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Old 10-28-2003, 07:36 AM   #1
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Default Free GMO articles from Nature Reviews

Nature has some interesting review articles on GMO (genetically modified organisms) available for free. Check them out at: Nature Reviews Genetics. Particularly interesting IMHO is the article on The production of recombinant pharmaceutical proteins in plants, or 'pharming.'

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Imagine a world in which any protein, either naturally occurring or designed by man, could be produced safely, inexpensively and in almost unlimited quantities using only simple nutrients, water and sunlight. This could one day become reality as we learn to harness the power of plants for the production of recombinant proteins on an agricultural scale. Molecular farming in plants has already proven to be a successful way of producing a range of technical proteins. The first plant-derived recombinant pharmaceutical proteins are now approaching commercial approval, and many more are expected to follow.
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Old 10-30-2003, 03:24 AM   #2
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Damnit this is stupid. "pharming" under domes, or in orbital habitats, yes, sure, bring it on, anywhere we can flush the whole batch if we have to. I agree, getting nature to make our stuff for us is great, and going to happen. But pharming on the planet, when we have so little idea about how to limit pollen spread, is extraordinarily stupid and possibly fatal.
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Old 10-30-2003, 04:37 AM   #3
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The pharmacology aspect concerns me. If this is going to be done, the plants producing the compounds should be sterile, no if ands or buts. There are a number of plants that reproduce by budding, that may work. The article seems to hint at hydroponic growth, which would hint at reproductive isolation. I would have grave concerns if medical compounds made their way into the environment.

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Old 10-30-2003, 05:43 AM   #4
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Originally posted by contracycle
Damnit this is stupid. "pharming" under domes, or in orbital habitats, yes, sure, bring it on, anywhere we can flush the whole batch if we have to. I agree, getting nature to make our stuff for us is great, and going to happen. But pharming on the planet, when we have so little idea about how to limit pollen spread, is extraordinarily stupid and possibly fatal.
On the other hand, such horizontal gene transfer is already happening, all the time, out in the natural ecology, without human intervention of any kind. In what way, then, would putting genes for, say, collagen, human serum albumin, IgM antibodies, or rabies vaccines, which are already known to be safe in humans, in a tobacco plant be any more fatal than the numerous instances of HGT that occur all around us since the origin of life? Could you explain to me how the pharm crops discussed in the review article be fatal to anyone? Its easy to see how many lives could be saved by the pharm crops (e.g. cheap mass production of medicines and vaccines) mentioned in the article, especially in poorer countries where it means getting medicines to many people who otherwise would not recieve it, but its harder to see how such crops are supposed to be 'fatal' to anyone, or in any way "extraordinarily stupid." And even if they were fatal, what reason is there to think that the net benefit in terms of lives and healthy years saved would not enormously outweigh the potential problems?

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simian:
I would have grave concerns if medical compounds made their way into the environment.
Obviously, many of the medical compounds humans use and benefit greatly from are already in the environment, because that's where we found them -- being produced by organisms in our environment. Opiates, digitalis, some antibiotics, and so on. Of course, the pharm plants would be specifically engineered to produce their proteins at higher quantities, and some of these proteins would be synthetic, so your point stands. On the other hand, it seems to me that what would primarily determine the spread of the pharm crop is its fitness in the natural environment, and adding genes for rabies vaccine is not likely to give a tobacco crop a selective advantage. Perhaps you could engineer the pharm plants to have very low fitness in the natural environment? I.e. make it deficient in some enzyme that has to be sprayed on the crop or something in order for the plant to produce pollen?

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Old 10-30-2003, 06:06 AM   #5
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By the way, the other free review article is on this very subject, the introgression of transgenes into their wild relatives: TRANSGENE INTROGRESSION FROM GENETICALLY MODIFIED CROPS TO THEIR WILD RELATIVES. Its very informative, and gives some good ideas about how to think about the relative risks of transgenic crops.

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Old 10-30-2003, 06:34 AM   #6
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There are things I will fight tooth and nail to keep out of crops. Every now and then somebody will decide that wheat has too low of a yield and will want to transfer the genes for gluten (the elastic protein in wheat) to corn. Corn can pollenate across great distances. Some people are celiacs. These two items together mean that if the wheat gluten gene reaches the general corn population, not only will celiacs have to avoid wheat (and possibly barley, triticale, oats, and rye), they will have to add corn to the grains they MUST avoid. Likewise, if antibiotics are proteins, and some people have allergies to them, then escape of genes means fatalities among the general population. Then there is the whole issue of how crops are handled in the US, the risk of unintentional release of the pharmaceutical crops into the food stream is significant (Starlink corn, don't remember the pharm, but Iowa had an issue the past year or two with a pharmafood nearly reaching the general food stream).

