Q63 We welcome Professor Robin Lovell-Badge, the principal group leader and head of the laboratory of stem cell biology and developmental genetics at the Francis Crick Institute, Royal Society; and Alessandro Coatti, the senior science policy officer at the Royal Society of Biology. Professor Lovell-Badge, would you like to start with a few words?
I should say that dealing with plants and animals is not my day job—I work at an institute that is better known for medical research—but I do know an awful lot about genome editing methods and genetically modified organism techniques. I chair the Royal Society’s genetic technologies group, in which we discuss plants, animals and humans in this context. I helped to develop the Royal Society’s submission to the whole process at various stages.
I guess the main point that the Royal Society has been trying to make is that we are a little uncomfortable with having yet more regulations based on techniques rather than outcomes. For us, it would make much more sense to focus on the outcome—the purpose of what you are doing—rather than on the method you are using, partly because scientific methods evolve so rapidly that it is hard to keep track. When reading the first part of the Bill, which includes the definitions, I struggle in some places to understand exactly how certain techniques would fit into it. That is one issue.
If the argument is that genome-edited plants and animals are essentially the same as those that could be bred by traditional methods, yes, that certainly can be the case, but it is not always the case. To give one simple example, if you have two genes right next to each other in the genome, and they both need to be altered to have the trait that you are after—that is possible in normal circumstances—you can do that with genome editing, because you can target both genes at the same time. To do that by conventional, traditional breeding methods may be impossible, however, and it would certainly take an awfully long time to ever get both changes together in the genome. When two genes are next to one another, it is very hard to separate them in normal breeding processes.
There are all these complications that I envisage because that is what I do—I think about the techniques all the time. If your approach is based on outcomes, it is easier to justify, “I’m doing this; the outcome is this.” You can also judge what effect your change has on other things like farming practices, environment and so on. This is a little bit narrower, I think, in that respect.
With pleasure. Thank you for having me today. I am one of the science policy officers at the RSB. I am biologist by training, and particularly a molecular and cellular biologist. At the society, I provide support to our animal sciences group. I look a lot at policy and research developments in the animal science field, so less so in the plant sciences, which are very important for the Bill. I have been involved, however, in writing our response to the Department for Environment, Food and Rural Affairs consultation on the future regulations in genetic technologies, and that is why I am here today.
I agree with Robin Lovell-Badge’s statement and with the approach that the RS takes. The RSB has also argued that it would be better to have regulations based on looking at the traits and products that you would develop using the technologies, and to monitor the impact in risk assessments of the outcomes, or the impact of the organisms. However, in our response we envisioned a bit of what is happening with the Bill, because there is a need to enable development and innovation on a faster timescale, in the sense that the United Kingdom has inherited the EU regulations that have a process-based trigger. They are designed to list a lot of technologies that are “modern” biotechnologies and not block their use, but make it subject to additional risk assessments simply because the technologies were new 30 years ago. They pulled out some of those techniques to create exemptions, to allow the use of mutagenesis in plant breeding in the past few decades.
Basically, we inherited that, so in a way I see what the Bill is trying to do: to define a new category of exempted organisms from that GMO framework that would allow research and innovation to progress faster in this country at this stage. However, this should not be the end of the story. There are good things in the Bill, but in order for the technologies to be properly regulated in the future, a move towards a truly trait and product-based regulation, which looks at the outcome, is really important.
I also commend the report of the Regulatory Horizons Council on regulations in genetic technologies. They consulted us and many other stakeholders, and they have provided a view on how the evolution of regulation in the UK could proceed.
Q Thank you and welcome to Professor Lovell-Badge and Mr Coatti. I believe, Professor, that you are at the Crick for your day job.
I would like to take a little from the narrative that you have given us, and from something that you stated in your returns to the consultation. Thank you for saying that the Bill has been consulted on widely; we are trying to get it right, so any advice would be gratefully received. You stated:
“If appropriately managed, precision breeding offers a route to achieving many potential and much-need benefits to society.”
That rather articulates your argument that it is outcomes-based. With that in mind, you stated that you support the advice of the Advisory Committee on Releases to the Environment that precision breeding poses no greater risk than traditional breeding methods. Can you explain why, and can you refer to whether you think the current regulatory framework has held up? I think that was what you were saying in the narrative about research and development. Where would you go with that regulatory framework in order to optimise the R&D so that we can evolve into being outcomes-based, both in environmental and human health terms?
