ISIS Report 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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