How About Glow-in-the-Dark Birthday Cake? 

Steven Levingston / International Herald Tribune 18jan01

Jellyfish Gene Leaps From the Test Tube to Tickle Entrepreneurs' Imagination

PARIS Martin Chalfie, a professor of biology at Columbia University, had studied the tiny worm Caenorhabditis elegans for nearly two decades - "far too many years," he muses - when his big breakthrough finally came.

In 1994, he and his team inserted the fluorescence gene of a jellyfish into his favorite creepy crawly with glowing results: the worm's nerve cells shone bright green.

Mr. Chalfie's triumph launched a scientific mad dash to set the world aglow. Now researchers are lighting up so many parts of life that bioluminescence has emerged as one of the hottest tools in genetics.

Today, things glow that were never intended to glow: cancer cells, zebrafish, potatoes, bunnies. In the latest feat, scientists announced last week that they had used the jellyfish gene in an attempt to create a glowing monkey.

The fluorescence-driven research is primarily aimed at shedding light on biological processes. A jellyfish gene inserted into an organism triggers a green glow to alert scientists of a particular cellular activity. What was once invisible is now witnessed in real time, allowing researchers to peer inside live cells and track the development of disease.

In the case of the monkey, scientists inserted the fluorescence gene as a first step toward creation of primates with human diseases in order to test therapies. If the monkey glows green under blue light, which is needed to activate bioluminescence, then scientists will know the gene transfer worked.

Success would raise the possibility of producing families of genetically modified monkeys with Alzheimer's, hereditary blindness and other diseases. So far, researchers have proof that the gene has entered the monkey's cells but they have not detected a glow.

Experimentation with the jellyfish gene is so popular that researchers have trouble keeping track of all the projects. "If it were something bad, you'd say it was an international plague - it's everywhere," says William Ward, a professor of biochemistry at Rutgers University.

Scientists now hope the fluorescence gene will serve as an aid in cleaning polluted waters, discovering how food poisoning spreads, perhaps even in creating Christmas trees that light up on their own. Already the business world is racing to cash in with production of luminous makeup and toy pistols that shoot glow-in-the dark liquid. Jokesters have discovered the humor of a man-made glow, and artists are attracted to the gene as a tool to expand the boundaries of their craft.

Such wide and novel use has ignited fears among ethicists and some scientists and has drawn the jellyfish gene into the long-running battle over biogenetic modification. The rancorous debate is widening to include, among other things, a cloned sheep named Dolly, genetically engineered corn containing a possible human allergen and now a monkey named ANDi that may glow green.

The ocean brims with creatures that glow. For 650 million years, jellyfish have lighted up the briny deep, and tiny plankton have turned swaths of the sea surface to glittering blankets. There are many luminous shrimp and squid and a luminous octopus, in Japan, and there is the aptly named flashlight fish in Indonesia that has large light organs below its eyes.

Scientists say that the light show beneath the waves may represent the most common form of communication in the natural world. Marine creatures recognize members of their own species by their glow, play luminous mating games, lure prey by flashing, and confuse attackers by squirting a cloud of light.

Things that glow have fascinated humans ever since the first clans stared into a fire or gazed up at the stars. A flickering candle can mesmerize the eye and the flash of the firefly delight the soul. In art and film, angels soar in radiant halos and ghosts drift in luminous bodies. "A glow has a beatific aspect," says Stuart Newman, professor of cell biology and anatomy at New York Medical College. "Something that emits its own light appears to have some kind of intrinsic virtue to it."

Nearly 2,000 years ago, the Roman naturalist Pliny the Elder was dazzled by a clam that spit phosphorescent green slime when frightened. Even more intriguing, he found, was that anyone who ate the bizarre mollusk was left with luminescent lips. The culinary novelty set off a first-century fad: Romans threw clam feasts in the dark and frolicked with glowing green mouths.

With advances in genetics, things that glow moved from the natural world into the lab. At the heart of the research is the jellyfish Aequorea victoria, whose genes instruct cells to produce a green fluorescent protein that is responsible for the glow. Insert the jellyfish gene successfully into another organism and its cells will produce the protein that stimulates the glow.

Efficient and time-saving, the revolutionary process has given life to several dozen genetically altered small minnows, called golden longfin zebrafish, that shine in polluted waters. Scientists at the University of Cincinnati hope that large numbers of the fish can be bred to flash early warnings of toxic chemicals in rivers and lakes.

Some researchers dream in rainbow colors. New genes have recently been discovered that offer the hope of a red protein and a blue one.

In a competition sponsored last year by the British Biotechnology and Biological Society Research Council, a team of postgraduate students at Hertfordshire University proposed the creation of a Christmas tree that lighted up on its own. They described how to genetically modify a Douglas Spruce and included a business plan for a company to produce and market the glowing tree.

Deri Morgan, one of the students, believes it would be possible to go beyond creating a Christmas tree that merely shines green, blue and red. Eventually, he says, the tree could be genetically instructed to glow just at its tips. The project was among the eight finalists in the competition but failed to garner the top prize. The team did attract some criticism, however. "Some people thought we were trying to take God into our own hands," Mr. Morgan said.

Biogenetics raises such delicate issues that many observers find it hard to accept even the most serious medical efforts, much less have any sense of humor about the most bizarre prospects.

Not so at Australasian Science, a popular science magazine in Australia. Its April issue last year carried a story about a brewer who planned to introduce a genetically altered beer that caused the faces of heavy drinkers to glow green. The article described how the yeast to brew beer had been engineered with the green fluorescent protein in a bid to help police identify drunk drivers.

Understandably, the piece set off a storm of concern and anger. But those who read the article carefully would have been tipped off to a ruse. The last sentence instructed readers to look at the first letter in each paragraph, which spelled out April Fool. "People killed themselves laughing when they realized it was a hoax," says Guy Nolch, editor of Australasian Science.

Few people were laughing when a Chicago artist, Eduardo Kac, persuaded the National Institute of Agronomic Research near Paris to loan him a genetically modified bunny to display as an exhibit at a show in Avignon.

The institute had created 10 bunnies with the green fluorescent protein as part of program aimed at cloning rabbits for research into cystic fibrosis. Louis-Marie Houdebine at the institute says that, viewed through special glasses under ultraviolet light, the bunnies glow green mainly at the eyes, and also at the ears, nose and hair roots. Mr. Kac wanted to display one bunny to inaugurate what he called a new era of transgenic art. The uproar was deafening as genetic ethicists howled that Mr. Kac had crossed a dangerous line by proposing to use altered life forms for artistic purposes.

Mr. Kac offered that he hoped the exhibit would spark meaningful discussion on all issues of biogenetics. In the end, the institute demurred, and the bunny was a no-show at the Avignon exhibition. Still, Mr. Kac is pushing forward with his dreams of transgenic art and hopes one day to put on exhibit a glowing dog.

In the world of bioluminescence, the serious and the frivolous merge at Prolume Ltd., a start-up company in Pittsburgh. Prolume, founded by a surgeon and an oncologist, does bioluminescence-based cancer research. In its bid for funding, the company also is working on glowing foods, beverages and cosmetics. Among its projects: cake frosting that will glow Happy Birthday after the candles are blown out. The company already has marketed a glow in-the-dark water pistol. George Finley, an oncologist and chief executive officer of Prolume, recognizes that critics may believe it is wrong to commercialize genetics research. "One could construe what we do as frivolous," he says. "But we don't think there's any harm in creating a revenue model to fund basic science. Bioluminescence is a great venue to introduce biotechnology to consumers. Our products are very compelling, really 21st-century in appeal, novelty and fun value."