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The main corporate players
The development of artificial minichromosomes and transformed organelles has followed the same pattern as earlier biotech developments: from publicly funded basic research to fully private application and use, with growing concentration in the hands of a few corporations. Two labs have led the way in research into artificial minichromosomes: one headed by Dr Daphne Preuss at the University of Chicago, the other headed by Dr James Birchler at the University of Missouri.
Dr Preuss, who joined the University of Chicago in 1995, worked with her team in the development of methods to build artificial chromosomes. In 2000 she founded Chromatin Inc. as a way of marketing minichromosomes. In 2004 Unilever became the first major corporation to invest in the new firm. In 2007 Chromatin granted Monsanto a non-exclusive licence for the use of minichromosomes and, just four months later, did the same with Syngenta. Both agreements include funds for research, but the amounts involved and the terms of the agreements have been kept secret. All along, Chromatin has continued to receive public funding. Chromatin lists on its web page twelve patents as its own. Six of those patents, however, were actually granted to the University of Chicago (1) and four others are shared with the University. Neither party has disclosed whether the University of Chicago has transferred its rights to Chromatin Inc.
Dr Birchler has long been a professor and researcher at the University of Missouri. His work on artificial chromosomes has been funded by the National Science Foundation, the US Department of Agriculture, and Monsanto. (2) He recently strengthened his links with Monsanto by becoming scientific adviser to Evogene, a biotech company based in Israel that specialises in computer-assisted identification of commercially promising genes. Monsanto currently owns 13.6 per cent of Evogene and will have a 20 per cent stake within 3 years. (3) Evogene will grant Monsanto exclusive licences over identified genes. Monsanto will, in turn, use the technology developed by Birchler or Preuss to engineer those genes into plant varieties. Transformed organelles have been developed by several University labs, and the privatisation processes have been similar. One of the leading labs, headed by Dr Pal Maliga of Rutgers University, is currently funded by public sources as well as by Monsanto. Another prominent laboratory is headed by Dr Henry Daniell at the University of Central Florida. Dr Daniell has raised record amounts of public money, and the work of his lab is "protected" by over 90 patents. In 2002 Dr Daniell set up a private firm, Chlorogen, to commercialise transformed chloroplasts.( 4) In 2005 Chlorogen signed a major agreement with Dow AgroSciences to produce veterinary drugs in plant cells. (5) The company closed in September 2007, selling its technology to undisclosed parties. (6)
Monsanto and Bayer seem to be the corporations to have done most to develop fully commercial applications for both technologies. Monsanto has been very active: it has co-funded, invested, reached research agreements and licensed applications from a variety of university research groups and has also carried out in-house research. It has been busy signing agreements and obtaining licences from biotech firms, including Chromatin, Evogen, Asgrow and BASF. It is already testing gene stacking through minichromosomes, and it expects to release commercially what it calls its SmartStax "platform" in 2010. On its web page for investors, Monsanto has highlighted the potential use of the technology to lower environmental requirements.(7)
Bayer is focusing its action in the field through Icon Genetics Inc. Founded by two University professors in 1999, Icon Genetics focuses on producing pharmaceuticals through plants. Throughout its life, it has managed to obtain important public grants and has displayed a highly diversified portfolio of agreements with pharmaceutical companies. It was bought by Bayer in 2006. Its products are mostly based on chloroplast engineering, but the company is also working on the engineering of other organelles. It holds at least one patent over a method to produce minichromosomes. It recently opened a new factory in Germany to produce biotech drugs in tobacco plants. (8)
Syngenta has licensed minichromosome technology from Chromatin Inc., and it has already stacked tolerance to glyphosate, rootworm resistance and European corn borer resistance in maize. (9) It holds at least one patent over a method to engineer organelles. Biofuels is one of its main areas of interest. Novartis, Calgene (owned by Monsanto), Pioneer Hi-Bred, and Assgrow are also using the new technologies.
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1 - They are US Patents 6156953, 6900012, 6972197, 7015372, 7119250, 7132240.
2 - University of Missouri College of Arts and Sciences press release, 29 September 2005.
3 - Evogene–Investor Conference, September 2008. click here />4 - "About Dr. Henry Daniell," Daniell Lab for Molecular Biotechnology Research, University of Central Florida College of Medicine, 2008.
5 - "Dow AgroSciences, Chlorogen to co-develop chloroplast transformation technology for plant cell culture and crop improvements," Dow AgroSciences press release, 16 September 2005.
