Australian Academy of Science|
Biographical Memoirs of Deceased Fellows
By F.C. Courtice
Bede Morris was killed instantly and his wife, Margaret, severely injured in a road accident while they were driving near Fontainbleau on the outskirts of Paris on 2 July 1988. Morris had just completed six months of study leave in London and he and Margaret had packed their belongings in preparation for the journey home. Before leaving, however, Morris had agreed to pay a short visit to the Basel Institute of Immunology to thymectomize some foetal lambs and, on their way back to London, to call on Marcel Bessis in his country home in Normandy. It was while skirting Paris on their way to Normandy that this tragic accident occurred, depriving Australia of one of its most distinguished medical scientists. For those who knew him well, Morris will be remembered for his outstanding skill in unravelling some of the mysteries of the lymphatic system, especially the role played by the lymphocytes in the development of immunity. His love of scientific experiments, his desire for excellence and his outgoing enthusiasm, coupled with his innate dexterity, served to inspire many young investigators from several countries around the world to come to Canberra to work in his laboratory. He was, indeed, a master in his chosen field of endeavour. Perhaps a wider audience will remember him in his later years for his forceful and fearless defence of what he believed to be right in many scientific and social issues related to his work, issues that were of considerable public concern.
Bede Morris was born in Sydney on 10 June 1927, the younger of two sons of Grainger and Evelyn Morris. His father, who owned a taxi business in Sydney, died in 1930 when Bede was barely three years old, leaving his mother in difficult financial circumstances. The young family, mother and two sons, went to live with Mrs. Morris's parents, Albert and Evelyn Chapple, who owned a bakery and small business at Emu Plains, in the western outskirts of Sydney. Bede's maternal grandparents had been born in Australia, but their parents, Bede's great-grandparents, had earlier migrated from England where his great-grandmother had been a seamstress for the Queen. Bede's paternal grandfather was a bank inspector in Sydney and his paternal grandmother, Ada Tilden-Smith before she married, was a talented opera singer, having studied with Percy Grainger after whom Bede's father and elder brother were named. Both were born in Australia of British stock. However, after the death of Bede's father there was little or no contact with this side of the family, although his father's uncle in England had left a small legacy that was of considerable help in the financially difficult days of Bede's early childhood.
When Bede was seven years old, his mother married Geoffrey Alton Gow and the new family moved into a house in Emu Plains adjacent to that of his grandparents. It is in Emu Plains that Bede's mother still lives near her son and daughter of her second marriage (Bede's step-brother and sister). So Bede spent all his childhood days in Emu Plains. At the age of 4 and a half he attended the Emu Plains primary school, somewhat earlier than usual at the time, in order to make up the numbers necessary to prevent the loss of a teacher. From this school he went to the Penrith Intermediate High School in 1938 and passed the Intermediate Examination in 1940 before going on to the Parramatta High School where he passed his Leaving Certificate Examination in 1942. Although not remarkable, his pass was sufficient for him to win a scholarship to the University of Sydney but, as he was only 15 years old, he was too young to be accepted. He refused to stay on at school to repeat the final year because he was tired of studying.
During his school days, Bede was a choir boy at St Paul's Church. He also played several sports with great enthusiasm and, as with most things, worked hard to achieve a standard of excellence which satisfied him. He eventually won the Metropolitan under-12 boys' tennis championship. With his brother, Grainger, he also spent much time fishing and boating on the nearby Nepean River. Bede also had a love of animals. His mother tells the story of her son proudly riding his horse to visit an uncle when the horse suddenly dropped dead; it took Bede a long time to get over the shock he received. Another story concerns Bede's cockatoo which he taught to say things that embarrassed the family, especially when the Minister came for afternoon tea. Cocky would sit on a stand attached by the leg with a light metal chain. On one occasion the chain broke and, with chain dangling, Cocky flew over the electric power lines in front of the house. When the chain made contact with both lines, there was a flash, a squawk and a cloud of feathers. Cocky picked himself up off the road, ruffled what was left of his feathers and, dragging the remains of the blackened chain, walked back down the garden path muttering to himself. Bede also kept racing pigeons and joined the local pigeon racing club. Training the birds involved long bicycle rides, with a basket of pigeons on the handle-bars, to some location where the birds were released to fly home where his grandfather waited to time their return. His veterinary career probably started when one of his favourite pigeons was attacked by a hawk and struggled back to the loft with a badly torn breast. Bede sewed up the wound with an ordinary needle and cotton and the pigeon recovered to go on and win races. Such stories - and there are a great many more - of Bede's childhood days in Emu Plains typify the carefree, busy life of a boy in the country environment in which he was brought up! In his later life Bede often spoke warmly of his childhood days, referring to himself as 'that baggy-trousered schoolboy from Emu Plains'.
After leaving Parramatta High School he got a clerical job at the Water Board, since he was too young to go to the University. But he did not like office work and, after a year, he began keeping Rhode Island Red fowls to supply eggs to poultry farmers in the district for incubation. Another interesting facet of his character in later years was very evident during his childhood. At Emu Plains, Bede and his friends used to enjoy livening up gatherings with stories and acts that got great laughter and applause from the audience (although at times the Minister did not seem to be amused). Bede also taught himself to play the piano and he played and sang his limited repertoire with style and flourish to provide a lot of fun and enjoyment for many people during those war-time years.
On 10 June 1945, Bede turned 18. Since the war in the Pacific area was still raging, he immediately enlisted in the A.I.F. As the war ended two months later, following the release of the atom bombs on Hiroshima and Nagasaki, he was not sent overseas but became an infantry sergeant doing instructional duties at Canungra, one of the Army's jungle training schools. 'His superiors would have noted his qualities; a lean physique, over six feet tall, raw-boned and lantern-jawed, with a hard flat Australian accent; an ideal type for platoon sergeant,' writes his friend, Dr E. J. Lines. In 1947 he was selected for officer training at Duntroon, but he chose instead to leave the Army to begin a veterinary course at the University of Sydney. He was now in his 20th year, and his army service made him eligible for financial assistance under the Commonwealth Reconstruction Training Scheme without which he may not have embarked on a university course. His choice of Veterinary Science seemed natural for a talented young man with his country background and his love of animals. He began his course in the University of Sydney in March 1947, completing his examinations in December 1951. During the course he was awarded the Martin McIlrath Scholarship and in his final year, the S.T.D. Symonds Memorial Prize for clinical subjects. He graduated with First Class Honours and the University Medal, the degree of Bachelor of Veterinary Science being conferred on him on 31 January 1952.
Having finished his undergraduate course with such distinction, Morris discussed his future with the Dean of the Faculty, intimating that he would rather try his hand at research than practise veterinary medicine. I had, a few years earlier, returned from Oxford in an endeavour to rebuild the research department of the Kanematsu Institute at Sydney Hospital. The Dean, whom I knew very well, rang to ask whether I would have a place for a brilliant young veterinary graduate who could be perhaps somewhat unorthodox at times. After an interview I offered Morris what facilities we had but, unfortunately, I had no funds to pay him a stipend. He was soon awarded the George Aitken Pastoral Research Trust Scholarship of Sydney University and early in January 1952 he began research on the fourth floor of the Kanematsu Institute, made famous in pre-war days by that distinguished triumvirate, J. C. Eccles, B. Katz and S. W. Kuffler.
During the war much emphasis had been directed to resuscitation of the severely wounded by intravenous infusions of blood or serum. I had been involved in some aspects of this work in England at that time and became especially interested in the role of the plasma proteins and of the lymphatic system in the restoration of the fluid balance of the body after injury. One of the projects in which we were engaged at the Kanematsu Institute when Morris arrived was the capacity of the lymphatic vessels to return to the blood stream protein-rich fluids which had, in various disorders, infiltrated the lungs and serous cavities. Morris began his research by undertaking an analysis of the factors involved in the absorption of protein from the pleural cavities and the lymphatic routes taken. This involved measurement of intrapleural pressures and pulmonary ventilation in rats, the separation of the effects of costal and diaphragmatic breathing and the capacity of the different lymphatic pathways to remove excess protein and red cells when they were introduced into the pleural cavity to simulate a pathological pleural effusion. He then extended his work in similar experiments with absorption from the peritoneal cavity.
