Genetically Engineered Rice Varieties – What Issues Do They Raise?
Peggy G. Lemaux
Annual Rice Growers Meetings – February 1999 Colusa and Yuba City, California
Genetic engineering will play an increasing role in the future, providing alternatives to the farmer and manufacturer. Methods have been devised to introduce one or a few genes into many different cultivars of rice. These can result in very specific changes in a specific trait without affecting the overall performance or characteristics of the plant (see Agronomic Issues section below).
In the future these might improve disease and pest resistance, change the nutritional or production qualities of rice and its starch or add value to the grain by producing an alternative product in the seed. These products are not likely to be “magic bullets” that will provide quick solutions to problems, but they will provide useful, complementary tools in the grower’s arsenal.
The New Product Pipeline for all Crops
In 1992, when I first started in this position, I had to focus on the promise of biotechnology. There were no products in the marketplace and most activity relating to biotechnology was taking place in the laboratory. Today biotechnology is no longer just a promise , much is reality. We have crops in the field and products in the marketplace that have been genetically engineered and are being eaten by consumers. We have seen enhanced flavor tomatoes, higher solids tomato paste, viral resistant papayas and squash, herbicide- resistant soybeans, and insect resistant maize and cotton. In the summer of 1998, the percentage of actual production acreage was 50% of cotton was genetically engineered in the U.S., 30% of soybean and 20% of maize. In 1999, these numbers are expected to be 50% for cotton and soybean and 25% of maize for a total of about 60 million acres will be devoted to genetically engineered varieties.
In addition there is much in the pipeline. A rather sizeable effort relates to engineering fungal, bacterial, viral and insect resistance. The first products resulting from these technologies are already in fields, but these are only the initial rather limited offerings of the technology. There are second and third generation strategies that hopefully will come along before significant problems with pest resistance arises.
Agronomic traits include enhanced nitrogen utilization and herbicide tolerance. Harvest and post-harvest characteristics include the slow or no-ripening and more uniformly ripening tomatoes; high solids tomatoes and high starch potatoes. In the arena of value-added products, those for which value exists but for which new or improved functions can be identified that increase the value of the product. Examples would be specialty oils from rape or soybean with improved heat stability or sugarbeets that produce fructans, a sweet, no-calorie sugar substitute.
One of the more unexpected applications is in the area of functional foods or neutriceuticals. These are foods in which products in the food are either enhanced to prevent disease or removed if they cause undesirable effects in humans. In the category of products that prevent disease, an example is a potato engineered to produce high quantities of protein that is believed to prevent type I juvenile diabetes. Examples of those that cause undesirable human effects include food allergies; plants have been engineered to reduce the allergenic potential of foods. Perhaps the ultimate functional food is the plant that has been engineered to vaccinate the human or animal consumer.
Background on Herbicide Tolerance in Rice
Before looking at the issues, I would like to give you a general overview of herbicide tolerance and where this trait is at the moment with respect to rice. I have obtained this information from a variety of sources, but the responsibility for the synthesis of this information rests with me. At the moment there appear to be three approaches to herbicide tolerance in rice being pursued by three different groups. Imi-rice: The first combination is Imi-rice coupled with imidazilinone-type herbicides. The development of these varieties resulted not from genetic engineering p�s and seed dealers. These seed may/may not be viewed by the public as a GMO. I do not know what is envisioned for this germplasm in terms of introgression into California varieties.
Liberty Link Rice: Liberty-link varieties, being developed by AgrEvo, are being pursued through the introductions of a single bacterial gene into rice that inactivates the herbicide. Of the herbicide tolerant varieties, these are the furthest along toward commercial development, I believe, and the expectation (or perhaps hope) is that varieties tolerant to Liberty will be available on the market in 2001. In late January or early February AgrEvo petitioned the USDA for deregulation of its Liberty Link varieties; the USDA is presently seeking public comment until March 29 on whether these lines pose a plant pest risk, the area of responsibility for the USDA. The lines are also under review by the EPA, which will release a separate report.Roundup Ready Rice: Roundup Ready varieties, being developed by Monsanto, also represent single gene introductions through genetic engineering. Instead of herbicide inactivation, this gene is responsible for the synthesis of a target biosynthetic enzyme that is unaffected by the herbicide. At this point, these lines are in the early phases of development; early material is being screened to try to find lines that are marketable. They hope these lines make it to the marketplace by 2003.
