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No 9/10 July 2001
Edited by Mae-Wan Ho
Institute of Science in Society
www.i-sis.org.uk
ISSN: 1474-1547 (print)
ISSN: 1474-1814 (online)
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ARTICLES

Gene Therapy with Your Salads, Anyone?

A virus is simultaneously being genetically modified to kill insect pests and to transfer genes into human cells in gene therapy. Prof. Joe Cummins points to a major gap in biosafety regulation.

Do our biosafety regulators know that a certain virus is being genetically modified to control plant disease and to serve as a gene carrier or vector for human gene therapy? This is the baculovirus, a virus previously thought to infect only insects, but has since found to get into all kinds of mammalian cells including those of human beings. Farm workers spraying the crop with anti-insect baculovirus and the public eating the crop not properly washed may both become genetically modified as a result.

Pests that infect and cause disease symptoms in both crops and human cells have never been described. Yet natural viruses that infects and slowly kills insects are also known to infect humans, but the infected humans do not seem to have symptoms. However, when the virus is genetically modified to eradicate insect pests, it may cause disease symptoms in those spraying crops or eating the sprayed crop. The baculovirus manipulated for insect control and for human gene therapy have both proven genetically unstable, and are prone to recombination and deletion at high frequency [1]. Such genetic instability has been noted repeatedly by those studying the virus, the genetic instability of the virus makes toying with it like playing with explosives.

Natural baculovirus, in contrast, is very stable and may remain dormant in the environment for years before infecting insects. The virus alone has a relatively low killing power and slow action. When a gene for a potent toxin such as scorpion toxin or a gene affecting a juvenile hormone is added to the virus, it kills faster and fewer insects survive infection. Numerous field tests of modified virus sprayed on crops have been done, despite protests from the public. Soon after GM baculovirus was developed for insect-control, the virus was discovered to be capable of infecting human liver cells and produced relatively little toxicity to the infected cells. For that reason, baculovirus vectors were developed to treat liver disease, and even to transfer genes to the human brain [2]. The fact that baculovirus can infect human liver or brain cells seems to have been ignored by those developing the virus for commercial pest control. There has been a great deal of pressure to hasten approval of the GM baculovirus for pest control especially in the United States and Canada, where human populations have already been used as guinea pigs for GM crops.

Ecological impacts of recombinant baculovirus insecticides have focussed on baculovirus containing scorpion toxin because that construction has been most widely used [3]. Impacts on non-target insects are simply extrapolated from findings on insects of related phylogeny, a practice that is full of pitfalls, for simply adding and deleting genes can change the host range of the resultant baculovirus in unpredictable ways [4]. Furthermore, the recombinant baculoviruses were very persistent, and capable of reshaping an ecosystem.

The scorpion toxins used with recombinant baculovirus have been selected to avoid toxicity to humans, and as much as possible, to non-target animals. However, the allergenicity other harmful effects in human liver infection has not yet been investigated.

Recombinant baculoviruses have also been constructed containing other genes, such as those coding for Bacillus thuringiensis (bt) toxins [5], which are known to produce allergic reactions in human beings and also harmful to rats [6]. A recombinant baculovirus has even been constructed containing an antisense fragment to the c-myc oncogene [7]. The c-myc oncogene is a modified form of an essential cellular gene. Thus, the antisense gene, which contains a DNA sequence complementary to the gene itself, may end up inactivating an essential cellular function.

Baculovirus vectors efficiently transfer genes into human liver cells [8, 9]. Hybrid baculovirus-adenovirus vectors have also been used to deliver genes to human cells [10].

In conclusion baculovirus vectors are being used to control insect pests because they are effective and persist for a long time in the environment. Baculovirus vectors are also being used in gene therapy of human liver and brain. These areas of research seem to exist as two solitudes and the risks of one are not evaluated in the context of the other. We may be treated to liver and brain gene therapy with our salad whether we need it or not.

  1. Wu Y, Lui G and Carstens E. Replication, integration, and packaging of plasmid DNA cotransformation with baculovirus viral DNA. J Virol, 1999, 73,5473-80.
  2. Sarkis C, Serguera S, Petres D, Buchet J-L, Ridet L, Edelman J, and Mallet. Efficient transduction of neural cells in vitro and in vivo by a baculovirus-derived vector. Proc Natl Acad Sci 2000, 97,: 14638-43.
  3. Richards A, Matthews M and Christain P. Ecological con-siderations for the environmental impact evaluation of recombinant baculovirus insecticides. Ann Rev. Entomol, 1998, 43,493-517.
  4. Thiem S. Prospects for altering host range for baculovirus bioinsecticides. Curr Opin Biotechnol 1997, 8,317-22.
  5. Martens J, Knoester M,Weijts F, Groffen S, Hu Z, Bosch D and Vlack J. Characterization of baculovirus insecticides expressing tailored Bacillus thuringiensis Cry1A9b) crystal proteins. J Invertebr Pathol, 1995, 66, 249-57.
  6. Fares NH and El-Sayed AK. Fine structural changes in the ileum of mice fed on endotoxin-treated potatotes and transgenic potatoes. Natural Toxins,1998: 6: 219-33.
  7. Lee S, Qu X, Chen W, Poloumieko A, MacAfee N, MorinB, Lucarotti C and Krause M. Insecticidal activity of a recom-binant baculovirus containing an antisense c-myc fragment. J Gen Virol 1997, 78,273-81
  8. Hofmann C, Sandig V, Jennings G, Rudolph Schlag P and Strauss M. Efficient gene transfer into human hepatocytes by baculovirus vectors. Proc. Nantl Acad Sci USA, 1995, 92,10099-103.
  9. Boyce F and Bucher N. Baculovirus-mediated gene trans-fer into mammalian cells Proc. Natnl Acad Sci USA, 1996, 93,2348-52.
  10. Palombro F, Mociotti A, Recchia A, Cortese R, Ciliberto G and LaMonica N. Site specific integration in mammalian cells mediated by a new hybrid baculovirus-adeno-associated virus vector. J Virol 1998, 72, 5025-34.

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