Love bites on the neck of the young female Tasmanian devil in my lap tell me she has recently had a sexual encounter. They also indicate something ominous: she might well be dead before she can raise her first litter of pups.
I (Jones) am sitting on the ground holding a devil that I trapped in Freycinet National Park on the eastern coast of Tasmania—a wild jewel of an island to the south of the mainland of Australia. It was here, in 2001, that I first witnessed a hideous disease that causes large, festering tumors on the face of these marsupials, impairing feeding and routinely killing them within six months of infection. Today the Freycinet population has almost disappeared—a reflection of what is happening across most of the animal’s range. First detected in 1996, up in the northeastern corner of the island, the cancer—now known to be contagious—has reduced devil populations across Tasmania by up to 95 percent, pushing the species, which lives only on this island, to the edge of extinction.
Fortunately, most cancers in the world are not “catching”: you can sit beside someone on a bus without fear of contracting a tumor. Some malignancies do stem from contagious viruses or bacteria. Human papillomavirus, for instance, can cause cervical cancer. But it does so by predisposing cells in infected individuals to become malignant, not by spreading tumor cells directly from one person to another. In the case of the devil’s disease, the cancer cells themselves are the infectious agents.
The rapid devastation of devil populations has spurred recent research into how their cancer managed to become contagious and what might be done to stop it. Anyone who has heard about the plight of the devils naturally wonders if such tumors could someday also become common in humans. Investigators are pondering this question as well. The short answer seems to be that the odds are in our favor for now, but we are behaving in ways that could potentially reverse the equation.
The Devil’s Curse
Aside from the devil’s affliction, just one other transmissible cancer is known in the wild: canine transmissible venereal tumor, which is estimated to have evolved about 10,000 years ago. This disease is spread in dogs by the transfer of cancer cells during sexual intercourse. Contagious cancers have also been generated by laboratory manipulations of animals. And tumors can occasionally be transferred from one person to another by organ transplantation or from mother to fetus. As a rule, though, cancers begin and end in a single host, because despite their considerable ability to wreck havoc in the body, they encounter a number of barriers that usually prevent them from hopping between individuals. Contagious cancer arose in Tasmanian devils because of an unlucky confluence of factors.
Typical, noncontagious cancers arise after some cells undergo genetic changes enabling them to divide uncontrollably and invade tissues. As tumors grow, they become complex communities of malignant and nonmalignant cells. At some point, the masses may outgrow their blood and nutrient supply and so, like wild animals and plants, come under pressure to disperse tumor cells from their “birthplace” and thereby perpetuate the cancer. Some cells may then break off, travel through the blood or lymph, and set up home in a distant site within the same body—that is, they metastasize. Often it is metastatic tumors, rather than the primary one, that kill a victim, destroying the tumors in the process. This fate puts malignancies under strong pressure to perpetuate themselves in a different way: by spreading to others.
Yet they are usually thwarted at every turn. Notably, for cells to get from one host to another, the trip has to be rapid. Cells are not adapted for survival in the outside world; they tend to dry up and die within minutes of leaving the body. To be transmitted, cancer cells need their original host to behave in ways that will place them directly in contact with the living tissue of a new host.
Once in that new host, invading tumor cells also need to evade immune recognition. The immune systems of higher animals have a number of mechanisms for detecting and destroying foreign cells. Immune system warriors, for instance, hunt down and eliminate cells that look different from the body’s own. Cells from a different organism display protein fragments on their surface unique to that organism, akin to flags that say, “I’m foreign,” and the immune defenses pounce when they detect those flags. The flags are encoded by a variety of genes, including the highly variable major histocompatibility complex genes. Indeed, some biologists think that the major histocompatibility genes, which evolved in early vertebrate animals, became so diverse primarily because they ensure that cancers do not become transmissible.
Sadly for the devils, they lack these blockades to transmissibility. The tumor now tormenting them—officially called devil facial tumor disease—typically forms near or in the mouth, and the animals frequently bite one another, both during sex and combat and often on the face. Hence, their behavior readily delivers malignant cells from one individual to another, either through bites by teeth coated with cells shed from a nearby tumor or through direct contact between a facial tumor and wounds on a partner. The dog venereal tumor similarly spreads through direct contact but, in this instance, as a result of abrasive genital contact during copulation. Both the devil and the dog cancers also become friable with age and size, facilitating the infectious spread by allowing cells to readily peel off from the original mass.
