BOX contained use in the environmental sense does not imply complete containment. Complete
containment is not possible, and the term confinement is more appropriate.
It is easiest to consider the risk if we start with procedures which finally result in a marketed
modified organism and begin in the laboratory. In some senses this is where most of the hazard is
likely to be found, or where risk potential is greatest, for the least is known about modified
organisms in the research environment, and scientists are more likely to modify pathogens or try
and identify genes which will be 'useful' from a variety of organisms which are not fully
characterised.
If the organisms are contained we have first to consider only the probable effect on human health
and assume that our containment system will isolate our organism from the environment.
The European Union defines "contained use" as being within physical barriers, whether or not
supplemented by chemical or biological barriers to escape or release into the open environment.
The definition includes the modification of organisms and their storage, culture, use,
transportation or destruction for which physical barriers are used to limit their contact with both
the general population outside the containment and the environment. A genetically modified large
animal might be considered to be in containment, if the definition depended on an ability to recall
the 'organism' in the event of a problem, rather than a physical fence between that organism and
the wider environment.
In order to assess the risk for contained use, it is usual to follow a scheme where we
- consider the predicted properties of the genetically modified organism to determine if there are
any potential mechanisms by which it could represent a hazard to human health.
- consider the likelihood that the genetically modified organism could actually cause harm to
human health.
- assign the control parameters which would be necessary to safeguard human health
- identify any hazards to the environment and assign any additional containment measures to
assure that the environment is not placed at risk.
Our modified organism is conceptually separable into the host organism, into which genetic
information is inserted; the donor organism, from which the genetic information has been derived;
the vector which shuttles the information between these organisms, and the insert, which contains
one or more genes which display biological activity. It is useful to consider each of these in
attempting to assess the likely hazard posed by the modified organism.
When working in containment all cells, whether they are microorganisms, plant, animal or human
cells, are considered to be micro-organisms when used in culture. This is only important in that
the European Community Directive (EC 90/219) deals with contained use of modified
micro-organisms. Animals and whole plants used in containment are not covered by a
Europe-wide Directive, although many of the countries have "over-implemented" the directive so
as to include all organisms.
In general, however, focusing on cells, it is only microorganisms which are considered pathogenic
to humans, although plant cells may produce toxic and allergenic substances which pose a hazard
to the worker in the containment facility. (The concept of toxicity includes mutagenicity,
carcinogenicity, neurotoxicity and environmental effects).
For each of the donor, host, vector and modified organisms we may consider the hazard they
pose, which will provide information which allows a first approximation to the hazard likely to be
posed by the modified organism.
Modified organisms may be used in containment in laboratories (or pilot plants) or may be used in
an industrial setting. It may be that the primary distinction here is not the size of plant or type of
organism, but rather the skill and training of those working in the facility.
It is likely that a research or development laboratory will be working with organisms which pose
a greater threat to either the individuals working therein or to the environment than do those
organisms developed for large scale factory use. The great majority of organisms used in
industrial production are well-characterised, 'familiar' organisms capable of being used under
conditions of 'Good Industrial Large Scale Practice' or GILSP. The same logic would apply to the
development stage where 'industrial' use of the modified organisms is being planned. There is a
possible extra hazard in that it is at this stage that the modified genes may be inserted into the
organism, and the unpredictability of insertion site may, arguably, require slightly greater care
than that taken at the production facility.
In the research laboratory, organisms may be pathogenic to humans and/or to the environment, as
it is here that fundamental research would be conducted. Experiments will involve organisms and
/or inserts which may be injurious to the health of the workers or to those who are incidentally on
site in the laboratory.
Large scale use of modified organisms in containment is different from use in the laboratory in a
number of ways. In the first instance, it is almost certainly true that the organisms used in
development or for industrial and commercial use are non-pathogenic. They are generally used
under conditions of 'Good Industrial Large Scale Practice' (GILSP).
The hazards posed by large-scale fermentation of genetically modified micro-organisms are of the
same nature as for other biological agents, in particular.
- infection hazards -- the potential for disease following exposure to the organism;
- toxic, allergenic or other biological effects of the non-viable organisms or cell, its components
or its naturally occurring metabolic products;
- toxic, allergenic or other biological effect of the product expressed by the organism
There is nothing intrinsically more hazardous about the large scale use of genetically modified
organisms in containment other than the potential for a greater degree of exposure to an organism
and its biologically active products or the possibility that workers in an industrial plant are less
skilled at handling biological material than laboratory workers.
The criteria for organisms to be used under Good Industrial Large Scale Practice conditions
include
- The host organism must be non-pathogenic to humans with no adventitious agents and an
extended history of safe industrial use, or there must be environmental limitations permitting
optimal growth in the industrial setting but limited survival without adverse consequences in
the environment.
- The modified organism must also be non-pathogenic and as safe in the industrial setting as the
host organism, but with limited survival without adverse consequences should it be released
either accidentally or inadvertently into the environment.
- The Vector or insert must be well characterised and free from known harmful sequences; it
should be limited in size as much as possible to the DNA required for the intended function;
should not increase the stability of the construct in the environment (unless that is part of the
design of the organism). It should not transfer any resistance markers, particularly to
microorganisms not known to acquire the naturally.
