AAS-Biographical memoirs-Gottschalk

With the passing of Alfred Gottschalk on October 4th 1973, at Tübingen, West Germany, in his 80th year, there ended a life of extraordinary dedication to research in biochemistry. He was active to the end; in fact his last fifteen years, from the time of his retirement from the Hall Institute, were among his most fruitful. He died acclaimed as the leading authority in the ever-expanding field of glycoprotein research.

Curriculum vitae

Gottschalk was born on April 22nd 1894, in Aachen/Rheinland, the third of four sons of Benjamin Gottschalk, merchant, and Rosa Gottschalk (née Kahn). The eldest son, Walter, became a distinguished orientalist but Alfred chose the study of medicine. His courses (1912-1920) at the Universities of Münich, Freiburg/Breisgau and Bonn were interrupted by the First World War in which he served in the Medical Corps and was decorated in 1915. On resuming his studies he graduated MD (with honours) from the University of Bonn in 1920. Postgraduate clinical work and research experience followed in association with the medical schools at Frankfurt/Main and Würzburg, while further training in physiology-biochemistry was undertaken at the Physiological Institute at the University of Bonn. During this period and, in fact, while an undergraduate, he had carried out research part-time and, by 1923, when he was invited to join Professor Carl Neuberg as an assistant at the Kaiser Wilhelm Institute for Experimental Therapy and Biochemistry (1) at Berlin-Dahlem, he already had a considerable number of publications and had received an award from the University of Madrid. Neuberg, already an international figure, exercised a lasting influence on his younger and hard-working colleague and probably helped determine the course of Gottschalk's later independent studies on the chemistry and biochemistry of carbohydrates.

He married, in 1923, Lisbeth Berta Orgler. Their only child, Rudolf, is now a successful civil and mechanical engineer in New Jersey, USA.

Towards the end of 1926 Gottschalk left the Kaiser Wilhelm Institute to become Director of the Biochemical Department at the General Hospital in Stettin, Pomerania, a position which he was forced to relinquish in 1934 as a result of the unhappy political upheavals in Nazi Germany. Following a period in private practice he was able to leave Germany with his family in the spring of 1939. After spending a few months in Liverpool, England, where, at the University, he was able 'to brush up his biochemistry', they left by ship for Melbourne in July 1939.

Through the good offices of an English Catholic Church organization – the family having embraced this faith some years earlier – and the interest of Dr Charles Kellaway, the then Director of the Walter and Eliza Hall Institute, Gottschalk had been offered a modest stipendium to work as a biochemist at the Institute. From 1942 to 1948 he taught at the Melbourne Technical College as a part-time Instructor in Organic Chemistry and Biochemistry, and from 1949 he lectured part-time on carbohydrates to senior students in my former Department of Biochemistry at Melbourne University. He became a naturalized British subject in 1945, and in 1946 his clinical training and experience were recognized by his registration as a Medical Practitioner with the Medical Board of Victoria, although he was never subsequently in private practice.

His early work at the Institute, mainly on carbohydrate fermentation, took a dramatic turn with the observations of the new Director, Dr F.M. (later Professor Sir Macfarlane) Burnet, on the enzyme-like activities of the influenza viruses. Burnet stimulated Gottschalk to join forces in 1947, with more far-reaching results than probably either could have foreseen.

When, in 1959, Gottschalk had reached retiring age, he transferred his activities to the John Curtin School of Medical Research at the Australian National University at the invitation of his friend and former colleague at the Hall Institute, Frank Fenner, who had become the Foundation Professor of Microbiology. Given adequate facilities and continuing support from the National Health and Medical Research Council in the form of a Senior Fellowship, he entered with enthusiasm into his post-retirement activities, but some four years later, early in 1963, he decided for personal reasons, and with reluctance, to leave Canberra to return to Germany. He had expected to come back to Australia and, in consequence, left much of his library and other personal effects in storage. However, this was not to be; even a planned lecturing visit early in 1972, sponsored by the Academy and by senior Australian biochemists, had to be cancelled on medical advice.

