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This issue of The Journal of Physiology, recording aspects of the fiftieth anniversary of the Howard Florey Institute, tells of how a successful basic scientific investigation attracted the enthusiastic interest of several Australian and overseas philanthropic leaders. It led to the building of arguably the world's best laboratories for long term survival experiments on large animals, and incorporated state of the art radiochemical and molecular biology laboratories.

It recounts the scientific work which was the basis of igniting the enthusiasm of people of high achievement and national profile who were prepared to foster a biomedical research endeavour, and it explains some of the institutional innovations which ensued.

In 1958, the data on the cross circulation experiments by the group in Melbourne, pointing to an undiscovered hormone controlling aldosterone secretion, were reported to the Physiological Society of Sweden, and described in the Swedish press. Then the results were presented in a lecture at University College London, where the audience included J. D. Bernal, J. B. S. Haldane and Sir Henry Dale. Considerable encouragement was given. Dale remarked that the demonstration on film of the adrenal transplants and parotid fistula ‘gave me the same excitement that seeing Pavlov's work first gave me.’

The results were also presented at the Rockefeller Foundation in New York and the National Heart Institute at the NIH, as a result of which Dr Robert Berliner, Deputy Director, that morning immediately initiated a discussion with the Director of Grants of the Heart Institute. They suggested an application for support be prepared forthwith. The publication of the lecture over two issues of the British Medical Journal (Denton et al. 1959) attracted strong interest in the media in Australia, and a direct effect followed.

Prior to going to Europe and the USA we had invited tennis playing friends Kenneth and Baillieu Myer, who directed the Myer Emporium, Ian Potter, the stockbroker and merchant banker, and Dr H. C. Coombs, Governor of the Reserve Bank of Australia, on separate occasions, to visit our ancient laboratories and see the surgically prepared sheep, and experimental results. Upon my return from Europe in 1958, Professor Wright and I held a dinner for the group, which included discussion of the international interest. Dr Coombs remarked that what was really needed was a first class laboratory with animal facilities. A week or so later he invited Kenneth Myer and Prudence Myer for a weekend at the Australian National University, where he was Pro-Chancellor, and showed them the new John Curtin School of Medical Research. I received a telephone call from Kenneth Myer on the day of his return to Melbourne, and the question to which an immediate answer was requested was how much would it cost to build internationally first class animal laboratories for the work? Taken by surprise, as it were, I said about a quarter of a million pounds, which was a great deal of money in those days. The reply was ‘Well I know someone who has some of that but let's have dinner on Thursday night with Ian Potter.’ Potter's immediate response to Ken and the small group, including Ken's brother Bails, was that he would go halves with the Myers. Further, reflecting his stockbroking ethos, he said ‘We will underwrite the total sum and Dick can go and get an architect tomorrow’. This was done, the speed of the exercise representing something of a course record for Australia. Kenneth Myer suggested that the Laboratories be named for an Australian scientist who had made a major contribution to medical science. Howard Florey was suggested, and he diffidently agreed, writing that ‘It is a great honour to have a laboratory named after one, and all I can hope is that dazzling work will emerge from it in the course of the next century or so’.

Following on, The Rockefeller Foundation, when approached in New York, immediately agreed to donate £50,000, and an approach to the Prime Minister of Australia, Sir Robert Menzies, resulted in the Commonwealth donating £100,000. The University provided a further £45,000, and the Reserve Bank of Australia £30,000, and the building – The Howard Florey Laboratories of Experimental Physiology and Medicine – was dedicated on 30th August 1963 by the Prime Minister, Sir Robert Menzies KT, CH, QC, in the presence of Sir Howard Florey, President of the Royal Society.

Menzies said that it was ‘A matter of gratitude, that in terms of talent, all human beings were not equal. Because then you get peaks of greatness expressed in people who not only do remarkable things themselves, but gather round them other people who are all the better because they have worked with a great man. And the result is that through the very inequality of talent that exists in human beings, the ordinary person, like most of us, is able to go along better, happier, with a better future and a better understanding.’– and much else laudatory of Florey.

