I should mention at this point that the people named above including Openshaw, but with the exception of Holland (whose present whereabouts is unknown to me) and Waring, represent the core of a remarkable dining-club known as the Toddlers Club. The club was formed in 1971 at the instigation of Ralph Gilson and its members dine together annually; membership is limited to myself and those who either moved with me from Manchester to Cambridge, or had arranged to work with me at this time. (These latter were A. W. Johnson [Deceased 5 December 1982] from Imperial College via wartime work in I.C.I., C H. Hassall from Dunedin, New Zealand and J. Davoll, a Cambridge undergraduate.) Although now widely scattered in the country and abroad, the Toddlers (eighteen in all) maintain close contact, and all gather in Cambridge for the annual dinner in May. So far one member (G. W. Kenner) has been lost by death, and only one has been added - Herchel Smith, who did his undergraduate work in Cambridge and, like Davoll, joined my group there.
I left Manchester after much hesitation and with much regret; the University of Manchester will always retain a very firm place in my affections. After all I was a very raw youngster when I was appointed, and, looking back, I think the university, and especially its Vice-Chancellor, were taking a considerable risk when they chose me in preference to at least two other well-known chemists (both my seniors) whom I later discovered they had also interviewed. As it turned out, however, and thanks in no small measure to the help I had from everyone in authority and the loyalty and friendship of my staff and students, I think I justified their faith in me. I learned a tremendous amount during those six years - in fact I grew up. I learned how to organise and administer a department without getting bogged down to the extent of allowing administration to interfere with research; I learned too how to choose a research topic and, having done so, to pursue it without allowing myself to be deflected into the interesting little side alleys which always turn up, and which have been the undoing of so many. In a way research is like golf- you must keep your head down and your eye on the ball!
Sometimes people say it is a pity my stay in Manchester was effectively during the war years. No doubt there would have been a wider social life had there been no war, but, against that, I doubt whether the intimacy between me and my students would have developed to anything like the same extent in peacetime. It is also to be remembered that Alison and I were recently married and that our first two children were born during our stay in Manchester. In the early days of a family, I rather think it would take more than a war such as we had to blunt in any way the happiness we enjoyed.
The move to Cambridge was successfully accomplished with little interruption in our researches, although I think the university was rather taken aback by the great invasion. By the time we moved, the uranium workers and St Bartholomew's had gone and Queen Mary College was due to leave shortly. We had got in a good supply of the equipment we needed, and, although we had not got rid of the gas lighting, its removal and replacement were imminent. Before it was replaced, however, we had several fires in the laboratory. One I remember was alarming, although it did not do a great deal of damage. A member of the research group - I think it was Norman Whittaker - held up a large flask of near-boiling petroleum ether to the gas light over his bench to see whether all the solid material in it had dissolved; the resulting conflagration was quite spectacular.
Our family removal to Cambridge also had its lighter side. I was able to purchase a house in Barrow Road, but could not get possession of it until the war was actually over. To bridge the gap, I was able to rent a furnished house in Sedley Taylor Road belonging to Sir John Cockcroft who was, of course, involved elsewhere in the wartime atomic bomb project; the house was to be vacated by its then tenants, the Rev. J. Boys-Smith and his wife, in September 1944. Now at this time, owing to acute housing shortages, a house left empty for more than twenty-four hours was liable to be seized by the local authority or by squatters, so we had to make rather unusual arrangements for the move. Using our penicillin talisman we hired a lorry in Manchester which would take a substantial part of our laboratory equipment (as well as the personal effects of most of the migrating research school and the bits and pieces of household equipment we needed urgently), and arranged that it should go to Cambridge on the exact day when Boys-Smith was moving out. With the lorry went three of my research group, who camped out in the Sedley Taylor Road house until I and my family came down a day or two later. My own most vivid memory of that move is of the trip I made back to Wilmslow a day or two later to fetch the family cat, a black and white animal of dubious ancestry who gloried in the name Sir Samuel Hall. Sir Samuel did not approve of either the basket in which he was confined or the journey, and said so vigorously; we had an uproarious half-hour while changing trains at Rugby, while Sam competed vocally with about a hundred cheerful Italian prisoners of war who were being transferred from one camp to another. Overall, however, the move to Cambridge went pretty smoothly, and by the end of September 1944 we had settled in both at home and in the old University Chemical Laboratory in Pembroke Street.
