REPORT ON GMOS AT WORLD ECONOMIC FORUM

Everyone assumes that the World Economic Forum, held annually in the small Swiss ski resort of Davos, is just about finance, big business, and politics. Certainly these hold center stage for most of the six days, but this year there was a healthy smattering of science. Unsurprisingly, information technology featured prominently, but the future of genomics, the role of national academies of science, and genetically modified foods also attracted considerable attention. Participants included Bill Haseltine, CEO of Human Genome Sciences in Washington, George Church, professor of genetics at Harvard, and E. O. Wilson, Harvard professor and author of Sociobiology.

The session on GM foods entitled "Frankenstein Foods or a Miracle?" took the form of a debate. There were four participants on the panel: Gordon Conway, President of the Rockefeller Foundation and author of books such as After the Green Revolution: Sustainable Agriculture for Development, Unwelcome Harvest: Agriculture and Pollution, and The Doubly Green Revolution: Food for All in the 21st Century; Thilo Bode, President of Greenpeace, Netherlands; Roberto Rodrigues, President of the International Cooperative Alliance; and the author. We were given five minutes each to state our case, after which a secret vote was taken. We then had a free-ranging debate with the audience who numbered about 200. At the end of an hour a second vote was taken. In answer to the question "Would you eat genetically modified food?" the initial vote was 72% in favor. By the end of the session this number had increased to 82%.

The main argument propounded by Thilo Bode was that organic farming is beneficial and could provide the answer to food shortages. I agreed it was good but in South Africa organic farming accounts for only about two percent of the food produced and, because of its expense, is only available to the reasonably affluent. Gordon Conway pointed out that one could consider African farmers to be among the world's greatest organic farmers simply because they cannot afford chemical fertilizers, pesticides, or herbicides. Despite the farmers' efforts, the productivity on African farms is decreasing at an alarming rate.

It was good to have data showing that use of herbicide resistant soybeans has resulted in decreased soil erosion due to diminished tillage, and that Bt corn resulted in less post-harvest fungal infection and a concomitant decrease in mycotoxin contamination, which is implicated in diseases such as esophageal cancer. In addition there is growing evidence that Bt crops are attracting more non-target insectivorous insects, thus decreasing crop damage due to pests such as spider mites. Factual information such as this obviously impressed the audience.

The World Economic Forum presents a unique opportunity for top decision-makers and scientists to converse in both formal and informal settings. The positive outcome at the Davos meeting offers hope that future gatherings of decision makers can address the question of GM foods with the same level of scientific integrity.

COMMERCIALIZATION OF PATH-BREAKING TRANSGENIC SALMON FACES STUMBLING BLOCKS

Transgenic Atlantic salmon could soon be the first commercially produced food product derived from a genetically modified animal. Transgenic Atlantic salmon produced by A/F Protein Inc. (Waltham, MA) reportedly grow up to four to six times faster than non-transgenic salmon and exhibit a greater than 20% improvement in feed conversion efficiency¹. The company has 10,000 to 20,000 transgenic salmon in indoor tanks at three facilities in the Canadian Maritime provinces. A/F hopes that these fish will become the broodstock for producing eggs for commercial aquaculture in Canada, New Zealand, Chile, and the United States. However, commercialization of this path-breaking product faces a number of stumbling blocks. Against the background of both favorable and unfavorable reports in the popular media, the anticipation of a key regulatory decision, and actions against production of transgenics by certain salmon producers, the commercialization of transgenic salmon is proving contentious.

Commercialization of transgenic salmon in the United States will depend upon regulatory approval by the Food and Drug Administration (FDA), which must approve the marketing of any products derived from animal biotechnology. An FDA decision on approval of the A/F transgenic salmon is expected in the near future. The FDA Center for Veterinary Medicine is regulating the transgenic salmon expressing an introduced growth hormone gene as a new animal drug². That is, transgenesis is being regarded as a means for delivering growth hormone to the tissues of the fish. Hence, regulatory approval of the A/F salmon will depend on rigorous demonstration that the transgenic salmon are safe to eat.

Approval of marketing transgenic salmon would constitute a "significant federal action" posing impacts to the environment. Under the National Environmental Policy Act, FDA must consider biosafety issues posed by commercial production of the transgenic salmon. Ecological concerns include competition of transgenic stocks with wild populations, introgression of the transgene into wild gene pools, heightened predation of transgenics on prey populations, and a range of other possible impacts. Because ecological concerns are site-specific, it may prove necessary to control the sites where transgenic fish are reared, as well as the level of confinement in production facilities². Regulatory authorities may require that production stocks be sterile triploids or all-female triploids. Any level of confinement other than absolute containment in indoor, recirculating aquaculture systems will have to be assessed for specific sites. Decision support tools have been developed to assess and manage any risks posed by research and development activities with genetically modified fish and shellfish³ and by larger-scale production and marketing of genetically modified organisms⁴.

