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David James Bell 1905-1972
1905-1972
DAVID JAMES BELL 1905-1972 David James Bell was born in Scotland on August 12, 1905, the only child of John J. and Helen Geddes Bell. His parents were living at Blairmore in Argyll, but, because there was no doctor there, his mother crossed the Firth of Clyde and he was born in Greenock. As a child, he looked eastward up the great river estuary to the city of Glasgow in which he was to receive his schooling and his university education; Glasgow had been created by the Clyde when, after the Act of Union with England in 1707, it became the chief port for the tobacco trade with the North American colonies. A century later, it was caught up in the industrial revolution, but, unlike the great industrial centres of Northern England, it had a university and a civic iradition when those places were little more than villages, When Bell graduated from the University of Glasgow in 1928, it was as the heir to a distinct Scottish culture, and, despite a long and scientifically profitable stay in Cambridge, he never lost his national characteristics and his affection for his native land. AIong the shores of the Clyde, the wealthier families of Glasgow had created summer resorts, of which Blairmore was one, Bell’s father came from such a family (tobacco manufacturers whose name is still known to the pipe smoker) and had given up a science course at the university to risk a career in journalism and writing. By the turn of the century, he had become a popular and successful author, and is still remembered today for his Wee Macgreegor stories. His writings show a mastery of language, a preoccupation with verbal humour, and a sense of fun. Thus, in a pleasantly written travel book he could not resist describing the Clyde paddle steamers as “plying to capacity” and calling the Old Man of Storr, a rock pinnacle 50 meters high on the Isle of Skye, a “rude obelisk.” A series of word pictures of a small boy on holiday with his father, “Jim Crow,” published in 1910, was based on his son’s early years. Echoes of the puns in it were still to be heard in laboratories fifty years later, and, without doubt, his son learnt much of his craft with words and his style of humour from his father. Although Scotland’s universities gave birth to and nourished the British school of carbohydrate chemistry, Glasgow University had least to do with it. Bell moved to St. Andrews in 1928, and took his Ph. D. under the supervision of J. C. Irvine. He investigated the chemistry of 1
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JOHN S. D. BACON AND DAVID J. MANNERS
the so-called a-celluloses of wood, namely, that fraction which is resistant to the action of 17.5% sodium hydroxide solution. The results were published in 1932 in the Biochemical Journal. The St. Andrews laboratory in this period is well described in the obituary notice of C. B. Purves [by A. S . Perlin, Aduan. Carbohyd. Chem., 23, 1 (1968)], whom he followed to J. J. R. Macleod's Department of Physiology in Aberdeen in 1931. This relatively brief period in St. Andrews had a determining effect on his research career, and, from this time on, he was never really happy unless he had at least one carbohydrate problem in hand. However, the subsequent years in Aberdeen were equally influential, and while continuing to make important contributions to carbohydrate chemistry, he had always an air of detachment from the intense activity then centred at the University of Birmingham. Physically, Bell was a Scottish type, small in stature but well built. He had none of the dourness that some might have expected. He was a clear and fluent speaker, equally at home as a lecturer or a raconteur, and fond of social intercourse. There was a great deal of mischief in him, but little malice. His Scottish background gave him less respect for social status than that of the average Englishman; this went well in the laboratory, but less well with administrative hierarchies, which he could never take sufficiently seriously, his comments often being too witty and too near the truth for his own good. To understand the form of his contribution to carbohydrate chemistry, two factors must be taken into account. The first is that, after leaving St. Andrews to go to Aberdeen in 1931, he was never again to work in a Department of Chemistry. He was, therefore, never to have the plentiful succession of Ph. D. students that most senior teaching-staff in chemistry could normally expect. In his whole career, he had only six research students. Secondly, it has never been easy for outsiders to establish themselves in Cambridge. When he arrived in 1936, university salaries were not generous, being set in the expectation that a lecturer would earn additional money by teaching in one of the colleges. As required by statute, Bell was attached to a college (Jesus), but the authorities could find him no teaching to do; until 1935, biochemistry had been taught almost exclusively to medical students, and these were already catered for. He looked for work in other colleges, and it was in this way that one of us (J.S.D.B.) first met him in 1936. Whether from this early discouragement or from deliberate choice, Bell did not pursue a college career, but applied himself assiduously to research and teaching in the university department, activities that could lead to internal promotion, or, more usually, to a better teaching-post elsewhere.
