Rothamsted Research

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Questions and Answers

Questions and Answers

General

Health and Safety

Ecology

Technical

Finance/Commercialisation

General

Why are omega-3 long chain polyunsaturated fatty acids (LC-PUFAs) important?

Omega-3 long chain polyunsaturated fatty acids (LC-PUFAs) are important for human health and nutrition.

Strong evidence shows that consumption of fish and in particular oily fish lowers the risk of death (36 per cent reduction) caused by coronary heart diseases (CHD) (Joint FAO/WHO Expert Consultation on the Risks and Benefits of Fish Consumption 2011 available at: www.fao.org/docrep/014/ba0136e/ba0136e00.pdf).

National and International guidelines have converged on consistent recommendations for the general population to consume at least 250mg/day of long chain Omega-3 LC-PUFAs or at least 2 servings/week of oily fish (J Am Coll Cardiol 2011; 58:2047-67) for optimal protection against CHD.

The omega-3 LC-PUFAs that are beneficial for health are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). They modulate both metabolic and immune processes and confer health benefits in areas of CHD and neurodevelopment (Nutrition Reviews Vol.71(10):692-707).

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What is the source of EPA and DHA omega-3 LC-PUFAs?

As with humans, most fish obtain EPA and DHA through their diets. Thus, fish oils aren’t actually made by fish, but rather they are synthesised by marine microbes, which form the base of aquatic food webs.

Farmed marine fish need to be provided with the dietary EPA and DHA fatty acids through their feed in order to be comparable with and as healthy as their wild counterparts.

For feed purposes of farmed fish, fish oil is in practice the only economically viable source of these essential fats, and around 80 per cent of all fish oil produced in 2011 was consumed by the fish-farming sector (Joint FAO/WHO Expert Consultation on the Risks and Benefits of Fish Consumption 2011 available at: www.fao.org/docrep/014/ba0136e/ba0136e00.pdf).

As the human population increases and the oceans and fish stocks become increasingly limited, fish farming (aquaculture) is becoming a major source of fish for human consumption. The UK aquaculture industry is a significant sector. EU aquaculture is valued at €3.2 billion and accounts for one-quarter of all EU production of fish, molluscs and crustaceans. According to the Centre for Environment, Fisheries and Aquaculture Science (Cefas), in the UK the total value of aquaculture finfish production in 2010 was £484 million (http://www.cefas.defra.gov.uk/publications/finfishnews/ffn13.pdf). Aquaculture is an excellent means by which high-quality protein for human nutrition is produced (more efficient than terrestrial farming) but is heavily dependent on marine-derived inputs (fish oil and fish meal).

Fish oil and meal is usually sourced through the harvesting of “feed-grade” species, which would not normally be suitable for direct human consumption. However, the so-called reduction fisheries are at their sustainable limits and so fish oil and meal are finite resources that cannot increase as demand increases.

There is considerable awareness and much effort in the aquaculture sector to make current fish feed production practices more sustainable, with less negative impact on the aquatic food web. This is why another source of omega-3 LC-PUFAs is required.

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Why do you need to do this experiment?

We have successfully developed a Camelina plant with high content of novel healthy fish oils in the laboratory/glasshouse http://www.rothamsted.ac.uk/news/crop-plants-green-factories-fish-oils.

We wish to test this under ‘real-life’ conditions in the field to see if this can provide a viable solution for fish feed production that may be proven in the long run to be beneficial for health, the environment and society as whole.

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Why do you have to use GM: is there another way?

The key LC–PUFAs that are beneficial to health are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). No higher plants are known to accumulate EPA or DHA.

Current plant sources of omega-3 PUFAs, e.g. Flax seed, do not produce EPA and DHA; instead they produce shorter chain omega-3 fatty acids such as alpha-linolenic acid (ALA). Similarly, some plants such as borage and Echium accumulate stearidonic acid (SDA), a related shorter chain omega-3 fatty acid. However, neither SDA nor ALA confer the health-beneficial properties associated with EPA and DHA, despite also being an omega-3 fatty acid. Not all omega-3 fatty acids are equivalent.

