Dandruff Genomics

Jonathan willis

When Thomas Dawson first interviewed for a position at Procter & Gamble 10 years ago, he was struck by how clean the hallways were in comparison to the university laboratories where he had spent most of his career. "Well," his host responded, "we are a cleaning products company."

Inside the glass-fronted lobby of the company's Miami Valley Innovation Center, nestled along a wooded stretch of the Miami River near Cincinnati, Ohio, a bronze plaque commemorates the development of Tide laundry detergent. The restrooms are all outfitted with household paper towel dispensers loaded with rolls of Bounty.

The company was founded by a soapmaker and a candlemaker in 1837, but over the last decade, biologists like Dawson have been redefining exactly what it means to be a "cleaning products company" - beginning with one of their flagship products, Head & Shoulders, the leader in the $6 billion anti-dandruff shampoo market.

Head & Shoulders took more than 10 years to develop as chemical engineers screened over 2000 chemicals before stumbling upon pyrithione zinc, an anti-microbial compound that works particularly well on the dandruff-causing fungi in the genus Malassezia. The new shampoo hit store shelves in November 1961, and the company's chemical engineers spent the following decades looking for clever ways to get that chemical to cling to the scalp surface while grime and oil were washed away.

But by the late 1990s, P&G scientists realized the only way to improve the shampoo further would be to take a deeper look at the causes of dandruff. "There was no biotechnology in the company," says James Thompson, head of the Global Biotechnology Division. "With the tools Tom [Dawson] brought on board, we're learning things that just seemed impossible five years ago."

"You learn something about fibers from carpet and you can reapply that to hair! Learn something about surfaces and apply that to skin!" - Tom Dawson

Jonathan willis

In the process, Dawson, 44, and his collaborators developed genetic tools to identify the scalp's abundant microflora and to figure out how fungus' digestive enzymes inflame the scalp and cause tell-tale flaking. In November 2007, Dawson and collaborators published the complete genome sequence for Malassezia globosa, the primary species that causes dandruff (Proc Natl Acad Sci, 104:18730-5, 2007). Their findings are already being tested in new formulations of Head & Shoulders.

Procter & Gamble boasts more than 8,500 researchers at 27 technical centers around the world, including 1,200 PhDs (20-25% of whom are biologists). As Dawson strides through the spotless hallways with the company's communications officer, he gets excited talking about the way that researchers in different areas work together. "You learn something about fibers from carpet and you can reapply that to hair!" he says. "Learn something about surfaces and apply that to skin!"

"There's a lot of cross-fertilization going on here," the communications officer chimes in.

"That's the corporate term for it!" Dawson says. "For scientists, it's just a bunch of cool stuff."

Although Dawson grew up in a house full of chemists in Charleston, West Virginia, he likes to emphasize his "App-a-latch-an" roots. Soon after receiving a degree in chemistry, Dawson moved to North Carolina to work as a technician in John Lemasters' biophysics lab at University of North Carolina, Chapel Hill, studying membrane electron transport and ATP generation. They used their results to help develop the once-standard Carolina Rinse Solution to preserve livers for organ transplant patients.

Dawson's successes in that lab propelled him to pursue a PhD in pharmacology, where he continued to blend his chemical and biological expertise in studying the gene expression of breast cancer. After receiving his PhD in 1994 from the University of North Carolina, he spent four years as a fellow in human molecular and biochemical genetics at Duke University Medical Center. There, Dawson was running clinical trials with children with serious metabolic disorders, but found it difficult to stay emotionally detached.

Two friends had recently taken jobs at Procter & Gamble, and Dawson noticed an advertisement for a biologist with expertise in skin sensitivity in the back of Science. Back in 1998, the company's chemical operations were state-of-the-art, but they lacked the infrastructure and talent to move into the biological realm. Although Dawson had no experience with skin sensitivity, his combination of research skills made him an ideal candidate for an entry-level scientific position, the level at which all P&G scientists are hired.

"You secrete lipids on your scalp at a rate of hundreds of micrograms per centimeter per hour," explains Dawson, now principal scientist in hair care in the beauty technology division. "It's an oil slick on your head. Your hair is on there. It's dark and wet and it's greasy. So it's a really great place for microorganisms to live." The fungus lives by digesting those oils, but Dawson and other scientists were not even sure what caused the scalp to flake. Was it the irritating free fatty acids that are released by the fungal lipase? Or was it some other byproduct produced by a lipid peroxidase also involved in digesting oils? In fact, they weren't even sure which of the nine species of Malassezia was actually causing dandruff-or if it was a combination of species.

Dawson's first approach to answering these questions was decidedly low-tech. He applied scotch tape to the scalps of volunteers at a local clinic, removed it, and a colleague examined it under an electron microscope. The idea was to link the 30-year-old semi-quantitative scale used to rank dandruff severity with a microscopic description of scalp health. Dawson then ran a double-blinded, randomized trial with 12 dandruff sufferers and demonstrated that Head & Shoulders reduced lipid droplets and dandruff-related structural anomalies on the scalp (J Am Acad Dermatol, 45:897-903, 2001). More importantly, the biological team was better able to assess a "facilitator" molecule coming out of the chemistry division that was supposed to help pyrithione zinc penetrate Malassezia cells. In 2006, Procter & Gamble began putting this new molecule, zinc carbonate, in every bottle of Head & Shoulders, speeding up treatment by 50% and boosting its efficacy. (The company reports no associated business growth.)

