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1400 lines
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<title>Molecular Biology for Real People by someone who's done it</title>
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<meta name="keywords" content="HTML"> <meta name="description"
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content="biotechnology problems, genetic engineering, molecular biology,
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genetics, tryptophan, golden rice, vitamin deficiency, substantial
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similarity, ANZFA, GMO, genetically modified organism, DNA vaccine,
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casein, cows, bananas, chloroplasts, protein, recombinant, Terminator
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Technology, roundup, roundup-ready, Exorcist">
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<body text="#000000" bgcolor="#FFFFFF"> <H2>>Molecular
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Biology and Genetic Engineering explained by someone who's done it</h2>
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<br>
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<h4> This site is dedicated to people like Pim Stemmer who says "People
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who continue to
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reject GM will be shown for what they are, non-rational and
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anti-technology. That's really good." </h4>
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<br>
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Last updated Feb 8 2003
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<br>
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<hr>
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<H3> Click on the questions to go directly to the relevant commentry: </H3>
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<P><A HREF="#gmo"> What is a GMO? </A>
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<BR><A HREF="#dna"> What is DNA? </A>
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<BR><A HREF="#bases"> How many DNA bases are there in a typical organism? </A>
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<BR><A HREF="#gene"> What is a gene? </A>
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<BR><A HREF="#humangenes"> How many genes does a human have? </A>
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<P>
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<BR><A HREF="#protein"> What is a protein? </A>
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<BR><A HREF="#engineering"> What is genetic engineering? </A>
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<BR><A HREF="#why"> Why are organisms being genetically engineered? </A>
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<BR><A HREF="#genome">Does knowing the human genome mean we know all
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about how a human being works? </A>
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<BR><A HREF="#junk"> What is junk DNA </A>
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<P>
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<BR><A HREF="#examples"> What are some examples of products made
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from genetically engineered organisms? </A>
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<BR><A HREF="#whoasked">If we eat it, how come we were never asked about
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this sort of stuff?</A>
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<BR><A HREF="#mistakes">Have there been serious mistakes resultant
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from genetic engineering?</A>
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<BR><A HREF="#coffee">So how is this sort of thing going to effect my life
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- my coffee will taste the same, won't it?</A>
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<BR><A HREF="#misses">Any near misses?</A>
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<P>
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<BR><A HREF="#aidsvaccine">There's a group in the Netherlands who, as of
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May 2001, say they engineered a strain of live HIV which be a good vaccine
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against AIDS, what's your take on this?</A>
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<BR><A HREF="#similarity">What is substantial similarity?</A>
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<BR><A HREF="#legislation">What sort of people are making the legislative
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decisions about GMOs?</A>
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<BR><A HREF="#flavr">What was the Flavr Savr tomato?</A>
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<BR><A HREF="#spidercow">There's a cow out there which makes spider silk in
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its milk. Is this a good idea?</A>
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<BR><A HREF="#weird">What sort of weird GM things have you heard of?</A>
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<P>
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<BR><A HREF="#ecosys">Can give some examples of bad effects a GMO might
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have in an ecosystem?</A>
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<BR><A HREF="#heirloom">Some people say we've been modifying plants for
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generations and that GMOs are no different. Is this correct?</A>
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<BR><A HREF="#paddocks">What sort of modifications are already in the paddocks?</A>
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<BR><A HREF="#roundup">What's a roundup-ready crop?</A>
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<BR><A HREF="#glyphos">What effect to glyphosate resistance genes have on
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the environment?</A>
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<P>
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<BR><A HREF="#lies">Some biotech companies say that they didn't add genes
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in or take genes out, yet they have modified the organism anyway, how does
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that work?</A>
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<BR><A HREF="#whoknows">There's an idea that a protein will do only one
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task, and that since it only does that task that it can be relied upon
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only to do that task and therefore is a known quantity. Is this a fair
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statement?</A>
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<BR> <A HREF="#terminator">There's this stuff out there called terminator
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technology (TT). It is promoted because it stops GM plants from
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propagating. Does it have any long-term consequences for the stability of
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the global food supply?</A>
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<BR><A HREF="#autonomy">What about terminator technology's effects on the
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autonomy of farmers?</A>
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<BR><A HREF="#exorcist">What's Exorcist technology, how does it work and
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does it really mean you can have GM-free GM crops?</A>
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<BR><A HREF="#starving">Are genetically modified crops going to feed the
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starving millions?</A>
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<BR><A HREF="#immuno">Are genetically modified organisms going to
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<B>eradicate disease?</B></A>
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<BR> <A HREF="#idiots"> Universities are the main institutions where
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molecular biologists are trained. Do university level courses have any
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components which inform young scientists about the long term consequences
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of molecular modification?</A>
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<BR><A HREF="#freesoft"> There is a concept called "free software" - how
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does that tie into genetic modification?</A>
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<BR><A HREF="#goodstuff"> You complain a lot about GM, do you think
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there's anything good about it?</A>
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<hr> <br>
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<A NAME=gmo></A>
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Q: what is a GMO? <br>
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A: a GMO (genetically modified
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organism) is any lifeform which has had its genetic material -DNA -
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deliberately changed by humans so as to accentuate or minimise particular
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aspects of a living organism, usually for commercial reasons but also
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sometimes for research reasons.
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<p> <A NAME=dna></A>
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Q: what is DNA?
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<br>A: DNA is short
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for deoxyribose nucleic acid. In each cell of a living thing you will find
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a long, long strand of this stuff, which is a sequence of sugar molecules
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and phosphate groups. DNA strands usually exist as pairs of these strands,
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wound around each other like a spiral. <p> DNA stores
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the program that tells the cell how to make proteins which can do certain
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necessary tasks to keep the cell alive and to enable it to do particular
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jobs, like make new cells or repair damage. <p>What
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enables DNA to store this information is the sequence of molecules called
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bases which are attached to the side of the DNA. Bases on one strand pair
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up with bases on the other strand. Life on earth uses four different
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bases, encoded in blocks of three, to encode all the usual amino acids
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from which we make proteins.
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<p>
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Particular sequences of DNA encode what are called
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genes.
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<p> <A NAME=bases></A> Q: How many DNA bases are there in a typical
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organism?
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<br> A: It depends, and varies widely (there is no such
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thing as a typical organism). To encode a bacteria you might need a few
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hundred thousand base pairs. Brewers yeast has about a million bases. A
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human usually has about thirty-two thousand million. Some plants have more
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than this. There is a theoretical limit to how few you need to run a
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metabolism because there is a requirement for a minimum number of genes to
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do the biochemistry required to keep something alive. Below this threshold
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are viruses, which depend on using the metabolism from other organisms to
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reproduce themselves.
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<p>Q: What is a gene?<A
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NAME=gene></A>
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<br>
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A: a gene is a sequence of DNA which stores the
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construction information for the manufacture of a particular protein. A
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given organism will have some genes in its DNA which are not present in
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other organisms, but also have genes which are similar to genes in other
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organisms.
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<p><A NAME=humangenes></A>Q: how many
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genes does a human have? <br>
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A: about 30,000. Not
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all of them are switched on and being used to instruct the manufacture of
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proteins all the time. Some genes are small, and others are large. Not all
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genes encode one protein... some encode a precursor peptide which is
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chopped up or derivitised in different ways (for example, carbohydrate
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molecules are stuck on them in a process called glycosylation) to produce
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something distinctly different to what the gene itself encodes. A lot of
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the immunoglobulins are "differentially spliced" to produce lots of
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different proteins from one gene. <p>
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<A NAME=protein></A>Q: What is a protein? <br>A: A protein
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is a substance which is made according to the specifications of one gene
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stored in the DNA. For each protein there are a range of possible variants
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on a given gene, and small changes can have large effects on the correct
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function of the protein.
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<P>All proteins are made of
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pretty much the same 20 subcomponents. The order in which these
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subcomponents are strung together differs. The subcomponents are called
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amino acids, and they are common to all carbon-based biological systems
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that we know about.
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<p>Different proteins have
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different sequences, so they are shaped differently and can do different
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structural or chemical tasks. Many of the proteins which do certain jobs
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are called enzymes and they enable the chemistry of life to operate. Some
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proteins dont do any chemistry that we know about, and mainly perform a
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structural role, like stopping your skin from being saggy. <p>
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Your hair is made of a protein called keratin. Your blood is red
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because of a protein called haemoglobin. People who have a gut enzyme
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called lactase can digest milk with lactose in it. Your tendons are full
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of a protein called collagen. Some proteins do special jobs like repair
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DNA damage. Some, like insulin, send signals from one part of the body to
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another. Most enzymes have ludicrous names... the one most directly
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responsible for incorporating carbon dioxide into plant sugars is called
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ribulose-1,6-bisphosphate carboxylase. Egg white is full of a gooey clear
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protein called albumin. Some proteins do amazingly specific, highly
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complex jobs, some of these jobs involve specific manipulation of
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subatomic particles, like hydrogen ions, or electrons. Usually they do
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tasks at the molecular level, moving whole atoms or groups of atoms
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arranged in a specific way. They are pretty remarkable things,
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actually.
