Gene-Editing: Food of the Future?
Could the potential food of the future be on its way to our supermarket shelves? Parliament is currently reviewing rules which would allow gene-edited food to be grown and sold in the UK, moving away from the more stringent rules it had adopted under EU regulations. The phrase 'genetically-modified' gained a bad reputation towards the end of the 20th century, with concerns around the safety of inserting foreign DNA into organisms, the mechanisms for doing so and the motivations behind its use. With the development of targeted gene-editing technologies, such as CRISPR-Cas9, modifying genetic material has become more feasible and accessible, potentially marking a revolution in food production. We will be exploring some of the proposed benefits of genetically-edited and modified produce - which include boosts to health, taste and sustainability - as well as seeing what stands in the way between edited foods and our shopping trollies...
In this episode
01:11 - Mice cloned from frozen cells
Mice cloned from frozen cells
Alena Pance, University of Hertfordshire
This week, in 1996, the most famous sheep in the world was born. Named after Dolly Parton, because her co-creator Ian Wilmut used an udder cell to make her, Dolly the Sheep was a giant leap forward in the field of animal cloning. And this week, right on cue, scientists in Japan have taken the technique used to make Dolly - which involved removing the DNA from a skin cell and inserting it into an egg cell deprived of its own DNA - and worked out how to make this process work with cells that have been freeze dried. This means, by banking cell samples from endangered species across the world, we could have a way of safeguarding species that are most at risk. Geneticist Alena Pance, from University of Hertfordshire, took a look at the paper describing the work for us...
Alena - It is mainly about using freeze dried, preserved cells to create new individuals. The main objective was to provide a way to preserve species and recover some of the species that are in great danger of extinction.
Chris - I thought we could sort of already do that because we even do this for human cells. Don't we store sperms, eggs and even whole embryos in freezers? And the law says we can keep them for decades and think they're all right, doing that.
Alena - Yes, but it is extraordinarily costly because it has to be very low temperatures. It's not just like the common freezer at home, which goes to about minus 20. It has to be minus 190, very low temperatures. And it's very costly to keep these conditions. And also they are very vulnerable because if anything happens, we run out of liquid nitrogen, there is a power cut, then all of these samples can be lost.
Chris - Got it. So if we've got cells that are any old cell from an animal and we freeze dried it, so it's a bit like the jar of coffee in the cupboard. It's not gonna go off at anything like the rate that something that has to be on liquid nitrogen is, so it means it's a safeguard for the future and it saves money.
Alena - It is indeed. And it allows to store particularly the genetic material, because what happens is that when cells are freeze dried, the cell dies, but the genetic material in the nucleus is preserved and that can be then revived and an organism can be created from it. And that's the importance of the process.
Chris - Talk us through what they actually did then and how they proved that that is the case in this paper.
Alena - So they have taken skin cells from mice, freeze dried them and stored them at minus 30 degrees. And then from these cells that are dead, they extracted the nucleus, which is where the genome, the genetic material is stored and transferred that nucleus into an egg from which the original nucleus was removed. And from that, they were able to generate mice pups and these mice pups were healthy and fertile and so on. Therefore they demonstrate that this approach can be used to preserve species.
Chris - What was their success rate with this? How many cells did they have to start with and do this on before they got mice back?
Alena - The success rate is very low as with any cloning procedure. They were able to improve their success rate by going through a second cycle. So the nucleus was first transferred, left to develop to a certain stage. And then from that cell lines were generated and then a nucleus from those lines was again, transferred into a new egg. And that increased the efficiency to about 1% to 7% from about 0.02%.
Chris - So it is quite an unlikely success rate, unless you go through this process, do we think that the animals arising from this process are gonna be fit and healthy though? Because I mean, you acknowledge that they appear to be okay and fertile, but are we sure that they're all right, because you can't ask a mouse to do an IQ test to see if it has some kind of mental decrement or something. We have a very limited pool of animals that have been studied here. So is there not the possibility that we have in some way, genetically damaged these animals and that in fact, although the aims are laudable, getting back rare species or safeguarding the future of rare species, we could end up with a very narrow damaged genetic repertoire if we did this?
Alena - So there are several things to consider here. One is that this sort of thing has been tried before, 20 years ago, really. But again, the success rate in those cases was very low. And actually what happened was that most of the babies in this case, it was sheep, died. So clearly they had health issues. In this case, of course it's a small sample, but there were 75 pups that they managed to get. And those appeared healthy. They grew all the way to adulthood and they were able to reproduce.
07:56 - What dark matter isn't
What dark matter isn't
Ben McAllister, University of Western Australia
It’s 10 years since the recently restarted particle accelerator in CERN, the Large Hadron Collider, discovered the elusive Higgs Boson or “God Particle” as some also refer to it. So let’s talk particle physics now! Most of the time in science, researchers tell us about what they have found. But occasionally important papers are presented that tell us what hasn't been found; and this can help to rule out how something doesn’t work or what something doesn't look like and points us more in the right direction for where we should look. This week Ben McAllister, from the University of Western Australia and Swinburne University of Technology, has done just this in grappling with what is literally a massive problem in physics, as he explained to Chris Smith...
