Robert Kenneth Callow
Born 15 February 1901,
[Died 12 April 1983, Maughold, Isle of Man]
Elder brother: Edward Cecil, born 1898,
died 11 Aug 1900, aged 19 months.
Younger sister, Joan, died in infancy, ca 1905.
Father: Cecil Burman Bannister Callow,
born 13 September 1865, Sandgate, Cheriton, Kent,
died 31 October 1912, Clapham, London.
Mother: née Kate Peverell,
born 2 February 1868, Newcastle-on-Tyne,
died 5 May 1955, Hampstead, London.
Mother and Father married 12 September 1896, West Ham.
[This is a transcript of handwritten notes left by R.K. Callow. The transcription was made by his daughter, A.R. Laidlaw, April 1985. Headings [and phrases within square brackets] have been added during transcription to aid reading. Although complete accuracy has been the aim, any mistakes are the sole responsibility of the transcriber.
These notes were available to Professor Neuberger during the preparation of the Royal Society Memoir (Biographical Memoirs of Fellows of the Royal Society, Volume 30, November 1984, pages 91-116.) This is referred to in the notes as the "memoir".] http://rsbm.royalsocietypublishing.org/content/30/92.full.pdf
I know little of my mother's family. They were Tynesiders and lived in Gateshead. Her father [George Samuel Peverell], described on her birth certificate as 'engine fitter' was a ship's engineer and also, I believe, held posts in India. My mother's brother [Alfred] was a ship's officer and was lost at sea. My mother's father died in 1884 leaving his three daughters [Kate b. 1868, Eleanor b. 1870, and Emma b. 1872], who, closely united, came to London to earn their living. The eldest [presumably Eleanor, second eldest] trained as a nurse. My mother [Kate] was employed by a photographer, retouching and tinting portrait photographs. She met my father in London and they were married in 1896.
My father's family was Manx, a circumstance of which he was proud, for his father, Edward Callow had been particularly interested in the Isle of Man and in the family history: he was the author of 'From King Orry to Queen Victoria', a history of the Isle of Man and of 'The Phynodderee and other legends of the Isle of Man', [as well as] 'Old London Taverns', first published in the newspaper City Press, 1897-8, book 1899. My own enquiries into the family history led me back to Ballafayle-e-Callow, a hamlet a few miles south-east of Ramsey. I could not confirm my grandfather's belief that he was in the direct line of descent from William Callow the Quaker (1629-1676), who is buried in the old burying ground of the Manx Quakers: Ruillick-ny-Quackeryn on a nearby hill. The churchyards of Maughold and of Kirk Braddon contain very many memorials to Callows, without much evidence of their relations to each other, and with the incompleteness of detail in early records, the Church Registers do not enable a family tree to be constructed with any degree of reliability. The earliest certain record I have of my forebears is of Edward Callow, a shipwright of Douglas (1754-1831). His grandson, Edward, my grandfather [born 1825], described himself in 1845 as "a clerk in a leading stockbroker's office", in 1846 as "of the Stock Exchange", in 1865 as "Ship Broker" and in 1896 as "Journalist". Some years later [after 1846] his fortunes changed for the worse owing to some financial disaster of which I have no record: he subsequently lived in retirement.
My father [Cecil B. Callow] was the youngest of six children and was apprenticed as an electrical engineer. He held posts with a number of firms including a firm of electrical contractors. He was in charge of the installation of electricity at Tring for Lord Rothschild in 1890 and remained there as engineer in charge from 1891 to 1895. [Other posts were with] the boatbuilders Thorneycrofts, in the Isle of Wight, and at Goring-on-Thames, where I was born. When my own memories begin he was managing the English branch of Kohler Brothers, an American firm of manufacturers of switch-gear for newspaper printing presses. His office was in Ludgate Hill and he was admitted into the Freedom of the City of London in 1910.
I remember him as a plumpish cheerful man with the white hair that runs in the family, popular, I believe, among his business friends, enjoying good living, keen on sailing and sea fishing and with a taste for handicrafts. In the technical side of his work, apart from the paper qualification of AMIEE 1899, the fact that he had "been through the shops", i.e. had served an apprenticeship was not only of itself valuable, but gave him the necessary authority over workmen. His aphorisms were of the type "If a job is worth doing at all, it's worth doing well". While he remained a man of his hands with a hobby workshop, he was fond of reading, with enthusiasms for Rudyard Kipling, Morley Roberts and W.W. Jacobs, and in addition to a miscellany of books of all kinds we had the Encyclopaedia Britannica as a compendium of general knowledge.
I learned to read with the aid of "Reading without tears" at my mother's knee, by the age of four years. I recall having a toy bear that, with inspiration from Nuttall's Dictionary I named John Xanthicus Bruin.
My schooling began with a 'dame's school' at Barnes, and continued with a rather depressing preparatory boarding school at Margate, but in 1911, with the necessary introduction of a City Alderman, I entered the lowest form of the City of London School, to which I travelled daily from our home in Clapham. I was a bookish boy, and got on well with the school. I seem to remember fifty in a class in the junior forms, but that didn't worry me and promotion came regularly.
