Devil Facial Tumour Disease: The Disease Decimating Tasmania’s Largest Marsupial

Devil Facial Tumour Disease: The disease decimating Tasmania’s largest marsupial.

INTRODUCTION

Tasmanian devils (Sarcophilus harrissii) are the largest extant marsupial carnivore and are endemic to the island of Tasmania off the coast of Australia. Found throughout the island range, they inhabit open eucalypt environments, coastal scrub and pasture mixed with native sclerophyll forests (Jones and Barmuta, 2000; Pukk, 2005). This sexually dimorphic species (male 7.5-13.0 kg; female 4.5-9.0 kg) are primarily nocturnal, lead hunter-scavenger lives, and usually live between 5-6 years in the wild (Guiler, 1978). In the last two decades the population of devils in Tasmania has drastically declined since the emergence of the fatal transmissible cancer; Devil Facial Tumour Disease (DFTD). Since 1996, the wild devil population has declined by 80% (Lazenby et al, 2018), and in areas where the disease has been present longest, local populations have declined by up to 95% (Lazenby et al, 2018; McCallum et al, 2007). Over the last twenty years, extensive research has been conducted to better understand the nature of DFTD and create conservation solutions in order to protect this ecologically important species.

BACKGROUND

DFTD appears to have evolved fairly recently, first photographed in 1996, with the first pathologically documented case occurring in 1997. No record of the disease appeared in any of the 2000 Tasmanian devil individuals captured between 1964-1995, by researchers conducting capture-mark-recapture studies (McCallum and Jones, 2006).

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Since its emergence in the north-eastern peninsula, DFTD is now present in populations across Tasmania. The spread of the disease supports that DFTD has single origin, rather than multiple ones (McCallum et al, 2007). Figure 1. shows how the disease gradually spread south and southwest at a mean rate of 7km/yr^-1 (McCallum et al, 2007). As of 2018, DFTD is prevalent across 80% of Tasmania (Woods et al, 2018).

Transmission of the disease between individuals most likely occurs through biting (Pearse, and Swift, 2006), associated with sexual behaviour and mating, though transmission through sharing food and cannibalism of infected carcasses is possible (Hawkins et al, 2006). Studies of smears from the canine teeth of devils with orally erupting DFTD tumours reported presence of DFTD cells (Obendorf, and McGlashan, 2008). The tumour cells appear to be easily dislodged (Pearse, and Swift, 2006), and with bites most frequently occurring around the mouth and neck matching locations where tumours tend to occur, there is strong evidence for DFTD passing between individuals in this way.

(Woods et al, 2018)

Figure 1. Spread of DFTD. DFT1 was first recorded in the north-east Tasmania (green) in 1996. The first recorded case of DFT2 was separated by distance and time to DFT1 as the first case of DFT2 (red) was in 2014 in south east Tasmania. DFT1 has spread over most of the island, whereas DFT2 is contained to a small area.

PATHOLOGY

DFTD comprises of two independent transmissible cancers, DFT1 (first observed in 1996) has caused the drastic decline of the species since its emergence. DFT2 was first observed as histologically distinct to DFT1 in 2014 (Pye et al, 2016a) though its observed range has been restricted to the Channel Peninsula. DFTD tumours can be caused by two genetically distinct transmissible cancers, that are grossly indistinguishable from one another, but the tumours they cause are histologically distinct (Pye et al, 2016a).

DFT1 is of neuroendocrine origin, the tumour originating in a Schwann cell (Murchison et al. 2010) of a female devil, evidenced by DFT1 having DNA from two homologous X chromosomes (Pye et al, 2016a). The genetic expression of tumours in all DFT1 cases are identical. Its cytogenetic profile is characterised by the absence of both sex chromosomes, both chromosomes 2, one chromosome 6 and a deletion on the long arm of chromosome 1, plus four unidentifiable marker chromosomes [Figure 2.] (Pearse, and Swift, 2006). The tumours only contain 13 chromosomes, unlike the devils 14 (Pearse, and Swift, 2006). DFT1 tumours are aggressive, poorly differentiated, malignant neuroendocrine round cell neoplasms, that primarily affect the face, neck, with frequently occurring metastatic spread to the regional lymph nodes and visceral organs (Loh et al, 2006).

DFT2 bares no similarity, genetic or cytogenetic to DFT1, causing histologically distinct tumours characterised by sheet of pleomorphic cells arranged in a solid pattern (Pye et al, 2016a). Cytogenetic analysis revealed that all individuals shared an identical aneuploid karyotype, that was missing the four marker chromosomes present in DFT1, and also carried both X and Y sex chromosomes [Figure 2.] (Pye et al, 2016a). The presence of a Y chromosome in DFT2’s karyotype is incompatible with a single origin for DFT1 and DFT2 (Pye et al, 2016a). This suggests that DFT2 evolved independently. Much less is known about the pathogenic nature of DFT2.

Only three transmissible cancers have been observed in nature, DFTD, canine transmissible venereal tumour (CTVT) (Murchison, 2008) and soft-shell clam disseminated neoplasia (Metzger et al, 2015), and such was this rarity that the emergence of these clonal tumours was believed to be highly improbable (Pye et al, 2016a). This discovery of a second transmissible cancer in devils makes it possible that transmissible cancers as pathogens in natural populations has been underestimated; alternatively, while rare in most species, species-specific vulnerability may promote emergence in certain hosts, this suggests that devils may be particularly at risk for the emergence of transmissible cancers (Pye et al, 2016a).

