2011 ATSE Clunies Ross Award: Antony Burgess, Ashley Dunn, Nicholas Gough - Medical Research
Professor Antony Burgess, Professor Ashley Dunn and Dr Nicholas Gough were the scientists who first purified and cloned GM-CSF, patented it and continued developing the biology of GM-CSF to guide current and future clinical uses of this agent. The process started in the early 70s when Professor Burgess spent a decade working through the technically challenging task of purifying to homogeneity the minute amounts of GM-CSF present in mouse lungs. Despite many sceptics insisting that it was a fruitless task due to the extremely low abundance, Professor Burgess and his team persevered. When new technology was developed in the US, he teamed with Leroy Hood at the California Inmstitute of Technology (Caltech) to use gas-phase sequencing to determine the N-terminal portion of the amino acid sequence of GM-CSF. In 1982 Drs Dunn and Gough teamed up to build on Professor Burgess’ work by cloning the GM-CSF gene. At that time cloning genes remained highly challenging, but they resolved to isolate the cDNA clone corresponding to GM-CSF. As only minute amounts of the protein, had been purified, only the N-terminal quarter of its amino acid sequence could be determined by Burgess and Hood to guide the search for the cDNA. However, the trio went about their research with enthusiasm and a flair for problem solving that buoyed their team and allowed for sustained progress. The biological source for making the cDNA library was critical due to the likely very low abundance of the cognate messenger RNA. Fortunately, the library they constructed was superb, and indeed two of the 100,000 clones screened proved to encode GM-CSF. Their subsequent Nature paper not only described the cloning but unequivocally established that GM-CSF was a specific regulator of white blood cell production. The success of their research changed the field of experimental haemopoiesis and cancer treatment forever and provided another means of treating cancer patients. Several companies and clinicians recognised the potential of GM-CSF as a therapeutic agent to assist patients with low white blood cell counts, especially after bone marrow transplantation. This knowledge encouraged the trio to request that the Ludwig Institute for Cancer Research (LICR) patent their discovery, an undertaking which was then quite foreign to medical researchers. Despite stiff competition from rival research institutes and biotechnology companies, the application was ultimately successful. Professor Dunn subsequently used molecular genetics to explore the role of GM-CSF in physiological systems, and together with his students engineered both mice making excess GM-CSF and mice making none. Analysis of these animals connected GMCSF to tissue inflammation and revealed its essential role in the normal clearance of surfactant from the lungs.