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<p><A NAME=engineering></A>Q: What is
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genetic engineering?<BR>A: DNA occurs in
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animals, plants, fungi, bacteria, and even viruses (which aren't actually
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alive). Since DNA is the same across almost all living things, and they
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all encode proteins the same way in DNA sequences, DNA code from one
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organism will theoretically do the same thing when put into another
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organism and modify the biochemical behaviour of the recipient.
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<P>Genetic engineers are paid to take DNA from certain
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organisms and splice it into the DNA code of organisms where it was not
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originally. Or, they take the original DNA and modify it so it makes a
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protein which works differently.
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<p>The tools used for genetic
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engineering are usually proteins derived from bacteria, which can do
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things like assemble individual bases into a sequence, or chop a DNA
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strand at a particular place.
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<p><A NAME=why></A>Q: Why are organisms being
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genetically engineered?
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<br>A: It varies. Sometimes it's for research purposes, since a researcher
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can often figure out why people get certain inherited diseases by seeing
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what genes do or dont work in certain ways, and engineering organisms like
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mice with genetic changes is one way to do this. This gives valuable
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medical information about things like cancer and birth defects or
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susceptibility to certain diseases. <p> But mostly, it's about making
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money. Companies will tell you they're trying to feed people or cure
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diseases but make no mistake - those aims are secondary to their main
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objectives, which are to make people dependant on their products, increase
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their market share and increase shareholder value.<P>
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Biotech companies engineer bacteria to make certain molecules, usually
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proteins, which have some kind of commercial value, for example some
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antibiotics. Insulin can be manufactured by engineered bacteria, which
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prevents the need to extract it from dead pigs. <p>
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Some companies are engineering
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existing organisms so that pesticides don't kill them, or so that insects
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don't eat them, or so that they grow really big really fast... there are
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lots of modifications that are planned. There is no way they have a clue
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about the long term impact of these organisms on the ecosystem.
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<p>The main motivation for the biotech companies is that
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they think they can make an astounding amount of money by making organisms
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make molecules which are profitable. They use living organisms as
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nanofabrication factories for specialised molecules, because living
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organisms are very energy efficient at doing this.
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<p><A NAME=genome></A>
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Q: The human genome
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project will give us the
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sequence of all the DNA in a human being. Doesnt this mean we know all
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about how a human being works?
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<br>
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A: No. <p>Knowing the sequence of all
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the genes doesn't say anything about how they all work or how they all
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interact. The genome project also only took DNA from a small number of
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humans, so most varieties (alleles) of human genes are not
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represented. Much of the sequence data originated from Craig Venter,
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who, upon the
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(incomplete) sequencing of the genome by Celera Genomics (which
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he runs) used the data from his sequenced DNA to diagnose that
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he had a lipid metabolism problem, for which he now takes
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corrective medication. <p>Further, there are functions we
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need to have which our genes don't encode, like the manufacture of folate,
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which is made for us to a limited extent by bacteria in our intestines, so
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in theory, to encode a complete human, it might help to include some of
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these genes too. Human mitochondria have been sequenced for some time,
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they were only forty thousand bases long, but they do very important jobs.
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<p>Some of our metabolic pathways
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are broken - we have, for example, some of the genes for the synthesis of
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ascorbic acid but we can't actually make it ourselves, we have to get it
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in our diet, by eating plants which make it.
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<p><A NAME=junk></A>Q: What is junk
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DNA? <br>
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A: DNA which does not encode genes
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which instruct the building of proteins. I think junk is really a poor
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label, it simply means we don't know how to figure out what it
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does. <p>It obviously plays a role in phosphate,
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deoxyribose, purine and pyrimidine metabolism, since at the very least
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this stuff had to be synthesised, and sits around behaving as a kind of
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storehouse of these materials - if a cell dies or undergoes programmed
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self-destruction (apoptosis) then all that noncoding DNA is made available
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for incorporation as raw materials into other cells. It also plays a
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role in DNA packing and maintaining telomere stability. It worries me that
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some people are arrogant enough to call it junk DNA and are so readily
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accepting of the recieved wisdom that simply because it doesn't encode a
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gene or regulate protein expression, it has no role. Einstein said we only
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use 10% of our brain but that doesn't mean that people who are missing 90%
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of their brain (eg: car accident victims, television evangelists, for
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instance) are fully functional. <p>I expect there
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will never be a human which could be engineered so that there was no junk
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DNA in its genome, or if it was so encoded, the human would be fragile...
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robust systems have lots of redundancy, things you can damage without
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serious consequences. This is, by the way, the reason organisms have what
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is called ploidy - a number of copies of each gene. Humans are diploid (we
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get one copy of each gene from mum and one from dad, making two copies),
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some plants are triploid or tetraploid. It means you can have an error in
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one copy but not be seriously affected because the other copy works
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fine. <p>There are arguments about the role of junk
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as a kind of protective agent amongst which the useful DNA can hide from
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damage, or the junk can act as a physical scaffold for useful DNA. It has
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been shown that it does have a role in packing DNA properly. The introns -
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non coding parts - of some genes, which are spliced out before
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transcription, intrinsically make it difficult for things like viruses to
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simply chop out our genes and use them for their own purposes. So I
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hesitate to assume that just because we don't know what it does, it's
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useless.
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<p><A NAME=examples></A>Q: What are
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some
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examples of products made from genetically engineered
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organisms? <br>A: They're all over the
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place. Enzymes in washing powder have been engineered so they last longer
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in the
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wash. This probably has unforseen consequences in terms of how long these
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enzymes last, and what they do, when they hit marine life near ocean
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sewage outfalls, for example. <p>A lot of antibiotics
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are made by bacteria with entire suites of genes in them, which enable the
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bacteria to make the precursors to the antibiotic, and the antibiotic
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itself, from regular things which the bacteria can eat. These bacteria
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aren't usually released into the environment, however. <p>
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These days a lot of human foodstuffs are derived from plants with
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non-indigenous genes in them. Some of these genes have never existed until
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recently, notably the ones which degrade pesticides - mainly because these
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pesticides didn't exist until recently. We don't know what these genes do
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out there in the ecosystems into which they are placed.
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<p><A NAME=whoasked></A>
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Q: If we eat it, how come we were never asked about this sort of
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stuff?<br>A:
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Companies have been doing this pretty much without the permission of the
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public, and the public are being kept pretty much in the dark about it by
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the mainstream corporate media, whose sound-bite architecture doesn't
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permit detailed complex information to be distributed to the public.
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People are interested but the media fail in their task of informing the
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public because the network bosses and TV moguls think it is more
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profitable to fill up the bandwidth with inconsequential drivel like
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olympics and sit-coms. <p>It is also totally obvious
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that what is called western democracy is actually a mechanism to prevent
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the public having a say. You are supposed to exercise your decision making
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power only very narrowly, as a consumer in the supermarket. That the
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public has a right to know, or even an interest in the biology of what
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they eat, or even their own biology, is not even permitted onto the agenda
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for discussion.
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<p> <A NAME=mistakes></A> Q: Have
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there been serious mistakes resultant from genetic
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engineering?<br>
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A: Yeah. They're just the
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first in what history will reveal to be a string of stupid and preventable
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screwups. The classical, and tragically stupid, example occurred around
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1990. It'll take a little while to explain, it's complex... that's partly
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why it happened, the complexity is subtle. <p>I
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mentioned amino acids and proteins... well, one of the amino acids acids
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we need is called tryptophan. You usually make it in your own body from a
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precursor called chorismate. Some people dont make enough of it, so they
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take it as a dietary supplement. <p>You could go to
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all the trouble of using synthetic organic chemistry to make tryptophan,
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but the reactions are complex, expensive and the yields are low. So
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generally nobody does that. <p> Another way to make it
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in a factory is to get a big vat full of nutrient and grow a certain
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bacteria in it, a strain called Klebsiella, which happens to make a lot of
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tryptophan. Usually you let the vat brew for a few days, then rupture all
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the bacteria, and extract the tryptophan. Humans have been doing this
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perfectly adequately and safely for decades. <p>We
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know what all the genes are which make the proteins which turn chorismate
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into tryptophan. Usually these genes are turned on and off in a regulated
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manner by the organism which is making the tryptophan. This makes sense,
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the organism doesnt make any more tryptophan than it needs, it allocates
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its resources in an efficient way. The regulation mechanism involves a
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stretch of DNA just before the genes which encode the proteins which make
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tryptophan. This stretch of DNA is called a promoter, and is involved in
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deciding wether or not a protein is going to be made. In klebsiella, the
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promotors switch the tryptophan-making protein-manufacture machinery on or
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off as needed. This sort of regulation goes on everywhere in all living
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things.<p>In the early 1990s a petrochemicals
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company called Showa-Denko reckoned that they could make a strain of
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Klebsiella with all the regular tryptophan-making genes turned on all the
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time - they replaced the usual promoters with ones which were turned on
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continuously. This was so bacteria would make loads of tryptophan. It did
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indeed make loads and loads of tryptophan. It also started making
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something else, something rather unexpected.<p>Anyway, since the
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tryptophan was manufactured in pretty much the
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same way as it usually was, it was decided that no special tests be
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performed on the end product, no labels need be put on the cans it was
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sold in, and so off it went into general consumption. 36 people were
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fatally poisoned. About 1500 now have permanent nerve poisoning, a
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syndrome called eosinophilia-myalgia (EMS)... permanent serious muscle
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pain and other problems. <p>So how did that
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happen? <p>It turns out that in the engineered
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klebsiella, the _precursor_ to tryptophan built up to such a high
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concentration that it formed a dimer - that is, two precursor molecules
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chemically bonded with each other, to form a molecule called
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1-ethylidene-bis-L-tryptophan, or EBT for short. This dimer never occurs
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in natural organisms, because the promoters switch production off when
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concentration gets too high. If biochemists were trained in physical
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chemistry they might have seen this coming, but physical chemistry in
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living things is hideously complex, and biochemists aren't much trained in
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physical chem, so they couldn't even begin to try and predict it. Physical
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chemistry in dead things is pretty complex, too.