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3
The Cambridge Biochemical Laboratory under F. G. Hopkins was, by any standards, a remarkable place, and Bell made the fullest use of it. At Aberdeen, he had worked single-handed most of the time, except for his collaboration with H. W. Kosterlitz and F. G. Young, but, in pre-war Cambridge, his enthusiasm and, particularly, his willingness to work long hours at the bench won him the collaboration of staff (E. Baldwin), students ( R . L. M. Synge, J. S. D. Bacon, J. Lorber), full-time research workers (M. Stephenson, E. Friedmann), and a senior technician (S. Williamson). During this period, the streak of restlessness in his character showed itself chiefly in daily wanderings (complete with pipe) round the Department-an important ingredient for the success of his collaboration-and in frequent moves from room to room. One of us (J.S.D.B.), who spent a total of five years with him, worked in four different rooms, and the other (D.J.M.) in two more. One detects a family influence, because he had lived with his parents in fifteen houses before he reached Cambridge at the age of 30. When the Second World War broke out, he lost his Ph. D. students, and as the laboratory turned towards war work, he became increasingly restless and dissatisfied with his own contribution, and so he joined the Army, becoming a Major in the Royal Engineers. Here he found pleasure in a new circle of acquaintances, among whom was Rowland Hilder, a painter well known for his East Anglian landscapes. He was also intrigued to receive memoranda signed by Nigel Balchin, author of “The Small Back Room.” He was recalled to his teaching post in 1944 and at once settled back into laboratory work and publication, although, somewhat later (again in uniform), he went to occupied Germany with Professor John Beattie to investigate cases of famine edema. Later still, in 1947, he went, at the request of the Foreign Office, to teach in the medical school of the Vniversity of Munster-Westfalen. Thereafter, he was busy with the post-war “bulge” of university students and with the gradual return to more normal conditions in the early fifties. During this time, he collaborated with staff (G. D. Greville, D. H. Northcote), research students (Anne Palmer, D. J. Manners, Nancy E. Hardwick), and workers in other laboratories, including J. Barcroft, P. H. Blanchard, R. Dedonder, J. Edelman, D. Gross, and F. A. Isherwood. It was during his stays in Aberdeen and Cambridge, spanning the years 1931-1954, that he made his chief contributions to carbohydrate chemistry, and for these he was awarded the degree of Sc. D. by Cambridge in 1950. In Aberdeen, he was first a Carnegie Teaching Fellow and then an 1851 Exhibition Senior Student in the Department of Physiology. Under
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JOHN S. D. BACON AND DAVID J. MANNERS
Macleod's influence, he showed that the low optical activities of blood filtrates and dialyzates were not due to the presence of D-glucofuranose, examined the action of adrenaline on the hexose monophosphate content of rat muscle, and began his researches on glycogen, a polysaccharide that was to become a continuing and major interest during the next 20 years. With F. G. Young, he critically examined the criteria for the isolation and purity of glycogen, and, with H. W. Kosterlitz, he studied the properties of acetyl and benzoyl derivatives of glycogen, and of the de-acylated polysaccharide esters. He carried out the first methylation analysis of fish-liver glycogen: the average chain-length of this and of a sample of rabbit-liver glycogen was found to be 12. Bell's major contribution to carbohydrate chemistry was undoubtedly in the development of methods for the preparation of numerous methylated sugars, particularly the methyl ethers of D-glucose, D-galactose, and, later, D-fructose, and for their quantitative separation. This work also began in Aberdeen, where syntheses of methyl 2,3,6-tri-O-benzoyl-a-~glucoside, 3,6-di-O-methyl-~-glucose,and &O-methy~-D-ghcose were performed, the removal of the dichloroacetyl group from various D-glucose derivatives and the reaction of acetone with methyl 2-0-methy1-D-ghcofuranoside were examined, and the preparation of 1,2:5,6-di-O-isopropylidene-wD-ghcofuranosewas improved. At Cambridge, these two major lines of research-on methylated sugars and on glycogen-were developed, and Bell's interest in other polysaccharides was expanded. This period saw the preparation, either for the first time, or in an improved form, of 3,6-,4,6-,and 2,6-di-0-methylA D-glucose, and 2-, 2,6- and 3,4-di-, and 2,4,6-tri-O-methyl-~-galactose. number of reactions were examined, including that between p-tolylsulfonyl derivatives of D-glucofuranose and sodium iodide, acyl migration in the D-galactose series, and the use of the benzyl group in syntheses of methylated sugars. On the analytical side, he developed a micromethod for the determination of the isopropylidene group in carbohydrate derivatives, and examined the relationship between refractive index and specific rotation in various methyl D-galactosides. ISubstantial progress was also made with glycogen. Whereas the results of previous methylation analysis had indicated average chain-lengths of 12 for rabbit-liver glycogen [compare also, W. N. Haworth and E. G. V. Percival, J . Chem. Soc., 2277 (1932)], glycogen formed in rabbit livers after the ingestion of D-galactose was found to have an average chainlength of 18. A similar value was independently obtained by W. N. Haworth, E. L. Hirst, and F. A. Isherwood [J. Chem. SOC., 577 (1937)l for a sample of muscle glycogen. This result emphasized that metabolic reserves of carbohydrate are not chemically static, but that their overall
