BUSINESS CATALYST A proprietary enzyme being developed by Xencor and Syngenta that might have personal care applications.
I under an agreement with GeneLink. The test examines seven markers. Taylor is not ready to say too much about the markers yet, but they identify oxidative stress and immune response mechanism. One he will identify is a marker for the enzyme superoxide dismutase (SOD). SOD begins the process of converting harmful superoxide (02~) into oxygen and water. If SOD activity is low, a person is more likely to develop wrinkles, age spots, and skin irritation. Initially, the test will cost about $200. But Taylor expects the cost to drop to about $100 as testing volume increases in the year or two following the system's introduction. By comparison, a similar test PERSONAL CARE for breast cancer could cost $1,500, and a DNA paternity test could cost between $200 and $300. Taylor ultimately hopes to sell the test through cosmetic companies that operate in upscale malls, on the Internet, or via door-to-door sales. Accommodations for genetic deficiencies will not overcome skin-damaging lifestyle choices. "If a person lies out in the MARC S. REISCH, C&EN NORTHEAST NEWS BUREAU sun or smokes, he or she will sustain skin OULD DESIGNER PROTEINS AND coming," says Monte Taylor, GeneLink's damage," Arch's Gruber says. "We can't say enzymes make skin supple, erase director of business development. And we've found the fountain of youth." But wrinkles, add color to hair, and what he calls "dermagenetics"—the study along with a healthy lifestyle, the test "may eliminate bad breath? Why not of how genetic variations affect the ap- help a person retain ayouthful appearance" produce advanced cosmetics pearance of skin—will, for a segment of as he or she grows older. with the tools biotech companies now em- the population, likely be as important as GeneLink's test will be a report card ploy to test, discover, and produce novel pharmacogenomics. that suggests a person's propensity to wrinpharmaceuticals? Some companies are beAn enthusiastic supporter, Vince Gru- kle by characterizing his or her resistance ginning to do just that. ber, technical marketing manager for to oxidative stress as "optimal, suboptimal, And why stop there? Doctors may one Arch Chemicals' personal care business, or minimal." If the marker shows optimal day be able to test individuals for genetic says a few years from now people will activity, nothing need be done, Gruber exmarkers, such as single-nucleotide poly- probably demand an SNP profile before plains. But ifresults are suboptimal or minmorphisms (SNPs), that could tell them they take a medication. And they will al- imal, "then using Arch plant and yeast exwhich medication would be appropriate so demand a similar profile before they tracts as key raw materials, we could help to treat an illness. Could a cosmetician al- apply a cosmetic. Arch has a strategic al- formulators come up with a tube for each so put the same principle of pharmacoge- liance with GeneLink and is developing suboptimal and minimal marker to help nomics to use to customize a skin care for- personal care ingredients to correlate with support skin deficiencies." mula for the individual consumer? Some of those key raw materials could GeneLink's tests. be biotechnology products. "GeneLink It's not so far-fetched. If DNA variations determine the way in which drugs af- "OUR WORK is based on findings of the has us thinking about these sorts of things fect people, those same variations could SNP Consortium," Taylor explains. The because of their test for markers," Gruber account for how people respond to differ- SNP Consortium is a pharmaceutical in- says. In the fall, Arch plans to introduce ent skin care formulations. And so com- dustry collaboration to develop a map of an entirely new line of standardized aning to a department store near you this fall genetic markers for disease. "But while we tioxidants based on nitrogen-fixing root or next spring could be a proprietary test can't patent the SNPs, we have patented nodule extracts. Gruber says these exthat can determine the oxidative stress pro- how we use them," he adds. A simple swab tracts could also be keyed to GeneLink's file of a person's skin. At least that's Mar- of the inside of a person's mouth collects test markers. gate, NJ.-based GeneLink's plan. enough live cells to run the test. The swab New testing methods are also providPharmacogenomics—the study ofhow is then sent to Princeton, NJ.-based Or- ing alternatives to animal testing of cosgenetic variations affect the way people re- chid BioSciences, which performs high- metics. A number of cosmetic companies spond to drugs—"is like a freight train throughput SNP genotyping of samples II have developed their own methods to test
DESIGNER COSMETICS
Ingredients makers take lessons from biotechnology to mastermind the latest in personal care
C
16
C & E N / MARCH 2 5 , 2 0 0 2
HTTP://PUBS.ACS.ORG/CEN
product safety and efficacy At least two companies —Organogenesis, Canton, Mass., and MatTek, Ashland, Mass.—now offer standardized test skins using tissue culture techniques. Mitch Klausner, vice president of scientific affairs at MatTek, says the company often constructs its tissue models from human cells derived from neonatal foreskins because they proliferate better than other tissue sources. MatTek dissociates the cells from the tissue, proliferates the cells, and then "cryo-preserves" the cells until it needs them to make a tissue model. "We can grow one piece of tissue into 10,000 pieces of similar tissue," he says.
