Robert Donald Bruce Fraser was born in England in 1924. Fraser began a part-time BSc at Birkbeck college in London University but this was interrupted by World War II. During the war, Fraser was a pilot in the Royal Air Force where he taught pilot navigation (1943–46). After the war, Fraser completed his BSc (1948) and PhD (1951) degrees at King’s College in London. Fraser’s PhD work focused on the use of polarised infrared radiation to study the structure of biological materials and he made important contributions to our ideas about the structure of DNA. In 1952 he immigrated to Australia with his wife Mary and baby daughter Susan, to take up a position with the Division of Protein Chemistry at the Commonwealth Scientific and Industrial Research Organisation (CSIRO) in Melbourne, Victoria. There he worked on the molecular structures of fibrous proteins including wool and feather keratins, and collagen. He retired in 1987 to take up a Fogarty Scholarship at the National Institutes of Health (NIH) in Washington undertaking collaborative research with several NIH scientists. After returning to Australia he spent some time writing software for his children, Andrew and Jane, and since then has continued to publish original contributions to the structure of fibrous protein until the present time.
Interviewed by Professor George Rogers in 2008.
I have been a colleague and friend of Dr Bruce Fraser for more than 50 years and it is a pleasure to provide a few words of introduction.
Bruce was elected to Fellowship of the Academy in 1978 for his distinction as a biophysicist in the field of the molecular structure of fibrous proteins. He was born on a farm in the Home Counties and grew up in the Harrow area, just outside London. His high educational achievements led him to study part time at London University for a BSc. It was wartime and, at the end of the first year, when he was 18, he volunteered for aircrew in the Royal Air Force. After qualifying as a pilot, he was selected for instructor training and specialised in teaching pilot navigation.
After the war, he finished his science degree full time at Kings College, London, and then completed a PhD. It was during this period that he met his future wife, who was setting up a biochemistry facility in the biophysics unit, and they were both involved in the work that led to the discovery of the molecular structure of DNA.
In the early 1950s, conditions in England for two young and successful people who wanted to raise a family were so dismal that they emigrated to Australia, where Bruce joined the CSIRO Biochemistry Unit in Melbourne, in which fundamental wool research was being carried out. It was here that Bruce’s career reached its pinnacle, and his X-ray diffraction research into wool keratin structure and other fibrous proteins became known both nationally and internationally. Furthermore, his research ventured further into developing robust mathematical and digital techniques for analysing X-ray diffraction data.
Bruce was awarded a DSc degree by London University in 1960. He has written two books covering keratin, collagen and other fibrous proteins, and has published some 175 papers. During his outstanding career, he has been invited as a visiting professor and as a keynote speaker to many institutions and conferences around the globe. He has also received numerous honours and awards, including the science medal of the Royal Society of Victoria, the S G Smith Memorial Medal of the UK Textile Institute and the Fogarty Scholarship to work at the US National Institutes of Health.
In 1987, having been Acting Chief and Chief of the Division of Protein Chemistry for five years, he decided to make way for some new blood and retired to the Sunshine Coast in Queensland. His retirement did not mean giving up science, however, and he has continued his intellectual work on fibrous protein structure and has published many papers in collaboration with several colleagues, especially his old colleague David Parry, who recently retired as Head of the Institute of Fundamental Sciences at Massey University. Of particular note is their recent publication of a proposed tertiary structure for the filaments of feather keratin. This is the most remarkable and detailed three-dimensional analysis of the structure of a keratin protein ever proposed.
Bruce, we first met in 1952, when you arrived from England to take up a post at the CSIRO Biochemistry Unit in Melbourne, but I know very little about your early life. Where were you born?
I was born on a farm near the little village of Ickenham, just outside London. My mother’s family were farmers who had migrated from Scotland a couple of years earlier, and my father’s grandfather had migrated from the Highlands of Scotland in the 1850s. So I have a very definite Scottish connection.
What are your earliest recollections?
They relate to when I was about four or five, when Britain was still recovering from the Great Depression. My father worked for the metropolitan railways, and he was more fortunate than a lot of people, because at least he was on ‘halftime’ – he worked half the time. But his salary was also halved, so when rent was paid there was virtually nothing left for food or clothing. I still remember the effects of this on the family. And I recall the awful taste and the grey colour of stewed mutton, which I suspect was the only meat my parents could afford.
Where did you go to school?
My first school was in a pretty rough area where a lot of the children’s fathers were out of work due to the Depression. One of the lads I was friendly with would arrive in the winter with very cold feet: his boots had holes in the soles and his family couldn’t afford socks. At the age of 11 we all sat a scholarship examination, and I managed to get a scholarship to Harrow Weald County School. That was very useful for my parents, because they couldn’t possibly have afforded the fees themselves even though we weren’t quite as hard up then – my father (who had won a similar scholarship to Harrow County School) had managed to get a much better job at the Kodak factory. Kodak, being an American firm, looked after their employees much better.
That county school was brand new and, unusually for that time, it was coeducational. Also, the teachers were of a much higher calibre than is customary nowadays – almost all of them had really good degrees. Several had been to Oxford and Cambridge, and some were actually working part time for higher degrees.
Did you develop any interest in science while at the county school?
The science and the mathematics teachers were particularly enthusiastic about their subjects and I think this was infectious. So that is where I first became interested in science.
Did you have any problems at school?
Yes. I’ve always had a dreadful memory. I probably was certifiably Alzheimic at that time! The mark I got for History was always ‘Very fair’, but I never really found out whether ‘Very fair’ was better or worse than ‘Fair’. The term report every year for History said, ‘Could do better if he tried,’ but I simply couldn’t remember a mass of unrelated facts.
What did you do when you left school?
At the end of the course I took the School Certificate examination and got the Matriculation and so on. That went fine, but the grant only extended to the end of the schooling period and there was really no question, economically, of my going to university. So I did the next-best thing: I found a job as a laboratory assistant at the Kodak factory, where my father was working. The great advantage of this was that they financed their laboratory assistants to attend Birkbeck College – the only place in London University where you could do a part-time course, normally by evening classes. Unfortunately, World War II was on then and the Germans were regularly bombing the part of London where Birkbeck was situated, so the lectures were transferred to the weekends and one spent five days in the laboratory and two days at lectures [laugh], making a seven-day week. That wasn’t very good for the social life.
What were the conditions like at Birkbeck College?
They were rather unusual, because pretty well all the staff had been posted off to government work and a lot of the old lecturers had been brought in to do the work. This was actually a great advantage, because they were all very experienced lecturers and very good teachers. The Professor of Physics was the distinguished scientist J D Bernal, who was also working for the government but took time off to come in and give a lecture to the students. I’ve never forgotten an extremely interesting lecture he gave about the sine wave and how that is the basis of almost the whole of physics.
What other impacts did the war have on your studies?
Well, at the end of the first year I took what was termed the Intermediate BSc examination and passed in the usual four subjects, physics, chemistry, and pure and applied maths. But, being 18 by then, I was old enough to volunteer for flying duties in the Royal Air Force. And, because there was an acute shortage of pilots, three weeks later I found myself in uniform. After five months of ground school and a couple of months getting a few hours’ flying in Tiger Moths, I was selected for multi-engine pilot training and sent off to South Africa under the Empire Air Training scheme – flying conditions in Britain were so awful for training that people were sent to somewhere with a sunny clime!
Canada was another one.
Yes. I was kept on as an instructor, because, with a background in physics and mathematics, I had obtained higher than average marks in such subjects as navigation, flight planning and meteorology. This instructing was not without its hazards, particularly when teaching really lowlevel pilot navigation. [laugh] All my classmates on the wings course, however, returned to Britain and many of them were posted to Bomber Command. They flew in the massive night bombing offensives against Germany and, sadly, many were lost over Europe. To this day, I still get pangs of survivor guilt when I’m reminded of that period.
Bruce, after the war, when did you manage to get back to science?
At the end of the war, the government introduced a Further Education and Training scheme, financing people to go back to university if their studies had been interrupted, and my period at Birkbeck qualified me for this. It paid the princely sum of £147 per annum, not enough to live on, but because I could live at home I was all right. The advantage to me was that I was then able to convert to full-time studies, and I commenced a degree in physics, with mathematics as ancillary, at Kings College, in the Strand in London.
After the first year, because the authorities were very sensitive to the fact that ex-service people were well behind all the others as regards time, careers and so on, they gave us the opportunity of doing the second and third years together. A couple of us chose to attempt this, and although the number of lectures and practicals was horrific, we did get through. I managed to get a first in physics, with ancillary mathematics.
How did you progress to PhD studies?
