The Young ones

The Young Ones.

With philanthropic support from an unlikely source, the Children’s Cancer Institute Australia is at the forefront in the search for a cure. Dani Valent meets four of its hopeful young scientists and their benefactor.

When Neil Balnaves ran television production company Southern Star, he was known for hit shows like Blue Heelers and Big Brother. He certainly wasn’t known for his patience. “More the opposite,” he says. “Whatever I wanted, I wanted it now. That’sthe nature of that business.” But the past decade has foisted patience upon him.
First, he had to take baby steps to recover from a motorboat accident in 2002. “I got badly smashed up,” he says. “I was in hospital on life support and I didn’t walk for six months. I spent a fair amount of time reflecting.” The effects of the accident led him to sell Southern Star in 2004. “I couldn’t work at the same pace, I couldn’t travel without help.” Then, nicely cashed up but worried about cursing his three children with unearned wealth (“I was scared of having the kids too well off”), he decided to give his money away – slowly and to slow-moving areas of endeavour. Balnaves, now 66, focused on the arts (“Because I’m interested inthe soul of the country”) and medicine, partly because of his boating mishap but also because he lives with the effects of the polio he contracted when he was seven.
One of the Balnaves Foundation’s biggest grants – $500,000 over three years, starting in 2008 – is to young researchers at theChildren’s Cancer Institute Australia (CCIA), based at the University of NSW. So far, grants have been given to four researchers, all of them with busy postdoctoral careers, but none with the long track record required to secure funding from large bodies like theNational Health and Medical Research Council. The grants are intended to help the scientists get the necessary runs on the board to attract funding for longer-term projects, but Balnaves won’t mind if they strike gold along the way.
“I’ve got to be patient, put the building blocks in place and wait,” he says. “You don’t get massive leaps in medical research, from what I can see.” Indeed, cancer research usually works on incremental gains rather than big leaps, though even minor developments can have huge health benefits for individuals. But the TV tycoon can’t help hoping for a dramatic breakthrough. “What we’re thinking is, if you’ve got someone young, someone who thinks outside the square, then they might just get lightning in a bottle.”

Marcia Munoz
A day at the office for biologist Marcia Munoz often involves working with cells from the CCIA’s basement tumour bank, a 25-year archive of biological samples in cryogenic storage. “The cells are probably from children who have died,” she says. “I work with neuroblastoma, a very bad tumour that generates along the spine and usually appears in children aged one to five.” Neuroblast-oma is a priority for CCIA because of its low survival rate. “More than 50 per cent don’t make it, even though they are treated with high-powered therapies,” says Munoz. “We are trying to find ways of treating it that are less toxic to the babies.”
“The babies” seem a long way from the sterile environment of the CCIA laboratories, where everyone wears latex gloves and machines that go “ping” are lined up alongside computers. Munoz is experimenting on trays of cells suspended in vials of a nutritious red broth and kept in humidity-controlled fridges at 37 degrees. She is investigating tiny “pumps” found in neuroblastoma cells: an abundance indicates a more aggressive tumour, in part because they pump chemother­apy medicine out ofthe cell. “They also make the cells more aggressive,” she says. “The cells divide more, they move more, they’re more resilient.”
Munoz suspects the pumps are related to inflammation, too, “which makes a nice, cosy environment for tumours”. She “silences”the pumps by adding RNA (a post-DNA cell building block) to the cells to stop pumps developing and checks the results under a microscope. Cells either look splotchy (bad) or develop star-like tendrils (good). “If I block the pumps, 48 hours later you see tendrils, which is what neurones should look like. The cells start to behave better, they’re not as angry.”
If her in-vitro experiments go well, Munoz will progress to experiments on mice. “I don’t like it but animals are a means to an end,” she says. “You can’t do cancer research without using animals.”
Munoz, 39, grew up in Venezuela and moved to Australia in 2000. “I always knew I wanted to be a scientist,” she says. “I used to think boys liked trucks, girls liked pink and the third type of person – me – liked nature and little bugs.” In her early career, cell biology was an entrancing intellectual puzzle, but working at CCIA “has ruined it a bit for me”, she says. “I used to be motivated by curiosity, but here I have lost that objectivity. Child cancer is horrendous. I have to admit I do have strong feelings about it.” She doesn’t think that compromises the science. “It makes it better because it gives it an extra dimension. It’s not just an intelligence exercise, it has meaning.”
Being a mother (of two girls, aged 11 and two) affects the way she thinks about her work. “Once you have kids, you’re in fear whether you work in cancer research or not,” she says. “But when you see children with cancer like I do, you worry much more about your children getting cancer.”
If anything, it has steeled her resolve. “I don’t think I’m going to wake up tomorrow and find the cure for cancer, but it’s going to happen,” she says.
“I do believe we are getting somewhere.”

