Fred Shafizadeh*

1924-1983

FRED SHAFIZADEH* 1924-1983

Fred Shafizadeh was born on January 26, 1924, and named Fraidoun, in Teheran, Persia, and died as Fred, on October 1, 1983, of a heart attack in Missoula, Montana. He is survived by his wife, Doreen; his daughter, Alexandra S. Startin; and his grandson, Taylor Startin. His premature death, at age 59, removed from the active mainstream of carbohydrate chemistry a major contributor. Fred was a unique individual, best described as a first-rank innovator, an enthusiastic teacher and scientist, and a strong believer in individual rights and responsibilities. A jovial man, he was 5ft 10” tall, somewhat portly, weighing 155 lbs, and had brown eyes and originally brown hair. Dr. Shafizadeh obtained his early education in Persia, receiving a B.S. degree in Chemical Engineering from the Technical College in Teheran in 1946, and then a Ph.D. in Organic Chemistry from Birmingham University, England, in 1950. In Birmingham, he adopted a long and unusual course, which included 2 years of undergraduate, 2 years of graduate, and 2 years of post-doctoral studies. During that period he established himself as a first-class carbohydrate chemist, with several publications on deoxy sugars, and considerable experience on DNA and the biochemistry of cancer to his credit. To broaden the scope of his interests, he spent another year as a postdoctoral fellow in the Physics Department of Pennsylvania State University, working on the X-ray analysis of biological compounds. Equipped with an exceptionally broad and multidisciplinary education and experience, he proceeded to The Ohio State University, Columbus, Ohio, to work with Professor M. L. Wolfrom. His initial job was to investigate the ignition of cellulose nitrate, a project left over from World War 11. In Fred’s hands, this project was turned into an isotopic investigation of the biosynthesis and degradation of cellulose. At this time, there was very little known about the preparation of specifically labeled sugars, let alone the biosynthesis of *The kind assistance of Drs. Donald F. Root, Keith Osterheld, Allan Bradbury, and Murray Laver, and Professor A. B. Foster is greatly appreciated.

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Copyright @ 1986 by Academic F’ress, Inc. All rights of reproduction in any form reserved.

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specifically labeled cellulose, or suitable methods for determining the isotopic distribution within the labeled polysaccharides. Furthermore, the modern methods for the isolation and radiochemical analysis of numerous degradation products of cellulose were not known. The preparation of labeled cellulose, involved, among other things, experiments with cultures of Acetobacter xylinurn and the growing and treatment of cotton plants north of the Mason-Dixon line, both of which exceeded the traditional expertise of a carbohydrate chemist. Despite all these problems, Fred’s achievements went far beyond his original expectations, and resulted in several publications on the incorporation of D-glucose from the metabolic pool into cellulose, determination of the distribution of the I4C label in labeled cellulose, the mechanism of the thermal decomposition of cellulose nitrate, and even the biosynthesis and fragmentation of cotton-seed oil. These are now considered to be classical achievements, but, at that time, they had to be presented to and argued with Professor Wolfrom in order to gain his acceptance. This in itself was not an easy task, especially when the more precise, isotopic data that Fred had obtained contradicted some of the previously published results. Professor Wolfrom’s exacting manners and standards provided a challenge, rather than a hurdle, for Fred, whose thorough handling of this project resulted in the incidental discovery of L-iduronic acid, a by-product of the synthesis of D - ~ ~ u c o s ~ -which ~ - ~ ~since C , has been found to be a component of heparin and chondroitin sulfate. Also, incidental to the problems of isolating, as phenylhydrazones, the fragmentation products of 14 C-labeled cellulose nitrate, it was found that reduction of the hydrazone provides a practical method for the synthesis of amino sugars. Wolfrom, being an astute and exacting research director, did not lose any time in getting Fred to develop the leads that he had found for the synthesis of biologically significant amino sugars, and provided him with some graduate-student help in order to proceed in this direction. In this way, some of the rare and hitherto unobtainable amino pentoses and amino hexoses were synthesized. This original procedure has since been modified, and used for the synthesis of a variety of amino sugars. Fred was not content with the idea of synthesizing new compounds, and, by combining the knowledge on DNA and modified sugars that he had acquired in Birmingham, he developed a major program at Ohio State for the synthesis of modified nucleosides for testing in cancer chemotherapy. After organizing the aforementioned program, which employed a number of graduate students and postdoctoral fellows, Fred decided to accept a job with the Weyerhaeuser Company in Seattle, Washington. At Weyerhaeuser, Fred was assigned to one of the most difficult problems of the wood-products industry, namely, development of a practical and economic

