Cancer, genetics, and the Tasmanian devil

A cancer is sweeping through the population of Tasmanian devils, plaguing these small, carnivorous marsupials with tumors on their noses, eyes, and mouths. The tumors kill these creatures in months by interfering with their ability to see, smell, or eat.

But this is no ordinary story of animal vs. cancer. The Devil Facial Tumor Disease (DFTD) is a rare instance of a transmissible cancer, making this an evolutionary battle for survival between the devils and a line of mutated cells that has taken on a life of its own. In 15 years, the cancer has wiped out 70 percent of the population.

On the side of the devils is biochemist Stephan Schuster of Pennsylvania State University, best known for sequencing the genome of the woolly mammoth and other extinct animals. More recently, he has been studying the genetic diversity of devils, both living and dead, to find the best strategy to save them from extinction. His work could help save other threatened species.

Working against the devils is a very limited gene pool, Schuster said. Individual devils are so genetically similar you could take a skin graft from one to another with no threat of rejection. That's why their immune systems don't recognize tumor cells from another devil as foreign, he said.

At the same time, some researchers have begun to see cancer in terms of natural selection. As tumors make new cells with slight genetic variations, natural selection preserves those that can most readily thrive at their host's expense.

University of Pennsylvania cancer researcher Peter Nowell noted this back in 1976, suggesting that the progression of precancerous growths into cancerous ones was a process of evolution by natural selection.

In the case of DFTD, the cancer cells have acquired a particularly frightening trick - they can jump from one animal to another.

The last 40,000 years have not been kind to Tasmanian devils, said Schuster. Fossil evidence shows they once thrived all over Australia, but their population took a nose-dive when aboriginal people arrived on the continent, introducing a competitor - the dingo.

The only place the devils survived was the island of Tasmania, south of the mainland, where there were no dingoes.

It's not even clear how the devils got there, said Schuster, since the channel between island and mainland is deep, with no land bridge possible in recent times.

The devils became threatened in Tasmania when farmers settled the area in the 1800s and began shooting at them, considering them pests.

And yet, by the early 1990s, there were still 100,000 animals, enough that conservationists took them off the endangered species list.

But then, in 1996, a wildlife photographer made the first official observation of the facial tumors. At first, Schuster said, scientists thought they might be spreading by a virus, the way human papillomavirus (HPV) spreads cervical cancer in humans.

But as scientists started trapping the animals and studying the tumors, they found that the cancer cells were jumping from devil to devil, no virus needed.

The animals tend to fight a lot, said Penn veterinarian Karen Rosenthal, who traveled to Tasmania this year and worked with doctors trying to save the devils.

The way they fight is by biting each other on the face, she said. They fight over mates, and when a male and female hook up, they bite each other while mating.

The only other incidence of a directly transmissible tumor happens in dogs, Rosenthal said. Certain breeds can get what's called transmissible venereal tumor, though it's rare. In the case of the dogs, inbreeding may lead to susceptibility. Is the same true of the Tasmanian devils?

To understand their history of genetic diversity, Schuster acquired hair from seven specimens preserved in museums, the oldest one dating to 1874. Even without a follicle, the long-dead hairs yielded enough DNA to do some key measurements of genetic diversity without damaging the specimens.

Museomics is the term Schuster uses to describe what he does, first with mammoths, then with the extinct Tasmanian tiger, which led him to the plight of the Tasmanian devils.

"If we look back in time, with museum specimens and with ancient DNA, we can make predictions about the future," he said. "We can learn about species that are extinct to try to do the right thing for species that are endangered today."

The old specimens show that the genetic diversity of these creatures had been low before the cancer epidemic began.

The next step was to do a complete genetic sequencing of modern devils. He used samples from two: Spirit, a female, already afflicted with the disease, and Cedric, a male, who had been captured while healthy and infected as part of research to develop vaccines for DFTD.

"Both are with the spirits now," Schuster said. They were chosen because they had lived at opposite ends of the island, maximizing the genetic differences they were likely to carry.

The analysis, done with Penn State's Webb Miller and collaborators in California and Australia, revealed one million genetic differences between Cedric and Spirit, which sounds like a lot but is really small considering that the devils' genome has more than three billion "letters" of genetic code.

The team picked 1,500 of these genetic differences, called single nucleotide polymorphisms, or SNPs, and looked for them in a sample of 175 live devils.

That wasn't as hard as it might sound, Schuster said. Despite their fighting instincts, captive devils can be quite angelic.

The ultimate goal of all this, he said, is to isolate populations of disease-free animals, and then use selective breeding to maximize genetic diversity before they are rereleased. This would not only help them beat this disease, but also give them a chance to survive whatever threat might hit them next.

In the most extreme case, Schuster said, they may end up losing all the wild devils to the disease, saving only a group of captive individuals.

"We need to pick the right group of animals for the new founder population," he said. "Then you can release them into the wild, and hope they will rebound."