In 1854, after two unsuccesful bids in 1850 and 1852, Bernard was finally elected to one of the sixty-six seats on the Académie des Sciences - and was simultaneously appointed chairman of its awards panel. Then a chair in General Physiology was created for him at the Sorbonne, where he was provided neither with a préparateur to assist him, nor a laboratory. His duties consisted solely of undergraduate student teaching within a fixed curriculum: "....a synthetic exposition of the entire range of scientific facts..." as he once described it.
He did not enjoy that type of orderly teaching: and as the examiners for his agrégation had anticipated many years earlier, his manner of presentation to an auditorium full of students was unimpressive. It was very different when he lectured at the Collège: there he enjoyed presenting his own discoveries and their significance, and accordingly he captivated the members of his audience. They came from every walk of life, and increasingly from every corner of the earth.
In 1855, a sad but important event took place which would shape his future life. His patron Magendie died, and Bernard was appointed to his Chair of Medicine at the Collège. Magendie had been an empirical and opportunistic scientist: "Everyone is fond of comparing himself to someone great and grandiose...." he once said, " ... I am more humble: I compare myself to a mere chiffonier (tr: ragpicker): with my spiked stick in my hand and my basket on my back, I traverse the field of science and I gather what I find." Bernard's approach was certainly different. He applauded, indeed insisted on the importance of observation and imagination; even intuition and instinct. Yet an idea or observation had to be followed by a hypothesis, and then a systematic series of experiments to either support or disprove it - so that he could find 'truth'. That was his experimental method.
Already in 1854, Bernard had began summarizing his work with a view to major publications. August Tripier - and later his other préparateurs at the Collège such as Mathias Duval and Albert Dastre - had the job of recording his lectures. Together with their master, they would then amalgamate them into Mémoires and Leçons, in which form they would be published. The first of these, Bernard's Mémoire sur le Pancréas was published in 1856TMB22 and promptly subjected to public attack by Bérard, the Sorbonne's professor of physiology and by Achille Longet. The latter had been a long-time adversary of both Bernard and Magendie, and their work on the phenomenon of recurrent sensitivity of spinal nerves17,33,TMB7.
During 1855, Bernard was overjoyed to hear from his German colleague, Carl Lehmann from Leipzig that he had confirmed his findings on glucose levels in abdominal blood vessels: so supporting the glycogenic theory.99,102 However, a serious conflict occurred when Louis Figuier, a chemist in the pharmacy faculty in Paris claimed to show that the portal vein contained glucose even in fasting animals; even more than in the hepatic veins. This contradicted Bernard's glycogenic theory, which had already been challenged by the chemist Mialhe, and again by Longet.
Figuier's series of challenges was not 'supported' by the Academy of Sciences, following an analysis of his divergent views by the Lyon physiologist, Jean-Louis Brachet and a collective report which it commissioned from Rayer, Pelouze and DumasTMB20p504. Figuier was accordingly obliged to resign his professorial post and later became an eminent popularizer of science, with many successful publications to his name. He was later shown to be partly correct in his dispute with Bernard: his glucose analysis, also a copper reduction method was more sensitive than Bernard's, and was capable of detecting the small amounts of glucose which are present in all blood vessels - even during fasting.
Bernard continued exploring his glycogenic concept97,98,100,101 by experimenting with liver extracts, still searching for the identity of the elusive glycogène. One day in 1857, he observed that one of the liver extracts had rather a milky appearance: a type of opalescence seen only in starch-containing solutions. Yet starch was understood to be present only in plants. He also found that although these extracts did not contain glucose, when he dried an alcohol precipitate and then moistened it again, it gave a positive test for glucose. He was therefore quite confident that these opalescent extractsTMB20,vol1p65 contained the parent compound of glucose - presumably glycogéne115.. Now that he knew that he was looking for a starch-like substance, he and Pelouze were able to rapidly confirm analytically the presence of 'animal starch' - indeed, with a structure almost identical to its plant equivalent.
