The 'Terminator Gene" and Other Genetic Use Restriction Technologies (GURTs) in Crops

Alejandro E. Segarra

Agricultural Biotechnology Analyst Resources
Science, and Industry Division

Jean M. Rawson

Specialist in Agricultural Policy Resources
Science, and Industry Division

Updated October 21, 1999

Contents

Background
What are Gene Use Restriction Technologies (GURTs)?
Future Potential for GURT Commercialization
Selected Issues
   Seed Industry Concentration and Vertical Integration
   Role of Publicly Funded Research in the Development of GURTs
   Food Security in Developing Nations
   Crop Biodiversity 
Current Legislation

Summary

Plant Genetic Use Restriction Technologies (GURTs) are a group of complex genetic transformations that insert a genetic "on-off switch" in plants to prevent the unauthorized use of genetic traits contained within. GURTs are one of the latest bioengineering products developed for agriculture, with over 30 patents issued in the United States and Europe since 1997. The current state of biotechnology may allow GURTs to be introduced into the commercial seed market in the next 5 to 7 years. Controversy over GURTs first arose in 1998 when the U.S. Department of Agriculture and Delta & Pine Land Company received a U.S. patent for the rights to use a new genetic process which blocks the production of fertile seeds in genetically engineered plants. Detractors dubbed this utility patent "the Terminator gene" and mounted an extensive campaign against its use. In general, opponents view the use of GURTs as an accelerator of seed industry consolidation and vertical integration, and link the technology to potential adverse effects on food security and crop biodiversity worldwide. Others have questioned the role played by the federal government in funding and developing this kind of technology. Proponents in USDA and biotechnology firms argue that this new technology insures against illegal use of their intellectual property and helps to create new industry incentives. They further maintain that the level of investment protection achieved through GURTs gives growers in developing countries better and expanded seed choices, and the opportunity to move away from subsistence farming and into modem production agriculture. USDA has asserted that its role as an active participant in GURT development will ensure that the public interest is represented. An issue before Congress is whether current laws are adequate to assure that biotechnology innovations are applied in ways that do not have unwelcome economic, social or environmental side effects. This report examines the latest technical advances in Genetic Use Restriction Technologies and discusses key issues related to their potential impact on farming and agriculture.

Background

Plant Genetic Use Restriction Technologies (GURTs) are a group of complex genetic transformations that insert a genetic "on-offswitch" in plants to prevent the unauthorized use of genetic traits contained within, i.e., GURTs ensure that farmers cannot replant genetically modified crops by simply saving seed. One view is that the use of GURTs provides biotechnology companies with a reliable "turn-key" mechanism to ensure against the illegal use of intellectual property through a biological lock. However, another set of views looks at GURTs as potential threats to the environment and to farmers in developing countries. Since 1997, over 30 GURT patents have been issued in the United States and Europe; however, the technology is not expected to appear in the commercial seed market for at least 5 years.

In March 1998, the U.S. Department of Agriculture's Agricultural Research Service (ARS) and Delta and Pine Land Co. (D&PL), a major developer and seller of cotton seed, received U.S. Patent 5,723,765 entitled "Control of Plant Gene Expression." This patent gives the holders rights for the use of three new gene sequences that block the production of fertile seeds in genetically engineered plants. According to the patent holders, this so-called "Technology Protection System" (TPS) would ensure intellectual property protection for investments in genetic engineering and help create incentives to develop new plant varieties that satisfy changing market demands.

Shortly after the patent's issuance, the Rural Advancement Foundation International (RAFI), an organization headquartered in Winnipeg, Canada and Pittsboro, N.C., that is concerned about issues of crop genetic diversity and the impact of intellectual property rights on agriculture, began to organize opposition to the patent. RAFI coined the term 'Terminator Gene" to label the technology as a negative one for farmers. Issues highlighted by RAFI were: the accelerating effect of these technologies on seed industry consolidation; the potential adverse effects of TPS on food security in the developing world; and the potential for worldwide losses in crop biodiversity. These issues have received wide press coverage, and other groups have joined RAFI in accusing ARS and the seed biotechnology industry of developing TPS with the intent of hastening monopoly control over global agricultural production.1

Concerns about the use of GURTs and seed sterility are now beginning to extend into the public policy arena. For example, on July 16, 1999 and acting on farm groups' concerns, the State of New Hampshire enacted a law to establish a 3-year study to examine "the threat to bio-diversity resulting from Terminator technology."2 However, seed sterility is not the only biotechnology-based form of intellectual property protection under development and patents have been issued on other types of GURTs, as examined below.

