|CHAPTER 16 - 1964 to 1970 (2)||
One of Reinet's reasons for going back to work as a teacher had been her dislike of housework and from the first she had employed someone to do it for her. The first woman to apply for the job put everything she needed in a box, which she pulled along the floor as she backed round the house on her knees, cleaning all the surfaces she came across from that position at high speed before going on to her next house. She was followed by a more conventional cleaner and then in the mid nineteen fifties, Mrs Dyer turned up in response to an advertisement and quickly became an important part of the family. She had been the eldest in a family of sixteen children brought up in the slums of Glasgow in the early years of the twentieth century, had gone into service before the age of twelve and had run away to London a few years later. She loved to tell us stories about her early life, stories of poverty and managing against all odds but not without humour. She shopped for groceries on the way to work each morning, cleaned, washed up the previous night's meal, cooked the next one ready for Reinet to warm up and looked after us if we were ill. She cheerfully accepted that things that had been left half done should not be significantly moved, especially John's belongings, although it made cleaning such a large house extremely difficult. He expected to be able to put a book or some papers down on a table, a chair or the floor, confident that they could be found in the same place either the following day or a week later. This of course also resulted in a fair degree of permanent untidiness because Mrs Dyer had no way of knowing if something was on the floor for some purpose or because it had just been left lying about. Other than creating these complications for her, John treated her with the same respect he afforded to everyone, listening to her stories, even if they were repeated, with interest and involvement.|
By 1968, Mrs Dyer had passed retirement age and was finding the work so tiring that she was not doing it at all well. However, as she frequently voiced a fear of 'getting the sack', it was difficult to suggest that she should think of retiring. She did not always get on well the students Reinet had accommodated in David's and my rooms once we had started University, especially if she thought that one was delaying her by lying in in the morning. As Reinet ran an easygoing relationship with her students, she objected to their being chased out of bed in the morning when she knew that they had been up late at night studying for exams, and this gave her the courage to suggest to Mrs Dyer that the time had come for her to go. Reinet offered her a small pension, aware of how much she had given the family over the years. Listening to people was something John did extremely well and students and colleagues often found him helpful when they had problems other than with work, although he hardly ever unloaded any of his own problems onto other people. A few people used his ability to listen to problems sympathetically to excess, which sometimes resulted in very long telephone calls. John gave no sign that he was being interrupted in his work, hoping that just by listening he was being of some help. Irene Petrie, the wife of John's old Cambridge friend Douglas, used to telephone John from time to time with long complaints about all her difficulties. These calls increased in length and frequency after Douglas' death in 1967 to the point that the whole family thought that she was taking advantage of John and sometimes told him he should be firmer with her, but he felt a degree of responsibility towards her and sometimes visited her in Reading to offer practical help if he was in that part of the country. John's sister Celia had the same characteristic of being an excellent listener while rarely airing her own personal problems; her daughter Geraldine once said that she had never ever heard her mother complain even of a headache. (However, the novels that Celia produced successfully from the 1950s onwards revolved round the multitude of problems any woman might have, which made it difficult to believe that Celia had encountered none of them herself!) Sometimes two good listeners run out of things to say to each other, but John and Celia still got on like a house on fire whenever they met, indulging themselves with cheerful and constructive conversation.
Yet more uses for the cyclotron were turning up all the time. Sometime in 1965, Dr Michael Chamberlain and Dr Keith Peters came to see John. They held posts in the Department of Experimental Pathology at the nearby Queen Elizabeth Hospital. They told John of a recent measurement of total body sodium by irradiation with slow (low energy) neutrons followed by counting the gamma rays from the resulting sodium-24. Could total body calcium be measured by a similar method and then be utilised in the diagnosis of various bone diseases? John didn't know, but promised to look up the nuclear data for calcium and let them know.
