The devil’s work


Ruth Pye investigating cancer in the Tasmanian Devil A veterinarian and a geneticist have joined forces to solve the puzzle of transmissible cancers in Tasmanian devils. Frank Leggett investigates.

It’s estimated that 90 per cent of the Tasmanian devil population has been wiped out by devil facial tumour disease [DFTD], an infectious tumour that causes cancers starting around the mouth and head. Thankfully, there has been progress made in developing a vaccine and in mid-2015, a test group of 19 vaccinated devils was released in the Narawntapu National Park in northern Tasmania. Unfortunately, researchers working in collaboration with the Save the Tasmanian Devil program [STDP] have recently discovered that a second transmissible cancer is also affecting Tasmanian devils.

Dr Ruth Pye, a Brisbane-born vet who’s now a PhD student at the Menzies Institute for Medical Research in Hobart, found the initial cases of this second cancer with members of the STDP. Dr Elizabeth Murchison, a leading authority on DFTD genetics, performed the genetic analysis at the UK’s University of Cambridge and confirmed it was a second form of cancer affecting Tasmanian devils.

The friendship of these two women is part of the journey to save the endangered Tassie devils. Dr Pye was working on a street dog sterilisation and rabies vaccination program with Vets Beyond Borders in India back in 2009 when she first came across Dr Murchison who’s based at Cambridge’s Department of Veterinary Medicine.

“Elizabeth had contacted Vets Beyond Borders to see if we could collect canine transmissible venereal tumour [TVT] samples for her,” recalls Dr Pye. “I met up with her a couple of times in England and then, when I came back to Australia, she put me in touch with Professor Greg Woods and Dr Alex Kreiss of the devil immunology research group at the Menzies. That’s how I started my PhD on immune recognition of DFTD by the Tasmanian devil.”

The devil and the details

The devil immunology group aims to understand the devils’ immune system and how DFTD escapes the immune response, and ultimately to develop a vaccine against the disease.

“We hope our work will shine light on how these cancers transmit so successfully,” says Dr Pye who’s planning to complete her PhD at the end of the year. “Ideally, we hope to find a way, through vaccine development, to slow the effects of the disease on the devil population.”

After Dr Murchison’s initial genetic analysis of DFTD, published six years ago, she released another report which made headlines around the world. Thanks to further collaboration with Dr Pye, a second transmissible cancer in Tasmanian devils was discovered.

“Until about two years ago, it was thought there were only two naturally occurring transmissible cancers in the world—canine transmissible venereal tumour and the Tasmanian devil facial tumour disease,” explains Dr Murchison. “We believed transmissible cancers, spread by the direct transfer of living cancer cells, to be extremely rare, having emerged only twice in nature.

“It was quite a surprise when early last year, a group in the United States found a transmissible cancer in soft shell clams. Using genetic analysis, they showed that clams along the east coast of North America had the same cancer and that the cancer first arose in one individual clam. Suddenly, there was a third transmissible cancer on the list.

Cancers growing

“Then we discovered what appeared to be another transmissible cancer in Tasmanian devils. It turned upside down everything we thought we knew about the rarity of transmissible cancers,” says Dr Murchison, who was born and grew up in Tasmania.

This second devil cancer was discovered by Dr Pye in 2014 when she found a devil from the Cygnet area south of Hobart with typical facial tumours of DFTD. She took some cell samples and surprisingly, their chromosomes were different to those seen in DFTD cells. Further investigation revealed that the tumour cells (histology) didn’t look like DFTD cells either.

“Initially, we thought this was just a coincidence,” says Dr Murchison. “We suspected that this devil may have developed a tumour from his own cells, and that visually, the tumour just happened to look a lot like the DFTD.”

A few months later, a second devil from Snug, about 25 kilometres from Cygnet, was found with the typical facial tumours of DFTD. Dr Pye took some samples and the chromosome arrangement of these cells was identical to that of the tumour cells found in the Cygnet devil.

