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Tasmanian Devil Facial Tumor is a Transmissible Cancer
This article was originally published on The Conversation. The publication contributed this article to Live Science's Expert Voices: Op-Ed & Insights.
On Monday this week The Conversation published a story under the headline “What’s killing Tassie devils if it isn’t contagious cancer?” The article suggested evidence that the Tasmanian devil facial tumor disease (DFTD) is a transmissible cancer is inconclusive and instead, environmental chemicals could be to blame. This misrepresents the state of the science.
All the latest research points to the fact that the deadly DFTD is a transmissible cancer that originated in a female Tasmanian devil. A single cell in this devil (patient zero) developed into a cancer cell.
This is nothing unusual as cancers, whether they are devil or human, originate from a single cell. This single cell divided uncontrollably to produce a tumor (mass of cells).
DFTD developed mechanisms to avoid being killed by the devil’s immune system. Again, nothing unusual – cancer cells usually develop such strategies.
What is unusual about DFTD, though, is that it is transmitted between devils. The same cancer cells from patient zero have spread throughout most of the Tasmanian devil population, killing every devil infected.
The disease spreads
The first case was identified in the far north-east of Tasmania in 1996. Trapping trips instigated by the government’s Save the Tasmanian Devil Program and the University of Tasmania have monitored the disease as it spread south and west throughout Tasmania.
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Each year DFTD has spread further. This pattern of spread is consistent with an infectious disease, rather than a disease caused by carcinogens present throughout the state. The far north-west of Tasmania remains disease-free.
Several independent lines of evidence support that DFTD originated as a single clone, from DFTD cells in patient zero. A study published in Nature in 2006 proposed devil-to-devil transmission of the cancer cells and the clonal origin of DFTD, based on chromosomal analysis.
More recent studies (including here and here) have indicated that all tumors share similar complex chromosomal rearrangement.
The tumors alike
The DNA sequencing work of the UK’s Elizabeth Murchison showed that the DNA of the cancer cells and the host devil are different. All DFTD tumors share the same or very similar genotypes at microsatellite loci, a small section of DNA that you can sequence.
They are also genetically distinct from their host. The difference is so large that DFTD could not have developed from each host.
Add to this whole genome analysis, which indicates that all DFTDs share point variants, structural variants and copy number changes, which are distinct from their hosts.
All of this research highlights that the karyotype and genotype are consistent between DFTD tumors and distinct from that of their hosts and supports the transmissible nature of the tumor.
A transmissible tumor requires a particular behaviour to allow the transfer of cells between individuals, as well as mechanisms to escape the immune response. DFTD was named facial tumor disease, because this is where tumors are found.
It is a cancer of Schwann cells which are cells that wrap around peripheral nerves. The face is rich in peripheral nerves and provides an excellent environment for Schwann cell growth.
Transmission in the bite
Devil biting behaviour accounts for the transmission. Devils typically bite each other on the face and neck and the bites penetrate and cause substantial wounds. DFTD cells have been identified on the teeth of diseased devils and the penetrating bites can transfer DFTD cells.
The transfer of DFTD cells occurs when diseased devils bite healthy devils or when healthy devils bite diseased devils and tumor cells become incorporated into the oral cavity, establishing DFTD inside the mouth.
The biting and location of DFTD growth accounts for the transmission, but the “transplanted” tumor cells must then escape the host devil’s immune response to avoid rejection as a “foreign graft”. A proposal to account for this was that devils lack genetic diversity and are not recognised as “foreign” by the host devil’s immune system.
Based on genome sequencing Tasmanian devils do have a reduced genetic diversity. But the low genetic diversity does not account for the lack of graft recognition as skin grafts between devils are immunologically rejected.
Although reduced genetic diversity may contribute to successful tumor transmission, further research was required to explain the mechanisms of immune escape. This research has been completed, but was not included in Monday’s article.
A breakthrough
Recent breakthrough research has identified the main reason that DFTD cells are not immunologically rejected. The tumor cells do not express major histocompatibility (MHC) antigens on their cell surface.
These are immune recognition molecules and without them the cells are “invisible” to the devil’s immune system. This is an effective strategy used by the transmissible tumor found in dogs, the canine transmissible venereal tumor (CTVT). This tumor has existed for centuries and the cancer cells are sexually transmitted. CTVT avoids immune recognition in the new host because the tumor cells do not express MHC molecules.
The pattern of DFTD distribution and spread also supports the transmissible nature of the tumou. If environmental carcinogens were causing DFTD, there should be random occurrences of DFTD throughout the state.
This has not been seen, and instead the disease is spreading across the state in a manner consistent with a contagious disease. All the scientific evidence points to DFTD as a transmissible cancer, rather than a carcinogen-induced cancer.
To save this iconic species, only found in Tasmania, the Save the Tasmanian Devil Program established an insurance population. This has been a major undertaking that has relied on the goodwill of many wildlife parks and zoos around Australia.
Safe in captivity
The devil is now safe from extinction, at least in captivity. The next challenge is to protect Tasmanian devils in the wild.
To this end much research effort needs to be directed towards a vaccine. This is the goal of my research group. We have been diligently analysing the devils' immune system. This research points to the devil having a competent immune system.
The Achilles heel of DFTD is that the genes for MHC are present, but turned off. We have discovered the “switch” to turn these genes on and this forms the basis for our vaccine research.
We may never know what caused DFTD in patient zero. It was most likely an accident of nature. Carcinogens may have played a role.
Although it would be of scientific interest to know the answer and undertake a large and expensive survey, the most important challenge is to save the devils in the wild. This is one of the major aims of the Save the Tasmanian Devil Program.
The past is history and the present learns from the past to inform the future. Habitat destruction does add extra stresses on our native wildlife and the future must take this into account.
The immediate task for us is to pursue vaccine development with the aim of protecting the healthy devils and repopulating the state with devils that have resistance to DFTD.
Greg Woods receives funding from Australian Research Council and Save the Tasmanian Devil Appeal.
This article was originally published on The Conversation. Read the original article. Follow all of the Expert Voices issues and debates — and become part of the discussion — on Facebook, Twitter and Google +. The views expressed are those of the author and do not necessarily reflect the views of the publisher. This version of the article was originally published on Live Science.