George Ernest Rogers was born in Melbourne, Victoria in 1927. He was educated at the University of Melbourne graduating with a BSc (1949) and MSc (1951). Rogers then went to the University of Cambridge in the UK on a CSIRO scholarship, graduating with a PhD in 1956. He returned to Australia and the Division of Protein Chemistry at CSIRO as a senior research officer (1957–62). He joined the Department of Biochemistry at the University of Adelaide in 1963 where he began as a reader (1963–77), before being promoted to professor (1978–92). Rogers also served as department head from 1988 to 1992. In 1992 Rogers became an emeritus professor at the University of Adelaide and in 1995 he was asked to be the program manager of Premium Quality Wool CRC (1995–2000). During his career Rogers made key findings in the field of hair research. In particular, he looked at the molecular structure of hair keratins and investigated how to manipulate their properties through gene expression and regulation.
Interviewed by Dr Bruce Fraser in 2008.
Professor George Rogers was elected to Fellowship of the Academy in 1977 for his outstanding contributions to our knowledge of the molecular structure of keratins and the biochemistry of keratinisation. I have been a colleague and a friend of George's for more than 50 years, and am privileged to have been invited to provide this introduction.
George's parents emigrated to Australia from England in the 1920s and he was born in Melbourne in 1927. When he was 15, he took a job as a laboratory assistant and enrolled for a diploma of chemistry at the Royal Melbourne Technical College. However, he was encouraged by the director of his laboratory to aim for a degree rather than a diploma and, after two years of study, gained admission to Melbourne University to study for a bachelor's degree in chemistry and biochemistry. After graduation, he was offered a scholarship to study for a master's degree in biochemistry. He investigated the purification of the protein hormone secretin and, after completing his MSc degree, was appointed as a research scientist in CSIRO's newly formed Wool Research Laboratories.
When I joined the same laboratory in 1952, George was working on the structure and biochemistry of the wool follicle, and over the next 10 years we collaborated on various aspects of the molecular structure and cellular structure of keratins such as wool, hair and feathers. After the Division acquired an electron microscope, George developed special techniques for sectioning keratins, and the quality of the micrographs that he obtained 50 years ago has still not, in my opinion, been bettered. During his years with CSIRO he was awarded an overseas studentship and completed a PhD at Cambridge.
In 1963 he left CSIRO to take up a readership in biochemistry at the University of Adelaide, where he continued his study on wool and other keratins. Over the next 30 years he fostered a large research group, and for five years served as head of department. When the new methods of gene manipulation came into use in the early 1970s, he pioneered their application to the proteins of wool, hair and feathers.
His research has been supported by various grants from the wool industry and, in 1952, he and three colleagues in the Department of Biochemistry were awarded funds to found a Commonwealth research centre for gene technology, which continued for nine years.
In 1976 George was awarded a DSc by the University of Adelaide and also the Lemberg Medal of the Australian Biochemical Society. He was a visiting fellow at Clare Hall in Cambridge in 1970, a visiting researcher at the University of Grenoble, France, in 1977 and a visiting scientist in 1985 at the National Institutes of Health, in Washington. He has been an invited speaker at scientific meetings in Europe, the United Kingdom and the USA, and has published over 170 papers and reviews and two books.
On retirement at the mandatory age of 65 he was made Emeritus Professor by the University of Adelaide, but he was able to continue his research interests after 1962 as a visiting fellow in the faculties of science and agricultural science. Currently, he continues his academic and bench research on the molecular structure of human hair, in a laboratory in the Medical School at the University of Adelaide.
George, we met first in 1952, and over the years I have learned quite a lot about your background. Could you tell me, however, about your childhood and early life?
I was born in Prahran, a suburb of Melbourne, in 1927. My parents had emigrated from England some four years earlier, together with their infant daughter, my only sibling.
My father, Percy, was born in London. When he was still an infant his father died, and so he and his younger brother, Ernest, were raised by their mother. Percy left school at the age of 14 and was thereafter largely self-educated. He served in the First World War as a transport driver in the Royal Naval Air Service, which later became the RAF, and after the war was a motor car buyer for a prominent export company in the City of London.
My mother, Bertha Baxter, came from Reading, Berkshire. Her father also died when she was an infant, so she too – with an older sister, Annie, and an older brother, George – was raised by her mother. During the war she was a shop assistant in Oxford Street, London.
My parents were married in 1916, a year my mother remembered for the bombing raids on London by German Zeppelins. She used to tell me how terrified she was by that. (She lived on her own while my father was away carrying out his duties.) Typically of many families in the United Kingdom at that time, my parents were devastated by the loss of their only brothers – one killed in France, and one lost at sea.
What are your earliest recollections?
They are partly of my home. When I was about a year old, the family moved to a new house in Caulfield, in Melbourne, where I grew up and lived until I left home. My father had been successful in the motor business in Melbourne and was, I believe, the first to establish second-hand car auctions. He later became a partner in a car dealership. Unfortunately, the 1929 Depression hit two years after I'd been born, and in the early '30s my father had some trouble with a mortgage, apparently. I remember that we had to leave our home and move temporarily to a friend's house.
One of the enduring memories I have of my early life is of some loneliness. We didn't have an extended family; for me, it was just my parents and my sister. I did have a grandmother in England, and one aunt, but I had no uncles or direct cousins who would have added to my early experiences. I think my parents too had quite a problem settling down in Australia, because they just didn't have family contacts. In fact, their original intention was to stay in Australia for only five years, but the Depression and the subsequent World War II rather stopped all that.
Where did you go to school, George?
At first I went to a kindergarten-primary school combination about half a kilometre from our home. I really enjoyed that, and I remember falling in love with my teacher. [laugh] When I was seven, however, the family finances had improved enough for a private education and I was enrolled at Caulfield Grammar School. I was there during the first half of the Second World War – those dark days. I remember digging air raid trenches and filling sandbags. We had blackouts, and I even had a shaded lamp on my bicycle, as the motor cars did. It was accepted as compulsory, really.
Did you develop any special interest in science at Caulfield Grammar?
Yes. I had no desire to follow my father into the business world, particularly his business; it always seemed to be full of balance sheets and sales, and it didn't really fascinate me as chemistry did. I was about 10 years of age when I got very interested in chemistry, although I can't remember now how it happened – my father was an avid reader, but my parents were not scientifically knowledgeable. I suppose it started when my mother bought me a Lott's chemistry set, produced by an English company. Also, I was doing chemistry and physics at school, and the masters in those subjects were excellent.
I then found that having a chemistry set was an outlet in the lonely hours that I, like many other schoolchildren, spent quarantined at home during the poliomyelitis epidemic of 1937. And I had rather severe childhood illnesses, such as measles, so the interest in chemistry occupied me during the time it took to recover.
I added to my chemistry laboratory over some years. I used to go to H B Selby & Co. in Melbourne to buy chemicals and equipment. I remember that a very nice man, a Mr Still, worked behind the counter and displayed quite a reasonable knowledge of chemistry. It is amazing that in those days I could purchase all sorts of dangerous materials like strong acids and mercury, and chemicals that were potentially explosive like iodine flakes and 880 ammonia, which make nitrogen triiodide, of course – and I used to do that – and I used to store them at home!
