A Thorny Tweak for the 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 20th century.

But beyond the monetary prospects, flower lovers are already fantasizing about what new emotional dimensions blue would bring to the rose.

“You think of blue as the ocean and sky, which are very powerful elements,” said Amulka Kitamura, a designer at the Flower Box in Santa Monica. “I think it would be stunning.”

To conjure the elusive color, scientists have plucked genes from blue petunias, fiddled with indigo-producing enzymes from the human liver and delved into the mystery of King George III’s occasionally blue urine.

So far, they’ve made some really nice purples.

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Humans have been growing roses for almost as long as civilization itself. The first cultivated varieties appeared in Asia 5,000 years ago, and mention of the flower is woven into tales across the ancient world.

An example is found in ancient Hindu legend. Brahma, the creator of the world, and Vishnu, the protector of the world, argued over which flower was most beautiful -- the lotus or the rose.

Vishnu supported the rose and Brahma the lotus. Brahma had never seen a rose before, but when he did, he immediately recanted and rewarded Vishnu by creating his bride, Lakshmi, from 108 large and 1,008 small rose petals.

Until the beginning of the 19th century, all roses in Europe were shades of pink or white, said Clair Martin, rose curator at the Huntington Botanical Gardens in San Marino.

The first scarlet roses came from China around 1800, he said. Unusual green roses arrived a few decades later.

Bright yellow roses entered the palette around 1900, when Frenchman Joseph Pernet-Ducher, after more than 20 years of breeding roses in a search for a hardy yellow variety, simply stumbled across a mutant yellow flower in a field, Martin said.

“All of our bright orange and yellow roses descend from that single rose,” he said.

Painstaking cultivation has revealed all of the remaining colors, except blue. Well, black is missing too, but the commercial possibilities of a black rose are, understandably, smaller.

“I wonder what it is in us that wishes so poignantly for blue roses,” said Luanne Wilson, a rose enthusiast in Richmond, Calif. Is it “a desire for the unique, a love of that color or only a twisted yearning to have something nature doesn’t provide?”

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.

Chris Warner, a rose breeder in Derby, England who distributes Cowlishaw’s roses, said that Rhapsody in Blue was an extraordinary breakthrough. “The ladies love it,” he said.

The rose, however, is purple.

“It fades to a lovely slate blue,” Warner hastened to add.

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The problem is that blue pigment does not exist in roses. No amount of breeding will bring it to life.

“We’re trying to attain the apparently unattainable,” Cowlishaw said.

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.

Scientists must also squelch any gene that produces other colors and find the right approach so the blue gene would be accepted by another plant.

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 it in 1996.

The carnations immediately caused an uproar in the cut-flower industry. Several million of them a year are now selling in Australia, Japan and the U.S.

The trouble is, they’re purple.

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Florigene was taken over by Suntory, a 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.

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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, who is now at the University of Queensland, Australia. Guengerich, who has been studying different versions of this enzyme for 30 years, had never seen anything like it.

After some thought, though, the researchers had a good guess of what they were seeing -- indigo, the same pigment that makes blue jeans blue.

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.

Then Guengerich realized that he had stumbled on the solution to an old medical mystery.

In 1811, Sir Henry Halford, personal physician to King George III, noted that the king’s urine was occasionally blue.

King George was not the only one to suffer from this odd ailment. In fact, modern doctors have noted a “purple bag syndrome,” in which the bag attached to a urinary catheter turns purplish.

The researchers knew that bacteria from a bladder infection could produce indole out of various compounds in urine. The human P450 enzymes that they were studying provided the last link in the chain, converting the indole into indigo.

Even though it was intriguing to explain how King George’s urine turned blue, Gillam suggested that they might make more money using the enzyme to turn roses blue.

Using indigo would avoid many of the problems Suntory and Florigene ran into using their anthocyanin-based blue pigment -- particularly their troubles getting rid of the flowers’ purplish hues.

Guengerich’s indigo-producing enzyme produces very little red pigment and indigo does not change color with acidity.

They have a long way to go, though. “In our initial attempts,” Guengerich said, “the gene didn’t know whether to turn the stem, the thorns or the flower blue.”

“It was just quite bizarre,” said Lisa Notley, who worked as a research assistant with Gillam.

They worked on the blue rose for five years, but never produced viable blue flowers or persuaded a company to invest in their discovery. Without funding, they turned to larger problems -- such as curing cancer.

“We thought we had such a promising thing,” Notley said. “Indigo is such a lovely blue color. It doesn’t get any more blue than that.”

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The blue rose has not been kind to its pursuers.

DNA Plant Technology in Oakland, 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.

And it can’t be just any shade of blue. “A blue that’s not a wonderful blue is not pretty,” said Ron Hasson, owner of Villa Florist in Los Angeles.

But some florists are optimistic, given the passion that many hold for the Western world’s most popular color.

Johnny Huynh, owner of California Floral in Los Angeles, said he got calls all the time for blue roses. “I had two requests this week,” he said.

Suntory and Florigene are continuing to tweak the rose genome, seeking to make their blue rose bluer. In two to four years, they hope to be selling roses that are blue, not purple.

Andrea McCullough, a rose lover in Orange County, is not holding her breath.

“My favorite color in a rose is purple,” she said.