Chromatin Inc. puts down roots, prepares to flower

It may be the best excuse ever. To prepare to launch her own company, Daphne Preuss, a plant geneticist, was auditing financial accounting in the Graduate School of Business to learn about running a start-up biotech firm. So when she skipped the midterm, her instructor Darren Roulstone, Associate Professor in the GSB, had to ask why.

“I was in New York,” she answered, “at the United Nations.” She had been invited to speak to the General Assembly and to have lunch with its Secretary General Kofi Annan, to explain to him how her work on genetically modified plants could help feed poor people in developing countries. It remains, Roulstone said, “the standard by which I now judge all excuses.”

Since then, the pace for Preuss, the Albert D. Lasker Professor in Molecular Genetics & Cell Biology, has picked up. In 2000, she and two of her post-doctoral students, Gregory Copenhaver and Kevin Keith, started Chromatin, their initially cautious foray into the business world. They wanted to see if their work on the genetics of Arabidopsis thaliana, a weed with no obvious commercial appeal, could gain a foothold in biotech.

They continued their research but focused more and more on ways they could use their technology for inserting multiple new genes, rather than one or two at a time—the current state of the art—into a plant.

Although the genetics community has long paid close attention to Preuss, the world of agribusiness initially did not. Advances in weed cultivation, even rapid dramatic advances, bring no clear reward. A robust weed, bred to resist insects, drought, salt and herbicides, is still a weed. But little by little, Preuss and her colleagues learned how to assemble and insert what they call mini-chromosomes, whole stacks of genes, a dozen or more, in a reliable, lasting, controlled and heritable way. They secured their first patent in 2000, three years after Preuss had submitted it, followed by many more. Slowly, these tools, along with the exclusive rights to use them, began to accumulate.

Six years later, on Oct. 10, 2006, the United States Patent and Trademark Office issued Chromatin its eighth patent, No. 7,119,250, covering plant centromere compositions. Although the company has 34 more applications pending, foreign and domestic, this was the big one. In 96 pages of small legalistic print, it extends the exclusive right to use of these mini-chromosomes, developed in Arabidopsis, to all plants. This includes “a crop plant,” the patent states, “a commercial crop plant, a vegetable crop plant, a fruit and vine crop plant, a field crop plant.” Then comes “a vegetable crop plant cell, fruit and vine crop plant cellÉ”

“This is a major asset,” said Alan Thomas, Director of UChicago Tech, the University’s technology-transfer office. It has “attracted the attention of some very big companies.”

Preuss envisions all sorts of applications. “We could have a real impact on world hunger,” she said, “increasing the hardiness, yield and nutrition of third-world crops. We could radically improve the production of ethanol or other biofuels. We could make inexpensive medicines.” The pacific yew, for example, a rare species, requires 14 genes to make taxol. “We could put all 14 genes into soybeans,” she said.

The technology opens doors for applications no one has thought of yet. In the current approach, scientists insert one or two genes at a time into hundreds or thousands of plants, a fairly random process. Then they have to breed the offspring selectively to get a consistent strain that expresses both new genes. Preuss and colleagues can put in, for example, a dozen new genes at once, all surrounded by the desired regulatory mechanisms. “It can cut one to two years out of any project,” she said. “You get a better product faster, which saves time, reduces costs and frees up resources for the next project.”

Her academic colleagues have referred to Preuss’ work as “groundbreaking,” a “once-in-a-generation advance.” Her rivals describe it as “disruptive,” complaining that she is “shaking everything up.” She sees it as “fun.”

In the last year or so, the work at Chromatin has started to “turn the corner,” said Thomas. In the fall of 2006, Preuss decided to resign from her position as a Howard Hughes Medical Institute Investigator and take a leave of absence from teaching and academic research to manage the company as its chief scientific officer and senior vice president.

It has been a learning experience. “I found the corporate culture fundamentally different from academia,” she reports. “It’s more focused, less inquisitive, yet oddly more collaborative. In a university lab if you saw something weird off to the side you could meander away from the path and go chase it down. In the corporate world you stick to the roadmap; you get the job done.”

Curiously, the business world has involved more teamwork. “Our students have always been fabulous but in an academic setting the principal investigator is always out front,” she said. “The students are never fully partners. At Chromatin, it’s more like teamwork.”

The next steps for Chromatin are likely to involve partnership with larger biotech firms, Preuss said. “The ideas, the technology are solid,” she said. “Now we need to engage the people and firms who know how to move our ideas and methods into the marketplace.”

It has been quite a thrill to take an idea so far, she said, from concept to corporation, “but we’re not yet to the end of this road. I think this technology can make a positive difference in the lives of all sorts of people,” she said.

“It has taught me that the road doesn’t end with a publication,” she added, or a follow-up study. It goes all the way to application, to spreading into and throughout an industry, and that does not happen unless it offers a tangible benefit. “We are close to that now,” she said, so close that, “if we don’t keep going, there’s just no good excuse.”