GM Rape Changes Character - Gene Silencing


September 2000

The scientific abstract (below) just released in the September 2000 edition of scientific journal 'Nature Biotechnology' is going to cause some interesting discussion.  

What this study found is that oilseed rape genetically modified to be resistant to a herbicide lost that resistance when it encountered a naturally occurring environmental pathogen (the Cauliflower Mosaic Virus).  In other words had the farmer sprayed this rape in the field with the recommended herbicide the oilseed rape would have been killed as well as the weeds - not quite the idea of this technology!  

This could lead to some interesting crop loss claims by farmers against biotech companies if it happened on a large enough scale in the field.   The Cauliflower Mosaic Virus (CaMV) is a common pathogen of brassicas (cabbage, caulifower, rape etc).  In this case genetically modified rape which became infected by it (a common occurrence with brassica crops) lost its resistance to the herbicide. The relevant gene conferring herbicide resistance appears to have become switched off.  The herbicide in this case is bialaphos.  

Such 'gene silencing' has previously been considered to result from an interaction between the invading environmental pathogen and the viral 'promoter' (itself taken from the CaMV) which is used to artificially fire up the foreign transgene in the first place.  This particular viral promoter is used in most transgenic crops, into whose every cell it is embedded.  

This study is particularly interesting as it concerns the bialaphos herbicide which is related to glufosinate-ammonium, the herbicide to which most of the crops in GM fieldscale trials in the UK have been developed by Aventis to have resistance. It would appear that the same transgene provides resistance to glufosinate-ammonium as to bialaphos (see footnote). How comfortable would most UK farmers feel about this if they knew about it (or for that matter Aventis's shareholders and insurers)?  

The use of the CaMV 35s promoter in most transgenic crops is one of the most controversial technical aspects of the use of GM in agriculture.  The risks associated with it go well beyond the 'gene silencing' apparently demonstrated in this case. For more information on those risks see: www.btinternet.com/~nlpwessex/Documents/camv.htm  

This particular paper abstract from Nature Biotechnology finishes with the words: "Our results show that transgene phenotypes can be modified by pathogen invasion".   In other words the characteristics of genetically modified crops may change when they are released into the environment and interact with naturally occurring pathogens such as viruses. 

It is interesting that this should be reported in the scientific literature literally years after the large scale introduction of these types of crop into the environment around the world, particularly when such introduction has been based on insistence from scientists and regulators that they know what they are doing and everything has been fully tested.  Draw your own conclusions!  

This latest paper on the subject was produced by scientists at the John Innes Centre which is an advisor to the UK government on safety aspects of GM crops. 

The JIC previously commented on such gene-silencing phenomena in a paper published in 1998 as follows:  
".....Recent research in our laboratory with Brassica napus plants containing the 35S promoter from the mosaic virus (CaMV) has shown that upon infection with the CaMV the driven transgene is silenced (Al-Kaff et al unpublished). Intensive research at present is directed towards understanding this silencing mechanism and its significance.  
 

As the 35S promoter is widely used to regulate transgenics in brassicas, it is important that we strive to obtain a clear understanding of the mechanisms of this silencing and its significance. This is important for two reasons, for assessing the use of the 35S promoter in agriculture and also for assessing the significance of this effect for biosafety. The presence of homology between the 35S promoter and the infecting virus is clearly important in determining this silencing phenomenon ....  

A knowledge of transgene stability, expression and inheritance is fundamental for the successful and safe use of transgenes in large scale agricultural production. Many factors influence the ways in which transgenes express, but a factor of crucial importance is the effect of DNA sequences that are homologous to areas of transgene constructs. For those concerned with the development of transgenic brassicas the take home message from this paper is 'watch out for homology' ".  [emphasis added]
www.btinternet.com/~nlpwessex/Documents/compliance.htm  

As the JIC commented in a further paper in 1998:   "One of the most challenging issues associated with assessing the environmental impact of transgenic plants when in widespread commercial production are scale dependent effects.  It is possible that a rare event may have insignificant consequences when transgenic crops are grown on a small experimental scale, but become more important when transgenic crops are grown over thousands of hectares......".   www. btinternet.com/~nlpwessex/Documents/gmrisk.htm  

Meanwhile this material continues to be released into the environment in the form of the UK fieldscale trials and commercial crops in other parts of the world.

NATURAL LAW PARTY WESSEX
nlpwessex@bigfoot.com
www.btinternet.com/~nlpwessex  

Footnote: *Bialaphos [L-2-amino-4-((hydroxy)methyl) (phosphinoyl)-butyryl-L-alanyl-L-alanine] is a commercially available natural phytotoxin. Glufosinate-ammonium [Ammonium-DL-homoalanin-4-yl(methyl)-phosphinic acid] is the synthetic version of bialaphos' herbicidal moiety, phosphinothricin. http://ext.agn.uiuc.edu/abstract/270.html  

It appears that the same transgene provides resistance to glufosinate-ammonium as to bialaphos: http://www.stanford.edu/~walbot/StableMaizeTransf.html http://www.uga.edu/~ispmb/vickers.html http://www.pgreen.ac.uk/a_bar.htm   ================================================================================   Nature Biotechnology
September 2000, Volume 18, Number 9, pp. 995 - 999


Plants rendered herbicide-susceptible by cauliflower mosaic virus-elicited suppression of a 35S promoter-regulated transgene

Nadia S. Al-Kaff, Maria M. Kreike, Simon N. Covey, Robert Pitcher, Anthony M. Page & Philip J. Dale, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK.
Correspondence should be addressed to N S Al-Kaff. e-mail: alkaff@bbsrc.ac.uk

Crop plants genetically modified for herbicide tolerance were some of the first to be released into the environment. Frequently, the cauliflower mosaic virus (CaMV) 35S promoter is used to drive expression of the herbicide tolerance transgene. We analyzed the response to CaMV infection of a transgenic oilseed rape line containing the bialaphos tolerance gene (BAR) from Streptomyces hygroscopicus, regulated by the 35S promoter.

Oilseed rape is susceptible to CaMV, but plants recover from infection. CaMV infection altered the expression of the herbicide tolerance gene such that plants became susceptible to the herbicide. The effect on transgene expression differed in infections with viral pathogenic variants typical of those found in natural situations worldwide. Susceptibility to the herbicide was most likely a result of transcriptional gene silencing of the transgene. Our results show that transgene phenotypes can be modified by pathogen invasion.


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