In a genetic twist on the plant that's blamed for killing millions of people, researchers at Pacific Northwest National Laboratory have found a way to use tobacco to save lives.

They're negotiating with pharmaceutical companies with the hope that by 2005, their work could mean a more normal life for children and others with the genetic disorder hemophilia.

For now, a playground tumble can be a life-threatening emergency for children with the disorder because they cannot produce enough of the clotting factors that control bleeding.

But researchers at the Richland laboratory have had success in producing one of the clotting factors hemophiliacs can't by using tobacco plants engineered to include human genes.

And they believe they can produce the clotting factor more safely and at a fraction of the cost of existing treatments, said Brian Hooker, a PNNL biochemical engineer.

Some people with hemophilia are given some of the missing clotting factor, called factor VIII, that's been removed from donated blood plasma. But factor VIII is in such small quantities in the blood, that donations from as many as 300 patients have to be pooled for a single dose.

Since several doses may be needed weekly, the patient may end up with blood factor VIII gleaned from the blood of 1,000 people each week.

Although blood is screened and purified, "there's no way to verify it's entirely virus-free," Hooker said. "There is still the possibility a hemophilia patient can pick up HIV or hepatitis C."

It's also expensive.

"A dose costs thousands of dollars," Hooker said. "The cost can approach $200,000 a year for a severe hemophiliac."

Alternatively, some hemophilia patients receive factor VIII produced from culturing animal cells. But that also carries the risk of viruses, which might include mad cow disease or other viruses with as-yet unknown effects on humans.

The cost is comparable to factor VIII from human blood - over $1 million a gram.

At PNNL, "Our direct cost is the cost to grow the plants," Hooker said. Factor VIII produced from genetically engineered plants could cost about $5,000 a gram.

"The nice thing about plants is there is no known plant virus that's active in humans," he said. "The chance of disease from viruses is virtually none."

Currently, doctors concerned about the dangers of existing supplies of factor VIII give patients the smallest dose possible. A treated hemophilia patient might still have just 1 percent of the normal amount of factor VIII to clot their blood.

The factor produced from plants could be safe enough to give patients enough of the clotting factor to allow those with hemophilia to lead more normal lives with less worry day-to-day injuries like a scraped knee will require a trip to the hospital.

Researchers at PNNL are working now on the process of purifying the clotting factor.

In a closet-sized greenhouse in the basement of a research building, they've got hundreds of genetically altered tobacco plants growing in petri dishes, test tubes and clear plastic boxes.

Genetically altering the tobacco is a relatively simple process, Hooker said.

A piece of DNA from human blood is genetically engineered into common soil bacteria that naturally modify plants. The bacteria donate a small part of their DNA into the plant's DNA.

Bits of tobacco plants and the bacteria are combined in a petri dish for a few days, then an antibiotic is added. Researchers use the bits of genetically engineered tobacco to grow new plants.

From the harvested leaves, researchers remove factor VIII.

The next step in their research will be to test the factor VIII in animals, most likely mice with hemophilia, although that's not expected to be done at PNNL.

Although researchers now are using tobacco, another plant may eventually be used for production. They chose tobacco initially because it's been studied extensively and has been genetically modifies since 1982.

Even if tobacco is eventually used commercially, it won't mean a shift from producing tobacco for cigarettes to producing the plant for medical use. The world demand for factor VIII could be supplied in 5,000 plants, Hooker estimated.

Some companies are interested in putting clotting agents into bandages, a possible role for one of clotting enzyme that could be produced by plants.

But the blood factors from genetically modified plants might one day play a bigger role for surgery patients. Factor XIII, one of the components researchers at PNNL are experimenting with, "works like Velcro," Hooker said. "It makes the blood stick to itself."

One day it could be used by surgeons to seal wounds in place of stitches.