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Biosciences

Tobacco’s Anti-Cancer Turn


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Tobacco and cancer—listen to the Centers for Disease Control, the World Health Organization, the National Cancer Institute, almost anyone, and you know how well the words go together.

Now comes St. Louis-based Chlorogen, which wants to turn that association on its head by using tobacco to treat cancer.

Here’s how it works: By genetically altering the tobacco leaf, the chloroplasts—microscopic bodies within the leaf cells—produce a protein that can kill certain cancer cells.

That’s the theory, anyway. By targeting the chloroplast, Chlorogen’s technique yields more copies of the gene that expresses the protein, which some believe can be effective in treating a variety of cancers.

Using plants to produce a multitude of proteins has become an increasingly popular technique among a number of companies. Dow, Bayer, and BASF are entering the space, licensing intellectual property and patents, and going after the biologics market, which by various estimates stands at around $15 billion worldwide, and is growing by 7 to 8 percent a year.

Research companies use different tech-niques to grow different cells, many working with cells in livestock like cows and sheep. But increasingly, some have turned to plants—in fact, the interesting thing about this particular protein is that it has to be grown in plant tissue.

David Duncan, Chlorogen’s CEO and president, says using plant cells is preferable to using animal cells, in part because when an animal cell develops the protein, the cell is killed. So each cell can be used only once, and basically becomes a spent cartridge after that.

Mr. Duncan won’t divulge its name but says Chlorogen has already succeeded in getting plants to produce the mystery protein aimed at treating ovarian, cervical, uterine, and prostate cancer.

“As it happens, there’s a protein that exists in the human body at the fetal stage of development,” Mr. Duncan says, adding that it can kill cancer cells. “But people can’t make enough of it for even a small clinical trial, because it kills the animal cells you try to grow it in.”

Biopharming

The challenge is how to get the protein out of the tobacco plant in useful quantities. Chlorogen will use $6 million in recent venture funding to develop techniques to extract the protein from the tobacco plant and purify it without destroying the delicate protein in the process.

“We’re going to have to finesse it out,” says Mr. Duncan. “We know we can make it. We know it’s the real thing. Now the problem is getting it out of the plant.”

Getting plants to make drugs or drug-precursors, a technique sometimes called biopharming, biomanufacturing, or molecular farming, is more often associated with edible crops than tobacco.

Genetic modification of food crops has drawn fire—and lawsuits—from citizen groups and government agencies in recent years, in part because a genetically modified plant can potentially pollinate a non-genetically modified plant, and contaminate entire strains of food crops.

Tobacco’s non-food status is among the weed’s main attractions. Moreover, Mr. Duncan points out, the much-maligned leaf has the innate ability to produce massive amounts of pharmaceutical-grade proteins and compounds, much as the unaltered plant is able to produce large volumes of nicotine.

Moreover, Mr. Duncan

“We could have used corn, but the fact is, we’d have to use a lot more plants to produce what we need. With tobacco, we avoid a lot of issues, and we don’t have to plant as much,” says Mr. Duncan.

The company’s method of chloroplast manipulation also avoids the wrangling typically associated with genetic modification. Called chloroplast transformation technology, or CTT, the technique introduces a new gene into roughly 100 chloroplasts within a plant cell, which then produce about 10,000 copies of the introduced gene. That’s more effective than changes made to a plant cell’s nucleus, which produce relatively few copies. Furthermore, chloroplasts are inherited maternally, and can’t be transferred to non-modified tobacco via pollen.

Development of CTT has been underwritten in part through a year-old partnership between Chlorogen and biochemical giant Sigma-Aldrich, also based in St. Louis. Under the terms of their arrangement, the two companies expect to share revenues from the finished protein products. It’s also likely that Sigma-Aldrich will help Chlorogen crack the purification and extraction process, given that it has core expertise in purifying proteins from biomass.

Placing Bets

Investors like the idea so far. In January, the company received $6 million in a second round of venture financing from Burrill & Co. of San Francisco, Harris & Harris Group of New York City, Prolog Ventures of St. Louis, and Redmont Venture Partners of Birmingham, Alabama. Finistere Partners of San Diego joined these investors in the second round, and took a seat on the board. Chlorogen’s first round of funding garnered $5.8 million, bringing its total funding to $11.8 million. Not bad for a company with a dozen employees.

“I think they’re in a position to become a leading company, where they could develop their own therapeutics, and start looking more like a drug company than an ag-bio company,” says Burrill General Partner John Hamer. “I also think their technology platform and intellectual property portfolio could be sufficiently compelling that they may decide an M&A-type event is a good thing.”

He says Chlorogen’s technology and relationships have come together at a good time, when agriculture, chemical, and biopharma giants—think Dow, Bayer, and BASF—are betting heavily on growing plants into profits.

Dow AgroSciences has made great strides in the development of using individual plant cells—not entire plants—to produce vaccines. In January, the company announced that it had obtained U.S. Department of Agriculture approval to use plant cells to produce animal health vaccines, a first for the industry.

Butch Mercer, Dow AgroSciences’ global business leader for animal health & food safety, says the company has signed two research agreements with Chlorogen, and plans to license Chlorogen’s technology to expand its biotech business. He reckons the market for animal health biologics is around $3.5 billion, with biologics in the human area perhaps twice that.

“We’re looking for agricultural applications of technology, and this is one that makes an excellent growth platform for the company,” says Mr. Mercer. “We want to build new business platforms with a market of $500 million or greater, and this area is more than viable.”

Patenting Plant Production

Dow AgroSciences has also acquired exclusive license for three patents related to using plants to produce various vaccines, and is currently working on treatments for the West Nile virus, avian flu, and canine diabetes.

All this is good news for American tobacco growers. Tobacco is a top 10 cash crop in the United States. The country is fourth behind China, Brazil, and India in world production, and third behind Brazil and China in exports.

While the U.S. still exports the largest number of cigarettes, tobacco-growing in the country has halved since the 1960s and continues to fall year by year.

U.S. growers have been hard-hit by anti-smoking forces, of course, but also by falling prices caused by escalated tobacco production in China, Brazil, and India.

In Missouri, Chlorogen’s home state, acreage devoted to tobacco production stands at a quarter of what it was in the 1950s, and has been shrinking steadily since 1992.

Paul Sloca, a spokesman for Missouri’s Department of Economic Development, says attracting companies in the agricultural technology sector is a key priority for the state, and he sees a bright spot where one would least expect it.

“Tobacco’s been a staple of the state for a long time, and if it can be turned into a pharmacological- or technology-based product, that’s going to go a long way to taking the state in a good direction.”