The answer turned out to be yes, but with a number of difficulties. One of the isotopes of calcium is calcium-48, which comprises a little less than two percent of all calcium. When an atom of calcium-48 is hit with a neutron it becomes the gamma emitting calcium-49. The idea would be to irradiate patients with neutrons (at a safe level of course) and count the gamma rays emitted afterwards as a measure of how much calcium-49 had been formed, which would be in proportion to the amount of calcium there was in the whole body. However, calcium-49 has a half-life of only 8.8 minutes. This may have been helpful in that it meant that most of the gammas could be counted in a reasonably short time but the time that would be taken to get patients from the cyclotron to the whole body counter in the Queen Elizabeth Hospital was a potential problem. Although the Hospital was next door to the University, the size of their campuses meant that the actual distance to be covered was about half a mile. Anyway, John, Mike and Keith chose to work on this isotope, the only alternative having a half-life of 80,000 years for which counting would not take a reasonable time.
To find out whether they could expect to generate a large enough calcium-49 activity in an adult patient, they tried a rather crude substitute first in the form of a large bucket of water containing half a kilogram of calcium phosphate. This gave an adequate count rate of calcium-49 gamma rays after a dose of radiation that would be acceptable to give a patient.
The next thing they wanted to try was irradiating cadavers a number of times to determine their overall random error. For this they asked to borrow one of the many bodies available in the Queen Elizabeth Hospital for student training. To get permission for that was unexpectedly difficult, requiring weeks of negotiation with a variety of people, starting with the University Radiation Protection Officer, who, after due consideration agreed there would be no danger to the health of the corpse, finally reaching the Inspector General of Anatomy in London. When they did eventually get permission, the body was supplied in a coffin that they were not allowed to open, and they were given no information about its dimensions, weight or other physical characteristics except for the unimportant fact that it was male. The body was not fixed in the coffin and evidently changed its position when the coffin was moved. However, the coffin itself turned out to be useful in slowing some of the neutrons in such a way that they could be captured by calcium close to the surface of the patient's body, while leaving plenty of fast neutrons to get through to the skeleton.
Two further cadavers were obtained and tested. Now they wanted to try the procedure on live humans and decided to experiment upon themselves. They needed a box with a lid in which each of them could lie in turn, and by far the cheapest way of obtaining one was to buy a suitable coffin from the Hospital. Each prospective patient was helped into the coffin, and the lid closed. After two minutes of irradiation, assistants opened the coffin, helped the occupant to turn around and shut him in again for the second irradiation. Then he was helped out to hurry to Keith's car, customised for the job with a large cross in red paint, and with its engine already running. The University site staff had been asked to keep people away from the route and arrangements had been made for the car to run the wrong way up the one-way road through the Hospital which it did with horn and headlights on, to deposit the 'patient' at the Hospital whole body counter in a few seconds over three minutes.
John was the first patient and he asked Mike to leave him shut in for five minutes before telling the control room to switch on. He remembered finding at Ilminster that if he put his head in a weak microwave electric field in the dark, he could see a glow, presumably due to induced currents in the visual cortex (the part of the brain concerned with vision) and wanted to see whether the same occurred with neutron bombardment. To his disappointment, no glow appeared when he heard the switch go on, but after some seconds he suddenly noticed that in his black field of view there was a series of temporary stars - infinitesimally tiny bright spots appearing and at once disappearing in a random way. It occurred to him at once that these must be due to fast neutron interactions in either his retina or in his visual cortex and that he would be able to tell which of the two were involved when he turned round. He was in contact with the outside world through an intercom system, and, thinking quickly, he decided to ask if he could be turned round in the dark before the second irradiation so that he didn't lose his adaptation to the dark. As soon as this had been achieved and the neutron beam started again, he saw his stars, but this time much fewer, convincing him that the fast neutrons concerned were hitting his retinas and had in the second case been reduced in number by absorption in his brain. John later calculated that this would mean that in the whole brain ten million or more cells would be struck, most of which would be expected to repair themselves, but he suggested that in real patient irradiations it might be better not to irradiate the head, the calcium content of which would be unlikely to be important.
