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Page 11 of Attachment H 
By all available risk assessment data, _E. coli K 12 is safe and 
non-pathogenic. Modifications, if any, have been in the direction of 
making the host more dependent on the support of its laboratory 
environment. The plasmids are always fully characterized — j_._e. , their 
genomic sequence is known; they were selected initially because they were 
of the non-con jugative, poorly mobilizable variety. The safe and 
non-pathogenic organism is fermented in a rigid, stainless steel closed 
vessel. Prior to harvesting and chemical extraction, the safe, 
non-pathogenic organism is chemically or thermally killed. 
In the future, one may expect that other host organisms will be used 
industrially — for example, streptomyces or saccharomyces. Again, the 
criterion of inability of the laboratory-modified strains to survive in 
their natural habitat should be met. We must examine new vectors selected 
for large-scale fermentation studies, to determine whether or not they 
modify their host organism's behavior. These organisms offer the obvious 
advantage of not having any normal interaction with humans or animals. 
The NIH has now published recommendations on physical containment for 
large-scale recombinant fermentation systems to be used as a guide by 
commercial firms. Lilly supports these and made recommendations during 
their development. At this point in time, sufficient knowledge exists to 
assure reasonable decisions on the design, construction and operation of 
industrial facilities for production of materials by recombinant methods. 
The exercise of that knowledge can occur at the local level of review in 
the same way as for any complex technological advance in American industry. 
The NIH Guidelines for Recombinant DNA Research have provided a prudent 
approach to applications of the technology. 
T4471 
