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Turning firefly genes into cancer killers

Lighting up the back yard on early summer evenings, fireflies seem so gentle, so benign. But researchers in London have succeeded in turning firefly genes into killers - illuminating cancerlike cells, and in so doing, destroying them.

If the technique reaches its potential, it could transform the way doctors treat not only cancer, but also a variety of deadly diseases, including AIDS, SARS and antibiotic-resistant bacterial infections.

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"It's a very strange hybrid between a Trojan horse and a guided missile system," says physicist Theodossis Theodossiou, who came up with the idea and spent nine months developing it with John Hothersall, a microbiologist.

In laboratory tests last fall, the firefly therapy needed only one treatment to kill almost 100 percent of fibroblasts - cells used often in research because they proliferate rapidly, like cancer. The results appeared in April's Cancer Research.

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Doctors have used light to fight surface cancers for more than 20 years, injecting photosensitive chemicals into tumors and then zapping the growths with lasers. But laser light can't pass through tissue, limiting the treatment to tumors on the skin or the surface of internal organs.

The firefly technique solves the problem by implanting a light source in the cancer cell.

"It takes photodynamic therapy to a new level, because you can use it throughout the body," says Theodossiou, who works at the National Medical Laser Centre at University College in London. "You switch that light on, and every bit of the cancer will be lit like a little lamp. And it will be destroyed."

Called BioLuminescence Activated Destruction, or BLADe, the treatment works by inserting a firefly gene into cancer cells. Once inside the cells, the gene produces an enzyme called luciferase which combines with a chemical called luciferin to produce light. Fireflies generate their lantern glow with the chemical reaction.

Hothersall and Theodossiou start by injecting the cancer cell with the firefly gene, then add another chemical known as rose bengal. Finally, they flip the "switch" by adding luciferin, lighting up the cell like a microscopic lightning bug. Once illuminated, the rose bengal produces a toxic form of oxygen called singlet oxygen that destroys the cancer cells by rupturing their membranes.

"That's the beauty of it," says Hothersall, of the Institute of Urology and Nephrology at University College. "We can make it so targeted that it only gets the cancer cells."

Since the treatment would have no side effects, he says, it could be repeated as often as needed if the cancer returned.

"This is real science fiction stuff, come to life," says Dr. Colin Hopper, a surgeon who works with the two researchers. "It's such a lovely, elegant idea. The challenge is to make it work in the clinical setting."

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Firefly genes have been used for years as molecular markers. A UCLA researcher recently connected them to cancer cells, allowing her to see where the disease had spread. But Hothersall and Theodossiou are the first to use the genes as killers.

The two researchers are beginning trials on mice with prostate cancer. If the study goes well, Theodossiou says, a human trial could begin next year.

BLADe could offer another big advantage over other treatments. Unlike many cancer therapies, which harm healthy tissue in killing the tumor, the firefly method would cause little or no collateral damage. When separate, the treatment's three elements - luciferase, luciferin, and rose bengal - are harmless to humans and animals.

Cancer treatment may only be the beginning. The two researchers believe BLADe could be used against other diseases. The tricky part, they say, is devising a way to insert firefly genes into these disease cells, and getting them to switch on.

But these complex questions may soon be getting much more attention, Hothersall says: "It's a new field. Once people get the idea of it, the number of applications could explode."


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