Brink of Extinction: The Tasmanian Devil

Many factors affect the Tasmanian devil but none so severe and urgent as Devil Facial Tumour Disease (DFTD) which has killed up to 90% of the wild population and continues to threaten the species with extinction.

Two Tasmanian devils lying on the ground

Sarcophilus harrisii, better known as the Tasmanian devil, is the largest carnivorous marsupial in the world and makes its home solely on, as you would imagine, the island of Tasmania, Australia.

Many factors affect the Tasmanian devil, such as habitat loss, introduced predators and roadkill, but none are more threatening to the entire species as Devil Facial Tumour Disease (DFTD).

DFTD is a very rare form of transmissible cancer found in Tasmanian devils. The cancer cells themselves act as the infectious agent, being transmitted from devil to devil most commonly via biting around the face. This behaviour is ubiquitous throughout the species and occurs when fighting over food and in mating.

Since its documented appearance in 1996, DFTD has killed approximately 90% of the population. So far, no subject has shown any natural immunity as the cancer does not seem to produce any immune response from the animal. Mortality rates are 100%. The IUCN has since listed the Tasmanian devil as “Endangered”.

The body has its own mechanisms in place to recognise foreign cells. When a foreign cell is located an immune response is triggered and the cell is usually destroyed. This is how animals, including humans, naturally fight bacterial infections and why blood transfusions require matching blood types. However, the DFTD cancer cells do not display any MHC-I (major histocompatibility complex class I) proteins on the surface of their cells. These MHC-I proteins are what the body uses to recognise if a cell is native or foreign. Therefore, without these MHC-I proteins no immune response is triggered in the Tasmanian devil and the cancer is free to grow, proliferate and spread, ultimately causing death via organ failure or starvation.

Tasmanian devils are apex predators and therefore play a vital role in the Tasmanian ecosystem. Their extinction could cause a huge population growth in foxes, feral cats and possums on the island, which could potentially result in further extinctions of other animals.

There is hope, however, as scientists around the world are exploring multiple avenues for a cure.

One avenue of research has been relatively successful in inducing the expression of the MHC-I proteins on the surface of the cancer cells. The study concluded that DFTD cancer cells possessed all the genetic machinery to produce and express MHC-I proteins on the cell surface. This allowed for the devil’s own immune response to destroy the cancer. However, the sample size was extremely small — an inherent problem when working with an endangered species — and there are still significant hurdles in this research before a potential vaccine can be produced en masse.

recent study from January 2019, published in the journal Cancer Cell, found overexpression of cell surface receptor proteins known as ERBB receptors. Human cancer cells also exhibit overexpression of ERBB receptors. These proteins bind to signalling molecules outside of the cell and thus initiate a cascade of processes within the cell which ultimately leads to the activation and/or repression of specific genes. In the case of DFTD, ERBB activates a series of processes which ultimately activates a protein called STAT3. STAT3 then activates genes related to metastasis (malignant growth) of the cancer cell (Figure 1).

Figure 1: A brief overview of ERBB receptor binding to a signalling molecule. A signalling cascade is initiated, ultimately activating STAT3. STAT3 initiates the expression of metastasis genes.

By inhibiting either the ERBB receptors or the STAT3 proteins from becoming activated, the study found that the cancer cells entered an arrested state. What’s more, the expression of MHC-I proteins on the cell surface was re-established with the inhibition of ERBB and STAT3, provoking a natural immune response in the devils. The study hypothesised that the overexpression of STAT3 inhibits the expression of MHC-I proteins.

There is still a way to go before an effective, large-scale treatment can be developed. In the meantime, captive breeding programs are in effect within Tasmania and mainland Australia in an effort to save the species and keep isolated populations disease free.

Further Reading

Hollings, T., McCallum, H., Kreger, K., Mooney, N. and Jones, M. (2015). Relaxation of risk-sensitive behaviour of prey following disease-induced decline of an apex predator, the Tasmanian devil. Proceedings of the Royal Society B: Biological Sciences, 282(1810), p.20150124.

Kosack, L., Wingelhofer, B., Popa, A., Orlova, A., Agerer, B., Vilagos, B., Majek, P., Parapatics, K., Lercher, A., Ringler, A., Klughammer, J., Smyth, M., Khamina, K., Baazim, H., de Araujo, E., Rosa, D., Park, J., Tin, G., Ahmar, S., Gunning, P., Bock, C., Siddle, H., Woods, G., Kubicek, S., Murchison, E., Bennett, K., Moriggl, R. and Bergthaler, A. (2019). The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease. Cancer Cell, 35(1), 125–139.

Tovar, C., Pye, R., Kreiss, A., Cheng, Y., Brown, G., Darby, J., Malley, R., Siddle, H., Skjødt, K., Kaufman, J., Silva, A., Baz Morelli, A., Papenfuss, A., Corcoran, L., Murphy, J., Pearse, M., Belov, K., Lyons, A. and Woods, G. (2017). Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils. Scientific Reports, 7(1).

Woods, G., Howson, L., Brown, G., Tovar, C., Kreiss, A., Corcoran, L. and Lyons, A. (2015). Immunology of a Transmissible Cancer Spreading among Tasmanian Devils. The Journal of Immunology, 195(1), 23–29.

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