This work was published in the British Medical Journal in 1968. Before real patients could be used, the whole procedure and what was hoped from it had to be put before the Medical Ethics Committee for their permission. Once this was granted, a special box was built for the patients, who, it was thought, would not appreciate being put in a coffin, and a thick perspex window was built in to slow down the fast neutrons in the region of the head. The intercoms between the box and the control room were left working, which made patients feel safer. The exciting race between the cyclotron and the hospital was abandoned for a more sedate ride in an ambulance taking around seven minutes. The method was not meant to be used to calculate the exact content of calcium in the body: far more calibration would have been necessary. Rather it was meant to quantify increases or decreases of skeletal calcium in one patient over a period of time or through a course of treatment. Mike and Keith used the measurements to look at calcium metabolism in primary hyperparathyroidism-1- and to compare the efficacy of several current treatments meant to reduce calcium loss in osteomalacia-2- . In both cases the work led to the abandonment of some ineffective treatments and research using the technique over the next few years led to a number of new insights into the mechanism of each of these diseases, which would not otherwise have been possible at the time. Their attempts to investigate osteoporosis-3- were not so successful as calcium losses due to this disease were too slow.
John was fairly sure that he was the first to knowingly see neutrons in the way he had done in the coffin. But being extremely busy with the activation analysis programme, he didn't publish this result until he saw an article in New Scientist to the effect that similar but much brighter phenomena were reported by the American crew who went to the moon in 1969 and who were irradiated by cosmic rays. He then wrote to New Scientist to explain their observations and report his own experience.
The technique was called in vivo-4- neutron activation analysis and over the next few years John, Mike and Keith evolved methods of measuring the quantities of other elements in the human body starting with nitrogen. Proteins contain nitrogen and most of the important nitrogen in the human body is in the muscles and internal organs so diseases involving abnormally low nitrogen levels are serious. At the time, treatments of such conditions required several checks of whole body nitrogen by collection and chemical analysis of all the patient's food, drink and excretions, which took a great deal of time. The new procedure measured whole body nitrogen in fifteen minutes and again it was used to compare the relative amounts of nitrogen within one patient before and after treatment rather than to give an absolute value for someone's nitrogen content. The method was to bombard the nitrogen-14 in the body (the most common isotope of nitrogen) with slow neutrons to produce gamma rays and nitrogen-15. However finding a suitable isotope wasn't the end of the story and more physics had to be done. If you irradiate a whole person, several elements might become radioactive and give off countable gamma rays and so the energy of the neutrons being used for the irradiation had to be specified, and the resulting gamma rays were only counted if they also came within a required energy band. So for the measurement of whole body nitrogen, gamma rays of energy greater than 10 MeV-5- were measured as coming from nitrogen, to avoid confusing them with gamma rays from other body elements such as carbon, which emitted the rays at around 7 MeV. The team also found that using a pulsed beam of neutrons for irradiation of the patient further increased the ability of the technique to differentiate the gamma rays given off by the nitrogen.
As John had mentioned in his 'Impure Physics' lecture, new experiments in radiobiology could be done relatively quickly and inexpensively, and the neutron activation analysis work resulted in plenty of interesting projects for research students. During one year while this work was going on, John had the highest number of students collecting PhDs at the annual degree ceremony and he and Reinet invited them all to a party afterwards. This meant, however, that John was beginning to spread himself fairly thinly, coming up with ideas and giving support and advice rather than doing the experiments himself.
The work on nitrogen led to a method of measuring cadmium because cadmium-113 picked up neutrons at the same energy level as did the nitrogen-14. Whereas calcium and nitrogen are essential constituents of the human body, cadmium is a contaminant, which is toxic when it is concentrated in the liver and kidneys. J S McLellan joined the group at this time and for her PhD she developed the system for in vivo cadmium measurement helped by Brian Thomas. Some of the first measurements were made on a few people who had worked in a nickel-cadmium battery factory during the second world war and high levels of cadmium were found in their livers. One of the people measured died shortly afterwards and the post mortem showed similar levels of cadmium to those estimated by the new method.
