Devil facial tumour disease

From Wikipedia, the free encyclopedia

Devil facial tumour disease causes tumours to form in and around the mouth

Devil facial tumour disease (DFTD) is an aggressive non-viral clonally transmissible cancer which affects Tasmanian devils, a marsupial native to the Australian island of Tasmania.[1][2] The cancer manifests itself as lumps of soft and ulcerating tissue around the mouth, which may invade surrounding organs and metastasise to other parts of the body. Severe genetic abnormalities exist in cancer cells - for example, DFT2 cells are tetraploid, containing twice as much genetic material as normal cells. DFTD is most often spread by bites, when teeth come into contact with cancer cells; less important pathways of transmission are ingesting of infected carcasses and sharing of food. Adult Tasmanian devils who are otherwise the fittest are most susceptible to the disease.

DFTD is estimated to have first developed in 1986.[3] There are two currently existing strains, both appearing to be derived from Schwann cells.[4] DFT1 is the main and older strain that infects most of the devil population. It was first described in 1996 in an animal from Mount William National Park in northeastern Tasmania.[2] DFT2 appeared around 2011[3] and was first detected in 2014; all cases are limited to the area of southern Tasmania near the D'Entrecasteaux Channel.[5] There still remain disease-free pockets in the relatively isolated south-west of the island.[6]

The disease poses a direct threat to the survival of Tasmanian devils as a species as the disease is almost universally fatal. In the two decades since the disease was first spotted, population of Devils (Sarcophilus harrisii) declined by 80% (locally exceeding 90%), as the condition spread through virtually entire Tasmania. However, by 2020 the spread has stabilised and the disease no longer appeared to be destined to exterminate all devils.[7] The Tasmanian Government, Australian universities and zoos are engaged in efforts to curb the disease. Culling infected individuals, the policy used by state officials until 2010, brought little success.[8][9] Thus the main prevention method became taking hundreds of devils into captivity and then releasing some of them into the wild. There is no cure for the cancer so far. Vaccination offers some promise in the fight against the pathogen, but researchers have not found a suitable candidate yet. A 2017 vaccine trial found that only 1 in 5 devils could resist DFTD; a DFT1 oral vaccine candidate is being tested in the captive devil population.[10]

Clinical signs[edit]

There is often more than one primary tumour.[11] Visible signs of DFTD begin with lumps of soft tissue around the mouth, which ulcerate.[12] Tumours are locally aggressive,[13] destroying the underlying bone of the jaw which interferes with feeding.[12] Tumours may also cover the eyes.[14] Devils usually die within six months from organ failure, secondary infection, or metabolic starvation.[15]

DFTD is rare in juveniles.[16] It affects males and females equally.[17]


The most plausible route of transmission is through biting, particularly when canine teeth come into direct contact with the diseased cells.[18] Other modes of transmission may include the ingestion of infected carcasses and the sharing of food, both of which involve an allogeneic transfer of cells between unrelated individuals.[19][20] The animals most likely to become infected are the fittest devil individuals.[21]


DFTD tumours are large soft tissue masses which become centrally ulcerated.[11] The tumours are composed of lobules of nodules of round to spindle-shaped cells, often within a pseudocapsule.[11] Tumours metastasise to regional lymph nodes involvement and systemically to the lungs, spleen and heart.[13] a study found evidence for an infiectous agent resembling a giant virus that was capible of turning heathy cells into cancer cells. It was found to be a huge retrovirus with similar viruses being found in human and canine cancer cells.[22]

Tumour characteristics[edit]

Karyotype of DFTD

Tasmanian devil cells have 14 chromosomes; the oldest-known strain of the tumour cells have thirteen chromosomes, nine of which are recognisable and four of which are mutated "marker" chromosomes.[23] More recently evolved strains have an additional mutant marker chromosome, for a total of fourteen chromosomes.[24][25] Researchers identified the cancer as a neuroendocrine tumour, and found identical chromosomal rearrangements in all the cancer cells.[26] The karyotype anomalies of DFTD cells are similar to those of cancer cells from canine transmissible venereal tumour (CTVT), a cancer of dogs that is transmitted by physical contact.[26] Among the mutations present in the tumour genome is trisomy in chromosome 5p, as well as several single base mutations, and short insertions and deletions, e.g., deletions in the chromosomes 1, 2 and 3. Some of the mutated or deleted genes in DFTD are RET, FANCD2, MAST3 and BTNL9-like gene.[27]

Classical DFTD likely originated in the Schwann cells of a single devil.[28][24] Schwann cells are found in the peripheral nervous system, and produce myelin and other proteins essential for the functions of nerve cells in the peripheral nervous system.[29][30] Researchers sampled 25 tumours and found that the tumours were genetically identical.[29] Using deep sequencing technology, the study authors then profiled the tumours' transcriptome, the set of genes that are active in tumours; the transcriptomes closely matched those of Schwann cells, revealing high activity in many of the genes coding for myelin basic protein production.[30] Several specific markers were identified, including the MBP and PRX genes, which may enable veterinarians to more easily distinguish DFTD from other types of cancer, and may eventually help identify a genetic pathway that can be targeted to treat it.[30]

