Infectious Cancers and Other Lessons in Animal Conservation

Tasmanian Devil Facial Tumour Disease

You may recall the Tasmanian devil (of Looney Tunes fame) from your childhood days. It may surprise you to learn that this character is based on a real animal that lives in Tasmania, a large island-state off the southeast coast of Australia. The Tasmanian devil is the world’s largest carnivorous marsupial. It feeds on small preys such as birds, snakes and even insects. They are also scavengers, feasting on carrion. As marsupials, the young develop in a protective pouch like the kangaroo. To me, the devil looks like a cross between a rat and a dog, and it weighs between 10-20 pounds. The animal gets its name for the ferocious cries and growls it emits and the threat displays it produces when faced with a predator, while fighting for mate, or defending a meal. Tasmanian devils often bite one another while fighting, particularly on the face and neck.

In 1996, conservation authorities in Tasmania noticed that some animals had peculiar ulcers on the face. Further investigation determined that the ulcers were cancerous in nature. The tumours grew relatively rapidly, eventually preventing the animal from eating and causing death. Alarmingly, many animals were affected, and now it is estimated that the population has been halved as animals die from this disease. It is estimated that the species could go extinct within the next 25-30 years.

Tasmanian devil with facial cancerBBC Natural History Unit

Infectious Cancer?

This later fact should trouble you for many reasons. First, from a conservation point of view, the disappearance of the largest carnivorous marsupial represents a loss of the biodiversity for the planet. When animals go extinct, they don’t come back. As a molecular biologist, this case concerns me for an entirely different reason. An animal population seems to be decimated by cancer. And not just any form of cancer, but the same type: facial cancer. But wait. How could this be? Cancer isn’t infectious, is it? How is it then that many animals are dying of facial cancer?

Let’s review what cancer is. Cancer could be described as one cell in the body deciding it’s had enough of working “for the good of the group” and becomes a selfish rogue. This cancer cell stops doing whatever its function was (e.g. if it was a lung cell, it stops helping to transport gases in and out of the body), and it starts replicating out of control. There are several other changes that must occur, notably being able to evade the immune system (note: cells in our bodies often become cancerous, but our immune system usually identifies these rogues and kills them before they can do any harm). Finally, cancerous cells detach from the tissue where they formed, and invade the body. If they find their way to the blood or lymph system, they can travel elsewhere in the body, and form tumours somewhere else where they lodge (this is metastasis). Note that there was one source of cancer cells, despite multiple occurrences of tumours in the body. The initial lung cell that became cancerous is now found in your liver, your brain, your stomach, and causes damage in all of these places. Ultimately, the body breaks down because the tumours are impeding the function of normal tissues.

The cancer process that I have described happens inside one animal. There is no transmission to another animal. Transmission between animals is where viruses and bacteria excel. Viruses and bacteria are very small foreign organisms that take over or impede your cells from functioning properly. You have experienced them as flus and cold and other infections. They infect one organism, replicate, and then spread to the next animal, where they cause identical symptoms. Looking at what is happening among the Tasmanian devils, it seems a bacterial or viral agent is at play. Yet when you look at what is causing the disease, it’s clearly cancer. What’s going on?

A solution to this enigma was first proposed in 2006 (1), when it was discovered that the cancerous cells found in the facial tumours of diseased devils all came from the same source. This was identified through chromosomal analysis which confirmed that the cancerous cells in all diseases animals were clones of one another (this was recently confirmed by another study (2)). How could this be? Well, in a way, cancerous cells are very good at replicating and invading other tissues, so it’s not that surprising. What is surprising is that they have spread to other animals. Let’s review a bit of the life history of Tasmanian devils. They often bite one another on the face in fights. Perhaps when an infected animal bit another it left some of its cancerous cells in the wound of the second. Those newly transferred cells then began to replicate and do what cancerous cells do, and the second animal developed cancer. Bingo: infectious cancer!

You should be very alarmed by now. If you have ever come in contact with someone with cancer, have you increased your risk of developing cancer yourself? In fact, in the scientific literature, there is one reported case of a surgeon who inadvertently cut himself while operating on a tumour and did get sick. There are also reports of organ recipients getting cancer from the organs they received, pregnant women transmitting cancer to their unborn child, and twins in the womb exchanging cancerous cells. There is also a report of an unusually infectious venereal cancer in dogs …But these are exceptions, and for a very good reason. Remember that the immune system is very good at recognizing cancerous cells. It’s also very good at recognizing “self” from “non-self” cells, i.e. cells that come from your own body and cells that do not. The general response when the immune system encounters a “non-self” cell is to destroy it. That’s why organs have to be typed and matched in organ donations. If the immune system of the organ recipient recognizes the organ cells as “non-self”, it will attack and destroy the transplanted organ. So, while it is theoretically possible for cancer to be passed between humans, many things have to go wrong for cancer to develop.

So what went wrong in the Tasmanian devils? One hypothesis was that Tasmanian devils are too similar to one another, and their immune system therefore has a hard time differentiating between self and non-self cells. In 2007 (3), a research group demonstrated that this was indeed the case. In the past, the devil population has gone through what is called a bottleneck, meaning that the population dwindled to a very small number. The animals that survived repopulated Tasmanian, but they had to do so with a substantial amount of inbreeding: close relatives were mating with one another. The problem with inbreeding is that the DNA of close relative tends to be very similar. There is not much variation. Effectively, it’s as though the current devil population are nearly identical clones. When a cancerous cell from another animal “infects” their body, their immune system is not able to tell it apart from their own cells, and they are prone to the disease.

So there you have it: the facial tumour disease probably developed in one animal around 1996. Ever since then, the cancerous cells from that one animal have been passed around. They are spread between animals through biting. All animals are vulnerable because they are too genetically similar and their immune system is not able to detect and defend against the cancerous cells.

Lessons Learned

So what are the lessons learned from this case?

First, cancers can be infectious. They don’t tend to be, but under specific sets of circumstances, they could be. Humans have a very diverse set of genes that control the “self” from “non-self” recognition system. In fact, it’s been suggested that the reason it is so diverse is to prevent infectious cancers. So you can rest soundly, this will probably not happen (but there are always exceptions!) in humans.

Second, given the low degree of genetic variability in the devil population, it’s unlikely that the devils will evolve a way to resist the infection. This is another reason why a large amount of animals need to be protected when establishing conservation strategies. If there aren’t enough animals protected and preserved, there is not enough genetic diversity, and inbreeding will cause this (and other) problems that threaten the viability of the species.

References

1. Pearse Am, and K Swift (2006). Transmission of devil facial-tumour disease. Nature 439:549.
2. Murchison Ep, Tovar C, Hsu A, et al (2010). The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer. Science 327:84-87.
3. Siddle HV, Kreiss A, Eldridge MDB et al (2007). Transmission of a fatal clonal tumor by biting occurs due to depleted MHC diversity in a threatened carnivorous marsupial. PNAS 104(41): 16221-16226.