Please note: I am not against GMOs in general, in fact, I think they are a good thing, properly managed. However without proper selection of the crop used to make the pharm, and isolation of the crop contamination of the food stream with the pharm crops is certain.

Also note my concern is not about gene escape to wild relatives as much as it is contamination of the general food supply with genes that escape from the same species of crop.

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Old 10-30-2003, 06:52 AM   #7
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Originally posted by simian
Likewise, if antibiotics are proteins, and some people have allergies to them, then escape of genes means fatalities among the general population.
The exact same thing holds true with existing plants. There are plenty of allergenic proteins in plants already, and they are as likely to be transferred naturally to a human food crop as those placed in pharm crops, probably more likley, since they are present in an enormously greater number of plants and the plants they are in were not engineered in a way to minimize risk of gene transfer to other plants.

And of course, transgenes dont just escape and take over the world just because they're transgenes. A transgene is not going to proliferate unless it offers some competitive advantage once it is transferred, which seems unlikely for any of the proteins that are being discussed currently in the context of pharming. So what I'm asking about is that, given the background of natural, uncontrolled gene flow between species, why shouldn't we exploit the process intelligently and with maximum attention to safety, to save lives and create cheap, abundant medicines? And again, I'm talking more about proteins like collagen and human serum albumin that either already are present in humans or are known to be safe in humans, rather than synthetic proteins. I concede that there are hypothetical risks, but I dont see how they outweight the enormous potential benefits.

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Old 10-30-2003, 07:03 AM   #8
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Originally posted by ps418
The exact same thing holds true with existing plants. There are plenty of allergenic proteins in plants already, and they are as likely to be transferred naturally to a human food crop as those placed in pharm crops, probably more likley, since they are present in an enormously greater number of plants and the plants they are in were not engineered in a way to minimize risk of gene transfer to other plants.

And of course, transgenes dont just escape and take over the world just because they're transgenes. A transgene is not going to proliferate unless it offers some competitive advantage once it is transferred, which seems unlikely for any of the proteins that are being discussed currently in the context of pharming. So what I'm asking about is that, given the background of natural, uncontrolled gene flow between species, why shouldn't we exploit the process intelligently and with maximum attention to safety, to save lives and create cheap, abundant medicines? And again, I'm talking more about proteins like collagen and human serum albumin that either already are present in humans or are known to be safe in humans, rather than synthetic proteins. I concede that there are hypothetical risks, but I dont see how they outweight the enormous potential benefits.

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In food crops, great care is taken to ensure that no allegens are transferred with the intentional gene transfer. If the allergen potential exists, the stock is destroyed. With Pharm foods, allergens are part and parcel of what may be needed.

If callagen and serum are albumin are desired, why not use mammals (pigs for example) which already have similar metabalisms and can be removed from the reproductive pool by surgical sterility?

As somebody who has seen the huge issues with allergen contamination in food systems, I don't want to see unneeded allergens present in the food system. Take a look at a box of corn flakes: almost all in the US will list the disclaimer that the product may contain soy. Soy and corn are marginally different densities, size and shape, yet can't be seperated with 100% accuracy. How do you seperate one corn from another when both are exactly the same in any manner likely to be measured?

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Old 10-30-2003, 07:25 AM   #9
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Originally posted by simian
If callagen and serum are albumin are desired, why not use mammals (pigs for example) which already have similar metabalisms and can be removed from the reproductive pool by surgical sterility?
Did you read the review article in question? The reasons are that production costs are high, production timescale is very long, and there are risks of contamination (of the product).

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As somebody who has seen the huge issues with allergen contamination in food systems, I don't want to see unneeded allergens present in the food system.
Compared to the diverse array of human medical problems that are the target of pharming technology, I hardly agree that allergen contamination is a "huge" issue, particularly when the products being produced are not even allergens and indeed are already present in every human being. As for proteins that are not already present in humans, you could test them for safety in a clinical trial, just like you do for every new drug, before you take the next step and produce a pharm crop. Obviously there should be safeguards as to what can be introduced in the natural environment.

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Old 10-30-2003, 07:47 AM   #10
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Originally posted by simian
Likewise, if antibiotics are proteins, and some people have allergies to them, then escape of genes means fatalities among the general population.
The article said nothing about producing antibiotics. It did, however, mention antibodies, which are another thing entirely.
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