Andrew Boyd returns to the institute after overseas postdoc studies. His analysis of the glue-like molecules on many blood cells provides new insight into immune processes. Later work in cancer cells leads to clinical trials for leukaemia and potential new treatment for patients with brain tumours.
From ward to lab
Professor Andrew Boyd suspects that he contracted the medical research bug from his mother. She was a nurse at Melbourne’s infectious diseases Fairfield Hospital during World War II. She also provided research assistance to a virologist there.
“She was always an influence on me deciding to do medicine, and making me want to do research,” Boyd recalls.
Then another woman gave him a defining nudge when, while doing specialist training in haematology at the Royal Melbourne Hospital, Boyd was taken aside by Dr Berta Ungar, a legendarily formidable if kind-hearted hospital identity, and asked what he planned to do with his life. When he indicated an interest in medical research, she insisted “you’ve got to see my friend Nossal”. His family, like hers, had fled Vienna as war loomed.
The challenging path of a clinician-scientist
Walter and Eliza Hall Institute director Gus Nossal was encouraging of medicos wanting to investigate research careers, though choosing to combine clinical and laboratory work would demand a long slog of study and a difficult career-long balancing act of priorities and interests.
“It’s interesting that when I committed to do a PhD, he asked my wife and I to come in together, and more or less said ‘you know what this will mean, there will be some years of penury’,” Boyd recalls. Starting again, at 30, as a PhD candidate in 1978 was tough. “At the end of the first year I wondered if I had done the right thing. But by the end, I was pretty happy.”
Why take such a difficult path, when he’d already done the hard yards to work usefully and lucratively as a haematologist? “Some of us are crazy enough thinking we want to do something original, and possibly something that might help more people than you could ever help with your own hands.”
Nossal had cause to be happy with his recruit quite early in the piece. As he reflects in his book Discovery And Diversity, Boyd “proved to be a champion producer of monoclonal antibodies, one of which was licenced to a leading biotechnology company and became a useful money-spinner for the institute.”
Homecoming
After completing his PhD, focussing on B cell immunology, with Professor John Schrader, and a brief post-doctoral period with Professor Don Metcalf, Boyd went to Harvard Medical School’s Dana-Faber Cancer Institute, where he spent three years before returning to the Walter and Eliza Hall Institute in 1985 to head his own cancer laboratory, where he remained until 1996.
“I was the first person in what is now the ‘old’ building,” Boyd recalls. He had to juggle his media and equipment around the balconies at the hospital to start work in the new laboratories.
Discoveries
Around this time, while studying malignant B cells, he started analysing glue-like molecules found on the surfaces of many blood cells. One of these was ICAM-1, “and it turned out to be a fairly central player in immune processes, binding together immune cells with their targets and other immune cells”, Boyd says. This work yielded some highly successful papers and collaborations with other institute researchers, including Professor Len Harrison.
But a couple of years later Boyd’s interest veered in another direction. “I was studying B cell leukaemias and normal B cells at the time, and I was particularly interested in pre-B ALL cells, the sort of precursor cells that come out of the bone marrow and are the commonest cause of childhood cancer.
“We came up with this molecule which was clearly expressed on some of these pre-B ALLs, but didn’t seem to be on normal cells. And as a clinician – as a scientist full stop – the thought of finding something on a cancer cell that didn’t seem to be there on the normal cellular equivalents was immediately something I had to take notice of. Because it was new and a bit weird I think Nossal patted me on the shoulder once and said ‘are you sure this is the right thing to be doing?’
“Subsequently he was very, very supportive, but I can understand it. It was a bit of a leap into the blue, and it might not have gone anywhere. But it turned out very well.”
It turned out to be a member of a very large family of receptors, the EPH receptors as they are now known, and which became the dominant theme of Boyd’s work over the past 25 years. The gene was cloned by Boyd’s then PhD student, now Professor Ian Wicks, today the institute’s Inflammation Division head.
Offering hope for leukaemia and brain cancer patients
“The most pivotal work I did on those molecules really all started at the WEHI in the mid-1990s. That’s the work that has now progressed to the point that the antibody we developed early on to identify this molecule is now in clinical trials for leukaemia, has completed phase 1 trials, and is now being put into phase 2 in leukaemia and possibly a trial starting this year on brain tumours.
“It’s really something scientists dream of, to see something completely novel. It’s one of the reasons you do the work.”
A discovery in neurology
Work on another member of the EPH family yielded another potentially powerful insight. One of the animal technicians noticed that mice lacking the EphA4 gene hopped like kangaroos. Realising this indicated a neurological problem, Boyd consulted neurobiologist Professor Perry Bartlett in the laboratory next door, “and it turned out to be a fairly major finding, showing that this gene was important in the development of the motor nervous system”.
Twenty years down the track, Boyd and Bartlett are lodging a patent on work that came out of that moment.
Reflections on working at the institute
Boyd moved to the Queensland Institute of Medical Research in 1996, part of a cohort of institute alumni who have helped shape Brisbane as a heavyweight research and biotechnology force.
“The thing I overwhelmingly admired about the WEHI was the intensity people showed toward their science,” Boyd says. “We talked about our experiments day in, day out. At morning and afternoon tea, at the pub on Friday nights, a lot of the conversation was about what experiments you did that week. And collaborations came out of those discussions.
“It was a much more fertile environment than probably I’ve seen since,” he says. The expansion of institutions, the bigger staff numbers required to bring in the skills of advancing technologies, means that spirit is “probably something that doesn’t exist in any institute now, even the WEHI, but I suspect it retains more of it than other places.”
“It did shape the way I tried to influence people who worked with me over the years. I tried to replicate that environment as much as I could, usually not as successfully as what I saw when I was at WEHI.”