What are Gene Use Restriction Technologies (GURTs)?

In general, GURTs are a form of protection against the illegal use of a plant variety based on genetic engineering of the plant rather that on license agreements or end-user contracts. Companies, such as the Monsanto Corporation, typically license their biotechnology products under certain conditions. Some of these conditions include agreements by the farmers who purchase their seed to use them solely for planting a single commercial crop and agreeing not to save any seed produced for replanting or trade. Monsanto has repeatedly taken farmers to court for violations to these agreements.

A recent report, produced for the Convention on Biological Diversity (CBD), breaks GURT patents into two major categories.3 Those that deny unlicensed access to the entire plant variety or "Variety-level Genetic Use Restriction Technologies" (V-GURTs); and those in which only the "value-added" transgenic trait is protected from illicit use, or "Trait-specific Genetic Use Restriction Technologies" (T-GURTs).4 Currently, V-GURTs account for most of the patents, but the line separating these categories is often blurred by the absence of current applications and many patents broadly describe GURTs which could be used in one way or another.5, 6

Both V-GURTs and T-GURTs feature metabolic "locks," which can be opened or closed only through the application of key "inducer" substances to the plant. Substances, such as plant-growth regulators, antibiotics, or herbicides are being researched as possible "genetic inducers" and will be under the proprietary control of the biotechnology companies.

Future Potential for GURT Commercialization

Most experts agree that it is unlikely that any GURT-containing crops will be available for at least 5 years. No GURTs have, to date, been produced or even left the scientist's bench for testing or trials. According to most specialists, the required technological breakthroughs needed to produce stable genetic expression and commercially viable GURT plants will require a very large undertaking. The process has to be tailored and tested individually for each variety and crop. In addition, the sheer complexity and unpredictability of present day genetic manipulation technologies greatly restrict the number of varieties that could be transformed.

In theory, any crop species could potentially be transformed to contain value- added genetic traits and GURTs. However, given the great number of technical barriers and the expected high cost of development, GURT-containing varieties will be limited initially to a small number of crops. These will likely include many of the most widely used crops, such as rice, wheat, cotton and soybeans. Another factor influencing the selection of crops for GURT transformation is the presence of current seed consumption trends that indicate continued declines in the use of saved-seed for replanting.

Selected Issues

An issue before Congress is whether current laws are adequate to assure that the benefits of biotechnology innovations help rather than hinder the public trust. The concerns raised below represent salient issues and are, to a large extent, an important manifestation of the broader economic, social and environmental concerns surrounding the use and development of agricultural biotechnology.

Seed Industry Concentration and Vertical Integration

While crop biotechnology is increasingly considered one of the most important agricultural innovations of this century, it has raised some concerns in the context of the current trends towards seed industry consolidation. Leland Swenson, president of the National Farmers Union, believes that recent developments such as biotechnology and the "Terminator gene" will hasten the process of vertical integration in agriculture and place the farmer at the mercy of agribusiness- conglomerates. Another concern is about "backward integration," a situation in which farmers might be forced to buy seed from one company in a conglomerate because the processing firm to which they wish to sell their crop requires specific genetic traits found only on those seeds. GURTs, according to this view, will greatly accelerate the already fast pace of vertical integration in seed companies.

That concern is not shared by those who view industry consolidation as part of a long continuing process in American agriculture. They contend that the economies of scale and the production efficiencies brought about by consolidation are naturally justified in view of the high costs of investment and of the high value of the results. Mark Drabenstott, director of the Center for the Study of Rural America, views consolidation in U.S. agriculture as a positive trend, and one that has led to lower-priced, higher quality food products for consumers and a leaner industry better able to compete in the global market place.7