The first question was about risk, I believe. Generally, on the risk of a random mutation versus a genome-edited one, you are actually better off with a genome-edited one because you know what you are doing. Of course, there can be some examples where you might not know exactly what is happening. There is very little mention of human health in here and so there is concern about zoonosis, where an animal virus can jump to humans, for example. You could, in theory, make what you think is a fairly simple change to give a trait that you want, but inadvertently you allow an animal virus to jump to humans. That needs to be looked at, in terms of risk. Exactly the same thing can happen with traditional breeding, but I imagine it is not generally looked at. That is a risk.
The case that Robin used before is quite important, where you think about adding multiple changes to genes in the same organism. The Bill covers plants and animals, but it does not cover micro-organisms, which are an interesting aspect that we can discuss later. You also really have to think about the fact that the dynamics of the genomic changes in different organisms are different, just like the way they reproduce is different. The type of gene flow that you would see in plants is different from the one you would see in animals.
The case that Robin was discussing of adding multiple changes in neighbouring genes in an animal is harder, through traditional breeding, than it has been in plants. For example, you can mutagenise into this very big screening. You might get to that point faster in plants than in animals. Perhaps the fast pace where this technology now allows development is not, as you say, either a morally or a practically neutral question. It is interesting that the Government have decided to frame it as something that could have arisen through traditional breeding or spontaneously. There is a reason why that is. However, at some point, it becomes a bit stretched, because in traditional breeding it would take many generations, and it would be quite hard to do it in certain animals.
However, this is again talking about the techniques. When it comes to adding those two traits in neighbouring genes, you might end up actually making the life of the animal way better. That is why you look at the outcomes. By using genome editing, people have corrected genetic defects that have arisen traditionally in breeding, for example of cattle. There is this Japanese breed of cattle that has a genetic syndrome. With genome editing, they corrected it because it was due to a single gene. In fact, even if it were very unlikely that you might have done it with traditional breeding, it is a very valuable use and we should do that because it enhances the welfare and the health of the animal.
That is sufficient, because everybody will want some time. I think I glean from what you have said that it would take many generations but it is still possible, particularly in plants. It therefore allows you to target derived beneficials, but this is caveated with the regulatory framework being appropriate.Q
The question would be: if someone made a plant or an animal where you have targeted two adjacent genes, would that be permitted or not under these rules? It is hard to think that it might be, because you could not simply do it by traditional methods. You might have to wait thousands of years and it would cost you a lot of money. That is the question.
I start by thanking you and your colleagues for your excellent evidence, some of it submitted to the consultation. It has certainly informed a lot of our thinking, although it also raised a lot of questions. In your introductions, you restated what was essentially in the evidence, which is that there is a problematic set of definitions and this would not necessarily have been the way that you would have gone.Q
I want to explore something slightly different: the role of advisory bodies. You began to touch on that in your last answer. The Bill at the moment is very thin on what the advisory bodies are there to do. In some of your written evidence, both your organisations suggested that the different bodies should have some kind of remit to look at the wider public good. Could you say a little bit about that? I have been taken by the example of the Human Fertilisation and Embryology Authority, or some aspects of the work that it does.
I have been very much involved in the HFEA public engagement exercises. When you are considering a broad area, or potential uses and outcomes, it is really important to have proper public engagement, including democracy, dialogue, or however you want to refer to it, where you really get to understand what the public will think about a topic.
When it comes to assessing technical aspects, it will be challenging. It is fine to have a lay member on a panel, but I do not know whether consulting the public about really detailed, technical issues might be challenging. It depends on what the advisory committee’s role is and whether it is to look more broadly at potential uses and outcomes or to focus on the specific techniques that are being used.
Q Let me press you on that slightly. In terms of some of the animal welfare issues, it is pretty clear that some of the things that could be done could be designed to make animals more resistant to heat or more liable to be able to survive certain conditions. That does not seem to us a good use of this technology. It is not entirely clear to me on what grounds the advisory bodies would make decisions. If it is just left to a market-driven system, you could argue that, provided it produces a better return, that is good enough, but the ethical issues would be wider than that.