Death of C.B. Callow
In 1912 near disaster came with the sudden and entirely unexpected death of my father at the age of 47. The cause of death might well be described as "faulty diagnosis". The circumstance that a diagnosis of "intercostal neuritis" could be followed by perforation of a gastric ulcer reflects perhaps on the medical knowledge of the time, but it has been the source of my acute interest in human medicine and of distrust of its practitioners since that day.
My mother was left with a residue of about £300 from an insurance policy after settling a few small debts. She attempted to keep the two of us afloat by taking in a lodger, but the money problem was just not solved in that way. My father's sister Frances then offered to take us in, with my mother employed as housekeeper. As my aunt had been deaf from childhood, always deferred to, was full of prejudices for example against even having an onion in the house for the servants to eat, and in times of crisis retired and then emerged saying that she had had a little talk with God, and that all must be done in accordance with Their wishes, the arrangement clearly could not continue for long.
In the autumn of 1914, soon after the war began, my mother found herself a job as "wardrobe mistress" dealing with the clothes sent to a charitable organization, the R.U.K.B.A. I think she was paid 15 shillings a week, and she found rooms for us in Pimlico at 11s a week, saying that she could not stay in this house a moment longer. [The rooms were on the] first floor, 17 Sutherland Street. Two communicating rooms and a small back room. Running water and W.C. on the landing below shared with tenants on second and third floors. Her sister in the United States made existence possible by sending £3 a week. I had won a scholarship that paid my school fees and we managed, and I remember my mother and I simultaneously sighing with relief that we were free from the oppressive household of my aunt.
Existence in these circumstances left two permanent impressions on me. The first was, naturally, carefulness with money - I retain still a reluctance to throw pennies about - and the second was the shock that a large property owner - the Duke of Westminster - could continue to be the landlord of the great area of slum property adjacent to where we lived without doing anything to improve conditions. He even refused some large sum, I think, one or two hundred thousand pounds, offered for the picture The Blue Boy, by Gainsborough, which he owned. I became very conscious of the "unsolved riddle of social justice", with a bias to the political left that persists to this day. On the other hand I feel that the "welfare state" can be overdone, and that struggle against adverse circumstances is the best way of developing such character as one's gene's have given one.
My mother and I used to be frequent visitors to the Old Vic in Waterloo Road, which was within walking distance and, at the cost of long waits in queues, we saw many operas - fourpence in the gallery or sevenpence in the pit. A personal interest of my own was a fairly long walk to South Kensington and back to browse in the museums, and I knew the Natural History, the Science and the Victoria and Albert Museums well. I would regard a visit with a school party such as is now organized with horror, and I thought that Lord Eccles's recent attempt to impose entrance fees on museums as a gross error of judgement. Such a charge on a penniless schoolboy would have been a complete bar to my private browsing. My mother spent twenty years in her post at the R.U.K.B.A. and lived to the age of 87.
City of London School
At the City of London School I moved to the Science Side and was fortunate in having as my chemistry master and head of the department, G.H.J. Adlam who came from Wadham College, Oxford and was active in the Science Masters Association (either Secretary or editor of their magazine). Typical of him was instruction at the bench. We were told for instance to construct an apparatus for preparation of a gas, with thistle funnel, corks properly bored and glass tube properly bent and the ends rounded off before being put through the cork. He would then ask the lab. assistant for a new triangular file and walk around the class inspecting our efforts: any weak and unsightly bends were broken by being struck with the file and the boy had to make it again. Another of his qualities was an insistence on good English writing and he was an enthusiastic supporter of the literary prize awarded in the Science Side, the "Bennet H. Brough" prize for English. I won this in 1916 and in that year was also awarded a Senior Science Scholarship, which ensured the continuance of my school career and subsequently, with Adlam's advice, entrance to the examination for scholarships at Oxford in 1918.
Among my contemporaries on the Science Side at school were Eric Ashby (later Lord Ashby and F.R.S.), the two Linstead brothers (Sir Hugh, Secretary of the Pharmaceutical Society and Sir Patrick, Principal of the Imperial College and F.R.S.), R.W. Scarff (professor of Pathology at the Middlesex Hospital), H.M. Bird (anaesthetist, Bury St Edmunds), and Norman F. Parker.
The war had no major effect on me except in so far as general conditions were difficult. A few bombs were dropped not far off - one on a school across the road. I was an active member of the O.T.C. in fact a Company Sergeant Major, and the deferment of my call-up until I could join an Officer Training Unit resulted in my avoiding conscription, for the war ended before I reached the age of eighteen.
University of Oxford
I was awarded an Exhibition in Science at Christ Church ("Carlton J. Lambert" scholarship), which had the advantage over the scholarship of carrying higher and more flexible emolument. With a university scholarship from the City of London School and a grant from the London County Council I felt that I was well provided for. I was, however, in for a bumpy ride. The University of Oxford still required Latin and Greek for the entrance examination, Responsions, and I had "small Latin and less Greek". In fact I had done no Latin for some four or five years and did not even know the Greek alphabet. Even a spell of frantic cramming was not sufficient to get me through. The college wrote to me telling me not to come up, but the letter was delayed and I arrived and presented them with a slight problem. Charitably they allowed me to remain and I was matriculated in the Michaelmas Term 1919. Disastrously I failed again, was sent down and only succeeded at my third attempt. Christ Church continued its charitable attitude - for which I shall ever be grateful - and at last I came into residence - I think in Michaelmas 1920, but it may have been the previous Hilary term - and began to read Chemistry.
