INFORMATION SYSTEMS FOR BIOTECHNOLOGY


February 2008
COVERING AGRICULTURAL AND ENVIRONMENTAL BIOTECHNOLOGY DEVELOPMENTS


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IN THIS ISSUE:



FIELD EVIDENCE: Bt CORN AND MYCOTOXIN REDUCTION
Felicia Wu

Introduction
Though many of the earliest transgenic crops introduced traits with primary benefits going to growers, some of those crops also provide secondary benefits to consumer health. Bt corn is such an example. It is one of the most commonly grown transgenic crops in the world today. It contains a gene from the soil bacterium Bacillus thuringiensis, which encodes for a protein that is toxic to certain members of the order Lepidoptera. These include the common corn pests European corn borer (ECB, Ostrinia nubilalis), Southwestern corn borer (SWCB, Diatraea grandiosella), corn earworm (CEW, Helicoverpa zea), and corn rootworm (CRW, Diabrotica spp). Bt corn is harmless to vertebrates and non-lepidopteran insects.

One indirect benefit from Bt corn adoption is lower levels of mycotoxin contamination. Mycotoxins are secondary metabolites of fungi that colonize crops. They are considered unavoidable contaminants in foods, as best-available technologies cannot completely eliminate their presence in crops. Insect damage is one factor that predisposes corn to mycotoxin contamination, because insect herbivory creates kernel wounds that encourage fungal colonization, and insects themselves serve as vectors of fungal spores. Thus, any method that reduces insect damage in corn also reduces the risk of fungal contamination. Indeed, in a variety of field studies, Bt corn has been shown to have significantly lower levels of common mycotoxins, the subject of which is reviewed in this article.

Four common mycotoxins in corn
Four mycotoxins that contaminate corn are fumonisin, aflatoxin, deoxynivalenol, and zearalenone. Fumonisins are produced by the fungi Fusarium verticillioides (formerly F. moniliforme) and Fusarium proliferatum. Consumption of fumonisin has been associated with elevated human esophageal cancer incidence in various parts of Africa, Central America, and Asia and among the black population in Charleston, South Carolina. Because FB1 reduces uptake of folate in different cell lines, fumonisin consumption has been implicated in connection with neural tube defects in human babies. Fumonisins can be highly toxic to animals, causing diseases such as equine leukoencephalomalacia in horses and porcine pulmonary edema in swine.

Aflatoxins, produced by Aspergillus flavus and Aspergillus parasiticus, are the most potent naturally-occurring liver carcinogens known. For people infected with hepatitis B or C, aflatoxin consumption raises more than tenfold the risk of liver cancer compared with either exposure alone. Acute aflatoxicosis, characterized by hemorrhage, acute liver damage, edema, and possibly death, can result from extremely high doses of aflatoxin. Aflatoxin consumption is also associated with stunting in children and immune system disorders. Aflatoxins cause a variety of illnesses in animals as well. In poultry, aflatoxin consumption results in liver damage, impaired productivity and reproductive efficiency, decreased egg production in hens, inferior egg-shell quality, inferior carcass quality, and increased susceptibility to disease. In cattle, the primary symptoms are reduced weight gain, liver and kidney damage, and reduced milk production.

Deoxynivalenol (DON, or vomitoxin), the most common mycotoxin in cereals, is produced by the fungus Fusarium graminearum and the related species Fusarium culmorum in cooler climates. It is a significant contaminant of corn, wheat, and barley in generally more temperate regions of the world, such as the United States, Canada, and Europe. DON is an inhibitor of protein biosynthesis and causes human and animal effects ranging from feed refusal, vomiting, and nausea to immunosuppression and loss of productivity.

Zearalenone, like DON, is produced by F. graminearum. Zearalenone is sometimes referred to as a mycoestrogen, as it causes estrogenic responses and vulvovaginitis in swine. At higher concentrations, zearalenone causes similar effects in poultry and cattle. In humans, there has been limited evidence of an association between zearalenone consumption and premature puberty.

Many nations have established regulatory standards on the maximum tolerated levels of mycotoxins in food and feed. Thus, aside from the health risks described above, mycotoxin contamination can also reduce the price paid or cause market rejection of entire corn loads.

