The text of my slides presented at the OECD Conference of the Health Aspects of GM-
Food in Edinburgh on 28 February 2000:


A concensus is emerging that genetically modified (GM) foodstuffs will not be accepted 
by consumers without first subjecting them to rigorous, transparent and independent 
chemical and biological safety testing whose results are published in peer-reviewed 
journals and posted on the internet for public view and debate before they can be 
incorporated into the human/animal diet.  My proposal for the biological testing of GM-
foodstuffs: 
     
The regulatory framework relying on the concept of substantial equivalence needs to be 
put on more rational and scientific foundations, particularly as the compositional 
comparison of transformed and parent (non-transformed) lines is presently flawed.  For 
true average values and their variability, the parent and transformed lines must be grown 
under identical conditions, treated and harvested the same way.  In addition to proteins, 
starch, lipids, etc, of the parent and GM-lines, their contents of known biologically active 
components should also be compared.        

The stability of GM-products, foreign DNA, including the gene construct and its parts 
such as the promoter, the antibiotic resistance marker gene, etc, to degradation by acid or 
pepsin or other intestinal/pancreatic proteases/hydrolases has to be established in the 
stomach and intestines of model animals in vivo.  With GM-lectins, including the Bt-
toxin (Bacillus thuringiensis toxin) the presence/absence of their epithelial binding 
should also be demonstrated by immunohistology.  

The stability, biological, immunological, hormonal properties and allergenicity of GM-
products must be established with the GM-product isolated from the GM-crop and not 
with the recombinant material from E. coli as these two have substantially different 
biological properties.

As GM-food is unlikely to be expressly poisonous, "toxicity" is an unhelpful concept and 
difficult to assay at doses found in GM-food.  In contrast, nutritional studies in which 
diets containing GM-foodstuffs are fed to young growing animals (based on animal 
feedstuff evaluation) should reveal their possible effects on metabolism, organ 
development, immune and endocrine systems and the gut flora which together determine 
whether the young will develop into 
healthy adults.  

Suggested protocol:	
  
  Iso-proteinic and iso-energetic diets need to be formulated in which most of the dietary 
protein is preferably derived from the GM-crop.  The composition of the control diets 
should be the same as the GM-diet but based on the parent-line with or without 
supplementation with the isolated gene product at the same level as it is expressed in the 
GM-line.  
  
  Groups of animals (at least 5 per group) of similar weight, are strictly pairfed in short- 
and long-term experiments.  Individual urine and faecal samples are collected for the 
determination of Net Protein Utilization (NPU), Nitrogen Balance, and Feed Utilization 
Ratios. 




  Blood-samples are taken before, during and at the end of the experiments for immune 
studies (i.e. lymphocyte proliferation assay, Elispot), hormone assays (insulin, CCK, etc) 
and for the determination of other blood constituents.

  The animals are weighed daily and any abnormalities observed after which the animals 
are killed, dissected, the gut rinsed out and contents saved for further studies (enzymes, 
GM-products, DNA), sections taken for histology, wet and dry organ weights recorded 
and analysed.  

Evaluation:

  With suitable statistical analyses (ANOVA, paired comparisons and multivariate 
analysis) the significance of differences, if any, in the parameters examined is 
established:  

  Differences between animals fed GM- and parent-line diets indicate that the genetic 
modification must have had a significant effect on the utilization and nutritional value of 
the crop and the GM-crop therefore cannot be accepted for inclusion in the human/animal 
diet.

  If similar to the GM-diet, the parent-line diet spiked with the gene product also shows 
differences, the use of this gene in GM-food/feed is not acceptable.  

  If the negative effects of the GM-food are not observed with the parent line diet 
containing the isolated gene product, it is likely that this is caused by the use of the 
particular construct or an unwanted and unforeseen effect of the gene insertion on the 
genome.  

  Finally, animal testing is but a first step and when there is no indication of harm to the 
animals the results will have to be validated with human volunteers in clinical double-
blind, placebo-controlled drug-type tests while keeping in mind that harmful effects can 
be most acute in the young, elderly and sick, particularly those suffering from HIV, 
hepatitis or other viral diseases.

These are but the first steps in a biological testing programme which can and need be 
further developed.  Since our GM-potato work with male rats showed some abnormalities 
in the development of their sexual organs, it is imperative that similar experiments should 
be done with female rats to be followed by investigating in detail the effects on the 
reproductive performance of rats (or other animals) reared and maintained on GM vs 
non-GM diets for several generations.  

The detailed protocols described in this submission underline my belief that, if there is a 
willingness on the part of the regulators to embrace the concept of biological testing (in 
addition to possible toxicological evaluation), the methods are there and available for the 
work to start.