What was your overall experience of school life?
I enjoyed it very much, and I did reasonably well scholastically. I took part in the sports, including gymnastics, which I liked, and football, boxing and some cricket – although I wasn't all that good at that. But I left school earlier than originally intended, when I was still too young to excel in sport. I was a top player in table tennis, however; not ping-pong but really vigorous table tennis. And I had two years as a lance corporal in the cadet corps, where we recognised that we were training for a war that was very much still on. Sadly, quite a few of the older cadets were to lose their lives on active service.
I did well in the subjects I took, except French. The master for that was very nice, but he had served in France in the First World War and told us stories about his experiences rather than teaching us the language. When I was around 11, I think, I jumped a year into a higher class because of when my birthday occurred, and I fell behind. So I had special instruction in algebra, which I remember enjoying, and did all right in that. The downside was that the mechanism at that school caused me to go into the lower stream; that wasn't a good thing, because some pupils there were not particularly keen on learning. Later on, though, I moved into a higher stream. I recall one episode when I was sorely disappointed at failing a physics exam at the end of term. But I worked very hard and passed well at the end of the year, with prizes in English and chemistry.
Did you continue at the grammar school?
No. My whole school life came to a rather abrupt end when my father's car business was in difficulty because of the war. This led to my early departure after completing only the Intermediate Certificate, when I had just turned 15. Because of the chemistry interest I had an ambition to be an industrial chemist. Really, it was very early in life to make such a definite decision, but that was where I thought I was heading. So, wisely or not, the headmaster advised me to apprentice myself in a chemical-type job, and I left private education and went looking for a job. In retrospect, I should have gone on to a public school; things might then have been different. On the other hand, of course, my career really began with all those events.
At the age of 15, in 1943, I started work as a laboratory assistant with Gordon Lennox, who was head of the fellmongery section of CSIR, as it was then. I quite enjoyed that, because I felt I was doing something for the war effort and I was working with adults who had a similar desire – it was the mission of the unit to do work for the war effort – and also it involved chemistry. I enrolled at the RMIT, when it was still the Royal Melbourne Technical College, to take the diploma of chemistry. I felt the loss of normal schooling, however, partly because the job was very hard, with long hours and little time for doing other things, and partly because at school one would have been doing things like sport and cultural activities.
I believe the research introduced you to the mysteries of skin and wool.
That's true. I was working on sheep skin and wool, not directly on sheep. We were looking at the early part of the process for making leather, and I enjoyed the biology–chemistry interface that existed at that time. Working with Gordon Lennox – who to me was then Dr Lennox, of course – I was able to be around in that lab when such interesting scientists visited as David Rivett, the head of the Executive of CSIR; Ian Wark, who was Chief; and Lionel Bull, the head of Animal Health. And Syd Rubbo, Professor of Microbiology at Melbourne, had quite a lot of interaction with the lab. There was Hedley Marston as well, from Adelaide.
I remember vividly that Gordon Lennox was very kind, fostering my interests and being a mentor to me, such a young lad. Also, in 1945 the famous Lord Florey came out to Australia and gave a lecture on penicillin at which the hospital lecture theatre was overflowing with people. That was a fascinating experience for me. (Florey was visiting because he was then going to set up the ANU.)
Gordon Lennox suggested you should change your study direction a bit, didn't he?
He did, yes. He'd had experience himself of doing a diploma and he said that, useful as it was, I would probably be better to circumvent that and go straight into getting my Leaving and Matriculation – which by then took two years. So, without giving up the chemistry component of the diploma, I went to a coaching college and took the necessary subjects to matriculate. We used to work five days a week from half past eight till something like six minutes past five, and also on Saturday until one o'clock. So that was a full week. I used to have a few hours off during the week to go to early classes, but mostly it was full on, and it was all very hard work. I used to go to the city, have a meal, go to school and then go home in the blackout. It was pretty tough because there was no time to do much for relaxation, but I did play tennis on Saturday afternoons.
You then went to Melbourne University. How did you find that transition?
I thought it was fabulous, because it enabled one to learn full time and to socialise, and it was really quite a change in my life pattern. At times, I think, I felt rather guilty not to be working hard enough! I took a mix of chemistry and biochemistry, but I started off with the usual first-year subjects, including zoology and physics and chem. My mathematics was weak, and I'm always sorry about that.
There would have been a lot of ex-servicemen coming home at that time.
Yes. In 1946 there was a scheme to offer returned service men and women a university course if they wanted to take it, and they did. The university experienced great problems because of the enormous increase in student numbers, and introduced a kind of ballot for first year through which you were selected either to go to the new Mildura campus or to stay at Melbourne. I was lucky enough to stay at Melbourne. There was a flavour injected by the influx of service men and women: before the war universities had been a bit of a playground, but it became quite a serious matter to take your education there. Only a small percentage of school leavers attended university, and it was a privilege to be there.
How did you find biochemistry there?
I found it very stimulating. This was only just post-war, and there was a tremendous boost to science coming out from, particularly, Britain and the USA because there had been an influx of refugees and others from Germany before the war and they'd made an impact on the science in those countries. And new discoveries about metabolism and structure were flowing out.
I believe that you met up at Melbourne with Victor Trikojus, one of the very early Fellows of the Academy.
He was the Professor, having been appointed during the war, and he wanted to develop biochemistry at Melbourne in a major way. In the post-war environment money was restricted, but there was a lot of enthusiasm to really develop the subject at the campus. He appointed new staff when he could, and also he brought people in to lecture the senior students. Jack Legge was one who was appointed; I found him an excellent lecturer. And there was Hugh Ennor (later Sir Hugh), the foundation Professor of Biochemistry and Fellow of the Academy. They were examples of people who had been working overseas and came back with the latest to give to us.
I did three years of chemistry as well as biochemistry, but by then I didn't want to become a full-time chemist and so I didn't take Chemistry IV. I enjoyed the chemistry, though, because Hartung, the professor at that time, was another excellent lecturer. I went to his famous public lectures on chemistry.
You graduated in 1949, didn't you, and shared the biochemistry prize.
Yes, and I was awarded a scholarship to take an MSc degree as a precursor to a PhD, because there wasn't an honours course at that time. I enrolled for that, and my supervisor through the course of my MSc was Jack Legge, a brilliant man with a very agile mind. When I joined him, he was involved with writing, with the famous Lemberg, a very large and seminal work which for many years was the standard work on haematin compounds. Legge was great to be working with or alongside, but he didn't do much lab work at that time. As a Socialist he was involved very much against the politics of the Menzies era, and interfered with his academic work but not with my studies.
Legge gave me a research topic outside his prime interest, which was in bacterial and animal cell metabolism, saying, 'Why don't you have a go at purifying this polypeptide hormone?' He was referring to the first 'hormone', so-named by Bayliss and Starling, which they called secretin. It is a gastrointestinal hormone. That was a fairly adventurous project for those times, because the methods for purifying proteins and polypeptides were pretty primitive, but I got some way along. It entailed biological assay, there being no chemical assay for it at the time, so one had to work with cats and dogs: I would anaesthetise them and with fairly straitforward surgery, insert a cannula into the pancreatic duct, and measure the secretion by injecting fractionated material and then recording the drops on a chymograph. It was only approximate but, if I got an increased activity during purification, I could detect it. I used to weigh the amount of material at each step, make it up to a volume, inject it and count the number of drops. It was a crude method, certainly, but through it I gained some confidence in biological assays and surgical technique. These days a person at student level wouldn't be allowed to do all that unsupervised.
