My bleary-eyed appearance at the Institute was noticed by my friend David Evans. He was a dark Welshman and a distinguished bacteriologist who later became famous through the development of a vaccine for whooping cough. He was one of a family of scientist brothers that included the able physical chemist AG Evans. David, along with the physiologist Hank McIntosh, decided that I needed taking in hand. Unwisely, although with good intentions, they arranged a match between the Institute’s receptionist, Helen Hyslop, and me. As they put it to me, ‘If you want to become a scientist you will have to stop behaving like a tom cat and then sleeping all day. You will have to settle down with a nice girl.’ At the time, it seemed to me that they were right and Helen and I began a low-key courtship that ended in our marriage on 23 December 1942. Looking back it seems that our marriage was in some sense arranged. We were both so encouraged by the Institute staff that it just happened. We were not really in love, we were just fond of each other, and we both believed that love would come in its time. We spent our honeymoon at a small hotel in Keswick in the Lake District. It was a wartime marriage solemnized at a Registry Office in London’s Euston Road. David Evans was the best man and the Institute’s chef, Madeline Scott, the maid of honour. The wedding reception was stark and held in the buffet at Euston Station.
Travel by train in wartime was unrestricted but made so uncomfortable that only those who needed to travel did. The train to Keswick took nearly twelve hours to reach its destination. It was packed with troops as far as Crewe, midway through the journey, but from then on almost empty of other passengers. When at last we arrived at our hotel in Keswick, we found it far better than we had expected. We were welcomed warmly and, although by now it was past midnight, the hotel provided hot cocoa and a fine choice of food. We retired to a warm and comfortable bed at about 1.30 am. In spite of Helen’s virginity we started our marriage well and spent a pleasant and fulfilling honeymoon walking the Lakeland mountains.
On returning to London in January 1943, Basil and Mary Large, friends of David Evans, invited us to stay with them while we hunted for a flat. Basil was then editor of the communist paper the Daily Worker and Mary his wife was a trade union organizer. They were both wonderfully kind and unstinting with their help and advice in finding a home. We soon settled in a flat in Willow Road, on the edge of Hampstead Heath and only a short walk from the Institute.
As the German bombing of London lessened during 1942, the population of the shelters also diminished. I spent my time testing aerial bactericidal substances designed to destroy the bacteria in the air without harming or irritating people. This was my first encounter with dogma in science. The conventional wisdom among my colleagues was that aerial collisions with the fine particles of disinfectant floating in the air killed the bacteria. My upbringing led me always to question certainties. Partly, I doubted my father’s dead cert of a horse bound to win the race. He was a hopeless gambler, even though his bets were always modest and did not adversely affect the family income. Partly, it was the endless political arguments and the religious dogma of those times that inoculated me against belief in the certainty of anything. My scepticism led me to calculate the probability of a collision between an airborne bacterium and a droplet of the disinfectant we sprayed in the air to kill it. The calculation suggested that even with the densest disinfectant aerosol we could sustain, collisions would be so infrequent that the bacteria would survive for as long as a day. We knew that the sprays did work and killed bacteria in seconds, not days. The agent most used in the experiments was a solution of hypochlorite. I began to wonder if the bactericide worked, not by collisions between bacteria and bactericide, but by the condensation of gas or vapour in the air on the airborne particles. To test this idea I sprayed some strong disinfectant, a cationic detergent that was not volatile, into the air. At the same time, I sprayed a suspension of mouth bacteria, Streptococcus viridans. The spray of non-volatile disinfectant had no effect whatever on the organisms. Next, I tried volatilizing some lactic acid, a harmless acid that is part of our normal metabolism but which, when it condenses on a bacterium, will make it so acid as to kill it. This did kill the bacteria, and far more effectively than anything else we had tried. This and some other experiments confirmed that it was the vapour, not the aerosol that acted as a disinfectant. Lidwell was a much more accomplished mathematician than I was at that time and he analysed the conditions under which the bactericide condensed on the particles. With this model, we established the vapour condensation theory of aerial disinfection.
The English by that time of the war had entered a state of grace that had not existed earlier and certainly has not existed since. Bourdillon was an old Tory, yet he told me that I must publish my lactic acid experiments as a Letter to the famous science journal, Nature. The reason for publication was not to help our reputations but to block the possibility that someone might patent the discovery and make money from it. So, my first paper to Nature was ‘Lactic acid as an aerial disinfectant’, and published in 1944. Later I synthesized a series of acids similar to lactic acid to see if one of them was a better aerial disinfectant. I published this also as a patent-blocking Nature Letter. The English distrust of entrepreneurs and of successful businessmen is much older than socialism. In the complex hierarchy of England the middle classes, professionals, and office workers looked comfortably down on the working classes but angrily disliked those in business—trade as they called it—who bypassed the normal routes to preferment. They saw it as queue-jumping and therefore wholly amoral. Continentals and Americans find this trait difficult to understand, but then their societies have not enjoyed the long period of internal peace that England had, during which there was time for social structures to evolve. Looking back, I find this refusal to market our inventiveness and so help establish advanced industries post-war in Britain, both perverse and unrealistic.
