Teachers Notes - Professor Henry Burger

Professor Henry Burger

Endocrinologist

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Introduction

Professor Henry Burger was interviewed in 2010 for the Interviews with Australian scientists series. By viewing the interviews in this series, or reading the transcripts and extracts, your students can begin to appreciate Australia's contribution to the growth of scientific knowledge and view science as a human endeavour. These interviews specifically tie into the Australian Curriculum sub-strand ‘Nature and development of science’.

The following summary of Burger’s career sets the context for the extract chosen for these teachers’ notes. The extract discusses the radioimmunoassay technique, which Burger used to measure growth hormone levels. Use the focus questions that accompany the extract to promote discussion among your students.

Summary of career

Henry George Burger was born in Vienna, Austria in 1933. Burger completed his secondary schooling at Xavier College in 1950. He then began his compulsory National Service in 1951 before beginning a medical degree. Burger graduated with an MBBS from the University of Melbourne (1956), winning eleven of the twelve prizes on offer. After graduation, Burger worked as a resident medical officer (1957-58) and then registrar (1959) at St Vincent’s Hospital. In 1960 he completed a Doctor of Medicine at the University of Melbourne. He then went to the Diabetic and Metabolic Unit at the Alfred Hospital as a research fellow (1960-61).

In 1961, Burger was awarded a Nuffield Dominion travelling fellowship to the Middlesex Hospital in the UK. While in the UK, he worked on measuring testosterone in various disorders in women. Burger then moved to the USA to take up a United State Public Health Service International postdoctoral fellowship at the National Institutes of Health in Bethesda, Maryland (1962-65). During this time his research focused on the biochemistry of bovine growth hormone. Burger returned to Australia in 1965 as associate director of the Prince Henry’s Hospital Medical Research Centre (1965-69). He was then promoted to executive director (1969-72) and director (1972-90) of the Medical Research Centre and the Department of Endocrinology and Diabetes at Prince Henry’s Hospital. He also worked concurrently as senior lecturer at Monash University (1965-78). Prince Henry’s became an Institute in 1990 and Burger continued as its director until 1992. He remained as unit head and director of Endocrinology at Prince Henry’s Institute until his retirement in 1998, but has continued in endocrine practice since then.

Professor Burger has received numerous honours throughout his career. Some of these include; Eric Susman Prize from the Royal Australasian College of Physicians (1975), Annual Prize for Endocrine Research from the Endocrine Society of Australia and the New Zealand Society of Endocrinology (1978), Officer of the Order of Australia (1993), Dale Medal of the Society for Endocrinology (1997), Distinguished Physician Award of the US Endocrine Society (1999), honorary doctorate from the University of Liege (1999), Perimenopause Research Award from the North American Menopause Society (2000), Centenary Medal (2003) and Androgen Research Award (2006). Burger was elected to fellowship of the Australian Academy of Science in 1994.

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Extract from interview

Protein hormones by radioimmunoassay

Bryan was immensely helpful in suggesting to me that the future of research in endocrinology would be in the protein hormone field, not in steroid hormones. He had been an expert in measuring testosterone, but he was also interested in other aspects of steroid endocrinology. But he said, ‘The future is in protein hormones.’ I had originally planned to go and work with the late Dr Fred Bartter, who was an eminent American steroid endocrinologist in the aldosterone field, and I had to make very last-minute arrangements not to go and work in his laboratory but to go and be trained in protein hormones. I had a US Public Health Service International Postdoctoral Fellowship, so when we went from London to the States, I went to work in a protein hormone laboratory rather than the steroid hormone laboratory.

That was a very critical decision, wasn’t it?

It was a hugely important decision and Bryan gave me absolutely the right advice. I went to work at the National Institutes of Health, and the advice to do protein hormones and protein chemistry was very important advice. It also gave me the opportunity to learn the relatively new technique of radio immunoassay. Radio immunoassay was a technique developed in order to be able to measure the very tiny circulating concentrations of protein hormones. It was subsequently applied to other molecules circulating in very low concentrations. But the initial developments were particularly for insulin – a protein hormone.

The radioimmunoassay technique relied for its sensitivity on the employment of a radioactive label which allowed detection of very small amounts of radioactivity. Its specificity was conveyed by the immuno part – namely, the use of an antibody to the hormone of interest. You had to have specificity to be able to measure a protein in amongst thousands of other proteins. One of the big advances was a technique of labelling protein hormones without destroying their tertiary structure, usually with radioactive iodine – a technique what was introduced by two Englishmen called Hunter and Greenwood. One was able to label a purified form of the hormone with radioactivity, purify it so that you just had the labelled hormone and then incubate the hormone with a limiting concentration of a specific and high-affinity antibody. You then added known amounts of unlabelled hormone to construct a standard curve where the unlabelled hormone would displace the radioactivity from the antibody. After that incubation, you separated the radioactively bound hormone from the free or unbound, which had been displaced. By measuring the ratio between bound and free as a function of the addition of increasing quantities of the unlabelled hormone, you constructed a standard curve. You then incubated a serum specimen, read the bound-to-free ratio and worked out what concentration of unlabelled hormone that was equivalent to.