What was the next step in your career?
Well, I graduated with first-class honours with my MSc in 1951. There was a prospect of carrying on to a PhD and of going overseas, and one of the major schools where I would have gone to work in this area of polypeptide hormones was in Sweden. But I ventured into my first marriage and that necessitated getting a job again.
Fortunately, there was an appointment available, and it happened to be in the Biochemistry Unit at the then Wool Research Laboratories of CSIRO – headed by my former boss Gordon Lennox. I was appointed a research officer, and renewed an association with wool, keratins and so on that has remained with me for the rest of my life. That was how I came to collaborate with you, Bruce, in those early days, on wool and hair structure. There was a lot to be discovered, and I'll always remember that the mission when we were appointed was to find out everything one could about wool. And in our various ways we slotted into doing that.
We knew that electron microscopy – TEM, as it's called now, transmission electron microscopy – with its new applications to biology in the 1950s, was essential for coordinating with your X-ray diffraction work, and there was also the protein chemistry going on. So there was a great unification of approach. For my part, I was very much interested in the biochemical events that produce a wool (hair) fibre; I wanted to delve into that 'black box', to combine morphology and biochemistry – and chemistry, for that matter. And the follicle is such a small structure that microscopy had to be an important part of it.
I remember you going out to the abattoirs and getting the skins from freshly killed sheep, and you plucking all the follicles out. It was quite a procedure.
Yes, it was fun. Luckily, around that time I was able to take some training in electron microscopy with Alan Hodge and John Farrant at CSIRO Chemical Physics Section, down in Fishermen's Bend. They had an RCA electron microscope that the late Lloyd Rees FAA had arranged to have shipped out from the USA to Melbourne just after the war. That became a superb machine, because Farrant was extremely clever with the electron optics and electronics and he improved its performance to be probably one of the best microscopes in the world at that time, as far as resolution was concerned. Alan Hodge had worked with F O Schmitt, a leading structural biologist at Caltech, and so it was good to work alongside him: I became familiar with the preparative techniques as well as using a TEM. And you and I used a very nice light microscope, a Leitz microscope, which was the best microscope we had around the place before our electron microscope came along.
You then realised, I think, that you could benefit from gaining a PhD.
I did, yes. I thought that at that time of my life – I was about 26 – I should really do that in order to progress properly in academic research. So in 1954 I applied for and gained a CSIRO scholarship and went over to England, via Italy, by sea. That was very interesting. I travelled on the Neptunia, which sailed from Melbourne through to Genoa.
Some people today may not know what a long time that would take.
I think it was nearly four weeks. But we stopped at various ports. This ship took a route via Jakarta, but the Italians on the ship wouldn't let people go ashore until several of us, of about my age, told an officer that we really wanted to go. He said, 'Well, you go at your own risk' – because the Dutch and Europeans generally weren't very much liked in Indonesia at that time and were getting out. Jakarta was interesting, and was very old world and underdeveloped compared with today.
George, which college did you go to in Cambridge?
I was admitted to Trinity College as a PhD candidate. I happened to arrive in Cambridge just at the time when Latin had been removed as a prerequisite – I was very relieved by that, because being required to have Latin would have been rather disastrous for me! I was admitted as a matriculant, and my supervisor was Arthur Hughes, A F W Hughes, a distinguished embryologist and cell biologist. The really important thing was that I was seconded to the electron microscopy group at the Cavendish Lab. Working there was a great experience.
I suspect that you benefited, as I did, from visiting Cambridge at a time when you could go to lectures by very famous scientists like Perutz, Kendrew, Sanger and Crick.
Yes, indeed. The head of the electron microscopy group at the Cavendish was V E Cosslett, a physicist who was distinguished by his contributions to the development of electron microscopy, and especially high-voltage electron microscopy. He was very keen on getting biological work going on in his group, and brought in people on secondment, you might say, from other laboratories.
We used an old, prewar Siemens microscope; it was horrible to use and there was no comparison between it and the machine in Melbourne at the time. But fortunately Cosslett obtained funding to buy the new Siemens Elmiskop, and when that was installed it made all the difference. I had access to it on limited time – it was a very popular machine and everybody who was interested in cell biology wanted to use it. It was excellently run by Bob Horne, an exRAF electronics person who had a great appreciation of biological preparations. In fact, he and Sydney Brenner devised the negative staining method for looking at viruses and other biological particles.
Wasn't it in Cambridge that you came into contact with the very first scanning electron microscope?
It was. At Trinity I was part of a group of research students who had a mentor; that was C E W Oatley, who became Professor of [Electrical] Engineering. As I talked to him I learned that he was developing the scanning microscope, the first one in the world, and I did a brief study with one of his students to look at hair and wool surfaces with this machine. We got a few pictures (I may even have sent them to you) but actually it was an interesting sidelight to what I was mainly doing. It didn't really attract me to continue there and do much about it. I was more interested in the internal structure of cells and so forth, and I didn't pursue that beyond taking a few micrographs – which were extremely good compared with the standard methods of making replicas of the surface and examining them in a normal electron microscope.
Having submitted your PhD, you came back to Australia but toured a bit on the way home, didn't you?
Yes. I corresponded with Gordon Lennox, the chief of the unit in Melbourne, and said, 'With so many things in this field going on in America, would it be possible to do a trip around, to visit the major labs and talk to the senior people in that area of biological electron microscopy?' He agreed and, thankfully, he was able to dig up some money for me to do that. It was fairly stringent; I had to go coach class and cattle class on aeroplanes which sometimes were a bit dodgy. But I flew around and went across to the West Coast, visiting some major labs. That left an indelible impression on me and also led to a network that was beneficial in later years. Afterwards I returned by ship to Australia and took up my job again in the group.
That was an exciting time: we were going to get our own Siemens electron microscope.
You played quite a role in that – probably you actually signed the order! You arranged things and when I got back from the other side of the world the microscope was going to be delivered about 10 months later in 1957. In fact, it ended up being delivered on the day Sputnik went up, a day I can readily remember. In the interim period I planned the layout of the lab and had to buy in ancillary equipment, but also I had time to think about doing other things.
You became interested in the inner root sheath at about that time, I believe.
That's true. The wool fibre, like hair fibres generally, grows up out of a follicle, and it has a surround of another cellular layer called the inner root sheath. This undergoes a differentiation process that resembles the hair cortex itself but, as I found out, is chemically widely different. Nothing really was known about the chemistry of that layer, but when I'd done some preliminary work on it, using histochemistry, it gave reactions which were markedly different from those of keratin. So I suspected there was something significant there, but I had to delve into it using some biochemical techniques.
