Tobacco Turns Over A New Leaf

The killer weed may have a benign side after all--as a factory for bioengineered drugs

Tobacco's public image couldn't be more stained these days, given the war on cigarettes in the courts, federal and state governments, the medical establishment--even in Doonesbury. But the tobacco plant is not an irredeemable ne'er-do-well. Because its genetic makeup is fairly straightforward and well understood, scientists believe tobacco could turn out to be the perfect biotech factory for protein-based drugs. By splicing human genes--a technique developed in the early 1990s--researchers have enabled tobacco plants to produce a number of drugs and vaccines and even human blood components. Within 10 years, researchers are hopeful that tobacco farmers might be raising millions of acres of biofactories rather than "the killer weed."

The latest breakthrough in tobacco "pharming" may bring such a vision one step closer to reality. Scientists at Monsanto Co. reported in the March issue of Nature Biotechnology that they were able to genetically engineer tobacco plants to produce human growth hormone, otherwise known as somatotropin--an extremely costly drug used to treat dwarfism. But the Monsanto discovery was more important for the process than the product. The scientists were able to induce the tobacco plants to manufacture the drug in an abundant piece of the plant cell known as a chloroplast, which is responsible for converting light into food. Other efforts to create drug-producing plants have altered plant nuclei instead--far less numerous cell components.

DNA DILEMMA. "We were able to produce 300-fold more human somatotropin in the chloroplasts than in the nucleus," says Jeffrey M. Staub, manager of the Monsanto team that developed the technique. "As an optimistic scientist, I think it is very reasonable to [believe] we will be able to produce commercial quantities of human proteins in the plants in the next couple of years."

The biotech industry has been seeking an inexpensive way to produce its products almost as strenuously as it has been searching for the treatments. Old-fashioned drugs are essentially chemicals that can be cooked up in factories, but bioengineered treatments are usually large proteins, and they need to be "grown"--typically in bacteria. Only very small amounts of a drug at a time can be produced this way, and only in a tightly controlled environment.

Some biotech drugs are also secreted in the milk of genetically engineered animals, but raising farm animals is expensive and time-consuming, and separating the drugs from the viruses and bacteria in the milk can be difficult. Plants, however, are both cheap to raise and carry virtually no risk of contaminating the drugs they are used to create--making them the ideal bioreactor.

There has been notable progress with gene-spliced plants in the past two years. In 1998, British researchers reported that a human antibody grown in tobacco plants prevented one of the bacterial infections that led to tooth decay in human volunteers. And last August, the Energy Dept.'s Pacific Northwest National Laboratory announced that its scientists had successfully transplanted the necessary human genes into tobacco plants to produce human blood components.

Even with plants, though, volume remains a problem. All plant cells contain subunits called organelles, two of which are the nucleus and the chloroplast. Gene splicing to date has focused on altering the nucleus--essentially the brain of the cell, because it controls all of the plant's activities. But drug production was limited, since there is only one nucleus per cell. Moreover, the genetic alteration is transmitted to the plant's pollen, making it difficult to control the spread of the reengineered plants. Chloroplasts, however, are abundant, and they do not spread their genetic changes to any other cells in the plant.

The Monsanto researchers caution that their work is in the very early stages and was done on a very small scale. "There are still a lot of questions that need to be answered," says Staub. Among them is whether the proteins created in the tobacco plant are modified in some way that would change their action in humans.

It seems clear, however, that tobacco may finally have a chance to transcend its societal role as a cancer-causing blight.