Frog Hearts and University Politics in 1950s London

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.

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.

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

The Golgi War: 2. A possible casualty

A.J. ‘Jock’ Marshall (1911-1967), whose irreverence was remembered by his contemporaries with reverence, was J.R. Baker’s postgraduate student at Oxford. But they had worked together before that. In 1933, Baker recruited him to work on his expedition to Esperitu Santo in the New Hebrides (now Vanuatu) alongside and then to replace Tom Harrisson. After many adventures and jobs and countries, including New Guinea, London and Oxford, and getting a degree from Sydney—and serving in New Guinea in the Second World War (the title of his biography, One Armed Warrior, denoting his service in 'Jockforce' and the fact that he had shot his own arm off in an accident with a gun as a boy) in September 1946 he returned to Oxford aged 35 as a postgraduate student.

After his Oxford D.Phil (the Ph.D. abbreviation possibly unique to that institution), Marshall was appointed Reader and Head of Department at St. Bartholomew’s Hospital Medical School (Barts). He was around Baker when the latter was attacking the existence of the Golgi Apparatus and was aware of the cytological methods that Baker was promoting.

Marshall wrote a review for Science Progress entitled, The structure of the so-called Golgi body. It was published in 1952 and took the side of Baker in the controversy—with knobs on. Marshall began by describing the work of Parat, a Frenchman who threw doubt on the existence of the Golgi. He wrote:

There was a swift and vigorous—some have said violent—reaction to Parat’s conclusions (see, for example, Gatenby, 1931) and although others observed Parat’s bodies and failed to substantiate the net of Golgi, the new concept seems to have been more or less swamped by the positive views of the traditionalists.

After dealing with Hirsch’s non-support for the Golgi in Germany he turned to Baker:

A determined attempt to resolve the problem has now begun by Baker (1944) of Oxford…He failed to find any evidence that the classical net of Golgi existed as a living entity……The next and perhaps most crushing blow to the classical concept of Golgi, Cajal, Aoyama and Gatenby was dealt by Thomas (1947-51). A Beit Memorial Fellow who came to Baker’s laboratory from New Zealand, Thomas used his own modifications of Baker’s and others’ techniques, as well as phase-contrast microscopy, in the investigation of living and fixed nerve-cells of common animals. He too failed to find a Golgi net in the living cell and declared flatly that, in the cells studied, the net was “shown to be an artifact”.

In his conclusions, Marshall divided the world into ‘traditionalists’ and ‘modernists’ and it is not surprising that those he dubbed traditionalist were infuriated:

The modernists, though they are too polite even to breathe it, generally seem to feel that the traditional so-called Golgi techniques merely show something funny about a particular part of the animal cell. By an arbitrary method a great man, Golgi, accidentally showed a net; and his followers have messed about until they have found even more certain methods of showing nets. The modernists imply that this is good wholesome fun, but not science. They believe that the Golgi apparatus, if it should be called that at all, is a system of lipoidal spheroids which are demonstrably concerned with cell-secretion.

However, he then started to backtrack:

The present author does not take sides in the controversy…

But clearly the whole tone of the review was taking sides and the reader by now will expect Gatenby to have responded in some way. He was, after all, told that what he was doing, as a ‘traditionalist’, was ‘not science’.

Marshall’s biography (compiled by his widow from his own notes and records) reads:

…it [‘professional knifing’] involved views he had put forward in support of John Baker's work on the Golgi body. Owen Thomas who was also working on it had just come back from seeing Professor Gatenby in Dublin. [Marshall wrote:] Thomas was “as scared as hell that Gatenby will discredit both John and myself. He is going to sue John too - so he says.” This referred to an article Jock had written for Science Progress on this rather esoteric cytological subject - the Golgi body. His article supported the research John Baker and Owen Thomas were doing in Oxford which appeared to negate some of the findings of Professor Gatenby. Thomas reported Gatenby was furious - “He will see to it that I [Jock] never get a better job than I've got [now]. Actually I quite like him although he has added me to his list - a long list - of hates.”

However, Marshall could not count on Baker either in support of any advancement. At about the time the article in Science Progress appeared, he applied for, without expecting to get nor did get, the chair of zoology at Reading. Later and by accident, he saw the reference Baker had written, and was shocked to learn that although Baker had praised his research he brought up, quite remarkably to those of reading it 65 years later, Marshall’s divorce from his first wife and ‘an assessment of Jock's alleged shortcomings as a classical zoologist’.

