Fish providing ethical alternative in drug research

SAN FRANCISCO

Doctor Philipp Gut believes genetically-modified zebra fish could soon light the way to major drug discoveries. "The big breakthrough was to use actually the firefly protein, which gives a really, really strong light signal," he explained. Gut and his colleagues at UCSF are part of an international team that's using the zebra fish to screen potential treatments for conditions ranging from obesity to diabetes.

To do that, they attached a kind of genetic light switch to an enzyme pathway that's associated with the production of glucose, or blood sugar. "Meaning when the fish produces glucose in the liver, a light shines up," Gut said. The result is a fish that can be used as a kind of living, swimming litmus test. The green glow they give off is not only visible to researchers, it's also measurable. A brighter light indicates a higher level of glucose, often used as a barometer in obesity research.

In one recently published study, the team was able to home in on a potential obesity drug after screening nearly 2,500 candidates using the genetically-modified fish. "For the test we put like three fish in every single well and then we add the drug compound, one drug per well, so we can test roughly100 drugs per plate," Gut said.

Depending on the type of research involved, Gut believes the zebra fish could cut down on the need for animal testing in mammals. "I think they can never replace testing in mammals, in rodents, but what they can do is they can gap the bridge. Let's say you find a drug in vitro, like in a protein or cell culture, and then they can test these in zebra fish, count down to the three best, and then test these three in mice," he said.

The fish are providing a cheaper and more ethical alternative as scientists search for breakthrough drugs to treat human disease.

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