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method for the dimensional stabilization of wood. Here, again, Fred adopted a basic approach to the problem. The processes that he developed in a short while were tested and patented. The results sufficiently impressed the management of that resource-oriented company that they created a new department for Pioneering Research, and promoted Fred to manage it. A new laboratory, close to the University of Washington in Seattle, was leased and remodeled, and Fred’s staff and responsibility were expanded to embrace a catalog of the hitherto-unsolved problems of the wood-products industry, including waste utilization, lignin utilization, new and better flame-proofing methods, new modifications of cellulose, and new methods of combining plastics with wood products. Several patents were issued to Weyerhaeuser as a result of Fred’s program, including the dimensional stabilization of wood (U.S. Pat. 3,284,231), levoglucosan (US. Pats. 3,305,542 and 3,414,560), and levulinic acid from hexoses of wood. Noteworthy among the areas of research that he directed were fire-retardant treatments of wood, wood preservation, sustained-release herbicide and nutrient formulations, and the polymer coating of wood products (U.S. Pat. 3,616,028). Some of the data that he had obtained on the combustion and pyrolysis of cellulose were presented at national meetings, and he was a participant in the United Nations F A 0 meeting on wood saccharification, October, 1960, in Tokyo, Japan. He became a naturalized American citizen in June, 1970. In 1966, the University of Montana chose Fred Shafizadeh to become Professor of Chemistry and Forestry, and the director of its newly created Wood Chemistry Laboratory. When Fred moved to Montana, there were minimal amounts of space, money, and equipment available for his program. Fred had two choices-he could be content with the facilities, and live the comfortable life of a professor in a small State University, or he could try to build a strong program by attracting external support. Fred decided on the latter course. The present national and international stature of that Laboratory is truly a memorial to the talents, the energy, and the dedication that he devoted to developing it. Under his leadership, important contributions were made to our understanding of a variety of topics, including the chemistry of plant constituents, the chemical taxonomy of plants, the mechanism of combustion of wood and cellulosic materials, the control of the combustion process in wood and paper, the chemistry of biomass gasification, and the chemical utilization of wood and cellulosic wastes. His unusual ability to design fundamental studies of problems of practical importance contributed greatly to the significance of his contributions. Fred’s major contributions were in the area of combustion and pyrolysis of cellulosic materials. At Montana, he developed a research program for unravelling the complex, consecutive and concurrent reactions involved in

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the pyrolysis, combustion, and flame-proofing of cellulosic materials. The interaction of natural fuels and energy, resulting in the formation of volatile, combustible materials and the spreading of flaming combustion, was investigated through analysis of the thermal properties and the pyrolytic reactions of the various components, including cellulose and hemicelluloses. The thermal degradation of these compounds was, in turn, investigated by using a variety of model compounds, in order to ascertain the mechanism of cleavage of the glycosidic bond and the decomposition of the sugar units at different temperatures. The methods of thermal analysis developed in this program threw a new light on an area of carbohydrate chemistry that previously was completely in the dark. The results, published in various journals, are of such a basic and broad nature that their significance transcends the chemistry of cellulosic fires, and covers many fundamental aspects of carbohydrate chemistry, such as the physical transitions and molecular motions, anomerization, polymerization, transglycosylation, dehydration, fission, and carbonization of the carbohydrate compounds. The thermal-analysis methods were also used to determine, not only the heat of combustion, but also the rate of heat release and the seasonal variation of combustibility, matters of practical significance for the protection and conservation of forest resources. In the area of waste utilization, Fred’s program on the heat content, gasification, and carbonization of forest fuel is now recognized as a major step in our understanding of forest fires. The acid-catalyzed pyrolysis of cellulosic waste to afford 1,6-anhydro-3,4-dideoxy-p-~-glycero-hex-3enopyranos-2-ulose (“levoglucosenone”) pointed the way to another method of chemical conversion of cellulosic wastes similar to “cat-cracking” in the petrochemical industry. On the sagebrush program, isolation of the minute amounts of the extractable sesquiterpene lactones, and structural determination thereof, mainly through interpretation of the n.m.r., mass, and i.r. spectra of various derivatives, were achievements of the first magnitude for any organic chemist. In this program, Fred had again gone beyond the traditional scientific barriers by correlating these compounds and their properties with the taxonomy, physiology, and ecology of the Artemisia species, showing the penetration and depth of his inquiries, and his understanding and appreciation of the biological problems involved. Fred’s courage, and his capability to delve into multidisciplinary problems involving a range of subjects from physical chemistry to cellular biology, are clearly reflected in his penetrating analysis and discussion in an article on the morphology and biogenesis of cellulose and plant cell-walls. This article unfolded more than a century of multidisciplinary developments in a critical and coherent manner that constituted a hallmark in cellulose