Herbicide Tolerant Germplasm Development in California
Rice lines with tolerance to both Liberty and Roundup are being tested here in California at the Rice Experiment Station (RES) and at other locations. Both tolerances have been engineered into the California variety, M202, developed by Carl Johnston at the Rice Experiment Station. The goal and participation of the Rice Experiment Station is to try to make these varieties available to growers at a reasonable cost and to bring value to these varieties in California.
At present this work is being done under a fee for services rendered basis; they are not focused on varietal development and there are no royalties being paid to the station. Contracts for future development of varieties are under negotiation. The hope is that second- generation varieties will involve a more active participation by the RES.
According to contacts at AgrEvo, genetically engineered seed produced by the RES will be “Foundation Certified Seed”, but it will be produced under contract to the company. Final marketing of the seed will “involve” AgrEvo, meaning that they will play a role in how it will be done.
Production contracts will be different from what they are now because of the need for tighter quality control. What does tighter quality control mean? It relates to the actual genetic makeup of the seed. In addition to current seed certification requirements, molecular certification requirements will be added. A corollary to this is that engineered and nonengineered plants grown for seed production cannot be grown together. In addition, the exact genetic makeup of the crop, including the precise location of the introduced gene in the genome, will have to be the same as that approved for commercialization. This will be carefully monitored by regulatory agencies. The regulatory structure is in place in part to help with consumer acceptance through the use of scientific review of human health and nutrition safety issues.
Issues Raised by Herbicide Tolerant Rice
The focus at the moment in rice is on herbicide tolerance but this is represents only the first application of this powerful technologyWith these positive benefits, however, come some issues raised by their use. Some of these issues are specific for the herbicide-tolerance trait and some are more general and relate to the genetic engineering strategies themselves. This list of concerns were relayed to me by Cass Mutters and they fall into six general categories: agronomic, environmental, regulatory, consumer acceptance, industrial and intellectual property concerns.
1. Reduced yield potential
2. Cleaning up the undesirable characteristics arising from the gene insertion.
3. Lines derived from direct insertions will be less adapted and produce less high quality seed.
4. Gene stacking (eg. herbicide resistance and Bt) will further reduce yield.
5. In long term there will be little genetic improvement for yield. Industry focuses on short term objectives with little concern for the importance of quantitative genetics in yield improvement.
6. Yield stability over years and locations not a concern of companies.
7. Terminator technology – what is it and how might it be used?
This represents my own area of research expertise, so I can speak to these points with some personal knowledge. While it is true that often the process of introducing a gene can result in plants that are less robust than their nonengineered siblings, there are ways to minimize this effect. This negative effect comes not from the gene itself that interferes with some plant function (the new gene only represents about 1/300,000th of the total genomic content of the cell).
The effects come from the actual process needed to manipulate the plant tissue during the genetic engineering process. These negative effects can be minimized by careful selection of the plants that are advanced during product development. This is another characteristic used to advance lines, in addition to the performance of the transgene. In addition to selection on the basis of performance, engineered plants can be outcrossed to nonengineered plants to remove any negative effects of the transformation process. Since the effects are due to the process and not the introduced gene, this is readily possible although it does take some years to accomplish and sometimes the defects are closely linked to the newly introduced gene. There is no reason why stacking of genes inherently will result in yield loss. After all, there are over 100,000 genes in a plant already and manipulating two of these is not going to cause a yield drag in and of itself.
I do not believe it is the intent of the companies to put forth agronomically inferior seed in the marketplace. According to Ron Vargas, a CE Advisor working on genetically engineered cotton, his suggestion to cotton growers is that they chose their lines based on their agronomic traits and not on the particular technology that will be used for weed control. This should be tempered, however, with considerations for weed resistance management control.
With regard to improvement of germplasm for yield, I believe that this goal will remain a responsibility of public sector breeders. Because of this, I believe is will be necessary and prudent for companies to develop good working relationships with these breeding programs and that both sides benefit. Portions of the royalties from the sale of these genetically engineered seed should return to the public breeding programs so that they can continue to focus on the development of next generation germplasm with improved overall agronomic traits, while companies focus on the identification and characterization of value-added genes. The two entities then work together to introduce the new traits into improved germplasm. This is the only scenario that makes sense for the long-term improvement of agricultural production. Neither side can accomplish these goals alone and both could and should benefit.
