In 2001 I prepared a witness statement for the New Zealand Royal Commission on genetically modified crops. My statement dealt several issues including that of genetically modified (GM) baculovirus as bio-pesticides and as gene therapy vectors. Baculoviruses are soil born viruses which are very persistent in the soil and multiply with relatively low killing power. Genetic enhancement with scorpion toxin, juvenile hormone or even a human cancer gene provided enhanced insect killing. However, the development of GM baculovirus insecticides was proceeding without reference to a growing body of studies preparing baculoviruses as gene therapy vectors because the viruses were capable of infecting mammalian cells but could not replicate in those cells but could deliver sizeable mammalian genes. Baculovirus were prevented from infecting humans by the action of compliment (innate immunity) but that barrier could be overcome by exposure to inhibitors of compliment or deficiency of compliment. Baculoviruses are inherently genetically unstable and prone to numerous small deletions that effect host range (reviewed with references in 1). Recently, the frequent deletions were reported to enhance viral infectivity in mixed virus infections (mixture of defective deletion strains and complete strains), thus the deletions were more effective than defective (2). The genetic instability of the baculoviruses question their usefulness as GM biopesticides and gene therapy vectors.

Baculoviruses cause pathological infections in susceptible insects but may also cause non-pathological infections of insects or other animals including humans. The virus is stable in the soil for long periods but when a susceptible insect succumbs to the virus infection it “melts” on the surfaces of the plant leaving an infectious scum on the plant surface. Commercial Baculovirus spray mixtures are available under trade names such as Cyd-X,Mamestrin,Spodoteran, Gemstar,Gypchek and Spod-x..Commercial producers include Novartis (Syngenta) Corporation, Natural Plant Protection of France and USDA Forest Service. The commercial production of virus sprays does not seem to have been considered a conflict of interest with the regulatory functions(3). Baculoviruses are often applied as an “occlusion body” a protein overcoat containing several virus particles, the occlusion bodies are registered as the pesticide (4). Combining baculovirus with a natural neurotoxin , Spinosad, produced from fermenting actinomycetes bacteria was found to be more effective in controlling tropical corn pests (5).

Many transgenic Baculoviruses have been produced in the laboratory and field tested . The Gulf ecology division field tested a number of Baculoviruses (nuclear polyhedrosis viruses) using marker gene inserts to identify host range and both full infections and symptom less infections (6). A gypsy moth Baculovirus modified with a marker gene and modified for non persistence was released in a forest plot (7). Patents have been granted on agicultural applications of recombinant Baculoviruses.

These US patent 5,770,192 covering Baculovirus with insecticidal toxins such as scorpion and spider venom genes (8). US patent 6,096,304 granted a Baculovirus with a synthetically enhanced scorpion neurotoxin (9). US patent 6,596,271 grants use of a recombinant Baculovirus (usually with synthetic scorpion neurotoxin) in combination with pyrethroid, carbamate or organophosphate chemical insecticides, the combination is directed towards insects resistant to chemical insecticides (10).

Recently it has been found that more than one scorpion toxin genes could be pyramided in a Baculovirus creating more effective control of insect pests (11). The thrust of current research seems to be use of recombinant Baculovirus with more synthetic neurotoxins toxins in each virus. None of the above recombinant Baculovirus insecticides has discussed the consequences of genetic recombination and the well know tendency of Baculovirus to mutate (through small deletions) frequently to extend host range for the virus nor has the consequences of mammalian infection been considered either by proponents or regulators.

It has been repetedly claimed both by proponents of Baculovirus insecticides and their regulators in EPA that the viruses are not known to effect mammals. Such comments are spectacularly deceptive. As indicated earlier (1) and following that there is a deluge of hundreds of publications dealing with Baculovirus vectors in gene transduction and gene therapy of mammals. The virus infects mammalian cells but the virus does not replicate yielding a desirable vector for delivering genes to mammalian cells. One complication has been that the healthy immune compliment inhibits virus entry in the intact animal. Recently that problem was overcome using synthetic inhibitors of compliment to enhance gene transfer by Baculovirus vectors (12). Notwithstanding that there are significant deficiencies in compliment among the members of the human population. The symptom less Baculovirus infections of cells described frequently are beginning to overturned by findings that the infections do create significant impacts. The most striking impacts are those of enhanced promoter activity and inhibition of apoptosis (13). Apoptosis (programmed cell death) is, among other important effects, a major defense against virus infection through the suicide of virus laden cells, the Baculovirus infection aids proliferation of any virus in the bearing the vector (14).

It is very distressing that the proponents of Baculovirus insecticides and the proponents of Baculovirus human gene therapy vectors have never gotten together to make a full and truthful risk evaluation on the commercial use of the virus. EPA regulators of the virus based pesticides seem to be suffering from tunnel vision and seem to prefer to ignore the innate genetic instability of the virus. Such tunnel vision will have disastrous consequences. USDA who produce Baculovirus commercially seem to have a clear conflict of interest in regulating recombinant viruses.

References are available on request , please state the name of the paper