ii. the use of random nucleic acid fractions that nay include any com- 
ponent of the genome introduces greater possible hazards; 
iii. nucleic acid sequences selected on the basis of their intrinsic patho- 
genicity, or of the known toxicity of their products, are still more 
likely to be dangerous. 
2.4 The sector host system 
Vettors for the recombinant nucleic acid include free DNA. plasmids, bacterio- 
phages and viruses, and the viable hosts into which the nucleic acid is linked 
maybe prokaryotic (bacterial or eukaryotic (eg animal and plant cells). The 
first two of the systems listed below employ the principle known as biological 
containment: 
i the safest system is considered to be a combination of a host bacterium 
that is "disabled" and has been shown by in nr o experiments to have 
a very small chance of survival in. or of transferring information to, 
man or animals (or plants as appropriate), with a vector that is specific 
and confined to that host. A less well-attested system, which might 
be as safe, is one differing from the above only in that the "disable- 
ment” of the bacteria has been demonstrated by in vitro rather than 
in tivo experiments; 
ii. phage or plasmid vectors used in conjunction with, and able to grow 
only in. attenuated laboratory strains of bacteria also provide a 
degree of biological containment 
iii. those systems in which the vectors are capable of infecting the cells 
of higher eukaryotes are considered the most potentially hazardous. 
2.7 Manipulative procedures 
Simple experimental procedures ifor example, the inoculation of culture plates 
with bacterial colonies) involving small volumes of material offer the smallest 
hazard. Special methods of manipulating hosts and their vectors with rigorous 
containment may be developed which could further reduce any hazard. Use 
of an increased volume of material or the introduction of operations such as 
centrifugation, fraction collection or sonic disintegration, with the risk of 
aerosol production, clearly increases the hazard. 
2.8 Containment measures 
The hazards have their origin in the nucleic acid but these may be reduced, 
depending on the vector host system into which it is to be introduced. When 
this system is such that the nucieic acid can survive and replicate only in highly 
artificial conditions, any hazardous element that might escape could not 
survive. This is the principle of biological containment. Physical containment 
measures, on the other hand, arc designed to ensure that any hazardous elements 
that are created do not escape from the laboratory. We have defined four 
levels of physical containment and associated safety measures in the code of 
practice referred to in Section 3 below and set out in full in Appendix II and 
we propose that an experiment should be assigned to one of these levels on the 
basis of the factors in paragraph 2.2 above Even though genetic material 
thought to be completely harmless is being used in an experiment it is con- 
ceivable that a hazardous product might result because of an unexpected 
interaction and for this reason we recommend that no genetic manipulation 
experiment should be undertaken in containment conditions less stringent than 
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