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structure reflects the state of the tissue at the time of isolation of the polysaccharide. Methylation analyses were also performed on glycogen from Mytilzls edulis, horse muscle, and Helix pomatia. Interest in the latter invertebrate also led to an examination of snail galactogen (galactan), which revealed that both D- and L-galactose are present therein. R. L. M. Synge, who began research in 1936 with N. W. Pine’s suggestion that he shouId investigate the chemistry of glycoproteins, sought Bell‘s help and published his first papers with him. Recalling this in his Nobel Lecture, he said, “Among many useful things, I learnt from Bell the power of liquid-liquid extraction, with or without salting out, for separating methylated sugars according to the extent of their methylation.” Synge and Martin’s first papers on partition chromatography appeared in 1941, while Bell was in the Army, but, immediately upon his return to Cambridge in 1944, he devised and published a small-scale method for the separation of methylated glucoses on a column of silica gel which he applied successfully to the methylation analysis of rice starch, and of glycogen from horse muscle and Ascark brnbricoides. In 1949, a similar method was developed for the separation of the methyl ethers of D-fructose, and was used for methylation analysis of fructans from higher plants and bacteria. Similar methods were used for the characterization of the oligosaccharides produced from sucrose by various invertase preparations, Synge [“Les Prix Nobel en 1952,” P. A. Norstedt & Soner, Stockholm, pp. 122-1351 commented: “Partition chromatography has proved almost ideally adapted for analysing the hydrolysis products of methylated polysaccharides, . . . . . . . , greatly increasing the scope of the methylation method . . . It gives me great pleasure that my teacher D. J. Bell was the first to use the method for this purpose.” In the post-war period, Bell characterized 2,6- and 2,3-di-O-methyl-~galactose and 3,4-di-O-methyl-~-glucose, prepared 2,4-di-O-methyl-~glucose for the first time, and examined the periodate oxidation of several methylated sugars. Studies on glycogen continued, with an examination of the liver glycogen from rabbits that had been fed with D-glucose, D-fructose, and sucrose, and of the molecular weights of several samples of glycogen by sedimentation-diffusion methods. The nature of the inter-chain linkages in glycogen had been the subject of some controversy, and these were finally characterized as ( 1+6) -a-D-glucosidic by periodate oxidation, A study of the beta-amylolysis of glycogen provided information on the relative lengths of the external and internal chains. Many of these results were reported in an excellent review [ B i d . Rev., 23, 256 (1948)l. Other studies in this post-war period dealt with the presence of D-fructose in fetal blood, the renal clearances of some fructans in the
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dog, the structures of yeast glucan and of the cellulose from Posidonia )-apiose in the same plant-tissue. He also wrote reviews on enzymic, in vitru syntheses of natural glycosidic derivatives [Ann. Repts. Chem. SOC., 44, 217 (1948)], on carbohydrate chemistry [Ann. Rev. Biochem., 18, 87 (1949)], on the methyl ethers of D-galactose [Aduan. Carbohyd. Chem., 6, 11 (1951)], and on monoand oligo-saccharides and acidic monosaccharide derivatives [Modem Methods uf Plant Analysis, Vol. 11, 1 (1955)l. Through all this period, he personally carried out a large proportion of the experimental work. His early training in St. Andrews had ensured that his glass-blowing skill was an example to others, and he had an uncanny ability in being able to crystallize the most intractable of carbohydrate syrups. His knowledge of the literature, particularly that of the 1920-30 period, was extensive. He shared these characteristics with his friend and former colleague, Dr. J. W. H. Oldham. Bell was the author or co-author of some 100 publications, constituting ample testimony to his industry and success in the laboratory. In the University of Cambridge, David Bell’s influence extended far beyond his own laboratory. He excelled as a lecturer to the large undergraduate classes in Part I biochemistry and physiological chemistry. In the advanced classes, his lectures had an air of quiet authority. These lectures were enlivened by humorous anecdotes, usually slightly exaggerated, concerning some personality from the literature, or stories from the St. Andrews’ laboratory, where hydrolyses of polysaccharides were apparently carried out while the chemists concerned (including Bell) were otherwise occupied on the nearby golf-course! He was the author of an “Introduction