Algae produce EPA and DHA and it could be possible to grow algae as a source of these fatty acids, but it would require vast amounts of algae, be very expensive and would require a quantum leap in existing technology. We currently remove 1 million tons of fish oil from the oceans every year, and the infrastructure to produce this by algal culture does not currently exist.

In contrast, to produce these oils in Camelina would only require the use of standard, established farming practices and machinery.

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Can we not just get algae to produce the omega-3?

It is possible, but it would require vast amounts of algae, be very expensive and would require a quantum leap in existing technology.

However, here at Rothamsted, we explore all possibilities for the development of sustainable sources of EPA and DHA omega-3 and we carry out research in algae and diatoms http://www.rothamsted.ac.uk/news/single-diatom-accumulates-epa-and-dha-high-value-omega-3.

Although we have recently demonstrated significant progress in this area, we are still at earlier stages in this work than with our work in Camelina plants.

Producing these oils in Camelina would only require the use of standard, established farming practices and machinery.

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What is the nature of the genetic modifications you have made?

Synthetic gene sequences encoding enzymes involved in the biosynthesis of omega-3 LC-PUFAs have been optimised so that they can be functional in Camelina plants. These synthetic sequences are based on the sequence of genes found in photosynthetic marine organisms, which are part of the phytoplankton, and other lower eukaryote species, which accumulate EPA and DHA, such as mosses and oomycetes.

We have produced three varieties of plants, one in which four synthetic genes have been introduced into the plant, one with five genes introduced and one with seven.

The reason why we needed to introduce this number of synthetic genes is that the synthesis of omega-3 LC-PUFAs requires multi-step processes. In order to achieve maximum production of these oils in the seed of Camelina plants, we had to help the internal biosynthetic machinery of the plant to shift from ALA towards the production of EPA and DHA.

All the genes producing LC-PUFAs are expressed (i.e. function) only in the seeds of the Camelina plant and are most active during the mid-stage of seed development.

Gene expression has not been observed in any other vegetative tissue during the life cycle of the plant.

All plants expressing the inserted genes look exactly the same as the control plants in the glasshouse. The inheritance of the inserted genes over five generations follows normal rules of Mendelian genetics. No difference has been observed in seed set, seed size or germination. No difference was observed in fertility. Vegetative performance of the transgenic plants was unaltered.

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How important is this research?

This research is very important at three levels:

Scientifically our work is very important as it makes significant advances in this field of research. It also brings with it the prospect of human health, environmental and hence societal benefits.

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How have you communicated this research and the possibility of a field trial?

We have been working on this area of research for the last 15 years and information has been available on our website over this period, for example as a factsheet produced in 2011, and through press releases regarding relevant publications.

We have also spoken to the public and scientific audiences, as well as the press, on many occasions about this work. For example the former Director of Rothamsted Research spoke at the Cereals 2012 event, as reported in Farmers Weekly http://www.fwi.co.uk/articles/15/06/2012/133442/39gm-oilseed-rape-could-cut-healthcare-bill39.htm

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Will the public be consulted?

As part of the Defra process, there was a period of a public consultation. People were able to make representations to Defra on any environmental risks that they thought might be posed by the field trial. These were considered by ACRE.

ACRE is a statutory advisory committee appointed under section 124 of the Environmental Protection Act 1990 to provide advice to government regarding the release and marketing of genetically modified organisms (www.defra.gov.uk/acre/).

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Why is there a need to carry out this research in the UK?

This research could benefit UK crop farmers, fish farmers and the environment.

The UK has world-class plant scientists who should be at the forefront of developing scientific and technological advances that can make agriculture more efficient and sustainable.

To promote the UK’s competitiveness, investment in biotechnology and therefore ensure long term benefits to the taxpayer.

The UK aquaculture industry is a significant sector. EU aquaculture is valued at €3.2 billion and accounts for one-quarter of all EU production of fish, molluscs and crustaceans. According to the Centre for Environment, Fisheries and Aquaculture Science (Cefas), the total value of aquaculture finfish production for the food chain in 2010 was £484 million (http://www.cefas.defra.gov.uk/publications/finfishnews/ffn13.pdf).

