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Genome editing - is it genetic modification?
Plant science is on the threshold of another new development. Recent advances in genome editing techniques have made it possible to alter DNA sequences in living cells. Genome editing is more precise than conventional crop breeding methods or standard genetic engineering (transgenic or GM) methods. By editing only a few of the billions of nucleotides (the building blocks of genes) in the cells of plants, these new techniques might be the most effective way to get crops to grow better in harsh climates, resist pests or improve nutrition. Because the more precise the technique, the less of the genetic material is altered, so the lower the uncertainty about other effects on how the plant behaves.
It is unclear whether regulations for genetically modified organisms apply to plants modified by genome editing methods. Should these new techniques be treated the same way? Does this make them too expensive for the public sector? Can we decide anything before we even have plants to grow?
The Biotechnology and Biological Sciences Research Council (BBSRC) released a position statement on 28th October 2014 on "new and emerging genetic techniques that have a potential to contribute to producing crops with improved performance".
On Tuesday 28th October 2014 our expert panel (Professor Robbie Waugh and Dr Glenn Bryan from the James Hutton Institute, Dr Huw Tyson from the BBSRC and Professor Jonathan Jones, Professor Ottoline Leyser) answered your questions.
If you have a question on a plant science related issue then get in contact with our plant science panel via Twitter, @senseaboutsci using #plantsci, or email us at firstname.lastname@example.org.
Start reading from Question 1.
22. "Why is there a problem if genome editing is considered a GM technique?" (Alice Turner)
JJ: "If genome editing is a considered a GM technique, it will be much more expensive to bring to market, with the result that many benign and useful applications of the method will never see the light of day. A likely and problematic scenario is that in the US, such modifications are regarded as non-GM and essentially unregulated, whereas in the EU they are stringently regulated like current GM. This could result in unhelpful international trade barriers."
21. "What kind of benefits could genome edited crops offer us?" (Rob Dawson)
GB: "For genome editing to be effective, we have to know the DNA sequence of genes that we know are likely to affect a trait if we alter them in some way. It is very different from breeding where we can modify a trait by selecting a genetic region that we know influences a trait, irrespective of whether we know the gene responsible. Now that we know the sequences of many genes, the trick is to know which genes are likely to influence a trait of interest. This usually involves a great deal of genetic, molecular and other research. In principle once we know the genes involved, we can use genome editing to alter any trait to some extent. I think that Genome Editing could provide crop plants that are more resistant to pests and diseases, that are more able to tolerate stresses (such as heat, drought, cold) and that have a higher nutritional value to name but a few. In the short term these advances could have major impact in countries where food security is an issue."
20. "I am scientist involved in fruit improvement especially apple Cherry. We need disease resistance and improvement in fruit quality. Will genome editing be helpful in these crops as in India we have reservations on GM foods." (Dr Khalid Mushtaq)
JJ: "It depends on the disease. There are credible targets for genes that when mutated will result in reduced susceptibility to fungi, bacteria or oomycete pathogens. So for example, if powdery mildew is a problem, you can edit mutations into the apple cherry Mlo gene, resulting in powdery mildew resistance. If you want to slow down fruit softening, you could edit in mutations in a polygalacturonase gene. If you know that the presence of a particular gene is a problem for fruit quality, it can be eliminated. To qualify as “non-GM” you will then need to make genetic crosses to remove the T-DNA carrying the CrispR or TALEN genes used for engineering."
19. "I think regulation should be at a global level. How can a product/process which has undergone rigorous testing in one country need to be tested again? You can argue that 'rigour' can be subjective hence my call for a global body which oversees this ... Do the experts believe this as a valid approach?" (Sushma Tiwari, via Facebook)
HT: "Ideally, a global regulatory system could have advantages, but practically it seems likely to be difficult to achieve. Cultures and views on a range of scientific issues vary greatly across the globe, and different political systems deal with regulation in different ways. The blockage in operating the EU regulatory process for GM is partly political, caused by different attitudes to GM among the EU member states."