Within that first year, Morris showed such skill as an experimenter that it was not difficult to predict for him a bright career in research in the basic medical sciences. Supported by a National Health and Medical Research Council Fellowship, he continued at the Kanematsu Institute for a further three years, investigating several aspects of the role of the lymphatic vessels in restoring fluid balance. He studied the rate of turnover of protein from plasma to lymph in various tissues, as part of an analysis of the factors concerned in the permeability of the capillary wall to macromolecules. Attention, however, was especially focused on the lipo-proteins which, at the time, were being implicated in the aetiology of atherosclerosis. His important papers on the exchange of lipids between plasma and lymph in normal and hyperlipidaemic animals indicated that certain lipoproteins crossed the blood-lymph barrier and it was postulated that a similar transfer of lipoprotein across the endothelium of arteries could be a factor in the formation of an atheroma in those vessels.
His experiments led him to an analysis of hepatic and intestinal lymph and of the chylomicron, the large fat particle with a surface coating of protein and phospholipid, which is formed in the mucosal cells of the small intestine and absorbed into the intestinal lymphatics during fat digestion. The fate of these chylomicrons once they entered the blood stream via the lymphatic vessels, the relationship between the chylomicrons and the alpha- (high density or HDL) and beta-(low density or LDL) lipoproteins and the possible transference of these substances across the vascular endothelium involved much experimentation and analysis. Morris studied these lipids in the blood of many species of animals. His love of fishing enabled him to determine the levels and patterns of lipoproteins in the blood of a wide variety of fresh- and salt-water fish. His close friend, E.J. Lines, who had been a contemporary in his undergraduate days in the University and who was now an intern at Sydney Hospital, tells many stories of their fishing expeditions off the coast of New South Wales when Bede would collect samples of blood from the fish he caught. 'We were both a bit crazy in those days, earning a living at last but anxious to get away, while we had the chance, from work and study not to mention an unknown future. It was an experience to see hardened professional fishermen go pale and wobble at the knees at the sight of Bede or me extracting blood with a syringe and needle inserted directly into the heart of a fish through its sternum,' writes Lines. I well remember Bede arriving at my home in Sydney in the early hours of the morning, having driven all night with the boot of his car filled with fish - my family ate fish for a week.
During these four years at the Kanematsu Institute, Morris did the work for sixteen of the papers listed in his bibliography. He showed that he was an outstanding investigator, certainly the most skilled young experimenter with whom I have had the privilege to work, with a tremendous love and enthusiasm for testing hypotheses by the experimental method. His fantastic zeal permeated every aspect of his work. If he anticipated a very long experiment, he would get things ready the night before, lie on the floor of the laboratory to get some sleep and when he awoke at 4 or 5 a.m, he would begin his experiment long before anyone else arrived for work. The success of a beautifully executed experiment always held first priority in his day's activities. Although Morris had published many papers while working at the Kanematsu Institute, one of his great regrets was that the rules of the University of Sydney did not allow him to enrol for the PhD degree even though Sydney Hospital was a teaching hospital in the university's Faculty of Medicine. Nevertheless, he wrote his work in the form of a thesis and had it bound, merely as a disciplinary exercise. This ineligible thesis still exists as an example of the enthusiasm of a young scientist embarking on a career of research in the medical sciences.
2. School of Pathology, Oxford, 1956-1958
In the latter part of 1965, Morris was awarded an Overseas Fellowship of the Australian and New Zealand Life Insurance Medical Research Fund. Early in 1966 he left Sydney for Oxford to work for two years in Sir Howard Florey's School of Pathology. Here he worked mainly with J.E. French and D.S. Robinson on the fate of chylomicrons, continuing the work he had undertaken in Sydney. He also enrolled for the PhD degree as a student of Magdalen College.
Morris spent two years at Oxford working in a field which was, at that time, receiving considerable attention internationally. The fatty acids in the chylomicrons were labelled with *l4C, the chylomicrons infused intravenously and the tissue distribution and oxidation of the labelled fatty acids monitored. Morris also perfected an isolated perfused liver preparation in the rat which enabled him to study the uptake of *14C-labelled fatty acids by the liver when chylomicrons containing these labelled fatty acids were infused. His work was published in four papers, and was successfully presented as a thesis entitled 'Factors concerned with lipid transport' for which he was awarded the degree of Doctor of Philosophy of Oxford University.
3. The John Curtin School of Medical Research, Canberra, 1958-1988
(a) 1958-1964. The merino sheep becomes his experimental animal of choice for studies on regional lymph flow and lipid metabolism
Morris returned to the Kanematsu Institute in July 1968 as a Senior Research Fellow at the expiration of his Overseas Fellowship. However, earlier in that year I had been appointed to the Foundation Chair of Experimental Pathology in the John Curtin School of Medical Research at the Australian National University in Canberra where facilities for the sort of work that we both wanted to undertake would be much better than those in Sydney at that time. Morris agreed to join me together with my head technician, Jack Harding, in this new venture. He remained in Sydney for a short time only, moving to Canberra as a Senior Fellow in the Department of Experimental Pathology in September.
While at the Kanematsu Institute our work was restricted to small animals because of the facilities available. I had, earlier in my career in England, worked with goats and found that these animals had a relatively large lymph flow. In Sydney, not long before he went to England, Morris acquired some goats, housed at the Veterinary School of the University, but he departed before beginning experiments. In Canberra, however, the facilities to use large experimental animals were excellent. Being in the heart of some of the richest merino sheep country in Australia, Morris decided to adopt the merino sheep as his experimental animal of choice.
His first research student to enrol for a PhD, in 1959, was A. K. Lascelles with whom Morris developed surgical techniques to monitor the lymph flow over long periods of time - days or weeks - from various lymphatic ducts in the conscious sheep. The mastery of these techniques in the sheep was essential for the many projects he planned to undertake. Morris was a superb experimental surgeon and his experiments rarely failed. With Lascelles, his main project was concerned with the lymph from the mammary gland of the lactating ewe. The large lymph flow reflected the blood flow in such an organ, but Morris was particularly interested in the barriers that separated blood, tissue fluid, lymph and the milk formed in the acini of the gland. It was only on rare occasions when the udder was extremely distended that the lipid and casein particles of the milk would enter the lymph, probably as the result of the rupture of an acinus. On the other hand, when a needle was inserted into the gland, milk readily entered the tissue fluid from torn acini and the lymph rapidly became milky in appearance. These experiments formed the basis of much experimental work concerned with mastitis that Lascelles undertook in the University of Sydney after he had left Canberra.
From 1960 to 1962 Morris gathered a group of young graduates who either continued his interest in the metabolism of the chylomicron in the small animal models that-he had perfected earlier, or embarked on new projects concerned with the lymphatic system of the merino sheep. M. W. Simpson-Morgan was one of the first of these and he extended the work on the metabolism of chylomicron fatty acids in the rat. After his return from Oxford, Morris had measured many quantitative aspects of the oxidation and transport of absorbed dietary fat by the intact unanaesthetized animal. While every attempt had been made to preserve the normal physiological state of the experimental rats used, he was troubled by the fact that in all of his experiments, single injections of chylomicrons had been used, whereas animals absorb fat continuously from their small intestine. Morris had also been concerned with some of the experiments that had been done by biochemists on physiological processes without paying due regard to the integrity of the experimental animals. There were some glaring examples of these in experiments that purported to show that with adequate available glucose, the oxidation of lipid was 'spared', but in which the amounts of glucose used were excessively high, and the lipid was administered as non-physiological artificial emulsions. He determined that future experiments should make use of continuous infusions of chylomicrons and of glucose at normal physiological rates of entry into the circulation. With this in mind, he acquired a Cary model 31 vibrating reed electrometer to measure minute electrical currents. With attached ionization chambers, this made it possible to record continuously the expiration of *l4CO**2 by animals as small as rats, so that the patterns of oxidation of *l4C-labelled metabolites could be determined. Simpson-Morgan studied the metabolism of chylomicrons infused at physiological rates and demonstrated the extraordinary efficiency with which these were metabolized, enabling them to provide for a large part of the body's immediate energy needs, and subsequently showed that glucose infused simultaneously with the chylomicrons at physiological rates had little effect on those that are oxidized rapidly. Subsequent experiments demonstrated unequivocally that the large particles of lipid were removed directly in the microcirculation of the heart to provide for a large part of its energy needs, and in so doing spared the oxidation of glucose by the heart.
With M. A. Mishkel, Morris investigated the metabolism of free fatty acids and chylomicron triglycerides in the isolated perfused choline-deficient liver of the rat. It was found that when *14C-labelled free palmitic acid or *14C-labelled chylomicron triglycerides were added to the perfusate, they were taken up by the choline-deficient liver as rapidly as by the normal liver, and the labelled fatty acids were also oxidized to *14CO**2 by the choline-deficient livers as efficiently as by normal livers. The synthesis of choline-containing phospholipids, however, was significantly reduced in the choline-deficient livers.