In Germany he was most warmly received as a biochemist of international standing. Professor Adolf Butenandt, Director of the Max Planck Institute for Biochemistry and President of the Max Planck Society for Advancement of the Sciences, offered him facilities and an honorarium as Guest-Professor to work for a period in his old institute (2). Gottschalk asked, however, whether this generous offer could be extended to Tübingen, which he thought might provide a better environment for the investigations he had in mind. To this the President readily agreed. Accordingly, there began a most happy and scientifically profitable association with the Max Planck Institute for Virus Research and a close friendship with its Director, Professor Hans Friedrich-Freska. In Tübingen he also enjoyed collaboration with university colleagues in the Institute of Physiological Chemistry (in particular with Dr E. Buddecke (3)).

The original two-year appointment as Guest-Professor in the Institute was extended year by year by mutual consent to 1968, when by special enactment he was admitted (March 5th 1968) as 'Foreign Scientific Member of the Max Planck Institute for Virus Research'. Thus he entered officially into the distinguished scientific circle of the Max Planck Society. This signal honour was a source of great pleasure to him. Professor Butenandt wrote: 'Das war für ihn eine Freude und Ehre, für mich personlich und für die Tübinger Kollegen zugleich der Versuch, ein wenig von dem Unrecht wieder gutzumachen, das ihm früher in Deutschland zuteil wurde. Durch die Annahme dieser Berufung durch Alfred Gottschalk ist eine echte unvergessliche Freundschaft zwischen ihm und seinen Kollegen in Tübingen und in München bergründet worden.'

Apart from his heavy research programme in the Institute his influence in teaching and research within the University of Tübingen was considerable. In appreciation, the University installed him in 1966 as an Honorary Professor in the Faculty of Mathematics and Science. In the same year (January 1966) he was notified of his election to Fellowship of the American Association for the Advancement of Science 'in recognition of your standing as a scientist'.

In further tribute to his 'life's work as Doctor and Researcher' he was admitted in 1969 to the honorary degree of Doctor of Medicine by the University of Münster on the submission of the Faculty of Medicine, an occasion also for the celebration of his 75th birthday.

Gottschalk became a Fellow of the Academy in 1954 following the first elections after its foundation. He took great pride in his election and strove to foster the welfare of the young Academy. He was largely responsible for the formation of the Victorian Group of Fellows and for the continued success of its regular meetings as its first Honorary Secretary (from July 1954 to December 1958) under the chairmanship of Macfarlane Burnet. As might be expected, the Minute Book was meticulously kept.

Other honours had come to him earlier while still in Melbourne. The University of Melbourne in 1949 conferred on him the degree of Doctor of Science for his distinguished contributions to the scientific literature and two years later he received the University's David Syme Research Prize (shared with H.W. Worner). In 1951 he was elected a Fellow of the Royal Institute of Chemistry (Great Britain) and a Fellow of the Royal Australian Chemical Institute, while in 1954 he shared with A.J. Birch the H.G. Smith Memorial Medal, awarded by the latter Institute.

Personal and general

'What always impressed me most was his absolute and unconditional devotion to the world of learning. That held for his own work but also for all other matters academic. For mundane things he had little time.' So wrote recently a friend of Melbourne days and with these assessments most who knew him well would agree. Moreover those who were associated with him as laboratory colleagues in Australia and in Germany would be unanimous in their admiration for his dedication and meticulous care and attention to detail in the design and execution of his experiments. He insisted on the same high standards from his co-workers but, as Fenner writes: 'Gottschalk was an excellent colleague for senior workers, although somewhat irritating because of his insistence on always seeing and checking evidence, and his persistence. These qualities, transferred to the daily and hourly checking of everything that a student did, made him a nearly impossible supervisor for research students' (4). However, the few post-graduate students who stood the grind had no cause to regret the years so spent and one has remarked: 'although he asked a high degree of dedication from his co-workers it was no more than that which he himself gave'. Moreover, he could be most generous and helpful to them. Although his circle of friends was never large he enjoyed relaxing with them when the demands of the laboratory and writing permitted. To quote Fenner again: 'Outside the laboratory we found Gottschalk to be a somewhat demanding but very enjoyable friend, with broad interests and conversation, a subtle sense of humour, and a great fund of interesting anecdotes about his early scientific life'. Professor Buddecke has expressed himself in similar vein and with the views of these two friends I am in agreement. I first met Gottschalk in 1943 and our friendship continued over the following thirty years.

