A Hell of a Illness: Can Science Save the Tasmanian Satan?

When the sun sets in Tasmania, a creature with fur as dark as the night emerges from its den to begin its search for food, scavenging for carrion and hunting small mammals and birds. To many, it’s best known as the inspiration for the whirling Looney Tunes character Taz. But to others, like University of Cambridge geneticist Elizabeth Murchison, it’s far more than a cartoon. To her, the devil is a national icon.

Growing up in Tasmania, Murchison recalled rare glimpses of these elusive creatures during camping trips in the remote wilderness, though they were more often heard than seen. She described their cries as “a really loud screaming sound, which is quite eerie.”

Though Tasmanian devil sightings are few and far between, in the mid-1990s, researchers noticed a devastating devil facial tumor disease (DFTD) that ravaged the Tasmanian devil population in northeast Tasmania. In the early 2000s, the Australian and Tasmanian governments, in collaboration with universities and zoos, launched the Save the Tasmanian Devil Program. This initiative began extensive monitoring of wild devil populations, which have since experienced an 80 percent decline following the emergence of DFTD.¹

The cause of this devastating disease remained a mystery, capturing the intense focus of researchers and conservationists, eager to understand the immune and evolutionary responses of Tasmanian devils, and to guide conservation efforts in the face of such a dire threat—though many believed the devils were on a path to extinction, especially after the loss of the Tasmanian tiger.

Today, the Tasmanian devil’s signature scream still echoes through the wild, a haunting cry in its battle for survival against DFTD, a disease that has proven both elusive and deadly. However, with emerging signs of resistance and promising vaccine trials, the future of this iconic species is beginning to look more hopeful.

Bite, Snarl, Spread: A Transmissible Cancer Moves from Devil to Devil

DFTD manifests as aggressive tumors that form in and around the mouth, severely impairing the devils’ ability to eat, which often leads to starvation. As the tumors metastasize rapidly in other parts of the body, the disease has proven devastating.

With the rising number of cases, researchers hypothesized that DFTD spreads through biting, a behavior common in Tasmanian devils during aggressive interactions over food or mates.² Adult Tasmanian devils are especially vulnerable. Transmission is most common during the mating season, when biting occurs frequently. Devils typically begin mating around two years of age, at which point they can contract the disease, survive just long enough to raise their young, and then die—leaving behind a largely juvenile population and an endangered status for the species. But the exact cause of this contagious cancer remained elusive. Could the culprit be a virus, as with other cancers, or perhaps a parasite?

In 2006, researchers studying DFTD cells from different devils discovered that the cancer cells shared the same chromosomal abnormalities across individuals but appeared distinct from their host.³ “They described the contagious cancer and the fact that it was transmitted as an allograft, a cell that was transmitted from animal to animal by biting. I got very interested straight away,” remarked Katherine Belov, a geneticist at the University of Sydney.

At the time, Belov was studying how major histocompatibility complex (MHC) genes, known as human leukocyte antigens (HLAs), play a role in marsupials’ immune systems and how genetic diversity influences population health. Because MHC molecules help the immune system differentiate between ‘self’ and ‘non-self,’ they play an important role in immune responses to tumors and tissue grafts. When MHC molecules are downregulated on cells, tumors can evade immune detection, and grafts can be accepted more easily, as seen in organ transplants.

Belov hypothesized that MHC diversity in Tasmanian devils might be very low. She based this idea on a lecture she attended, which discussed the work of geneticist Stephen O’Brien on cheetahs. “They did skin grafts on cheetahs…They concluded that MHC diversity in cheetahs was low because the cheetahs were able to accept allografts from unrelated cheetahs,” said Belov. “So here I was thinking, ‘Maybe this is what’s happening with devil facial tumor disease…Animals are accepting cancer cells from other animals and not seeing them as foreign and not mounting an immune response.’”

When Belov and her colleagues genotyped 21 Tasmanian devils, they discovered extremely low genetic diversity, especially in MHC class I genes.⁴ This lack of diversity was initially thought to be the result of historical population crashes, potentially caused by events such as European colonization or climate fluctuations like El Niño events.

