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Sympathy for the devil

5 Jan, 2010
C0059053 Dr Liz Murchison. Image credit: Wellcome Images

Dr Elizabeth Murchison in the lab

Last century, the Tasmanian tiger was declared extinct. Now, a similar threat hangs over another famous inhabitant of the Australian island – the Tasmanian devil. Chrissie Giles met Dr Elizabeth Murchison, who works on a transmissible cancer threatening these distinctive creatures, to find out what can be done to save them.

The small plastic tube is cloudy with condensation, but just visible inside is a pale chunk of tissue, floating in a colourless liquid. Holding the tube is Dr Elizabeth Murchison, who is telling me about her travels across the world to pick up samples for her research at the Wellcome Trust Sanger Institute, near Cambridge.

Unlike the other researchers working on the Cancer Genome Project there, Elizabeth isn’t concerned directly with human disease. The samples she’s holding are from dog tumours, and there’s also a freezer drawer containing tissue from Tasmanian devils (Latin name: Sarcophilus harrisii).

Also unlike her colleagues, she’s dealing with a type of cancer that is transmissible – spread by the physical transfer of cancer cells from one animal to another. These rare cancers have been noted in the dog, devil and hamster, but – thankfully – not in humans.

Devilish history

The Tasmanian devil, a marsupial the size of a small dog, is now found in the wild only on the Australian island of Tasmania, after becoming extinct on the mainland some 400 years ago.

Diseased Tasmanian devil.

Diseased Tasmanian devil.

Ferocious predators of lambs and poultry, devils were often trapped and poisoned, until a law was passed in 1941 to protect them. Now a new scourge threatens the devils: a transmissible cancer called devil facial tumour disease.

This tumour first appears on the head and mouth of devils. It grows and grows, eventually preventing the animals from feeding, causing them to starve to death typically 6-9 months from the onset of symptoms.

There is no treatment for the disease, and the effects on the devil population have been devastating. It’s estimated that there could be as few as 20 000 devils left on the island, and in 2008, the devil was listed as endangered by the International Union for Conservation of Nature.

Hailing from Tasmania herself, it may not seem surprising that Dr Murchison ended up working on the devil.

“I’d always been interested in biology and Tasmanian wildlife,” she says. “I became aware of the Human Genome Project as I was finishing school – I was quite disappointed as it was just ending and I thought there’d be nothing left to do!” Discovering that a whole field of molecular biology existed, she completed a biology degree in Melbourne.

In 2002, she left Australia to start a PhD in genetics at Cold Spring Harbour Laboratory in the USA. The devil disease was relatively unknown then, but updates from friends working on programmes to protect the devil back on the island showed Dr Murchison how serious a threat it was.

She got some devil tumour samples sent over from Tasmania and began working on the cancer, research that she continues today, having moved to the Sanger Institute in January 2009.

Rapid spread

The first case of the devil disease was noted in 1996, and it spread across Tasmania rapidly, showing all the signs of an infectious disease.

This got scientists thinking: was this a transmissible cancer, spread by an allograft – the transfer of tissue between different devils? Certainly, the mechanics could work: devils bite each other frequently (during feeding, fighting and mating), and the tumours can crumble, so cancer cells could, in theory, be passed from one animal to another.

The allograft theory gained more weight in 2006 when scientists showed that the chromosomes from tumours from 11 different devils were rearranged in a similar way.

Dr Murchison and colleagues subsequently used microsatellite markers (repeated sequences in DNA that vary greatly between individuals) to confirm that the devil tumours were genetically identical.

No rejection

Why isn’t the tumour rejected by the devils? Research has shown that the devil immune system does not recognise these tumours as foreign, and so doesn’t destroy them.

In part, this is thought to be because of a lack of genetic diversity in the devil population, caused by inbreeding within the island-bound population. This means that the tumour cells (which originated from a devil) are recognised as ‘self’ rather than ‘non-self’ and are not flagged for destruction.

How can the genetic particulars of the tumour be used to understand its biology? In work published recently in ‘Science’, Dr Murchison and colleagues set out to identify genes unique to the cancer.

They found that tumour cells expressed many genes, but only one set at markedly different levels compared with non-tumour devil cells. Somewhat unexpectedly, the genes were unique to Schwann cells, which insulate nerve fibres with a fatty substance called myelin. Why would this be?

“It’s a clue to the tumour’s cell of origin – we propose that the devil cancer might have evolved from a Schwann cell that became cancerous,” says Dr Murchison.

But how does a humble nervous system cell become a transmissible cancer? “We think that a Schwann cell accumulated mutations and became a cancer cell, somewhere in the body of the devil with the first tumour,” says Dr Murchison.

How it became transmissible remains poorly understood, but she suggests that the original devil may have been cannibalised, or that a tumour was growing on its face and it spread to others from there.

From this work, Dr Murchison was able to define a diagnostic marker for the cancer, to differentiate this tumour from others.

In future research she plans to look at tumours taken from devils in different parts of Tasmania, to explore how the tumour has evolved to improve its ability to ‘live’ in the devil.

Saving the devil

Ultimately, it’s hoped that research to understand the tumour will prove useful in finding ways to prevent and treat the disease. There are also many other avenues being explored to save the devil (see ‘Cedric: saviour of a species?’ below).

Tasmanian devil.

Tasmanian devil.

What does the future hold? Well, unlike the transmissible cancer in dogs that Dr Murchison also studies, the devil cancer is rapidly fatal, and looks to be spread in a frequency-dependent manner.

This means that the spread depends more on the frequency of interactions between the devils, rather on than the number of devils. “The devil tumour is effectively wiping out its host, and there’s real potential that the disease could drive the population to zero.”

Our interview over, Dr Murchison returns the samples to the freezer box. Undoubtedly, things look bad for the devil, but with work such as that of Dr Murchison, there’s still hope that, nearly 75 years since the Tasmanian tiger went extinct, the devil will be spared the same fate.

References

At a glance: transmissible cancers

  • Transmissible cancers spread by the exchange of cancer cells from one individual to another.
  • As well as the Tasmanian devil facial tumour disease, there is a transmissible cancer in the dog that may have arisen thousands of years ago.
  • No such cancers are known in humans.

For more see Murchison EP. Clonally transmissible cancers in dogs and Tasmanian devils.Oncogene 2009;27:S19-30.

Cedric: saviour of a species?

The devil cancer was first observed in 1996 by a wildlife photographer in Mount William National Park, north-east Tasmania. Initially dismissed as a freak of nature, the disease began to spread.

More and more devils with tumours were seen along the east coast of the island. The tumour’s rapid spread had all the hallmarks of an infectious disease, but it was too late by then to contain the condition geographically. Only one small corner in the north-west of the island seemed safe.

Devils in this region are genetically distinct, which led some people to believe that the north-west devils recognised the tumour cells as foreign and could clear them from their body.

In 2007, two healthy north-west devils, Cedric and his half-brother Clinky, were injected with live tumour cells. Clinky went on to develop tumours, but Cedric didn’t, prompting much speculation about the existence of resistant animals.

However, after being challenged with a different strain of disease he developed two small tumours, extinguishing hopes of finding a resistant devil population.

Other projects to protect the devil include Tasmania’s Save the Devil Program, which is breeding genetically diverse devils from disease-free animals taken from the west coast. The Tasmanian Government is considering plans to find an island to house healthy devils.

Image credits: Wellcome Image, Save the Tasmanian Devil Program,  Ian D Williams, Anaspides Photography.
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