Technology Protection System or “Terminator Technology”. This approach is a relatively new one patented by a small cotton company, Delta and Pine Land, and the USDA; the Monsanto Corporation has made a bid to buy DP, but that deal is still awaiting approval by the Department of Justice. The fundamental idea with this technology is to prevent a plant from reproducing itself by interfering with seed development, thus insuring that the user of the seed cannot replant a field without repurchasing the seed, thereby protecting the company’s investment in developing the variety. Plants produced from germplasm that has been engineered with the terminator system will produce sterile seeds incapable of reproducing. DP&L is currently pursuing this technique in cotton and wheat and expect these products to be on the market by 2005. With the entry of Monsanto into the equation, application of the technology could accelerate into many more crops and the advent into the marketplace could be much more rapid.
There has been much furor and debate about this technology since obviously it can be viewed as an interference with farmer’s rights and insures that farmers return every year to purchase a new lot of seeds. The appeal of such a technology is that it affords the companies a way to protect their investment in the development of the new varieties by making it compulsory for the grower to return to purchase seed each year. This eventuality has led a large, international, not-for-profit agricultural research organization, the Consultative Group on International Agricultural Research, or CGIAR, to consider banning the use of the technology in crop development programs. While certainly there is a negative aspect to the technology related to farmer’s rights, I would offer a counter perspective on the use of such a technology. Another concern held by environmentalist and certain agriculturalists is that certain traits, like herbicide tolerance and certain other traits, will escape from the crop plant and enter into wild species located nearby, thereby creating situation where it is difficult to control the wild species or it has some other new, adverse characteristic. This issue has been raised with rice and red rice. The use of such a technology for engineering rice that has red rice nearby is a prudent approach to preventing the dissemination of genes to the weedy population.
1. Outcrossing to related species may create super weeds.
The major issue here is red rice. The specter of outcrossing with red rice has been a consideration in the introduction of herbicide resistance in rice. Since this is not as big a problem in California (or Australia and Japan) as it is in other rice-growing areas in the U.S., there are fewer worries here as long as red rice is kept in check. At this point, there are no plans to market Roundup Ready Rice in the southern states because of red rice problems; if this occurs, it is likely at least five years away.
Tests have been conducted to look at the rate of outcrossing of red rice with conventional rice varieties. If flowering of red rice and conventional rice occurs at the same time, outcrossing frequencies can be as high as 50% when panicles are touching. Under conditions of normal distances between plants (10-20 feet), outcrossing frequencies are considered to be very low.
In the case of Liberty Link Rice, if conventional and herbicide tolerant rice are planted at the same time and sprayed with different amounts of Liberty at sublethal levels, red rice will be delayed in flowering. This will drastically reduce the opportunity to outcross since rice pollen remains viable for only a few hours.
Pricing strategies could also influence the re-development of the red rice problem. Twenty-five years ago, red rice was a problem in the state. If seed is priced too high, there is a possibility that growers will be tempted to find a lower quality source of seed that is not certified and the red rice problem could return.
2. Development of resistant/and or harder to kill weeds.
Perhaps the greatest protection against the development of herbicide resistant weeds is the rotation of herbicides and herbicide tolerant crops from year to year. The charge implied here is that it is prudent for all of these traits to be introduced into California rice varieties; germplasm within the state should not in my opinion be made exclusively available to a single company.
With competing chemistries available, the grower should be encouraged to change chemistries from year to year to avoid the problem of herbicide-resistant weeds. The development of imidazlinone-resistant weeds is well-documented, so care must be taken in utilizing this chemistry when repeated in successive years. With respect to Roundup, it has been stated that as a result of the inherent properties of the biochemistry of the herbicide and its resistance, the rate of resistance development would be very low, if it occurred at all. However, in recent years in Australia and now in Northern California, examples of herbicide resistance in weed populations have been confirmed. Liberty is a relatively new chemistry and, although I have not heard of documented cases of resistance developing, this is likely to occur. If it is going to be possible to retain these varieties as options for weed management, it would be wise to rotate herbicide-tolerant crops and chemistries on a yearly basis. This means that popular rice varieties in the state should be made available with all the tolerance genes in them.
3. Spray drift from one farm to another
This seems to be a major issue with the deployment of herbicide-tolerant crops. It would not be possible for each grower to know precisely what, if any, herbicide-tolerant crops are being grown in his neighbor’s fields. In addition, it would not be possible to protect his/her own crops from drift from a neighbor, who might have Roundup Ready varieties of cotton, while your acreage might have Liberty Link varieties of rice. Since there are no outward signs that would alert one grower to the varieties in his neighbors’ fields this could lead to a serious problem with drift damage and it is not clear how this could be managed.