“This was clearly suggestive of a transmissible cancer that wasn’t the original DFTD (DFT1),” says Dr Murchison. “Ruth sent samples to me at Cambridge and we did a genetic analysis. Our results showed that the tumours from Cygnet and Snug were genetically identical. They were distinct from their hosts so it was clear that these tumours were transmissible and didn’t arise from their hosts. Then, importantly, we found that these tumours were totally different to the genetic profile we see in DFT1.”

Catching cancer

A transmissible cancer is able to survive beyond the death of the original animal that first gave it life by the transmission of living cancer cells between animals. It has been known for some time that DFT1 carries two X chromosomes indicating that it originally arose in a female devil.

Dr Pye found something different in the second cancer. “When we looked at this new cancer, which we’re calling DFT2 for devil facial tumour 2, we found that the cells carry a Y chromosome. It’s clear that DFT2 must have originated in a male.

“Now we have a situation where there are two independent transmissible cancers in the Tasmanian devil population that cause tumours that, at a visual level, are virtually indistinguishable from each other. It’s a bizarre and surprising situation that we couldn’t have contemplated a few years ago,” says Dr Murchison.

Of course, it raises the question to why, within the past 20 years, there are suddenly two of these transmissible cancers in devils. They were never seen before 1996 when DFTD was first discovered.

“It suggests that Tasmanian devils are prone to acquiring this type of disease because of the way they bite each other on the face,” says Dr Murchison. “While this behaviour might predispose them to passing on a disease like this, it doesn’t actually explain it. There are many other animals that interact in the same way, yet show no signs of this kind of disease.

“These tumours are so horrible and disfiguring that it seems impossible they would go unnoticed if they had appeared at an earlier time point. That makes us wonder if there’s some environmental factor or some pathogen that might be predisposing the animals to getting this type of disease.”

Saving devil spawn

As a security measure, around 700 healthy, quarantined devils, representing 98 per cent of the species’ genetic diversity, now live in secure populations in Australia and New Zealand at zoos and animal parks.

One of the milestones in the effort to save the devils was the first release into the wild of immunised animals in mid-2015. Nineteen captive-bred devils were immunised with a trial vaccine developed by the Menzies group working with the Save the Tasmanian Devil program.

The largest conservation breeding program is Devil Ark located at Barrington Tops west of Newcastle in New South Wales. In the past five years, 180 joeys have been born.

“They’re breeding at the moment but we’ll soon start trapping all the females in the breeding yards to get an updated count,” says Devil Ark manager Dean Reid, who turns to Greencross Vets in Wyoming and Ellerston Veterinary Clinic for medical help. “With up to 150 devils at Devil Ark that are safe within 25 hectares of security fences, we’re hoping to double our population by next year.”

Last November, Devil Ark sent 22 devils to Forestier Peninsula in Tasmania after sending 17 earlier. The good news is that two three-year-old females, Brandy and Bree, have both had four joeys each in the wild, and the Devil Ark team is planning to send more devils in August.

What the future holds

While Dr Pye is hopeful about the future of the devils, she has no idea when the problem of transmissible cancers will be solved. “I never know how optimistic to be,” she admits. “The past three years has seen some encouraging results from the vaccine research and I do think there’s hope. However, that has to be tempered with the discovery of the second transmissible cancer in the devils.

“We don’t yet know what impact that will have on the population along with the impact of the initial tumour. However, I’d say on the whole, the results in the field and in the lab are encouraging.”

Dr Murchison tends to agree. “Unfortunately, I don’t think we’re going to see a solution in the short term. There’s simply a long way to go before we really understand what’s going on with these diseases in devils,” she says. “We’re moving as fast as we can.”

Reference: Pye RJ, Pemberton D, Tovar C, Tubio JMC, Dun KA, Fox S, Darby J, Hayes D, Knowles GW, Kreiss A, Siddle HVT, Swift K, Lyons AB, Murchison EP, Woods GM, 2015. A second transmissible cancer in Tasmanian devils. PNAS. pii: 201519691.



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