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World Scientists’ Statement
Update #2 (22.9.99)
Written and compiled by Mae-wan Ho and Angela Ryan
Institute of Science in Society
A. Biopatents
1. African group tables important proposal at the World Trade
Organisation which may revoke and ban biopatents. The full proposal can be
found at the WTO website.
The African group questions TRIPS requirement for mandatory
patenting of some life forms and some natural processes. They
propose that all plants, animals and microorganisms should not be
patentable. They seek clarification that "sui generis"
system of plant varieties protection can include systems that protect the
intellectual rights of indigenous and farming communities. They have
also asked for TRIPs to be made to harmonize with the biodiversity
convention and the FAO’s International Undertaking on Plant Genetic
Resources.
This proposal is most significant. ISIS have given it our wholehearted
support, as it may lead to international agreement that all biopatents
will be banned.
Please support the African Group’s position by sending your name,
organization and address to twnet@po.jaring.my ,
so that the issue can be made high priority for the WTO Seattle Conference
December 2-3, 1999.
2. Anglo-American Agreement to protect Human Genes
British Prime Minister Tony Blair has initiated an extraordinary deal
with US President Bill Clinton to negotiate an Anglo-American agreement to
protect the 100,000 genes of the human body. The deal aims to
prevent entrepreneurs profiting from gene patents and to ensure that the
benefits of research are freely available world wide to combat or even
eliminate diseases.
The two leaders aim to ensure that the world’s largest medical
charity, the British-based charity, Wellcome Trust, and the US government’s
National Institute of Health, publicize gene-sequences within 24 hours of
their discovery so that the benefits accrue entirely to the public. It
is thought that research institutions, universities or laboratories would
be obliged to waive their rights to patent their work in the public
interest.
ISIS welcome this move by Blair and Clinton. The next step is to prevent
all living organisms, seeds, genes and cell lines from being patentable.
B. New Evidence of Hazards and Potential New Hazards
1. The human mouth and pharyngx contain bacteria that can take
up and express transgenic DNA, including antibiotic resistance marker
genes. This confirms the ability of transgenic DNA to spread by horizontal
gene transfer.
The findings: A genetically engineered plasmid was found to survive (6
to 25%) up to 60 min. of exposure to human saliva. Partially degraded
plasmid DNA was capable of transforming Streptococcus gordonii,
one of the bacteria that normally live in the human mouth and pharynx and
are naturally transformable. The frequency of tranformation dropped
exponentially with time of exposure to saliva, but it was still greater
than 10-7 after 10 mins. Transformations were also
obtained when plasmid DNA was mixed directly with filter-sterilised human
saliva. Approximately 107 transformants were
obtained per microgram plasmid DNA. Whole (unfiltered) saliva had a
background of erthyromycin-resistant bacteria, but transformation of the
test strain occurred nevertheless at a high frequency of 10-4
of all colonies of S. gordonii isolated. Human saliva contains
factors that promote competence of resident bacteria to become transformed
by 'free' or 'naked' DNA.
Our comment: Transgenic DNA from food is unlikely to be completely
broken down in the mouth, and may transform bacteria normally present in
the mouth. One main danger is the uptake of transgenic DNA containing
antibiotic resistance marker genes by the bacteria, but other genes and
novel constructs involving viral promoters/enhancers may also be
hazardous.
Reference: Mercer, D.K., Scott, K.P., Bruce-Johnson, W.A. Glover, L.A.
and Flint, H.J. (1999). Fate of free DNA and transformation of the oral
bacterium Streptococcus gordonii DL1 by plasmid DNA in human saliva. Applied
and Environmental Microbiology 65, 6-10.
2. Special Report comissioned by UK Ministry of Agriculture
Fisheries and Food (UK MAFF) shows that DNA is not readily degraded by
most commercial processing procedures. Animal feeds are likely to contain
gene-size DNA fragments. One main conclusion is that there is significant
risk of transmitting transgenes in the gut of farm animals, and recommends
against using ensilaged GM crops as animal feed.
The findings: Samples of oil seed, linseeds, soya and wheat were
analysed for DNA fragments after various treatments. Grinding and milling
left DNA largely intact, as did treatment with dry heat for 30 mins. at 90
deg. C. Degradation to less than 100bp occurred only after treatment with
dry heat at 96 deg.C or moist heat at 93 deg. C. DNA was completely stable
in silage.
Reference: Forbes, J.M., Blair, D.E., Chiter, A. and Perks, A. (1998).
