Pharmacom^TM Transgenic Effect Detection Microsystems

Background

Genetic engineering is based on a reductionist scientific paradigm that presupposes that each specific character of an organism is codified in one or a few specific and stable genes, in such a way that the transfer of these genes has as a result the transfer of a concrete character. Nevertheless, given the enormous complexity of the genetic code, even in very simple organisms such as bacteria, it is not possible to predict the consequences of the introduction of new genes in any organism or plant. This is because: (i) the transferred gene can act in a different form when it functions inside another organism, (ii) the original genetic code of the organism is altered, (iii) the new combination of the genes of the organism and the transferred gene will have unpredictable effects, and (iv) there is no way to know a priori the global and long-term effects of the genetically manipulated products on health.

Bacillus thuringiensis (Bt) is a valuable environment-friendly biopesticide, which occupies 90% of the world biopesticide market. Its insecticidal properties are attributed to the presence of δ-endotoxins which are synthesized during the sporulation phase of the bacterium. δ-endotoxin or crystal toxin is a multi-domain protein molecule comprising of three distinct domains. Domain I is made of seven a-helices, domain II comprises three antiparallel β sheets, which are folded into loops and domain III is made of a b sandwich of two antiparallel β strands. Molecular studies on the structure and functional properties of different δ-endotoxins revealed that the domain I by virtue of its membrane spanning hydrophobic and amphipathic α-helices is capable of forming pores in the cell membranes of the larval midgut. Domain II being hyper variable in nature determines the insecticidal specificity of a toxin and domain III is involved in varied functions like structural stability, ion channel gating, binding to Brush Border Membrane Vesicles and insecticidal specificity. Recent studies on toxin aggregation and interaction revealed that the three domains interact closely to bring about the insecticidal activity of Bt.

Since 1996, a wide range of crop plants have been genetically engineered to contain the δ-endotoxin gene from Bacillus thuringiensis. These "Bt crops" are now available commercially in the USA. They include "Bt corn", "Bt potato", "Bt cotton" and "Bt soybean". Such plants have been genetically engineered to express part of the active Cry toxin in their tissues, so they kill insects that feed on the crops. In some respects, this is an important technological and practical development, because it ensures that only those insects that attack the crop will be exposed to Bt toxins - there is no risk to other types of insect. It also ensures that the range of uses for Bt is extended to insects that feed on the roots or that bore into the plant tissues - for example, the European corn borer - because such insects cannot be controlled by Bt suspensions sprayed onto plant surfaces. However, there is also a "downside", because the target insects are perpetually exposed to toxins and this creates a very strong selection pressure for the development of resistance to the toxins. Various crop-management strategies are being developed to try to minimize this risk.