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Re-writing the vegetal code
In two decades, plant biotechnology has opened the doors to a huge range of possibilities in the way we use plants. Public concerns about this technology in Europe have changed the emphasis of the research and persuaded scientists to make more effort to communicate.
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Genetic engineering involves artificially inserting a new piece of genetic code into the genome of an organism. If the process works, the new gene, carrying instructions for a particular protein, is carried in all the cells and passed down the generations. In theory, one can create a plant that produces any protein one wants. Plants we use for food, biofuel, and medical purposes can be engineered to meet our needs.
Scientists first found a reliable way to transfer a gene into the chromosomes of a plant cell in the mid-80s. The breakthrough was a technology using a soil bacterium called Agrobacterium tumefaciens. In nature, this microbe inserts a piece of its own DNA into the nucleus of a plant cell, inducing the plant to grow a gall. The breakthrough consisted in the development of methods to alter the bacterium into an efficient delivery system for gene engineering. Techniques for harnessing Agrobacterium's method of DNA transfer were patented (1) , and are still widely used today, although the original patents have expired. Since then, new methods of transferring genes have been devised. One that is quite widely used involves bombarding cells with tiny particles carrying the desired genes; another involves tiny fibres, called silicon whiskers.
Andrew Maddox says:
“The metabolism of
plants is well known,
and there is huge potential
for manipulating it,
either to help plants or improve
industrial processes.”
It was nearly a decade before the technology was successfully applied to major agricultural crops. "For a long time, the holy grail was getting gene transformation to work in cereals," says Andrew Maddox, a patent examiner at the EPO in The Hague who specialises in plant biotechnology. They cracked it in the early 90s by targeting certain tissues, and the door was open to transforming the world's staples - wheat, barley, maize and rice.
European concerns
The first genetically modified (GM), or transgenic, crops were sown on American soil in the early 90s. By 1999, 45% of cotton fields, 38% of soy fields and 25% of cornfields in the USA were GM. There were 40 different food products on the market and plenty more on the way.
In Europe, things were different. Environmental groups resisted the technology, arguing there were unknown risks to the environment and human health. In 1999, the European Union effectively shut the door on new GM crops for at least three years, by placing strict controls on the licensing of new crops. Requirements for extensive risk assessment and labelling of GM food made the path to European markets virtually impassable. The decision had a major impact on the number of patent applications being filed for plant engineering (see chart).
Why did Europe react like this? Wilhelm Gruissem, who heads the European Plant Science Organisation (EPSO), suggests there is a different attitude to farming in Europe. "In the USA, agriculture is much more industrialised," he says. In addition, the first few products that were commercially developed had no clear benefit for the consumer. In some cases, such as when herbicide resistance was bred into the plant, there was a potentially negative effect on the environment.
Now, eight years on, licences have been granted to grow and import GM crops in Europe, but several countries still oppose the technology. France, Germany and Sweden are still resistant and, in the UK, the government is sticking by the results of its own tests, which found that some herbicide tolerant GM crops adversely affect farm wildlife. In 2005, the people of Switzerland voted for a further five-year ban.
According to Gruissem, the whole of plant science suffered a decrease in funding and opportunity in Europe, because of backlash on plant biotechnology. "Only three plant genomes have been sequenced," he says, "but I have lost track of how many animal genomes we now know." These days, he says, plant scientists make much more effort to publicise their research and interact with the public.
Engaging with the public
Scientists have been looking more carefully at the environmental risks of transgenic plants. "There has been a lot of effort to remove extraneous DNA," says Maddox. Marker genes, often conferring antibiotic resistance, were originally used to help scientists select plants that had taken up the new gene. Now, these are removed. And there are new methods that avoid the transgene from being dispersed, like putting it into the plant's chloroplasts.
Increasingly, genetic technology is being used to speed up natural plant breeding, instead of directly engineering new plants. Scientists identify the genes for plant traits like yield, or disease resistance. Once one knows the sequences, one can find codes to recognise them in a similar plant and then breed them into a crop using age-old methods of cross-pollination. This is called marker-assisted breeding. "It avoids the whole regulatory issue surrounding transgenic crops," says Maddox.
Research has been redirected. "We are still seeing patents filed for all kinds of applications of genetic engineering," says Maddox, and he mentions several new developments related to biofuels - increasing biomass, producing more oil or changing the lignin content of plants. "The metabolism of plants is well known, and there is huge potential for manipulating it, either to help plants or improve industrial processes."
Reaping the benefits
Nowadays, scientists are working out how to control where the new gene is expressed in a plant. "Controlling expression using miRNA is a very hot topic," says Andrew Maddox.
Improving the nutritional benefits of foods is an active avenue of research. Scientists are working on tomatoes with added antioxidants, for example, and plants that make omega-3 fatty acids, which are good for the heart
(2)
. One well-publicised effort is the creation of rice that contains vitamin A
(3)
. It has been called ‘golden rice', because it produces orange-coloured carotenoids in the grain. A similar project to improve the nutritional quality of cassava is being funded by the Bill and Melinda Gates Foundation
(4)
.