In 2015, a second genetically distinct strain of DFTD was identified,[31] which was tetraploid, not diploid like the main form of the cancer. The tetraploid form has been linked to lower mortality rates.[32] The cell type origin of this strain of DFTD is unknown.[33] Increased levels of tetraploidy have been shown to exist in the oldest strain of DFTD as of 2014, which correlates with the point at which devils became involved in a DFTD removal programme.[citation needed] Because ploidy slows the tumour growth rate, the DFTD removal programme has been suggested as a selective pressure favouring slower-growing tumours, and more generally that disease eradication programmes aimed at DFTD may encourage the evolution of DFTD.[34] The existence of multiple strains may complicate attempts to develop a vaccine, and there are reports of concerns that the evolution of the cancer may allow it to spread to related species such as the quoll.[35]

In 2023 both DFTD strains were sequenced in a family tree indicating that the main strain DFT1 emerged around 1986 while DFT2 arose around 2011 and is found in only a small region of the island but it mutates around three times faster.[36][3]

Preservation response[edit]

Wild Tasmanian devil populations are being monitored to track the spread of the disease and to identify changes in disease prevalence. Field monitoring involves trapping devils within a defined area to check for the presence of the disease and determine the number of affected animals. The same area is visited repeatedly to characterise the spread of the disease over time. So far, it has been established that the short-term effects of the disease in an area can be severe. Long-term monitoring at replicated sites will be essential to assess whether these effects remain, or whether populations can recover.[37] Field workers are also testing the effectiveness of disease suppression by trapping and removing diseased devils, with the expectation that removal of diseased devils from wild populations would decrease disease prevalence, allowing devils to survive beyond juvenile years and so to breed.[37] One study reported that a system of culling prior to 2010 did not impede disease spread.[9]

A plan to create "insurance populations" of disease-free devils has been ongoing since 2005. As of June 2012, the insurance population has reached a combined total of 500 animals and representing over 98% of the genetic diversity of this species.[38] Most of these devils are living in Australian zoos and wildlife reserves. Beginning in November 2012 however, in an effort to create a population that is both wild and disease-free, Tasmanian devils have been relocated to Maria Island, a mountainous island off the east coast of Tasmania.[38] The Maria Island population has grown from a starting population of twenty-eight to 90, and experts will soon begin transferring healthy devils back to the mainland population.[39] A study on the survival rates of the Maria Island population found that in contrast to other carnivores raised in captivity, the Tasmanian devils were not adversely affected by being born in captivity when released on Maria Island.[40]

Due to the decreased life expectancy of the devils with DFTD, affected individuals have begun breeding at younger ages in the wild, with reports that many only live to participate in one breeding cycle.[41] Hence, Tasmanian devils appear to have changed breeding habits in response to the disease;[42] females had previously begun to breed annually at age two, for about three more years, dying thereafter of a variety of causes.[citation needed] Populations are now characterised by onset of breeding at age one, dying of DFTD, on average, shortly thereafter.[43] Social interactions have been seen to contribute to spread of DFTD in a local area.[44]

The decline in devil numbers is also an ecological problem, since its presence in the Tasmanian forest ecosystem is believed to have prevented the establishment of the red fox, with the most recent known organism accidentally being introduced into Tasmania in 1998.[45][26] Tasmanian devil young may now be more vulnerable to red fox predation, as pups are left alone for long periods of time.[46]

In response to the impact of DFTD on Tasmanian devil populations, 47 devils have been shipped to mainland Australian wildlife parks to attempt to preserve the genetic diversity of the species. The largest of these efforts is the Devil Ark project in Barrington Tops, New South Wales; an initiative of the Australian Reptile Park. This project aims to create a set of one thousand genetically representative devils, and is now a major focus of the insurance policy.[47]

In August 2023, the Devil Ark at Barrington celebrated the birth of the 500th devil since the project was launched.[48]

The Tasman peninsula is being considered as a possible "clean area" with the single narrow access point controlled by physical barriers. The Tasmanian Department of Primary Industries and Water is experimenting on culling infected animals with some signs of success.[49][50]

A diagnostic blood test was developed in mid-2009 to screen for the disease.[51] In early 2010, scientists found some Tasmanian devils, mostly in the north-west of Tasmania, that are genetically different enough for their bodies to recognise the cancer as foreign. They have only one major histocompatibility complex, whereas the cancerous cells have both.[52]

Oocyte banking may be useful in the conservation effort for Tasmanian devils, as the survival rate of cryopreserved oocytes is 70%.[53]


Spread of the disease as of 2015[54]

In 1996, a photographer from The Netherlands captured several images of devils with facial tumours near Mount William in Tasmania's northeast.[55] Around the same time, farmers reported a decline in devil numbers.[56] Menna Jones first encountered the disease in 1999 near Little Swanport, in 2001 capturing three devils with facial tumours on the Freycinet Peninsula.[57]

