Book 4: Genetically modified organisms (GMOs) and related issues

The basic guidelines in this work are that maximum care be exercised in the interests of workers, human or animal subjects and research. The terms genetic modification, genetic manipulation, genetic engineering or recombinant DNA technology are interchangeable. These terms are usually defined to mean the propagation of heritable material by the insertion of that material, prepared by whatever means outside a cell or organism, into a cell or organism in which it does not occur naturally, either directly or into a vector system which is then incorporated into the cell or organism.

Considerable differences exist in the technology and techniques required to deal with prokaryotic or eukaryotic organisms used in genetic manipulation. Research utilising cultured organisms such as prokaryotic or eukaryotic single cells (with the exception of fertilised ova) may be regarded as ethically acceptable, provided the necessary containment facilities are used.

The application of this technology in animal research may be subdivided into various categories. The release of a recombinant organism or cell which may be cultured in vitro and then inserted either by DNA technology, as with the use of a virus, or by surgical means, in replacement of bone marrow cells, may be regarded as gene therapy by cell transplantation. This technology as applied in animals is ethically acceptable, provided the guidelines with regard to animal research are followed (see Book 3). The manipulation of genes in animal research must be limited by biohazard considerations. The manipulation of animal embryos or germ-line cells to create transgenic animals is ethically acceptable where the guidelines regarding animal research are followed.

A detailed discussion of recombinant agents is beyond the scope of this book. However, each case should be considered for risk potential. Many experiments involving recombination are done in non-pathogenic, disabled organisms and present no known risk, while others may present risk. Risk, in the case of GMOs, may involve the environment and containment may be required, although no direct risk to human or animal health is evident.

Risk may be assessed as a function of the following factors:

1. access: the risk that a micro-organism containing recombinant DNA sequences might infect a person or animal exposed to it;
2. expression: the risk that polypeptides coded for by the recombinant DNA could be produced or expressed by the organism;
3. damage: the risk that polypeptides expressed by the organism might damage the host.

The risk may be estimated in terms of the probability per unit micro-organism. A value of 1 means that all micro-organisms are expected to have access and to express a polypeptide that could cause some damage to the host. A value of 10 - 3 means that the likelihood of this occurring is 1 in 103 micro-organisms. The product of the three factors indicates the required category of containment.

Risk increases with large-scale growth, and extra containment may be required for a given organism.

Any GMO that is potentially viable as a free-living organism and is to be grown, cultured, propagated or used as a vaccine outside a contained environment, should be regarded as posing some risk unless assessed otherwise. Assessment is beyond the scope of this document and must be done by the relevant national authority, at present the GMO Advisory Committee or the Directorate: Genetic Resources, National Department of Agriculture. If the organism is approved, the Department will issue a permit for the work in terms of the GMO Act, No. 15 of 1997.

There are three different aspects of genetic engineering as applied directly to humans.

1. Determining genetic lesions in individuals has relevance in genetic counselling and in therapy, for example, and is covered in Book 2.
2. Where the health status of the patient indicates that the use of somatic gene therapy may be helpful, in the replacement of engineered bone marrow cells, for instance, provided the guidelines on ethics for working with humans are adhered to, the work may be regarded as ethical (see Book 2).
3. At this stage, manipulation of human germ-line cells is a complex issue and subject to the same guidelines as research in reproductive biology (see Book 2).

A number of other genetic engineering issues affect humans and animals less immediately or indirectly, but are nonetheless important. These include, but are not necessarily limited to:

1. the origins of the foreign gene or gene fragments;
2. the level of expression of the foreign gene;
3. whether the gene product is subject to post-translational modification and whether this process changes its nature;
4. the market sector targeted;
5. the potential benefit;
6. the possibility of legal or illegal export of the GMO and the potential for harm in a different environment;
7. whether the GMO will enter human or animal food chains;
8. potential toxicity of the new GMO;
9. potential allergenicity of the new GMO;
10. any effects that the GMO may have on the environment;
11. disposal of waste;
12. socio-economic impacts.

There are accepted protocols for evaluating many of these potential biohazards, ranging from assessing food allergenicity,
http://www.who.int/fsf to the economics and politics of GMOs, http://www.aphis.usda.gov/ or biotechnology issues, provides links to US web sites, http://www.biodiv.org provides links to EU documents. Scientific perspectives may be found at http://biotech.nature.com