My tutor was A.S. Russell, a man of great charm who inspired great affection in his pupils and colleagues but who, although he had a record in research (in the promising work on radioactive substances) that was nothing to be ashamed of, was no great scientist or teacher. Encouragement and critical advice on the choice of lectures were his contributions and it is not unfair to say that his pupils felt that success would depend on their own efforts. Biochemistry was just beginning at Oxford at that time and it was possible to take Biochemistry as a subsidiary subject in Chemistry Finals. Russell firmly discouraged me, saying that "in biochemistry you just deal with doctor's messes". I did not approach the field again until 1927, when I went to R.A. Peter's lectures.
I was critical then, and remain so, of the standard of teaching and lecturing at Oxford at that time. The most memorable lectures were those few given by W.H. Perkin junior. He was to be seen pacing up and down the big teaching laboratory for an hour before the lecture studying notes on a small sheet of paper with the result that the lecture went smoothly, without further reference to any notes. In the lectures on indigo there was annually a demonstration of the formation of indigo blue from the leuco-compound on a hank of wool, the success of which obviously gave intense pleasure to the prof. and was greeted by subdued cheers from the audience.
I did sufficiently well in the written examination (Part I) of Chemistry Finals in 1922 to go on to Part II, for which I chose to ask N.V. Sidgwick to be my supervisor and I undertook one of the items in his series of investigations of the solubility of benzene derivatives with special reference to the liquid-liquid systems and the behaviour of the isomers of the disubstituted compounds. I made a great effort to work out a system of numerical relationships using all the data accumulated from others' work as well as my own on the isomeric amino-phenols. This led to much discussion with Sidgwick. My own ideas did not survive, but Sidgwick produced his theory of chelation in the ortho-substituted compounds and in acknowledgement of, as he put it, the part I had played in emphasising the difference between ortho-substituted compounds on the one hand and the meta- and para-substituted compounds on the other, and making him think about the subject my name was put on the paper that summed up the series of experimental papers and put forward the theoretical background.
I had taken the Intermediate Science Examination of the University of London when I was at school, and it seemed worthwhile to complete taking the external honours degree of BSc. Christ Church provided a tutor, T.W. Chaundy, in the subsidiary subject of Applied Mathematics and with a good deal of pain and tribulation to both of us I scraped through and then took the Final Examination in the principal subject, Chemistry, in the summer of 1922 with first class honours.
In 1923, having been awarded a first at Oxford I found it impossible to get the sort of job I wanted - my ambition was to go into industrial chemical work - but I obtained a grant from the Department of Scientific and Industrial Research that enabled me to do a year's further research under the supervision of Edward Hope, still in the Dyson Perrins Laboratory.
I admired N.V. Sidgwick greatly but I had no enthusiasm for following him in his physico-chemical electron-theoretical and mathematical themes. He had a powerful mind, but was an arm-chair scientist. Another research student of his pointed out how helpful Sidgwick was in discussion until one raised some experimental matter or manipulative problem; he would then break off the discussion and trot away as quickly as possible. I wanted to widen the scope of my work to organic chemistry, which attracted me, and I was always happier working with my hands.
At that time the BSc degree at Oxford was given only for a year's work after the work submitted for Part II of the Finals. My thesis on "The action of acyl chlorides and anhydrides upon isatin derivatives", was submitted in June 1924 and I gained the degree of BSc. Part of this work was published some time later jointly with E. Hope under the title "Isatin anils. Part I. The isomerism of isatin-2.anil". (What happened to Part II? Look up J.C.S.)
The employment situation for chemists in industry was still a difficult one in 1924 and I think I wrote some two dozen letters at least to firms that I thought might have a job for me. Most of these were not answered. I had an interview with British Celanese Limited at Spondon and I took the post they offered at £250 a year. Nominally I was a research chemist, but there was no laboratory except a shed with a bench and a tap. There was a mechanical vacuum pump and when I wanted to do a bit of volumetric work, I was advised to approach the analytical laboratory and borrow a pipette. I had a problem handed to me, I think something to do with preparing films of cellulose acetate by evaporation of solutions, and reported that I could not find an answer. "Ah well!" they said, "we had someone else working on it for some time and he couldn't find an answer either". The idea of secretly competitive research did not appeal to me. I moved to textile departments and probably did some useful work, but, avoiding the temptation to go into tedious detail, I can only say that this experience was not a happy one. This was not an intellectually satisfying job and, after Oxford, I found myself in a social vacuum. Perhaps my experience is no worse than that of many young graduates who are quite unprepared for the abrupt change of environment when they leave university.