This is another point. I was a bit confused because there is quite a lot of emphasis in the Bill on animal welfare and how they would have a role to play in that. If you are doing an experiment with an animal, you have to have Home Office approval. Animal welfare is a top priority. Many of the things that you might want to do would already be weeded out at that stage. If you wanted to make an animal that felt no pain, for example, you might just about be able to get away with justifying that for research purposes, but certainly not for developing any product.
The regulations about welfare are already there. Sure, it is important to have some input into your advisory committee that says, “This has to be looked at. Have they thought about all the consequences of what they are doing?” Exactly how you would achieve that under the Bill, I am not certain.
Q There is now a new player in town: the animal sentience committee, which is not established yet. How would you see the interplay with that, given what you have just said?
It is an interesting new player, welcomed by many parties across the House. It looks like it will be an expert committee. Mostly the members will be people with relevant expertise in veterinary sciences, potentially neuroscience, so it would not be an arena for a public dialogue, but that is not to say that they cannot commission it and then take recommendations on board. In my view, they could play a role, but it would be hard. The new animal welfare committee that would overlook the authorisations in the Bill would look at a notifier that said, “We want to do this on an animal, but we do not foresee any health or welfare implications for it.” That committee would focus very much on the health and welfare of the single individual animal, but it is not clear to me whether it would consider higher-level questions such as, “What does it mean for the production of that livestock, the density, the husbandry and so on?”
Of course, the existing DEFRA Animal Welfare and Animal Sentience Committees could be brought in. You could say, “We have a new line of pigs that are resistant to this disease. On paper, it looks very good, because we made a very small, tailored change to a part of it, not a rough deletion of an entire gene. The animals under research and development look fine in contained circumstances and they are well. Would you be happy for us to license them to go on to a breeding trial to expand the number of animals from the 20 in the research study to 200, and to map whether there are any health and welfare impacts on a bigger number of animals?” Those committees could advise the new animal welfare committee on that matter.
Following on from that, the bigger question is: “What do we want for UK farming, agriculture and so on?” That is one of those pillar questions that bigger Government policy, not the Bill, will resolve.
My colleague makes a very good point. If you take things out into the field, the conditions are different from lab conditions in which you originally generated the animals. If you introduce another breeding programme, or a different genetic background, the consequences of what you have done could change. It is the same with traditional breeding, but on all those things, there needs to be long-term feedback. As you would have with humans in clinical trials, you get a phase 3 clinical trial in which you get a lot of people feeding back information—much more than in a phase 2 trial—and then there is always post-market reporting whereby any adverse effects are notified over the years.
Under clause 11, when a marketing notice is given in relation to a precision bred animal, the Secretary of State reserves the right to get information from the notifier, over a specified period of time, about the health and welfare of the animal, so that is already covered in the Bill.
No, and a lot will depend on very good guidance from DEFRA or ACRE about how to do that. But that power is in the Bill, at least.
Again, the need for post-marketing monitoring comes down to the trade that you are introducing, not whether you use a technique. It will be important for whoever advises the Secretary of State to be able to tell them, “This change warrants longer-term monitoring, but this other one does not, because we have seen it in the species over many years. This is just a better way of doing it, and it will not dramatically alter what we already know about the trait.”
Remember, many genes have effects in multiple tissues, so you may be focused on changing something—modifying CCR5 for HIV resistance, for example—but not realise that it may also be active and play some role in the brain. That is a clear example of where you may have an issue.
The Regulatory Policy Committee brought out a report just a few days ago that concludes that the Government have not made a convincing business case for the deregulation of precision bred organisms in the food system, and it suggests that more narrative aroundQ
“competition, innovation, consumer and environmental impacts” should be included in the Bill. Would you agree that there is insufficient detail on that in the Bill currently?
I think I would agree it is insufficient. You have to factor in everything: the environment, farming practice—how whatever you are doing, whether it is with plant or animal, is going to fit in with or change farming practices. I think there needs to be a lot more thought about those issues.
Q Yes, it is insufficient currently. They feel that there is a need for wider discussion of the impacts on the environment—woven throughout the Bill, I think—than currently. I wonder what kind of environmental impacts you would like to see included.
The case for deregulation—let us put it that way—is that basically, with these technologies, you can achieve changes in the genome that are potentially done already in traditional breeding. You are just doing it in a more energy and resource-efficient way—faster, etc. So there is definitely a policy case for this Bill, because research and innovation in this country can really provide those beneficial traits in plants and animals that we desperately need at the moment.