However, further studies analyzing DNA from devils in both Tasmania and mainland Australia—where devils once lived—painted a different picture. The researchers found that the low genetic diversity had remained relatively unchanged, even in samples dating back before European contact.⁵

So perhaps this low genetic diversity also meant that the devils were immune incompetent and therefore unable to reject invading cancer cells. However, Belov noted that this was not the case. In skin graft experiments between different Tasmanian devils, she remarked that it took longer to reject than expected, but the devil did reject the skin grafts after 14 days.⁶ This suggested that the devils did not have a defective immune system, but rather a tumor with an escape mechanism.

But what enabled these cells to hide in plain sight? While devils have low MHC class I diversity, Belov’s group found that the way the tumor hides from the immune system is through downregulating the antigen-processing pathway. They also found that this was a reversible process, occurring through epigenetic deacetylation of histones, to switch off the expression of cell surface MHC, hiding in plain sight from the immune system and thus evading the devil’s defenses.⁷

So, the discovery of DFT2 really changed our perception of transmissible cancers in Tasmanian devils.

—Elizabeth Murchison, University of Cambridge

While researchers explored how this cancer spreads and avoids the immune system, others, like Murchison, delved into the genomics behind the devils and their cancer’s origins. “At that point, we didn’t really have any reference genome, so it’s quite challenging to do any genetic work,” remarked Murchison.

She and her colleagues sequenced the genome of two geographically distant tumor samples, complemented by an analysis of the genetic diversity of more than 100 different tumor samples collected during the past years.⁸ All the tumors had the same genetic markers and two inherited X chromosomes, suggesting that the cancer first arose from a female Tasmanian devil from the 1980s that subsequently spread across the island.

From this work, they also identified that the cancer originated from Schwann cells—nerve cells involved in myelin production and nerve repair—by analyzing microRNA patterns in healthy tissue and DFTD tumors.⁹ DFTD tumors expressed proteins like periaxin, which is part of the myelin-making biochemical pathway. While some questions about DFTD had been answered, a new and unexpected mystery emerged: a second, genetically distinct transmissible cancer.

Double Trouble for Devils: A Second Cancer Emerges

In the early 2010s, researchers received a call about a moribund devil with facial tumors that had wandered into someone’s yard in southern Tasmania. Andrew Flies, a cancer immunologist at the University of Tasmania, recalled that his colleague, veterinarian Ruth Pye, went down, trapped, and euthanized the devil and brought back samples to the lab thinking it would be DFTD. But to their surprise, it wasn’t. Then, a few months later, another call from the community came in about another devil in the area.

Murchison received some of the samples collected to examine the genetic components. “They were identical, the two tumors, and there were differences to DFT[1]. So, at that point, we realized it’s a different, independent transmissible cancer [we called DFT2].” These strains both fall under the umbrella of DFTD. While DFT1 (the original disease described in the 1990s) became widespread across the population, DFT2 was found to be more localized, confined to a small peninsula in southern Tasmania.¹⁰

“It was the most startling moment in my entire career,” Murchison said. “I don’t think I’ll ever be as surprised as that ever again, because we thought at that point that transmissible cancers were just really rare things.” DFTD is one of three known transmissible cancers: The other two include a transmissible venereal tumor in dogs and a water-borne leukemia in marine bivalves.¹¹ Murchison added, “So, the discovery of DFT2 really changed our perception of transmissible cancers in Tasmanian devils. It seems like the species has some kind of susceptibility to producing these types of cancers.”

However, researchers were keen to better characterize DFT1 and DFT2. The conditions spurred questions like: What were their commonalities and differences, what caused these cancers to emerge in Tasmanian devils, and what were their key genetic factors?

According to genomic sequencing, both cancers emerged from Schwann cells. Because Schwann cells mainly insulate peripheral nerves, an injury, like a bite from another devil, can prompt the cells to go into repair mode. “What we think has happened in both DFT1 and DFT2 is that there’s been a blockage in this repair mode, which has then continued to proliferate and then spread,” explained Murchison. “So, we think biting and injuries might have actually been a kind of trigger for the cancer itself to emerge as well as a transmission mechanism.”

