Beginnings
The St Vincent’s School of Medical Research (renamed St Vincent’s Institute in 1984) was established thanks to 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. Known locally as the “The Wizard of Mordialloc”, Holt lived his entire life together with his two sisters, Margaret and Catherine, in a small eight-roomed cottage called ‘Lethe’ which he built himself.
While Holt’s business acumen and skill as a trainer led to the development of a rather large fortune, above all he 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.
Pehr Edman, SVI’s first Director (1958-1972)
A Swede, Pehr Edman was appointed the first director of St Vincent’s School of Medical Research after a worldwide search. Edman took up his appointment in May 1957, and the laboratory doors 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 20 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 create a hugely diverse range of proteins.
In 1950, Edman published a method for determining the order of amino acids in a protein. 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 recognising 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 St Vincent’s School of Medical Research designing and producing a machine that could automate this painstaking process of protein sequencing.
Matilda: ‘The Sequenator’
In 1958, Geoffrey (Geoff) Begg was employed as a junior laboratory assistant to Edman and became intimately involved in the automation 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 asked if I could make a model of a possible machine.”
The next day, Begg brought an electric motor from home in to work. Aided by his glass-blowing skills, he 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 six years to perfect, pushing the men’s ingenuity to the limit. More than once they had to produce parts in the Institute workshop, having discovered that no manufacturer in the world could 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.
In 1972 Edman resigned as Director and moved to the Max-Planck Institut of Biochemistry in Germany.
More on ‘The Sequenator’
Morgan and the birth of protein crystallography at SVI (1973-1988)
After being appointed director in 1973, Frank Morgan extended the Institute’s research activities from Edman’s field of protein purification and sequencing to the relatively new area of protein crystallography.
Morgan lured Australian-born crystallography pioneer Neil Isaacs from the UK to Melbourne, to found the first protein crystallographic laboratory for the three-dimensional study of protein molecules in Australia (outside of CSIRO).
Defining the three-dimensional structure of proteins is not just academic. These molecular structures help us develop ‘smart drugs’ specifically designed to interact with a particular disease-causing protein.
The black swan
In the foyer of SVI there is a rather beautiful but somewhat dusty installation of Perspex and wire. This is the architecture of the first protein structure ‘solved’ at SVI, in 1978 – a protein called lysozyme isolated from the egg of an Australian black swan.
Enabling biological processes to be seen at their most fundamental level, the process for solving a protein’s molecular structure had been developed overseas. Neil Isaacs brought this knowledge to Melbourne.
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 these basic tools and primitive computing facilities available at the time, Isaacs and an assistant spent an entire summer painstakingly hand-building a model of their discovery.
From this hand-fashioned beginning, the protein crystallography effort at St Vincent’s Institute continued to develop under the leadership of Professor Michael Parker, who arrived at the Institute in 1991.
Martin brings focus to cancer, bones and kinases (1988-2002)
SVI’s strengths in cancer and bone research steadily increased from the time Professor TJ (Jack) Martin AO joined SVI as Director in 1988.
Martin and his colleagues – including SVI’s current Deputy Director, Professor Natalie Sims – have significantly advanced our understanding of bone biology and bone diseases, including osteoporosis, osteoarthritis and skeletal complications of cancer.
SVI research helped establish that the bone microenvironment profoundly influences cancer’s ability to grow in bone as secondary deposits. SVI work showed that, to establish in bone, cancer cells need to be able to control the growth and breakdown of bone. These are now key concepts in thinking about this common complication of cancer, and how it can be prevented and treated.
The study of protein kinases – enzymes that change protein function through the addition of phosphate groups, driving cellular processes – also featured strongly in the 1980s and 1990s. SVI’s Protein Chemistry team, headed by Professor Bruce Kemp AO, was recognised internationally for outstanding work on protein kinases. The team’s attention more recently has focused on the protein, AMP-activated protein kinase (AMPK) – which has a key role in regulating the body’s energy expenditure, with implications for obesity, type 2 diabetes, cardiovascular disease and cancer.
Kay builds, diversifies and translates (2002-present)
Professor Tom Kay was appointed as the Institute’s fourth director upon Jack Martin’s retirement in 2002 and has overseen diversification of SVI’s research into new areas, as well as growth in the number of scientists and the funding base supporting them.
SVI opened its current building in 2003, and a new sense of energy accompanied this development.
Type 1 diabetes is the focus of Professor Kay’s research. His team’s work brought to reality pancreatic islet transplantation for treating people affected by severe and unstable type 1 diabetes, with the first such transplant taking place in 2008, in close collaboration with St Vincent’s Hospital colleagues.
More recently, the team – also led by SVI Associate Director Professor Helen Thomas – have focused on immunotherapy as the biggest step forward for treatment of type 1 diabetes since insulin was first used a century ago.
SVI’s research scope has expanded during the past two decades to include infectious diseases (through the NRL division), regenerative medicine (through a merger with the O’Brien Institute), bioinformatics, RNA biology, and blood cell-forming stem cells.
There has been continued emphasis on structural studies of proteins, cancer cell biology and cancer metastasis – particularly to bone – alongside bone cell biology research relevant to osteoporosis and arthritis, and the control of metabolism, applied particularly to heart disease and diabetes.
SVI is a proud partner in developing the Aikenhead Centre for Medical Discovery (ACMD), and we collaborate nationally and internationally for greater reach and impact.
With our values of integrity, open-mindedness, dedication and excellence, our 250 scientists and students continue to tackle critical health challenges – committed to improving the health and life-expectancy of Australians.