To Understand Contagious Cancer Is to Understand Cancer Itself

Catching cancer is extremely rare in the entire animal kingdom, but a few representative cases are enlightening.

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Sep 15 2016, 11:00am

Image: Popartic/Shutterstock

The cell pulled from the man's body did not belong. It was cancer, yes, but even cancer belongs, in a sense. We bring our cancers into being. This was different. It wasn't the man's, nor was it human at all. It would take the CDC two years to definitively reach this conclusion.

The 41-year-old man who appeared at a clinic in Medellín, Colombia in January 2013 had received an HIV diagnosis in 2006. He was sick, dwindling; beset by fatigue, fever, cough, weight loss. His immune system had faded to all-but-nothing. The median incubation period for untreated HIV to progress to AIDS is 10 years, and he had traversed that space in seven.

Blood tests revealed his CD4 count to be 24 cells per cubic millimeter. This metric, which counts T-cells and serves as a general indicator of immune health, ranges in healthy individuals from 500 cells/mm3 to 1200 cells/mm3. The threshold for the development of AIDS, the stage of HIV infection in which the immune system becomes dangerously compromised, is 200 cells/mm3.

The sickness that ensues at this stage could be viewed as a "meta-sickness"—it does not itself kill, but instead invites in killers. It invites in everything really, from relatively superficial oral thrush to fungal pneumonia to cancers that no one has ever seen before. These are AIDS-defining illnesses.

The Columbian patient had somehow acquired cancer from another organism. Transmissible cancer is rare, but it happens. It requires extreme conditions: the transfer of tissue between organisms and an immune system caught off-guard, or, in this case, completely depleted.

Read more: Tasmanian Devils Are Becoming Resistant to Species-Ending Infectious Cancer

That transmissible cancer is so rare is a good thing, clearly, but there's another side to it. The non-transmissibility of cancer points directly back at what makes cancer, the regular old cancer our own bodies deliver and that kills more than 8 million people globally per year, so insidious.

Mussels chilling in water. Image: Elena Grigorieva/Shutterstock

Swapping seawater

It's common and fashionable to think of cancer as a human disease, a punishment for human overconsumption and first-world diets. But where there is cell division and undifferentiated cell types, there is cancer, and this includes mollusks.

Shellfish don't pack much in the way of an immune system, which is unfortunate given that the primary life activity of a bivalve is filtering its surrounding aquatic environment. It would be as if you or I found and consumed food by systematically licking everything around us. That's the sort of thing an immune system is built for.

Cancer is not just common in shellfish, but it is particularly villainous here as well. It's now known that several species of shellfish are susceptible to one form of transmissible cancer known as disseminated neoplasia, which is similar to leukemia. Bivalves catch routinely cancer from other bivalves.

This was revealed only recently in a study published in Nature describing a form of transmissible cancer found among three different species of bivalve spread widely across the globe.

Transmissible cancer is rare, generally. There are only a few known instances of it in the animal kingdom at all: Tasmanian devils, domestic dogs, and, now, shellfish.

The mammalian cancers, which are both quite grim, seem to be more just dumb evolutionary luck—more on that later—but with shellfish, it's almost obvious.

"Clams live in the ocean environment where the cells can be transmitted through the water," Stephen Goff, a biochemist at Columbia University's Howard Hughes Medical Institute and lead author of the new study, explained in a recent interview. "They filter enormous volumes of seawater. Even just a few cells in the seawater can be picked up and transmitted."

"They don't have the sophisticated immune system that higher organisms do," Goff said. "They don't have the ability to detect and eliminate cells that don't come from themselves." They simply lack the hardware needed to recognize foreign cells as foreign and to eliminate them.

These images are from the study into the malignant growths of the Colombian patient. As described in the paper, panels A and B show chest scans of the patient, including lung nodules. Panel C shows a biposy specimen of a cervical lymph node "containing firm, solid masses," and D shows "small, atypical cells" in lymph node material. Image: Muehlenbachs et al

Colonization I

Initial tests performed on the Colombian patient found an internal hellscape of growths, cysts, and eggs. The latter were traced back to the tapeworm species Hymenolepis nana.