When the results came out, Professor Randall – the Wheatstone Professor of Physics – called me up to his office. He was quite famous because in the early part of the war he had invented the magnetron, which made radar possible and gave the Allies a huge advantage, putting them far ahead. I think Winston Churchill once said it was the greatest single contribution by any individual to winning the war.
I believe Randall had received a substantial grant from the MRC, the Medical Research Council.
Yes. He’d got almost everything by that time. He was a Fellow of the Royal Society and a Member of the Athenaeum, and the government had given him a £10,000 reward. Also, when he applied with the idea (which he had started up at St Andrews University) of a multidisciplinary approach to biology and molecular science, he got a huge grant from the Medical Research Council to establish a biophysics unit at Kings College.
Besides being Wheatstone Professor of Physics, then, he was head of this MRC unit. He offered me a grant, an MRC studentship, which paid £250 a year – almost enough to live on, which was good – and lasted for three years. The idea was for me to get a PhD, and since that was exactly what I’d been hoping for, I was very pleased.
Who was your PhD supervisor?
That was the eminent spectroscopist Bill Price, who was Reader in the Physics Department at the time. He suggested that I should look into the application of infra-red spectroscopy to the study of biological materials. Not only was he an absolutely brilliant experimenter, but he had the great background of an understanding of the theory. He had an infectious, boyish enthusiasm, and a total disregard for fame and fortune.
So you collaborated with him – and you were associated with Wilkins.
He encouraged me to collaborate, because it was supposed to be multidisciplinary, and I quickly formed a friendship with Maurice Wilkins, the Assistant Director of the MRC unit. Wilkins was an expert on the design of precision instruments and taught me a great deal about microscopy and the design of instruments. I collaborated also with Arthur Elliott, another distinguished spectroscopist. He was not in the university but worked in the then Courtauld Research Laboratory, which had been established by the Courtauld fibremakers. He taught me a great deal about polarised infra-red radiation, having pioneered the use of infra-red dichroism to measure bond directions in polymers. Put simply: if you take polarised radiation, you would look first one way and then the other, just as you do with a piece of Polaroid on the sky, and you get changes in intensity as you do this. By applying this to a polymer, you can determine which way bonds are pointing, and that is sometimes a vital bit of information.
Your association with Elliott was extended some years later when you had him out to Australia, as well as visiting him at Courtaulds. But what did you find from those initial studies?
I found that useful information could be obtained from almost all the biological specimens I examined. The big problem was that the focus in normal infra-red spectrometers was quite large – perhaps 15 millimetres by two to three millimetres – and really you want to be on a much smaller scale than that. But glass won’t transmit ultraviolet or infra-red radiation. It is completely opaque to both of them. So you cannot use an ordinary microscope to reduce the size of the beams.
I was very fortunate, in that a friend of mine, Keith Norris, was working with Maurice Wilkins and designing reflecting microscopes. In a reflecting microscope, you have a little mirror so placed that when the light comes in it is reflected onto a much larger mirror that concentrates it into a tiny spot. A second pair of mirrors then reverses the process and a magnified image is produced. Keith knew a great deal about the design of these mirror systems, so I worked with him to design one for infra-red spectroscopy. Because of the requirements of the optical path the larger mirrors were like a pudding bowls and were very expensive to make. Anyway, we completed that and it worked extremely well, and the use of polarised infra-red radiation combined with the microscopy formed the basis of my thesis.
Who were your mentors and role models when you were doing your PhD and your postdoc?
The people I had closest contact with were Bill Price, Maurice Wilkins and Arthur Elliott. Curiously, they had similar properties: they all had a boyish enthusiasm for their subject, they were all meticulous experimenters, and they were all very objective about results they obtained – they never got carried away with theories they wouldn’t change. [laugh] I really regarded those as my role models, and I’ve always tried to emulate them in being very objective about any scientific findings I make and also in making sure I acknowledge all the previous people who have studied and produced results. Today that is a dying thing, which is very sad. I think you should always acknowledge all early work.
While you were at Kings, the search for the structure of DNA was developing there. Maurice Wilkins was central to that, but what part did you play?
Well, Maurice Wilkins was very, very interested in the structure of DNA. He had found that there were some fibres that could be drawn out of samples of DNA, and he did a lot of work on that. I have here a graphic depicting the people who were working there. Shown at the top are John Randall, the Wheatstone Professor of Physics and Director, and Maurice Wilkins, the Assistant Director. He and his research student, Raymond Gosling, together obtained an X-ray diffraction pattern from the little fibrils that he pulled out of the DNA samples which showed that they were helical. That was a very important piece of work. The little sample that Wilkins had was provided by a Swiss biochemist, Rudolf Signer – and it became the focal point of a great event in the department which caused a great deal of animosity, as I’ll tell in a minute.
At the bottom left is Rosalind Franklin, who was, actually, recruited by Randall to work on denatured proteins. When she arrived, Wilkins was away at a conference in Italy and she was told that she wouldn’t be working on denatured proteins but had been switched to DNA, and later she was given Wilkins’ precious little sample of DNA to use. His research student, Raymond Gosling, was also reassigned to her. There is no doubt that Randall himself, quite an eminent crystallographer, could see the glory that would come from finding the structure of DNA and took this rather drastic action regarding Wilkins’ domain. Later Rosalind made the very important discovery that these little DNA fibres could exist in two forms, A and B, depending on the humidity. Details of the beautiful X-ray diffraction patterns that Gosling took of the B form were leaked to Watson and Crick in Cambridge, and in fact used by them to formulate their famous double helix model.
I am pictured at the bottom also, in the middle. I showed that the purine and pyrimidine rings in the bases exhibited strong perpendicular dichroism, indicating that they were stacked like a pile of plates, and later I developed a specific model for DNA. The remaining person here is my wife, Mary, who prepared the high molecular weight DNA used in the infra-red studies. Not shown is Alex Stokes, a lecturer in the Physics Department who formulated the theory of diffraction by a helix, confirming that Maurice Wilkins and Raymond Gosling had proved that DNA was helical.
Speaking of your wife, Mary: 1950 was a special year for you, wasn’t it?
It certainly was. Professor Randall had decided in the previous year to set up a biochemistry facility to supply materials for the various projects that we had going, and he had recruited Mary Nicholls, who had just completed her PhD degree at Birmingham University for this task. Mary was a very competent and very attractive girl, and she added a new dimension to the otherwise dull environment of the Physics Department! She had a great many admirers but, in 1950, she accepted my proposal of marriage, and we were married later that year.
Two years later we had a little girl, Susan – delightful but another mouth to feed – and since the academic salaries for women and the postdoctoral grants for students like me doing a higher degree were so bad, we decided to emigrate. (I’d been totally spoiled by spending three years in the glorious sunshine of South Africa, and Mary was game for anything.) So I accepted a post in Melbourne, Australia, with CSIRO’s Biochemistry Unit. We left in September 1952.
Tell me about the work on DNA that you and Mary did before you left Kings.
Well, since the sample Wilkins had obtained from Rudolf Signer was very precious, that was what he wanted to produce more of. But there were several problems. Mary didn’t have any cold room facilities in the Physics Department; and, secondly, his write-up of the preparation was rather vague and – not uncommonly, I’m afraid, in descriptions of new advances like that – several vital steps in the preparative procedure weren’t mentioned. The preparation that Mary did had a lower molecular weight, only slightly lower but sufficient to prevent it from drawing the lovely fibres that were used for the X-ray work. However, I then used a totally different method for preparing infra-red specimens, where you smear the preparation on a plate. It turned out to be absolutely ideal for the purpose, much better than the Signer stuff, so I was able to use that, with polarised infra-red radiation, in my studies.
I presume that means the DNA was cleaved, or something like that, so it wouldn't align.
Yes, it just wasn’t quite long enough. What happens, actually, is that the molecules are subject to all the normal thermal motions and, the longer they are, the more time they will stay lined up when you apply a shear.
At one stage, James Watson, of Watson and Crick fame, applied for a post at Kings.
It was quite interesting. While I was doing this work, Watson came around the laboratory and was shown around; I showed him all the work I’d done and the results I’d got. I learned later that Randall didn’t accept his application, because he didn’t think he brought any new skills into the laboratory. But I suspect that this was the first leakage of information from Kings to, as it turned out, Watson and thus Crick, whom he teamed up with when he got a job at the Cavendish under Lawrence Bragg – the first leakage of results between the two groups.
Tell me about developing your model for DNA. Apart from the number of chains, it turned out to have been very similar to the final model that Crick and Watson developed in 1953.
When I finished my thesis, I got a Nuffield Foundation fellowship to continue working in the biophysics department, and Maurice Wilkins asked if I would think about possible models for DNA. Probably he asked me because I had learned a great deal from Bill Price about the distances between atoms, the angles they make and the forces which hold molecules together.
