Researchers' quixotic quest for blue rose

Roses are red, violets are blue.
But what if roses were blue?
Florists might stand to make a lot of green.
Modern biochemists and geneticists are now closing in on a prize that has obsessed rose lovers for centuries — the creation of the true blue rose.
The flower does not exist in nature, and despite centuries of effort, no breeder has managed to even come close. They have called many roses blue — Blue Girl, Bleu Magenta, Blue Moon.
They're purple.
The only way to create the elusive and unnatural color blue is by manipulating the genetic code of the rose, and millions of dollars are being spent on the effort by genetic-engineering companies.
The prize is a hefty piece of the $25-billion global cut-flower market, which hasn't seen a major twist in roses since the introduction of yellow around the turn of the last century.
To conjure the elusive color, scientists have plucked genes from blue petunias and fiddled with indigo-producing enzymes from the human liver.
So far, they've made some really nice purples.
Frank Cowlishaw, an amateur rose breeder in Derbyshire, England, has spent 25 years trying to tease the color from nature through careful breeding.
His "Rhapsody in Blue" variety is one of the bluest roses that does not rely on genetic tricks for its color.
The rose, however, is purple.
The problem is that blue pigment does not exist in roses. No amount of breeding will bring it to life.
Many flower pigments have the same basic chemical structure — a molecule called an anthocyanin. Extra chemical decorations, called hydroxyl groups, determine the color. One extra hydroxyl group makes a dark, brick red; two is a light pinkish red; and three is blue.
Roses do not have a gene that allows them to add the third hydroxyl group, which makes the blue pigment delphinidin.
Purple roses, which you might think contain blue pigment, actually get their color from a reaction between a red anthocyanin pigment and other molecules in rose petals. Unfortunately, there is no way nature can get rid of the reddish tinge.
So why not pull a blue gene from, say, a petunia and put it into a rose?
"It's not as simple as taking one gene from one plant and putting it in another," said John Mason, research manager for Florigene, a biotechnology company in Melbourne, Australia.
To begin with, anthocyanin pigments are sensitive to acidity. That's the reason hydrangeas can be blue or pink. Gardeners say that if you want blue hydrangeas, add aluminum sulfate to the soil to make it more acidic. Any blue rose also would have to be modified to increase the acidity in its petals.
A blue carnation
Which is why Florigene, formed in 1986 to develop genetically modified flowers, decided to start with carnations. For some reason, carnations seem easier to manipulate genetically than roses.
After about $18 million and four years of work, Florigene scientists managed to create the Moondust carnation. They began selling them in 1996.
They immediately caused an uproar in the cut-flower industry. Several million of them a year are now selling in Australia, Japan and the United States.
The trouble is, they're purple.
Florigene was taken over by Suntory, the Japanese beverage company, in 2003.
The company aimed to produce blue roses using the "blue gene" from petunias. "But the petunia gene did not work at all in roses," said Yoshikazu Tanaka, the director of Suntory's blue-rose effort.
After trying genes from several flowers, Tanaka's group eventually settled on the blue gene from pansies. Roses seem to understand pansy DNA best.
Their difficulties were not over. "We cannot insert the gene into whole roses," Tanaka said. They had to insert the gene into one rose cell and then cajole it to grow into an entire plant.
Developing the process to grow a rose from a cultured cell took several years.
But then, even though they had a rose that produced the blue pigment delphinidin, they had to disable the old pigment forming genes and modify the acidity in the petals. With any small amount of red pigment in the flower or too low acidity, the petals aren't blue enough, Tanaka said.
Finally, in a triumphant news conference June 30, Suntory announced it had produced "a synonym for the impossible" — the blue rose.
Well, sort of. It's purple.
"The flower is a nice color, but not sky blue," Tanaka admitted.
Blue in bacterial cultures
Meanwhile, serendipity arrived in a beaker full of bacteria at Vanderbilt University.
In 1999, biochemists Fred Guengerich and Elizabeth Gillam were studying a group of enzymes called cytochrome P450s, which help the body to deactivate and eliminate toxins.
Their research, which has implications for Alzheimer's disease and cancer therapies, focuses on understanding how the P450 enzymes help the liver to remove both carcinogens and helpful drugs from the body.
To produce a large quantity of one particular form of the enzyme, they pulled the gene out of humans and inserted it into bacteria.
"My students noticed some of their bacterial cultures were turning blue," said Gillam.
After some thought, though, the researchers had a good guess of what they were seeing — indigo.
They surmised that the bacteria took an amino acid called tryptophan and converted it into a compound called indole. The new P450 enzyme changed the indole into indigo.
Guengerich's indigo-producing enzyme produces very little red pigment and indigo does not change color with acidity.
They worked on the blue rose for five years, but never produced viable blue flowers or persuaded a company to invest.
The West's favorite color
The blue rose has not been kind to its pursuers.
DNA Plant Technology in Oakland, Calif., which also tried to discover a viable blue gene, closed its research and development wing in 2002. Japan's Kirin Brewery, another competitor in the quest, is now more interested in developing disease-resistant plants.
Even with a truly blue rose, there are still many hurdles to clear.
"Just because it's a blue rose does not guarantee success," said Terril Nell, president of the Society of American Florists. The flower must hold up during shipment, last a long time in the vase and have a good fragrance, he explained.
But some florists are optimistic, given the passion that many hold for the Western world's most popular color.
Suntory and Florigene are continuing to tweak the rose genome. In two to four years, they hope to be selling roses that are blue, not purple.
Andrea McCullough, a rose lover in Orange County, Calif., is not holding her breath.
"My favorite color in a rose is purple," she said.
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