Letter to the Glyco-Forum

Karl Meyer, lysozyme, and penicillin

Nathan Sharon

Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot 71600, Israel

I enjoyed greatly the letter to the editor of Vincent Hascall (2004)Go about Karl Meyer, especially because I was privileged to know Meyer and become close to him from 1956, when he came to the International Symposium on Macromolecular Chemistry held at the Weizmann Institute to lecture on hyaluronic acid. The letter is a fine tribute to Meyer and his seminal contributions to our field. Although Meyer is best known for his glycosaminoglycan research, he also did pioneering work in other areas. I wish to describe briefly his studies of lysozyme and penicillin during the late 1930 s and early 1940 s. A couple of decades later, I did research on these substances myself and discussed them several times with Meyer at our meetings in New York and especially during his month-long stay in 1965 as my guest in Rehovot.

Meyer initiated his studies of lysozyme in 1933, soon after joining the Department of Biochemistry at Columbia's College of Physicians and Surgeons and becoming Head of the Biochemistry Department of the Eye Institute of the Columbia University Presbyterian Hospital (Hobby, 1985Go). As a chemist in the latter institute, he was assigned to investigate diseases of the eye. At a loss for readily obtainable human tissues or fluids for analysis, he accepted the suggestion of Richard Thompson, a microbiologist of the same institute, to study lysozyme, which Alexander Fleming had discovered lysozyme in 1922 in tears and shown to be present there at a high concentration. With Thompson, J. W. Palmer, and Deborah Khorazo, Meyer (1936a)Go purified lysozyme. He then showed for the first time that it is an enzyme that initiates bacterial lysis by splitting the glycosidic bonds in a polysaccharide component of the cell wall (Meyer et al., 1936bGo); this polysaccharide is now known as peptidoglycan. Considering the highly viscous vitreous humor as a possible lysozyme substrate, he isolated from the humor a polysaccharide that he named hyaluronic acid, which became a major interest of his until the end of his life. Still, he had not left lysozyme completely (Meyer and Hahnel, 1946Go). Much later he told me that he was the first to propose that lysozyme is ß-4-N-acetylhexosaminidase.

Through his involvement with lysozyme and his association with Henry Dawson, a clinician interested in infectious diseases, and Gladys Hobby, a fellow microbiologist, Meyer became aware of penicillin, the other major discovery by Fleming. At the time, penicillin did not attract much attention, little was known about its antibacterial spectrum, there were no methods for its purification, and its enormous potential as an antibacterial drug was hardly appreciated. Work on the antibiotic began in his laboratory one year after the start of World War II, in collaboration with Dawson, Hobby, and a few others. It was the first research effort on penicillin in the United States, and for a time the only one. During 1941 and 1942 Meyer and co-workers reported that penicillin is effective only on Gram-positive and multiplying organisms and does not act on Gram-negative ones (Dawson et al., 1941Go; Hobby et al., 1942Go). Their major achievement was the development of a procedure for the extraction of the antibiotic from the Penicillium notatum culture medium, which afforded preparations that were six times more active than those obtained at that time by Howard Florey and Ernst Chain in Oxford (Meyer et al., 1942Go). By fall 1941, the Columbia group obtained sufficient quantities of penicillin, which although not completely pure, could be used successfully for clinical trials, the first application of penicillin to humans in the United States.

Large-scale production of penicillin was soon thereafter undertaken by Pfizer, based in part on the purification procedure of the Meyer group. Meyer stopped working on penicillin sometime in 1943.

Readers interested in additional information on the subject are referred to the excellent book of Hobby (1985)Go.

References

Dawson, M.H., Hobby, G.L., Meyer, K. and Chaffee, E. (1941) Penicillin as a chemotherapeutic agent (abstract). J. Clin. Invest., 20, 434.

Hascall, V.C. (2004) The Karl Meyer Award for glycoconjugate research. Glycobiology, 14, 3G–6G.[CrossRef][ISI]

Hobby, G.L. (1985) Penicillin: meeting the challenge. New Haven, CT: Yale University Press, 1985.

Hobby, G.L., Meyer, K. and Chaffee, E. (1942) Observations on the mechanism of action of penicillin. Proc. Soc. Expt. Biol. Med., 59, 281–285.

Meyer, K. and Hahnel, E. (1946) Estimation of lysozyme by a viscometric method. J. Biol. Chem., 163, 723–732.[Free Full Text]

Meyer, K., Thompson, R., Palmer, J.W. and Khorazo, D. (1936a) The purification and properties of lysozyme. J. Biol. Chem., 113, 303–309.

Meyer, K., Thompson, R., Palmer, J.W. and Khorazo, D. (1936b) On the mechanism of lysozyme action. J. Biol. Chem., 113, 479–486.

Meyer, K., Chaffee, E., Hobby, G.L., Dawson, M.H., Schwenk, E. and Fleischer, G. (1942) On penicillin. Science, 96, 20–21.





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