Further, if genetic diversity in a population becomes depleted—if most individuals possess highly similar versions of genes that once occurred in multiple, more divergent forms in the group—the immune system of one individual will have trouble distinguishing cells from a different individual as foreign and will thus attempt no attack at all or will, at best, mount a weak immune response. Tasmanian devils have low genetic diversity, especially in their major histocompatibility complex genes—probably resulting from a catastrophic reduction in populations sometime in the past and possibly from past disease challenges that spared only a group of animals that had a very similar genetic makeup. The dog cancer, too, is thought to have evolved in a small, genetically restricted and inbred population, either in an isolated group of wolves or in a population that lived around the time of domestication.
(The conditions promoting contagion in the devils and in dogs also explain why cancers sometimes travel from mother to fetus in humans or from organ donors to recipients. In both cases, tumor cells pass quickly from the original host to the next one. Also, fetuses have immature immune systems, and transplant recipients take medications that suppress immunity to protect the new organ from rejection.)
Genetic analyses have revealed that the tumors of afflicted devils descend from cancer cells that originated in a single, long-dead devil; notably the growths share a telling loss of certain chromosomes and chromosomal segments that are not missing in other cells of the victims. Because the originator of the tumor is long gone, no one will ever know for certain what caused the initial mutations that allowed the devil’s cancer to become transmissible. The cancer might have arisen, though, from mutations that occurred in cells in or near the face as a result of repeated injury and chronic inflammation, an etiology known as wound carcinogenesis. Elizabeth P. Murchison of the Wellcome Trust Sanger Institute in England provided added specificity in 2010; in a paper published in Science, she reported that the devil tumor originated in Schwann cells, which ensheath neurons outside the central nervous system.
The mix of factors that led the devil facial tumor disease and the canine transmissible cancer to become contagious might suggest that cancers become infectious only rarely in nature because the required conditions—intimate contact permitting transfer of live cells, together with low genetic diversity—hardly ever coincide in nature. Yet other observations suggest contagious cancers might be more common than is generally believed. All birds and mammals, for instance, fight and copulate, and many populations are highly inbred. It is possible, then, that infectious cancers arise more often than is recognized but usually do not persist in the world for long—say, because they kill off infected host populations, and thus themselves, quickly.
The dog cancer does not fit that pattern but hints at another way contagious cancers could exist without being known to us. Today the canine tumors manage to “hide” from the immune system initially, but eventually the system “sees” the malignancies and destroys them, leaving the animals immune to future infection. Other contagious cancers that also do not kill their hosts could be out there. Only detailed genetic work, such as has been done with the dog and devil tumors, will clearly identify whether a wildlife cancer is in fact infectious.
What Lies Ahead
Hosts and pathogens usually co-evolve over time in nature—with the host developing adaptations that control the pathogen, the pathogen taking countermeasures and both persisting in the end. We wondered, therefore, if we might see signs of this evolutionary dance between the contagious cancer and its devil hosts and thus find some glimmer of hope for the animals. We did.
The devils are under intense evolutionary pressure to develop any kind of trait that could improve survival or increase reproduction. And in the years since the devil cancer emerged, it has indeed induced a response in its host: devils are resorting to teenage sex. In the past, females began reproducing at two years old and raised about three litters in a lifetime of five to six years; the disease has cut the litter number to one for many of the animals. Juvenile females that grow fast enough in the first few months after weaning can raise a litter a year earlier than is usual if they have their joeys before winter sets in; this early procreation gives them a chance to nurture at least one, and perhaps two, litters before succumbing to the cancer. Given enough time, such behavior could help maintain species numbers.
With our Ph.D. student Rodrigo Hamede, we are seeking other signs of evolution in animals living in the somewhat isolated northwestern region of Tasmania. The northwestern devil population harbors many genes that differ from the versions found further east, and the group seems better able to resist the disease. As the tumor encounters different genotypes for the first time, it is not causing any population decline. Disease prevalence remains low, and infected devils there survive with the cancer much longer than is the case in eastern Tasmania. We return to several sites in the northwest a number of times a year to observe disease trends and to collect tissue and blood samples, which our collaborators, Katherine Belov of the University of Sydney and Greg Woods of the Menzies Research Institute Tasmania, help us to analyze. By looking at genes and immune responses, Belov and Woods, respectively, are trying to discern whether any particular combinations of genetic variants make the animals’ immune systems particularly good at fighting the cancer. If we can find resilient devil genotypes, we may be able to help spread good genes through wild populations—for instance, by establishing the resistant animals in other parts of Tasmania—and speed up recovery of the species.
