Another piece of work which led to no useful result (as far as I was concerned at least) was that which we carried out on blood anticoagulants. During my first year in Manchester I was asked by my friend C. H. Best of Toronto if I would have a look at heparin, which the Canadians were producing at their Connaught Laboratories. He sent over one of his technicians (Arthur Charles) with a modest supply of material so that we could do some work on it, but we had no time to do much with it before war broke out and Charles had to return to Canada. I would probably have paid no further attention to the problem, since I really was not very interested in carbohydrate chemistry, had it not been for the panic about spies and Nazi sympathisers which occurred following the German invasion of France. All German subjects, including many Jewish refugees, were suddenly rounded up and interned (quite arbitrarily as far as I could see). One victim of this was my valued colleague and friend Dr Anni Jacob. She was arrested, put for a time in Holloway Prison in London, and then moved to an internment camp at Port Erin, Isle of Man. This was a tragic waste of scientific talent at a time when this country needed all it could find, and was equally tragic from a human point of view, since Anni was one of those Germans who, although without any Jewish ancestry, nevertheless elected to leave her country rather than live there under Hitler. I had a long battle with the Home Office before I finally obtained her release, but, between times, in an effort to relieve the boredom of her stay at Port Erin, I arranged with the Director of the Marine Biological Station there that she could collect and process various types of seaweed, and, in collaboration with me in Manchester, look for possible blood anticoagulants in them (it was known that the Irish seaweed product carragheen had anticoagulant properties). Although we carried on some of this work for a short time after Anni was released, it really did not lead us anywhere and we abandoned it; but it probably helped her to retain her sanity during her internment. While we were still in Manchester Anni married Dr Juan Madinaveitia, who had been associated with me in Edinburgh, London and Manchester, and who was himself a refugee from the Franco regime in Spain. Madinaveitia subsequently joined I.C.I. (Pharmaceuticals) Ltd and he and Anni settled down happily in Cheshire and brought up a family.
Needless to say, I took part in the wartime Anglo-American cooperative research project on penicillin, but I was not involved in the early stages and our efforts beginning in, I think, 1943, were on a relatively modest scale. Looking back at it now, I find it rather amusing that, by showing that penicillin readily formed a sulphoxide, we did indeed establish that it was a true lactam; furthermore, our sulphoxide has, in recent years, sprung into prominence as a starting material for much synthetic work on beta-lactam antibiotics in general. I confess that I got little pleasure from our penicillin work, and that, I believe, for two reasons. In the first place I found the constant stream of research reports from all participants in the cooperative venture, amounting almost to a flood, very distracting, and, indeed, counterproductive in that they hampered the free development of my own ideas. Secondly -and this applied in variable degree to all our war work - I have always found it difficult to do good research unless the subject is one in which I have a strong personal interest. I think this latter point applies to many academic research scientists, and that is why they are usually not very efficient in industrial contract work. Indeed, my advice to an industrial firm with a research problem which it wishes to solve expeditiously, is to do it within the firm, taking external advice as appropriate but not to contract it out to a university. I know, of course, that in recent years several industrially oriented units for contract research have been set up in a number of universities; but these are quite different in outlook and staffing from normal university departments, and have had variable fortunes. I still think that the proper place for industrial research is in industry.
I have already explained how chance in the shape of George Barger introduced me to the vitamin field; from that introduction grew an interest in vitamins, and especially in the chemical reasons for their importance. These interests are at the heart of what most people would probably regard as my main contributions to research - the chemistry of vitamins, of nucleosides, nucleotides, coenzymes and nucleic acids. Such a view is entirely reasonable, since there can be little doubt that our nucleotide work and the establishment of the chemical structure of nucleic acids form the base on which molecular biology and modern genetics have developed in such spectacular fashion during the past quarter of a century. Yet, in addition, I have always had a deep interest in natural colouring matters - an interest triggered by my association with Robert Robinson in research on the beautiful red and blue colouring matters of flowers known by the generic name of anthocyanins. As a result, I have, during my career, done a good deal of work on natural colouring matters and especially on those remarkable pigments found in aphids, those well-known sucking insects which are the bane of many gardeners' lives; I shall recount something of that research later.
In Manchester we had laid the ground for our foray into the field of nucleotide coenzymes. We had developed new methods for nucleoside synthesis and for phosphorylation of nucleosides with dibenzyl phosphorochloridate, and had discovered a new method for phosphorylating amines using diesters of phosphorous acid and polyhalogen compounds. (This latter reaction was, in fact, accidentally discovered by F. R. Atherton when he tried to remove acid impurities from a solution of dibenzyl hydrogen phosphite in carbon tetrachloride by shaking it with ammonia; the whole mixture set to a semi-solid mass of dibenzyl phosphoramidate.) I need not elaborate in detail, but during the first few years in Cambridge we had effected the first of our coenzyme syntheses — that of adenosine triphosphate (ATP), the substance which is involved in phosphate transfer and acts as the necessary reservoir of energy for muscular activity in animals. We also not only settled the structure of the known natural nucleosides and nucleotides by synthesis, but established their stereochemical configuration as well.