The theory that cancer cells themselves could be an infective agent (the Allograft Theory[58]) was first offered in 2006 by Pearse, Swift and colleagues,[58] who analysed DFTD cells from devils in several locations, determining that all DFTD cells sampled were genetically identical to each other, and genetically distinct from their hosts and from all other individual Tasmanian devils whose genetics had been studied; this allowed them to conclude that the cancer originated from a single individual and spread from it, rather than arising repeatedly, and independently.[58][59] Twenty-one different subtypes have been identified by analysing the mitochondrial and nuclear genomes of 104 tumours from different Tasmanian devils.[27] Researchers have also witnessed a previously uninfected devil develop tumours from lesions caused by an infected devil's bites, supporting the contention that the disease is spread by allograft, with transmission via biting, scratching, and aggressive sexual activity between individuals.[60] During biting, infection can spread from the bitten devil to the biter.[61]

Initially, it was suspected that devils had low genetic diversity, so that their immune system did not recognise the tumour cells as foreign.[31] However, it was later demonstrated that devils are sufficiently genetically diverse to mount a strong immune response to foreign tissue.[31]

Since June 2005, three females have been found that are partially resistant to DFTD.[62]

The devil population on the peninsula decreased dramatically. In March 2003 Nick Mooney wrote a memo to be circulated within the Parks and Wildlife Services calling for more funding to study the disease, but the call for funding was edited out before the memo was presented to Bryan Green, then Tasmania's Minister for Primary Industries, Water and Environment.[63][64] In April 2003, a working group was formed by the Tasmanian Government to respond to the disease.[65] In September 2003, Nick Mooney went to the Tasmanian daily newspaper The Mercury, informing the general public of the disease and proposing a quarantine of healthy Tasmanian devils. At the time, it was thought that a retrovirus was a possible cause. David Chadwick of the state Animal Health Laboratory said that the laboratory did not have the resources needed to research the possibility of a retrovirus. The Tasmanian Conservation Trust criticised the Tasmanian government for providing insufficient funds for research and suggested that DFTD could be zoonotic, posing a threat to livestock and humans.[66] On 14 October 2003, a workshop was held in Launceston.[67] In 2004, Kathryn Medlock found three oddly shaped devil skulls in European museums and found a description of a devil in London Zoo dying, which showed a similarity to DFTD.[68]

Calicivirus, 1080 poison, agricultural chemicals, and habitat fragmentation combined with a retrovirus were other proposed causes.[69] Environmental toxins had also been suspected.[70] In March 2006 a devil escaped from a park into an area infected with DFTD. She was recaptured with bite marks on her face, and returned to live with the other devils in the park. She wounded a male and by October both devils had DFTD, which was subsequently spread to two others (an incident that in retrospect would be understood in the context of the allograft theory of transmission).[71]

In 2006, DFTD was classed a List B notifiable disease under the Government of Tasmania's Animal Health Act 1995.[72] The strategy of developing an insurance population in captivity was developed. It was reassessed in 2008.[73] A 2007 investigation into the immune system of the devils found that when combatting other pathogens, the response from the immune system was normal, leading to suspicion that the devils were not capable of detecting the cancerous cells as "non-self".[74] In 2007, it was predicted that populations could become locally extinct within 10–15 years of DFTD occurring, and predicted that the disease would spread across the entire range of the Tasmanian devils causing the devils to become extinct within 25–35 years.[75]

In 2016, devils are endangered as the localised populations were shown to have declined by 90 per cent and an overall species decline of more than 80 per cent in less than 20 years, with some models predicting extinction. Despite this, devil populations persist in disease-stricken areas.[7] The devils have, in a way, fought back the extinction by developing the gene that is immune to face tumors. The genes have already existed in the Tasmanian devil as part of their immune system. They increased in frequency due to natural selection. That is, the individuals with particular forms of these genes (alleles) survived and reproduced disproportionately to those that lacked the specific variants when disease was present.[54]

A devil population in the far southwest of Tasmania has been reported to be free of DFTD.[76]

Society and culture[edit]

In 2008, a devil—given the name Cedric by those who treated and worked with him—was thought to have a natural immunity to the disease, but developed two facial tumours in late 2008. The tumours were removed,[77] and officials thought Cedric was recovering well; but in September 2010, the cancer was discovered to have spread to the lungs, leading to his euthanasia.[78]

Research directions[edit]

Vaccination with irradiated cancer cells has not proven successful.[79]

In 2013, a study using mice as a model for Tasmanian devils suggested that a DFTD vaccine could be beneficial.[80] In 2015, a study which mixed dead DFTD cells with an inflammatory substance stimulated an immune response in five out of six devils injected with the mixture, engendering for a vaccine against DFTD.[81] Field testing of the potential vaccines has been undertaken as a collaborative project between the Menzies Institute for Medical Research and the Save the Tasmanian Devil Program. Strong immune responses were induced by the vaccine,[82] but the vaccine did not protect all devils from developing DFTD. An oral bait vaccine for DFTD is in the early stages of development as of 2020.[83]