Field evidence of Bt corn’s reduction, or lack thereof, of mycotoxins
Several different factors can predispose corn to fungal growth and subsequent mycotoxin accumulation. In pre-harvest corn, high or unusually fluctuating temperatures, drought stress, incompatibility of the corn hybrid for the region in which it is planted, and insect pest damage increase mycotoxin levels. Notably, insect damage is well recognized as a collateral factor in mycotoxin development. Insect pests create wounds on the corn kernels and act as vectors for certain types of fungal spores. In post-harvest corn, storage conditions such as high humidity, pre-harvest presence of fungi, and the presence of stored grain insects may contribute to further fungal development and accumulation of mycotoxins in corn. Again, insects in storage create grain wounds and spread fungal spores to cause further post-harvest accumulation of mycotoxins.

Where insect pests are present, Bt corn has lower levels of certain mycotoxins than non-Bt isolines. The insect pests ECB, SWCB, and CEW have been shown in field trials to contribute to the concentration of mycotoxins in corn. Insect-damaged corn is also prone to mycotoxin accumulation in storage. Therefore, to the extent that Bt corn has lower levels of insect damage, it indirectly controls for one of the most important predisposing factors of mycotoxin accumulation.

In the Corn Belt region of the United States, field studies have demonstrated that when insect damage from ECB or SWCB is high, fumonisin concentrations are significantly lower in Bt corn compared with conventional corn. Importantly, in multiple locations across the US, Bt corn (compared with non-Bt isolines) had fumonisin levels that were below the Food and Drug Administration (FDA)’s 2-ppm guideline for fumonisin in food1. Yet another study showed that Bt hybrids can reduce fumonisin levels when ECB is favored, but not in seasons when CEW is favored. In Europe and in other parts of the world, Bt corn has been shown in field trials to have significantly lower fumonisin levels than non-Bt isolines. Significantly lower levels of fumonisin were measured in Bt hybrids when compared to controls in 288 separate test sites in France, Italy, Turkey, Argentina, and the United States. Fumonisin concentrations in Bt grain were often lower than 4 mg/kg, with a significant proportion of these below 2 mg/kg2.

Compared with fumonisin, insect pest damage is less strongly correlated with aflatoxin concentrations in corn, as multiple factors predispose corn to accumulation of aflatoxin. The lepidopteran insects that are controlled by currently commercially available Bt corn varieties are not as important in predisposing plants to infection by A. flavus as they are for F. verticillioides; and A. flavus can infect corn not just through kernel wounds caused by insects, but through the silks. Indeed, field tests of aflatoxin reduction in Bt corn show a mixed record. Bt hybrids were shown to have lower aflatoxin levels than non-Bt isolines in the southern US in years when aflatoxin levels would otherwise have been high, but there was no significant difference when aflatoxin levels were low in both Bt and non-Bt isolines. Other studies show no significant effect of Bt corn, or mixed results. Studies have shown that other factors, such as drought stress and individual hybrid vulnerability, are more important in determining aflatoxin contamination levels than insect damage. Two field studies in Italy independently showed no impact of Bt corn in reducing aflatoxin levels. Importantly, however, new events of Bt corn are being developed that provide better protection against corn earworm and fall armyworm, insects that are closely associated with aflatoxin accumulation in corn3. Field trials have demonstrated that these Bt corn varieties do indeed have significantly lower aflatoxin levels than non-Bt isolines4.

F. graminearum is similar to A. flavus in that it can infect corn without insect damage. Correspondingly, the evidence for lower levels of deoxynivalenol in Bt corn is also mixed. In Canada, where European corn borer pressure was high, the use of Bt hybrids reduced the level of DON by 59% compared with non-Bt isolines. In these cases, Bt corn consistently had levels of DON that were acceptable by FDA standards (i.e., below 1 mg/kg)5. Where ECB pressure was low, however, there was no significant difference between DON levels in Bt vs. non-Bt hybrids (which were below 1 mg/kg in either case). One study showed that in animal feed, the only nutritional difference between Bt and non-Bt corn feeds was that Bt corn had lower levels of DON and zearalenone6. However, in a central European field study, the association between European corn borer damage and DON concentrations was not consistent across years.