D.Phil. University of Oxford
My old tutor, A.S. Russell, came to the rescue with a suggestion that I should apply for a Senior Research Scholarship at Christ Church. This I did, with great eagerness and gained the award in 1927. I left British Celanese I am glad to say with friendly feelings on both sides, and a valediction from the manager, a Swiss named Soller, "so you leave us to become a professor".
Back in Oxford I took a little time to get my hand in and look around me. I now found the university atmosphere surprisingly parochial, but I settled down quickly. I found that in the Dyson Perrins Laboratory the professor was ailing in health and I chose to work as a D.Phil. student with J.M. Gulland, who seemed to me to be both a pleasant personality and one of the brighter young chemists about the place. I was actually his first research student. He was working with R.D. Haworth, formerly at Oxford but now at Sheffield (Sheffield at that date?), on a series of syntheses in the aporphine alkaloid series - a very suitable subject for a thesis. Three joint papers were published, the third of these including work by C.J. Virden. He was a friend of mine who joined the firm of Guinness as a brewer when he left Oxford and later had special responsibility for their research and their pharmaceutical interests, for the latter of which F.A. Robinson was recruited. Minor subjects in my thesis included work on some phenanthrene derivatives and an attempt to isolate taxine, the toxic material of the yew, Taxus baccata. This was my first natural product and the attack was really premature in the absence of the methods of separation and analysis that only became available many years later.
I submitted my thesis in May 1929 and had a successful, though mildly comic viva voce examination by Robert Robinson as external examiner and S.G.P. Plant as internal examiner. Robinson came in, slammed my thesis on the table and then turned to Plant and asked him to begin. Plant was a gentle and extremely shy character and, taken aback by the very idea of preceding the great Professor Robinson, begged to be excused, in such terms that Robinson had no alternative but to begin, which he did by opening the thesis and starting on the Abstract. This was written in the compressed and dessicated style of Chemical Abstracts and was evidently a hard nut for even Robinson to crack. His first remark was that it was a pity that I had not put in some formulae. My reply, in an injured tone - and I can only suggest that extreme terror inspired my bluntness - was that there were one hundred and seven formulae in the main thesis. However, this was a winning card; Robinson closed the thesis with a bang and asked me to tell him briefly just what I had been doing. I passed this test successfully.
National Institute for Medical Research
I now had to find myself a job and had, in fact, no great difficulty. I was interviewed by I.C.I. at Billingham and offered a post at £400 a year. Then the National Institute for Medical Research, I think on the initiative of R.B. Bourdillon, offered me a post to work on the chemistry of Vitamin D at a salary of £350 a year, joining Bourdillon's team and being research assistant to Otto Rosenheim. I remember my interview with Henry Dale and my asking "what about holidays", and his reply, "My dear Callow, don't ask me to lay down any regulations. If you are away from the lab. we shall know that you have been working hard and want to take a rest. If you want a guide-line you can consider yourself a first-class civil servant. I believe they are entitled to six weeks, but don't ask me to make any rules or put anything in writing". The subject, the people, the surroundings all appealed to me. I wrote my regrets to I.C.I. and began in October 1929 my career with the Medical Research Council that was to last until I reached retiring age in 1966.
The position at the National Institute was not as simple as it appeared at first sight. In fact the letters that followed from Dale himself did not entirely confirm my impression from the interview and the letter offering appointment from the M.R.C. head office was more reserved, and introduced some modifications, thus my appointment was not "to work with Dr Rosenheim, Dr Bourdillon and Mr Webster", but to work "under the direction of Dr Rosenheim". Rosenheim, who had retired from his lectureship at King's College London was invited by Henry Dale to come to the Institute at Hampstead as a voluntary worker so that he could develop his ideas about the origin of vitamin D. R.B. Bourdillon was a remarkable character, Fellow (?) and Tutor at Exeter College, Oxford, and a physical chemist. As a result of a dream he was persuaded that he was called to do medical research. He resigned his College post and qualified in medicine. He came to the Medical Research Council enthusiastic to investigate the treatment of burns by ultra-violet radiation. It was suggested to him by Dale - and Dale had tremendous powers of persuasion - that he could be useful if he applied his knowledge to vitamin D and led a team of young workers in an investigation of this problem, together with Rosenheim. This was a typical Dale activity, spotting a problem that looked ripe for attack and thereby bringing possible prestige to the Institute that was effectively his creation. The rub was that Rosenheim was a "loner" and not prepared to work in a team. This I failed to realise at first, but I had a pleasant year or so of introduction to sterol chemistry under the invariably kindly guidance of Rosenheim. I was soon, however, drawn into closer cooperation with the team in the laboratories downstairs - R.B. Bourdillon, an inspiring leader whom we all regarded with affection, though we didn't always agree with him, T.C. Angus, physicist, F.A. Askew, chemist, Hilda M. Bruce, biologist, Kate Fischmann, biologist, J.St.L. Philpot, physical chemist and T.A. Webster biologist.