In the ruminant, digestion is affected by the rumen and so differs from that of the monogastric animal. With T.J. Heath, Morris set out to investigate the absorption of long-chain fatty acids, using the sheep model. *14C-labelled tripalmitin introduced into the abomasum or duodenum of lambs was promptly absorbed into the lymphatics draining the intestines. When labelled fat was introduced into the rumen of the adult sheep, however, absorption occurred much more slowly and continued for two or three days. It was evident that young lambs showed a pattern of fat absorption similar to that observed in monogastric animals, whereas in adult sheep the pattern was different. Heath went on to study the role of the bile and pancreatic juice on fat absorption in the sheep.
With the advent of gas-liquid chromatography, E.P. Adams, in 1962, joined Morris's team to investigate further the digestion and absorption of fat in the sheep. A characteristic feature of the lipids in the intestinal lymph of adult sheep was the high concentration of 18C saturated fatty acids which are not characteristic of the lipids of pasture grasses. When maize oil, which contains a high concentration of 18C unsaturated fatty acids, was given into the rumen, the lymph lipids recovered during the period of fat absorption showed a high proportion of 18C saturated and mono-unsaturated fatty acids and a greatly reduced content of 18C diene acids. When the rumen was by-passed and the maize oil given into the abomasum or small intestine, these changes did not occur, nor did they occur when maize oil was fed to young lambs. It was thought that the ruminal miero-organisms were responsible for the hydrogenation of a large part of the dietary unsaturated fatty acids.
Adams went on to study the actual changes that occur in the rumen as well as the fatty acid patterns of lipids in lymph from many tissues of the body. It was concluded from the results of these investigations that the ruminal micro-organisms impressed their metabolic activities on the host animal in terms of the characteristically high content of 18C saturated fatty acids which were found in the lipids of sheep lymph and plasma. These findings were very relevant at a time when studies had shown that the ingestion of fats containing high concentrations of polyunsaturated fatty acids lowered the plasma cholesterol level in man. Morris who, as a veterinarian, was an ardent supporter of the natural products of the primary industries of Australia, did not dispute these scientific findings, but he could never bring himself to believe that the level of serum cholesterol in man affected the development of atherosclerosis which underlies coronary heart disease. As a consequence of these beliefs he did not advocate the manufacture of polyunsaturated margarines nor did he support efforts by others to produce beef containing a high proportion of polyunsaturated fatty acids.
At this time Morris also undertook an investigation of lymph from the reproductive organs of the ewe. He found that relatively large volumes of lymph flowed from the ovary during the luteal phase of the oestrus cycle and during pregnancy. These findings indicated significant alterations in the exchange of fluid and protein across the capillary wall following the development of the corpus luteum. Ultrastructural changes were found in the blood capillaries of the corpus luteum to explain these findings. One of his interests in these experiments was the mechanism of transfer of hormones, which were mainly protein-bound, from the ovarian cells to the blood stream.
With Maureen Sass, Morris undertook a study of the lymph flow from the pregnant uterus of the ewe. Lymph flowing from the main duct into which the uterine lymphatic vessels drained was collected continuously over periods of many weeks in conscious, unrestrained pregnant ewes. The lymph flow from the non-gravid uterus was less than 10 ml/hr, but during pregnancy this flow increased to as much as 200 ml/hr while the protein content of the lymph fell to about 0.1 to 0.2 g/100 ml. These changes reflected the increased blood flow and capillary pressure in the uterus during pregnancy. About 24 to 48 hours before parturition, red cells appeared in the lymph, but during the actual expulsion of the foetus lymph flow ceased as the uterus contracted. Following the birth of the lamb, the lymph flow returned to pre-parturition levels and then gradually decreased over the next two weeks as the uterus underwent involution. These experiments not only demonstrated the important role of the lymphatic vessels in maintaining the fluid balance of the uterus during pregnancy, but showed that the lymph from an organ could be monitored over very long periods of time in a physiologically normal, conscious sheep.
A prominent feature of the lymphatic vessels of the sheep in all regions studied was their intrinsic rhythmic contractility. So evident was this that Morris was an ardent proponent of the view that the magnitude of this form of lymph propulsion greatly exceeded propulsion by extrinsic mechanisms.
During his first five years at the John Curtin School of Medical Research, Morris had pursued his interest in lipid transport and metabolism, but perhaps more importantly he was perfecting his techniques of long-term lymph collection from many different tissues of the sheep. Most significantly with regard to the direction that his future research would take, Morris in 1962 developed with J.G. Hall a model in the sheep to study the cell population in lymph from the popliteal node and the changes that occur in this population when an antigen is introduced into the lower part of the leg. Morris was working in the School of Pathology in Oxford in the late 1960s when J.L. Gowans was demonstrating the recirculation of lymphocytes in lymph nodes. He now saw his sheep model as ideal for studying the long-term trafficking of lymphocytes throughout the body. In his first experiments with Hall he showed that the introduction of an antigen led initially to an increase in the output of mature lymphocytes followed by the appearance of primitive stem cells and finally what were at the time thought to be plasma cells. Antibody was detected in both the cells and the lymph plasma. With a particulate antigen, a second dose led to a shorter but more vigorous response, but when human serum globulin was used as the antigen the secondary response showed little change from the primary. This model in which the cell population and volume of lymph coming from a single lymph node, challenged by an antigen, could be monitored over long periods of time in an otherwise physiologically normal conscious animal, was to form the basis of many of Morris's future investigations.
By 1964, at the age of 37, Morris had gained considerable experience using the sheep as a model for long-term monitoring of lymph flow from many regions of the body. His papers, represent the wide field of interests that his work covered during this time. Professor W.J. Simmonds, who was a member of our team at the Kanematsu Institute in those early years and who has closely followed Morris's career in medical sciences since that time, writes: 'From his earliest days, moulded by his veterinary training and by his apprenticeship at the Kanematsu Institute, Bede was an uncompromising whole animal physiologist. He saw ymph collection as a window on the tissues at work in the whole animal. When he turned to immunology his interests remained the same - the whole animal was the test-bed, mechanisms inferred from in vitro experiment should always be testable in the whole animal...He was not denigrating the in vitro approach but was merely saying that isolated cells in a simplified medium might work differently from the same cells assembled as tissues in their normal environment - so why not test such concepts wherever possible in the whole animal.'
Perhaps more importantly, however, Morris was aware that young scientists were interested in coming to Canberra to learn the techniques of which he was certainly a master. He was an excellent teacher at the post-graduate level, working with and guiding his students through the intricate mazes of creative research. He, however, imposed on them the same stern discipline that he applied to himself in order to attain excellence. A.K. Lascelles, who was to become Morris's first PhD student, tells how he received instruction in writing a scientific paper:
In Sydney in July 1968 the Morris family had just returned from England and were staying in the Mosman home of Professor Courtice who was overseas. It was here during a couple of very long evenings that Bede gave me instruction in scientific writing. I had recently completed some experimental work on wound healing and had prepared a draft which I though was good; indeed I was rather proud of the factorial design I employed with the help of Dr Peter Claringbold from the Department of Veterinary Physiology. Bede went over the paper sentence by sentence, word by word. It was a humbling experience, but a truly valuable exercise and a practice which I subsequently adopted for all my research students. When I went to work with him in Canberra, I found that he and all around him worked very hard and all-night sessions were not uncommon. He was full of ideas and very generous in the way he shared these with scholars. In those early days Morris was a hands-on supervisor and those who were fortunate enough to work with him came to know the extent of his laboratory and surgical skills.Towards the end of 1964, Morris went overseas on study leave to revisit the School of Pathology at Oxford and later to work for the first time with Dr Marcel Bessis in Paris. He wanted to familiarize himself with the latest techniques, especially in electron microscopy, since he felt that he could never ask a student to excel with a technique that he himself had not mastered. In Oxford he set out to perfect his electron microscopic techniques in Professor Florey's laboratory. Florey wrote at the time:
Starting from scratch Morris mastered in three months the techniques of embedding, cutting and photographing with the electron microscope. I consider his illustrations first class and it is a great tribute to his energy, skill and perspicacity that he was able to accomplish so much in such a short time. He made some splendid observations on the lymphatics and on the blood vessels of the corpus luteum and the results of this work are now about to appear in the press.In Paris, Morris continued his work on the effects of antigenic stimulation on the cells in the lymph emerging from the popliteal node. He and Hall had shown that antigenic stimulation led to the appearance of large numbers of basophilic lymphoid cells in the lymph, and that these cells rather than antigens act to amplify and propagate the immune response by being disseminated throughout the body by way of the lymphatic system. With Bessis and others, Morris examined these cells with the electron microscope to try to relate this messenger function with their ultra-structural characteristics. It was found that their structure differed considerably from that of classical plasma cells, containing only a small amount of endoplasmic reticulum arranged in a haphazard fashion in the cytoplasm. No classical plasma cells were found in the lymph although these cells occurred in large numbers in the lymph node from which the basophilic cells originated.