They found that DFT2’s mutation rate is three times faster than DFT1, likely due to its rapid cell division.¹² Because of this, it may be a more aggressive cancer and kill its host more quickly; consequently, it may have fewer opportunities to spread, which is why it remains localized. DFT2 also arose from a male devil as the tumor cells had a Y chromosome, whereas DFT1 originated from a female devil. One of the most perplexing aspects to researchers is that DFT2 does express MHC class I molecules, so it is unclear how exactly these cells escape the immune system.¹³

Both cancers have similar mutations which seem to intersect with the platelet-derived growth factor (PDGF) signaling pathway; they each have extra copies of different components of the PDGF receptor (PDFGR).¹⁴ Andreas Bergthaler, an infectious disease researcher at the Medical University of Vienna, further homed in on the molecular basis of this cancer by studying Tasmanian devil cell cultures.

He and his team examined primary DFT1 biopsies and nontumor tissue, as well as different cell lines like fibroblasts. Using pharmacological screens and proteomic analysis, he and his team found that DFT1 was dependent on growth signals through the erythroblastic oncogene B (ERBB) family of tyrosine kinase receptors, which activate signal transducer and activator of transcription 3 (STAT3) proteins to alter the cell’s genetic programming.¹⁵

He added, “We showed that hyperactivation and dependence on ERBB signaling not only activate a whole signaling cascade, including STAT3, which is a master transcriptional regulator and activator, but it also [at] the same time, inhibits STAT1. And STAT1 is one of those molecules that is needed to express MHC genes.”

Pharmacological blocking of either ERBB or STAT3 prevented tumor growth in xenograft models, which consisted of immunocompromised mice transplanted with devil tumor cells. This helped reveal not only how the tumor grows but also how it evades the immune system, though other factors may be at play.

Bergthaler and his team are now exploring how plastic these signal transduction pathways are between DFT1 and DFT2, with a focus on ERBB and PDGFR signaling. “If there was a trend or a tendency, at least with ERBB and PDGFR signaling, they can be potentially used interchangeably by the tumor cells,” said Bergthaler. “So, it’s a bit like whack the mole. If you block one signal transduction, then at least some cell lines would then rather rely on the other receptor for signaling, which also gives further evidence and strengthens the notion that even though these two Tasmanian devil tumor types have emerged independently, they do share fundamental features of [signaling].”

Flies added that there are insights into how DFTDs parallel what researchers know about human cancers. “The surprising part is how much the placental animals split with marsupials about 180 million years ago. So, I think what’s surprising is how similar the cancers are. They’re using the same pathways to keep proliferating. They’re susceptible to some of these same kinase inhibitors. They’re downregulating MHC. They upregulate [programmed death-ligand 1] PD-L1. So, there’s a lot of what’s known in human cancers that applies directly to devils.”

As researchers deepen their understanding of DFTD’s genomic landscape and cancer biology, they are also investigating how Tasmanian devils may evolve in response to the disease since the cancer first emerged.

The Evolution of Devils and Their Contagious Cancer

Despite the drastic cut to the wild population, Tasmanian devils persist. Researchers are now looking into the genetic and evolutionary shifts that may be helping devils adapt.

“[The devils] certainly have lower genetic diversity than is expected, and that’s one reasonable hypothesis for why there appears to be universal susceptibility to getting this cancer. [But] that doesn’t mean that the population doesn’t have the evolutionary capacity to adapt,” said biologist Andrew Storfer from Washington State University. Storfer’s team employs predictive ecological models coupled with genome-wide association studies data to better understand devil-DFTD coexistence.