I devised a model which had a helical structure, with stacked bases. I reasoned that the charged phosphate groups would repel each other and so they should be on the outside – this determined the orientation of the bases – and pointing inwards would be the hydrogen bonding groups.
Brenda Maddox, in her book on Rosalind Franklin to celebrate the 50th anniversary of the discovery of the structure of DNA, wrote:
Fraser’s model of DNA, completed very quickly, was a simple structure that had what would turn out to be all main features correct except for the number of chains. It had a helical shape, phosphates on the outside, and bases stacked like a pile of pennies, separated by the 3.4 Å distance worked out by Astbury.
A big step in the right direction, Fraser’s November 1951 model was another glaring example of King’s’ institutional hesitancy. Its details were never published …
The reason I had three chains was that, when I first started the investigation, I went to both Rosalind Franklin and Maurice Wilkins and said, ‘How many chains are in the molecule?’ At that time they were sure there were three, as was everybody who had worked on DNA, including Linus Pauling. So I didn’t bother to consider anything other than three.
But you had everything there, apart from the chain number, whereas Linus Pauling made the critical mistake of putting the phosphates on the inside, in the middle. That was extraordinary for a chemist of his stature.
Yes, and he never recovered from that mistake. He was one of the leaders in chemical thought, yet he made this almost ‘schoolboy’ mistake. Who was I, however, a mere physicist, to question somebody like Linus Pauling? [laugh]
Anyway, in 1952 – after we had arrived in Australia – Wilkins sent me a cable. He was aware that Crick and Watson had realised that their original model, which also had the phosphates in the middle, was quite untenable. Their thinking had taken a new twist after the Kings group had gone up, at their invitation, to see the structure that had been developed in Cambridge. Rosalind Franklin was very supportive of the idea that phosphates were on the outside, and in 1951 she told Crick and Watson in no uncertain terms that they’d got it all wrong. By 1952 they had a new model in which there were only two chains, and they had put the phosphates on the outside and the bases on the inside and so on. Wilkins’ cable was asking me to write up the work I had done (because it was so close to what they had done) in order for the thinking at Kings to get publicity at the same time. I sent him a draft manuscript with a couple of figures illustrating everything, but unfortunately he never published it.
It was, however, mentioned in the actual 1953 paper, ‘Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid’, by Watson and Crick. In the introduction they have this rather grudging acknowledgement:
Another three-chain structure has also been suggested by Fraser (in the press). In his model the phosphates are on the outside and the bases on the inside, linked together by hydrogen bonds. This structure as described is rather ill-defined, and for this reason we shall not comment on it.
That comment is extraordinary, when their initial model was rubbish.
With three chains and the bases down the middle, yes! Also, I had gone to great lengths to try to work out standard patterns of bonding between the bases, which of course was the key to the final model.
Did you have any further involvement?
Yes. I had made only that minor excursion – perhaps two or three months maximum – into the DNA field, but to me it raised a lot of interesting questions. The first one arose when Horace Judson approached Mary. An extremely objective author whom Wilkins knew quite well, he had produced the book The Eighth Day of Creation describing the makers of the revolution in biology. He tried to put to rights the distortions of the situation at Kings that had arisen due to a book by Anne Sayre, who was a very great friend of Rosalind’s, about the awful rows that Rosalind got involved in and the terrible conditions at Kings. Maurice Wilkins had lost his research subject, he’d lost his research student and he’d lost his precious DNA – and she was very uncompromising. Jim Watson, in his famous book The Double Helix, spells all this out in, perhaps, a rather biased way. Anne Sayre hoped to set it right in her publication, but it was, in turn, factually inaccurate and quite misleading. Horace Judson did a good job in straightening some of it out, helped by a lot of correspondence with Mary.
Later, a couple of interesting things happened. Firstly, when Brenda Maddox was writing her book, for two or three months she had emails going backwards and forwards about impressions of all the things that had happened at Kings, and she gave a very fair account of what had happened.
But of most interest to me was something that was set up in the United States – initially, I think, as a private venture – that is, to form an archive of all the material that could be assembled on the discovery of DNA. It was precipitated in my case by a phone call at some ungodly hour of the morning. I got out of bed and answered it, and a strong American-accented voice asked me did I still have a copy of my thesis? I said, ‘Yes, but it’s sitting beside Mary’s on an old bookcase in an outhouse, and it’s very mouldy,’ and he replied, ‘Fine, fine, that’s exactly what I want.’ He explained that since he was compiling an archive, a bit of mould on the surface was a good thing! He said to me, ‘Look, if you send it over to the United States, I’ll have it copied, I’ll do a bound copy for you and send it back, and I’ll give you $US8000.’ So it wasn’t a hard decision to make.
That was more than you got as support when you were doing the work.
That’s right. The other interesting thing was that I had an approach, in that same celebratory period, from the editors of the Journal of Structural Biology. They said they knew about the manuscript I had prepared for Wilkins and, if I sent them a copy, they’d love to publish it. But when I left CSIRO in 1987, I had drawers full of old correspondence which I just swept up and put in the bin; I didn’t keep any of it, because I never thought anybody would be interested in my three months’ excursion into DNA and I wasn’t particularly interested in it myself. So I had no record. I got onto Maurice Wilkins, though, and eventually he found the original manuscript I had sent and gave me a copy – but he had lost the diagrams, which are a vital part of it all. Nonetheless, the journal published it, saying in the introduction:
Although Fraser's model of DNA did not correctly describe the B-form of duplex DNA, it came close to describing the triplex polynucleotide forms with three chains that have since been characterized, first for RNA in 1957 and then as a "high energy" state of DNA (H-DNA).
It perhaps wasn’t so wrong after all – and it was very nice of them to say so. I also supplied copies of a number of photographs I had kept from Kings College days. One which was featured on the front of the journal shows some of the Kings College DNA workers at a departmental cricket match (before the arrival of Rosalind Franklin). Maurice Wilkins was sitting in a deck chair, not watching the cricket match – he wasn’t interested in sport at that time, only DNA – and was studying a sheaf of notes from which he was trying to ensure that what he’d done in describing the helix was all correct.
Alongside Wilkins was his offsider, Bill Seeds, who had some blazing rows with Rosalind Franklin about the workshop. She had brought with her, from France, designs of X-ray cameras and things. But both Bill Seeds and Maurice Wilkins were experts at instrument design and recognised that the designs contained some terrible examples of ‘overconstraint’, and when Seeds made the suggestion that she ‘change this’ and ‘change that’, she blew her top, I’m afraid. So there wasn’t a very good atmosphere in the department.
I am shown next, with Mary; standing is Raymond Gosling, a great friend of ours; and sitting is Geoffrey Brown, who was in the Physics Department and had interests in biochemistry. He and Mary set up the department – jointly, but I think Mary did most of the work of setting up the biochemistry part.
Would you like to talk about your arrival in Australia, and what your first impressions were?
Well, we were surprised that Australians were so friendly and accepted migrants so cheerfully and gladly. We never met any sort of opposition or criticism or anything like that. The other great thing was the joy of escaping from the dismal scene in Britain. This was five years or so after the end of the war, yet the meat ration was tenpence a week, which would buy you one scrawny lamb chop if you were lucky, and you could have one egg a week; petrol was rationed, clothing was rationed. It was a pretty dismal scene, even after all that time.
But in Australia it wasn’t easy to find somewhere to live.
No. We were given some temporary accommodation by CSIRO, but there was very little available for them to offer us. We were actually put into a pub – above the public bar – in the back streets of Melbourne. We had a sink in the room and a communal bathroom down the corridor, and Mary managed to look after a fourmonth-old baby there for several weeks. It was interesting. When we left and signed the documents for CSIRO, Susan had been so good that the landlord said, ‘Oh, I didn’t know you had a baby.’ [laugh]
The people in the lab were wonderful. Everybody helped us. In particular, Gordon Lennox –the chief of the laboratory – and his wife Fran used to look through the ‘To Let’ columns, and we went around Melbourne trying to find somewhere to stay. But if you had pets or young children you were crossed off immediately. Eventually we found a funny little semi-detached house in Flemington near the saleyards and the racecourse. The lady would have us, but first she raised another aspect of Australian life I hadn’t yet come across, asking me, ‘Are you a drinker?’ When I said, ‘Oh … yes,’ she replied, ‘Ohhh, but how much do you drink?’ I told her, ‘I occasionally have a dry sherry,’ to which she said, ‘Oh, that’s not drinking!’ (I found out later what she was scared of.)
I remember visiting you there all those years ago.