The manager of a local factory which produced cadmium compounds was worried that stringent safety restrictions were not being observed by his employees and he invited John and his team, to check if workers had taken in too much cadmium. Unfortunately, their first attempts to persuade the workers to be tested met with considerable resistance. The elderly ladies for whom they had measured whole body calcium had shown no fear of irradiation; rather they had appreciated the privilege of being allowed to use so much science. The cadmium workers took several weeks of persuasion, probably fearful of the technique and definitely worried about losing pay during any time taken off for treatment if they were found to be contaminated with cadmium. John went up to the factory himself and began by getting the general manager to be tested. Next he gave the whole staff a lecture, emphasising the medical advantage of knowing early if treatment would be needed. Then he talked to the shop stewards and stressed how important their example would be and got all of them to be tested. Lastly, the management agreed that no-one would lose any pay if they were found to have abnormal levels of cadmium in their bodies. After the shop stewards had been measured, the rest of the staff didn't want to look cowardly. Luckily no abnormally high levels of cadmium were found by the tests.
Patients requiring whole body calcium and nitrogen measurements were often already in hospital and so bringing them to the cyclotron for irradiation was relatively easy. Cadmium measurements were clearly going to be done more often on workers in factories who were not obviously ill and who would not therefore appreciate trekking over to a hospital or university. So the group turned its attention to creating mobile units for cadmium measurements using a plutonium-beryllium neutron source instead of the cyclotron: the plutonium gave off alpha particles which in turn knocked neutrons off the beryllium. This source had to be stored securely in lead and portable gamma ray detection equipment had to be built. Dr David Chettle, who had attended the radiobiology MSc course, became involved in setting up and using the mobile units which went all round the country, and even to Belgium, to perform studies at plants which produced or used cadmium.
During this period a cadmium scare occurred in the village of Shipham in Somerset, where the soil was found to contain considerable concentrations of cadmium that had been left in the spoil heaps from Roman mines. The vegetables growing in the soil had now been found also to be contaminated but no one knew if people had absorbed toxic amounts of the metal. John went down to Shipham to discuss the matter with the local doctors and to offer his team's services to find out if people had been affected. The doctors were much in favour of this. Somehow some section of the Ministry of Health got to know of the proposal and informed John that they were not to proceed without written approval. As they had not taken any notice of the cadmium measurement work that had been going on for a while by this time, John could not see what they might know about the subject and indeed, how they could proceed themselves without knowing if people had been contaminated. John asked the mobile team to pack its van and get ready to go. He took no notice of a message asking him to return a telephone call to the Ministry until the van had left when he 'allowed' himself to be found to return the call which was indeed a demand that the work should not go ahead. He was able to say, quite truthfully, that he had no way of recalling the van and would only hear from the team when they arrived. When he did hear from them, he told David Chettle to ask the local doctors again before proceeding, which he did. The doctors decided that their job was to promote the health of their patients over and above listening to what the Ministry said, and allowed the team to carry on with the measurements. John sent the results to the Ministry, showing some considerable, but not dangerous, levels in some people, resulting in an official statement that all vegetables in Shipham should be destroyed. Research on cadmium levels in the soil, vegetables and people of Shipham continue to this day.
