A Time to Remember

by Alexander Todd

  When we went to Manchester in 1938 my wife and I rented a largish typical Manchester villa in Broadway, Withington, and found ourselves living directly opposite another very well known organic chemist, Arthur Lapworth - one of the great figures in the development of modern views on the mechanism of organic reactions. Before this I had met him only once and that for a few minutes when Robert Robinson, one of his friends and a great admirer, introduced me to him at a Chemical Society meeting. Lapworth was Professor and Director of the Chemical Laboratories when Heilbron came to Manchester but was dogged by ill-health and finally resigned his chair in 1935. From 1938 until we moved to Wilmslow in 1941 I used to visit him each Sunday morning and chat about chemistry and chemists over a cup of coffee. These coffee mornings were kept under careful control by his wife, Kate Lapworth - a dragon-like lady who would storm in after about three-quarters of an hour, collect the coffee cups and unceremoniously send me about my business. I greatly enjoyed those talks with Arthur Lapworth and learned a lot from him. Mrs Lapworth made little attempt to conceal her view that I was something of a come-down as occupant of her husband's former chair. For one thing I was not a Fellow of the Royal Society when I took office and I remember vividly her reaction when, greatly to my surprise and delight, I was elected to the Fellowship in 1942. On being told by someone about the election she merely grunted and said 'And about time too!'

  During my first year in Manchester we completed our studies on vitamin E and effected the total synthesis of alpha-tocopherol and its analogues. We were forestalled in the synthesis of the alpha-compound by Paul Karrer of Zurich who completed it a week or two before we did. The reason for this was rather absurd; to do the synthesis we needed the complex alcohol phytol which is a component of chlorophyll. Heilbron was the only man in England who was said to have any of it and he sent me a sample to carry out my synthesis. Unfortunately he made some mistake, and the material he sent me was not phytol. It took me a little time to find this out and get hold of some genuine phytol, (from Hoffmann La Roche) and while I was doing so Karrer completed his synthesis. Such things happen in research, but in the long run are not really important. We also pushed ahead with our work on Cannabis using column chromatography extensively in attempts to isolate the active principle or principles in a pure state. In this we failed, largely because our purification procedures, including preparative chromatography, as it was at that time, were too crude to make such isolation possible; indeed, something like twenty years were to elapse before it became possible for Israeli workers to take up the fractionation of Cannabis resin again using improved techniques, and succeed in isolating the active principle. However, when we set about the synthesis of cannabinol, an inactive constituent which had been first isolated and studied by Cahn some years before, our route took us via an intermediate tetrahydrocannabinol which showed powerful hashish-like action in rabbits. Our view at that time that the physiological effects of Cannabis were due primarily to another of the several possible isomeric tetrahydrocannabinols was vindicated much later, but we did little more work in this field since by that time (1940) the tempo of war work was increasing and we were forced to abandon the Cannabis research and never really went back to it. The synthesis of a variety of analogues of tetrahydrocannabinol was the subject of a good deal of work by Roger Adams and his school at the University of Illinois, they being still free of wartime restrictions. I had something of a contretemps with Adams on priorities in synthesis and publication in the Cannabis field at that time; with hindsight it now seems rather trivial, and it did not prevent us from becoming fast friends when we met after the war ended in 1945.

  When Germany invaded Poland in 1939 Alison and I were on holiday at Ballantrae in Scotland. We at once drove back to Manchester where we got busy with blacking out the laboratory windows and doing the same job at our house in Withington where we also had to carry out the conversion of our cellar into a tolerable air-raid shelter. Our first child - a son - was born to our great joy on 11 November 1939 during the quiescent period known as the 'phony war' which lasted until the spring of 1940 when the Germans overran France. We then had to make a difficult decision, for many university people were sending wives and children to Canada or the United States to spare them from the intensive bombardment and possible invasion of Britain which everyone expected, and we had urgent invitations from the Bests in Canada and the Paulings in California. After much thought we decided that we should face as a family anything that was to come rather than separate, possibly for years, and perhaps for ever. In the same way we decided, after a few weeks' trial later on, when Alison and our son Sandy stayed with some friends in the Vale of Clywd, north Wales, that we would also eschew even that degree of separation. We never regretted our decision to stick together, although, when the heavy bombing of the Manchester area took place in the winter of 1940-41 and we were expecting our second child, we moved out of Manchester proper and in the summer of 1941 went to live in Wilmslow, some miles out to the south, whence I commuted daily to the university.