"Cassava is very low in protein, and lacks vitamins," Gruissem explains, "yet it feeds more than 200 million Africans." One important aspect of the project is to ensure the new crops are effectively delivered to African farmers, without undue cost. "There has to be a concerted effort to develop this technology in both the public and the private sector," says Gruissem. "Academics can look at the utility of a crop and work on educating farmers. The private sector would not be interested in cassava." Public funding fills this gap.
Crops are also being engineered to produce vaccines. A Japanese study published in June 2007
(5)
showed that, when a gene from a disease organism is inserted into rice, eating the rice confers immunity to the disease. In this respect, Maddox says the medical applications of plant transgenics have not been fully realised yet, although the technology has been available for a while.
Climate change is a new motivation for engineering crop plants. "Companies are screening for genes involved in responses to environmental stress," says Maddox. Providing stable yields in unpredictable weather, and added drought resistance, may soon be a pressing need in some parts of the world.
The genetic modification of energy crops is underlying third-generation biofuel technology. A review in the journal Science
(6)
suggests that the "grand challenge for biomass production is to develop crops with a suite of desirable physical and chemical traits while increasing biomass yields". Scientists are thus working to improve the efficiency of photosynthesis, carbon capture, nitrogen fixation and many other cellular processes that boost biomass yields or sugar content, or achieve faster rotation.
But will the European public go for it? According to Gruissem, they will have to, in the long run. "Agriculture is a technological process," he says. "New technologies will be necessary, if we are to create more sustainable agriculture over the next hundred years."
From the perspective of patenting
There is no doubt that public opposition to GM technology changed the commercial outlook. "The European industry has consolidated into just a few companies, because the risks are too great for small players," says Ashok Chakravarty, a patent examiner at the EPO in Munich who specialises in plant science. After steadily growing for a long time, the yearly number of European patent applications for plant engineering collapsed in 1999, amid social concerns and political interventions. It then started to grow again in 2004.
Can you patent a plant? In general, plant engineering patents refer to the method of transferring the gene - the vector that is used, or the protocol of targeting it to a particular tissue. Some patents are specific to one plant - banana or water melon for example. Others apply to a group of species, like cereal crops. The technology has thrown up a major issue in patenting.
In particular, can a patent apply to a plant that carries a new gene? The European Patent Convention (EPC) clearly says you cannot patent a plant variety, because they are protected by a different international convention known as UPOV
(7)
. The issue has now been decided, after the long-running case of a patent filed in 1991 by Ciba-Geigy (now Syngenta) covering genes to reduce fungal infections
(8)
. The patent was finally granted in 2000. Patent examiner Ashok Chakravarty explains the outcome saying: "If the invention is restricted to one plant variety, there is no patent. But if the technique is more general, then we will grant the patent, and it will cover any transgenic plant containing that gene."
After steadily growing for years, the yearly number of European patent applications for plant engineering collapsed in 1999, amid social concerns and political interventions. It then started to grow again in 2004. (Click to enlarge )
Bruxelles, July 2007
- Journalist: Lynn Dicks, ESN
- Expert Opinion: William Gruissem (European Plant Science Organisation); Andrew Maddox, Ashok Chakravarty, Peter Burkhardt, Robert Lejeune, François Couzy, Marc Heirbaut, and François Lepretre (EPO).
- Chart and Data Research: Henry Lehtiniemi, EPO
- Photo Portrait: Robert Lejeune, EPO
- Research and Co-ordination: Leo Giannotti, EPO
(1) For example, see EP0120516, WO8402920 and EP0116718.
(2) See the Technology Watch article Eating for Health at http://www.epo.org/topics/innovation-and-economy/emerging-technologies/eating-for-health.html
(3) See Paine et al. (2005), Nature Biotechnology, 23, 482-487.
(4) See Biocassava Plus http://biocassavaplus.org
(5) Nochi et al. (2007). Proceedings of the National Academy of Sciences, 104, 10753-10754.
(6) Arthur J. Ragauskas,et al. The Path Forward for Biofuels and Biomaterials, Science, 311 (2006), 484-489.
(7) International Convention for the Protection of New Varieties of Plants, known as the UPOV Convention, first signed in 1961.
(8) EP0448511 B1, appeal case G1/98, followed by appeal cases T356/93 and T1054/96.
Additional links:
- European Plant Science Organisation (EPSO): www.epsoweb.org
- An overview of the patents covering plant transformation: http://www.patentlens.net/daisy/AgroTran/835.html
- UPOV: http://www.upov.int/index.html
- IRRI golden rice fact sheet: http://www.knowledgebank.irri.org/factsheets/Health_and_Nutrition/fs_Golden_Rice.pdf