GMAG 
reference 
Genetic Manipulation Advisory Group 
at Medical Research Council 
20 Park Crescent, London W1 N 4AL 
telephone 01-636 5422 
31 January 1980 
Dear Dr Gartland, 
Guidelines for large-scale use 
I apologise for taking so long to respond to the invitation contained in 
your letter of the 20th December to Dr Keith Gibson. 
When I accepted the invitation to succeed Sir Gordon Wolstenholme as 
Chairman of GMAG, I anticipated that it would soon be necessary to move into the 
area of "scale-up". I, therefore, reconstituted the GMAG Sub-committee for this 
subject and decided to chair it myself. It appeared to me to be of fundamental 
importance to ensure that our biotechnology industry was permitted to operate with 
the minimum of constraints while maintaining an adequate degree of safety; also, 
that if the benefits of genetic manipulation were to be fully realised, we must be 
prepared to move rapidly from the bench to the industrial scale. 
As a result of our discussions at Sub-committee level followed by those at 
GMAG, we were in unanimous agreement on certain principles which are reflected in 
our GMAG Note 12 (copy enclosed). 
These principles are: 
1. "Scale-up" in the context of genetic manipulation is different from the accepted 
use of the term in, say, the chemical industry. It will invariably mean use 
not manipulation . 
2. Any risks related to use will not necessarily be the same as those related to 
manipulation . 
3. A different type of assessment may well be required because of the different 
risks. 
4. The skill and experience of chemical engineers is well proven and the type of 
large-scale plant used for antibiotic production provides a pattern for that 
required for the industrial application of the results of recombinant DNA 
research. 
5. The very high cost of mounting the commercial operation of large-scale 
biotechnology, eg. the cost of the medium to fill an industrial-scale fermenter 
and the consequences of any contamination tend to ensure that the safety 
desirable for the growth of genetically manipulated organisms is likely to be 
achieved. 
6. For these reasons, GMAG decided that the use of categories of containment was 
quite inappropriate for large-scale use. 
[ 271 ] 
