by Garrett Dunlap
figures by Aparna Nathan

Perhaps no animal is better suited to its name than the Tasmanian devil. While it might look cute and cuddly, in reality this animal is quite the opposite. With the strongest bite of any mammal and an infamous blood-curdling scream, the Tasmanian devil is a fierce and formidable creature known to attack animals many times its size. But even this devil is no match for its greatest foe: an unusual, transmissible face cancer ravaging the population.

The first glimpse of a mysterious disease

Around 20 years ago, sightings of large tumors on the faces of Tasmanian devils began to grow more and more common. Over time, animals suffering from these facial tumors could be seen all throughout Tasmania, an island off the coast of Australia and the devil’s only natural habitat. By 2003, Australian news reported that a third of the population had already died off from this mysterious disease. These tumors, which grew uncontrollably until they eventually covered the mouth and eyes, indicated the disease may be a type of cancer. Yet, neither scientists nor island inhabitants could puzzle out the cause of such a large, pervasive, fast-acting cancer.

Normally, cancer begins as the result of a single mutation, or a change to a section of DNA. Most mutations are harmless, but occasionally, they can cause the cell to grow and divide uncontrollably. This unrestricted growth causes the rogue cells to pile up, forming the masses that we recognize as cancerous tumors. As cancer cells continually grow and divide, they tend to acquire more and more mutations in their DNA, resulting in tumors that harbor a broad landscape of mutations. However, because mutations are random events, cancer often looks pretty different in each individual; two people with breast cancer, for example, may have tumors with vastly different arsenals of mutations. This is what makes the case of the Tasmanian devil so intriguing: it would have been nearly impossible for so many animals to independently develop similar-looking cancer so quickly through the classical mutation method.

Nearly a decade after the first sightings, in 2006, scientists began to better understand the mysterious origin and spread of this disease, by then called “devil facial-tumor disease” (DFTD). When scientists collected and compared cells from healthy and diseased devils across the island, they found something strange: the chromosomes of tumor cells looked strikingly different from those of healthy cells. Chromosomes are long strands of DNA that have been coiled up to form rod-shaped structures inside cells that are visible under microscopes (Figure 1). Normally, a Tasmanian devil cell has 14 chromosomes, which together contain all genes necessary to live. In the tumor cells, though, some of the chromosomes were absent, while other seemingly random chromosomes appeared.

Figure 1. Chromosomal changes in devil tumor cells. Observing differences in chromosomes, numbered above, allowed scientists to see vast changes between healthy devil cells (top) and tumor cells (bottom) collected on the island. They saw parts of some chromosomes—like 2 and 6—disappeared, while parts of others containing extra bits of information appeared (shown in red).

Even more intriguingly, every tumor sample showed the same pattern of modifications in the Tasmanian devils’ chromosomes. This finding was quite strange, especially compared to how cancer has been generally shown to emerge, through a series of random mutations and further changes to DNA. The fact that all Tasmanian devil samples showed the same irregular chromosome patterns made researchers suspected that the devils weren’t suffering from a typical type of cancer, as it would be almost impossible for so many individuals to accrue the same exact mutations in their DNA. Instead, the deadly cancer spreading through the population might be transmissible, spreading from one animal to another through bites to the face during bouts of fighting.

This cancer spreads how?!

If transmissible cancer sounds strange, it should. Nearly all forms and types of cancer that we as humans experience are born of some form of mutation to our DNA. This includes both randomly acquired mutations and those caused by environmental damage to DNA, such as following prolonged exposure to risk factors like tobacco, environmental pollutants, and sun (Figure 2, top). A small number of cancers in humans, though, form following infection by specific types of viruses termed oncoviruses (Figure 2, middle). One notable example of an oncovirus is the human papillomavirus (HPV) family, which has been shown to cause cervical and other types of cancer following infection.

Figure 2. Transmission of the devil’s facial cancer. Cancer can be caused in many ways. The most common method involves random damage to a cell’s DNA, which then causes the cell to lose its ability to control its growth and division. Another method involves infection by viruses, which insert their genetic information, like DNA, into cells, causing them to begin uncontrolled growth and division. The cancer that affects Tasmanian devils is clonally transmitted, which means cancer cells from one animal can spread directly from one animal to another and begin dividing. Notably, while viral cancer transmission has been noted in several species, including humans, scientists haven’t yet identified a case of this in Tasmanian devils (though it remains possible).