Research by Professor Greg Woods from the University of Tasmania's Menzies Institute for Medical Research has shown encouraging evidence for the potential development of a vaccine using dead devil facial tumour disease cells to trigger an immune response in healthy devils. Field testing of the vaccine is being undertaken as a collaborative project between the Menzies Institute for Medical Research and the Save the Tasmanian Devil Program under the Wild Devil Recovery program, and aims to test the immunisation protocol as a tool in ensuring the devil's long-term survival in the wild.[84]

In March 2017, scientists at the University of Tasmania presented an apparent first report of having successfully treated Tasmanian devils with the disease, by injecting live cancer cells into the infected devils to stimulate their immune system to recognise and fight the disease.[85][86] In 2019, researchers from University of Sydney reported constricted diversity of the T cell repertoire in devils with DFTD, suggesting that DFTD may impact the host immune system directly.[87] Several studies of immune checkpoint molecules, such as PD-1 and PD-L1, have been undertaken in devils and suggest that potential immune evasion pathways used by human cancers could also be active in DFTD.[88][89][90][91]

There is some evidence suggesting that the DFTD tumour is evolving to be less fatal to the Tasmanian devils.[92]


  1. ^ Taylor RL, Zhang Y, Schöning JP, Deakin JE (August 2017). "Identification of candidate genes for devil facial tumour disease tumourigenesis". Scientific Reports. 7 (1): 8761. Bibcode:2017NatSR...7.8761T. doi:10.1038/s41598-017-08908-9. PMC 5562891. PMID 28821767.
  2. ^ a b Bender HS (2010). "23. Devil facial tumour disease (DFTD): Using genetics and genomics to investigate infectious disease in an endangered marsupial". In Waters PD, Deakin JE, Marshall Graves JA (eds.). Marsupial genetics and genomics. Dordrecht: Springer. pp. 499–516. ISBN 9789048190232.
  3. ^ a b c Stammnitz MR, Gori K, Kwon YM, Harry E, Martin FJ, Billis K, et al. (April 2023). "The evolution of two transmissible cancers in Tasmanian devils". Science. 380 (6642): 283–293. Bibcode:2023Sci...380..283S. doi:10.1126/science.abq6453. PMC 7614631. PMID 37079675. S2CID 249172974.
  4. ^ Patchett AL, Coorens TH, Darby J, Wilson R, McKay MJ, Kamath KS, et al. (May 2020). "Two of a kind: transmissible Schwann cell cancers in the endangered Tasmanian devil (Sarcophilus harrisii)". Cellular and Molecular Life Sciences. 77 (9): 1847–1858. doi:10.1007/s00018-019-03259-2. PMID 31375869. S2CID 199389366.
  5. ^ James S, Jennings G, Kwon YM, Stammnitz M, Fraik A, Storfer A, et al. (October 2019). "Tracing the rise of malignant cell lines: Distribution, epidemiology and evolutionary interactions of two transmissible cancers in Tasmanian devils". Evolutionary Applications. 12 (9): 1772–1780. doi:10.1111/eva.12831. PMC 6752152. PMID 31548856.
  6. ^ Cunningham CX, Comte S, McCallum H, Hamilton DG, Hamede R, Storfer A, et al. (May 2021). Ostfeld R (ed.). "Quantifying 25 years of disease-caused declines in Tasmanian devil populations: host density drives spatial pathogen spread". Ecology Letters. 24 (5): 958–969. doi:10.1111/ele.13703. PMC 9844790. PMID 33638597.
  7. ^ a b Patton AH, Lawrance MF, Margres MJ, Kozakiewicz CP, Hamede R, Ruiz-Aravena M, et al. (December 2020). "A transmissible cancer shifts from emergence to endemism in Tasmanian devils". Science. 370 (6522). doi:10.1126/science.abb9772. PMID 33303589. S2CID 228084546.
  8. ^ Beeton N, McCallum H (Dec 2011). "Models predict that culling is not a feasible strategy to prevent extinction of Tasmanian devils from facial tumour disease: Modelling removal of diseased devils". Journal of Applied Ecology. 48 (6): 1315–1323. doi:10.1111/j.1365-2664.2011.02060.x.
  9. ^ a b Lachish S, McCallum H, Mann D, Pukk CE, Jones ME (June 2010). "Evaluation of selective culling of infected individuals to control tasmanian devil facial tumor disease". Conservation Biology. 24 (3): 841–851. doi:10.1111/j.1523-1739.2009.01429.x. PMID 20088958. S2CID 13424807.