Two studies have examined whether Bt corn has lower levels of zearalenone, also produced by F. graminearum. One study found that though zearalenone levels were generally low in field tests in France and Spain, Bt hybrids did show significantly lower zearalenone at certain test sites. As described above, animal feed made from Bt corn was shown to have lower zearalenone levels.

Table 1 summarizes the available literature on currently commercially-available Bt corn events and mycotoxin reduction, or lack thereof, evidenced in field trials around the world. Specific references for all these studies are summarized in reference 7 (below).

Table 1. Studies demonstrating current events of Bt corn’s control, or lack thereof, of fumonisin, aflatoxin, DON, and zearalenone in field trials.

Bt corn lower mycotoxins than non-Bt isolines?

Yes

No

Fumonisin

· U.S. Midwest

· Throughout U.S.

· U.S. Midwest when European corn borer favored

· France, Italy, Turkey, Argentina

· Germany

· Philippines

· U.S. Midwest when corn earworm favored

Aflatoxin

· U.S. South when aflatoxin levels high, or fungus applied through non-wounding technique

· U.S. South, some years

· U.S. South, new varieties controlling corn earworm and fall armyworm

· U.S. South when aflatoxin levels low, or fungus applied by wounding technique

· U.S. South

· U.S. South, some years

· Italy

Deoxynivalenol

· Canada

· Germany (animal feed)

· Eastern Europe, some years

· Eastern Europe, some years

· Germany

Zearalenone

· France and Spain

· Germany (animal feed)

Summary
Bt corn is being planted at an ever-growing rate around the world. Aside from its primary benefit of insect pest protection, it has the important secondary benefit of reducing mycotoxin concentrations, because of the relationship between insect pest damage and fungal colonization. The currently-available varieties of Bt corn have shown strong evidence in field conditions worldwide of having significantly lower fumonisin levels than non-Bt isolines. There is also limited evidence for lower levels of DON and zearalenone in Bt corn, although there are fewer field studies on these relationships. The more extensive work on aflatoxin reduction in Bt corn has yielded mixed results, but new varieties of Bt corn that may be commercialized soon are likely to have a more significant impact on aflatoxin levels. Hence, Bt corn is an important potential tool for mycotoxin control, both in the US and in other nations.

References

1. Munkvold GP, Hellmich RL, Rice LG. (1999) Comparison of fumonisin concentrations in kernels of transgenic Bt maize hybrids and nontransgenic hybrids. Plant Disease 83(2), 130-138

2. Hammond B et al. (2003) Reduction of fumonisin mycotoxins in Bt corn. The Toxicologist 72(S-1), abstract 1217

3. Munkvold GP. (2003) Cultural and genetic approaches to managing mycotoxins in maize. Annual Review of Phytopathology 41, 99-116

4. Headrick J.M. (2006) Application of multiple approaches toward reducing aflatoxin contamination of corn grain. Proceedings of the 2006 Annual Multi-Crop USDA Aflatoxin/Fumonisin Elimination & Fungal Genomics Workshop, Oct 16-18, 2006. Ft Worth Texas, p. 33

5. Schaafsma A et al. (2002) Effect of Bt-corn hybrids on deoxynivalenol content in grain at harvest. Plant Disease 86(10), 1123-1126

6. Aulrich K et al. (2001) Genetically modified feeds (GMO) in animal nutrition: Bacillus thuringiensis (Bt) corn in poultry, pig and ruminant nutrition. Archives of Animal Nutrition 54, 183-195

7. Wu F. (2007) Bt corn and mycotoxin reduction. CAB Reviews: Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources 2(060), 8 pp

 

Felicia Wu
Department of Environmental & Occupational Health, Graduate School of Public Health
University of Pittsburgh, 100 Technology Dr., Pittsburgh, PA 15219
few8@pitt.edu



ENHANCING PLANT CAROTENOIDS VIA MANIPULATION OF SINK STRENGTH
Xiangjun Zhou & Li Libr

Carotenoids represent a large group of naturally occurring pigments found in many flowers, fruits, and roots. They provide essential phytonutrients, such as provitamin A, and confer many health benefits, such as reducing the incidence of certain diseases, including cancer, cardiovascular diseases, and age-related eye diseases. Therefore developing carotenoid enriched food may offer a sustainable avenue for improving human nutrition and health.

