Gridlocked bridges over the Fraser River are just a part of life for commuting Vancouverites. But the industrialized motif of North America's longest dam-free river belies a rare natural treasure: a sockeye salmon run with a historical average of eight million fish worth over $1 billion. Since the early 1990s the numbers of Fraser sockeye have steadily dwindled, reaching a particularly troublesome nadir in 2009 when more than 11 million sockeye were forecast to return and only 1.4 million showed up. Since the mid-1990s, something began killing large numbers of returning sockeye on the Fraser—anywhere from 40 to 95 percent of fish in some years—before they could spawn.

Now a study bolsters the hypothesis that a mysterious pathogen working in concert with other anthropogenic stressors may be the culprit.

Led by Fisheries and Oceans Canada, a team of scientists tracked returning Fraser River sockeye to see whether the genetic activity of those that successfully spawned differed from the activity of those that perished prematurely en route.

Sure enough, salmon with a certain pattern of gene expression in their gill tissue were 13.5 times more likely to die than those that didn't carry the "you've not got long to live" signature, as co-author and University of British Columbia (U.B.C.) fish physiologist Tony Farrell puts it. Most intriguingly the mortality-related genomic signature in the fish resembled that triggered by a viral infection. "This was a needle-in-haystack investigation, so we were more than pleased that we identified a signature, and then to narrow it down to what might be a viral signature was surprising," says Farrell.

Months after the study came out mid-January in Science the research continues to make waves on Canada's west coast as journalists and environmentalists speculate as to whether the genomic signature identified in the study might be evidence of an epidemic of salmon leukemia, known to have plagued salmon fish farms along British Columbia's coast.* Lead study author Kristi Miller-Saunders, a molecular geneticist at Fisheries and Oceans Canada in Nanaimo, has not been given the green light to speak freely with the press, however she did respond to questions from Scientific American via e-mail.

"One of the most important findings of this study was the fact that salmon were already compromised before entering the river" on their journey home to spawn, she wrote. The scientists are currently studying juvenile salmon to see if the genomic signature is already present before they go out to the open ocean. Miller-Saunders also reports "there is some indication that the signature may be in Chinook and coho" salmon, too.

View a slideshow of salmon species potentially affected by the virus

Unpublished studies have found the signature in other cohorts of Fraser sockeye, suggesting that the phenomenon spans different years. But the mystery virus remains unidentified. Attempts by Miller-Saunders's lab to culture the virus from affected tissue and do molecular screenings of known pathogens have come up empty. Currently she is attempting to sequence the pathogen from the tissues of affected fish.

"The possibility of a disease affecting these fish has been on the table long before this paper came out and the usual suspect has been fish farms," says John Reynolds, a salmon conservation scientist at Simon Fraser University in Burnaby, British Columbia. "My impression is that the hard evidence isn't there yet to either implicate fish farms or to let them off the hook."

Death by a thousand cuts
The study only correlates a genomic signature with mortality, rather than proving any causal relation, but it also hints at how genomic markers can inform better management of the dwindling sockeye stocks.

"The question is: Is disease getting worse by combinations with other either natural or anthropogenic stressors?" says Jim Winton, a microbiologist at the U.S. Geological Survey's (USGS) Western Fisheries Research Center in Seattle.

He runs through a laundry list of factors that could amplify virus-driven disease mortality: fisheries shifting food chains, global warming, marine pollutant–triggered toxic algae blooms, marine pollution in the form of chemical contaminants, and endocrine disruptors altering the host–pathogen balance.

In Chinook salmon in Alaska's Yukon River, for example, the prevalence and mortality from the parasite Ichthyophonus has recently risen in concert with climate change, which has increased river temperatures by an alarming 5 degrees Celsius. "At these higher temperatures, this disease goes much faster," Winton explains.

The rise in mortality of Pacific herring in Puget Sound tells a similar story. There, Winton's lab has identified "three candidate diseases that we believe are now much worse than they used to be…. So there are cases in wild populations where we believe changes, and many of them man-induced, are altering the impact of natural mortality from disease."

The Fraser River itself has undergone considerable warming. Seven of the past 10 summers have broken records as the warmest. River temperatures are nearly two degrees C warmer than 50 years ago, a problem for these cold-blooded fish.

In the twilight of their brief lives adult Pacific salmon migrate back to their river of birth to spawn, perpetuating a four-year life cycle that boomerangs thousands of kilometers into the ocean. "These are very old fish, imagine these are like your grandmothers and grandfathers," says Scott Hinch, a salmon ecologist at the U.B.C. who co-authored the Science paper. By the time Pacific salmon close in on their spawning grounds, they are senescent and naturally immunosuppressed. "So any small disease, parasite, illness that is naturally occurring that is there they will pick up, and then it's often a race against time."

The salmon naturally expire after the Herculean effort of swimming upstream and spawning, but too many fish perishing prematurely before they've had a chance to lay eggs and fertilize them spells trouble.

