The Big IF in Cancer

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Some of that frustration may be eased over the next few years, as the pharmaceutical companies develop techniques for mass-producing interferon. Most of that IF will be produced initially by scaling up existing techniques: the stimulation of either white blood cells or fibroblasts cultivated in the laboratory. But less conventional routes are also being explored. One is to provoke the body into boosting its own manufacture of IF by injecting inducers, usually double strands of synthetic RNA* that resemble viruses. The method was tried in the 1960s by Maurice Hilleman and others at the Merck Institute. But inducers were virtually abandoned when they proved largely ineffective and, on occasion, highly toxic. A new inducer, though, has been showing some promising early results.

Other researchers are concentrating on unraveling IF's molecular structure. Caltech scientists are working with a "sequencing" machine that needs as little as ten picomoles (less than a millionth of a gram) of pure IF to determine the composition and sequence of the IF molecule's amino acid chain, which consists of about 150 links. Explains Molecular Geneticist Leroy Hood: "It's like having pearls of different colors on a string and clipping them off one by one and identifying the color of each."

So far, the Caltech researchers have sequenced 40 of fibroblast interferon's amino acid "pearls." When the structure of the chain is fully determined, which it probably will be before the end of 1980, chemists will try to re-create IF in the laboratory. That promises to be a difficult task: so long a chain tends to break apart in synthesis. But if they succeed, pharmaceutical companies may some day be able to mass-produce this and other types of interferon using only off-the-shelf chemicals.

Perhaps the most promising avenue to ample IF supplies is the recombinant DNA technique being tried by Biogen and other companies. Scientists chemically snip a gene from the DNA of one organism. The gene, which contains the code for producing a certain protein, is then chemically spliced into the DNA of another life form, usually a harmless laboratory strain of the common intestinal bacterium Escherichia coli. Now the genetically reprogrammed bug has the ability to produce something new. It begins cranking out the protein and, given the proper nourishment, making millions of carbon copies of itself, each capable of producing the same protein. Though each creates only a tiny amount, the cumulative output can be substantial. Biogen's accomplishment, brought off by Swiss Molecular Biologist Charles Weissmann and his international team of colleagues, was to re-engineer E. coli so that it would produce largely complete molecules of human leukocyte IF. At Harvard, Biochemist Tadatsugu Taniguchi, who first isolated an interferon gene while at the Japanese Foundation for Cancer Research, and Molecular Biologist Mark Ptashne seem on the verge of getting their restructured E. coli to spew out human fibroblast IF.

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