Terminator Technology: Boon or Curse to Farmers

Jogendra Singh, Vijayata Singh and Ashwani Kumar Central Soil Salinity Research Institute, Karnal, Haryana-132001 The plant breeder rights in present version have a provision of breeders and farmers exemption so that a protected variety can be used by plant breeders for experimental purpose and farmers can save seed for planting another crop. The private industry has thus innovate a novel method of enforcing automatic protection popularly dubbed as terminator technology to impose biological restriction on production of their varieties for re-cultivation. Terminator technology is the colloquial name gives to proposed method for restricting the use of genetically modified plant by causing second generation seeds to be sterile. The technology was patented by USDA and Delta & Pineland Company in 1998. terminator technology is one form of Genetic Use Restriction Technologies (GURT) there are two types of GURT viz., V-GURT (means seed could not be saved for future planting) and T-GURT (means crop seed does not function potentially until the treated with a chemical that sold by company). Possible advantages of terminator technology are an incentive to development of new plant varieties, improve farm management, improved grain quality and biosafety and disadvantages are transmission of terminator trait to wild plants, inequitable distribution of means, the targeting of vulnerable classes. Terminator Technology is the colloquial name given to proposed methods for restricting the use of genetically modified plants by causing second generation seeds to be sterile. The technology was under development by the U.S. Department of Agriculture and Delta and Pine Land Company in 1990s and is not yet commercially available. Because some stakeholders expressed concerns that this technology might lead to dependence for poor smallholder farmers, Monsanto, an agricultural products company, pledged not to commercialize the technology even if and when is becomes commercially available. Terminator technology is one of the biggest and most controversial issues concerning genetically modified crops. The goal of Terminator technology is to allow a plant to produce a fully mature yet inviable seed. This technology's success depends on a cleverly controlled sequence of interactions among the spliced-in genes. The last engineered gene comes into play very late in seed development when a special switch under the control of the inducer turns on the gene causing it to produce a toxic protein. This protein kills the embryo that is part of each mature seed. Terminator Technology is one form of Genetic Use Restriction Technologies (GURT). There are conceptually two types of GURT. 1. V-GURT This type of GURT produces sterile seeds meaning that a farmer that had purchased seeds containing v-GURT technology could not save the seed from this crop for future planting. This would not have an immediate impact on the large number of farmers who use hybrid seeds, as they do not produce their own planting seeds, and instead buy specialized hybrid seeds from seed production companies. The technology is restricted at the plant variety level - hence the term VGURT. Manufacturers of genetically enhanced crops would use this technology to protect their products from unauthorized use.

2. T-GURT. A second type of GURT modifies a crop in such a way that the genetic enhancement engineered into the crop does not function until the crop plant is treated with a chemical that is sold by the biotechnology company. Farmers can save seeds for use each year. However, they do not get to use the enhanced trait in the crop unless they purchase the activator compound. The technology is restricted at the trait level - hence the term T-GURT. METHODS The following is a general scheme of 3 approaches that can be employed in creating sterile transgenic plants (Oliver and Shapiro, 1995). Although the techniques differ in the specific approaches that can be adopted to carry out this task, they all share a common scheme of utilizing known gene mechanisms to control the expression of genes of known function. (1) Transfection of a plant cells with 3 different transgenes: This method involves the use of 3 different, but functionally-related transcriptional units. One of these transcriptional units contains a protein-coding segment called Ribosome Inhibitory Protein (RIP) whose expression results in tissue-specific death via inhibition of cellular translation (Barthelamy et al., 1993). Expression of RIP is controlled through 2 mechanisms (a) Use of a transiently-active promotor called the Late Embryogenesis Abundant (LEA) promotor. As the name suggests, this promotor becomes active only in the late stages of seed embryogenesis (Galau et al., 1992; 1993). Thus, not only is expression of RIP restricted to embryotic tissue, but also temporally restricted to a certain stage of development. However, to allow for germination of plants containing sterile seeds, this gene also contains a stretch of DNA (blocker sequence) located between the promotor and the RIP sequence. The presence of this sequence prevents expression of the lethal phenotype, allowing the plant distributors to grow many generations of these plants before selling their seeds to farmers. (b) The CRE/LOX site-specific recombination system, derived from bacteriophage P1, mediates the removal of the blocker sequence, and thus, expression of RIP (Sadowski, 1993). The 2nd transcriptional unit codes for the CRE protein, preceded by a repressible promotor such as tetO. The "silencing" of this promotor is mediated through the Tn10 tet system (Gatz and Quail, 1988; Gatz et al., 1992). Release of inhibition of CRE expression, and thus, induction of RIP expression is initiated by treating cells with an external stimulus, tetracycline. Tetracycline displaces the TetR repressor protein from the tetO promotor site, inhibiting its expression. If seeds are treated just after embryogenesis (i.e. after the time period in which RIP is expressed), they will be allowed to germinate into adult plants, which will eventually produce seeds expressing RIP, rendering the plant sterile. (2) Hybrid seed production This is an alternative method to produce sterile hybrid plants via cross breeding of two fertile transgenic plants, containing the following transgene: (a) Transgenic plant 1: Plant cells are transfected with a single transcriptional unit composed of the LEA promotor, LoxP sequences, blocking sequence, and RIP coding sequence. (b) Transgenic plant 2: Plant cells are transfected with a single transcriptional unit composed of a promotor that is active during germination and a CRE coding sequence.

