In the early 1980s, investor George Rathmann had big plans for his new company, Amgen Inc.: Not only did he hope to use biotechnology to revolutionize drug development, but he envisioned using gene-spliced bacteria to turn cheap chemicals into plastics, lubricants, and other high-value industrial products. Rathmann later abandoned the second goal, but an experiment-gone-wrong from that pursuit could soon be making blue jeans a little greener.
The experiment began when Amgen researchers discovered that an enzyme found in certain bacteria could convert inexpensive naphthalene, the key ingredient in mothballs, into a much more expensive ingredient called alpha-naphthol that is used in making dyes and some plastics. By splicing the gene for that enzyme into another kind of bacteria, Rathmann envisioned a cheap way to make commercial quantities of alpha-naphthol at a big profit. After the first experiments, though, something odd happened: A mysterious stain turned all of the experiments blue. "We teased the scientist that the cells were in pain," recalls Rathmann. Soon after, a visiting British chemist saw the blighted beakers and recognized the "contaminant" immediately. "That's indigo!" he said.
While some researchers laughed, Rathmann made some calculations: Indigo, used to dye denim blue, is the world's most popular dye. It was then selling at about $10 per kilogram. Alpha-naphthol was going for under $2 and naphthalene for a few pennies. Plus, existing indigo synthesis requires noxious chemicals, such as cyanide and formaldehyde. And it produces toxic effluent. Amgen's process simply required some cornstarch to "feed" the cells--and had no toxic byproducts. "We thought we had the Holy Grail," says Rathmann. Indigo, not alpha-naphthol, became the target.
That was almost 15 years ago. With big profits much more likely from new drugs, Amgen--like many biotech companies--dropped its industrial enzyme research. Today, the indigo technology, sold to Genencor International Inc. in 1989, is still on the launchpad. It has long been regarded as an example of how biotechnology can offer important new approaches for industry well beyond new drugs. Using nontoxic, renewable resources, genetically engineered enzymes have made headway in treating textile products, improving detergents, and making food additives. But industry has so far been waiting for a high-profile blockbuster product.
Will it be indigo? Like other projects in this arena, delays have stemmed from two sources: The first is the technical trick of turning test-tube science into reliable, large-scale production. But a more fundamental block for bio-indigo is that established manufacturers have been loath to alter decades-old production processes--citing both economic and quality concerns about the new dye.
Now, those concerns may be lessening. Genencor, a joint venture of Eastman Chemical Co. of Kingsport, Tenn., and Finland's Cultor Ltd., has used some nifty chemistry and molecular biology to increase indigo yields more than ten-thousandfold. Genencor's vice-president for technology development, Karl Sanford, says the cost is finally competitive with the traditional process. And rising environmental concerns around the world may work in Genencor's favor. While it's far from certain that the dye can crack the $250 million indigo market, conditions have never been better.
Indigo is the best known of "nonreactive" dyes. It coats only the outside of textile fibers and so wears off over time, making it perfect for achieving the lived-in look and feel of denim jeans. It accounts for some 3% of all dye colors used today--impressive against a universe of thousands of colors that are mixed together to form various shades.
Indigo has a rich and peculiar past. Marco Polo was the first to describe the dye, made from indigofera plants growing in Asia and Africa in the 13th century. Europeans protecting the market for native dyes made from blue woad plants initially threatened death to anyone using indigo. By the mid-19th century, demand for indigo was soaring in the U.S. thanks to a Bavarian peddler named Levi Strauss, whose denim work pants became the uniform of the California Gold Rush.
Indigo's big commercial turning point came in the late 19th century. After 17 years of research, German chemist Adolf von Baeyer invented a synthetic indigo dye process in 1897 that later won him a Nobel prize in chemistry. Over the next several decades, British owners of large plantations in India planted indigo in a failed effort to compete with the cheap and reliable German chemistry. Villagers starved in the process when food crops were uprooted.
ENTRENCHED. By the time Rathmann's team began considering the blue stain in its experiments, the world's major indigo producers--including Germany's BASF Group, Japan's Mitsui, England's Imperial Chemical Industries, and Buffalo Color in Buffalo, N.Y.--were making a tidy profit. They had long ago written off their plants and carved up most of the market. So Rathmann got a cool reception to his inquiries. At the same time, he was increasingly distracted by the huge potential of EPO, Amgen's blockbuster anemia drug.
That was one reason Amgen sold its technology. Another was that the fervor for biotech versions of industrial chemicals had died down. It looked as if only startups that won patents on products had a chance to break into major chemical markets. Rathmann could never hope to get a patent on ancient indigo. In offering just process improvements, "you'd be overwhelmed by entrenched competition," he says.
There were technical snags, too. In fine-tuning the process, scientists were involved in a complicated balancing act with the enzymes in the bacteria. Tweaking one enzyme more than another could send the target byproducts in the wrong direction--making them weak, unstable, even the wrong color. The most notable flub came after Genencor's first big production run of 150,000 yards of denim. The result was too red because the bugs were now squirting out a byproduct called indirubin. After two years of work, researchers spliced in a gene for yet another enzyme that could convert the culprit to a colorless, nontoxic compound. Recently, experts from the textile industry have evaluated Genencor's dye and proclaimed it equivalent to the chemically produced standard.
Genencor CEO W. Thomas Mitchell says the company is committed to the enzyme business and is moving to find a partner to produce the dye. Likely indigo partners still seem unconvinced, however. A spokesperson for BASF, for which von Baeyer worked and which holds 40% of the world's indigo market, says the gene-spliced dye is too weak, adding that the process "is not to be taken seriously." Craig McKibben, chairman and CEO of Buffalo Color's parent, Lanesborough Corp., passed on an offer to do joint research and development into biosynthetic indigo. He has no qualms about the technology in theory. "It's really just a cost issue," he says.
Neither the industry nor Genencor will reveal their exact costs, though worldwide prices of indigo concentrate range from $8 to $17 per kilogram. One issue, however, is how you measure costs. There is pressure on specialty-chemical makers to figure in the costs of storing, disposing, and cleaning up the toxic byproducts of their processes as environmental regulations become more stringent. Old-timers in the Buffalo area remember the days when a rainbow of effluent from the dye plant, then making hundreds of different colors, sometimes streamed over Niagara Falls.
ACID SPILL. Companies have tightened their controls substantially since then, though in January, the Buffalo Sewer Authority fined Buffalo Color for what company officials said was an accidental discharge of sulfuric acid into the sewer system. Even BASF concedes that runoff from its dye process is a concern and says the company has been trying to create greener methods.
Another factor in bio-indigo's favor is that consumer demand is shifting to greener products. Organic cotton is a growing textile category, as is hemp. Oppenheimer & Co. apparel analyst Leslie McCall thinks an eco-friendly ad campaign for jeans based on gene-spliced dye could be a hit. "The younger generation is really sensitive to environmental issues," she says.
Controlling that spin could be tricky, though. Would bio-jeans represent progress to consumers--or conjure ethically itchy reminders of cloned sheep? Genencor's Mitchell wouldn't even touch the question of whether end-users of bio-denim would or should promote that element. Levi Strauss & Co., the world's largest jeans maker, wouldn't comment on the new technology or its prospects.
Genencor says it will find a partner by yearend--but not necessarily an established dye maker. So if Sanford's forecasts of improving yields hold, it may only be a matter of time before bio-dye becomes a low-cost, eco-friendly antidote to the industry's pollution blues.