The story of our ultimate success in competition was written out in a document that was deposited in the Institute library and a copy may be, I hope, annexed to these notes. [Neuberger's memoir, p 99-101 gives more background and details of the isolation of pure vitamin D.] My own contribution of importance was to find an esterifying agent, 3,5-dinitro-benzoyl chloride, that yielded crystalline derivatives not only from the partially crystallised material obtained by distillation from the crude product of irradiation of ergosterol, but even from the undistilled material. From the unheated irradiation product we separated a material with a light-yellow dinitrobenzoate, that was identical with Windaus's lumisterol. It gave immense satisfaction to be able to separate manually the orange-coloured crystals of the dinitrobenzoate of the thermal decomposition product, "pyro-calciferol", from the lemon-coloured crystals of the dinitro-benzoate of vitamin D, strictly ergocalciferol. Dale invented the term "calciferol", and insisted that the name should be retained when the relations between "vitamin D1 and "vitamin D2" became clear, and the terms ergocalciferol and cholecalciferol were adopted when the nature of "vitamin D3" was determined.
Bourdillon's health was precarious during the last stages of the vitamin D work. His absence through illness led to the omission of his name from the Nature letter and subsequently, on this account and because of a disagreement mainly between myself and him on the form of presentation of the second Proc. Roy. Soc. paper, he wished to have his name left out again, but was overruled by the unanimous protests of his team. Bourdillon was a strange character: I have already mentioned the origin of his entry into a career of medical research. Perhaps as the consequence of the frustration he suffered in not being able to get his own way in following the rather improbable plans he had set out for himself, but being set the vitamin D task by Dale, he developed a hypochondriasis that took the form of belief that any deviation from perfect health must be due to a centre of tuberculous infection, and insisted on undergoing a series of operations. In Bourdillon's case his psychoneurosis (if it may be called that) was not a "creative malady" in the sense defined by Sir George Pickering (1974). One of his sons climbed Everest; the other became a farmer in Canada and was joined there by his parents. I last heard from him in 1958 when he wrote to me from Ganges Island, British Columbia, congratulating me on my election into the R.S. and enquiring earnestly about the current state of theories of arteriosclerosis "in which of course, I have a lively interest".
The vitamin D team was broken up - F.A. Askew went to work with N.K. Adam, with whom we had already some consultation over the spreading of films of sterols.
A note on the industrial application of our work on vitamin D is relevant here. The policy of the Medical Research Council at that time was to avoid patenting any discoveries so that, if medically useful, they were open to all. Publication of the vitamin D work did not, however, open up the field for the Steenbock patents were masters. However, the separation we had devised could be applied on the industrial scale and we had interesting and satisfactory contact with Glaxo Laboratories, in the course of which I first met Harry Jephcott, with whom I was to have close contact again twenty years later when hecogenin was shown to be a possible source for the preparation of cortisone.
Looking back, I think I may have missed an opportunity after the successful completion of the isolation of ergocalciferol, but did not feel either qualified or enthusiastic to work on the constitutional problem of the sterol compounds, for which the old Windaus formula was the only one current, or that of calciferol. I played a minor part in the final solution in virtue of having crystalline materials available for X-ray examination. J.B.S. Haldane, J.D. Bernal and Dorothy Crowfoot came to see Rosenheim and myself. J.B.S. sat on a table, swung his legs and said, "When I die they may not say that I did much original scientific work, but I hope they can say that I was a good catalyst". In this instance it was his initiative that brought the party together since he had been impressed by Bernal's work and thought that the sterol and vitamin D series might yield results of interest by X-ray crystallography. This was indeed the case, for it was demonstrated that the sterol molecules were flat, and the Windaus formula could not be accommodated in the unit cell.
Rosenheim took this as the starting point, together with Diel's hydrocarbon, for a renewed attack on the sterol problem, which had for long been one of his major interests. He had retired - for the second time in his career - but still occupied himself with pencil and paper speculating. These speculations reached a stage at which he wanted discussions and criticism, which he came back to the National Institute to seek and obtained from Harold King. I played no useful part in this exercise - structural theory was not my forte, my knowledge of the extensive and complicated literature was negligible in comparison with Rosenheim's, and, finally, I wanted to go into the biological side of vitamin D.
Hilda Bruce was prepared to join me and, [had] a licence to do the animal experimentation side of some work on vitamin D. Edward Mellanby's work on the rickets-producing factor of cereals, especially oatmeal, seemed to provide a starting point for a combined chemical and biological investigation, with the object of isolating such a factor should it be a chemical entity. In the event no such entity seemed to exist and the effect was one of lack of calcium in cereal diets, or even deprivation as a result of calcium being bound by the phytic acid (inositol hexaphosphoric acid) of the cereal. We prepared an account of this work and our conclusions for publication in a form rather acidly criticising Edward Mellanby. The appointment of Edward Mellanby as Secretary to the Medical Research Council prompted second thoughts on the style of presentation of our paper after discussion with Sir Henry Dale, and we tried, without success to demonstrate the postulated calcium-depriving action of phytic acid. Edward Mellanby took the work a step further, but the subject was exhausted by this time.
A.S. Parkes had come to the Institute in with a group of people working on the physiology of reproduction. Dale arranged that I should join the group to deal with the chemical side, and so began an active collaboration that lasted for some years until I was able, with some effort, and a little friction, to break away and follow lines which I could call my own.
