Rod Gregory made fundamental contributions to the study of gut hormones through his isolation of the gastric acid stimulating hormone gastrin, the characterisation of its spectrum of actions, the identification of structure-activity relationships and discovery that gastrin was produced in excess in the tumours of patients with Zollinger-Ellison syndrome.
In the mid-1950s the existence of gastrin was regarded by many as not yet proven. At the time, Gregory together with his long standing co-worker Hilda Tracy was attempting to characterise the gastric acid inhibitory factor in urine known as urogastrone (this was later shown by Harry Gregory, no relation, to be epidermal growth factor).
Gregory and Tracy required a stable background of acid secretion against which to test preparations of urogastrone, and for various reasons the available acid secretagogues were unsatisfactory. They set out, therefore, to make preparations of gastrin and in due course this became their main interest. By the late 1950s new methods of column chromatography were becoming available (notably ion exchange media suitable for small acidic peptides, and gel filtration media such as Sephadex). Using these, and working on a large scale with the antral part of pig stomachs obtained from local abattoirs they quickly produced gastrin preparations that were far superior to any generated hitherto from which it became possible to obtain essentially homogenous peptide in suitable quantities for sequencing.
The sequence of two gastrins was subsequently determined in collaboration with George Kenner who was a distinguished peptide chemist in the University of Liverpool, Chemistry Department at the time. The peptides were shown to be identical heptadecapeptides differing in the presence or absence of a sulphate group on a solitary tyrosine.
Kenner’s group then synthesised these peptides, and prepared many fragments and analogues which allowed the elucidation of structure-activity relationships including the crucial discovery that the C-terminal tetrapeptide amide was the minimal fragment with full biological activity. Shortly afterwards it became clear from the work of Viktor Mutt and Erik Jorpes on the intestinal hormone cholecystokinin, and that of Vittorio Erspamer on the amphibian skin peptide caerulein, that all three peptides shared an identical C-terminal pentapeptide amide and that this accounted for similarities in their biological properties.
Gregory and Tracy went on to show that the pure gastrins acted on a variety of different organs in addition to stimulation of acid secretion by the stomach, including stimulation of gastrointestinal motility, and weak stimulation of pancreatic secretion and gall bladder contraction. In due course they also identified other gastrins including peptides of 34-amino acid residues that are now known to be intermediates in the biosynthesis of the heptadecapeptides. Importantly, they also showed that gastrin could be isolated in large amounts from tumours of the Zollinger-Ellison syndrome and so providing a mechanistic link between these tumours and the acid hypersecretion that characterises the syndrome. They also made purified gastrin freely available to many researchers around the world which stimulated activity in the area including the subsequent development of radioimmunassays.
Rod Gregory was trained as a physiologist in the Department of Physiology at University College London in the early 1930s. He was introduced to gastrointestinal physiology in the laboratory of Andrew Ivy at Northwestern University, Illinois, where he obtained a PhD. His work on gastrin was carried out while he was Holt Professor of Physiology, and Head of Department, at the University of Liverpool (appointed in 1948) and while he had full teaching and administrative roles.
His qualities as a teacher influenced many generations of students including Professor Sir David Weatherall FRS, FMedSci (founder of the Institute of Molecular Medicine, University of Oxford) who recently noted that his own interests in medical research were stimulated by Rod Gregory “whose brilliant lectures were clearly from a man who was creating science as well as teaching it”.
Gregory’s work has proved enduring because he was one of the first to see, and to show, that progress in regulatory physiology depended on a rigorous understanding of molecular mechanisms and that work on the gut hormones required the widespread availability of pure peptides of defined sequence.