The Tasmanian devil and its transmissible cancer : physiology of the devil-DFTD interaction

The Tasmanian devil, the largest living marsupial carnivore, has been threatened with extinction because of a rare form of infectious disease, a transmissible cancer known as Devil Facial Tumour Disease. The disease emerged in the early 1990's in the northeast of Tasmania and has since spread across 90% of the wild Tasmanian devil range. Fatal in almost 100% of cases, DFTD has dramatically impacted devil numbers which have declined more than 90% at local scales and more than 80% on average. In this thesis, I apply concepts from host-pathogen theory to understand the interaction between DFTD and infected devils at the individual level. I use field-based empirical and experimental observations in two devil populations in the wild to understand the pathogenicity of the cancer and the responses from the hosts. By applying host-pathogen theory to this unconventional infectious disease, I assess patterns of tolerance and resistance in hosts which I discuss from an evolutionary perspective. Metabolic and immune condition of devils interact with DFTD infection and progression in ways that suggest a level of tolerance and resistance to DFTD. There are consistent sex differences across metabolic and immune responses in how devils experience and respond to DFTD progression. DFTD increases the metabolic demand on infected individuals and may eventually present a constraint on the host energy budget and on the tumour itself. This is evident in an overall decline in body condition with tumour progression. Sex-differences in tolerance to DFTD are suggested by different rates in decline of body condition among the sexes, with body condition of males declining at approximately five times the rate of females at a similar cancer burden. Evidence for resistance to DFTD is provided by the positive association between the number of antigen-presenting cells in tumour tissue and the propensity of tumours to grow more slowly than expected and even to fully regress. Males and females also appear to differ in their capacity to respond to infection, with sex differences in the relationship between antibodies to DFTD and infection status. Analysing the devil-DFTD system within the framework of host-pathogen theory helps to understand how this cancer interacts with its hosts. This study provides the first evidence of patterns of tolerance to disease progression and resistance against infection by DFTD in wild devil populations. The enhanced metabolic rates that infected devils may experience is expected to act as a constraint on both tumour and devil physiology, and eventually favour natural selection for slower growing tumours and/or hosts with low maintenance costs. The sex differences in devils in tolerance and resistance to DFTD suggest both that the selective forces deriving from the infection affect males and females differentially, and that the selective forces acting on tumours will depend according to whether they are harboured by a male or a female devil. The findings of this study have important implications both for the conservation of Tasmanian devils and in the broader context of disease and cancer ecology and evolution. Although Tasmanian devil populations are still declining as DFTD reaches the last na‚àövòve populations in the northwest of Tasmania, the species persistence in long-term infected areas suggests an ongoing evolutionary process between devils and DFTD. Studies to understand the genetic basis of the patterns of tolerance and resistance that are reported here are important to inform conservation management. The main conservation strategy implemented to date is the maintenance of disease-free populations in captivity and semi-wild on islands and fenced reserves to reintroduce individuals into the wild. In this context, the introduction of devils from those populations into the wild is expected affect the disease epidemic which may eventually dilute local adaptations. The ongoing evolutionary processes between devils and DFTD need to be explicitly incorporated into conservation management. In a broader context, study of the ecological interactions between hosts and pathogens in emerging infectious diseases, such as the devil-DFTD system, provide important insights into host and pathogen co/evolution. DFTD is a young disease in evolutionary terms and provides the opportunity to observe how host and pathogen evolve on ecological time scales. By studying novel host-pathogen interactions under natural conditions in the wild we can formulate predictions about evolution of traits, test them and eventually advance theory. One of the main limitations in cancer research has been the individual nature of the disease: tumours emerge and die within the same organism. This individual-case basis of most cancers limits the study and understanding of cancer as a pathogen subject to ecological and evolutionary forces. In this context, the capacity of DFTD to be transmissible among hosts provides a unique opportunity to study cancer-host evolution in vivo with potential implications in the emergent field of cancer therapy such as immune and adaptive therapies.