be handled with care because of the possibility that they might have 
unpredictable, harmful biological properties. A potentially hazardous 
experiment that was commonly cited as an exanple at the time is the construction 
of hybrid £. coli bacteria able to produce diphtheria toxin. Appropriately, 
biological studies of diphtheria toxin cloned in E. coli are performed at the 
highest available level of containment to avoid any possibility of accidental 
release; safety precautions are also appropriate during testing of recently 
developed hybrid vaccinia viruses potentially useful as vaccines against AIDS, 
herpes, etc., to ensure that these virues are not inadvertently released before 
their safety has been adequately assessed. 
The Pseudomonas and pseudorabies strains, however, do not pose the same 
safety issue precisely because they were not produced by joining genes from two 
or more species; instead, they represent an entirely different application of 
gene splicing, namely a precise, accurate, and virtually fail-safe method of 
eliminating a single specific gene from any microorganism. In this method, the 
unwanted gene is first cloned into a laboratory strain of E. coli . where it 
can be conveniently manipulated. An essential segment of the gene is then 
snipped out (deleted) and the now inactive gene is returned to its parent 
organism where a natural recombination process inserts the defective gene in 
place of the native, active one. The net effect is the precise removal of an 
essential part of the unwanted gene; no foreign genetic material is involved. 
The power of gene splicing technology in this case is that it permits the 
isolation, anplification and manipulation of the gene in the test tube. All of 
the test tube steps are, of course, performed in accordance with the Guidelines, 
since these do involve gene splicing. This type of genetic manipulation is, 
basically, nothing but a more sophisticated method of accomplishing what plant 
Recombinant DNA Research, Volume 1 1 
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