Marketing Molecules

At a time when high-tech business headlines are dominated by biotechnology, nanotechnology, and computer science, it's easy to overlook chemistry. It may not be as sexy as some other disciplines, but it's at the heart of any industrial process or product you can name. "Sometimes not even the chemists are aware when they look at a product how much chemistry is there. If you peel back the mechanism, they get it right away, but they're looking at a shiny box," says Thomas J. Meade (pictured left), a professor of chemistry at Northwestern University in Evanston, Illinois, who has founded or co-founded three companies-- Clinical Micro Sensors, MetaProbe, and Ohmx--that are based on his work on electron transfer and paramagnetic lanthanides.

George Whitesides also emphasizes chemistry's commercial importance. "Most of what goes on in the world is catalyzed, whether it's cracking crude oil or powering automobiles. If you think about what biotech sells, it sells molecules. Materials science companies sell molecules, and chemists have a particular ability to make new forms of matter. Molecules is what we do." Whitesides, a longtime professor of chemistry at Harvard University, has founded a dozen or so companies during his storied career. Even he isn't sure of the exact number.

Chemistry is uniquely suited to drive new industry. But starting a company isn't just a matter of shopping around some whiz-bang new discovery. Basic research, some of it esoteric, drives academic chemistry. But the key to founding a successful company, say experts, is finding the right application.

George Whitesides

Finding a Problem for Your Solution

After finishing his Ph.D. at Ohio State University, Meade was a National Institutes of Health postdoctoral fellow at Harvard Medical School and Massachusetts General Hospital before he joined Caltech's Beckman Institute in 1991. When he started out, Meade had no plan to commercialize his research. He viewed industry merely as an alternative to traditional funding sources. When he filed his first patent in 1993, applied research was still frowned upon in academia. "I didn't have much motivation to pursue this, but I realized if I could score industry money, that was one less grant [application] that I had to write," he recalls.

One of his early projects focused on long-range electron transfer through pi-stacked systems. Photosynthesis particularly intrigued him. "You have electron density everywhere. I thought perhaps that electrons might go faster through pi systems if they were close together and stacked," he says. Searching for a system to study, he decided to save himself a lot of synthetic effort by turning to double-stranded DNA, in which the aromatic nucleotide bases lie stacked on top of one another. "I saw a computer-generated structure of DNA and realized I didn't have to create a new system--I could just borrow DNA, attach an electron donor on one end and an electron acceptor on the other, and we might have a system to study these phenomena."

He soon observed that electrons transferred faster through double-stranded DNA than single-stranded DNA. "When you realized that, you could put your hands around what it is: It's an electronic DNA hybridization assay," says Meade. After an initial boost from a Small Business Innovation Research (SBIR) grant, Meade and his postdoctoral fellow and co-founder Jon Kayyem raised the seed money to start a company. "Back then, biotech was the darling and you could raise money without a great deal of data," he says. The research became the foundation of Clinical Micro Sensors, which was sold to Motorola in 2000.

MetaProbe grew out of Meade's research applying bioinorganic chemistry to the study of developmental biology. His team was particularly interested in linking gene expression to specific developmental processes. They turned to magnetic resonance imaging (MRI) because this noninvasive technique provides images of whole animals. They developed MRI agents that shielded the paramagnetic ion from surrounding water, making it undetectable by MRI. They designed the molecules so that enzymatic cleavage would open the floodgates, allowing the paramagnetic ion to interact with the protons from water and causing the agent to light up in the presence of a specific enzyme. "You could follow an embryo through the entire course of development with these bioactivated probes and watch the unfolding of the developmental biology of the whole animal," Meade says.

The commercial potential of the technique became clear when they started to consider the implications for cancer treatment. "These bioactivated agents may add a great deal to the portfolio of diagnostic radiology," Meade says; such agents can be used to determine whether a tumor responds to a given drug therapy. Currently, a physician must wait for pathology reports or observe shrinkage of the tumor to know whether a drug works. Bioactivated MRI agents can report on a tumor's metabolism in real time within a few hours after a chemotherapy session. That technology formed the basis of MetaProbe, which Meade started in 1998.

The application of Meade's pi-stacking electronic DNA hybridization assay was hard to miss, but the development of the new MR imaging agents wasn't quite as obvious. Meade was able to find the right application because of his time spent at Harvard Medical School and Massachusetts General Hospital, where he worked with clinical contrast agents. "Without that background, I might not have recognized the significance of developing new bioactivated probes," he says.

Practical Considerations

Meade emphasizes the importance of patents, pointing out that you can't commercialize a technology if you haven't protected it. But patenting every last innovation is far too expensive and time-consuming for an academic, so Meade recommends an alternative: the provisional patent, which was introduced by the U.S. Patent and Trademark Office in 1995. The provisional patent provides a 1-year grace period during which the invention is protected, but only if you file a full patent within that year. With a provisional application on file, if your graduate student is standing in front of a poster and an investor reads it and waves a fistful of cash at her, you have IP protection and you can rush out to fill out the rest of the paperwork.

A provisional patent needn't even delay the publication of a paper, Meade says. Typically, the lead researcher writes the first draft of a paper and then passes it on to co-authors for further review. That first draft isn't good enough for the journal editors, but it's plenty good enough for patent lawyers, who can use it to draft a provisional patent. "By the time you're ready to pull the trigger to send the manuscript to the journal, they're done. It doesn't delay the publication or the disclosure process, ... and you have a line-in-the-sand protection date," says Meade. Patents are complicated, however, so Meade recommends getting plenty of support from the tech-transfer office.

Now that you have your hot new invention all locked up, it's time to look for an application. There are a host of problems for chemists to solve, says Whitesides. Energy shortages, national security, water supplies, and the high cost of health care are all issues that chemistry can help address. But not every novel solution is going to be useful. "Some of this will be just engineering applications of technology that already exists, and some will require fundamental new science. It depends on the problem, and it depends on the scientist's understanding what the real characteristic of the problem is--the real problem, not just the scientific aspect of it. Sometimes the problem is cost reduction, sometimes it's providing a solution that is usable by people in a particular circumstance, such as overworked nurses."

Still, this leaves plenty of areas in which new fundamental technologies can address particular, marketable needs. Whitesides sees a need for chemists to start new companies, because a lot of existing companies are scaling back on research: "Younger chemists should think seriously about starting companies. If you're young and you want a job that involves very intriguing research in industry, you might have to create the company that allows you to do it."

Jim Kling writes from Bellingham, Washington.

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