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[SANET-MG] ban gm probiotics



http://www.i-sis.org.uk/BanGMprobiotics.phpISIS Press Release 22/04/05
Ban GM Probiotics
Beneficial bacteria living in the human gut are now subject to extensive
genetic modification that could turn them into pathogens. Prof. Joe
Cummins and Dr. Mae-Wan Ho call for a ban on releases of GM probiotics

The fully referenced article is posted on ISIS members’ website. Details
here.

Probiotics for health
‘Probiotics’ are naturally occurring beneficial bacteria found in the
human gut, and are being added to food for their health-promoting
effects. The probiotics studied most extensively are Bifidobacterium and
Lactobaccilus, both derived from fermented milk products. The efficacy
of probiotics has been clearly established in recent years. For example,
double blind, randomized trials with probiotics added to milk reduced
respiratory infections and the severity of illness among children in a
day care setting . Another study showed that probiotic treatment
relieved diarrhea in children.

This success has attracted the attention of genetic engineers, who want
to "improve" on the successful applications, which probably date back to
the beginning of written history.

The cross-talk between the human host and the gut bacteria has evolved
over millions of years. Its contributions to the health of the human
host depend on an intricate network of bacteria-bacteria and
bacteria-host interactions that, if thrown out of balance, will very
likely result in disease.

Can GM "improve" probiotic bacteria without turn them into dangerous
pathogens?
Probiotic bacteria modulate the immune system and provide an ecological
balance in the gut that excludes disease-causing microbes. Germ-free
mice bred in the laboratory have less immune cells, and tend to leak
more food antigen across the intestinal barrier. These conditions
improve after about a month of exposure to bacteria. Probiotic bacteria
must not be pathogenic, however; and it is essential for probiotic
treatments to be tested for safety. The vast majority of applications
have been free of pathological outcomes; but there has been one case of
local infection from a rogue Lactobacillus strain. The prospect that
genetic modification might "improve" probiotic microbes must be
seriously balanced against the potential of turning harmless, beneficial
microbes into dangerous pathogens ("No biosecurity without biosafety",
ISIS report 16 March 2005), particularly in the case of bacteria that
naturally inhabit the human gut.

The complete genome sequence of the probiotic Lactobacillus acidophilus
has been determined and features contributing to survival in the gut and
promoting interactions with the intestines have been identified. The
genome sequence of Bifidobacterium longum, similarly, reflects its
adaptation to the human gastrointestinal tract including potential
immuno-modulating proteins. Milk-fermenting bacteria harbor
bacteriophages (viruses), including those that cause diseases, and
‘temperate phages’ capable of integrating their viral genome into the
bacterial genome. Temperate bacteria phages play an important role in
horizontal gene transfer among bacteria residing in the same
environment, in this case, the human gut.

Genetic modification of bacteria can be done by DNA transformation
(direct uptake of DNA), transduction (transfer of genes by temperate
bacterial phage) or by the use of plasmids (small circular DNAs that
replicate with the bacterial cell but stay outside the bacterial
chromosome). Normally, transgenes are propagated in bacteria in plasmids
because DNA transformation is not successful unless the DNA shares
homology (sequence similarity) with the bacterial chromosome.

Lactic acid bacteria (Lactobacillus spp) have been genetically modified
to increase proteolytic activity, to resist viruses, to metabolize
complex carbohydrates or to enhance metabolism. The only modified lactic
acid bacterium approved under the EU directive so far is a strain with a
modified luciferase gene to detect antibiotic residues in milk, but that
strain does not enter the food chain because it is used on a small test
sample of milk that is then destroyed.

Dangerous experiments with probiotics
It has been suggested that a random ‘gene-shuffling’ technique should be
employed to improve lactic acid bacteria for use as probiotics.
Gene-shuffling is an inherently hazardous procedure that can generate
millions of recombinant bacteria in a matter of hours; it will be
impossible to predict how many of those might be lethal pathogens
("Death by DNA shuffling", SiS 18 http://www.i-sis.org.uk/isisnews.php).

A United States patent application for recombinant lactic acid bacteria
for treating allergy includes fermented milk product (yogurt) containing
lactic acid bacteria modified with synthetic genes specifying epitope
IgE antibodies (allergy antibodies) on the surface of the bacterium.
Allergy therapy would include eating the recombinant yogurt to suppress
the allergy as the natural allergen is encountered. This kind of
‘therapy’ must be treated with extreme caution. Experience tells us that
interfering with the immune system can lead to nasty surprises, as in
the case of the harmless mousepox virus that turned into a lethal
pathogen when a gene that was supposed to boost antibody production was
inserted into it. In another experiment, a Lactobacterium strain of
human origin was modified with a gene for tetanus toxin to produce
antigen to immunize against tetanus. The recombinant lactic acid
bacterium was delivered as a nasal spray to provide a strong
immunization. No consideration has been given to the distinct
possibility that the tetanus toxin gene could easily be passed along to
a pathogen.

Genetic engineers are also identifying Bifidobacteria probiotic strains
and thinking of ‘enhancing’ them by genetic modification. Plasmid
vectors belonging to Bifidobacteria or shuttle plasmid vectors for
transferring genes between E. coli and Bifidobacteria are being used, so
far, to study the role of Bifidobacteria in the gut ecosystem rather
than in the production of modified probiotic strains. The instability of
recombinant plasmids has proved an obstacle to industrial exploitation
of GM Bifidobacteria. Furthermore, gene transfer was observed in the
digestive system of previously germ free mice between Lactobacteria and
Bifidobacteria, suggesting that GM probiotic strains would alter the
entire microbial ecology of the digestive tract in an unpredictable manner.

A recent review stressed the huge market for probiotics in Europe,
pointing to the value of molecular genetic technology in characterizing
and identifying many probiotic microbes. An earlier review discussed
bacterial replacement therapy as a form of "germ warfare" to prevent and
control infections of skin, oral cavity, ears and uro-genital tract. The
friendly probiotic bacteria are used to colonize the gut microflora to
eliminate or minimize pathogens from establishing themselves. That
approach has proved successful in controlling dental caries, ear
infections and streptococcal diseases. In some rare instances, the
"friendly" bacteria had antibiotic resistance markers or were
genetically modified.

No GM bacteria must be allowed for probiotic use
The study of bacteria colonizing the human gut has only just begun.
There are ten times more bacteria than there are cells in the intestine,
consisting of more than 400 different species; the overwhelming majority
of the species still unknown. Prof. Tore Midtvedt, who pioneered the use
of germ-free mice to study gut bacteria, was among the first to
demonstrate the importance contribution of individual bacteria to the
development of the immune system of the gut. In view of our vast
ignorance of gut ecology, we cannot allow genetically modified probiotic
bacteria to be used, unless and until we fully understand the intricate
ecological balances that have co-evolved with the human species. There
should be a ban on the use of any GM probiotic bacteria in human subjects.



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