When resultant hybrid seeds undergo germination, the floxing reaction occurs. However, since the LEA promotor is inactive after late embryogenesis, expression of RIP is specifically restricted to the seeds of resulting mature plants. (3) Inducible Promotor As another alternative method, the patent holders suggest a set up similar to that in (2), only in this case instead of using a germination-specific promotor upstream of the recombinase gene, using a promotor in which activity can be directly controlled by an exogenous substance. Modus operandi of Terminator genes

Gene operation at breeders field

PC gene C PB gene B PA Blocking sequence Not Excised LOX sequence (No RI P and embryo develops and seed viable) Gene A

Repressor Protein of gene B

(No recombinase)

Gene operation at farmers fields

PC gene C

PB gene B
Recombinase

PA

Gene A

Repressor Protein of gene B

(Derepressed B)

Excised LOX sequence & gene A expressed

RIP

Tetracycline

Degenerates embryo and seed is unviable

How Terminator Technology could affect the Farmers

Terminator Technology can provide a regulatory framework for agricultural development and fair trade. Farmers will lose substantial influence and control over production of their own crops. Terminator Technology can prevent farmers from other countries from pirating varieties of crops out of the country. Farmers will have to buy new seeds every season, which may not be affordable to everyone especially farmers in developing countries. Farmers will still have a choice: they can choose varieties that don't carry the terminator gene. The terminator gene will decrease the variety of wild plants, which decreases the natural plant diversity; they are adapted to the local environment in order to protect against crop failure, to provide a continuous and varied food supply, and toward against hunger and malnutrition. Monsanto stated its commitment to transgenic crops. "When biotechnology is used with proven agricultural methods and practices, it will offer environmentally responsible options to meet continued consumer demands for sustainable and healthy food production."

Monsanto: "Terminator technology does not exist; it is only a name given to the theoretical concept 'Gene Protection Technologies' (GPR)".

OPINIONS Activist group Rural Advancement Foundation International (RAFI) is strong opponents to this seed sterilizing technique.

RAFI strategically coined the term "Terminator Technology". Their website encourages Terminator Technology opponents to protest by mass-mailing the U.S. Department of Agriculture. Pat Roy Mooney, head of RAFI said 'its a delightful profit-making platform' for seed companies although he argued that subsistence farmers in developing countries would be most adversely affected. Dr. M. Swaminathan, touted 'father of the green revolution in India', voiced his rage towards Terminator Technology in a Rediff Business interview, comparing it to 'putting a virus into computer software'.

This technology does not offer the necessary free choice of a cafeteria: 'in a cafeteria, you can eat for 10 dollars, you can also eat for one dollar...it all depends upon how much money you have and what you want to eat.' It is thus unethical to deny poor farmers more risk-free technology when they do not have the money or capital to adopt profit-maximizing strategies.

IN REALITY

Genetically modified foods can potentially solve the global hunger crisis that has been a looming reality coupled with the unprecedented exponential increase in the world's population since the turn of the 20th century. U.N. predicted world population increases to 8 million by the year 2020 and pressing shortage of arable land urgently call for higher crop yield capacity and improved stress resistance in food crops. Monsanto argues that this seed sterilizing technology exists to protect its intellectual property and must also generate revenue for continued research into refining the transgenic food crops that could potentially feed the neediest. Pollen produced by activated terminator plants would not contain blocker DNA in front of the RIP gene. If this plant were able to fertilize another plant, the resulting seeds would carry one copy of the RIP gene that could be transcribed in the late stages of seed development. It could be that having only one copy of RIP would still be lethal to the seed. Some seeds might for some reason not respond to, or might not have soaked up enough of the tetracycline to activate recombinase. In this case the blocker DNA would not have been removed in the resulting plant, and any progeny resulting from a cross of this plant to a wild type plant would be viable. These seeds would contain both terminator and other novel genes. A promoter that acts very late in seed development ensures that seeds killed by the toxin would be almost identical to normal seeds in all other respects. These seeds might then be crushed for oil and protein, and consumed by humans and other animals. Although the RIP toxin described earlier is thought to be not directly poisonous to animals (i.e. it is broken down and inactivated in the gut), it may cause allergic reactions.

