This blog is currently on hiatus owing to work commitments. Whilst I still keep an eye on the goings on at RiAus, and contribute to the work of the good folks at eLife, little will be added to this blog for the foreseeable future. Simon Says remains open for business, albeit at a reduced capacity. Thanks for stopping by, and I hope the archive of content found here will prove to be of interest.

Saturday, 27 March 2010

Save the Tasmanian Devil

THE FIVE devils in the pen below us bounded around happily with not a care in the world. They were small, fluffy bundles of energy, running around and around, almost skipping, happy-go-lucky and enjoying their freedom. Every so often they would fail to look where they were going and smack head-on into one of their friends - immediately they would stop, step back, assume an aggressive posture and growl for a second. But such aggression would be short-lived and they would be off again, bounding away. La la la! They were happy little devils.

This is a difficult post to write, for it is about a small marsupial that lives in Tasmania. Chances are that if you are reading this you live in Britain, or at least not in Tasmania. How, then, do I make you care about a creature that lives so far away, that is so far removed biologically and symbolically from our national consciousness? The Tasmanian devil? Some people I know don't even believe it exists at all, that it is an invention by folklore and Warner Bros.

But there is a creature, very much real, called the Tasmanian devil (Sarcophilus harrisii). And it is in serious trouble.

A new disease

In 1996, a new disease called Devil Facial Tumour Disease (DFTD) was first observed. Its effect has been devastating: between 1996 and 2009, devil populations in Tasmania have decreased by 80% and it is entirely possible that DFTD and its consequences could lead to the extinction of the species within 25-35 years. DFTD appeared very suddenly, it was catastrophic, and nobody really knew what it was.

Slowly, the puzzle is being pieced together.

DFTD is a form of cancer, an unnatural overproliferation of cells in the face that leads to death by an inability to feed, secondary infection or - because the disease metastasizes to other parts of the body - the failure of organs. Over 70% of the total population of Tasmanian devils have been affected by the disease, although there is one isolated population in the northwest of the island that, for now (touch wood), has not been affected.

Fig. 2. Interpolated time of disease arrival, overlaid with confirmed reports. McCallum, H. et al. Distrubution and impacts of Tasmanian Devil Facial Tumour Disease. Ecohealth 4, 318-325 (2007)

The curious thing about the disease is that tumours from different devils are genetically identical. It means that cancer cells are being spread as clones between animals, probably by biting. That's highly unusual, as cancer is not a contagious disease - it does not work like an infection. Indeed, only one other kind of transmissible cancer is known in animals.

A curious absence of an immune response

Normally when the body is invaded by a foreign pathogen an immune response is initiated to get rid of it, or at least to neutralise it. This is what happens in transplant patients and is why they have to take a hefty cocktail of drugs to fight the body's natural tendency to defend itself. The transmission of a cell is a much bigger (and less common) challenge than that presented by a virus or bacteria, but the same principle should apply. But this doesn't happen with devils, and for a long time it was assumed that it is the result of two effects: that devils are so genetically alike, with very little variation; and that the tumour is derived from a devil itself. This would mean that devils are unable to identify the tumour as foreign, because they're all too alike.

A recent study by Siddle et al., published this month by the Royal Society's Proceedings B journal, looked at sequence variation in a gene family called the major histocompatibility complex (MHC), of which there are two classes. MHC molecules are used to present foreign particles to the cells of the immune system so that the immune response can be initiated. MHC molecules are vital in distinguishing self from non-self, and it is these molecules that lead to rejection during organ transplantation. Siddle and colleagues had previously shown that MHC Class I variation in the population is very low and that this could explain the absence of an immune response following infection. Their new study is more comprehensive, but again finds low genetic variation in MHC Class I types and common variants in most individuals. Interestingly, they find that the apparently resistant subpopulation in the northwest has 14 unique sequences that are different - although only just - from the rest of the population. They propose that, counterintuitively, it is a restricted MHC repertoire that protects against infection: if most individuals have types X, Y and Z and you only have Z, it makes it much easier for you to spot X and Y as foreign instead of part of you. As far as I understand their paper, however, they do not go so far as to say that the northwestern population has this necessary restricted repertoire.