Among other thoughts, Florey stated in reply:

I suppose that in general, most academic people do not wish to be associated with anything that is not likely to be absolutely first class. Happily, I have no doubts about the future of physiological work at this University.’ He noted that his successor in the Chair of Pathology at Oxford University, Dr Henry Harris, did his first real piece of research in Professor Wright's physiology department. He added:

Scientific research is an intellectual activity demanding at its best the exercise of great imagination, great technical skill and persistence of no mean order. One of the functions of a University is to be a place where intellectual activity is given every encouragement, and it is not merely a place for routine teaching … the value of a Laboratory such as this is that it will make discoveries, and that in the ambience of a university it has a maximum chance of stimulating the powers of enquiry of young men and women to come. There are always some whom a university will influence and educate to appreciate the beauty of experiments carefully planned, elegantly executed and clearly described, and by so doing it will help them orientate their thoughts to the tasks of enlarging mankind's understanding of himself and his environment.

The study of instinctive behaviour: instinct is a trinity neural organization

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References

In recounting history, it is appropriate at this point to return to the basic preparation of the permanent parotid fistula in sheep. It was observed in 1953 that sheep with a parotid fistula constantly licked dried saliva on the side of the metabolism cage, and they avidly attacked a salt block. If offered NaHCO3 or NaCl solution (e.g. 300 mequiv l-1), the excited animal immediately and avidly drank a volume of it in 2–10 min, providing sodium intake commensurate with its salt loss. The question which presented at this early stage was – how did the animal detect the amount of sodium it had lost? Secondly, how did it ‘know’ to stop drinking after 2–10 min when the amount taken repaired its deficit? The cessation of drinking was long before the material drunk could be absorbed from the gut and alter blood composition?

It was strikingly evident that this behaviour was instinctive, and here was a beautiful model to study. Darwin in The Origin of Species stated that he would not attempt any definition of instinct, but everyone understood what is meant when it is said that instinct impels the cuckoo to migrate and lay her eggs in other birds’ nests. Contemporary knowledge, much of which derives from the comparative behaviour studies of Craig, Lorenz, Tinbergen, Thorpe, Hinde and many continental zoologists, embodies the concept that there are genetically ‘hard wired’ or programmed neural organizations that subserve the arousal of behaviour, and the consummatory act of apt gratification. In our eyes an instinct can be considered as organized as a trinity. Considering moderate to severe thirst as an exemplar, there are the sensory inflow components such as dry mouth, tongue and lip cracking, sensations which, with severe desiccation may be imperious. There is the compelling intention to drink if water is encountered. The subjective element of the instinct, in effect the integrating element of the trinity, is the powerful primordial emotion of thirst which conscious process is subserved, inter alia, by neural organization in the anterior wall of the third ventricle. William James remarked a century ago that ‘Every object that excites an instinct excites an emotion as well’.

In the course of the study of sodium appetite in our sheep, it was found that the behaviour was innate, being exhibited by naive animals within 2–4 days after fistula surgery (Denton, 1982). It was specific for sodium salts. The intake was significantly related to deficit, and this was true also if the animals were adrenalectomized and maintained on deoxycorticosterone acetate (DOCA) or aldosterone. Decrease of sodium concentration in the cerebrospinal fluid (CSF) contrived by infusion of isotonic mannitol into the cerebral ventricles significantly increased sodium appetite, whereas increase of sodium concentration in CSF reduced appetite in the Na-deficient animal (Weisinger et al. 1979).

Furthermore, studies with infusion of phloridzin into the CSF which interfered with Na+-coupled glucose transport, as well as ‘push–pull’ experiments in the dorsal anterior third ventricle using ouabain which increased intracellular sodium, supported the concept that intracellular concentration of sodium was determinant of activation or reduction for sodium appetite (Weisinger et al. 1985).

Major contribution to this knowledge of ionic effect on sodium appetite was made by Dr Richard Weisinger, Dr Eva Tarjan, Dr David Mouw and Professor Michael McKinley. Dr John Blair-West, by cerebroventricular infusion in the brains of cows, showed these ionic changes were similarly operative. However, species differences existed in that no effect of reduced CSF sodium concentration was evident in rats or mice (possibly reflecting that the major impact of a sodium-deficient environment falls much more on the herbivores than on omnivores).

It was obviously of primary interest to study thirst in parallel with sodium appetite. If animals were made concurrently deficient of water and sodium, and then presented with the two solutions, they would drink rapidly whichever they encountered first, and in apt amount, and would take no more. However, they would immediately avidly drink the alternative fluid if presented (Denton, 1982).

