16 
Dr. Sharpies suggested the term "proposed guidance" be substituted for the 
word "guidelines" in the title so the guidance document would not be confused 
with the NIH Guidelines for Research Involving Recombinant ENA Molecules. 
Dr. Miller said the guidance document is analogous to a FEA document entitled 
Points to Consider in the Production and Manufacture of Pharmaceuticals Using 
Recombinant ENA Technology . He suggested the term "Points to Consider" 
has no regulatory connotation and might be an appropriate title for the 
guidance document. Dr. Gottesman accepted Dr. Miller's suggestion as did 
Dr. Fedoroff. 
Dr. McKinney suggested the word "requirements" be changed in the last 
sentence of paragraph two. Dr. Gottesman amended her motion to change this 
sentence to read: "Information to be submitted should include, but not be 
limited to:" Dr. Fedoroff agreed. 
Dr. Vidaver suggested the term "as appropriate" be added to the language of 
item C-2-d as monitoring procedures may not be necessary in every case. 
Drs. Gottesman and Fedoroff agreed. 
By a vote of twenty-two in favor, none opposed, and no abstentions, the 
motion as amended was carried. The document as endorsed by the RAC appears 
as Attachment II. 
VI. PROPOSAL TO CLONE SHIGA-LIKE TOXIN GENE FROM E. COLI 
Dr. Gottesman introduced the proposal (tabs 1153, 1156/11, 1162, 1165, 
1168, 1170) of Drs. Alison O'Brien and Randall Holmes of the Uniformed 
Services University of the Health Sciences (USUHS) to clone at P3 contain- 
ment the Shiga-like toxin gene of coli in JL_ coli K-12 host-vector 
systems. Shiga-like toxin has activity similar to the activity of 
Shigella dysenteriae toxin. 
Dr. Gottesman reviewed the history of the proposal . In their first 
submission in September 1982, the investigators proposed to clone the 
Shiga-like toxin gene in coli EKl host-vector systems using plasmid, 
cosmid, or lambda cloning vectors. In support of their proposal, 
Drs. O'Brien ard Holmes offered the following arguments: 
(1) Clinical isolates of E. coli have already been demonstrated to 
elaborate large amounts of toxin indistinguishable frcm that 
produced by Shigella dysenteriae 1 (Shiga). Therefore, the genes 
for Shiga-like toxin production are present in the |L_ coli gene 
pool found in nature. 
(2) Human volunteers fed large numbers of Shigella dysenteriae 1 
organisms that produced Shiga toxin but could not colonize the 
bowel did not became ill. Therefore, any accidental ingestion of 
the organism to be manufactured, a toxin-producing EL_ coli K-12 
[ 469 ] 