In order to do that, I realised, after removing the follicle by plucking it out of the skin one could actually micro-dissect off the sheath – it would come away quite easily – under a dissecting microscope. But analytical techniques then were not what they are today, so it was a quantitative business, and I had to get enough material. The follicles in the sheep skin were too small to be dissected like that, and I had to go to something bigger. I had thought about getting seal whiskers or something like that, but in the end I used rats. I used the snout that has large whisker, vibrissae, follicles. I was able to obtain about 100 rats and dissected some hundreds of follicles to get enough of the inner root sheath. [laugh] I intended to clean up the tissue and then just hydrolyse it to obtain the amino acid composition; the cells fill up solidly with protein, in the same way as the fibre fills up with keratin. Our protein chemistry colleagues said, however, 'Oh, you're wasting your time; it's going to be like keratin'. In those days we knew very little about amino acid sequences of complex proteins like keratin.
I was delighted by the first qualitative analysis. It was done by the old method of paper chromatography, and, lo and behold, there was a pattern of spots of amino acids distributed on this twodimensional chromatogram that were different in intensity from what you see if you hydrolyse keratin and separate its amino acids. And there was a spot which was not in keratin. That was a moment for jubilation. I was able to show my protein chemistry colleagues that they were not right.
Then that strange spot was finally identified. I took a lot of pains to make sure the identification was correct, and it turned out to be the amino acid citrulline, which is related to arginine. There had not been any substantiated identification of citrulline in proteins. Arginine has a so-called guanidino side chain, which is basic, whereas citrulline has an ureido, urea-type side chain, which is not basic but neutral. The worry was that there might be some peculiar linkage between citrulline and a protein that was perhaps not covalent, but it proved to be definitely covalently linked.
So, where did it come from? In the late 1950s it was not known how proteins were synthesised. Although transfer RNA, which is one of the intermediates in the protein synthesis sequence, was known, the actual mechanism hadn't been worked out; we didn't know anything about the code at that time. There were all sorts of lateral thinking as to what might be going on. I will discuss that a little later.
Talking about wool proteins reminds me that Ian O'Donnell, when he dissolved up a seagull feather or emu feather, found only one protein, whereas the work done in your laboratory on the chick feather found dozens of proteins. How do you explain that?
The simplest explanation is that there is a family of genes and they are closely linked; they appear to have arisen, back in evolutionary history, through gene duplication. There are several tens of different genes, maybe 50, but the encoding DNA sequences differ only slightly. There have been mutations between these members so that in total properties, in terms of protein isolation and characterisation, you can't separate them; they behave very much the same. So, with his techniques at the time, he couldn't show the difference. He could now with techniques like mass spec, I suppose. But we were able to show that there are many genes encoding these families, and that was a major finding at that time.
To return to your story: would you tell us something about the research that you undertook after your beautiful new electron microscope had been set up?
It was a superb machine, a quality machine that was ahead of the market, as it were. In resolution it was, I think, the best. A filamentous structure had been shown years before to exist in hair, but the organisation was not known. Edgar Mercer and M S C Birbeck had published some work they did in the mid-'50s, where they could see some filaments in human hair follicles. But noone had tried to find what was in the mature fibre. So I undertook to have a look at this, and for that I had to devise some preparative methods.
One useful circumstance was that, when I was in Cambridge, I had become firm friends with Dr Audrey Glauert, who was on staff at the Strangeways laboratory, headed by Honor Fell (a cell biologist) who was one of the few female members of the Royal Society. Audrey spent a lot of time working on TEM of bacteria in the Cosslett group. Her brother Richard was a chemist nearby in Ciba-Geigy, at Duxford, the makers of Araldite so we went to him and explained that we wanted some sort of embedding medium that was better than what was available. We played around with bottles and made many mixes until we settled on an embedding medium. When I returned to Australia Araldite became very useful for doing the TEM studies. At Protein Chemistry we also had an ultramicrotome to cut thin sections so we could look at wool fibre structure.
The remarkable thing in the TEM examination of the para- and orthocortex was the contrasting orientation of the filaments. In the paracortex there is, in a sense, a quasi-crystalline arrangement, with the filaments fairly well aligned with the fibre axis. In the orthocortex part of the bilateral structure of a fine wool fibre, however, the filaments are organised in a 'whorly' pattern: they are twisted around, and in the image that one obtains in a TEM the pattern resembles a thumb print. The para- and the orthocortex had been discovered by Horio and Kondo some years before by staining with dyes and using a light microscope. They showed that the paracortex was inside of the curl of the wool fibre and the orthocortex was on the outside of it. So we had the correlation here between filament organisation and curliness. We still don't fully understand the physics of curliness, but the bilateral structure is sure to have some function.
One of the things I never got quite clear, George, was whether the one half being longer than the other was related to the supposed oscillation of the wool fibre within the back of the sheep, when it is growing. Do you know if that's been solved?
Well, I've had thoughts about it. It's not that something in the skin imposing the rotation or oscillation of the follicle; it's the cell proliferation and the hardening process that imposes this movement. But noone has actually seen the movement. It would be rather good if you could cinematograph the event, but I don't know how that could be done.
By the way, we had been working with quills off porcupines and echidnas, and I think you took a very nice picture of one of those, too.
Yes. Using these techniques it was a revelation to see the filament structure and the organisation in which the filaments are separated by a matrix. A matrix had always been suspected. Years before all of this, just by mushing up a fibre and homogenising it, breaking it into pieces and by examining it in TEM you could show that there was gluey stuff between the filaments. But we were able to show it more precisely, and also we used some knowledge of the chemistry of the sulphur bond to reveal the organisation. One of the tricks I introduced to display this structure was to partially reduce the disulphide bonds where they are more prevalent in this matrix material. I used the partial reduction and then applied electron stains – osmium tetroxide, lead salts and so on – and revealed this structure in all its beauty. And because you were using the quill tip we had a go at that too, obtaining some of the best pictures we had ever seen.
In 1963 you left CSIRO and moved to the University of Adelaide. What precipitated that?
Much as I was interested in structure, I was very much interested in the biochemistry of the formation of these keratinous tissues. We had done some work on feather keratin as well as mammalian keratin, and you were bowling along at a great rate with the highresolution cameras and all that sort of thing. I really wasn't looking around to move, but I was rather lucky, I suppose. There were few biological electron microscopists around in the late 1950s, early'60s, and I had a reasonable knowledge of how to use a TEM and to prepare tissues. And I gave some talks about the new cell components that had been discovered, such as endoplasmic reticulum, the Golgi apparatus and mitochondrial structure – that was all a hot topic and much discussed in those times. In the early '60s I received a letter from R K Morton, a Fellow of the Academy who was Professor of Agricultural Biochemistry at the Waite Institute, the agricultural campus of the University of Adelaide, on the outskirts of Adelaide. He had grants for work related to cancer and he wondered whether I'd be interested in applying for a job as a biological electron microscopist (which I suppose I was for that period). I turned it down, feeling I just wasn't ready. But a year later he asked me again and, I guess as a sort of carrot, the University had raised the appointment to a Readership. I decided to take the job, which entailed moving to the Adelaide environment in 1963.
I've often heard of the Darling Building. What can you tell us about that?
That is a heritage building on the campus of the university, and it's where the Biochemistry department began. In fact, the department was the first such department in Australia; it had the first Professor. And when Morton took the chair there, he started to change the building's internal arrangements and structure.
