This story began shortly before my time. My involvement came about through wartime work for the Navy on survival at sea, and an eccentric professor. In 1942 Hetherington & Ranson in the USA found that lesions in the ventromedial nuclei of the hypothalamus in rats cause obesity. The suggestion that a hormone was involved came from my Ph.D. project, published in the Journal of Physiology as a Communication in 1957 and a full paper in 1959. In a number of rats in parabiotic pairs (i.e. artificial Siamese twins), which permanently exchange blood, I made ventromedial hypothalamic lesions in one rat. Surprisingly, their partners became very thin, evidently from ceasing to eat. Subsequently my colleagues and I and others have demonstrated that the severe reduction of feeding and loss of body fat in parabiotic partners of obese rats occur after different ways of inducing obesity: electrical stimulation of the lateral hypothalamus; offering the rats foods they find particularly tasty; the use of congenitally obese Zucker rats; and over-feeding by stomach tube. In our last experiment we used graded levels of tube-feeding and were able to demonstrate a linear relationship between the body fat content of rats made obese by over-feeding, and the diminished fat content in their free-feeding partners. This, I believe, is good evidence for a feedback control system, which maintains approximate energy balance by stabilising fat content. The relationship gives a measure of the control system's gain'. I have never been in a position to identify the agent, demonstrably blood-borne and presumably generated by fat, that the hypothalamus detects. Latterly I could not get grant support for a co-worker, and of course had teaching and departmental commitments. But surely, particularly at present, there is an opportunity here.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.