Wednesday, Sep 6, 1978
South San Francisco, Calif. -- September 6, 1978 --Genentech, Inc. and City of Hope National Medical Center, a private research institution and hospital in Duarte, California today announced the successful laboratory production of human insulin using recombinant DNA technology.
Insulin is a protein hormone produced in the pancreas and used in the metabolism of sugar and other carbohydrates. The synthesis of human insulin was done using a process similar to the fermentation process used to make antibiotics. The achievement may be the most significant advance in the treatment of diabetes since the development of animal insulin for human use in the 1920's. The insulin synthesis is the first laboratory production DNA technology.
Recombinant DNA is the technique of combining the genes of different organisms to form a hybrid molecule. DNA (deoxyribonucleic acid), the substances genes are composed of, contains the chemical record in which genetic information is encoded.
Scientists at Genentech and City of Hope inserted synthetic genes carrying the genetic code for human insulin, along with the necessary control mechanism, into an E. coli bacterial strain which is a laboratory derivative of a common bacteria found in the human intestine. Once inside the bacteria, the genes were "switched-on" by the bacteria to translate the code into either "A" or "B" protein chains found in insulin. The separate chains were then joined to construct complete insulin molecules.
The development of genetically engineered human insulin was funded by Genentech. However, the work was a cooperative effort between Genentech and City of Hope. The synthesis of human insulin gene was accomplished by four scientists at City of Hope Medical Center led by Roberto Crea, Ph.D., and Keichi Itakura, Ph.D. Scientists at Genentech, led by David Goeddel, Ph.D. and Dennis Kleid, Ph.D., joined the genes that were made in sections and inserted them, along with the control mechanism into the E. Coli bacterium. Arthur Riggs, Ph.D. at the City of Hope and Dr. Goeddel of Genentech were responsible for developing the final assays, purification and joining techniques.
Approximately 1.5 million diabetics take injections of insulin. At present, this insulin is extracted from the pancreas glands of swine and cattle slaughtered for food. It takes about 8,000 pounds of animal pancreas glands to produce one pound of insulin. The new process will produce ample quantities to meet the growing demand, and more importantly, produce a chemically identical human insulin.
One of the advantages of producing insulin using the recombinant DNA method is to reduce the dependency on animal glands. Also, by using insulin that chemically is identical to human insulin, scientists hope that certain allergic reactions by some diabetes to insulin derived from animals can be eliminated.
"The development of human insulin demonstrates the viability of using recombinant DNA technology to produce products with practical application," said Robert Swanson, president of Genentech.
"While extensive testing and refinement of the process is needed, we want to see human insulin and other genetically engineered products benefiting the people who need them in the shortest possible time," said Swanson.
Genentech, a privately financed corporation, and City of Hope have established a joint cooperative program to conduct basic research to develop commercial application of molecular genetic technology. Less than one year ago, Genentech announced its first product, the hormone somatostatin which was developed in a cooperative program with City of Hope Medical Center and the University of California San Francisco Medical Center.
Insulin is a protein hormone composed of two chains of amino acids: an "A" chain and a "B" chain linked together by two disulfide bonds. The "A" chain is composed of 21 amino acids and the "B" chain of 30 amino acids, each arranged in a uniquely ordered sequence.
Proteins are made by translating the genetic information which is carried in a cell's genes. Scientists synthesized in the laboratory genes for the two insulin "A" and "B" chains. This was accomplished by chemically linking together small pieces of DNA sequence and then joining them in a specific manner to form complete genes.
Once the genes were synthesized, they were stitched into circular DNA strands called "plasmids" using special enzymes to perform the molecular surgery. Plasmids are rings of DNA which are found within the cell. The newly constructed plasmids containing the transplanted genetic material were introduced into a benign E. coli bacterial strain.
Once inside the bacteria, the genes were "switched-on" by the bacteria to translate the code into either the "A" chain or the "B" chain proteins found in insulin. The process is the same as that used by bacteria to produce its own proteins. When the cells produced sufficient amounts of the "A" and "B" chains, they were harvested to isolate these proteins from the bacteria and purify it. The two chains were then combined chemically in the laboratory to form the complete Insulin molecule which is identical to that produced by the human body.
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