18. "Isn't this just another silver bullet that won't get out of the lab?" (Natural Steve)
OL: "There are no silver bullets in food security. But there are plenty of examples of scientific discoveries making a contribution."
17. "Are these techniques patented or can anyone try it out?" (Steve Parkinson)
OL: "My understanding is that the techniques have been/are being patented, but for research purposes they are freely available to use. They involve GM plants and/or GM microbes, which in the UK require a licence from DEFRA, but if you have one of those, you can use the techniques for research."
16. "How long (in months/years) would GM take to add a new trait? And how long is three generations? (follow up to question 1)" (Victora Murphy @vic_biku)
GB: "In principle GM could be done in about a year to modify a trait for most crops. However field trialling and subsequent testing (equivalence, safety etc) of a GM modified food crop variety would take a few more years (at least three to four I would say) before it could be grown as a food crop for commercial use. This latter phase would be largely to satisfy legislative requirements that are not yet in place so it is hard to pre-judge it!
Three generations would mean a minimum of three years for most crops. For some seed propagated crops it is possible to get two generations per year so it could be as little as two years. For vegetatively propagated crops (potato, cassava etc) it could mean a little longer - four to five years maybe."
15. "The UN says small farmers are already providing food security. So more GMOs are not needed then?" (@watervole)
OL: "As described in my answer to question 10 food security is a multifaceted problem that needs a multifaceted solution. Crop genetic improvement is one attractive target among many, because of the relative ease with which seed can be distributed and because of its power to improve preharvest, harvest and postharvest performance. This is true for small, medium and large farms. In my opinion, no methods for crop improvement should be ruled out because the best one to use will depend on the trait, the crop and the environment in which it will be grown. What is needed is governance systems to improve the equitable distribution of the costs and benefits of different technologies, so that the choice of technology deployed in each situation is more open."
14. "Is there any way to tell plants of the same crop, produced by different plant breeding methods, apart?" (Sile Lane)
RW: "In general it would be difficult to tell the products of these different methods apart. If GM were involved and the transgene (the new gene added by scientists) was still embedded in the genome of the new variety – then new techniques such as next generation sequencing could be used to distinguish the GM from non GM lines. But there are a whole raft of plant breeding methods that do not rely on GM technologies. Examples include mutation breeding (treating a plant with a chemical or radioactivity that induces changes in the genome), marker assisted selection (using a relatively small number of ‘diagnostics’ to select superior individuals), genomic selection (using information from across the genome of a plant to predict which of its progeny should perform best), doubled haploidy (culturing and doubling the haploid gametes - the sex cells which have one half of the chromosome of the plant - to create a plant with an identical set of genes for a trait) and so on."
13. "By asserting that genome engineering is distinct from #GM, are scientists at risk of being seen to imply that GM is dangerous?" (@popupcamptrout)
RW: "I disagree. I would argue that most scientists already support the rational use of GM as one tool in the breeders toolbox that may be required (or can assist) in the drive to make better and more productive crops. They don’t deny there is a perceived risk by the general public over GM (though I suggest relatively few would subscribe to the more extreme anti-GM opinion), and I suggest that a relatively small number of antagonists make a big noise that may sway public opinion (or at least seed doubt). So, given most scientists that I know don’t consider GM a risk (quite the opposite in fact) I can't see any reason why their stance on genome editing would imply that it is."
GB: "I disagree. GM itself is not a single entity- every application of GM is different and has to be assessed on its merits. GM can be used to overexpress, silence or otherwise modify the expression of plant genes. GM usually involves the insertion of a new copy of a gene in the genome of a plant in a location that is not necessarily where the gene is normally situated. Genome editing is somewhat different in that it leads to modification of the existing copy of a plant gene ‘in situ’ (in its normal genomic location). Both GM and GE are complex entities with many different methods, vectors etc. Just by saying that they are slightly different conceptually is not to say that one of them is more dangerous."
