Washington State Magazine

Summer 2009 cover

Summer 2009

In This Issue...


Living Large: In search of the elusive large animal veterinarian :: Nearly 500 counties in the United States have large herds of cattle, but no veterinarians to care for them. Although veterinary student Sam Nielson claims that it's the life of the large animal veterinarian that he's after, not money, fewer and fewer feel that way, moving to other types of practices that offer both better working conditions and compensation. by Hannelore Sudermann

{ WEB EXCLUSIVE–Gallery: Photos of large, medium and small animals By Chris Anderson and Ingrid Barrentine }

A Seat at the Table :: When Patty Murray '72, after a year as a state legislator, set her sights on the U.S. Senate, she got little encouragement. "You haven't paid your dues," they said. "You don't have enough money. You don't know the right people." None of that made any difference to Murray. by Hannelore Sudermann

Straight Shot to a Breakthrough? Don't count on it :: There are two sides to everything, says entomologist William Snyder of his biocontrol research. Along the way to developing a "practical" approach for crop defense, he answered a fundamental evolutionary question: Why are there so many species? by Cherie Winner

{ WEB EXCLUSIVE–Story: Pasteur's Quadrant }




:: SPORTS: Rowing 101

:: SHORT SUBJECT: Home economics revisited


Cover photo: Senate Majority Whip Richard Durbin, Senator Patty Murray, and Senator Edward Kennedy speaking to reporters at the Capitol by Michel du Cille/The Washington Post.

WSU entomologist William Snyder.

WSU entomologist William Snyder. Robert Hubner

WSU post-doctoral researcher Deborah Finke.

WSU post-doctoral researcher Deborah Finke. Courtesy Deborah Finke.

WSU Regents Professor B.W. (Joe) Poovaiah.

WSU Regents Professor B.W. (Joe) Poovaiah. Robert Hubner

Straight shot to a breakthrough? Don't count on it.
by | © Washington State University

A fight to the death is playing out in Beetle-size cages straddling rows of radish plants in fields near Othello, Washington. Orchestrated by WSU entomologist William Snyder and post-doctoral researcher Deborah Finke, the opponents are aphids, which munch the radish leaves, and parasitic wasps, each about the size of the period at the end of this sentence, that kill the aphids in gruesomely spectacular fashion.

The wasps reproduce by laying their eggs in the body of an aphid. When the larvae hatch out of the eggs, they eat the aphid from the inside, eventually emerging into the air as adults. Under magnification, it looks like something out of a horror show. (Actually, it’s something that went into a horror show; the gut-busting parasites of the Alien movies were based on these wasps.)

The outcome is clear. In one set of cages, the wasps decimate the aphids; in another, they leave many aphids untouched. The experiment provides solid evidence for one of the main claims of organic agriculture and offers farmers guidance in the choice of pesticides. It also answers one of the oldest and most stubborn questions in ecology.

Dual results like these are not rare in today’s research world. It used to be that basic research done by one kind of scientist produced fundamental information about nature, which was then used by another kind of scientist in applied research that led, in a reasonably short time, to a useful product, process, or service. Those days are gone.

It’s not that there’s no longer a distinction between basic and applied research. There is. It’s just that much research today fuses the two, providing fundamental insights about the natural world and contributing to the development of practical applications.

Furthermore, even the most basic research is rarely driven by curiosity alone. The scientists who do it may be immersed in the esoteric details of their field, but they have an overarching interest in a real-world problem: environmental toxins, dementia, energy independence. Today’s “basic” scientists may not have practical applications in sight, but they certainly have them in mind.

“There are two sides to everything we do,” says Snyder of his research team. “We work in these biocontrol systems, so it obviously has some applied value to agriculture, but we’re also interested in basic questions in ecology.”

In the Othello experiment, the basic question was one that has puzzled biologists ever since Darwin: Why are there so many species?

A given forest won’t have one kind of seed-eating bird or one kind of early-spring flower; it will have dozens of species that do approximately the same thing. Why so many?

The key is in the word “approximately.” The explanation Darwin came up with is that no two species use exactly the same resources in exactly the same way.

“If there was just a single resource that all the species were using, there would be one species that was best at getting at that resource, and that species would outcompete all the others,” says Snyder. “So the idea has been that they must use different resources. This is the idea of the niche, the ecological niche, that people are familiar with.”

