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Re: Substantial equivalence - what is it?



At 21:24 21/06/1999 -0600, Trevor wrote:

>> 1. New Scientist 8/May/1999 - Even with the right gene, you might not see
>> green.
>...
>I may not be answering the question, but I think you are saying that
>regulatory assessments do not consider the function of a new organism,
>only the Genes within - regardless of their order.  I don't know about
>the application of SE in other countries (I hear there are serious
>problems with the US system) but in Canada, where I live, an organism
>with the exact same genes is definitely NOT SE if the order (and
>function) is changed.  Sequence has long been known to have a
>fundamental role in genetic function.

Modifying an organism by inserting new genes must involve disrupting the
original gene sequence. People have genes that produce pigments that
respond to red and green light, many also have a third hybrid version of
these genes. In men with full colour vision the researchers found the genes
in the order red, green, hybrid. In colour blind males the sequence was
red, hybrid, green. In other words the insertion of the hybrid before or
after the green has a major effect.

The point I am making is how do we know that the whether or not a GE
modification has had a significant effect on an organism ? Colour blindness
has been around for a long time, but this appears to be the first time that
a link has been made to genetic sequence.

>
>... 
>> 2. New Scientist 15/May/1999 - Fiendish Fungus, ...
>...
>> The above is an example of the problems that can be caused just by
>> physically relocating organisms. Can we pedict the effect of gene transfer
>> when we release "substantially equivalent" organisms ino the wild ?
>...
>
>It sounds like you are commenting on the general philosophy of scaling
>future risks to match the level of risk that have existed naturally in
>the past.  This is an important area for discussion in my opinion.  We
>must consider the population, economic globalization, mass agriculture
>and monocultures, and the prioritization of other human issues when we
>form our opinions on whether the historical level of risk is still
>acceptable in a new world.  My feel (so far, and for now...) is that we
>need to accept the same risks that existed in the past and possibly
>prepare better to react quicker and with more widespread research
>commiserate with the population increase we are experiencing.
>

Not really. What I am saying is that we appear unable to predict the
consequences just of moving organisms from A to B. On the basis of that
apparent ignorance how can we claim to know the effect of releasing
modified organism ? Also the fact that organisms are SE presumably means
that gene transfer is more likely to take place.

>> 
>> 3. BSE. ...               ...I imagine
>> that in terms of "substantial equivalence" PrPc and PrPsc would be regared
>> as totally equivalent....
>
>Certainly NOT.  Not even in the USA! <wink>
>Variances in protein expression are a direct result of variances in
>DNA.  SE has to apply to every aspect of an organism, not just the DNA,
>genes, Proteins, or function.  Substantial Equivalence does not just
>apply to a physical substance in an organism; "Substantial" is used in
>the sense of a more strict version of the word "Significant".   In
>Canada (The only system I've studied in depth), Every variation in the
>organism must be outlined as well as all possible effects of each
>variation and all possible combinations of those variations and
>effects.  The result is that only the most minor of changes in a plant
>are approved through Substantial Equivalence.  If the regulations and
>assessment techniques we have now were in place in the forties, I bet we
>would not yet have many of the grains that came out of the Green
>Revolution that are so widespread today.

Would the scientists have spotted that PrPsc was being produced and not PrPc ?
My understanding is that these are the same protein, just in a different
spatial configuration.
Even if they did spot the difference would it have been considered
significant ?
At the moment they still don't agree if PrPsc is a symptom or cause of BSE
and they don't know what the heck PrPc does anyway!

>Variances in protein expression are a direct result of variances in
>DNA.

In BSE there appears to be a spontaneous chain reaction of PrPc refolding
into PrPsc.

>In
>Canada (The only system I've studied in depth), Every variation in the
>organism must be outlined as well as all possible effects of each
>variation and all possible combinations of those variations and
>effects.

How on earth can you make a claim like that ? Surely there must be an
almost infinite number of possible effects ? You must be looking for
effects that you expect might result. If something unexpected happens you
might not be looking for it or the test you use might not see it (eg. that
PrPsc is not identical to PrPc).


Regards

Robert
Robert@tiamat.sonnet.co.uk