to Carbohydrate Biochemistry” which was produced in three editions between 1940 and 1952, and, with his great friend Ernest Baldwin, he revised, for the benefit of the medical classes, Cole’s ”Practical Physiological Chemistry.” During the early fifties, his longing to return to Scotland intensified, and he eventually achieved this in 1954 by abandoning teaching, a step that had seemed an impossibility to his friends, and taking a full-time research post in the Poultry Research Centre at Edinburgh, one of the Institutes of the Agricultural Research Council. Here, he began to investigate various aspects of the metabolism of the domestic fowl, in particular, the nitrogen-containing metabolites, and the enzyme levels in various tissue-fluids. It is a measure of his wide range of interests, his breadth of knowledge, and his enthusiasm for experimental work, that, during the next 11 years, he was the author of 21 publications devoted to this area of physiology and biochemistry. His collaborators in this period included I. E. Lush (his fifth Ph. D. student), P. E. Lake, T. P. uust7aZis, and the presence of D(
+
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Bird, J. G. Campbell, J. Culbert, W. M. McIndoe, and W. G. Siller. He also edited, with B. M. Freeman, a three-volume treatise on the “Physiology and Biochemistry of the Domestic Fowl” (Academic Press, New York, 1971), accepted as the major authoritative work on the subject. He retained some contact with undergraduates by serving as an honorary, senior lecturer in the Department of Physiology in the University of Edinburgh, and, in 1965, he left the institute to become a full-time member of that department. Once again, he was able to devote himself wholeheartedly to his beloved carbohydrates. He examined the transport of monosaccharides within certain tissues, and their excretion in urine. Here, his chemical expertise was used to develop appropriate, analytical techniques, and, with M. Q. K. Talukder (his last Ph. D. student), he devised a thinlayer chromatographic technique for estimating pentoses in the presence of other sugars. At a time when many of his contemporaries and junior colleagues were “desk-bound,” Bell was still carrying out experiments himself, handling minute amounts of sugars with the complete confidence that had developed from years of experience. In 1970, he officially retired, but he continued in the department, both as a teacher and a research worker, with the aid of grants from the Medical Research Council and from the British Diabetic Association. During his years in Edinburgh, he wrote a comprehensive account of the “Structure and occurrence of natural monosaccharides and oligosaccharides” [Comparatiue Biochemistry, 3A, 288 (1962)l and an essay for sixth-formers on the energetics of biochemical processes for “Four Aspects of Energetics” [by A. Finch and others, Wm. Collins Sons & Co. Ltd., London, 19701, which reads like a transcript of his very lucid, extempore lecturing-style. Within the United Kingdom, Bell was well known amongst carbohydrate chemists. He was a meticulous examiner of Ph. D. theses, as some candidates found to their dismay, and an active member of the British Carbohydrate Nomenclature Committee, where he had a particular interest in branched-chain sugars. He served as a member of the Publications Committee of The Chemical Society from 1951-1955, and as Senior Reporter for the biochemistry section of the Annual Reports of The Chemical Society. He frequently travelled to Europe, notably to the foreign meetings of the Society for Experimental Biology, and he particularly valued his contacts with the carbohydrate biochemists at the Institut Pasteur. In 1950, his first wife, Joan Collie, whom he had married in Aberdeen, died after a lengthy illness, and, in 1951, he married June Cross, a medically qualified biochemist. He is survived by his widow and their two
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JOHN S. D. BACON AND DAVID J. MANNERS
daughters, and by a son and daughter and three grandsons from his first marriage. His return to Scotland had been marked by his election to the Royal Society of Edinburgh, and by renewed contacts with many friends within and without the Scottish universities. It was a special pleasure for him to be within walking distance of Sir Edmund Hirst’s department. He settled close to the centre of Edinburgh with his young family, became active in the Episcopalian Church, and was able to indulge his enthusiasm for golf again. His friends saw little change in him from his Cambridge days, and so it was a shock to all when he died suddenly, of a heart attack, on April 3rd, 1972. Those who have had the privilege of working with him have always found it difficult to explain fully the particular pleasure of his company at the bench. The intent was serious, but the execution was often lighthearted, extending even to the labels on the bottles. Where else in the world was there a M/100cockroach solution? Recently, one of us asked the other ‘What was Bell’s reagent?” Neither of us can really remember, but one thing is certain-that without it on the shelf, our laboratories are duller places. S . D. BACON DAVIDJ. MANNERS
JOHN