Gottschalk showed extraordinary determination towards achieving his objectives: his scientific work exemplifies this pre-eminently, but this determination carried through, for example, to his decision, after he had turned 65, to buy his first car. This, in Canberra and later in Germany, was always a Volkswagen (5). I 'enjoyed' a drive with him on several occasions in Canberra and in Tübingen. After a while one relaxed, convinced that a guardian angel hovered continually over Alfred and other drivers in the neighbourhood. As far as I know there was only one accident (in Tübingen) with extensive damage to both cars but none to either driver.

Scientific contributions

Gottschalk's output of published work was immense: in all, 216 research papers and reviews, and four books. He wrote clearly and concisely in both German and English and for practically all of his output he insisted that the preparation of the manuscripts was his personal responsibility, even in the case of joint publications. He never seemed to tire and even at the close of his long life he would, according to Professor Buddecke: 'after dinner at home, several times each week, return to the laboratory quite early in the evening, where he would write until one or two o'clock in the morning'.

The German period (to 1939)

By the age of 29 when he joined Professor Carl Neuberg his list of published work was already impressive – 34 papers over a wide range of projects, partly clinical but mainly physiological and clinical biochemistry. His first four publications were written while he was still a student and one of these, as a contribution to the theory of tissue respiration, indicates that quite early he was in command of the relevant literature, setting a pattern for the many excellent reviews and books which were to issue from his pen over the following fifty years.

Two articles, (Beziehungen der Influenzaagglutinine zur Klinik der Grippe. Klin. Wschr., 1 (1922), pp. 935-937 & Fettabbau bei schwerem Diabetes mellitus. Z. ges. exp. Med., 35 (1923), pp.159-176) are worthy of special mention in view of his subsequent investigations: the first on influenza agglutinin (foreshadowing his work at the Hall Institute?), the second on diabetes, which became an absorbing interest during his period at the General Hospital in Stettin some years later.

The three years spent at the Kaiser Wilhelm Institute were particularly fruitful. Gottschalk was introduced by the master to biochemical fundamentals, with particular reference to carbohydrate metabolism and enzymology, while his contributions to scientific literature continued apace. Of 30 publications 13 were contributed jointly with his chief. Together they were responsible for the classic concept of 'coenzyme' and 'apoenzyme'. Four long reviews also appeared at this time on basic aspects of biochemistry. They are noteworthy for their clarity and scholarship, and are indicative of the wide range of his reading. Finally, a series of four papers, written in collaboration with the Physiological Institute of the University of Berlin (Director: Professor H. Steudel), climaxed his departure for Stettin in 1926 after a period of truly extraordinary activity.

With his background of physiological and biochemical research, Gottschalk was well equipped to assume the Directorship of the Chemical Institute of the General Hospital at Stettin, a city at that time of around 250 000 inhabitants. He introduced micro-methods for blood analysis and gaseous exchange equipment for use in cases of thyroid disease. He also acquired new laboratories. In the five years, 1926-1930, the number of investigations in clinical chemistry in his Institute rose from 9500 to 30 000. In spite of these demands on his time, the output of research publications continued unabated – in the nine years of his tenure of office another 40 were added to his already impressive list. The first twelve or so were largely in extension of his investigations in Berlin but he then became deeply involved in the biochemistry, physiology and pathology of carbohydrate and fat metabolism, particularly as related to diabetes. Apart from his research findings, this gifted scientist played a leading role as clinician in the organization of the diagnosis and treatment of diabetics, in Stettin and also throughout Pomerania. Judging by the content of his library he had read widely on the history of the disease (from the time of Claude Bernard), on various aspects of nutrition and on the controlled use of the recently-discovered insulin. He had also visited Minkowski, then in retirement in Wiesbaden,who with von Mehring had first established, in 1889, the link between the disease and the pancreas, while he had translated and extended 'The Fuel of Life' by J. J. R. McLeod, who had been associated with the discovery of insulin.

Among other innovations he started a diabetic kitchen where, under a qualified dietitian, a daily hot meal was available to each diabetic in accord with his or her prescribed treatment. The success of this organization, 'The Stettin System of Diabetic Aftercare', may be judged by the fact that in the years 1928-1930 there was only one case of diabetic coma (0.3%) whereas in other large centres such as Berlin, Frankfurt/Main, Halle, Leipzig and Breslau the incidence ranged from 3.6 to 16.1 %. His system became a model for other parts of Germany, and an international meeting on diabetes was held in Stettin while he was still in office.

