"I prefer fishing in a stocked pond," Platika continues. "Go to where all bone is being created at once, in the embryo. The signal-to-noise ratio is much better, since the signal is being given over and over again." Consequently, developmental biologists study organisms such as the mouse, whose gestational cycle takes only 21 days, with most organs built in the second and third week. Another useful species is the zebra fish, whose skin is transparent during early life: "You can watch everything being built as they swim around," Platika says.

Ontogeny has identified and owns proprietary rights to several inducing molecules, including members of the "hedgehog" family, so named because the original discoverer identified them in a fruit fly that grew spikes on its back--and thus resembled a hedgehog. "One member of that research group was an avid video game player and named a molecule after Sega's video character Sonic Hedgehog," Platika says.

At work in the Ontogeny lab, from left to right: Ling Chai, David Israel, Doros Platika, and Ping Jin

In the real world, the inducing molecule "sonic hedgehog" plays a key role in differentiating neurons for the central nervous system and may some-day help alleviate nerve-related disorders such as Parkinson's disease. Other hedgehogs include "Indian hedgehog" (related to bone and cartilage differentiation), "desert hedgehog" (sperm and male fertility), and "patched" (skin and hair formation). "Patched" potentially could help treat basal cell carcinoma.

Platika explains that the actions of inducing molecules are "specific and limited. That greatly expedites the transition from discovery to therapeutic use. We don't even need to know the rest of the cascade. Using the natural pathways, the natural controls are there--the process doesn't go haywire. Contact inhibition shuts it off after the needed cells have been replaced."

Platika explains that stream-lining the path to market is desirable in the pharmaceutical and biotech industries, where finding and marketing a new drug typically takes five to seven years and costs $150-250 million. Ontogeny now has five product candidates, and so has formed partnerships to spread out the $750 million to $1.25 billion investment that these five could require. Last year, Ontogeny and Biogen, Inc. cut a hedgehog-driven deal whose license fees and milestone payments could approach $90 million. Another collaboration, with the German pharmaceutical firm Boehringer Mannheim, is potentially worth $30-40 million, and a third agreement will give Ontogeny access to novel secreted proteins supplied by Genetics Institute. The firm has also raised $41 million in capital from private investors.

Such hefty investments in young biotech firms generally come at the price of substantial ownership positions, but these partnerships are built around individual product candidates. This allows the investing company to confine its risk to a specific biotechnology, such as a hedgehog protein. If the molecule eventually develops into a drug-industry hit, both parties enjoy the payoff. "Obviously, they don't do it because they like our pretty blue eyes," says Platika, his own eyes twinkling at the thought.

Such financial arrangements may also stem from the deflation of the biotech balloon after an early rush of enthusiasm that young scientists and brash venture capitalists sired in the 1980s. Another bullish factor was Amgen, a California biotech firm that had two big winners early on--the red blood cell stimulant erythropoietin, which has $2 billion in annual sales, and neupogen, which stimulates certain white blood cells--and $1 billion per year in revenue. Both are inducing molecules, which Platika says have fueled the only big success stories in biotechnology to date.

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