Concurrently I did some work on sterols originating from Rosenheim's observation of the oxidation of sterol by selenium dioxide and continuing with work on the cholenic acids, in which I investigated the possibility of diagnosing the composition of a mixture of two isomeric optically active compounds by measurements of the specific rotation at two different wavelengths.
I think this interest in optical activity may have led to my joint paper with Frank Young in 1936. At that time the National Institute for Medical Research at Hampstead was still small enough for people of different laboratories to know what the other chaps were doing, and even to understand it. Frank Young talked to me about Hudson's Rule in the carbohydrate group and wondered whether something analogous might not be found in the sterols and their relatives. This idea was followed up and resulted in our joint paper in 1936 on relations between optical rotatory power and constitution in the steroids - the term "steroid" was invented and first used on this occasion as a general name for the group of cyclopentenophenanthrene compounds including the sterols, bile acids, heart poisons and the like.
Work with Alan Parkes and other members of his group was highly interesting and amusing - at least to look back on - with a new subject being opened up by the energy and the enthusiasm for publishable results of Alan Parkes. While acquiring a smattering of knowledge of the biology of reproduction I think I helped to secure that the chemical foundations were sound and contribute some intelligent cookery to the elaboration of extraction processes. In particular the extraction of a steroid fraction from human urine and the application to it of the colour reaction of dinitrobenzene with substances containing the grouping -CH2.CO-, the Zimmermann or 17-ketosteroid reaction, was developed, with the collaboration of C.W. Emmens on the biological side and the help of Nancy Newman in the chemistry laboratory. By the time we reached the stage of publication she had become my wife, N.H. Callow. S.W. Strand also joined us for a short period.
An early outcome of this work was the discovery that there was no sharp distinction betwen the excretion of 17-ketosteroids by men or women or even by eunuchs: the importance of the adrenal cortex in the formation of these compounds was realised and in one direction a beginning was made in examining the metabolism of testosterone0, whilst in another the extraordinary levels of 17-ketosteroid excretion by individuals with adrenal cortical tumours was recognised. This latter subject was developed as a result of work with AC Crooke of the London Hospital - a very happy collaboration indeed in which the chemist of the partnership was not confined to the laboratory but saw the patients, had a personal interest in the problem and enjoyed equal status with the clinician. But not quite equal, for, surprisingly a proposed publication by Crooke and myself jointly, with our names in the conventional alphabetical order met with vigorous opposition from Parkes and Dale until the order was reversed. For one thing, Dale, who is reported to have said that the Institute did medical research, but "Thank God, we never see a patient", evidently was concerned that a paper illustrated by photographs of patients in full frontal nudity was going too far for a mere chemist. In the early part of 1939 there was some discussion of the possibility of my going to the London Hospital, perhaps changing places with C.J.O.R. Morris, but Mellanby found that Professor Ellis was unwilling to lose Morris and extra room was not available.
World War II
I took one precaution against the outbreak of war - which appeared inevitable: I ordered a large batch of Merck's alumina for column chromatography from Germany, and this proved of great value. I had been following Reichsteins's work with adrenal cortical extracts and applying column chromatography to urine extracts.
The collaboration with A.C. Crooke would have been continued but for the outbreak of World War II, which clearly ruled out any such wild plans as an investigation of the steroid metabolism of a group of bearded women to be accommodated in a ward of the London Hospital. Crooke was directed to a provincial hospital and our work abandoned.
In the National Institute itself the main activity before the war began and for some time after was concerned with the organization of Air Raid Precautions, in which G.L. Brown and I played a major part. The basement was protected by a wall of sandbags, the filling of which was carried out by gangs under the command of G.L.B. The large room that was Dale's office was prepared as a shelter, in part by shoring up the ceiling with heavy timbers. These were designed by Bourdillon and only some months later was it pointed out that the bases of the pillars rested on a floor over a cavity. In the course of fire-watching, air raid warnings and so forth, the members of the Institute got to know each other much better. This was particularly remarked by Dale, a rather awesome and unapproachable figure. However, he found that in the evenings when we anticipated night bombing one of the stokers made a very satisfactory fourth at a bridge game before retirement to the shelter. Dale used to come in from Mount Vernon House next door when warnings were received. Once at 3 o'clock in the morning he arrived in some haste and embarrassment and insisted on explaining that he had been hurried so much that he was "edentate - no, I think edentulous is the word", having left his dentures behind.
Personally, I was impatient to do something for the war effort, for the Nazi attack was an assault on my personal conception of decent human life and, at ground level, so to speak, my own plans for scientific research had been wrecked. Nor did I feel that I could submit much longer - literally at ground level - to regular bombing by the Nazi air force as a passive civilian. There was a glimpse of possible useful work when a committee (or working party) met to consider what might be done to investigate routes to synthesis of the adrenal cortical hormones, since rumour had it that the Luftwaffe pilots were being treated with these substances in order to boost their courage and physical endurance. The meeting was an appalling disillusionment: ideas of wide cooperation between academic research workers and manufacturing firms dissolved before a vigorous and vicious campaign by Robert Robinson to get the plums for himself, to be dealt with by a group under his supervision. The National Institute (myself) and Glaxo took on the unpromising task of investigating some gunk obtained as residues of sterol manufacture.