  10. ^ Conroy G (June 2023). "Tasmanian devil cancer vaccine approved for testing". Nature. 619 (7969): 233–234. Bibcode:2023Natur.619..233C. doi:10.1038/d41586-023-02124-4. PMID 37391612. S2CID 259303561.
  11. ^ a b c Loh R, Bergfeld J, Hayes D, O'hara A, Pyecroft S, Raidal S, Sharpe R (November 2006). "The pathology of devil facial tumor disease (DFTD) in Tasmanian Devils (Sarcophilus harrisii)". Veterinary Pathology. 43 (6): 890–895. doi:10.1354/vp.43-6-890. PMID 17099145. S2CID 1377732.
  12. ^ a b Bryant B, Reiss A (2008). "9 Wombats 1.3 Tasmanian devil facial tumour disease (DFTD)". In Vogelnest L, Woods R (eds.). Medicine of Australian Mammals. Csiro Publishing. ISBN 9780643099289.
  13. ^ a b O'Neill ID (October 2010). "Tasmanian devil facial tumor disease: insights into reduced tumor surveillance from an unusual malignancy". International Journal of Cancer. 127 (7): 1637–1642. doi:10.1002/ijc.25374. PMID 20473867. S2CID 23770150.
  14. ^ McCallum H (November 2008). "Tasmanian devil facial tumour disease: lessons for conservation biology". Trends in Ecology & Evolution. 23 (11): 631–637. doi:10.1016/j.tree.2008.07.001. PMID 18715674.
  15. ^ Deakin JE, Belov K (2012). "A comparative genomics approach to understanding transmissible cancer in Tasmanian devils". Annual Review of Genomics and Human Genetics. 13 (1): 207–222. doi:10.1146/annurev-genom-090711-163852. PMID 22657390.
  16. ^ Grueber CE, Peel E, Gooley R, Belov K (September 2015). "Genomic insights into a contagious cancer in Tasmanian devils". Trends in Genetics. 31 (9): 528–535. doi:10.1016/j.tig.2015.05.001. PMID 26027792.
  17. ^ Lachish S, McCallum H, Jones M (March 2009). "Demography, disease and the devil: life-history changes in a disease-affected population of Tasmanian devils (Sarcophilus harrisii)". The Journal of Animal Ecology. 78 (2): 427–436. doi:10.1111/j.1365-2656.2008.01494.x. JSTOR 27696382. PMID 19021786.
  18. ^ Hawkins CE, McCallum H, Mooney N, Jones M, Holdsworth M. (2009). Sarcophilus harrisii. In: IUCN red list of threatened species. Version 2009.1.[full citation needed]
  19. ^ Janeway CA, Travers P, Walport M, Shlomchik M. (2001). Immunobiology. Garland Publishing, New York, NY.[page needed]
  20. ^ McCallum H, Jones M, Hawkins C, Hamede R, Lachish S, Sinn DL, et al. (December 2009). "Transmission dynamics of Tasmanian devil facial tumor disease may lead to disease-induced extinction". Ecology. 90 (12): 3379–3392. doi:10.1890/08-1763.1. hdl:10072/33909. PMID 20120807.
  21. ^ Wells K, Hamede RK, Kerlin DH, Storfer A, Hohenlohe PA, Jones ME, McCallum HI (June 2017). "Infection of the fittest: devil facial tumour disease has greatest effect on individuals with highest reproductive output". Ecology Letters. 20 (6): 770–778. doi:10.1111/ele.12776. PMC 6759051. PMID 28489304.
  22. ^ TY - BOOK AU - Lusi, Elena AU - Caicci, Federico AU - Cristarella, Santo AU - Quartuccio, Marco PY - 2020/03/20 SP - T1 - A transforming giant virus discovered in Canine Transmissible Venereal Tumour: Stray dogs and Tasmanian devils opening the door to a preventive cancer vaccine DO - 10.1101/2020.03.18.996900 ER -
  23. ^ "Bites spread fatal 'devil' cancer". BBC News. 2006-02-02. Retrieved 2018-01-27.
  24. ^ a b Deakin JE, Bender HS, Pearse AM, Rens W, O'Brien PC, Ferguson-Smith MA, et al. (2012). "Genomic restructuring in the Tasmanian devil facial tumour: chromosome painting and gene mapping provide clues to evolution of a transmissible tumour". PLOS Genetics. 8 (2): e1002483. doi:10.1371/journal.pgen.1002483. PMC 3280961. PMID 22359511.
  25. ^ Pearse AM, Swift K, Hodson P, Hua B, McCallum H, Pyecroft S, et al. (March 2012). "Evolution in a transmissible cancer: a study of the chromosomal changes in devil facial tumor (DFT) as it spreads through the wild Tasmanian devil population". Cancer Genetics. 205 (3): 101–112. doi:10.1016/j.cancergen.2011.12.001. PMID 22469509.
  26. ^ a b c Bostanci A (February 2005). "Wildlife biology. A devil of a disease". Science. 307 (5712): 1035. doi:10.1126/science.307.5712.1035. PMID 15718445. S2CID 54100368.
  27. ^ a b Murchison EP, Schulz-Trieglaff OB, Ning Z, Alexandrov LB, Bauer MJ, Fu B, et al. (February 2012). "Genome sequencing and analysis of the Tasmanian devil and its transmissible cancer". Cell. 148 (4): 780–791. doi:10.1016/j.cell.2011.11.065. PMC 3281993. PMID 22341448.