In 1968 a double tragedy hit John's sister Celia. Her marriage to Elia had produced three children, Nicholas, Geraldine and Sylvia. The family lived in Hampstead and visits had been exchanged regularly between the children of both families as we were of similar ages. After leaving school Sylvia had spent some time in France, a country for which she had a passion and had become pregnant by, and married, a young man she met there. When he left her shortly afterwards, she hunted for him in France, and despairing of ever finding him she took her own life by throwing herself beneath a train. John found that he urgently wanted to know the facts surrounding the tragedy, disliking answers to his questions which started "I think she felt that .." but still did what he could to comfort Celia. Later in the year, Elia, who had frequently suffered from depression and who had become severely depressed following Sylvia's death, died from a massive overdose of barbiturates. At the time we were told that Elia, having had a heart attack a year earlier, had actually suffered another one and had feared being disabled by this second attack and had therefore taken the pills. While this was still the accepted public reason for the suicide, John took the opportunity to explain how he believed he would deal with any impairment of his own health or strength. He was quite sure that he would find his way around a disability, that he would search for and find something he could enjoy doing whatever his physical condition and indeed his later years showed him doing just that in cruel circumstances. But this conviction about his own ability to cope would never lead him to say that other people should behave in the same way, and he would always defend a person's right to die if they wanted, even stating that suicide should be seen as a courageous act, while at the same time wishing that such waste didn't have to happen. I cannot tell you what John's inmost thoughts were about anything, but this concatenation was common: a person's trauma or disaster might be discussed, usually with sympathy, rarely with empathy, but he would always seek a solid explanation and end with an opinion of his own that was highly optimistic.
In 1969 John took a sabbatical and went to Ghana as visiting Professor for a term. He was given a bed sitting room in the block of University flats at Legon not far from Accra and a car was arranged to take him to his office in the Science department half a mile away. After a day or two, he dismayed his hosts by saying that he preferred to walk, finding that this was much more comfortable and also quicker as the car drivers were not particularly punctual. His first official function was to give an open lecture to a packed audience. This was essentially the same as his Birmingham University 'Impure Physics' lecture. After it, Professor Reuter, a food technologist, came over to say that he had enjoyed every minute and that it was always inspiring to see a first class craftsman exercising his craft.
Getting down to some work, he was asked to look into a problem with a radiation monitor unit near Tamale, 250 miles north of Accra. This had been set up by the Atomic Energy Establishment to give warning of possibly serious fallout from French nuclear tests in North Africa but had not been visited for a long time. A local boy had been taught to operate the Geiger counter and to pass on the results. A small rise had indeed occurred following the French tests and then, as expected, after a few months the counting rate had reduced to the original levels. John was asked to investigate because the reported measurements had then suddenly dropped and persisted at half the original background level. John first checked the way the Geiger counter was being operated and found that this was satisfactory. Samples for counting were collected by sucking air through a cloth with a fan. Any dust caught on the cloth was then analysed with the Geiger counter. When John asked to see a sample being collected, he discovered the problem as soon as the fan was switched on when it made an ear-splitting noise. He explained to the operator that although it was out of sight, he was sure it had some broken blades, knowing that this would adequately explain the low readings, for there would have been a sudden drop in the quantity of dust particles collected on the cloth when the fan was first damaged. A new run after the fan had been mended produced the expected readings at the level of the original background. Fetching a nuclear physicist from England was possibly a slight overreaction to this problem.
Another task was to visit the agricultural research station at Kpong, 55 miles east of Legon. The station was run by an elderly but capable man called Khan and John had to spend some time convincing him that he had not come to tell him how to grow rice for Khan had had some unfortunate experiences with the Food and Agriculture Organisation. But convince him he did, and Khan explained one of his real problems with iron deficiency in the soil and the odd losses of iron under certain conditions. John took him some radioactive iron and suggested some experiments to try and pinpoint the problem.
Advice on problems that might be solved by radioactive tracer methods, lectures and a lot of sightseeing filled the rest of the time. One of his colleagues at Birmingham had suggested that he visit Lake Bosumtwi, widely believed to have been gouged out by a large meteorite. A Dr Sam White who was in charge of biological research there agreed to take him. John wanted to walk down to the lake from one of the villages that surrounded it, but was told by his hosts that he must on no account do this, the route being a steep rocky path, which they thought he would never be able to get up again. Sure that he was a lot fitter than they were, John was not inclined to take their advice and started down confidently enough, especially as he was told that the village women came back up carrying thirty pounds of fish on their heads. However, he continually studied the route ahead of him, prepared to give up and go back if the going looked really hard as he did not want to make a fool of himself by becoming stuck after such warnings. He had no difficulty either way. One of the Ghanaian boys who came with him insisted on bringing his rucksack up for him, balanced on his head. (John's perception of danger, however, often tended to be influenced by his usual optimism: once Mike Chamberlain accompanied him on a flower-hunting trip to Llandudno. A few years ago Mike wrote to me of the experience: 'The Great Orme was very slippery and hazardous in the rain and the gale that was blowing made things worse. I feared for my life as we clambered on and over the edge but John was in pursuit of some wretched Cotoneaster and continued to chirrup in excitement as he tracked it down regardless of the danger.')