Regardless, many U.S. farmers appear to have adopted the type of value-added, genetically modified (GM) crops that may eventually get GURTs. According to the USDA Economic Research Service (ERS), the adoption of genetically engineered crops by U.S. farmers has increased rapidly.8 For example, GM corn increased from 3.5 to 23.7 million acres between 1996 and 1998 (i.e., from 4.4% to 36% of total planted area). In other crops, such as soybean and cotton, increases have been even larger, with GM varieties accounting for 44.8% and 52.8% of total 1998 acreage, respectively. In addition, U.S. farmers nowadays depend less on saved seed for their planting. According to ERS figures, soybean grown from saved seed decreased from 23% to 14.9% from 1990 to 1997. Similarly, cotton planted from saved seed dropped from 26.5% to 17.8% between 1991 and 1997. In U.S. corn, the longstanding availability of high yielding hybrid seed (whose beneficial traits do not all reappear in a second generation) have virtually eliminated saved seed as a farming practice in corn production.9 Presently, seeds for GM corn, soybean, canola and cotton are distributed through dozens of brand varieties, but the underlying biotechnologies are still restricted to a handful of trademarks owned by the Monsanto Company, Mycogen, AgrEvo GmbH, and the Novartis Corporation.

Large U.S. farm organizations have generally welcomed biotechnology as part of the agribusiness revolution in America Michael Yost, president of the American Soybean Association, considers biotechnology ". . . an unqualified triumph of modem science by, so far, reducing production costs and increasing the crop's value." According to Mr. Yost, soybean farmers understand the legitimate motivations of biotechnology companies to protect their investments by using license agreements or (eventually) GURTs. For him, the concern is that seed from generally less expensive conventional varieties might continue to be available, and that farmers are treated fairly under licensing agreements, end-user contracts, and other such devices.10 Others, although supporting licensing agreements, contend that it is important to maintain a business environment that fosters competition and that facilitates the entry of new biotechnology firms with new products, thus providing farmers with a continuous broad array of seed choices.

Role of Publicly Funded Research in the Development of GURTs

USDA's development of "Terminator-type" technology has fueled a controversy over federal funding of GURT research. Margaret Mellon, director of agriculture and biotechnology programs at the Union of Concerned Scientists (UCS), has charged that USDA's research agenda is insufficiently focused on the public interest. Mellon has also argued that the Department has a direct conflict of interest in the development of these types of biotechnologies while simultaneously being one of its principal regulators.11 UCS believes that this type of state-sponsored research solely benefits the large biotechnology corporations.12 RAFI has also accused USDA of not representing the public interest and has called on the Department to renounce its part of the TPS patent.

USDA is the joint holder of the TPS patent under the terms of a Cooperative Research and Development Agreement (CRADA) signed with Delta & Pine Land (D&PL). Congress authorized CRADAs in the Federal Technology Transfer Act of 1986 (P.L. 99-502) to enhance the ability of federal research laboratories to work with industry to commercialize technology. This act and various other federal laws—including the Stevenson-WydIer Act of 1980 (P.L. 96-480) and the Bayh-Dole Act of 1980 (P.L. 96-517)— make the transfer of new technology to the private sector and industry a responsibility of all federal research agencies.

Currently, USDA and D&PL are negotiating license agreements for the use of the TPS patent. USDA-Agricultural Research Service (ARS) officials have declared that, as these negotiations evolve, ARS will be an active participant in deciding how the technology is applied, and that ARS involvement will ensure that the public interest is represented. According to these officials, it is ARS policy that technology in which it has an ownership interest will be made widely available, and it has announced that TPS will be available for research purposes to public and private researchers. In line with ARS policy, D&PL has agreed to make the technology widely available for sublicensing to other seed companies.

The statutes governing the use of CRADAs guarantee to the industrial partner, such as D&PL, the option to choose, at a minimum, an exclusive license for a pre- negotiated field of use to the resulting invention made in whole or in part by a government laboratory employee. CRADAs also protect the government's right to use the invention for its legitimate needs. ARS maintains that, in the spirit of the Federal Technology Transfer Act, its scientists have used CRADAs to expand expertise and speed development of many new technologies of direct benefit to farmers and consumers as well as to multinational biotechnology firms.

Food Security in Developing Nations

Advocates of GURTs and other use restrictions claim that these technologies will help stimulate private efforts to breed and market new and improved crop varieties in countries which have not benefited from these advances. For them, GURTs are only the latest in a long list of ways of compelling farmers to buy seeds from the companies that have developed them. They also maintain that this type of restriction against unlicensed use of their products is perfectly reasonable for most researched goods, including commonly available hybrid seeds. Ultimately, they affirm, GURTs and other restriction technologies will give growers in developing countries the option of moving from subsistence farming into modern production agriculture.

Supporters also argue that GURTs will ensure that U.S. farmers will compete on a more level playing field with respect to other farmers worldwide. North American farmers, they maintain, have been paying for seed biotechnologies, while at the same time, some of these same technologies have been pirated into other countries without payments by farmers receiving their advantages.

