Another detector I invented was the photoionization detector. In this device, a low-pressure electrical discharge in argon, helium or hydrogen generated hard ultra-violet radiation that ionized vapours coming from a chromatograph column, and it was described in a Letter to Nature in 1960. The great practical utility of the flame ionization detector satisfied most analysts’ needs and the photoionization detector was only occasionally used.
It was a glorious May morning in 1960, and as I walked across the fields to work at the Mill Hill Institute, birds were in full chorus and the wildflowers bloomed. The scent of May from the hawthorn hedges filled the air. This island of countryside in suburbia was part of London’s Green Belt and off limits, then and perhaps even now, to conniving developers. I should have been counting my blessings, fortunate to be securely placed in a well-paid tenured post at one of the world’s most distinguished scientific institutes. I could do whatever science I felt inclined to follow within the wide field of medical research. I was accountable only to that benign authoritarian figure, Sir Charles Harington, the Institute’s director. My post was equivalent to that of a research professor at a famous university. I had a large, well-equipped laboratory, two technicians and a postdoctoral scientist, Dr Rowe, working for me. In many ways, it was a scientist’s dream employment. My salary was then edging towards £3,000 per annum. Our five-bedroom house in Westbury Road, Finchley, was in good condition and spacious, and with an outlook over the Dollis Brook and the small park that lined its banks. The house cost us £3,500 when we bought it in 1959 and with house prices rising yearly, our equity was sound. The same house would now cost fifty times as much. It would require a salary of over £50,000 a year to sustain the mortgage payments. In addition to all this, we had a new car, a Riley, costing between £800 and £900, and paid for from the fees of American lecture tours. Best of all was our cottage in Wiltshire where we could escape for weekends and holidays. The Medical Research Council allowed six weeks’ paid holiday a year and one week of so-called uncertificated sick leave. In spite of all this, I was uneasy, and as I walked along the footpath to work, I wondered how I could honourably resign and start an independent practice of science.
There were many unsettling things. My mother’s presence in a nearby flat, to which she had moved after my father died, led to endless quarrels involving Helen and the family. They were both good women, but obstinate and as bitterly opposed as members of warring tribes. We would spend weekends and holidays at our cottage in Bowerchalke, but this was no substitute for a full life in Wiltshire. We placed the cultural benefits of working in London below that of country living. To cap it all, I had a vague and ill-defined ambition to widen my scientific horizons beyond that of medical research. I could not have known it then but somehow Gaia was beckoning me away from the security of the civil service. The peculiar physiological changes that seem to affect men approaching forty years old amplified this urge to escape the nest and the phrase, ‘life begins at forty’ sums it up. Some men change their wives, some their jobs; I felt the urge to make a complete change in my way of life. There were formidable obstacles. First, where would the money come from? Perhaps I could write science fiction; perhaps I could start as a consultant to one of the firms who forever sought my advice on gas chromatography detectors and other inventions. And then, as a deterrent, there was the scorn and powerful persuasion against taking so foolish and insecure a path. This would come from Sir Charles and from my colleagues at the Institute. My mother would be even more difficult to persuade. To her nothing was better for her son than a secure and safe government job and the idea of an uncharted future working privately was anathema to her. As I walked, these thoughts jostled for attention in my mind and I could find no easy answer. Although we were comfortably well off, there was no reserve; far from having a private income or a rich family to fund the new life, I had Helen and four children to support and, in addition, my mother needed five per cent of my net income to supplement her pension. I shrugged as I climbed the hill to the Institute and tried to turn my thoughts to the work of the day. It was no good—the need to make a decision about my future nagged in my mind like the unforgettable itch of the malignant pustule of anthrax.
Three weeks later my mother came to spend an afternoon and evening with us. Over the teatime meal, a fierce row developed over the trivial topic of Christine’s homework. Christine, my elder daughter, was as much at odds at her grammar school, the prestigious Henrietta Barnett School in Hampstead Garden Suburb, as I had been twenty-five years earlier with the Strand School. She could see no point in homework that they insisted she do; she remembered all she had been taught that day and saw no need to recapitulate it. I supported her. My mother invested education with near magical properties and saw Christine’s rebellion as a wicked rejection of a wonderful opportunity for betterment. My mother was living out her own lost opportunity when, as a young girl, family poverty had denied her the chance of a good grammar school education. A wiser woman would have kept quiet, but not Nell Lovelock, and with blazing eyes and waving arms she shouted her disapproval. Helen, who feared above all any overt show of emotion, was distraught, and pleaded for calm. It went on for at least an hour and left us all cross, unrepentant, and exhausted.