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<p>EBT is chemically similar to tryptophan (it is just two
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tryptophans bolted together, after all) so it came through with the
|
|
tryptophan in the extraction procedure, to about 0.5% contamination by
|
|
weight. Showa Denko settled out of court for a large sum of money. The
|
|
dead people are still dead, others EMS victims gradually die off as the
|
|
years roll on. <p>Tryptophan became a
|
|
restricted chemical after that. How can legislators call a molecule
|
|
restricted if it is a component of most of the proteins in every living
|
|
thing? What really should have been restricted is the freedom which
|
|
companies have to spread GM derivatives around the planet. <p>When I did
|
|
biochemistry/molecular genetics in 1996-1998, we were
|
|
told lots about how tryptophan is synthesised in cells and how it is
|
|
regulated, but not a peep about this screwup, which is a heck of a
|
|
cautionary tale.<p>
|
|
|
|
|
|
<p><A NAME=coffee></A>Q: So how is
|
|
this sort of thing going to effect my life - my coffee will taste the
|
|
same, won't it?
|
|
|
|
<P>
|
|
|
|
A: Nobody really knows. Probably not. I read recently that the genes
|
|
responsible for the synthesis of caffeine in the coffee plant (Arabica
|
|
robusta) has been identified and some biotech startup thinks there's money
|
|
to be made by turning that gene off and thereby producing a coffee bean
|
|
without caffeine in it, which in turn produces a decaffeinated coffee
|
|
which still has all the full caffeinated coffee flavour in it because the
|
|
other flavour molecules aren't lost (co-extracted) during the
|
|
solvent-based caffeine extraction procedure currently employed in
|
|
industry. <p>Apart from the zero-diversity problems
|
|
attendant to having zillions of hectares of identical GM arabica robusta
|
|
all over the world (the diversity of the coffee tree genome is already
|
|
pretty restricted) there is no mention of the possible biochemical
|
|
consequences of this engineering : if you turn off the gene which produces
|
|
the protein which transforms all the precursors to caffeine into actual
|
|
caffeine, then what happens to all that precursor? Does it build up to a
|
|
concentration at which it can biotransform into something poisonous to
|
|
humans or damaging to the surrounding environ? Does it influence the
|
|
kinetics of some other part of the plant's biochemistry which renders the
|
|
crop able or not able to do something else, for example will a GM caffeine
|
|
incapable plant make more dimethylxanthines instead (gotta do something
|
|
with all that xanthate precusor, if it can't make caffeine, the plant
|
|
might increase the synthesis of theobromine or theophylline, the latter of
|
|
which is toxic to some people). We aren't learning the necessary lessons,
|
|
we're keeping on making the same fucking stupid mistakes over and over
|
|
because we aren't learning to ask the questions which we should have asked
|
|
when we discovered we messed up the first time around.
|
|
|
|
|
|
<p><A NAME=misses></A>Q: Any near
|
|
misses?
|
|
<br>A: Absolutely. My god, this one 'll make you dirty your
|
|
pants, it's so scary. Again, it's a bit of a long story. <p>A German biotech firm engineered a
|
|
bacterium (again, Klebsiella, the particular subtype was called
|
|
planticula) to help dispose of rotting crop waste on farms. It happpened
|
|
that when it did this it also produced ethanol, which is in demand as a
|
|
fuel. <p>The engineered bacteria
|
|
was sent off to Oregon State University in the USA, to be tested. Usually
|
|
when labs test an organism they use sterile soil, basically it's normal
|
|
dirt which has been processed in such a way as there's nothing left alive
|
|
in it, which means all the variables are controlled, you don't have
|
|
earthworms or nematodes or fungi or whatever in the dirt to mess with your
|
|
results. But that means you're testing it in dirt which is totally
|
|
unrealistic compared to the dirt in which you typically grow plants in,
|
|
which is usually packed full of living things.
|
|
<p>Anyway a doctoral student named Michael Holmes thought
|
|
that testing this bacteria in sterile soil was senseless so he did the
|
|
test in various sorts of living soil with lots of organisms already in
|
|
it.<p>He found that every plant
|
|
put into the living soils with the engineered Klebsiella died. <p>
|
|
Why did this happen? It turns out that
|
|
the Klebsiella interfered with, and often killed, the mycorrhyzal fungi in
|
|
the dirt, which are responsible for making soil nutrients available so the
|
|
plant can absorb them in its roots. Plants are dependant on these soil
|
|
organisms to live. <p>Think
|
|
about it. The engineered Kleb was producing ethanol, the stuff
|
|
which, when you drink it in beer, makes you drunk and kills cells in
|
|
your liver and brain. Ethanol is a widely used biocidal agent, we usually
|
|
wiped down the benches with it in the lab where I used to do my
|
|
research, for this reason. Of COURSE it's gonna kill things in the soil,
|
|
including the plant roots too, if my experiences in plant biochem lab are
|
|
anything to go by. The experiment is easy enough to do - pour some ethyl
|
|
alcohol on the grass outside and come back in a few days, and it'll be
|
|
dead. Well, duh.<p>But it gets
|
|
astoundingly worse. <p>Suppose
|
|
this stuff had been tested in sterile soils, and given the OK by the EPA
|
|
(like the FDA did with tryptophan) to be released, in processed plant
|
|
waste, onto soil on farms throughout the world. You'd never stop it.
|
|
It would adapt to every treatment you'd throw at it. It would be
|
|
impossible to contain its spread. It would just distribute itself on
|
|
vehicle tyres, dust storms, the claws of birds which happened to land on
|
|
the soil. It would spread throughout the planet gradually resulting in the
|
|
eradication of agriculture and most the plant
|
|
kingdom as we know it.<p>(See: Suzuki, Dressel, "Naked Ape to Superspecies" p120-121, Allen
|
|
and Unwin) <p>If Holmes hadn't
|
|
done his experiments in real dirt, we'd never have known the effects
|
|
in living soils. The guy deserves a Nobel Prize for bringing these results
|
|
to light and averting the collapse of the civilised world, which is
|
|
entirely dependant on agriculture.<br>
|
|
|
|
|
|
|
|
<p><A NAME=aidsvaccine></A>Q: There's
|
|
a group in the
|
|
Netherlands who, as of May 2001, say they genetically engineered a strain
|
|
of live HIV which might be good as a vaccine against AIDS. What's your
|
|
take on this? <p>A: I
|
|
think I'd rather be shot than take this stuff. They've engineered the
|
|
virus so it's dependant on the presence of a chemical called doxycycline
|
|
to permit it to replicate. The theory is that they infect you with this
|
|
stuff and give you doxycycline and it gives you a very weak form of AIDS
|
|
for a few days, and then they stop giving you doxycycline and the
|
|
doxycycline-dependant virus dies out. During which time the immune system
|
|
learns to recognise the HIV virus and generate antibodies and white cell
|
|
defences to that virus. <p> The people who think live attenuated vaccines are useful as
|
|
vaccines fail to understand that they are dealing with a dynamically
|
|
adaptive, self-interested, evolving and replicating data construct - a
|
|
virus. Viral DNA and RNA replication is *intrinsically* error prone -
|
|
that's how HIV becomes specific for CD4+ T-cells and macrophages and
|
|
certain kinds of neurons, it's also how it generates escape mutants to
|
|
become immune to sodium phosphonoformate, and protease inhibitors, and
|
|
chain terminators (like AZT and ddI) and even to recently developed
|
|
error-inducing nucleotide analogues which are supposed to push the virus
|
|
over its error-catastrophe threshold. <p>
|
|
If you stick live AIDS into someone,
|
|
even if it's attenuated, it'll become virulent in the long term, period.
|
|
After all, you've put it on an evolutionary topography where the virus
|
|
will 1) benefit by not replicating any more of its own RNA than it has to
|
|
and 2) benefit by losing the gene or promoter which encodes its
|
|
controllability by doxycycline. Eventually there will be a variety of it
|
|
which *ignores* the presence of absence of doxycycline and replicates
|
|
anyway.
|
|
|
|
<p>For heaven's sake, viruses lose virulence genes when you passage them
|
|
in cell culture, *because* it's more efficient for the virus to do that in
|
|
the context in which it finds itself - a cell culture context where it
|
|
does not need to be virulent. Over a few generations of infecting cultured
|
|
cells in a sealed environment in which its every need is catered for, the
|
|
virus throws its virulence genes away because it doesn't need them, Any
|
|
virlogist with half a clue knows that.
