Tetrodotoxin 101

A good way to hook students into the wonderful world of toxicology is tetrodotoxin. Sound familiar? It’s what makes fugu, or puffer fish, what it is - a potentially deadly Japanese delicacy. Or does it? Would the delicacy be so appealing if the consumer didn't risk death or paralysis?

For those unfamiliar with fugu or tetrodotoxin, note that a mere “taste” of the stuff can and does kill. Although not the most potent toxin in the toolbox (recall that we’re talking toxin - or naturally produced poison) that honor most likely goes to either C. botulinum toxin (the toxin whose presence may be indicated by those puffed up cans – like the tuna can I once pulled from a grocery shelf,) or ricin – most recently of Las Vegas fame – and produced by the lowly castor bean.

Although non-toxic preparation of fugu has been raised to an art by highly skilled Japanese chefs, and although not all wild puffer fish contain enough toxin to kill, one article estimates that upwards of 50 mortalities may occur each year in Japan following puffer fish ingestion.

But now there’s good news for those who just must nibble – yet who’d prefer to avoid death or illness (tetrodotoxin inhibits muscle contraction causing paralysis). A recent article in the New York Times by Norimitsu Onishi reveals not only some interesting fugu history, but also describes the current trend towards raising tetrodotoxin free fugu.

For years, scientists seeking out the source of fugu (and many other marine species) tetrodotoxin had been baffled – where did it come from? Was it produced by the fish themselves or was it in the food they ate? And why didn’t it kill puffer fish and other tetrodotoxin laden marine animals?

Recent studies now suggest that, like many other potent toxins, tetrodotoxin is produced by the smallest of small, bacteria. By providing a home for bacteria, the boxy puffer is offered protection (and fortunately for the puffer fish, they’re at an advantage thanks to a genetic mutation, which makes them immune to its toxicity.)

As you might guess, here’s where the non-toxic fugu come in. By knowing the source, fish farmers can now feed fugu tetrodotoxin-free food (say that ten times fast) producing a risk free meal.

Although, for some the thrill of fugu may be in the risk – for others writes Onishi,, fugu liver is just plain tasty – like foie gras but without the guilt.

Fishing for disease

Just a brief note as I prepare a longer (and more depressing article) on farmed fish - salmon in particular. Hearing how local wild caught Connecticut River brood stock salmon, and their offspring, had to be killed off this month after Infectious Pancreatic Necrosis (IPN) virus was detected in a few returning fish, I decided to take a closer look at the relationship between farmed fish and disease in wild fish.

It’s not a pretty picture, and although the link between IPN in our few and very precious local salmon is unclear, there’s plenty of evidence indicating that fish farming has increased disease in wild fish populations. Additionally there are a multitude of other problems that require attention – before farmed fish in a safe (and by this, I mean environmentally sound) manner.

For a quick read on the topic check out “Farming the deep blue sea,” an article about moving fish farming from near shore or coastal areas to offshore, published last spring in Environmental Science and Technology or more recently, Parasites from fish farms driving wild salmon to extinction in the news section of the journal Science.

So - enjoy your salmon in ignorant bliss over the holidays while you can. I'll be posting more on this, particularly the impacts of coastal and near-shore salmon farming in excruciating disease ridden detail later, after the new year.

Drugs Down the Drain

Many years ago a study out of England reported the discovery of mixed-sex fish (primarily male fish with eggs). Although nothing new now, this was one of the first reports of feminized fish. What I remember most about that study, was how we laughed (I was working with some fish physiologists) at some of their possible explanations, which included hormones from the pill or just every-day urine that had been flushed down the toilet.

Years later, the USGS routinely measures drugs, or the remnants of drugs flushed after passing through our bodies, or intentionally flushed by folks wanting to discard old or unused drugs. Scientists are increasingly concerned about the impacts of pharmaceuticals not only on aquatic creatures (imagine swimming in a sea of heart medication, pain killers and birth control pills) but in some cases on drinking water.

Now the American Pharmaceuticals Association (APhA) has teamed up with the U.S. Fish and Wildlife service to educate the public about proper drug disposal through a campaign called SMARxT DISPOSAL.

I don’t have the numbers on how much is estimated to come from intentional disposal and how much is excreted, (although either way – giving drugs a proper burial as described in the disposal guidelines has got to be better than ditching them down the tube – and some, they actually suggest you do flush), but it will be interesting to monitor the impact of this program.

So, should I order the fish?

Much to my embarrassment, shortly after graduating with my Ph.D. and directing my attention to PCBs and other toxics in fish, whenever we stood by the fish counter at the local seafood restaurant, my father would announce that I was an expert on contaminants in fish. “So, should I get the fish?” he’d ask.

I’d turn red and shrug my shoulders, muttering something like, “I don’t know, depends where it comes from, I guess.” Truth was that I studied the impacts of chemicals on reproduction in fish not humans, so really, I could only answer as an expert for fish concerned about their reproductive health.

But even for those who study the human health impacts of chemicals, the issue of evaluating the risk associated with contaminants in seafood has always been tricky. Risk from contaminant exposure depends on the contaminant, the particular health effects associated with the contaminant, the species of fish (some fattier than others), the age of the fish, where it was caught (if wild), if farmed, what it was fed, how much one eats fish how often, and even on who’s eating the fish!