Early ecological models predicted a grim fate for the devils: extinction.¹⁶ But when evolution is added to the equation, Storfer noted that there is a “higher probability of persistence,” as populations decline and recover over time.¹⁷

“We have plenty of evidence that the tumor is evolving, and that’s no surprise to anybody, because it is a cancer, and they evolve really rapidly,” said Storfer, and he added that the same pattern can be seen in Tasmanian devils. “We’re starting to see evidence of, not necessarily recovery, but vastly decreased disease prevalence, which might point toward resistance, but it’s really anecdotal, seeing prevalence go down, which certainly suggests the populations are evolving resistance.”

Indeed, while researchers observed natural DFT1 regression in the wild, additional studies by Storfer and colleagues identified two chromosomal regions showing signs of selection across three devil populations. These regions contained genes associated with immune function and cancer susceptibility in humans.^18-20

Saving Face: How Scientists Are Vaccinating Devils Against Cancer An oral bait vaccine is being developed to defend Tasmanian devils against a fatal cancer jeopardizing their species. Devil facial tumor disease (DFTD) is a transmissible cancer that devastated the Tasmanian devil population since its emergence in the late 1990s. Since then, scientists have identified two forms of this disease (DFT1 and DFT2). This prompted researchers to understand this enigmatic disease and turn to pharmacological approaches such as vaccines. Early Vaccine Efforts When DFTD first emerged, scientists were puzzled—was the cancer spreading unchecked because it was invisible to the immune system, or because the devils’ immune defenses were failing? The culprit was camouflage. In DFT1 tumors, cancer cells downregulate MHC molecules—critical immune markers—allowing them to slip past the body’s defenses unnoticed.4 However, research has shown that Tasmanian devils can, in fact, mount an immune response to the disease.22 Early vaccines used killed tumor cells paired with immune-boosting adjuvants to “retrain” the immune system to recognize and attack the cancer.21 While lab tests showed promise, scaling up was the next step. From Lab to the Wild Inspired by the success of oral rabies vaccines in foxes, researchers began testing bait-based delivery systems in the wild. So far, devils have readily consumed placebo baits in both ground and automated dispenser trials.23,24 Next-gen vaccine strategies now use adenoviral vectors to stimulate stronger immune responses, particularly enhancing components related to MHC class I activity.25 These are being tested against DFT1, DFT2, and healthy devil cells. As both vaccine design and delivery systems advance, oral baits could revolutionize devil conservation, helping entire populations resist DFTD and reclaim their place in Tasmania’s wild landscape.

The Development of an Oral Bait Vaccine

With increasing knowledge about DFTD’s spread and crafty evasion of the immune system, researchers, like immunologist Gregory Woods at the University of Tasmania, have set their sights on developing a DFTD vaccine.

Early experimental vaccines immunized healthy Tasmanian devils with killed DFTD tumor cells in the presence of adjuvants to promote an immune response, such as cytotoxicity and antibody production.²¹ An additional study showed that devils with serum antibodies against DFTD also had evidence of regression.²²

“They had some good results using it as a therapy, but it wasn’t scalable in the field,” Flies said. While 19 immunized devils were released into Narawntapu National Park in northern Tasmania in 2015, he added, “You couldn’t vaccinate enough devils that way to make a real difference in conservation.”

During this time, Flies admitted, “I completely had my blinders on and focused on the types of immunotherapies they were using for humans. I focused on checkpoint inhibitors, PD-1, PD-L1, CTLA-4, which have become one of the four pillars of cancer for human medicine now. I made monoclonal antibodies to recognize those proteins [in] devils, and I found that the patterns look the same in devils as they do in humans, but [after] a couple of years, it became clear that this is not going to help a lot of devils.”

Around 2018, Flies switched gears to focus on a vaccine, and not only a vaccine, but one that could be distributed in edible baits.²³ He drew inspiration from the oral rabies vaccine distributed across Europe, which placed attenuated rabies virus in dead chickens for foxes to eat. First, they had to see whether the devils would even take the placebo baits.²⁴

Initially, when the researchers dropped placebo baits on the ground, other species enjoyed a free meal. Flies noted that devils were only getting seven percent of the baits, so then they transitioned to a timed bait dispenser, and this time, “they got 55 percent of the baits.”