Before going to Paris, Morris enrolled in a special course in French so that he would be able to communicate with his French colleagues in their own language. He later derived much pleasure telling me how he gave his first seminar in French. He burst into loud laughter when he told me how Bessis interrupted his seminar with, 'Bede, why don't you speak in English, we would understand you much better. You are really persecuting our language.' This, of course, only stimulated him to become more fluent in French which he did on subsequent visits to Paris. In this regard E.P. Cronkite of Brookhaven National Laboratory, New York, writes: 'On several occasions I was visiting in France with Marcel Bessis when Bede was also present. I love to hear him talk in French with his unmistakeable Australian accent. I believe that it confused our French associates when I told them that I could understand his French better than theirs.'
(b) 1965-1970. The immune system in the foetus and in organ transplantation
While on overseas leave Morris had become proficient in electron microscopy which he wanted to use in relating structure to function in his investigations of the cellular components of the lymphatic system in the development of immunity. With J.B. Smith he continued his studies on characterizing the cells in lymph from many tissues of the body. It was shown that in afferent lymph, 10 to 20 per cent of the cell population were macrophages and monocytes. In the liver following the injection of particulate material intravenously, the cell output in afferent lymph from that organ increased many times: for a period of several weeks after the injection of colloidal carbon intravenously, macrophage cells containing carbon were identified in the lymph. This suggested that the Kuppfer cells are not an entirely residential population of cells. In another situation, an antigen was localized beneath the skin of the lower leg, thereby establishing a granuloma. The cell output in the afferent lymph draining this area increased 20-fold with increased numbers of macrophages. The efferent lymph of the regional lymph nodes concerned in all these experiments was, however, free of macrophages.
It was at this time that Morris began, with G.J. Cole, an investigationof the development of the lymphoid apparatus in new-born animals in relation to immunological reactivity. The plasma of new-born unsuckled lambs does not contain gamma-globulins which are acquired from the mother's colostrum soon after birth. Morris and Cole found that in these agammaglobulinaemic new-born lambs the popliteal node is capable of producing a cellular reaction to a primary challenge with antigen. Very large numbers of basophilic lymphoid cells leave the lymph node in the efferent lymph, although no anti-body could be identified in the lymph. A secondary challenge led to a cellular reaction together with antibody formation.
These findings led to the study of the role of the thymus in influencing cellular immune responses in single lymph nodes. The thymus was removed in foetal lambs as early as 60 days in utero (gestation period 160 days) and after they were born, chronic lymphatic fistulae were established in the efferent ducts of lymph nodes to study the capacity of the nodes to react to an antigen. Although thymectomy reduced the no. of lymphocytes in the lymph to about 10 per cent of normal levels, the nodes reacted in essentially the same manner as in non-thymectomized lambs when challenged with an antigen such as influenza virus, Salmonella muenchen organisms or chicken red cells. In these lambs the 'wasting syndrome' described for thymectomized mice was not seen; the lambs subsequently grew and developed at a normal rate. These thymectomized lambs were also capable of rejecting grafts of allogeneic skin as vigorously as normal lambs, the cellular reactions seen histologically being the same as in controls. They were also able to mount an immediate type hypersensitivity response to ferritin although the delayed type hypersensitivity response to tuberculin was severely reduced. Thymectomy also resulted in a reduced ability of the lymphocytes of these lambs to cause a normal lymphocyte transfer reaction when injected into the skin of normal sheep. The reaction in the skin of thymectomized lambs following the intra-dermal injection of lymphoeytes from normal donors was also greatly reduced.
These studies suggested that while the thymus is a source of lymphoeytes, it is not the only source and that a considerable proportion of the lymphocytes present in normal animals is not derived directly from the thymus. Although the thymus was not essential for the development of an adequate cellular or humoral response to an antigen, the experiments showed that it is the source of some of the cells that take part in delayed hypersensitivity responses and in the capacity of lymphocytes from lambs to produce and resist graft-versus-host reactions.
In 1967, techniques were devised to collect lymph over long periods of time from foetal lambs in utero. Using these techniques, the nature of the free-floating cells in the lymph draining the intestines was established and followed by a study of the changes that occur in this population of cells after birth. A catheter was introduced into the intestinal lymph duct of the foetal lamb in utero near to term and the cells in the lymph monitored. The lamb was then delivered by caesarian section and the cell population of intestinal lymph studied over the ensuing seven days. In utero and for the first two days after birth, the cell population of the lymph consisted of uniformly small lymphocytes and less than 0.1 per cent of these cells incorporated *3H thymidine when incubated with the labelled material in vitro. By the third day, however, a significant change occurred when large numbers of blast cells and basophilic cells appeared and as many as 15-20 per cent of the cells incorporated *3H thymidine and were in the proccess of dividing. During the first three months of life the output of cells in the intestinal lymph increased about 10-fold and was associated with an enlargement of the gut-associated lymphoid tissue, particularly the Peyer's patches.
During this time Morris also developed a model for studying cells in the lymph draining a transplanted organ, the kidney. First, however, he had to master the technique of collecting lymph over a long period of time from the kidney of a normal sheep. With G.H. McIntosh he introduced a catheter into the main vessel in the hilus of the kidney and so established a fistula that kept flowing continuously for periods of up to four weeks. With this model, studies were made of the effects of ureteral occlusion and of intra-venous infusions of large volumes of Ringer-Locke solution.
These experiments were essential preliminaries to investigations of lymph from a transplanted kidney during the period of graft rejection. With N.C. Pedersen, Morris developed a model in which a kidney with catheters in the ureter and in the lymphatic duct of the hilus was transplanted into the neck of the sheep, the renal artery being connected to the carotid artery and the renal vein to the jugular vein. With this model Morris and Pedersen were able to obtain an isolated population of lymphoid cells that had migrated through the graft, and to characterize accurately the origin, fate and morphology of these cells. It was found that cells, which were collected within 24 hours of grafting, had become sensitized to the graft. Within the graft the main pathological changes were found in the vascular endothelium, and many of the peritubular capillaries became plugged with emboli comprised of lymphoid cells. The migration of cells from the circulation through the graft was very large - about 4-6 days after grafting, up to 4 x 10*8 lymphocytes were passing through the grafted kidney each hour. Towards the end of the life of the graft, large numbers of red cells appeared in the lymph and the lymph protein concentration rose to near the levels in the plasma, by which time extensive destruction of the vascular endothelium was observed. Antibodies were detected in the cirulation of the host, 48 hours before the graft was rejected. This antibody had both cytotoxic and agglutinating activity against the lymphocytes of the kidney donor and was of both IgM and IgG classes. Renal grafts that were removed within 120 hours of grafting did not evoke an antibody response in the host, which suggested that antibody synthesis in the host was regulated by events occurring in the graft. Although antibody production depended on the presence of the graft for a minimum period of 120 hours, a much shorter period of exposure to the graft sensitized the host so that a second graft was more rapidly rejected.
In October 1969 Morris left Canberra to spend a year's study leave in Paris with Bessis at the Institut de Pathologie Cellulaire, during which time he also visited many centres in England and in Europe to give lectures on his work. In 1970 the Australian National University established a Department of Immunology in the John Curtin School of Medical Research, and in November of that year Morris was appointed Professor and Head of the new department. In January 1971 several immunologists and research students who were members of the Department of Experimental Pathology transferred to form the nucleus of the new Department of Immunology.
(c) 1971-1988. Professor and Head of Department of Immunology. Work on foetal immunology intensified.
The creation of this new department gave Morris greater scope to develop the main lines of research that he had established in the Department of Experimental Pathology over a period of twelve years, first as a Senior Fellow and, since 1963, as a Professorial Fellow. These lines of research concerned the mechanisms of discriminationbetween 'self' and 'not-self' materials, the way in which immune reactivity develops in the foetal animal, the regulation of immune responses and the biochemical changes that occur in specifically stimulated lymphocyte populations involved in cell-mediated and humoral antibody reactions. The capability to distinguish 'self' from 'not-self' is crucial in all types of immune responses. In order to control or eliminate the reactions that occur in responseto foreign tissue and organ grafts, to induce states of immunological tolerance or non-reactivity against foreign substances, it is imperative to understand the nature of the immunological recognition processes. In addition, the interactions that occur between allogeneic lymphoid cell populations and the relationship between malignant tumours and the tissues of the host are important aspects of the general biological problem of how an individual animal retains its own special uniqueness.
