Feeling better? Say thanks to the fruit fly, the zebrafish, the mouse
Mike Terry, Deseret News
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SALT LAKE CITY — Watch a life-saving drug flow into the arm of a loved one who has cancer or reach for prescription medication to ease your allergies or lower your blood pressure and there's a good chance you owe some thanks to a fruit fly, a zebrafish or a mouse. Or maybe all of them.
It's unethical to experiment on humans; the road to helping them has been paved with yeast, worms, flies, fish and mice, among others. Worms are easier to manipulate than fish, which are easier than mice — the beginning of research in mammals — which are easier than humans.
It's what they have in common that has proven beneficial: protein-coding genes.
For instance, of the fruit fly's 14,000, half are the same in humans. Zebrafish and humans both have about 25,000, many of them the same. Mice are even more similar genetically to humans, says Dr. Mary Beckerle, CEO and director of the Huntsman Cancer Institute. Research in one can offer insights into the others.
President Richard Nixon declared war on cancer 40 years ago. But it hasn't been cured because, it turns out, cancer is more than 200 different diseases — some with effective treatments now and even cures, some not. Some cancer can be lived with as a chronic disease. Still others are most often a death sentence. But consider this: Where 50 years ago childhood leukemia killed more than 95 percent of its victims, 80 percent now survive. The research is building futures.
And cancer is just one example. AIDS was always deadly. Now, "overall, survival is way up. It's a difficult life, but you can survive," says Carl Thummel, professor of human genetics at the University of Utah and an expert in the fruit fly Drosophila.
Progress in individual diseases has hinged on studies that moved through a hierarchy of creatures, from simplest to more complex, until there was enough known and enough promise to justify human testing.
Humans also have a role in early research, using a population database and genetic samples from people with particular conditions. With those, researchers seek defects in the same genes in multiple people. It's part of the patchwork of building treatments and furthering scientific understanding of what happens when the body works well and when things go wrong.
But that's looking back at what happened. To look forward requires a model system that's alive, whether it's yeast or a mouse. "You can't do a human experiment to answer a precise question," Thummel says. "This is the next best thing. Working with simple animals provides a bedrock of research and scientific discovery."
For instance, the nematode worm, C. elegans, has been invaluable to scores of researchers for how well it explains the basics of how cell numbers are regulated during development, says Dr. Nikolaus Trede, associate professor in the Department of Pediatrics at the U. School of Medicine and a HCI investigator.
Thummel calls the worm essential to understanding the nervous system, too.
For a long time, the cause of cancer was fodder for wide-ranging theories: It's a virus. No, it's a pathogen.... In the late '70s and early '80s, research suggested that genetic changes could cause cancer. The RAS gene, a major regulator of normal cell growth, was implicated in bladder cancer. In flies, mutations in the RAS gene revealed a major pathway controlling cell growth and proliferation. The work was bolstered by worm studies that gave important insights into how RAS controls growth.
When it was shown that some cancer resulted from such cell growth run amok, cells proliferating too quickly, it was assumed that accounted for all cancer types. But worm researchers found that the failure of appropriate cell self-destruction, called apoptosis, controls cell number. Some cancers, like leukemias, are caused by that misregulation of cell death pathways.
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