  The outbreak of war soon brought other preoccupations and responsibilities. The chain of events leading to my appointment to Manchester had begun with the death of Sir Jocelyn Thorpe who was head of the chemistry department at Imperial College. He with Robert Robinson and Ian Heilbron made up the Dyestuffs Group Research Committee of I.C.I. Ltd, which held monthly meetings with the research chemists and management of the Dyestuffs Group at the Group's headquarters at Blackley in north Manchester. Since Thorpe's death the Committee had been one short. I.C.I. Dyestuffs Division (as it was now to be called) was beginning to awaken to the possibilities of synthetic drugs, and clearly this was likely to be a field which would undergo substantial development under wartime conditions. Whether or not it was due to my interest in and connections with that kind of activity I cannot say, but, at any rate, I was invited in the autumn of 1939 to join Heilbron and Robinson on the Group Committee now re-named the Dyestuffs Division Research Panel. To it as the pharmaceutical activity developed under Dr C. M. Scott, there were added the pharmacologists A. }. Clark and J. A. Gunn, and Warrington Yorke, an expert in tropical medicine; years later the pharmaceutical activities were hived off into a new Division, I.C.I. Pharmaceuticals, the chemical members of the D.D.R.P. continuing to act as advisers thereafter to both Divisions. This association with I.C.I. Dye-stuffs and Pharmaceuticals begun in 1939 continued formally for over twenty-five years; it remains today a happy informal association which has given me many friends over the years.

  Very soon after the outbreak of war I found myself involved with chemical defence research and development. There was at the time an unwarranted assumption that chemical warfare would be let loose on the civilian population and (in my view) a grossly exaggerated idea of the attendant dangers. As a result it was not surprising that there was a good deal of time wasted initially in investigating potential chemical warfare agents and in trying to devise new ones by completely hit and miss methods. To say that we were ill-prepared for chemical warfare in this country (apart from the provision of gas masks for civilians) would be to put it mildly, and it seemed that in the matter of considering new agents, or even the manufacture of known ones, virtually no progress had been made since the First World War. I soon found myself drafted, first as a member then as Chairman of the Chemical Committee which, under the Chemical Board of the Ministry of Supply, was responsible for development and production of chemical warfare agents. The research establishment mainly involved in this work was at Sutton Oak, St Helens, not very far from Manchester and manufacturing facilities were available through I.C.I. plants at Runcorn, Widnes and Blackley. All these are convenient to Manchester and so I remained stationed there throughout the war and was able to keep a reasonable measure of my own research going in the university in addition to work for the war effort. The Chemical Committee used to make occasional visits to the Sutton Oak establishment during the first couple of years of the war while the fear of chemical warfare was still very much to
the fore. I recall much discussion about the virtues of the 'brass still' in the purification of mustard gas; as far as I could discover, however, its only virtue lay in the fact that, for one reason or another, and probably merely because of its availability at the time, a brass still had been incorporated in a plant that worked successfully in 1918. Now in 1940 a similar item, it seemed, had to be put into any new plant which was to be built!