In his report for 1973 Morris described the research in his department as being concerned with foetal immunology, the control of antibody formation, transplantation biology and tumour immunology. He pointed out that it was being carried out at two levels of complexity: (a) physiological studies of immune reactions in the whole animal and (b) analytical studies in tissue culture designed to elucidate cellular mechanisms underlying immune reactions. This division of research effort allowed analytical studies to be related to events occurring in the whole animal.
It was the immunological system in the foetus that continued to excite his interest most. The earlier studies of foetal immunology were preliminaries to a comprehensive account of the ontogeny of the lymphomyeloid complex in foetal lambs. The techniques already described for collecting lymph from the foetal lamb had been used by T.C. Smeaton and M.W. Simpson-Morgan to determine the absorption of macromolecules from the foetal gut. With the expertise gained from these experiments coupled with that which he and G.J. Cole had gained from their work on foetal thymectomy, Morris and his colleagues, L.D. Pearson and M.W. Simpson-Morgan, in 1971, began a classical study of lymphocyte recirculation in the normal and the thymectomized lamb. Subsequently, beginning in 1973 with K.J. Fahey, an extensive study was made of the immune response of foetal lambs in utero to a range of antigens in terms of histological changes and circulating antibody production.
These experiments led to elaborate studies in collaboration with J.D. Reynolds and later H.A. Gerber in 1976 on the development and role of Peyer's patches and the gut-associated lymphoid tissue in foetal lambs in utero. The results of these experiments suggested that free-floating lymph-borne small Ig*+ve lymphocytes originated from the Peyer's patches. To elucidate this role of Peyer's patches, it was necessary to remove all the mesenteric lymph nodes from the foetus, and/or a metre length of the ileum containing Peyer's patches. This resulted in the multitudinous lymphatic vessels afferent to the extirpated gut lymph nodes re-establishing continuity with the major efferent lymphatics, and it was possible to cannulate them after the lambs were born. An unexpectedly high lymph-borne cellular traffic between the gut and its regional nodes was found that proved to be greater than had been described in any other tissue. An unforeseen consequence of this heroic experimental surgery and tenacious dedication to achieving the almost impossible was the development of techniques that made it feasible to collect large quantities of peripheral lymph from many regions. These techniques are being used increasingly in a no. of animal species.
When Reynolds completed his PhD he went to work with J.G. Hall in the United Kingdom. He showed R.N.P. Cahill who was then working at the Basel Institute with another of Morris's former students, J.B. Hay, how to operate on foetal lambs. This led to an extensive study of lymphocyte 'homing' in the foetal lamb by the researchersat Basel, work that is being continued in Melbourne by Cahill. The concept of different pathways of lymphocyte migration in the body and of heterogeneous populations of lymphocytes with preferred sites for leaving the blood stream interested Morris greatly and various aspects of this were studied in collaboration with his student A.V. Fahy, visitor C.F. Zukoski, and colleague Wendy Trevella. His last contribution in this area was the demonstration with his student, M.T.H. Alsalami, that the high endothelium venules in lymph nodes thought to be necessary for lymphocyte recirculation in many species (other than the sheep), were only obvious in the foetal lamb before lymphocyte recirculation began.
It is interesting to note that despite his continuing use of foetal lambs as experimental animals, fifteen years elapsed before the demonstrated utility of collecting lymph chronically from foetuses in utero was applied to the study of immune reactions of single foetal lymph nodes in utero. With A.R. Hugh, Wendy Trevella and M.W. Simpson-Morgan, a study of the response of single lymph nodes of foetal lambs to a variety of antigens was begun in 1982, providing the first descriptions of the time-course of unequivocal primary immune responses. This line of work was still being actively exploited at the time of Morris's death. By then the full scope of experiments that might be done using the foetal lamb as an experimental animal was beginning to be appreciated. Experiments had been planned to make use of identical twins produced by J.N. Shelton, that would allow the transfer of cells between co-twins in a way previously only possible in highly inbred strains of laboratory rodents, or animals made pathological by treatment with radiation or cytotoxic immunosuppressants. Needless to say, Morris was highly critical of extrapolating too far from such highly contrived experimental artifacts.
Morris's experiments in foetal immunology required considerable attention over long periods of time, especially in the early post-operative period. Like most distinguished medical scientists, especially those engaged in chronic animal experiments, Morris relied to a considerable extent on his research assistant for the success of his experiments. Many of his extraordinarily complex surgical operations, which needed intensive post-operative care, were successful largely because he had an assistant, Wendy Trevella, as dedicated to success as he was himself. Their working association spanned the time from when he started working with foetal lambs until he died. Wendy Trevella not only assisted Morris in his own experiments but was also invaluable in the Department, helping many of Morris's students and visitors to make their experiments the successes they became.
Apart from his work on the foetus, some of Morris's most elegant work was the description of the lymphatics and lymphatic drainage of the ovary and uterus of the ewe which, as we have seen, he began with Maureen Sass in 1961, and which gave a whole new perspective into the endocrinology of the ovary. This line of work was allowed to lie dormant until his student, W.R. Hein, extended it to cattle before bringing it back to sheep. One of Morris's last experiments in Canberra was to collect lymph from the ovary of a sheep throughout the oestrous cycle, something he had previously not thought possible. These results have not yet been published. Getting similar data for the entire oestrous cycle in rats or mice, as was obtained from this one sheep, would require single point collections from a large no. of individual animals, tens or hundreds, which would guarantee acceptance for publication even though inherent between-animal variation would greatly reduce the value of the results. This raises ethical and philosophical considerations that Morris would have loved to debate. Such points were made forcefully in his preface to the book he edited with Masayuki Miyasaka to record the proceedings of a conference to honour the retirement of Zdenek Trnka from the Basel Institute (Book 1). He writes:
Most immunological experiments are now done on conglomerates of cells in test tubes or with conventional laboratory animals, predominantly rats and mice. These species have been refined by innumerable incestuous matings to give inbred strains whose genetic constitutions make it impossible for them to behave like normal animals. As a consequence what we know about the immunology of man is largely the immunology of the factitious mouse and rat...The study of the immune response as an aspect of lymphatic physiology demonstrated from the outset the limitations of small laboratory species. Developments in techniques of lymphatic cannulation in sheep and cattle have enabled physiological experiments to be done on single lymph nodes in conscious animals and regional responses have been defined for various antigens and allografts. These physiological approaches have told us much about the immune response and about the way the lymphoid apparatus works as a bodily system...Sheep and cattle are different from mice and rats but they are certainly as noble and certainly as relevant for studying the immune system.It is certain that none of the work presented at that conference in Basel on the 'Immunology of the Sheep' would have been possible without Morris's signal contributions to science.
(d) Work on Cattle
Although the sheep remained his experimental animal of choice, Morris began working with that much larger species, in some ways a more difficult species to handle experimentally because of its size, the bovine species. He had spent his study leave in 1974 in the Pathology Institute in the University of Bern supported by the award of an Eleanor Roosevelt International Cancer Fellowship, and in 1976, after his return from Europe, he decided to use cattle for certain projects that he had in mind. His interest in cattle, however, went back several years before this. In 1963, in his private sphere of life, he had bought a property, 'Lockhart', just out of Canberra, which he used for the first five years to produce wool from his Merino flock. Subsequently, however, he disposed of most of his sheep and became involved in the newly approved use of imported bovine semen to introduce genetic material safely from countries affected by diseases exotic to Australia. So began the production of a purebred Charolais herd, a long and difficult process but one that gave him great pleasure.
Morris's love of the land and especially the breeding of sheep and cattle in his private life dovetailed in very well with his work in his laboratory. Sundry cattle had been acquired by members of his Department for various projects. It is interesting that the first such cow was bought in the late 1960s with twin calves at foot. Morris had often commented on the tremendous contribution that had been made to understanding immunology by the natural phenomenon of mutual tolerance demonstrable in a large proportion of non-identical twin calves for each other's tissues. However, it was not until 1976 that he indicated some of his thoughts in his Presidential Address to Section 16 of ANZAAS and the real thrust into exploiting this valuable research model was begun, using techniques that had been well worked out and that had proven so valuable in sheep. By the end of that year a new student, D. Emery, and his supervisor, P.J. McCullagh, reported that 36 sets of mixed-sex twin calves had been collected; this no. reached 60 during the following year. It is important to stress that Morris's contribution to much of this work cannot be gleaned from his bibliography; but those who were associated with his Department know his generosity with respect to authorship, as well as the tremendous effort that he put into acquiring animals and facilities, and encouraging staff and students in using them. His first publication arising from the new work with cattle did not appear until 1980 and reported genetic differences between the two species of domestic cattle Bos taurus and Bos indicus with respect to transport of antibodies into their tears.