Engineering carotenoid biosynthesis
In past decades significant progress has been made in the dissection and genetic engineering of carotenoid biosynthesis in plants. Through a combination of molecular, genetic, biochemical, and genomic approaches, a nearly complete set of the genes and enzymes involved in carotenoid biosynthesis has been isolated and characterized1. The availability of a large number of carotenogenic genes from various sources provides the necessary molecular tools for enhancing the carotenoid content and composition in food plants to benefit humans. One of the best known successful examples of improving crop nutritional value is Golden Rice. In "Golden Rice 2," ectopic expression of genes in a mini-carotenoid biosynthetic pathway results in the accumulation of up to 31 μg/g β-carotene in rice endosperm, a level adequate to provide most of the recommended dietary allowance of vitamin A for children consuming an average amount of rice daily2. Manipulation of the biosynthetic genes that control the committed steps of carotenoid biosynthesis offers an effective approach to quantitative and qualitative alteration of carotenoids in food crops.

The orange cauliflower and the Or gene
Unlike Golden Rice, which was generated using a genetic engineering approach, the eye-appealing orange cauliflower (Fig. 1) arose from the spontaneous mutation of a single gene, designated as Or for Orange gene. The orange cauliflower was first discovered in a white cauliflower field in the early 1970s in Canada. Besides orange curd, the orange cauliflower mutant also exhibits visible orange coloration in the apical shoot and the stem pith. The orange color is due to the accumulation of high levels of primarily β-carotene.

Interestingly, mRNA from the expression of carotenoid and upstream isoprenoid biosynthetic genes is detected not only in the curd tissue of the mutant that accumulates β-carotene but also in the comparable unpigmented wild type tissue. The expression of carotenoid biosynthetic genes is not dramatically altered by the mutation; neither is the expression of upstream isoprenoid biosynthetic genes. Microscopic analysis showed that β-carotene accumulation in the Or mutant occurs in chromoplasts, predominantly as sheet structures. Furthermore, only one or two large chromoplasts are found in each affected cell in the apical meristem and curd meristem tissues of the Or mutant, suggesting limited plastid division in the Or mutation3. These results collectively imply that rather than regulating the capacity of biosynthesis, the Or gene may exert its effect on carotenoid accumulation through a novel mechanism.

The Or gene was isolated via a map-based cloning strategy and successfully verified by phenotypic complementation4. Sequence analysis revealed that the Or gene mutation is due to the insertion of a 4.7 kb copia-like LTR retrotransposon in the mutant allele, which results in a likely gain-of-function mutation that positively controls carotenoid accumulation. Three alternatively spliced Or mutant transcripts were produced following excision of the retrotransponson4. All of the spliced transcripts can read through, and they share the same start and stop codons as the wild type gene. Interestingly, overexpression of any one of the spliced transcripts does not cause the orange phenotype with associated carotenoid accumulation in transgenic plants, which suggests that Or-induced carotenoid accumulation may require the expression of more than one alternatively spliced transcript.

The most prominent feature of the OR protein is the presence of a cysteine-rich zinc finger domain in its C terminal. This domain is highly specific to DnaJ-like molecular chaperones, which participate in protein folding, assembly and disassembly, and translocation into organelles. Because OR lacks the typical N-terminal J domain that defines DnaJ-like molecular chaperones, OR is more likely a novel protein with a unique cellular function, and may exert its functional role in association with the molecular chaperone system. The OR protein is predicted to be targeted to the plastid. Indeed, the Orwt:GPF fusion protein was associated with non-colored plastids4.