Clearly the visit to Ghana was thought to be useful for John was invited twice more. For the second trip a year later, Reinet was able to take two weeks unpaid leave from her teaching and went out with him. She found herself to be much more distressed by the heat and the difficulties of getting comfortable and sleeping in new places than John, which highlighted his love of travelling and his ability to fit in anywhere. However, she enjoyed some sightseeing when John was available to take her out and was interested by visits arranged for her to see some schools and their physics lessons. In some cases she was horrified by the poor teaching of physics especially when she saw a child reprimanded for what she considered was a correct answer given in different words from the text-book sentence the teacher required.
John again spent the time travelling around Ghana suggesting solutions to various problems. Some work had already been done by Ghanaians themselves using radioactive tracers to investigate the usefulness of phosphate fertilisers in growing cocoa trees. Now John was asked to help to find a way to discover which parasites and predators could be useful in reducing a problem caused by a caterpillar that ate the leaves. John suggested collecting some of the caterpillars, feeding them on cocoa leaves contaminated with the radioactive phosphorus-32 and then releasing them on a cocoa tree. John then helped to get this experiment under way. After a few days, the tree was sprayed with a powerful pesticide and everything that fell off it was tested for phosphorus-32. Several sorts of spiders, ants and beetles were found to be radioactive showing that they had eaten some caterpillars suggesting that one or all of them could be used as a biological form of control. Another of his tasks involved helping a Dr Coker with his research on mosquitoes: John cheerfully lent his arm to help in the feeding of some freshly hatched females.
On his first trip to Ghana, John had had some of his payment made in English money and the rest in an unexportable allowance for living expenses. His expenses had turned out to be very low as he never got charged for his room or the car he used, and as usual he didn't run up large bar bills, which resulted in some money being left in Ghana. The same was clearly going to happen after the second trip, so John and Reinet decided to get a large cabinet made in which he could keep flower slides. They hoped to get this done in good Ghanaian mahogany and took a small drawer from an existing cabinet with them when they went, together with a sketch made by Reinet to show what was wanted. A cabinet-maker was found who had just started the work by the time John left. When the cabinet came to England, it seemed to be largely made of plywood although the front was of better material, but the crate in which it came ended up in John's workshop and provided some good wood for shelving. John used the remainder of the money that was left in Ghana to help a physicist who had been one of his hosts and who lost his job when there was a change of government.
During the summer after the second Ghana trip, both Jane and I got married, to Duncan Wilkins (her sweetheart from her school days) and Bernard Kettlewell respectively and, as was to be expected, John produced excellent speeches at the receptions. At my wedding, which came first, he started his speech with the usual 'Unaccustomed as I am ...' and at Jane's, three weeks later, he started with 'Accustomed as I am ...'
A few months later Reinet found a lump in one of her breasts, it was found to be malignant and she had a mastectomy. John was distressed by this turn of events but immediately turned his distress into action by looking up figures of mortality from breast cancer and asking his medical colleagues for any information they could give him. The results of his research led him to be reasonably optimistic and both he and Reinet decided that the important thing was to get her back into reasonable health so that she could get on with her life. Never liking to be without an occupation, Reinet spent her convalescence fixing strips of corrugated cardboard into the divided drawers of John's slide cabinets to act as runners for the slides. In the event, after one small relapse that responded to an unpleasant course of radiotherapy, it turned out that their optimism was well-founded.