The three years between the end of my second stay in Pasadena (August 1954) and my move to Zurich (October 1957) were approximately equally divided between the U.S. National Institutes of Health in Bethesda, Maryland, and the Davy Faraday Laboratory at the Royal Institution in London. At Caltech I had worked for a time with Alex Rich, who wished to learn something about diffraction methods for studying molecular structure. For instruction purposes, Pauling had placed him under my supervision, carefully adding that I would be responsible for any damage caused to X-ray equipment. One of Alex's first tasks was to visually estimate intensities of reflections on my X-ray diffraction photographs from ferrocene crystals, a task that he passed on to his wife Jane, who thus earned our indebtedness. (33) Alex was offered a position to develop structural research under Seymour Kety at the National Institute of Mental Health and asked me to help setting up the new laboratory. My wife and I were attracted by the idea of spending some time on the East Coast and also by the offer of a post of Visiting Scientist at a salary more than double what I was earning as Research Fellow at Caltech, so I accepted Alex's proposal.
NIH was a completely new world for me. In the first place, in contrast to what I had previously experienced, there was no shortage of funds to buy the latest scientific equipment. And moreover, since most of the scientists there lacked any deep knowledge of physical chemistry, I found myself suddenly transformed into an expert, relatively speaking, on this branch of science. Accordingly, for example, I was called on to give advice on problems in infrared, visible and ultraviolet spectroscopy, subjects in which I possessed only a smattering of knowledge. After a month or two, Alex left for more exciting collaboration in Cambridge with Francis Crick on the structure of collagen and I was left to my own devices. I learned that sodium dithionite Na2S2O4 was much used as a reducing agent in biochemistry but also that no one seemed to know the structure of the compound or why it was a reducing agent. Since it was a solid, I decided to determine its crystal structure. This information indeed provided the answer to the problem. The anion turned out to be a dimer of SO2-, with a remarkably long S–S bond. In solution, deprived of the surrounding shell of sodium ions, the dimer would clearly dissociate into SO2-, which would then donate its extra electron to any suitable acceptor. (34) In support of this, sodium dithionite is diamagnetic but its solution shows an ESR signal that gradually decays. (35)
Most X-ray crystallographers have never seen a burn caused by exposure to X-rays. I have. During the experimental work on sodium dithionite, I committed a stupid sin of carelessness in the laboratory. This was just after the birth of our daughter Marguerite. Perhaps my main attention was directed towards her. While adjusting a crystal on its mount, I noticed that the X-ray window was open and realized that my fingers must have been exposed to the invisible radiation. Naturally, I closed the window immediately but could not help asking myself how much damage had been done. An X-ray burn is different from an ordinary burn; as there is no heat there is no charring of the skin or flesh. The damage is deeper down and takes some time before there is any outward expression. After a few days, the thumb and forefinger of my left hand began to itch. Erythema soon developed into swelling and formation of blisters. The medical staff of the NIH Radiation Safety Office were outspokenly pessimistic about the outcome of my accident. They talked about possible amputation of the injured finger and thumb because of radiation damage to the underlying bone. It gradually became clear to me that the experience of the medical staff was limited to burns caused by high-energy X-rays, the kind used in medical X-ray equipment. The doctors reasoned that for an X-ray exposure to produce such extensive skin damage as in my case, the damage to the bone must be considerable. I knew this reasoning was wrong. The radiation produced by a copper X-ray tube (the kind I was using) would be almost entirely absorbed by the upper skin layers. For copper radiation, with a linear absorption coefficient of about 12 cm-1 for water and organic matter, only a tiny fraction of the incident intensity would penetrate to any depth and be absorbed by the bone tissue. Therefore the doctors, in judging from the skin damage, were vastly overestimating the damage to the underlying bone, protected by, say, half a centimeter of tissue and fluid. I insisted that I wished to keep my damaged fingers. But as the weeks passed, and the open sores that developed became infected, I did become worried. The healing process was slow, but all that was left to remind me of my stupid error was scar tissue on the finger tip. Later, I used to show this to beginning students as a warning.