Next morning in bed, Helen and I decided to move at once to Bowerchalke and to sell our house in London. I would stay during the week with my mother at her tiny flat in Finchley. Helen and the children would live in the Bowerchalke cottage until we could find a house in the village. At the back of my mind was the thought that I would never be able to endure the ninety-mile journey each weekend, nor the company of my mother every evening of the working week. The discomfort of such a life would force my hand and make me resign from the Institute. At first, it was bearable; my mother was pleased to have my company, and there was the break from Thursday night until Monday morning in Bowerchalke as something to look forward to. It was usual for senior scientists to do the writing work they had at home, the constant interruptions during the working day at an Institute or university lab make serious thought difficult and, for me, impossible. Many tried an early start before the chatterers had picked up their telephone handsets, but it did not often help. There would be a knock on the lab door at 8.30 am. The caller would enter saying, ‘I know you’re not busy just now so I thought I would call in to ask if you would mind giving something for our cricket fund. We need two new bats for this year’s match against Middlesex Hospital.’ Of course, he received the token gift, but his thoughtless interruption had broken thirty minutes of deep thought. To catch the fleeting fragments took another thirty minutes, and by that time, the chatterers were at work. It often seemed to me that there was a conspiracy among the staff of the Institute to stop me working, but I was wrong. Conspiracies are rare events; they take too much effort and organization. It was just that I am odd and do not enjoy the ceaseless verbal grooming of human existence. Perhaps if we had been content to pick nits from each other’s fur, and not learnt to groom by chattering, deeper thought would be more normal. Those of us at Mill Hill who preferred thinking to chattering often worked at home. Our wise director knew it happened and turned a blind eye.
One Thursday, at lunch in the cafeteria, I was at a table with Sir Charles and several other scientists. One of them turned to me and said in a loud voice, ‘I suppose you’ll be off to the country this afternoon as usual, Jim.’ Sir Charles gave him a baleful look but said nothing. Indeed, he made no further comment about my four-day working week until I left the Institute in 1961, when he explained that he valued the Institute staff for what they produced, not how they worked to do it.
As the summer of 1960 lengthened, so the battle against traffic along the old and twisty English roads made Monday mornings and Thursday evenings a nightmare. The journey from Bowerchalke was not bad for the first thirty miles, but the remaining sixty involved travel through commuter land and across the whole width of London. I was lucky to survive those journeys without an accident. There was no
speed limit then, except the 30 mph in built up areas, but driving at 90 mph or more along the few open stretches of country road was unwise. The stress of this broken existence did not seem to force my hand at resignation; instead, I began to smoke and drink far more than before, until one morning at the Institute an encounter with my technician, Peter Simmonds, brought me to my senses. I had run out of cigarettes and he kindly went to the cafeteria to purchase a replacement package for me. When I thanked and paid him, he replied, ‘Think nothing of it: if you go on smoking as you do you will soon drop dead and then I can market your inventions and make myself a fortune.’ It was a fair comment about my new way of life.
The biochemist and Nobel Laureate, Rodney Porter, occupied the lab next to mine and further down worked Archer Martin and Tony James. Opposite, across the corridor, was Philip D’Arcy Hart and RJW Rees, who worked on tuberculosis and leprosy. The best and worst of my researches at Mill Hill were done in collaboration with D’Arcy Hart and Rees. Sir John Cornforth, Kappa to his friends, whose laboratory was elsewhere in the building, had produced an intriguing family of compounds. They were polyoxyethylene ethers of alkyl phenols linked together by methylene bridges. It is not what they were that is interesting but what they did. Rees and Hart had found that they ameliorated infections of animals with tuberculosis organisms. I had found that they did strange things to red blood cells. In particular, they selectively removed cholesterol or phosphatides from their membranes according to how many oxyethylene groups were present. I noticed by accident one day that these substances also appeared to protect red blood cells against the harmful effects of acidity. If suspended in a medium that is too acid, red blood cells haemolyse, that is to say, split apart and release their red oxygen-carrying pigment, haemoglobin, to the solution. A small amount of Cornforth’s agent seemed to stop this happening. Rees and Hart were interested and tried the same experiment with their organisms and with the same results. We were excited and published our findings as a Nature Letter in 1958.
