Frederick William Pavy

In the 19th century London teaching hospital consultants were not, unlike their counterparts in Germany and France, scientific researchers. Frederick William Pavy (1829-1911) was unusual in being an indefatigable experimenter and, certainly in the early part of his career regarded himself as a physiologist. He was described in his obituaries as “the leading authority on diabetes” and “the last survivor of a distinguished line of physician-chemists who….during the earlier and middle years of the last century, did much to lay the foundations and advance the study of metabolic disorders.”

He spent every morning seeing patients and by 1894 claimed to have seen 2,642 with diabetes.[1] Afternoons were spent in the lab. He was a prolific writer and between his first paper in the Guy’s Hospital Reports in 1853 and his last in the Journal of Physiology in the year of his death published at least 60 papers and 6 books. Most of his papers were about diabetes which he called ‘one of the most inscrutable of diseases’. His fellow Guy’s Hospital physician, Sir William Gull, asked satirically ‘What sin has Pavy committed or his fathers before him, that he should be condemned to spend his whole life seeking for the cure of an incurable disease?’

His 1862 monograph On the Nature and Treatment of Diabetes is full of astute clinical observations. For example he described night cramps and white spots on the shoes as presenting symptoms. In an opening address at the meeting of the British Medical Association in Cardiff in 1885, Pavy drew attention to the neurological accompaniments of diabetes and gave the following description which would not be out of place in a modern textbook:

The usual account given by these patients of their condition is that they cannot feel properly in their legs, that their feet are numb, that their legs seem too heavy - as one patient expressed it, ‘as if he had 20lb weights on his legs and a feeling as if his boots were great deal too large for his feet’. Darting or ‘lightning’ pains are often complained of. Or there may be hyperaesthesia, so that a mere pinching of the skin gives rise to great pain; or it may be the patient is unable to bear the contact of the seam of the dress against the skin on account of the suffering it causes. Not infrequently there is deep - seated pain located, as the patient describes it, in the marrow of the bones which are tender on being grasped, and I have noticed that these pains are generally worse at night.

He pointed out that neuropathy in the leg placed the feet ‘in an exceptionally vulnerable position. A very trivial injury may suffice to lead to the establishment of serious mischief, involving often a more or less extensive loss of living parts and, it may be, even the loss of life.’ He had noticed unusual presentations such as a 67 year old who complained of ‘lightning pains on the right side of the waist’ and occasional cases in which the third nerve was affected with ‘dropped lid and external squint’.

Pavy’s interest in physiology began in 1852 when he spent several months with Claude Bernard (1813-1878), the founder of experimental medicine. In the late 1840s Bernard had discovered the glycogenic function of the liver. The crucial experiment was that when he took a slice of liver immediately after death and put it in boiling water, he obtained an opalescent liquid which gave no reaction for sugar; if he added saliva, the liquid cleared and now gave a very strong reaction for sugar. He called the raw material in the liver, glycogen and regarded it as analagous to starch in plants. His hypothesis, the glycogenic theory, was that sugar absorbed from the intestine was converted in the liver into glycogen and then constantly released into the blood during fasting.

Pavy disagreed with Bernard’s interpretation and between 1853 and 1911 published over 30 papers dealing directly or indirectly with the glycogenic theory.[2] After Pavy’s death, the future Nobel laureate Frederick Gowland Hopkins, who knew him well from his time at Guy’s between 1888 and 1898, wrote rather dismissively that, ‘Almost any one of the series might well have received the title of the first.’ The content and language of these publications is nearly identical; he always begins by paying homage to Bernard with phrases such as ‘I do not for one moment impeach the accuracy of the results mentioned as obtained by this celebrated physiologist’ and then claims that what he objects to is their interpretation. Pavy thought Bernard had been misled into inferring a physiological condition from post-mortem findings. Pavy agreed that ‘After death and under certain unnatural states during life, there is a large escape of sugar from the liver’ but in life, he insisted, there was only a trace of sugar in the blood between the liver and lungs. Far from being a sugar-forming organ, the liver, for Pavy, was a barrier preventing sugar reaching the general circulation. To him liver glycogen was an intermediate stage between sugar and fat and, since both were constituents of liver cells, there was some logic to this although he never produced any experimental evidence. Another point on which Pavy disagreed with Bernard was whether there was a renal threshold for glucose. Bernard had suggested that sugar did not appear in the urine until the level in the blood exceeded 200 mg/dl (11.1 mmol/l), whereas Pavy maintained that sugar ‘passed through the system in accordance with the laws of physics’, so that if any was present in the blood it would be excreted in the urine. As late as 1908 he described the renal threshold as ‘a pure fiction invented to escape the difficulty arising from not finding sugar in the urine as an outcome of the imaginary flow of sugar into the circulation from the food and the liver.’ Scientifically, Pavy was misled by two assumptions. The first was that the kidney was a simple filter. The second was the natural theology argument that nature would behave in a common-sense way and that changing sugar into glycogen and back again was ‘improbable’ or ‘not what we should expect from the notion we possess of the manner in which the operations of nature are conducted.’

In 1855 an act of Parliament decreed that all districts in London should appoint a medical officer of health. Pavy became the first incumbent in the pairsh of St Luke, Middlesex, a post he held for 30 years. He was instrumental in founding the Society of Medical Officers of Health.[3]

As he aged Pavy’s views became more polarised and inflexible. Having begun by regarding himself as a physiologist, he had, by the end of his life, decided that physiologists were dilettantes whose work had little relevance to the real world and in particular to the problem of diabetes.

References

  1. ^ Tattersall RB. Frederick Pavy (I829-1911). The last of the Physician Chemists. J Royal Coll Phys 1996;30:238-245

  2. ^ Tattersall R. Frederick Pavy (1829–1911) and his opposition to the glycogenic theory of Claude Bernard. Annals of Science 1997;54:361–74.

  3. ^ Chave SPW. Frederick William Pavy (1829-1911). Br Med J 1957;2:300-301.

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