At NIH my wife and I were much occupied with the question: should we stay in the U.S. or return to Europe? There was much to be said on both sides. Since our married life had been spent entirely in America, far from our families, we felt we needed some experience of life together in Europe. I wrote to Dorothy Hodgkin, asking if she knew of any suitable openings. She informed me that Sir Lawrence Bragg, recently retired from his professorship at the Cavendish Laboratory in Cambridge, was building a new research group to carry out crystallographic research at the Royal Institution in London. I applied and soon received a warm and enthusiastic answer from Bragg. In a letter dated August 12, 1954, he described the preliminary results obtained by Perutz on haemoglobin and by Kendrew on myoglobin; the final paragraph read:
"There is every chance that with a concerted drive on the problem, light will suddenly break and some key to the general structure of protein emerge. The more good people we get to work together here the better, and if you would like to be one of them, I will do all I can to make it possible."
I replied that although I was very interested in the possibility of working at the Royal Institution, I was not enthusiastic about the prospect of concentrating exclusively on protein research.
"Had I complete freedom to choose a line of research for myself, I do not think I would concentrate on protein analysis. I might choose to apply modern X-ray techniques to some of the problems of inorganic structural chemistry which survived the attacks by yourself and others in the early days of crystallography. Especially in the complex coordination compounds of the transition metals there are many problems left. Another study interesting to me would be that of the specificity of molecular compound and complex formation, where apparently very weak forces can achieve a high degree of specificity. Both of these fields would, of course, tie in with the study of proteins although in an indirect fashion. The first would be a good starting point for finding out something about the important prosthetic groups containing transition metals. The second might tie in with a study of the specificity of enzyme systems. But perhaps this is building castles in the air, and I only mention it to emphasise the fact that my present interests are in regions far from direct protein structure analysis."
Today I am not displeased with this statement of my intentions, but I had serious misgivings about it then, once my letter had been posted. While I did not wish to tell outright lies to Bragg, surely a little prevarication would have been preferable to this blunt statement. As the months went past without any word from London, the prospect of joining Bragg's group at the Royal Institution became more and more remote. I began to look into other possibilities.
In April 1955, Bragg wrote to apologize for his delay in replying to my letter and offered me a five-year appointment as Senior Research Fellow at the Davy-Faraday Research Laboratory. He wrote:
"I cannot see my way clearly in all directions yet. I am not clear of the financial tangle and many plans are still uncertain, but if you would like to join in the venture and help with the research side, I will do all I can to give you a good time. Once again, I am very sorry I did not write to you at once. I could not have been more definite about plans at that stage but I should have acknowledged your letter."
With all my misgivings about the tone of my letter, here was Bragg apologizing to me! I agreed to join and suggested that I might initiate X-ray work on haem itself or some other simple porphyrin derivative (sans protein!), a proposal that found immediate favor with Bragg, although nothing ever came of it because of lack of suitable crystals. We moved to London in January, 1956.
I knew from the start that I was going to enjoy my work at the Royal Institution. With its superb position and noble facade in Albemarle Street, just off Piccadilly, round the corner from Burlington House, the home of the Royal Academy, the Royal Society and many other learned societies, it was obviously a most attractive place to work. Its well stocked and renovated library and reading room and its lecture theatre, surely one of the most beautiful anywhere, added to its attraction. And most of all, I felt the historic aura of its connection with the past century and a half of science. At the back of the building was the Davy-Faraday Research Laboratory, situated on several floors to which one gained access by an old, dangerous-looking, rope-drawn lift. The basement contained the X-ray facilities, including impressive high-voltage equipment protected by a metal wire trellis. I forget how many kilovolts and kilowatts could be generated but I have the impression that the X-ray intensities produced ald were at that time the highest available anywhere. My office was on the third floor. For the first few weeks I had it to myself, but then I was joined by David Phillips, just arrived from Canada, who was to become famous with his X-ray crystallographic analysis of lysozyme. We became life long friends. Other members of Bragg's team were Uli Arndt (involved in the development of the linear diffractometer and computer controlled diffractometers), Tony North, David Green, and Helen Scoloudi, formerly with Bernal and Dorothy Hodgkin, and all presided over by the benign Sir Lawrence.