Ben - We have been trying to get to the bottom of one of the biggest mysteries in the universe, as I like to call it. For about a hundred years, we have known that all of the stuff we can see in the universe, that's the kind of matter that makes up you and me and the planet and the sun, is not even close to all the stuff that there is. We can't explain the way things move around. If we only consider the stuff we can see, particularly, it seems like the gravity that's provided by the stuff that we see, wouldn't be strong enough to pull stuff in space around as strongly as we see it pulled, if you like. So we infer that there must be a lot of invisible stuff out there about five times as much as there is of all the stuff we can see providing additional gravity. So it's this huge cosmic mystery. And we've known it's for a long time. And we just don't know exactly what it is.
Chris - If we are only inferring its existence, we can't see it. And we don't actually know how to detect it. How can we therefore work out what it is?
Ben - Yeah, it's a great question. So there's lots of different ways that people try and get to the bottom of dark matter. The most popular theories rely on introducing new particles. So new kinds of matter that are different to the kinds of things we already know about that can account for the dark matter. But generally speaking, the lines of attack for detecting dark matter are you can do something like what they do at the large Hadron Collider at CERN. Take particles we already know about and smash them together and hope that some interactions occur that cause them to generate dark matter. Or you can look in space with telescopes and hope that maybe some dark matter particles out there are interacting in such a way that they generate particles we can see like photons, particles of light, or other things like that, and we can catch them with telescopes. Or you can do what we are doing here in the study that we're talking about today, which is called direct detection, where you build a detector on earth and you try and catch an interaction of one of the dark matter particles that's passing through the earth with something in your detector.
Chris - You've therefore, presumably got in mind some kind of model for what shape or structure that dark matter entity might take. So you are saying, if it looks like this, it should do the following things in our detector, can we detect it?
Ben - Yeah, that's exactly right. So again, you need a hypothesis to start with of what the dark matter is. There are a few of them. In particular, the work we're talking about here is trying to detect, a very popular dark matter candidate, a thing called an axion, which is a new particle that was proposed in the seventies. Funny story it's actually named after a brand of dish soap, for the way it cleans up problems. And the nice thing about the axion is that it is supposed to have an interaction with photons, which are particles of light, which is great because it means we can take dark matter, this invisible thing that we can't see at all and convert it into a little flash of light, a thing that we're great at trying to detect. So that's what we do with the organ experiment, which is the work that is being published this week.
Chris - And what have you seen so far?
Ben - Well, that's actually the funny thing. When you do these kinds of experiments, you obviously hope to see something you hope to see that little flash of light in excess of the background that says, oh great, we found this dark matter signal, but more often than not, you don't. What you can then do as we've done here, and as other experiments have done in the past is you can place stringent limits on the existence of the dark matter. You can say, okay, our experiment is this sensitive in this region of parameter space of dark matter? And we didn't see anything, which means we can put a big block through it and say, okay, the dark matter is not here. So what you can do is you set it to be sensitive to a certain axion mass. You wait some amount of time to see if you get a signal and then you move to another axion mass and you do that for some range of masses. And if you don't see the axons, you say, okay, we can rule them out to this level of sensitivity within this mass range. And that's what we've done here. We've ruled out some new parameter space, the most sensitive search for axions to date in the mass ranging question.
Chris - How do you know your machine's just not broken?
Ben - Yeah. Right. Well, you can do all kinds of different calibrations and tests where you inject signals. That would mimic what you'd expect to see from an axion converting into photons and see if you pick those up. But the fundamental answer is really that it does depend on your model. You're saying, we're assuming for this thing, where the axion is the dark matter and it's interacting in this way inside the detector. And then we can generate simulated versions of that signal and see that we would see them and, say with some confidence, some degree of confidence that we have ruled out the axions in that range.
Chris - If they don't exist in that range and your experiments are correct. What effect does that have in terms of constraining what axion are?
Ben - Yeah, it's quite funny to be reporting a negative result, but it is really the way science works isn't it? I mean, we're doing a big search here. It's sort of like the wild west. There's all this territory that we have to go out and search. And what we're doing is essentially saying in concordance with the international community, well, we've looked here and it's not here, so we don't need to spend any more time looking here and we can start moving our detectors into other ranges and work with international collaborators in the field to gradually sweep through this huge range and hopefully eventually detect the dark matter.
Chris - And if it turns out your right and you find the elusive axion, what does that do to physics?
Ben - Well, I mean, that would be like a huge paradigm shift because we would have answered one of the biggest mysteries in the universe, what the nature of the dark matter is. And at the same time detected this new particle, and it would be the start of a sort of new era of axion physics. You could imagine doing all kinds of interesting things. You can do astronomy using these axons. People have various proposals for different kinds of seemingly futuristic technologies that they might be able to be used for. But it is one of those questions where we almost don't wanna get too far ahead of ourselves in terms of possible applications of these things at the moment. I think it's more like we know there's this huge unexplored realm out there. There's all this dark matter and we just don't know what it is. And we will never learn anything new if we only ask questions we already know the answer to, like we never would've discovered radio waves, we never would've discovered modern electricity, if we'd only set out to do experiments where we said, okay, we know exactly what's gonna come out of this by the time we're finished doing it. We just need to start probing away at these mysterious things that seem at the time, like just unexplained physical phenomena. And that's exactly what we have here. And we know throughout history, when we probe these big unexplained physical phenomena, we make big discoveries and we change the way the world works.
