July 26, 2001 — Back in 1979, Donald Tomalia discovered how to make synthetic molecules branch out like trees. But until recently, he has not been able to get money to grow the same way.

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Now, the former Dow Chemical Co. chemist says he

nearly has the venture capital lined up to get his new company, Ann Arbor, Mich.-based Dendritic Sciences Inc., up and running. It’s this company, Tomalia says, that will help him realize his two-decade-old dream of using his discovery — what he dubbed dendrimers — for everything from drug delivery to nanoscale machines.

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But about nine years ago, he had similar hopes that never materialized. In 1992, as co-founder of Dendritech Inc., he had said he was going to make dendrimers by the ton — a goal that he did not have the means to attain.

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Tomalia was touting the virtues of a unique branch of chemistry that had the potential to clean up all the messy problems for scientists trying to recreate nature. Dendrimers are synthetic products built on the nanoscale. What they have is precision. Tomalia and his Dow co-workers stumbled on a way to translate the branched structures of trees into chemical structures. That’s where the name “dendra,” a Greek word meaning tree, sprang up.

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“I was trying to imitate the branch of a tree with polymers,” Tomalia said.

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The significance is that until then, polymers, which are long, unruly molecules used to produce plastics, paints and coatings, had ruled the world of artificial products. Polymers were chaotic and the way they were made resulted in molecules in a range of sizes.

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But Tomalia had found a way to bring order to the artificial. Dendrimers grew with uniformity, each time doubling the number of tips, just like branches on a tree. The mass doubled with every generation.

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The result was the ability to produce precise, pristine, pure macromolecules. By 1990, Tomalia’s discovery was dazzling the scientific community. The largest dendrimers, which could be the size of proteins in living cells, intrigued Tomalia with biological possibilities. The potential seemed endless. Dendrimers could be used to build microscopic capsules for drug delivery or to build nanoscale machines.

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There was only one problem. And in the world of the small, it was a big problem. Money. The cost to produce dendrimers has been prohibitive and has not resulted in major commercial applications for the products. Tomalia has yet to make dendrimers by the ton.

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“An incredible amount of science has gone into developing many, many different (dendrimer) structures, but I would say hope springs eternal in terms of substantive commercialization,” said Robert Nowak, president and chief executive officer of the nonprofit Michigan Molecular Institute (MMI) and former director of central research and development and chief scientist for Dow Chemical.

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“Dendrimers are incredibly expensive to make,” Nowak said. “They intrigue scientists and polymer chemists who have never seen these structures, but we’ve been having a terrible difficulty finding what they are good for.”

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Dendrimers are so expensive because they grow in generations. The bigger they get, the more time it takes to grow them. For instance, a 10th generation dendrimer would have to go through 22 different chemical reactions. “That could take three months,” Nowak said. And time is money.

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“If you start getting up to the levels for gene therapy or amino assays, you can’t afford it,” he said. The cost, for instance, for generation four Polyamidoamine dendrimers, which is a trade name for one type of the product that has the potential to be used as a drug delivery system, would be about $15,000 a pound, Nowak estimated.

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Dr. James Baker Jr., chief of allergy and immunology at the University of Michigan, agreed. Baker has been doing work on dendrimers related to drug delivery. “This is ongoing research,” Baker said, adding that most of the work now is at a “nascent” level. “We don’t view this as an explosive area right now.”

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Tomalia remains determined to prove the concept is a good one.

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When he is not earning accolades in academia, Tomalia tends his 50-acre tree farm. “It’s these branching patterns of trees that have always fascinated me,” he said. “I’ve been growing trees since I was a teen-ager.

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“I was trying to imitate the branch of a tree with polymers,” Tomalia said.

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He became fascinated with the artificially manufactured synthetic molecules. “We filed patents extensively at Dow,” Tomalia said. However, according to Tomalia, Dow didn’t see how dendrimers fit its business at the time.”

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“I really believed in the technology, so I asked for a leave of absence” to continue research, Tomalia said. That decision led him to MMI, which offered him his first taste in business. In 1992, he co-founded Dendritech, a subsidiary of MMI that was licensed by Dow to manufacture and sell certain types of dendrimers.

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But last year, Dendritech imploded. Dow ended up acquiring Dendritech’s assets, which included the original patent portfolio licensed in 1991 to MMI, and new technology developed after Dendritech was incorporated, Nowak said.

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The only commercial application that Dendritech sells for now is very small additive for ink jets. “A couple of companies still use that material, it seems to enhance some of the attributes of writing with ink, particularly in very moist environments,” Nowak said.

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Tomalia is no longer with Dendritech. In a deal recently struck with Dow, Tomalia said the giant chemical company gave him licensing rights globally for his science applications in dendrimers. In return, Tomalia said, he waived future royalty rights that he had. “So I waived those (royalty) rights in return for these patent rights.” That created the basis for Dendritic Sciences, he said.

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“We expect to be the premier producer of dendrimers by the end of the year,” Tomalia said last week at a nanobiotechnology conference in San Diego. As for start-up capital, he said, “we’re talking multimillions we feel we’re close to, or will be.”

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During the conference, Tomalia told a Ph.D.-laden audience about the biomedical applications of a certain type of dendrimers that have all the qualities of proteins. The technology is “quite remarkable,” Tomalia said. “I’m very excited.”