An recent analysis by Sam Luoma and Ragnar Lofstedt titled "Contaminated Salmon and the Public's Trust" published in Environmental Science and Technology addressed the complexity of that simple question “Should I get the fish?” and “If so, what kind?” They refer to a study published in Science several years back, which reported on concentrations of PCBs and similar chemicals in farmed and wild salmon, and which reported that farmed salmon were, in general, more highly contaminated than wild-caught salmon.

According to Luoma and Ragnar, this set off a “contentious dialogue….mostly because the risk analysis for salmon did not consider a balance of risks,” the end result (at least for a time) was a drop in consumer confidence for farmed salmon resulting in a heavy burden on wild salmon populations.

While the authors don't answer the question "to eat or not to eat", they do provide an interesting discussion about communicating and evaluating risk for complex scientific issues, even ones that seem simple, check out it.

How About Tuna (with a dash of mercury?)

I search the pantry and the fridge for a quick nutritious dinner.

“How about tuna,” suggests Sophie, my youngest. Tuna is her favorite protein, besides cheese, cheese, peanut butter, and cheese.

“I haven’t had it since last weekend,” she adds, turning on the charm.

My concern is mercury. And these days, most of us are aware that there is plenty of it in both fresh water and ocean dwelling fish. For parents with young children who find tuna one of the few foods with protein that their youngsters will eat, the situation is particularly worrisome. As a mother of two and a toxicologist, environmental contaminants are of particular interest constantly intruding upon our lives, while at the same time presenting unfortunate but interesting examples of human impact upon the natural environment.

Mercury, like all metals, occurs in nature and is present in the earth’s crust. While natural sources of mercury include volcanoes and geologic deposits, as most folks know, mercury is also released into the air by other processes such as incineration of medical waste (for example, burning thermometers) and, more importantly, burning coal.

Although the role of mercury as a potent neurotoxicant (a chemical which impacts the brain) has been known for centuries, the exact mechanism by which it causes toxicity remains frustratingly elusive. The term “mad as a hatter,” for example, is thought to originate from early observations of mercury’s neurotoxicity on those in the business. In the 1800s and early 1900s mercury was used in the felting process of hat manufacturing, likely resulting in large exposures and crazy hatters. In modern days, mercury was responsible for the neurotoxic and teratogenic effects (impacts the developing fetus) observed in villagers of Minamata, Japan, in the 1950’s and now known as Minamata disease. The disease was first noticed in the village cats, consumers of discarded or dead fish. The cats apparently danced and stumbled around the village prior to dropping dead on the street. Eventually, the disease manifested in humans, and was traced to mercury which for decades had been released into the water by local industry and accumulated in the fish and shellfish of Minamata Bay.

But mad hatters and Minimata were caused by exposures to much greater concentrations of the metal than are present in the workplace and the environment today. Present concerns for public exposure to mercury involve tiny amounts - in the parts-per-million range – in fish tissues. But even at these very low concentrations (a part-per-million is approximately the concentration of ink when four drops of ink are released into a 55 gallon drum) there is increasing evidence of potential health impacts, particularly on the developing brain. And although release of mercury into the environment is more tightly controlled, it is still released by industrial incinerators and coal-burning power plants (in 2005, the EPA issued its first ever rule to permanently reduce and cap mercury emissions.)

Once released into the atmosphere mercury may travel across state and country lines before it eventually settles and is transformed from metallic mercury into other forms including highly toxic methylmercury. It is this form of mercury, methylmercury that becomes incorporated into the diet of aquatic creatures and those that eat them.

Here is where the tuna comes in. We all know the story, big fish eat little fish, and bigger fish eat those fish. Big fish include tuna, swordfish and other large ocean species, as well as some freshwater species including lake trout and largemouth bass. Methylmercury concentrates as it moves up the food chain. Generally the larger older predators tend to have the greatest concentration of mercury in the flesh. This is why the EPA and FDA suggest that pregnant or nursing mothers and young children stay away from large predatory fish. According to the EPA, ingestion of chunk light tuna should be limited to 12 ounces a week, while albacore tuna should be limited to 6 ounces. Albacore tuna is a different fish than the tuna used for chunk light, which can be skipjack tuna and in some cases yellowfin tuna. Differences in the size, age and life histories explain the difference in accumulated mercury.

I pull a 6 ounce can of chunk light from the shelf, and hand it to Sophie. It is sad that we need to consider “how much,” of a contaminant we’re willing to ingest, or expose our youngsters to, but until mercury emissions into the environment are fully controlled if fish is part of your diet, then it’s a necessary consideration.

If you want to learn more, there are many good sites that provide greater detail on mercury in fish, mercury toxicity and mercury controls that you may want to explore:

EPA sites: http://www.epa.gov/waterscience/fishadvice/advice.html http://www.epa.gov/air/mercuryrule/basic.htm; Physicians for Social Responsibility: http://www.mercuryaction.org/uploads/PSR_Hg3_FishC.pdf; MA Department of Environmental Protection: http://www.mass.gov/dep/bwp/hgres.htm. Specific fish advisories for freshwater fish in the state may be found by searching: http://db.state.ma.us/dph/fishadvisory/.