Surgical ablation of the anterior wall of the third ventricle caused adipsia which was sometimes permanent. However, if the animal also had a parotid fistula and was allowed to become Na deficient as well as water depleted, it would avidly drink 300 mmol l-1 NaHCO3 solution even if the water depletion had increased plasma [Na+] to e.g. 160 mmol l-1. Thus it would kill itself if the sodium solution was not withdrawn. The thirst and the sodium appetite systems were functionally and anatomically separate.

McKinley led investigations of the neuro-anatomical organization of vasopressin secretion and thirst.

In 1926 Verney showed that incorporation of the head of a dog in the circuit of the heart/lung/kidney preparation, which Starling and he had developed, stopped the characteristic watery diuresis.

This early discovery dominated the remainder of Verney's investigational life, and perhaps, culminated with his discovery of the osmoreceptors determinant of antidiuretic hormone secretion announced in his Croonian Lecture at the Royal Society in 1947.

Verney attempted to localize the osmoreceptors, but the outcome was not definitive, and he was left with the conclusion that the osmoreceptors were the magnocellular elements in the supraoptic nucleus.

McKinley and colleagues made intracarotid infusions of hypertonic NaCl, sucrose and urea, and, whereas all elevated the Na+ concentration in the CSF, urea was ineffective in stimulating thirst. In McKinley's eyes this pointed to a role of the circumventricular organs (which lacked a blood–brain barrier) and he postulated that the organ vasculosum of the lamina terminalis (OVLT) and the subfornical organ, could be the site of the osmoreceptors (McKinley et al. 1978).

He showed that lesions of the OVLT left the sheep largely unresponsive to hypertonic infusion. Further, with intravenous infusion of hypertonic saline there was major expression of c-fos confined to the neurons in the OVLT.

The Florey group made a neuroimaging approach in San Antonio, Texas, in collaboration with Professor Peter Fox. Regions of the telencephalon, particularly Brodmann area 32 of the anterior cingulate and the insula, were highly activated by systemic infusion of hypertonic saline to cause thirst in humans. The activations reduced rapidly with the act of drinking of water (Denton et al. 1999). Furthermore, ageing reduced the effectiveness of the gratification process.

Following this discovery of specific regions of the telencephalon possibly subserving consciousness of thirst, McKinley and Dr Brian Oldfield used retrograde and anterograde fibre pathway tracing, as well as pseudo rabies virus tracing, to show connections via the thalamus between the anterior cingulate and the OVLT (Hollis et al. 2008).

These studies embody the evolutionary issue of the successful migration of vertebrates from the rivers and estuarine areas to colonize diverse ecosystems of the earth, including the arid and desert regions. The investigations also have great significance in the field of clinical medicine. Some of the great figures of British physiology and the Royal Society have been involved, and McKinley's contribution, in terms of showing the locus of the osmoreceptors, was very important.

The financial support of the research, and institutional organization

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References

We return now to the financial support of the research. In the early 1960s the National Heart Institute of the USA sent a group led by Dr Gregory Pincus to Australia to evaluate the research proposal that Dr Robert Berliner had suggested Dr Denton initiate. It was decided to grant $690,000, a considerable sum in those days. However, the Director of the International Research Office of the NIH, Dr Martin Cummings, blocked the grant on the basis that it would upset the ecology of research funding in Australia – it being too much. Contemporaneously, Sir Ian Potter and Dr H. C. Coombs were going to Washington for the World Bank meeting. Sir Ian knew Robert Garner, the financial advisor to NIH, and the two Australians were introduced to Cummings. The context of the launching of a new Institute in Melbourne was explained (including the private finance) and the outcome was that Dr Cummings and they agreed that the grant be paid in four tranches. There was, however, a most important tangential development. Shortly afterwards Dr Cummings became the Director of the National Library of Medicine of the USA, and soon introduced the highly innovative ‘Medical Literature Analysis and Retrieval System’ (MEDLARS). Dr Cummings, who had now developed close relations with Australia, came out and met Kenneth Myer, who had become the Chairman of the National Library of Australia. The result was that Australia was the first country, with Sweden, to have full access to the system, which was of inestimable benefit to the whole Australian medical research community – not just the Florey Laboratories.

For the first 5 years of the function of the Laboratories the financial provision of the NIH was predominant. Only from the late 1960s onwards did Australian support of ongoing investigations predominate (Hewat, 1990).