To digress for a moment: the construction of the Darling Building had been organised by the first Professor of Biochemistry, Thorburn Brailsford Robertson. He interacted with the Darling family, a rural family, which contributed the money. Robertson was a brilliant biochemist and was the first to manufacture insulin outside of Canada. He had been a very young professor at Toronto and knew Banting and Best, and when the isolation of insulin came about through their work – published in early 1922 – he wrote to them and requested the protocol. With that he immediately started making insulin in the Darling Building, and it was used for the first Australian to be so saved by insulin injection, at the then Adelaide Hospital. Robertson improved that protocol about a hundred or a thousand times. He would go to the abattoir, collect pancreases and put them into ice, but it was not cold enough to prevent the proteases in the pancreas from starting to digest the insulin before it could be extracted. In those days you didn't have cold rooms, you didn't have the low temperatures that you can get now with liquid nitrogen or even dry ice. So he put salt on the ice and reduced the temperature to minus 10, and the yield increased.
I was so impressed by this example of his entrepreneurial spirit that I investigated what he'd done and wrote a biography of him. I've been fascinated by the man ever since. Actually, he was the second chief of a division in CSIR. Rivett was the first Executive of CSIR, which was set up by the Commonwealth government in 1926, and in 1928 he asked Robertson whether he would like to set up a division on sheep nutrition – he knew that, in addition to all the insulin work, Robertson had done a lot on animal growth and wool growth. So Robertson had two jobs: he ran the biochemistry department, and taught science and medical biochemistry, and he ran the Division of Sheep Nutrition. He worked so hard, that he contracted influenza and died at the age of 42. I am quite sure that he would have been a leader in Australian science, had his life not been shortened.
Well, towards the end of 1963, R K Morton received fatal burns from a lab fire in the Darling Building and died at about the same age as Robertson did, 30 years earlier. There seemed to be a jinx on the building. Not only had both Robertson and Morton died but then we had earlier tragic deaths of a staff member in the department and our caretaker.
After Morton's death, since I was the senior member of the department I had to take over as Acting Head. That was a bit of a shock, when I had been there for only six months. It was a difficult time administratively, because Morton had been a very vigorous man who generated tremendous enthusiasm, got grants, had people appointed, and was changing the building. Everything was developing, but it all fell in a heap when he died. People left, grants were curtailed and so forth.
Despite all that, we got through all the problems for a couple of years. I had help from other heads of department to sort out the administrative matters, and I was able to establish my own research group and get on with the work. It was all solved by the appointment of Bill Elliott in 1965 as the Professor and Head of the department, leading to 25 or 30 years of fantastic science.
Did you undertake much teaching?
Those first two years after Morton's death were pretty busy and rather difficult. Because of the loss of staff, only four of us were left who could undertake the second- and thirdyear teaching, but we shared the load. Being a new boy anyway, I'd had to develop courses for my own teaching pretty rapidly, and I gave secondyear lectures on amino acid metabolism; the third year was on the rapidly changing field of protein chemistry.
Over the ensuing years the protein chemistry lectures changed, of course, and I could introduce new findings. One concerned the tertiary structure of proteins as worked out by X-ray crystallographic procedure. I decided that it would be a good idea for us in the third year to build a model of lysozyme, which was the first enzyme to have its tertiary structure solved in this way. I bought the various spoke-type components from Cambridge and – through you, I think – I got in touch with Tony North, in Leeds, who sent me the coordinates. (He was in the Oxford group where the structure had been solved by Phillips.) With some advice from you, the students and I put the thing together in 1968, 40 years ago, and after being used in teaching it is now a demonstration in the foyer of the molecular biosciences building. It has been refurbished a little bit, so it lights up with fluorescent tape.. [laugh]
What was your main interest at that time?
Well, Morton had wanted me to work on egg development, or embryonic development, and he said that the frog embryo might offer a good way to approach it. As interesting as that might have been, I don't think the frog embryo would have been the best model. I wanted to develop my own ideas that I had initiated in Melbourne, and so I finally talked him round to look at the cellular and molecular events of hair growth, of wool growth. That slowly became the central focus.
You'd have had various students at that stage, no doubt.
At that early stage I had my first PhD student, an honours student and two technicians. I had a grant from the Australian Wool Corporation, as it was then, and also the Australian Research Council. That was for studies of the keratinisation process, which involved looking at mechanisms of protein synthesis that we were learning by studying other systems, and to enable us to examine the hardening process.
I have always been fascinated by that step in which the final changes take place, the disulphide bonds link up in the 'region of fibre hardening'.
I didn't get very far with that, but certainly on the protein synthesis side we made big advances. And I used the electron microscope for parallel studies of the morphology to integrate with the biochemistry.
Wouldn't it have been about that time when you got onto some new methods of looking at citrulline?
That's true. In addition to wanting to find how keratin was synthesised, which we certainly did as time went on, I wanted to jump straight in and see if we could solve the problem of how citrulline arose in the inner root sheath, in particular. It was quite clear to me that, because the precursor had to be arginine – its structure is the same, except it has an oxygen instead of a nitrogen on the side chain – there were two possibilities. The arginine could be converted at some level of protein synthesis, such as at the tRNA level, and then be incorporated. That is, an arginyl-tRNA could be converted to citrulline tRNA and that could be inserted on the same code as for arginine. But the alternative, which turned out to be what actually happens, was that when certain arginine residues in the protein were acted on by an enzyme that enzyme would lock into arginine residues in the main chain and convert the side chains to a citrulline-type side chains.
And this would occur later than the arginyl-tRNA possibility, would it?
Yes. It was a post-translational conversion. We had then to develop an assay for looking for the enzyme and we had to have not only an assay but a substrate, which had to be a protein substrate. So we bought and used argininerich histones which are present in chromatin. As our animal we used guinea pigs: having a colony of them, we were able to use young guinea pigs, in which all the follicles are active. We prepared follicle homogenates to look for the enzyme – which we found. It was a very interesting time. When we found the activity, we called it an arginine deiminase. That work was published in a conference.
Now, however, I really regret having focused only on the follicle and not spreading widely, because Japanese workers – especially Kiyoshi Sugawara, who became a friend of mine – looked at other tissues and found the enzyme similar to the hair follicle type. It was logical, then, to call it peptidylarginine deiminase (PAD) because the arginine had to be blocked at both the amino and carboxyl ends. The Japanese workers showed that this enzyme was ubiquitous and it turns out that there is a whole family of PADs. They have now been studied in considerable detail.
We had a stroke of luck, in that we were able to purify enough of the enzyme from guinea pig skin to do an N-terminal analysis, getting just enough sequence that we could make a nucleotide probe, probe DNA and isolate the gene. We were able also to sequence the coding region, and obtain the amino acid sequence of the enzyme. But I would have to say that, because we were doing so many other projects, it was a very long passage to reach that end point!
It is important to mention that PAD turns out to be an enzyme that causes proteins to denature. When it acts on the arginines there is a radical change in charge, and the protein changes conformation. What happens in the inner root sheath of the follicle is that this change occurs and the substrate in the inner root sheath is trichohyalin. It is an argininerich protein like a histone, in a sense, and has been known for decades, being first discovered by a German histologist. It is acted on by this enzyme and then just disperses and permeates as a matrix between filaments also present in the inner root sheath that belong to the same big family of intermediate filaments as are found in the keratin fibre. The chemistry of the events in the inner root sheath is entirely different from those in the fibre keratin because the matrix comes from trichohyalin but the morphological changes are similar, namely the formation of complexes of filaments and matrix.