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Are there any fish feeding trials planned with the oil that you may obtain from the plants used for this field experiment?

No, there are no fish feeding experiments planned as part of this field trial. The seeds collected from the plants grown at the proposed field trial will be used only for analysis of oil content in the laboratory and not as a source of oil to be used for feeding experiments of salmon. We have, however, other experiments using plants grown in the glasshouses where we use the oil from the seeds for fish feeding experiments.

As part of this wider programme of research carried out at Rothamsted Research there has been a high-value Industrial Partnership Award (IPA) funded mainly by BBSRC, and with BioMar Ltd. contributing 10% of the overall project costs. Professor Johnathan Napier at Rothamsted Research and Professor Douglas Tocher at the Institute of Aquaculture, University of Stirling are collaborating for this project. The aim of this project has been to develop a novel sustainable source of omega-3 LC-PUFA, specifically tailored for the aquaculture industry, through de novo production in metabolically engineered terrestrial oilseed crops. The platform crop to be utilised for transgenic oil production is Camelina sativa or false flax and the LC-PUFA oils produced will be tested and validated as sources of sustainable omega-3 enriched feeds for the UK salmon industry. For this project, the seeds from Camelina plants that have been grown in the glasshouses will be used for validation as sources of sustainable omega-3 enriched fish feeds for the UK salmon industry. The feed will be given to salmon used for experimental purposes and not to salmon produced for human consumption.

The planned field trial is being carried out independently of the IPA project described above, which is part of the overall strategic programme of research carried out at Rothamsted Research and funded by BBSRC.

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Health and safety

Will the trial be safe?

Rigorous regulations govern the planting of GM crops in the UK. The Government's independent group, ACRE (the Advisory Committee on Releases to the Environment), will be risk assessing the application for permission to conduct the trial.

At Rothamsted Research we have an internal GM Safety Committee, which thoroughly carries out risk assessments of proposed field trials prior to submission to ACRE and no major safety concern has been raised.

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Will anyone inspect the trial?

The Government's Food and Environment Research Agency (Fera) will conduct inspections throughout the trial. Fera's over-arching purpose is to support and develop a sustainable food chain, a healthy natural environment, and to protect the community from biological and chemical risks http://www.fera.defra.gov.uk/aboutUs/

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Could you give us a brief overview of the process of approval for research using genetically modified organisms (GMOs)?

At Rothamsted, like many universities and research institutes around the world, work is taking place using GM plants and microbes for a variety of projects and to address specific scientific questions. Research is conducted in our laboratories, in our glasshouses and in some instances, in the fields of our research farm. For each of these areas where research using GMOs is undertaken, there are a series of relevant regulations that are followed and risk assessments procedures that are carried out.

Rothamsted Research’s activities are compliant with the law and our GM Safety Committee oversees all projects that involve GMOs. There are several key pieces of legislation specifically concerned with the contained use of genetically modified organisms (GMOs). The main piece of legislation, covering both human health and environmental aspects of work in laboratories and glasshouses with genetically modified organisms), is the Genetically Modified Organisms (Contained Use) Regulations 2000, as amended (referred to hereafter as the Contained Use Regulations). In risk assessment of our procedures we follow best practice as specified by the Compendium of Guidance http://www.hse.gov.uk/biosafety/gmo/acgm/acgmcomp/index.htm that has been put in place by the Health and Safety Executive (HSE), in conjunction with the Department for Environment, Food and Rural Affairs (Defra) and the Scottish Government.

