The New Insulin
For more than 50 years following Banting’s breakthrough discovery in 1922, the primary source for insulin remained the pancreases of slaughtered cows and pigs. In the mid-1970s, however, a worrisome rumor arose that because consumers were generally eating less meat while the number of diabetics continued to increase, a shortage of insulin was absolutely inevitable. In actuality the concern was unfounded, but the strength of the rumor proved invaluable to a new and very troubled field of science.
By 1976 researchers in molecular biology seemed to be stalled on the verge of a monumental breakthrough. Having honed most of the skills necessary to re-engineer DNA within living cells, they were confronted by widespread resistance, on moral grounds. To most people outside the field, genetic engineering was nothing more or less than meddling with the very stuff of life, joining different genes together to create anything the biologist intended.
Very few leaders in government or academia liked theidea of DNA research in the mid-1970s. Numerous rules and laws barred researchers from creeping too close to alteration of human genes. Yet when the specter of an insulin shortage loomed, most of the same leaders turned, however timorously, to genetic engineers. At conferences in 1976 and 1977, researchers calmly insinuated that the only real question was how soon the new methods would result in infinite supplies of human insulin. With restrictions falling and encouragement rising, genetic engineers finally had the freedom to tinker with DNA.
One team, based at the University of California at San Francisco, managed in 1977 to clone the gene that produced insulin in rats. A rival team at Harvard also worked with rat insulin. In both cases biologists attached the isolated gene to DNA in healthy E. coli cells, which would then perform as though they were pancreatic cells and produce insulin. The key was recombinant DNA— that is, DNA with genes introduced from a different species.
Insulin happens to be well suited to recombinant DNA techniques because it is made by cells with a relatively simple genetic pattern. Even as the rumored shortage was giving genetic engineering an imperative, the characteristics of insulin gave it a good chance of success. The commercial possibilities were hardly lost on those involved in the research, and two of the leading companies in the genesplicing field today were formed in the midst of the insulin research: Genentech was formed by members of the San Francisco group, and the head of the Harvard team, Walter Gilbert, was among the founders of Biogen.
In August 1978 researchers at Genentech succeeded in combining synthesized genes with DNA in E. coli bacteria cells, and the re-engineered cells produced human insulin. Harvard’s researchers, working with cloned genes rather than synthesized ones, were hampered by more extensive legal restrictions, but they did move forward into areas of resounding significance, tracing, for example, mammalian evolution through the movement of a particular gene in the DNA pattern of the insulin-producing cells of various species.
By 1982 Eli Lilly & Company was ready to begin production of genetically engineered insulin for use by diabetics. “Human insulin,” as it was called, never proved to be more effective than animal-source insulins, but it did cause fewer allergic reactions than beef-derived or unpurified pork-derived insulins. (A highly purified form of pork insulin is practically equivalent to human insulin as a treatment.) Today nearly all injectable insulin is produced through genetic engineering. Animal-source insulin has been almost completely phased out.
Human insulin didn’t change life noticeably for diabetics, but it was at the center of one of medicine’s greatest revolutions as recombinant DNA became the basis for vast new areas of pharmaceutical research. In the case of genetically engineered insulin, it was the scientists, not the patients, who needed the medicine most.