OL: "As described in my answer to question 3 this only matters because the current regulatory framework is focused on method. In my opinion we need to move to a trait-based system because a methods-based system is not effective and not sustainable."
12. "How important for #farming and #food security?" (@luciadesouza)
HT: "Genome editing is a relatively new technique and is becoming an important tool in helping researchers understand what genes are important and how they work. It has the potential to help develop the crops that farmers will need to meet future demand for food as the global population grows. We will need crops adapted to future conditions as the climate changes, and crops that can resist pests and diseases, or drought or flooding. Genome editing will be one useful tool in the toolbox for plant breeders."
11. "Please define 'standard genetic engineering'. Is it a bit like 'standard civil engineering'?" (Lucy Bailey)
JJ: “'Standard genetic engineering' usually involves one of two techniques. The first technique takes advantage of the capacity of a microbe called 'Agrobacterium tumefaciens' to deliver DNA to plant cells. Researchers have learned how to ensure that it only delivers DNA specified by the researcher. As an alternative technique, DNA is sometimes delivered coated on microprojectiles that are bombarded into plant cells. The delivered DNA usually includes a genetic marker so that it is easy to distinguish or select for cells that have received the DNA of interest. In both these 'standard' genetic engineering techniques, the introduced DNA (the 'transgene') is likely to have inserted into the plant genome at a different and essentially random location. There may also be varying numbers of copies of the introduced DNA each time. If a plant modified in this way is to be sold commercially, it is required to prove that the DNA insertions are a simple and single copy, that all the intended genes are expressed, and that there are no adverse consequences of the insertion location. Such events are easily found by screening hundreds of events and selecting those that meet these criteria."
10. "Why do we need to GM anything when superfoods already exist for food security?" (@watervole)
OL: "The food supply chain and food security involve not only the interdisciplinary science underlying food production, harvesting, storage, distribution and consumption, but also the social, political and economic factors that influence all these things. Providing a reliable supply of nutritionally complete food to everyone will take changes throughout this complex system. Crop genetic improvement is one attractive target among many, because of the relative ease with which seed can be distributed and its power to improve preharvest, harvest and postharvest performance. GM is one approach among many that can be used for crop genetic improvement. It is not the case that the crops we currently have are "super". They could all be improved. For some traits in some crops, GM is a good way to achieve this. For example, where crops are sterile, as is the case with bananas, conventional breeding approaches are virtually impossible, and here tools such as GM and genome editing become extremely important."
9. "Are the big companies like Monsanto and Syngenta using these new techniques?" (Rachel Arnold)
RW: "Without doubt Monsanto and other big companies are using both traditional breeding and GM-based technologies (including genome editing) in their breeding programs, and are anxiously awaiting the outcome of the debate about whether editing is considered GM or not. I wouldn’t know precisely how they are using them because they have commercial interests to protect – but I would bet they will have some possible products in their pipelines"
8. "The Sharpo [sic] potato is blight resistant and didn't use GM. Why do we need genome editing?" (Ross Dawes)
GB: "Indeed some of the so called Sarpo varieties (e.g. Sarpo Mira) have very good resistance to late blight, the most important potato disease. Potato breeding is a very complex business – potato is an autotetraploid – this means it has 4 sets of chromosomes rather than the normal two. It is also an outbreeder which makes life very difficult for breeding and genetics. Potato breeders have to select for at least 20 different traits to breed a successful variety depending on its intended use (table, processing, starch etc) and blight resistance is only one of them, albeit an important one. While Sarpo Mira has good blight resistance it is not ideally suited to a number of uses and is not a variety that is likely to be widely grown. Genome editing can potentially be very useful for adding a trait to an already highly successful variety with good quality attributes."