1. Isolation requirements.
2. Maintenance of identity from field to processing to shipment could require substantial and costly changes in the infrastructure.
Industry is developing a very robust regulatory package, which if carefully adhered to, should result in no restrictions on the movement of grain in international trade. These shipments will be monitored using molecular methods to show that the grain is identical to the specified product. Each variety will have its own “genetic fingerprint” and it will likely be up to the importing county to confirm this identity. AgrEvo is attempting to get import clearances into all major markets, Canada, South America, Europe and Japan. These packages will be put forward after the data from this winter’s trials are analyzed. They project it will require 1-2 years to get clearance in Europe; the new directive is that each application for clearance will be on a case-by-case basis. AgrEvo just obtained clearance on their Liberty Link Soy.
It is not anticipated that there will be labels put onto food containing transgenic rice in the U.S. If this were enacted then there would be a substantial requirement for careful tracking of varieties and maintenance of identity, requiring substantial changes in the infrastructure of grain movement and manipulation. In Europe and Japan, it is not known for sure what will be required by the time these foods reach the marketplace.
PUBLIC ACCEPTANCE ISSUE
In part, regulatory structure is put into place to assure adequate scientific assessment of the safety of these crops, thereby aiding in consumer acceptance. That this system of regulation is in place and generally being regarded as effective by the U.S. public marks a major difference between the U.S. and Europe. Much of the unrest in Europe is due to the fact that the governments there are often viewed as being controlled by the very industry they attempt to regulate.
At this point no one knows what the consumer acceptance issues are going to be in Europe in particular. At this point, however, acceptance issues appear to be much bigger than the technical and mechanical aspects of creating or growing engineered plants. Over the last five years the situation has changed dramatically in the U.S., as well as Europe. Some change has been toward greater acceptance, some toward lesser.
In another five years who knows what the situation is likely to be, although it is likely to be much different. GMOs will be very prevalent; it will be difficult to purchase a processed food that does not have some component that is GMO. This should lead to consumer familiarity and loss of skepticism. In addition there will be products in the marketplace with real consumer appeal (unlike herbicide-tolerant varieties, which have grower-appeal but not many consumers share the enthusiasm). Products seen as desirable by consumers will likely lead to greater acceptance, as has been shown by the widespread use of Olestra, the fat substitute that bears a label with warnings about antinutritional factors.
To date, the major crops that have been genetically engineered have been used as processed products, food ingredients and/or animal feed, products such as soy lecithin, cottonseed oil or high-fructose corn syrup. Rice might be the first directly consumed, major staple food to hit the market.
Issues relating to acceptance will likely be the same for all members of industry and should be approached in unison by all. AgrEvo is approaching the acceptance issue as Calgene approached this for the Flavr Savr tomato. The regulatory package will be more extensive than that prepared for BollGard Cotton or Roundup Ready Soybean. It should be kept in mind, however, that rice is a cooked food and thereby some issues related to the potential for DNA transfer to gut bacteria will not apply here as they did with Flavr Savr. In addition in the case of Liberty Link Rice, there will be no antibiotic resistance gene product associated with the food; however, the herbicide tolerance protein, PAT, will have to undergo extensive food safety testing, as was done for the antibiotic resistance gene product (Kan) in the Flavr Savr. AgrEvo will do extensive scientifically conducted tests to assure food safety of PAT itself as well as the whole food.
1. Chemical personnel are overselling the value of herbicide resistant varieties; they are just an additional tool for weed control. 2. Some of these concerns have been realized in cotton, corn , soybean, and canola transgenics.
I spoke about these issues with Ron Vargas. He told me that 7,000 acres of Roundup Ready cotton was grown in California in 1998 to perform agronomic testing. These data indicated that this trait provided excellent weed control and few if any problems with cotton injury or loss of yield due to improper application timing. It has completely eliminated the need for hand hoeing and this resulted in a considerable cost savings to growers.