It is left to the imagination as to what might have been the future course of his career had the political climate been different. Would he have continued to combine the intensity of the research scientist with the humanity of the clinician ? What is most likely is that the elucidation of the structures of the sialic acids and the resultant stimulus to glycoprotein research would have been left to other investigators and perhaps delayed by many years.

Melbourne (1939-1959)

The initial studies at the Hall Institute developed, in part, from his investigations during the Berlin period and were concerned with fermentation by yeast. An underlying theme, however, reflected his growing interest in enzyme specificity and in mechanisms of enzyme action. His reputation as an authority on carbohydrases was enhanced and the experience thus gained was undoubtedly of value in his subsequent investigations on the glycoproteins.

The Swedish biochemist, Gunnar Blix, in 1936 obtained a crystalline acid by heating the mucin, prepared from bovine submaxillary glands, in water. The compound, later named by him 'sialic acid', possessed reducing power, contained nitrogen and two acetyl groups and gave a series of colour reactions. A substance with somewhat similar properties was isolated by methanolysis from a brain glycolipid by Klenk (1941) in Germany and given the name 'neuraminic acid' (changed (1942) to 'methoxyneuraminic acid'). The full significance of these findings was not realized, however, until the early 1950s when there was an upsurge of interest in the 'sialic acids' and in the elucidation of these unusual structures Gottschalk was to play a dominant role. The stimulus came initially from observations of biological phenomena – those concerned with the influenza virus. G.K. Hirst reported from the Rockefeller Institute in 1942 that the virus adsorbed to erythrocytes at 4°, and agglutinated them. By raising the temperature to 37° the virus was eluted, but whereas the cells were now no longer agglutinable the virus retained its activity to agglutinate fresh cells. These and other observations led Hirst to interpret the phenomenon as an enzyme-substrate interaction, the enzyme being a component of the virus and the substrate consisting of receptor sites on the erythrocyte surface. By the mid-1940s Burnet and colleagues had become deeply interested in such activities of the virus. Following the observation of T. Francis (1947) they found that a wide range of mucins (mucoproteins) from both human and animal sources inhibited the action of the virus on erythrocytes or on suitable cells in the mouse lung. Again, incubation of the inhibitory mucoproteins with the infective virus (or by a soluble enzyme (RDE) (6) purified from cultures of Vibrio cholerae) destroyed irreversibly the activity of the inhibitors.

In 1947 Gottschalk accepted an invitation to join the 'Virus Department' of the Institute (7) putting aside entirely his studies on yeast enzymes and fermentation (8). He insisted, however, that 'you could not call an action enzymic until you could demonstrate the nature of the substrate and of the 'split product''. He set out to do just that and at the same time was led to the recognition of a new enzyme – neuraminidase – and to define its specificity characteristics.

In his early observations within the new project it was found that, concomitant with the loss of activity of inhibitory mucoproteins (e.g. ovomucin and purified urine mucoprotein) following their incubation with influenza virus or RDE, a low molecular weight dialysable compound ('split product') was released. It was also clearly demonstrated that the enzyme associated with the virus is an integral part of the virus structure and not an adsorbed artefact. At this stage (1951) Gottschalk seemed unaware of the earlier observations of Blix or those of Klenk (vide supra). However, following a communication from Professor Blix in 1952, two publications on the properties of the urine mucoprotein appeared, by agreement, simultaneously in 'Nature', the one by Gottschalk and the other by Odin from Blix's Department in Uppsala. Gottschalk's paper is noteworthy for the suggestion that the mucoprotein has the configuration of a protein backbone to which are attached numerous small oligosaccharide units, which yield the 'split product' by enzyme action. Odin drew attention to the close similarity between the properties of Gottschalk's 'split product' and those of Blix's 'sialic acid'; he also demonstrated the presence of 'sialic acid' in a number of other inhibitory mucoproteins.

