In the 1970s, scientists noticed that soft-shell clams along the east coast of North America were dying from a strange type of cancer. Their blood, which was typically clear, would fill with so many cells that it would turn milky. The rogue cells clogged and infiltrated the clams’ organs, often killing them.
This cancer—this clam leukaemia—seemed to be transmissible. If you took the blood of infected clams and injected it into healthy individuals, some of those recipients would develop the disease. For years, scientists suspected that a virus was involved
Michael Metzger from Columbia University has a different explanation. His team has discovered that the thing that transmits the cancer isn’t a virus, but the cancer itself.
The clam leukaemia is a contagious cancer—an immortal line of selfish shellfish cells that originated in a single individual and somehow gained the ability to survive and multiply in fresh hosts.
The vast majority of cancers are not like this; they’re not contagious. Some are caused by contagious things, like viruses (HPV causes cervical cancer) or bacteria (Helicobacter pylori causes stomach cancer), but the cells themselves cannot leave one host and start growing in another. Once their host dies, so do they.
Until Metzger’s discovery, there were just two exceptions to this rule. The first is a facial tumour that afflicts Tasmanian devils. It spreads through bites, and poses a serious threat to the survival of these animals. The second is a venereal tumour that affects dogs. It arose around 11,000 years ago and has since spread around the world.
That was it: two transmissible tumours. Now, there’s a third—and perhaps more on the way. “Maybe this is way more common than we thought in invertebrates, and especially in marine ones,” says Stephen Goff, who led the study. “We’re all sitting in the same ocean here.”
Goff studies viruses that cause leukaemia in mice. His interest in clams began with a phone call from Carol Reinisch, a marine biologist at Environment Canada. “She said: We have this disease in clams. It’s a leukaemia. Can you help us check if there’s a virus involved?” he recalls. He agreed, and she sent over some blood samples.
The team discovered that the disease is associated with a jumping gene—a stretch of DNA that can copy and paste itself into a new part of the clam genome. They called it Steamer. Healthy clams have between 2 and 10 copies of it in their genomes, but the ones with leukaemia have between 150 and 300 copies. Perhaps some virus was causing Steamer to multiply extravagantly. As it jumped into new places, it disrupted important genes, and triggered cancer. Here was “an example of catastrophic induction of genetic instability that may initiate or advance the course of leukaemia,” the team wrote.
If this idea is correct, Steamer should jump into different positions with each new affected clam. Instead, the team found Steamer in many of the same positions in clams from New York, Maine, and Prince Edward Island in Canada. “That’s when we were really surprised,” says Goff. “There was something fishy going on.”
Next, they compared other positions in the genomes of healthy clams, diseased clams, and tumour cells. Right away, they saw that all the tumours are genetically identical, and none of them matched the genes of their host clams. That’s the same pattern that scientists see in the dog and Tasmanian devil tumours. It’s a clear signature of a contagious cancer. These tumours hadn’t arisen in their hosts; they had arrived there.
“It certainly fits,” says Anne Boettger from West Chester University, who has studied the clam cancer. Still, she notes that Steamer’s positions aren’t always the same in all the clams. There are some variations between animals at different sites, and that’s still unexplained.
The discovery does raise more questions than it answers. For example, when did the cancer originate? The dog tumour is several millennia old, while the devil tumour arose just a few decades ago. The clam cancer was certainly discovered in the 1970s, but it may be much older than that.
How did a normal clam blood cell turn into cancerous one, and how did that leukaemia gain the ability to spread? Was Steamer responsible? “We’re very eager to know,” says Goff. “Did the expanding copy numbers [of Steamer] cause the tumour or are they simply passengers? I think it’s likely that one of these new copies is the cause.” His team are now trying to recreate those original events, by deliberating introducing Steamer into new places in normal clams and seeing if new tumours arise.
How is the cancer spreading? Unlike dogs and devils, clams aren’t mounting or biting each other. But they are filter-feeders: they sieve bits of food from the water, so they could easily draw in floating cancer cells too. Certainly, the disease can spread between animals that share the same aquarium tank, even if they aren’t touching. “It’s not efficient or quick but in the course of months, it happens,” says Goff. It’s a terrifying thought: transmissible cancer in the water. Thankfully, it’s just the clams that are affected.
Or is it?
“We are actively looking in other species too,” says Goff. “There are leukaemias like this in other molluscs in Europe.” In his paper, he already hints that he has discovered a contagious cancer that affects cockles. He also wants to know if these cancers can spread from one species of shellfish to another.
“We normally think of cancers as evolutionary dead ends that emerge and die within the confines of their hosts’ bodies,” says Elizabeth Murchison from the University of Cambridge, who studies the Tasmanian devil tumour. “However, we now know of three runaway cancer clones which have evolved the potential to survive beyond their hosts and become parasitic clonal cell lineages. Understanding how clonally transmissible cancers emerge, spread and escape the immune system may help us to understand fundamental mechanisms of cancer evolution.”
Reference: Metzger, Reinisch, Sherry & Goff. 2015. Horizontal Transmission of Clonal Cancer Cells Causes Leukemia in Soft-Shell Clams. Cell http://dx.doi.org/10.1016/j.cell.2015.02.042
More on contagious cancers: