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Theodor Emil Kocher (1841-1917)

by Bertil Hamberger


Theodor Kocher was born in Berne, Switzerland in 1841. He finished his medical studies in 1865 and went into surgery, where he had teachers like Demme, Lycke, Billroth and Langenbeck. In 1872, only 31 years old he was appointed professor of Surgery and Head of the University Clinic in Berne. He held this position until retirement. He was one of the first surgeons to apply the aseptic principles of Lister. Kocher was very early scientifically active and published a large number of experimental and clinical work in various surgical fields. He had a particular interest in infections, especially how to prevent surgical infections. He made early and important contributions to the condition of osteomyelitis and its relation to chronic staphylococcus infection.

Contributions to General Surgery

Theodor Kocher made tremendous contributions to a wide variety of surgical fields including hernias, abdominal surgery from all parts of the gastro-intestinal tract as well as various orthopedic fields including hereditary malformations and fracture treatment. Also, new surgical areas were covered by Kocher who wrote scientific articles on traumatic epilepsy, brain damages and trepanation. In this field he cooperated with Harvey Cushing, particularly on the effects of increased intra-cranial pressure. A special contribution known to all surgeons today is Kocher's study of the mobilization of duodenum for exploration of the inferior caval vein and the head of the pancreas, today called the "Kocher mobilization". He published this study in 1902. His surgical textbook on procedures was published in many different languages including German, English, French, Spanish, Russian and Japanese. In this textbook he described the abdominal and orthopedic surgery with a general principle of atraumatic technique. There he also made a foundation for the new ideas of how to select surgical incisions.

One of Kocher's contributions was to report his statistics regularly. This has made it possible to follow the development of the results which improved so tremendously at the end of 19th century.

Prize Awarded Work

Theodor Kocher received the Nobel Prize in 1909 for his work on the physiology, pathology and surgery of the thyroid gland. In the years around 1850 thyroid surgery was performed on vital indications only. The mortality was often high, up to 40%. The reason for death was usually uncontrollable bleeding or infection. With this background a few European surgeons, including Kocher and Billroth, started to improve surgery and report their results. In 1883 Kocher's mortality was 13%.

Also, at this time other complications were recognized, particularly damage to the recurrent laryngeal nerve, causing hoarseness. It was soon known that it was important to preserve this nerve. The complications of tetany and hypoparathyrodism were not understood. However, Kocher in contrast to Billroth had a very neat and precise operating technique and worked in a relatively bloodless field. Probably because of this he had less problems with postoperative tetany. Also well-known to all thyroid surgeons is the "Kocher incision", a transverse, slightly curved incision about 2 cm above the sternoclavicular joints.

Kocher's studies on one of his patients, who was operated on in 1874, led to an early discovery. This eleven year old girl had a successful removal of her thyroid, but afterwards she became very tired, showed no signs of initiative and became cretinoid. She remained small and had an ugly and idiotic appearance in contrast to her sister.

The Kocher patient together with her sister before the operation. The patient was then taller than her little sister.
(From Kocher, T. Arch Klin Chir 29:254-337,1883)

Nine years after the operation she stopped growing and became cretinoid.
(From Kocher, T. Arch Klin Chir 29:254-337,1883)

This prompted Kocher to reinvestigate all his thyroid patients. Almost all of them, particularly the children, had evident symptoms of hypothyroidism which he named "Cachexia Strumipriva". However, at this time Kocher did not understand that this was due to the removal of the thyroid gland but ascribed it to tracheal injury. These data made Kocher decide not to remove the whole gland in his future patients. After description of the myxedema condition, transplantation and injection of extracts of thyroid tissue was tried. In 1892 also oral therapy was introduced.

The number of thyroid operations increased rapidly and 2,000 operations had been performed by Kocher in 1901. When he died in 1917 more than 7,000 thyroid operations had been done in his clinic; three quarters by himself. The mortality decreased steadily from 14% in 1884 to 2.4% in 1889 and 0.18% in 1898.

Concluding Remarks

Theodor Kocher was a world leader in the surgical revolution in the last third of the nineteenth century. His major discoveries were in the fields of physiology and pathology of the thyroid gland. The contributions of Theodor Kocher still today have a great impact on thyroid surgery.


Richard B. Welbourn: The history of endocrine surgery. Praegel, New York 1990.


by Lewis Wolpert


How responsible are scientists for science and its applications? In a recent issue of the journal Science the 1995 Nobel Peace Prize laureate, Sir Joseph Rotblat, proposes a Hippocratic oath for scientists. He is strongly opposed to the idea that science is neutral and that scientists are not to be blamed for its misapplication. Therefore, he proposes an oath, or pledge, initiated by the Pugwash Group in the United States (Science 286, 1475 1999). "I promise to work for a better world, where science and technology are used in socially responsible ways. I will not use my education for any purpose intended to harm human beings or the environment. Throughout my career, I will consider the ethical implications of my work before I take action. While the demands placed upon me might be great, I sign this declaration because I recognise that individual responsibility is the first step on the path to peace."

These are indeed noble aims to which all citizens should wish to subscribe, but it does present some severe difficulties in relation to science.

Contrary to Rotblat's view I claim that reliable scientific knowledge is morally and ethically neutral and ethics only enter when science is applied to making a product, for example genetically modified foods (Is science dangerous? Nature 398, 281). If genes are responsible for determining some of our behaviour, that is the way the world is - it is neither good nor bad. Knowledge can be used for both good and evil. Of course, scientists in their work have the responsibilities of all citizens to do no harm and be honest. Their additional responsiblity is to put their work and its possible applications in the public domain.

Rotblat does not want to distinguish between scientific knowledge and its application, but the very nature of science is that it is not possible to predict what will be discovered or how these discoveries could be applied. Cloning provides a nice example. The original studies related to cloning were largely the work of biologists in the 1960s. They were studying how frog embryos develop and wanted to find out if genes which are located in the cell nucleus were lost or permanently turned off as the embryo developed. This involved putting the nuclei of cells from later stages in development, including adult cells, back into an egg from which the nucleus had been removed to determine whether the genes in that nucleus would allow the egg to develop. Nuclei from some adult cells could allow the egg to develop and this showed that the genes were still capable of being expressed in the correct way. It was incidental to the experiment that the frog that developed was a clone of the animal from which the nucleus was obtained. The history of science is filled with such examples.

There are, indeed, few cases where scientists as a group have behaved immorally, the main example being the false claims of eugenics. In terms of the pledge, no scientist should ever work for the army or be involved in the defence industry. Should Western scientists have refused to be involved in the building of the atom bomb? That could have been their ethical stance. But imagine if the Germans then had built a bomb and then won the war. Would one then have praised the scientists for their lofty, moral position?