Effect of Feed Processing Conditions on DNA Fragmentation Section 5 –
Scientific Report,UK Ministry of Agriculture Fisheries and Food,
London.
Our Comment: It should not be assumed that processed food contains no
DNA. The degradation of DNA is defined as less than 100bp. We now know
that (see below) nucleic acids as small as 25bp can stimulate autoimmune
reactions.
3. Gene therapy and naked DNA vaccines can trigger autoimmune
reactions. New research shows that any fragment of double-stranded (ds)
DNA or RNA introduced into cells can induce these reactions. (Thanks to
Brian Goodwin for drawing our attention to this item.)
The findings: Immune reactions are normally mounted by white blood
cells against substances (antigens) foreign to the body, and involve the
expression of many different genes. Autoimmune diseases are associated
with abnormal reactions of other cells directed against the body's own
constituents, and can be triggered by viral infections. Autoimmune
diseases can be specific to organs or cells, examples are rheumatoid
arthritis, insulin-dependent diabetes and Graves disease of the thyroid.
The researchers found that introducing any fragment of dsDNA or dsRNA into
the cells by transfection stimulate the abnormal expression of major
histocompatibility complex (MHC) class I and class II genes as well as
other genes involved in presenting antigens on the surface of the cell
membrane. This in turn induces activation of immune cells against the
antigen-presenting cells. The effects were indifferent to the sequence of
nucleic acid introduced, so long as it is double-stranded; and fragments
as short as 25 base pairs were effective. The authors conclude, "This
phenomenon may contribute to the development of autoimmunity when plasmid
DNA is introduced during gene therapy and may be important when dsDNA is
used in plasmid DNA vaccinations."
Reference: Suzuki, K., Mori, A., Ishii, K.J., Singer, D.S., Klinman,
D.M., Krause, P.R. and Kohn, L.D. (1999). Activation of target-tissue
immune-recognition molecules by double-stranded polynucleotides. Proc.
Natl. Acad. Sci. USA 96, 2285-90.
Our comment: This research not only raises serious safety concerns over
gene therapies and the use of naked DNA vaccines, it also emphasises the
need to regulate the ever-increasing use of all kinds of naked DNA and RNA
such as plasmids and vectors and to prevent their discharge into the
environment. In view of the fact that fragments as small as 25bp can
stimulate autoimmune reactions, naked DNA or RNA should be fully degraded
before being discharged.
4. A scientist from the Center for Complex Infectious Diseases
in Rosemead, California, claims to have found a new virus associated with
chronic fatique syndromes which is part bacteria. Could genetic
engineering have contributed to creating it?
The findings: More than 50 bacterial genes were found in a virus
isolated from patients with various chronic fatique syndromes. The
scientist regards this as a new organism and coined the term, "viteria"
to describe the hybrid virus-bacteria. The virus most closely resembles a
cytomegalovirus. And top of the list of bacteria from which the virus has
captured genes are E. coli and Bacillus subtilis.
Our comment: This new discovery should be seen in the light of a report
on the possible links between genetic engineering biotechnology and the
resurgence of infectious diseases co-authored by seven scientists, four of
whom have signed onto the World Scientists' Statement (Ho, M.W., Traavik,
T., Olsvik, R., Tappeser, B., Howard, V., von Weizsacker, C. and McGavin,
G. (1998). Gene technology and gene ecology of infectious diseases. Microbial
Ecology in Health and Disease 10, 33-59.) The report was among the top
ten 'Project Censored' stories in 1998. It drew attention to, among other
things, pathogenicity islands coding for many virulence genes that
transfer horizontally as a unit, so non-pathogens can be converted into
pathogens in a single step.These pathogenicity islands are thought to have
originated from bacterial viruses which have integrated into bacterial
genomes and picked up a range of virulence genes. They are highly mosaic,
consisting of parts of plasmids and bacteria, particularly of those parts
that might have been assembled into artificial vectors for genetic
manipulation. Could genetic engineering have inadvertently contributed to
creating pathogenicity islands? Could the newly discovered 'viteria' be
pathogenicity islands that have gained independent existence as infectious
particles? These are question which urgently need to be addressed.
Cytomegalovirus, which the viteria most resembles, is one of the first
viruses to be used as vector in genetic manipulation of animals, while
E. coli and B. subtilis the top two bacteria from which it
has acquired genes are also the two most commonly used bacteria in genetic
engineering.
Reference: Martin, W.J. (1999). Bacteria-related sequences in a simian
cytomegalovirus-derived stealth virus culture. Experimental and
Molecular Pathology 66, 8-14.