Other laboratories, in particular those of Klenk in Köln and of R. Kuhn in Heidelberg, also became active in the search for the chemical nature of the elusive 'sialic acids' (or 'neuraminic acids' in Klenk's nomenclature). Gottschalk had tentatively suggested an N-substituted isoglucosamine (fructosamine) formulation for the 'split product', although he was still uncertain of its homogeneity (9). Carbohydrate was accepted as a component, but the evidence as to the nature of the nitrogen linkages was equivocal.

Critical observations were made by Gottschalk when he identified 2-carboxypyrrole as a product arising from the mild alkaline treatment of (a) sub-maxillary and urine mucoproteins and (b) the 'split product' itself. Subsequent progress was rapid. He postulated in 1945 structures for sialic acid and neuraminic acid based on their relationship to 2-carboxypyrrole, and he reported the synthesis of this substance from D-glucosamine and pyruvic acid.

In the development of these highly important conclusions Gottschalk acknowledged his indebtedness to Dr J.W. Cornforth – then at the National Institute for Medical Research, London – for valuable suggestions. Cornforth was also associated with the successful synthesis of crystalline N-acetylneuraminic acid from the simple reactants N-acetyl-D-glucosamine and oxaloacetic acid.

With the structure of the 'split product' now established and his views generally accepted, Gottschalk turned his attention to the specificity characteristics of the enzyme, neuraminidase (10). Using as source of the enzyme both the influenza virus and purified RDE, and employing a simple substrate 'neuramin-lactose' (diacetylneuraminic acid joined to the disaccharide lactose) isolated from rat mammary glands, he was able to define the action as a cleavage of an O-glycosidic-type linkage involving the keto group of neuraminic acid and a sugar molecule. In bovine submaxillary mucoprotein the sugar was shown to be N-acetylgalactosamine.

Appropriately, his last publication before he went to Canberra and the Australian National University was in the nature of a review article in which he critically examined the mechanism of infection by influenza virus; here he brought together, in masterly fashion, all the then known biological and biochemical data.

Canberra (1959-1963)

In Canberra he found the environment most conducive to the successful continuation of his Melbourne studies. Besides Professor Fenner, two other distinguished virologists who had previously worked at the Hall Institute, S. Fazekas de St Groth and H.J.F. Cairns, were senior members of the Department. He was thus able to renew active collaboration with Dr Fazekas while his expert assistant (E.R.B. Graham) rejoined him from Melbourne. He also had a reliable young associate in W.H. Murphy (a PhD student), and on occasions he collaborated in joint projects with a neighbouring and well-equipped department of Physical Biochemistry.

In the early part of this period he was able to bring to fruition his assignment with the Cambridge University Press on 'The Chemistry and Biology of the Sialic Acids and Related Substances'. Although this now classical monograph consists of but 115 pages, growth in the field had been so rapid that less than 10% of the material covered was known prior to 1950. Subsequently he was in considerable demand as a lecturer in and reviewer of his special areas of research, a tribute to his enhanced reputation.

His laboratory investigations in Canberra and subsequently in Germany were dominated by his overall interest in the biochemistry, physical chemistry and biology of the mucoproteins, in particular those located in the submaxillary glands of sheep and cattle (referred to, respectively, as OSM and BSM), which had played such an important role in the elucidation of the mechanism of the cellular action of the influenza viruses (11). The published results of this work formed a series, Parts I-XVIII, of which Parts I-X were issued from the Department of Microbiology, the remainder from Tübingen. Among the major findings within the first group of papers were those that showed a close similarity between the structures of OSM and BSM in that the carbohydrate moiety (prosthetic group) consists of a single disaccharide, in each case sialyl-N-acetylglucosamine. The greater potency of OSM as a haemagglutinin inhibitor with certain strains of the influenza virus may be concerned with the nature of the sialic acid; in OSM it is uniformly N-acetylneuraminic acid whereas in BSM this terminal group is modified by other acylated forms. However, the inhibitory property in both cases appears to be related not only to the size of the molecules but to the presence of multiple points of attachment to the virus surface provided by the acidic terminal groups. In highly purified OSM, 58/59% of the macro-molecule (of molecular weight, 1.0 × 10⁶) is a protein backbone to which is attached 41/42 % carbohydrate divided into approximately 800 strongly acidic disaccharide units each of molecular weight 512. The disaccharide units in both OSM and BSM appeared to be linked predominantly (80-85%) in ester form with the residual free carboxyl groups of the aspartic acid and glutamic acid components of the polypeptide chain. The remaining links were considered to be O-glycosidic. However, on Gottschalk's return to Germany, re-examination of the methods used led to a reconsideration of these proposals (see below). The high viscosity of the mucoproteins was shown to be greatly reduced by removal of the terminal neuraminic acid by neuraminidase.

