When writing about an article in the famous series, New Biology, published by Penguin between 1945 and 1960, I was reminded of another influential article of the time and how its author came to feature—completely unintentionally—in a London academic promotion battle that turned into a loss to Britain and a win for Australia.
The article in New Biology in 1952 was on the working of the frog’s heart which has three chambers, two atria and just one ventricle into which both atria empty. George Eric Howard Foxon (1908-1982*), then Reader in Biology at Guy’s Hospital Medical School, outlined what he called The Old Story, dating from the mid-1800s, of how oxygenated blood from the lungs is preferentially diverted to the rest of the body after it (along with blood from the body) enters the single ventricle. According to this scheme, oxygen-rich and oxygen-poor blood do not mix to an great extent in the ventricle, and blood is pumped sequentially into the three major arteries: blood low in oxygen from the body is the first to leave for oxygenation in the lungs and skin; as the ventricle continues to contract, the next lot goes to the body generally while the blood remaining until the final squeeze of the ventricle, that rich in oxygen having arrived from the lungs, goes to the brain. Mixing of oxygen-rich and oxygen-poor from from the left and right atria was, it was argued, prevented by the trabeculae of the ventricle forming rough compartments.
Over the decades there had been doubt cast on this ‘old story’ notable amongst them the observation that there was no difference in time of movement of the blood into the three main arteries. In other words, the story of a sequential separation of flow into those arteries appeared to be wrong.
Foxon sat himself the task of trying determining if the blood from the right atrium was kept largely separate in the ventricle from that entering from the left atrium. He was following up work published in Paris in 1933 in which it had been found that particles from Indian-ink injected into the pulmonary vein were found in all three arteries; on other words there was mixing. Similar results, using starch grains, from the other side of the heart had also been reported.
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| This is Foxon's diagram of the frog's heart |
Foxon used an X-ray opaque suspension of thorium dioxide to follow its passage through the heart by taking a series of X-ray photographs in rapid succession—pioneering technology in those days. While blood from the lungs via left atrium was found to fill the left side of the ventricle that from the body filled the right side. However, during ventricular contraction the movement was found to be so violent that all the blood was mixed together in the conus arteriosus, from which the major arteries (three on each side of the body) arise, such that there was no separation as the blood was forced into the three arteries.
But that story did not last. Later research using more modern technology showed that deoxygenated blood from the right atrium is directed preferentially to the lungs and skin through the pulmo-cutaneous artery. More and more evidence was produced to indicate Foxon was wrong; the ‘old story’ was right in essence if not in detail. It is that version of events—of partial separation of blood streams from the two atria during ventricular relaxation and contraction and flow through the conus arteriosus—which has entered the textbooks.
However, circulation within the heart and major arteries of the amphibian heart has continued to excite the interest of those exploring what happens in different environmental and physiological conditions, in diving and conditions where concentrations of oxygen in the immediate environment are low for example, as well as in several different species. Technological advances in measuring blood flow and pressures in small blood vessels have meant that physiological measurements can be done in conscious undisturbed animals, in the relatively large Cane Toad† (Rhinella marina) for example. In Foxon’s day, ‘pithed’ frogs—those in which the brain has been destroyed—were used perforce. Thus physiological control mechanisms affecting pressures in the various blood vessels may have been disrupted compared with an intact animal in the wild.
The story does not end there. More recent research indicates that there are conditions in which there is a high degree of mixing of the two blood streams within the heart, as claimed by Foxon, and others in which there is a high degree of separation. One example will suffice: in the resting Cane Toad at 10°C mixing was 85% complete but at 30°C mixing was only 17%.
So having been dismissed as anomalous results, Foxon’s conclusions have been supported—in some conditions. The great mistake by a number of authors was to assume that what happens under particular experimental conditions happens under all, as an invariant mechanism for operation of the frog’s heart. Variation in the amount of blood directed to various parts of the body through the three major arteries and variations in mixing of the two streams of venous blood, provide a whole host of different tactics that can be be employed by an individual frog, or by different species, to enable them to adapt to the vicissitudes of life amphibian.
It is, it should be noted, misleading to state that blood arriving into the right side of the heart is, as in mammals, deoxygenated after passing through the tissues of the body. This is because some of it has passed through the skin and skin is an important site of oxygen uptake in amphibians. I have read studies in which the skin in resting animals accounts for a third of all oxygen uptake. The lungs provide a greater proportion during activity or if the oxygen content of the water or the water film over the skin falls. The implication is that blood from the right side of the heart recirculated through the body will still be supplying some oxygen to the tissues in frogs but not, of course, in mammals.