7. "How long will it take for genome editing techniques to change farming?" (Gary Childs)
"GM takes ages to go from lab to field. Will genome editing be any quicker?" (Nina Schmidt)
JJ: "This is primarily down to the regulatory authorities. If genome editing is regulated in the same way as 'conventional GM,' then it will take a long time, especially in Europe. If the crops produced by these methods were regulated like natural variation deployed by plant breeders, then they could be making useful contributions within 5 years."
RW: "Very much depends on how the proposed regulations on genome editing proceed. If it is not considered GM then the time line will likely be shorter or the same as a traditional plant breeding program. If the approach is considered GM, then the time line will be the same as for any GM plant – with the exceptionally high associated costs of taking a GM plant to market."
6. "Will these new techniques be used for more than increasing yield or reducing pesticide use?" (Ruth Elizabeth Foxglove)
JJ: "We can already envisage methods whereby editing could be used to increase disease resistance. There are several genes that can be mutated resulting in a plant that is less capable of supporting growth of a plant pathogen but this is less clear in the case of pests such as insects or nematodes. Genes that when mutated give yield increases are rarer, but can also be envisaged. The new techniques can in theory be used for any kind of crop improvement."
GB: "These ‘new technologies’ may have very wide application for addressing many issues affecting crop plants and domestic animals. Obviously one of the major applications is going to be the amelioration of threats to crop production caused by biotic (pests, diseases etc) and abiotic (drought, heat, flooding etc) factors. These methods could indeed lead to reduced use of pesticides (insecticides and fungicides especially). They may also be used to improve yields or quality of our crops. One key aspect is the reduction in crop wastage – many crops suffer from problems associated with storage and in some cases storage could conceivably be improved by the use of genome editing technologies. Another important aspect is food safety – for example many foods produce the toxic and carcinogenic compound acrylamide when fried or baked (e.g. potatoes). The genes underlying the production of compounds that lead to acrylamide formation are well known and it has been shown that by using GM the production of acrylamide can be abolished or severely reduced - a very good thing! Here is a link to the research"
OL: "These techniques, like all other crop genetic improvement approaches, can be used in many different ways. An interesting question is how to democratise the selection of traits for inclusion in breeding programmes."
5. "The media lumps everything together as GM, which seems a little counterproductive. Should we be doing the same with genome editing? There is more than one type I think." (Carl Borthwick)
HT: "It is correct that there are several methods for genome editing, and this is a fast-moving field, so there are likely to be further new techniques developed in future. GM and genome editing are different tools to make genetic changes, and very similar genetic changes can be introduced using a variety of techniques. What's important is the effect a genetic change makes to the plant. This leads to the conclusion that it would be better to consider the characteristics of the plant, rather than how a genetic change was made."
4. "Shouldn't we wait until we've tested these new techniques before we decide whether they are considered GM or not?" (Robert James)
JJ: "Plants derived from editing have already been produced. We have been using GM methods for over 31 years, and we also understand a lot about how TALEN and CrispR methods could make changes in plant genomes - in other words we understand the science well enough to make sensible provision for regulating the technology. Since sequencing is so cheap now, it will be easy to ensure there are no 'off-target' changes in a commercialized variety derived from editing, by simply sequencing the genome of an edited plant to ensure that no changes have occurred other than those intended."
3. "What do the panelists think - should genome editing techniques be considered GM?" (Adam Gillett)
Dr Huw Tyson: "This is quite a complex question and there have been numerous detailed reports looking at a range of 'new plant breeding technologies', for example by the EU and UK advisory bodies. The EU authorities are currently deliberating on what their definition of GM covers. The BBSRC position statement published today makes the point that a regulatory system based on the characteristics of a novel crop, by whatever method it has been produced, would provide more effective and robust regulation than current EU processes, which consider new crop varieties differently depending on the method used to generate them."