It was a nice little house, and it had the great advantage of being very close to the laboratory. I was able to save money by buying an old bicycle and cycling just a few kilometres to work every day. That was good.
Well, you had to be looked after, because you were a very important addition to the lab: you became its only physicist! The Biochemistry Unit was a new venture. What were your first impressions of it as a scientific unit?
CSIRO was a wonderful place to work, at that stage, concentrating on ‘oriented basic research’ – in other words, fundamental studies of direct application to Australian problems. I found a very friendly atmosphere in the Biochemistry Unit, where everybody was just so cooperative. That was great, after the unhappy environment I had come from: a department where Wilkins was disillusioned, and Rosalind Franklin had more or less shut herself off and wouldn’t work with anybody (though that was not her fault). Coincidentally, something about the laboratory that struck me as odd was that, whereas at Kings, Randall was a sort of God, here we all used to sit and have lunch and afternoon tea in the boss’s office. That gave a very good impression. Also, the people at the top of CSIRO at that time were really brilliant scientists. Whenever Sir Ian CluniesRoss, the head, and Sir Frederick White, the CEO, had a spare moment, they would go out to the Divisions and chat to scientists, and I found that a remarkable morale booster. You’d have had the same experience.
Oh yes. Well, Bruce, there you were in Melbourne and you had to set up a structure group. How did you go about that?
Pretty well all my experience at Kings had been on fibrous proteins of various sorts – muscle, collagen, keratin – and one of the first instruments I was going to use in Melbourne was the infra-red spectrometer. They had already ordered a beautiful machine, the latest and greatest, made by Perkin Elmer, and it was there when I arrived. But I had to alter it so that I could incorporate some sort of condensing unit, because I was going to work with small specimens. This involved putting it in the workshop, getting a milling machine and sawing it in half. So the first thing I did with this beautiful new machine was to take it all to bits and store the sensitive parts in desiccators and so on. When the Chief saw the thing set up in the workshop with a milling machine ready to cut it in half, he looked a bit dismayed! The word soon got around among the rest of the staff, ‘What is this new guy up to?’ It was an essential first step, though, toward putting in a microscope.
While this was going on, to keep myself busy I took the opportunity to try to work out the theory of how you could interpret infra-red dichroism in polymer materials. This was later published in the Journal of Chemical Physics and was the first of a series of papers which laid the groundwork for understanding how you could relate this dichroism, which is the ratio of the absorption measured one way to the absorption measured another way, to polymer materials. Anyway, the infra-red spectrometer all went together again and everybody heaved a sigh of relief when it was working again. And I think the Chief was absolutely delighted when he saw a spectrum I had taken which had a higher resolution than when the machine had been delivered – but this was not so much my doing as that of Sir Alan Walsh, who was quite brilliant at adjusting spectrometers. (I quickly teamed up with him when I first arrived and he gave me a lot of good advice about it.)
Next you turned your attention to microscopy, and you and I interacted on a number of problems. We got an electron microscope some three or four years later, as I recall, but before that you started to investigate metal shadowing for looking at the surface of fibres.
Yes. It’s an interesting technique and is much used in electron microscopy as well. The apparatus includes a bell jar where you create a vacuum, and you have a little piece of metal – it might be gold, aluminium, almost anything – which you heat and evaporate so that the atoms come off and deposit to form a thin film. Now, if you do this at an angle, you get a lovely ‘shadow’ of anything which is sticking up from the surface.
We applied this to studies of wool, which has the very special feature of scales which stick out and are responsible for quite a lot of its unusual properties. And even though the images we took of the surface of wool fibres had to be at low resolution, they greatly resemble the scanning electron microscope pictures that were taken later. So we were able to study a lot of features of wool. In particular, treating wool with chlorine cures some of the difficulties of wool shrinkage, and looking at the same sort of picture after treatment with chlorine you can see very clearly that the scale edges have been blunted. If you have wool fibres going in both directions, the scales interlock; without chlorine treatment, each move causes one to be shunted up and everything gets smaller and smaller. So this was a great help.
About the same time, two Japanese scientists, Horio and Kondo, published what actually had been scattered throughout the literature without anybody ever recognising it - that in a fine merino wool fibre, for example, the cortex inside the outer tube of scales is actually in two parts which have different chemical properties. Once these scientists formally recognised that and named the parts and so on, we wondered where the difference occurred. Did all cells start the same in the follicle, where the fibre grows, and then change, or did it go right down to the base layer, where the cells are dividing and producing the elongated cells that finally form the fibre? You had techniques available which you had learned and were very good at, George, and they enabled us to look at plucked fibres – fibres actually in the follicle. And, using some special techniques that Maurice Wilkins had taught me, we were able to follow this right back to the base of the follicle and to show quite clearly that two different types of germinal cells were present.
That was a very early finding, and led to great excitement. You moved on, then, into X-ray diffraction. Would you tell us something about that?
Well, Astbury and his colleagues in the 1930s, working in Leeds, had shown the value of using X-ray diffraction for studying keratins. In X-ray diffraction, you take something like a wool fibre or a hair and you pass an X-ray beam through it to get the diffracted rays, which will record in a pattern. Astbury’s measurement of spacings had shown that wool, in particular, and hair, had a curious structure: the polypeptide chains of which proteins are made were not extended in a line, as silk-like proteins are, but coiled in some way. We decided that this would be a very good thing to apply in wool studies, and as I had learned a lot of new techniques from the people at Kings College – there had been big developments since the 1930s – it seemed logical to think about setting that up in the Division.
So you needed money for a new X-ray tube with special properties!
[laugh] Yes. We put in a special grant proposal, and went along to a meeting with Sir Frederick White and Sir Ian CluniesRoss where we discussed it with them. Fortunately, they didn’t have any hesitation in allotting us the money to set up with a microfocus tube and special cameras, which we needed to build. So that was the start of that era.
Then Tom MacRae joined you.
Yes. I knew a little bit about X-ray diffraction but I was no expert, and we got permission to recruit someone. The best applicant was Tom MacRae, who had been working for his MSc at Bradford using X-rays to do exactly what I had in mind, and he was appointed. It was the start of a lifelong friendship. We worked together for the next 32 years, actually.
You had a common interest in flying as well.
We did. He had been a navigator during the Second World War and, when things got a bit too much and we were lying on the floor, covered in oil from the X-ray machine, with a sore back and broken fingernails, we’d say, ‘Damn it,’ go out and hire an aeroplane from a little airfield near Melbourne, and fly over the Victorian countryside. It really put things in perspective. When we came back from that we worked much better, I think.
So Tom came to Australia and you proceeded with X-ray diffraction. And the electron microscope was acquired. But also you had your first post-doctoral fellow, Andrew Miller.
Yes. We got permission to apply for a post-doctoral fellow and we were fortunate enough to recruit Andrew Miller, who had done his initial training at Edinburgh University. He’d actually been on conventional crystallography, but he was able very quickly to apply all the techniques that he had learned to fibre diffraction. He was an extremely bright student, and went on to an absolutely brilliant career, working in Oxford and Cambridge and later in EMBO, the European Molecular Biology Organisation. Eventually he was involved in setting up facilities for the Synchrotron. Later still, he became Professor at Edinburgh University – funnily enough, of Biochemistry – and then got the vice-chancellorship at Stirling. Mind you, he was well trained!
In the early ’50s you had a request from the Japanese government, to do with Eikichi Suzuki.
That was very interesting. The next person we recruited into the department was another extremely bright student – I think he’d done an MSc at the time – who liked what we were doing and elected to come and work with us. By regulation he had to spend about a month familiarising himself with Australia and the Australian language, and he was allotted a tutor who, apparently, was keen on sailing. So he spent all his lessons in a dinghy sailing around Sydney Harbour, and when he arrived in Melbourne he had a wonderful command of yachting terms! But he was a very good scientist.
He was a good mathematician, wasn’t he?
Oh yes. At the end of the year, because we were very taken with him and he was taken with the work we were doing, we managed to arrange for him to get a permanent appointment with us – and he brought his wife and family over at the end of the year. We worked together for many, many years.
The next appointee was David Parry, who had been working at Kings College in London, where I’d done my PhD. He’d also been working with Arthur Elliott, so he knew all about X-ray diffraction; that was great. He worked with us for three years and did some extremely good work. Later he worked with Andrew Miller, who had gone to Oxford. Eventually he got a professorship at Massey University, New Zealand, and we still collaborate to this day.
You had a reunion in ’82 with some of the members of your group, didn’t you?
It was one of those chance meetings where all our paths crossed at the same time: Andrew Miller, who was then Professor of Biochemistry in the University of Edinburgh, David Parry, who was Professor of Physics in Massey University, New Zealand, Barbara Brodsky, who came from Rutgers University, Tom MacRae, Eikichi Suzuki and myself. It’s a pity you weren’t there, George!