Occasionally, a research project requires experimentation using GMOs in the field and for this, approval/permission from Defra is required. The procedure is as follows: We have to carry out a full risk assessment of the project and submit an application to Defra where we describe clearly the aims of our experiment, the type of plant material and the specific genetic modifications that we have carried out. We are also required to make an assessment of the risks to human health and the environment. The application becomes publicly available on the Defra website and our application is then independently assessed by the Advisory Committee on Releases to the Environment (ACRE). During the period that the application is being considered there is also a 60-day public consultation carried out by Defra where any member of the public can comment or ask any relevant question. Once the risk assessment process has been carried out, ACRE make their recommendation to Defra who may or may not then grant a consent to conduct an experimental field trial (with specific conditions if appropriate). The trial and the management procedures are regularly inspected and reports made publicly available at http://www.gm-inspectorate.gov.uk/deliberateRelease/exptreleases.cfm

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What security measures will you be taking?

Completely surrounding the site will be a 2.4m high chain-link fence (with lockable double gates) to prevent the entry of rabbits and other large mammals including unauthorised humans.

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Will you need fences and why?

Unfortunately, in the past, GM field trials in the UK have been damaged by people who believe that no GM crops should be planted. Although these GM plants pose no danger to the public, we have felt it necessary to put in place various security measures, including surrounding the trial by a tall fence, to prevent unauthorised access.

This will be a controlled experiment and we want to ensure that the experiment is conducted with the scientific rigour and high standards expected at Rothamsted Research.

To do this, we need to ensure that rabbits, dogs, other large animals and people do not wander into the field and damage the experiment.

We hope that nobody will attempt to damage the experiment as the results of this trial could be very important in determining whether this type of technology works or not.

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In the US, modified genes have transferred into local wild plants creating 'superweeds', which are resistant to herbicides. Will this happen here?"

The Camelina plants that will be used for this experiment have not been modified for herbicide resistance and therefore they are as susceptible to herbicides as their non-modified counterparts.

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What about cross-pollination?

It is highly unlikely that these modified genes will get into other crops.

C. sativa is known to cross-pollinate with other close members of the Camelina tribe. Hybridisation with more distantly related Brassicaceae such as members of the Capsella tribe may be possible (Julie-Galau et al., 2013; Seguin-Swartz et al., 2013). In the cases of Camelina species which readily cross-hybridises with C. sativa (such as C. alyssum, C. microcarpa), there are no observed or reported cases of these species present on the Rothamsted farm (which is 330 ha in size). Querying the National Biodiversity Network database (www.nbt.org.uk) for the presence of C. alyssum, C. microcarpa and C. rumelica, returns no reports of these species being present within 15 km of the Rothamsted farm.

No cross-pollination, either natural or forced, has been observed between C. sativa and members of the Brassica genus, such as B. napusB. junceaB. rapa and B. nigra.

In the laboratory, artificial hybridisation between protoplasts (plant cells without cell walls) of C. sativa and B. napusB. carinata and B. oleracea has been reported, but with low success and/or sterile hybrids (http://www.inspection.gc.ca/plants/plants-with-novel-traits/applicants/directive-94-08/biology-documents/camelina-sativa-l-/eng/1330971423348/1330971509470).

Whilst potential cross-hybridising species such as Capsella bursa-pastoris are widely distributed across the UK and commonly found in Hertfordshire, the ability of C. sativa and C. bursa-pastoris to form viable offspring has experimentally been demonstrated to be very limited (Julie-Galau et al., 2013).

Pollen dispersal will be minimised through the placing of wild-type C. sativa on the external strip of the experimental plot – this will serve as a pollen-trap for pollen released from the GM C. sativa. In addition, the entire site is contained by two chain-link fences, which also serve as physical barriers to impede foraging bees. A fine mesh net will be used to isolate the crop when it reaches flowering, preventing pollen transmission by insects

The outer edge of the trial will have a 1.8m barrier of non-GM C. sativa to function as a pollen barrier as well as 6m separator strip to provide additional isolation distance. The machinery for sowing seeds will be filled on the trial area and will be thoroughly cleaned before leaving the trial area. Harvested seeds and plant material from the trial will be disposed of by incineration or deep burial at a local authority-approved landfill site using an approved contractor.