|
|
|
|
|
|
<p><A NAME=similarity></A>Q: What is substantial similarity?
|
|
|
|
<br>A: It's a term which signifies that the GM food crop regulatory
|
|
authorities and legislators have absolutely no idea about molecular
|
|
genetics. They pass legislation which says "if a GM plant is substantially
|
|
similar to the natural plant, then they can be treated as if they are the
|
|
same."
|
|
|
|
<p>This is
|
|
absolute crap piled on top of arrogant stupidity. I guess it is to be
|
|
expected, since most of the people who write these laws are economists or
|
|
lawyers, business types who haven't the slightest idea about how real
|
|
living systems work.
|
|
|
|
<p> Ok, yes, technically, chimpanzees are substantially similar to
|
|
humans... mainly humans who write this kind of legislation. There are lots
|
|
of examples in nature where the tiniest little difference can have
|
|
massive, often fatal differences. <p>There's a protein I mentioned
|
|
earlier, haemoglobin. Its main job is to sit around in red blood cells,
|
|
pick up oxygen in the lungs and dump it in the other tissues. There are
|
|
two genes which encode the subcomponent proteins in haemoglobin. Regular
|
|
haemoglobin molecules float around independantly inside the red blood
|
|
cell, so the red blood cells can squeeze through tiny blood vessels,
|
|
called capillaries.
|
|
|
|
<p>Some people have a blood disorder called sickle cell anaemia. This
|
|
occurs because the amino acid sequence in the haemoglobin has changed
|
|
slightly, which in turn occurs because ONE DNA BASE has changed. The
|
|
consequence of this is that the haemoglobin molecules stick together, and
|
|
form rods, which turn red blood cells into a kind of stretched curved
|
|
donut shape, which stops them from going through capillaries easily, and
|
|
this starves your flesh of oxygen.
|
|
|
|
<p> At a DNA level you might be substantially similar, but at a functional
|
|
living being level you've got serious problems if this single base is
|
|
changed ... one base in 3 billion. Basically because you multiply that
|
|
error in ALL of your red cells.
|
|
|
|
<p>There's a load of other examples... genes which predispose you to
|
|
getting cancer... genes which, because they dont work, mean that you bleed
|
|
for days when you get a tiny cut... all substantially similar, but
|
|
nevertheless different to the usual version which most humans have.
|
|
|
|
|
|
<p><A NAME=legislation></A>Q: What sort of people are making the
|
|
legislative decisions about
|
|
GMOs? <br>A: I don't
|
|
know, but they aren't the people who use or understand the technology. I
|
|
went to a public forum at NSW state parliament in 1999 about this, sat and
|
|
listened to the suits at the front, and to the questions asked by the
|
|
journalists. I stood up and said, "Is there anyone in this room, aside
|
|
from me, who actually does molecular genetics, uses restriction enzymes,
|
|
can sequence and clone a gene, or has any idea how this genetic technology
|
|
works?" I was the only person, in a room with five hundred people in it,
|
|
who had ever actually gloved-up and gowned-up and done molecular
|
|
genetics.
|
|
|
|
<p>This isn't actually surprising. Molecular biology takes a while to
|
|
learn, it's hard stuff. Also most gene jockeys who have jobs are employed
|
|
by biotech firms, which would sack them instantly if they said anything
|
|
about what they do... non-disclosure agreements are a part of getting
|
|
employed. So they shut up. Most of the ones I've worked with don't
|
|
actually have a clue about the distributed interactivity of the ecosystem,
|
|
'cos they are confined to a narrow specialty. I can talk about this 'cos I
|
|
get paid to be a computer geek.
|
|
|
|
<p>Most journalists don't even know what are the right questions to ask.
|
|
<p> They focus on wether or not the GM crops are safe to eat. My bet is,
|
|
after it's been killed and processed and frozen and seasoned and oven
|
|
roasted, it's probably safe to eat, but really we just don't know until
|
|
some people die because of some wierdo interaction we didn't know about.
|
|
The Showa Denko lesson is there for the learning, if you look for it.
|
|
|
|
|
|
<p>Food safety is peripheral to the main questions, which are: Is it safe
|
|
to have this casually modified molecular software running our global food
|
|
supply? Is it stable for the next few million years? Is it diverse enough
|
|
to be robust? (If it crashes as often as most commercially available
|
|
software, we're in deep shit, soon). Should it be owned by a few large,
|
|
unaccountable, immortal transnational companies, who employ
|
|
biology-clueless accountants to decide about "how to manage" it for
|
|
maximum profit? <p>
|
|
|
|
Currently I think the respective answers are
|
|
no, no, no and no. I am unlikely to change this stance in the forseeable
|
|
future.
|
|
|
|
<p>The stake we should be interested
|
|
in is long-term survival, that is what you play for when you're playing
|
|
a game called Darwinian Selection. Species too stupid to realise this
|
|
are eventually edited from the gene pool. This is a fate for which I think
|
|
h.sapiens is a prime candidate.
|
|
|
|
<p>Besides which, we already HAVE safe, not-modified food plants, which
|
|
have a track record of centuries of safety. Let's eat 'em while we can
|
|
still get them.
|
|
|
|
<p><A NAME="flavr"></A>Q: What was the
|
|
flavr savr
|
|
tomato?<br>A: Tomatos
|
|
rot because there are genes which turn on when the tomato ripens, which
|
|
make enzymes which dissolve the structural components of the cells in the
|
|
tomato.<p>The idea was
|
|
that to make tomatos last longer on the supermarket shelf, you just turned
|
|
these genes off. Anyway this was done and it produced a tomato which was
|
|
more fragile than the ones already on the shelf. They were then used to
|
|
make tomato soup since they're easier to process than regular tomatos. I
|
|
don't know if they tasted any better. <p>
|
|
While we're on the subject of tomatos, the
|
|
ones we get look really red and juicy, and are firm as tennis balls, but
|
|
taste like wet cardboard. These were not genetically engineered to be that
|
|
way... farmers and consumers bred them that way. How?<p>
|
|
For years grocery
|
|
and supermarket
|
|
managers complained that soft, mushy tomatos (which also tasted good) were
|
|
not profitable. Shoppers would judge their tomato by the firmness and the
|
|
look of it. Tomatos which allocated their resources to making flavour
|
|
molecules, were mushy and were easily bruised and looked unattractive on
|
|
the shelves, so shoppers didn't buy them even if they probably tasted
|
|
good.<p>The call went
|
|
out, we want firmer tomatos. So tomato growers started to select strains
|
|
which were physically tougher. A plant which allocates resources to
|
|
structural strength is not allocating them to making itself tasty. Over
|
|
several decades we have arrived at a tomato which is optimised for
|
|
profitable supermarket distribution, is as red, firm and shiny as a
|
|
cricket ball and tastes about as good, too. They don't even go splat when
|
|
you drop them. We brought this on ourselves without GMOs.
|
|
|
|
<P> <A NAME="spidercow"></A>Q: There's a cow which has been engineered to make
|
|
spider silk in its milk udder. Is this a good idea?<BR>
|
|
|
|
A: Well, we don't know. It probably isn't going to help any calves the cow
|
|
might have, when they try and grow up drinking milk with spider silk proteins
|
|
dissolved in it. In any case, again, nobody is sure what this gene (fibroin)
|
|
will do in all the other cells in the cow, if it gets expressed; I'm yet to
|
|
hear wether the cow has immunologically reacted against the fibroin or its
|
|
derivatives. <P> Why is this being done? Well, it's for the fibre. Cows are
|
|
going to get a lot of modifications, I suspect, since that udder of theirs is
|
|
a convenient thing from which to extract all sorts of engineered protein
|
|
products, because the technology for it already exists (automated cow milking
|
|
machines). But, it's being plugged right into the nutrient supply of the new
|
|
calf. This isn't a very clever thing to do, I think. <P>
|
|
|
|
I heard in 2003, someone has engineered cows so they make more than twice
|
|
the normal amount of casein in their milk. They used multiple copies of
|
|
the normal cow genes
|
|
for casein, so it's the same two proteins beta-casein and kapa-casein,
|
|
which cows usually secrete into their milk, but the engineered cow makes 2
|
|
times more kappa-casein and 1.7 times more beta-casein - they're not in
|
|
their usual proportion. These cows also have a genetic marker for
|
|
resistance to an antibiotic engineered into them too, as an artefact of
|
|
the cell selection procedure used to select the individual engineered
|
|
cells from which these cows originate. It hasn't been mentioned if all the
|
|
cow's cells express proteins which destroy a particular antibiotic, but if
|
|
they do, and the cow gets a bacterial infection, there's at least one
|
|
antibiotic you can't use to help the cow recover from any infections it
|
|
might get, because its cells just destroy it. I'm sure veterinarians
|
|
aren't going to like that. <P>
|
|
|
|
Now, the cheesemakers are saying this casein overexpression is a great
|
|
idea, they get more cheese from milk, more money per cow, etc. But think
|
|
about it for a moment... by changing the promoters for the expression of
|
|
these casein genes, they have altered the animal's normal tissue-specific
|
|
allocation of amino acids. All animals have a daily amino-acid budget, and
|
|
these cows are now allocating a hell of a lot more of their amino acid
|
|
pool, to excretory casein synthesis than they normally would. In addition
|
|
they will be depleting their amino-acid pool most severely of the exact
|
|
same amino-acids which will now be used up in the process of making lots
|
|
of casein - not all amino-acids are depleted equally. Normal cows make as
|
|
much secretory casein as their body thinks is necessary, and these ones
|
|
have been engineered to make heaps, in an unregulated way. Are these cows
|
|
going to experience illness as a result of amino-acid deficiencies
|
|
elsewhere in their system as a result of placing all their resources into
|
|
their milk glands? Nobody knows yet.