I do not believe that scientists, or any other group of experts, should have the right to take ethical decisions on their own that affect the lives of the public. Their ethical beliefs may not reflect the public view and that is why I have always argued that their responsibility is to put their knowledge, and its possible applications, in the public domain. As Robert Oppenheimer made clear in relation to the bomb, the duty of scientists is to understand how the world works; but how this knowledge is used ultimately lies in a democracy, with the people's elected representatives. Moreover, scientists rarely have power in relation to applications in science; this rests with those with the money, industry and government. The way scientific knowledge is used raises ethical issues for everyone involved, not just scientists.

Should ethical issues relating to the application of genetics for example, lead to stopping research in this field? The individual scientist cannot decide for a science like genetics is a collective activity with no single individual controlling the process of discovery. I regard it as ethically unacceptable and impractical to censor any aspect of trying to understand the nature of our world.

The Walter and Eliza Hall Institute

by Frank Fenner and Suzanne Cory


Medical Research in Australia in the Early 20th Century

Although politically independent since 1901, in the 1920s Australia was still culturally, scientifically and industrially a dependency of the United Kingdom. The total population then was some 7 million and there were three medical schools, in Sydney, Melbourne and Adelaide. The few professors in each were overwhelmed with teaching responsibilities, and medical research was essentially a part-time activity. All medical graduates who aspired to do more than general practice, whether as physicians or surgeons or, for a very few, to do research, went to England for further training. Some of the best stayed: Howard Florey, Grafton Elliot Smith, Hugh Cairns, and Neil Hamilton Fairley.


The Beginnings

The Walter and Eliza Hall Institute of Pathology and Medicine was founded in 1915 as a privately funded research institute associated with the Melbourne Hospital. Because of the First World War, it did not commence operations until 1920, with an English physician, Sydney Patterson, as Director, primarily as an adjunct to the pathological and bacteriological laboratories of the Melbourne Hospital. Having graduated in medicine at the University of Melbourne in 1922, Frank Macfarlane Burnet joined the staff in 1923 as pathological registrar, and became senior resident pathologist a few months later. In 1923 Patterson resigned to return to England, and in 1924 Charles Kellaway, a Melbourne graduate who had been working with Sir Henry Dale in London, arrived as the new Director.

C. H. Kellaway (on left), as new Director, being met in Melbourne by F. M. Burnet in 1924.


The Kellaway Years (1924-1944)(1,2)

In 1918 Kellaway was discharged from the Australian Army while in London, and went to work with Sir Henry Dale at the National Institute of Medical Research. Enthused by this experience, when appointed to be Director of the Hall Institute in 1923 he wished to establish a tradition of full-time research in the biomedical sciences in Australia. He set up three departments; physiology and pharmacology, of which he took charge, biochemistry, and bacteriology. He appointed Henry Holden, from the University of Cambridge, to head biochemistry and Burnet to head the bacteriology department. However, cognizant of the importance of overseas experience, in 1925 Kellaway sent Burnet to London to work at the Lister Institute, where he worked on bacteriophages until 1927, and secured a PhD degree.

Hamilton Fairley, already a man of standing in tropical medicine, was available and worked with Kellaway for two years on hydatid disease and snake venoms. Harold Dew, later long-time Professor of Surgery at the University of Sydney, collaborated in the study of hydatid disease. Then, in 1929, came the Great Depression, and finances did not resume an upward trend until 1933-34. Kellaway himself made important contributions to the pharmacology of venoms of snakes, spiders and mussels,(3). E.R. Trethewie, working with Kellaway, made pioneering discoveries of 'slow-reacting substances', later famous as leukotrienes. In 1937 Wilhelm Feldberg, already a famous pharmacologist, came via Hampstead as a refugee from Nazi Germany, but returned to London just before the outbreak of war. By 1939 the Institute had reached a peak of prosperity and productivity; by far the best medical research in Australia was being done there. Four of the small staff; Kellaway, Fairley, Feldberg and Burnet, were to become Fellows of the Royal Society. Since its establishment in 1915, the Institute had been housed in part of the old Melbourne Hospital, sharing with the clinical pathology department of the hospital three floors and a basement, without even a service lift. Now was the time to acquire new, custom-built laboratories, and the fact that the Melbourne Hospital was to move to new premises offered the opportunity, which Kellaway seized. The new building provided much better accommodation, with a floor each for each department, service rooms and an extensive basement for heavy equipment. Staff moved across in 1942.

The premises occupied by The Walter and Eliza Hall Institute of Medical Research in the Melbourne Hospital, 1923-1942. Laboratories of The Walter and Eliza Hall Institute in the new Royal Melbourne Hospital, 1942-1985.

The man who was to make the greatest contribution to the international stature of the Hall Institute, from that time until he retired in 1965, was Macfarlane Burnet. Returning to Melbourne in 1927, he concentrated on bacteriophage studies, making seminal discoveries in lysogeny and bacterial genetics. (4) However, in January 1928 there was a disaster in the country town of Bundaberg, in Queensland, when 18 of 21 children who had received injections of a toxin-antitoxin mixture became ill within the next twelve hours and 12 died. Kellaway was appointed Chairman of a Royal Commission to investigate the fatalities, and Burnet was given responsibility for the laboratory investigations. Having shown that Staphylococcus aureus could be isolated from the fluid in the bottle and lesions of survivors, Burnet commenced a study of staphylococcal alpha toxin and on staphylococcal bacteriophages. This event was significant in the history of the Hall Institute for two reasons. Firstly, the effective work of Kellaway and his staff on a matter of great public interest impressed the name of the Walter and Eliza Hall Institute and the significance of medical research on the Australian public. Secondly, almost as an aside to his study of the staphylococcal toxin, Burnet made observations of the antibody response of rabbits to injections of the toxoid. He observed the small and slow response to the first injection and the immediate and rapid rise in the antitoxin level after the second injection. He interpreted this as indicating that something was duplicating itself every twelve hours or so to produce the antibody. His paper on these results and their implications was rejected by the British journal to which it had been sent, and this, his first rejection, stimulated him to collect further information on the production of antibodies and publish all this data in an un-refereed Hall Institute monograph, The Production of Antibodies.(5) Data on the primary and secondary responses also figure prominently in the second edition; for Burnet this was overwhelming evidence that the then fashionable "instructive" hypothesis of antibody production could not be correct. It was in this second edition that he made theoretical observations on immunological tolerance for which he was to share the Nobel Prize with Peter Medawar in 1960.