This project had been suggested to his student, M.R. Banyard, because of the empirically established different susceptibility of the two species to the serious eye infection 'pink-eye' caused by a specific bacterium Moraxella bovis. Twenty-six years had elapsed between his first publication on cattle, written when a recent recruit to research, and his second. By this time he had established a department that probably was unique in the world with respect to making use of the latest technologies of lymphocyte typing and embryo transfer to make custom-designed experimental animals. This was foreshadowed in his 1977 report where he stated:
This year the Department began a program of research into disease resistance and susceptibility in cattle. It has been possible to undertake research on large animals of economic importance because of the acquisition of a farm by the John Curtin School. The earlier experimental studies on the immunology of natural chimeric twin calves are being extended to include investigations into the major histocompatibility complex of cattle, studies on local immunity to eye infections of cattle and the maternal interactions that occur in sheep and cattle during pregnancy. Further developments in these projects will include the synthesis of mixed breed chimeric calves by embryo transplantation using Bos indicus and Bos taurus embryos. These chimeras will have mixed lymphoid cell populations and they will be used to study differential reactivities between lymphoid cells of different breed origins to infections.Large amounts of external funds were obtained from the livestock industries over a period of ten years and, coupled with Morris's energetic efforts to obtain a farm for the School, the realization of these goals became possible. The acknowledged expert in bovine embryo transfer in Australia, J.N. Shelton, was recruited with external funds in 1977 and, working with a new PhD student, P.M. Summers, achieved the production of chimeras in 1979. The characterization of their immunological responsiveness was published in 1984. Morris's involvement with the new technologies of embryo transfer, embryo manipulation and embryo surgery aroused in him an acute awareness of some of the potential benefits that might accrue from their use in the animal industries, and also of the awesome ethical and legal problems that might arise from their use in the human clinical situation. He became intensely interested in some of these philosophical issues and, in 1979, organized a major exhibition entitled Creation and Copyright at the celebration of the 26th anniversary of the Australian Academy of Science. This brought the public directly into contact with what new technologies in reproduction had achieved and where they might lead. Morris became widely sought after to speak on these issues, and some of his lectures have been published.
A major contribution was made to the classification of bovine MHC, initially Class I MHC antigens, and later Class 11. A number of people played a role in this including T.E. Adams, M.R. Brandon, M.J. Newman, M.J. Stear and J.T. Mackie. Some associations between MHC classes and disease resistance or susceptibility were found. Work with cattle also involved extension of some of the classical studies of lymphatic physiology and foetal immunology that had been previously done in sheep. Thus together with W.R. Hein, J.N. Shelton and M.W. Simpson-Morgan, Morris studied extensively the lymphatic drainage of the pregnant uterus of cattle and of the corpus luteum of pregnancy, and the foetal calf contained in the pregnant uterus was finally used as an experimental animal. The foetal calf proved to be a much less obliging animal than the foetal lamb, and its physical size with resulting problems proved almost insurmountable. Some initial successes were achieved, but these were what Morris might have colloquially described as the 'burley to get you in' because consistent success with experiments involving foetal calves subsequently became more elusive. Nevertheless, as a result of his foresight and industry, we now know that it is possible to consider using what he termed 'inconceivable animals', synthesized in the laboratory for immunological and physiological experiments. Only a small proportion of the full contribution that these animals can make to an understanding of the immune system has yet been realized.
Another type of synthesized animal that held his interest was the identical twin produced by embryo division, but this is considered above with his work on sheep. The cyclical functioning of the ovary, especially as reflected in the lymph it produces, was a proposition that also interested him greatly. It led him to question a fundamental tenet of homeostasis enunciated by one of his 'heroes', Claude Bernard, and this was argued in 'The inconstancy of the milieu interieur'.
Some colleagues questioned the need to use cattle as research animals, thinking them to be too expensive. It should be recorded that many of the experimental animals used for the cattle research were lent to the University by Morris. He took great satisfaction in equating the cost of maintaining such large animals with the cost of providing and maintaining more conventional experimental animals, and he remained certain that their use alone could answer some of the most important biological questions. In describing the advances made in his department during its first ten years, Morris, in his report for 1980, highlighted one of his keenest interests, the manner in which the genetic constitution of an animal influences its capacity to mount an immune response against infectious disease: 'The decision to explore this relationship in cattle entailed an extensive survey of the nature and pattern of inheritance of molecules on the surface of cells of the immune system. Successful characterization of these molecules together with a description of the manner in which they are genetically controlled would facilitate description of the nature of their influence on disease susceptibility.'
In the last report he wrote of the work of his department, the annual report of the John Curtin School of Medical Research for 1987, he stated:
Scientific research is a continuing activity of shifting interests and emphasis determined by new ideas, discoveries and techniques. Research in Immunology which originally concerned aspects of immunity and the immune response, antigens and antibodies, now embraces molecular and cellular genetics, cell ecology and ethology, cell proliferation and differentiation, lymphatic physiology, protein chemistry and molecular biology. Given that there are undeniable restrictions on the range of research projects that can be serviced within the School's budget, the Department of Immunology decided in 1986 to coordinate its research around the crucially important biological questions of how the immune discriminatory system develops in the foetus, and the immunological implications of pregnancy both in terms of the effect of hormones on the comportment and reactivity of cells and the immune interactions that occur between the conceptus and the mother. The approach to these questions has continued to be developed around studies in the embryo and foetus throughout their development and the effects of pregnancy on the immune system of the mother. Our experiments have integrated the disciplines of immunology, endocrinology, reproductive biology, foetal surgery and lymphatic physiology in investigating the status of self-tolerance versus acquired tolerance, the genetic basis of self-recognition, the control and regulation of lymphocyte recirculation and the physiological basis of the metastatic behaviour of cells. Large animals with long gestation periods offer particular advantages for these studies, especially when their reproductive processes and even the genetic constitution of their foetuses, can be determined by experimental design.When Morris wrote this, shortly before his untimely and tragic death, he had spent thirty-six years of his life in research. During the last seventeen of these years, he had guided the destinies of the Department of Immunology. He realized that to tackle the many problems that came to his fertile mind he had to develop a multi-disciplinary department that embraced all the latest technologies in his field of endeavour. Although his work had a direct relevance to many disease states and also a potential for considerable commercial benefit to the community, Morris was always a strong advocate of the importance of supporting ideas that arise from all sorts of inconceivable sources, without consideration of any immediate cash benefit. He wrote:
Ideas come from unexpected events, incongruities of thought and the inspirations of people with imagination. If one looks back 20 years few scientists would have predicted the development of techniques of gene analysis, the transfection of embryos, the production of monozygous mammalian clones, the significance of peptides in brain function, the genetic engineering of drugs and so on. It is this very uncertainty and unpredictability of outcome in science that requires the fostering of a research environment that will allow creative scientists to pursue difficult, fundamental research problems that may have no immediate commercial or social relevance. Such environments must be protective of the fragile new idea and not the target of destructive inputs from research managers whose imaginations scarcely extend beyond the bottom line of a balance sheet.Morris himself was certainly a man of ideas and also a man of action. To help him develop his ideas, he relied to a great extent on mastering the latest technologies and, perhaps to an even greater extent, on his ability to attract and inspire able young graduates. Morris supervised thirty research students for higher degrees, mainly the PhD. In addition he influenced the work of numerous researchers who came from many countries. Of these, eleven came from various centres in Japan. In extending his sympathy on behalf of his Japanese colleagues, Professor Kazuhiko Awaya, President of Yamaguchi University, writes:
Truly his scientific exploitation of large animals has characterized JCSMR's emergence as a world leader in immunology. The Latin phrase "Proles sine matre creata" may be apropos for his creative works. His leadership at JCSMR has significantly advanced immunology research throughout Japan and in no small measure at our School of Medicine at Yamaguchi University. Professor Morris visited our University in January of last year (1988) at which time he presented me with a book "Images: illusion and reality" written in his inimitable fashion and eloquent enthusiasm. I never expected this would come to be his last gift to me.