Later, D’Arcy Hart and Nash showed that our remarkable experiments were not due to a specific protective action by these compounds against acidity but to an experimental error. The glass test tubes used in these experiments were contaminated by a film of fatty acids and these came either from soap that was used for washing, from the cotton-wool plugs that we used to stopper the tubes, or from our fingers. Fatty acids are more destructive toward cell membranes when the solution they are in is itself acid. What we had observed was not damage by acidity but by fatty acids. Cornforth’s polycyclic compounds inactivated these fatty substances and stopped them from damaging the cells. It was a serious oversight on my part not to have checked that this effect was occurring and it was fortunate that D’Arcy Hart’s integrity and persistence led him to make the checks and not someone outside our lab. At his insistence, I joined with him and Thomas Nash in a paper in the Journal of Hygiene, retracting our observations. Mistakes like this, a near miss to disaster, are no bad thing. Their heuristic value overcomes the pain of hurt pride and the small harm to one’s reputation.
The work I did with Dr Rees on the way Cornforth’s compounds protected animals against experimental tuberculosis, for me, made up for this blunder. In a short paper in Nature in 1955, we reported our finding that these compounds accumulated in the white cells, the macrophages, of an animal’s blood. There they had the potential to act like detergents and strip away the fatty coat that protects tubercle bacteria. Macrophages exist to remove and destroy foreign bodies in the blood and if the tubercle organisms were made bare by the detergents, they would be easier to digest. To confirm this idea we added a small quantity of powdered blue dye to the blood. The dye chosen was insoluble in blood but soluble in the presence of a high concentration of Cornforth’s compounds. Macrophages taken from untreated animals rapidly ingested the particles of dye. They could be seen as dark granules inside their cells. When the detergent compounds were present in the blood also, the macrophages showed up as bright blue cells, showing that they had concentrated Cornforth’s compounds to a level much higher than in the blood, and sufficient to dissolve the dyestuff. I wonder, now that the tubercle organism has grown resistant to antibiotics, if these odd substances should not be re-examined for therapy, either alone or as an adjuvant for use with regular antibiotics.
I spent much of my last year at Mill Hill fending off instrument companies who wanted my expertise about gas chromatography. By the late 1950s, the Government had allowed us to patent inventions for the benefit of the nation and it was our duty as quasi civil servants to give free advice to firms who wanted to market our inventions, especially where they were using our patents under licence. After a while I found it best to advise one company only and I chose WG Pye of Cambridge, partly because they had taken out a licence on my argon detector patent, and partly because they seemed to be the firm most likely to build a successful gas chromatograph using my detectors. Tony James, who also spent much of his time giving free advice, supported me in this decision. The two representatives of Pye, Ron Evans and a talented engineer, were both honest and considerate men. They were practical but not pushy and never tried, as did the staff of some companies, to bribe. On one occasion, a firm offered me a substantial sum for some simple advice; when I refused to talk further, their response was to increase the offer and say that they would pay in cash. Many of us at Mill Hill were originators of unusually valuable intellectual property. It was hardly surprising that those outside sought to get it by fair means or foul, but we were not tempted because we had a strong sense of loyalty to the Institute and we were in those days well paid and well treated. Now that the profession of science has declined and is poorly rewarded, the temptations must be much harder to resist. One thing that I did get from Ron Evans of Pye was an estimate of how much the firm would pay me as their consultant if I did leave Mill Hill and go to work independently. It was £2,000 a year; more than enough on which to survive.
In 1959, my fortieth birthday loomed and I wondered if it was already too late for me to achieve my ambitions. As I write, forty years older, I cannot help laughing at the foolishness of such a fear, but at 39 my response was to grow ever more unhappy about tenure. Tenure meant that my life ran on predestined tracks; it wouldn’t matter what I did, I was sure of a salary and employment and a place there all the way down to the day of my retirement. Even then, my tracks to the grave would be supported by an adequate pension. Every day I would go to the Institute, do my research, and come home again. I felt like the man in the limerick:
There was a young man who said, ‘Damn’,
It appears to me that I am,
A being who moves
In predestinate grooves;
Not a bus, not a bus, but a tram.