Netting will be fixed over the whole trial to keep birds out when the C. sativa is in flower. This is standard practice and is currently being used on our farm to keep woodpigeons out of trial plots. Other measures (suspending wires across the area to provide bird scaring as well as gas guns and hawk kites) will be used to keep out birds for the rest of the season. At drilling all care will be taken to ensure that no seed remains on the surface after drilling because this encourages pigeons in to try and find seeds. Therefore the risk is minimal at sowing and the bird scaring measures specified above will be enough to mitigate the risk. Appropriate husbandry steps will be taken to minimise the potential for seed dispersal by molluscs such as slugs.

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Would any trace of gene transfer affect where farmers can sell their produce?

The chances of gene transfer affecting farmers if this experiment is conducted are exceptionally low.

See also above "cross-pollination"

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Are you going to test the safety of the omega-3 oil produced?

The aim of the proposed trial is to only test the performance of the plant under field conditions and its ability to produce omega-3 oils in the seed, as has been observed in the glasshouse experiments.

If the trial gives successful results and there is consideration in commercialising the plants then the omega-3 oils will be tested for safety but separate strict regulatory processes will be followed.

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Ecology

How is this Camelina better for the environment?

We hope the experiment will help tell us whether we can use plants to produce a more sustainable source of healthy fish oil.

Substantial efforts are being made internationally by the research community and the aquaculture feed industry to increase the sustainability of fish feed production practices. Our approach may contribute to reducing the fishmeal used in aquaculture.

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Do you foresee any environmental problems from Camelina? For example down the food chain? Or on wild plants?

No. C. sativa originated in Europe, and was historically grown across South-Eastern Europe and South-Western Asia. It is a native species in many European countries, including the United Kingdom.

In recent years C. sativa has not been widely cultivated as a crop in the UK.

C. sativa is grown as a crop in Canada and parts of the USA.

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What are the effects on biodiversity of this research?

This is a small-scale highly controlled experiment over the course of four years. We do not anticipate any effects on biodiversity.

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Technical

How did you make the GM plants?

Synthetic gene sequences involved in the biosynthesis of omega-3 LC-PUFAs have been optimised so that they can be functional in Camelina plants. These synthetic sequences are based on the sequence of genes found in photosynthetic marine organisms, which are part of the phytoplankton, and other lower eukaryote species, which accumulate EPA or DHA, such as mosses and oomycetes.

We have produced three varieties of plants one where four synthetic genes have been introduced into the plant, one that five genes have been introduced in the plant and one that seven synthetic genes have been introduced into the plant

The reason why we needed to introduce this number of synthetic genes is that the processes that result in the synthesis of omega-3 LC-PUFAs are multi-step processes. In order to achieve maximum production of these oils in the seed of Camelina plants we had to help the internal biosynthetic machinery of the plant to shift towards the production of EPA and DHA.

All the genes are expressed i.e. function only in the seeds of the Camelina plant and are maximally active during the mid-stage of seed development.

To achieve expression of the inserted sequences only in the seed of the Camelina plants we used gene-switches (genetic sequence that is part of other genes) which determine when and where the synthetic gene sequences will give the information to make the useful enzymes for making the oil. The “gene-switches” (also known as promoters) originate from genes in other plants such as Brassica napus, Arabidopsis and Linum usitatissimum and in one instance from the Cassava vein mosaic virus.

Since we have inserted a number of genes next to each other into the plant, in order to make sure that each gene stops making protein at the correct point we have inserted some genetic “end-signal” sequences in between the genes that facilitate that. In our system these end-signal sequences originate from various organisms including Arabidopsis, Agrobacterium tumefaciens and Cauliflower mosaic virus.

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Can you see any differences between normal plants and the GM ones?

All plants expressing the inserted genes look exactly the same as the control plants in the glasshouse. The inheritance of the inserted genes over 5 generations follows normal rules of Mendelian genetics. No difference has been observed in seed set, seed size or germination. No difference was observed in fertility. Vegetative performance of the transgenic plants was unaltered.

Gene expression has not been observed in any other vegetative tissue during the life cycle of the plant.

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Where did the genes come from?

All the genes used in order to engineer these Camelina plants are synthetic i.e. they have been custom-made by chemical synthesis based on gene sequences found in algae, diatoms, moss and oomycetes.