At this stage a plan was to make the Florey Laboratories a self-governing institute affiliated with the University. This would permit independent international negotiation. It would have its own Board, and a binding agreement with the University which would make the buildings available to the Institute for a token rent. Appropriate research led to the view that the ideal governing structure could be that of Harvard University, which had a small self-perpetuating group of Trustees. To do this required an Act of Parliament, with provision for State Government and Commonwealth representatives, as well as the Originating Members. The Howard Florey Institute of Experimental Physiology and Medicine was incorporated by Act of The Parliament of Victoria on the 31st March 1971.

The Originating Board Members were Kenneth Myer, President; Sir Ian Potter, Vice-President; Sir John Phillips, Governor of the Reserve Bank, Treasurer; Dr H. C. Coombs, Pro-Chancellor of the Australian National University; Dr Derek Denton, Founding Director; S. Baillieu Myer; Professor R. Douglas Wright, later to be Chancellor of the University of Melbourne; Mr Ray Marginson, Vice Principal of the University of Melbourne; Professor Leslie Ray; Sir Ernest Coates, Director of the State of Victoria Finance; Dame Hilda Stevenson DBE; and Sir Evelyn de Rothschild was the first international Originating Member, and he gave great assistance to the Institute investigations and negotiations, as well as the establishing of the Howard Florey Institute of Experimental Physiology and Medicine Foundation of the United Kingdom (Hewat, 1990).

In the late 1960s the National Health and Medical Research Council of Australia accepted a proposal by Sir Gustav Nossal FRS, Director of the Walter & Eliza Hall Institute, to implement an Institute Block Grant system. The basic consideration, applicable also to the Florey, was that scientific work was largely supported hitherto by three year Project Grants. The outcome was that groups with outstanding track records spent one to two months each year preparing several three year Project Grants and Fellowship applications when they could have been involved more creatively with scientific experiment. Central to it was the concept of staff positions, with several at each level. There was a Fellowship Committee to advise the Director and Board. The external membership of this Committee ensured a strong extramural scholastic audit. Professor Geoffrey Burnstock, FRS, was one of the leading members of this Florey Committee. The total performance of the Institute, and its budget were reviewed every 5 years by a separate Institute Scientific Review Committee. The first Florey Review Committee appointed by NH&MRC after 5 years included Dr Roger Guillemin, Nobel Laureate from the Salk Institute, and Dr Robert Berliner, Deputy Director of the National Heart Institute of the USA. They stated in a letter separate from the formal report, and read by the Prime Minister …‘That the Florey medical research had placed Australia in the forefront of quality anywhere in the world.’

Two appointments of enormous value to the Institute and to Australian science generally were made under the Block Grant system. It involved two outstanding Australian scientists who were working on peptide sequencing and synthesis at Harvard's Massachusetts General Hospital: Dr Hugh Niall and Dr Geoffrey Tregear. Niall and colleagues soon sequenced the hormone relaxin, showing it was composed of two chains, with a disulphide bridge similar to insulin. Then Tregear and colleagues synthesized relaxin. The latter was a collaborative project with Dr Du from the Shanghai Biochemical Institute of the Chinese Academy which had first synthesized insulin.

Tregear subsequently, with special financial assistance resulting from an approach to the Prime Minister, Mr Malcolm Fraser, taught gene synthesis, both the Caruthers and Gait methodology, to scientists from a variety of Australian institutions, including CSIRO and the Walter & Eliza Hall Institute. It was a valuable national contribution.

The relaxin group sequenced relaxin-1 and relaxin-2, and subsequently isolated relaxin-3, which is prominent in the mesencephalon, but the precise function of it is yet to be determined. The Institute was the first in Australia to have the five cards in the hand for molecular biological investigations: gene sequencing, gene synthesis, peptide sequencing and peptide synthesis and cloning. One outstanding advance was led by Professor John Coghlan, Dr Hugh Niall and Dr Geoffrey Tregear with a technique termed Hybridization Histochemistry, which involved marking specific mRNAs in a tissue by hybridization with synthesized complementary DNA. The DNA probes were labelled with 32P. It provides the precise cellular address of gene expression in functionally diverse and morphologically heterogeneous tissues.

Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References

In early 1970, Sir Rupert Clarke, Chairman of the National Bank of Australia, became a Board Member. He had a very deep interest in the pastoral industry, and was enthused by the basic knowledge being revealed about ruminants. He had, with two other Australian colleagues, entered into an Australian partnership with Robert Kleberg Jnr, President of the King Ranch, Texas, the largest cattle operation in the world. The ranch held about 13.5 million acres of Australia, predominantly with a string of cattle stations across Northern Australia. Clarke invited Denton to a dinner party with Robert Kleberg and a visit to the Howard Florey ensued the next day. Kleberg invited Denton to visit Texas as soon as feasible. Part of the trip involved going to Florida, where Kleberg had a property called ‘Big B’, which was just below Lake Okerchobee. It had about 30,000 cattle on lush grass, and was divided into 80 acre paddocks, each with a large concrete water tank and several mineral boxes per paddock containing all known trace elements involved in cattle nutrition. Other boxes provided molasses to supplement nutrition. Despite these conditions the ranch was losing up to 300 pure bred Santa Gertrudis cattle per month with a general wasting condition – the ‘thin cow’ syndrome. There were several university and State agricultural teams working on the property endeavouring to solve the problem, somewhat it seemed on a ‘shot gun’ approach. Mr Kleberg proposed the Florey might take over, suggesting that it could be on a consultant contractual basis. We said it was a very interesting problem. We would do it in any event, on an expectation that he would support the Florey science. There was a handshake, a laboratory was built on the ranch, and we divided a series of pastures on a Latin square basis. Dr Jim Morris, an Australian, at the University of California, Davis, joined us. The pastures were divided vertically on nutritional and parasite control, and horizontally in relation to provision of intrarumen cobalt bullets brought from Australia, copper injections, and both or none. The result fell out clearly on the basis of severe anaemia in pastures without cobalt bullets, normal haemoglobin in pastures with cobalt provided. There are no specific appetites for trace elements which would have driven animals to mineral boxes. Other adjustments emerged later in relation to provision of copper and also selenium. The animals with cobalt had a 30% superior reproduction rate and the weaning weight of calves with cobalt was 17 kg greater. Administering the cobalt in the pastures, each with a concrete water trough, turned out to be simple. A cowboy with a 50 ml syringe would add cobalt to the water every fortnight. The calf turnover each year from the property was ca. 15,000, so that with the extra animals born, with the extra weight of the total, the financial advantage at about 35 cents per kilogram was very large indeed, and altered the economics of the Ranch. The cost of cobalt chloride per head of cattle for the water troughs was a few cents per month.

Robert Kleberg was very pleased, and helped directly. We had known Mr Alfred Hayes, President of the Federal Reserve Bank of New York, through Dr Coombs. He had visited Australia, and was enthusiastic about the science he saw. He arranged, as an exercise, for some junior lawyers in the Bank to prepare a Constitution for a Howard Florey Biomedical Foundation, as a public foundation incorporated in the State of Delaware. This became the basis of many millions of dollars of support over the years, particularly from the Kleberg Foundation. Inter alia, it supported overseas scientists to work at the Florey. The initial Board of the US Foundation included Alfred Hayes, Robert Kleberg, Leroy Denman (the King Ranch Attorney) and Dr Seymour Farber (Vice Chancellor of Public Programs at the University of California, San Francisco). Mr Hayes invited the Director to address a lunchtime meeting of the Federal Reserve Board in New York on scientific organization and work, and thus, inter alia, attracted a generous donation from Mr David Rockefeller to the Foundation. After 36 years successful work, the Foundation concluded function in 2009.

Salt intake and the genesis of high blood pressure

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References

In the late 1970s the controversy over the role of salt content in the human diet in aetiology of hypertension, stroke and other diseases of the cardiovascular system was vigorous. The case against the role of salt was heavily backed by the Salt Institute, a lobby group based near Washington DC, and supported by the food and drink industry. At this time, we learned Southwest Foundation in Texas had found, with their colony of 250 chimpanzees, that blood pressure rose with age, very much like a Western industrialized society. It was judged that to experimentally examine this situation, it would require placing the colony on a low Na diet. The cost of bananas was prohibitive. The chimpanzees refused to eat their biscuit diet if the salt content was significantly reduced.