15:44 - 30-minute intervention to help reduce stress
30-minute intervention to help reduce stress
David Yeager, University of Texas at Austin
Since the pandemic started, rates of mental health issues in young people have soared; many teens and young adults trying to map out their futures say they’re dealing with extreme pressure. But a study published in Nature puts forward a 30 minute intervention that can dramatically turn things around. Psychologist David Yeager, from University of Texas at Austin, took Julia Ravey through the process, and explained how learning to harness stress is the key…
David - There's this tension, which comes from the fact that young people need to be spending a lot of time, gaining skills, preparing for a contribution and that's stressful. But that also is what brings meaning and purpose to our lives. And so it's kind of like a dilemma. Do you give in and not feel any stress, but then get off the path to a good future? Or do you burn out because you're always working and you're always pushing yourself.
Julia - You've come up with an intervention to help people in this situation handle stress. And so how did you come up with this?
David - The path we started down was the question of, okay, if you have someone who is, let's say about to do a major presentation at work, what do you say to that person about the stress that they're experiencing? And if you look around in society, the main message you hear about stress is that stress is bad and it should be avoided. If you are about to do a major presentation for your boss's boss, that's not the time to take a nap and go do yoga. You should be like preparing to do really well in that presentation. So we tried to figure out a way to help people embrace challenges, to use their stress as a resource, rather than as a deficit. And then in doing so, maybe help people cope with this feeling that everything is more than you can handle.
Julia - What is the mechanism in which you landed on? And then how have you tested this out?
David - So what we try to do is try to change adolescents and young people's beliefs or mindsets. So we give them real scientific information about the brain and about the body's stress system. And there are two different types of psychologies. We pull from one is the really well known concept of growth mindset. The idea that when you're challenged, it's a sign that you're growing. It's not a sign that you are dumb or that you lack ability in some way, the way we teach that is scientific information about how the brain can grow and develop like muscle. And then we pair that growth mindset idea with something that Alia Crum has called the stress can be enhancing mindset. And this is the idea that when the heart is pumping more blood through the body, when you feel your breathing rate increase, when you get that kick of adrenaline, that's actually your body preparing to move more oxygenated, blood to your brain, into your muscles, to optimise your performance. And then we have them read stories from older students like them, who've experienced stress in the past and who use this information. And last we have them write their own essay or story about how they could use this info.
Julia - I've just done the test before actually. And I thought it was really useful to think about how these hard situations are training us to better handle stressful situations in the future, and that our hearts racing, being helpful to get oxygen to our brains. So how has this reframing been found to help people in your studies?
David - We took a few hundred students and we put them in a rather intense stressor in the laboratory, and it's called a trier social stress test. It's kind of a hilarious test. And what you do is you bring people in, you hook them up to all the physio equipment to protect their heart rate and their breathing and so on. And then you say surprise, it's time for you to give a public speech about what makes someone popular. And then they have to give that speech for five minutes in front of a panel of judges who we've trained to kind of give you no positive feedback. They just are stone faced looking at their clipboards, judging and evaluating you. And the minute that speech is over, we say surprise again, it's time for you to do mental math. And so you have to count backwards from 968 in increments of 17 as fast as you can. So, as you can imagine, people's hearts are racing and their blood's flowing and, and they're sweating, and so on. What we find is that in the middle of that stressful speech and that stressful math, if you got our mindset intervention first, your physiology is actually different. Your body is pumping more blood to your extremities. And what we think that does is it means your brain is getting more oxygenated blood to actually optimize your performance. We went back to the university context. We did the intervention in January of 2020. We had this real world stressor, everyone was sent home from college because of COVID. And we found that especially in people who were the most vulnerable, there were fewer anxiety symptoms, three months later, among the people who got our treatment.
Julia - What situations would this test maybe not be applicable to?
David - We don't think this is something to give to people to say embrace the stress of trauma abuse or a panic attack. But apart from that, we think that a lot of people can benefit from this treatment just because they're anticipating stressors. And they're, they're thinking about what's gonna happen to them.
21:15 - Formula 1 Halo: Life-saving technology
Formula 1 Halo: Life-saving technology
Kit Chapman, Falmouth University
F1 fans were treated to a thrilling race last weekend with the British Grand Prix. But, for all the dramatic overtakes and frantic final laps, many will reflect gratefully on what, fortunately, didn’t happen. The race was delayed for an hour after a spectacular crash at the first corner when Alfa Romeo’s Zhou Guanyu (JO GWAN-YOO) was flipped upside down onto the tarmac and span into - and over - the barriers at nearly 200mph. James Tytko spoke with science journalist Kit Chapman to find out how Guanyu came out of the incident unscathed…
Kit - When you go round a track at 195 miles per hour, there is of course an element of risk. There has been since the early days of formula one. But since the 1990s, in particular the death of Ayrton Senna, safety has become a major priority. There have been countless accidents where people have learnt, they've improved the cars and they've made them safer.
James - It's quite unfathomable for someone like me, who doesn't watch that much F1, to get my head around how someone comes out of a crash like that. And I think the term that was officially used to pronounce his state was 'uninjured.'
