September 6, 2005
I am writing this letter as a microbiologist.
Many scientists appear to consider that they should be allowed to carry out any
experiments they like unless those experiments can be shown to be dangerous. I havefound, by chance, that a very dangerous experiment on an anti-microbial peptide,
defensin, is being undertaken in Japan. Defensins are made by plants and animals, andare very important in providing them with protection against pathogens.
Zhang et al. (2002) have reported that long-term nonprogressors with HIV-1 infection
secreted alpha-defensins, and that the alpha-defensins inhibited HIV-1 replication. If
human defensins were effective in killing HIV-1, and were used as a specific medicine forHIV-1, defensin-resistant HIV-1 would then appear, and those infected with this virus
would develop symptoms more rapidly and die more quickly. Thus, defensin-resistantpathogens would enhance their pathogenicity and infectivity, and cause far more terrible
problems than antibiotic-resistant pathogens.
We already know that the abuse of antibiotics has induced the spread of resistantpathogens, and that as a result we have to use anti-microbial substances very carefully.
The defensins in plants and animals are regulated so that they are produced in response topathogen attack, and resistant pathogens will not easily appear or spread in naturalconditions.
However, in Japan this June, genetically modified rice that constantly produces a large
amount of a defensin from mustard (Brassica sp.) was planted in an isolated paddy field.
The developers of this modified rice have stated that they introduced a promoter tostrongly express the inserted defensin gene, and that this transgenic rice was resistant topathogens such as rice blast and white leaf blight. They made sure the gene wasexpressed in every sample they tested by western blotting method.
Thevissen et al. (2000) have reported that by cultivating yeast with the defensin fromdahlia for 2 days, they got resistant strains. From this finding, we can assume that
defensin-resistant microbes are likely to soon appear in the paddy field where thistransgenic rice is being cultivated.
It is true that the plant defensins are different from animal defensins in their structure, butmicrobes can obtain the resistance to both defensins if the mechanism of the action is thesame. Therefore, the resistant microbes may be dangerous to human beings. Althoughstudies on the mechanism of action have been intensively carried out by many
researchers, it still has not been fully understood.
I have asked the developers to stop this experiment until the knowledge of the mechanismof action is sufficiently developed to discuss the potential danger of resistant microbes.
However, the developers denied the possibility of resistant microbes emerging, and they
are continuing to grow the rice without any care as regards microbes. The water in thepaddy field is being discharged into the surrounding area without any sterilization. They will
harvest the seeds of the rice in late September, and plant the seeds again next April.
Microbiologists are able to recognise the danger of resistant microbes more readily thanresearchers in other fields. This means that some researchers will not be alert to thedanger. I think microbiologists should discuss the danger of the abuse of antimicrobial
peptides, and give a warning to the scientists who make use of antimicrobial peptides intheir research.
With best wishes,
Dr. Takahiro Kanagawa
Senior Research Scientist
E-mail: chaondo@ybb.ne.jp
References
Thevissen et al. (2000) Molecular Plant-Microbe Interactions, 13: 54-61.
Zhang et al. (2002) Science, 298: 995-1000