The St. Vincent’s School of Medical Research (renamed St Vincent’s Institute in 1984) was established as a result of a generous bequest from racehorse trainer, Jack Holt.
Holt’s life had been devoted to racing, where he achieved great success and distinction as a trainer and a judge of quality thoroughbreds. Holt lived his entire life together with his two sisters, Margaret and Catherine in a small 8-roomed cottage that he had constructed in Mordialloc. While his business acumen and skill as a trainer led to the development of a rather large fortune, above all Holt was known for his good humour and generosity. The death of his beloved sister Catherine in 1945 provoked him to bequeath the majority of his considerable assets to found a school of medical research at St Vincent’s Hospital, Melbourne. Upon Holt’s death in 1951, the St Vincent’s School of Medical Research was established under the control of the Sisters of Charity at St Vincent’s Hospital.
A Swede, Pehr Edman was appointed the first director of St Vincent’s School of Medical Research after a world-wide search. Edman took up his appointment in May, 1957, with the title of John Holt Director of Research, and the School was officially opened on April 23, 1958.
Edman’s research interest was the structure of proteins. Proteins are essential for life – they are needed to make new cells; to build muscle; to act as messengers; and to support the immune system – virtually every action performed in the body is dependent upon them. Proteins are made up of chains of amino acids, of which there are twenty different kinds. Each protein has a different number and order of amino acids in its chain. Just as different combinations of the 26 letters of the alphabet can make a huge variety of different words, so too do the 20 amino acids make up a hugely diverse range of proteins.
In 1950 Edman had published a method that allowed the order of amino acids in a protein to be determined. Using his method, the last amino acid in a protein chain was tagged with a chemical, allowing it to be removed from the chain and identified without disrupting the order of the rest of the amino acid chain. This is a bit like recognizing a word after having it spelled out to you. When the ‘letters’ were assembled at the end of the reaction, they spelled out the protein sequence.
Edman spent his early years at the St. Vincent’s School of Medical Research designing and producing a machine that automated protein sequencing. In 1958 RMIT graduate Geoffrey Begg was employed as a junior laboratory assistant to Edman and became intimately involved in the project. Describing how the idea came to fruition, Begg said, “I was sitting having a cup of tea with some of the research blokes one day, just after I’d joined in 1958, and we were talking about how repetitive their analysis work was…I asked them why they didn’t invent a machine to speed up all the repetitive work. I was only a laboratory assistant and they all laughed, so I forgot about it. But apparently Dr Edman had been thinking about the same thing. He heard about this and asked me if I could make a model of a possible machine.” The next day, Begg brought an electric motor from home and aided by his glass blowing skills, showed that the idea was feasible. Begg spent much of the following year working on the machine, which came to be known as ‘Matilda’.
‘Matilda’ took nearly 6 years to perfect, and pushed the mens’ ingenuity to the limit: more than once they had to produce parts in the Institute workshop, having discovered that no manufacturer in the world would make the part to the necessary specifications. A description of the automated method and the machine, renamed more prosaically ‘The Sequenator’, was published by Edman and Begg in 1968. Edman refused to patent the invention, believing that the scientific world should be able to benefit from it without charge. Beckman Instruments in Palo Alto (California) subsequently developed a commercial version, which became widely used in laboratories in America and Europe.
While maintaining the international reputation of the Institute in the area of protein purification and sequencing, after being appointed Director in 1973, Frank Morgan made the notably valuable decision to extend the research activities of the Institute by establishing the first protein crystallographic laboratory for the three-dimensional study of protein molecules in Australia (outside of CSIRO).
If you’ve ever wandered the back corridors of the Institute, you might have come across a rather beautiful but somewhat dusty installation of Perspex and wire. It represents the architecture of the first protein structure ‘solved’ at SVI – a protein called lysozyme from the egg of an Australian black swan. In 1978, Neil Isaacs, who went on to become the Joseph Black Professor of Chemistry at the University of Glasgow, was lured to SVI by Frank Morgan to establish a protein crystallography laboratory. The process had been developed overseas some years before, and gave researchers the ability to work out the 3-dimensional structure of a protein, which allows biological processes to be seen at their most fundamental level.
Today, these structures help us develop ‘smart drugs’ that are specifically designed to interact with a particular disease-causing protein. Remarkably, in 1978, Isaacs and his team gathered much of the information on the structure of the black swan lysozyme from a low-power X-ray generator and a single camera.
Using the basic tools and primitive computing facilities available at the time, Isaacs and an assistant spent an entire summer painstakingly reconstructing their discovery by hand; today it sits in wire and Perspex in the halls of the Institute.
From this hand-fashioned beginning, the protein crystallography effort at St Vincent’s Institute, now under the leadership of Deputy Director Professor Michael Parker, has gone on to solve more crystal structures than the efforts of all the other labs in Australian medical research institutes combined.
From the time that Jack Martin joined SVI as Director in 1988, the strength of the Institute in cancer and bone research steadily increased. Particular contributions were made by SVI scientists towards understanding how the cells of the immune system contribute to the formation and activity of bone-dissolving cells, and how locally generated growth factors and other molecules can influence bone structure. All of this work is relevant to the prevention and treatment of osteoporosis.
SVI’s work on skeletal complications of cancer has been important in establishing what is now a major interest in this area – that the bone microenvironment profoundly influences the ability of cancers to establish and grow in bone as secondary deposits. This came from SVI work showing that cancer cells, in order to be able to establish in bone, needed to be able to control its growth and breakdown. These are now key concepts in thinking about this common complication of cancer, and how it can be prevented and treated.
In these years SVI also became known for its studies of protein kinases, the enzymes in the body that change protein function through the addition of phosphate groups. The Institute’s Protein Chemistry Unit, headed by Professor Bruce Kemp, was recognised internationally for its outstanding work on protein kinases, and throughout the 1990s concentrated its attention on one particular protein, the AMP-activated protein kinase (AMPK), which has a key role in regulating energy expenditure.
Thomas Kay was appointed as the Institute’s fourth director upon Jack Martin’s retirement in 2002. Trained as a physician and endocrinologist, Tom Kay applied his extensive experience in immunology to the study of transplantation of pancreatic islets as a treatment for diabetes. In 2008 the first transplant of human pancreatic islet cells into a diabetic person took place successfully under the direction of this group and in close collaboration with St. Vincent’s Hospital colleagues.
The Institute’s research continues with great emphasis on structural studies of proteins, cancer cell biology and cancer metastasis – especially to bone – the cell biology of bone and relevant diseases, osteoporosis and arthritis, and the control of metabolism, applied particularly to heart disease and diabetes.
In 2008 the Stem Cell Regulation Unit was established, when Carl Walkley and Louise Purton joined the Institute after several years of great research success at Harvard University. Their research is on the formation of blood constituents from stem cells, and specifically how the bone microenvironment influences the development of blood cells, both normally and in malignancy, in the case of lymphomas and leukemia.
Today the Institute has a dedicated team of over 160 staff and students, who are committed to improving the health and life-expectancy of Australians. We focus on common diseases that represent major health issues for Australians today, including diabetes, bone diseases, cancer, cardiovascular disease, obesity and Alzheimer’s disease. With an ever-increasing pool of talented researchers and state-of-the-art facilities, an exciting time lies ahead for SVI.