Siddle believes the results may offer all the pieces needed to develop a vaccine against DFTD. One strategy would be to take devil tumor cells from the wild and turn on their MHC genes in the lab, making them recognizable to devils’ immune systems. Then, with their evasion strategy disabled, those cells could be injected into healthy devils, whose immune systems could learn to mount a defense when they encounter the cancer in the wild.
“I think there’s a good chance that this vaccine will work,” Siddle says. “Whether we get something that’s effective and cost-effective [enough] to be used in the field before DFTD moves through all of Tasmania is another question.”
Even if researchers could protect large numbers of Tasmanian devils with a vaccine that was 100 percent effective, those animals’ immunity would not be passed on to their offspring; any vaccination program would need to go on indefinitely, a formidable challenge.
Evolution in Fast-Forward
While Jones hopes Siddle and Belov succeed in developing a DFTD vaccine, she’s not expecting the devils’ salvation to be delivered through a needle. Instead, she looks to another strategy: helping the devil and the cancer evolve their way into peace.
Currently, the devil cancer is far too deadly for its own good: By killing its host, the cancer is limiting its future prospects. That glaring evolutionary stumbling block should cause it to become less virulent, while also causing the devil to become more resistant over time.
CTVT, the infectious cancer that affects dogs, may point to the devil tumor’s future. At perhaps 11,000 years old, CTVT is the oldest known line of mammalian cells on Earth, so it’s no longer evolving much. Through random mutations in the past, it has already found the most advantageous arrangement of its DNA. In particular, it has evolved to show itself three to nine months after infection, allowing its own destruction by displaying antigens on its cell surfaces so the dog’s immune system can destroy it. It’s a smart evolutionary tactic, allowing infected dogs to survive and breed, thus continuing their own species and providing future hosts for the tumor.
With time, most parasites pick up similar tricks, killing their hosts more slowly or not at all. Left to its own devices, the devil tumor may likewise evolve to be less deadly. The problem is time. Because the devils are so geographically restricted and because there are so few of them, the cancer may kill them all before it has time to evolve in the ways CTVT has.
Jones’ colleague Elizabeth Murchison, a geneticist at the University of Cambridge in the U.K. (and a Tasmanian expat), is working to understand the evolutionary process. The tumor is indeed evolving rapidly, she has found. Sequencing the cancer in 2007, she found that the tumor had picked up about 20,000 mutations. (By now, it undoubtedly has many more.) Most of those mutations are irrelevant, but a few of them are key, including those allowing the cancer to spread among devils. She has sequenced hundreds of tumor samples from across the island in an effort to understand how it evolves and how that affects the devils’ survival rates.
Jones and Pearse hope that with this genetic knowledge in hand, it might be possible to nudge evolution along by selectively breeding devils that are particularly resistant to the cancer, or to cancers altogether. “I think there is a light at the end of the tunnel, but it’s a very long tunnel,” Pearse says.
Such insights could not only help rescue the devils, Murchison hopes they might help advance cancer biology more generally. A cell that evolves a mutation allowing it to divide endlessly will outgrow its neighbors. One of its progeny might pick up a mutation giving it the ability to gobble up nutrients faster; or to enslave other cells and force them to form blood vessels to feed it; or to hide from the immune system; or to resist a particular chemotherapy. Each of these mutations gives the cell an advantage over its brethren, which it then outcompetes.
The cells from that one, long-dead female devil somehow picked up another highly valuable evolutionary trick: the ability to survive in another devil’s body. Researchers studying the devil tumor hope to learn what cancer does when the inconvenient obstacle of its host’s death isn’t enough to stop it. “Cancers are evolution in action,” Murchison says. “Understanding the underlying evolutionary mechanisms that drive all cancers, not just the devil cancer, will help us understand and treat the disease.”