A new Medical Research Centre with plenty of talent

Once we had that solved, we ran the immunoassay very heavily and received samples from many different laboratories because it was the first immunoassay for growth hormone in Australia. I fairly quickly established a collaboration with the late Norman Wettenhall. He was a paediatric endocrinologist and there were very few in the world at that time. He had a big population of children with short stature and the assay technique enabled us to determine who was truly growth hormone deficient, and therefore who might be expected to benefit from therapeutic growth hormone preparations. These preparations were just starting to become available at that time, particularly through the offices of Kevin Catt, one of my colleagues at Prince Henry’s. Kevin was a skilled protein chemist/clinician scientist. With his efforts and those of a few others, we started to develop growth hormone for therapeutic use, and the assay clearly provided a way of making an appropriate diagnosis in those short children. Growth hormone therapy for them was a huge boon and produced some quite spectacular improvements in their growth velocity and final height.

See the transcript of the full interview.

Focus questions

  • What is endocrinology?
     
  • Which part of the radioimmunoassay technique provided the specificity and which part provided the sensitivity? What is the different between specificity and sensitivity?
     
  • Four different hormones are mentioned in the extract: testosterone, aldosterone, insulin and growth hormone. Which of these four are steroid hormones and which are protein hormones? Extension activity: Draw the molecular structure of testosterone and aldesterone and print out a picture of the crystal structure of insulin and growth hormone.

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Activities

Select activities that are most appropriate for your lesson plan or add your own. These activities align with the Australian Curriculum strand ‘Science Inquiry Skills’ and the New South Wales syllabus Stage 5 Science outcomes 5.8.4 and Stage 6 Biology outcome 9.6.6. You can also encourage students to identify key issues in the preceding extract and devise their own questions or topics for discussion.

  • Professor Burger is an endocrinologist who has spent his career studying how hormones control our biology. Divide students into small groups of two or three and assign them a particular hormone to research. Using library and internet resources ark students to prepare a poster on their allocated hormone, with emphasis on a pictorial rather than a text-based presentation of their research. The poster should include the hormone structure, its synthesis, regulation and transport, the effect of the hormone on the body and an example of a disease that results when the hormone is under or over produced.
  • Body System Communication (State Government Victoria, Department of Education and Early Childhood Development, Australia) This excellent resource for teachers of year 10 students includes pedagogy of endocrinology, teaching activities, further resources and links to Concept Development Maps for this topic.
  • Investigating the Human Body: The hormonal system (Museum Victoria, Australia)
    This resource was developed for year 9-12 students visiting The Human Body exhibition at Museum Victoria. However, the student activity sheets could be used in the classroom using a text book to find the answers. Pages 143-144 of this pdf deals with the endocrine system.
  • Those Powerful Hormones (Ann Nelson, the Educator’s Reference Desk, USA)
    This three-lesson course, aimed at students in year 10, includes suggestions for lectures, student activities, questions and answers, homework and assessment. The course covers endocrine anatomy, exocrine vs endocrine glands, function of the endocrine glands, feedback mechanisms and hormone receptors.
  • In the extract, Burger talks about treating children of short stature with growth hormone. Students may already be familiar with growth hormones as they have made headlines for decades. Using internet and library resources ask students to investigate a growth hormone news topic, e.g. growth hormone extracted from human brains leads to Creutzfeldt-Jakob disease, the use of human growth hormone by athletes, effects on humans of bovine growth hormone in cow’s milk and meat, etc. Students should prepare an essay which answers the following, what is the controversy? what is the scientific evidence? how has government or industry responded to the issue? was the response reasonable in light of the scientific evidence? Encourage students to use primary sources for their research, not just sensationalised media, and include a reference list or bibliography.
  • Roslyn Yalow won the Nobel Prize for Medicine in 1977 for her work, with Solomon Berson, in developing the radioimmunoassay. This technique was then applied by Professor Burger to growth hormone. Ask students to read the press release from the Karolinska Institutet, the journal article by Rosalyn Yalow (in particular noting Figure 5) and the webpage on Radioimmunoassay (RIA) from Kimball’s Biology Pages. Ask students to write a paragraph on the impact of this technique to medical science. Also, to describe radioimmunoassay in their own words. Extension activity: research the next-generation high sensitivity/specificity assays currently being used and developed, e.g. ELISA.

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Keywords

antibody
growth hormone
hormone
protein
radioactive
radioimmunoassay
specificity
sensitivity
standard curve
steroid

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