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chemistry. It started with a consideration of the composition and ultrastructure of the fibers, and ended with a discussion of the role of various cell-organelles in producing them. Other reviews and contributions by Fred, on pyrolysis and combustion of cellulosic material and on cleavage of the oxygen ring, showed the same qualities of timeliness and scholarship. Fred Shafizadeh published over 160 research papers and review articles, was co-editor of two books, and was the inventor or co-inventor for six patents. He was frequently invited to speak at national and international meetings, and, in June, 1975, he visited laboratories in Moscow, Leningrad, Riga, and Tashkent, U.S.S.R., under an exchange program of the National Academy of Sciences of the United States of America and the Academy of Sciences of the U.S.S.R. In 1972, the University of Birmingham, England, awarded Professor Shafizadeh the D.Sc. degree in recognition of his important contributions on carbohydrates and sesquiterpene lactones. He was a member of the American Chemical Society, and of its Carbohydrate Division (Chairman, 1972-1973) and its Cellulose, Paper, and Textile Division (Chairman, 1971-1972). He was also a member of The Chemical Society (London), The Society of the Sigma Xi, the Combustion Institute, the Torrey Botanical Club, the Technical Association of the Pulp and Paper Industry, and the Montana Academy of Sciences. He served on the editorial boards of the Journal of Analytical and Applied pVrolysis and the Journal of Wood Chemistry and Technology. He chaired a number of symposia and conferences, including the July, 1983, Gordon Conference on Analytical Pyrolysis. Through election by the University of Montana faculty, he served on the Faculty Senate and on the Executive Committee of the Senate. In 1980, he was awarded the University of Montana’s first Distinguished Research Award. Some of the contributions of Fred Shafizadeh the scientist have just been detailed but that description represents only a part of Fred Shafizadeh the man, and fails to recognize what a complex and colorful man he was. He came from Persia (now Iran), a country of people having a 3,000-year-old cultural tradition, in which devotion to thought, to education, and to freedom were then central. That cultural tradition continued to be important to Fred, even after he had acquired his pragmatic, scientific education in our western culture. Despite his international stature in research, it was important to Fred Shafizadeh to be involved in teaching. In fact, he insisted each year on teaching a freshman-chemistry course. It was imperative to him to teach the meaning of inquiry, and to convey the spirit and thrill of discovery. His absolute devotion to academic excellence came as much from Persian as from western culture. At the advanced level, his graduate students and postdoctoral fellows left his laboratory remarkably able to move into respon-

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sible positions. Fred always, to an unusual degree, delegated responsibilities to his students and research staff. On leaving his laboratory, these investigators were ready to proceed with research independently, from the conception of a problem to reporting the results obtained. The successes of these people were a source of great pride to Fred. As hardworking and demanding as he was at the University, Fred was at home a quiet, relaxed, and devoted family-man. Fred’s house-parties were superbly hosted by him and his wife, Doreen, and were enjoyed by us all. Although Fred did not himself partake of alcoholic .beverages, he and Doreen would sometimes join the rest of the lab. workers at the Friday-night get-together at a local bar. Any who worked for Fred in his Wood Chemistry Laboratory will invariably say how fortunate they were to have had the experience. Fred’s lab., like the man himself, was one of a kind. Whether it was the inevitable odor of a pyrolyzed carbohydrate, the scenic backdrop of the Rattlesnake Mountains from the lab. window, or just the sight of an exuberant Fred discussing the latest data, the Wood Chemistry Laboratory under Fred Shafizadeh will remain a fond memory for all of us who ever worked there. Fred was a backgammon player, a fisherman at Flat Head Lake, a collector of Oriental rugs, and our good and respected friend. His presence will be missed, but his memory and his contribution will live on through his many friends and students. GARYD. MCGINNIS Forest Products Utilization Laboratory Mississippi State University Mississippi State, Mississippi 39762