Scientists focus on the tobacco plant as possible cancer-fighter
Tobacco may be the most maligned crop growing on Earth, a plant blamed for millions of deaths around the globe. But today, in a greenhouse in Giles County, Va., a scruffy patch of tobacco is being cultivated for a singular, ironic purpose - to see if it h
In its most familiar state, cigarettes, tobacco has proved to be deadly. But scientists are learning that, once genetically altered, tobacco has the potential to produce vast quantities of crucial drugs to combat a range of human ailments that could well include cancer.
''The possibilities are exciting,'' said David T. MacLaughlin, a researcher at Massachusetts General Hospital, whose group is working with CropTech, an 8-year-old biotechnology company in Virginia, to harvest potential medicine from the tobacco. ''But there is a great deal of work to be done before we know more.''
The Virginia greenhouse is just one of dozens of locales in the United States in which medical and agricultural know-how have combined to try to find faster, safer, and cheaper ways to produce drugs and vaccines to combat anemia, herpes, hepatitis B, E. coli and nearly a dozen other afflictions. For consumers, that could translate into lower prices for the resulting drug treatments and greater worldwide availability for drugs now produced by fermentation systems in expensive laboratories.
The crop of Asian xanthi tobacco in the Virginia greenhouse has been scarred so it can absorb a cloned and altered human gene. When the plant correctly follows the instructions of that gene, it secretes a protein that occurs naturally in a human body called Mullerian Inhibiting Substance, or MIS.
MacLaughlin, along with Dr. Patricia K. Donohoe and Shyamala Maheswaran at Mass. General's Pediatric Surgical Research Laboratory, is amassing data about the substance because it may inhibit the growth of ovarian, breast, prostate and other reproductive cancers. Until now, MIS, which is also a protein, has been difficult for researchers to reproduce using more conventional methods.
''We're asking plants to do something they normally wouldn't do,'' MacLaughlin said. ''We know the tobacco is making proteins and secreting it in a place where we can get at it. What we don't know is if it works well enough to produce the quality and quantity we will need.''
In the last decade, 14 companies and universities have applied for permits from the US Department of Agriculture for field trials in 24 different states to use plants to manufacture pharmaceuticals, industrial enzymes and other nonfood proteins. Genetically manipulated corn, tomato, tobacco, rice, barley, wheat, and soybean all have been planted in the hope of solving human health problems.
Similar experiments are also taking place in animals. Genetically altered cows and goats can produce milk containing human proteins that can then be separated from the milk and used for therapeutics.
But proponents of ''biopharming,'' as the plants-to-drugs experiments are commonly called, note that it is faster and less expensive to plant additional acres of modified tobacco than to produce an additional herd of cows. In addition, drugs made from mammalian cells and animal milk might carry viruses that could affect humans, while plant viruses pose no known risk to people.
So far, only a handful of antibodies potentially useful to humans have been successfully grown in plants, according to Dr. Henry Daniell, a professor in the Department of Molecular Biology and Microbiology at the University of Central Florida.
The most clinically advanced is a product from genetically modified tobacco called CaroRX, an antibody against streptococcus mutans, which causes tooth decay.
A tasteless, colorless gel containing the antibody was applied to the teeth of 84 human volunteers at Guy Hospital in London three years ago and was found to keep the tooth-decaying bacteria at bay for four months after treatment. Keith Wycoff, research director at Planet Biotechnology, producer of CaroRX, said the drug is now in second-phase trials at the University of California at San Francisco's School of Dentistry and results of that study should be published in the next month. It is still more than a year away from market.
Tobacco, it turns out, has unique properties that make it an especially welcoming host to human genes that have been cloned in a lab. Because it can be grown like grass, with several cuttings each season, those who work with tobacco say they can see the results of their experiments much more quickly. In addition, unlike corn, it can be grown separately in a greenhouse, isolated from other plantings.
That message has not been lost in tobacco country. The Virginia Farm Bureau established its own small biotechnology company, ToBio, in 1999 to work with tobacco-growing farmers and medical researchers.
''This is a major cash crop,'' said Chris Cook, chief executive officer of ToBio. And while the quantities being grown today for drug experiments are small, ''We really like the idea of using tobacco for medicinal purposes. ... It certainly wouldn't hurt [tobacco's] image.''
Rob Gustines, vice president of corporate development at CropTech, said he is excited by the possibilities tobacco offers to drug producers. He is also mindful of the hurdles, including acceptance by the drug industry and the public, but hopes that people will react positively to the concept of altering plants when the goal is human health. In addition, Gustines noted that tobacco is not used to feed humans or animals, lessening the likelihood that a modified tobacco plant will accidentally end up on someone's dinner table.
Just such a mistake has already cost the genetically altered-foods industry dearly. In 2000, StarLink, a corn product genetically altered for pest resistance and approved for use only in animal feed, was found in a series of snack products that had to be recalled from the market. Many consumer groups and others worry that crops planted for medicinal purposes might contaminate the nation's food supply as well.
For example, what happens when pollens from the genetically modified plants intermingle with weeds, insects or other crops? Can the same farm safely grow genetically altered lettuce as well as lettuce for salad?
''They are dealing with compounds that you know are biologically active,'' said Michael Hansen, research associate with Consumer Policy Institute, the advocacy arm of Consumer Reports. ''What do they do to ecosystems? What do they do to the crops around them? Nobody knows.''
Academics and consultants who study biopharmaceuticals are reluctant to predict whether fields of genetically altered plants will become as much a part of the American health care landscape as HMOs, but they agree that market forces are compelling researchers and drug manufacturers to give it a try.
A recent study by the consulting firm Arthur D. Little noted that demands for drugs containing human proteins will dramatically increase in the coming years. In addition, today's cell manufacturing plants eventually will be taxed by the need to produce more monoclonal antibodies that may be useful for the treatment of many long-term illnesses such as HIV, asthma and arthritis.
But growing plants to produce drugs to fight diseases is only a small part of a larger effort to manipulate plants for human health gains.
A vaccine against E. coli has been successfully grown in both tobacco and potatoes. Epicyte, a small company in San Diego, is using corn to try to grow a contraceptive. And giant Monsanto Corp. last year released its rice genome sequence to aid in the development of vitamin-A enriched rice worldwide.
What's next? A cure for the common cold?
Well, maybe. Wycoff of Planet Biotechnology said his company has just received a small grant from the National Institutes of Health to study the possibility of growing an antibody that would inhibit human rhinovirus - the common cold - in transgenic tobacco. Already, it's been dubbed RhinoRX by Wycoff's team. Wycoff said: ''We'll have to see how that one goes.''