  The situation regarding arsenical sternutators which had been developed and, I believe, used by the Germans in the First World War was also rather ridiculous. After that war our chemical defence people had undertaken a study of the German manufacturing process of diphenyl chloroarsine by what was known as the double diazotisation process, starting from aniline and proceeding via a procedure well known in the dyestuffs industry called diazotisation modified so as to permit the introduction of arsenic into the molecule. The result of the study was recorded in a voluminous report purporting to show that it was theoretically(!) impossible to get more than about thirty per cent yield of product. This appeared to me to be such nonsense that I undertook to show that I could produce an effective process for manufacturing diphenyl chloroarsine by this method. I was, rather reluctantly, given permission to have a go, and with two research students and a dyestuffs chemist we borrowed from I.C.I. we not only demonstrated that we could get yields approaching the theoretical in the laboratory, but we went up to Blackley Works and there made the necessary arylarsonic acid successfully on a pilot plant producing five tons per week. This was a great experience for me and for the boys in the laboratory; we not only vindicated our criticism of the government report, but we learned quite a lot about the problems encountered in passing from a chemical experiment in the laboratory to large-scale manufacture. Subsequently we used our experience to develop a pilot plant for the production of the so-called 'nitrogen-mustard', but abandoned it when we had a disastrous explosion while chlorinating a sample of methylamine which, unknown to us, was contaminated with ammonia; we wrecked a laboratory, but by sheer luck no-one was injured. I need hardly add that our efforts in these areas contributed precisely nothing to the war effort since chemical weapons were never used.

  However, my chemical defence commitments had their lighter moments. I recall being called upon to travel down to the Defence Research Establishment at Porton to watch a demonstration of a new chemical weapon for use against tanks. It must have been in 1941, because air-raids were heavy and frequent, tobacco was very scarce and, as petrol was equally hard to come by, I travelled down from Manchester by train through Bristol to Salisbury. As it happened Bristol had a big raid on the night my train was passing through and we had to lie stationary in the railway yards with bombs dropping uncomfortably close until the raid ended. We then trundled on through the placid countryside of south-west England and arrived at Salisbury around 8 a.m. where I was to breakfast before setting out in an army car for the demonstration on the open plain near Porton. Now, in those days I was quite a heavy cigarette smoker and the modest supply I had wheedled from my supplier in Manchester had long since gone and I was rather desperate; but, needless to say, I could find no-one in Salisbury who would supply me with any. So I breakfasted, trundled off to Porton, watched gloomily a rather unconvincing weapon demonstration and was taken to the local officers' mess for lunch. After having a wash I proceeded to the bar where - believe it or not - there was a white-coated barman who was not only serving drinks but also cigarettes! I hastened forward and rather timidly said 'Can I have some cigarettes?'

  'What's your rank?' was the slightly unexpected reply.

  'I am afraid I haven't got one,' I answered.

  'Nonsense - everyone who comes here has a rank.'

  'I'm sorry but I just don't have one.'

  'Now that puts me in a spot,' said the barman, 'for orders about cigarettes in this camp are clear - twenty for officers and ten for other ranks. Tell me what exactly are you?'

  Now I really wanted those cigarettes so I drew myself up and said 'I am the Professor of Chemistry at Manchester University.'

  The barman contemplated me for about thirty seconds and then said 'I'll give you five.'

  Since that day I have had few illusions about the importance of professors!

  In wartime air-raids, fire was perhaps the greatest danger we had to contend with, and the university - and especially departments such as chemistry - took fire precautions very seriously. At the outbreak of war word was sent to all departments to examine all attics and ensure that they contained no inflammable materials. I well remember our venture into the attics in chemistry. We must have been the first entrants for many years, and we were somewhat taken aback to find in straw-lined open boxes a considerable number of sealed bulbs containing metal alkyls which dated from the last century and evidently belonged originally to Frankland (their discoverer). As these compounds are spontaneously inflammable they represented a considerable but entirely unsuspected fire risk even in peacetime! Another somewhat alarming discovery was made when we decided to look at our basement as well as our attics. Here we found several large bottles of mustard gas and a substantial amount of rather ominous looking decaying cordite; these we decided not to touch ourselves but to have dealt with by an army bomb-disposal unit.

