he delicate hybrids thriving in the balmy climes of Provence, southern France's traditional perfume region, include sweet jasmine, May roses -- and fresh layers of artificial human skin.
Scientists here are working feverishly to develop new technologies to test cosmetics before a EU ban on animal testing begins in March 2009.
These advanced materials -- including reconstructed eye tissue and tiny circles of skin developed from donor cells harvested from cosmetic operations -- are a vital part of the industry's future as it faces rapidly tightening European regulations, rules that apply to any company wishing to sell in the 27-nation EU.
ILLUSTRATION: MOUNTAIN PEOPLE
The looming European ban is not only forcing multinational companies to adopt new practices. It is also bringing together regulators in Brussels with agencies from the world's other large cosmetics markets -- the US Food and Drug Administration and the Ministry of Health in Japan -- to harmonize regulation.
Even more surprising, the new standards are pushing longtime secretive rivals to cooperate, grudgingly and sometimes with prodding from regulators and politicians.
European Commissioner for Science Janez Potocnik appeared this month at a meeting for multinational companies and chided them for slowing the search for alternatives by failing to share information.
The stakes are high. Europe is the world's leading cosmetics market, and it exports more than US$23.4 billion in cosmetics every year. Products imported from the US to Europe amount to nearly US$2 billion a year, about 7 percent of all cosmetics purchased by Europeans. After the US, Japan is the second leading provider of cosmetics to Europe.
"Without question these regulations are having an impact," said Alan Goldberg, director of the Center for Alternatives to Animal Testing at Johns Hopkins University in Baltimore. "What company is going to want to eliminate 450 million customers by not complying?"
The cosmetics giant L'Oreal has devoted more than US$800 million in the last 20 years to the development of alternatives to animal testing, while its US rival, Procter & Gamble, maker of the Cover Girl line, has spent almost US$225 million.
"For the cosmetics industry, it's a race," said Herve Groux, 45, a French immunology scientist who presides over a year-old research lab in Grasse that aids smaller companies lacking the resources of titans like L'Oreal and Procter & Gamble. "The rules are pushing everyone to move faster and to put more money into research."
The European Commission itself is spending almost 25 million euros (US$36.5 million) yearly on the search for animal alternatives, while many countries are seeding programs with annual budgets of 15 million euros to 20 million euros.
Groux's lab, Immunosearch, had its official debut party last week in a boxy industrial park, where Groux and his wife, a molecular biologist, and other newly recruited veteran researchers are striving to shape a new world of beauty research -- and at the same time spare the lives of thousands of rabbits, mice, rats and guinea pigs.
As the 2009 deadline approaches, European regulators issue periodic tallies of the number of laboratory animals potentially spared by alternatives to animal tests, across all kinds of industrial uses. Part of the pressure for alternatives also stems from additional legislation, known as Reach, requiring companies to develop safety data on 30,000 chemicals over the next 11 years -- research that could raise the prospect of increased animal testing.
ACTUAL NUMBER
In fact, the actual number of animals tested for cosmetics is small compared with medical or educational uses, according to a new European Commission report. But from 2002 to 2005 the tally grew 50 percent in Europe, to 5,571 animals.
Much of that testing was taking place in France, the country that leads Europe in testing and vigorously fought the ban, ultimately appealing, in vain, to the European Court of Justice.
But it is also in Provence -- a region fabled for its fragrances and the professional "noses" who create them -- where scientists are gathering to work on alternative testing research in vitro, literally "in the glass."
In nearby Nice, SkinEthic, a 15-year-old company, is developing and manufacturing a line of cellular tools that includes a wide range of human tissues. Last year, SkinEthic was purchased by L'Oreal, which propelled the parent company into a dominant position in the testing field with two critical patents on reconstructed skin. SkinEthic produces its own form of reconstructed skin, RHE, while L'Oreal holds the patent to Episkin, which its scientists developed in Lyon.
Episkin was validated this year by European regulators as a test tool that could fully replace animals. Its closest competitor, EpiDerm -- developed by MatTek, a company in Ashland, Massachusetts -- received only qualified approval for research use because the artificial skin reacted too sensitively, producing different results than natural skin would.
To make Episkin, donor keratinocyte cells collected after breast and abdominal plastic surgery are cultured in tiny wells of collagen gel, immersed in water, amino acids and sugars and then air-dried for 10 days or aged to mimic mature skin by exposure to ultraviolet light.
Cosmetics are tested by smothering the almost babylike skin with the cosmetic material. The skin is checked for dying cells by adding a yellow chemical, MTT, which turns blue against living tissue, and then checked again for irritation.
"We have finally succeeded in showing that artificial skin can fully replace rabbit testing," said Thomas Hartung, the head of the European Center for the Validation of Alternative Methods in Italy.
His agency, which is part of the European Commission, is also in the midst of evaluating 12 methods for testing eye irritation to replace the classic Draize test on rabbits that dates back to the mid-1940s.
"If there's a holy grail that we're searching for, it's a test for eye irritation," Hartung said. "The issue has a very strong emotional factor."
Other alternatives include using tiny membranes within chicken eggs for testing chemicals, because the blood vessels mimic human eye membranes. The center has also approved the use of cow and chicken eyeballs cast off from slaughterhouses.
The mighty research budgets of the large multinational companies threaten to sweep aside smaller players with limited resources and different needs. But out of necessity, historic rivals in the secretive fragrance industry have joined to back Immunosearch, their homegrown research project, as a "deterrent force" to L'Oreal and P&G.
NATURAL INGREDIENTS
Robertet, founded in 1850, and Mane Fils, dating to the late 19th century, are supporting Immunosearch's ambition of adapting L'Oreal's Episkin to be more suitable for testing natural ingredients. Immunosearch is also benefiting from millions of dollars in private investments and government grants, as well as alliances with France's National Science Research Center nearby and its National Institute for Research in Computer Science.
Robertet and Mane Fils, perfume companies run for four generations by rival families, acted out of self-interest. Both said they were alarmed that European regulations would force them to submit complex natural ingredients, like lavender essence, to the same tests intended for chemicals.
"Our industry has poorly defended natural ingredients because our essences have been classified as chemicals," Robertet president Philippe Maubert said. "It's unfortunate because these ingredients have existed for centuries."
The companies worry that costly new European testing regulations could spell the end of many essential oils used in perfumery because the substances are a blend rising out of a distillation process that could fail existing chemical tests for safety.
"Those tests were developed to make tests on pure substances with few impurities," said Eric Angelini, the regulatory affairs manager at Mane. "But our essential oils are a natural blend of materials coming from the plant that is part of the distillation process."
At the champagne party to celebrate Immunosearch's debut, city and regional officials crowded into the pristine laboratory, where kits of artificial skin layers that are sold by the dozen were stocked in a special machine warmed to human body temperature.
Jean-Pierre Leleu, the mayor of Grasse, toasted the future with a reminder that the industry has come full circle.
In the 16th century, Grasse was a leather-tanning town that specialized in perfumed gloves. In the 18th century, the glove makers and perfumers split from the tanners to concentrate on perfumery.
Now, Leleu said, the industry has turned its attention back to skin, albeit human.
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