Bruce, you had established the electron microscope, X-ray diffraction equipment and polarised infra-red spectroscopy instrumentation, working together in one unit. In addition, there were all those chemists in the Division of Protein Chemistry separating and sequencing the proteins of wool. So we were in a very good position to look at the determination of the histological and the molecular structure of the wool fibre. What would you say were the highlights of those endeavours?
Well, the fact that there were filaments and a matrix in the structure of wool had already been established, but I think it was your highresolution studies which really kicked it all off – you showed that these filaments were embedded in a matrix, and you were able to take pictures of them in the electron microscope. Engineering studies of composites have shown that special properties result if you do this. You can have a material which is very difficult to extend and yet has flexibility laterally. Much later, we decided this was what was going on in wool, and we extended the work to X-ray diffraction studies.
The point about the X-ray diffraction studies was that no staining was needed and so we could look at native material, whereas the sections you were cutting for electron microscopy had to be fairly heavily treated chemically and were subject, perhaps, to a little distortion when you were actually cutting the ultra-thin sections needed for electron microscopy. It had been important to find a way to do measurements on the native material.
We looked at the theory of diffraction by cylinders and took lowangle diffraction patterns, and were able to identify the expected features in those patterns. Now, once you’ve identified them, if you have the right theory, you can use them to measure, firstly, the diameter and, secondly, the distance apart, and that is what Tom MacRae and I did. It was quite fascinating to find that, if you had more matrix in wool (and very often there is big variation across wools) in the X-ray results you could see the filaments getting further apart. So we got a quantitative method of looking at the native material.
Rubber can be toughened introducing disulphide linkages – in other words, you have a chain in rubber and you can use sulphur–sulphur, a disulphide bond, to link them together; it makes the whole thing much tougher. I think it is called vulcanisation. Our chemists were finding that the matrix was composed of sulphurrich proteins, and so a rather similar thing is going on in wool. There are a few sulphur atoms in the fibrous part, and it was of interest to know if they were linked to the matrix. But I think the main thing was that we were able, by using X-ray stains for these sulphur-containing groups, to parallel the work you were doing, where you used fairly aggressive stains to highlight the filaments. It was a very interesting period.
During that period you went off for a break, a sabbatical year with Arthur Elliott.
Yes. Arthur Elliott, who had been so good to me when I was a research student, was still working for the Courtaulds research laboratory in Maidenhead, in the Thames Valley. At that time it was becoming possible for chemists to make synthetic polypeptides: long polymers made up of amino acids joined together by peptide linkages, just like proteins. Courtaulds had an eye on the huge market for wool fibres and were investing an immense amount of money in trying to make a synthetic fibre which had all the properties of wool – and Arthur Elliott was working in a laboratory where that was, in fact, the aim.
There was obviously a lot to learn from the work they’d done, so when I got a sabbatical leave at the end of seven years in CSIRO, I elected to go and work with him, mainly because he was a brilliant scientist and an expert in infra-red spectroscopy. I had a very productive year indeed there and learned a great deal about how particular amino acids affect the properties of polymers. This was of intense interest to us, as it had direct relevance to our work in the Division of Protein Chemistry on manipulating the properties of wool for particular end uses – because it is possible for the bright chemists there to take a thing like a wool fibre and to change the nature of the groups and the side chains, and so to change the properties of wool.
Advanced though it was, the methodology for producing synthetic polypeptides was not what it is today – in other words, you would make a homopolypeptide or maybe a couple of amino acids but not a proper protein chain with a whole 20 amino acids. Nevertheless, you did great things with what you could have on hand.
Yes, we understood quite a lot.
Would you like to say something about going to the UK for that sabbatical year, and what you did afterwards?
Well, the standard mode of travel in those days between Australia and Britain was by ocean liner, and it took between four and five weeks, depending on the age of the liner. Places on the ships were very difficult to obtain, and although CSIRO managed to organise berths for Mary and the three children, unfortunately it was on an old Italian liner, nothing like the posh one that you used later! The children, who were still young, didn’t like spaghetti, and my youngest daughter, Jane – 18 months old at the time – spent the entire trip climbing the ship’s rails. [laugh] It was a rather harrowing trip for Mary, I’m afraid.
But you went by air.
Yes, because I wanted to go across the United States and I’d had invitations from one or two laboratories to talk about the work we were doing in Australia. We flew up to Sydney, and set off in what was then the Constellation service. The Constellation was a beautiful old aircraft, but I’m afraid it didn’t have a great range. The first stop was Fiji; next we had to stop at Canton Island in the mid-Pacific; then it was on to Hawaii and finally to San Francisco. It took a long time and was very noisy indeed, but was thoroughly enjoyable for me, as a pilot.
When you got to Britain, how did you find that after your seven-year absence?
Things had changed quite a lot. I suppose it was a big contrast with life in Australia. You know, it always happens to a migrant, going to the home country after a while, that you wonder if you have done the right thing in moving. The laboratory facilities, equipment and things like that, however, left me in no doubt it had been a good move.
The weather there was better than usual, wasn’t it?
Kings had pretty dismal surroundings in the Strand, in London, and the year that we’d left had been a bad, wet, cold year, so it didn’t compare too well with Australia. We really enjoyed the sunshine and living in a part of Melbourne that was very close to the bush. But that sabbatical year was a freak year in Britain. For perhaps six months of the year it was reasonably warm or even hot in the summer and there was no rain – no nothing! After a year we found we were missing Australia and looking forward to getting back to its informal atmosphere of life and the easy access to bushland.
Then you were awarded the DSc.
Yes, whilst I was in Britain I was awarded a Doctor of Science degree. This turned out to be a great help to us, because it enabled me to supervise PhD students and I could be an external examiner, and it brought me into contact with quite a lot of interesting people. An additional benefit arose when John Cowley left Melbourne University to take up a post in the USA and I took over his research student Peter Tulloch, who was studying electron diffraction and who became an absolutely vital part of our team, eventually, working on structure.
How did you apply your work in the UK with Arthur Elliott, on synthetic polypeptides, to fibrous protein studies such as in wool?
When I first got back, one of the big questions was, as always whenever you are interested in wool, the disulphide linkages. I can remember all the years you spent harvesting follicles! But perhaps a word of explanation is appropriate here. When wool is produced in the follicle, the cells synthesise keratin – of which wool, hair, nail, porcupine quills and other epidermal appendages are made – and initially it has no disulphide linkages; the proteins all assemble separately. Just before the fibre pops out of your head or the sheep’s back, however, a big change takes place and -SH [sulphhydryl] groups join up in pairs – boom, like that – and so you get the disulphide linkage. That is an absolutely essential part of making hair, wool or any other appendage completely water insoluble. One of the gruesome things I notice when I am trekking in the country is the skeletons of animals that have died, with the hair still there. It’s quite remarkable.
That’s right. It’s found in mummified animals, too.
Anyway, we coaxed Ian Stapleton, a very brilliant organic chemist in our laboratory, to make synthetic polypeptides, where you start with an amino acid – and join a string of them together. The first one was a derivative of cysteine. And the question we asked was: can those sulphur-containing, linking residues fit into the alpha helix, which is a vital part of the filaments? He managed to make the synthetic polypeptide for us, and we were able to take X-ray pictures and infra-red spectra which proved conclusively that it would adopt the alpha helix conformation. It means that a scheme was there for the filaments to link to other filaments and to the matrix through those disulphide bonds.
You did an equivalent thing with a silk-like peptide.
Yes, similar to that. For the next step we teamed up with another organic chemist, Fred Stewart. By this time it was just becoming possible to link together amino acids in some specified order. You could write down a sequence that you wanted to investigate, and Fred Stewart was an utter expert at joining them together. He did some excellent work there.
One of the things you could do, for example, was to ask the question: why is an alpha helix an alpha helix, and what happens if I incorporate in there this residue that is a little bit different? Can it still be an alpha helix? He made a whole series of sequential polypeptides for us. The first was an extremely interesting one, proving a point which you hinted at just now, that in silk there is a special sequence. (It’s actually got an extended chain, it’s not an alpha helix, but it was a good test of the whole concept.) A repeating sequence is the key to the structure of a lot of proteins, and this one, actually, was a very simple one. It was glycine, alanine, glycine, alanine, glycine, serine – and so it went on like this, and that repeated. He managed to make quite a high-molecular-weight synthetic one with exactly that sequence, and when we took the X-ray picture we could look at the pattern and hold it beside the one of actual commercial silk, the Bombyx mori silk that the Japanese produce, and see that they were identical. So it showed that the method could be used to check conformation in fibrous proteins. We were very excited about it.