The Londoners were surprisingly non-tribal. Whatever Churchill, the old war horse, might say otherwise, many of us viewed German aircrews, especially when caught by the searchlights, with more compassion than anger. They were clearly targets, but few of us regarded the bombs they dropped as personally intended. The war was against the Nazis, we said, not against the German people. Lunchtime talk at the National Institute in Hampstead often involved the war, but usually in a strategic sense, such as the victories and reverses in North Africa, for example, and it was rarely about air-raids—they were too close at hand. M Van den Ende, a virologist, was the exception. He was an Afrikaner and a committed nationalist. He would often tease the more stolid Englishmen by taking a pro-German stance. I well remember two bruising rows over lunchtime. Van den Ende and his English opponent, a physical chemist named Elford, almost came to blows. We had few doubts about Van den Ende’s commitment to the war against the Nazis, but equally we knew he disliked the English as a tribe.
Perhaps because I was twenty-two, young compared with the other staff members, or perhaps because he knew I was a Quaker, Van den Ende became for me a confidant and a friend. I grew to respect him and soon discovered that he had the cool bravery of a professional warrior. At this time, the Institute became involved in an extraordinary and dangerous project. The war had progressed to a point where the allies contemplated the invasion of Southeast Asia and there was not just the enemy to consider; some parts of that vast region carried a high risk of infection with scrub typhus, an often-fatal disease. The government ordered the virology department of the Institute to develop a vaccine against the scrub typhus organism. In the 1940s, there was no Health and Safety Executive to oversee dangerous experiments and, in any event, the daily risk to life of the war itself made us all less finicky about risk-taking. In fact, the scrub typhus project started with a rehearsal using murine typhus, a comparatively mild disease in humans.
Because of the deadly nature of the organisms, the virologists took unusual precautions. All work was in sealed chambers through which air was drawn and vented through disinfectant-laden filters. Here they inoculated exp
erimental animals, rats, with the virus by pipetting a small quantity of a virus suspension into their nostrils. In spite of the precautions, several members of the virology department caught the mild infection of murine typhus. There was a post mortem on the experimental procedures and they made all apparent steps at which infection could have occurred virus-proof. The team now decided to do a second rehearsal, this time with human typhus, a serious but rarely fatal disease, before going on to scrub typhus. Again, several virologists, including Van den Ende and the departmental head, Christopher Andrewes, were infected and were seriously ill, and the prospect of moving on to work with scrub typhus was daunting. An unknown leak of virus existed somewhere and it placed the whole team in hazard. At this stage, they began to wonder about the risk to all of us in the Institute, and to those living nearby, because the Institute was an old hospital building with no ventilation, other than by air movements from open doors and windows, and there was no way to isolate the virology department. In peacetime they would have moved the experiments to an isolated safe unit in the countryside, but the pressures of war gave no chance to do this. Instead, our group—Bourdillon, Lidwell, and I, now joined by Frank Raymond—were given the task of finding the source of the infection. We suggested that they try inoculating their animals with a suspension of the organism Serratia marcescens, a more or less harmless bacterium, but one that we could grow on agar culture plates. Its bright red colonies distinguish it from other naturally occurring bacteria and a single bacterium collected from the air will grow on the culture plate into billions of organisms and become a colony—bright red—visible to the eye. By this means, we could detect the escape of even a small number of potentially infective organisms. The virologists ran through their rehearsal again using our scarlet bacteria. We soon found that these organisms were in the air of the lab and the corridor outside that led to the rest of the Institute and to the animal house. We found that the recently inoculated rats sneezed as they sat in their open cages awaiting transfer to the animal isolation unit. Their sneezes spread the organisms through the air. The virologists then constructed sealed cages and repeated their rehearsal. This time they found no organisms in the lab or Institute air.
Van den Ende and his team immediately went on to work with scrub typhus and soon had developed a vaccine, but there were casualties. An Australian scientist, Dora Lush, died after accidentally injecting herself with the virus, and a technician named Joyner also died from the disease. We all felt that this brave man and woman who had given their lives in this cause, who had spent their days in the company of so deadly an agent, should have received more acknowledgement. The authorities rewarded Van den Ende by making him responsible for the safe manufacture of scrub typhus vaccine on a scale sufficient to inoculate the troops who would invade South-East Asia. He had the awesome task of setting up a plant in the village of Frant near Tunbridge Wells to grow this deadly organism in cotton rats on a near industrial scale. They called us in again to help design a safe procedure and building. Bourdillon and Lidwell did some pioneering research on the air temperature needed to destroy all organisms, including this virus. They discovered that heating the air to a temperature above 120° C was effective, and from this information, they designed a ventilation unit for the Frant operation. It drew air from the building through a furnace that heated the air to over 120° C and then passed it through a heat exchanger so that the heat was not wasted. The air, now free of infectious organisms, escaped to the countryside. Women soldiers who had no previous virology training were taught to handle the virus and the rats by Van den Ende and his team and they made the vaccine without a single casualty. They never used the vaccine in military operations: the atom bomb ended the war and there was no invasion of South-East Asia. With today’s morbid fears of pollution, we would never have attempted this dangerous project, but then we obeyed orders and faced the risks of war, whatever form they took.