The Or gene shares no sequence homology with the carotenoid biosynthetic genes and appears to exert no direct effect on the capacity of carotenoid biosynthesis. By contrast, analyses of the gene, the gene product, and the cytological effects of Or indicate that Or-induced carotenoid accumulation is associated with a metabolic process that triggers the differentiation of non-colored plastids into chromoplasts. Indeed, introduction of the Or transgene into white cauliflower results in the formation in the curd cells of large membranous chromoplasts containing increased levels of fusion protein β-carotene.

Or as a new molecular tool to enhance carotenoid accumulation
To examine the application of Or as a new genetic tool to enhance carotenoid content in a staple crop, the Or gene was transformed into potato plants under the control of a tuber-specific promoter. Remarkably, the Or transgenic potato plants produce tubers with a deep orange-yellow flesh. HPLC analysis showed that these transgenic tubers exhibit more than a 6-fold increase in total carotenoid content. The transgenic tubers contain not only increased levels of the violaxanthin and lutein that are normally present in nontransformed controls, but also accumulate significant levels of β-carotene. In addition, three other metabolic intermediates, phytoene, phytofluene, and ζ-carotene, which were not detected in the controls, also accumulated. The accumulation of these metabolic intermediates suggests a hindrance in desaturation in the carotenoid biosynthetic pathway. Such a hindrance may restrain the extent of Or-induced carotenoid accumulation in the transgenic potato tubers.

An examination of the cytological effects of the Or transgene by light microscopy revealed that expression of the Or transgene in the heterologous system leads to formation of chromoplasts with orange structures in transgenic potato tubers5. However, analysis of dark yellow-flesh potato cultivars with high levels of carotenoids revealed that they do not contain chromoplasts, demonstrating that high levels of carotenoid accumulation do not necessarily result in the formation of chromoplasts. Moreover, the Or transgene caused no dramatic changes in the transcript levels of endogenous carotenoid biosynthetic genes. Collectively, these results demonstrate that the induction of chromoplast formation is the cause of the Or-associated carotenoid accumulation.

Chromoplasts found in many flowers, fruits, and roots are characterized by high levels of carotenoids. Chromoplasts frequently derive from fully developed chloroplasts, as seen during the ripening process in tomato and pepper fruits. They also arise from other non-colored plastids, as in the case of carrot, squash, and the orange cauliflower. Chromoplasts have a unique mechanism for accumulating massive amounts of carotenoids: they generate carotenoid-lipoprotein structures, which create a chemical disequilibrium to effectively sequester the end products of biosynthesis. Such structures function as a deposition sink to store carotenoids, and also may prevent the end products of the carotenoid pathway from overloading chromoplast membranes, which are the site of carotenoid formation. A number of studies have demonstrated that biosynthesis of an appropriate sink structure correlates directly with increased carotenoid accumulation. Thus, chromoplasts serve as an effective metabolic sink to facilitate the sequestration and storage of carotenoids.

Alternative strategy for engineering carotenoids in low-pigmented crops
Carotenoid accumulation is not dependent solely upon the catalytic activities of carotenogenic enzymes, but also involves a network of other processes such as metabolite turnover and the stable storage of end products. The study of the Or mutant gene provides strong evidence showing that an increase in sink strength exerts a strong influence on carotenoid accumulation, and thus sink strength offers a novel approach for genetically engineering the carotenoid content in food crops.

Many important crops such as wheat, rice, barley, maize, potato, and cassava contain low levels of carotenoids in edible seeds or roots. These vitamin A-poor foods contribute to the prevalence of vitamin A deficiency in many parts of the world, because the population is dependent upon them as primary food sources. Despite low levels of carotenoid accumulation in these storage tissues, carotenoid biosynthetic enzymes are active. A number of possible reasons, such as low metabolic flux into the pathway, limited catalytic activity of particular enzymes in the pathway, or high turnover rate, could contribute to low levels of carotenoid accumulation. Moreover, lack of a suitable metabolic sink for effectively sequestering carotenoid end products could also be causative in some cases. For example, although white cauliflower curd accumulates negligible amounts of carotenoids, the genes involved in carotenoid biosynthesis are expressed at levels comparable to the orange cauliflower. The absence of a suitable sink structure restrains the accumulation of carotenoids. The Or gene mutation confers the formation of a storage sink structure, resulting in a dramatically increased accumulation of β-carotene, without alteration of the expression of carotenoid biosynthetic genes. Thus, it is likely that the introduction of an effective metabolic sink for carotenoid sequestration and deposition will facilitate the genetic engineering of carotenoid content in low-pigmented tissues of staple crops.