5. A new genetic engineering technique, 'chimeroplasty' claims
to overcome the current hit or miss transgenic technology that results in
random gene insertions and rearrangements; instead, it can change a single
base at a predetermined position in a specific gene in the plant cell. But
it may not be as precise as claimed and introduces new dangers. (Thanks to
Suzanne Wuerthiele for drawing our attention to this paper.)
The findings: A technique of directed gene conversion involves
introducing a palindromic inverted repeat of a sequence of 25 bases
composed of DNA and modified RNA residues, which forms a stable hairpin.
The sequence is homologous to that of the target gene, except for the base
to be substituted, which is in the middle of the sequence of 25 bases.
When introduced into the cells by a gun that shoots tiny gold particles
coated with the hairpins, the hairpins will basepair with both strands of
the target sequence in the gene. DNA mismatch repair enzymes will then
convert the sequence of the gene to that specified by the hairpin. Using
this technique, the researchers attempted to convert a gene in tobacco
coding for the enzyme acetolactate synthase to a herbicide-resistance
phenotype, by changing the codon (CCA) for proline at amino-acid position
196 to CAA for glutamine and CTA for leucine respectively, with two
different hairpin constructs. The results show that the target sequence
was converted, but not at the base intended. Conversions were at
neighbouring bases. For example, ACA for threonine was obtained instead of
CAA intended, and TCA for serine resulted, as well as ACA and TCA instead
of the intended CTA. Another complication is that the gene is capable of
undergoing spontaneous mutations to herbicide resistance. The directed
mutation rates were up to 20-fold those in controls, but were variable
from experiment to experiment.
Our comment: It is very unlikely that the technique is as precise as
claimed. The mere act of introducing nucleic acid sequences into the cells
by bombardment with a particle-gun will trigger injury responses that can
cause nonspecific recombination. In addition, the technique depends on
imprecise basepairing between the target sequence and the introduced
hairpin. Can one be sure that nontarget sequences are never affected? The
hairpins themselves are a hazard to biodiversity and health if released
into the environment. All kinds of unintended gene conversions could take
place in species exposed to the constructs, including human beings.
Reference: Beetham, P.R., Kipp, P.B., Sawycky, X.L., Arntzen, C.J. and
May, G.D. (1999). A tool for functional plant genomics: Chimeric RNA/DNA
oligonucleotides cause in vivo gene-specific mutations. PNAS 96,
8774-8778.
6. "The Herbicide, Glufosinate, used with millions of acres
of GM crops including corn, canola and soy, causes birth defects on
exposure of father alone as well as mother!" submitted by Joe Cummins
Joe Cummins has written a number of previous notes on the danger of the
herbicide ,glufosinate, used with GM and normal crops and on the false
claims by officials of EU , US and Canada that the herbicide has no
harmful side effects. The previous evidence showed that pregnant females
fed food containing the herbicide gave birth to children with birth
defects, as well as defects in behavior and learning. Learning defects
were also experienced by young children exposed to the herbicide. Recent
studies showed that fathers exposed to glufosinate gave birth to children
with birth defects while most other pesticides did not produce the same
effect.
Reference: Garcia,A.,Benavides,F.,Fletcher,T. and Orts,E. (1998).
Paternal exposure to pesticides and congenital malformations. Scand J
Work Environ Health 24, 473-80.
Joe Cummins comments: The glufosinate birth defects suggest that the
large chemical companies have undue influence over government bureaucrats
. Such bureaucrats turn their backs on clear evidence of danger from
pesticides and promote dangerous genetic engineering.
7. A new study looks at the prevalence and spatial distribution
of viruses in natural populations and discusses the implications of
widespread multiple viral infections in natural plant population with
respect to the release of transgenic plants expressing virus-derived
genes.
A quote from this paper: " The presence of transgenic virus
resistant plants expressing viral proteins or virus-derived nucleic acids
introduces a substantially new dimension into the dynamics of plant-virus
co-evolution, even though virus-derived nucleic acids are normal
constituents of plant populations. There is a possibility that the
spread of virus-derived transgenes through seed and pollen will
substantially alter the distribution of viral nucleic acids, for example,
gene flow might reduce temporal and spatial variation in the incidence of
virus-derived nucleic acids and so increase the potential for
recombination."
Reference: Raybould et al (1999) The prevalence and spatial
distribution of viruses in natural population of Brassica oleracea .
New Phytol 141, 265 275
8. "Virus-Resistant Crops Could Help Weeds" Says
Professor Alison Power.
