Monday, Jan. 28, 1980

Genetic Coup

E. coli makes interferon

Almost from the time of its accidental discovery by scientists in England in 1957, interferon has been the stuff of researchers' dreams. A complex bodily protein, it possesses both antiviral and antitumor properties, which means it could become an important new weapon against a wide range of diseases, from the common cold to certain cancers. But it takes 65,000 pints of blood to get just 100 mg (.0035 oz.) of the protein, so testing of the possible miracle drug has been severely limited. Now, as a result of another application of gene-splicing, or recombinant DNA, techniques, all that may change. In Boston last week molecular biologists announced that they had induced tiny bacterial "factories" to copy human interferon.

Ordinarily, interferon is produced by virtually all cells in the human body, which get their instructions for making it from a specific gene in their DNA; these are passed on to the cells' protein-manufacturing sites by a genetic molecule known as messenger RNA. But for Hungarian-born Charles Weissmann of the University of Zurich, and his Swiss, Finnish and Japanese colleagues, the natural process was only a starting point. After extracting messenger RNAs from human white blood cells, which were producing interferon, they used these molecules to generate sections of DNA that they hoped would include the required gene. They then spliced these fragments into the genes of a laboratory strain of E. coli bacteria. The bacteria began to make copies, or clones, of their altered selves.

Eventually, the team produced some 20,000 clones. But which ones carried the crucial interferon DNA? Analyzing them in successively smaller groups--first 500 at a time, then 64, then eight--the scientists isolated their genetic needle in the haystack: the bacteria that carried the DNA for interferon. After they found one such bug, they could easily identify others and extract the DNA fragments. The team spliced them into different places in E. coli, and, presto, the bacteria began cranking out a close facsimile of the human protein.

The amount of interferon made by these bacterial minifactories was extremely small and impure. But the researchers, who did their work on behalf of Biogen S.A., a Swiss-based firm set up to exploit recombinant DNA technology, hope to produce larger quantities of purer material. The ultimate goal: to bring down the cost of an injection of interferon from today's price of $75 a shot to as little as $1.

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