Dr Robbie Waugh: "To use genome editing you first need to make transgenic plants with two components (an enzyme and a guide RNA) that then combine to make the desired targeted changes. The beauty of the system is that after the desired changes have been made and identified, researchers can easily separate the transgenic part from the ‘edited’ target by performing a traditional cross or self-pollination. The resulting plants are themselves non-GM (but they do contain a very specifically targeted mutation). I would argue that as there is no remaining foreign DNA they should be considered non-GM."
Prof Ottoline Leyser: "This only matters because of the way GM crops are currently regulated. The regulatory process in the EU emphasises the technique used to make the crop rather than the trait introduced.
When GM was first introduced it seemed like a radically different way to introduce genetic variation into crops, because it involved the deliberate insertion of a new piece of DNA into the genome. However, our increasing understanding of plant (and animal) genomes over the last 30 years has revealed that insertion of additional bits of DNA into the genome is very common. This mostly involves so-called jumping genes, or transposable elements, that move about the genome and have provided an important source of genetic diversity for plant breeders for 1000s of years. For example Mendel's famous round and wrinkled peas differ due to the insertion of a transposable element into a gene involved in starch synthesis in the seed. Because of this, the most important distinction between GM approaches compared to conventional approaches is the wider range of genes that can be introduced.
Consistent with this, the specific concerns that have been raised about the possible negative impacts of GM crops are related to the trait introduced (such as herbicide tolerance), not the fact that GM was used to introduce the trait. Since similar traits can be introduced without GM. Therefore more robust protection for the environment and the food chain would be provided if it was the trait rather than the method of introduction that formed the basis for pre-registration risk assessment for new crops."
JJ: "The new genome editing techniques usually involve a phase of “standard genetic engineering” to insert genes for enzymes such as TALENs or Cas9 designed to make DNA breaks at specific locations in the genome. Once a DNA break has been made, and a new (often a mutated) form of the targeted gene created by error-prone repair, the gene for the TALEN or Cas9 can then be genetically segregated away by standard breeding methods. The result is plants that carry the desired change at an endogenous gene, but that no longer carry the gene that made the change. There is no scientific reason to suggest that a plant that does not carry a transgene, but which derives from a GM plant that did, should be treated as a GM plant. Some applications of these methods result in insertion of new genes but at tightly defined locations (unlike in “standard genetic engineering”), or that replace the recipient plant’s form of a gene with that from another plant (for example to confer disease resistance), or that introduce specific nucleotide changes in the target gene."
2. "Marker assisted breeding is touted as a safe alternative to GM - how does it compare to these new genome editing things?" (Helen Curtis)
Dr Glenn Bryan: "Marker assisted breeding (MAB) involves using genetic markers linked to a trait of interest (eg. size, disease resistance) to incorporate beneficial trait genes into plant breeding material. To achieve any sort of precision the marker used needs to be very close to the trait gene, and this is often not the case, so MAB can be extremely imprecise, often resulting in ‘linkage drag’ whereby genes not influencing the target gene can be selected, often with deleterious consequences.
GM, in its many forms, offers the possibility to modify the function of a single gene affecting a trait in a very controlled manner and in my view is no less safe than using MAB. The new ‘genome editing’ technologies, of which there are several different types, offer further refinements in that they aim to make specific targeted modifications to the DNA sequence of a particular gene or genes in its normal genomic location. These new technologies, unlike older GM technologies, do not create new copies of the trait gene in the genome.
My view is that so long as the proper experiments are done, the new genome editing technologies are no less safe than use of MAB. MAB can take a very long time, whereas some of the new technologies can be used more quickly. This is especially important when considering issues of major disease threats and abiotic stresses - such as high winds or extremes of temperature - which can have major impact on food security, especially in developing countries."
Dr Jonathan Jones: "Genome editing usually involves making GM plants that carry enzymes that will impose the desired change on the genome, and then breeding out the genes for the enzymes. This could be carried out quite quickly- within 3 generations. Conventional plant breeding is a never-ending process of genetic improvement by cycles of controlled pollination and planting of derived seed, followed by selection."
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