Genetic engineering cereals to resist the barley yellow dwarf virus
(BYDV) might indirectly cause farmers difficulties in controlling related
weeds. A report presented at the Ecological Society of America1s annual
meeting indicates that the resistance engineered into oats could spread to
wild oats, a weed. Transgenic barley and oats that can resist BYDV have
been developed, but there is concern that because these crops can
hybridize with wild relatives, that the introduced genes will escape into
related weeds. Alison Power, an ecologist at Cornell University says that
if wild oats gain resistance to BYDV, they could become a much larger
problem for farmers, and might also disrupt natural habitats, outcompeting
other native species. Power grew oats and wild oats in greenhouses
and infected them with the BYDV. She found that infected wild oats did not
perform well: they were much thinner and had shorter roots than uninfected
controls and infected oats. Infected wild oats also produced fewer seeds
than normal. "A BYDV-resistant transgene transfer seems likely to
help wild oat survivability," concludes Power.
Reference: Contact: Alison Power, Department of Ecology and
Evolutionary Biology,E331A Corson Hall, Cornell University, Ithaca,
NY 14853,USA.
9. An independent study has shown that the phytoestrogen
concentrations in two varieties of GM herbicide tolerant soyabeans were
reduced by an average of 12-14 % compared to their non GM counterparts.
Most of the reduction was attributable to reductions in genistin and to a
lesser extent diadzin levels, which were significantly lower in modified
compared to conventional soybeans in both strains.
Soyabean-based food products are of growing medical interest as they
contain two key biologically active ingredients, notably genistin and
diadzin, which are phytoestrogen. A number of studies have indicated
that phytoestrogen content of ingested soybeans can modify the
pathogenesis of some hormone-dependent and hormone-independent diseases
and may constitute a natural estrogen replacement therapy in post
menopausal women. In the United States approximately one half of the
1998 soyabean crop consisted of GM, herbicide-tolerant soyabeans, of which
33% are slated for export, thus the phytoestrogen content of GM soyabeans
is of international interest Given the high biological potency of
isoflavones and their metabolic conversion products, these data suggest
genetically modified soybeans may be less potent sources of clinically
relevant phytoestrogens than their conventional precursors. In order
to ensure uniformity of clinical results the scientists who conducted this
study strongly suggest there is a need to establish baselines of expected
isoflavone levels in transgenic and conventional soy products so as such
data will be available when making clinical decisions.
Reference: Lappe et al (1999) Alterations in Clinically Important
Phytoestrogens in Genetically Modified, Herbicide-Tolerant Soybeans.
Journal of Medicinal Food, Vol 1, no 4.
Our comment: The unpredictability in the composition of GM crop
plants is highlighted by this study and further confirms the inadequacy of
the regulatory protocols, which rely on the principle of ‘substantial
equivalence’ for approving GM crops and products.
10. An investigative safety assessment study carried out at
the Scottish Crop Research Institute in Dundee (completed in 1997) has
shown that Agrobacterium used in the production of GMOs is a
possible vehicle for gene escape, or horizontal gene transfer.
The findings: The study shows that the use of frequently used
antibiotics, carbenicillin, ticaracillin and cefotaxime failed to
eliminate contamination of Agrobacterium even after 13 months of
repeated subculture from transformed and weaned plants. Furthermore
a significant percentage (12.5%) of Agrobacterium containing the
binary vector was detected in tissue culture after six months, even
without selection pressure being maintained. The MAFF, R&D
Surveillance report No. 395 states that:
" The presence (contamination with) of disarmed (but foreign gene
containing) Agrobacterium in GMO plant tissues would not represent
a risk if the binary vector had been ‘lost’, but the discovery
that it survives, even without selection advantage, indicates that gene
spread is a real possibility."
The presence of latent Agrobacterium was also observed during the
tissue culture phase of GMO production. The scientists who conducted
this study stress the need for sampling tissues for contamination and not
merely relying on the lack of visual symptoms. They strongly suggest that
such procedure should be adopted routinely, for in the case of Agrobacterium,
sampling is the only reliable method of indicating contamination.
References: McNicole et al (1997) The Possibility of
Agrobacterium as a Vehicle for Gene Escape. MAFF. R&D and
Surveillance Report: 395.
Carol Barrett et al (1997). A risk assessment study of
plant genetic transformation using Agrobacterium and implications
for analysis of trangenic plants. Plant Cell. Tissue and Organ
Culture 47: 135-144.