DAVID JAMES BELL 1905-1972 David James Bell was born in Scotland on August 12, 1905, the only child of John J. and Helen Geddes Bell. His parents were living at Blairmore in Argyll, but, because there was no doctor there, his mother crossed the Firth of Clyde and he was born in Greenock. As a child, he looked eastward up the great river estuary to the city of Glasgow in which he was to receive his schooling and his university education; Glasgow had been created by the Clyde when, after the Act of Union with England in 1707, it became the chief port for the tobacco trade with the North American colonies. A century later, it was caught up in the industrial revolution, but, unlike the great industrial centres of Northern England, it had a university and a civic iradition when those places were little more than villages, When Bell graduated from the University of Glasgow in 1928, it was as the heir to a distinct Scottish culture, and, despite a long and scientifically profitable stay in Cambridge, he never lost his national characteristics and his affection for his native land. AIong the shores of the Clyde, the wealthier families of Glasgow had created summer resorts, of which Blairmore was one, Bell’s father came from such a family (tobacco manufacturers whose name is still known to the pipe smoker) and had given up a science course at the university to risk a career in journalism and writing. By the turn of the century, he had become a popular and successful author, and is still remembered today for his Wee Macgreegor stories. His writings show a mastery of language, a preoccupation with verbal humour, and a sense of fun. Thus, in a pleasantly written travel book he could not resist describing the Clyde paddle steamers as “plying to capacity” and calling the Old Man of Storr, a rock pinnacle 50 meters high on the Isle of Skye, a “rude obelisk.” A series of word pictures of a small boy on holiday with his father, “Jim Crow,” published in 1910, was based on his son’s early years. Echoes of the puns in it were still to be heard in laboratories fifty years later, and, without doubt, his son learnt much of his craft with words and his style of humour from his father. Although Scotland’s universities gave birth to and nourished the British school of carbohydrate chemistry, Glasgow University had least to do with it. Bell moved to St. Andrews in 1928, and took his Ph. D. under the supervision of J. C. Irvine. He investigated the chemistry of 1
2
JOHN S. D. BACON AND DAVID J. MANNERS
the so-called a-celluloses of wood, namely, that fraction which is resistant to the action of 17.5% sodium hydroxide solution. The results were published in 1932 in the Biochemical Journal. The St. Andrews laboratory in this period is well described in the obituary notice of C. B. Purves [by A. S . Perlin, Aduan. Carbohyd. Chem., 23, 1 (1968)], whom he followed to J. J. R. Macleod's Department of Physiology in Aberdeen in 1931. This relatively brief period in St. Andrews had a determining effect on his research career, and, from this time on, he was never really happy unless he had at least one carbohydrate problem in hand. However, the subsequent years in Aberdeen were equally influential, and while continuing to make important contributions to carbohydrate chemistry, he had always an air of detachment from the intense activity then centred at the University of Birmingham. Physically, Bell was a Scottish type, small in stature but well built. He had none of the dourness that some might have expected. He was a clear and fluent speaker, equally at home as a lecturer or a raconteur, and fond of social intercourse. There was a great deal of mischief in him, but little malice. His Scottish background gave him less respect for social status than that of the average Englishman; this went well in the laboratory, but less well with administrative hierarchies, which he could never take sufficiently seriously, his comments often being too witty and too near the truth for his own good. To understand the form of his contribution to carbohydrate chemistry, two factors must be taken into account. The first is that, after leaving St. Andrews to go to Aberdeen in 1931, he was never again to work in a Department of Chemistry. He was, therefore, never to have the plentiful succession of Ph. D. students that most senior teaching-staff in chemistry could normally expect. In his whole career, he had only six research students. Secondly, it has never been easy for outsiders to establish themselves in Cambridge. When he arrived in 1936, university salaries were not generous, being set in the expectation that a lecturer would earn additional money by teaching in one of the colleges. As required by statute, Bell was attached to a college (Jesus), but the authorities could find him no teaching to do; until 1935, biochemistry had been taught almost exclusively to medical students, and these were already catered for. He looked for work in other colleges, and it was in this way that one of us (J.S.D.B.) first met him in 1936. Whether from this early discouragement or from deliberate choice, Bell did not pursue a college career, but applied himself assiduously to research and teaching in the university department, activities that could lead to internal promotion, or, more usually, to a better teaching-post elsewhere.