Marshall’s friends and wife put it down to jealousy. Baker was not a professor, and at this time and in the Oxford grading system that differed from that in other universities, he was a university demonstrator—he was promoted to a readership in 1955, three years before his election to the Royal Society.

Application—and rejection—by Marshall for another chair (this time in Canberra to set up a new department) in 1958 brought the suspicion of Gatenby’s revenge:

…while camped near Kalgoorlie, he received a telegram telling him that the Committee had chosen Professor [J. Desmond] Smyth from Dublin University for the Canberra Chair. Smyth, a parasitologist, came from Professor Gatenby's Department. It transpired that Gatenby, the good hater, had been in Australia at this time. It was tempting to conjecture whether his threat of six years before to prevent Jock from ever getting 'a better job' than the one he then occupied had come home to roost; especially when reading part of a letter he sent to another zoologist in England (the first page is missing): “Marshall threw his weight about so much, they were determined not to have him.”

There is no doubt that Jock Marshall upset the easily upset Australian university establishment by his behaviour. I am not surprised. Of all the university administrative systems I have dealt with all over the world over the years as an external assessor for appointments to chairs and for internal promotions, Australia occupies bottom position. Rigid, po-faced, stuffed shirts are phrases that came to mind, quite the antithesis of what the world sees Australia as like and quite the antithesis of Jock Marshall.

After the quite disgraceful failure of the University of London (described in excruciating detail in his biography) to elevate his readership at Barts to a chair, he did return to Australia—to the then new Monash University in Melbourne in 1960.

As to his support for Baker’s ‘modernist’ views on the artifactual nature Golgi Apparatus, there is a twist. In 1954 and only shortly after the first electron micrographs of the Golgi were published, Dennis Lacy in Jock Marshall’s own department at Barts found the Golgi apparatus in the exocrine pancreas and other cells and followed that up by finding it for the first time by electron microscopy in nerve cells—where Golgi had first described his eponymous organelle.

Marshall Jane. 1998. Jock Marshall: One Armed Warrior, Australian Science Archives Project, Melbourne.

Marshall AJ. 1952. The structure of the so-called Golgi body. Science Progress 40, 71-77.

Lacy D. 1954. Recent studies on the Golgi apparatus of the exocrine and endocrine cells of the mammalian pancreas and the cytoplasmic inclusions of other cells. Journal of the Royal Microscopical Society 73, 226–240.

Lacy D. 1957. The Golgi apparatus in neurons and epithelial cells of the common limpet Patella vulgata. Journal of Biophysical and Biochemical Cytology 3, 779–796.

Lacy D, Challice CE. 1957. The structure of the Golgi apparatus in vertebrate cells examined by light and electron microscopy. Symposia of the Society for Experimental Biology 10, 62–89.

Lacy D, Rogers GE. 1955. Recent observations by light and electron microscopy on the cytoplasmic inclusions of the neurons of Patella vulgata. Journal of the Royal Microscopical Society 74, 172–175.

A Jock Marshall story I had forgotten

Stories of the exploits of ‘Jock’ Marshall (1911-1967) when he was Reader in Zoology at Barts in London and later in Monash University abounded in zoological academia in the 1960s. Even before Brian Lofts (1929-2015) arrived in Hong Kong in 1967 from Marshall’s old department at St Bartholomew’s Medical School in London, there were stories of his visit in the late 1950s. But one which Brian recounted I had forgotten until reminded of it in Jock Marshall - One Armed Warrior by Jane Marshall. This biography appears only to be available online here.

One year there was a very pompous ceremony at the University of London - the Queen Mother, as Chancellor, was holding a reception and the red carpet was stretched out for the hierarchical heads to follow Her Majesty into the building while we lesser members waited to follow on. Jock spotted Sir Gavin de Beer emerging from his limousine and setting sail up the red plush. As he came abreast of us he noticed Jock - 'Ah Marshall' he intoned - 'Ah Sir Gavin' replied Jock 'Sober I see’.

Sir Gavin de Beer (1899-1972) was Director of the Natural History Museum from 1950 until 1960. The Queen Mother was Chancellor from 1955 until 1980. Marshall left London for Australia at the end of 1959.