Oliver Wrong

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, but in a quite different gene OCRL1. This gene had been identified earlier as mutated in patients with ‘Lowe Syndrome’. 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.

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.

Wrong was unusual in the breadth of his medical interests. His 1981 reference book, The Large Intestine: Its role in Mammalian Nutrition and Homeostasis, 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.”

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 hereditary clinical syndrome very similar to that reported some 20 years earlier by Dent (his predecessor as Professor of Medicine at UCH) and Friedman in 1964. Dent and Friedman originally reported two unrelated patients with the condition they termed ‘Hypercalcuric Rickets’ without identifying any hereditary component. Wrong, based on his own additional clinical work, discovered that this was a new hereditary disease and with his co-workers Norden and Feest reported it as a form of the renal ‘Fanconi Syndrome’.

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. His clinical analysis of this process and the impact of kidney disease made this paper a ‘Citation Classic’. 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’. 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 Dundee University in 1969 and a return to UCH in 1972 to succeed Professor Charles Dent F.R.S. as a Professor of Medicine.

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 molecular genetics in this area. By rigorous phenotypic classification, Wrong and other workers showed that ‘Type 1 RTA’ could have either dominant (SCL4A1 mutation) or recessive inheritance. It was further shown that there were three forms of recessive RTA distinguished clinically and on the basis of molecular generics divided into disease due to SLC4A1 mutation and either the B1 or a4 subunits of the kidney H+-ATPase due to mutation of the ATP6V1B1 andATP6V0A4 genes respectively. Hereditary ‘Proximal’ or ‘Type 2 RTA’ may be caused by mutation of the SLC4A4 gene and yet a further ‘Type 3 RTA’ with combined features of proximal and distal RTA is due to mutation in the CA2 gene for carbonic anhydrase II. These developments in the molecular biology of the kidney may be traced back in large part, though not exclusively, to Wrong’s original 1959 paper.

Oliver Wrong married Marilda Musacchio, a primary school teacher from the Val d’Aosta, Italy, in 1956. They had three daughters, one of whom is the author and journalist Michela Wrong.

Professor Oliver Murray Wrong (7 February 1925 – 24 February 2012) was an eminent academic nephrologist (kidney specialist) and one of the founders of the speciality in the United Kingdom. From a background as a “salt and water” physician, he made detailed clinical observations and scientifically imaginative connections which were the basis of numerous advances in the molecular biology of the human kidney. Wrong himself contributed to much of the molecular work after his own “retirement”. He dictated amendments to his final paper during his final illness in his own teaching hospital, University College Hospital (UCH), London. Though academic in his leanings, he was a compassionate physician who established a warm rapport with patients, a link he regarded as the keystone of his research. He belonged to a generation of idealistic young doctors responsible for the establishment of the UK’s National Health Service in the post-War years.