Common in temperate climates, H. nana is among the most frequently seen species of parasitic flatworm. Its MO is to latch onto the interior of its host's intestines and then grow and grow and grow, extending itself further and consuming progressively more nutrients, leaving progressively less for the host to absorb themselves.

Samples of abnormal lymph node tissue taken from the Colombian man were sent to the CDC for evaluation. "The lymph nodes were grossly abnormal, solid, nodular masses, from which a touch preparation showed small, atypical cells with scant cytoplasm and prominent nucleoli," describes a report published last fall in the New England Journal of Medicine. "Histologic examination showed effacement of normal architecture by irregular, crowded nests of small, atypical cells."

The CDC docs were faced with a "diagnostic conundrum," according to the paper. The cells were almost certainly the result of some malignant process—growing chaotically, invading neighboring tissues—but they also bore the traces of infection by some foreign organism. Were they dealing with a cancer or an infection?

"It looked like cancer, acted like cancer, but the cells were just too small to be considered what would be possible for human cells."

"We got these specimens from Colombia asking for diagnostic assistance because it was a very unusual disease," Atis Muehlenbachs, the lead author of the CDC paper, recalled in an interview. "It looked like cancer, acted like cancer, but the cells were just too small to be considered what would be possible for human cells. It pushed at the limits of our understand at the time."

Over the next few months, most of the masses discovered within the patient remained stable, but his lymph nodes continued to enlarge dramatically. In May of 2013, he entered palliative care, passing away soon after.

The CDC team expected DNA analysis of the growths to yield the presence of something fungal, possibly Myxogastria, a slime mold. What they found instead was a 99 percent match with the aforementioned tapeworm. And yet the growths that they were seeing was clearly not tapeworms or tapeworm eggs. The cells were tapeworm, but in a form never seen before.

What was growing in the Colombian patient was tapeworm cancer. Malignant cells had launched from a common parasitic infection and made their way through his body, unresisted.

Advanced DFTD afflicting a Tazmanian devil. Image: Menna Jones/Wiki

Dogs and devils

The transmissibility of cancer among shellfish seems natural and reasonable given their biology and environment. This should perhaps be comforting to those likely to reflexively imagine wildfire plagues of infectious cancer spreading among humans. After all, we have well-developed immune systems and generally do not go around licking everything all of the time. If our biological complexity weakens us to cancer—providing more cells and tissue types for malignancy to emerge—it also protects us.

And yet, higher organisms—large mammals even—have not entirely been left out: both domestic dogs and Tasmanian devils are vulnerable to infectious cancer. In the latter case, cancer threatens the species with extinction.

This isn't disquieting so much because it portends some future likelihood of humans catching cancer from other humans, but because the mechanisms behind these cancers, Tasmanian devil facial tumor disease (DFTD) and canine transmissible venereal tumor (CTVT), are extreme and completely horrifying. Both were described in a 2008 review in Oncogene.

DFTD has an incredibly high mortality in Tasmanian devils. It's characterized by tumors on the animal's face, mostly around the mouth. The cancer grows quickly, with death following not more than nine months later, most likely due to a cancer-related secondary infection.

Its mode of transmission, and what most likely accounts for its transmissibility at all, is via bite. Simply, Tasmanian devils fuck each other up, slashing and biting at each other's faces. This is what allows for the sufficient transfer of cancer cells: wound-enabled transfers of cancerous tissue. What then allows the cells to proliferate in a new host is thought to be a lack of genetic diversity among the species, resulting in foreign cells that nonetheless look familiar to the recipient devil's immune system, which is otherwise very well-developed.

The transmission route among dogs is similarly gnarly, only instead of faces, it's genitals.

"CTVT transmission may be enhanced both by the extended period of canine sexual intercourse, which involves the mates being 'tied' due to the expansion of the penis within the female genital tract, and by the injuries to the genital mucosa that are frequently incurred as mates attempt to separate," the 2008 paper reports.

"We have to be sort of humble about how complex the natural world is."

