Since the early 1990’s Tasmanian devils have been facing a novel thereat: devil facial tumour disease (DFTD), a clonal transmissible cancer. During the following 20 years the cancer epidemic caused severe population declines throughout Tasmania, resulting in the species listed as Endangered by IUCN. The recent discovery of a second and independently evolved transmissible cancer, devil facial tumour 2 (DFT2), suggests that devils are predisposed to the emergence of clonal malignant cell-lines and warrants integrative approaches to manage wild and captive populations. The severity of the epidemic and predictions of disease-induced local extinctions led to the creation of captive and free-range insurance metapopulations, as well as targeted strategies for population management such as disease eradication trials, reintroductions and translocations. Over the last decade, multi-institutional research teams have developed transdisciplinary approaches to understand the broad effects of DFTD at individual, population and ecosystem levels. Here I discuss recent advances in research, including evidence of rapid evolutionary responses to the epidemic, adaptive immune responses leading to tolerance and resistance to infection, devil - tumour interactions and their effects on epidemiology and population dynamics. I emphasise how understanding the interplay of disease ecology, epidemiology and evolutionary processes provide a solid bridge for integrating applied science to wildlife disease management. The Tasmanian devil and its transmissible cancers have become an ideal model system to understand how species respond and evolve to novel threats in nature and highlights the need for developing integrative and adaptive management strategies in the face of emerging infectious diseases.

The life histories of organisms are shaped by trade-offs in the allocation of resources to biological processes that maximise fitness. As resources are often limited, investment of energy into reproduction could result in less energy being available for immune function, resulting in a higher susceptibility to pathogens and parasites, including transmissible cancers.
Despite marsupials having an immune system of similar complexity to eutherians, the majority of research has focussed on the life history and immune trade-offs in northern hemisphere herbivorous eutherians or in male semelparity in small dasyurids. Tasmanian devils (Sarcophilus harrisii), the largest species of the Dasyuridae family (characterized by the predisposition for post-reproductive senescence), potentially face extinction in the wild due to the recent emergence of two transmissible cancers, Devil Facial Tumour Diseases (DFTD, DFT2).
Here we investigate how various factors, including age, sex, seasons, variation in exposition time to DFTD/DFT2 etc., influence Tasmanian devil innate and adaptive immune functions, and concomitantly disease progression and epidemiology. By unrevealing the underlying host responses to transmissible cancers, the project will contribute to improving the long-term conservation prospects of this iconic species.

We will give a brief update on recent advances in devil immunology and previous devil facial tumour disease vaccination efforts. We will lay out a road map for developing an oral bait vaccine (OBV) platform to combat and control the spread of devil facial tumours (DFTs). The OBV approach has an extensive safety record and was the primary approach for rabies virus elimination from wild carnivores across broad and diverse landscapes. Like rabies virus, DFTs are transmitted by oral contact, so a DFT OBV that immunizes the oral cavity and induces resident memory cells could be advantageous. The viral vector used in the OBV could also be used as a standard vaccine in key areas and prior to release of translocated devils. Additionally, exposing infected devils that already have tumours to OBVs could serve as an oncolytic virus immunotherapy. The primary challenges may be identifying appropriate DFT-specific antigens that stimulate protective immunity and optimization of field delivery methods to immunize an adequate fraction of the target population. As DFT2 is currently detected only in the channel region of southern Tasmania (~550 km2), we will focus initially on an OBV that could halt the spread or eliminate DFT2. Translation of an OBV approach to control DFT transmission will be challenging, but the approach is feasible and necessary to combat ongoing and future disease threats.