The idea makes intuitive sense and is supported by mathematical models, but it had never been conclusively shown in real-life experiments. In fact, says Snyder, “It’s been thought to be impossible to test” because there was no way to change the use of resources by different species while holding everything else constant. We could find out that two kinds of squirrels eat different kinds of nuts, for instance; but how could we know that the difference is due to their species, rather than to their body size or reproductive rate or any number of other differences?

To really test the niche idea, researchers needed a way to have different members of one species do different things (such as eat different prey), and members of different species do the same thing (such as eat the same prey).

Finke and Snyder realized the parasitic wasps were ideal candidates for such an experiment because they can be “trained” to attack just a single species of aphid. An adult wasp will strongly prefer to lay her eggs in the same kind of aphid in which she herself grew up. After a few generations on one kind of host, the preference is so strong that a wasp may forego the chance to reproduce if her favored prey is not available.

So Finke and Snyder produced colonies of wasps that honed in on a single kind of aphid. They used three species of wasp, raising some individuals of each species to parasitize one species of aphid. Then they placed aphids and wasps in various combinations into the cages enclosing the radish plants.

All the cages held three kinds of aphids. By changing the number of wasp species and whether each wasp species attacked just one kind of aphid or all three, Snyder and Finke were able to separately test the effects of species number and resource use.

They found that more species of wasps killed more aphids than just one kind of wasp only when each wasp species targeted a different species of aphid. If the wasps overlapped in their use of the aphids, they competed with each other and left some aphids unmolested.

“Species diversity in and of itself doesn’t seem to do anything,” says Snyder. “It’s only when you have species diversity and they’re partitioning the resource that you see this improvement.”

For farmers and gardeners, the study shows that selective insecticides that kill just one or a few kinds of insects are a far better choice than broad-spectrum insecticides that kill many kinds, including those that could help battle the pests. Likewise, for organic farmers and others trying to manage pests with biocontrol, the diversity of the biocontrol agents is important—but not just any diversity. You need to use species that play different roles in the ecosystem, for instance, by attacking different pests.

“That’s sort of a basic mantra in organic agriculture, that you need more diversity,” says Snyder. “But it’s been hard to pin down, what specifically does that mean? The important thing is [to have] species that have different specialties, that fill different roles.”

The findings were just as significant in the larger context of planetary biodiversity, says Snyder.

“Diversity is beneficial because at some point as you’re adding more species, you’re adding species that do different things. It’s not biodiversity that you need to preserve, so much as it is species that do different things, species that are functionally different.”

The editors of Science, one of the world’s top journals for reporting experiments of fundamental scientific interest, agreed. They published the work in September of 2008.

Snyder says if he did only basic or only applied work, his research program would suffer, because each benefits from the ideas and results of the other. The same is true of many other scientists. Those who worked out the prey preferences of parasitic wasps in the 1980s and 90s, for instance, went back and forth between curiosity about the wasps’ peculiar behavior and a desire to find a way to control a crop pest.

“The only reason anyone knows anything about these wasps, besides some small amount, is that they’re important in agriculture,” he says. “What’s nice about working in these agricultural systems is, whatever insect you think of, there’s often an awful lot of information [already known] about it.”

Unfortunately, information gleaned from agricultural systems isn’t held in high regard in some corners of the scientific establishment. While the public generally wants to know the practical value of a research project, scientists sometimes face pressure in the opposite direction from their own community. A few years ago a colleague advised Snyder that a paper he submitted to one major journal would stand a better chance of acceptance if he camouflaged its agricultural origins.

“It’s on potato, but I never used the word ‘potato’ in there,” he recalls. “I just used the scientific name, Solanum tuberosum. And that flew. So maybe I’ll do that now [with other papers]. Just act like it has no relevance to agriculture at all.”

A close look at Snyder and Finke’s Science article turns up no mention of crops or pests. The aphids are “herbivores” and the wasps are “predators.”

“I don’t think we said anything about agriculture,” says Snyder. “As a practical matter, it was best to bury the agricultural connection.”

