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In attempting to make comparisons between human insulin produced by 
recombinant ONA technology and the situation with asparaginase during its 
early years of clinical evaluation, one finds more points of divergence than 
of similarity. While intracellular production in _E. col i may be the common 
source for both proteins, unlike the case with asparaginase, the human 
insulin will be highly purified at the start of clinical testing. 
Asparaginase was originally produced by the relatively simple purification 
techniques of 1967-70 technology. Human insulin will be produced by 
extensive purification using 1980 technology. 
The mode of administration of these two proteins is q uite different. Large 
doses of asparaginase in the order of 200 to 1400 mg per day were 
administered intravenously to patients over a four to six-week period. The 
daily dose of asparaginase approximates 100 to 700 times a clinical dose of 
insulin based on protein. Also, asparaginase has at times been used 
intermittently in two courses of treatment several months apart, this is not 
an ideal way to administer a protein with respect to minimizing immunologic 
complications. Insulin, on the other hand, is generally given continuously 
in small, daily subcutaneous doses of one to three milligrams over the span 
of a life-time. Perhaps the most important contrast of all is that _E. col i 
asparaginase is a high molecular weight foreign protein while human insulin 
is a small, autologous protein. 
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