The Tasmanian devil (see video) is endangered by a contagious facial cancer. Credit: Anaspides Photography/I. D. Williams

Researchers have identified the cellular origin of the contagious cancer threatening Australia's Tasmanian devils, paving the way for a new diagnostic test and hopefully an effective vaccine.

First documented in 1996, devil facial tumour disease is a fatal cancer that spreads from animal to animal through biting, which scientists think could wipe out the wild devil population in 25–35 years. Researchers hope to combat the cancer through a vaccination programme and by establishing uninfected, captive 'insurance' populations. But both efforts have been stymied by a lack of understanding of the cancer's origins.

In a genetic study published this week in Science1, an international research team shows that the tumours arise from cells that insulate nerves, and that these cells' characteristic proteins can be used as markers for the disease.

"It's a very neat piece of work," says Vanessa Hayes, a geneticist at the Children's Cancer Institute Australia in Sydney, who was not involved in the research. Her team is sequencing the genomes of Tasmanian devils to identify gene variants that confer resistance to the cancer (see 'Genome scans may save Tasmanian devils from cancer'). "It is very complementary to what we are doing," she says.

Devils' disease

The research team, led by Elizabeth Murchison while she was working at the Cold Spring Harbor Laboratory, New York, and at the Australian National University in Canberra, compared gene expression in cancerous cells with that in normal testis cells taken from Tasmanian devils.

The team identified gene networks that may play a role in tumour transmission and development, and also found that tumours strongly express a gene for myelin basic protein — a key constituent of the sheaths that protect nerve fibres, formed by Schwann cells in the peripheral nervous system. Furthermore, out of the 20 other tumour-specific genes identified by the team, 9 were involved in the myelination pathway. Murchison and her colleagues then found that devil facial tumours, along with cancerous cells that had spread to other organs, tested positive for a Schwann-cell protein called periaxin. Other tumour types from devils did not test positive for this protein, suggesting that periaxin could be a suitable diagnostic marker for the disease.

Devil facial tumours spread between animals through biting. Credit: Save the Tasmanian Devil Programme

"Devils are particularly susceptible to cancers," says Anthony Papenfuss, a geneticist at the Walter and Eliza Hall Institute of Medical Research, Melbourne, and part of the research team. "Differentiating between the devil facial tumour disease and some other tumour is particularly important, especially when it comes to the insurance population programme." Currently, a captive population of less than 200 uninfected Tasmanian devils is held at zoos and parks in Tasmania and mainland Australia, and conservationists hope to increase that population to at least 500.

"The biggest problem at the moment is there is no test to see if an animal is carrying the disease," says Tamara Keeley, a reproductive biologist at the Taronga Western Plains Zoo in Dubbo in New South Wales, Australia. To prevent disease spread in the wild, conservation workers kill devils that have signs of the disease, but many sick animals can go undetected. "If we had a blood test, we could remove disease carriers in the hopes of managing the wild population," she says. Although the insurance programme has not captured wild devils since 2008, future efforts would make use of such a diagnostic test.

The latest results also shed light on how the tumours evade the immune system, says Alexandre Kreiss, one of the research team who is working on a vaccination programme at the University of Tasmania's Menzies Research Institute in Hobart. Tasmanian devils are all genetically very similar to one another, and scientists had previously suspected that cancer cells from another devil were not recognized as foreign when they infected a new host.

But the connection with the peripheral nervous system may suggest an alternative explanation. "The immune system doesn't usually attack the peripheral nerves," Kreiss explains, which may allow cancer cells from there to proliferate freely. That may be one reason why vaccination experiments with irradiated cancer cells at the Menzies Research Institute have been disappointing so far, he suggests. Only one out of six devils mounted an immune response following recent vaccinations, he says.

Papenfuss says that although a vaccine against devil facial tumours is still a long way off, "now we have a good start on a set of genomic tools we can move forward with".