Our Comment: It is claimed that other more effective antibiotics
are now used to eliminate Agrobacterium from GM plant material and
the above mentioned sampling procedures are now thought to be implemented.
But, before the results of the above study became available,
it is likely that most GM plants transformed by Agrobacterium were
contaminated with residual Agrobacterium containing antibiotic
resistance genes. Most of the present generation of GM crops
commercially grown or being field-tested were, in fact, created before the
results of this study were published and therefore carry this risk. The
above study demonstrates that major flaws in safety assessments are being
uncovered only after the products have been approved.
A new study on the effects of a genetically engineered microorganism
(GEM) on soil biota and plant growth has shown that GEMs can persist under
conditions found in some soil ecosystems for long enough periods of time
to stimulate major changes in soil biota that could affect nutrient
cycling processes. Nematode community composition and plant growth were
also affected following the introduction of the GEM.
Reference: Holmes M T et al (1999). Effects of Klebsiella
planticola SDF20 on soil biota and wheat growth in sandy soil. Applied
Soil Ecology 11 (1999) 67-78
Our comment: Further investigations are needed to determine the long term
effects of these observations and whether the release of GEMs have a
viable future. The potential for an ecological effect to occur after the
release of GEMs is now apparent and of global concern.
And now the goood news...
11. Non-functional genes in patients with Fanconi anaemia
undergo corrective mutations spontaneously to restore normal function.
These are the latest examples of functional corrections that can occur in
a range of different hereditary defects which show how fluid and dynamic
genes and genomes are. Molecular geneticists should investigate the
physiological and environmental factors favouring such functional
corrections of defective genes instead of concentrating exclusively on
changing and transferring genes.
(Thanks to Wytz de Lange for drawing attention to this paper.)
The findings: Somatic cells in individuals with non-functional
pathogenic alleles (forms of a gene) have recently been discovered to
revert spontaneously to functional, wild-type alleles. The best known
mechanisms occur in heterozygous patients, ie, patients with two different
alleles of the gene and involves recombination within the gene during
ordinary cell division, in which the two alleles present exchange parts,
or gene conversion, in which the functional allele converts the
non-functional. New mechanisms of corrections are described for
non-functional alleles in homozygous patients (those with two identical
alleles). Frameshift alleles in two different patients were restored to
the correct reading frame, in one case, by deletions of two single
base-pairs, and in the second, by insertion of 5 base-pairs. A missense
mutation in another patient (T to G in position 1749) was compensated by a
C to T mutation in position 1748. Although the protein in all three cases
differed in amino-acid sequence from the wild-type, they were functionally
equivalent to the wild-type.
Our comment: These are the latest examples of the fluidity of genes and
genomes which has completely invalidated the genetic determinist science
driving and promoting genetic engineering biotechnology. Evidence
accumulating since the mid 1970s indicates that there is nothing constant
about genes and genomes.The new observations that even nonfunctional genes
can revert to functional wild-type or wild-type equivalents take genomic
fluidity one step further. Rather than concentrating exclusively on
changing and transferring genes, molecular geneticists ought to direct
their attention to the physiological and environmental factors that favour
the regulation of gene function and structure in the whole organism, even
to the extent of correcting the structure of non-functional genes.
Reference: Waisfisz, Q., Morgan, N.V., Savino, M., et al (1999).
Spontaneous functional correction of homozygous Fanconi anaemia alleles
reveals novel mechanistic basis for reverse mosaicism. Nature Genetics
22, 379-383
C. New Postings on ISIS website: www.i-sis.org.uk
- Open Letter to all governments from world
scientists. It re-iterates our World Scientists’ Statement call for
a 5 year moratorium and a ban on biopatents. We are encouraging other
scientists to sign on and non-Government organisations to endorse our
Statement and Letter. Either sign on to our
statement on our website, or e-mail us at
jules@i-sis.org.uk
- From BSE to GMO – What Have We Learned?
by Dr. Harash Narang, with Introduction by Angela Ryan. This is a new
ISIS publication in collaboration with the Millenium Debate, due to be
released 26 September, 1999.
- The precautionary principle by Dr. Vyvyan Howard and Prof. Peter
Saunders, published in Nature correspondence, 16 September, 1999.
- Head to Head, by Mae-Wan Ho, to appear in
Sovereign magazine.
- No to GMO, Civil Society versus Corporate
Empire, talk presented in Progressive Farm Leaders Summit on
Genetic Manipulation and Agriculture, Coalition of Family Farmers, USA,
Mannassas, Virginia, September 11, 1999.
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