Kit - Absolutely. So Zhou was completely uninjured in the crash and that's for several different reasons. When you look at the design of a formula one car, what you've got is the monocoque, which is where the cockpit, where the driver is sitting, and that is designed around a crush zone. So that crush zone will dissipate energy when there's an impact. That's why the tyres end up twisted and bent around. Behind them, in the fuel tank, that's protected by kevlar and so it's very unlikely you're going to get a sort of spectacular fireball. Then, if you look at the actual design around the cockpit, you've got this roll bar, which basically is designed to protect the driver if the car does flip around. But of course the most important part is the halo, and this is a titanium beam that is just above the cockpit, and that is able to withstand the impact of 15 cars on top of it. And that is really what saved Zhou's life. Even if you have a perfect situation with your car and all the crumpling happens exactly where you need it to be, your halo works, your roll bars work, you're still suffering a huge amount of G force. Now 1 G is normal for us, six G is what you get on a roller coaster - this could be an impact of 60 to 80 G, which is huge. And that normally would be fatal for humans. They'll suffer what's called a basilar skull fracture, which is basically the bottom of your neck, your skull, fracturing and snapping. And so drivers also use something called the Hans device. It's basically a yoke that goes over your shoulder, and then there's a tether that attaches to your helmet and that prevents your neck from snapping forward. It keeps everything in line and it protects the head and neck and makes sure that you don't get that injury.
James - And if we can go back to talking about the halo, because there was some controversy wasn't there when it was initially introduced?
Kit - Yeah. The halo was one of the most unpopular ideas. People thought, "why do we need this extra layer of safety?" It was influenced by the death of a driver called Jules Bianchi, who was killed from complications during a race and drivers weren't particularly happy with it. Roman Grosjean was actually a huge critic of it when it was introduced. After the 2020 crash in Bahrain, the halo unquestionably saved his life. It actually bent over a barrier that would otherwise have decapitated him. He has become a complete convert. And now when we look at the halos, multiple drivers, including Lewis Hamilton, who had Max Verstappen's car land on him last season, have been saved because of this halo device.
James - And what have the F1 organization and community learnt from this, other than the effectiveness of the halo? Is this time for a pat on the back for everyone involved, or is this more of a reason to re-energise, to redouble the efforts on making sure the sport is as safe as possible?
Kit - It's always something that you have to improve. Formula one operates on a Swiss cheese model. Famously, Mark Gallagher of Red Bull has talked about this. And the whole idea is that you don't want a hole going all the way through the cheese, you want to make sure that there are barriers in place. And so those barriers are human; training, making sure that the medical staff are there. They're technological, making sure that there's safety features. They're just things like track layouts and making sure that the right type of barriers are used. But this crash will be analysed and poured over by F1's teams. Already, there's a load of dissection going on about the roll bar, on whether or not it crumpled effectively, or whether or not that's something that needs to be improved. And so they're going to look at this from every single angle, from angles we are never going to see. They've got black boxes on the cars and they're going to figure out exactly how they can prevent it ever happening again.
26:48 - Modifying foods: Past, Present and Future
Modifying foods: Past, Present and Future
Helen Anne Curry, University of Cambridge & Gideon Henderson, Department for Environment, Food and Rural Affairs
At the end of May, the UK’s Department of Environment and Rural Affairs - DEFRA - announced they were presenting a new bill to parliament to potentially relax laws around the growth and sale of gene-edited foods in the UK. This has implications for the food that ends up on our supermarket shelves, as Julia found out…
Julia - I've just popped to the supermarket to do my weekly shop. I always start off in the fruit and veg aisle, favourite part of the supermarket. I was looking at the fruit and veg in front of me and I wondered, "how much has this produce actually changed over the years?" There's such a vast selection of fruit and veggies in our supermarket, but have they always looked and tasted this way? I asked Helen Anne Curry, a historian of science and technology at the University of Cambridge. I asked her how much influence we've had over the produce that's ended up on our supermarket shelves.
Helen - Humans have clearly been modifying plants knowing that they're changing them over time for many hundreds of years.
Julia - Selective breeding really took hold in the 18th century with agriculturalists like Robert Bakewell separating livestock and intentionally pairing animals together to get offspring with beneficial features before we even knew what genes were. We could see that our parents' traits were passed on to their children and plants were the same.
Helen - In breeding plants to make the appearance of traits more persistent and consistent over multiple generations. And that intensifies in the late 19th century.
Julia - This in breeding is a form of genetic selection; genes which make plants bigger or tastier get passed on as the seeds from those crops are chosen for sewing. So, as I'm walking around the supermarket today, what produce on our shelves has undergone this type of transformation?
Helen - Any crop that you might pick up will have transformed dramatically over time as different individuals, different communities, have become interested in different qualities. Whether it's wild tomatoes or quite tiny fruits, nothing like the plump juicy vine ripened tomatoes that you might get. Berries over time, things like blueberries or blackberries in some cases, have been selected as larger varieties appear in part because of chromosomal changes. So they might be tetraploid or octoploid, meaning they have greater numbers of chromosomes, which can be a process that happens spontaneously, but gets selected for when it happens. And someone sees the larger fruit and takes that.
Julia - This in breeding can increase the yield of beneficial traits in plants, but it can also have its downsides if the majority of produce carry very similar genetic material?