As an aside, a dangerous side effect of the study of ‘types’ as the main part of courses in biology was the impression created in the student that as one moved from the type fish to the type amphibian and so on to the type mammal, there was a progress from a primitive to an advanced organism. It was, therefore, easy to get the impression or to be told that the poor old frog having just three chambers in its heart was in some way inferior to the mammal or bird which had evolved four and had achieved the perfect double circulation, i.e. complete separation of blood streams through the body and through the lungs. Foxon was quick to dispel this line of thinking:
..the heart of the frog does not represent an unsuccessful attempt at the division of the heart into arterial and venous sides. It seems we must regard the frog not as any form of intermediate stage between fish and higher vertebrates but as an animal suited par excellence for a true amphibious made of life…
Foxon appeared in the biography A.J. ‘Jock’ Marshall (1911-1967), his opposite number at St Bartholomew’s Hospital School. Both schools fell under the aegis of the University of London. Foxon and Marshall were Readers and heads of their respective departments. The biology departments within the old medical school were, even by the standards of the day, very small with formally a lowly rôle; their teaching consisted of instilling a knowledge of elementary biology in very junior medical students who had taken on the study of medicine never having studied a biological subject at school. They had no honours students but could ,of course, do research and supervise postgraduate students. Through the latter route they could be promoted to Professor. Indeed Mr Foxon (he did not have a Ph.D. just like many British academics of the time) became Professor Foxon in 1955.
In 1957 Jock Marshall was put forward to the University by his medical school for promotion. Foxon encouraged Marshall, thinking the whole matter a formality for one so clearly qualified. But Marshall’s case was blocked by one external member and one internal member of the committee, as explained in detail by his widow here. Marshall was incandescent with anger at his treatment. The Cambridge mafia he blamed; the formerly supportive internal member was reliant on the external member for supporting his candidature for the Royal Society. The treatment Marshall received in London appears to have been the main reason for his looking for a job in his native Australia. He left to become the first Professor of Zoology at Monash University in Melbourne in 1960. However, he managed a parting shot at the internal member of the committee (who was elected FRS in 1958) who later approached him in a friendly manner: 'I told him to "Piss off you little bastard". He pissed off.’
Foxon, a Cambridge graduate who had previously worked in Glasgow University in the unenviable job of Assistant in Zoology (essentially the Professor’s dogsbody in a Scottish university) and at University College, Cardiff before, being appointed to Guy’s, continued his research on the heart and circulation in vertebrates.
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| Günther's Golden-backed Frog (Indosylvirana temporalis) Sri Lanka, 2013 How was its heart working? |
*Date of death is incorrect in the archives here
†The world seems to have adopted the Australian name for this South American species, introduced into the cane fields with a devastating impact on the wildlife. Until recently it was also and inaccurately called the Marine Toad (Bufo marinus).
Foxon GEH. 1952. The mode of action of the heart in the frog. New Biology 12, 113-126
The following can be referred to for some idea of the amount of work that has gone into determining how the frog heart and circulation work:
Gamperl AK, Milsom WK, Farrell AP, Wang T. 1999. Cardiorespiratory responses of the toad (Bufo marinus) to hypoxia at two different temperatures.
Graaf AR de. 1957. Investigations into the distribution of blood in the hear and aortic arches of Xenopus laevis (Daud.). Journal of Experimental Biology 34 143-172
Hedrick MS, Palioca WB, Hillman SS. 1999. Effects of temperature and physical activity of blood flow shunts and intracardiac mixing in the toad Bufo marinus. Physiological and Biochemical Zoology 72, 509-519
Hillman SS, Hedrick MS, Kohl ZF. 2014. Net cardiac shunts in anuran amphibians: physiology or physics? Journal of Experimental Biology 217, 2844-2847
Langille BL, Jones DR. 1977. Dynamics of blood flow through the hearts and arterial systems of anuran amphibians. Journal of Experimental Biology 68, 1-17
Pinder AW, Burggren WW. 1986. Ventilation and partitioning of oxygen uptake in the frog Rana pipiens: effects of hypoxia and activity. Journal of Experimental Biology 126, 453-468
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