|
|
<P>
|
|
|
|
It should also be noted here that since this animal has several copies of
|
|
casein engineered into it, that this animal is no longer totally a diploid
|
|
mammal any more - the ploidy for the casein genes is much higher than the
|
|
ploidy of the genes for the rest of the animal. Generally if you have
|
|
changes in ploidy you get odd changes in the physiology of the animal;
|
|
when humans get ploidy changes they exhibit things like Klinefelter's
|
|
syndrome or Turner's Syndrome - which are brough about by excessive copies
|
|
of things like the genes on X chromosomes.
|
|
|
|
<P>
|
|
|
|
|
|
<p><A NAME=weird></A>Q: What sort of weird GM things have you heard
|
|
of?<br>A: Someone's trying to develop blue roses. You can, from certain
|
|
research institutions, get hairless mice which faintly glow green in the
|
|
dark, they have been engineered with genes from bioluminescent organisms.
|
|
There's also a mouse which has been engineered with its
|
|
pigmentation synthesis genes placed under the control of the bacterial
|
|
<i>lac</i> operon, so it'll change the colour of its growing coat-hair
|
|
depending on wether or not you feed it a particular material (IPTG). I
|
|
imagine these sorts of things will eventually become available for sale,
|
|
and pollute our ecosystem even more than it is already, just because
|
|
someone thinks there's a buck to be made and no legislator will have the
|
|
nouse or guts to prevent it.
|
|
|
|
<p>Another whacky one is, someone has engineered potatos to glow in the
|
|
dark when they're in need of water (using the same luciferase genes, but
|
|
different promoters, to the ones spliced into the mouse mentioned above) .
|
|
Um, can't people just look at them and see if they're wilting, like we did
|
|
for a few thousand years? More recent examples of utterly idiotic GM
|
|
projects include engineering grass so it doesn't grow so fast, therefore
|
|
needs less frequent attention with a lawnmower (I'm not kidding... instead
|
|
of planting something other than grass, our solution to lawn maintenance
|
|
is evidently to engineer grass to be slow-growing... you're still going to
|
|
have to waste resources growing it and you'll still have to mow it!) -
|
|
and there's an Israeli chap engineering chickens to have no feathers. I
|
|
don't suppose it ever occurred to this guy that feathers actually do
|
|
useful things for chickens, like say, keep them warm,
|
|
and provide abrasion resistance, waterproofing, and so on? I imagine
|
|
someone will get the idea that it might be good to engineer humans to have
|
|
12 fingers, so they can type faster, play the piano better, etc - and when
|
|
it eventually happens it will never be asked why evolution decided, after
|
|
millions of years of testing, on five digits per hand.
|
|
|
|
<P> Just because we can do these sorts of things does not mean they're a
|
|
good idea. It concerns me that living organisms are being engineered to
|
|
suit the requirements of sometimes demonstrably stupid sales droids and
|
|
marketing analysts.
|
|
|
|
|
|
<p><A NAME=ecosys></A>Q: Can you give some examples of bad effects a GMO
|
|
might have in an ecosystem? <br>A: Yeah. There's a cotton crop you can get
|
|
with a bacterial enzyme engineered into it. This enzyme (from
|
|
Bacillus Thuringiensis) attacks the internal structure of insects, so when
|
|
the insects eat the plant, the enzyme attacks the insect, which kinda
|
|
dissolves into mush from the inside out, in a day or so. <P>This means
|
|
that the crop is protected, but it also means that the dead insect isn't
|
|
out there doing its particular job in the ecosystem. It might be that it
|
|
had other jobs like pollenating nearby plants, or becoming food for local
|
|
bird life. Obviously if it has dissolved into brown sludge from the inside
|
|
out, it can't perform those roles any more. Sometimes these roles are
|
|
critical. Say your engineered plants also slowly kill every bee in the
|
|
district... where will the beekeepers go? Where will the new saplings
|
|
germinate?
|
|
|
|
<p> There's an additional consequence to doing this - you set the scene
|
|
for the evolution of insect pests which are resistant to attack by this
|
|
enzyme. So over the years, the organic farmers who use bacillus
|
|
thuringiensis as a natural pesticide of last resort are going to find that
|
|
it doesn't work any more. And, in the very long term, the adapted insects
|
|
will just eat the engineered crop anyway, so the farmer will have to get
|
|
the same crop but engineered to have a different poison in it. <p>Some
|
|
additional things go wrong with the crop, like sometimes its leaves are
|
|
warped, or the toxin doesn't actually work against pest weevils (they have
|
|
resistance, maybe?), or the plant has very little foliage so it doesn't
|
|
grow very quickly, or the cotton bolls on it were shaped stragely and
|
|
yielded no fibre. Whatever the Bt gene was doing, we didn't completely
|
|
know about it. <P>
|
|
|
|
Here's some other examples; there's genes for various lectins implicated
|
|
in actually raising the susceptibility of potatos to sucking insects,
|
|
because these GM-introduced protein are thought to be responsible for
|
|
decreasing the amount of glycoalkaloids produced when expressed in
|
|
genetically engineered potatos, and glycoalkaloids are what potatos use
|
|
naturally to repel sucking insects. (See: Annals of Applied Biology Vol
|
|
140 p143). It's known also that when Pioneer-Hi-Bred engineered Soybeans
|
|
to express a methionine-rich Brazil nut protein in 1996, the protein was
|
|
later shown to cause allergies in the people eating it (the idea here was
|
|
to make the food more methionine-rich). There's various people also
|
|
engineering the genes controlling the process of synthesis for lignin in
|
|
trees, so they are more easily able to be processed into paper... who
|
|
knows what this modified lignin will turn into when the organisms
|
|
responsible for breaking it down try and eat it, or what structural
|
|
effects it will have on the trees growing it? (See Nature Biotechnology
|
|
Vol 20 p607).
|
|
<P>
|
|
|
|
By 2003 a gene encoding an enzyme called Cystatin has been inserted into
|
|
many of the world's banana crops. Cystatin originates in a totally
|
|
different plant, namely rice, and blocks the action of an enzyme called
|
|
cysteine proteinase. Cysteine proteinase chops up proteins which possess
|
|
an amino acid called cysteine. The idea behind this is that cystatin
|
|
expressed by engineered bananas prevents nematodes, which are a worm which
|
|
eats banana plants, from completing their life cycle by preventing the
|
|
nematodes from digesting the banana flesh (by blocking the nematode's
|
|
cysteine proteinase which is part of the way nematodes chop up banana
|
|
proteins during their digestion). Does anyone know if the engineered
|
|
inhibition of cysteine proteinase changes anything else, like the way we
|
|
digest bananas, or the function of the hundreds of kinds of bacteria in
|
|
our gut, or the way bananas run their own internal cysteine
|
|
proteinase biochemistry? What about cystatin... does it interfere with
|
|
anything else? What happens if all the nematodes die out where these
|
|
engineered banana crops are planted? What are we going to do if the
|
|
nematodes don't die out, but instead become resistant to the effects of
|
|
cystatin? What about all the other things which live on bananas... fungi,
|
|
bacteria ... what will cystatin do to them? <P>
|
|
|
|
<p>Carson wrote
|
|
Silent Spring what, thirty years ago? What happens when the only organism
|
|
which survives in an ecosystem is the one which has eliminated all the
|
|
neighbours with engineered molecular trickery?
|
|
|
|
<p>If you plant vast areas with the same
|
|
identical plant, you have a monoculture, and anything that damages it will
|
|
damage the entire crop because there is no variation. Diversity creates
|
|
robustness. If you have a crop with 5 strains of wheat, a frost might kill
|
|
some of it, a drought might kill some of it, a flood might kill some of
|
|
it, an insect might kill some of it, a fungus might kill some of it, but
|
|
any one of those will only kill 20% of your crop. A crop with one strain
|
|
of wheat is uniformly vulnerable, and that's exactly what the GM plants
|
|
are - pretty much genetically identical. <p>And - a field full of some
|
|
GM crop is a
|
|
field with no natural crop in it. So what happens when the planet is
|
|
planted with this? Where does the diversity of heirloom strains go? They
|
|
go extinct, that's where. Extinct is for a long, long time. Its software
|
|
we can't afford to lose.