Unknown to Bernard, the German scientist Victor Hensen from the University of Kiel had been following his earlier discoveries closely, and had identified the starch-like nature of glycogen just ahead of Bernard: the glycogenic theory was therefore well confirmed116,118. Bernard went one step further. Having found that glycogen content was reduced - even absent - in the livers of patients dying from diabetes, he proposed (to be validated only a century later) that excessive glucose production from glycogen was likely to be the major determinant of raised glucose levels in diabetesTMB20,vol1p101. The starch-like structure of glycogen also made him aware of the remarkable similarities of plant and animal biology, leading to his later comparisons of the two kingdoms210,219,TMB49.
There were further challenges to Bernard's discoveries, including those of F. William Pavy, a young English physiologist and physician who had visited Bernard in 1853. When Pavy finally returned to England, he denounced Bernard's conclusions in the journal Lancet, and later at the Royal Society of London. He claimed that any discovery based on a post-mortem liver was irrelevant to what was happening during life. He also presented his own experimental results on glucose concentrations in vessels around the liver - findings that (like Figuier) contradicted those of Bernard. Pavy opposed the glycogenic theory for more than twenty years - even beyond Bernard's death. He had found a substance that he named Bernardin, which had some of the characteristics of glycogen. Yet he refused to concede that either Bernardinp418 (or indeed glycogen) represented the source of glucose - despite the eventual confirmation of the theory by many other workers and Bernard's definitive articles244,247 published in the year before he died.
Perhaps it was through seeing patients in hospital wards being treated for, and even dying from carbon monoxide inhalation that Bernard's interest in poisons was rekindled in the 1850's: certainly such poisoning was common enough in that period, from blocked chimney flues and poor ventilation. He carried out innumerable experiments which showed that carbon monoxide prevented red blood cells from taking up, and hence delivering oxygen to the tissues111. Affected patients were dying from yet another form of asphyxia.
For Bernard, carbon monoxide had declared itself as a tool for dissecting the intricacies of normal physiology. For example, by using carbon monoxide to displace oxygen from red blood cells in the test tube, he developed a method for measuring the oxygen content of blood127, in turn enabling him to better understand normal blood gas transfer within the body. Together with his previous work on curare and other poisons he published another series of lectures: the Leçons sur les Effets de Substances Toxiques et MédicamenteusesTMB24. Over the next twenty years, he would return many times to the subject of carbon monoxide188,189,193.
Already in his first years of research, Bernard had assisted Rayer and Magendie in passing thermometers into the heart of horses via their neck vessels. In 1856, he used this procedure to dismiss Lavoisier's theory that the body's heat was generated exclusively in the lungs. Using small diameter thermometers inserted into different vessels, he showed that contrary to Lavoisier's teaching, blood leaving the lungs was cooler than that arriving there, while blood leaving the liver110 and limbsTMB44p32 was considerably warmer. Thus, body heat was generated in tissues throughout the body. This discovery led to many further experiments on the subject of heat generation (la chaleur animale) and the central role of the nervous system in its modulation195,196,TMB44p123,194,222,252,314,360.
In 1858 Bernard returned to yet another incomplete project. He was at last able to correct his earlier error, and show that the chorda tympani nerve did indeed stimulate flow of saliva. Furthermore, he observed an increased blood flow through the salivary glands in response to stimulation of that nerve119. By contrast, when he stimulated the sympathetic nerve (some fibres of which terminate in the salivary glands), it resulted in a reduced blood flow and a corresponding reduction in salivary secretion122,123,146,198. He had thus identified an important principle: that organ function was modulated by the opposing effects of the somatic and autonomic nervous systems131,148, and that these actions were mediated by corresponding alterations of nutrient blood flow. In this way, he had clearly defined one of the most important actions of the vasomotor system124.
Finally, Bernard's health began to suffer. It was a strange illness: recurrent abdominal pain and diarrhoea, and sometimes vomiting. For a while he struggled on, receiving little sympathy or support from his wife. Both Rayer and Davaine were puzzled: they considered that some form of colitis - even a chronic form of cholera - might have been responsible. Bernard was also suffering from rheumatic pains and recurrent migraine attacks and his friends felt that the damp, unhygienic conditions in his basement laboratory might also have contributed to his illness. One wonders if stress - from overwork, professional challenges and his traumatic domestic situation - might also have been part of the problem.
Retreat and recovery.........