Both DFT1 and DFT2 cause large malignant facial and oral tumours. DFT1 leads to death within 6 months of the outward appearance of the tumours (Lane et al, 2012). The tumour lesions are prone to secondary infection which may lead to septicaemia (Pyecroft et al, 2007).  Other factors include oral cavity lesions preventing mastication of food, damage to eyes or whisker beds, production of factors causing appetite loss, caloric diversion to the tumour, necrosis of tumour releasing toxins, and metastases to other organs such as the heart and brain (Pyecroft et al, 2007). DFT1 devils eventually succumb to infection or die of starvation. Mortality rate of DFT2 has not yet been studied.

IMMUNE EVASION

Tasmanian devils have a competent and functioning immune system yet fail to amount an immune response to DFT1 cells, histological analysis showing that T-lymphocytes does not infiltrate the primary tumours or metastases (Siddle et al, 2007). Devils have a low genetic diversity due to a “founder effect” in the population occurring 10,000-12,000 years ago (Jones et al, 2004). Low diversity at MHC loci was thought to be responsible for the lack of immune response (Siddle et al, 2007). MHC (major histocompatibility complex) is the genetic region containing genes for antigen presentation and determine graft recognition (Playfair and Bancroft, 2013). As skin graft rejection occurs, low genetic diversity cannot fully explain how DFT1 evades the immune system.

It was discovered that most DFT1 cells do not express MHC molecules on their cell surface, due to down regulation of genes essential to the antigen-processing pathway (Siddle et al, 2013). As MHC class I downregulation results in decreased sensitivity of tumour cells to T lymphocytes (Bubeník, 2005), this absence of MHC molecules is likely a major cause for the failure to mediate an immune response in the host, making cells ‘invisible’ to T lymphocytes.

CONTROL

Due to the rate of spread of the disease and early estimates predicting extinction in the wild within 25-35 years (Hawkins et al, 2006; Lachish et al, 2007; McCallum et al, 2007), there was a risk that devils would be decimated by DFT1 with no hope of genetic recovery before a vaccine could be produced and successfully administered to wild devils. Therefore, insurance populations have been established consisting of more than 700 devils held in 37 Australian zoos, fenced enclosures, a fenced peninsula (Forestier peninsula) and an island population (Maria island) (McLennan et al, 2018).

Insurance populations protected from the disease should maintain genetic and phenotypic diversity until either the evolution of resistance to DFT1, or wild devil extinction throughout Tasmania which would, by extention, cause disease extinction and allow for reintroduction (Jones et al, 2007). Insurance populations needed to maintain >95% genetic diversity for about 50 years to allow for reintroduction of wild populations (Jones et al, 2007).

Maria Island was ranked highly as a Tasmanian devil introduction site due to its large size, biodiversity, prey, land tenure and water availability, as well as having appropriate habitat and a lack of other threats such as vehicles and dogs (McLennan et al, 2018). Between 2012 and 2013, 28 devils were introduced, and a highly successful population ‘colonisation’ has been observed. Population on Maria Island is estimated to be around 92 individuals (95% CI 77-122; STDP unpublished data) as of January 2016 (McLennan et al, 2018). However, in order to maintain 95% wild-sourced gene diversity for the next 40 years, 10 new female founders need to be introduced into the population every three years (McLennan et al, 2018).

There has also been no conclusive evidence that culling on the Forestier Peninsula has reduced the rate of transmission, or a decrease in prevalence in the population of DFT1 compared to a comparable unmanaged site (Freycinet Peninsula) after 2.5 years (Lachish et al, 2010). Culling programmes are very expensive, costing the Tasmanian government in excess of $200,000 per year. Beeton and McCallum (2011) have suggested that culling should only be used once models can show its effectiveness.

There have been a few documented cases of cell mediated and humoral immune responses against DFT1 in wild devils (Pye et al, 2016b), which have helped to further vaccine research. Siddle et al, (2013) showed that after treatment with IFN- there was an increase in the number of MHC cells found on the surface of DFT1 cells. Tovar et al (2017) studied whether this could be exploited to produce a vaccine against DFT1, highlighting the viability of developing a vaccine.

CONCLUSION

It is highly important that we conserve Tasmanian devils in order to also protect Tasmania’s unique ecology and biodiversity. Devils control the introduction of feral cat and fox populations, which threaten many mammal species which have declined hugely in Australia, but which persist in Tasmania (Jones et al, 2007), which include but are not limited to, the Tasmanian bettong, the Eastern Barred Bandicoot and the flightless endemic Tasmanian hen would be highly threatened. The loss of these top predators from the ecosystem would predictably result in 1) and increased abundance of smaller predators, and a decreased abundance in their prey (Schmitz et al., 2000) 2) increased abundance of top predator prey, resulting in increased herbivory (Switalski, 2003) and 3) changes in ecosystem function due to changes in productivity, and community composition (Gehrt and Prange, 2007).

Therefore, protecting this endangered species is critical to the preservation and biosecurity of Tasmania, along with its unique flora and fauna.

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