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Ian Morris Heilbron. 1886-1959

by Alan H. Cook

Ian Morris Heilbron, younger son of David Heilbron, was born on 6 November 1886 in Glasgow. He received his early education at the High School, Glasgow, where he became fired by an enthusiasm for chemistry. In later years he often recalled the disfavour with which his father, who was prominent in both the commercial and social life of Glasgow, viewed his determination to take up chemistry as a career, for, at the time when science still seemed to have little relation to industry, the choice appeared to offer only a limited academic career. Fortunately for chemistry and indeed eventually for all science, the young Heilbron was allowed to follow his own bent and entered the Royal Technical College, Glasgow, where he quickly came under the enduring influence of G.G. Henderson, F.R.S., an influence which Heilbron fervently acknowledged to the end of his days. It was at Henderson's insistence that he took up a Carnegie Fellowship at the University of Leipzig where he studied under Hantzsch from 1907 to 1909 and took his Ph.D. degree. Having come from an unusually cultured environment in Glasgow, he particularly enjoyed the musical life in Leipzig. At this period he began a life-long friendship with R. Robison, F.R.S., later to achieve distinction in the biochemical field, but in later years he rarely referred to his work in Germany although it clearly had a pronounced influence in impressing on him the immense assistance which the organic chemist could derive from the application of physical methods. There is little doubt that this early experience led Heilbron directly to pioneer in due course the development in particular of spectroscopy, high vacuum distillation and chromatography in this country.

On his return, Heilbron, again on the ‘advice' of G. G. Henderson (see the first Henderson Memorial Lecture, Roy. Inst. Chem. 1947) became Lecturer at the Royal Technical College, Glasgow, until the outbreak of World War I. He had taken a Commission as Lieutenant in the R.A.S.C. in 1910, was posted overseas in the 52nd Division in 1915, and in 1917-19 served brilliantly, ultimately with the rank of Lieut.-Colonel, as Assistant Director of Supplies at G.H.Q. Salonika. He was three times mentioned in despatches, was awarded the Medaille d'Honneur of the Greek Order of the Redeemer, and at home was honoured with the award of the D.S.O.

After the war he worked for a short time in industry with the British Dyestuffs Corporation with which, in the later form of I.C.I. Ltd he maintained a close contact as Consultant until 1949. However, academic life continued to attract him and from 1919-1920 he was Professor of Organic Chemistry at the Royal Technical College, Glasgow, from 1920-1933 Heath Harrison Professor of Organic Chemistry in Liverpool, 1933-1938 Professor of Organic Chemistry (1933-1935), later Sir Samuel Hall Professor of Chemistry in Manchester, and from 1938-1949 Professor of Organic Chemistry at the Imperial College of Science and Technology, University of London. In each of these centres Heilbron came at an opportune moment to reorganize the teaching of organic chemistry and mostly this necessitated extensive physical refashioning of the whole department. To have carried out these tasks with the energy, brilliance and foresight which Heilbron so successfully brought to them would alone have indebted the scientific world to him. There are, however, still more substantial memorials to his work. One is surely reflected in his many publications, to some of which reference is made below. Another and possibly the most lasting and productive outcome of his efforts is associated with the capacity which he had to gather round him from many parts of the world young chemists of promise. Many of these proved apt pupils in the study of his personal approach to the organization of scientific work and have themselves since become leading figures in either academic or industrial life at home or abroad. It may be mentioned in passing that Heilbron, who was a member of the community of Liberal Jews, sometimes remarked that he found difficulty in accepting the conventional religious view of `life hereafter', but that he was happy to feel that his scientific life would continue after his physical life had ended, through his many former colleagues.

He retired from academic life in 1949 to become in effect the first Director of the Brewing Industry Research Foundation where he remained until 1958. At the outset the Foundation was still but a general conception and it was largely Heilbron's indefatigable energy, wide experience and lively imagination touching upon every detail of the new organization which eventually gave the establishment a form and cohesion such as few others could have achieved.

