Science: Creating Insulin

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With a little help from E. coli

So many public alarms have been sounded lately about the possible perils of genetic engineering that its vast potential for good has often been overlooked. Now that imbalance should be somewhat corrected. Last week, after months of careful, skillful and imaginative use of the new gene-splicing techniques, California scientists announced that they had achieved a long sought goal: the creation in the lab of a microbe that can manufacture human-type insulin.

For those diabetics who either cannot make enough of the vital hormone or cannot use it effectively, the feat is potentially a double boon. In years ahead, it should ensure them of an abundant supply of insulin, which is needed by the body to metabolize sugar and other carbohydrates. It will also reduce their dependence on insulin extracted from cattle and swine, which causes allergic reactions in some 5% of the diabetics who need it.

The successful work was a joint effort of two five-man research teams—one at the City of Hope National Medical Center in the Los Angeles suburb of Duarte, under Dr. Keiichi Itakura, the other led by Biochemist David Goeddell at a small South San Francisco biochemical firm, Genentech Inc. Though scientists had already produced a precursor of rat insulin with bacteria, making the finished human variety posed greater difficulties. For it consists of two distinct molecular chains, a so-called A strand and a B strand, each of which is produced separately inside the cells of the pancreas under the direction of its own characteristic gene.

Synthesizing copies of these genes, or segments of DNA (deoxyribonucleic acid), was difficult enough. But much harder was the job of getting the genetic instructions inside the potential bacterial factory, a weakened lab strain of the intestinal microbe Escherichia coli. The scientists resorted to a little molecular chicanery. Using their new gene-splicing or recombinant DNA techniques, they hitched their two synthetic insulin genes individually to one of the bacterium's own genes. Then they inserted both the synthetic and the natural material into fresh E. coli. As a result, E. coli's DNA-reading machinery was unable to distinguish the foreign genes from its own and began ordering up production of the two chains of insulin. When the bacteria divided, each new generation of E. coli retained the insulin-making ability. Boasted City of Hope's Arthur Riggs: "We have tricked the bacteria." All that he and his colleagues had left to do was extract the two chains and join them to make whole molecules of human insulin.

Much more research is required before bacterial-made insulin reaches the retail pharmacy. City of Hope Diabetologist Rachmiel Levine suggested that this might happen in two to five years. Eli Lilly & Co., which produces most of the insulin now used in the U.S., shied away from such optimistic projections but announced an agreement with Genentech to begin a program for mass-producing insulin with the help of the tiny bacteria.