Pharmaceutical-producing tobacco could become reality
By Stewart MacInnis
Spectrum Volume 21 Issue 13 - November 19, 1998
The results from a summer of research show that pharmaceutical-producing tobacco can be grown on a commercial scale, according to Virginia Tech scientists.
Carole Cramer, professor of plant pathology, physiology and weed science, said additional field trials next summer are expected to confirm and extend the findings from this year.
Jim Jones, an agronomist and director of Tech's Southern Piedmont Agricultural Research and Extension Center in Blackstone, said the summer's field tests produced encouraging data as well as experience in managing tobacco grown for medical uses.
"We're not looking at growing tobacco in the way it has been grown in the past," Jones said. "In fact, what we've got is really a new crop."
Jones said the field research included increasing the population of tobacco plants from about 6,000 plants per acre in traditional tobacco growing practices to as much as 100,000 plants per acre.
The growing pattern of tobacco to produce leaf for tobacco companies is well established, he said. What Cramer is looking for, however, is the optimum cultural practices to produce protein. With that in mind, the transgenic tobacco was harvested multiple times during the summer at a point far earlier than tobacco is harvested for traditional uses.
In 1995, a team consisting of Cramer and her associates at Tech and CropTech, a Blacksburg biotechnology company, was the first to induce a plant to express a human protein with enzymatic activity. That achievement has opened the possibility of using plants as factories to produce human proteins that can be used in pharmaceuticals.
The tobacco planted at Tech's agricultural research and Extension centers in Blackstone and in Glade Spring last summer used a "marker" gene rather than the human genes. The marker gene allowed scientists to evaluate the ability of tobacco grown in different densities to produce a target protein, Cramer said.
So successful have been the results that Cramer hopes that next summer's field trials will include limited quantities of plants with target proteins that CropTech hopes eventually to convert into pharmaceuticals on a commercial scale.
CropTech has genetically engineered tobacco plants so far grown only in greenhouses. The genes inserted into the tobacco DNA orders the production of human enzymes, which can be extracted, purified and used to develop pharmaceuticals.
The gene that produces the protein cannot be "turned on" until scientists give it a specific signal or inducer. Thus, the process can be controlled so that drugs will be made only after the leaves have been harvested and taken to a regulated manufacturing facility, Cramer said.
Some tobacco plants have been modified to produce an enzyme that can be used to treat Gaucher Diseases, a rare and often fatal condition. Other plants have been modified to produce human protein C, which is used to prevent blood clots. Both tobacco-based products are still in development and have not undergone clinical trials.
Cramer said tobacco has the potential to serve as the host for many other pharmaceutical proteins as well. Tobacco is exceptionally suited for use in producing pharmaceuticals because it is one of the most productive crops in growing leaf biomass quickly and efficiently, she said. It is also one of the easiest plants to genetically modify. As a very prolific seed producer, it will allow production to be scaled up very rapidly.
The field trials indicated that flue-cured tobacco is the best variety for producing the target proteins in the quantities needed for commercial production. However, both burley and oriental varieties of tobacco also performed well in protein production.
"That means it looks as though we have great flexibility in regard to varieties," she said. "That, in turn, means that we won't necessarily be limited to any particular growing region in Virginia. The results have shown that we can grow this tobacco at very high densities. In fact, the higher the density the better, from the viewpoint of extracting proteins."
With the support of state Senator William Wampler Jr. of Bristol, former Governor George Allen and Governor Jim Gilmore included $554,000 in the state budget over the biennium for transgenic medicinal-tobacco research. During the 1998 legislative session Wampler sponsored an amendment which earmarked an additional $200,000 specifically for the field trials. That funding was in part provided to help develop a new, high-value use to hundreds of acres of tobacco land state wide.