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ISIS Report 19/09/05
The article below has been submitted on behalf of the Independent
Science Panel to the Niigata Prefecture in Japan, in support of legal action
taken by 12 Japanese citizens seeking to halt the trial of transgenic rice producing
antimicrobial peptides. Please circulate widely and send to your elected representatives.
Submit it also to the US Environmental Protection Agency and demand
comprehensive risk assessment for transgenic plants producing another antimicrobial
peptide that have been widely field-tested and may be poised for deregulation.
No to Releases of Transgenic Plants with Antimicrobial Peptides
Professor Joe Cummins and
Dr. Mae-Wan Ho
Anti-microbial
peptides provide the first line of defence against invading microbes
in both plants and animals. The peptides are involved in innate immunity,
and are 15 to 40 amino acids in length, most of them hydrophobic (water-hating)
and cationic (positively charged). They provide protection from bacteria,
fungi and viruses, acting mainly at the cell membrane of pathogens [1,2].
The peptides are beginning to be employed in
medicine and in crop protection.
A synthetic
peptide D4E1 based on
the cecropin B peptide toxin (obtained from the moth, Cecropia),
consists of a linear sequence of 17 amino acids: FKLRAKIKVRLRAKIKL (F for
phenylalanine, K for lysine, L for leucine, R for arginine, A for alanine,
I for isoleucine, V for valine). The peptide protected against Aspergillus and Fusarium fungi. It acted by binding to ergosterol, a sterol
present in fungal cell walls [3]. On further tests, D4E1 was found to have
broad-spectrum antimicrobial action, and was active against fungi belonging
to the orders Ascomycete, Basidiomycete, Deuteromycete and Oomycetes, as well
as bacterial pathogens Psuedomonas
and Xanthomonas [4]. The D4E1
toxin also proved effective in the treatment of human Chlamydia infection [5].
Transgenic tobacco plants transformed with a gene for the peptide D4E1 (driven
by a double CaMV promoter and terminated by the nos transcription terminator,
accompanied by a kanamycin resistance marker) was resistant to fungal pathogens
[6]. Poplar trees transformed as in the transgenic tobacco was resistant to
bacterial pathogens A. tumefacians and X. populi but not to the
fungal pathogen Hypoxylon mammatum [7]. Cotton plants transformed similarly
with the gene coding for D4E1 showed resistance to fungi including Fusarium,
Verticillium and Aspergillus, hence the synthetic peptide was
proposed to be effective against mycotoxin-causing fungal pathogens [8].
Field tests have been conducted on D4E1 transgenic plants in the United States,
transgenic cotton in Arizona and California, and transgenic potatoes in Idaho
[9]. It seems inevitable that petitions to remove the transgenic crops containing
D4E1 from regulation are not far off. As the D4E1 gene and its peptide product
are both fully synthetic, it will be a stretch to assume that the product is
“substantially equivalent” to the natural product.
Meanwhile, researchers at the National Agricultural Research Center, Niigata, in Japan have created transgenic rice
with genes of the antimicrobial peptide, defensin, from Brassica. The transgenic rice plants were
resistant to rice blast disease caused by the fungus Magnaporthe grisea. The researchers
went a step further and systematically altered the genetic code for defensin to produce synthetic peptides
that were far more toxic to the fungus than the natural peptides [10]. Rice with the synthetic genes and peptides are being proposed for field-testing
prior to commercial release in Japan, and little effort appears to have been devoted
to evaluate the safety for human health and the environment.
We agree with microbiologist Dr. Takahiro
Kanagawa, a senior scientist at one of Japan’s leading research institutes
that releases of transgenic plants containing anti-microbial peptides are
dangerous [11]. Defensins and other peptides are, for plants and animals,
their first defence against pathogens. Just as D4E1 was effective against Clamydia infections [5], alpha-defensins,
identified in long-term nonprogressors with HIV-1 infection [12], may well
have applications in preventing AIDS disease.