Helen - Hybrid corn in the United States in the 1970s had been bred to incorporate cytoplasmic genetic material from a particular plant that had had a quality that seed producers really wanted. Something like 70% shared this one set of cytoplasmic genetic material and it made them all simultaneously susceptible to a new strain of Southern leaf blight, a fungal pathogen. And there was a collapse of the corn crop that year.
Julia - Diversity within crops is very important. So pretty much all foods in our stores have been selectively bred to harbour genes which produce enhanced traits. This technically is genetic modification, but that's not how we currently define this term.
Helen - The contemporary use of genetically modified often refers to trans genetically modified plants and animals. A transgenic organism is one in which a portion of genetic material from one genome often, potentially from a different species, has been transferred into the genome of an entirely different organism
Julia - In our supermarket, very little food is genetically modified in this way with pieces of foreign DNA inserted into the produce. In the UK, we don't have direct GM foods on the shelves. There are even some labels on foods that claim they're GMO free, but that doesn't mean we don't come across them
Helen - Around the world, a significant number of genetically modified crops are grown. They're chiefly maize or corn, soy, cotton. There are some additional crops as well. For example, genetically modified eggplant and papaya. And so irrespective of what the particular regulations are, it is likely that consumers have come across, in their diets, genetically modified plants, either as primary products in industrial food processing or that they have eaten animals that have consumed genetically modified foods.
Julia - There's a chocolate bar here that says on the back, it has a little asterisk, saying that it contains genetically modified sugar beets and soya beans. Transgenic modification of foods can be done to enhance or add novel characteristics, potentially to our benefit. But the term GM is still in the shadow of bad press from the 1990s, when the British media sparked a tirade against modified produce, describing them as Frankenfoods. Why a proportion of the public sided against GM may have come from their initial use -
Helen - There was a lot of initial pushback around the kinds of traits that were being developed and who they were seen to benefit. One of the main traits that was of interest to seed companies was a trait that made crops resistant to herbicides, which were then sold as a package in which you purchased both the herbicide that the plant didn't respond to as opposed to all the other weeds growing around it and the seed itself.
Julia - When these resistant seeds were released, petrochemical companies were just entering into the seed company space.
Helen - In an instance like that, I think it was very quickly perceived by activists, and by many consumers as well, that new technologies were being put on the market without any obvious benefit to them.
Julia - Given how much food means to us, this modification by big companies sparked worry about what the goal was behind using these technologies and if the companies holding the power to edit our food could be trusted. GM arising in these circumstances means it's not really surprising that the public are wary. As the UK and EU have a de facto ban on the sale and consumption of these goods for humans, our supermarkets here have remained pretty devoid of modified foods. But, in the UK last month, it was announced that a new bill was being presented to parliament, called the Genetic Technology or Precision Breeding bill. This bill states that gene edited food could be grown and sold in the UK. Gene edited food differs from those transgenically modified crops which cause the public uproar in the nineties as Gideon Henderson, the chief scientific advisor at DEFRA, explains.
Gideon - Tools have come along that enable very precise editing within the genetic material of a species. It's what's sometimes called cisgenic in that you're working within the material of a species rather than inserting material from elsewhere. And these genetic editing tools also enable us to make very precise changes, changes that very closely mimic those that you could do by natural breeding, but much more slowly and less precisely.
Julia - Editing the genes of food using biology could essentially do what we've been doing for centuries in selectively breeding beneficial traits in crops, but in a fraction of the time. If this bill is passed, we could be seeing changes to the foods on our supermarket shelves.
Gideon - Perhaps the most immediate change that we might see as consumers in this country is that products that have beneficial qualities for us as humans, or for the way that they're grown,. I think we're going to see new crops developed which will provide significant benefits to the environment and significant benefits to human health through their consumption.
35:47 - Tomatoes gene-edited to boost vitamin D
Tomatoes gene-edited to boost vitamin D
Cathie Martin & Jie Lie, John Innes Centre
A game changer in targeted gene editing is the technique called CRISPR-Cas9. This won a Nobel Prize in 2020, and allows researchers to target and alter precise parts of the DNA genetic code. Using CRISPR-cas9 to edit crops could lead to a revolution in food production. One of those foods is tomatoes augmented to make Vitamin D. Vitamin D is essential to human health, but we do not make it naturally. During the COVID19 pandemic, the UK government permitted the prescription of vitamin D tablets as its levels were correlated with reduced severity of illness. Having a food product packed with this vitamin may have huge knock-on implications for the health of the population. And Cathie Martin, a plant scientist at the John Innes Centre in Norwich, decided to use CRISPR-cas9 in attempts to generate such a product using the world's most popular fruit. Julia Ravey popped to the John Innes Centre to speak to Cathie and see these tomatoes for myself. Firstly, Jie Lie, a researcher in Cathie’s lab, explained why tomatoes were prime candidates for making a vitamin-D enriched food…
Jie - Because tomatoes naturally accumulate provitamin D3 in leaves, but at very low levels - in ripe fruit it is not detectable at all. We targeted a specific enzyme, which converts this provitamin D3 to other molecules. If we block the function of this enzyme, it should accumulate the substrate, which is provitamin D3.
