05 July 2009
Genetically engineered insulin
The invention: Artificially manufactured human insulin (Humulin) as a medication for people suffering from diabetes. The people behind the invention: Irving S. Johnson (1925- ), an American zoologist who was vice president of research at Eli Lilly Research Laboratories Ronald E. Chance (1934- ), an American biochemist at Eli Lilly Research Laboratories What Is Diabetes? Carbohydrates (sugars and related chemicals) are the main food and energy source for humans. In wealthy countries such as the United States, more than 50 percent of the food people eat is made up of carbohydrates, while in poorer countries the carbohydrate content of diets is higher, from 70 to 90 percent. Normally, most carbohydrates that a person eats are used (or metabolized) quickly to produce energy. Carbohydrates not needed for energy are either converted to fat or stored as a glucose polymer called “glycogen.” Most adult humans carry about a pound of body glycogen; this substance is broken down to produce energy when it is needed. Certain diseases prevent the proper metabolism and storage of carbohydrates. The most common of these diseases is diabetes mellitus, usually called simply “diabetes.” It is found in more than seventy million people worldwide. Diabetic people cannot produce or use enough insulin, a hormone secreted by the pancreas. When their condition is not treated, the eyes may deteriorate to the point of blindness. The kidneys may stop working properly, blood vessels may be damaged, and the person may fall into a coma and die. In fact, diabetes is the third most common killer in the United States. Most of the problems surrounding diabetes are caused by high levels of glucose in the blood. Cataracts often form in diabetics, as excess glucose is deposited in the lens of the eye. Important symptoms of diabetes include constant thirst, excessive urination, and large amounts of sugar in the blood and in the urine. The glucose tolerance test (GTT) is the best way to find out whether a person is suffering from diabetes. People given a GTT are first told to fast overnight. In the morning their blood glucose level is measured; then they are asked to drink about a fourth of a pound of glucose dissolved in water. During the next four to six hours, the blood glucose level is measured repeatedly. In nondiabetics, glucose levels do not rise above a certain amount during a GTT, and the level drops quickly as the glucose is assimilated by the body. In diabetics, the blood glucose levels rise much higher and do not drop as quickly. The extra glucose then shows up in the urine. Treating Diabetes Until the 1920’s, diabetes could be controlled only through a diet very low in carbohydrates, and this treatment was not always successful. Then Sir Frederick G. Banting and Charles H. Best found a way to prepare purified insulin from animal pancreases and gave it to patients. This gave diabetics their first chance to live a fairly normal life. Banting and his coworkers won the 1923 Nobel Prize in Physiology or Medicine for their work. The usual treatment for diabetics became regular shots of insulin. Drug companies took the insulin from the pancreases of cattle and pigs slaughtered by the meat-packing industry. Unfortunately, animal insulin has two disadvantages. First, about 5 percent of diabetics are allergic to it and can have severe reactions. Second, the world supply of animal pancreases goes up and down depending on how much meat is being bought. Between 1970 and 1975, the supply of insulin fell sharply as people began to eat less red meat, yet the numbers of diabetics continued to increase. So researchers began to look for a better way to supply insulin. Studying pancreases of people who had donated their bodies to science, researchers found that human insulin did not cause allergic reactions. Scientists realized that it would be best to find a chemical or biological way to prepare human insulin, and pharmaceutical companies worked hard toward this goal. Eli Lilly and Company was the first to succeed, and on May 14, 1982, it filed a new drug application with the Food and Drug Administration (FDA) for the human insulin preparation it named “Humulin.” Humulin is made by genetic engineering. Irving S. Johnson, who worked on the development of Humulin, described Eli Lilly’s method for producing Humulin. The common bacterium Escherichia coli is used. Two strains of the bacterium are produced by genetic engineering: The first strain is used to make a protein called an “A chain,” and the second strain is used to make a “B chain.” After the bacteria are harvested, the Aand B chains are removed and purified separately. Then the two chains are combined chemically. When they are purified once more, the result is Humulin, which has been proved by Ronald E. Chance and his Eli Lilly coworkers to be chemically, biologically, and physically identical to human insulin. Consequences The FDA and other regulatory agencies around the world approved genetically engineered human insulin in 1982. Humulin does not trigger allergic reactions, and its supply does not fluctuate. It has brought an end to the fear that there would be a worldwide shortage of insulin. Humulin is important as well in being the first genetically engineered industrial chemical. It began an era in which such advanced technology could be a source for medical drugs, chemicals used in farming, and other important industrial products. Researchers hope that genetic engineering will help in the understanding of cancer and other diseases, and that it will lead to ways to grow enough food for a world whose population continues to rise.