The same approach is required with some of the agencies that fund research. Since early in the Clinton administration, proposals submitted to the National Science Foundation must include a statement about how the research will be of use to society. For grants submitted to NSF’s Ecology program, though, the use had better not involve crop health or pest control.

“If the relevance to society is agriculture, you will almost certainly not get funded,” says Snyder. He thinks that’s partly due to the assumption (often correct) that the research could find support elsewhere, such as through the USDA. But that’s not the whole story.

“There’s the argument that in agricultural systems, you can’t learn anything about fundamental ideas in ecology,” says Snyder. Such a belief doesn’t have to be widespread to have a big effect. The intense competition for grant money—the Ecology Program funds only about seven percent of the proposals it receives—gives every one of a proposal’s six reviewers veto power.

If you work in an agricultural system, says Snyder, “you’re pretty much guaranteed to get one review that will say, ‘You can’t learn anything about ecology from agricultural systems.’ And that is most likely going to sink the grant.”

Policy-makers at journals and agencies may simply be trying to maintain programs where scientists don’t have to claim their work will reach a specific practical goal within a short time, and Snyder doesn’t begrudge them that.

“I actually feel that purely basic research has a place; but I don’t feel that doing research in an agricultural system ‘dirties’ it to such an extent that you can no longer learn fundamental things.”

The notion that a concern with practical matters is impure or low-class has a long history. The revered Greek scientist/mathematician/engineer Archimedes (c. 287-212 BC) invented bilge pumps, catapults, and other useful devices for his king, but his writings—what he wanted posterity to know about him—were all math and theory and thinking about the nature of things. As the biographer Plutarch said of him, “He placed his whole affection and ambition in those purer speculations where there can be no reference to the vulgar needs of life.”

In 19th and early 20th century Europe, scientists motivated by curiosity about how nature works held forth in the universities, while those pursuing “vulgar needs” were relegated to the more profitable but lower-status technical schools and industrial labs. Not everyone adhered to that model; Louis Pasteur worked on fermentation chemistry for commercial firms, and in the process invented the field of microbiology. Each aspect of his work fed the other.

Despite Pasteur’s brilliant example, the split system persisted. American institutions blurred the class distinction but largely kept the framework that said basic research leads to applied research, which leads to practical (marketable) applications. They set up funding sources and programs that supported primarily one form of research, protecting both arms of the research enterprise but further entrenching the division between them and assuring continued battles for prestige and money. As each group of scientists fought for a share of the available research dollars, they became loath to give up their designated piece of the funding pie. Today, the split is firmly embedded in the scientific establishment despite the fact that it does not reflect the views and the experience of many of our most original and productive scientists.

“It’s totally artificial, and probably not a super-good idea, but there’s no way to change it now because of the way the funding works,” says Snyder. He sees hope for a more sensible approach in programs such as WSU’s School for Global Animal Health, which deals with the fundamental biology of how diseases spread and the practical concern of how we can stop them, and in projects such as the new plant biotechnology building currently under construction.

“That’s why we’re doing things like this—to bring together people who do exactly the same thing from the IBC [Institute for Biological Chemistry] and from Biology, which will then be in the same building. Which seems pretty logical to me.”

The pop-psychology maxim that “you only hit what you aim at” may be useful in some endeavors, but in science, the biggest breakthroughs are often by-products of work that had been aimed at something else. Bill Snyder’s interest in pest control led to the answer to a fundamental question in ecology. Plant scientist Joe Poovaiah’s interest in calcium has led to a place no one anticipated.

Poovaiah is a basic scientist who is very much inspired by real-world concerns. When he describes his work related to nitrogen fixation, he talks about the farmers who tell him the cost of nitrogen fertilizer is one of their biggest problems, and about the millions of tons of fertilizer that wash into the Mississippi River every year, producing a dead zone in the Gulf of Mexico where the tainted river water empties.

Poovaiah has been fascinated by the role of calcium in plants ever since grad school in the late 1960s, when he did a paper on the subject for extra credit in a tough class. At the time, calcium was known to be a structural component in bones, teeth, and shells, and to be essential for a variety of functions including the transmission of nerve impulses and the contraction of muscles. What he unearthed while researching his paper convinced Poovaiah that it might be equally important in plants. He finished up his doctoral work on another aspect of plant biology and turned full-time to the study of calcium.