On the other hand, critics of GURT use argue that these technologies will result in unacceptably limited seed choices for farmers. Patrick Mooney of RAFI, maintains that marketplace competition will force farmers to choose only seeds that promise the highest crop yields, and which are often genetically modified (GM) varieties. Farmers could become dependent on the biotechnology companies for an ongoing supply of the GURT seeds. "What happens if a company decides one area is not a profitable marketplace?" asks Mooney. Moving away from crops with viable seeds could threaten developing countries' ability to insure a reliable food supply from one year to the next, he says.

In a recent speech to Monsanto executives, Gordon Conway, president of the Rockefeller Foundation, called upon the biotechnology industry to disavow the use of "Terminator technology.13 Conway contends that current legal mechanisms and international trade agreements adequately protect against unlicensed use of patented plant varieties. For example, Conway asserts that the plant variety protection afforded by the International Union for the Protection of New Varieties of Plants (UPOV) is adequate against commercial pirating, and that UPOV qualifies as an acceptable crop intellectual property system under the World Trade Organization (WTO) Trade-Related Aspects of Intellectual Property Rights (TRIPS).14 Terminator-type technology that causes seed sterility, he declares, could cause widespread negative public reaction against biotechnology in general if farmers, unaware of the characteristics of purchased "Terminator gene" seed, attempt to re-use it. The issue of "dead seeds" and the potential loss in food security are seen as legitimate issues of national security by many governments.

Recently, in a move expected by some biotechnology analysts, Monsanto sided with Mr. Conway's views. In an open letter from Monsanto's CEO, Robert B. Shapiro, to the Rockefeller Foundation's president. Monsanto announced that it would not pursue or commercialize "Terminator gene" technology.15 Nevertheless, Mr. Shapiro did not rule out the possibility of using other technological approaches to gene protection that do not render seeds sterile, such as trait level-GURTs, as a means to protect and gain a return on investments in biotechnology innovation.

Experts examining GURTs for the Convention on Biological Diversity suggest that the greatest risk to food security is associated with wide adoption of Variety level-GURTs (as opposed to Trait level-GURTs). V-GURTs, they argue, may lead to increased farmer dependence on seed from a few commercial suppliers, and lead to increased levels of vulnerability during war, social unrest or natural disasters. T- GURTs, they assert, could contribute positively towards responding to private sector concerns of secure investments, while notably increasing farmers' choice on the decision to activate the trait if they so choose.

Some in the industry, like the Monsanto Corporation, have agreed that concerns about GURTs should be heard and carefully considered before any decisions are made to commercialize them. One important issue which must be tackled, according to Monsanto, is that of small farmers who rely on saved seed to provide seed stock for next year.

Crop Biodiversity

Another important set of issues relates to the impact of GURTs on genetic diversity in crops. One common concern is that GURTs could limit the sharing of germplasm among plant breeders worldwide. This potential for "locking up" of useful genetic variation, they argue, would be contrary to the spirit and intent of the Plant Variety Rights convention adopted in Paris in 1961. One reaction by the Consultative Group for International Agricultural Research (CGIAR), an important public source and repository of germplasm worldwide, has been to adopt a "non-use policy": CGIAR will not incorporate into its breeding materials any genetic systems designed to prevent seed germination.16 For its part, USDA has announced that it has no intention to introduce TPS into any germplasm in their National Plant Germplasm System (NPGS) collection or into its crop development research. CGIAR, with its 16 affiliated International Agricultural Research Centers, and USDA-NPGS are considered among the largest public germplasm repositories in the world.

GURT critics also argue that farmers, who already face a small pool of genetically uniform varieties, will face an even more restricted genetic make-up in their crops due to GURTs' faculty for stopping natural gene exchange processes, such as cross pollination and the formation of locally adapted crop varieties (i.e., land races). They caution against the risk of allowing such limited gene pools, as crops may become more susceptible to new diseases or pests.

Some scientists and GURT advocates who consider these negative scenarios unlikely, respond that there is no correlation between GURTs and lack of genetic diversity. They argue that GURTs should increase incentives for many private seed companies to breed crops which have not received sufficient attention in the past, and that it is likely that genetic diversity will increase as breeders focus on providing unique and improved versions of germplasm to farmers.

