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l-asparaginase (L-asparagine amidohydrolase) is the first enzyme to be 
applied successfully to the treatment of cancer. This protein from 
Escherichia coli, with a molecular weight of 130,000 daltons now has a 
12-year record of usefulness for the induction of remission in the acute 
lynphatic leukemias, especially those of childhood. The systemic 
administration of asparaginase kills tumor cells that are dependent on 
L-asparagine, and, that also have an impaired ability to synthesize that 
amino acid. As with all other cancer drugs, the use of asparaginase is not 
without risk. It has an innate toxicity which must be considered. 
Of more immediate interest to us today is the fact that asparaginase is the 
first example of a commercially available E. col i fermentation product to be 
used clinically. We are now concerned with the development of proteins such 
as human insulin and growth hormone, derived from _E. col i by recombinant DNA 
technology. What problems will we have with contamination by extraneous 
bacterial proteins and lipopolysaccharides such as endotoxin And, what are 
the clinical implications Bacterial contaminants, even at a relatively 
low concentration, conceivably could give rise to objectionable side 
reactions of an immunologic nature. How serious were such problems, and how 
were they resolved during the development of asparaginase What lessons can 
we learn from the experience with asparaginase that could be applied to our 
present situation These are questions that are relevant to this 
conference. The concept of administering human proteins derived from 
bacteria has the connotation of unknown risks. Perhaps in considering the 
example of asparaginase we may be able to assess at least some of those 
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