Finally, an earlier observation during this period is worthy of comment as indicating another role for terminal sialic acid. The follicle-stimulating hormone of the anterior pituitary gland (FSH) lost essentially all physiological activity with the removal of its sialic acid on incubation with purified neuraminidase. Incidentally, although it contains 5% sialic acid, FSH, with a low molecular weight of 29 000, is not inhibitory towards influenza virus (see also footnote 11).

Germany (1963-1973)

Although a major commitment in his latter years was with the preparation of 'THE BOOK' (Glycoproteins. Their Composition, Structure and Function), the laboratory was far from neglected. He was fortunate in having a number of able collaborators. Most of these collaborations deal with renewed investigations of the structures of OSM and BSM, in particular the former.

It was soon established, in agreement with other laboratories, that the dominant linkages between the N-acetylglucosamine component of the di-saccharide-repeating unit and the protein backbone were O-glycosidic involving the free hydroxyl groups of serine and threonine rather than linkages of the ester type (12). In the new approach OSM was subjected to proteolysis, the intermediate glycopeptides were treated with neuraminidase and the sialic acid-free peptides were separated and hydrolysed with weak alkali; N-acetylglucosamine was released in molar amounts equivalent to the loss of hydroxyamino acids. Subsequently, an enzyme was located in and prepared from ox spleen, from the snail and from the common European earth-worm (Lumbricus terrestris), which specifically hydrolysed the O-glycosidic linkages in OSM and intermediate glycopeptides, providing the sialic acid groups were first removed. A particularly pure sample of the enzyme was obtained from L. terrestris. The results of these studies left no doubt that the only amino acid residues joined to sugar in the disaccharide-repeating unit of OSM are those of serine and threonine.

In 1960 Gottschalk accepted an invitation by Elsevier to bring together all relevant data in the rapidly developing field of glycoproteins, and to incorporate the information as Volume 5 in the BBA Library. A steadily increasing number of proteins had been shown to contain carbohydrate and sialic acid. These included hormones, enzymes, blood group-specific substances, immunoglobulins, casein and constituents of cartilage, apart from the group of influenza virus-inhibitory glycoproteins. In addition to editing the monograph with its twenty contributors, Gottschalk was also author or co-author of seven of the articles. Since his departure from Australia we had maintained a steady correspondence which was augmented during the preparation of the book, since I was co-author of one of the sections. Thus I was able to appreciate more than ever his fanatical attention to detail. The first edition was acclaimed by the critics and led, after a short period, to a demand for a second edition which, now double the size, appeared in 1972, the Editor still managing to contribute ten articles as author or co-author.

Between editions, Gottschalk somehow found time to travel extensively, either attending conferences or as peripatetic lecturer. In 1967 he was in England, Japan and India while during the latter part of 1968 he was in residence at Vanderbilt University, Nashville, Tennessee, where he lectured, conducted seminars and wrote for the second edition. During this period he also travelled widely in the USA, discoursing on glycoproteins en route.

In 1971 he was invited by the Chancellor of the University of California to become the Regents' Lecturer located at the Riverside campus in the Department of Biochemistry headed by Professor Leland M. Shannon. Here he was in residence for the first three months of 1972. Apart from his duties at Riverside he gave lectures or seminars at the other campuses of the University. He found the total experience most rewarding and enjoyable, but exhausting towards the end of his term. However, the students and staff at Riverside were so impressed by his contributions that on the students' petition to the University a return visit was arranged and accepted for the corresponding period of 1973. Professor Shannon has written as follows: 'Professor Gottschalk taught two courses, delivered several seminars and led numerous discussions. We all marvelled at his breadth and depth of knowledge. His contributions to our campus were legion and his influence will remain with us for many years.' '...his sharp wit, his ease among people, his breadth of wisdom, his expectation of perfection, his insistence upon punctuality, are a few of the cherished and indelibly imprinted trademarks Professor Gottschalk left with us.'