Concern has also been raised about accidental transfers of GURT gene(s), particularly in open pollinated species such as corn, which could lower the productivity of nearby conventional (i.e., non-GM) fields. USDA, for its part, says that the TPS is intended for deployment only in self-pollinating crops to ensure that the risk of pollen transfers to conventional fields remains extremely low.17

Current Legislation

One legislative proposal that potentially affects CRADAs (such as the one that resulted in "Terminator-type" technology) has been under consideration in the 106~ Congress. Section 6 of the proposed Technology Transfer Commercialization Act of 1999 (H.R. 209, as reported, and S. 804), would amend the Stevenson-WydIer Technology Innovation Act of 1980 to, among other things, require federal agencies with laboratories that are engaged in CRADAs to provide to Congress a review of their general policies and procedures for entering into major CRADAs involving critical national security technology, or that could impact domestic or international competitiveness.18 Future USDA CRADAs —particularly those dealing with biotechnology such as TPS and GURTs— could potentially be required to undergo this review process.

Footnotes

1 RAFI. Terminator seeds rejected by global network of agriculture experts. News Release- November 2,1998 ( http://www.rafi.org/pr/release23.html   ).

2 New Hampshire State General Court. HB 291. Adopted by both Houses on July 1, 1999 and signed by the Governor on July 16, 1999. Chapter 0282.

3 CBD: Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA). 4th Meeting. Montreal, June 21-25, 1999. Item 4-6 of the Provisional Agenda.

4 Many such "value-added" genes are currently on the market, including genetic modifications for insect and virus resistance, herbicide tolerance, production of specialty oils, controlled ripening, low lignin, and others. Seed companies currently protect these traits by patents.

5 One example of a V-URT is USDAD &PL 'TPS' patent. Other V-GURT patents had been issued previously, including: the Novartis Corp. (US-5650505 issued July 22, 1997), and the Monsanto Company (WO-9744465 issued Nov. 27, 1997).

6 Examples T-GURT patents are Zeneca Ltd's (UK), entitled "Cysteine protease promoter from oil seed rape and a method for the containment of germplasm" (WO-9735983) issued on October 2, 1997; and Purdue Research Foundation's "Selective expression of Genes in Plants" (WO-9911807) issued on March II. 1999.

7 Testimony before the U.S. House of Representatives, Committee of Agriculture hearing on Agribusiness Consolidation. February 15, 1999.

8 USDA-Economic Research Service. Genetically Engineered Crops For Pest Management. (http://www.econ.ag.gov/whatsnew/issues/biotech). July 1999.

9 Dr. William McBride. USDA-ERS. Personal communication. July 6, 1999.

10 Testimony before the U.S. House of Representatives, Committee on Agriculture. Subcommittee on Risk Management, Research, & Specialty Crops. Hearing on Agricultural Biotechnology. March 3, 1999. Personal telephone communication, July 7, 1999.

11 A thorough discussion of regulatory issues concerning food biotechnology in the U.S. can be found in CRS Report RL30198, Food Biotechnology in the United States: Science, Regulation, and Issues, by Donna Vogt & Mickey Parish.

12 B.A. Baker, A new advisory panel will help USDA tackle the thorny issues raised by agricultural biotechnology. Bioscience. Vol 49: 438. June 1999.

13 Gordon Conway, President Rockefeller Foundation. Speech to Monsanto Board of Directors. Washington, D.C. June 29, 1999

14 The TRIPS Agreement was concluded at the Marrakesh, Morocco WTO conference on April 15, 1994 and came into effect on January 1, 1995.

15 Shapiro, R.B. Open letter from Monsanto Open Letter From Monsanto CEO Robert B. Shapiro To Rockefeller Foundation President Gordon Conway. October 4, 1999. http://www.monsanto.com/monsanto/gurt/default.htm

16 CGIAR has issued no policy position regarding the use of T-GURTs. Personal communication with Dr. Manuel Lantin, Science Advisor. CGIAR Secretariat. Washington D.C. July 2,1999.

17 Knipling, E.B., -USDA-ARS Associate Administrator.- Letter to the United Nations Environmental Programme. May 14, 1999

18 A detailed discussion on CRADAs in U.S. research policy is found in CRS Report 98-862, "R&D Partnerships and Intellectual Property', and Issue Brief 89056, "Cooperative R & D: Federal Efforts to Promote Industrial Competitiveness" by Wendy Schacht.