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Tobacco Plants Are Used to Produce Anti-Cancer Agents

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Times Science Writer

California scientists have developed a way to subvert the genetic machinery of tobacco plants so that the plants produce anti-cancer agents and other biological drugs.

The technique uses the plants to produce such drugs but does not remove carcinogens from tobacco, one of the prime causes of cancer.

Researchers from Biosource Genetics Corp. of Vacaville said Monday in Irvine that they have developed an artificial virus that can be sprayed on fully grown tobacco plants to convert them into “mini-factories” producing immune-system stimulants. Such agents include interleukin-2, tumor-killing agents such as tumor-necrosis factor, sun-blocking agents such as melanin, or virtually any other material that can now be produced by genetic engineering techniques. The plants would then be harvested and the products purified from their leaves.

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Geneticist Robert L. Erwin, president of the company, said at the American Cancer Society’s 31st annual symposium for journalists at the Irvine Hilton and Towers that field tests could begin within 12 months.

Cancer specialist Vincent T. DeVita Jr. of Memorial Sloan-Kettering Cancer Center in New York City, the former head of the National Cancer Institute, said the irony of using tobacco to combat cancer is “kind of cute” and noted that Biosource’s success is “real enough to pursue.”

Erwin said the Biosource researchers assembled the artificial virus by combining genes from several viruses that normally infect plants. The gene that serves as the blueprint for a desired anti-cancer product is inserted into the virus.

When the researchers envelop the viruses’ genetic material in a synthetic protein coat, the virus can enter a fully grown plant through cuts or abrasions on the plant’s leaves. Inside the plant, the virus spreads from cell to cell so that the whole plant becomes infected, but the virus cannot produce the protein coat and thus cannot escape from the plant and infect other plants.

The virus does not become part of the plant’s own genetic information. Instead, it takes over the cellular protein-making machinery to produce large quantities of whatever protein it carries the gene for. Theoretically, Erwin said, the desired protein could account for up to 40% of the weight of the tobacco leaves, but a “realistic goal would be 10%.”

Current tobacco yields are about 2,000 pounds per acre, so a 10% yield would produce 200 pounds of a drug or enzyme at a cost of about 4.5 cents per gram, Erwin said. Even when the costs of extraction from the plant and purification of the product are added, he said, the technique would be cost-competitive with conventional techniques, in which the drugs are produced in engineered bacteria.

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He noted that the virus would be sprayed in combination with an abrasive that would scratch the leaves’ surfaces, allowing the viruses to enter. Viruses that fall onto the ground during spraying are biodegradable and would fall apart rapidly. Weeds and other plants accidentally infected by the virus would die from the effects of the high-protein production. And because the virus does not attack the plant’s genetic information, it would not be passed along in seeds and would produce no long-term threat.

Erwin said the 2-year-old company has no agricultural fields of its own and is searching for another genetic-engineering company to collaborate with in field trials. He said that the procedure can be done using virtually any plant, but his company used tobacco because it is normally grown under carefully controlled conditions.

Other highlights of Monday’s seminar:

- Researchers at the University of Florida in Gainesville have improved the survival rate for victims of Ewing’s sarcoma, a rare form of bone cancer that affects “a few hundred victims” in the United States each year, by removing the patients’ bone marrow before therapy, then reimplanting it afterward.

The technique allows the physicians to use higher-than-normal doses of chemotherapy and radiation to destroy all tumor cells. Such doses would normally destroy the bone marrow--a key component of the immune system--leaving the patient susceptible to life-threatening infections. Reimplantation of the stored bone-marrow tissue allows the immune function to be completely regenerated within 3 to 4 weeks.

- Radiologist Bjorn E. W. Nordenstrom of the Karolinska Institutet in Stockholm reported that tumors could be shrunk or killed by passing a small current of electricity through them from implanted electrodes.

Around the positive electrode, he said, cancer tissue is destroyed by strong acidity that causes blood vessels supplying the tumor to be blocked. The electric field at the negative electrode attracts white blood cells that attack tumor cells.

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- Psychologist Thomas G. Burish of Vanderbilt University in Nashville reported that patients undergoing chemotherapy and radiation therapy experience “significantly less” nausea, vomiting and other side effects if they are educated about the expected effects of the therapy and given behavioral counseling to improve their relaxation.

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