Feeling better? Say thanks to the fruit fly, the zebrafish, the mouse

Published: Monday, July 4 2011 9:20 p.m. MDT

Major cancer pathways have been explored and worked out in flies, worms, mice. The signaling pathways of human development were learned from yeast, worms, flies. When researchers looked at roughly 300 genes in humans known to cause diseases when mutated, 60 percent of those genes were also found in fruit flies, Beckerle says. When scientists looked at known human cancer-causing genes, more than 70 percent were present in the fruit fly, too.

Scientists verify a gene is the same across animal types in various ways. "The first experiment is on the computer, before the experiment in the lab," Beckerle says.

Once a gene that causes human disease is identified, scientists can search gene databases to see if that gene is present in a model organism. Next, they remove the gene from a worm, fish, fly or mouse or introduce a modified version of the gene and see what happens.

In an invertebrate creature like a fruit fly, it's not unethical or as difficult to study the mechanisms of disease. They lack a political lobby and don't attract much concern. You can't study those pathways in the same way in humans. You can't engineer human model systems. But the researchers note that institutional committees create high standards for research involving vertebrates, like fish and mice. Thummel says that ensures they are used only when necessary and under humane conditions.

Researchers have learned much of what they know about development from the eye of fruit flies. Insights include how a highly specialized cell emerges from something undifferentiated, turning a fertilized egg into an infant. Knowledge keeps growing.

The other "huge advantage of flies, worms and zebrafish" is you can see the process in real time under the microscope. Generations and life cycles are much, much shorter. Changes happen faster, crucial to move research forward, Beckerle and Trede say.

They are also plentiful. A fruit fly, for instance, has several hundred offspring on a two-week cycle, says Thummel, who uses them in diabetes, obesity and circadian rhythm research, among others. He quips that he chose fruit fly research because he's too impatient to study animals with slower life cycles.

The simpler the animal, the cheaper the research is.

Both collaboration and competition mark such genetic research. But as Beckerle notes, researchers also build upon each others' findings. Collaborations between departments, institutions, even specialties is common and fruitful.

The results can be powerful, she says. The gene that causes most colon cancers in humans is called APC. In model systems (where the equivalent of a human disease is created in an animal to learn about it and perhaps shed light on potential cures) the biochemical pathways APC controls were found, affording opportunities to study both how it should work and what can go awry.

Of all childhood cancers, 15 percent are bone cancers called sarcomas. "We know a lot about the genetic changes that cause sarcomas," says Beckerle. Less is known about how to treat them effectively. One barrier is the need for good pre-clinical models.

In the fly, the mouse, the fish, researchers are unlocking secrets that lead to therapy, medications, even prevention of disease. But Thummel says some view the war on cancer as a failure. And they think of research in organisms and simpler animals "as a joke."

Scientists aren't laughing. They view the discoveries with fascination, excitement — and hope.

Although so many genes are the same, they don't just do the same things across the different creatures. A gene crucial to wing development in a fly might help build an organ in a human. And it has been shown that genes can serve multiple functions.

It is the different ways that the genes are used that informs knowledge, Beckerle says. Ditto the difference in defects a mutation can cause. One mutation in the C. elegans worm kills it; in a fly, eyes don't form with the same mutation but the creature lives.

Sometimes, says Trede, the unexpected result provides the greatest insight. That happened when researchers tried to make a model of one leukemia and instead created a different kind of sarcoma.

The fish proved to be a particularly useful creature for sarcoma research, Trede says. Local spread of Rhabdomyosarcoma can be observed in zebrafish. That's impossible in mice or humans.

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