REBUTTAL

Advantages of Terminator technology An Incentive to the Development of New Plant Varieties

Where effective intellectual property protection systems don't exist or are not enforced, GURTs could be an alternative to stimulate plant developing activities by biotech firms. Non-viable seed produced on V-GURT plants will reduce the propagation of volunteer plants. Volunteer plants can become an economic problem for larger-scale mechanized farming systems that incorporate crop rotation. Under warm, wet harvest conditions non V-GURT grain can sprout, which lowers the quality of grain produced. It is speculated that this problem would not occur with the use of V-GURT grain varieties.

Improved Farm Management

Improved grain quality

Biosafety

Use of V-GURT technology could prevent escape of transgenes into wild relatives and prevent any impact on biodiversity. Crops modified to produce non-food products could be armed with GURT technology to prevent accidental transmission of these traits into crops destined for foods.

Disadvantages of Terminator technology Transmission of the "Terminator" trait to wild plants, or cultivated plants whose seeds are saved

There is a concern that V-GURT plants could cross-pollinate with non-genetically modified plants, either in the wild or on the fields of farmers who do not adopt the technology. Though the V-GURT plants are supposed to produce sterile seeds, there is concern that this trait will not be expressed in the first generation of a small percentage of these plants, but be expressed in later generations. This does not seem to be much of a problem in the wild, as a sterile plant would naturally be selected out of a population within one generation of trait expression. This is however a problem in some farming systems, especially for indigenous groups who save seed rather than purchase it from developers. The loss of the ability for such farmers to save seed may lead to decreased agro-ecological biodiversity on their farms and decreased yields of affected crops. As with all Genetically Modified crops the food safety of GURT technology would need to be assessed when and if a commercial release of a GURT containing crop was proposed. In addition to potential biological and ecological harms, there is both an economic and normative concern that small farmers, indigenous peoples, and entire rural communities could be made dependent on agro-industry corporations for seed. As with many other technologies, there is debate as to the role and responsibility implicit in the normative assumptions involved in producing GURTs. The issue is distinct from the conflict surrounding the production of GM foods generally, in that GURT products are specifically designed to affect future generations and potentially have a distinct impact on human and ecological health and livelihoods. Thus, some believe that in making decisions regarding such products, considerations should extend beyond what is legally permissible.

Safety of Food produced from Terminator technology crops

The inequitable distribution of means; the targeting of vulnerable classes

A presumption of entitlement

It is important to note, that although there exists a wealth of information on terminator technology in opinions and patents, there is little information in published scientific papers. This is because no field tests have been done with terminator plants. In order to directly assess potential dangers associated with this technology, further tests would be needed. References: Barthelamy, I., Martineay, D., Ong, M., Matsunami, R., Ling, N., Benatti, L., Cavallaro, U., Soria, M. R. and Lappi, D. A. (1993). The expression of saporin, a plant ribosome inactivating protein, in E. coli., J. Biol Chem. 268:6541.

Galau, G. A., Wang H. Y- C., and Hughes D. W. (1992). Cotton Lea4(D19) and LeaA2(D132) Group 1 Lea genes encoding water stress-related proteins containing a 20-amino acid motif, Plant Physiol. 99:783-788. Galau, G. A., Wang H. Y- C., and Hughes D. W. (1993). Cotton Lea5 and Lea14 encode atypical late embryogenesis-abundant proteins, Plant Physiol. 101:695-696. Gatz, C., and Quail, P. H. (1988). Tn10-encoded tet repressor can regulate an operator-containing plant promoter, Proc. Natl. Acad. Sci. USA. 85:1394-1397. Gatz, C., Frohberg, C., and Wenderburg R. (1992). Stringent repression and homogeneous derepression by tetracycline of a modified CaMV 35S promoter in intact transgenic tobacco plants, The Plant Journal 2:397-404. Oliver, M. & Shapiro, T. (1995). Black wealth/White wealth: a new perspective on racial inequality (New York, Routledge).