When M. James Barrett knocked on the doors of big drug companies in 1987, he was peddling dreams.
He had no magic cure in a vial, no recipe for a drug, just a good hunch that a technique called gene therapy could revolutionize the way diseases are treated.
"We got a polite reception, but we were not taken seriously," said Dr. Barrett, the 49-year-old biochemist and chief executive of Genetic Therapy Inc. of Gaithersburg.
Today, Genetic Therapy is among a dozen or so companies across the nation poised to turn the stuff of science fiction into reality. In five years, gene therapy and another gee-whiz technology called antisense have gone from fantasy to experimental treatments aimed at big targets: cancer, AIDS, heart disease, cystic fibrosis, sickle cell anemia and other life-threatening diseases.
"We are looking at something that will fundamentally change the pharmaceutical industry," said James W. Hawkins, a molecular biologist and chief executive of Synthecell Corp., a Rockville antisense company.
Instead of searching through thousands of compounds for a new drug, scientists could use advances in genetic engineering to custom-design a cure or treatment for a disease. Theoretically, a defective gene that causes a particular disease could be pinpointed and "fixed" with gene therapy by putting cells with "good" genes into the sick person's body. Or the instructions a defective gene is sending the body could be blocked with antisense.
Treatments based on antisense could be developed in a fraction of the time and at a fraction of the cost traditional drugs require. And, although gene therapy may not turn out to be cheap, it could cure diseases now treatable only at great cost.
Proponents say these therapies will expand or take over drug markets worth billions of dollars.
Already, Genetic Therapy has worked with pioneers in the field at the National Institutes of Health to treat two girls with adenosine deaminase deficiency, a usually fatal condition that forces children to live in sterile bubbles or seclusion in their homes because their immune systems are deficient. The children have improved to the point that they are attending school, surviving chicken pox and leading more normal lives.
Dr. Barrett is betting that the first gene therapy products will be on the commercial market in 1995. And Dr. Hawkins' company already has begun selling synthetic molecules for research and diagnostic purposes.
A person's genes contain the hereditary information that determines whether he or she has green eyes, a good singing voice or susceptibility to a particular disease.
The children with adenosine deaminase deficiency, for instance, have a faulty gene that makes their bodies incapable of combating even the common cold.
With gene therapy, a person with a faulty gene would receive cells containing a good gene. These genes would direct the body to produce either a protein that is lacking or a protein to fight a disease. A cancer patient might be given a gene to boost the body's immune system so that it destroys the malignancy.
Antisense technology, also known as code blocking, combines biotechnology's genetic engineering with traditional chemistry. Companies would make a synthetic chemical that could shut off the disease-causing messages the gene sends to the body. The chemical is designed to block the cell's genetic material -- DNA or RNA -- from making a protein that causes a disease.
The beauty of the process is that it provides a road map for making the antisense product: Scientists examine the structure of the culprit DNA or RNA strand and then make a mirror-image strand that blocks the messages it sends by chemically binding to it. That approach could cut costs by as much 45 percent, Dr. Hawkins said.
Traditional drugs, in contrast, can require searching through thousands of plants or chemical compounds before the right one is found. Some have compared the process to trying a key on thousands of cars until it unlocks one. Even after a promising natural or synthetic compound is found, it can take years to prove its safety and effectiveness.
The average cost of developing a traditional drug is $231 million, according to the Pharmaceutical Manufacturers Association.
Still, genetic therapy and antisense face major hurdles.
With antisense, there are the complicated problems of how to get the new treatment into the body and of determining its effects.
Paul Miller, a professor of biochemistry and leader in antisense research at the Johns Hopkins University working in collaboration with researchers at the University of Maryland Medical School, has shown that antisense inhibits the herpes virus in cell cultures.
"What isn't known," he said, "is how these molecules behave when they are injected" in humans. Much work remains before antisense is proved safe and effective, said Dr. Miller, co-founder of Genta Inc., an antisense company in San Diego.