Weed on Parole

The art of manipulating the genes of living organisms so they will produce medically or industrially useful proteins.

By Jiri Weiss Jr.|Sunday, March 01, 1992
Of the 265,800 acres of tobacco harvested in North Carolina last year, one was remarkable. It was not so much that the plants were a few inches smaller than usual, or that the leaves were a mosaic of dark blotches and pale, almost translucent ones: those are the symptoms of tobacco mosaic virus, a common plant disease. The remarkable thing about these tobacco leaves was that they contained the components of human hemoglobin, as well as an experimental AIDS drug called trichosanthin. Those substances, too, were symptoms of infection by tobacco mosaic virus-- but a virus whose genes had been rearranged by biotechnologists.

Biotechnology is the art of manipulating the genes of living organisms so they will produce medically or industrially useful proteins. Right now it is usually done with bacteria, and it works like this: You find the gene for the protein you want to produce, insert the gene into bacteria, grow the bacteria in huge vats in a warehouse somewhere, and then grind up the bacteria to harvest the protein. But Biosource Genetics Cor- poration, a small California biotech-nology company, is pursuing a different approach. It wants to grow its proteins in vast, verdant fields of plants. The acre of tobacco in North Carolina is its test plot.

The advantages of plants over bacteria are twofold. First, you get more protein for your money. Second, plant cells are more sophisticated, and so they can make more-complicated proteins.

Biosource has developed a way of getting new genes into tobacco plants using the tobacco mosaic virus. TMV, as it is called, is an ideal carrier, in part because it has been studied so extensively over the past half-century and its structure is well known. Also, it has only four or five genes of its own, packaged on a single strand of RNA. Biosource has found it can add the genes for just about any protein to TMV and get those genes expressed in the leaves of a tobacco plant.

Like natural TMV, the modified virus infects a tobacco plant through a small wound on the leaf surface. Once inside, the virus hijacks the ribosomes, the cell’s protein-producing modules. It uses them to reproduce its own protein coat as well as the proteins encoded by the inserted genes. Within days thousands of copies of the virus flood the infected cell; within a couple of weeks the infection spreads throughout the tobacco plant. Within about a month the plant can be harvested and ground up, and the genetically engineered proteins--which the plant cells extrude into the spaces among them--can be extracted by means of a centrifuge.

The tobacco itself is not genetically modified, because the viral RNA does not get incorporated in the tobacco plant’s DNA. As a result, says Laurence Grill, head of research at Biosource, there is no danger of mutant tobacco spreading in the environment. In last year’s successful test--the first environmental release of a genetically engineered plant virus-- Biosource harvested small amounts of hemoglobin components, trichosanthin, and alpha amylase, an enzyme used in the food-processing industry. But that was just a start. By 1993 Biosource hopes to have built a processing plant in North Carolina and to be producing various proteins on a commercial scale. To do so the company plans to pay tobacco farmers a competitive price for their crop.

About a month before harvest, the farmers will spray a tiny quantity of modified TMV on their tobacco fields, less than an ounce per acre. As far as Biosource is concerned, the great thing about tobacco is that it grows fast and puts most of its energy into leaves, which have the highest concentration of protein. It produces no fruit or tubers, which are high in sugars and starches.

It’s an ideal plant, says Grill. Even ignoring the smoking side of it, if I had to choose a plant, this would be it. But given that smoking is estimated to have killed 434,000 people in 1990 in the United States alone, there is a pleasant tinge of irony to Biosource’s project--to the notion that the tobacco plant, for so long an agent of death, might someday soon become a factory for life-saving drugs as well.
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