In the laboratory Gilson and I began the process of reorganisation and revitalisation forthwith. We met with very little opposition, and even F. G. Mann who, perhaps not unnaturally, felt he had greater claims to the Cambridge chair than I had, gradually, if reluctantly, came round, after some rather tiresome behaviour, to the view that our reorganisation made life easier and better for everyone, including himself. From the start we had the full support of B. C. Saunders and of Hamilton McCombie, who, until his retirement not long afterwards, was a tower of strength and a mine of information about Cambridge in general and its chemistry school in particular. We began by tackling the library and introducing a centralised system for the purchase and issue of chemicals and equipment. My predecessor had used the departmental library as his private room; I gathered that access had been possible only through the goodwill of Miss Stoakley (the daughter of the former laboratory steward) who acted as a kind of secretary, although she had no shorthand and was a rather indifferent typist. This had two results - firstly that the library was inadequately used, and, secondly, that there was considerable uncertainty about the ownership of some of the contents (I discovered, to my surprise, that many of the books bought by the laboratory were stamped with my predecessor's book-plate). This uncertainty of ownership may explain why, following Pope's death and before I came to Cambridge, Pope's executors had sold a considerable section of the library, presumably in all good faith, including a complete run of Liebig's Annalen der Chemie to Boots Ltd, and added the proceeds to the estate. Fortunately, I was able to restore the position by getting some journals on permanent loan from the University Library, so that we did not suffer too much. But I remember well Charlie Lister's astonishment when I told him I did not wish to have my book-plate put in any books purchased by the laboratory! In setting up a central store (and incidentally reorganising the whole office administration) we called in everything lying around in private stores of present staff members and in the forgotten stores of those who had gone before, and combined them with a weird collection of stuff (including a dozen Lewis guns fitted with cameras and several gross of milk bottles) which was housed in a basement room called 'the store'; we did meet a little resistance from the owners of private stores, but they soon came round when they found how much better the new system was.
During the first year or so we were without two senior members of the Cambridge staff, F. B. Kipping and P. Maitland, who were serving with the armed forces. When they returned they both contributed a lot to our progress. Kipping I put in charge of all academic administration, and this he did excellently until his untimely death some fifteen years later. During that first year I was also able to persuade H. J. Emeleus to leave Imperial College and join us as Reader in Inorganic Chemistry. Emeleus was the outstanding inorganic chemist in the country, and we were extremely fortunate to get him; his Readership was soon converted into a Professorship, and inorganic chemistry was back on the map in C
ambridge to everyone's advantage. We had a little trouble at first getting hold of some laboratory space for Emeleus' research. What would normally have been his area had gradually been taken over by U. R. Evans and his corrosion group (which really should have been in metallurgy and which, indeed, I transferred to that department when it was reorganised under Professor Austin). Corrosion work kept on acquiring space, because its progress appeared to demand that a continually growing series of laboratory benches should be covered with little glass beakers containing a variety of fluids into which pieces of metal had been placed, and which were simply left to stand there for months, or even, in some cases, years. The problem was solved when I pointed out to Evans that there was no need to cover all the benches with his beakers, and that these might be stacked somewhere in much less space. This apparently novel idea was accepted, and at once a substantial amount of laboratory space became available for Emeleus!
When I went to Cambridge I found that the university was run very differently from Manchester - and, I would guess, less efficiently. From my standpoint as head of a big scientific department, the Cambridge system of making a block grant which was paid into a departmental bank account each year was a very useful one, for it meant that the distribution of expenditure over various items in the budget could be varied a good deal, provided always that the auditors gave a satisfactory report on the accounts for transmission to the university's Financial Board. We did very well out of it in the early years, since our reorganisation soon revealed that the departmental budget was really much more adequate than had previously been believed, and the university was always prepared to listen sympathetically to us when we had a good case for increasing it. The university's contribution, together with generous grants placed at my disposal (especially by the Rockefeller Foundation and Hoffmann La Roche) in support of my researches, greatly facilitated the rapid build-up of my research school in Cambridge. Nevertheless, it seemed to me that the university's control was too slack during my early years in Cambridge; I was probably right in this, because it was tightened up very considerably later on. Although it, too, was changed within a few years, the system under which the university teaching staff was paid struck me as quite extraordinary. The stipend of a university lecturer was quite derisory (I think it was £150 p.a.) and included payment for a few hours of teaching. Undergraduate teaching over and above this was paid at an hourly rate. If the lecturer was a Fellow of a college he would receive in addition a college stipend plus payment for teaching or other work in college; in this way he could make quite a reasonable living. If he were not a Fellow, however, he received from the university a modest 'Fellowship Allowance', but if he were to get a living wage he had to do a lot of extra teaching. I well remember each year sitting down with a list of my staff members and, having first worked out what would be a reasonable salary for each individual, calculating the almost astronomical number of hours extra teaching (largely fictitious) they must do to get it and solemnly entering it in the official departmental return to the university.
After just about a year in Cambridge the war came to an end and the pace of our life quickened. We became finally settled as a family by moving into our own permanent home in Barrow Road in the late spring of 1945 and in the summer of the following year on 25 June our daughter Hilary was born. But even before then the influx of overseas students - soon to become a flood - had begun and I found myself becoming increasingly involved in a variety of activities in Cambridge, London and overseas. Throughout all of these my researches were continuing, and indeed expanding, as a result of the increasing number of young chemists seeking to join our school. It is not easy to incorporate the progress of research in a narrative of one's career, and I think it will be simplest if, at this point, I set down a brief outline of the development of my major research interests over the years in a separate chapter.
