Hi Joe and other sanet subscribers following this important thread:
Prof. Cummins wrote:
Thank you for the interesting questions. I read the paper in
science along with its accompanying on-line 32 page description of
the genetic methodology used to create the high ethanol yeast.
Before answering your questions I will go into the methodology a
bit. I will mention that I taught Microbial Genetics for over
twenty five years and published in both yeast and fungal genetics
and molecular biology.
The system developed for making high ethanol yeast is certainly
genetic engineering but it is not genetic modification with
transgenes.
Key regulators for production of high level ethanol in the
presence of high level glucose were identified in yeast. Those
genes DNA sequences were altered by a process called site specific
mutagenisis then reinserted into the yeast at a particular locus
(the uracil gene).
Could you describe the process of "site specific mutagenisis" used
to alter the DNA sequences of the high level ethanol production
genes; and explain how researchers were able to reinsert these DNA
sequences into the yeast genome at a particular locus (the uracil
gene) with such great precision?
The fact that they were able to do this seems strange to me, because
as I understand it, when the GE organisms sold by Chem/Gene/Seed
companies like Monsanto and DuPont (which apparently participated in
the creation of the GE yeast referred to), were created, there was
no way to determine where within the genome the inserted gene would
end up, thus shifting the rest of the genome's components in the
process and as a result, making the genome itself unstable. Is that
correct, Professor? And if so, how is the process used by the MIT
group different? How were they able to take out specific genes and
reinsert them into the exact same place?
One significant difference may be the fact that no new genes are
inserted in this process, I suppose. Another significant difference
may be the fact that yeast is a much simpler organism (which
therefore, has a much simpler genome) than the genomes of the plants
cultivated by man. Likewise, more is known about yeast genetics than
is the case with corn, soy, cotton, rice and potatoes etc. Is that
correct?
The regulatory genes controlled a number of genes in a metabolic
network for ethanol production and most importantly, [the]
ability to tolerate high levels of ethanol and glucose.
The current work on such key regulators follows work on E coli
ethanol production by modifying a sigma factor regulator of
transcription. Douglas asked "However, we could call the effect I
refer to "genome shifting", which adds an unknown, unforeseeable
and uncontrollable element to the expected results. Do you agree?"
I do not entirely agree.
Yeast genetics are far more precise than the crude methods used in
crop plants and the genes in the yeast have been precisely altered
by mutations on knowingly altered DNA. Manipulating a metabolic
network is new and breathe taking but could lead to unexpected
toxins being produced.
These will have to be checked on in the near future but since the
yeast is not for very strong beer but for commercial ethanol fuel
the toxins could be ignored. A former student and colleague, Inge
Russel, developed a very high ethanol yeast by breeding and
selection alone and her strain is presently better than the
promoted higher tech system because it was bred from a commercial
ethanol yeast rather than into the laboratory strains used in the
high tech version. Lab yeast tend not to do all that well in
commercial operations for brewing, wine making or ethanol making.
The gene regulators are somewhat similar to the MADS box
regulators growing popular in crop genetic manipulation that I
discussed previously. However, the MADS box alterations have been
transgenic while the network ethanol yeast are not.
Douglas asks "To what extent is the GE yeast likely to cross with
native yeasts existing in nature? Is the threat similar to that
created by GE crops, or are GE yeasts likely to be less
threatening? You ask an important question Douglas. My feeling
this that regulators will have a hard time getting their teeth
into genes that are precise;y altered within a particular
organism.
If unexpected toxins are produced because of metabolic network
alterations then we are in real trouble. Bakers yeast is not a
pathogen to anything , I believe, but it has been used as a
probiotic. Killer beer is every boy's nightmare! However, the
toxins should show up early and be dealt with promptly or even
ignored for making fuel. However, toxic ethanol yeast in the gut
would not be any fun at all.
Manipulating metabolic networks is brand new but clearly here to
stay. Organic farmers and the industry will soon be faced with
difficult decisions about organic foods. Can genes and networks
manipulated by engineered DNA code word changes within a crop be
considered organic? We will soon have to decide.Let us hope the
decision is ours and not the bureaucrats.
Finally, many recollect that I objected to GM wine and I still do.
That stuff is transgenic and should be labeled, dammit all. You
cannot imagine the abuse I get from the developers of GM wine!
Thanks so much for the important questions, excuse my rambling
answers.
Your answers were clear and to the point, Professor. And we are very
fortunate to be able to be able to draw on an information source
coming from the highest possible level, both in terms of your
technical competence and scientific credibility but also (and
very significantly), in relation to the critical social and
environmental factors that come into play in the context of this
issue.
And for that all of us here thank you, Joe.
Douglas
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