"Naturally our success has invited a lot of competitive activity," says Bruce Brown, vice president of Procter & Gamble's beauty division. "The way we're going to win this game over time is on investment in research." In the 2006 fiscal year, P&G spent $2.1 billion - about 2.8% of net sales - on research and development, which puts them in the ballpark with Pfizer, Merck, and DuPont. The company has about 3,500 active patents in beauty care, which ranks them with such behemoths as Microsoft or IBM.

Upstairs in Jay Tiesman's office, a Mr. Clean doll sits next to a James Watson action figure. Tiesman, the Genomics Group Leader at P&G, has two coffee machines, two flat-screen monitors, two printers, and a plethora of personal electronics arrayed on the black lab bench he uses as a desk. As the resident gadget guru, Tiesman has been responsible for the logistics of transforming Miami Valley into a world-class biotechnology facility with spotting robots, microarrays, and a laser capture skin biopsy system. Most recently, he purchased an Affymetrix Gene Chip Array System, which automates the fluorescent labeling of 96 gene chips in a day. "It's not an uncommon thing for pharma," Tiesman boasts, "but I can't think of a single consumer products company that does GCAS."

Back in 1999, GCAS was not on Tiesman's radar, nor was it on Dawson's. Dandruff genetics, let alone genomics, seemed out of reach. Dawson needed an efficient way to count Malassezia numbers and identify species on the scalp surface with the aid of an electron microscope. At the time, scientists believed that Malassezia furfur was the dandruff-causing species and Dawson expected that people with severe dandruff must have been harboring high numbers of that one species.

But developing genetic fingerprints for M. furfur and the other eight species would be a challenge to confirm by microscopic examination of cultures. At the International Symposium on Yeasts in the Netherlands in 2000, Teun Boekhout, a basic scientist who worked on Malassezia at the Central Bureau of Fungal Cultures in Utrecht in the Netherlands, remembers stepping into the conference hall and being chased down by this tall, enthusiastic American. Dawson "had just started at P&G and was desperately looking for expertise," says Boekhout. "We chatted between sessions," and the two leaders decided to collaborate.

What did the duo discover? "We were wrong," Dawson says. "Everyone has the same microflora on their scalp." In fact, dandruff is not caused by high numbers of M. furfur, but by two other species, M. globosa and M. restricta, present on everyone's scalp (J Clin Microbiol, 40: 3350-7, 2002). The severity of dandruff depended on a complex interaction between skin sensitivity and the scalp microflora, a question company scientists are still looking into. "You can have one person with a couple million cells per square centimeter and it doesn't affect them," says Dawson, "A couple people with a hundred, and they're ate up!"

In 2001, with some understanding of scalp ecology, Dawson's team began looking into lipase metabolism of M. globosa and soon identified LIP1, the gene it uses to break down scalp oils (J Invest Dermatol, 127:2138-46, 2007). The chemical engineers capitalized on this discovery by synthesizing a lipase inhibitor, which they soon tested on human subjects. Dawson refuses to disclose how much improvement they've achieved over current formulations of Head & Shoulders but says, "It was statistically significant."

It must have been. Within a year, Procter & Gamble was moving full speed ahead with their biotech capabilities, contracting with Integrated Genomics in Chicago to sequence the entire genome of M. globosa. P&G bioinformatics expert Jun Xu's analysis revealed that the M. globosa genome was tiny, consisting of only 4,285 genes, and it completely lacked the ability to synthesize fatty acids on its own. Instead, the genome contained sequences for 12 hydrolases, which break down oils and could all become potential targets for anti-dandruff compounds. The company patented the 12 genes for their anti-dandruff promise.

Procter & Gamble still needs to navigate The Food and Drug Administration's dandruff monograph, which limits the active ingredients companies can use in over-the-counter products that make anti-dandruff claims. But this is only a small hurdle for a cleaning products company that's survived 160 years of change. Vice President Bruce Brown says that, "The chances of us bringing an innovation to Head & Shoulders based on this genome understanding is 100%."

Correction (posted May 5): When originally posted, the story referenced Proctor & Gamble misspelled. That correct reference is Procter & Gamble. The references have been corrected, and The Scientist regrets the errors. The article also misspelled Jay Tiesman's name, an error that has also been corrected.

Correction (posted May 6): When originally posted, the story incorrectly stated Tiesman is a Seattle native. He lived there many years, but was not born there. The story also said adding zinc carbonate doubled the efficacy of Head & Shoulders. In truth, it sped up treatment by 50% and boosted its efficacy, but did not double it. The original story also stated P&G had 9,000 employees at 18 research centers. The correct figure is more than 8,500 employees at 27 technical centers. The Scientist regrets these errors.

Correction (posted June 5): When originally posted, the article misspelled Teun Boekhout's name. The error has been corrected.