GGAGG—five letters that launched a biotechnology revolution
As a PhD student at the Australian National University, John Shine discovered the importance of a brief sequence of genetic code. It took him three years to determine that sequence and what it does. At its core are five letters—GGAGG—which tell ribosomes, the protein factories in all living things, to start making a protein.
Today’s gene sequencers would take a fraction of a second to do the same job. But John’s discovery and his subsequent gene cloning work at the University of California helped kick-start a biotechnology revolution, giving rise first to cloned insulin and then to thousands of cloned medicines.
John returned from the US biotechnology world to lead the Garvan Institute of Medical Research in 1990. Under his leadership the Garvan’s staff has grown fourfold and its budget tenfold. Along the way he’s mentored the growth of biotechnology in Australia while maintaining his own research program. And next year, when he stands down from his leadership role, he will focus fully on research and, with his team, expand their investigation of neural stem cells as potential therapies for neurodegenerative disorders.
For his scientific research and research leadership, John Shine receives the 2010 Prime Minister’s Prize for Science.
As children living in Turramurra in outer Sydney, John Shine and his brother Rick caught diamond snakes and kept them as pets. Rick is now a world expert on reptiles. John turned to veterinary science. But neither the biochemistry nor the practical aspects of animal husbandry engaged him.
John moved to Canberra and undertook a part-time science degree at the Australian National University where a lecturer, Lynn Dalgarno, turned him on to the excitement of the emerging field of molecular biology.
As an Honours student, John looked at insect and mammal cells. In the course of his work he realised that certain gene sequences were common to both. That observation determined the focus of his PhD and changed the course of his career.
These conserved gene sequences turned out to be responsible for turning on and turning off the production of proteins—telling the ribosomes in the cells where to start reading a gene and making a protein, and where to stop.
In bacteria he found that at the core of this simple sequence are the letters GGAGG. It’s now known as the Shine-Dalgarno sequence. In essence, it tells the bacteria to begin making a protein and to make a lot of it. These few letters turned out to be critical for the biotechnology industry.
John had postdoctoral fellowship offers from Boston, Berlin and San Francisco. Boston was too cold and he didn’t speak German, so he chose San Francisco. It was 1975 and John arrived just in time to contribute to the birth of modern biotechnology.
“It was an exciting time. We were the first to clone mammalian genes, the first to manipulate them, the first to clone the insulin and growth hormone genes,” says John.
“Insulin was the Holy Grail because diabetes was being treated with pig or cow insulin which were in short supply and had side effects. There was a real demand for human insulin. Although we had cloned the insulin and growth hormone genes into bacteria, the Shine-Dalgarno sequence had to be joined to them to program the bacteria to synthesise insulin or growth hormone itself.”
“This was really the birth of modern biotechnology—using bacteria as protein factories—and we were creating the tool-kit that the industry needed.”
John and his colleagues started California Biotechnology and created many new products.
In 2003, Cal Bio was bought by Johnson and Johnson for $US3 billion, but John was long gone. As the company grew, John decided he didn’t want to be a businessman. So he returned to Australia and in 1990 was appointed Executive Director of the Garvan Institute of Medical Research in Sydney.
The Garvan has grown rapidly in size, budget and prestige. It now has over 500 staff from 55 countries, and an annual budget of $50 million. It has five major research areas in cancer, immunology, diabetes and obesity, osteoporosis and neuroscience, and dozens of research achievements.
And John has brought the Garvan closer to the clinic and to business. The Garvan has a strong patent portfolio and a company to spin-out its discoveries to industry.
John has also acted as a mentor for biotechnology in Australia, serving on the board of dozens of organisations including the Australian Academy of Science, the Australian Research Council, CSL and many others.
He led the creation of the Australian Genome Research Facility. And he’s helped redefine Australia’s medical research infrastructure.
As chairman of the National Health and Medical Research Council from 2003 to 2006 he headed up the transformation of the NHMRC into a statutory body that is much more effective than previously as a granting agency and as a contributor to health policy.
The Garvan is continuing its expansion with the construction of the $110-million Kinghorn Cancer Centre in collaboration with St Vincent’s Hospital. When it opens in 2011, the Centre will bring clinical researchers in close contact with cancer clinicians—helping move cancer discoveries rapidly to the clinic.
By then John will have returned full-time to the lab bench. He is stepping down from his leadership of the Garvan. His major focus will be neural stem cells—using the rich supply of stem cells found in the nose, he will explore ways that we can repair nerve damage or replace nerve cells lost in disorders such as hearing loss, Alzheimer’s and Parkinson’s.
|1975||PhD (Molecular biology), Australian National University, Canberra|
|1972||Bachelor of Science (Honours), Australian National University, Canberra|
Career highlights, awards, fellowships and grants
|1990-present||Executive Director, Garvan Institute of Medical Research, Sydney|
|1990-present||Professor of Medicine (conjoint), University of New South Wales, Sydney|
|1987-present||Professor of Molecular Biology, University of New South Wales, Sydney|
|2006||DSc (honoris causa), University of New South Wales, Sydney|
|2003-2006||Chairman, National Health and Medical Research Council (NHMRC)|
|2003||Honorary Fellow, The Royal College of Pathologists of Australasia|
|2001||Centenary Medal for service to Australian society and science in molecular genetics|
|1996||Officer in the General Division of the Order of Australia (AO)|
|1994||Fellow, Australian Academy of Science|
|1986-1987||President and Chief Scientific Officer, California Biotechnology Inc., California, USA|
|1984-1986||Senior Vice President, Research and Development, Director of Research, California Biotechnology Inc., California, USA|
|1983-1987||Senior Fellow, Department of Genetics, Research School of Biological Sciences, Australian National University, Canberra|
|1982||Gottschalk Medal for distinguished research in biological or medical sciences, Australian Academy of Science|
|1980-1983||Fellow, Department of Genetics, Research School of Biological Sciences, Australian National University, Canberra|
- Discovery of the Shine-Dalgarno sequence and the basic mechanism of initiation and termination of protein synthesis
- Development of gene cloning technology
- The first to clone a human hormone gene and isolation and cloning of genes for insulin and growth hormone
- Creation of a series of gene cloning and expression tools that underpinned the growth of the biotechnology industry and the creation of a new era of drugs
- A series of discoveries of the genes responsible for important neuropeptides and neurotransmitters.