A disease in disguise: DFT2, the second transmissible cancer in the Tasmanian devil
Creators: name: Broeren, Regi
Publisher: name: University of Tasmania
Year: 2024

description: Cancer is a ubiquitous disease across multicellular organisms, which affects the competitive abilities of individuals, their fitness and survival. There is increasing evidence that oncogenic phenomena can have an important role in shaping ecological and evolutionary processes, from individuals to ecosystems. Directly transmissible cancers, however, are rare in nature but can have devastating effects on host populations. Tasmanian devils have been threatened by a clonal transmissible cancer, devil facial tumour disease (DFTD), which emerged more than 30 years ago causing severe population declines throughout Tasmania. In 2014, a second transmissible cancer devil facial tumour 2 (DFT2) was discovered in south-eastern Tasmania. DFTD and DFT2 evolved independently, which suggests that devils are particularly susceptible to transmissible cancers. There remain many unknowns about DFT2’s epidemiology and it is yet unknown if and to what extent this second transmissible cancer poses an additional threat to the Tasmanian devil. <br>This thesis highlights that transmissible cancer research outcomes are transdisciplinary and can aid answering analogous epidemiological questions. Specifically, I aim to 1) identify and compare DFTD and DFT2’s disease characteristics, 2) improve our understanding of the impacts of DFTD and DFT2 progression, on an individual and population level, and the occurring host defences, and 3) compare the metastatic characteristics of DFTD and DFT2. To address urgent knowledge gaps, I use longitudinal epidemiological and population dynamics data as well as biological samples, derived from co-infected regions. <br>First, I conducted a literature review (chapter 2) to synthesise the oncological perspectives developed through recent research on naturally occurring clonally transmissible cancers (CTCs). Determining communalities and divergencies between CTCs may allow predictions about parallel processes in the epidemiologies of these diseases. The devil-DFTD-DFT2 system presents a unique research opportunity due to the high trackability of the ecological and evolutionary processes of both cancers and host populations. Furthermore, I discuss why transmissible cancers can be considered as true pathogens, and how host-pathogen theory can guide research into oncogenic processes. <br>Second, I compared bite-injury patterns with infection characteristics for DFTD and DFT2, to improve our understanding of what causes the varying trends in anatomical manifestation and demographic infection rates between DFTD and DFT2, which can be caused by differing exposure patterns or possible molecular variation between pathogens. The study did not find a clear indication of biting patterns instigating the observed differing cancer characteristics. Furthermore, the results support that the cancers manifest in different fashions: opposed to DFTD, DFT2 occurs more frequently on the body and displays lower female infection rates. Lastly, tissue type is associated to individual tumour volume, with oral tumour subceeding cutaneous tumour volumes, and tumours manifesting in mixed tissue having the greatest volume. These findings may bear implications for the differentiation of transmission features between DFTD and DFT2, and their health impacts on the Tasmanian devi. Advancing knowledge of this multi-pathogen system has implications for Tasmanian devil conservation as well as understanding ecological and epidemiological processes in other emerging infectious diseases. <br>Third, I evaluated 1) long-term trends of internal metastatic occurrence in DFTD, 2) identified the external tumour threshold around which DFTD metastasis is likely to occur and 3) compared DFTDs and DFT2s metastatic rates and the tissues commonly associated with metastasis. Although internal metastasis is the primary cause of cancer-induced mortality, underlying processes and long-term trends are not well studied. I found that prolonged population exposure had no effect on DFTD’s metastatic prevalence and cancer progression leading to metastasis. Furthermore, DFTD’s external tumour burden threshold is low, and DFTD and DFT2 show similar spatial distribution patterns of internal metastasis. The findings improve our ability to predict long-term disease impacts in devil populations and provide further insights to understand cancer progression in wildlife. <br>Fourth, I reveal how the devil’s coping mechanism compares between DFTD and DFT2 infection. Given that the expressed composition of host defences has fundamental implications on epidemiological dynamics and the evolution of pathogen virulence, it is crucial to understand how and to what degree the devil minimises the cost of DFTD and DFT2 infection. Results show that DFTD and DFT2 progression affects the body condition equally, without sex-based variation. However, females with pouch young cope better with infection compared to non-carrying females. Evaluating how devils respond to the emergence of DFT2 and the cascading effects on the ability to cope with DFTD, represents an important milestone in our ability to predict disease dynamics and selective processes. <br>This thesis generates new knowledge on the ecological and epidemiological interactions of DFT2 and DFTD, at a highly dynamic evolutionary point of their epidemiology. The results can be used as a benchmark to understand the eco-evolutionary pressures underpinning adaptive processes in wildlife cancers and informs management interventions to ensure the conservation of the Tasmanian devil and other species threatened by emerging diseases with high mortality rates.