2.2 The techniques oogenetic manipulation with which we have been con- 
cerned usually involve the use of a restriction enzyme to cut a fragment of 
nucleic acid from an organism in such a way that the fragment can be recombined 
with a similarly cut fragment of nucleic acid (the "vector", often a plasmid or 
bacteriophage) in a different organism. The multiplication of the nucleic acid 
fragment in the vector occurs by its growth in a host cell, often a bacterium. 
The hazards involved depend on the following factors: 
i. the source of the nucleic acid from which the fragment to be linked 
is derived; 
ii. the degree of specification, that is the purity, of the nucleic acid 
sequence; 
iii. the vector/host system to be involved in the recombination and in 
which the sequence is to be multiplied: and 
iv. the manipulative procedures proposed. 
2.3 In the following paragraphs we refer in general terms to the weight which 
should be given to the four factors referred to in paragraph 2.2. It will be 
important for the GM AG to obtain quantitative assessments of hazard wherever 
possible but in our opinion this cannot be done with anv precision at this stage 
and we have not therefore attempted to give figures either for the purity of the 
nucleic acid sequence needed to meet the criterion of sub-paragraph 2.5.i below 
or for the degree of biological containment required in sub-paragraph 2.6.i. 
In paragraphs 2.4 - 2.7 we lav most emphasis on the risk to man. since laboratory 
workers will be involved in all experiments: but in particular circumstances the 
hazard of the nucleic acid for animals or plants may be equally important. 
2.4 Source of the nucleic acid 
Sources of the nucleic acid are of three main types: 
i. nucleic acid from bacteria, fungi or protozoa should be categorised 
according to the known ability of the source microbe to infect or 
cause disease in man, animals or plants; 
ii. nucleic acid from viruses should be categorised according to the 
“hazard classification” of their host or for viruses with a range of 
hosts, of the highest class of host indicated in paragraph iii; 
iii. nucleic acid from higher organisms is generally considered to offer a 
hazard related to the closeness of the evolutionary relationship 
between the organism constituting the source of the nucleic acid and 
the organism at risk. On this basis we should regard nucleic acid 
from plants and invertebrates as carrying a low hazard to man (except 
perhaps for invertebrates that may harbour microbes pathogenic for 
man); nucleic acid from amphibia, reptiles and birds would be assigned 
an intermediate hazard classification, and nucleic acid from mammals, 
including man, would be the most hazardous. 
2.5 Specification of the nucleic acid sequence 
i. The safest nucleic acid fragments are well-characterised sequences 
that do not specify a known hazard. One way of initially purifying 
such sequences would be by selection and growth in a vector/host 
system under rigorous containment conditions; 
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