VEGETABLE VACCINES?; BIOMED INDUSTRY BOOMING WITH RENEWED INTEREST IN DNA THERAPY.

Byline: David R. Baker Daily News Staff Writer

Tinkering with plants in her USC lab, Lisa Welter dreams of one day vaccinating people against a potentially deadly disease by feeding them genetically altered vegetables.

In Duarte, John Rossi is testing a way to implant kind of a molecular version of scissors in human cells to shred the virus that causes AIDS.

Throughout Southern California, scientists searching for new ways to fight disease have begun looking past drugs to deoxyribonucleic acid - DNA, the chemical blueprint that shapes everything living.

And the Los Angeles region has become a hotbed for a field - and an industry - that promises to change the way doctors understand, prevent and treat illnesses. Instead of attacking symptoms, scientists are studying how a person's genes, which determine everything from hair color to height, cause or contribute to disease.

Tinkering with faulty genes to combat disease is called gene therapy.

``We used to look at the patient, and then we got sophisticated and looked at the proteins involved, and now we're looking right at the gene,'' said David Rimoin, the Stephen Speilberg Chairman of Pediatrics at Cedars-Sinai Medical Center.

This revolution has been under way for years in Los Angeles universities and biotech companies, and it has already made great strides.

Scientists have pinpointed genes that play a part in ailments ranging from gum disease to various kinds of cancer, and the list continues to grow.

``Virtually every human disease has a genetic component,'' said Laurence Kedes, who heads the Institute of Genetic Medicine at the University of Southern California.

For all the strides that have been made in gene therapy, however, scientists caution that progress often takes years. Many experiments replacing defective genes or adding new ones have met with little success. And even the basic work of tracking down individual genes and understanding their functions can be maddeningly complex.

``It's a slow, slogging process,'' Kedes said. ``You can have hundreds of people working on a single gene, and it will take them a decade to understand it.''

As they discover the links between genes and disease, doctors become better able to spot people prone to ailments before illness strikes. Researchers at the University of Southern California Genetic Medicine Institute, for example, are developing a test that would tell men whether their genes make them susceptible to prostate cancer, which can kill if left undetected for long.

Other efforts focus on tampering with the genes within cells. The institute at the University of Southern California is working on a way to insert genes into heart cells in hope of triggering growth of new, healthy tissue and mending damage caused by heart disease.

For all the inherent difficulty, the field is filled with attempts to attack some of humanity's most devastating diseases.

At City of Hope in Duarte, Rossi is working on a way to delay, or even prevent, the onset of AIDS in people already infected with HIV, the human immunodeficiency virus that demolishes the body's immune system. The idea: Into certain strategic cells, insert molecular strands called ribozymes that destroy HIV.

The idea holds enormous promise, Rossi said. People infected with HIV now try to control the virus by taking a combination of powerful drugs, which often have equally powerful side-effects. In addition, the virus can quickly mutate to resist medications, Rossi said.

Ribozymes, however, can be designed to cut up the very genetic material that HIV would need to reproduce itself.

``We can hit it as it comes into a cell,'' Rossi said. ``These ribozymes will attack the target, cut it, destroy it, and then recycle themselves and attack more.''

In the laboratory, at least, the idea seems to work. Researchers have taken cells from patients, inserted the ribozymes and then exposed the altered cells to HIV.

Some of the cells showed low levels of infection. Others were completely free of HIV.

Rossi and others need to see what happens when the altered cells are planted, en masse, inside human beings. They have already begun signing up patients for the next phase of the trial.

``We know these ribozymes are effective,'' Rossi said. ``If we get the right number of cells into a patient, it should work.''

While Rossi and others at City of Hope focus on changing human cells, Lisa Welter is focusing on the DNA of plants like potatoes, tobacco and corn. She hopes to alter plants genetically so they can serve as vaccines, priming the immune systems of animals and people.

Her idea hinges on the way the human immune system spots and destroy invading germs. The immune system usually springs into action when it recognizes substances - called antigens - on the surface of viruses or bacteria. These antigens, in turn, can be used to teach the body how to recognize troublesome germs and attack them in force when they appear.

So Welter plans to insert genes into plants to create antigens for several diseases. Eat a regimen of altered vegetables, the theory goes, and gain protection against infection.

``It's not quite there yet, but it will be,'' she said.

Welter has formed a small company called AgriVax to pursue this vision. She is working on a plant-vaccine for cryptosporidium, a parasite that can cause intestinal disease in cows and humans and can kill people with weakened immune systems.

She also hopes to develop a treatment for multiple sclerosis, which is caused when the immune system mistakenly attacks a protein normally found in the human body.

Welter said her approach holds the greatest promise in developing countries. Those that don't have the facilities to store large quantities of traditional vaccine can easily store barrels of altered seeds and grow them when needed.

``Plants are the next wave,'' Welter said. ``They're very economical. You just need sunshine and a little water.''

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Photo: (Color) Scientist Lisa Welter works with plants in an effort to alter them genetically to vaccinate humans against disease.

Phil McCarten/Daily News