In 1987 he and A.S.N. Reddy, a post-doc in his lab in the horticulture department, wrote a major review laying out the case that in plants, calcium is part of an internal signaling system that affects a range of necessary functions including the production and release of growth hormones, cell division, and fruit ripening.

The review forecast much of what has played out in Poovaiah’s and other labs around the world since then. Calcium, when bound to a protein called calmodulin, turns on some genes, turns off others, and generally acts as a translator of information about the environment—information the plant needs to protect itself from harm and send its progeny out into the world.

In February, Poovaiah learned that the National Science Foundation would feature his work in the Highlights section of its web page, which is designed to show taxpayers that their research dollars are being well spent. It’s a lovely bit of recognition for more than three decades of effort that started out as a tough sell. When Poovaiah started his career, he knew there was something to the calcium story, but few other plant scientists agreed. He struggled to get funding for the work and faced considerable skepticism even in his home department. His encouragement came from elsewhere.

“My inspiration came not from plant people, but from animal [researchers],” he says. About 25 years ago he attended a seminar given here by Tony Means of the Baylor College of Medicine. Means was the guy in the study of calmodulin, the key calcium-binding protein in animal cells. The calmodulin he worked with had come from chickens.

Poovaiah realized that calmodulin, or a protein like it, could help explain how calcium had the effects he’d traced in plants. But nobody knew if plants even made calmodulin. After the seminar he asked if Means would send him some of the chicken calmodulin gene.

“And that’s how we got into this calmodulin [work]. Using this animal gene we fished out the plant version. Now it’s no big deal to do, but at the time...”

At the time, trying to isolate a protein or gene from scratch could have taken years. Having an exemplar of the thing he was looking for was like taking the express train. Plants and animals are far apart on the evolutionary tree, but genes with essential functions tend to be similar even in such distantly-related species. Poovaiah thought the calmodulin gene qualified. He was right.

With the chicken calmodulin gene in hand, his lab cracked open the calcium/calmodulin system in plants. When new molecular techniques of cloning came into use a few years later, progress in his lab took off. They found that pulses of calcium are involved in the interaction between root hairs and nitrogen-fixing bacteria, which could lead to the development of crops that, in effect, produce their own fertilizer. They discovered one calcium-related gene that controls the size of the plant and another that helps the plant make salicylic acid, a form of aspirin, in response to attack by bacterial pathogens.

The work clearly has implications for the development of new strains of crops, an application Poovaiah had in mind from the beginning. But along the way, another possibility has emerged. It turns out that calmodulin is not the only calcium-related protein that plants and animals have in common. CCaM kinase, a protein involved in communications between plants and nitrogen-fixing bacteria, strongly resembles a protein that functions in the formation of memories in animals. AtSR1, a protein involved in protecting the plant against infection and stress, is almost identical to a protein that helps control the growth of human heart muscle.

Now Poovaiah, whose lab discovered these proteins and genes in plants, is providing expertise and material to scientists working in animal systems. The grad student who studied CCaM kinase was recruited by three of the top neurobiology labs in the nation, and Poovaiah is developing a collaboration with one of the leading scientists working on the heart growth protein. Plants with mutant forms of the protein are much easier and quicker to produce than comparable animals. Just as chicken calmodulin gave his research a kick-start 30 years ago, the plant protein AtSR1 might now provide valuable clues about how the corresponding protein works in mammals.

It’s not something he aimed at, or even thought about, when he started following the calcium trail, but Poovaiah is now on the verge of using plants as “experimental animals” to explore processes that are important in human health.

“Plants don’t have a heart, but at the same time, there are some pathways that we understand in plants that could apply in humans,” he says. “There’s now enough molecular evidence, enough biochemical evidence, enough knowledge in general, that scientists know how this signaling works in plants. As a result, this is a fantastic model to understand how the calcium system works in humans.”

Reflecting on the path that brought him to his unexpected destination, Poovaiah says the way ahead was never clear more than a step or two at a time.

“We spent the last 33 years learning to do this signaling research,” he says. “My concept is, today’s ‘basic’ is tomorrow’s ‘applied.’ You never know how quickly things go.

“We are a research institution. Our job is to open new doors, and this we have done.”

Categories: Biological sciences | Tags: Research, Innovation

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