The plant blamed for millions of lung disease infections and cancer-related deaths could help save lives. While doctors shun tobacco for its cancerous effects, plant scientists at Arizona State University and around the world are embracing the plant family for its genetic flexibility.
Now, ASU researchers have seen the plant’s potential to help protect soldiers and citizens against biological weapons. With $200,000 from a U.S. Department of Defense grant, a team of ASU plant scientists created small tobacco plants holding key ingredients for a vaccine to fend off plague. Their results were published last week on the online early edition of the Proceedings of the National Academy of Sciences.
The plague may seem like a distant worry. Many people associate the disease with the Black Death, which killed millions in Europe during the Middle Ages. But the illness hasn’t disappeared. It still infects 1,000 to 3,000 people worldwide every year, with five to 15 cases in the United States, the World Health Organization says.
Federal health officials are more worried about the illness today, fearing that terrorists could weaponize the bacterium, creating a plague aerosol that could infect hundreds with its spray.
Currently, there are no plague vaccines. Before 2001, plague vaccine production tapered off and stocks were eliminated because companies did not see a need to invest in defense of such a rare illness. But after anonymous, anthraxlaced letters killed five people in 2001, the U.S. Food and Drug Administration launched anti-bioterrorism initiatives calling for applications for new vaccines.
Pharmaceutical companies make vaccines with their own unique technology, but production capacity is limited. So scientists have sought other ways to make more ingredients for medicines faster. Research shows the largest potential medicine factory is rooted in the earth: Plants.
Tobacco is receptive to changes in its genetic makeup, allowing researchers to easily add genes from other organisms into the plant and get results quickly.
Scientists have toyed with tobacco since the 1980s, inserting different characteristics such as a jellyfish gene that makes the plant glow when exposed to ultraviolet light.
Recent testing is focused on manipulating tobacco’s genetic structure to address human health issues.
Rutgers University, for example, has tested tobacco’s capacity to produce a protein to fight tetanus, an infection usually associated with puncture wounds. University of Virginia researchers are working with a California company, Planet Biotechnology, to make a tobacco plant that grows ingredients for cold medicine.
The Defense Department was "looking for a very robust production system that would allow very large-scale production of a vaccine," says Hugh Mason, one of the ASU researchers who developed the vaccine-producing tobacco plant. "We’ve had this idea for a number of years now that plants might be able to very economically up production of antigen proteins" for immunizations.
The tobacco plant that ASU researchers modified is Nicotiana benthamiana, a short member of the tobacco family. Its compact size allowed them to easily grow it in a small laboratory at the Biodesign Institute in Tempe.
Scientists had to fiddle with the plant’s genetic responses so it would create the proteins, F1 and V, to fight plague. They did this by injecting a plant virus, tobacco mosaic, into the leaves, sickening the plant. The virus causes some damage, turning the leaves various shades of green and yellow. Under a microscope, the illness appears as patches of stiff bars interlocked in a mosaic pattern.
Using a virus to introduce new DNA to a plant sounds unusual, but it’s a method proven by a German company, Icon Genetics, which worked with ASU. The procedure actually prompts the tobacco to grow two proteins for the vaccine, F1 and V, said Luca Santi, ASU scientist and lead author of the paper.
Both proteins also are found in plague. The goal is to use them to prompt an immune system reaction that protects the plant — and eventually a soldier or citizen —from plague.
F1 alone, though, can slip past the immune system, which watches for foreign invaders. Mason said the protein secreted by the bacteria "becomes like a gelatin capsule around the bacterial cell. It’s sort of stealthy, difficult to recognize by the immune system."
The V protein is found in nearly all strains of plague. Once it’s spotted in the body or plant, antibodies attack, pinning down the harmful bacteria in a violent effort to protect against the disease.
To harvest the proteins, scientists grind the tobacco leaves, making a green juice. Mason said researchers ran the solution through a column with a matrix inside that sifts the proteins. "You collect fractions at the other end of the column," he said.
The proteins were tested in vaccines injected into guinea pigs at the U.S. Army Medical Research Institute of Infectious Disease in Maryland. Researchers found a combination of F1 and V was most effective in fighting off plague.
The vaccine is not ready for use yet. Scientists need to develop a stable, engineered crop of tobacco that can continue to produce the proteins from one generation to the next — a steady and large supply for vaccine. More testing is needed to ensure it is effective.