How did the development of recombinant DNA technology affect your work?
Very greatly, as it turned out, because it was an incredible tool. It appeared gradually, but suddenly became accessible and ultimately was initiated in our Department. Bill Elliott, who had been appointed as the Professor of Biochemistry, was very keen to see it used. But that was in the early 1970s, when there was much discussion about the dangers of 'molecular engineering'. And following the Asilomar conference in 1975 where the famous Berg letter was revealed, there was an embargo put on the procedures. Meanwhile, Bill had been able to get money to send one research student, and a member of staff who was keen to follow this up, to Edinburgh to learn the methodology. Then that work was stopped, and they couldn't do very much there and had to come back to our department. They did learn how to do it, but couldn't bring it back to us. Some time had to pass before eventually it was given the green light.
After that my research benefited greatly in terms of gene discovery, in both mammalian and avian keratin systems. We were able to isolate genes through the cloning technique and then sequence them. A lot of excellent students joined our group and undertook that work, including Barry Powell, who was a PhD student of mine. He stayed on as a postdoc and continued with me for many years, becoming my major right hand.
At about that time, also, you went off to France for a break, didn't you?
I decided to go to France because of the work of a major contributor to the knowledge of induction of epidermal differentiation, Philippe Sengel. With his student Danielle Dhouailly – later a postdoc and, finally, a professor – he demonstrated the inductive power of the dermal component of the epidermal structure of skin.
They worked mainly on chick, but I and many others realised that this tied in with work already done on the mammalian system. We had found that the proliferation of cells in the follicle and the continuous proliferation to make a keratinous structure is dependent upon the vitality of the dermal papilla – which is a dermal component inside the bulb (an epidermal structure) of the hair follicle and is itself a modification of the general dermis: a collagenous fibroblastic tissue that is in skin, be it avian (chicken) or mammalian (sheep or human).
Sengel and his student had shown that, in simple terms, if you take embryonic chick skin and you dissect out the dermal part from the epidermal part of scales, feathers, beak, claw and implant the dermal component from one region under the epidermis from another region, the dermal tissue will induce the epidermal product belonging to where the dermis originally came from. You can turn scale into feathers, as it were, or vice versa.
I was very interested in what was going on molecularly in this – and we still don't know. I wanted to have a look at the process, using gel electrophoresis and looking at the protein compositions of the products. Does a scale that has been produced this way have scale proteins, or does it have feather proteins? Anyway, we did this work together and it was quite successful.
A nice thing about my time in France was that I was able to work in the labs that your friend Andrew Miller was heading up at the EMBL [European Molecular Biology Laboratory] outstation in Grenoble. Not only did he have space there, but he had equipment which I didn't have access to in Sengel's department. So, although I spent some time at the university, I spent most of my time in that lab, which was extremely fortunate. Our old colleague Hugh Lindley was there also, working on muscle proteins.
I believe that later, after returning to Australia, you worked for a while on amino acid sequences.
When I got back to Adelaide from study leave, our main thread of funding was for wool research so the mammalian keratin work was the main focus. As you know, there are two major families, the proteins that make the filaments and the proteins that make the matrix, in which again there are separate families. In the course of our studies we sequenced the genes for many of these. It was pioneering work – noone had done it before – and we could achieve a lot more than the protein chemists. That changes a little bit now because of mass spectrometry, but with gene cloning we gained a pretty good picture of the details of these sequences, their organisation and their chromosomal location.
Along the way with that work, we examined the expression of the genes of these keratin families during the growth phase. Intermediate filament proteins are expressed, very low down in the follicle. Next, another family comes in: the so-called glycine/tyrosine proteins are turned on. Of course, the others are still being expressed. And then the high-sulphur proteins start to be expressed, followed by the ones that are even richer in cysteine – the ultrahigh-sulphur proteins, as the protein chemists call them. They turn on late, and some of those are in the surface cells of the fibre cuticle. Our findings relate back to the point you were making about the establishment of the ortho-para condition that is in wool, in that the IF, the intermediate filaments, are turned on very early, low down, and the disposition on one side can be seen.
Were you able to extend your findings beyond animal keratin?
Well, the wool funding was very fortunate. But the work on wool had a downside, because it wasn't work on human material which was of much more interest to the biomedical people, and particularly dermatologists, who were interested in diseases associated with hair growth and with the epidermis. We didn't bridge that gap; we were confined to working on sheep. Even so, there is a very close relationship. Pioneering as that early work was, it was overwhelmed by subsequent work by German colleagues in Heidelberg, who did a superb job, an amazing amount of very fine work. They just had so many people working on the same things: the genes of the human hair and of the human epidermis.
Barry Powell and I published the major review in the field in the second half of the 1990s, when he was the senior scientist in my group. Helmut Zahn had written to me saying, 'We're producing a book on hair' – somewhat like the one you published in 1972 and of which I was an author, but with a slightly different aspect. So Barry and I wrote what we believed was a seminal review of everything we had done and what had gone before. It is still frequently referred to by other people. Although we were unable to do very much in the human model, I was able to go to conferences on differentiation in keratinising systems and to keep up with what was going on in the human field regarding hair growth, which is now seen as an amazing system with all sorts of regulatory factors. And it's actually a model for terminal differentiation regulation; it has become a model for people beyond those interested in hair. Going to Gordon research conferences, for example, I was able to interact with people who were in the human field and talk about our sheep work, so there was an interweaving of findings. That went on over the years until I retired. I still have photographs of two or three American colleagues in the field, and of Joe Rothnagel, who was a PhD student of mine and did a postdoc, and then went to the United States and stayed in Baylor [College of Medicine], in Houston, for nearly 10 years. He used to go to the conferences, so we met up there.
The early 1980s brought a change in your research funding. How did that come about?
The Commonwealth government decided to establish special centres for research. Such a centre was a prestigious thing to gain and there weren't too many of them. Several of us were interested. Bill Elliott, the head of the department took up the whole idea and encouraged it, becoming part of the subsequent arrangement. Anyway, after discussion in the department, four of us applied for one of these Commonwealth special centres. It was a bit sad, in that we had to make a judgement about who would apply. I can't remember now whether there was a restriction, but we felt that we couldn't go beyond four because there would be just too much dilution of the funding. It had to be concentrated. Also, the projects from whoever participated had to be able to be interlinked. Gene technology was the underlying aspect of the application, although mainly it focused on differentiation and cell growth, and we successfully obtained a Commonwealth Special Centre for Gene Technology.
This was a bolus of money that made an enormous difference, because you could anticipate doing things that you couldn't do with normal funding. You could make big plans for five years, as against the threeyear cycle of much lower funding. We were able to take on many more postdocs and postgraduate students, and it brought in a new phase for the department. And even though other members of the department were not included, there was obviously a spillover of facilities and interactions.
With that sort of development, I myself was able to enlarge my group. I feel very fortunate that the people who wanted to come and work with us, and were then appointed, matched together in personality extremely well. I really never experienced any problems between students beyond one or two minor hiccups. That was by luck rather than planning, I think, but we gained a lot from that kind of established group culture.
