Claude Bernard's route to the isolation of glycogen: the journey that changed scientific views on the physiological role of the liver and animal metabolism.

Claude Bernard (1813-1878) studied medicine in Paris from 1834 to 1843. During his studies, he attended the physiology lectures at Collège de France provided by François Magendie (1783-1855). Magendie was the world's leading experimental physiologist, and Bernard became his assistant in 1841. Bernard's training in vivisection, anatomy and physiology was the foundation for his success as an experimental physiologist. Bernard's first years of independent research were not successful, but his dexterity in vivisection allowed him to collect pancreatic juice from living dogs in 1848. With fresh pancreatic juice available, he demonstrated the lipolytic action of the fluid. Bernard's first successful finding had been made. The young chemist Barreswil had established a method for the measurement of glucose in Paris in1845 and became Bernard's collaborator. In 1848, they reported that the liver contained sugar, whereas other tissues did not. Bernard continued these studies and established the glucogenic function of the liver the same year. This finding transformed the existing view of animal metabolism. Serendipity helped in his next big achievement, enabling him to isolate glycogen. Bernard made always double determinations of sugar but during an experiment in 1855, he was unable to make both the determinations of sugar in the liver on the same day. Bernard had perfused a liver with cold water to remove all glucose but found much glucose in the liver the next day. Bernard acknowledged the surprising result and systematically investigated the formation of glucose in water-perfused livers, finding that the "glucose forming" material was insoluble in alcohol and sensitive to heat. Finally, in 1857, Bernard described a method for isolating glycogen and characterized it as "animal starch", which could produce sugar. The method Bernard used to isolate glycogen is still used, with some minor modifications. Bernard's legendary status is unquestionable. He characterised glycogen and introduced the concept of the constancy of the internal environment (la fixité du milieu intérieur), which today is known as homeostasis. His fame also survives through the book "An introduction to the study of experimental medicine" published in 1865. The book is still worth reading and should be read in all courses on the theory of science. In this review we discuss the findings that directed Bernard toward the isolation of glycogen.