In his dual role as a breeder of Charolais cattle and a distinguished research scientist interested in the prevention of animal diseases, Morris was in an ideal position to make a contribution on many issues of concern to our animal industries. One of these issues, of great importance to Australia, was the proposed establishment of the Australian National Animal Health Laboratory (ANAHL), now the Australian Animal Health Laboratory (AAHL). This became the centre ot a major controversy in the 1980s in which Morris played a leading role.
The Laboratory, which was built by the Commonwealth Government, was designed to handle safely such exotic agents as Foot and Mouth Disease (FMD) virus. Its broad objective was to complement the existing State and Commonwealth facilities for the diagnosis, control and eradication of exotic diseases and to provide diagnostic services and technical back-up for the off-shore quarantine station. The concept of a maximum security laboratory had been in existence for a long time. However, the real impetus for its construction came in 1964 following the visit of Dr Eichorn of the Food and Agricultural Organisation of the United Nations, at the invitation of the Commonwealth Department of Health, to advise on Australia's ability to cope with outbreaks of exotic disease. There followed over the years a flurry of committee activity and a major project evaluation was undertaken. Eventually the Agricultural Council endorsed a recommendation from State and Commonwealth animal health authorities for a maximum security laboratory that would provide trained staff and facilities for diagnosis of exotic diseases and vaccine testing. It was agreed that the laboratory should not introduce FMD virus and other highly virulent exotic agents in advance of an outbreak. Other committee assessments essentially endorsed those of the Agricultural Council. The report of the Parliamentary Public Works Committee (PPWC) was accepted by Parliament in 1974. It was surprising, given the official advice provided at the PPWC enquiry, that its report should recommend, inter alia, that the Laboratory, after a suitable proving period, should be authorised to handle FMD virus prior to an outbreak of the disease in Australia.
There was a long delay following acceptance of the Parliamentary Public Works Committee's report and the starting date of construction in March 1978. The question of importing dangerous viruses in advance of an outbreak remained a 'sleeper' issue until after construction had started. It was the impact of the cost of this most elaborate facility that first came to be appreciated by those on the outside as it were. This concern exploded publicly in March 1981 when Morris expressed his serious misgivings about the high security laboratory and offshore quarantine facilities on Cocos Island, during an address to the annual conference of the Cattle Council of Australia. He argued that new technology in animal breeding had overtaken the Cocos Island developments and that the exorbitantly expensive ANAHL was a waste of public funds. He asserted that the proposed FMD vaccine facility was unnecessary, especially in view of likely developments with new recombinant vaccines. He went on to say that the enormous expenditure on ANAHL would draw diminishing resources away from other areas of research, and that the existence of ANAHL would not improve the lot of farmers in Australia 'one iota'.
Until that time, the question of importing highly infectious exotic virus into ANAHL in advance of an outbreak had not entered the public arena. The majority of Commonwealth and State veterinary officials and the official view of CSIRO held that exotic viruses, including FMD virus, should be imported into the laboratory shortly after commissioning, even if it were not used immediately. However, a minority view held that a suitable proving period for the laboratory should be three years after commissioning and that FMD virus should not be introduced even then unless this was considered absolutely essential for diagnosis. It was again Morris who brought this issue into the public arena, expressing the view that live FMD virus in particular was not essential for developing a diagnostic capability, and that its importation in advance of an outbreak would represent an unnecessary threat to Australia's livestock industries as the record overseas had shown that its containment could not be guaranteed.
In the subsequent debate, Morris pointed to the history of escapes of FMD virus from high security laboratories in other parts of the world. He was greatly respected by livestock producers as a scientist and was well known as a successful Charolais breeder. These attributes understandably gave him a credibility in the eyes of rural Australia that his opponents in the debate were unable to diminish. Morris had strong support for his stand from the leadership of most commodity councils, many scientists in universities and even CSIRO, a large no. of veterinarians, but not the Australian Veterinary Association leadership. Even so, he was rightly seen as the most effective and influential antagonist of the laboratory itself and exotic virus importation. As a result, high level meetings were convened to develop strategies to counter his arguments and neutralise his influence on the livestock industries. Morris's strength was tested during this bitter period from 1981 to 1986. Public debate was extremely acrimonious and hurtful to all participants but especially so to Morris, who had to fight the entrenched positions and reputations of individuals and large organisations.
An ANAHL forum held at Geelong on 22-23 August 1983 was an initiative of the National Farmers' Federation (NFF) to allow all participants in the debate to express views without fear of reprisals from their employing organisations. Prominent overseas speakers, well-known for their strong support of the facility and for the most part in favour of working with FMD virus in advance of an outbreak, were flown to Australia at CSIRO expense. The forum failed to resolve any of the major issues. It did become clear, however, that the scientific justification for the vaccine facility, which proponents were by now claiming was required to make FMD stocks in advance of an outbreak, could not be sustained. The facility would simply not be large enough to make the necessary number of doses of the various strains of FMD virus judged to be a potential threat, given that stocks would have to be turned over at intervals of less than two years. At the end of the meeting, Directors General of Agriculture could not agree on the issue of virus importation.
Subsequently the Australian Academy of Science, the Senate Standing Committee on Natural Resources and the Australian Science and Technology Council conducted their own inquiries, seeking submissions from all quarters regarding the need for live virus, especially FMD virus, for diagnosis, research and vaccine manufacture. Morris made telling formal contributions and was supported by many colleagues in universities, CSIRO and State Departments of Agriculture. It was relatively easy for Morris and his colleagues to dismiss arguments for FMD virus research and even for vaccine manufacture, but proponents continued to argue that FMD could not be diagnosed adequately without live virus. Finally these arguments were shown to be wanting and the government came to the firm decision that consideration of the importation of FMD virus would be deferred for three years after commissioning the laboratory, after which the safety issue and the needs arguments should be reassessed. In the meantime, the laboratory would develop a diagnostic capability for FMD based on complement fixation and the recently developed highly sensitive enzyme-linked immunosorbent assay using non-infectious reagents from overseas laboratories - precisely as Morris and colleagues had advocated. The government also accepted the view of the NFF that livestock industries should be closely consulted prior to any decision to import or work with any other exotic disease agents.
While the government decision brought the public debate to an end, at least for the time being, it was not until 1987 that the fight by protagonists to import FMD virus was irretrievably lost. At this time the vulnerability of the high security laboratory was demonstrated by what was an effective escape of virulent Newcastle Disease Virus (NDV) as a result of a series of human errors. This was a major blow to the credibility of those responsible and received wide publicity. The general consensus of official opinion was that the incident served as a salutary experience, fortunately without cost, destroying the notion that this high security facility could fully take account of imperfections of the human condition.
One of the initiatives taken by the Board of Management of AAHL following the NDV incident was the institution of an independent review of the justification for using various exotic pathogens in AAHL for diagnosis, training and research. The list of pathogens that laboratory personnel had considered necessary was examined on a case-by-case basis by a committee of four comprising a senior veterinarian, a distinguished virologist, a distinguished animal geneticist representing the CSIRO Staff Association, and a nominee of the NFF. Morris was the NFF nominee. Strong representations were made by AAHL staff in an attempt to force rejection of Morrls's nomination. The NFF stood firm and the Board of Management finally accepted its nomination. So Morris toiled for two weeks with the committee, deferring his departure for what turned out to be his last study leave. It was a source of considerable satisfaction to Morris and others involved in the controversy, that the committee was able to agree on the major issues. Among other things, the committee recommended that the following viruses not be imported at this time (or in most cases in advance of an outbreak of the relevant disease): African swine fever (virulent strain), Avian influenza (additional strains), Foot and mouth disease, Rabies, Rift Valley fever (virulent strain) and Sheep pox (virulent strain).
So, after a long fight and shortly before his death, the live exotic virus issue was brought to a resolution that largely satisfied Morris's earlier concerns. Viewed in hindsight, the position that he and his colleagues had taken had been vindicated. In the absence of a Morris-led opposition with its high public profile, it is probable that FMD virus would have been introduced into the laboratory in 1984, shortly after commissioning.
2. The administration of science
Morris was elected to the Fellowship of the Australian Academy of Sdence in 1969 and played an active role in the administration of the Academy for several years. He served on Council from 1977-1980 and from 1981-1986, was Vice-President, 1979-1980, and Treasurer,1981-1986. He also served on the Science and Industry Forum of the Academy from 1981 to 1986.