Ron made some specific points about Roundup Ready CottonThe availability of these varieties doesn’t offer anything new, per se, but simply provides another tool for weed control and an additional option for resistance management. The choice of varieties to use should be driven by considerations of agronomic traits, not based on the particular technology. It would not make sense to pick a variety with the Roundup Ready gene and poor yield potential or poor disease resistance. Research studies on application of the herbicide revealed that a wise alternative to through-season application of Roundup might be to use it to control early emergence (no later than the 4-leaf stage), but to use a different chemistry for late season control. This could lead to better weed resistance management and prevent damage to bolls that occurs with later application.
With regard to Liberty application rates and times, Matt Elhardt and Jim Hill have done field research that will help to define the label for Liberty. As with all agricultural chemicals, will define the application rate, method and timing of application; this is developed in consultation with the EPA. These recommendations are aimed at minimizing crop damage, maximizing weed control and limiting the chemical residue in the grain. Because of the latter, the label will define a certain period after which the herbicide cannot be sprayed. The label will likely be similar to labels currently in place where red rice grows. There is currently a debate as to whether the label will state that you must spray if you have red rice growing in the vicinity.
3. Growers must enter a licensing agreement with companies to inspect fields, seed storage etc. Violators may suffer substantial economic losses.
Monsanto has taken to court farmers who have attempted to save seed and replant genetically engineered varieties in their own fields. Fields apparently are monitored by the company to assure compliance. The practice of saving seed is in violation of a company rule that requires farmers to buy the seeds every year. The obvious reasoning here is so that the company can recoup the millions of dollars spent developing the seed. Some farmers claim that the seed that Monsanto has found on their property is not “saved” seed but must have entered into their fields from nearby neighbor’s fields. The issue of saving seed appears not to be such an issue with rice growers in California since few farmers replant their own seed anyway, probably due to the red rice issue.
INTELLECTUAL PROPERTY ISSUES
1. Confidentiality agreements and lawyers.
This is a reality of the new technology. While cumbersome and unfamiliar, it has happened to protect and encourage investment in the technology. Perhaps with time, this aspect of the technology will change in how it affects the industry and the development of germplasm. But, for the moment, it is the reality with which we must live and grow rice. There are alternatives, however, and that relates to the types of practices and germplasm that were used before these varieties were available; these can still be used.
2. How to protect the genes in CA varieties.
AgrEvo, for example, has a patent on the herbicide tolerance gene and on the methods to introduce the gene. This leads to their having made a major investment in using these methods and identifying genes for germplasm development. It is estimated by Monsanto, for example, that each new engineered seed requires 10 years and $300 million to create as a commercial product. For every new engineered seed that makes it to field trials, 10,000 failed during the development. Alternatively public breeding programs have spent thousands of hours. drawn on years of experience from the breeders and taken decades in the development of their finely tuned varieties. Each side in this equation has a significant investment in the final product.
The Rice Experiment Station has developed the basic germplasm into which genes are placed by the private sector partner. The private partner has invested resources into identifying and characterizing the genes and herbicides used and for the technology to introduce the gene. In addition companies are taking responsibility for and paying for obtaining regulatory clearances for the varieties and this is no small matter. Therefore it seems prudent that both sides should ultimately benefit from the creation of the new, engineered varieties.
3. A variety containing the gene will be controlled by the patent holder.
In the long term, I believe that companies realize they will need access to the latest germplasm. This will lead to cooperativity with the developers of germplasm adapted to particular areas. This is not the last value-added gene that will be introduced into rice and the technology is not likely to “go away” in the near or long-term. Therefore it would be short-sighted to overlook a “win-win” situation for them. The stated intent of the private sector is to share value with the growers. If the company can realize, for example, $20 benefit from a particular improvement, they intend to charge $15 not $30 because they consider the grower a customer and want to share the benefits with them.
There will be a grower agreement when purchasing the seed. Although the precise details of this agreement for rice are not known at present, it is likely to look like agreements that are in place with computer software in that you are free to use it for your own benefit, but you are not to share it with others. According to my sources, most growers do not save seed at present, only about 2-5%.
In summary, it is important to realize that the new technologies bring benefit, but with that benefit change that is often uncomfortable. Herbicide-tolerant rice varieties can be a benefit for weed management, as they are proving to be in cotton. But with this new tool come some responsibilities for resistance management. Different combinations of engineered plants and herbicides need to be available to growers and rotation of these chemistries should be encouraged. This is most likely to occur if the traditional sources of germplasm development are involved in the development of the varieties. Both the private and public sector, as well as agriculture in general and the consumer, will benefit from the cooperation of these two sectors in future germplasm development.