|
|
|
|
<p><A NAME=heirloom></A>Q: Some
|
|
people say we've been modifying plants for generations and that GMOs are
|
|
no different. Is this correct? <br>
|
|
A: No. What we're doing is taking genes and
|
|
inserting them into organisms in which they did not evolve. Genes and
|
|
proteins do not come with an instruction manual. Suppose there is a strain
|
|
of wheat which has been selected over centuries for its resistance to
|
|
frost. The particular makeup of that plant is is full of genes which
|
|
evolved entirely in wheat, and is going to be more predictable in the long
|
|
term than say, a genetically modified wheat plant which has had a gene
|
|
from, say, a jellyfish engineered into it to improve frost resistance. We
|
|
have no way of knowing what the jellyfish gene will do in the metabolism
|
|
of the wheat, or in the ecosystem local to the wheat crop.... it evolved
|
|
in the ocean, after all. Who knows what it could do in the
|
|
paddocks?
|
|
|
|
<p><A NAME=paddocks></A>Q: what sort of
|
|
modifications are already
|
|
in the paddocks? <br>A:
|
|
I'm finding it hard to keep track of them all. A chap named
|
|
Herrera-Estrella from Mexico is engineering crops to tolerate droughts by
|
|
making them synthesise sugars (for instance, trehalose) which tend to make
|
|
it easier for the plant to retain water (this trick is widely practised in
|
|
a lot of natural succulent plants like the cacti). Yeasts will
|
|
ferment trehalose, so are we looking at accidentally
|
|
engineering the plant so that its relatively moist, sugary products rot
|
|
faster in storage silos?
|
|
|
|
<p>Tobacco is being engineered with proteins which enable the roots to
|
|
pump salt out of the plant, which enables the plant to grow in soils
|
|
otherwise rendered useless by salinity. I suspect this might be a good way
|
|
to engineer a salt-tolerant weed, but anyway, what *are* we growing
|
|
tobacco for - it causes millions of people to die painful deaths every
|
|
year, many of them become a drain on government resources when they're
|
|
busy being treated in hospital. Tobacco doesn't feed anyone except
|
|
the tobacco company shareholders.<p> But wait, there's more. Someone's
|
|
engineering cats so they are non-allergenic to humans... but there's no
|
|
discussion amongst the proponents that cats might be secreting their
|
|
allergenic protein for a good reason. Someone else is planning to engineer
|
|
bacteria that convert your sweat into pheromones. This isn't going to feed
|
|
anyone either.
|
|
|
|
<P>Some other bunch of people
|
|
are in the process of engineering cattle to be immune to trypanosomes,
|
|
which would have the undesirable long term effect that feral cattle in
|
|
Africa would undergo a population explosion in that country because
|
|
trypanosomiasis is one of the major things keeping them in check. But they
|
|
never talk about that scenario.
|
|
|
|
<p>I've heard of
|
|
engineered plants which lower the pH of the soil around them, which makes
|
|
it easier for them to extract phosphate ions from the dirt. Too bad if
|
|
you're a soil organism and you prefer not to have your environmental
|
|
acidity increased.
|
|
|
|
<p>Somewhere else rice has been engineered to contain more
|
|
precursors to vitamin A. It's been given away free to impoverished nations
|
|
supposedly to prevent blindness due to vitamin A deficiency. It's called
|
|
Golden Rice. It's causing some problems already. People aren't getting
|
|
visual defects from vitamin A deficiency like they used to but now they're
|
|
getting vitamin A toxicity, you only need about 33 milligrams of this per
|
|
day in your diet before you start to exhibit poisoning, it's a
|
|
lipid-soluble vitamin so it's not like Vitamin C any excess of which you
|
|
can excrete in your urine. The way to fix this is to eat less vitamin A by
|
|
eating less of the engineered rice, but uhhh, they can't do that, they
|
|
were offered it for free and planted all their fields with it and it's
|
|
their staple diet and they cant afford to buy rice from anywhere else.
|
|
Brilliant, not.
|
|
|
|
<p>There's potatos which
|
|
have been engineered to be resistant to various viruses, too, but I can't
|
|
see why in the long term the viruses won't adapt to the engineered crop,
|
|
as has been the experience with other pest organisms. I can't see why when
|
|
the spuds eventualy flower (as, the variety Lemhi Russet will do) they
|
|
won't spread this gene around amongst other spuds.
|
|
|
|
<P>I brew my own beer, and I have heard a rumour which I have not been
|
|
able to pin down concerning the engineered strains of yeast (saccharomyces
|
|
cerevisiae) used in commercial breweries. I don't know yet but it wouldn't
|
|
surpise me, yeast are an industrial workhorse and modified strains exist
|
|
in laboratories all over the world.
|
|
|
|
|
|
<p><A NAME="roundup"></A>Q: What's a
|
|
roundup ready crop? <BR> A: A crop which has been engineered with enzymes
|
|
which protect it
|
|
from being poisoned by glyphosate sodium, which is a plant poison and
|
|
widely used weedkiller. The company which has the patents on these plants
|
|
also owns the patents on the roundup herbicide. They engineer crops so
|
|
they cant be killed by glyphos, so you can spray a crop and it will only
|
|
kill the weeds.
|
|
|
|
<p><A NAME=glyphos></A>Q: What effect
|
|
do glyphosate resistance genes have on the ecosystem?
|
|
<br>A: Certainly their presence
|
|
encourages farmers to spray more glyphos on weed plants, which increases
|
|
the amount of residue in the overall crop, and also in the
|
|
soil.<p>If you look on
|
|
a drum of Monsanto Roundup, it says that "glyphosate breaks down on
|
|
contact with soil" ...which is not completely true. It doesn't all break
|
|
down instantly, which means that the label is misleading. It has a half
|
|
life of several months. So it builds up from repeated application. Check
|
|
the Merck Index entry for it. <p>It isn't known if these genes have
|
|
spread into other plants, but
|
|
it wouldn't be surprising, given that all lifeforms want to do is to
|
|
spread their genes around, after all, that's what they evolved to do. Do
|
|
we need weeds which are resistant to weedkiller? I think
|
|
not.
|
|
|
|
<p><A NAME=lies></A>Q: Some biotech
|
|
companies say that they didn't add genes in or take genes out, yet they
|
|
have modified the organism anyway, how does that work?
|
|
<br>A: Word-play. You can have all the
|
|
original genes, just driven under different promotors - genes which are
|
|
usually switched on or off are engineered to be permanently turned off or
|
|
on, or made to turn on/off under different circumstances to the ones under
|
|
which they used to turn on or off, and this has a significant effect on
|
|
the behaviour of the organism. Or, a gene is reinserted backwards so the
|
|
protein it encodes doesn't get made. The effects of this aren't known, but
|
|
you can say "we didn't take out or add any _genes_." Its like saying
|
|
glyphos breaks down on contact with soil. Its a half-truth, they rely on
|
|
people not to ask anything else. Usually it works because they don't know
|
|
what to ask.
|
|
|
|
<p><A NAME=whoknows></A>Q: There's an
|
|
idea that a protein will do only one task, and that since it only does
|
|
that task that it can be relied upon only to do that task and therefore is
|
|
a known quantity. Is this a fair statement?<p>A: No. All complex proteins
|
|
have an
|
|
evolutionary history. For example, we have a protein in our liver called
|
|
alcohol dehydrogenase, it breaks down ethanol (which is produced by our
|
|
gut bacteria). It happens that a protein in the lens of human eyes, called
|
|
crystallin, will also break down ethanol. This is probably because
|
|
crystallin evolved over billions of years from the same sequences of DNA
|
|
which encode alcohol dehydrogenase. Check out their genes, they're pretty
|
|
similar. Other proteins and enzymes probably used to do other jobs
|
|
millions of years ago, but we don't know what they did because we don't
|
|
even know how to look. Their behaviour is very context
|
|
dependant.
|
|
|
|
|
|
<p><A NAME=terminator></A>Q: There's
|
|
this stuff out there called terminator technology (TT). It is promoted
|
|
because it stops GM plants from propagating. Does it have any long-term
|
|
consequences for the stability of the global food supply?
|
|
|
|
<br>A: Yes. TT
|
|
makes crops produce seeds which can't germinate. It generally works by
|
|
inserting into the plant genome a gene encoding a protein which interferes
|
|
with germination (and there are several ways to do this) and putting this
|
|
protein under the control of a DNA promotor sequence which is activated
|
|
during seed germination. So the seed starts to germinate and then poisons
|
|
its own germination process.
|
|
|
|
<P> If the company which
|
|
makes the F1 (parent) crop suddenly can't provide new seeds to the farmers
|
|
each year, then the result is shortage of crops because the farmers can't
|
|
grow next years crops from the seeds they have already from the last years
|
|
harvest. The word "crippleware" applies here. Destabilising the software
|
|
which feeds you is uh, suicidally insane if you're interested in
|
|
long-term survival.<P>In the long term you can't guarantee a
|
|
mutation won't enable the
|
|
TT engineered crop (and any other genes it might have) to propagate,
|
|
because you're dealing with a living organism. _All_ it wants to do is
|
|
spread its genes around. Say a TT crop pollenates a nearby wild type crop.
|
|
Does that mean that the wild crop's progeny is now not going to germinate?
|
|
This is like a self-destruct sequence but with a distribution mechanism.
|
|
The epidemiological analogy with a plague disease is exact.
|
|
|
|
|
|
<p><A NAME=autonomy></A>Q: What about
|
|
terminator technology's effects on the autonomy of farmers?