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Could the genetic changes end up in other organisms and cause problems?

The chances that this could happen are exceptionally low given the scale of this experiment and with the safety measures in place.

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Will your experiment be legal?

Yes. GM experiments are allowed in Europe as long as the strict regulations to ensure safety are followed. This GM field trial will only proceed if it is authorised by Defra after a careful evaluation of the evidence.

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Logistics

Where and when is the trial taking place?

The GM field trial will be carried out over a period of four years in the spring/summer seasons of 2014, 2015, 2016 and 2017.

The plants will be sown in April/May and harvested in Aug/Sept of each year. The trial will take place on the experimental farm at Rothamsted Research in Harpenden, an agricultural research establishment that receives strategic funding from the Government via the Biotechnology and Biological Sciences Research Council (BBSRC).

Rothamsted has many experimental plots in its 330 ha farm. Some of these experimental plots have been running continuously for nearly 170 years, helping to shape our knowledge of agriculture and ecology. The field dedicated for GM experiments is ~3.2 ha and the actual experimental plots within that field will be ~30x30m.

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Will I be able to come and look at it?

Yes, it will be possible to see the trial but you will require permission from Rothamsted Research in order to do this.

The plot is surrounded by a perimeter fence that has been erected to prevent the entry of rabbits, other large mammals, and unauthorised people to ensure the experiment is conducted with the scientific rigour and high standards expected at Rothamsted Research.

There is a public footpath, which runs about 50-80 metres from the fence and there will be information points around to inform members of the public what the trial is about.

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How big is it?

The area of the proposed trial, including controls and spacing between GM plots will cover ~30mx30m (in the first year). In subsequent years the size will be doubled.

How long for will the trial be carried out? i.e How many seasons, how many replicates?

If approved, the trial will be carried out over a period of three years in the spring/summer seasons of 2014, 2015, 2016 and 2017. The plants will be sown in March/April and harvested in Aug/Sept.

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Finance and commercialisation

How much will it cost? Who will be paying for it?

Rothamsted Research will fund this trial from the strategic funding that it receives from the Biotechnology and Biological Sciences Research Council (BBSRC).

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Isn’t this just a waste of taxpayers’ money?

No. On the contrary. This research has been undertaken for many years in the lab and the glasshouses. This experiment will assist in determining whether this technology could provide environmental benefits and maintain the UK at the forefront of this research supporting the growth of bio-economy.

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Have you received industry funding for this work?

Rothamsted Research does receive some funding from industry and aspects of the development of this technology over the last 15 years have been made in collaboration with industrial partners, but this particular trial is publicly funded.

Aquaculture and fish feed manufacture are modern progressive industries working together with many research organisations and international networks to explore ways of producing fish oil in an environmentally sustainable manner.

Working with industry forms a crucial component of this if we are to turn our scientific knowledge into technologies that can benefit farmers, because it is only industrial partners that have the necessary infrastructure to develop and distribute innovative technologies to those who need it.

However, we also recognise that the UK taxpayer is the main funder of our research. We are currently undertaking a formal public dialogue in order to listen to the views of the public and our stakeholders on our collaborations with industry and to receive their input in developing guiding principles of how we should work with industry.

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Who owns the existing patents in this area, and who will own the results of this research?

There have been many patents filed over the years covering various aspects of this area of research and various methods producing Omega-3 oils from plants. They are owned by a number of organisations.

Rothamsted has filed patents for Camelina to be used for a number of applications. Rothamsted could potentially license these to recover investment to the UK taxpayer.

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Are there any potential economic returns from this research, and who will gain from it?

Rothamsted Research holds Intellectual Property over the methodology that has been developed to make these plants. Potentially this technology could be licensed to one or more companies under Rothamsted Research terms and conditions to produce oil from the seed. 

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Is there a market for this product?

Yes – Fish oils are now more valuable than vegetable oil and currently estimated to be worth over £10 billion/year globally.

Are you going to put the knowledge gained from this trial in the public domain?

Yes the results will be published after peer review in the appropriate Open Access scientific journal.

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See also