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Volume 5, Number 2
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The Missing Link
MSX Middleman Remains Elusive

Erica Goldman, with reporting by Michael W. Fincham

sketch showing howlittle we know of MSX life cycle
A lingering mystery, the suspected alternate host for MSX remains unknown to scientists despite years of dedicated effort. Knowledge of the parasite's complete life history could provide clues for controlling the spread of the disease. Drawings adapted from The Eastern Oyster: Crassostrea virginica,/SPAN> by Kennedy, Newell, and Eble.

Measures to control malaria improved nearly overnight after the 1897 discovery that mosquitoes play a role in the life cycle of the malaria parasite, Plasmodium spp. This ancient disease, according to recent research, probably played a part in the downfall of the Roman Empire in the 5th century and nearly stopped the building of the Panama Canal in the 20th century. When simple pest control measures were put in place around the Panama Canal dig, the number of deaths from malaria dropped nearly eight-fold in the span of just three years. Even in the 21st century, reducing mosquito abundance remains a reliable control strategy for harnessing the spread of this global disease.

What if the mosquito's role as intermediate host in the life cycle of the malaria parasite had remained stubbornly hidden? It's hard to guess at the impact. But the prolonged mystery of the missing host for the MSX parasite has no doubt hastened the decline and fall of the oyster empire of the Chesapeake Bay.

Since the 1960s, generations of scientists studying MSX have searched for answers to the transmission question. They've found that native oysters never "catch" an MSX infection in the lab from infected oysters placed next to them. But when scientists place healthy oysters in a Bay area empty of oysters, the clean oysters "catch" a heavy MSX infection — and very quickly. Since other oysters apparently do not release infective particles, some other animal — the alternate host — must be releasing MSX.

What is this alternate host? A crab, a copepod, a worm? In 2006, scientists still don't have the answer — but not for lack of trying. Every two weeks, over a three-year period that started in 1999, scientists sampled an array of organisms for MSX, using both conventional and molecular techniques. "We sampled literally every organism we could get our hands on," says VIMS oyster biologist Gene Burreson."As you can imagine, the number of possible organisms is huge," says Rutgers biologist Susan Ford, who worked with Burreson on this study.

Burreson and Ford no longer have targeted funding to pursue the search for MSX's alternate host but they haven't given up. They are still sampling. "We hope we are going to get lucky," Burreson says.

Burreson feels strongly that MSX's alternate host must be something that eats the spores that form as one stage of the parasite's life cycle. But the spores are tiny, just 7 microns, and almost anything could eat them. "If we had narrowed it down and could say, 'look, it's in worms,' that's one thing, but we can't say anything still," he says.

Part of the problem, explains mathematical biologist Marjorie Wonham, is that disease cycles in marine systems in general are much less well-known than those in terrestrial systems. "When you are living in the water, you are in a soup of organisms that range from the nano to micro-scales. There are a lot more options available as potential intermediate hosts."

And water is so much harder to search, Wonham continues. "We don't live in the ocean. We don't have the same ease of access and intuition about marine systems as we have with terrestrial systems," she says. Wonham, who works at the Center for Mathematical Biology at the University of Alberta in Edmonton, Canada develops models to predict outbreaks of West Nile Virus and invasive species introductions through ballast water exchange in the Great Lakes.

Until they unveil MSX's intermediate host, scientists will lack the ability to control the transmission of MSX. Generally speaking, "if you don't understand the life cycle [of a parasite], you have no hope," says ecologist Andrew Dobson of Princeton University, who studies the role that parasites play in the population ecology of infectious disease.

In the case of malaria, Dobson explains, once British medical officer Ronald Ross discovered that mosquitoes enter into the parasite's life cycle twice, once to transmit the disease to humans and once to receive the parasite back from human hosts, he rapidly concluded that controlling mosquito abundance would be key. "Targeting the right point of the parasite's life cycle gives you a lot of insight," Dobson says.

But in the case of MSX, just knowing the alternate host likely would not be enough. "It might help," says Ford, "but how would you control copepods or worms? Remember, we do know how Perkinsus marinus [Dermo] is transmitted and it continues to kill oysters in large numbers."

The unknown intermediate for MSX also clouds the question of the parasite's introduction to Chesapeake Bay. It is possible that MSX came to the Chesapeake, not with Japanese oyster (Crassostrea gigas), but inside this hypothetical intermediate host by some yet uncharted route.

Solving the mystery of MSX's middleman would open new doors in understanding the disease. But detectives Burreson and Ford may be up against a funding roadblock in continuing their search. "You have to sample a lot of organisms and that's been the problem. It's risky research for people willing to give you money," says Burreson. "If you do solve it, then I think the payoff is certainly worth it."

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