6 - "Biotech Startup Chlorogen Shuts Down, Starts Selling Off Its Technology," BioSpace, 12 September 2007.7 – See Monsanto's 2008 Investors.8 - " Pilot plant for future-oriented technology opens in Halle," Icon Genetics press release, 16 June 2008.9 - See Syngenta's Research & Development front page on its website.
What can be done with these technologies?
The biotech industry expects to solve some of its major hurdles by using minichromosomes. First, they will be able to insert several genes in a cell and thereby expect to make complex traits a feasible target for genetic engineering (although the actual feasibility is still to be seen: complex traits are exactly that and the presence of multiple genes does not guarantee the expression of a complex trait). Minichromosomes will also make "gene stacking" possible: several of the current single genes present in GM crops could be accumulated in one variety, providing a new opportunity to reap profits out of them. "Gene stacking" is currently possible, and is being done by companies such as Monsanto and Syngenta, but the time and work it requires make it far less profitable. Second, artificial minichromosomes should make genetic engineering more efficient by decreasing the type of side-effects that make so many engineered organisms unviable. Third, they will be by-passing many genetic control mechanisms so that the engineered genes will obtain higher and more stable levels of expression.
If the industry is to be believed, artificial minichromosomes will make the engineering of complex traits possible, which means that it will possible to produce almost any substance through genetic modification. What does this mean for the future of genetic engineering? The industry puts forward two versions. When it is being careful about its public image, it presents this new technique as an effective and safe technology for – yet again – saving the world from hunger and environmental problems. Daphne Preuss, a leading scientist from the University of Chicago, who is now the president of Chromatin Inc., has made presentations for the Gates Foundation and the United Nations on how this technology could herald a breakthrough for African agriculture. [10] However, when discussing the possible applications of the new technology in patent applications, the biotech industry deals with the genetic engineering of crops for food production as only a secondary target, the main goal being pharming (the production of drugs and chemicals through engineered crops). Companies want to create GE plants that will produce drugs, human and animal proteins, and biofuels, as well as specific industrial raw materials, including toxins. Other possible uses include "the production of nutraceuticals, food additives, carbohydrates, RNAs, lipids, fuels, dyes, pigments, vitamins, scents, flavours, vaccines, antibodies, hormones, and the like." [11]
The idea of using crops to produce drugs is an interesting one for industry for two reasons: crops can be employed more efficiently in this process than animals or bacteria, with a larger output achieved with fewer resources; and it is easier for the drugs produced to be delivered orally to people and animals. [12] Other types of organisms have not been discarded, however. Bacteria remain an important target, because they are easier to engineer and they can be more easily used to produce high-value molecules in small quantities; they may, however, face important regulatory problems. Other species being transformed and tested as possible drug factories are insect larvae and moss.
The application of minichromosomes does not end there. As well as promising higher yields, nitrogen fixation and resistance to salt, drought, heavy metals, viruses, insects, diseases and changes in climate – or any combination thereof – companies are consistently claiming in their patent applications to have the ability to alter plant architecture and physiology, including the process of photosynthesis. In the words of WIPO patent 2007/030510, it may be possible to obtain "resistance or tolerance to drought, heat, chilling, freezing, excessive moisture, salt stress, mechanical stress, extreme acidity, alkalinity, toxins, UV light, ionising radiation or oxidative stress; increased yields, whether in quantity or quality; enhanced or altered nutrient acquisition and enhanced or altered metabolic efficiency; enhanced or altered nutritional content and makeup of plant tissues used for food, feed, fiber or processing; physical appearance; male sterility; drydown; standability; prolificacy; starch quantity and quality; oil quantity and quality; protein quality and quantity; amino acid composition; modified chemical production; altered pharmaceutical or nutraceutical properties; altered bioremediation properties; increased biomass; altered growth rate; altered fitness; altered biodegradability; altered CO2 fixation; presence of bioindicator activity; altered digestibility by humans or animals; altered allergenicity; altered mating characteristics; altered pollen dispersal; improved environmental impact; altered nitrogen fixation capability." [13] There is, it would seem, a huge range of biologically possible alterations, and industry will establish its targets by seeing which GE modifications are most profitable.
The genetic engineering of organelles offers another set of rewards for the biotech industry, especially through the engineering of plant chloroplasts. The most important of these is much higher levels of productivity of whatever substance the engineered plant will make. If, for example, each cell holds tens of chloroplasts and each chloroplast holds over 200 copies of the foreign DNA, the potential production of the engineered substance will, in theory at least, be many times more than it is with the use of current techniques. And tests have, indeed, shown "hyperexpression" of the transgenes.
