Oliver Wrong
Professor Oliver Murray Wrong (7 February 1925 โ 24 February 2012) was an eminent academic
Background
Wrong was born in
Education
Oliver Wrong studied Medicine at Magdalen and completed his clinical studies at the Radcliffe Hospital, Oxford. His 'National Service' โ military conscription - was spent with the Royal Army Medical Corps in Singapore and Malaysia. This was a geographical region to which he would return several times in his research.[4] After internships in Toronto and at Massachusetts General Hospital with Alexander Leaf, he was appointed University Tutor in Medicine at Manchester Royal Infirmary. Leaf was a formative influence and an important paper was jointly produced on the role of Anti-Diuretic Hormone and the kidney.[5]
Research and academic appointments
It was at Manchester with Dr. H.E.F. Davies, in 1959, that Wrong wrote a ground-breaking paper on the mechanisms leading to the excretion of acid in human urine.[6] His clinical analysis of this process and the impact of kidney disease made this paper a 'Citation Classic'.[7] Reviewing his time at Manchester, Wrong noted: 'I realise what an excellent education [my years at Manchester] provided by giving me time to tackle my own problems under a benign yet critical supervision. Because of earlier marriage and the rigidity of our postgraduate medical training programme, few of our present graduates feel able to afford such self indulgence'.[8] After an appointment at UCH, Wrong became senior lecturer in medicine at the Hammersmith Hospital. This was followed by appointment to the Chair of Medicine at
At UCH over the following years, and following retirement in 1990, Wrong developed major insights into the physiology and pathophysiology of the human kidney. Wrong had a parallel interest in the role of the large intestine in salt and water balance and developed much of his own experimental work into a short monograph published in 1981. However, it was his renal work, based initially on the urine acidification test which he developed with Davies, for which Wrong is best known.
Research highlights
The original paper by Wrong and Davies examined the effect of the 'short ammonium chloride loading test' on acid excretion by the kidney.[9][10] A key insight was that in the group of diseases termed 'Renal Tubular Acidosis' (RTA), urinary excretion of ammonium was relatively well preserved. This was unlike the situation in chronic kidney failure. Furthermore, the paper identified a subset of patients with 'incomplete' RTA. In large part due to Wrong's work, it is now recognized that classical 'distal' or 'Type 1 RTA', due to the disease of the distal tubule, is only one form of the disease.[11] 'Proximal' or 'Type 2 RTA' is another.
The identification of several hereditary forms of RTA was developed by Wrong and co-workers and forms the basis of many of the advances of
Nephrocalcinosis was a subject on which Wrong was an international expert and he wrote the relevant chapter on this subject for one of the standard nephrology textbooks.[13] It is a summary of his experience of this finding based on almost his entire professional life.
Wrong was unusual in the breadth of his medical interests. His 1981 reference book, The Large Intestine: Its role in Mammalian Nutrition and Homeostasis,[14] summarised research into a part of the human anatomy he felt was neglected due to unprofessional squeamishness on the part of the scientific establishment. "There is a curious reluctance in the medical profession to handle faeces," he said. He began a 1965 paper on the electrolyte content of human waste with the characteristically playful: "Stool is the Cinderella of electrolyte studies."
A great believer in self-experimentation, Wrong invented the "Wrong bags", which allow precious "in vivo" insights into the
In a major medical insight, Wrong realised that a number of the patients he was seeing in one of his clinics at UCH had an apparently
A very similar hereditary clinical syndrome was reported by Scheinman and colleagues.[17] This clinical work was put on a very firm basis by Thakker, Scheinman and Wrong and colleagues who determined that mutation of the chloride channel gene CLCN5 was the cause of many, though not all, of these disorders including one of the two original patients described by Dent and Friedman.[18] Wrong had already been 'retired' for 6 years when this was published. It became clear that several similar clinical conditions were, on the basis of genetic analysis, the same as that which Wrong had originally termed 'Dent's Disease' in honour of his late mentor. This disease is variously termed Dent's disease or Dent disease. Wrong's insights, which made this previously relatively neglected disease well-known, have prompted the suggestion that the disease should more properly be termed 'Dent-Wrong' disease.[19]
Wrong's identification of Dent and Friedman's second patient as having 'clinical' Dent Disease was expanded when, in 2005, Scheinman's group identified this patient and his family as having mutations not in CLCN5, the gene mutated in most of the families with Dent disease originally identified,[20] but in a quite different gene OCRL1. This gene had been identified earlier as mutated in patients with 'Lowe Syndrome'.[21] Wrong's discoveries had led to the identification of two new 'new' hereditary diseases, each based on one of Dent and Friedman's original patients, and one 'Dent Disease Type 1' due to CLCN5 mutation and the other, 'Dent Disease Type 2' due to OCRL1 mutation.
Wrong, who had been diagnosed with idiopathic pulmonary fibrosis seven years earlier, was working on his final paper when admitted to Intensive Care Unit at UCH, the hospital at which he had spent most of his professional life. The paper, published posthumously, describes a variant of autosomal dominant distal RTA, due to SLC4A1 mutations, originally found in SE Asia. In that final paper, Wrong presented a novel hypothesis to explain the frequency of the mutations in the tropics despite their adverse clinical effects.[22] He suggested that changes in red cell metabolism might protect against malaria, a major killer in the region.
Professor Wrong's papers are stored at the Wellcome Trust Library, 183 Euston Road, London.[23]
Family
Oliver Wrong married Marilda Musacchio, a primary school teacher from the
References
- PMID 22919024.
- ^ "Professor Oliver Wrong". The Times. 15 March 2012. Retrieved 18 November 2012.
- PMID 12949207.
- ^ "Professor Oliver Wrong". The Times. 15 March 2012. Retrieved 18 November 2012.
- PMID 13084753.
- PMID 13658353.
- ^ Wrong, O (1978). "This Week's Citation Classic". Current Contents: 50.
- ^ Wrong, O (1978). "This Week's Citation Classic". Current Contents: 50.
- PMID 13658353.
- PMID 22855286.
- PMID 17557941.
- PMID 17557941.
- ^ Oliver Wrong (2005). Oxford Textbook of Clinical Nephrology. Oxford: Oxford University Press. pp. 1257โ1280.
- ISBN 9780470271674.
- PMID 7922301.
- PMID 14169453.
- PMID 1908057.
- S2CID 4364656.
- ^ "Professor Oliver Wrong". The Times. 15 March 2012. Retrieved 18 November 2012.
- PMID 7922301.
- PMID 15627218.
- PMID 22919024.
- ^ "Wellcome Library Western Manuscripts and Archives". Retrieved 9 October 2013.
External links
- Oliver Wrong on the History of Modern Biomedicine Research Group website