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risks more objectively, and place them in proper perspective. I would like 
to review asparaginase as a case study of the use of a protein from E. col i 
in humans and emphasize primarily the side effects and clinical toxicity of 
enzyme preparations in which bacterial contaminants were at least a 
contributory factor. 
Certainly, the first preparations of asparaginase to be used clinically in 
1967 were crude, even by the standards of protein purification at that 
time. However, the clinical effectiveness of these crude preparations in 
reversing a life-threatening situation justified their use and the 
toleration of a moderate degree of side effects. A hypothetical curve of 
the specific activity of clinical trial lots of asparaginase during the 
first three-year period of evaluation of this enzyme would look similar to 
that depicted in Figure 1. Early lots of the enzyme had specific activities 
in the range of 25 to 35 International Units per milligram, roughly 10 
percent of the specific activity of the highly purified material made 
available by 1969 and 1970. Although the specific activities of these early 
lots of enzyme were low, this curve does not imply that these preparations 
were contaminated by 80 to 90 percent of extraneous bacterial components. 
The enzyme was readily inactivated or denatured during isolation, and a 
major part of these first preparations may have consisted of inactive forms 
of the enzyme. 
The total time to progress from crude to highly purified preparations of 
asparaginase was about two and one half years. Contrast this with the slow 
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