Commercialization of transgenic fish also faces issues of consumer and commercial acceptance. A number of salmon producers groups feel that growing public distrust of genetically modified foods can create a potential marketing problem for the salmon industry. The industry already faces heightened public scrutiny because of controversies regarding possible environmental impacts of ocean net-pen aquaculture of salmon. Against this background, certain salmon producers or producers groups have distanced themselves from production of transgenic salmon. On February 25, King Salmon of New Zealand announced that it had killed all of its transgenic chinook salmon and disposed of them in accordance with containment protocols. The action came days after New Zealand environmentalists had convinced the government to conduct a review of the licensing and inspection process for the experiments. In a unanimous vote of its Board of Directors on February 24, the British Columbia Salmon Farmers Association adopted a ban on use of transgenics by its members. In 1996, the Scottish Salmon Association distanced itself from experiments with transgenics carried out by Otter Ferry Salmon.

Elliot Entis, CEO of A/F Protein Inc., feels that environmental concerns can be addressed by producing transgenic salmon in closed aquaculture systems or by producing sterile fish, and consumer concerns by showing that there are no food safety issues to hide. The company hopes to gain FDA approval and to begin commercial production and marketing of its fish by 2001.

Sources

1. Fletcher GL, Shears, MA, Goddard SV, Alderson R, Chin-Dixon EA, and Hew CL. 1999. Transgenic fish for sustainable aquaculture. In Sustainable aquaculture: Food for the future?, eds. Svennevig N, Reinertsen H, and New M, 193-201. Rotterdam: AA Balkema.

BOOSTING PHYTOESTROGENS A BOON FOR PEOPLE AND PLANTS

The insurgence in the nutriceuticals market has driven a commercial interest in producing specialty crops to support this emerging industry. Estrogenic compounds, such as the isoflavones, are generating attention because of their potential health benefits. These phytoestrogens, particularly daidzein and genistein, are believed to reduce the risk of osteoporosis, improve serum cholesterol levels, and abate the development of hormone-mediated cancers. Therapeutic isoflavones are currently selling in over-the-counter soy extract pills and soybean milks.

This interest in phytoestrogens has prompted efforts to find plants that have naturally high levels of these compounds and also plants in which the expression of these compounds can be manipulated¹. In addition to their alleged nutritive value, isoflavones are involved in plant defense reactions to bacterial and fungal invasion, insect predation, and oxidative damage. They also have a role in establishing mutualistic relationships between plant roots and nitrogen fixing bacteria².

Isoflavones are most pronounced in legumes and a few non-legume plants, such as sugar beet. However, not all plants express isoflavones in sufficient amounts for commercial use as nutriceuticals. In addition, not only does the isoflavone content vary widely due to species differences and environmental conditions, but also processing can account for losses of up to 50%. Consequently, researchers Brian McGonigle et al. at DuPont's Agricultural Biotechnology department are seeking to manipulate isoflavone concentration in both legume and non-legume crops.

Isoflavone synthase (IFS) constitutes the committed step in isoflavone biosynthesis. IFS is a cytochrome P450 that catalyzes the oxidation of intermediates liquiritigenin and naringenin to daidzein and genistein, respectively. As reported in Nature Biotechnology, McGonigle's group has successfully identified two soybean IFS genes and subsequently expressed them in Arabidopsis thaliana³.

The group first identified cDNA clones with homology to known cytochromes P450 in soybean EST libraries and screened them for functional activity using a yeast expression system. They optimized their search by preferentially choosing cDNAs from libraries constructed from fungal infected soybean leaves, as pathogenic fungi enhance isoflavone synthase activity in the soybean leaf cells.

They identified two similar soybean isoflavone synthase genes, IFS1 and IFS2. Both genes proved capable of synthesizing daidzein and genistein from their respective precursors. After sequencing the soybean IFS1 and IFS2 genes, the researchers were then able to confirm the presence of multiple IFS homologs in mung bean, red clover, snow peas, white clover, hairy vetch, alfalfa, and lupine. They also found the two isoflavone synthase genes in the non-legume sugar beet, whose encoded proteins shared 95% homology to soybean IFS1 protein—surprising due to the distant relationship of these two species.

McGonigle's group introduced the soybean isoflavone synthase gene into Arabidopsis thaliana using a CaMV promoter and kanamycin reporter in the chimeric gene construct. Arabidopsis has no known isoflavone synthase activity and does not contain any genes homologous to the soybean ISF1 and ISF2. Their assays detected the presence of genistein in the transformants, indicating successful expression of soybean ISF1 gene.

The results of McGonigle et al. emphasize the feasibility of engineering both medicinal transgenic plants and a variety of crops with enhanced nitrogen fixing capability. Isoflavone expression may also be used to produce seeds, seedlings, and adult plants that better resist insect attack and soil borne diseases. A valuable advance could be the regulation of isoflavone synthase expression in monocots such as banana, corn, and wheat. In addition, recent developments in large-scale plant cell culture make it feasible to produce large amounts of isoflavones in vitro.

Sources

1. Anonymous. 2000. A new crop of transgenic plant technologies. Genetic Engineering News 20(4):8, 35, 43.

2. Rolf BG. 1988. Flavones and isoflavones as inducing substances of legume nodulation. Biofactors 1(1):3-10.

3. Jung W, Yu O, Lau S-M C, O'Keefe DP, Odell J, Fader G, and McGonigle B. 2000. Identification and expression of isoflavone synthase, the key enzyme for biosynthesis of isoflavones in legumes. Nature Biotechnology 18(2):208-212.