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3
The Cambridge Biochemical Laboratory under F. G. Hopkins was, by any standards, a remarkable place, and Bell made the fullest use of it. At Aberdeen, he had worked single-handed most of the time, except for his collaboration with H. W. Kosterlitz and F. G. Young, but, in pre-war Cambridge, his enthusiasm and, particularly, his willingness to work long hours at the bench won him the collaboration of staff (E. Baldwin), students ( R . L. M. Synge, J. S. D. Bacon, J. Lorber), full-time research workers (M. Stephenson, E. Friedmann), and a senior technician (S. Williamson). During this period, the streak of restlessness in his character showed itself chiefly in daily wanderings (complete with pipe) round the Department-an important ingredient for the success of his collaboration-and in frequent moves from room to room. One of us (J.S.D.B.), who spent a total of five years with him, worked in four different rooms, and the other (D.J.M.) in two more. One detects a family influence, because he had lived with his parents in fifteen houses before he reached Cambridge at the age of 30. When the Second World War broke out, he lost his Ph. D. students, and as the laboratory turned towards war work, he became increasingly restless and dissatisfied with his own contribution, and so he joined the Army, becoming a Major in the Royal Engineers. Here he found pleasure in a new circle of acquaintances, among whom was Rowland Hilder, a painter well known for his East Anglian landscapes. He was also intrigued to receive memoranda signed by Nigel Balchin, author of “The Small Back Room.” He was recalled to his teaching post in 1944 and at once settled back into laboratory work and publication, although, somewhat later (again in uniform), he went to occupied Germany with Professor John Beattie to investigate cases of famine edema. Later still, in 1947, he went, at the request of the Foreign Office, to teach in the medical school of the Vniversity of Munster-Westfalen. Thereafter, he was busy with the post-war “bulge” of university students and with the gradual return to more normal conditions in the early fifties. During this time, he collaborated with staff (G. D. Greville, D. H. Northcote), research students (Anne Palmer, D. J. Manners, Nancy E. Hardwick), and workers in other laboratories, including J. Barcroft, P. H. Blanchard, R. Dedonder, J. Edelman, D. Gross, and F. A. Isherwood. It was during his stays in Aberdeen and Cambridge, spanning the years 1931-1954, that he made his chief contributions to carbohydrate chemistry, and for these he was awarded the degree of Sc. D. by Cambridge in 1950. In Aberdeen, he was first a Carnegie Teaching Fellow and then an 1851 Exhibition Senior Student in the Department of Physiology. Under
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JOHN S. D. BACON AND DAVID J. MANNERS
Macleod's influence, he showed that the low optical activities of blood filtrates and dialyzates were not due to the presence of D-glucofuranose, examined the action of adrenaline on the hexose monophosphate content of rat muscle, and began his researches on glycogen, a polysaccharide that was to become a continuing and major interest during the next 20 years. With F. G. Young, he critically examined the criteria for the isolation and purity of glycogen, and, with H. W. Kosterlitz, he studied the properties of acetyl and benzoyl derivatives of glycogen, and of the de-acylated polysaccharide esters. He carried out the first methylation analysis of fish-liver glycogen: the average chain-length of this and of a sample of rabbit-liver glycogen was found to be 12. Bell's major contribution to carbohydrate chemistry was undoubtedly in the development of methods for the preparation of numerous methylated sugars, particularly the methyl ethers of D-glucose, D-galactose, and, later, D-fructose, and for their quantitative separation. This work also began in Aberdeen, where syntheses of methyl 2,3,6-tri-O-benzoyl-a-~glucoside, 3,6-di-O-methyl-~-glucose,and &O-methy~-D-ghcose were performed, the removal of the dichloroacetyl group from various D-glucose derivatives and the reaction of acetone with methyl 2-0-methy1-D-ghcofuranoside were examined, and the preparation of 1,2:5,6-di-O-isopropylidene-wD-ghcofuranosewas improved. At Cambridge, these two major lines of research-on methylated sugars and on glycogen-were developed, and Bell's interest in other polysaccharides was expanded. This period saw the preparation, either for the first time, or in an improved form, of 3,6-,4,6-,and 2,6-di-0-methylA D-glucose, and 2-, 2,6- and 3,4-di-, and 2,4,6-tri-O-methyl-~-galactose. number of reactions were examined, including that between p-tolylsulfonyl derivatives of D-glucofuranose and sodium iodide, acyl migration in the D-galactose series, and the use of the benzyl group in syntheses of methylated sugars. On the analytical side, he developed a micromethod for the determination of the isopropylidene group in carbohydrate derivatives, and examined the relationship between refractive index and specific rotation in various methyl D-galactosides. ISubstantial progress was also made with glycogen. Whereas the results of previous methylation analysis had indicated average chain-lengths of 12 for rabbit-liver glycogen [compare also, W. N. Haworth and E. G. V. Percival, J . Chem. Soc., 2277 (1932)], glycogen formed in rabbit livers after the ingestion of D-galactose was found to have an average chainlength of 18. A similar value was independently obtained by W. N. Haworth, E. L. Hirst, and F. A. Isherwood [J. Chem. SOC., 577 (1937)l for a sample of muscle glycogen. This result emphasized that metabolic reserves of carbohydrate are not chemically static, but that their overall