Julia - So it's almost like if you think of the tomato as a factory, and you've got this enzyme, it's like a worker and they're doing a specific job to move this one thing on the line, along to the next. You've taken that worker out of the chain. And what you'll get is the provitamin D that would have been moved along the line to become the next substrate that it's going to be. That's just building up and building up because the worker isn't there to move it along.
Jie - Yeah, exactly. And the good thing is, this pathway is a partially duplicated pathway from brassinosteroid. Brassinosteroid is really important for plant growth. If you block or touch this pathway, you may get dwarfism.
Julia - And with the tomatoes, we're getting a buildup of provitamin D which is great for us, but what does it mean for the tomato? What does the tomato normally use that provitamin D for down the line that we are now taking for ourselves?
Jie - Oh yes. Vitamin D is a converted to cholesterol, and then to these anti-pathogen compounds. The good thing is we've reduced, but not eliminated this process. So we can still maintain the pathogen resistance of the plant.
Julia - After learning about the method behind how gene editing can be used to generate provitamin D3-enriched tomatoes, Cathie Martin, the plant scientist behind this project, took me to their greenhouse to see the resulting fruit with my own eyes. And they look like, well, tomatoes.
Cathie - I don't think you can tell the ones that are enriched in provitamin D compared to the wild type. So that one's a wild type and that one's a provitamin D enriched one as are these. That's a good thing in terms of getting something that people will grow and use, because we don't want to have a big yield impact or anything like that.
Julia - Are the conditions exactly the same? So you've just grown these in the exact same way as the regular wild type tomatoes?
Cathie - Yes. We had to make sure that following the edit that we made, that the machinery that we use to make the mutation has all segregated away. So these are the progeny of the initial transformation event. So we've lost all the machinery that we use to make the edit and just has the edit left in the lines. And that's very important that we can classify them as qualifying higher plants that don't contain any foreign DNA.
Julia - A big player in this process was the leaves and the plant itself. Also containing these enriched levels of provitamin D.
Cathie - I think that it's really important for any consumer trait that you have something that makes farmers, producers, growers want to grow it because otherwise it tends to be a boutique variety that disappears off the shelves. But if you have a producer trait, whether it's disease resistance or improved nitrogen use efficiency or improved water use efficiency, then you've got something that will make people grow it because you get lower inputs. And for these provitamin D enriched rich tomatoes, there's massive levels of provitamin D in the leaves. And although these plants don't look fantastic at the moment, that can be taken and you can make extracts of provitamin D or vitamin D from the leaves, and those can go to feed supplements. And so you can get value from the waste.
Julia - And side by side. I couldn't tell the difference.
Cathie - No, I can't either.
Julia - I have to look at the labels, because they're all mixed in with the wild type plants next to each other. But in terms of, they may look the same, but are these plants exactly the same, except for that one change? Can we see if there's any other knock-on impacts within the tomato itself?
Cathie - We've done quite a bit of metabolite characterisation to check that. I mean, that's part of the process of engineering a new step, you want to know whether there are any knockout effects and we have done a lot of analysis to show that there was no effect. For example, there was a risk that we might affect brassinosteroid production, which is a hormone that affects the height of the plants. But as you can see, they're normal height -these ones are a bit bigger than the wild type over there. As far as we can tell so far, we can say that that's the only change in the genome.
Julia - Have you tasted them? Are they allowed to be tasted yet?
Cathie - Yes. I think the one I tasted was a bit over ripe. But they taste like a tomato.
Julia - That's brilliant. So you couldn't tell the difference?
Cathie - I'd say squishy, but that was what was available.
Julia - And these tomatoes are enriched with provitamin D but what if we want vitamin D from them? What has to happen next?
Cathie - As in humans, provitamin D3 has to be converted to vitamin D3 and you need exposure to UV light to do that. So we've done it experimentally in the lab, we've taken leaves or fruit and exposed them to UV light. And you can get the conversion at about 30% efficiency to vitamin D3. In humans you're recommended to go out for half an hour, a day in sunlight to be able to convert your provitamin D3 to vitamin D3. So we're quite interested to test whether that works in tomatoes as well. Simple kind of idea but maybe we can get away from having to treat with UV by growing the plant outside. So that's why we have applied for a field trial to expose them to the sunlight. And we've been very lucky the last few weeks that there's been plenty of sunlight. So they're just growing down the corridor.
Julia - Cathie took me along the corridor to see the vitamin D three field trial.
Cathie - You Ready?
Julia - Ready for this. The field trial field trial! It's less of a field and more of a stoney patch in between greenhouses.
Cathie - That's right. And I don't know which ones which, again, you have to look at the label on the plants to know whether they're edited or not. So we've got wild type in here as well as provitamin D enriched ones, but we're waiting to see what the effect of sunlight, which is really quite strong.
Julia - Yeah. I'm glad I've got factor 50 on!
Cathie - They're doing quite well I think. And we just have to harvest all the leaves and fruit and see how much vitamin D we get.
Julia - And obviously here, it's out with the sun from the sky coming in and there isn't a control over that. So is there a way you're going to say, okay, well, this plant we know has had this much sunlight based on the weather forecast. So you can do a correlation of sun to vitamin D?