Throughout his life Burnet felt a strong obligation to respond to local outbreaks of infectious diseases, especially if a viral etiology was suspected. In the 1920s and 1930s poliomyelitis epidemics were a recurring problem in Melbourne, and in 1931 Burnet isolated a strain of poliovirus from a case which he showed was serologically unrelated to the Flexner strain; this was the first indication that there was more than one serotype of poliovirus. He returned to the study of polioviruses in 1939, following a very severe outbreak of poliomyelitis in Australia. His major contributions then were to show that cynomolgus monkeys could be infected orally and that poliovirus could be recovered from pharyngeal tissue and the mesenteric lymph nodes. He also carried out one of his very few experiments using tissue culture, demonstrating that poliovirus would multiply in cultured human foetal intestinal and buccal tissues.

In 1932 Burnet travelled again to London, at the invitation of Sir Henry Dale, who had secured funds from the Rockefeller Foundation to develop laboratory studies on animal viruses. He joined C. H. Andrewes and his colleagues at the National Institute of Medical Research, but proceeded to work quite independently. His main effort was converting Goodpasture's method of growing vaccinia virus on the chorioallantoic membrane of the developing egg to provide a method of titration of viral infectivity and anti-viral antibodies, for several different viruses. By this time he had developed a pattern of publishing a long review article after he had published a number of research articles on a particular subject; he had done this for the bacteriophage work, for his speculations about the production of antibodies, and now for the use of the chick embryo in virus research.(6) Also, while at Mill Hill Laidlaw's comment "The ferrets are sneezing," which signalled the first isolation of influenza virus from a human case, made a deep impression. Influenza virus was to be the centre-piece of his experimental research for many years, from 1940 to 1957.

In 1934 Burnet came back to the Hall Institute. He rounded off his work on bacteriophages and continued to study the growth of different viruses on the chorioallantoic membrane. Following his principle of working on infectious diseases that had impinged on the Australian public and might have a viral etiology, he undertook studies on psittacosis and a novel disease that had been in Queensland abattoir workers, Q (for query) fever. The studies on psittacosis brought home to Burnet the importance of latent infections in diseases of vertebrates as well as in bacteria, in which he had long before recognized the nature of lysogeny. This work with psittacosis activated his interest in the ecology of infectious diseases, which he developed in his first semi-popular book Biological Aspects of Infectious Diseases,(7) written "from the point of view of a biologist as much interested in how the parasite species survives as in how the host resists it". Under a different title, it went through three further editions, was translated into German, Italian, Japanese and Spanish, and had a major impact on the thinking of many microbiologists and biochemists world wide.

Q fever had been recognized in 1935 as a typhoid-like disease of abattoir workers from which no bacteria could be cultivated, but which could be passed to guinea pigs. It was presumed to be due to a virus, and as Australia's only recognized virologist, material from guinea pigs was sent down to him.(8) On histological examination of tissues from an infected mouse he noticed a "vague herringbone pattern" which recalled what he had seen in psittacosis and had read about for rickettsiae, and using Castaneda's stain he had no doubt that the organism was a rickettsia. It was subsequently named Coxiella burnetii.

He made important contributions to two other viral diseases, herpes virus infections and ectromelia, showing that aphthous stomatitis in infants was often due to infection with herpes simplex virus and that the virus then went into a latent phase, recurrent facial herpes occurring later in life, in the presence of high titres of antibody. Then, after a colleague had shown that vaccinia virus produced a unique type of haemagglutination, Burnet went on to demonstrate that ectromelia virus showed the same type of haemagglutination and that ectromelia and vaccinia viruses were cross-protective in animals.

From about 1940 Burnet's main interest in virology was influenza virus.(9) He showed that influenza virus could be isolated from human cases by inoculation of throat washings into the amniotic sac, and a year later that virus isolated in this way could be quickly adapted to grow in the allantoic sac. This provided a method for large-scale production of virus for the manufacture of vaccines that is still in use. Exploration of the mechanism provided his first essay into influenza virus genetics, the demonstration that the "O-D change" which made possible growth in the allantoic sac was due to a mutation, a phenomenon that had not been demonstrated with animal viruses at that time.

With the onset of the Second World War Kellaway became scientific liaison officer on the staff of the Director General of the Australian Army Medical Service. As Assistant Director, Burnet now took on much of the administrative work of the Institute. Remembering the terrible scourge of influenza after the First World War, he decided that his war effort would be to develop a live virus vaccine. This got through what we would now call phase 1 and phase 2 trials, and he was set to carry out a trial on 20,000 troops when word came that the US Army was producing a killed virus vaccine. Further trials were abandoned. In 1944, as the end of the war approached, Kellaway accepted an invitation to become head of the research laboratories of Wellcome Foundation Ltd. in London. In the same year, Burnet made his first trip to the United States, to give the Dunham lectures at Harvard University. Before he left, Kellaway told him of his impending departure and said that he would strongly recommend that the Board should appoint him as Director, a position to which he was appointed later in 1944.


Burnet as Director of the Hall Institute, 1944-1965

F. M. Burnet in the laboratory in the early 1950's. He was experimenting on influenza virus genetics, using the developing hen's egg.

Burnet was greatly impressed by what he had seen at Harvard University, and set out to achieve something of that pattern in Melbourne. Conscious that "medical research" was seen by the public as something associated with curative medicine, his first innovation was a Clinical Research Unit, to which he appointed Ian Wood, a leading gastroenterologist. Then, seeing that modern science required larger teams than the two or three persons that had worked in various departments of the Hall Institute before the War, he decided to concentrate all laboratory work in the Institute on virology, and with the discovery of influenza virus haemagglutination in the United States in 1941, on influenza virus. Holden was deputed to set up new biophysical equipment, Alfred Gottschalk, a highly skilled yeast biochemist who had come as a refugee from Germany in 1939, was called on to unravel the enzymology of the "receptor-destroying factor", as neuraminidase was called, and in 1948 a young Sydney graduate in biochemistry, Gordon Ada, was appointed to back up the biochemists. Arising out of Burnet's discovery that ectromelia virus was closely related to vaccinia and smallpox viruses, Frank Fenner was appointed in 1947 to study the experimental epidemiology of ectromelia. He showed that it caused a rash in mice; these studies led much later to his involvement in the WHO smallpox eradication campaign and the award of the 1988 Japan Prize. Other appointments over the next few years included Gray Anderson, Eric French, Eric Saint, Donald McLean and Donald Metcalf; Stephen Fazekas came in 1947 as a refugee from Hungary. All were to become distinguished in various fields in Australia or overseas. Another feature that demonstrated the international stature that the Hall Institute had then attained was the number of overseas visitors who came as postdocs or on a sabbatical. Young men whose names were later known internationally included Bernard Briody and Carleton Gajdusek (who discovered kuru at this time, for which he was awarded the Nobel Prize in 1976) from the USA, and John Cairns, Alick Isaacs (whose early death deprived him of adequate recognition for the discovery of interferon), and Barrie Marmion from England.