To improve their dispensing system, PhD student Prithul Chaturvedi, with support from neuroscientist William Connelly, implemented an artificial intelligence (AI) system in a new bait dispenser equipped with a motion sensor. When activated, it takes 10 photos to assess whether the visitor is truly a devil, then rotates the carousel to release bait. Equipped with a microchip scanner, it also scans tagged devils, providing valuable data to help researchers track these animals.

As for the development of the bait vaccine itself, Flies and his team engineered an adenoviral vector-based vaccine that they had tested in the laboratory on DFTD cells and tissues.²⁵ “All the signs so far look promising, but we can’t say if it works until we put it into a devil,” said Flies.

Recently, Australia approved a single shot vaccine aimed to protect koalas from chlamydia. For Tasmanian devils, Flies remarked that the idea is to vaccinate them with a priming dose before the mating season. “That’s when the females and males are most likely to really fight and transmit tumors.” Then, he hopes to drop more bait after the mating season to get them a booster. “So, if they were exposed and didn’t get the tumor, then we give them a booster and hopefully protect them into next year if they did have a tumor. We’re hopeful that the vaccine can actually work as an immunotherapy.” Bergthaler also added that the strategy might work even better with a second line of attack, such as a drug to kill cells and promote an immune response against the tumor.

“The goal is, in early 2026, to be testing vaccines with captive devils. First, we just put the vaccine in to make sure it’s safe and that it induces an immune response. Then, we vaccinate some devils, and we challenge them with tumors to see if they can be protected.” The small trial is expected to include roughly 22 devils, and Flies noted that if all goes well, they can further refine the vaccine.

From Cancer to Conservation: The Tasmanian Devil’s Struggle for Survival

While vaccine development and the potential use of pharmaceuticals for DFTD have gained traction, researchers have arrived at another crossroads: How do these insights inform conservation efforts? Scientists are divided on the best way to ensure the species’ survival but acknowledge that it is a complex problem.

“As with everything, there’s potential pluses and minuses, but we are now convinced with our models and field tests of those models and lots of genomic data that we think until we know otherwise, our group is of the scientifically informed opinion, we shouldn’t do anything because we’re seeing evidence of recovery,” explained Storfer. He added that DFTD appears to be transitioning from emergence to endemism. “We have not seen any evidence of populations going extinct,” he said.

[The devils] certainly have lower genetic diversity than is expected…[But] that doesn’t mean that the population doesn’t have the evolutionary capacity to adapt.

—Andrew Storfer, Washington State University

So, he believes that it is better to leave Tasmanian devils alone, stating that there are also risks associated with translocating individuals from a disease-naive population. If these individuals have no adaptation to the disease, it could be like “adding fuel to a fire” if DFTD further evolves. Thus, well-intentioned interventions may do more harm than good.

He anticipates that more sophisticated models and AI can help researchers understand the predictability and repeatability of evolution—for devils and other species globally—to inform management of conservation and how the process of evolution works. But for now, it’s best to leave the devils be.

In contrast, other researchers, including Belov, who alongside conservation biologist Carolyn Hogg at the University of Sydney, believe in actively managing the Tasmanian devils to improve genetic diversity. Leaving devils alone may lead the populations to become increasingly inbred; instead, Belov believes that insurance populations are one piece of the solution.²⁶

In these programs, captive Tasmanian devils are intentionally mixed to boost genetic diversity.²⁷ “We were mixing Eastern and Western devils to increase MHC diversity in progeny, and we were able to show that those progeny were healthier than their parents…It has increased genetic diversity locally for populations. It’s increased genetic resilience, but it doesn’t seem to have had a negative impact on the prevalence of disease in those populations,” Belov explained.

Either way, the Tasmanian devil’s fate has come a long way from DFTD being practically a death sentence and many believing they were hellbent on extinction. The devils are just as feisty in battling this contagious cancer, showing signs of population persistence. From the concerted efforts of many—researchers, conservationists, and the community—the future looks much brighter for this iconic species.