It should be noted that the extent of carotenoid enrichment in food crops via enhanced sink strength may be limited by a number of factors—most importantly, the maximal catalytic activity of the carotenoid biosynthetic pathway in particular crop tissues or organs. Thus, a concomitant increase in the sink capacity to effectively sequester and deposit carotenoids, along with the catalytic activity of this pathway to increase metabolic flux, would be a promising strategy to engineer increased carotenoid content in food crops to levels required for optimal human nutrition and health.

References

1. DellaPenna D, Pogson BJ. (2006) Vitamin synthesis in plants: tocopherols and carotenoids. Annu. Rev. Plant Biol. 57, 711-738

2. Paine JA, Shipton CA, Chaggar S, Howells RM et al. (2005) Improving the nutritional value of Golden Rice through increased pro-vitamin A content. Nat. Biotech. 23, 482-487

3. Li L, Paolillo DJ, Parthasarathy MV, DiMuzio EM, Garvin DF. (2001) A novel gene mutation that confers abnormal patterns of beta-carotene accumulation in cauliflower (Brassica oleracea var. botrytis). Plant J. 26, 59-67

4. Lu S, Van Eck J, Zhou X, Lopez AB et al. (2006) The cauliflower Or gene encodes a DnaJ cysteine-rich domain-containing protein that mediates high levels of beta-carotene accumulation. Plant Cell 18, 3594-3605

5. Lopez AB, Van Eck J, Conlin B, Paolillo DJ, O’Neill J, Li L. (2007) Effect of the cauliflower Or transgene on carotenoid accumulation and chromoplast formation in transgenic potato tubers. J. Exp. Bot. (in press).

Xiangjun Zhou & Li Li
U.S. Department of Agriculture-Agricultural Research Service
Plant, Soil and Nutrition Laboratory
Department of Plant Breeding and Genetics, Cornell University
Ithaca, New York
ll37@cornell.edu



SUPREMES CONSIGN THE MONSANTO – MCFARLING LITIGATION TO REST IN PEACE
Phill Jones

On January 7, the US Supreme Court announced that it would not take up an appeal in McFarling v. Monsanto. The Court might well have pulled the plug on a dispute that has shuttled up and down the federal court system for eight years.

In 1997 and 1998, Mississippi farmer Homan McFarling purchased Monsanto’s Roundup Ready®, genetically engineered (GE) soybean seeds. The farmer also signed a Monsanto Technology Agreement that required him to use the seed for planting a commercial crop in a single season. The contract prohibited McFarling from supplying seed to any other person for planting, saving any crop produced from the seed for replanting, or supplying saved seed to anyone for replanting. Nevertheless, McFarling saved 1,500 bushels of Roundup Ready soybeans from his 1998 harvest and planted them the following year. He saved 3,075 bags of soybeans from his 1999 harvest and planted them in 2000. McFarling reportedly stated that, unless prevented by a court, he would plant soybeans saved from his 2000 harvest in 2001.

Before McFarling replanted soybeans collected from the 1998 harvest, he had sent them to a third party for cleaning. Monsanto obtained a sample and had the DNA analyzed at Mississippi State University. Genetic analysis revealed that McFarling had saved Roundup Ready seeds.

In January 2000, Monsanto sued McFarling in the Eastern District of Missouri, alleging breach of contract and infringement of US Patent Nos. 5,633,435 and 5,352,605. The company requested a preliminary injunction to prohibit McFarling from "planting, transferring or selling the infringing articles to a third party." The district court granted Monsanto’s motion for a preliminary injunction. McFarling appealed to the Court of Appeals for the Federal Circuit and lost. He then filed a petition for a writ of certiorari to the US Supreme Court. The Court denied the petition.