  28. ^ Murchison EP, Tovar C, Hsu A, Bender HS, Kheradpour P, Rebbeck CA, et al. (January 2010). "The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer". Science. 327 (5961): 84–87. Bibcode:2010Sci...327...84M. doi:10.1126/science.1180616. PMC 2982769. PMID 20044575.
  29. ^ a b Kinver M (1 January 2010). "Tasmanian devil facial cancer origins 'identified'". BBC.
  30. ^ a b c Walsh B (1 January 2010). "Decoding the Tasmanian Devil's Deadly Cancer". Time. Archived from the original on January 8, 2010.
  31. ^ a b c Flies AS, Lyons AB, Corcoran LM, Papenfuss AT, Murphy JM, Knowles GW, et al. (9 December 2016). "PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment". Frontiers in Immunology. 7: 581. doi:10.3389/fimmu.2016.00581. PMC 5145852. PMID 28018348.
  32. ^ "Tasmanian Devil tumor type linked with survival rates". Australian Broadcasting Corporation. 2 September 2015.
  33. ^ Siddle HV (April 2017). "Cancer as a contagious disease". HLA. 89 (4): 209–214. doi:10.1111/tan.12980. PMID 28205368. S2CID 1557336.
  34. ^ Ujvari B, Pearse AM, Swift K, Hodson P, Hua B, Pyecroft S, et al. (February 2014). "Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours". Evolutionary Applications. 7 (2): 260–265. doi:10.1111/eva.12117. PMC 3927887. PMID 24567746.
  35. ^ "New Tas devil tumour strands 'harder to vaccinate' – ABC News (Australian Broadcasting Corporation)". 2008-07-25. Retrieved 2010-01-03.
  36. ^ Conroy G (April 2023). "Genetic map of Tasmanian devil cancers hints at their future evolution". Nature. doi:10.1038/d41586-023-01349-7. PMID 37081271. S2CID 258721052.
  37. ^ a b "Department of Primary Industries, Parks, Water and Environment" (PDF). Department of Natural Resources and Environment Tasmania. 2014-03-27. Archived from the original (PDF) on 2005-10-02. Retrieved 2017-04-26.
  38. ^ a b "Insurance population". Save the Tasmanian Devil Program. Hobart, Tasmania: Department of Primary Industries, Parks, Water and Environment. 18 January 2013. Archived from the original on 8 February 2011. Retrieved 28 November 2013.
  39. ^ Shine T. "Bid to save birds from predatory Tasmania devils on Maria Island haven". ABC News. Retrieved 28 November 2014.
  40. ^ Rogers T, Fox S, Pemberton D, Wise P (2016). "Sympathy for the devil: captive-management style did not influence survival, body-mass change or diet of Tasmanian devils 1 year after wild release". Wildlife Research. 43 (7): 544. doi:10.1071/WR15221.
  41. ^ Owen & Pemberton 2005, p. 6.
  42. ^ Jones ME, Cockburn A, Hamede R, Hawkins C, Hesterman H, Lachish S, et al. (July 2008). "Life-history change in disease-ravaged Tasmanian devil populations". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 10023–10027. Bibcode:2008PNAS..10510023J. doi:10.1073/pnas.0711236105. PMC 2481324. PMID 18626026.
  43. ^ Jones ME, Cockburn A, Hamede R, Hawkins C, Hesterman H, Lachish S, et al. (July 2008). "Life-history change in disease-ravaged Tasmanian devil populations". Proceedings of the National Academy of Sciences of the United States of America. 105 (29): 10023–10027. Bibcode:2008PNAS..10510023J. doi:10.1073/pnas.0711236105. PMC 2481324. PMID 18626026.
  44. ^ "DRAFT - Recovery Plan for the Tasmanian devil (Sarcophilus harrisii)" (PDF). Department of Primary Industries, Parks, Water and Environment. Tasmania, Australian Government. 2010. Archived from the original (PDF) on 2011-03-04. Retrieved 2010-11-14.
  45. ^ "Sarcophilus harrisii – Tasmanian Devil". Species Profile and Threats Database. Canberra: Department of the Environment. 2017.
  46. ^ "DPIW – Fox Impact on Wildlife". Department of Natural Resources and Environment Tasmania. 2010-05-25. Retrieved 2010-09-11.
  47. ^ "The Tasmanian Devil Needs a Saviour". Devil Ark. Retrieved 2011-04-19.
  48. ^
  49. ^ Holtcamp W (March 2007). "Sympathy for the Devil: Ideas emerge to save the dying tasmanian devil". Scientific American. 296 (3): 27. doi:10.1038/scientificamerican0307-27. PMID 17348152.
  50. ^ Quammen D (April 2008). "Contagious cancer: the evolution of a killer". Harper's Magazine.