To give an example of how we used to get on together: if anybody in the group had a very successful experiment that was quite significant, we used to have an afternoon tea with champagne or cake, or both, to celebrate the finding and discuss what was done. It was a great occasion.
The other thing we used to do was to have Lumberjack Day in June each year, in the middle of winter. We would all put on lumberjack jackets and sing the Monty Python lumberjack song, because most of the people in the group were Monty Python fans. But I remember that a postdoc we had from China at the time just couldn't understand what was going on.
Around that time, George, you had another period as head of biochemistry, didn't you?
Yes. Bill Elliott was the long-time head and in a major way the intellectual leader of the department – until he decided to retire about two or three years earlier than required, in order to write a textbook of biochemistry. He has been extremely successful in that and I'm glad it happened, but I wasn't so glad at the time, because I had to do a second stint as head. Because I wasn't far off retirement myself, I had a kind of watching brief rather than being able to do anything very positive. There was some stress, because the university was undergoing lots of changes because of money shortage, and a reduction in ancillary staff, in particular, caused difficulties. Also, we turned over to a semester system, which meant reorganising the system of teaching. The staff were a marvellous support and did a lot of the hard yakka, so it wasn't too bad, but it meant that there were a lot more committee meetings and such things to take one away from the lab.
What about your retirement? You continued your work in the Commonwealth centre, I think.
I reached the age of 65 just a year before the rules changed – otherwise I might have stayed on! Actually, I felt I wasn't ready for retirement. Things were still bowling along with the wool research, in particular, and we still had funding from the Wool Corporation. We had funding from the South Australian Research and Development Institute (SARDI), a research branch of the agricultural department, as well. But the university was kind enough to recognise my 30 years of service at that time, 15 of them as Reader and 15 as Professor, and I was given the title of Emeritus, which I very much appreciated. And I was able to organise myself to continue, so retirement brought not only a change in my lifestyle, as it were, but also a change in research direction.
We had already decided that we would look at using the new method of transgenesis, of introducing new genes into animals to see what happens, you might say. (Barry Powell, in particular, had taken this on.) We were very interested to see what would happen if we introduced keratin genes and drove them with the promoter which is necessary to initiate expression – if we linked some of the keratin genes that we had sequenced to a promoter sequence which could target them to the follicle so that they would express there and nowhere else. Barry Powell, in particular, had taken this on.
Did you succeed in producing transgenic sheep?
Well, we started with mice, testing the idea to see what might happen. Indeed, we showed in various ways, morphologically and chemically and by gene sequencing approaches, that we were able to get expression of genes. It meant that, initially, we could overexpress certain genes, be they keratin or anything else, and target them to a follicle. When this happened in mice, and we got changes, I said to Barry that we'd better do the same with sheep, to see what would happen. So we set up a program, with the collaboration of SARDI because we already had links for other reasons with reproductive biologists at Turretfield research farm and a group there had been developing the transgenic technique. When, finally, SARDI agreed to allow some of that funding to go to a collaboration, we started introducing genes into fertilised sheep ova, using all the reproductive biological techniques that were necessary then to reimplant an injected ovum with the new DNA and look at the sheep when it was finally born and grew up, after 150 days of gestation. We were able to show that we could do it: we could get expression in the sheep and we could change the wool properties.
Of course, we were looking to do things that would be advantageous to the wool producer – to make finer wool or wool with different physical properties to overcome felting, say, and with improved dyeing properties. We presented all kinds of possibilities to ourselves. We could not only look at overexpressing a gene, or a number of genes, by coincident injection, but perhaps also look at ways and means of knocking them out. Knockout in mice is hard enough to do, but a knockout procedure in sheep was almost beyond belief. So that really wasn't an option, and we had to look for overexpression. These days, with microRNA and interfering RNA, you can knock out gene function in other ways. But we had to restrict ourselves to overexpression.
You had to move from the university, though, didn't you?
Yes. I had to move out of the biochemistry department at the Adelaide City campus and go to the Waite Institute, in the suburbs. I joined Animal Science and carried out my function as program manager of the transgenesis program from there. People moved with me, and we were able to set up a big lab.
We took on a program of introducing some of the keratin genes we'd characterised, and drove them with the appropriate promoter to make them function. One very interesting thing about the transgenic sheep was that, when we overexpressed one of the filament genes, it gave rise to a change from curliness to straightness. We didn't lose all of the crimp, but we lost most of it. Not only that, but the wool became more lustrous as a result of that overexpression. The counter-aspect was that the fibres were weakened, yet when we had a conference in which some textile manufacturers were present they said, 'Don't worry about that; we can handle that. If it has softness, in particular' – which this wool had – 'then we don't mind. It could be a good thing.' As time went on, however, I'm afraid we were unable to capture that, and a lot more work needs to be done. The number of parameters that one could investigate here was enormous. And so, even though over the time we had about $2 million to do this work, we just couldn't get far enough.
Would you like to talk about any other work you did at that time?
In addition to looking at altering wool structure, when we got the Commonwealth centre we had an inside conference about what we might do, things that we could open up. One of the central things in wool growth is the availability of sulphur amino acids, cysteine in particular. When cysteine is absorbed down the lower gut, it goes into the blood and around the body to the follicles. But when the sheep eats the pasture, it takes the proteins into the rumen, where they are broken down by micro-organisms – and not only do these break the proteins down into amino acids; they start to demolish the amino acids, particularly cysteine. So the animal suffers a loss of cysteine input. The sulphur that comes away as H2S gets oxidised as sulphate and is excreted and is a sulphur loss. The idea was: could one devise a biochemistry in the rumen that would grab that sulphur and bring it back into metabolic use?
As I looked at the literature, I found that there were two steps where bacteria could do this. I set up a program with two or three postdocs to isolate the bacterial genes, and then we had to couple those with a promoter which would act in the wall of the rumen so the sulphur, as it was flowing through into the blood supply, would be grabbed by this biochemical pathway and turned back into cysteine, to be swept into the blood supply. We took that quite a long way, even as far as transgenic sheep that carried those genes, and we were able to show some expression – but very low.
Funding started to drop away, however, for two reasons. First, this work is very expensive; in addition, even genetic engineering in plants was having a difficult time being accepted but to have a genetically engineered sheep – harmless though that would be – was regarded as completely unacceptable to the public. Our funder said, 'We're not going to pursue this, because you won't be able to go through with it.' So that remains something for the future, Bruce.
I think that all of this transgenic work in engineering animals, particularly sheep, will happen eventually if it can be shown to be economically of advantage to the producer, if desirable changes to wool or to the metabolism of the sheep can be made. But it's a matter of the efficacy of the methodology one develops, and of economic applicability.
What happened about the Commonwealth research centre?
Well, we were able to use the money to really expedite my research and that of all the other members of our 'gang of four'. So it did enormous things. But, unfortunately, we just couldn't go beyond the nine years' funding we had. Then it had to come to an end.
