader in Pathology in 1955 and Professor of Morbid Anatomy in 1967. John Squire had become interested in the nephrotic syndrome and a critical event happened in 1955 when the clinical team under his direction began to take renal biopsies. Douglas took this opportunity to develop his interest and expertise in interpretation of them. The other main members of the team were John Hardwicke, Denys Blainey and John Soothill.
At that time, when renal biopsies were just beginning to be used, understanding of glomerular disorders was rudimentary and almost entirely based on autopsy findings. Ellis’s 1942 division of glomerulonephritis into types 1 and 2 was widely used, but Douglas was dissatisfied with this crude classification. He had the foresight to have serial sections prepared on biopsies, and to keep all material from them. This not only allowed detailed study of glomeruli and other structures in three dimensions, but also provided the opportunity for later investigations, such as his description of the glomerular tip lesion in 1984.
The work on the nephrotic syndrome by the Birmingham team culminated in the 1960 Quarterly Journal of Medicine paper that Professor Stewart Cameron has described as ‘the magnificent summary paper which I remember reading with awe’. This defined minimal change nephropathy as a clinicopathological entity by the apparent normality of glomeruli on light microscopy, its association with selective proteinuria and its response to steroid treatment, and differentiated minimal change from membranous nephropathy and other glomerular diseases.
Some nephrologists, including Clifford Wilson and Hugh de Wardener, noted that all the Birmingham patients had been treated with steroids and were in favour of a controlled trial. The Medical Research Council organised a multicentre controlled trial of prednisone against no prednisone in adults with the nephrotic syndrome, which ran from 1962 to 1966. Douglas Brewer was one of the two pathologists in the trial and with Douglas Black and Geoffrey Rose was an author on the 1970 British Medical Journal report. The trial confirmed that prednisone was effective in minimal change nephropathy, although given time patients would improve any way, and showed that prednisone in the doses used was not demonstrably effective in membranous nephropathy or the miscellaneous group called proliferative glomerulonephritis, and that prednisone was associated with more cardiovascular deaths. Douglas said that John Squire thought that it was unethical to withhold steroid treatment and no Birmingham patients were entered in the trial.
Both the Birmingham 1960 series and the MRC trial had such clear-cut differences in response to steroids between minimal change nephropathy and the other conditions because of the strictness of Douglas’s definition of minimal change. Throughout his career, Douglas stressed that even slight changes in glomeruli on light microscopy were against this diagnosis. Other pathologists were less rigorous and would have diluted series of minimal change nephropathy with other things.
Douglas realised quite early the need for a practical book to help pathologists while nephrologists were making more use of renal biopsies in their everyday practice. His book Renal Biopsy, for which he is most widely known, was first published in 1964. It was certainly one of the earliest texts on the interpretation of renal biopsies, and could well have been the very first. It is a superb book, written from Douglas’s own experience, and those who knew him can hear the man talking to them as they read the text. One of the attractions was its size, because the words and pictures filled only 89 pages. It deserved Adrian Morley’s praise, when reviewing books on renal biopsy pathology in 1992, that it was the earliest and most welcome example, with an extremely high value:weight ratio. The second edition in 1973, which can still be seen on the shelves of many departments of pathology and nephrology with its distinctive cover image of membranous nephropathy (see Figure), had only a slightly larger 95 pages of text. In comparison, the seventh edition in 2015 of Heptinstall’s Pathology of the Kidney had 1497 pages.
Douglas continued experimental and clinical work on the kidney. This included early electron microscopic studies in diabetic glomerulopathy, an intensive study of various experimental models of proteinuria, and many other topics. His fertile and enquiring mind continued to be active after his retirement in 1984, and his last peer-reviewed paper was published in his ninetieth year. This was on the physical optics that explain the anomalous colours seen in Congo red-stained amyloid. Included was the history of Congo red staining, most of which he had derived himself from the German literature. Douglas learnt German from scratch after he retired, and reached degree standard. He was still hoping to complete another electron microscopic project when he died, which was after several falls with cerebral trauma.
The Queen sent Douglas and his wife Mary a seventieth (platinum) wedding anniversary card a couple of months before he died. Mary and their three daughters survived him.
Alexander J. Howie