Science in Society Archive

Transgenic Pink Bollworms FONSI?

The US Department of Agriculture returned a verdict of FONSI – finding of no significant impact – on transgenic pink bollworms. Prof. Joe Cummins condemns the decision as deeply flawed.

The United States Department of Agriculture (USDA), through its regulatory agency the Animal Plant Health Inspection Service (APHIS), has been actively promoting development of genetically modified (GM) insects to eradicate insect pests. The first field release of GM insects includes the cotton pest, the pink bollworm (PBW) moth, modified with a gene for green fluorescent protein. It is to be released in a cage near Phoenix, Arizona. This will be followed by a number of full-scale field releases. In response to a notice published in the Federal Register on June 21, 2001 (66 FR 33226, Docket no. 01-024-1), APHIS received 9 comments on the environmental assessment (EA) prepared for permit application number 01-029-01r during the designated 30-day comment period which ended July 23, 2001. The decision of FONSI was published October 1, 2001.

Comments made by myself and Dr. Mae-Wan Ho [1] were considered in the review, and my reading of the decision leaves me with grave concern on the reasons for the decision. Michael J. Firko of APHIS stated, "Two commenters claimed that the planned confinement measures, namely the field cage study, would not contain the possible interaction of certain insect viruses, e.g., baculoviruses, and the transgenic PBW. Such interaction is highly unlikely because these viruses are host specific and few infect PBW, the viruses are fragile and will be adversely affected by the strong Phoenix sun, and only adult PBW will be used in the test and adults are not normally susceptible to infection by such viruses. Further, the numerous confinement measures proposed include specific provisions which preclude the interaction of insect viruses and PBW. The same commenters expressed concern that baculoviruses are a possible source of human and mammalian infectivity through the rescue of the inactivated piggBac transposon in the transgenic PBW by baculoviruses. However, baculoviruses are highly specific to a few species of insects for each virus. And while laboratory experimentation appeared to support the possibility that baculoviruses might be used for gene therapy in mammalian cells, later work shows that baculoviruses are not infectious in mammalian cells. The potential of a very selective insect virus somehow becoming a human pathogen, or even a non-pathogen gaining access to human cells, or cells of any vertebrate or of the virus carrying genetic material from an insect to a vertebrate has never been demonstrated, nor has that been a basis upon which to design an experiment to test any hypothesis (Miller and Peloquin)."

The publication by Miller and Peloquin cited was not listed in the reference list accompanying the EA document. The significance of the reference was not made clear in the EA. The EA is simply mistaken about the infectivity of baculovirus in mammalian cells and the continuing use of baculovirus as a gene therapy vector. The abstracts of current articles reproduced in part or in full below show that baculovirus can infect mammalian cells and it is being applied as an effective gene delivery vector in mammals.

Towards the use of baculovirus as a gene therapy vector.
Pieroni L, La Monica N. Curr Opin Mol Ther 2001, 5, 464-7.
"The use of baculovirus vectors for gene expression in mammalian cells is in continuous expansion. These vectors do not replicate in mammalian cells, do not cause a cytopathic effect upon infection and are able to carry large DNA inserts. Baculovirus vectors have been shown to transduce various cell types in vitro and in vivo with significant efficiency leading to stable gene expression. This review focuses on recent developments with baculovirus that highlight its potential use for new gene therapy strategies."

In vivo gene transfer in mouse skeletal muscle mediated by baculovirus vectors.
Pieroni L, Maione D, La Monica N. Hum. Gene Ther 2001, 12, 871-81.
"Baculovirus vectors are efficient tools for gene transfer into mammalian cells in vitro. However, in vivo gene delivery by systemic administration is hindered by the vector inactivation mediated by the complement system. To characterize further the gene transfer efficacy of baculovirus we examined the vector transduction efficiency in skeletal muscle. …. Thus, these results indicate that baculovirus may be considered a useful vector for gene transfer in mouse skeletal muscle and that persistence of expression may depend on the mouse strain used."

Combination treatment for osteosarcoma with baculoviral vector mediated gene therapy (p53) and chemotherapy (adriamycin).
Song SU, Boyce FM. Exp.Mol.Med. 2001, 33, 46-53.
"The insect baculovirus Autographa californica multiple nuclear polyhedrosis virus (AcMNPV) has been evaluated as a vector for gene delivery to human tumor cells. A human osteogenic sarcoma cell line, Saos-2, was found to be highly susceptible to infection with a baculoviral vector, with nearly 100% of Saos-2 cells being able to express a lacZ reporter gene after a brief exposure to the virus at a m.o.i. of 30 pfu/cell. The production of beta-galactosidase protein was 18-times greater than that in HepG2 cells which were previously thought to be the mammalian cells most susceptible to the baculovirus. The possibility of developing a baculovirus as a cytotoxic vector for p53-defective cancer was tested by destruction of Saos-2 cells (p53-/-) with a recombinant baculovirus containing the wild type p53 gene (BV-p53) in vitro. The p53 baculovirus induced apoptotic cell death in tumor cells in a dose-dependent manner with approximately 60% killing at an m.o.i. of 160 pfu/cell. Combined treatments of gene therapy (p53) and chemotherapy (adriamycin) resulted in synergistic and potent killing of the osteogenic sarcoma cells. For example, greater than 95% of Saos-2 cells were killed by the combination of BV-p53 (m.o.i. of 100) and adriamycin (35 ng/ml), whereas approximately 50% and approximately 55% cells were killed by BV-p53 and adriamycin alone, respectively. These results indicate that a baculoviral gene delivery vector can be used to efficiently target certain types of mammalian cells and the combination treatment of gene-therapy mediated by a baculovirus and chemotherapy may enhance induction of apoptosis in cancer cells."

The abstracts of publications above are taken from a large body of publications. The studies show that baculovirus infects a wide range of mammalian cells and that the virus is a potential vector for gene and cancer therapy. Previously, it has been argued that complement in normal adults prevents infection by the wild virus. However, people with complement defects, well known to medicine, would be susceptible to penetration by the virus. APHIS seems to ill-prepared to consider the evidence that the transposon piggyBac used to modify PBW was discovered first in baculovirus. A disabled piggyBac insert can easily be rescued by complementation or homologous recombination with a complete piggyBac in an infecting baculovirus. Potential human interactions should not have been dismissed summarily by APHIS.

Finally, APHIS appears to put blind faith in the wire cage used to isolate the GM insects from the environment. The cage is certainly readily penetrated by soil (as dust particles) containing virus, bacteria and fungi along with soil arthropods. An ideal cage that never breaks, nor scratched and damaged by rodents, dogs or coyotes or for that matter by machines or people seems to be what the bureaucrats at APHIS have in mind.

In conclusion, USDA is actively participating in developing commercial products through patents and public relations, and is taking a cavalier attitude towards matters of human health and environment protection. USDA should be held responsible in case of harm that is forseen on the basis of existing scientific evidence.

Article first published 14/12/01



References

  1. Comments on GM Pink Bollworms to United States APHIS, by Joe Cummins and Mae-Wan Ho www.i-sis.org.uk

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