Puzzlingly, the cancer affecting the Tasmanian devils showed no sign of viral transmission, and, as mentioned above, the similarity among tumors did not support the mutation model. How, then, could this be spreading from one animal to another? As it turns out, the answer lies in what’s called the major histocompatibility complex, or MHC.

MHC is a group of proteins present on the surface of almost every cell in the body. The job of MHC is to communicate with the immune system, which is a group of cells that protect the body from foreign invaders that threaten our health, like viruses and bacteria. For example, consider an immune cell encountering a cell of your lung: when the immune cell recognizes the lung’s MHC, it knows that your lung cell belongs to you and poses no threat, and thus the immune cell passes by without attacking your lung. While MHC is vital for protecting our own cells from immune attack (in other words, autoimmunity), its protection has a short reach. MHC is highly specific to each individual, and as such, the MHC on my cells would likely be recognized as foreign by your immune system, and vice versa; this is what contributes to the problem of transplant rejection in the medical setting. At the same time, this detail generally prevents things like transmissible cancers: if a cancer cell from one person somehow infiltrated the body of a second person, the immune system of the latter would likely see the cancer cell’s MHC as foreign and would thus eliminate it, preventing the cancer’s growth.

So how does this relate to the Tasmanian devil’s facial cancer? As it turns out, the devil’s cancer cells have lost this MHC. As a result, their immune systems are unable to recognize the cancer cells as foreign and dangerous. Scientists hypothesize that, when the devils fight and bite one another, cancer cells are transferred from one animal to the next, and the lack of MHC allows these foreign cancer cells to go undetected by the bitten animal’s immune system (Figure 2, bottom). Such a phenomenon would explain the rapid growth of identical tumors throughout the devil population.

Saving face with the Tasmanian devil

An estimated 60% of the Tasmanian devil population has been decimated by the disease in the last ten years. Even worse, since the discovery of the initial devil cancer (DFT1), a second variation has arisen and begun ravaging the population (DFT2).

Figure 3. MHC in general and in the devil’s cancer. Normally, MHC is used to alert the immune system that a foreign invader has entered the body, or that the cell has become mutated beyond recognition, like in the case of cancer. When immune cells are alerted in this way, they’ll spring into action (shown in red) and try to clean up the mess by destroying infected or cancerous cells (here denoted by the foreign cell). In the case of DFT1, the cancerous cells don’t have MHC and thus can sneak past the immune system. With DFT2, there’s working MHC, but it isn’t able to coax the immune system into attacking the cancerous cells.

It is worth noting that the Tasmanian devils aren’t the only animals facing a non-viral transmissible cancer. Clams and mussels have also been observed to have transmissible forms of cancer spreading within their populations. Even dogs suffer a sexually-transmitted disease called “canine transmissible venereal tumor” (CTVT). Combined, the damaging effects these spreadable cancers have on animal populations impact ecosystems far and wide.

But one intriguing factor sets the Tasmanian devil apart: the rapidity with which two types of transmissible cancer have appeared and spread. For instance, CTVT is thought to have emerged 11,000 years ago but still affects less than 10% of dogs around the world, while multiple forms of DFTD have arisen in only the last few decades and are already threatening the Tasmanian devil’s existence. Unfortunately, it’s still not entirely clear to scientists why these creatures are so vulnerable to this type of disease.

As nearly all wild Tasmanian devils are thought to have contracted the disease, efforts are underway to isolate and protect healthy animals. The “Save the Tasmanian Devil” campaign has pioneered a breeding program in captivity, with tumor-free devils being sent to zoos ranging from Australia to Denmark. Simultaneously, work is underway to test the efficacy of vaccines and treatments in preventing further spread of the disease in the wild.

Tasmanian devils are a truly unusual species—with an equally formidable disease to contend with. But while it may seem we don’t have much in common with these curious little creatures, studying this devastating transmissible cancer can teach us a great deal about both wildlife conservation and the ongoing threat of cancer in our own species.

They may be loud. They may be vicious. But Tasmanian devils are absolutely worth saving.

Garrett Dunlap is a third-year Ph.D. candidate in Biological and Biomedical Sciences at Harvard University. He can be found on Twitter at @dunlap_g.

Aparna Nathan is a second-year Ph.D. student in the Bioinformatics and Integrative Genomics program at Harvard University.

For further information:

  • For a more detailed look at the different types of DFTD, check out this article.
  • To learn more about transmissible tumors, read this in-depth review.
  • To read about further efforts to save the Tasmanian devil, visit Devil Ark.

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