|
|
<br>A: it induces dependancy on the GM
|
|
crop because farmers can't grow their crop from seeds they might have
|
|
adapted to their particular environment over decades. They become
|
|
dependant on an agribusiness co for their annual seed supply, for which
|
|
they pay a lot of money, and they used to get it for free.
|
|
|
|
<p><A NAME=exorcist></A>Q: There's a new technology (2002) called Exorcist.
|
|
How does it work and does it really mean you can have a GM but GM-free plant?
|
|
<br>A: Supposing you had modified a plant genome to include a transgene
|
|
like, say, one which encoded a protein which made the GM plant herbicide
|
|
resistant.. Once that gene has been transcribed into mRNA and the
|
|
protein has been produced, the GM technology has done its work, but
|
|
after that, the "Exorcist" is a neat way of chopping that gene out
|
|
of the plant's genome - in fact it will chop the transgene out, and also
|
|
most of the DNA which has been spliced into the plant genome to enable
|
|
the Exorcist mechanism to work.
|
|
<P>
|
|
|
|
Naturally, Exorcist itself is a genetic modification which leaves
|
|
traces of itself behind after it has done its work (which includes chopping
|
|
itself out of the genome of the modified plant), and these traces remain
|
|
both in the modified plant genomic material. Also, the chopped-out
|
|
sections encoding foreign genes are not reliably destroyed, they sometimes
|
|
remain after excision, floating around in the cell, doing whatever it is
|
|
they do when they're chopped out (which isn't known).
|
|
<P>
|
|
|
|
The "Exorcist" protein is called Cre, which is actually a (bacterial) virus
|
|
recombinase enzyme which chops out anything between two specific DNA
|
|
sequences (called loxP, 34 bases long) then re-joins the cut loxP ends,
|
|
between which the rest of the GM DNA is deliberately placed.
|
|
An engineered-in recognition sequence remains in the genome wherever
|
|
it was initially placed, because the two of them initially present
|
|
are not completely chopped out.
|
|
<P>
|
|
Once the Exorcist, its promotor section, and the other modified genes under
|
|
their control have done their work, you'll *STILL* have a modified plant,
|
|
the metabolism of which was doing engineered processes during the period
|
|
when the intended-for-removal transgenic gene, and its protein were still
|
|
there in the plant cell, doing whatever nonstandard biochemistry
|
|
they were doing (rather like a worn sock is still a worn sock even though
|
|
you've taken your foot out of it).
|
|
<P>
|
|
|
|
You might have much less of a chance of identifying that it was a modified
|
|
plant. If there was a remnant loxP site there, which didn't exist in the
|
|
wild-type plant, you'd be able to say "this is a modified plant." However,
|
|
if there was such a loxP site in the wild-type plant, you'd be dealing with
|
|
an organism which would behave unpredictably when engineered with the
|
|
Exorcist system since the Cre protein would probably make an attempt at
|
|
chopping out DNA which just happened to fit Cre's recognition requirement,
|
|
but you couldn't say definately the plant had this loxP site due to
|
|
engineering or not if you didn't know it was engineered... because the
|
|
transgenes have been chopped out and might not remain in a condition which
|
|
a PCR search could recognise.
|
|
|
|
<P> We don't know the recognition error rates for the Cre recombinase, nor
|
|
what else it might do in organisms where it didn't evolve, nor wether the
|
|
loxP sequences Cre works on also occur naturally elsewhere in the plant to
|
|
be engineered. To me, having a foreign recombinase running around in your
|
|
plant's genetic material, chopping-out whatever it happens to find between
|
|
the required sequences, is a brilliant way to destabilise the genome of
|
|
the organism. It might be worth asking, too, why develop a means to chop
|
|
out an engineered gene, if these things we're engineering in there in the
|
|
first place are supposedly safe? Doesn't it seem like Exorcist is a fix-up
|
|
for a mess we should not have created in the first place?
|
|
|
|
<P>There's someone else out there saying that if you do engineering on the
|
|
DNA of the chloroplasts in plants (the photosynthetic sub-component of
|
|
plant cells) that it's ok since that DNA can't spread ... well, again,
|
|
even if you have engineered the plant chloroplasts to behave differently
|
|
for few weeks, the effects of those engineered chloroplasts can remain for
|
|
a very long time. I think the no-spread claim is dubious
|
|
anyway, since chloroplasts and mitochondria have to be passed down the
|
|
generations along with normal nuclear material, so if the plants with
|
|
engineered chloroplasts can reproduce, their chloroplasts probably will
|
|
find a way to do so too.
|
|
|
|
|
|
<p><A NAME=starving></A>Q: Are
|
|
genetically modified crops going to feed the starving
|
|
millions?<p>A: No. This
|
|
is because the starving millions don't have the money to pay the
|
|
agribusinesses for the privelage of using them. Simple and callous as
|
|
that. This is peripheral to the question of wether we need more people on
|
|
a planet with six billion humans on it, which I think we definately do
|
|
not. Or the question of where to get the hydrocarbons and synthetic
|
|
fertilisers to run our mechanised
|
|
mono-agriculture for the next century. Or the question of where to get
|
|
land to
|
|
grow enough crops to feed so many people. <p>
|
|
|
|
Did the last green revolution feed everyone? Well, actually, no. <p>If
|
|
there is a plague organism on this planet, we're it. We need distributed
|
|
immunocontraception. Maybe genetic engineering will provide that in one
|
|
form or another. If history is any guide, it will happen by accident.
|
|
Probably something stupid like we woke up to the sudden realisation that
|
|
we engineered all our food crops to die out after one season with
|
|
terminator technology and planted it everywhere so the wild types pretty
|
|
much became extinct, creating widespread famine. Sheer genius.
|
|
|
|
|
|
<p><A NAME=immuno></A>Q: Are
|
|
genetically modified organisms going to eradicate disease?
|
|
<p>A: No.
|
|
|
|
<P>Problems of resistance aside, enough people won't be able to get access
|
|
to things like engineered vaccines, because they won't be able to afford
|
|
them, so there will be persistent reservoir populations of pathogenic
|
|
organisms in hosts, and probably resistant ones evolving everywhere. <P>
|
|
Similarly, many diseases which are inborn errors of metabolism and which
|
|
dont have many sufferers or a sexy media profile, will largely lose out in
|
|
the competition for research funds.
|
|
|
|
We've already got one GMO which _causes_ a disease (vitamin A poisoning,
|
|
see above).
|
|
|
|
<p>There are some GM crops which have
|
|
in them proteins from disease causing organisms, and the idea here is that
|
|
people eat these crops, and their immune system learns to recognise the
|
|
pathogen protein, so they get immunity to that disease. I think that's a
|
|
good idea except the disease organism only needs to slightly change and
|
|
the immune system won't recognise it, necessitating a new release of a
|
|
newly modified crop.
|
|
<P>
|
|
The crops are often modified with no consideration about how the plants
|
|
are processed in the societies where they are eaten : someone released a
|
|
potato with a gene encoding a bacterial protein from a disease-causing
|
|
bacteria in it, but since the locals always cooked their potatoes before
|
|
eating them, the protein was denatured by heat before the immune system
|
|
ever got a change to recognise it. OF COURSE they did. Potato rinds are
|
|
poisonous, they contain things like prussic acid. You yourself probably
|
|
don't eat potatos raw either.
|
|
|
|
<P> Again we dont know what viral proteins will do in food crops, for
|
|
reasons I already mentioned. In any case, some companies think this is a
|
|
bad idea because they make money out of selling cures, and this sort of
|
|
prevention strategy is bad for their profitability.
|
|
|
|
|
|
|
|
|
|
<p><A NAME=idiots></A>Q: Universities
|
|
are the main institutions where molecular biologists are trained. Do
|
|
university level courses have any components which inform young scientists
|
|
about the long term consequences of molecular modification?
|
|
<br>A: Universities are not places
|
|
where the molecular biologists of the future are informed of the
|
|
consequences of their interference with the genomes of organisms. They are
|
|
places where you are trained to use the tools, but not to have any
|
|
understanding of the consequences of application of those tools. It is the
|
|
same as it was with training people in the 1930s to synthesise pesticides,
|
|
or hormones, which turned out to be oestrogen analogues which induced
|
|
unusual vaginal cancers and male mammal infertility decades later at
|
|
parts-per-million concentration and which we only became aware of in the
|
|
1960s and 1970s.
|
|
<p>Modification of organisms is something which doesnt go away, once
|
|
you release an organism it stays released, and uaully evolves into
|
|
something else. Australia has a history of this... feral rabbits, foxes,
|
|
cats, birds, grasses, trees, and to a significant extent, humans who did
|
|
not evolve locally. Australia is never going to be rid of them and they
|
|
aren't even genetically modified. Our successes with smallpox and prickly
|
|
pear are aberrations.
|
|
|
|
|
|
<p><A NAME=freesoft></A>Q: There is a concept called "free software" - how
|
|
does that tie into genetic modification? <br>A: Living organisms run
|
|
molecular transformation programs which are encoded in their DNA, and
|
|
executed by proteins. This molecular information, which is actually
|
|
"software" is free... it is available to benefit all organisms. For
|
|
example, you have three billion base-pairs of DNA in each of your cells,
|
|
and this is the software which tells them how to run. You inherit this
|
|
software from your parents, for free - they both contribute to your genome
|
|
and when they concieve you are effectively contributing their working code
|
|
to a collaborative software development project - you. They donate this
|
|
code without copyrights attached to it, and you as a human being don't
|
|
have to pay them a license fee for running their code in your metabolism.
|
|
There are no laws against you giving your code to other people - once
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people reach a certain age they are legally allowed to share their genomic
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data to whomever they choose, provided the other party consents to share
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as well. Currently there is no law against you sequencing parts or all of
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your own DNA. The only things which stand between you and modifying your
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own DNA are technical hindrances, such as, how good are you at molecular
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biology lab technique. <P>
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Lots of agribiotech businesses take this kind of software from say, a
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plant, modify it slightly and then claim the entire plant as theirs. This
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is, technically, on most electronic platforms, software piracy. It is
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exactly like micro$oft taking an open standard and modifying it so it
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becomes proprietary to them. <p>The planetary genome should remain free
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software. It is too important to have it any other way. I recommend a look
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at <a href-"http://www.gnu.org"> GNU.org </A> for some essays about Free
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Software. Stallman's comments about electronic data apply very much to
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biological data.