Burnet's team unravelled the function of influenza virus neuraminidase and Ada demonstrated that the influenza virus genome was RNA, while Burnet himself concentrated on influenza virus genetics. After clarifying the mutational nature of the "O-D change," he demonstrated that when cells were mixedly infected with strains with different properties they recombined readily. Indeed, they recombined with such high frequency that other scientists, believing that what happened with bacteriophages must happen with all other viruses, did not believe it. Always ready to speculate, Burnet himself suggested that perhaps the genome of influenza virus "may fracture and the fragments replicate themselves independently". Some ten years later it was demonstrated that the influenza virus genome was indeed fragmented, and that high frequency recombination was indeed due to reassortment of these fragments. During this period he further consolidated his reputation as one of the world's greatest virologists by the publication of the first comprehensive book on animal viruses.(10)

Burnet was curiously conservative in not taking up tissue culture as a virological tool, and was hostile to the ideas of molecular biology. In 1957 he had published a short paper on the clonal selection theory of antibody production, later elaborated as a major book.(11) He felt that he had done as much as he could in virology, and he wanted to devote the last seven years of his life as Director to the implications of this theory, for which he had been groping ever since his first speculations about the significance of the secondary response in 1929, and he abruptly switched the focus of the Institute to immunology. A few years later his hunch that immunology would be a more "rewarding" field than virology was confirmed by the award of the 1960 Nobel Prize to him and Peter Medawar for the discovery of immunological tolerance, a discovery in immunology of minor importance compared with the clonal selection theory.

The diploma of the 1960 Nobel Prize in Physiology or Medicine for F. M. Burnet and P. B. Medawar.


Nossal's Term as Director, 1965-1996 (12)

F. M. Burnet with PhD student G. J. V. Nossal, who became Director of the Institute in 1965, at the age of 34.

Burnet stayed on for one year after his nominal age of retirement, to see a new floor erected to make more space, and when he retired he became President of the Australian Academy of Science for a four year term. His successor was his former student, Gustav Nossal. By this time, the Hall Institute was world famous and Burnet's contemporaries judged that Nossal would have a difficult task in matching Burnet's record. But Nossal's many skills were in tune with the new era of biomedical science. He possessed a formidable scientific intellect and a great appreciation of the power of new technologies. Coupled with his outgoing personality and a great gift for communication and public oratory, the stage was set for a dramatic expansion and diversification of the Institute.

In 1965, the Institute was almost entirely devoted to cellular immunology. This remained a central theme. Nossal continued his work on B cells and tolerance and brought back from England his outstanding Sydney University contemporary, Jacques Miller, to further explore the immunological significance of the thymus. Ian Mackay continued clinical research on autoimmunity initiated under Burnet. Don Metcalf, another contemporary from Sydney, was already making an international reputation in experimental haematology and this was brought into the mainstream of the Institute's research effort. The next decade saw several additional recruitments: Thomas Mandel initiated electron microscopy and, later, transplantation biology; Noel Warner established a strong base in immunogenetics; Ken Shortman succeeded Gordon Ada and established a new tradition in cell separation; Jerry Adams and Suzanne Cory introduced molecular biology, initially to investigate antibody production and later to study the origins of cancer; Graham Mitchell initiated a vigorous program in immunoparasitology, focussed on schistosomiasis, leishmaniasis and malaria. Later, Len Harrison, Mackay's successor, focussed the clinical group on diabetes.

Nossal realized that it was essential to broaden the funding base of the Institute, and succeeded exceedingly well in this endeavour. In 1965, 81 people worked at the Hall Institute and the recurrent expenditure was $A360,000; upon his retirement in 1996, the Hall Institute had a staff of about 320, and an annual budget of $A23 million. He also appreciated the need for state-of-the-art technology, and built up sophisticated centralized services: in mouse husbandry, mouse genetic modification, computer science, flow cytometry and protein analysis. In the early 1980s, Nossal and Sir Andrew Grimwade, then President of the Institute Board, successfully lobbied the State and Federal Governments to commit money for a new building, to be located on the northern boundary of the Royal Melbourne Hospital site. In 1985, the magnificent ultramodern Hall Institute comprising about 15,000 square metres was dedicated. It ushered in a new era of growth and increased visibility and allowed a marked expansion of the Institute's training function, with far more postgraduate students and postdoctoral fellows. The Institute's interface with clinical medicine at the Royal Melbourne Hospital was broadened with several joint appointments. The increased space also enabled the Institute to take part in the Cooperative Research Centre scheme, which was established to further collaborative connections between University departments, Government laboratories and industry. By 1996, the Hall Institute was the host institution for the CRC on Cellular Growth Factors, under the direction of Dr Nicos Nicola, and a partner in the CRC for Vaccine Development.

Present laboratories of The Walter and Eliza Hall Institute of Medical Research, occupied since 1985.

The intellectual accomplishments of the Nossal era were many and varied. Key contributions to cellular immunology included the discovery that T cells derived from the thymus 'helped' B cells to produce antibody, proof of the clonal selection theory, delineation of the earliest stages of T cell development in the thymus, and the nature of self-tolerance. The colony stimulating factors (CSFs), a new class of hormone-like growth factors which stimulate blood cell production were discovered, characterized and taken to the clinic---they have now been used to treat over 1.3 million cancer patients. A major effort was mounted to develop a malaria vaccine and the first clinical field trials are now imminent. The molecular basis of Burkitt's lymphoma was established and the oncogene responsible for initiating follicular lymphoma was shown to regulate programmed cell death (apoptosis). Very early stages of neuronal and heart development were clarified.

Over the thirty-one years of Nossal's directorship, the Institute went from strength to strength, still the pre-eminent medical research institute in Australia and one of the great medical research institutes of the world. In 1994 Nossal, a Fellow of the Royal Society and Foreign Associate of the US National Academy of Sciences and recipient of numerous prestigious international awards, became President of the Australian Academy of Sciences.

