Dr. Donald S. Fredrickson 
-4- 
August 24, 1978 
B. The present Prohibitions (Sec I-D) are Insufficiently precise. 
For Instance on page 33070, Sec I-D-3, the use of the phrase 
"beyond that which occurs by natural genetic exchange" allows 
a researcher to produce any pathogen duplicated by natural re- 
combination, even If that agent has been eliminated through 
selection. Similarly, Section I-D-5 permits the same "natural" 
test to apply to the acquisition of drug resistance. Thus, 
the fact that a rare strain of Francisella pestis or Tularemia 
species has on occasion been found with antibiotic resistance 
genes acquired by R factor transfer would sanction the Inten- 
tional Introduction of similar genes by artificial means. 
The additional stipulation In I-D-5 which states that such a 
transfer would only be prohibited "if such acquisition could 
compromise the use of a drug to control disease agents In hu- 
man or veterinary medicine or agriculture" is vague, and shifts 
the burden of proof to the public health official to demonstrate 
such a case. 
1 ) Recommendation 
Strike the phrase "beyond that which occurs by natural genetic 
exchange" In I-D-3. 
Strike the phrase "that are not known to acquire It naturally" 
In I-D-5. 
Delete the remaining phrase "If such acquisition could comprise... 
and replace with "except when the researcher can document that 
such acquisition would not compromise the use of a drug to 
control disease agents In human or veterinary medicine or 
agriculture. " 
C. The exemption given to certain species which are known to exchange 
DNA molecules In nature, (Sec I-E-4) Includes known human pathogens 
(l.e. Shigella, Salmonella, Klebsiella and Pseudomonas species). 
In exempting them from meeting all requirements of the NIH guide- 
lines, a false sense of security may be generated. Certainly, 
the attempt here was not to Imply that normal laboratory safe- 
guards employed In handling such organisms were not to be circum- 
vented. 
1 ) Recommendation 
Add the necessary specification In Sec I-E-4 on page 33070 
that reminds the researcher that laboratory procedures ap- 
propriate to the known pathogenicity of such organisms must 
still be followed. 
[A-45] 
