The Discovery of Hyaluronan by Karl Meyer

The Polysaccharide of the Vitreous Humor (Meyer, K., and Palmer, J. W. (1934) J. Biol. Chem. 107, 629–634) Karl Meyer (1899–1990) was born in the village of Karpen, Germany, near Cologne. In 1917, he was drafted into the German army and served in the last year of World War I. After the war, he entered medical school at the University of Cologne and received the M.D. degree in 1924. He then went to Berlin for a year of study in medical chemistry and met several promising young biochemists including Fritz Lippman, Hans Krebs, and Ernst Chain. To gain more training in chemistry, he enrolled as a graduate student with Otto Meyerhof. For his Ph.D. thesis work, he investigated lactic acid formation in yeast and muscle demonstrating the requirement for a “co-enzyme” later identified as ADP. His research career was launched. After three years as a Rockefeller Fellow in Zurich studying heme-catalyzed oxidation of unsaturated compounds with Professor Kuhn, he was offered a position as Assistant Professor at the University of California at Berkeley with Herbert Evans. In 1932, while at Berkeley, he attended a conference in Europe. During the conference, he received notice that Evans had terminated his position with the suggestion that he stay in Germany. He decided, no doubt in part because of the rising anti-Semitism in Europe and the increasing probability of war, to go back to the United States. His return was facilitated by Hans T. Clarke at Columbia University who provided interim fellowship support until 1933 when he received a position as Assistant Professor in the Department of Ophthalmology at the College of Physicians and Surgeons. In part because of the mission of his department, Meyer began to study the lysozyme present in tears and undertook to identify a physiological substrate for the enzyme. Examination of the viscous vitreous humor of the eye as a plausible source of substrate quickly led to the discovery of hyaluronan, which is reported in this Journal of Biological Chemistry (JBC) Classic. Meyer and his assistant John Palmer isolated a novel, high molecular weight polysaccharide and reported that it was composed of “a uronic acid, an amino sugar, and possibly a pentose.” (The last is incorrect.) They proposed “for convenience, the name hyaluronic acid, from hyaloid (vitreous) + uronic acid.” Nearly 25 years of work were required to establish the structure of the repeating disaccharide that is the basic unit of the hyaluranan polymer, namely glucuronate-β-1,3-N-acetylglucosamine-β1,4-. Hyaluronan is one member of a family of glycosaminoglycans that includes chondroitin/dermatan sulfate, keratan sulfate, and heparin/heparan sulfate, each with a characteristic disaccharide-repeat structure of an amino sugar, either glucosamine or galactosamine, plus a negatively charged sugar, a carboxylate and/or a sulfate. The polymers are found as cell surface molecules and in the extracellular matrix. Glycosaminoglycans, with the exception of hyaluronan, are covalently bound to proteins to form proteoglycans. These ubiquitous and structurally diverse macromolecules are found as cell surface molecules and in the extracellular matrix. The multiplicity of their functions that is now recognized was not always appreciated. In a symposium at the 1958 annual meeting of the American Society of Biological Chemists entitled“ Acid Mucopolysaccharides of Animal Origin,” which was chaired by Meyer, he states in an opening remark, “It is my opinion that the mucopolysaccharides will never be a highly popular field in biochemistry, but they will probably not be relegated again to the insignificance and disregard in which they were held not so long ago.” Meyer's scientific contributions were not limited to the discovery of hyaluronan. He is considered the father of glycosaminoglycan chemistry and received many honors including election to the National Academy of Sciences in 1967. On the occasion of his induction he commented as follows: “Looking back on my scientific career, I have often wondered whether it was worthwhile to stick so tenaciously to a technically difficult and conceptually apparently unexciting field, while my colleagues and friends shifted over to more fashionable and rewarding areas. The reasons for my persistence are manifold, among them a distaste for jumping in on ground broken by others. Besides, I felt committed to problems such as the biological functions of the mucopolysaccharides of connective tissues to their role in differentiation, in cell membranes and in inherited diseases.” His persistence was biochemistry's gain. 1A recent overview of glycosaminoglycan biochemistry and additional information about Karl Meyer are included in the JBC Hyaluronan Minireview Series edited by John McDonald and Vincent Hascall (1McDonald J. Hascall V.C. J. Biol. Chem. 2002; 277: 4575-4579Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar). 1A recent overview of glycosaminoglycan biochemistry and additional information about Karl Meyer are included in the JBC Hyaluronan Minireview Series edited by John McDonald and Vincent Hascall (1McDonald J. Hascall V.C. J. Biol. Chem. 2002; 277: 4575-4579Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar).