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Orion Genomics, a local biotech firm, is helping to decode the genome of
much-maligned tobacco - work that could make the plant more useful to
scientists and, perhaps, safer to smoke, September 2004 by Rachel Melcer .

The company, based at the Center for Emerging Technologies incubator in
midtown, has contracted with North Carolina State University in a $17.6
million project paid for by cigarette maker Philip Morris USA. Orion will
receive "multimillions" of dollars for its work, said Chief Executive Nathan
Lakey.

The goal is to outline the genetic makeup of the tobacco plant to better
understand why it grows, looks, acts and reacts as it does. As individual
genes are linked with particular traits, scientists may be able to breed or
genetically engineer changes.

For example, tobacco contains an enzyme that reacts during the curing
process to produce nornicotine, which causes cancer. NCSU crop scientist
Ralph Dewey is working to identify the gene that produces this enzyme, in
hopes of removing it from the plant. If he succeeds, the result would be
tobacco that is less harmful to smokers - and a potential marketing coup for
Philip Morris.

"A lot of people are going to choose to smoke, whether or not it's healthy.
So, it's incumbent upon the industry to make it healthier," Lakey said.
"This is something someone could do with the tobacco genome, not something
I'm working on or suggesting."

His mission - and that of the overall NCSU project team - is to supply the
raw data. But sequencing the tobacco genome is no easy task: It is roughly 1
1/2 times as large as the human genome, containing 4.5 billion base pairs of
genetic material, or DNA.

Orion's technology, called the GeneThresher, should simplify the matter. It
rapidly weeds out large chunks of repetitive DNA that scientists believe is
useless, so that they can focus on the active portion of the genome.

Orion believes that just 18 percent of the tobacco genome is useful.

"Orion's technology is a very big part of the project," said Charles
Opperman, professor of plant pathology and genetics and leader of the
initiative at NCSU.

Philip Morris gave his team 4 1/2 years to map more than 90 percent of the
tobacco genome, so speed is of the essence. They are about halfway through
and "very much on schedule," Opperman said.

Orion has been involved with the project since the beginning. Its success to
date led last month to the expansion of its role.

In the end, the map will be available at no charge to public researchers,
Opperman said.

"The vast majority of people who are interested are not working on tobacco
per se. They are interested in other plant systems," he said.

Genetically, tobacco is very closely related to the tomato, pepper,
eggplant, petunia and nightshade plants. Scientists will be able to use the
tobacco genome to shed light on research into those species, Opperman said.

What's more, the tobacco plant may contain genes that confer traits that
would be useful in other species, such as resistance to drought or
particular pests. These could be isolated and genetically transferred.

Tobacco already is used as a model system in a range of plant research,
because it is well understood and easy to alter. With greater information
about tobacco, it could become even more useful.

Some companies and researchers already are using tobacco as a living factory
to produce proteins and enzymes, which can be extracted, purified and used
for pharmaceutical drugs or plastics. For example, Chlorogen, a startup in
Creve Coeur, has genetically altered tobacco to produce a component of human
blood plasma that may be useful in medical research and treatments.

Orion, which has 25 employees, has dedicated nearly half of its staff to the
tobacco-genome sequencing project. The company also has contracts to assist
in mapping sorghum, corn, white clover and ryegrass, Lakey said.
Six-year-old Orion has been profitable since 2002, a rare achievement for a
biotech startup.

"A lot of biotech companies get into trouble because they grow really fast
and then they don't have products to support their growth," he said. Orion,
by contrast, is funding additional product research with services revenue.

The company also plans to hit the road soon to raise venture capital. Lakey
said he hopes to bring in $9 million by year's end.

Tobacco genome mapping

What it is: A genome is the genetic map of a living organism. Plant
scientists analyze genomic data to understand how and why an organism
develops, looks and acts in a particular way; and how it can change or add
traits through genetic engineering or breeding.

Why tobacco is important: It's used as a model system for much early plant
research. Genetically, it's closely related to peppers, eggplant, tomatoes,
petunias and nightshade.

How it stacks up: It contains about 4.5 billion base pairs of genetic
material; the human genome has 3 billion. Lined up, the DNA of the tobacco
genome would stretch 10 feet; human, 6 feet; corn, 5 feet; soybean, 2 feet.

Who's doing it: Scientists at the North Carolina State University College of
Agriculture and Life Sciences, with help from corporate and public partners
and funding from Philip Morris USA.


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