melanocytes in the skin models could come from a source appropriate to the target audience for which a formulator is developing a product. MatTek's EpiOccular model is made of human-derived epidermal keratinocytes cultured to make them similar to human cornea tissue. "Colgate-Palmolive is sponsoring validation studies of our ocular tissue," Klausner says, to test household and personal care products. The model releases many of the pro-inflammatory cyTHE FIRM NOW offers three in vitro tests. tokines important in EpiDerm is a test model of human skin ocular irritation. made up of normal epidermal kerIf the test proves atinocytes. MelanoDerm contains both out, it could make the standard Draize rabhuman epidermal keratinocytes and bit eye test a thing of the past. The cost of melanocytes—the cells responsible for conducting such in vitro tests is close to pigmentation. This model may allow a the cost of tests that use animals. But the company to test the effectiveness of sun- in vitro tests don't alienate consumers who screens, skin lightening agents, and skin are opposed to animal tests, Klausner tanning agents, Klausner says. And the points out.
Soon MatTek plans to introduce a fullthickness skin model including the surface epidermis layer and the underlying dermis layer. The new model will make possible studies on skin wrinkling and may be useful in studying the effects of aging on skin, Klausner says. Independent labs have also adopted tissue cell testing kits. "We can help cosmetic companies shorten the development time for new cosmetics," says Robert W Holtz, director of laboratory studies for Biolnnovation Laboratories in McKinney, Texas. iCWe can validate the efficacy of a raw material to substantiate an advertising claim, or determine the toxicity of a raw material." Using the tissue culture models available from companies like MatTek, "we can screen 30 to 40 materials in a week" and can provide results that are "less expensive than clinical studies on people, and more
"We can screen 30 to 40 materials in a week and can provide results that are less expensive than clinical studies on people, and more consistent."
ex-po-sure 1: the fact or condition of being exposed: a s . . . a.
Defining the difference in long-lasting stability between Z-C0TP and avobenzone! All trademarks are owned by BASF Corporation.
We don't make the sunscreen. We help make it last longer.™
BASF
BUSINESS consistent," Holtz says. "%u can't always count on people coming back" tofinishup clinical tests. On the other hand, in vitro tissue samples never leave the lab. Biotechnology techniques aren't just used to test skin and cosmetic ingredients; increasingly, they are the source of the ingredients themselves. Roger Shamel, president of Consulting Resources, says the value of biotechnology ingredients used in personal care products is now only about
Avon with selected proteins, terpenes, and flavinoids for screening, says Prakash G. Kadkade, chief scientific officer of the 11year-old firm. "With our cell cultures, you don't have to depend on Mother Nature," Kadkade points out. A poor growing season may cause a crop failure. But cell culture provides a more dependable and controllable source of supply And "since we can grow cells from rare and endangered plants, we help to preserve endangered germplasm and also protect the environment," he maintains. Like Phytera, Phytoris focus has been on developing plantderived pharmaceuticals. About five years ago the company interrupted a cosmetic ingredient development deal with the ItalianfirmIndena to pursue a project with Bristol-Myers Squibb. As a result, Phyton now supplies Bristol-Myers with all the plantcell-derived paclitaxel it requires. The active ingredient for the breast cancer treatment no longer comes from the endangered Pacific yew or from yew needles. "The plant cell is a fantastic BREAKING IN Enzyme specialist Genencor chemist," Kadkade says. "It can has only recently started developing products for make all kinds of goodies if it is personal care. handled properly" Introduction of transgenic genes into plant cells could in the future make $30 million. However, their use is grow- novel proteins available, he says. And the ing at 15% annually, and he expects per- company can employ high-throughput sonal care formulators will use $100 mil- screening to assess the potential of novel active ingredients for personal care and lion of biotech ingredients by 2012. Among those working on biotech in- other applications. gredients for personal care products is En2yme specialist GenWorcester, Mass.-based Phytera. Since encor, with annual sales of early 2000, it has been supplying Unilever more than $300 million, with active extracts from tissue cultures. has mostly supplied enThe consumer products maker is using its zymes for industrial appliproprietary assay screening systems to cations such as laundry examine the extracts; it will have rights of detergents and grain procommercialization if any should prove cessing until now. Thomas useful. J. Pekich, group vice presiThe work with Unilever is an expan- dent of bioproducts, says sion of Phytera's traditional focus on drug the company wants to discovery with partners such as Eli Lilly "broaden the way we apply and Chiron. "Our unique, natural-prod- biotechnology Personal care is a natural uct-derived chemistry and genetic libraries fit." can deliver products relevant to a number The company commercialized its first of industries," says Malcolm Morville, protease enzyme for personal care almost president and CEO of Phytera. two years ago in Procter & Gamble's Dawn Also focusing on compoundsfromlarge- Special Care dishwashing detergent. The scale plant cell fermentation is Ithaca, enzyme softens skin without causing any N. Y.-based Phyton. The privately held allergic reactions. "By addressing the epicompany has worked with cosmetics for- topes responsible for allergic reactions, and mulator EOreal, and it is now providing understanding how they work, we can re-
