In the 1970s, soft-shell clams started mysteriously dying off in Maine and the Chesapeake Bay. Years later, scientists identified the culprit: a bizarre form of cancer that spread like an epidemic.
When people get cancer, it typically arises when some of their own cells gain mutations and multiply out of control. But the clams were being invaded by free-floating cells that came from other clams. The alien cancer cell multiplied inside its new victim, and then some of its descendant cells escaped to attack other clams.
Other species of shellfish turn out to be victims of contagious cancer as well. And now researchers have found that these lineages of cancer cells have been jumping from one shellfish to the next for centuries, perhaps even thousands of years, picking up a surprising number of telltale mutations along the way.
“It doesn’t seem biologically possible that these cancers are doing this,” said Adrian Baez-Ortega, a computational biologist at the Wellcome Sanger Institute in England and an author of one of two studies on the cancer published on Monday. “And yet they are long-lived.”
In 2015, researchers sequenced short pieces of DNA in cancer cells collected from soft-shell clams in Canada, Maine and New York. The genetic analysis showed that the cancer cells did not belong to the animals they came from. Instead, they were all related to each other, descending from a single ancestral cell.
Before then, researchers knew of contagious cancers only in two mammals: the Tasmanian devil and dogs.
The cancer in Tasmanian devils forms tumors on the marsupial’s face. When the animals bite each other during fights or mating, they can pick up the cancer cells. The disease has wiped out 90 percent of the entire species.
Dogs, in contrast, can acquire a fairly benign cancer that spreads during mating. The cells form growths around the genitals, and the dogs’ immune systems typically destroy the invaders in a matter of weeks.
The discovery of contagious cancers in soft-shell clams spurred a search in other shellfish. So far, scientists have published details on contagious cancer in eight more species, including mussels and cockles.
“More will be coming — more that we know of, and probably more that we don’t know,” said Michael Metzger, a biologist at the Pacific Northwest Research Institute in Seattle.
In recent years, Dr. Metzger and his colleagues have tried to catalog all the mutations that have arisen since the cancer cells left the original clam and became transmissible. Dr. Baez-Ortega and his colleagues carried out a similar study on the common cockle, which lives along the Atlantic coast of Europe.
Instead of sequencing tiny snippets of DNA from the cancer cells, the researchers sequenced the entire genomes as well as those of the animals. The scientists could then compare the DNA both from the animals’ healthy cells and from their diseased ones to find the hundreds of thousands of mutations that arose in the contagious cancers.
Certain cancer cells had mutations in common not found in other ones. That pattern revealed how they descended from a common ancestor, branching out in a family tree. In the soft-shell clams, Dr. Metzger’s team found that the tree has two branches, one leading to cancer cells around Prince Edward Island, and the other leading to those found off the Northeastern U.S. coast.
Dr. Metzger and his colleagues looked at the number of mutations that have accumulated in the different branches to estimate how long ago the original ancestral cancer cell broke free. They estimated it became contagious more than 200 years ago or perhaps a few centuries earlier.
Dr. Baez-Ortega and his colleagues concluded that the cockle cancers are similarly ancient, although they were unable to come up with an estimate. “They are probably thousands of years old,” he said.
In both species, the cancer likely started off as an immune cell that mutated and multiplied. Those cells were then shed into the water, taken up by another shellfish and grew like a cancer again. Eventually, the cancer cells gained mutations that allowed them to survive in the water for months before finding a new host.
Studies on Tasmanian devils and dogs have revealed that the DNA of their cancers has changed relatively little. That finding is not too surprising in the case of Tasmanian devils, which probably gained their cancer just 40 years ago. But dogs gained their cancer 11,000 years ago. And in all that time, the cancer cells have gained only modest changes to their genomes.
By contrast, in both clams and cockles, cancer cells have experienced repeated rounds of drastic change. Some cancer cells ended up with extra chromosomes — hundreds of them, in some cases. Some have lost long stretches of DNA. In other cases, the entire genome has been duplicated.
“This level of instability is usually lethal to a cancer cell,” Dr. Baez-Ortega said. Neither he nor Dr. Metzger can explain how the contagious cancers have survived for centuries in this state of genetic chaos.
Beata Ujvari, an evolutionary ecologist at Deakin University in Australia who was not involved in the study, said that the massive mutations might be explained by the way the contagious cancers reproduce. Instead of combining two sets of DNA from a shellfish egg and sperm, the cancers clone themselves.
In that way, they’ve become more like bacteria than animals. And like bacteria, they might try to beat their competition — other cancers — by mutating faster, Dr. Ujvari said. She noted that the new cockle study revealed that two different contagious cancers will sometimes invade a single animal.
Dr. Metzger hopes that by solving this puzzle, he and other scientists may be able to uncover some hidden rules of cancer that might apply not just to shellfish but to people.
It may be possible to zero in on the few parts of the genomes that have changed in the cancer cells to find new targets for drugs. He is also looking at the genomes of shellfish to see if they have evolved new ways to resist the invading cancer.
“Nature has basically run an enormous experiment,” Dr. Metzger said. If there’s a way that an animal has evolved resistance to cancer, I want to know what it is.”