Soon after coming to the Imperial College, Heilbron's services were being sought in connexion with the war effort. So he acted as one of the Scientific Advisers to the Ministry of Supply from 1939 to 1942 and Scientific Adviser to the Ministry of Production from 1942 to 1945. During this period he played a leading part in the introduction of D.D.T. which had a significant effect on the conduct of the war in the Far East, in Africa and in the later phase in the Mediterranean area. He had improvised sleeping accommodation at his laboratory in London and was thus with exceptional energy able to maintain also the direction of the University department. Indeed, during the war and shortly afterwards, publications under his name appeared with increased frequency on a diversity of topics. For his war service he was knighted in 1946 and received the American Medal of Freedom in 1947, but his public service continued, for at different times after the war he was Chairman of the Colonial Insecticides Committee, Member and also Chairman of the Advisory Council on Scientific and Industrial Research, and Member and Chairman of the Advisory Council of the Royal Military College of Science. Moreover he was still, with so many other commitments, able to give valued advice over a wide field of industry and also for some years after the war was a leading figure in reorganizing the International Union of Pure and Applied Chemistry.

His great distinction led to many academic honours. He had been elected a Fellow of the Royal Society in 1931, received honorary degrees from Glasgow and Edinburgh, served as President of the Chemical Society (1948-1950), and was an Honorary Member of the French Chemical Society and a Foreign Member of the Royal Netherlands Academy of Sciences. In addition he had been honoured by many learned societies as by the award of Longstaff, Hugo Muller and Pedler Medals and Lectureships (Chemical Society, 1939, 1940 and 1947 respectively), Davy and Royal Medals (Royal Society, 1943 and 1951), Priestley Medal (American Chemical Society, 1945) and Horace Brown Medal (Institute of Brewing, 1959).

Apart from some 300 publications which dealt with his original contributions to knowledge, mention should be made of his part as Chairman of the Editorial Board in producing the latest edition of Thorpe's Dictionary of Applied Chemistry and in particular of his part, with H.M. Bunbury in compiling his Dictionary of Organic Compounds and piloting its several volumes through a number of editions as Editor-in-Chief.

Perhaps the most marked characteristic of all Heilbron's work was the meticulous attention which he paid to detail. None of his papers, lectures or even ordinary correspondence was ever merely ‘written'. All was written, then recast and rewritten, often several times over. Frequently a whole morning might be spent on one paragraph. Often the sole outward result, despite numerous passing references to dictionaries and scientific journals, was the insertion of a single adjective or some similar minor alteration. The outcome, however, usually seemed worth while for he would say ‘I always knew there was something wrong with it' and there was an obvious satisfaction in having perfected what to many would have earlier seemed beyond criticism. In the same way each of his spoken contributions, irrespective of whether it was for an international audience or perhaps for a much less formal occasion such as a meeting of a students' society would be prepared to the extent that literally each word was selected to express precisely and logically what he had in mind. Each illustration was purposefully designed so that all the essential data were included while unnecessary features were excluded. The result was invariably a performance which held his audience by its seeming spontaneity and at the same time by its obvious directness and unhesitating logic. Indeed, it was an important part of his artistry in this respect that first he always formulated a distinctive narrative and then told it in his own distinctive way. As the years went by so that he drew upon an almost unsurpassed experience in University teaching, Government service and as well in industrial research, his reminiscences became more cogent, for right up to the time of his death he was constantly looking as much to the future as to the past, always in touch with reality. There must be many colleagues on the numerous committees on which he served who will recall the seemingly psychic clarity with which he came to view every issue. A topic might have been discussed at great length apparently without a satisfactory course of action having emerged, when Heilbron would often put forward a proposal of almost dramatic simplicity which filled his colleagues with admiration and at the same time baffled them for having themselves failed to arrive at so obvious a solution. Certainly in later years he was well aware of his ability to anticipate in general terms with seemingly uncanny accuracy the reactions of those with whom he had to deal. Indeed he himself ascribed it to a well-developed but innate Jewish acumen though to most it was but one facet of his extraordinary mental ability.

All this, however, had to do with his public work. In private life he was one of the most delightful companions imaginable. Everything around him, for instance, his old English furniture, his collection of modern paintings and his fine antique porcelain, betokened the sensitive nature and those who were privileged to know him more closely were constantly being surprised by his wide appreciation of music, literature, other forms of art and indeed of human nature in general.

Between the extremes of public and home life there was the professor of chemistry known to some thousands of former students, several hundred of whom had carried out research under his direction. To them he, despite his small stature, could be frightening for he was always impatient of delay or of a lack of direct and constructive thought. The research student who sought to play for time by making such remarks as ‘I want to characterize it as a semicarbazone' soon learnt to exercise nicer distinction when silenced by the reply ‘I'm not stopping you'. The man who, to offset criticism of his report, might refer to it as a ‘rough draft', would be reduced to a state of acute anxiety by withering opinions of what was to be expected from ‘educated university graduates'. Heilbron's nature as a professor was, however, really one of scrupulous fairness and great kindness for he was always ready to help the student who responded to what was offered him. It would be difficult to imagine a professor who showed more concern for the welfare of his students, a concern which mostly continued in an unobtrusive but exceptionally generous manner long after his proteges had been launched on their own careers.

Heilbron's earliest research work (with the late G.G. Henderson) emphasizes today the immense span of his experience. It was concerned with various reactions of pinene, bornylene and camphene, more particularly in the latter cases with the structural relationship between the two. The formula of camphene accepted today had some time earlier been proposed by Wagner but the rearrangement which now bears his name was not at the time understood and Henderson and Heilbron still felt on the basis of their painstaking work that the two hydrocarbons were identical in ring structure as regards the greater part of their respective molecules.

On his return to Glasgow from Leipzig, Heilbron in association with F.J. Wilson took up what was at the time the novel study of semicarbazones, especially with regard to the phenomenon by which various carbonyl compounds such as phenylstyryl ketone and m-nitrobenzylidene- deoxybenzoin gave rise to two or more forms of semicarbazone. It is remarkable that from the first Heilbron in a pioneering manner placed great value on evidence derived from absorption spectra and was soon distinguishing with confidence between cases of stereoisomerism as in the case of phenylstyryl ketone, of structural isomerism as with mesityloxide and of tautomerism as in the ‘semicarbazones' of various quinones (with J.A.R. Henderson). At the same time the ability of semicarbazones to combine loosely with acids such as anhydrous hydrogen chloride was discovered (with F.J. Wilson, M.M.J. Sutherland and J.A.R. Henderson) but these investigations lapsed soon after the outbreak of World War I.

On returning to academic life in Liverpool in 1921, Heilbron appeared at first to be still mainly interested in structural questions in that a series of papers appeared (with J.S. Buck) dealing essentially with chromotropism and varying chemical reactivity among doubly conjugated unsaturated ketones and particularly among various distyrylketones (I). The high degree of reactivity among such compounds was believed to be due to internal complex formation. Interest indeed shifted to the benzopyrilium salts (II) of distyryl ketones in which ring formation could be given definite structural expression. In the case of the p-hydroxy compounds (II, R' = p-OH) the colour changes which followed on treating the chlorides with alkali were regarded as being due to the formation of p-quinonoid structures (III). Analogous quinonoid anhydrobase structures were suggested on this basis for the anthocyanidins. It is of interest to note that it was appreciated that this suggestion made it necessary to revise the structure proposed by Willstätter for malvidin which failed to make provision for the necessary phydroxyl group, a necessity which was later borne out.

During this period when he was clearly feeling his way towards still more sustained research, Heilbron carried out a certain amount of tentative work in other fields still concerned with ‘classical' organic chemistry. This included studies on such diverse topics as the chemistry of meso-thioanthracene compounds (with J.S. Heaton, W.H. Cooke and G.H. Walker) and the reactivity of methyl groups as for instance in the 2-position of the chromone (with H. Barnes and R.A. Morton) and of the 4-quinazolone rings (with F.N. Kitchen, E.B. Parkes and G.D. Sutton). Heilbron was always ready to turn his attention to a new aspect of organic chemistry and such miscellaneous studies continued over the next thirty years, but he was destined to make a still greater impact on the study of natural materials.