Nossal's successor as Director of the Walter and Eliza Hall Institute is Suzanne Cory, also a Fellow of the Australian Academy of Science and the Royal Society and a Foreign Associate of the US National Academy of Sciences. She is a distinguished molecular biologist, known particularly for her work on antibody genes and oncogenes. The major themes of the Institute remain in place, with an increased attention on genetic predisposition to disease and bioinformatics.


G. J. V. Nossal in 1994, when he became President of the Australian Academy of Science. Susanne Cory at the age of 54, when she became Director of the Walter and Eliza Hall Institute.




(1)Kellaway, C. H. (1928). The Walter and Eliza Hall Institute of Research in Pathology and Medicine. Medical Journal of Australia, 2, 702-708.

(2)Burnet, M. (1971). The Walter and Eliza Hall Institute 1915-1965. pp. 16-42. Melbourne University Press.

(3)Dale, H. H. (1953). Charles Halliley Kellaway. Obituary Notices of Fellows of the Royal Society, 8 (22), 503-521.

(4)Fenner, F. J. (1987). Frank Macfarlane Burnet 1899-1985. Biographical Memoirs of Fellows of the Royal Society. 33, 113-116. Stent, G. S. (1963). Molecular Biology of Bacterial Viruses. pp. 15-16. W. H. Freeman, San Francisco.

(5)Burnet, F. M. (1941). The Production of Antibodies: a Review and Theoretical Discussion. Monograph from The Walter and Eliza Hall Institute of Research in Pathology and Medicine, No 1. Macmillan, Melbourne. Burnet, F. M. and Fenner, F. (1949). The Production of Antibodies. 2nd edition. Macmillan, Melbourne.

(6)Burnet, F. M. (1936). The Use of the Developing Egg in Virus Research. Medical Research Council Special Report Series No. 220. His Majesty's Stationery Office, London.

(7)Burnet, F. M. (1940). Biological Aspects of Infectious Diseases. Cambridge University Press, Cambridge.

(8)Burnet, F. M. (1942). The rickettsial diseases in Australia. Medical Journal of Australia, 2, 129-134.

(9)Fenner, F. (1996). Burnet's contribution to influenza research. In Options for the Control of Influenza III. (L. E. Brown, A. W. Hampson, and R. G. Webster, eds.), pp. 3-13. Elsevier, Amsterdam.

(10)Burnet, F. M. (1955). The Principles of Animal Virology. Academic Press, New York.

(11)Burnet, M. (1957). A modification of Jerne's theory of antibody production using the concept of clonal selection. Australian Journal of Science. 20, 67-69. Burnet, M. (1957). Clonal Selection Theory of Acquired Immunity. Cambridge University Press, Cambridge.

(12)Nossal, G. J. V. (1985). The Walter and Eliza Hall Institute of Medical Research: 1915-1985. Medical Journal of Australia, 143, 153-157. Nossal, G. J. V. (1995). The Walter and Eliza Hall Institute of Medical Research 1965-1995: from basic research to clinical triumphs. Medical Journal of Australia, 163, 600-603.


Other sources of information about the Institute

Burnet, M. (1968). Changing Patterns. An Atypical Autobiography. Heinemann, Melbourne.

Burnet, M. (1971). "The Walter and Eliza Hall Institute 1915-1965." Melbourne University Press, Melbourne.

Sexton, C. (1991). The Seeds of Time: The Life of Sir Macfarlane Burnet. Oxford University Press, Oxford.

Marchalonis, J. J. (1994). Burnet and Nossal: the impact on immunology of the Walter and Eliza Hall Institute. Quarterly Review of Biology, 69, 53-67.

Wood, I. J. (1984). Discovery and Healing in Peace and War. Acton Graphic Arts, Hawthorne.

The Walter and Eliza Hall Institute of Medical Research. Annual Review 1978-79. Special Volume: A Tribute to Sir Macfarlane Burnet. A Lifetime of Creativity. Burnet at Eighty.



Photos were kindly provided by John Wilkins, Head of Communication Services, Walter and Eliza Hall Institute.

The Tinbergen Brothers

by Auke R. Leen


In 1969, Jan Tinbergen, aged 66, received the first Bank of Sweden Prize in Economic Sciences in Memory of Alfred Nobel, often mistakenly referred to as the "Nobel prize in economics." Jan shared the prize with Ragnar Frisch. Four years later, Jan's younger brother, Nikolaas (Nico), too, was awarded the Nobel Prize in Physiology or Medicine. Nico was 66 years old. He shared the prize with Karl von Frisch and Konrad Lorenz. What lucky coincidence! Or was it? What made it possible for these two siblings to win the prestigious prizes? Was it their genes or their educational and social upbringing? Which brings us to the classic tug-of-war between nature and nurture. Which has the strongest influence on a person's life, nature or nurture? A look at the brothers' family background as well as the educational and social environments in which they grew up, might throw light on these questions. We shall also take a look at their work, their groundbreaking ideas and the opposition to these ideas, and the uncanny way in which their lives seemed to duplicate each other.


Jan: Quiet Mathematician

Jan was born in April 12, 1903, the eldest of five children: four boys and a girl. Nico, the third child in the family, was born in April 15, 1907. The Tinbergen children grew up in a warm, open and intellectual atmosphere. Before her marriage, their mother, a spontaneous person, worked as a primary teacher. Their father, a real pater familias, always stressing the harmony of family life, studied medieval languages at Leiden University. Next to his occupation as high-school teacher, he also became an expert on medieval Dutch literature. The Tinbergen family lived in a house in The Hague, a town near the Dutch coast, where the parents often organized discussions with the children's teachers and classmates. The family regularly had outdoor drawing lessons together, went on bike rides or took long walks.

Jan was a quiet child with a strong interest in mathematics and the natural sciences. During high school, he joined a group of students who would meet after school to do experiments in a physics lab. He faithfully attended the weekly lectures, especially those on physics, organized by a learned society. Jan did not only develop in a purely intellectual way. World War I was brought closer to home when his mother gave assistance to war casualties. Children from war-torn Belgium received shelter in the Tinbergen home. The war had a great influence on Jan's negative attitude towards militarism. He would later refuse to join the compulsory Dutch military service.

In 1921, Jan graduated from high school with the highest honors. Right after graduation, he started his studies in mathematics and the natural sciences at the University of Leiden. To save on boarding expenses, he commuted by train during his first year. To spare his parents even more, he accelerated his studies by attending second year classes in advance. During his spare time, he gave math lessons to high school students. He donated the money he earned to the Dutch Red Cross to help in their relief efforts for the children of Russia, who were suffering from food shortage.