Soon after his return to Europe he attended what was to be his last congress, namely that at Lille (France) arranged by Professor Montreuil as a CNRS Workshop Meeting on Glycoproteins with most of the internationally known authorities present. At this stage he designated himself (in a letter to Professor Buddecke) as the 'Nestor of the world's students in glycoprotein research' – in many ways an apt assessment.

Although his mind remained clear to the end, few knew that he had lived with a heart condition for some years. His physical strength eventually deteriorated and he died in his sleep just a few days after his close friend and colleague Professor Friedrich-Freska, Director of the Max-Planck Institute for Virus Research. They were buried in Tübingen in adjoining graves.

The formal announcement of his death as sent to relatives and friends and which was issued jointly by The Max-Planck Institute for Virus Research and The Friedrich-Miescher-Laboratory of the Max-Planck Society, Tübingen, contained this tribute:

Sein wissenschaftliches Werk trug unter anderem grundlegend zu unserem heutigen Verständnis der Virusinfektion bei. Wir verlieren in ihm einen grossen Biochemiker von internationalem Ansehen, einen bescheidenen und hilfsbereiten Menschen.

Notes

(1) Subsequently the Kaiser Wilhelm Institute for Biochemistry which became independent in 1925.

(2) Professor Butenandt had succeeded Professor Carl Neuberg in 1936 as Director of the Kaiser Wilhelm Institute, then still in Berlin. After the War, the Institute transferred to Münich with a change of name as indicated.

(3) Also a close friend who continued collaboration after appointment as Professor at the University of Münster, Westphalia.

(4) It seems likely that this attitude in part reflected that of his former teacher, Carl Neuberg, who, as Gottschalk himself related, was wont to peer over the shoulder of his assistant during titrations to make sure 'the values were obtained objectively'. Another incident as told to Bruce Graham was of Neuberg handing a paper in Japanese to Gottschalk with a demand for a translation by next day. The outcome is not recorded but, knowing Gottschalk, the German version was almost certainly ready as requested.

(5) Fenner comments: 'This was maintained 'as new', but turned in for a new model every two years. His care for the vehicle extended to wiping his feet (and seeing that passengers did likewise) before entering – but he never learnt to drive properly, in that he never travelled fast but crossed intersections at the same pace as he used on the open road, undeterred by cross-traffic.'

(6) Receptor Destroying Enzyme.

(7) It is appropriate at this stage to quote a tribute to Burnet from the Preface to Gottschalk's subsequent monograph on the Sialic Acids: 'Finally, I would like to take the opportunity to express sincere thanks to Sir Macfarlane Burnet, OM, FRS, who in 1947 suggested that I should approach the problem of interaction between influenza virus and mucins from the biochemical side. His stimulating and ingenious biological approach was a safe guide for many of my moves in the field. There must be few laboratories where the 'give and take' between biology and biochemistry is so closely wedded as at the Walter and Eliza Hall Institute. It is the biological flavour which makes the cold beauty of the chemical structures displayed in this book attractive'.

(8) Except to solve sometime later the problem of an Australian firm of whisky distillers. Thousands of gallons of the fluid were being spoilt by an acrylic flavour the source of which was rapidly pinpointed by the expert with the encyclopaedic knowledge; no laboratory work was needed.

(9) Crystallization of the 'split product' was not achieved until 1955 (by Klenk and colleagues).

(10) The neuraminidase from the more accessible Vibrio cholerae (RDE) was crystallized in 1959 by Ada and French (Hall Institute) and by Schramm and Mohr (Tübingen).

(11) It may be noted here that with the recognition of the wider distribution of carbohydrate-protein complexes of biological importance the vague term 'mucoprotein' was replaced by 'glycoprotein'. Moreover, complexes of the same type were already known which, although containing sialic acid, were 'non-inhibitory' and of much smaller molecular weight than the highly viscous macromolecules, OSM and BSM.

(12) Later findings with the reagent used earlier (lithium borohydride) suggested a source and explanation of the misinterpretation.

Emeritus Professor Victor Martin Trikojus, CBE, DSc, Head, School of Biochemistry, University of Melbourne, 1943-1968. Elected a Fellow of the Academy in 1954 and member of Council, 1958-1961.

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