In any case, the University of Adelaide decided to open up the Roseworthy campus, which was actually near Turretfield where we'd been working with the biologists, some 60 kilometres out of Adelaide. It was decided by the powers that be that Animal Science should move from the Waite campus, which was devoted mainly to plants, and go out to Roseworthy. In addition, there was an alliance between SARDI and the university to develop the Roseworthy campus. I was retired and I really didn't like facing up to such a move, with travel every day, nor did two of the people who were with me. So I said, 'Well, can we still stay in Adelaide?' and SARDI decided that we could. But that was only for a short time. I continued on in a honorary capacity and we still maintained our lab, but we had to move it to a site which was run by SARDI, and we became beholden to SARDI. Even that came to an end, because SARDI wanted the two people with me to go out to Roseworthy campus, which they did despite commuting problems. It has all turned out to be relatively successful, but I was then on my own after all those years and I had to do something about it. [laugh]
Did you do any contract research or anything like that?
I had discussions, with Peter Rathjen, a graduate of our department and who had become the Professor of Biochemistry. In 2002, when I spoke to him, he had been appointed as Executive Dean of the Faculty of Sciences. I said I would like to continue doing some research, he made it possible for me to have a lab in the new Molecular Biosciences Building and to share an office. And I was able to get some contracts from overseas companies to do hair-type investigations of the molecular kind. I have continued that to the present time.
I made another move in 2006, though, when I had to give up that office space. The Molecular Biosciences were growing very rapidly with new grants, some quite big, and there was not enough space. By then the school mechanism had come in, in which Molecular Biosciences consisted of biochemistry and genetics, and physiology and microbiology, and so all these groups were becoming bigger. The Head of the school, Professor Richard Ivell, said I would be welcome to move into his area, where he had spare office and lab space. I've been there for two years and it's been very successful, because I've had everything there in the one school for most of the work that I want to do, which is in gene discovery. (It sounds rather grand but it is of a limited kind, not all that grand.) I can go downstairs to do something there, and then come upstairs and do the rest, instead of having to cross campus or whatever. Physically, on an ageing body it has been good. That work is going quite well. It is funded from overseas – not a magnificent grant, but enough to keep the lab work going, with just my two hands. In addition, I've written several papers and chapters and lectures, and I intend to stay on until the money runs out. [laugh]
Good for you!
When you look back over your academic studies and your research at the bench, what do you consider to be the greatest contributions you've made?
I suppose I'd start with teaching. I enjoyed lecturing to students – which was rather different, when I first moved, from what I had been used to in CSIRO. I don't think I was any more than in the middle range as a lecturer, although in my day there was no compulsory feedback from students. I was never hissed out of the lecture theatre; on the other hand, I didn't get any formal assessments such as are now compulsory for the staff. I taught protein chemistry and quite a lot of cell and molecular biology, but my teaching to senior years was restricted in that keratins were not a 'hot' topic compared to the reaearch of some other members of the staff who could actually draw on their research in giving their lecture course. But I got round that. I certainly enjoyed teaching, and from time to time I miss it somewhat. I think it's a very responsible job and we need really good teachers in universities to inspire students to continue on in science.
As to research, I had the advantage of full-time research in those early years in CSIRO, which included collaboration with you, and that was a good experience. I believe that the work my group did over so many years has been something which other groups in the area have drawn on. We pioneered some aspects which people have developed – not that we get all that much recognition, because we worked on sheep and not humans. We still do get referred to by workers in the field.
Citrulline has turned out to be something more than I ever thought it would be. It was the first time that this amino acid had been shown in a protein, but the arginine deiminase enzyme that we were able to find as well has led to an enormous amount of discovering of effects such as nerve degeneration by demyelination. It has been shown that the enzyme can work on the basic protein that is part of the myelin sheath and break it down. That's why the myelin sheath can disappear: it is the effect of that enzyme getting rid of the arginine of the basic myelin. And now there's all sorts of citrulline transformations of proteins – or citrullination, as it's now called –a post-translational event. Phosphorylation is the major modification in post-translational changes in proteins, but citrullination is also one, and has been shown to occur with transcription factors in the nucleus. The ramifications are quite enormous, which I could never have suspected because I had the very clear focus on the follicle.
I suppose, looking back, that the best thing has been the multidisciplinary approach which you and I have each enjoyed in investigating the biology of keratins, and their physical and chemical properties, and keratinisation. It was around 1961 that we first saw the internal structure of the wool fibre in a mature fibre, and that was really a day to remember. The transgenesis work didn't go as far as we would have liked, but I'm sure that if it's feasible to do it, it can be done, and real changes can be made to what happens in the growth of hair and wool.
Perhaps we could turn for a few minutes to more personal things. Do you have any hobbies or other interests?
I'm not really strong on hobbies. I've always enjoyed fishing – but in the sea, not in rivers. In my 20s and 30s I took up fishing as a family thing. When I was in Melbourne, there were boats in which to go out into Port Phillip Bay, and later I was able to fish around the Adelaide environs. I've enjoyed sailing, and I built a small sailing boat in my late 30s and afterwards upgraded to something faster, which I had fun with. I couldn't be bothered competing, though. I just enjoyed sailing around reasonably close to the shore. When I had a small fishing craft I used to go out with neighbours or students and have some fun.
I've always liked swimming and so I've kept that up, right to the present time. And I used to have a tennis court on which I played on the weekends. Also, of course, I kept the house going and in order. As to hobbies, I'm a handyman – I keep things and maintain things – but I don't have any yearning to give up research. I think research is my hobby.
Would you tell me something about your family?
My wife, Lynn, is a graduate in biochemistry, and assisted in immunological research in the department of medicine at one of the hospitals in Adelaide. We met nearly 40 years ago at a Christmas party in one of the departments. (Christmas parties are very dangerous!) We later married and built a house in the foothills of Adelaide.
Of our two daughters, only one has shown any great interest in science; she ended up doing medicine. She is a renal consultant and does clinical work but is mainly at the bench doing science – she's doing molecular work in transplantation for a PhD degree.She can speak French, plays the piano beautifully. We all hope our children will do better than we did as we grew up and had our families, and for me and, I imagine, for you also that has happened. My younger daughter, in her early years, suffered from an illness, but she recovered from that and has done a BA at RMIT. She is now successful as an associate producer in television, doing freelance-type work. It is a very tough industry but she is skilled, and enjoys it, which is good.
Has your wife maintained any interest in biochemistry?
Yes, indeed. When the children were old enough to be looked after in a university creche, Lynn came and worked for me for a bit, because she had skills in using antibodies and doing immunochemistry at the light-microscope level. She helped us with some of our questions and identified the expression of some of the proteins, using those techniques. But one day when she was in the department she was asked if she would like to do some tutoring in biochemistry, and she said yes. So she deserted me and went to do tutoring, up on the top floor of the building. She made quite a good fist of it, and Bill Elliott asked her if she'd like to take over his bracket of second-year lectures on metabolic biochemistry. She has really developed that and has taught very successfully for nearly 20 years. She has graduated in a diploma course at the university in higher education and has won several prizes for her work. She is now a lecturer, although she doesn't have a PhD and has no postdoc or postgraduate students. She does do educational research and would like to do more, but she's too busy teaching. She has surpassed me in teaching excellence. [laugh]
George, thank you very much for giving us this unique insight into your career and the events that have shaped it.
Thank you, Bruce.
© 2017 Australian Academy of Science