duce or remove the allergic potential of protein enzymes," Pekich says. The company plans to use what it calls its LowGen technology platform to develop other personal care ingredients. OTHER PEPTIDES for skin could help remove rough or dead surface skin to reveal a new, smooth layer of skin below These peptides could be bottled in sunburn treatments or cleansing products, Pekich says. Kline & Co. industry consultant Gillian Morris estimates the size of the world market for "antiaging" enzymes at $5 million ayear today But she expects it to grow 10% annually over the nextfiveyears. Two other Genencor technology platforms, DestiGen and FunGen, also have personal care applications, Pekich says. DestiGen is a family of peptides designed to target an ingredient to specific human tissue. "We could direct whitening agents in mouth rinses to go straight to tooth enamel," he says, "but the agents would not attack the gums or soft tissue in the mouth." And FunGen exploits information Genencor has gleaned from the Human Genome Project. "We can now recognize changes that make hair turn gray or cause skin tissue to grow old and wrinkle," Pekich says. Applying the technology of functional genomics, Genencor could, for instance, use its peptide technology to help develop hair coloring agents that only target gray hair. Novel plant-based ingredients need not only be grown in a fermentation tank. Agribusiness company Syngenta signed an agreement with privately held Xencor, Monrovia, Calif., that could help Syngenta'sTorrey Mesa Research Institute develop plants that express novel proteins for food, pharmaceutical, and cosmetic ingredients. Bassil Dahiyat, president and CEO of Xencor, won't comment on specifics of the project, but he says it could, for instance, develop plants that express "pseudo-antiaging enzymes that might help rejuvenate the skin." Xencor's part in the project is to determine the interactions and functions of a cell's protein complement and to identify proteins ofinterest. Thefirm,a California Institute of Technology spin-off, can apply its advanced computational methods to screen for and optimize proteins, and in the process "de-
"The plant cell is a fantastic chemist. It can make all kinds of goodies if it is handled properly."
18
C & E N / MARCH 2 5 , 2 0 0 2
HTTP://PUBS.ACS.ORG/CEN
sign sequences nature never found," Dahiyat says. Like Phyton and Phytera, the core focus of Xencor's work is in pharmaceutical development, but Dahiyat sees a faster payback in the development of personal care ingredients. Pharmaceutical development requires rigorous testing, but the development of cosmetic ingredients is not nearly so onerous. And so, as the effort with Syngenta comes across active compounds with potential for use in cosmetics, it is worthwhile to go after what Dahiyat expects will be a large potential market for biotech products in the personal care market. OTHER PRODUCTS of biotechnology are already in use. Ralph Macchio, senior vice president of R&D at cosmetics giant Coty, says his firm has incorporated enzymes from Applied Genetics in its Tan Maximizer. Applied Genetics is conducting clinical trials of a purified version of the enzyme—T4 endonuclease V—to treat xeroderma pigmentosum. The disease keeps sufferers indoors because they do not produce an enzyme that repairs DNA
damage induced by ultraviolet radiation. Macchio says the enzymes in the Tan Maximizer group pf products not only "help repair DNA damage from the sun, but as a side benefit react with skin cells to increase melanin protection.,, Someone who uses the Tan Maximizer can even get a tan without exposure to the sun. "We are looking at other products, too, that rely on enzyme activity " Macchio says. The Hydra Lip line of lipsticks, for instance, increases lip moisture. The lipsticks contain a dehydrated natural polymer sphere that swells in the lip when it reacts with natural digestive enzymes. Biotechnology products and processes directed at personal care are likely to explode in the next 12 to 18 months, the Coty executive predicts. "We will be competing with bigpharma," Macchio admits, but he is confident personal care makers will see their share of developments. Among the developments coming onto the personal care market is hyaluronic acid—a viscosity enhancer and humectant used in creams—from a nonanimal source. According to Jon E. Anderson, vice president of technology for Actives
International, Ramsey, N.J., the acid is extracted from fermented yeast and will replace hyaluronic acid that now comes from rooster combs. Cosmetic makers have been trying to avoid animal-based ingredients since the mad cow disease scare. The yeast source of hyaluronic acid gives cosmetic makers another alternative, Anderson says. Ifeast derivatives have been available for years, but they are getting a new boost from the interest in biotech materials. Privately held Biologies International, Florence, Ky, has supplied yeast-derived active ingredients in the over-the-counter pharmaceutical Preparation H. But it is now pursuing skin care markets for its baker's yeast extracts, says Philip Courie, the firm's technical director. Traditional cosmetic ingredient suppliers have also taken on biotech methods to produce novel ingredients. For example, EM Industries, an affiliate of Germany's Merck, has isolated a cyclic amino acid from the Halomonas elongata bacteria discovered in the Egyptian desert, says Ratan K. Chaudhuri, EM's technical director. Called RonaCare Ecotoin, and pro-
ex-po-sure 1: the fact or condition of being exposed: as . . . b.