Back in the district court, Monsanto moved for summary judgment on its claims for patent infringement and breach of the Technology Agreement. The company also sought breach of contract damages. Monsanto argued that the Agreement’s liquidated damages clause should be interpreted to spawn an amount equivalent to 120 times the $6.50 technology licensing fee per 50-pound bag times the number of bags of seed replanted by McFarling. In the court’s view, however, this approach would result in a penalty of 120 times the actual damages. Since penalty clauses are illegal in Missouri, the court settled on an amount of $780,000, or 120 times 1,000 bags purchased by McFarling times the $6.50 technology licensing fee.

McFarling appealed to the Federal Circuit for the second time. He claimed that the district court judge erred by ruling against his two asserted defenses – a patent misuse defense and a defense under the Plant Variety Protection Act – and an antitrust counterclaim. In 2004, the Federal Circuit endorsed the district court’s decision holding McFarling liable for breach of contract and dismissing McFarling’s counterclaims and defenses. The farmer also appealed the judgment on damages. On this matter, the Federal Circuit agreed with McFarling. The court characterized the liquidated damages provision as an unenforceable and invalid penalty clause as applied to McFarling’s breach for replanting saved seed. Rather than attempting to rehabilitate the invalid clause, Monsanto’s recovery must be limited to actual damages. The Federal Circuit sent the case back to the district court to compute actual damages based on the number of bags of seed that McFarling had saved and replanted.

In a second petition for a writ of certiorari to the US Supreme Court, McFarling pressed his patent misuse defense and antitrust counterclaim. The Court requested a brief from the Acting Solicitor General, who recommended a denial of the petition. The Court decided that it would not review the case.

Once again in district court, a jury returned a damages verdict of $40 per bag of saved seed, adding up to about $375,000 owed to Monsanto. McFarling appealed.

"This is the third time this case has been before us," begins the Federal Circuit’s 2007 decision. McFarling argued that the amount of the damages award should be limited to $6.50 per bag, the fee that Monsanto charged licensees who purchased Roundup Ready seeds under its Technology Agreement.

The Federal Circuit disagreed. Under the Monsanto license agreement, soybean farmers paid the company a Technology Fee and promised to refrain from planting Roundup Ready seed saved from a previous season’s crop. The promise ensured that farmers would purchase Roundup Ready seed from an authorized distributor seed company, which also charged a fee for soybeans. Monsanto effectively split its royalty fee into a $6.50 direct payment and a payment of $19 to $22 to the seed companies that promoted and distributed Monsanto’s products. In addition, Monsanto presented evidence on contract benefits beyond payments, such as the bargaining chip for signing up new seed companies provided by the no-saving-seed requirement. The total benefits to Monsanto, the Federal Circuit decided, justify the jury’s finding for a dollar amount exceeding the $6.50 fee per 50-pound bag.

The jury had also considered the value of the Monsanto agreement to farmers. Monsanto’s expert had testified that the use of Roundup Ready seeds, as opposed to conventional soybeans, offered certain advantages. For instance, use of the GE soybeans increased yield in an amount of $14 to $25 per acre, the area of farmland that can be sowed with a 50-pound bag of soybeans. The expert also testified that the use of GE soybeans reduced the costs of weed control by $26 to $36 per acre. "Based on these advantages alone," the Federal Circuit concluded, "it was reasonable for the jury to suppose that, in a hypothetical negotiation, a purchaser would pay a royalty of $40 per bag for the Roundup Ready seed."

For the third time, McFarling filed a petition for a writ of certiorari to the US Supreme Court. News reports of January 7 proclaimed that the Supremes had "backed" Monsanto on the case. This spin is incorrect. What happened is that, once again, the Court denied McFarling’s petition without comment.

Phill Jones
Biotech-Writer.com
PhillJones@nasw.org



More meetings can be found at http://www.isb.vt.edu

THE FUTURE OF AGRICULTURAL BIOTECHNOLOGY:
Creative Destruction, Adoption, or Irrelevance?