Cathie - Of course in the UK, we do not grow tomatoes commercially outside because they don't do very well. So we were hoping to do these experiments in Italy. But because the Italians are under EU regulations, it's going to take them about two years. So we've just actually got really lucky - as is everyone else - it's been sunny for the last few weeks. And so, we're dependent on what we can get, but I think that this would give us a minimum value of whether it works outside. Of course it may not work. I don't know the answer, but that's the most exciting thing about outside doing sciences when you don't know the answer.
Julia - It's really exciting! Well, I'm definitely getting my vitamin D out here today. Move the ginger inside! Fingers crossed the tomatoes are getting it as well.
44:59 - Could CRISPR improve decaf coffee taste?
Could CRISPR improve decaf coffee taste?
Thomas Merritt, Laurentian University
As well as allowing the nutritional value of foods to be enriched, gene-editing could also be used to enhance the taste of certain items, and one of my favourites has been highlighted as a potential target: coffee. The delicious taste of the bitter beans are one of the main attractions. But not everyone is keen on caffeine, although many are not fond of decaf either; and while modern varieties are better than their predecessors, many still claim it just doesn’t have the same edge. So could gene-editing hold the key to crafting the perfect non-caffeinated joe? Here to help us answer that is geneticist Thomas Merritt from Laurentian University, who spoke to Chris Smith...
Chris - Thomas, you must be one of the first guests actually to do the experiment before the interview even started! He's tweeted a picture of himself holding a cup of coffee. And in fact, one of our other Twitter followers, Thomas has said, "was that a much bigger mug before you did CRISPR-Cas9 on it, because it looks far too small to me!"
Thomas - It is not. And I will say full disclaimer, that's also not decaf. I tried to convert myself and I didn't make it.
Chris - I'm in good company then. When we make decaf, Thomas, how is that actually done?
Thomas - So there are a couple of different answers to that. It all comes down to extraction. We try to take out the caffeine and leave everything else in. Historically, this was done with benzene, which is just terrible. There's some better processes. Now we can use something called the Swiss water method, or we can actually use super critical CO2. It really comes down to, can you pull out the caffeine and leave everything else there? With Swiss water, we actually try to put everything else back and then take the caffeine out. In all cases, you never get quite the same coffee at the end of the process.
Chris - So how might gene editing solve this for us then?
Thomas - It ends up that there's some really interesting coffees out there. Most of the coffee that we're drinking is Arabica, and there are varieties of Arabica out there that don't make caffeine. There are sort of natural mutations that have happened and have knocked out the pathway. And so we're looking at those thinking, well, could we do the same thing and knock out the genes? There are a series of enzymes that are part of the caffeine process and we could simply turn those off.
Chris - And if you do that, does that not in and of itself effect the flavour because caffeine is a bitter tasting chemical?
Thomas - I think that's an unknown. It seems like maybe but we can certainly get closer to a coffee that tastes like coffee, the coffee that you expect by creating a coffee that just doesn't have it in the first place. So a caffeine-free coffee, whether it's going be exactly the same, I don't think anybody knows the answer to that yet.
Chris - What could be the consequences for the coffee itself? It presumably makes caffeine for a reason. Some have speculated that plants put caffeine into their nectar to addict bees to their flowers so bees are more likely to pollinate them. I mean, there is some evidence to support that, but it's also a natural insecticide. So if we started robbing this stuff out of the plant, does it have knock on consequences?
Thomas - That's a really interesting point. And again, we're not going to know the answer until we try it. Traditionally, we think of caffeine as being an insecticide. It's a way that has evolved in a number of different plants, not just coffee, to limit the way that insects chew on the plant. So what happens when we take that away? We're not entirely sure. I think we're looking at an agricultural situation and not a wild plant, and there are other ways that we could be able to manage those pests.
Chris - In the past when we've wanted a crop with a certain characteristic. What we've done is to go and find crops that have another characteristic, cross them together and hopefully get the best of both worlds. Could we not do that with coffee to find a low caffeine variety, cross it into an Arabica that tastes great and get a low caffeine, good tasting Arabica?
Thomas - Coffee Arabica in particular really doesn't like to cross. It's one of the reasons that varieties of coffees taste like varieties. It's easier with Robusto, which is the other really dominant coffee that's grown in the world. But it's a long process and coffee takes about 25 years or so, to get an adult plant that's producing enough beans to be a commercial plant. With genetic editing, we could do this in something like five to seven years, and we could actually be testing much sooner than that. So in the space of a couple of years, you could test whether the editing was efficient and you'd actually created a plant that was potentially caffeine free.
Chris - So slightly longer than it takes to make a cup of coffee, but not much. Thomas Merritt. Thank you very much, indeed, for explaining it for us.
49:22 - Crops modified to make fish oils
Crops modified to make fish oils
Johanthan Napier, Rothamsted Research
A huge issue on the sustainability front is overfishing. Fish oils are an important part of our diets, with molecules such as EPA and DHA being beneficial for brain health. But excessive harvesting of ocean stocks is damaging marine ecosystems. Johnathan Napier, research leader at Rothamsted research, has potentially found a solution to this problem using genetic modification. This differs from gene editing, but he hopes that the precision breeding bill marks an important first step to gateway other GM produce down the line. He explained to Chris Smith what his lab has been working on…
Johnathan - What we've done after decades of effort is we can make fish oils in plants.