Soon after, Jan became the assistant of Paul Ehrenfest, professor in Theoretical Physics at the university. Later, Jan became a frequent visitor to the Ehrenfest home when he became the private tutor of Ehrenfest's son. He also took part in the discussions when Ehrenfest was visited by Einstein, Bohr, Heisenberg and Pauli. Notwithstanding what must have been such impressive visits with these famous physicists, Jan shifted his interest to economics on his second year. He explained his move by saying that he realized that self-interest was a major factor that steered his interest towards physics, instead of a genuine concern about his own usefulness in society. At the time, Jan and his future wife whom he met in high school, had decided to dedicate their lives to the goals of the Social Democratic Labor Party. Ehrenfest made a last ditch effort to bring Jan back to the field of physics by advising him to spend the summer of 1923 studying physics at Goettingen in Germany. To no avail. After a fruitless attempt to contact the local Socialist-Communist Student Club, Jan left within a few weeks of staying in Goettingen, overcome by homesickness. Ehrenfest was not totally averse to Jan's interest in economics. In fact, he was interested in the analogies that could be used in the study of both these fields. Jan's thesis entitled "Minimum Problems in Physics and Economics" was certainly parallel to this line of thinking. But in the end, Jan's concern for the causes of poverty made him switch from physics to economics.

Physicists at Leiden, 1924. From left to right: Dieke, Goudsmit, Tinbergen, Ehrenfest, Fermi, Kronig. Jan Tinbergen would later shift his interest to economics.
Photo: Chicago University Press


Nico: Outgoing Adventurer

Nico was the adventurer in the family. He liked sports such as running and playing hockey. Outdoor activities like camping appealed to him. He loved taking pictures of nature. He hated institutionalized activities such as going to school and taking piano lessons. He often missed his classes. Instead, he would wander to the nearby dunes. Except for gymnastics and drawing, in which he excelled, he had poor marks in all other subjects. His parents, however, were not too hard on him. When his report card showed poor marks, his father would eventually ask him if the poor grades were really necessary. And Nico knew what to do. Though it did gnaw on him that he just did what he liked most. In his later studies, he felt compelled to say that he was not merely indulging in his hobbies. With his overriding love for nature (save his youngest brother), Nico was aware that he was an exception to the family nature (norm) of serious study combined with left-liberal thinking. Just for the aesthetic pleasure of it, he could watch the activities of sticklebacks for hours on end. During his high school years, he joined a club that studied wildlife in its natural surroundings. Given his dislike for any formal education, he was still undecided what to do when he finished high school. Only later on in life did he follow his brother Jan's example by applying his research to social problems.

On the advice of Professor Ehrenfest, Jan's mentor and family friend of the Tinbergens, Nico went to the German coast of Königsberg in the company of the famous experimental biologist Thienmann, to watch the autumn migration of the wild moose. Back home, he decided to study biology at Leiden University. His studies, however, did not have much influence on his biological fieldwork. Still, he was primarily interested in watching and photographing the behavior of wildlife, for example, herring gulls. He saw all of this, more or less, as a sport. Only gradually did he develop a more scientific attitude towards bird watching. Which meant a painstakingly continuous observation of animals and an ingenious experimentation to check scientific hunches. This would become Nico's trademark. This was, however, not sufficient. The thesis he wrote, though an uncommon subject at that time, was only accepted after grave doubts. (Maybe because it was less than 30 pages long!) His thesis about the orientation of the digger wasp was more or less the result of a summer family holiday, during which he made the chance discovery of a nearby colony of digger wasps. The day after receiving his doctor's degree at the age of 25 (the same age that his brother got his doctor's degree a few years earlier), he married his high-school girl friend and fellow member of the youth nature club. Jan himself, got married years earlier to his high school sweetheart and fellow member of the socialist youth organization.


Introducing Econometrics

In the 1930s, Jan devised the first macro-economic model ever. In this model, the focus of economic analysis was no longer on the abstract relation between individual goods and prices. Instead, it was shifted to the concrete relationships between economic aggregates like total income, consumption and investment. His work involved the statistical observation of theoretically founded concepts, namely mathematical economics working with concrete numbers. He was later invited by the League of Nations to analyze the American economy in much the same way that he studied the Dutch economy. This resulted in his time-honored study of 1936, in which he introduced mathematics and statistics to test the different existing trade-cycle theories to the rest of the world. The study, among others, posed the question: is it overinvestment or underconsumption that causes depression? Or is it something else? A confrontation with the facts was necessary to find the answer. This was, however, not a common method in those days - empty theoretical boxes and measurements without theoretical basis characterized economic analysis then. Jan's model introduced econometrics, a synthesis between mathematics, economic theory and statistics. In this model, it is the task of economic theory to formulate hypotheses, which are in turn formed into mathematical relations that are subsequently tested by the use of statistical data.

For Jan, econometrics is essential in economic research, a vision that was, and still is, being contested. An analogy would best describe the issue. It is an acceptable truth that a city that can be reached by train can also be reached by foot. Applied to the study of economics, one will get the same results, whether using mathematics or plain language, but using the former is more efficient. The argument against Jan's model runs like this: suppose that using mathematics is the same as taking the night train. The train runs through territory that you cannot see in the dark and thus, you could end up in the wrong station. Translated into economics it means: You may not have looked at the real empirical meaning of each equation and would therefore arrive at the wrong conclusion. But then, counters Jan, suppose there is no day train?

In a Dutch paper in 1950, Jan posed the question: "Can economic theorems be proven without the use of mathematics?" Unlike in physics, economic causes cannot be separated and analyzed in real world experiments. Wages determine prices, prices determine quantities sold, quantities sold determine employment and employment determines wages. It is a shortcoming of our natural languages that these interdependencies cannot be discussed without the use of mathematics. At the end of the same paper he cited an examination in which students were made to solve mathematical problems by verbal logic, something that could have been easily done by using simple mathematics. For Jan a ridiculous situation, indeed, although it can be appreciated as a form of puzzle sport. He compared this situation to that in the world of business and politics and hoped that in the future there would be no need to solve economic problems in the style of the puzzle sport. One day, there would be enough trained econometricians in business and politics who would understand and appreciate its importance in economic analysis.