Besides the work of the Academy, Morris became particularly interested in the application of science to the rural industries, especially the livestock industries. He was a member of the Wool Research Production Advisory Committee of the Australian Wool Board, Chairman of the Rural Credits Development Fund of the Reserve Bank, a member of the Scientific Advisory Committee of the International Laboratory for Research in Animal Disease, Nairobi, and a scientific and technical consultant on cattle production to the French government.
Professor Bessis writes, inter alia:
Bede Morris loved France where he had many friends. For more than 20 years, from 1966, he came to France very often, on Study Leave or after attending a Congress in Europe, always accompanied by his wife Margaret who shared his love of France and often by one or other of the children. He especially loved French literature - he knew by heart many of Beaudelaire's poems - and French wines. He spoke of French wines with knowledge and humour whether they be from Bordeaux, Bourgogne, Jura or elsewhere. All of his friends in France have memories of Bede Morris's discourses on the making of champagne or on the comparable value of Bordeaux wines from the year 1907 to 1986.
In 1983 he participated, in Paris, in a seminar of the French Academy of Sciences to which he brought greetings from the Australian Academy of Science. Many members of the two Academies knew one another and it was decided to establish official relations between the two Academies. These were sealed in 1986 when Professor Jean Bernard went to Canberra where he was elected a Corresponding Member of the Australian Academy of Science. That same year Bede Morris had organized a photographic exhibition the greater part of which consisted of the treasures of the French Society of Photography. Since photography was born in France in 1826, this Society takes great care of the photographic plates and prints of its first fifty years. This exhibition, entitled "Images: illusions and reality", was shown under the auspices of the two Academies in galleries throughout Australia. It was a great success, thanks to the enthusiasm and indefatigable activity of Bede Morris.
For a long time Bede Morris wanted to write a book in which he would bring together all his scientific and philosophical reflections on the physiology of the immune system. The opportunity was given him by the Fondation de France which invited him to Paris as Professor at any time of his choosing from 1988. It was while he was happily preparing this stay and making plans for the lectures he would give to the College de France and to the Centre d'Ecologie Cellulaire that a car accident deprived the world of a very distinguished scholar and his friends of an unrivalled human being. Bede Morris has made contributions of extreme importance on the physiology of the lymphatic system of man and animals, work which his pupils are continuing across the world. Mais ceux qui l'aimaient, savent que cette oeuvre n'était qu'une petite partie de tout ce qu'il allait ecrire, de tout ce qu'il pouvait apporter au monde d'idées profondes, paradoxales, plaisantes, geniales.
Distinguished scientist that he was, recognized throughout the world for his contributions to our knowledge of the function of the lymphatic system and of the immune system in particular, Morris never forsook that lighter side of his character, his prowess as a raconteur and an entertainer, which, as I have mentioned earlier, he showed as a schoolboy. His somewhat boisterous joie-de-vivre at scientific society dinners, which at times can be rather dull occasions, will be remembered by all of his colleagues; his repertoire was sufficient to suit all occasions. In this regard, Dr E.P. Cronkite of the Brookhaven Laboratories in New York writes:
Knowing of his work on the cannulation of diverse lymphatic vessels, I invited him to visit us and demonstrate his technique, particularly in cannulation of hepatic lymph vessels. He gladly accepted my invitation and spent a few days showing us how to cannulate various lymphatic vessels in sheep and goats. He gave some seminars and entertained us with a movie on the bursa of Fabricius. We had a small reception and party at home in his honour and, after dinner and a few Fosters beers, he entertained us with a riotous and ribald story and dance. My daughter was home from the University of Rochester for a short vacation and said to me "Dad, I wish all of your scientific friends were like Dr. Morris."Morris was a man of many callings - soldier, scientist, cattle breeder and entertainer, in all of which spheres he strove for and attained the highest standards of excellence. From his childhood days he drove himself at a fantastic pace to reach such standards in everything he did. Above all else, however, he was a family man, deeply devoted to his wife, Margaret, their five children and three grandchildren. To him, his family formed that rock-solid foundation in life without which his other activities would have been meaningless. Bede and Margaret were married in Sydney in 1963, when he was a young research worker at the Kanematsu Institute. In those early 1960s on the fourth floor of the Institute we all knew when it was Friday, the day Margaret Gibson, that beautiful, softly-spoken young lady who worked in the city nearby, would come to the laboratories with a bag of fish and chips for Bede's lunch. With one eye on his experiment and the other on Margaret he would sit on a stool in his laboratory and eat his fish and chips.
He also expressed an interest in Long Island oysters and bluefish, so at low tide I took him out into the mud flats where one wallows in two or three feet in the black goo that is loaded with luscious oysters. Then, upon the rising tide, we went fishing for bluefish. In trolling for this fish, we use what is called an "umbrella rig" that consists of crossed, foot and a half stainless steel wires, at the tip of which there is a large hook on each and then another central hook with surgical rubber of different colours. As this moves through the water, bluefish attack it and not infrequently one will get three, four and on rare occasions five bluefish at the same time. This was the time when five hit. I tried to explain to Bede to please let me bring them into the boat the first time so that he could become more familiar with how we get them in and off the hook without being bitten by these voracious and aggressive fish. With his energy, strength and enthusiasm, he brought all five aboard in one fell swoop, a total of about fifty pounds of fighting bluefish.
With his fun-loving spirit, his zest - indeed zeal and ardour - for making life as humorous as possible, it was difficult to believe that he also had a very serious and reflective attitude. He gave the opening lecture at our International Conference that was held in my honour at Brookhaven National Laboratory, 6-7 October 1983. His lecture on "The development of immunological reactivity in foetal lambs" was delivered with beautiful, expressive language, elegant photomicrographs and electron mierographs, illustrative graphs that within a half hour or so described nearly the results of an entire, productive, innovative career.
Although my family and associates thoroughly enjoyed the person of Dr. Morris with his joie de vivre, his enthusiasm, his zest for life and his exuberant mirth always on the surface and ready to burst out, it did not disguise that, in reality, he was a very innovative, thoughtful, serious and productive scientist and a most warm and gracious human being.
When, after their return from England, the Morrises moved to Canberra in 1968 with their young children, Simon and Sally, one of Bede's high-priority tasks was to establish the garden at their new house at Yarralumla. As with all his other activities, Bede strove for excellence as a gardener. He excelled as a vegetable grower and his vegetables were always bigger than anything the rest of us could grow. But I well remember one Sunday morning when he visited me, in a neighbouring suburb not far away. I was in my garden, harvesting my onions. When he saw them he was speechless. He could not understand how anyone, let alone myself, could grow onions that were so much bigger than his. When he got over his shock, he was full of praise and admiration for my prowess as an onion grower, and from that day he held me in much higher regard as a gardener.
Naturally, I have numerous personal memories of incidents that we shared throughout our scientific careers together. For several years in the early 1960s we would both walk to work, a distance of about five kilometres, and at the end of the day we would walk home together. He would drop into my office and first take me down to the animal house to show me proudly his latest experiment with lymph flowing freely from catheters in various lymphatic ducts and the sheep quite unconcerned munching on its chaff. It was only a few years earlier that I had taught him how to insert glass cannulae into lymph ducts of small anaesthetized laboratory animals. His use of plastic cannulae and of sheep as his experimental animal was a great advance in our techniques, which he was always proud to display. On our way home we discussed all manner of topics from science to politics to gardening, and on Friday evenings we would call into the bar at the back of the old Canberra Hotel, our half-way house, always the public bar where we would have a beer and a chat with the many workmen of Canberra, also on their way home. One historic occasion was in 1963 when Lake Burley Griffin was filling after the Molonglo River was dammed. Our route took us across the low-level Lennox Crossing bridge over the Molonglo. In the morning the water level was below the bridge, but in the evening it was a foot or more above. Like two schoolboys we took off our shoes and socks, rolled our trousers up above our knees and waded across, shoes in one hand and briefcase in the other, careful not to step over the side of the narrow bridge into the deep water. This was the last time that any-one walked across Lennox Crossing bridge, which since that day has lain submerged beneath the waters of Lake Burley Griffin. Although it was not Friday, we called in at our half-way house to celebrate.
To some of his fellow scientists, Morris was an enigma - easy-going, humorous, full of fun and laughter, yet with strong views on many issues that he would express with considerable force and vehemence. For those who really understood him, he was a delightful colleague. In my old age I feel that I have lost a true friend and an extremely loyal colleague. More importantly, however, Australia has lost in tragic circumstances one of her most colourful and distinguished scientists.
F.C. Courtice is Emeritus Professor of the Australian National University and Honorary Visiting Professor at the University of New South Wales.
This memoir was originally published in Historical Records of Australian Science, vol. 8, no. 1, 1989