Through conversation with Ronald Nyholm, recently appointed to the chair of inorganic chemistry at University College, London, I decided to study the crystal structures of cobalt dipyridine dichloride, CoPy2Cl2 and its copper analogue CuPy2Cl2. There were two known forms of the cobalt compound, one violet coloured, the other blue. The blue form was known to contain discrete molecules with tetrahedral bonds at the cobalt atom, while the violet form was believed to contain polymeric chains with octahedral bonds at the cobalt atom, each chloride ion linked to two cobalts, each cobalt to four equidistant chloride ions and to the pyridines. Indeed, this turned out to be the case. The copper compound was found to have a very similar structure, except that the four chloride ions were not equidistant from the metal atom; instead, there were two short Cu–Cl bonds and two long ones. (36)
This result led to another collaboration with Leslie Orgel, who, a couple of years earlier, had suggested that such distortions of octahedral complexes could be interpreted in terms of crystal-field theory as structural expressions of the Jahn-Teller effect. The differences between the octahedral coordination in the cobalt compound and the distorted octahedral coordination in the copper compound seemed a perfect illustration of this, and I soon found that similar differences between other pairs of structurally related compounds occurred according to a quite regular pattern. (37) We also saw that crystal field theory could be applied to minerals with the spinel structure. Spinel is a mineral with composition MgAl2O4, built from a cubic close-packed arrangement of oxygen atoms with the Mg2+ ions at tetrahedral cavity sites and the Al3+ ions at octahedral ones. There are many other AB2O4 minerals with essentially the same structure, with the A2+ ions in tetrahedral sites and B3+ ions in octahedral ones. However, in "inverted" spinels the tetrahedral sites are occupied by B3+ ions, with the A2+ ions and the remaining B3+ ones distributed at random over octahedral sites. We found we could explain all the known experimental evidence on the metal ion distributions in the normal and inverted spinels. Moreover, the existence of tetragonally deformed spinels could also be explained by our theory in terms of the Jahn-Teller distortions expected to occur when certain metal ions were present. (38) When I told Bragg about these results he was delighted. He was just then working on a new edition of his classic The Crystal Structures of Minerals and could now include an explanation of the problem of the inverted and tetragonally distorted spinels. (39) Probably this helped to reconcile him to my reluctance to work on crystal structure analysis of proteins.
In London I acquired my first two doctoral students. One was Peter Pauling, Linus's son, who had decided to work for his doctorate in Britain, and the other was David Brown, who later became a well known inorganic crystallographer in Canada. They were officially enrolled as graduate students of the University of London, but because of the delicate and intricate relationship between the University and the Royal Institution, they were nominally under the direction of the professor of Inorganic Chemistry, Ronald Nyholm, although in fact they worked with me. Peter studied the polymorphism of anhydrous cobalt sulfate, three forms with very similar structures but differing in the site symmetries of the tetrahedral sulfate groups. (40) David worked on the structure of the crystalline cuprous chloride-azomethane complex (41) and of diazoanobenzene copper (I), which turned out to contain a remarkably short Cu..Cu distance of 2.45 Å. (42)
In December 1956 Edgar Heilbronner telephoned out of the blue to ask if I could come to Zurich to talk to Professor Leopold Ruzicka about the possibility of my starting a crystal structure analysis group at the Swiss Federal Institute of Technology (ETH Zurich). Ruzicka was due to retire the following October from his position as Professor of Organic Chemistry. Impressed by Dorothy Hodgkin's success ín deciphering the structure of vitamin B12, he saw that a strong organic chemistry team would be incomplete without this new method. Ruzicka offered me a post as associate professor (Ausserordentlicher Professor) with a start-up grant of about 100,000 Swiss Francs for equipment. He explained that he needed a quick reply. He wanted to fill the post before his retirement. If I were unwilling or unable to come, he would look for someone else. He gave me fourteen days to decide. When I returned to foggy London just before Christmas, my wife and I weighed the pros and cons of London and Zurich, England and Switzerland. There was also the problem of my post at the Royal Institution. I had promised Bragg to stay for five years and now I was thinking of leaving after less than a year had passed. Bragg advised me to go for, as he said, I might never get such an opportunity again. A few days before the end of the year I sent a telegram to Ruzicka to accept the offer. Nine months later, on October 1st, 1957, I began my new career at the ETH.