Eddy Pasquier
As a small child in marseilles, Eddy Pasquier was fascinated by the natural world. But collecting caterpillars didn’t cut it: he was interested in the biological nuts and bolts. “We have this amazing body, we start as an embryo somewhere, the brain is so complicated,” he says. “I was passionate about all of it.” Then, when he was 10, Pasquier thought hard about death. “My grand­father died and I didn’t grow up in a religious family, so I never had any thoughts that he might go to heaven,” he says. “Instead, I really tried to understand how you can move from being alive to not being alive any more. It was a bit metaphysical, but I was trying to find answers for myself.”
Now living in Sydney, Pasquier, 28, is searching for answers about angiogenesis, the formation of blood vessels, especially in cancer cells. “If a tumour doesn’t have blood vessels, it can’t grow or spread,” he says. “There are new therapies targeted at preventing the formation of blood vessels inside tumours. I am trying to understand the mechanism of this process and I’m studying new therapeutic agents that are targeting it.” Much of his work involves changing the frequency and dosage of pre-existing drugs to reduce the side effects of treatment and, hopefully, increase the efficacy. He works with clinicians on hospital patients and, at CCIA, on cells in flasks. “The structures they form are a few millimetres long, which is tiny for the layman but huge for us. You can even see them by eye, if you squint a little bit.”
Pasquier loves life in Sydney, as a surfer (“I can work crazy hours and still surf in the morning or night”) and as a scientist. “People talk about the American dream but I think in Australia, if you are committed, you can become anything.”
But it will be his mother who draws him back to France. “I grew up by myself with my mum. She is a cleaner and worked really hard to help me do my studies.” Extended family pushed him towards business, but money was never his motivator. “My mum never had anything and always helped everyone. I feel much more reward when I am helping someone, or thinking my research might help someone, than counting the notes in my wallet.”
Pasquier was already studying cancer when his best friend died from Hodgkin’s lymphoma. “It was really tough, but it helped me focus on what I was doing. I felt more sure than ever that this was what I wanted to do. Curing cancer, curing childhood cancer, isthe only thing I want to do with my life.”

Jamie Fletcher
Jamie Fletcher points to images of a spreadeagled mouse on his computer screen, indicating purple patches where limb meets torso: they grow in size as he scans the images from left to right. “That’s tumours growing in the bone marrow of the mouse,” he says. “We inject the tumours with a luminescent material, the same material that makes fireflies light up.” The luminosity means mice can be monitored via scans, rather than dissection.
Fletcher, 36, is investigating the genes that control whether cells live or die in the hope that this will help find a cure for neuroblastoma. “Cells have a finite life cycle,” he says. “But some cells fail to die when they should and that’s part of what drivesthe formation of cancer cells. They also can be difficult to kill. But their defects sometimes make them easier to kill, if you understand what the defect is and can exploit it.” He’s looking at protein molecules known as the Bcl-2 family, which manage cell survival. Drugs trialled for some adult cancers target Bcl-2 and signs are promising, but less is known about their role in neuroblastoma.
Life in the lab is very different from the grain farm near Quirindi, in northern NSW, where Fletcher grew up. “I was a kid in the ’80s when interest rates were high and lots of farms were being sold. It seemed like a bad business to be in.” The three Fletcher kids were encouraged to go to university or get a trade. Fletcher studied science, specialising in structural biology. “It’s entirely unrelated to the things we do here,” he says. “My PhD began by looking at insecticidal spider toxins, potentially for agrochemical application.”
In 2003, he had a change of heart after encountering researchers from Melbourne’s Walter and Eliza Hall Institute of Medical Research. “They spoke about the proteins that control cell life and death. I thought that looked a whole lot more important, more interesting, than what I was doing.”
He worked at Walter and Eliza Hall for four years before shifting to CCIA. “I wanted to work on something related to a disease.The chance to work on something with a tangible endpoint for somebody’s well-being, not just a theoretical scientific endpoint, is really exciting. Neuroblastoma has a really poor outcome, so there’s room for a big impact.” Being a dad to toddler Benjamin has made a difference, too. “When you have an appreciation of how valuable a child is, it can keep you going when the work doesn’t go well. It’s not that you have to have a kid to feel it, but it helps.”

Joshua McCarroll
There’s no hesitation when Joshua McCarroll, 37, is asked why he’s working in cancer research. “For me, it’s easy,” he says. “When I was 12, I had Hodgkin’s disease.” In 1984, when McCarroll fell ill, the standard treatment was a barrage of chemo-therapy. “They just smashed you with it,” he says. Two years of treatment cured him but left him with permanent side effects. “One of the drugs attacks the smooth muscle cells of the heart,” he says. “It mucked around with the heartbeat. Now it doesn’t pump as much and it’s a bit irregular. I take a fair bit of heart medication just to make sure it continues on. Every day those tablets remind me of the past. You don’t escape. But I’m alive, I lead a normal life. Five or 10 years earlier I would have died.”
His motivation is clear, but McCarroll’s career path wasn’t. While he was ill, he didn’t go to school. “I basically lived at the hospital,” he says. Then, when he was ready to resume his education, his school sent him packing. “They pretty much told me to go away. ‘Be happy you’re alive, your education isn’t going to be important.’ I was 15. I knew that wasn’t acceptable.” He hit the books at home, then went to TAFE to do a year 10 certificate and, eventually, matriculate. “That enabled me to go to university. When I got into science and realised I could apply it to cancer, that’s when I got excited.”
At CCIA, McCarroll is working on improving drug delivery to tumours to avoid the sorts of side effects he suffers. He’s using buzz techniques of medical research: nanoparticles and siRNA (“RNA designed to knock down a gene of interest”). The siRNA is attached to nanoparticles to create a treatment that, hopefully, leaves normal cells alone.
His focus is brain cancer, a common cause of cancer death in children. “It’s a terrible cancer,” he says. “One of the biggest challenges with it is drug delivery, due to the blood-brain barrier. The brain protects itself from the outside environment by only letting very small molecules in.” McCarroll is developing nanoparticles that he hopes will sneak past the blood-brain barrier and deliver siRNA that targets cancer cells without harming healthy cells.
“It’s really personal for me because it’s all about reducing side effects,” he says. “Before I had cancer, I was one of those really sporty, cool kids. The day I got diagnosed, that person basically died and a new one came about. It was tough. But I knew after my treatment that I had to come out of it and help people in some way.”