Creve Coeur Startup Develops Human Plasma from Tobacco

Rachel Melcer
Of the Post-Dispatch

Patented technique could reduce cost of producing protein-based drugs

In a twist on the "Little Shop of Horrors," with its blood-eating plant, a Creve Coeur startup is developing a way for tobacco plants to produce human plasma.

Chlorogen Inc., which recently set up shop in the Nidus Center for Scientific Enterprise incubator, is commercializing technology that uses the cells in tobacco leaves as a factory for pharmaceutical proteins.

The patented technique could drastically reduce the cost of producing protein-based drugs, which are widely believed to hold the most therapeutic promise, said David Duncan, Chlorogen's president and chief executive.

The method also holds none of the environmental dangers of cross-pollination with other plants, because the chloroplast cells it modifies play no part in reproduction, he said.

And, because tobacco is not eaten, the protein cells cannot get into the food chain -- alleviating another common concern about plant-based pharmaceuticals, which are being grown elsewhere in corn crops.

"The pharmaceutical industry is very interested in plant-made pharmaceuticals. (So) it's not a matter of if we can stop doing it," Duncan said. "It's about how to manage this to be in harmony with nature."

Chlorogen already is growing human serum albumin, or HSA - a component of blood plasma - in tobacco plants on a 2-acre test plot in South Carolina. By year's end, Duncan said, the company hopes to have extracted and purified HSA in a way that is safe for use, first in pharmaceutical research and, later, as a clinical treatment.

"That's when we'll know if it will all work," he said.

A slew of investors is counting on it, said Bob Calcaterra, Nidus Center president. Chlorogen is getting "a substantial amount of money" from a syndicate of six venture-capital funds, in a deal expected to close in the next few weeks, he said.

A science community

Among those investors is Burrill & Co. of San Francisco, one of the nation's most prominent life-sciences funds. Managing Director Roger Wyse, who is familiar with St. Louis' biotech assets, established the company here, Calcaterra said.

And he did so despite the fact that Chlorogen's lead researcher is based in Florida, and its eventual production facility will have to be built nearer tobacco fields.

"It's a very exciting opportunity. And I'm particularly pleased that we 've brought something in from another area," Calcaterra said. "One of our primary goals (at Nidus) is to develop agricultural biotechnology companies, so it really adds to our quiver as far as that goes."

Duncan said the company will hire about 10 people over the next few months.

It also expects to work with researchers at the Donald Danforth Plant Science Center, located across the street from Nidus. Their projects would complement the primary research being done by Chlorogen's founder, molecular biologist Henry Daniell, and 20 scientists at the University of Central Florida.

"We're here (in St. Louis) because of the community of scientists that's here," Duncan said.

And there also are potential business partners.

As it develops non-therapeutic HSA, which is used by researchers and in diagnostic labs, Chlorogen will need a bigger partner to handle sales and distribution. Sigma-Aldrich Corp., which serves that market, could be an ideal choice, Duncan said.

Other local companies - most notably Monsanto Co. - are likely to be interested in licensing Chlorogen's technology for modifying plant genes. The technique, which is more precise and efficient than current methods, could be used to add traits such as Monsanto's herbicide and insect resistance to a variety of crops.

It has the added advantage of preventing the spread of modified genes through pollination, an issue that has plagued Monsanto and its competitors.

"So long as things are all neatly packaged in the chloroplasts, you don't have that concern. It's a real advantage," said Terry Woodford-Thomas, an immunologist and plant molecular biologist at the Danforth Plant Science Center. Chloroplasts also produce greater quantities of the protein than do nuclear cells, which are currently used for genetic modification.

Tobacco advantage

While other companies might want to license the technology to modify all types of plants, Chlorogen has found compelling reasons for sticking with tobacco.

Its broad, green leaves hold a large number of chloroplasts, which are the cells plants use to photosynthesize sunlight, carbon dioxide and water into food. So, each genetically modified plant can produce a large quantity of pharmaceutical protein, Woodford-Thomas said.

Tobacco plants also can be cut multiple times per growing season, resulting in a bigger overall harvest. And each plant can produce up to 1 million seeds.

Chlorogen estimates that a few acres of tobacco can produce as much protein as a $100 million factory using traditional methods. Today, therapeutic proteins are produced in the cells of mammals, such as cows and pigs - which carries the added risk of spreading diseases that couldn't live in plant cells.

Chlorogen's goal is to license the formula for a blockbuster, protein-based drug from a pharmaceutical company, Duncan said. It would produce the drug at low cost, reaping profits while making the final product cheaper for consumers.

"I took a hard look at this, both as a scientist and as a businessman, and this really got the juices flowing. We could lower drug costs in the United States," said Duncan, who had retired from Monsanto but was lured back to work by Chlorogen.

Scientists also are excited by the prospect of giving tobacco farmers a market other than cigarette and chewing-tobacco companies.

"It's really good for the farmers to have an alternative ... It saves the crop and gives it a different image," Woodford-Thomas said.

Tobacco-growing states, including South Carolina, are forming research centers and offering themselves as test beds for companies like Chlorogen. They are offering incentives to lure biotech companies which, Duncan said, Chlorogen might take advantage of when the time comes to build a production facility.

Chlorogen has "an opportunity for something that could create large value, if we can pull it off," Duncan said. And with changes in the pharmaceutical industry seeming increasingly inevitable, "we've got a whole opportunity to ride the wave."

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Cash crop

Growing pharmaceutical proteins in tobacco chloroplast cells makes financial sense for several reasons:

• A single plant can produce up to 1 million seeds.
• Its leaves can be harvested several times per growing season.
• The chloroplast cells can produce a greater quantity and concentration of protein than other plants.
• Chlorogen scientists estimate a few acres of tobacco can produce as much protein as a $100 million factory.

. . . and it makes environmental sense because:

• Tobacco is not eaten or used for animal feed.
• Genetically modified chloroplasts can't spread to other plants through pollination.
• Tobacco can't carry animal viruses, like the mammals currently used to produce pharmaceutical proteins.
  

Source: Chlorogen Inc

Published in the Business section of the St. Louis Post-Dispatch on Friday, June 20, 2003.
Copyright (C)2003, St. Louis Post-Dispatch

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