Jan Tinbergen
Photo: Jan Tinbergen Institute, Amsterdam


Criticism from John Maynard Keynes

Jan met the hardest criticism from the man who started the macroeconomic revolution in economics - John Maynard Keynes. Keynes was opposed to the method of multiple correlation which Jan used in trying to quantify the relative importance of the different elements that caused a business cycle. He thought that the method was merely "hocus pocus" since it did not contain all the variables, especially those that cannot be measured, for instance social, psychological, and political factors. And how about expectations and the role they play in making investments? Tinbergen maintained that a residual variable that would touch on the other influences would address this question, and expectations can always be based on the past and thus be extrapolated. Wittily, Keynes asked for an experiment. He remembered that the seventy translators of the Septuagint were shut up in separate rooms with the same Hebrew text and came out with seventy identical translations. What is the chance, he asked, that the same miracle would be vouchsafed when seventy multiple correlators are similarly shut up with the same statistical material? Keynes considered Jan's method as weak since the materials and relations described in the model were non-quantifiable, variable and non-homogenous. It was a model of thinking that lost is use as soon as one tried to give it an empirical content. A critique echoed in those days by the so-called modern Austrians, of whom Tinbergen's contemporary Hayek, was an early exponent. Notwithstanding, Tinbergen held Hayek, who was director of the Austrian Business Cycle Institute, in high esteem.

In his Prize Lecture, Jan Tinbergen admitted as much that Keynes may have been right in that he never succeeded in predicting the fluctuations in business investments. After the war, Jan's interest changed to developmental economics. He became more interested in the structure of the world economy itself and not in its fluctuations.

Keynes' last comment on Jan's method, just before World War II, brooked no further discussion. He said that notwithstanding the high opinion he had of Jan as a person, he was still not persuaded that his "statistical alchemy" was ripe enough to become a branch of science. "But," he continued, "Newton, Boyle and Locke all played with alchemy. So let him continue."

To get an idea of the awarded work of Jan Tinbergen, the lively correspondence between Keynes and Tinbergen is a stimulating way to start. See Collected Writings of John Maynard Keynes. Volume XIV. Macmillan, Cambridge, 1973. For a recent book of this most important period in economics see Albert Jolink, Jan Tinbergen: The Statistical Turn in Economics: 1903-1955, Chimes, Rotterdam, 2003.


Nikolaas Tinbergen vs Colleagues in the Medical Profession

Criticism to Jan's work happened at an early stage of his career. The opposite happened to Nico - the work that got him the Nobel Prize went uncontested; the clash with his colleagues came later. By the time Jan held his Prize Lecture, econometrics was firmly accepted in mainstream economics and today, it is still accepted all over the world as a universal benchmark to check the results of different economic policies, debunking Keynes earlier prediction. But the things Nico said in his Nobel Prize Lecture made him almost the laughing-stock of the medical profession. In his lecture, Nico took up the issue of autism, i.e a child's inability to relate to people and situations in a normal way starting from infancy. He maintained that it was possible to restore an autistic child to normalcy by establishing a secure mother-child bond; thereby suggesting that the cause of early childhood autism is due to the failure of the mother and child to establish or maintain a normal bond.

This, however, was not the kind of research that got him the Nobel Prize. He got it for his work in reviving and developing the biological science of animal behavior: ethology. His first work looked at the landmark orientation of homing wasps. He showed the importance of visual cues that enable the female wasps, despite the many different nests they build, to return to the correct one.

What made Nico really famous is his demonstration of the "hawk/goose effect." His work explained the behavior of chicks to defend itself from danger: when a goose flies overhead the chick will show no response but if it is a hawk it crouches as if to fend itself from danger. This response was initially thought to be an inborn ability but it is now proven to be learned. The relation between his earlier work and his later theory on autism is obvious. To say that autistic children are "ineducable" and remain dependent all their lives reveals a lack of knowledge about the problem according to Nico, since we still do not have any idea of the causes of autism. What we do have is a mass of disconnected information in search of a theory. All negative predictions about the future are, in reality, no more than statements about the failures of past attempts. According to him, the opinion of experts cannot be trusted since they cannot look into the future. And, he continued, was it not equally the case that until the causes of cholera, smallpox and many other illnesses were discovered, they were considered incurable too?

The strong point in Nico's ethology-based research on "human animals" echoes his earlier work on ethology: a painstaking and continuous observation of animals and humans in their natural habitat. Zoos and natural history museums had always bored him. Much like parents or persons involved in the day-to-day care and education of autistic children, ethologists have always studied children in their home environment. No wonder it is the first group that supports him most. Nico presented a plausible hypothesis and the design of a promising therapy. To him, adaptedness is fundamental and autism is the result of an emotional imbalance. Contrary to mainstream idea, it is not a result of a disorder in the working of neurotransmitters. Neither is it genetic.

Of the works of Nikolaas Tinbergen, the following books can be recommended: The Study of Instinct, Clarendon Press, Oxford, 1951 and (together with his wife) Autistic Children. New Hope for a Cure, George Allen & Unwin, London, 1983. The first book was a remarkable success. It made continental ethology known all over the world. It is clearly written and is a handbook to do ethological behavior research. The book on autism gives the "animal" ethological base to be used for "human" ethology. For a recent biography of Nico Tinbergen see: Nico's Nature: The Life of Nico Tinbergen and his Science of Animal Behaviour, Hans Kruuk, Oxford University Press, 2004.



In the introduction we posed the question: nature or nurture? Two brothers with different natures seem to duplicate each other's fate. The adventurous Nico did not have his brother Jan's quiet nature and love for study. Still, both were rewarded for their individual efforts, arrived at through different methods. They did share several factors: genes and family upbringing that encouraged intellectual curiosity and independent thinking. And they certainly got the same encouragement from their family to do what they liked best, and to do it well. Well enough to be given the highest accolade one can get for their respective fields. No matter what the critics may say.

August Krogh and the Nobel Prize to Banting and Macleod

by Jan Lindsten



August Krogh became an internationally well known biomedical scientist during the first decade of the 20th century. A series of works published in 1910 ("the seven little devils") attracted special attention because he could demonstrate that "the absorption of oxygen and elimination of carbon dioxide in the lungs take place by diffusion and by diffusion alone. There is no trustworthy evidence of any regulation of this process on the part of the organism." He thereby corrected his master, professor, Christian Bohr and created a conflict with him that was never resolved. Krogh’s original works on "the capillary motor regulating mechanism" for which he was awarded the Nobel Prize in Physiology or Medicine in 1920 were, however, not published until 1918 (in Danish) and 1919 (in English).

Having obtained this prestigious distinction, August Krogh was invited to the U.S.A. in 1922. His wife Marie, who, probably in 1921, had been found to have maturity onset diabetes, joined him on the trip. At a private dinner, Marie Krogh was told by the renowned American diabetologist Eliot P. Joslin that insulin had just been discovered and purified in Toronto. August and Marie Krogh therefore extended their journey and spent the November 23-25 in Toronto as John Macleod’s guests.