C.R. Harington chaired the meeting: some years later I was glad to hear his comment, "that was a horrible meeting". I never heard any more of Robert Robinson's pre-empted field of work: not surprisingly the Glaxo gunk was unproductive.
Before this I had a more directly personal disappointment. In September 1939, with the agreement and support of E.L. Kennaway, I made a formal application for the University chair of chemistry at the Royal Cancer Hospital, formerly held by J.W. Cook. I had every expectation of being appointed, but the Chairman Sir Kenneth Wigram decided to postpone the whole matter or rather, actually to abandon it. The question of an appointment was revived in 1942, but by that time I was with the Air Force in India and, although my wife put in my application, it was ignored.
I was occupied for some of my time as A.R.P. Officer at the Institute and also trained as a Gas Detection Officer, neither very satisfying jobs. The M.R.C. had in May 1939 already warned their Staff that they should not undertake any obligation that would interfere with their ordinary work and that certain occupations, including my own were "reserved". Sir Henry Dale assured me that useful work would certainly turn up, but I think in fact that he was mistaken. I finally volunteered for service in the R.A.F. and was accepted for training as an Armament Officer. Dale told me that I was a bloody fool, but he softened the comment with a kindly smile.
Service in the RAF
I shall not describe my service in the Air Force in detail, for it is not relevant to my scientific career. I became an armament officer on a Polish training station and was then posted to India, serving in the North-West Frontier - Rissalpur, Kohat, Miramshah, Peshawar, Rawalpindi and a trip to Srinagar. To my amusement - for it seemed so out of character - I was mentioned in despatches for activity in the relief of Datta Khel. The only brave thing I did was to undertake the "demolition" of a number of unexploded bombs that the Political Officers and the Army had collected and which were beyond their capacity to deal with themselves. With some trepidation, as our only equipment was a car battery and a length of telephone wire (with of course, detonators and guncotton) I approached two 500 lb. bombs and decided that they had been dropped "safe", defused them and took them back. [See also memoir p. 104.]
The cessation of the campaign against the frontier tribesmen and the absence of any development of a drive by the enemy through Iran and Afghanistan to India, the apprehension of which had provoked the heavy reinforcement of the air forces in the N-W Frontier, left me with very little to do and I asked for some occupation in which my scientific knowledge could be applied. The only possibility seemed to be a transfer to the Army Ordnance Corps in Kanpur with a loss of rank. However, I had acquired malaria and after two relapses and some suspicious pulmonary symptoms it was decided that I was no longer fit for service in India.
The Inter-Services Research Bureau
Back in England and convalescent, A.G. Ogston recruited me for the Inter-Services Research Bureau - a back-room job surrounded with considerable secrecy, but interesting and amusing. The head of the Station was E.G. Cox (later Sir Gordon Cox). [See memoir, p.105.] I was finally released from service, in the rank of Squadron-Leader, in October 1945.
Far from considering my war service wasted time, I am happy to look back on it. I joined up because I had something worth fighting for (not "King and Country"!) and I should do the same again. True, I did no fighting in person, but others were set free to do it. For myself, I learned a great deal about the way of the world and about people, very much more than I should have learned in the cloistered life of a scientific research worker.
After the War
Coming back to civilian life presented some problems. I had to decide whether I wanted to return to the hard slog, the disappointments, the anxieties, that I remembered were the accompaniment of dedicated research work. There was another problem: the Medical Research Council had kept me on the established staff and continued to pay the difference when my service pay was below my salary, and I was most grateful for this. In the National Institute for Medical Research, however, things were not easy, rather disconcertingly. In line of succession to Harold King, the head of the Department of Biochemistry, was James Walker, once junior to me. There was a new Director, C.R. Harington, who had evidently been given the impression that I would not fit in with the organization foreseen for the division, and I found him in fact antipathetic. I made an honest effort to find some other post, but without success, and finally, a little incensed by what was happening, wrote to Harington saying briefly that I was returning to the Institute. We knew, of course, that the M.R.C. was under the obligation to keep my post open for me. Ultimately the situation sorted itself out decently. Perhaps fortunately, I was never burdened with internal administrative work; the head of the division did that, and that unfortunate man found himself running a department in which there were two obstinate characters, J.W. Cornforth and myself, both of whom became Fellows of the Royal Society, whereas it became plain that his own ambition was not to be achieved. Sir Charles Harington had, so I deduced, no part in my election and surprised me, in the course of congratulating me, by saying that his one regret was that James Walker would be made even more bitter. Sir Charles and I had, by this time, reached a basis of friendship, even if not of complete understanding.
My problem was to find a subject for research. A gap of five years since the androgen work had tailed off had left no base from which to launch. Harington suggested a collaboration with P.M. D'Arcy Hart and R.E. Glover who had found antibiotic activity against mycobacteria in Bacillus licheniformis. This work, at first tackled rather clumsily, was interesting but not brilliantly successful from the point of view of practical application, from which much had been hoped, because of the toxicity of the material. I applied, as one of the first in this country, the method of counter-current separation to the mixture of polypeptides from the bacterium, and ultimately T.S.Work was able to unravel their constitution.