Aquatic pollution may further exacerbate things. "We believe that some of the classes of contaminants that are now in the environment, such as these endocrine disruptors coming out of sewage treatment plants, are having an impact on the immune function in fish and altering disease resistance," Winton says.  Likewise, the Fraser River sockeye are met with sewage outflows from Vancouver at the river's mouth in the Strait of Georgia.

"Personally, I think changing the environmental quality in the Strait of Georgia is a major part of this explanation for the Fraser sockeye as well," says Brian Riddell, CEO of the Pacific Salmon Foundation in Vancouver.

Dead fish swimming
To further muddy the already murky waters are the "early migrating late runs". If it sounds paradoxical, that's because everything about these fish runs counter to reason. These are sockeye that historically migrated late in the spawning season but recently have begun to jump earlier by several weeks. All one really needs to know about this cohort is the term Hinch has coined for them: "dead fish swimming". That and the fact that the majority of fish sampled in Miller-Saunders's study, the ones carrying the mortality-related genetic signature, were part of these early migrating late runs.

"Generally the earlier migrating fish are the ones that are dying," Hinch says. "The grand picture is that these fish are screwed basically when they come back."

Since 1996 a larger and larger percentage of the late runs have begun to come back two to three weeks (at most, a month) early. These days, anywhere between 40 and 95 percent of the late runs are migrating earlier when river temperatures are much higher than what they would historically encounter. Research by Hinch and his colleagues found that the early migrating late-run fish differ physiologically from their normal-timed counterparts. They are more reproductively mature, stressed, and their physiology is precociously oriented toward the freshwater environment. "So not only are they forced to deal with [river] temperatures that are potentially lethal, they're also what appears to be compromised in some fashion," Hinch says.

The nearby Columbia River's sockeye, along with steelhead (also known as rainbow trout), which face temperatures 2.5 degrees warmer than the historical average, have shifted their migration times to avoid peak summer temperatures. Not so with the Fraser's early migrating late runs, which migrate right when the river is warmest. "Clearly this is not an adaptive strategy to climate change," Hinch says. "The fact that it's not getting selected against suggests that there's something annually causing this to happen and a disease makes a sense."
Even though the Columbia River's fish seem to be better at adapting their migration patterns than the fish on the Fraser, that's not to say that it's the model to follow. "The Columbia [River] is a great cautionary tale as they consider what to do about the salmon situation up there," says the director of a new PBS documentary, Salmon: Running the Gauntlet, Jim Norton. The film investigates collapsing Pacific salmon populations all down the Pacific Northwest and examines how biologists and engineers are trying to better manage the region's threatened salmon runs.

"The Columbia's message to the Fraser is: In the consideration about how to respond to changes you don't yet understand, be very clear that once you break the system, no amount of money, creativity or engineering will ever get the pieces back together again," Norton says.

Can science save the salmon?
The large number of missing Fraser River sockeye in 2009 prompted a Canadian federal judicial inquiry into the matter, the Cohen Commission. And just to underscore how little scientists understood of the fish, the sockeye run in 2010 was a once-in-a-century bonanza, with 34 million fish flooding the river. "From a historic low to a historic high almost—that creates a lot of uncertainty for management but it also raises questions on why it's swinging so much," says U.B.C.'s Farrell. The USGS's Winton points out that the sockeye run of 2010 was an anomaly, in the face of a steady and worrisome decline in Fraser sockeye over the years.

The Cohen Commission is currently underway and study co-author Hinch was called to the stand as a witness in mid-March. "Moving forward the real issue is whatever this is, what do we do now and how do you manage in the face of it," he says.

Miller-Saunders, for her part, will go on the stand later this summer to speak about her research, which has already been referenced in the enquiry's proceedings. Up until then, it is unlikely that she will be allowed to speak freely to the media about her research. British Columbia Supreme Court Justice Bruce Cohen, the commissioner who is overseeing the investigation, is in the unenviable position of hearing everyone out and making recommendations to ensure the future sustainability of the fishery by June 2012.

"We will have a full hearing session on diseases and the impact, if any, of aquaculture. The interplay between climate change warming and pathogens, if any, will be part of that subject," says Brian Wallace, senior commission counsel.

The Canadian Department of Fisheries and Oceans also has to juggle an immense number of stakeholders and their needs when managing the Fraser sockeye: coastal fisheries with different gear types, the in-river First Nations harvest, and one of the largest recreational fisheries in Canada.

"They were hoping that our research would tell them what do you do and our research is telling them this is tough," Hinch says. "So we're probably never going to come up with the exact cause but we may be well able to piece together a series of potential causes."

--Francie Diep wrote and produced the slide show that accompanies this

*Clarification (5/5/11): This sentence was modified after publication to change the tense of the verb describing when leukemia has plagued salmon fish farms along British Columbia's coast.