Ideal conditions for an experiment existed at the primate colony at the Centre International de Recherche Medicale, at Franceville, Gabon, directed by Dr Alan Dixson. This was 300 km inland up the Ogouie River from Dr Albert Schweitzer's station at Lambarene. The chimpanzees had an exemplary low sodium diet of bananas and various fruits (e.g. pineapples, papaya, mangoes) and vegetables (cabbage, lettuce, etc.). They received about 10–25 mmol of sodium and 200 mmol of potassium a day. All animals also received a protein supplement of Cerelac twice a day, providing liberal calcium. The colony was divided into age- and sex-matched halves, with one half receiving progressive addition of salt to their Cerelac. The two groups had also been matched in terms of social compatibility with long association without conflict.

The experimental programme lasted over two and a half years. No significant change in blood pressure occurred with the control group. Addition of 5 g day-1 of salt (100 mmol of Na+) during 5 months caused a significant rise in systolic blood pressure of 12 mmHg. Thereupon the intake was increased progressively, and after 21 months, during which intake had been at 15 g day-1, blood pressure had increased by systolic 35 mmHg, diastolic 10 mmHg, and mean blood pressure by 15 mmHg (Denton et al. 1995). For comparison, the mean intake in Akita province in Northern Japan was 25 g day-1.

At this point, we terminated the addition of salt and by 20 weeks later the mean blood pressure of the experimental group had fallen to their control pre-salt level, and to that of the control group. Within the experimental group there were a few animals that did not show any rise of blood pressure with salt, somewhat akin to the human situation where some people are not reactive, as are others, to an increase of sodium in the diet. The publication of the chimp data attracted an editorial in Nature Medicine. The New York Times published a two page commentary stressing that it was a one-variable experiment which appeared to be decisive in the species closest to humans. In a human community the confusing effects of other variables such as smoking, stress, alcohol intake and steroid administration would cause controversy.

A second experiment evaluating smaller changes of sodium intake was carried out on the colony with additional collaboration with Intersalt investigator Professor Paul Elliot of Imperial College (Elliot et al. 2007). The Gabon chimpanzees were studied under the same conditions except that a component of their diet was biscuits, and it was contrived that blood pressures were compared with intakes of 75 mmol, 35 mmol and 120 mmol of sodium per day, a modest range considering the data from the Intersalt study on humans. Increasing sodium intake from 35 mmol day-1 to 120 mmol day-1 increased mean systolic blood pressure by 10.3 mmHg and diastolic by 7.6 mmHg after 9 months. Reduction of intake from 75 to 35 mmol day-1 reduced systolic blood pressure by 5.4 mmHg and diastolic by 3.4 mmHg after 7 months. The correlation of blood pressure with Na intake was highly significant (Elliot et al. 2007).

Two other scientists to join the Florey from the UK under the Block Grant during 1987–89 were Dr Robin McAllen from Bristol University and Dr Clive May from Sir Stanley Peart's Department of Medicine at St Mary's Hospital in London. Their outstanding studies in electrophysiology, and the sympathetic nervous system, in cardiac failure, have attracted international attention (Ramchandra et al. 2009).

The track record of Howard Florey Institute scientists

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References

By the late 1980s the postgraduate degrees awarded to scientists working in the Florey included 58 PhDs. Further, many senior Florey scientists have taught in the University departments, particularly Physiology, giving a wide ranging contribution to academic life. Dr Marelyn Wintour-Coghlan, who made pioneering studies on fluid control of the fetus, and Professor John Coghlan, Director of the Florey Institute 1990–1997, were both awarded DSc degrees by the University of Melbourne. Marelyn Wintour-Coghlan became Professor at Monash University and Professor Coghlan received the Dale Medal of the British Endocrine Society. Dr G. W. Boyd became the Professor of Medicine at the Medical School of the University of Tasmania, Dr Bruce Scoggins, who played a major role in the Florey hypertension studies, became Secretary of the Medical Research Council of New Zealand. Professor Judith Whitworth, who also worked in the blood pressure control programme, became Chairperson of the National Health and Medical Research Council Committee responsible for grants, and subsequently the Director of the John Curtin School of Medical Research at the Australian National University in Canberra. Dr John Funder, who was awarded both PhD and MD while at the Florey, became Director of the Baker Medical Research Institute in Melbourne. The election of the Founding Director of the Howard Florey Institute as one of the 18 Foreign Medical Members of the Royal Swedish Academy of Science in 1974, The Royal Society (London), the National Academy of Sciences of the USA, the American Academy of Arts and Sciences, the Academy of Science of the Institute of France, and the Royal College of Physicians (London), is indicative of favourable overseas evaluation of the experimental work.

This issue covers present work in the Institute, as well as over the past decade, and also recounts the change to the Florey Neuroscience Institutes, and the amalgamation of three Institutes and the Melbourne University under this title in the new Kenneth Myer Building. This account ceases here except for the necessity to record two changes from the status earlier set out. That is, the amalgamation of the Institutes resulted in the recent Board of the Florey Neuroscience Institutes deciding to repeal of the Act of Parliament rather than changing the Act to embody the three Institutes and the University's major position. The second change was that in his role as Secretary of the Medical Research Council, Professor Warwick Anderson succeeded, near the turn of the century, in abolishing the Institute Block Grant system. The reasons included the notion that these were not on a level playing field in funds allocation, the scientists in the Institutes having an advantage by virtue of the power of their very influential Boards – essentially that the system was elitist and a sheltered workshop. With the abolition of the system and the institute scientists having to apply for Project, Programs and Fellowship grants, the end result was that by 2–4 years in open competition, the Institutes were receiving 2–3 times the amount of Federal money as hitherto under the Block Grant system, a change inconsistent with the arguments used. The Block Grant system, with Institute Boards involving the participation and enthusiasm of persons of very high eminence and leadership in other fields now joining in the national medical research endeavour was a very great strength particularly internationally. As Sir Ian Potter, who has been the greatest philanthropist to scholarship in Australia, remarked ‘We want responsibility – not a University sherry party Committee’.

References

  1. Top of page
  2. The study of instinctive behaviour: instinct is a trinity neural organization
  3. The financial support of the research, and institutional organization
  4. Serendipity and the advent of Robert J. Kleberg of King Ranch Inc.
  5. Salt intake and the genesis of high blood pressure
  6. The track record of Howard Florey Institute scientists
  7. References
  • Denton DA (1982). The Hunger for Salt: An Anthropological, Physiological and Medical Analysis . Springer Verlag, Heidelberg .
  • Denton DA, Goding JR & Wright RD (1959). Control of adrenal secretion of electrolyte-active steroids. Br Med J II, 447456, 522–530.
  • Denton DA, Shade R, Zamarippa F, Egan G, Blair-West J, McKinley M, Lancaster J & Fox P (1999). Neuroimaging of genesis and satiation of thirst and an interoceptor driven theory of origins of primary consciousness. Proc Natl Acad Sci U S A 96, 53045309.
  • Denton DA, Weisinger RS, Mundy RI, Wickings EJ, Dixson A, Moisson P, Pingard AM, Shade R, Carey D, Ardaillou R, Paillard F, Chapman J, Thillet J & Michel JB (1995). The effect of increase of salt intake on blood pressure of chimpanzees. Nat Med 1, 10091016.
  • Elliot P, Walker LL, Little MP, Blair-West JR, Shade RE, Lee R, Roquet P, Leroy E, Jeunemaitre X, Ardaillou R, Paillard F, Meneton P & Denton DA (2007). Change in salt intake affects blood pressure of chimpanzees. Implications for human populations. Circulation 116, 15631568.
  • Hewat T (1990). The Florey: The Story of The Sheep Hilton . Collins/Angus and Robertson, Australia .
  • Hollis J, McKinley MJ, D'Souza M, Kampe J & Oldfield BJ (2008). The trajectory of sensory pathways from the lamina terminalis to the insular and cingulate cortex: a neuroanatomical framework for the generation of thirst. Am J Physiol Regul Integr Comp Physiol 294, R1390R1401.
  • McKinley MJ, Denton DA & Weisinger RS (1978). Sensors for antidiuresis and thirst – osmoreceptors or CSF sodium detectors. Brain Res 141, 89103.
  • Ramchandra R, Hood SG, Denton DA, Woods RL, McKinley MJ, McAllen RM & May CN (2009). Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure. Proc Natl Acad Sci U S A 106, 924928.
  • Weisinger RS, Considine P, Denton DA, McKinley MJ & Mouw D (1979). Rapid effect of change in cerebrospinal fluid sodium concentration on salt appetite. Nature 280, 490491.
  • Weisinger RS, Denton DA, McKinley MJ, Muller AF & Tarjan E (1985). Cerebrospinal fluid sodium concentration and salt appetite. Brain Res 326, 95105.