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structure reflects the state of the tissue at the time of isolation of the polysaccharide. Methylation analyses were also performed on glycogen from Mytilzls edulis, horse muscle, and Helix pomatia. Interest in the latter invertebrate also led to an examination of snail galactogen (galactan), which revealed that both D- and L-galactose are present therein. R. L. M. Synge, who began research in 1936 with N. W. Pine’s suggestion that he shouId investigate the chemistry of glycoproteins, sought Bell‘s help and published his first papers with him. Recalling this in his Nobel Lecture, he said, “Among many useful things, I learnt from Bell the power of liquid-liquid extraction, with or without salting out, for separating methylated sugars according to the extent of their methylation.” Synge and Martin’s first papers on partition chromatography appeared in 1941, while Bell was in the Army, but, immediately upon his return to Cambridge in 1944, he devised and published a small-scale method for the separation of methylated glucoses on a column of silica gel which he applied successfully to the methylation analysis of rice starch, and of glycogen from horse muscle and Ascark brnbricoides. In 1949, a similar method was developed for the separation of the methyl ethers of D-fructose, and was used for methylation analysis of fructans from higher plants and bacteria. Similar methods were used for the characterization of the oligosaccharides produced from sucrose by various invertase preparations, Synge [“Les Prix Nobel en 1952,” P. A. Norstedt & Soner, Stockholm, pp. 122-1351 commented: “Partition chromatography has proved almost ideally adapted for analysing the hydrolysis products of methylated polysaccharides, . . . . . . . , greatly increasing the scope of the methylation method . . . It gives me great pleasure that my teacher D. J. Bell was the first to use the method for this purpose.” In the post-war period, Bell characterized 2,6- and 2,3-di-O-methyl-~galactose and 3,4-di-O-methyl-~-glucose, prepared 2,4-di-O-methyl-~glucose for the first time, and examined the periodate oxidation of several methylated sugars. Studies on glycogen continued, with an examination of the liver glycogen from rabbits that had been fed with D-glucose, D-fructose, and sucrose, and of the molecular weights of several samples of glycogen by sedimentation-diffusion methods. The nature of the inter-chain linkages in glycogen had been the subject of some controversy, and these were finally characterized as ( 1+6) -a-D-glucosidic by periodate oxidation, A study of the beta-amylolysis of glycogen provided information on the relative lengths of the external and internal chains. Many of these results were reported in an excellent review [ B i d . Rev., 23, 256 (1948)l. Other studies in this post-war period dealt with the presence of D-fructose in fetal blood, the renal clearances of some fructans in the
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JOHN S. D. BACON AND DAVID J. MANNERS
dog, the structures of yeast glucan and of the cellulose from Posidonia )-apiose in the same plant-tissue. He also wrote reviews on enzymic, in vitru syntheses of natural glycosidic derivatives [Ann. Repts. Chem. SOC., 44, 217 (1948)], on carbohydrate chemistry [Ann. Rev. Biochem., 18, 87 (1949)], on the methyl ethers of D-galactose [Aduan. Carbohyd. Chem., 6, 11 (1951)], and on monoand oligo-saccharides and acidic monosaccharide derivatives [Modem Methods uf Plant Analysis, Vol. 11, 1 (1955)l. Through all this period, he personally carried out a large proportion of the experimental work. His early training in St. Andrews had ensured that his glass-blowing skill was an example to others, and he had an uncanny ability in being able to crystallize the most intractable of carbohydrate syrups. His knowledge of the literature, particularly that of the 1920-30 period, was extensive. He shared these characteristics with his friend and former colleague, Dr. J. W. H. Oldham. Bell was the author or co-author of some 100 publications, constituting ample testimony to his industry and success in the laboratory. In the University of Cambridge, David Bell’s influence extended far beyond his own laboratory. He excelled as a lecturer to the large undergraduate classes in Part I biochemistry and physiological chemistry. In the advanced classes, his lectures had an air of quiet authority. These lectures were enlivened by humorous anecdotes, usually slightly exaggerated, concerning some personality from the literature, or stories from the St. Andrews’ laboratory, where hydrolyses of polysaccharides were apparently carried out while the chemists concerned (including Bell) were otherwise