The Future of Recombinant DNA Technology in Medicine

PERSPECTIVES IN BIOLOGY AND MEDICINE Volume 23 ¦ Number 4 · Summer 1 980 THE FUTURE OF RECOMBINANT DNA TECHNOLOGY IN MEDICINE THOMAS H. FRASER* We are now on the verge of a medical revolution owing to the development of recombinant DNA technology. In the last 2 years this field has made some giant strides toward the realization of its potential. The idea of producing large amounts of animal, viral, and human proteins in microorganisms has progressed from plausible theory to proved reality. Although there is still a great deal ofcreative work to be done in order to make a significant impact on medicine, the field at this time looks more promising than ever. Even some of the most optimistic predictors of a few years ago have had to shorten the time frame in which they foresaw practical applications of recombinant DNA technology. As most readers know, recombinant DNA technology is the art of cutting and splicing pieces of DNA. The three major components involved in DNA splicing are a host cell or organism, a vector molecule containing a selectable genetic marker and capable of replicating within the host, and the DNA to be cloned. The almost limitless possible combinations of hosts, vectors, and genes give this technology incredible power both to solve important scientific problems and to directly add new weapons to the physician's armamentarium. Many of the new products to be produced will result from the development of microbial factories for the synthesis of specific polypeptides and proteins. Other products will include antibiotics for combating infectious diseases. Within the next several years, virtually unlimited amounts of human hormones, human interferon, human blood proteins, specific human ?Research scientist, Infectious Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.© 1980 by The Upjohn Company. Perspectives in Biology and Medicine · Summer 1980 \ 499 antibodies, and viral antigens (for use as vaccines) will be made available as a result of the application of recombinant DNA technology. As important as these products will be, they represent only the first generation of medicináis that will be produced by microbial factories. The acquisition of new knowledge in many of the basic medical sciences is proceeding at an explosive pace. As more clinical researchers become sensitized to the opportunities that recombinant DNA technology offers for synthesis of large amounts of specific proteins and polypeptides, it is virtually certain that rational therapies using these proteins and polypeptides will be tested and refined. At this time it is feasible to attempt the cloning of any animal or viral gene into a microorganism if a probe for that gene is available. Gene Cloning and Screening The first step in the synthesis of a foreign protein in a microorganism is to obtain and clone the gene coding for a protein of interest; several different approaches have been successfully carried out. The general strategy of most approaches is to first obtain DNA preparations enriched for a specific gene and then biochemically insert the DNA into a cloning vector and propagate it in£. coli. A certain proportion, depending upon the enrichment of the original DNA preparation, of the transformed E. coli clones will then carry the gene of interest. The successful isolation of a gene, therefore, ultimately resides in the unambiguous identification of that gene cloned in either E. coli or another host. There are only two possible sources of a gene: (