Synthesis of Cortisone
In 1949, Hench, Kendall, Slocumb and Polley (Proc. Mayo Clin.,1949 24:181) made their startling announcement that 17-hydroxy-11-dehydro-corticosterone had a curative (or at least palliative) effect on rheumatoid arthritis. The only known source of the compound in quantity was a long and complex synthesis from bile acids, in the hands of Merck and Company, and it was regarded by the M.R.C. as of prime importance that alternative sources and methods should be made available in this country. A committee of representatives of manufacturers who might be interested and of the M.R.C. research staff was brought together by the M.R.C., and from the National Institute J.W. Cornforth and I were selected as having the requisite backgrounds. Study of the literature suggested two lines of exploration. One was the steroid heart poison sarmentogenin obtained from an inadequately identified seed believed to be that of Strophanthus sarmentosus.
Authentic seed from this species had however, not yielded sarmentogenin. The potential value of sarmentogenin, with a hydroxyl group in the important 11-C position was such that it was decided to organise a search for the seeds in Nigeria and, with R.D. Meikle from the botanical staff of the Royal Botanic Gardens, Kew, and a laboratory assistant from the National Institute, I went to Ibadan where, as guests of the University College and its Principal, Kenneth Mellanby, a small laboratory was furnished and headquarters set up for an exploration and preliminary chemical examination of plant specimens that might contain steroids of potential use. The whole affair was tremendous fun, but hard work. I remember being told that I could not last long in that climate if I kept up the pace I was going, and I remember replying that I had only six months to live anyway, referring to the period set for the expedition. I arrived back in London 7kg lighter than when I left.
The expedition was a scientific success, in that sarmentogenin-bearing strains of S. sarmentosus were found in savannah areas - a result confirming the simultaneous research of Reichstein and his collecting organisation - but as a commercial proposition for cultivation and manufacture the use of S. sarmentosus was not practical.
The other line of investigation arose from studying the work of Russell E. Marker. Hecogenin, with an oxygen atom at C-12, was a possible starting material, but not obviously very accessible. However, Marker, in his wide ranging search which included 16 species of Agave that yielded hecogenin, had not examined Agave sisalana, the sisal plant cultivated widely in East Africa. An examination of extracts was begun before I left for Nigeria, but was then handed over to J.W. Cornforth. This line was in the event the one that yielded useful and practical results.
Intermediately, however, what I might term political matters led to a hitch. Sir Harry Jephcott announced that his firm, Glaxo Laboratories, had been working for some time on a process of extracting ergosterol from the food-yeast that was being grown on a manufacturing scale in the West Indies, and that the plentiful supply of ergosterol would give a suitable raw material for cortisone manufacture. This apparently confident pronouncement, with a declaration of lack of interest in the activity of the Joint Committee convened by the M.R.C., led to the break-up of that committee: the other manufacturers were ready to leave Glaxo in possession of the field.
Not long after this happened Sir Harry Jephcott came to see Sir Charles Harington and myself. He told us that he was now anxious to collaborate with the M.R.C. in development of the use of hecogenin as a starting material: the ergosterol process was a failure. (I believe the trouble was that the yield of ergosterol indicated by the analytical methods they were using was very much greater than the actual amount that could be extracted).
In the meantime P.C. Spensley had gone out to Kenya and, in cooperation with the firm of Mitchell Cotts, set up a trial pilot plant for extraction of hecogenin concentrate from the juice derived from the crushing of sisal leaves. The next stage was a close cooperation of the N.I.M.R. staff, including Cornforth and myself, with the research staff of Glaxo, including B.A. Hems, to devise a production process for cortisone. Considering that Cornforth was the originator of a chain of reactions and that the Glaxo team had the task of developing a practical manufacturing process of which critical stages would be patented or kept secret, the arrangement worked splendidly. A third partner in the enterprise was the National Research Development Corporation, who acted to dispose of the rights to Glaxo. Rumour has it that there was a luncheon party of Lord Halsbury and Sir Harry Jephcott, beginning with champagne cocktails and lasting for some hours, at the end of which Sir Harry was able to announce that Glaxo had acquired the whole of the rights from extraction of hecogenin to the final synthesis. Cornforth, Spensley and I received substantial awards from the N.R.D.C. and I think the whole affair was a model of how government-sponsored research, undertaken on the grounds of national interest, could lead to commercially valuable results that, adequately protected, could be offered to commercial interests for development. It was interesting to contrast this with the policies followed by the M.R.C. some twenty years earlier in the case of calciferol.
A future biographer may be referred to an article by myself in Medical World 1956, in which the story of "The Source of Cortisone" is told.
[Manuscript ends here. See memoir p.109-111 for work on bee pheromones.]
0 My first contact with Solly Zuckerman was on two trips to Oxford to photograph a baboon that Solly proposed to castrate, and to photograph it again after operation, when it had female pelage but, in contrast to its previous temperament, was now uncontrollably fierce.