occupied on the nearby golf-course! He was the author of an “Introduction to Carbohydrate Biochemistry” which was produced in three editions between 1940 and 1952, and, with his great friend Ernest Baldwin, he revised, for the benefit of the medical classes, Cole’s ”Practical Physiological Chemistry.” During the early fifties, his longing to return to Scotland intensified, and he eventually achieved this in 1954 by abandoning teaching, a step that had seemed an impossibility to his friends, and taking a full-time research post in the Poultry Research Centre at Edinburgh, one of the Institutes of the Agricultural Research Council. Here, he began to investigate various aspects of the metabolism of the domestic fowl, in particular, the nitrogen-containing metabolites, and the enzyme levels in various tissue-fluids. It is a measure of his wide range of interests, his breadth of knowledge, and his enthusiasm for experimental work, that, during the next 11 years, he was the author of 21 publications devoted to this area of physiology and biochemistry. His collaborators in this period included I. E. Lush (his fifth Ph. D. student), P. E. Lake, T. P. uust7aZis, and the presence of D(
+
OBITUARY-DAVID
JAMES BELL
7
Bird, J. G. Campbell, J. Culbert, W. M. McIndoe, and W. G. Siller. He also edited, with B. M. Freeman, a three-volume treatise on the “Physiology and Biochemistry of the Domestic Fowl” (Academic Press, New York, 1971), accepted as the major authoritative work on the subject. He retained some contact with undergraduates by serving as an honorary, senior lecturer in the Department of Physiology in the University of Edinburgh, and, in 1965, he left the institute to become a full-time member of that department. Once again, he was able to devote himself wholeheartedly to his beloved carbohydrates. He examined the transport of monosaccharides within certain tissues, and their excretion in urine. Here, his chemical expertise was used to develop appropriate, analytical techniques, and, with M. Q. K. Talukder (his last Ph. D. student), he devised a thinlayer chromatographic technique for estimating pentoses in the presence of other sugars. At a time when many of his contemporaries and junior colleagues were “desk-bound,” Bell was still carrying out experiments himself, handling minute amounts of sugars with the complete confidence that had developed from years of experience. In 1970, he officially retired, but he continued in the department, both as a teacher and a research worker, with the aid of grants from the Medical Research Council and from the British Diabetic Association. During his years in Edinburgh, he wrote a comprehensive account of the “Structure and occurrence of natural monosaccharides and oligosaccharides” [Comparatiue Biochemistry, 3A, 288 (1962)l and an essay for sixth-formers on the energetics of biochemical processes for “Four Aspects of Energetics” [by A. Finch and others, Wm. Collins Sons & Co. Ltd., London, 19701, which reads like a transcript of his very lucid, extempore lecturing-style. Within the United Kingdom, Bell was well known amongst carbohydrate chemists. He was a meticulous examiner of Ph. D. theses, as some candidates found to their dismay, and an active member of the British Carbohydrate Nomenclature Committee, where he had a particular interest in branched-chain sugars. He served as a member of the Publications Committee of The Chemical Society from 1951-1955, and as Senior Reporter for the biochemistry section of the Annual Reports of The Chemical Society. He frequently travelled to Europe, notably to the foreign meetings of the Society for Experimental Biology, and he particularly valued his contacts with the carbohydrate biochemists at the Institut Pasteur. In 1950, his first wife, Joan Collie, whom he had married in Aberdeen, died after a lengthy illness, and, in 1951, he married June Cross, a medically qualified biochemist. He is survived by his widow and their two
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JOHN S. D. BACON AND DAVID J. MANNERS
daughters, and by a son and daughter and three grandsons from his first marriage. His return to Scotland had been marked by his election to the Royal Society of Edinburgh, and by renewed contacts with many friends within and without the Scottish universities. It was a special pleasure for him to be within walking distance of Sir Edmund Hirst’s department. He settled close to the centre of Edinburgh with his young family, became active in the Episcopalian Church, and was able to indulge his enthusiasm for golf again. His friends saw little change in him from his Cambridge days, and so it was a shock to all when he died suddenly, of a heart attack, on April 3rd, 1972. Those who have had the privilege of working with him have always found it difficult to explain fully the particular pleasure of his company at the bench. The intent was serious, but the execution was often lighthearted, extending even to the labels on the bottles. Where else in the world was there a M/100cockroach solution? Recently, one of us asked the other ‘What was Bell’s reagent?” Neither of us can really remember, but one thing is certain-that without it on the shelf, our laboratories are duller places. S . D. BACON DAVIDJ. MANNERS
JOHN