Top predators have suffered staggering global declines, with flow-on effects through food webs. Tasmania’s largest carnivore, the Tasmanian devil, has suffered severe population declines (~80%) following the emergence of a transmissible cancer, devil facial tumour disease. Here, using multiple lines of enquiry, I will outline the growing evidence that suggests devils impose top-down control on ecosystems, including feral cats. In the absence of devils, cats increasingly scavenge. Tasmania-wide camera trapping shows that devil and cat abundance is negatively associated; where devils are abundant, cats are typically rare. This has seemingly had a cascading effect on the southern brown bandicoot, a species with similar characteristics to the many mammals already driven extinct by introduced predators. Bandicoots seem able to withstand moderate cat densities but were never observed at sites with high cat density. Conversely, the native mesopredator, the spotted-tailed quoll, has not increased in abundance in response to devil declines. Using empirical examples from the introduction of devils to Maria Island, I will discuss the role that devils could play in restoring top-down control in ecosystems that lack apex predators and how this could benefit the conservation of other threatened species.

An outbreak of epidemic disease in a population can have dramatic impacts, not just on mortality rates, but on the individual development trajectories and life history of survivors. Tasmanian devil facial tumour disease (DFTD), a transmissible and deadly cancer of Tasmanian devils (Sarcophilus harrisii), was first detected in the Northeast of Tasmania in 1996, and rapidly spread across the island. Following infection, the disease proved to be nearly 100% fatal, and the epidemic led to population declines of up to 95%, and an overall decline in devil abundance of approximately 80%. However, populations have generally persisted. We analysed 18 years of longitudinal capture records from devil populations across Tasmania in a hierarchical Bayesian model framework, incorporating weight, head width and number of tooth wear and eruption measures to improve estimates of birth date. We identify disease-induced shifts in the timing of reproduction and a loss of population-level synchrony in reproduction, including precocial breeding congruent with the arrival of DFTD to the local area. These shifts can have significant ramifications for the life history of surviving individuals. We also discuss the potential implications of these results for management of disease in devil populations, with particular emphasis on the role of precocial breeders, and the offspring of precocial breeders in population persistence following the introduction of DTFD.

Animal behaviour is key to the disease transmission process. In the case of the Tasmanian devil, spread of its transmissible cancer, devil facial tumour disease (DFTD), is driven by aggressive encounters between individuals. Investigation of how devil's interaction patterns influence their likelihood of involvement in the transmission process is critical to our understanding of DFTD. We studied the social networks of devil populations both pre- and post-DFTD emergence to determine 1) how interaction patterns drive involvement in potential transmission events, and 2) whether behaviour of devils changes post-infection. The interaction patterns of males during the mating season were a strong driver of bite wound accrual. Positive DFTD infection status was linked to both a reduction in interaction rate and centrality within a devil's social network. These results will be discussed in the context of Tasmanian devil conservation in the face of DFTD.

The Tasmanian devil (Sarcophilus harrisii) is highly endangered in the wild due to Devil Facial Tumour Disease (DFTD), a lethal transmissible cancer. The disease is caused by a clonal cancer cell allograft which is transmitted by biting. DFTD is characterised by tumour growth on facial, oral and neck regions of the host, with infected devils usually dying within 12 months after clinical evidence of infection. The only available method of diagnosis is by detection of macroscopic tumours and confirmation in the laboratory from tumour biopsies. The lack of a pre-clinical diagnostic test represents a current limitation in understanding transmission dynamics and proposing management actions.
A potential biomarker for DFTD is tumour derived exosomes, which are nanosized extracellular vesicles produced by tumour cells. These also may contain molecules from their cell of origin which have the capacity to modify host-tumour interactions. Tumour derived exosomes modulate the interaction between cancer cells and their microenvironment, with increasing evidence of playing a role in metastasis, angiogenesis and modulation of the immune system.
This study characterises a qualitative and quantitative proteomic analysis of exosomes derived from DFTD cells, with the key finding of expression of proteins involved in metastasis and immune suppression. Additionally, we report the protein expression profile of plasma exosomes from healthy and diseased wild devils, showing clear differences between them. The results open possibilities for a preclinical diagnostic and prognostic biomarker for examining DFTD progression and immunity in wild populations.