On the question whether this Bill captures all the potential impacts on the environment, for example, from a release of one of these organisms, you would think that the organisms that are passed through this Bill will not particularly need extra monitoring relative to the traditionally bred counterpart, if you see what I mean.
However, there could be boundaries or grey areas where a change could have arisen traditionally but it is not so common. Therefore, the committee should be able to trigger an additional risk assessment; and in my view, it looks like it can. Now, the question is this. On the environmental risk assessment, there is not much detail in the Bill—that is true—so it will be down to ACRE to provide more detailed guidance and analysis on how it would want the environmental risk assessment to be done.
Q If I may, I will ask one very quick question—well, it will not be that quick, actually. The answer will probably be quite long. I want to ask about the difference in regulatory regimes, potentially, between the UK and the EU. No matter how long that might be—we do not know; obviously, the EU will come back after its consultation next year. I just wonder what you think the impact might be, and whether in your view that will affect trade and potentially investment in the UK. Is that a tricky one?
That is a hard one. The EU will have to change—that is my view—because it is going to be way behind other countries, too. We are not talking just about the UK and the EU; we are also talking about the US, Canada, Argentina and other countries. If the whole regulation about genetically modified organisms and genome editing is not made more compatible with actually getting on and doing stuff that is useful, the EU will suffer, because it will ultimately—
But the impact here, in the UK, on trade? Obviously, it is the UK’s largest trading partner, so if it continues to be—
Yes, I would not be able to discuss in detail how that might be. You probably need to have experts on it. But I am aware that the Food Standards Agency has produced a report on these changes in regulations and this evolution across the globe, and there is definitely a case for the UK to try—we say we would like the UK to lead the way, as it has done with the Human Fertilisation and Embryology Act 2008. The UK could still lead the way by making legislation—regulation—that other countries would copy, but there is already a lot out there, so it has to harmonise with the regulations in other countries, such as Japan and Canada. It seems like the Bill is going one step in that direction. In terms of the relationship with the EU, as the closest economic partner and one of the biggest markets that the UK trades with, it is important for the UK, not necessarily to slow down excessively, but to maintain dialogue with the EU Commission while it reviews. The UK in the past has created legislation that the EU has then taken on. For example, when it comes to animals and research, the UK has led the way on the protections—eventually the EU adopted some of those elements. Even though the EU is not politically obliged to anymore, it could still value that.
We have already established that the Bill covers plants and animals, but not micro-organisms. Given that there were suggestions from DEFRA that animals would be considered later down the line, I wondered if you had any thoughts on the fact that they are now included in this Bill.Q
In our response we commented mainly on plants and animals, while making some reference to other uses. There are already leading labs in the UK looking at genome-edited livestock species, for example, and how doing genome editing in those species could be beneficial on many levels. I am quite sympathetic to the fact that animals are included in the Bill, even though there is less of a history of genome editing, and genetic modification, in animals than there is in plants.
It seems to me that more safeguards are added here for animals than for plants. There is animal health and welfare assessment as part of the Bill. With animals, it seems clear to me—but Robin can correct me—that genome editing can be used quite safely. We are talking about the techniques and the process, not the outcomes and the traits. If you look at the techniques with the animals, with a number of species you can be pretty sure that you are making the right change in the genome that you wanted and that you are not adding unwanted changes anywhere else. We can say that there are not many additional risks when it comes to technique, relative to traditional breeding. However, that still has to be caveated a bit.
Some of the methods of genome editing are now so efficient and precise that I do not think it is a great concern, but you always have to check. There are good ways of checking what you have done and what you have got. I would not be that concerned. You would have to check the original animal that has been modified, but once you get to subsequent generations, you will be pretty certain of exactly what you have, and of anything wrong. The methods are being used in humans for somatic genome editing. We know a lot about them and how accurate and safe they can be.
We pointed out two things in relation to the methodological aspects. Robin mentioned one aspect before: how the gene relates to the phenotype. You change something and then you have a trait change in the animal. Some genes have functions in different organs and tissues, so you want to ensure that by doing something you are not messing up something else. That can be done and has to be done as part of the Bill—you should make sure that it will be done.
The other question is about the reproductive techniques you sometimes use to work on the embryos. Those can also have health and welfare implications for the animals, but it should all come down to an expert committee reviewing the application for the genome edited animals, which could say, “Okay, it looks like they checked everything they should have on the technique.”