The definitive case for gentle, long-lasting UVA protection with Z-COTE®! All trademarks are owned by BASF Corporation. We don't make the sunscreen. We help make it more gentle.™
BASF HTTP://PUBS.ACS.ORG/CEN
C&EN
/
MARCH
25, 2002
19
Quality Jobs, Quality Chemists...
The C&EN Classifieds are the best source of high-quality chemistry jobs. Find them every week in the print edition of C&EN, or go online at http://pubs.acs.org/cen to find the two most recent weeks of C&EN print classified ads. Chemists/Chemical Engineers: Find your dream job. Search by title, organization, and/or geographical location. Click on the "Employment Outlook" link to gain insight on the chemical industry's future, and our "Wages & Trends" link to compare your salary with industry averages. Employers: Find your dream candidate. For your top-quality jobs, reach an audience of over 145,000 highly qualified
chemistry professionals. For more information on placing a classified ad in C&EN, please contact Matt McCloskey via email at
[email protected] or call 610-964-8061. With the C&EN Classifieds, you get access to quality jobs and quality chemists.
Pick up your print edition or log on today!
http://pubs,acs.orq/cen
CHEMICAL & Engineering News
The Newsmagazine of the Chemical World
BUSINESS duced in a fermentation tank in Darm- the trade name Erase, that can be used as liant, and used alone, it may irritate the stadt, Germany, Ecotoin protects im- a mild alternative to the skin peeling in- skin. Lersch says that by linking phymune cells in the skin, prevents cell death gredient alpha hydroxy acid. Another, phy- tosphingosine with salicylic acid, Degussa from UV exposure, and moisturizes the tosphingosine SLC, combines phyto- has created a "designer" ingredient that is skin. Chaudhuri says the ingredient is sphingosine—a derivative from pichiae both mild and effective. "useful in age-defying and daily New biotechnology methods are skin care formulas." And while "it likely to show the way to new active is a little expensive," he says use ingredients. And these methods are levels of 0.2% are effective. also likely to provide diagnostic tools that predict a person's Degussa Care Specialties has propensity to wrinkle and show commercialized enzymatically proother signs of aging. duced emollients: Tegosoft CR and Tegosoft DC. The emollients— Cosmetic makers and ingredicetyl ricinolate and decyl cocoate, ent suppliers don't intend to offer respectively—are low-color and up the fountain of youth. They low-odor products.Janet C. Kosiek, are too wary of the Food & Drug personal care marketing manager, Administration and other regulasays the enzymatic process yields a tory agencies to make such higher purity emolient than a heatclaims. Another reason is that processed synthetic emolient. people's lifestyle choices will take GROWING Phyton's 75,000-L fermentation facility a toll on their appearance. But by Peter Lersch, head of active in- in Ahrensburg, Germany. using tools more closely associatgredient development at Degussa, says the firm is adapting high-through- yeast—with salicylic acid to make a skin ed with pharmaceutical developments, put screening and genomic techniques to smoothing ingredient. Phytosphingosine, cosmetic makers and their suppliers are develop new products. And it has suc- explains Lersch, exists in human skin as developing an arsenal of purer and more powerful ingredients and technologies cessfully developed new bioengineered part of the lipid structure. ingredients. By itself, phytosphingosine soothes and that will feel good and ameliorate the efOne is a purified protease, sold under protects the skin. Salicylic acid is an exfo- fects of time. •
• Protect your customers from the risk of UVA exposure by formulating with Z-COTE® zinc oxide. • Gain exposure as a market leader by adding the competitive advantage of Z-COTE® zinc oxide to your products.
Call BASF for formulation assistance, technical data and more information about the definitive benefits of Z-COTE® over avobenzone. 1-800-880-5768 E-mail:
[email protected] www.cosmetic.basf.com
Z-COTE® UVA protection defines competitive advantage! All trademarks are owned by BASF Corporation. We don't make the sunscreen. We help make it better.™
BASF HTTP://PUBS.ACS.ORG/CEN
C&EN
/
MARCH
25, 2002
21