Perhaps we could now move on to your interest in computing for scientific purposes. You’re still doing that sort of work, but how did you first become involved?
I think it was in 1959, when I came back from the UK. Maurice Wilkins had been stressing the value of using digital computers – but remember that in 1959 there weren’t many around and they were incredibly difficult to use. They had to be programmed in ‘machine language’, where you couldn’t even multiply two numbers together without worrying that there would be an overflow, giving you a false result. Anyway, Tom MacRae and I went up to Sydney and did a residential instruction course on the new SILLIAC computer that had been installed in Sydney University. We learned how to use it, but the machine language was extremely unforgiving, and no user friendly items at all had even been thought about. And if you’d made a mistake in your program, the computer blew a horn, threw the tape out, and that was it. That was the only information it gave you! It wasn’t until the English firm Ferranti brought to Melbourne a computer which was meant for business applications and used a simple ‘Autocode’ language – a pushover to program – that we really got back into applying the knowledge we’d gained in Sydney.
And also you met up with Hans Freeman FAA.
Yes. Hans Freeman was very good. He had an interesting background, having worked with Pauling and Corey at about the time when they developed the alpha helix. He had later come back to Australia and was a good friend of Tom MacRae’s. He was very kind to us, and did some calculations for us. He could use that awful machine language! (Nobody uses it any more, of course.)
The first application we attempted was for an automatic amino acid analyser that we had. The output from that comes in a graphical form, with little bumps in it, and you measure the area under the curve. But every so often you get a couple of bands which overlap, and you’ve somehow got to sort out how much belongs to each. Suzuki and I found that a bit of a challenge, and so we wrote some software for separating bands, a little program in the Autocode language which would sort that out. That was then used in the lab so you could get the required accurate estimates. It’s quite a complicated business, because you have to match the band shape very accurately to get a really meaningful answer.
So that each amino acid could be properly quantified?
That’s right. Later, when higher-level languages like Fortran came in, we could do much more sophisticated programming. We could write a suite of Fortran programs which could be applied to any graphical output from any instrument – at that time, a huge number of results were coming out in continuous curves which needed to be sorted out and separated. We applied it to a number of problems, of course, around the laboratory. Also, Suzuki and I were asked to write chapters for books and goodness knows what else.
There was a great deal of interest in the techniques you developed, especially for digital processing of fibre diffraction patterns.
Yes. There was an interesting situation, in that a lot of very bright people were writing software for work with the diffraction patterns from protein crystals, which are absolutely regular in every one of three dimensions and generally have a lot of water in them. It had become fairly highly automated at that time. But as regards fibre diffraction – where the molecules are not so well ordered, the crystallites are small and everything is a bit airy-fairy, even wobbly – there was virtually nothing, and the methods being used were not much better than those of the 1930s.
The idea that we had was to use the Photoscan instrument which the crystallographers were using: you take a piece of X-ray film with your diffraction pattern on it, wrap it round a drum, scan it at high speed and do a complete collection of optical densities along rows so the whole thing is digitised. We were actually allowed to buy one of these instruments, which was a great help, but we then had the problem of interpretation. It took us quite a long time to work out means of extracting meaningful intensities for all the little diffracted beams. Eventually, however, we did do so, and that is now the standard method that is used – and the paper we published at the end of it all is used today as the standard paper for people who do fibre diffraction patterns. It was about 10 years ago, I think, when I was asked to go to Daresbury, in Lancashire, England, where they’ve got a huge Synchrotron, and found to my amazement that there was actually a society devoted to this one topic. They wanted to see what the old dinosaurs looked like, I think. In fact, at breakfast one morning a young American guy, who obviously hadn’t read his conference program very carefully and didn’t realise I was giving the introductory lecture, introduced himself. And when I said, ‘Oh, my name is Bruce Fraser,’ he said, ‘Not the Bruce Fraser! I thought you were dead.’
For crystals, digitising the diffraction is the way it’s done now, isn’t it? It would be the same sort of principle.
Yes, the same sort of principle – except, as we said, because of all the imperfections in fibres. They’re all mixed up and broad; they’re a right mess, in other words. [laugh] Later I managed to convince the Chief to buy the companion machine, a Photowrite. Nowadays it’s old hat technology, but then it was quite exciting that you could take a digital array, convert it to something like a film and be able to produce hard copy. That is, if a digitised image has a lot of background in it, you can write programs to take out the background, and reprint it so that it’s much clearer. That was all pioneering work in those days.
To turn to perhaps a slightly different aspect: 1972 and 1973 were busy years when you produced a book chapter with Suzuki and several other things, including two books.
Yes. A publishing house in the United States, named Thomas, approached me in 1971 and said they would like to publish a book on keratins, because the composition and the structure had been investigated quite a bit and there was beginning to be an overall picture. By then you had moved to Adelaide as Reader in Biochemistry, and had done a lot of good work on the biosynthesis of keratins, studying the way that the cells produce keratin. I suggested to you that, since medicos and all sorts of people were going to be reading this book, we should include that aspect as well, and do the whole thing. I approached Thomas and asked, ‘Could we broaden the subject to the composition, the structure and the biosynthesis of keratins?’ They said, ‘Even better,’ and so that is what we did. The book came out at the end of 1972, and was very well received. I notice that even though that was a long time ago, there are still lots of references to it today. So we felt it was all worthwhile.
Indeed, it became a standard reference.
No sooner had we finished this book than I had a request from Academic Press to put together a book to be entitled Conformation in Fibrous Proteins and Related Synthetic Polypeptides. I recruited Tom MacRae to help me in this, as we had done so much of the work together. It took a year to collect all the information we needed, because there wasn’t any publication at that time where you could get an overall, comprehensive view that was well referenced to the subject; it was scattered in incredible places. Fibrous proteins are studied partly by people who are applied scientists, and so the information was in the ‘Journal of Cosmetic Chemists of Timbuktu’ or something like that. [laugh] Also, we did a huge number of illustrations for the book, which finished up as, I think, 630 pages. It sold extremely well. And again quite often people will cite this in their introduction to something they are writing about, saying, ‘If you want anything before 1973, look at that.’ So we did a lot of hard work for a lot of people! It was received very well and we were very gratified, because we’d put a lot of work into it.
Did it have any effect on the Division, and the work you did there?
It had a profound effect, actually, because from then on we kept getting invitations to open overseas conferences and things like that (always with an offer to pay all expenses). This was pleasant but it was also very valuable scientifically, because it meant that you were bang up to date on a lot of fields where otherwise you might not have bothered reading up – if it was a conference, inevitably you sat through all the lectures, however boring they might have seemed. We gained a huge amount from that.
Also, I received a number of invitations to go and stay in various places and either give lecture courses or collaborate with people. It was a very interesting time for Mary and me, because the children were old enough to look after themselves and we went to places like Israel, to the Weizmann Institute, for an extended period. We did a lecture tour of New Zealand and made several visits to Oxford University, where we stayed for conferences and gave lectures and things like that. It was really very rewarding.
Besides the benefits you derived from those contacts, did the book cause much change to what you were able to do in relation to new techniques?
It made a huge change in the Division itself, because it brought us right up to date. Writing the book made it quite clear that lots of work had been done that either had not been interpreted fully or was, clearly, incorrectly interpreted. So it gave us a whole new dimension to work in, and we’ve never regretted doing it. All in all, it was nothing but beneficial for the work in the laboratory.
One example would be that you went then into low-angle X-ray diffraction measurements.
Yes. I’d learned a great deal about low-angle X-ray diffraction and the progress that had been made in Britain with the use of rotating anode tubes, microfocus tubes and things like that. So we invested in a lot of equipment and were able to study all sorts of features of the microfibril matrix texture in wool, and we studied feather and other fibres.
There is an important point, it seems to me, about the repeating pattern along the wool fibre, the filament. It had been thought to be 200 Ångstroms per step, but you showed that it was actually 470.
That was very interesting. It had been an article of faith for about 30 years, I think, that the repeating pattern along the axis of the filament in wool was 200 Ångstroms – or 198, as it was usually quoted.
Which could have been the molecular length of the extended molecule.
One didn’t know, but yes, it could easily have been. Once we got onto highresolution X-ray diffraction, we found almost immediately that 200 would not fit all the observed reflections. There was only a minute difference, but we were able to detect it. We found that, in fact, the repeat distance along the filament, which the structure repeats, was 470 Ångstroms, over twice as much. Later on, when chemistry advanced a bit further, it turned out to be the length of the molecule we were detecting. So it was very interesting. And we found a number of other things like that.