It's thought that canine inbreeding may be partially to blame for the weak immune responses that allow CTVT to progress once inside of a new host.

There are likely more incidences of transmissible cancer among higher-level animals, but in every case, the cancer must still overcome those two inescapable hurdles: immune responses and the transmission of actual living tissue from animal to animal.

Research published earlier in August in Nature Communications suggests that Tasmanian devils are as a species evolving immune systems better able to fight off DTFD. This adaptation is occurring at an incredible rate too, likely owing to the intense selective pressure imposed by the species-threatening disease. Transmissible cancer is extreme, and it would seem that in this case it's eliciting a likewise extreme genetic response.

Cancer or tapeworm

Finally, in 2015, CDC scientists were able to say definitively that the Colombian patient had been overrun by cancer transmitted from a parasitic tapeworm. "It wasn't anything that we had knowledge of and it was incredibly hard to diagnose and figure out what it was," Muehlenbachs told Motherboard.

The transmission event raises some very deep and fundamental questions about the meaning of cancer in the very first place. After all, cancer as we understand it is us. It is not an invader, but our own cells running rogue. It's easy to imagine them as cells mutated into self-destructive monsters, but they are mostly just behaving as undifferentiated, immature cells do. They are unaccustomed and uninterested in activities other than multiplication. They do not find function, or they do not find greater function, which is arguably synonymous with differentiation.

"Malignant cells concentrate their energies on reproduction rather than in partaking in the missions a tissue must carry out in order for the life of the organism to go on," Sherwin Nuland wrote in How We Die, which contains a full two chapters of absolute cancer poetry. "The bastard offspring of their hyperactive 'fornicating' are without the resources to do anything but cause trouble and burden the hardworking community around them. Like their progenitors, they are reproductive but not productive. As individuals, they victimize a sedate, conforming society."

A Hymenolepis nana egg. Image: Dr. Moore/CDC

When Goff and his team peered at these alien cancer cells they saw something beyond cancer. Spread throughout the patient's tissues had not just been cancer originating within a tapeworm as though the nematode had functioned as some kind of malignancy launchpad, but the tapeworm. The thing itself—living within and among human tissues and organs.

"We struggled with how to think about it," Muehlenbachs said. "Could drugs against tapeworms work? Could chemotherapy work? Both are possibilities. It would be hard to say that the patient really had cancer." Again: cancer is us. Tapeworms are not.

Colonization II

The transmission of cancer from human to human requires both the transfer of tissue and incredible amounts of bad luck. There are two documented cases of health care workers, a surgeon in 1996 and a lab tech in 1986, who managed to contract cancer via accidental needle stick, but to say that they're outliers would be a massive understatement.

Goff noted, however, that cancer is transmissible, but not in the usual sense of the word. In fact, cancer is deadly because of its ability to be transmitted from tissue to tissue and from organ system to organ system. This is metastasis.

In time, unchecked cancer develops the ability to move from organ to organ or from tissue to tissue. If a malignant growth can be detected before it's had the opportunity to become mobile, survival rates are very often better than 50-50 (based on a rough sampling of prognosis statistics), depending on the variety of cancer and the health of the patient. However, survival rates quickly plummet to the single digits when cancer has become metastatic—that is, when the cancer has become transmissible among the myriad systems of the body.

"It's likely that these transmission events that we're looking at in the mollusks could be comparable to the metastasis of cancer within a single person," Goff explained. "Metastasis is a big deal. A primary tumor is shedding cells that move to a new location, a new organ within that same person, so there's an enormous effort to try to understand that and to try to understand the mutations that allow for metastasis in human cancers."

"Whatever the mutations that are happening in these mollusks could be very relevant to that process," he said.

The poor luck of clams and mussels then offers a new way into understanding the very thing that makes cancer kill in the first place. After all, we don't need to catch cancer. Our own bodies produce cancer so effectively that one in two males and one in three females will develop cancer in their lifetimes, while one in four males and one in five females will die of cancer. There is really no transmissible illness that can boast numbers like that. Cancer is the plague that figured out that it need not bother with transmission in the first place.

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