Stepping Back

In 2009 I had a phone call from Prof. Bill Marshall, a Canadian comparative physiologist who I had never met before, telling me that the Editorial Board of the Journal of Comparative Biochemistry and Physiology had selected some of my papers on electrolyte transport by eel gills to celebrate the 50^th anniversary of the launch of the journal. He asked if I was interested in producing a joint paper for the celebratory edition. He had assembled the following lead-in paragraphs to my work.

“Fish gills were long suspected to be major metabolic organs as well as being specialized for gas exchange, but the complexity of the organ made it difficult to attack experimentally. The first attempts to separate the ion transport function of the gills from the rest of the body were estimated through examination of the total body ion transport flux and partitioning the gill, suspected to be the largest fraction because of its large surface area. Whereas Homer Smith (1930) worked very successfully on transport budgets in whole animal experiments, Ancel Keys developed a heart-gill preparation that allowed the gills to function isolated from the rest of the body, whilst being perfused at physiological pressures by the heart. In this way, the gill function could be separated from the rest of the body surface and from urinary and fecal losses (Keys 1931). This preparation did not attract many followers, perhaps because the ion detection systems were chemical and radioisotopes were not in wide use at the time. In the process, Keys made an acutely brilliant observation about the heart-gill preparation. Keys found that the pressure needed to perfuse the heart-gill preparation was lower than that needed to perfuse the gills by themselves and that single gill arches perfusion pressure climbed with time. To quote Keys: “The only explanation which offers itself is that the perfusion medium derives a hormone or hormones from the heart which acts to preserve capillary tone”. Keys’ observation was correct and we now know of these factors as a family of hormones, the Atrial Natriuretic Peptides. Fish physiology moved forward for three decades mostly through budget-based whole animal experiments similar to those of Homer Smith (1930) but the mechanisms of ion transport remained enigmatic”.

“The second chapter of the development of the isolated gill occurred in University of Sheffield, 1961, when Denis Bellamy made the first attempts at isolated gill ion transport. Bellamy simply excised eel gill arches separately and incubated them in a bath of sea water or fresh water to measure the rate of ion gain or loss (Bellamy and Chester Jones CBP 1961). Bellamy mentioned that one advantage of separate gill arches over the heart-gill preparation was that several replicate paired experiments could be performed from one animal. Simultaneously, Bellamy (CBP 1961) worked with a system that would measure ion movements across the whole animal, in this case the European silver eel, but would isolate the anterior portion where the ion fluxes would mostly occur through gill transport (Fig. 1). Restraint devices that allowed isolation of the anterior from posterior portions of the fish unfortunately involved an uncontrollable amount of stress for the animal that could easily affect the transport rates. There was also no guarantee that anaesthetics that would reduce stress would not also affect ion transport events. Hence, verification of these in vivo experiments by isolated gill arches provided a robust two-pronged approach, each with a different set of assumptions. There was an obvious drawback to the isolated gill tissue, because the blood vessels were open to the environmental solution, so that leaks were possible and parts of the unperfused tissue could easily become hypoxic over time. For unknown reasons, that is where the intact eel and gill superfusion experiments stopped for Bellamy. Denis moved on to the animal science department to study corticosteroid function in mammals (Bellamy CBP 1963; Bellamy and Leonard CBP 1964) and thence to University of Wales (Cardiff) and continued a stellar career in an eclectic mixture of endocrinology, marine biology and ageing. There are contributions to three major works, the books Integrative Biology (Hill et al. 1971), Environmental Physiology (Bellamy and Phillips 1975) and a solo book Ageing: A biomedical perspective (Bellamy 1995). Ageing research commenced with work on the regression of rat thymus (Bellamy et al. 1976). The latest research papers combined ageing with marine biology, a study that concluded that marine mussels recover from hyperthermia differentially depending on their age (Hole et al. 1995). Denis Bellamy’s story is an example of the way that animal-based fundamental physiological research can evolve and produce expertise and profound benefit to the human population, while remaining faithful to basic physiology”. (Published)

This prompted me to think about creativity in general and my own innovations as a career scientist I soon realised that in order to give a full answer to Bill Marshall’s question about why I did not follow my 1961 paper on the workings of fish gills, I have to take a big step back to the late 1950s and my postgraduate research at Oxford .