12th ICABR Conference, in Honor of Vittorio Santaniello

June 12 to June 14, 2008
Ravello, Italy

Organized by International Consortium on Agricultural Biotechnology Research (ICABR) in collaboration with: CEIS - University of Rome "Tor Vergata"; Rutgers University; Yale University; University of California, Berkeley; Leibniz University of Hannover; University of Missouri; University of Saskatchewan; Wageningen University

The conference theme this year is "What does the future hold for agricultural biotechnology?" Based on that theme, ICABR has issued a Call for Papers in four general areas that will contribute to assessing the future of biotechnology:

· Measuring the impacts on farmers in developed countries.

· Have past studies exaggerated the economic impacts in LDCs?

· Who gained and lost from trade in biotech products?

· What are the rates of return to government or private investments in biotech research?

· Assessing the environmental, health and ethical impacts of biotech.

2. Future demand for agricultural products produced by biotechnology:

· Biofuels.

· Grain.

· Consumer attitudes.

· Demand for food quality and safety, labeling, environmental quality.

· Ethics, income distribution.

3. Farmers' demand for biotechnology:

· Global climate change - the need for technologically sustainable crop systems - new and growing demand for biotech due to drought and flooding, pests and diseases and a generalized increase in environmental uncertainty.

· $100/barrel for oil and increasingly expensive modern inputs.

· Increasing needs for capability building to adapt to climate change on the part of farmers and rural communities, also through expansion and improvement of local agricultural research.

4. Impact of government investments, policies and regulations on future demand for technology:

· Government investments in research

· Food and Biosafety Regulations

· Intellectual Property Rights.

· The political economy of biotechnology.

· Industrial policies - state enterprises, anti-trust policies.

· Tax policies, liability laws, incubators, research parks.

· Role of Foundations and foreign aid donors in biotechnology investment and policies.

For more information:
Contact: Anna Santaniello
Email:
anna.santaniello@tiscali.it; santaniello@economia.uniroma2.it
Telephone: +39 06 7259 5928
Website: http://www.economia.uniroma2.it/icabr/index.php?p=2



AGRICULTURAL BIOTECHNOLOGY FOR A COMPETITIVE AND SUSTAINABLE FUTURE

ABIC2008 Conference

August 24 - 27, 2008
University College
Cork, Ireland

The theme for ABIC 2008 will be "Agricultural Biotechnology for a competitive and sustainable future." At a time when global agricultural faces significant challenges, an in depth discussion of how agbiotech can influence the sustainability of global agriculture while maintaining competitiveness is both timely and necessary.

Taking a global perspective, industry and scientific leaders along with visionaries will address agricultural biotechnology and its impact on world agriculture from food production to maximizing bioenergy potential. This big picture of agbiotech, its global opportunities, and its impact at both local and regional level, will be of great interest to decision makers and leaders in Governments, industry, academia, and the public.

The conference format will facilitate authoritative speakers to address a wide variety of issues across 12 parallel and 2 plenary sessions. Present session themes include:

· Agbiotech: The sustainability challenge facing society (plenary sessions)

· The role of agbiotech innovation for national and international competitiveness

· Biofuels and bioenergy biotechnology research

· Seed and reproductive biotechnology

· Marine and algal biotechnology

· Domestic animal genomics and biotechnology

· Crop genomics

· Molecular pharming in plants and animals

· Developments in plant genetic transformation

· Coexistence in agricultural supply chains

· Functional foods, nutrition, nutraceuticals and bioactives

· Ag-biotech and third world development

· Food and dairy ag-biotech

For more information:
Contact: Platinum One
Email:
info@platinumone.ie
Telephone: +353 1 206 2900
Fax: +353 1 206 2999
Website: http://www.abic.ca/abic2008/




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The material in this News Report is compiled by NBIAP's Information Systems for Biotechnology, a joint project of USDA/CSREES and the Virginia Polytechnic Institute and State University. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the U.S. Department of Agriculture, or Virginia Tech. The News Report may be freely photocopied or otherwise distributed without charge.

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Ruth Irwin, Editor (rirwin@vt.edu)

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Information Systems for Biotechnology, Virginia Tech, 1900 Kraft Drive, Suite 103, Blacksburg, VA 24061, tel: 540-231-3747, fax: 540-231-4434, e-mail: isb@vt.edu