Monthly Archives: March 2013

Sympathy for the Devils

This work by Mike Lehmann is licensed under a Creative Commons Attribution 3.0 Unported License.

Tasmanian devil, a marsupial native to the Australian island of Tasmania
[This work by Mike Lehmann is licensed under a Creative Commons Attribution-Share Alike 3.0 Unported License.]

Last week, I was lucky enough to attend the TedX DeExtinction event in Washington, DC. The event, hosted by National Geographic and Revive & Restore, was a day long series of short talks about the science and ethics of “de-extinction.” De-extinction is the idea that you can use new reproductive and stem cell biology techniques to revive extinct species, from the recently disappeared (e.g. bucardos and gastric brooding frogs) to the long lost (e.g. wooly mammoths  and giant ground sloths). The event raised quite a few questions on the ramifications of bringing species back from the dead: would de-extinction take funding away from conservation efforts? Would a de-extinct mammoth really be a mammoth? Would there even be a place for these new old species in our changing world? Is de-extinction, like the moon landing, a vehicle to inspire scientific wonder and progress?

We can (and should) argue about the ethics and reasons for reviving lost species, but we should also explore how to use synthetic biology to save dwindling species from imminent extinction. Take for example, the Tasmanian devil. Though these large marsupials were once common across Tasmania, their population has been devastated by a strange form of contagious facial cancer.

In the late 1990’s, facial tumors were spotted on devils in northeastern Tasmania. The cancer was deadly, killing the animals it infected within six months. More importantly, the cancer jumped from devil to devil with ease by taking advantage of the species’ aggressive nature: when Tasmanian devils fight (which they often do), cancer cells can be transferred from the teeth of an infected devil to the face of their uninfected sparring partner. The facial cancer has caused a 90% drop in devil population since it appeared, and total extinction of the species within 30 years is a distinct possibility.

This work by Menna Jones is licensed under a Creative Commons Attribution 2.5 Generic License.

Tasmanian devil face tumors
[This work by Menna Jones is licensed under a Creative Commons Attribution 2.5 Generic License.]

Transmissible cancer isn’t unheard of. Dogs can pass on a form of venereal cancer, and there’s a contagious sarcoma that affects Syrian hamsters. Cancer transmission has also been known to happen in humans after organ transplants or by passing between mother and fetus. However, in most animals, the immune system recognizes and destroys foreign cells (cancerous or otherwise). In fact, this is one of the main hurdles with organ transplants. Recipients have to take immunosuppressive drugs and in some instances immune system reactivity leads to organ rejection. In the case of Tasmanian devils, however, this immune hurdle doesn’t exist.

Immune system recognition of “self” and “other” relies on molecules on the surface of the cell called major histocompatibility complexes (MHCs). MHCs act as signaling flags to the immune system, telling your immune cells whether a cell is normal, infected with a pathogen, cancerous, or an invader. There are two main classes of these molecules, and each one has regions that vary among members of the population. Variation in MHC molecules allow immune cell to differentiate your cells from other cells, kind of like knowing members of your sports team because you all wear the same jersey. Human MHC class I molecules have six sites where they can vary, and hundreds of variations available for most sites.

Tasmanian devils, on the other hand, have very little population diversity in MHCs. At some point in the past, the devils experienced what’s known a genetic bottleneck. A large portion of the population was killed (cause unknown), leaving only a small gene pool, and thus a small sampling of MHC variations.

Tasmanian devil MHC complexes are so similar that their bodies can’t  tell the difference between their own cells and those of other devils. Every team’s jersey is so similar that it’s hard to know who’s on the home team and who’s the visitor. So when cancer cells from an infected devil latch onto an uninfected devil, they go undetected by the immune system and spread unhindered. Genetic studies of the cancer have shown that the DNA of tumor cells is extraordinarily similar across the infected devil population. Furthermore, the tumor DNA is significantly different from the infected devil’s DNA. These facts point to a tumor that arose in one devil and spread as a tissue graft to other devils through bites. Because of their lack of immune diversity, the Tasmanian devil population is being wiped out by one giant tumor run amok.

What can we do to stop the eradication of Tasmanian devils? Synthetic biology may have the answers. Developing technology may allow scientists to create Tasmanian devils with more MHC diversity, devils with immune systems that would spot and destroy the invading cancer cells before they took root. In my next blog post, I’ll talk about the discoveries and technology that could save the Tasmanian devil, and other species that are near (or already) extinct.

716px-Tasmanian_devil_head_on

How can we save these guys? Tune in next time to see!
[This work by KeresH is licensed under a Creative Commons Attribution-Share Alike 3.0 Unported License.]

Sources:

O’Neill, Iain. “Tasmanian devil facial tumor disease: Insights into reduced tumor surveillance from an unusual malignancy.” International Journal of Cancer. 127.7 (2010): 1637-1642.

 Siddle, Hannah et al. “Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial.” PNAS. 104.41 (2007): 16221-16226.

Siddle, Hannah et al. “MHC gene copy number variation in Tasmanian devils: implications for the spread of a contagious cancer.” Proceedings of the Royal Society: Biology. 277.1690 (2010): 2001-2006.

Woods, Gregory et al. “The Immune Response of the Tasmanian Devil & Devil Facial Tumour Disease.” EcoHealth. 4.3 (2007): 338-345.

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