We are also seeing evolutionary changes in the tumor itself. Anne-Maree Pearse, a geneticist at the Save the Tasmanian Devil Program—an initiative supported by the Australian and Tasmanian governments—has found that a number of strains have arisen. That variety may or may not be good news. On one hand, some strains could evolve to become less virulent. But on the other hand, different strains may evolve to overcome any resistance that develops in the devil population.
The history of the dog cancer’s evolution offers grounds for some optimism. As is true for many diseases, the canine transmissible tumor probably started off as highly virulent, like the devil’s, and then co-evolved over time with its host canines to decrease virulence, thus increasing the overall success of the tumor: that is, the reduced virulence enabled hosts to live longer with the disease and to spread it to more animals. That pattern would explain how the dog cancer became the generally nonlethal infection it is today.
Contagious tumors not only evolve, they probably also manipulate their hosts, much as parasites manipulate the behavior of their hosts to increase transmission. The canine tumors induce the female dog to produce chemicals that increase sexual receptivity, thus improving the odds of the cancer being passed on to males. Strains of the devil tumor that induce aggression in their hosts could conceivably be selected for, which would increase transmission rates. But it is also possible that low aggression would be selected for because milder animals would be less likely to fight and become infected. We watch the evolutionary dance between the devil and its cancer with close interest.
We hope that, given the will and sufficient resources, the devil can be saved from extinction, allowing it to fulfill its historic role as a top predator in many parts of its range. Devil loss in those areas is expected to precipitate cascading changes in the ecosystems—such as increases in predation by introduced cats and foxes—that could lead to the extinction of various other species. The same pattern has already led to the extinction of several small marsupials on mainland Australia; Tasmania is now their last refuge. Whether efforts to prevent devil extinction can succeed will depend on what we learn in northwestern Tasmania.
Is Infectious Cancer a Risk to Humans?
Given that humans have great genetic diversity and can avoid behaving in ways that would foster tumor transmission, it might seem safe to assume that our species can readily avoid the fate of the Tasmanian devils. Indeed, even if a person were bitten by an infected devil or by a dog with the canine transmissible tumor, the person’s genetic makeup, being so different from that of the animals, would probably ensure a strong immune response able to detect and kill the invading cells; the bitten individual would not get sick or start spreading the disease to others.
There are grounds for concern, nonetheless. Contagious cancers could, in theory, arise in a group of great apes (such as chimpanzees, gorillas or orangutans) having low genetic diversity because of population declines. If these animals were hunted by human populations with many members having impaired immunity, the close contact might enable tumor cells to transfer to humans and then spread. Such conditions exist where humans with a high HIV prevalence hunt endangered apes. Although this scenario is possible, we suspect that cross-species transmission is not the most likely way that a contagious cancer would arise in humans. We hold this view in part because no known cases of cross-species transmission of the dog cancer have occurred in nature—although the disease has been experimentally transferred to closely and distantly related canids in the laboratory.
Still, burgeoning human populations are changing the world in unprecedented ways. HIV has infected millions of people, suppressing their immune systems and leading to the emergence of many once rare cancers. This situation is conducive to the evolution of a contagious cancer. The possibility of an infectious cancer arising in immunosuppressed humans and subsequently evolving the ability to infect the general population is very real. That exact pattern occurred in dogs: the canine transmissible cancer, after probably evolving in an inbred, genetically invariant population, is now able to infect genetically variable dog and wolf populations. That the dog cancer is usually not lethal these days is not terribly reassuring. As we noted earlier, most likely the disease went through a period of being lethal to many of its hosts, as HIV is today, before populations of individuals naturally able to control the cancer expanded and came to predominate.
The devil cancer provides biologists with a unique opportunity to learn about contagious cancers. It also serves to remind us, in the most brutal manner, of the consequences of human activities on our planet. We are releasing copious amounts of carcinogens into the environment, and we are destroying the wild habitats of the world, causing losses of both species and genetic diversity. Global trade and habitat destruction are bringing humans and wildlife into contact with pathogens they have never previously encountered. As a consequence, we can expect to see an increase in new kinds of cancer in wildlife, both contagious and induced by viruses and other pathogens. It is not inconceivable that these malignancies could jump species—even to humans.