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<p><A NAME=goodstuff></A>
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<BR> You complain a lot about GM, do you think
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there's anything good about it?<P>
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Sure. DNA vaccination is a very good thing, so far, though it has
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helped the human population explode. Recombinant insulin is a good thing,
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so far, and there are a lot of diabetics alive today who would otherwise
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be dead (the pigs from which insulin used to be extracted are probably
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still processed into bacon and pork roasts, however, so they have not been
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so lucky). I think these are examples of what good there is to be had from
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GM technology. Provided everyone is being fed adequately, and the number
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of humans on earth isn't adversely affecting the ecosystem, these sorts of
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life-preserving and life-extending things are a really good idea. The
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food-and-population problems are not going to be solved by GM technology,
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they're social problems, artefacts of how our corporate-run society is
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operated.
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<P> I think cloning humans is sort of pointless, since it already happens
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in nature to some extent (homozygotic twins). It's certainly cheaper and
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easier, at the moment anyway, to make humans the same way we have been
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making them for several hundred thousand years. If it is applied on a
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large scale to animals which currently reproduce sexually, we'll have the
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same monoculture problem we have with a lot of plants, which is, they're
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genetically all the same and hence all vulnerable to the same
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|
diseases. (Bananas and coffee plants are examples of plants with
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restricted variety because mostly they're clones - they need specialised
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attention and things like fungicides and pesticides frequently applied.)
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<P> The cloning mostly happening at the moment is from somatic cells,
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which are damaged. Cloning will work when expeimenters begin with fresh
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embryonic stem cells. People are now preserving their kids stem cells at
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birth.
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<P> Now, on the other hand if I could clone my own organs, that would be
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kind of useful, but I expect that organ cloning is going to give rise to a
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new class of individual in society - the more-or-less-immortals, who can
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afford a couple of million bucks for a new lungs, livers, hearts, spleens,
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skins, and other replacable organs every few decades. Does the rest of
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society really want sly corporate CEOs and government dictators and so on
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to live longer than they do already?
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<p>I can think of a pile of modifications I'd like to try on myself. More
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resources allocated to things like free radical scavenging, DNA error
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correction, cytochrome P450 optimisation to degrade the new and wierd
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|
poisons I absorb because I live in an industrial society. An immune system
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which was better at spotting metaplastic cells before they became tumors.
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|
Ability to synthesise my own vitamin C and folate and essential amino and
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|
fatty acids. More melanocytes so I don't get sunburnt so easily. CNS
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|
neurons which could metabolise lipids (they currently can only metabolise
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ketones and glucose) for energy. That's molecular stuff. I don't know if
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any of it would work, or perhaps drastically skew my metabolic resource
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allocation so I died.
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<p>I caught myself thinking the other day that I could modify my visual
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pigment, rhodopsin, so I could see shorter or longer wavelength photons
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that is, see in the ultraviolet or infrared parts of the spectrum. But
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|
there are problems... - as with all the preceding screwups, I cannot just
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modify one gene and expect it to work. If I modified it so I could detect
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infrared, I'd have to have my eyes located somewhere other than in a big
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skull full of metabolically active (and therefore very warm) brains (on
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|
stalks, maybe?!) otherwise I'd just percieve a blank wall of the same
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|
temperature because of all the waste heat being dumped into my eyeballs.
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|
If I had visual pigment which could detect short wavelength radiation, how
|
|
is it going to get through my cornea and aqueous humour, which absorb in
|
|
the UV to a considerable extent? I'd need to do an awful lot of serious
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|
and extensive modification to my basic embryology and biochemistry to do
|
|
these things.
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<p>With some of these modifications we could live a very long time,
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however, currently I do not think the long term consequnces of my being
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able to live to 190 years of age are being planned for in the social
|
|
infrastructure sense. It means I would consume lots more food, energy,
|
|
resources; more of the disposable, designed-to-break junk which is sold to
|
|
us by profiteering corporations. I'd rather die
|
|
than live 190 years of wage slavery.
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|
<p>At the organ level, how about otoliths which
|
|
regenerate so my hearing doesn't degrade? No loss of skin's ability to
|
|
synthesise collagen so I don't get saggy as I age? What about a new set of
|
|
natural teeth every thirty years? Nerves which correctly knit when
|
|
severed?<p>What about things like
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|
heavy structural
|
|
modifications ... redundant fingers, redundant organs, backs which aren't
|
|
so prone to blowing a herniated disc, nerves routed away from impact
|
|
sensitive locations, more anastamosed arteries. Bigger pelves to enable
|
|
less traumatic delivery of neonates with bigger heads and brains? Bigger
|
|
brains are metabolically costly to run, is that a good idea? Brains which
|
|
are optimised for certain abilities... are we engineering a species which
|
|
consists of people so standardised for obediently working in an office
|
|
environment that we lose the philosophers, the radicals, the
|
|
visionaries?
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<p>(I
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|
wonder if we're not breeding that civil disobedience out of ourselves
|
|
already.)
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<p>I do not think these sorts of
|
|
things should be inflicted upon neonates. Maybe if you could prevent a
|
|
child from suffering some kind of genetically inherited disorder, you
|
|
might want to do that. I do not think that interfering with the
|
|
neurochemical or developmental architecture of our brains is likely to be
|
|
optimal for us in the long term, simply because the direction this will
|
|
take will fit the social whim of the day... we shouldn't try to engineer
|
|
humans to fit some trendy social model, or the diversity which we
|
|
absolutely depend on to run our social organism will go away. People
|
|
conventionally considered stupid or ugly or insane have contributed to
|
|
what we call the human experience.
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<p><I can forsee a day when some person needs a
|
|
gene in their body modified and they purchase the modification and it
|
|
becomes integrated in all of their cells including their gametes. This
|
|
would mean that their offspring has a good chance of expressing the new
|
|
gene, and that the company which produced that gene would then start
|
|
asking for license fees from any offspring who happened to inherit that
|
|
gene. The courts would, in their infinite stupidity, probably grant the
|
|
company the right to prosecute the person for having the temerity to run
|
|
that part of their metabolism without paying the company for it. I'm glad
|
|
I'm freeware, but then I live in a body with operator-friendly genes in
|
|
it. Maybe if I had a choice between, say, being freeware and paying for a
|
|
gene which meant I grew up to be a normal height instead of being an
|
|
achondroplastic dwarf, I'd dance with the devil, sign and pay up and cop
|
|
the gene which gave me socially normal abilities. Where would the
|
|
inspirational artwork of VanGogh or the writings of Helen Keller or
|
|
Lorenzo Milam come from in a world without genetic difficulties or
|
|
diseases to overcome? Is this a part of the human experience we should
|
|
lose? This is something for the sufferers to tell us.
|
|
<p>
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|
|
|
None of us asked for the bodies we
|
|
are born in or the brains in which our personalities operate. Neither will
|
|
any humans who grow up to discover that they've had their genome tinkered
|
|
with. Hopefully they won't curse us for giving them a gene which was
|
|
fashionable ten years ago but which is now though of as a social stigma.
|
|
Would male pattern baldness become a thing sported proudly, which says "I
|
|
run wild type human DNA - a bunch of software proven stable over thousands
|
|
of years"?
|
|
|
|
<p>Every
|
|
conception is an experiment in applied embryology and, as gynaecologists
|
|
will tell you, nature is the ultimate eugenicist - lots of embryos are
|
|
spontaneously aborted, some before they get out of the first trimester,
|
|
many of these are just intrinsically not viable at a molecular biology
|
|
level, something went awry with some serious part of the developmental
|
|
process. It won't be very different with germinal modifications. I'd tend
|
|
to not tinker with crucial things I don't understand. I hope biotech firms
|
|
learn this posture before they rob us of our own
|
|
indentities.<p>Q:
|
|
sheesh, can I go now? <br>A: Certainly.<br><a
|
|
href="mailto:predator@cat.org.au"><predator></a>
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</body> </html>
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