During his stay in Toronto, Krogh obtained a license which allowed him to use the protocol for insulin purification developed there. Production was started immediately upon his return to Copenhagen on December 12. The first patient was treated as early as March 13, 1923. Together with the Danish physician H. C. Hagedorn, Krogh then founded the Nordic Insulin Laboratory and the Novo Nordisk Fund (formally approved by the authorities in 1927). This became the starting point of a very successful Danish pharmaceutical company and a research fund, which today constitute the company Novo Nordisk and the Novo Nordisk Fund, respectively. However, soon thereafter Krogh left the business so he could concentrate on his scientific work. Marie Krogh’s diabetes was successfully treated with insulin, and when she died of breast cancer in 1943 none of their four children were aware that she had, in fact, also suffered from diabetes.


The 1923 Nobel Prize

The Nobel Prize in Physiology or Medicine in 1923 for the discovery of insulin was divided between Frederick G. Banting and John J. R. Macleod. The choice of this combination of Laureates has been much debated ever since the prize was awarded. Thus, for instance Banting shared his part of the prize amount with his younger coworker Charles Best.

It is very unusual for someone to receive the Nobel Prize in Physiology or Medicine the same year as he or she is nominated for the first time. However, as can be seen from the archive material of the prize awarding institution (The Nobel Assembly at Karolinska Institutet in Stockholm) this was true for both Banting and Macleod. They published their work on the discovery of insulin in 1922 and were nominated for the first time in 1923: Banting by G. W. Crile (Cleveland), F. G. Benedict (Boston) and August Krogh; and Macleod by G. N. Stuart (Cleveland) and August Krogh. Charles Best, on the other hand, was never nominated at this time (only nominated candidates can be considered for the prize).

In his nomination, August Krogh summarized his reasons for proposing Banting and Macleod in the following way: "With the information which I personally have obtained in Toronto, and which also, although less clearly so, emerges from the published works, one may conclude that the credit for the idea behind the work which led to the discovery, undoubtedly goes to Banting, who is a young and apparently very talented man. However, he would definitely not have been able to carry out the investigations, which from the start and during all stages, have been supervised by Professor Macleod."

Written evaluations of Banting’s and Macleod’s scientific contributions were provided by two members of the Nobel Committee, John Sjöqvist (professor of chemistry and pharmacy) and Hans Christian Jacobaeus (professor of internal medicine). Sjöqvist arrived at the same conclusion as August Krogh, i.e. that the prize should be divided between Banting and Macleod.

Jacobaeus, on the other hand, found it more difficult to decide who should be awarded and wrote: "Dr. Banting, who undoubtedly was the first to have the idea and who has carried out the investigations, should be the one who in the first place is awarded the prize. On the other hand, it is difficult to evaluate Macleod’s contribution. It is not apparent from the literature. Macleod, who is the head of the department in Toronto, has previously carried out investigations on blood sugar. Banting came to Macleod with his idea and purified insulin under the direction of Macleod. I have been told that it is very likely, that the discovery would never have been made if Macleod had not guided him, at least not as early as it turned out. It has even been declared that Banting planned experiments that would not have been successful unless corrected by Macleod. On the basis of what has been said I am most inclined that Banting and Macleod jointly receive the Nobel Prize."

Professor Göran Liljestrand was the secretary of the Nobel Committee during the years 1918-1960. He was a great friend of August Krogh and had been in close contact with him since his time as a visiting scientist in Copenhagen. It is therefore of interest to study the correspondence between Liljestrand and Krogh, which today is included in the archives of the Royal Swedish Academy of Sciences. In this correspondence, the Nobel Prize for the discovery of insulin is only mentioned on two occasions and very briefly.

  • Letter from August Krogh to Göran Liljestrand dated January 20, 1923. "As you understand from my discourse it is my opinion that the discovery of insulin is of extraordinary both theoretical and practical importance and it will hardly surprise you that I intend to submit a nomination that the Nobel Prize be awarded to Dr. Banting and Professor Macleod."

Part of the second page of a four-page letter from August Krogh to Göran Liljestrand dated January 20, 1923. "Du vil se af foredraget at jeg anser insulinets opdagelse for at vaere af ganske overordentlig baade teoretisk og praktisk betydning og det vil naeppe overraske Dig at jeg agter at indsende forslag om at Nobelprisen tildeles Dr Banting og Prof Macleod i forening." For translation from Danish into English, see text above.

  • Letter from August Krogh to Göran Liljestrand dated February 4, 1924. "I understand that the prize to Banting and Macleod ignoring other coworkers has not been met with absolute consent on the other side of the Atlantic Ocean and that especially Banting is offended by the fact that Best was not included. However, I am convinced that the correct choice was made."

  • Thus, it seems reasonable to assume that Krogh’s nomination had some impact on the awarding of the prize to Banting and Macleod. After all he was a Nobel Laureate and had, in addition, personal knowledge of the situation in Toronto.


As already mentioned the Nobel Prize to Banting and Macleod has been questioned ever since it was announced. Why was Macleod included, and why was not only Charles Best but also James Collip excluded? Bliss (1982) arrived at the conclusion that the choice made was the best possible. Others are of the opinion that Nicolas C. Paulescu, Joseph von Mering and Oskar Minkowski would have been as worthy, perhaps worthier, Laureates for this prize (e.g. Luft, 1971).

Some additional information that might shed some light on the situation can be obtained from the Nobel Archives. Thus, Paulescu was never nominated; Collip and Best were nominated but not until 1928 and 1950, respectively; von Mering was nominated but only in 1902 and 1906; while Minkowski was nominated in 1902, 1906, 1912 and 1914 as well as in 1924 and 1925. Thus, according to the statutes of the Nobel Foundation, none of these candidates could have received the prize in 1923.

So perhaps "the choice made was the best possible." Or would it have been wiser if the Nobel Committee at that time had explored the situation in greater depth rather than proposing to the Medical Faculty of Karolinska Institutet (the decision-making body) that Banting and Macleod be awarded the prize at such an early stage after their discovery?



The author gratefully acknowledges the Center for History of Science at the Royal Swedish Academy of Sciences and the Nobel Assembly at Karolinska Institutet for allowing me to study and reproduce the correspondence between August Krogh and Göran Liljestrand and to use the archive material related to the present topic, respectively.


Bliss, M: The Discovery of Insulin. McClelland and Stewart, Toronto, University of Toronto Press, 2000 (originally published in 1982).

Lindsten, J: Schack August Stenberg Krogh – a versatile genius. Nobel e-Museum, 2001.

Luft, R, Vem upptäckte insulinet? Läkartidningen 1971, 68, 4997-5004.