A modern-day Noah's Ark

The Save the Tasmanian Devil Program, a joint strategy of the Australian and Tasmanian state governments in partnership with the University of Tasmania, has the daunting job of protecting this animal. It is the world's largest carnivorous marsupial, and a marvellous little beast. Its name would suggest otherwise, of course, so-called because early European settlers would hear its disturbing screeches at night and assume, because they couldn't see what it was, that it must be the devil. It is also the perfect scavenger, leaving no trace behind, not even bones, when it has finished a meal. This did nothing for its fearsome reputation, and like the thylacine it was hunted almost to extinction. But the extinction of the thylacine made people sit up and notice, and the devil was saved. But the thinning of the population did few favours for its genetic diversity, which is, as we have seen, part of the problem.

To aid conservation efforts, isolated disease-free populations have been established on the Australian mainland. These Noah's Ark communities are an essential endeavour, but very much an insurance policy. In 2009, 57 new joeys bolstered the insurance population to 196. But to make more of these populations, we need to be sure of choosing disease-free individuals. But when the symptoms aren't always immediately obvious, how can this be done?

The devil transcriptome

Late last year, an excellent study by Elizabeth Murchison and colleagues was published in Science, and told of a particularly interesting find. They screened tumour cells and non-infected cells to see what makes them differ. Again they found that the genotype of tumours across individuals are the same, and that this differs from non-tumour cells, which you would expect. They then looked at micro RNA (miRNA) expression between tumour and normal cells - of 114, those expressed in tumour cells formed a unique profile most similar to brain tissue. In addition, two miRNAs, miR-29b and miR-126, had reduced expression in DFTD. These normally suppress tumours - their reduction increases the risk of cancer.

The key discovery of the paper, however, followed an investigation into the DFTD transcriptome, the genes expressed in DFTD. Because these cells are genetically distinct from non-infected cells, you can imagine that they act differently too, especially if they seem to behave closer to brain tissue. The team found that 20 genes are expressed at least twice as much in DFTD as in a control cell line. Of these, the most expressed gene encodes myelin basic protein - in fact 9 of the 20 genes are used in the myelination pathway. But what is myelination, and why is this significant?

Myelin is a protein that ensheaths nerve fibres, insulating them and, through a clever method beyond this already overlong tale, indirectly accelerates nerve impulses. It is essential for the neurology of any animal, because without it we'd function as rapidly as a vegetable. It is so important that the immune system never, ever touches it.

So could this be it? Could it be that the DFTD tumour, through a quirk of nature (and possible common origin), is sufficiently similar to components of the nervous system that the immune system simply leaves it well alone? If so, this is fascinating and very, very clever (although unintentionally of course). No sympathy from the devil, however. Murchison goes on to propose one of the myelination components, periaxin (PRX), as a suitable marker to test for non-facial and metastasized DFTD tumours, which are currently difficult to diagnose. It's not a cure, but it will help with confirming the disease status of insurance populations.

Why all this matters

Nature is a funny thing. It's a self-sustaining web of relationships, niches and battles that existed before us and will exist beyond us. In Yellowstone National Park in the USA, wolves were exterminated as vermin by 1926 and the whole ecosystem fell apart. Elk, no longer kept in check by the wolves, overbrowsed the streamside willows and shrubs; birds consequently lost their nesting spaces and the riverbanks were no longer protected from the sun or from erosion; waters consequently became broader, shallower and warmer, so fish and other aquatic species suffered. The elk also overgrazed on sprouts of young aspen, preventing their full growth, and coyotes thrived, preying too much on small mammals, depriving badgers and foxes of food. Wolves were reintroduced in 1995, and since then the elk population has halved, aspens can regrow, coyote numbers have reduced (allowing a pronghorn resurgence), stream banks have been stabilized by the return of willow and other vegetation, providing nesting sites for birds and shade over the water. Beaver colonies have increased, their dams creating microhabitats for fish, amphibians, birds and insects. And carrion from wolf kills has boosted scavengers such as eagles, bears and, to complete the circle, coyotes.