  51. ^ "A pre-tumour diagnostic test for DFTD". 2009-06-15. Retrieved 2010-09-11.
  52. ^ Siddle HV, Marzec J, Cheng Y, Jones M, Belov K (July 2010). "MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer". Proceedings. Biological Sciences. 277 (1690): 2001–2006. doi:10.1098/rspb.2009.2362. JSTOR 25706413. PMC 2880097. PMID 20219742.
  53. ^ Czarny NA, Rodger JC (June 2010). "Vitrification as a method for genome resource banking oocytes from the endangered Tasmanian devil (Sarcophilus harrisii)". Cryobiology. 60 (3): 322–325. doi:10.1016/j.cryobiol.2010.02.007. PMID 20219455.
  54. ^ a b Epstein B, Jones M, Hamede R, Hendricks S, McCallum H, Murchison EP, et al. (August 2016). "Rapid evolutionary response to a transmissible cancer in Tasmanian devils". Nature Communications. 7: 12684. Bibcode:2016NatCo...712684E. doi:10.1038/ncomms12684. PMC 5013612. PMID 27575253.
  55. ^ "Devil Tumors". Retrieved 23 April 2017.
  56. ^ Owen & Pemberton 2005, p. 170f.
  57. ^ "Tasmanian devils threatened by facial tumour disease". Science Show. Australian Broadcasting Corporation. 2007-04-21. Retrieved 2010-10-08.
  58. ^ a b c Pearse AM, Swift K (February 2006). "Allograft theory: transmission of devil facial-tumour disease". Nature. 439 (7076): 549. Bibcode:2006Natur.439..549P. doi:10.1038/439549a. PMID 16452970. S2CID 4409863.
  59. ^ "Tasmanian devils felled by rare cancer". New Scientist. 1 February 2006. Retrieved 2018-01-27.(subscription required)
  60. ^ Obendorf DL, MacGlashan ND (2008). "Research Priorities in the Tasmanian Devil Facial Tumor Debate". European Journal of Oncology. 13: 229–238.
  61. ^ Hamede RK, McCallum H, Jones M (January 2013). "Biting injuries and transmission of Tasmanian devil facial tumour disease". The Journal of Animal Ecology. 82 (1): 182–190. doi:10.1111/j.1365-2656.2012.02025.x. PMID 22943286.
  62. ^ Dennis C (February 2006). "Endangered species: time to raise the devil". Nature. 439 (7076): 530. Bibcode:2006Natur.439..530D. doi:10.1038/439530a. PMID 16452951. S2CID 28726802.
  63. ^ Owen & Pemberton 2005, p. 177.
  64. ^ "Tasmanian Devils - Spread of Disease". Parliamentary Debates (Hansard). Tasmania: House of Assembly. 29 October 2003. Part 2: pp. 31–104. Archived from the original on October 9, 2010. (part 2) 3:30 pm (Jeremy Rockliff, Shadow Minister for Primary Industries, Water and Environment; Nick McKim, Tasmanian Greens; Bryan Green, Minister for Primary Industries, Water and Environment).
  65. ^ Bryan Green, Minister for Primary Industries, Water and Environment (20 August 2003). "Tasmanian Devils and the Spread of Cancer". Parliamentary Debates (Hansard). Tasmania: House of Assembly. Part 1: pp. 1–29. Archived from the original on October 9, 2010. (10:58 am) (part 1)
  66. ^ Wood D (1 September 2003). "Tassie devil under threat". The Mercury. Hobart Town, Tasmania. p. 1.
  67. ^ "Wildlife specialists concerned about Tassie Devil disease". Australian Broadcasting Corporation. 2003-10-14. Retrieved 2010-10-08.
  68. ^ "Devil Disease". Stateline Tasmania. Australian Broadcasting Corporation. 2004-09-10. Archived from the original on 2012-11-11. Retrieved 2010-10-08.
  69. ^ Owen & Pemberton 2005, p. 178.
  70. ^ Owen & Pemberton 2005, p. 184f.
  71. ^ "Research priorities in the Tasmanian devil facial tumour debate" (PDF). European Journal of Oncology. 13: 229–238. 2008. Archived from the original (PDF) on 2016-05-28. Retrieved 2010-10-23.
  72. ^ "Frequently Asked Questions About Devil Facial Tumour Disease" (PDF).
  73. ^ Conservation Breeding Specialist Group (2008). "Tasmanian Devil PHVA Final Report" (PDF). Apple Valley, Minnesota: IUCN/SSC Conservation Breeding Specialist Group. Retrieved 2 October 2010.
  74. ^ Woods GM, Kreiss A, Belov K, Siddle HV, Obendorf DL, Muller HK (2007). "The Immune Response of the Tasmanian Devil (Sarcophilus harrisii) and Devil Facial Tumour Disease". EcoHealth. 4 (3): 338–345. doi:10.1007/s10393-007-0117-1. S2CID 22762914.
  75. ^ McCallum H, Tompkins DM, Jones M, Lachish S, Marvanek S, Lazenby B, Hocking G, Wiersma J, Hawkins CE (2007). "Distribution and Impacts of Tasmanian Devil Facial Tumor Disease". EcoHealth. 4 (3): 318–325. CiteSeerX doi:10.1007/s10393-007-0118-0. S2CID 11311742.