Shortly after assuming the professorship in Liverpool, Heilbron was collaborating with E. C. C. Baly and their colleagues on the apparent photocatalysis of the conversion of carbon dioxide into formaldehyde and thence into carbohydrates and other substances in presence of various coloured materials including chlorophyll. The findings were extended to a consideration of the origin of various nitrogenous compounds in plants. Although Baly believed passionately that the formaldehyde in question was formed by photosynthesis, Heilbron repeatedly related in later years that the results were vitiated by uptake of organic material from the rubber tubing used in the apparatus and he turned to a different and seemingly even more difficult field in the chemistry of fish liver oils, in the first instance of squalene (spinacene). Largely by his unwavering eagerness to draw upon all possible aid from physical measure ments, Heilbron was soon convinced of the identity of squalene with spinacene and at an early date (with E.D. Kamm and W.M. Owens) had correctly assigned the empirical formula C30H56, had put forward the structure which in all essentials is accepted today and drawn attention to the probable relationship between this compound and various sterols. From this point, his interest became mainly centred on the chemistry of natural compounds, at first on the antirachitic activity developed in ‘ordinary' cholesterol upon irradiation, an activity soon shown (with R.A. Morton and E.D. Kamm) to be due to the production of vitamin D from ergosterol. Soon structural changes undergone by cholesterol (with W.A. Sexton), the occurrence of zymosterol in yeast and of monoglyceryl ethers (selachyl and batyl alcohols) in fish oils (with W.M. Owens) and other topics were being investigated, but the characterization of ergosterol, its occurrence and spectroscopic identification in a wide variety of fish liver oils (with W. A. Sexton, E.D. Kamm, R.A. Morton and later J.C.E. Simpson) were a main interest and, within the context of the structures accepted at the time, revealed a number of new interrelationships as well as establishing correctly the empirical formula C28H44O. Simultaneously, Heilbron took up related work on the nature of the substituted naphthalenes and other products obtained on dehydrogenating squalene (with J. Harvey and D.G. Wilkinson) and broadened the interest of the whole line of inquiry by showing (with R.A. Morton) that the content of vitamin A in fish liver oils could also be assessed spectroscopically, observations which still provide the basis of the most reliable method of assaying the vitamin. From this point the chemistry of the sterols generally and also of vitamin A permeated most of Heilbron's work for several years.

A spate of publications from his pen did much to establish the general nature of vitamin A, the extent of its occurrence in various fats and oils, the preparation and characterization of its derivatives and in due course, the detailed structure in which, however, he was narrowly anticipated by Karrer and his co-workers. There can be no doubt on the other hand of the great permanent value of the painstaking and essential if sometimes unspectacular work which Heilbron carried out, largely in association with R.A. Morton, F.R.S., and the late J.C. Drummond, F.R.S.

The flood of diverse communications on such topics as vitamin D-, vitamin A-, carotene- and xanthophyll-contents of butter, the occurrence of vitamin A in small quantities of egg yolk (with A.E. Gillam) which went on for some years from about 1932-1937, was broadened still further by a growing interest in carotenoids as well as sterols and bile acids themselves. Shortly after the revolutionary proposals regarding the general structure of the sterols by Rosenheim and King and by Wieland and Dane in 1932, Heilbron (with J.C.E. Simpson and F.S. Spring) had correctly deduced in all important essentials the structure of ergosterol. With this background, he embarked on a detailed study of the chemistry of the algae and (with R. F. Phipers and H. W. Wright) discovered and worked out the structure of fucosterol (IV), the characteristic sterol of the seaweeds,