There was a series of dining rooms on the top floor of the Institute. One for members of the scientific staff, which included all qualified staff from the Director, Sir Henry Dale, down to the youngest and newest, a bottom-second graduate from Manchester. We were the officers and our dining room was the best. There was a dining room for the administrative staff, which included the librarian, the office staff, and the Director’s secretary; and there were dining rooms for the technicians and maintenance workers. The social apartheid of those days was as intense and unbreakable as was the racial segregation of South Africa. Few among the socialist majority of the scientific staff, even Marxists, complained about or suggested changing the dining arrangements. My seniors and I gathered in the coffee room after lunch and were unrestrained in our conversations. Socially and politically incorrect it may have been to have no women or other ranks present, but for me it was fulfilling. We freely discussed good things and terrible things without thought of the needs for security. I first heard of the Manhattan Project, the source of the first atom bombs, in 1944 from a biologist who had just returned from an operational research posting. Soon it was all round the Institute. The idea fascinated Robbie Bourdillon, who had the idea that atom bombs were small things about the size of a pea but with the explosive power of a blockbuster. We did not have detailed information about design or critical masses but we did know that neutrons and uranium-235 were involved. One of the more awful things discussed was a suggestion from an Anglo-American source to use Arabs in the North African desert as experimental animals in the testing of the scrub typhus vaccine. Fortunately, it was never more than a suggestion. There were strange things also. The after-lunch coffee was diluted with bull’s milk. Yes, under wartime conditions of scarcity we feminized experimental bulls and turned them into milk producers. Then there was the suggestion that we should use stilbestrol, the synthetic female hormone, as a chemical warfare agent. The proposer of this idea wanted stilbestrol powder dropped from the air over German troop concentrations. The conversion of tough soldiers into quasi women, he said, would sap their morale. Moreover, its effects were reversible and it would therefore be a most humane weapon. This idea also never flew. I do not know why, but guess that the idea was discarded because it could have been seen as chemical warfare.
My senior colleagues were wonderfully kind to me. I think now they saw me as their personal graduate student, for as an apprentice I was always eager to learn and would listen and sometimes help them by inventing something for their own problems. I spent a lot of time with M Van Den Ende and he unstintedly completed my bacteriological education. Whenever there was spare time, I would go to his lab for a tutorial on topics such as Koch’s Postulates, the scientific criteria used by bacteriologists to confirm that an organism and a disease are causally connected. The physiologists, led by GL Brown, soon took me to their bosom also, as a fixer of electronic apparatus and an inventor. One day Hank McIntosh of that department, a Canadian physiologist over in Britain during the war, came to me and asked, ‘Can you make something to measure mercury vapour in the air by this evening?’ It was quite a challenge. It meant parts-per-billion analyses and I could think of no chemical way to do it in this short time. Then suddenly I remembered that we had made and used an ultraviolet absorption instrument for measuring ventilation rates. It used ultraviolet-absorbing tracer substances. I knew that mercury vapour is the strongest absorber of ultraviolet coming from a mercury vapour discharge lamp. So I asked my colleague, Lidwell—who had actually constructed the apparatus, although the suggestion to make it was mine—if it was still working. It was and Hank McIntosh took it into their diving chamber to see if it was safe to spend hours there in a simulated deep-dive experiment. Our equipment found the chamber air saturated with mercury vapour. It came from a broken manometer, which had spilled liquid mercury on the floor. To breathe this air for several hours could have led to irreversible brain damage, if not death. It was a joy when in Canada, forty years later, Hank McIntosh, by now Professor of Physiology at McGill University, greeted me with the words, ‘Here is the man who s
aved my life.’ During the war, Hank and I spent time making a thumb sphygmomanometer to measure continuously the blood pressure of divers. I discovered using it that my own blood pressure at age twenty-three was high, 150/70, something that seemed to worry McIntosh, who was medically qualified. He said I ought to do something about it. It increased over the years until the onset of angina nearly thirty years later convinced my reluctant GP that something indeed should be done about it. He then prescribed anti-hypertensive medicine, which I have taken ever since.
Towards the end of the war, there was an open day at the Institute where we showed off our inventions. My bacteriologist friends were always complaining of the difficulty of writing with coloured wax pencils on cold damp glassware. They often needed to write on the glass of culture plates and tubes, which came straight from the refrigerator. In the damp air of England, a film of water immediately condensed on the cold surface. It was almost as difficult to write on these cold wet plates as it would be to strike a match on a piece of soap. I made a batch of special wax pencils which would write on cold wet glassware. They were a roaring success, and I could have spent the rest of my time at the Institute making these pencils for the staff and their friends in hospitals around London. The new Director, Sir Charles Harington, suggested that I publish the formula in a Letter to Nature. This I did and within a month received a letter from a pencil firm in the United States asking if I would sell the patent to them. Of course, I had to reply that there was no patent.
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