article noted that "The UCSF team was in competition with a group at Harvard which was known to be working with a better source material" (Wade, 1977, p. 1342). The exposé highlights both competition between labs for scientific primacy and the potential commercial applications of the insulin research. The UCSF experiment was of interest to both the academic and commercial community. True, the UCSF researchers were still far from expressing human insulin in bacteria; but the experimental steps towards that goal were now far more clear. Conversely, understanding of gene regulation and expression was still developing, and the insertion experiment provided important tools for this basic research agenda.

While both the Goodman-Rutter collaborators and the Gilbert group experimented with insertion and expression of the rat insulin gene, Genentech contracted with researchers for the purpose of refining and expanding upon methods of gene synthesis and expression. Genentech contracted with Herbert Boyer's own gene cloning and plasmid construction lab at UCSF, as well as with Arthur Riggs and Keiichi Itakura of City of Hope National Medical Center just outside of Los Angeles. Upon the advice and requests of Riggs and Itakura, Genentech funded experiments whose goal was the expression of synthetic somatostatin, a simpler human hormone than insulin.24 While somatostatin was not perceived to have any direct commercial value, it was viewed by its Genentech funders as an acceptable first step toward the synthesis of the insulin gene. Itakura's goal in synthesizing somatostatin was to improve upon, refine, and expand the Khorana technique announced in early 1976. Itakura's technique reduced the time necessary for the synthesis procedure from years to weeks. While building upon the group's earlier research,25 the somatostatin project provided an opportunity to standardize procedures as well as build up a library of "codons," nucleotide triples that are translated into the intracellular production of an amino acid.26

By early 1977, Itakura, refining his method, was able to produce purified somatostatin DNA. To clone and express the gene, artificial somatostatin genes

24  

Riggs and Itakura, while negotiating with Boyer and Swanson, also applied to NIH for funding of the same project. The grant request was turned down on the basis of its lack of applicability (Hall, 1988, p. 83).

25  

The group's earlier "non-Genentech-funded" collaboration involved synthesis and insertion of the lac operator, a small strand of genetic material that regulates expression. The research team, headed by Itakura and Riggs at City of Hope, included Boyer, Herbert Heynekker, John Goodman, and John Shine of UCSF, as well as researchers from the California Institute of Technology and the University of Ottawa. Ironically, the experiment was inspired by Walter Gilbert, who suggested a critical experimental technique. Thus, the lac operator experiment involved collaboration by researchers in all three of the distinct research teams involved in the insulin research.

26  

Similar to Khorana's research, Itakura's utilized commercially available chemicals to construct DNA strands. The speed of the synthetic method greatly increased as the number of ready-made codons increased. To provide context, the expression of a protein (such as the insulin hormone) involves the production of a specific sequence of amino acids that "fold" to create the desired protein.



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