Turning to the carotenoids, various remarkable facts emerged. For instance, it became apparent that fucoxanthin, the characteristic pigment of the brown algae and in particular of Fucus vesiculosus, could be isolated only from fresh material, the drying of which was associated with the conversion of the pigment into zeaxanthin, the typical colouring matter of maize (with R.F. Phipers). Wider study revealed that each group of algae were associated with characteristic carotenoid pigments in which a gradual transition from the normal composition of land plants in this connexion could be discerned (with E.G. Parry and R.F. Phipers). This work was delightfully summarized in the Hugo Muller lecture in 1941 in which it became clear that the culminating point was the finding that in the dioecious Fucales such as Fucus serratus the female gametes are pigmented largely by fucoxanthin (apart from chlorophyll) whereas the male gametes owe their colour almost entirely to ß-carotene. Heilbron (with P.W. Carter, L.C. Cross and E.R.H. Jones) clearly appreciated the possibility that this differing pigmentation may be associated with the mobility of the male gametes and perhaps with their attraction to the egg, but the full significance of these findings still remains to be elucidated.

Naturally the possibility of synthesizing vitamin A and even polyene pigments themselves proved an early attraction. Much of the laborious work was at first concerned with attempts to use ß-ionone (V) to develop methods of building up the necessary extended side chain in the vitamin (VI) itself and, while obstacles were being overcome, to put accumulating experience to good use by obtaining analogous compounds. For instance, considerable effort was first devoted to synthesizing the C15-aldehyde (VII), e.g. by the condensation of ß-ionone with acetylene followed by rearrangement of an intermediate acetylenic carbinol. A satisfactory synthesis of the vitamin, however, proved elusive by routes of this type owing to the anomalous behaviour of fl-ionone and many of its derivatives. In consequence, Heilbron's attention became focused on the potentialities of the C14-aldehyde (VIII) or its equivalent (IX). He soon perceived that an aldehyde which had been claimed to have structure (VIII) in 1937 was actually derived from ß-ionone and therefore useless. There is, however, no doubt that his painstaking work (with A. W. Johnson, E. R. H. Jones and A. Spinks) in synthesizing the required aldehyde from ß-ionone provided the basis on which the synthesis of the vitamin itself was ultimately based. Heilbron envisaged the synthesis as involving the incorporation of (IX) with acetylene and a ketobutanol derivative to give the required carbon skeleton:

This scheme permitted many variations but unfortunately the conditions during war-time and particularly the lack of ßionone prevented its full exploration. Its correctness was nevertheless completely established by the synthesis carried out by Isler et al. (Hela. Chim. Acta, 1947, 30, 1911). Meanwhile Heilbron and his school were taking full advantage of the opportunity to study the condensation of aß-unsaturated carbonyl compounds with acetylenic compounds of various types. Here perhaps one of the most fruitful results has been to establish the generality of the anionotropic rearrangement whereby acetylenic carbinols typified by (X) undergo a change such that completely conjugated compounds of type (XI) are formed (with E.R.H. Jones and co-workers). These basic reactions together with numerous variants and elaborations led to many quite new types of compound and indeed the diverse possibilities so opened up will undoubtedly continue to form the subject of research efforts in widely separated laboratories for many years to come.

While this voluminous work was gathering momentum, other sections of Heilbron's growing school of research were pursuing quite different but still remarkable lines of inquiry. He had become interested in studies on the Gomberg reaction carried out in his Department (W. S. M. Grieve and D. H. Hey, J. Chem. Soc. 1938, p. 108) whereby the interaction of diazonium compounds with various other benzenoid substances led to union of the aromatic rings (with D. H. Hey and R. Wilkinson) :

These studies led, among other results, to the synthesis of many substituted diphenyls, phenylnaphthalenes, terphenyls and even to a range of phenylpyridines and pyridyldiphenols (with J.W. Haworth and D.H. Hey). Even this rich harvest failed, however, to satisfy Heilbron who turned the accumulated experience in this field to the synthesis, mostly via appropriate nitro- and aminophenylpyridines, of a wide range of pyridylquinolines which acquired considerable interest because of their promise as antispasmodics in the therapeutic field (with H. Coates, A.H. Cook, D.H. Hey, A. Lambert and in part F.B. Lewis and others) : (see over)