Along with that work, you investigated the collagen structure in a similar way.
Yes. That was interesting too, because nobody had any idea about the collagen molecules which form part of the tendons that are generally in connective tissue in your body. In the electron microscope you can see these thin filaments, but nobody was sure how the collagen molecules packed. We were able, first of all, to find what was the equivalent of the so-called unit cell. A curious feature in it was that the molecules went straight with a slight tilt for quite a long way and then did an abrupt turn, followed by another straight section with the opposite tilt. This has a very interesting property, if you think about it, because you can apply a sudden force and produce hardly any change in length, but if the thing is elastic, it can absorb a lot of energy. If tendons, for example, were all straight and you applied a sudden force, you would snap them. But this enabled the tendon to extend by a very small amount and to absorb energy without being snapped. (Otherwise, if you were running you would soon snap your Achilles tendon.) An exciting discovery indeed.
In 1986 you were awarded a Fogarty Scholarship by the National Institutes of Health in the USA. What did that entail?
The Fogarty Scholarships were founded to enable people with special skills to go and live on the National Institutes of Health campus and collaborate with workers in the various institutes there. The Scholars were given rooms in Stone House – a beautiful old former homestead on the site that had been taken over to develop the National Institutes of Health – and treated like royalty. There was a grand candelabra-festooned dining room downstairs, where Scholars dined with their wives and invited guests once a month. In addition, a generous amount was provided for the Scholars, for anything to benefit science; it was not made very specific. I chose to organise an international conference to bring together leading workers on keratin and intermediate filaments. Also I took the opportunity, while I was there, to learn new skills, and collaborated with Alasdair Steven, Peter Steinert and Benes Trus in their structural studies of proteins and viruses.
How long did you take that scholarship for?
It was actually for a year, but it could be broken into two parts. I had recently taken on the task of running the CSIRO Division of Protein Chemistry and I didn’t want to be away too long, so I split it into two sixmonth periods, which turned out in many ways to be very good.
But CSIRO had for some time had morale problems, with frequent internal and external reviews and the power structure changing as each political party came and went. When I got back from the first period of the scholarship, it was very different indeed from when I had joined, when there were three brilliant scientists virtually running the thing: they were truly appreciative of the problems that scientists take on and how long it takes to produce anything – sometimes you can go for a couple of years and produce nothing, and in the next one you get top marks for something. Also, a rumour was going around that the whole of CSIRO was going to be reorganised, with changes to the names of some Divisions, some Divisions being abolished, some being split up. So again, of course, morale went phut. I decided it was probably a good time for me to leave, because I had only a couple of years to go until I was 65 and would be retiring anyway.
You had an apposite quote on the wall of your office, I think.
[laugh] It was a notice I’d put up on the wall of my office many years ago when the reviews started. The old Roman Gaius Petronius had written, in around AD60, I think:
We trained hard … but it seemed that every time we were beginning to form up into teams we would be reorganized. I was to learn later in life that we tend to meet any new situation by reorganizing; and a wonderful method it can be for creating the illusion of progress while producing confusion, inefficiency and demoralization.
It’s also recorded, I found later, that the Emperor Nero never took kindly to any sort of criticism, and Gaius Petronius was mysteriously mortally wounded one dark night in a street brawl. I felt very much that the people who are responsible for major decisions on the reorganisation of science are not fully appreciative of the demoralising effect on someone of getting a couple of years into a problem, only to find that everything is changed again. Doing any sort of basic research is a longterm business.
You and Tom MacRae retired at the same time – the team broke up, as it were.
Yes. He still had three or four years to go, I think, but he chose to retire on the same day that I did, and I found this very touching. In my speech just to the lab staff, when we had a little celebration, I commented that it was odd to me that he and I had worked together for something like 32 years yet I couldn’t ever remember a cross word between us. I attributed this to his absolutely wonderfully tolerant nature.
It was surely an instance of good chemistry between the two of you – or maybe good physics!
When he gave his little speech, he said he didn’t think it was that at all. Rather, the clue was that we’d both been flying in World War II and, under those circumstances of service life, you really have to learn to laugh at adversity. In addition, I was very touched by the fact that you flew over from Adelaide for the official farewell dinner.
That was a pleasure. I enjoyed it, sad though it was to see you retiring. What have you been doing since then?
Well, there were lots of loose ends. And just when I thought I was happily retired, my son asked me to write software for the civil engineering business in which he was a partner. So I wrote him software to help in the laying out of plans and things like that. Also, having learned quite a lot about various mathematical techniques from Benes Trus at NIH, I applied those to the work my daughter Jane was doing in market analysis. It is called cluster analysis, and, provided you plot things correctly, you can pick up all sorts of things about the habits and interrelationships of people you’re trying to sell stuff to!
How did it come about that you decided to move from Melbourne to live in Queensland?
We both felt, after being in Melbourne since 1952, that we would like a change of environment. So we packed up and set off up the coast in our old Volkswagen camper to find some place where we might like to retire – we’re both very fond of sun, the warm weather, and we’re both very fond of the countryside. We kept going up through New South Wales and it wasn’t until we reached Noosa that we found a combination of sun, sea, surf and countryside (in this case, rainforest) that we really liked.
We bought a little house on the edge of the forest, and off we went to the United States to complete the Fogarty.
Then you came back and got on with life in Noosa?
Yes. But it didn’t last long! I received a request from Peter Steinert, with whom I’d worked in the United States, to come and look at a problem that he’d been working on for some time. He was introducing cross-links into the structure of keratins and then dissolving it up and trying to identify which parts of the molecule were opposite which other parts, because the links had been formed and they resisted the hydrolysis. He had a mass of data, but it needed some sorting out. It was the sort of thing I’d done before, so I tried to ‘systematise’ it, and eventually I finished up with a computer program that we could use to get all the relative positions to interact and give us a picture of the way these groups were distributed. David Parry was working on that as well.
Later, after Peter Steinert’s tragic death, the US people got in touch with us again: they had another mass of data he’d collected. Again I worked with David Parry, and we managed to salvage quite a lot about the way in which the disulphide linkages form up in those final stages before wool or hair emerges from the follicle. It is interesting that parts of the molecule, sitting near each other, do a big shift when the disulphide bonds join up. Some of them are not initially opposite each other, but so powerful are the forces for them to join up that things shift. We were able to decipher the actual dimensions of the shifts that take place and produce a physical model of what was going on.
When the chemistry changes?
Yes. This was great fun.
We’ve dealt with the mammalian work on linkages that you did with Peter Steinert, but there was still a loose end to do with merino wool, wasn’t there?
Oh yes, and I have here a graphic taken from your work – done so long ago that I doubt whether you can remember it.
I remember vividly the great excitement.
That was important in being the first occasion on which one could see real structure in the highly crimped merino wool fibre. Shown on the left is the paracortex, which is the shorter of the two strands in the fibre. The filaments are reasonably straight and are packed in a very orderly way – in fact, it is almost like a hexagonal crystal in some places – whereas on the right the orthocortex (as it is nowadays called) has a curious whorl-like structure, a bit like a thumb print. At its centre the filaments are straight, just as they are in the paracortex; but as one goes outward the tilt increases and ultimately becomes too big to be stable, and so the whorls there are of limited size.
The contribution that you, David Parry and I were able to make when the three of us got into this again was an extension of a very simple formula developed by Francis Crick. After his famous DNA work he looked at molecules which were twisted, and found that, depending on the twist of the molecules, when they aggregated one could get exactly that effect of an increasing tilt as one went out. And if this idea was extended to the much larger structures, I am sure exactly the same thing applied. We’d already shown that the origin of the difference is in the germinal layer – they are producing different proteins – and that, because of differences in composition, one of them had very little twist and the other had a very, very slow twist. When the ones with the slow twist came together, the tilt would gradually increase in angle, and we were able, in fact, to correctly predict the diameter of the whorl.
In addition to that, you worked on feather keratin and, particularly, reptilian keratin because the goanna claw had been sequenced.
Yes. Before I left the Division, I had initiated a project to determine the amino acid sequence – the order of the amino acids – in the keratins that could be isolated from reptiles. One of the simplest sources for me was the claws from the goanna. This project took several years to complete, because, curiously enough, there were a lot more amino acids in these keratins than in feather keratins. I should say that the feather and the reptilian keratins give very similar X-ray diffraction patterns, which means that at least parts of them are very similar, even though the molecular weights are different and the compositions are different.
When this was eventually published, David Parry and I looked at these sequences. He’d worked with me way back in the 1970s on a model for feather keratin filaments, where we reasoned that there must be extended chains quite different from the alpha keratins in hair and wool and that there were 32 residues, in four strands of eight, folded up like a Chinese firecracker. This time we looked at it in relation to the new sequence – lizard – that had just come out. It turned out that we could find a 32residue sequence in the lizard analysis (even though it was a lot bigger protein) that was almost identical with the one we’d identified in feather. This was very exciting.
