Seeking prostate cancer treatments in the DNA of ancient tribes

Professor Vanessa Hayes spends much of her time working in a gleaming laboratory on a leafy Sydney street. But there is another side to her work – one that takes her to the Kalahari Desert in northern Namibia. When she works in Africa, her only tools are a folding table, a notebook and the basic venesection equipment she uses to take blood samples from members of tribes such as the Ju/’hoansi people.

Hayes has spent a decade studying the Ju/’hoansi and other indigenous southern African groups. They are key to her quest to understand the genetic origins of humanity and the diseases that afflict us.

Cancer research powered by philanthropy

As the Petre Chair of Prostate Cancer Research, a position shared between the University of Sydney and the Garvan Institute of Medical Research, Hayes leads a team dedicated to using genetics for earlier diagnosis and more targeted treatment options for prostate cancer. The disease kills an estimated 3500 men in Australia each year.

Hayes' role was established thanks to a $2 million gift from the Petre Foundation in 2011. Donor Daniel Petre is among more than 64,000 people who have donated to support research and education at the University over the last decade.

In that time, a total of $368 million has been donated to medical research. 

The oldest genomes on the planet

Hayes' work in the lab seems a long way from Namibia, where groups including the Ju/’hoansi live a traditional forager lifestyle with little use for Western medicines.

“How the two connect – it is a question I am asked all the time,” she says. “But it is all one piece of work. We spend a lot of time as geneticists studying diseases but we have no idea what it is to be healthy.”

The hunter-gatherers from the Kalahari have the oldest genomes on the planet. The longer a population has existed, the more time it has had to build up genetic variations. This diversity makes these groups more genetically fit – better able to adapt than other populations.

Using African DNA as a baseline, Hayes is developing a reference genome for healthy people that is more representative than those derived from European DNA. To unravel the genetic risks to health, it is crucial to use the complete range of genes that make us human.

On the other hand, while populations outside Africa are less genetically diverse, they have adapted some resistance to diseases such as malaria and tuberculosis.

Prostate cancer is a particular problem in Africa, where people tend to get the disease earlier, in highly aggressive forms. “It’s really important that we study this disease within Africa if we want to understand prostate cancer globally,” says Hayes.

In her laboratory, she uses state-of-the-art genetic mapping equipment that allows for what she describes as a “bird’s eye view” of the DNA samples she collects. The instruments were purchased thanks to the Petre Foundation gift. The technology is both unique within Australia and indispensable to Hayes’ work.

“Without the Petre Foundation, our lab wouldn’t exist,” Hayes says. “Funding for high-risk science through the normal mechanisms isn’t easy, but donor Daniel Petre is a forward-thinking person. He likes the idea of high risk and high gain.”

Hayes sees her research as high risk and high gain because it looks beyond Australia to the rest of the world, and its wide-ranging benefits cannot always be predicted.

“People often think you need to study at your doorstep to make a difference, which simply isn’t true,” she says. “By going further afield, we open up new understanding.”

Thanks to the Petre Foundation’s generosity, Hayes’ team was the first in Australia to obtain next-generation mapping technology, and the first in the world to apply it to understanding an individual tumour. They used the technology to generate whole genome maps for prostate cancer – the most complete picture to date of the cancer’s genomic landscape.

Such mapping could be used to characterise an individual’s tumour, enabling more precise treatments. Currently, it is difficult to determine when prostate cancer is likely to spread and become life‐threatening, so patients sometimes receive gruelling treatment they may not need. Understanding the genetic drivers of individual tumours could help clinicians target treatment to the needs of particular patients.

Prostate cancer's 'holy grail'

Hayes says finding an identifiable gene, like those that predict risk for breast cancer, remains the holy grail of prostate cancer research in order to better target screening programs and help patients and clinicians decide on treatment options.

“My interest and passion for prostate cancer comes from the fact that this is a cancer with no known modifiable risk factor. It has a 58 percent hereditary rate but no single magical gene.”

Born in Cape Town, Hayes completed undergraduate and master’s degrees in science at the city’s Stellenbosch University, researching African gene variants and susceptibility to HIV. Later, she moved to the University of Groningen in the Netherlands to complete her PhD in cancer genetics.

She moved to Sydney in 2003. In her first role at the Garvan, she explored genetic risk factors for prostate cancer. This was followed by work at the Children’s Cancer Institute of Australia, establishing one of the first next-generation sequencing laboratories in the country.

She represented Australia as a Fulbright Professional Scholar at Penn State University before returning to Sydney for her role as chair.

In Australia, Hayes says she has been allowed the freedom to pioneer next-generation sequencing in what she describes as “out-of-the-box science”, including sequencing the genome of Archbishop Desmond Tutu, the first African and eighth complete human genome to be sequenced.

She has spent 10 years working on the Southern African Genome project, the evidence from which is now being used by researchers around the world to better understand the genetic drivers of human disease.

She is now applying the same open inquiry to her work with prostate cancer. With relatively scant understanding of the risk factors for prostate cancer and limited treatment options for those who develop it, this is an ideal avenue for Hayes’ out-of-the-box science.

“Safe research is where you are building from your own story, or someone else’s story,” she says. “But why should we keep asking the same question in the same way?”

On 17 September, we celebrated University donors with Thank You Day. Learn more about how our donors are changing the world.