During World War II when all these farreaching investigations were being pursued at a phenomenal rate, especially considering the demands of government service, Heilbron's tireless energy still made it possible for him to take up the question of the chemistry of penicillin. So, in association with the writer and numerous colleagues, methods of purifying the antibiotic were devised so as to provide concentrates suitable for structural studies. There followed, as part of the collaborative Anglo-American effort in this connexion, a succession of reports, mostly reflected in later contributions to The chemistry of penicillin (Princeton University Press, 1949). Among the more general topics mention may be made here of the recognition of the formation of a dihydropenicillin-I (dihydropenicillin-F or n-amylpenicillin) as distinct from the penicillins-I and -II (2-pentenyl- and phenylacetyl-penicillins or -F and -G respectively) then being studied notably in Oxford and the United States. This led at length to the view that dihydro-penillaldehyde had the structure (XII) as was speedily proved by synthesis, a finding which at once opened up the possibility of synthesizing n-amylpenicillin. As is now well known, the synthesis of the various penicillins continued to tax the combined efforts of many chemists. However, the early synthesis by Heilbron and his team of n-amylpenillamine and later, among many other key substances, of a DL-compound with the ring structure of the penillic acids (XIII) did much to stimulate efforts towards obtaining the antibiotics by synthesis. Heilbron's contribution to this general topic was by no means limited to synthetical approaches. It is noteworthy, for instance, that his group was the first to recognize the existence of p-hydroxybenzylpenicillin (penicillin-III or -X) and to establish the feasibility of obtaining it by deliberately bringing about its biosynthesis.

It will be evident that it was characteristic of Heilbron's approach to a problem that he was never content to direct his efforts solely to the prime object. Each project was seen as opening up wide fields of exploration often in directions which for a time seemed widely divergent from the major goal. So his work on the attempted synthesis of the penicillins soon led to other achievements including a new synthesis of methionine and similar aminoacids (with J.R. Catch, A.H. Cook and A.R. Graham) and, more significantly, to the synthesis of a variety of new classes of heterocyclic compounds such as (XIV) typified by the reaction (with A.H. Cook and A.L. Levy) :

Where R' was specially reactive as with .OH, SH and NH2 the ring compounds were found to undergo a variety of reactions under mild conditions. For instance, when R=H and R'=SH, the cyclic aminocompound was readily converted into the thiazolone (XV) which in turn by a neat sequence of reactions was made to yield a variety of substituted cysteines (XVI).

Furthermore, by the introduction of appropriate substituents, the 5-membered ring was made to form the basis of numerous new pyrimidines and pyrimidine analogues (e.g. with A.H. Cook, S.F. Macdonald and A.P. Mahadevan).

Heilbron had in 1924 married Elda Marguerite Davis, daughter of H. J. Davis of Liverpool, and had two sons both of whom survive him. Lady Heilbron had in every possible way shared his love of the arts and in addition, as was soon obvious to all who had the privilege of knowing her, possessed to a rare degree a kindly and sympathetic understanding of human nature. Her sudden passing at a comparatively early age in 1954 was understandably a great shock to Heilbron, one from which he possibly never fully recovered. His mental powers remained as keen as ever they were and his physical capacity was still quite exceptional, but the ‘thoughts that breathe and words that burn' were perhaps coming with rather less vigour for some time before his sudden death on 14 September 1959.

In this necessarily brief account of Heilbron's life and work much has had to be omitted. Let it be hoped, however, that what has been written may convey some reflexion of a great man. For Ian Heilbron was more than a unique chemist. He came to belong to all science in the university, industry and government service both at home and abroad. Nor did he excel only in the politics of scientific advance for he became to an extent that few others have become, an elder statesman of science.

A.H. Cook

The above is reproduced with the kind permission of the Royal Society. The full version of this article, containing an extensive bibliography, is published in Biographical Memoirs of the Royal Scoiety, Vol. 6 (November 1960), 65-85.

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