Tasmanian Devil road signA year or so ago, the first time I mentioned transmissible tumors, I dismissed Tasmanian Devil Facial Tumor disease as not particularly surprising. As I said more recently, I’ve changed my mind about that, almost entirely because of a chat with Elizabeth Murchison at the Origins of Cancer symposium last month, who told me a couple of things I hadn’t known about the situation.

TDFT is a transmissible tumor, a cancer that arose in one Tasmanian Devil some time ago (at least a decade ago, and maybe much longer) and that is now spreading throughout the Tasmanian Devil population — killing a vast number of them. It’s a tumor that’s spread when these highly territorial animals1 bite each other on the face; the tumor then grows on the bitten animal’s face and eventually makes it unable to eat properly. Nearly 90% of Tasmanian Devils, in affected areas, have died. This is a catastrophe.

(The good news, such as it is, may be that the Devils as a population are adapting to the tumor to some extent — not by resisting the tumor, though, but through rapid selection for much earlier breeding. 2 By reproducing earlier, the population may be maintained even though the Devils are dying as adults. Of course, the population that “survives” won’t be the same as those the existed earlier — they’ll be younger, they’ll have all kinds of different characteristics because they’re no longer being selected for adult survival — but at least it might open a window to save the species.)

Orphan Tasmanian DevilCancers are not, in general, transmissible.  Each new cancer is a new event, that arises from normal cells of the affected individual.  A transmissible cancer would be like an organ transplant — it would be rapidly rejected, because individuals in a population have different MHC molecules, and the immune system rapidly and aggressively rejects cells with the wrong MHC. So there are two possible reasons why a tumor could, in fact, become transmissible. Either the individuals in a population do not have different MHC molecules on their cells, or the tumor can transmit between individual in spite of different MHC molecules.

The explanation for the spread of TDFT seemed to be the former: It was claimed that Tasmanian Devils have very little MHC diversity, so that they can’t reject the tumors3. Even though MHC is normally highly diverse in a population, there are certainly populations — especially small, island, threatened populations, like Tasmanian Devils — that have very limited MHC diversity, so this seemed reasonably plausible. 4 This would be a fairly well-understood mechanism of tumor spread, which is why I said it wasn’t that interesting.

Tasmanian Devil skeletonThe other possibility is that the tumor could spread between individuals in spite of them having different MHC molecules. This is not supposed to happen, according to our understanding of MHC and organ transplants; but in fact, it’s the way the only other extant transmissible tumor (Canine Transmissible Venereal Tumor) spreads.  We have no idea why that happens, which makes it interesting. (A number of ways have been proposed by which CTVT avoids rejection. I won’t go into them in any detail here: none of them, as far as I can see, are unique to CTVT, but rather are very common molecular changes in tumors of all kinds, and yet other tumors are not transmissible; so I don’t consider any of these suggestions to explain the unique feature of CTVT.)

Anyway, as I say, the explanation for TDFT was simple enough: The tumor spread because Tasmanian Devils aren’t genetically diverse. But there are three major arguments, I’ve learned, that say that explanation is wrong.

First: Tasmanian Devils are not, in fact, spectacularly genetically homogenous. 5 They’re not as diverse as you’d like to see, but they’re not completely homogenous. In particular, there are two clear, genetically distinct, populations of Devils in Tasmania, one in the East, and another in the Northwest.

Second: Murchison told me that Tasmanian Devils — even those in the same sub-population — vigorously reject each others’ skin grafts. This is what’s supposed to happen with skin grafts, of course. It implies that the Devils do not, in fact, have the same MHC; and in my opinion it’s a much stronger experiment than those in the original homogenous-MHC paper. 3 If Devils reject skin grafts from each other, then they ought to reject tumors from each other — in other words, even if the tumor can take in one individual, then it should be rejected in another, so the tumor should not spread throughout the population. The skin graft finding hasn’t, as far as I know, been published, but if it holds up, it’s a strong argument against homogenous MHC.

Third: Murchison also told me that the tumor is spreading into Devils in the Northwest. 6 As I said, the Northwestern and Eastern Tasmanian Devils are clearly distinct populations, with different genetic characteristics. 7  If the tumor can spread between them, then the tumor isn’t relying on genetic homogeneity for its transmission.

So the evidence for MHC homogeneity is not good, the evidence that the tumor requires MHC homogeneity is not good, and the only precedent we know of, CTVT, does not require MHC homogeneity for its transmission.

It seems that the two transmissible tumors we know of may be much more similar than I had thought.


  1. Incidentally, when I was looking for images of Tasmanian Devils, I found it interesting that the great majority of images I found using Google Image Search showed an open-mouthed, angry Devil, about to take a chomp out of something.  I was going to comment on that, and then I went to Flickr and did the same search, finding instead thousands of pictures of peaceful, timid, close-mouthed Devils.  I think the popular images, put by Google at the top of the list, as so popular because they reinforce the Devil stereotype, and the Flickr photos are a more accurate reflection of their true nature.[]
  2. Jones, M., Cockburn, A., Hamede, R., Hawkins, C., Hesterman, H., Lachish, S., Mann, D., McCallum, H., & Pemberton, D. (2008). Life-history change in disease-ravaged Tasmanian devil populations Proceedings of the National Academy of Sciences, 105 (29), 10023-10027 DOI: 10.1073/pnas.0711236105[]
  3. Siddle, H. V., Kreiss, A., Eldridge, M. D., Noonan, E., Clarke, C. J., Pyecroft, S., Woods, G. M., and Belov, K. (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. Proc Natl Acad Sci U S A 104:16221-16226[][]
  4. Olivia Judson had a very good summary of the argument in her blog; she also made the important point that MHC diversity, or lack of it, is clearly not the only factor involved in the tumor spread.[]
  5. JONES, M., PAETKAU, D., GEFFEN, E., & MORITZ, C. (2004). Genetic diversity and population structure of Tasmanian devils, the largest marsupial carnivore Molecular Ecology, 13 (8), 2197-2209 DOI: 10.1111/j.1365-294X.2004.02239.x[]
  6. Again, as far as I know this isn’t published yet.[]
  7. The authors of the 2004 paper didn’t specifically look at MHC diversity, though; so it remains possible, if unlikely, that the MHC is relatively homogenous while the rest of the genome is diverse.  This is completely the opposite of the usual situation, so I think it’s not likely.[]