Useful Proteins from Bacteria :

A living cell is a protein factory. It synthesizes the enzymes and other proteins that maintain its own integrity and physiological processes, and (in multicelled organisms) it often synthesizes and secretes other proteins that perform some specialized function contributing to the life of the organism as a whole. Different kinds of cells make different proteins, following instructions encoded in the DNA of their genes. Recent advances in molecular biology make it possible to alter those instructions in bacterial cells, thereby designing bacteria that can synthesize nonbacterial proteins. The bacteria are "recombinants." They contain, along with their own genes, part or all of a gene from a human cell or other animal cell. If the inserted gene is one for a protein with an important biomedical application, a culture of the recombinant bacteria, which can be grown easily and at low cost, will serve as an efficient factory for producing that protein.

Many laboratories in universities and in an emerging "applied genetics" industry are working to design bacteria able to synthesize such nonbacterial proteins. A growing tool kit of "genetic engineering" techniques makes it possible to isolate one of the million-odd genes of an animal cell, to fuse that gene with part of a bacterial gene and to insert the combination into bacteria. As those bacteria multiply they make millions of copies of their own genes and of the animal gene inserted among them. If the animal gene is fused to a bacterial gene in such a way that a bacterium can treat the gene as one of its own, the bacteria will produce the protein specified by the animal gene. New ways of rapidly and easily determining the exact sequence of the chemical groups that constitute a molecule of DNA make it possible to learn the detailed structure of such "cloned" genes. After the structure is known it can be manipulated to produce DNA structures that function more efficiently in the bacterial cell.

In this article we shall first describe some of these techniques in a general way and then tell how we and our colleagues Argiris Efstratiadis, Stephanie Broome, Peter Lomedico and Richard Tizard applied them in our laboratory at Harvard University to copy a rat gene that specifies the hormone insulin, to insert the gene into bacteria and to get the bacteria to manufacture a precursor of insulin. In an exciting application of this technology Charles Weissmann and his colleagues at the University of Zurich recently constructed bacteria that produce human interferon, a potentially useful antiviral protein.