You went back to that topic last year, and the results have just appeared as a featured article in the Journal of Structural Biology. How did this come about?
Well, there’d been a lot of information gathered. It has become quite popular and much easier using DNA analysis, to do sequences of these keratins. You don’t have to go through a huge process of determining each individual amino acid and its order; it can be done very quickly from the DNA. And we found that, no matter whether you were dealing with snakeskin or bird feathers or bird claws, the 32-residue segment was always present. You yourself had done some work, too, on chick scales and beaks.
So the temptation was to look at whether one could take this 32residue segment and patch it onto the model we’d derived so many years ago, to see how it would fit. David Parry and I collaborated on this and we eventually found that the filament matrix texture you had discovered in 1962 was there. I have here a picture of it with a superposed view down one of the little white filaments, showing the model we derived. It was interesting: in synthetic polypeptides and things like silk, extended chains always form up into flat sheets, but way back then we had found we could only fit the X-ray diffraction data if we assumed that the sheet was twisted. In this model, two twisted sheets come together and mesh. The green spheres shown here represent the hydrophobic residues, which hate water. When the protein is forming into filaments, of course, those residues are going to be away from the cell fluids. They are concentrated in the centre, while the sulphur-containing residues coloured yellow here – with the charged residues coloured red and blue – are concentrated on the outside.
In recent times, amino acid analyses of a wide range of keratins from birds and reptiles have become available. Although they differ widely, we were excited to find at that stage that they all have this 32residue segment similar to feather and similar to the one shown here. I believe there have been electron microscope studies of lizard as well, or certainly of a reptilian claw.
Yes. But also a lot of sequencing has been done on the proteins that are in lizard skin. It is fairly complex, because keratins themselves differ. Nevertheless, it is interesting that in the feather structure you found that the molecular arrangement conforms with what you find in globular proteins, with a hydrophobic core and ionisable chains and other links on the outside.
It all fitted in rather well. And no fiddling was needed – you simply laid the sequence onto the old structure and that’s how it came out.
It was a wonderful advance in our knowledge of the structure.
I would like now to ask you just a few personal questions. Firstly, besides all of your professional work you have had an interesting time fishing and flying, haven’t you?
Yes. When I first came to Australia, Fred White introduced me to fly fishing, which at that time could be done in some quite nice little streams in Victoria. I’d never had the opportunity in Britain, where to fly-fish you might be paying £500 a fortnight to fish on the left bank for 300 yards! Thanks to a slight difference in the law, here you could wander anywhere. It is hard to beat for relaxation, to be wading up a crystal clear mountain stream and, from your knowledge, from all the things you have learned, to be able to pick where the big trout is sitting. Then you flick a fly so that it comes down the surface, and, pop, it’s gone – sucked down. That is particularly good when the fly is one you’ve tied yourself.
It was rather interesting that Fred always fished with a fly that had been brought from Norway by Dr Wark, who was a very big name in CSIRO. I used that particular fly - the Doctor Walk Special - in many parts of the world when I went to conferences and I’ve never known a trout to refuse one.
As regards flying, I think any pilot will tell you of the wonderful feeling you get when you line up accurately on the runway for the final approach – ‘in the slot’, as it is called. Things can go horribly wrong, but to have everything right and be in that slot, and to round out over the stripes and then feel the wheels touch down gently astride the centre line is a very satisfying experience.
You did have a few hairy moments with flying, though. I remember one when you were flying with Bob Thomas and you really lost power.
Oh yes. We were doing aerobatics at Elstree, an airfield outside London, in an old aircraft. I didn’t have an English licence at the time, only an Australian one, but he was letting me fly. I’d just completed a loop and was coming out again, and I had got it nicely lined up on the horizon. Then I closed the throttle a bit – and nothing happened. The throttle was stuck. A linkage through to the engine had dropped off, or something had broken. We weren’t too sure what to do, but eventually we made contact with the airfield and let them know what the problem was. An instructor came up on the radio and said, ‘I’ll guide you in.’ Bob and I both had a lot of flying experience but I don’t think this guy had very much, because although there were some big elm trees near the start of the runway he said, ‘Righto, switch everything off now and you can just glide in.’ Bob obeyed, of course; that’s the sort of thing you do. And I said, ‘We’re not going to make it.’ There was not enough urge left to miss those elm trees.
How did you get out of that white-knuckle experience?
Bob managed to start the engine again, taking us just over the top. We were up for an extra half an hour, I suppose, while the guy messed around and ‘instructed’ us on how to get in, and he actually charged us for it – when it was his aircraft that had gone wrong! Bob wouldn’t pay, I’m pleased to say.
Even today I love doing aerobatics. It’s getting harder and harder to find a Tiger Moth, though, to do it in. In a Tiger Moth you really are back to World War I, there’s no doubt about it.
Well, you don’t have flaps.
No – but you have helmet, goggles and everything. And every so often you look behind you to see if the Red Baron’s there. [laugh]
Tell us about your family. I remember you and Mary arriving at 343 Royal Parade in 1952 with Susan, who was then four months old. What is she doing now?
Susan won a Commonwealth Scholarship to go to Melbourne University to study medicine, and has spent the major part of her career working in breast cancer detection and treatment. Her two children both won scholarships to Bond University: Kim graduated in business studies and is a banker in London with the big German firm Deutsche Bank, and Maylin graduated in information technology and is currently working on the application of computer methods to pattern design in the fashion industry – the ideal combination, fashion and IT.
After our arrival in Australia we had a son, Andrew, who studied civil engineering at the Royal Melbourne Institute of Technology and now leads a team specialising in the planning and design of building developments, and a second daughter, Jane who has an MBA and works in Market Research. Her son, Russell, is a computer programmer, and her daughter, Rebecca, is studying medicine at Queensland University.
You must be very proud of that clan, Bruce. Computing seems to be quite prevalent amongst the things they do. Is that due to your influence?
[laugh] Perhaps it’s a genetic thing.
It’s all to do with DNA, I’m sure! Over the years of raising three children, Mary must have had her hands very full. Did she manage to maintain her interest in chemistry?
Yes. When we first arrived here she had a four-month-old baby to look after, but she contacted Melbourne University. They had a great need for people to help Asian students who were having difficulty with English to catch up in first-year university, and they were delighted when she offered to coach in chemistry. It was ideal for her, because the students could come out to the house and be taught. Later she worked as a demonstrator at the Victorian College of Pharmacy – located, very conveniently, two or three doors from where I was working. And throughout the whole of the period we have been talking about, she’s been tutoring the children and then the grandchildren in chemistry, and also, during the early part of their careers, in English literature and English language. I used to handle the physics and computing, and we shared the mathematics. [laugh]
When you look back, what do you regard as your most important contributions to your subject? I realise that is not an easy question to answer, when you have done so much.
The development of the digital method of processing fibre diffraction patterns, which is now the standard method, is probably one of them. And we’re just been talking about the feather keratin.
There were a couple of very exciting moments, I suppose. The first was when we had got the beautiful new cameras and X-ray machines all working and looked at keratins – in this case, I think, in porcupine quill – and discovered straight away that the spacings everybody had believed in for 30 years, as an article of faith, were wrong.
The 200 Ångstroms versus the 470?
Yes. It was the revealing moment! Excitement resulted also when I undertook, with Eikichi Suzuki and Tom MacRae, a study of the basic configuration of the collagen molecule. This had been messed about with for, again, about 30 years, and for the past 20 years there had been a ‘standard’ model devised by the great Indian physicist Ramachandran and so named because he was certain it was right. We picked up a method with a funny name that had been used on DNA – the Linked-atom Least-squares Refinement Method – and applied this to some new data that Tom MacRae had collected with all the new cameras and things. You could put in the structure that Ramachandran had developed, and the computer would ‘move’ the atoms to make the structure fit the pattern better. And the thing this method finished up with was a model that Francis Crick (again) had suggested 30 years earlier.
This was the Rich-Crick hypothesis?
Yes. It was just brilliant. That was a great thrill, because you were sitting watching the computer going through all these steps of refinement, shifting the atoms around, when I thought, ‘My goodness, I recognise that! That’s Crick’s old model.’ I wrote to Francis Crick, and he was absolutely jubilant after all those years. He had done that work with Alexander Rich, who was another big name of that time.
Well, thank you very much, Bruce, for giving a fascinating insight into your great career and all the things that have brought it about.
A pleasure, George.
© 2017 Australian Academy of Science