Funding Deters Scientists from Developing New Models

In the 1950s, a young psychiatrist sought an animal with neurons large enough for electrophysiology experiments on learning and memory. The animal, Aplysia californica, eventually got dissected in neurobiology labs around the world. The psychiatrist fared a little better; he was awarded the Nobel Prize.The tale of Eric Kandel and Aplysia, like that of Thomas Hunt Morgan and Drosophila or Sydney Brenner and Caenorhabditis elegans, has become a scientific bedtime story. The moral: Choose the right

Karen Heyman
Mar 14, 2004
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In the 1950s, a young psychiatrist sought an animal with neurons large enough for electrophysiology experiments on learning and memory. The animal, Aplysia californica, eventually got dissected in neurobiology labs around the world. The psychiatrist fared a little better; he was awarded the Nobel Prize.

The tale of Eric Kandel and Aplysia, like that of Thomas Hunt Morgan and Drosophila or Sydney Brenner and Caenorhabditis elegans, has become a scientific bedtime story. The moral: Choose the right animal, work very hard, and you, too, may have a legendary career. But Kandel and others say that few scientists will risk experimenting with an untried organism. Skeptical funding agencies, elusive animals, and a potential dearth of appropriate literature discourage young scientists from branching out.

The failure to explore new models is bad for science, Kandel says. "I think because several model systems have emerged as predominant forms, people are...

RISK, NO REWARD

Kandel and others agree that part of the problem starts with the National Institutes of Health. The screening and peer review systems encourage the use of familiar models, they say, and offer few incentives for trying new ones. "It's terrible, it's unfair; you can't expect young people to do something that's going to damage their careers," he adds. "Special programs on the part of the NIH are the only way to encourage it. It's not something you can initiate by telling people to sacrifice their lives."

Nancy Wayne concurs. She works on Aplysia as a model for reproductive neuroendocrinology at University of California, Los Angeles. "The feeling I and many of my colleagues have been getting from the NIH for the last five years is very conservative," says Wayne, an associate professor. "You can have your offbeat model system work published in the highest rated journals and then not get the work funded by NIH." Although she has published multiple papers using Aplysia, she has begun working with the more popular zebrafish, partly because she hopes it will be viewed more favorably by the NIH.

Wayne recently chaired a two-day conference at UCLA entitled "Neural Control of Behavior – Convergent Principles from Divergent Model Systems." The conference sessions showed how similar problems were approached by researchers working in animals as different as C. elegans, sheep, and tropical birds. Wayne says many participants told her they were hearing ideas for the first time. "I think there was a 100% consensus ... that there are systems where you can ask questions that you can't do in a similar way in the accepted model systems," she says. "If people are working on just a few model systems, it really makes for a much duller science."

Emmeline Edwards, a program director at the National Institute of Neurological Disorders and Stroke, agrees that new model organisms are important. She asserts that the NIH encourages researchers to develop them. "Many of the NIH institutes have existing programs that support the development of new model systems," Edwards adds in an E-mail. "Moreover, the new Roadmap initiatives developed under the of the new NIH Director, support high-risk research." Most of the people interviewed recommend pioneering with a new species during only two phases in ones' career: as a postdoctoral trainee in a well-funded lab with a supportive principal investigator, and as a well-established researcher with tenure.

Even with tenure, you may need to look beyond NIH to the more welcoming, but less well-funded National Science Foundation for grants. Nevertheless, there's reason for courage, says David Glanzman of UCLA. "Some of the greatest science ever done [was] by young investigators who fearlessly plunged ahead in the face of overwhelming skepticism."

NEW ANIMALS, NEW PROBLEMS

And if you do plunge ahead, what then? Even with funding and career risks resolved, there are other issues to consider. If you're weak in your understanding of the animal's behavior, you will draw mistaken conclusions about correlation effects, cautions Scott M. Williams, associate professor at Vanderbilt University Medical Center, Nashville, Tenn. You must question the assumptions that come with your training. "If you're trained as a molecular biologist, you're not going to know anything about the natural world," explains Williams, "People will read a paper at a journal club, and it's a Cell paper, and nowhere in the paper will they even say what organism they were looking at."

For reasons both financial and humane you must ask: How will you care for and house your animals, and what are the consequences of your choices? Malcolm Burrows, professor and head of the zoology department at the University of Cambridge, says that even laboratory insects should be housed and fed as humanely as possible. William Dement did pioneering work with narcoleptic dogs because the only other animal known at the time to get narcolepsy was the horse. Horses are prohibitively expensive to raise; worse, narcoleptic horses lead tragic lives, severely injuring themselves when they fall asleep and drop to the floor. By contrast, when narcoleptic dogs fall, the fall is relatively harmless and the dogs are often adopted at the end of experiments, according to Emmanuel Mignot, who isolated the hypocretin (orexin) receptor in narcoleptic dogs.

But smaller animals don't always mean smaller challenges: Burrows, known for his work on locusts, found his latest model animal in his garden: the leaper known as the froghopper or spittle-bug. Though easy to procure, in the lab they present a husbandry hurdle. "I have no idea how to keep them alive in the lab," says Burrows, who for the moment, simply catches them at home.

While Burrows searches in his backyard, Michaela Hau, assistant professor at Princeton University, looks for spotted ant birds in the Panamanian jungle. Her model was determined in part, she says, "[because] the spotted ant birds actually flew into our nets," after unsuccessful attempts to capture her first-choice species. Given how hard it is to capture any wild animal, you may get only one data point a day, Hau warns. "You might get higher variability in the data. In the field, you don't know what the animal has just experienced." The reward is a richer dataset since you get the full spectrum of an animal's behavior, rather than the downregulated behavior in the lab.

Rob LaSalle, curator in the division of invertebrate zoology at the American Museum of Natural History in New York, warns would-be pioneers not to forget that invertebrates can have unexpectedly large genomes. "You don't want to be sequencing ... amphibians with 200 billion base pairs, a thousand times bigger than our genome," he says. Another consideration, cautions the neuroscientist, is that you may have to devote a nontrivial amount of time to mapping the whole brain, or at least the concerned brain region, of a novel animal. Given all of that, it may be tempting to stick with a known model and extend the experimental possibilities; several researchers are now doing electrophysiology in Drosophila.

Ultimately, the hardest questions are not scientific but personal. Taking on a new animal model requires an honest assessment of your own skills, commitment and talent. You will be dedicating years of your life to something that may not pay off. You must ask yourself, "Am I that good? Can I stomach the risk?" If the answer to both questions is yes, then Kandel's advice is succinct: "Do it."

Karen Heyman klhscience@yahoo.com is a freelance science writer in Santa Monica, Calif.

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