Likewise, the Tasmanian devil is the glue that holds together their environment. Without them, unwanted guests can prosper at the expense of more vulnerable native species, such as Tasmanian bettongs, eastern quolls and eastern barred bandicoots. Without the thylacine, and because Tasmania's other top predator, the wedge-tailed eagle, is endangered, the ecosystem heavily relies on the devil to keep it together. The effects are already being seen: without devils to clean up carcasses, foxes and feral cats are moving in, especially in the northeast, where devil numbers have dropped by 90% and abandoned biomass has increased by 50-100 tonnes per night. This brings a whole host of further problems. In the September 2009 newsletter of the Save the Tasmanian Devil Program there is a particularly revealing story. A pheasant-shooting tourist venture has been forced to close because of the loss of devils. Feed for the pheasants used to attract flocks of other birds, enriching the environment - there were quails, bronze-wing pigeons, parrots and robins. But when the devils disappeared, in came the feral cats to fill their niche in what must have been, as a result of the birds, a feline paradise.

"There are more than 600 species of plant and animal currently threatened in Tasmania. The loss of the Tasmanian devil would impact, even devastate, many of them."

We have become all too familiar with tales of extinction as a result of mankind, through hunting, greed or indirectly as a consequence of us simply not realising how stupid we can be. I live in a country where there used to be bears, wolves and wild boar. All across Australia there used to be giant marsupials, the so-called megafauna, but for whatever reason, they've all gone. The familiar faces around the world may also soon be gone: the gorilla, the tiger. The northern white rhino might be gone already. But the Tasmanian devil is not a lost cause. It is not going extinct, refreshingly, because of us. But if we work at it, supporting the scientists and ecologists and hard-working individuals who are out there in the field, there's no reason why we can't crack the mysteries surrounding this horrible disease and why we can't save the world's largest remaining carnivorous marsupial. You may not have believed that such a creature existed until you read this, but now you can go away believing that we can do right by it.

A hefty list of references - all relevant and used above in an unprofessionally disorganised fashion:

Borrell, B. Hopes of a tumour test for Tasmanian devils. Nature News 31 Dec 2009
Alderton, G. K. The details are not so devilish. Nature Reviews Cancer 10, 79 (2010)
Murchison, E. P. et al. The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science 327, 84-87 (2009)
Siddle, H. V. et al. MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer. Proceedings of the Royal Society B 10 March 2010 (doi:10.1098/rspb.2009.2362)

From EcoHealth (journal) volume 4, September 2007:
Dobson, A. P. Sympathy for the Devil. pp241-243
McCallum, H. et al. Distrubution and impacts of Tasmanian Devil Facial Tumour Disease. pp318-325
Jones, M. E. et al. Conservation management of Tasmanian Devils in the context of an emerging, extinction-threatening disease: Devil Facial Tumor Disease. pp326-337
Woods, G. M. et al. The immune response of the Tasmanian Devil (Sarcophilus harrisiii) and Devil Facial Tumour Disease. pp338-345
Pyecroft, S. B. et al. Towards a case definition for Devil Facial Tumour Disease: what is it? pp346-351

Save the Tasmanian devil (www.tassiedevil.com.au)
Newsletters: March 2010; Sept 2009

The wolf bit: National Geographic, March 2010 pp50-51

Encyclopedia of Life (www.eol.org): Sarcophilus harrisii

If any of the images used require permission, I apologise and will happily apply/change their use. The photographs seem to appear in various websites and I am uncertain of their source(s).