  Following this preliminary clean up, firewatching was put on an organised footing. In the chemistry department we had a rota system in which no distinction was made between teaching staff, technical staff and research students although it happened that most of the technical staff were engaged in firewatching or Home Guard duties in their home areas so that our departmental firewatching teams were made up for the most part of staff and research students and included about once or twice a week Ralph Gilson, F. S. Spring, at that time Lecturer in Organic Chemistry, and myself. These were rumbustious nights with every conceivable practical joke laid on and very little sleep for the participants even in the absence of raids. In my view the firewatching system was a huge success in a quite unexpected way. It brought into intimate contact research students and staff and I believe it made the Manchester chemical school of those days into a tightly knit group and set up relationships of mutual trust and respect that have endured to this day. I for one shall always cherish the experience of those nights on duty.

  By the summer of 1941, when I moved with my family to our house in Pownall Park, Wilmslow, we were glad to have a good garden where we could grow vegetables and keep a few hens, for food was none too plentiful and at times not very good. We were especially fortunate because with the house we inherited a part-time gardener and odd job man, Harry Hardy (or 'Arry' Ardy as he would have put it), an ageing native who had worked locally on the land all his days, and who lived in a minute cottage nearby on the edge of Lindow Common. Hardy had a smallholder friend, George Potts, on whom we used to drop in of a Sunday morning, and through him we were able to get a decent supply of fruit, of potatoes and other vegetables, and even the odd chicken or duck. Petrol was, of course, also difficult to come by and I recall when my wife was in the maternity hospital a mile or two away at Prestbury for the birth of our first daughter, Helen (on 13 July 1941), I used to traverse the hot dusty road from Wilmslow to visit them on a 'utility model' bicycle which Ralph Gilson had somehow or other obtained for me from a little shop in one of the less salubrious sections of Stockport Road near Ardwick.

  One evening in the late winter of 1943 - I seem to remember that it was in February or March - I was on firewatching duty in the laboratory and had gone to do some writing in my room when about 9 p.m. the telephone rang. I picked it up and heard a voice say 'This is the Vice-Chancellor of the University of Cambridge. The electors to the chair of biochemistry have just met and it is their unanimous wish that I ask you to accept the chair as successor to Sir Frederick Gowland Hopkins. We wish to publish the name of Sir Frederick's successor on the Senate House wall tomorrow and would like to have your agreement.' To say that you could have knocked me over with a feather would be something of an understatemen
t. I knew, of course, that Hopkins was retiring; but I not only knew that I was by no means a biochemist as the academic biochemists understood the term, but I also knew the person who was generally expected to succeed Hopkins and his name was not Todd. So I stammered 'Do you mean you would like me to give you an answer to your question now?' 'Yes,' came the reply. 'Then Vice-Chancellor the only reply I can give you is no.' There was a moment of silence at the other end and then the Vice-Chancellor said 'Would you hold on for a moment while I have a word with the electors.' I then heard sounds of a discussion in the background and after a moment or two I had in succession my father-in-law Sir Henry Dale, Sir Robert Robinson and Sir Charles Harington on the line. The burden of their song was ' Don't insult Cambridge by turning it down flat - at least agree to come and have a look at it.' The upshot was that I agreed that I would go to Cambridge, look at the biochemistry department, and defer my answer until I had done so.

  Accordingly, a week or so later I travelled down to Cambridge and stayed at Emmanuel with the Master (Dr Hele), himself a biochemist, and spent the following day looking at the position in the Sir William Dunn Department of Biochemistry. It quickly became clear to me that it was no place for me. It is difficult now to summarise my reactions without appearing to be unfair but briefly they were as follows:

  (1) There was no real unity of purpose in the department. It was a series of little independent kingdoms sharing the departmental budget between them and the only gesture to unity was an almost sycophantic attitude to Hopkins on the part of the leaders in each of them.

  (2) With the exceptions of Robin Hill and F. G. Hopkins himself the staff seemed to have little or no interest in the only aspects of biochemistry in which I had any expertise.

  (3) The teaching courses were to my mind thoroughly inadequate as regards their chemical content and could produce no students who would fit into my type of work.