5. Chance and design in research. The road to vitamins, coenzymes and DNA
During the wartime period in Manchester I was able, despite other preoccupations (and the need to attend far too many committees which multiplied alarmingly in the university), to make, with my colleagues, surprisingly good progress with research aimed towards nucleotide coenzymes. Thus, we devised new methods of phosphorylation and began to understand the chemistry of the organic phosphates and polyphosphates, and we produced new methods of synthesis, not merely for pyrimidines and purines, but for their glycosides (the nucleosides). Alongside research, however, we were making some notable improvements in laboratory equipment. Ralph Gilson was quite remarkable for his appreciation of laboratory needs, and for his skill in the design of new equipment to meet them. In the exercise of this talent he had my full support, and we turned it very much to our advantage in the following way. Ralph would design and build a prototype; he would then offer the design to one of the scientific equipment firms which would be allowed to take up and market it, with the proviso that it first supplied us with what we needed, and that, thereafter, when we required a particular item we would have priority over other customers. This worked excellently, and so we developed new evaporators, shakers, drying pistols, etc. and, in due course, also electromagnetically stirred autoclaves for pressure hydrogenation and other reactions. Most of these came into general laboratory use in due course, but we were normally first in the field and so, even during the war years, we became perhaps the best equipped chemical laboratory in Britain.
In addition to work for the Chemical Defence Research Department we had a number of other projects in our laboratories in Manchester which were regarded as being 'of national importance'. These included work on antimalarial and other drugs, but one of the most interesting was an attempt to isolate and identify the so-called 'hatching factor' for the nematode Heterodera rostochiensis (the potato eelworm). This parasite attaches itself to the growing roots of the potato plant and causes the disease known as potato sickness; it is found all over Europe, and in Britain alone is responsible for losses amounting to millions of pounds annually. The fertilised female worm remains attached to the potato root, its body swells up and, with the death of the worm, the posterior portion drops off into the soil as a leathery cyst containing some hundreds of larvae. The cysts lie dormant but viable in the soil until potatoes are planted again in their neighbourhood, when the larvae emerge and attack the potato rootlets. The reason for this hatching is that the growing potato roots secrete into the soil a substance (or substances) which specifically triggers the hatching of the encysted worms. My attention was drawn to this fascinating problem by Professors Leiper and Raistrick of London, who had made some preliminary examination of the problem to ascertain its feasibility; they had found that the mysterious hatching factor was produced by other solanaceous plants so that tomato plants could be used as a much more convenient source than potatoes, and had devised a rather crude but apparently effective biological assay. They decided to abandon the project when war broke out and I was invited to take it up. This I did and, with the help of Dr C. T. Calam who had been doing the preliminary work in London with Raistrick, I got the project under way in Manchester. We failed to isolate the hatching factor in Manchester and the same lack of success attended further efforts I made later in Cambridge with my colleague A. W. Johnson. We were, however, able to establish that we were dealing with a relatively small molecule or molecules (< 1000 in molecular weight and probably around 500) containing an unsaturated lactone group, but we could not isolate it. True, it was not very stable, but the real reason for our failure was twofold. Firstly, fractionation procedures such as chromatography and countercurrent distribution were insufficiently advanced, and, secondly, our biological test reached its limit when we were dealing with fractions active in dilutions of about 1 in 10^6, and which were evidently still heterogeneous. It is perhaps only fair to say that our isolation work in Manchester was brought to a standstill in 1944 when the greenhouses at Cheshunt where we grew our tomato plants were demolished by a flying bomb. Long before then we had found the physical separ
ation from our tomato cultivation rather tiresome, and we did indeed make one abortive effort to alter it by cultivating another easily grown solanaceous plant - the black nightshade - on a piece of ground owned by the university in Fallowfield. This experiment had to be brought unobtrusively to an end about a year after we started it, when black nightshade, to the concern of local residents, began to appear in gardens all over south Manchester! Our work on the eelworm problem was thus rather disappointing, although we did synthesise a few compounds on the basis of what we knew about it, and some of these had weak hatching activity. It is, however, some consolation that, even today, the factor remains unisolated, and that the efforts of quite a number of investigators in several countries have, in essence, only confirmed what we established about it many years ago. The potato eelworm hatching factor is, of course, only one example of the many fascinating problems presented by the phenomenon of obligate parasitism, and analogous substances influencing the germination of a number of parasitic plants also occur. My colleague, Dr R. Brown, who was a lecturer in botany in Manchester and subsequently became professor of that subject in Edinburgh, was interested in, and drew my attention to, the probable existence of specific germination factors for Orobanche and Striga species secreted by the host plants upon whose roots they battened. We did have a look at these problems later on in Cambridge, but again had little success. The first breakthrough in this general field of research did not come until 1971, when workers in the United States succeeded in isolating a small amount of the Striga germination factor to which they gave the name strigol and established its structure by X-ray crystallographic analysis. Interestingly enough, its molecule has some of the structural features which we suspect occur in the eelworm hatching factor.
A Time to Remember Page 9