The danger highlighted by Dr. Kanagawa is that environmental
releases of these antimicrobial peptides will lead to the evolution of resistance
among microbial pathogens. As Dr. Kanagawa points out, there is already a
report of yeast evolving resistance to defensin from Dahlia after two days
of co-cultivation [13].
The evolution of resistance
to antimicrobial peptides will severely compromise both the natural defence
of the human immune system against disease and the possibilities of effective
therapies emerging in the wake of the disaster of widespread antibiotic resistance. As versions of the peptides also provide defence against pathogens in other animals and
plants, the ecological impact of resistant pathogens could be devastating.
Another factor adding to the hazards to health and
the environment is that the synthetic transgenes code for peptides that are
significantly different from the natural versions. This may itself be responsible
for toxic or other harmful effects that cannot be known unless thoroughly tested.
References
- Bulet P, Stocklin R. and Menin L. Anti-microbial peptides: from invertebrates
to vertebrates Immunol Rev. 2004 ,198,169-84,
- Boman, H. Antibacterial peptides: basic facts and emerging concepts. J
Intern Med. 2003, 254(3), 197-215.
- De Lucca AJ, Bland JM, Grimm C, Jacks TJ, Cary JW, Jaynes JM, Cleveland
TE and Walsh TJ. Fungicidal properties, sterol binding, and proteolytic resistance
of the synthetic peptide D4E1. Can J Microbiol. 1998, 44, 514-20.
- Rajasekaran K, Stromberg KD, Cary JW and Cleveland TE. Broad-spectrum antimicrobial
activity in vitro of the synthetic peptide D4E1. J Agric Food Chem.
2001, 49, 2799-803.
- Ballweber LM, Jaynes JE, Stamm WE and Lampe MF. In vitro microbicidal
activities of cecropin peptides D2A21 and D4E1 and gel formulations containing
0.1 to 2% D2A21 against Chlamydia trachomatis. Antimicrob Agents Chemother.
2002, 46, 34-41.
- Cary JW, Rajasekaran1 K, Jaynes JM and Cleveland TE. Transgenic expression
of a gene encoding a synthetic antimicrobial peptide results in inhibition
of fungal growth in vitro and in planta. Plant Sci. 2000, 29,154,171-181.
- Mentag R, Luckevich M, Morency MJ and Seguin A. Bacterial disease resistance
of transgenic hybrid poplar expressing the synthetic antimicrobial peptide
D4E1. Tree Physiol. 2003, 23,405-11.
- Rajaskaran K, Cary J, Jaynes J. and Clevland T. Disease resistance conferred
by the expression of a gene encoding a synthetic peptide in transgenic cotton
(Gossypium hirsutumL.) plants. Plant Biotechnology Journal 2005,
3 in press doi: 10.1111/j.1467-7652.2005.00145
- Environmental Releases Database for the U.S. 2005 http://www.nbiap.vt.edu/cfdocs/fieldtests3.cfm
- Kawata,M, Nakajima,T, Yamamoto,T, Mori,K, Oikawa, T, Fukomoto, F. and Kuroda,
S. Genetic Engineering for Disease Resistance in Rice (Oryza sativa
L.) Using Antimicrobial Peptides JARQ 2003 , 37 (2), 71 – 76 http://www.jircas.affrc.go.jp
- Open letter from Dr. Takahiro Kanagawa 6 September
2005, forwarded by Akiko Frid, http://www.gmwatch.org/archive2.asp?arcid=5689
- Zhang L, Yu W, He T et al. Contribution of human a-defensin
1, 2, and 3 to the anti-HIV-! activity of CD8 antiviral factor. Science
2002, 298, 995-1000.
- Thevissen K, Osborn RW, Acland DP and Broekaert WF.
Specific binding sites for an antifungal plant defensin from Dahlia (Kahlia
Merckii) on fungal cells are required for antifungal activity. Molecular
plant-Microbe Interactions 2000, 13, 55-61.
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