  76. ^ "Healthy Tasmanian devils found in mission to save species from extinction". ABC News. 28 April 2018. Retrieved 30 April 2018.
  77. ^ "BBC NEWS - World - Asia-Pacific - Fence hope for Tasmanian Devils". Retrieved 23 April 2017.
  78. ^ "Cancer-related death for Cedric the devil – ABC News (Australian Broadcasting Corporation)". 2010-09-01. Retrieved 2010-09-11.
  79. ^ Borrell B (31 December 2009). "Hopes of a tumour test for Tasmanian devils". Nature. doi:10.1038/news.2009.1169. Retrieved 23 April 2017.
  80. ^ Pinfold TL, Brown GK, Bettiol SS, Woods GM (27 May 2014). "Mouse Model of Devil Facial Tumour Disease Establishes That an Effective Immune Response Can be Generated Against the Cancer Cells". Frontiers in Immunology. 5: 251. doi:10.3389/fimmu.2014.00251. PMC 4034705. PMID 24904594.
  81. ^ Kreiss A, Brown GK, Tovar C, Lyons AB, Woods GM (June 2015). "Evidence for induction of humoral and cytotoxic immune responses against devil facial tumor disease cells in Tasmanian devils (Sarcophilus harrisii) immunized with killed cell preparations". Vaccine. 33 (26): 3016–3025. doi:10.1016/j.vaccine.2015.01.039. PMID 25708088.
  82. ^ Pye R, Patchett A, McLennan E, Thomson R, Carver S, Fox S, et al. (19 Feb 2018). "Immunization Strategies Producing a Humoral IgG Immune Response against Devil Facial Tumor Disease in the Majority of Tasmanian Devils Destined for Wild Release". Frontiers in Immunology. 9: 259. doi:10.3389/fimmu.2018.00259. PMC 5826075. PMID 29515577.
  83. ^ Flies AS, Flies EJ, Fox S, Gilbert A, Johnson SR, Liu GS, et al. (January 2020). "An oral bait vaccination approach for the Tasmanian devil facial tumor diseases". Expert Review of Vaccines. 19 (1): 1–10. doi:10.1080/14760584.2020.1711058. hdl:11343/273489. PMID 31971036. S2CID 210872744.
  84. ^ "Save the Tasmanian Devil Program moves closer to immunized devil trial". Department of Natural Resources and Environment Tasmania. 25 February 2015. Retrieved 14 April 2015.
  85. ^ Tovar C, Pye RJ, Kreiss A, Cheng Y, Brown GK, Darby J, et al. (March 2017). "Regression of devil facial tumour disease following immunotherapy in immunised Tasmanian devils". Scientific Reports. 7: 43827. Bibcode:2017NatSR...743827T. doi:10.1038/srep43827. PMC 5343465. PMID 28276463.
  86. ^ O'Connor T (9 March 2017). "Live cancer cell injection helps beat devil facial tumour disease". ABC News. Retrieved 2018-01-27.
  87. ^ Cheng Y, Makara M, Peel E, Fox S, Papenfuss AT, Belov K (2019-03-13). "Tasmanian devils with contagious cancer exhibit a constricted T-cell repertoire diversity". Communications Biology. 2 (1): 99. doi:10.1038/s42003-019-0342-5. PMC 6416256. PMID 30886908.
  88. ^ Flies AS, Lyons AB, Corcoran LM, Papenfuss AT, Murphy JM, Knowles GW, et al. (9 Jan 2016). "PD-L1 Is Not Constitutively Expressed on Tasmanian Devil Facial Tumor Cells but Is Strongly Upregulated in Response to IFN-γ and Can Be Expressed in the Tumor Microenvironment". Frontiers in Immunology. 7: 581. doi:10.3389/fimmu.2016.00581. PMC 5145852. PMID 28018348. S2CID 10226811.
  89. ^ Flies AS, Blackburn NB, Lyons AB, Hayball JD, Woods GM (3 May 2017). "Comparative Analysis of Immune Checkpoint Molecules and Their Potential Role in the Transmissible Tasmanian Devil Facial Tumor Disease". Frontiers in Immunology. 8: 513. doi:10.3389/fimmu.2017.00513. PMC 5413580. PMID 28515726.
  90. ^ Ong CE, Lyons AB, Woods GM, Flies AS (14 Jan 2019). "Inducible IFN-γ Expression for MHC-I Upregulation in Devil Facial Tumor Cells". Frontiers in Immunology. 9: 3117. doi:10.3389/fimmu.2018.03117. PMC 6340284. PMID 30692995.
  91. ^ Flies AS, Darby JM, Lennard PR, Murphy PR, Ong CE, Pinfold TL, et al. (July 2020). "A novel system to map protein interactions reveals evolutionarily conserved immune evasion pathways on transmissible cancers". Science Advances. 6 (27): eaba5031. Bibcode:2020SciA....6A5031F. doi:10.1126/sciadv.aba5031. PMC 7458443. PMID 32937435.
  92. ^ "It's hard, long and sometimes stinky work, but this marathon effort may have found hope for Tasmanian devils". ABC News. 2023-09-01. Retrieved 2023-09-02.


External links[edit]