Great as was my wish to break away from Mill Hill’s cosy nest, I could not give up a vocation for science just to become a consultant. Instead of expanding my horizons, this would be restricting me to working on a single technique. I may have grown richer but this was not my ambition. I enjoyed working with Pye and seeing their ideas for commercial gas chromatographs evolve into a practical, saleable instrument. It provided a welcome change from academic research. My invention, the argon detector, reduced Archer Martin and Tony James’s invention of gas chromatography to practice. It was a simple, easy-to-make, and adequately sensitive device. Biochemists worldwide used it for the analysis of lipids, something that previously had been impossible. In its heyday I was sought after like a bride and could have moved to work for any of several American companies at double or more my salary. I could have taken good posts at American universities and been sure of a rich source of grant funds. Perhaps the one mistake I did make was to decline the offer from Dr Keene Dimmick, the owner of a firm called Wilkins Aerograph. He invited me to become a partner in his enterprise. I went to visit him at his home in Walnut Creek in the early days of their business. It had much to recommend it. Keene and his wife, Adele, built chromatographs in their garage, assisted by their ch
ildren. They took me into the hill country nearby and we walked and enjoyed talking science in a country environment, much in the way that I did at home. Had I accepted, we would probably have shared some of the many millions that Keene received when he sold his company to Varian Instruments. As it was, I made real friends among the instrument fraternity of the United States of America.
The abrading and tantalizing year of 1960 rolled on into 1961, and in January I found myself worn out and unable to think or to work. The spell lasted about five weeks, but by resting and walking at Bowerchalke, I recovered and resumed my commuting to Mill Hill. I knew it could not last but could discern no break in the clouds of uncertainty. Around about this time the United States National Institute for Health offered me a grant of $50,000 a year for three years to continue my work on lipid biochemistry and detectors for lipid analysis at Mill Hill. This generous offer did not fit in with my plan to resign, but I had no option but to tell Sir Charles about it. He was enthusiastic. It seemed to him a wonderful way to lessen the damage of the brain drain, the flow of talent from the United Kingdom to America. He promised to discuss it at a council meeting of the Medical Research Council the next week.
I went to his office a week later and, for the first time, found him confused and uncertain. ‘I have bad news for you,’ he said. ‘The council turned down that idea of yours to work here supported by a grant from the NIH. I think they were wrong but there was nothing I could say that would change their minds.’ This rejection was a relief to me, for I saw its acceptance as yet another silken rope tying me into the cosy environment of Mill Hill. Instead of showing chagrin or even anger at this reactionary decision by the Medical Research Council, I said, ‘Oh, never mind, I’ll continue as before.’ Sir Charles was amazed; he had expected a difficult interview. He saw me storming out, threatening to take up the offer in Washington instead of Mill Hill. He said, ‘You have the most peculiar way of taking setbacks but I am indeed grateful.’ He was so surprised that he revealed what ordinarily he would not have done—that it was the Secretary, the Chief Executive Officer of the Medical Research Council, Sir Harold Himsworth, who was most opposed to the idea of external funds coming to Mill Hill. I saw it then as part of the battle between the older science-based Medical Research Council with Mill Hill as its flagship, a world-leading scientific institute, and the new guard led by the clinicians and consultants of medicine. The new men thought that practical medicine, not science, was what the MRC should be doing. They would have preferred to fund an institute dealing with such problems as varicose veins and hernias. The many Nobel Prizes that came the way of the old science-based Medical Research Council were to them just an irritant sustaining what they saw as the wrong way to spend money set aside for medical research. I am sure that had the grant been offered for clinical research, it would have been welcomed. Himsworth and his colleagues won the battle for the redirection of United Kingdom medical research into a clinical not a scientific course and the Clinical Research Centre at Harrow was built at considerable cost. After Sir Charles retired in 1962, Mill Hill sustained its excellence under the directorship of Sir Peter Medawar. Sadly, and like Alick Isaacs, the discoverer of Interferon, he suffered a brain haemorrhage and was unable to continue as its director. In spite of these discouragements, Mill Hill has remained a significant centre for medical research.
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