46 
(6) Experiments involving more than 10 liters of culture fluid 
with recombinant DNAs known to make harmful products are 
prohibited. This is because the probability of escape from 
containment barriers, especially in the case of accident, 
increases with increasing scale. 
The list of prohibited acts and experiments reflects the assumption, 
implicit throughout the Guidelines, that recombinant organisms may 
present greater possible dangers than are present in the most hazardous 
component used to construct the recombinant DNA. 
As noted in Appendix A, the Center for Disease Control's "Classifica- 
tion of Etiologic Agents on the Basis of Hazard" (fourth edition, July 1974) 
lists the following Classes of etiologic agents: (1) agents of no or minimal 
hazards under ordinary conditions of handling, (2) agents of ordinary 
potential hazard, (3) agents involving special hazard, (4) agents that 
require the most stringent conditions for their containment because 
they are extremely hazardous to laboratory personnel or may cause 
serious epidemic disease, and (5) foreign animal pathogens that are 
excluded from the United States by law or whose entry is restricted 
by USDA administrative policy. 
Cloning of recombinant DNAs derived from organisms in Classes 
3, 4, and 5 are prohibited. Prokaryotic hosts other than E. coli strain 
K-12, to be used for recombinant DNA experiments, must conform 
to the definition of Class 1 agents. The CDC classification consists 
primarily of agents etiologic in man. The use in the Guidelines of 
the CDC classification is based on the recognition that the laboratory 
worker conducting recombinant DNA research has the highest potential 
for exposure, and is the most likely route for transmission of micro- 
organisms to other living things. 
Special guidance is also provided for strictly animal and plant 
pathogens. The Guidelines prohibit the use of animal pathogens excluded 
from the United States by law and USDA administrative policy, and plant 
pathogens where experiments may increase their virulence and host 
range. In addition, general guidance for the use of animal and plant 
host-vector systems is provided. 
Experiments Permitted by NIH Guidelines. The permissible exper- 
iments include all those for which the risk of producing hazardous 
agents is thought to be exceptionally low. Further, experiments are 
only permissible provided that the information to be obtained, or the 
practical benefits anticipated, cannot be obtained by conventional 
methods. For the permitted experiments, the safeguards provided 
by the Guidelines are at least as stringent as those generally used to 
handle the most hazardous parent of the recombinant. 