Chris - Isn't that what eating fish is for though? I mean, I could go out and buy some salmon and eat that, couldn't I. Why do I need plants for that?
Johnathan - Actually, lots of people don't eat enough fish. And contrary to popular belief, There aren't plenty more fish in the sea. There's not enough fish oils to go around to ensure that everybody on the planet gets correct nutrition.
Chris - I thought one way of combating this was we were just farming fish and growing enormous amounts of fish to make sure we don't deplete ocean stocks?
Johnathan - We do farm lots of fish. Now most of the fish that people would consume has been farmed. All the fish you buy in the supermarket, almost all of that's probably been farmed. But the Achilles heel, if you like, of fish farming, is that actually - this is the really bizarre thing - fish don't make fish oils, but they need them as part of their diet. So we have to feed the farmed fish fish oils that have been extracted out of the oceans. So you have this unsustainable cycle of extracting fish oils out of the ocean to feed to farmed fish.
Chris - Hang on a minute. So you are saying, I need to eat lots of oily fish to get fish oils, but fish need to eat oily fish to get fish oils. So where do the fish get it from then?
Johnathan - So the fish get it from their diet. You can think of our oceans as a soup of omega3 fish oils - but we've already decided that's not really a good name because fish don't make omega3 fish oils. It's actually the marine microbes; the little plankton and the microalgae that are in the base of the food web in the ocean. They're the things that are making the omega3 oils. And just in every layer in the food web in the oceans, those fatty acids are accumulating.
Chris - How did you (a) find out what the algae were doing to make these essential fatty acids in the first place? So how did you know what to take from them? And how did you get that to work in plants and indeed what sort of plants?
Johnathan - We started our project to try and make these particular omega3 fatty acids. And it was well known that algae were making them, but nobody knew what the genes were. And so we really had to embark on a project to find the genes in the algae that make the omega3 polyunsaturated fatty acids, and identify those genes and introduce them one by one into plants to effectively rebuild the algal pathway in a higher plant so that the plant was now making these long chain omega3 fatty acids.
Chris - And what plant have you put them in?
Johnathan - The one that works really well for us is a plant called camelina, which is like a cousin of oil seed rape canola.
Chris - What's the concentration that you achieve? How many cod liver oil capsules do I have to pop to be equivalent to a handful of the seeds of one of these plants?
Johnathan - In terms of the amount of EPA and DHA that we make in our oil, the levels that we make are actually a little bit higher than you would find in cod liver oil. You should be taking probably a couple of teaspoons of cod liver oil a week. Well, probably you could only take one teaspoon of our GM camelina oil. We've done human studies with these oils, and we now know that our plant fish oil replacement is exactly the same in terms of how it's taken up by the human body as a regular fish oil.
Chris - Have you actually gone through chemical by chemical what your plants make in order to prove that in stitching in these additional genes the biochemistry of the plant hasn't changed in some other unpredictable way?
Johnathan - There's always variation between one plant and another. We've done a great deal of analysis of our transgenic plants, and we've not seen any difference we think is significant or cause for concern.
Chris - At the moment, the legislation forbids you from doing what you are doing in terms of using it for direct access into the human marketplace. People are lobbying to try to change that. You've been one of those people who've been advocating for that. How's it gone down? How are your arguments being received?
Johnathan - The government, in general, knows that the legislation that was developed within the EU for covering GM and gene editing is too restrictive and impedes innovation. We've got something useful and we know that it's safe and we know that it works well. The mechanisms to bring this to market are too complicated, too burdensome, too expensive, that doesn't really help anybody, but I think we're still somewhere away from the government moving towards changing how GM foods are regulated. But I think their direction of travel is clear, which I think is really exciting and really promising.
55:13 - What stands in the way of gene-edited foods?
What stands in the way of gene-edited foods?
Gideon Henderson, Department for Environment, Food and Rural Affairs & Helen Anne Curry, University of Cambridge
A final benefit gene-edited crops - covered by the precision breeding bill - could bring is combating disease and climate change, as Gideon Henderson from DEFRA explains…
Gideon - As an environmental scientist, some of the most exciting possibilities that come out of gene editing is our ability to make crops that will help us to look after the environment. So something like a third of world's crops are lost at the moment to pests or to diseases. And if we're able to make crops that are resistant to those pests or diseases through gene editing, which we have good evidence we can do, then we'll be able to cut down that loss of food and therefore be more productive with our land and also use significantly fewer pesticides and fewer herbicides on our land. Biodiversity gains are a substantial gain, as well as all the climate benefits that we can get from gene editing, we will have more resilient crops in the future.
Julia - Some of these ideas for gene-edited food sound pretty good, but public opinion about this produce is just one part of the puzzle, as Helen Anne Curry from Cambridge University explains...
Helen - I think there really remains a question about what kind of intellectual property controls there might be on some of these gene editing tools when patents are tightly controlled by their owners. Some of these possibilities for diverse users and diverse uses get shut down simply because institutions or individuals can't afford say the licensing fees on the technologies. So you then see only heavy hitting actors, such as the really big corporations involved in crop development. It also depends on what the regulatory structure looks like. So there are structures in place, for example, in the UK food system that ensure the quality of seeds that the crops that are produced conform to certain standards that make recommendations about what seeds farmers can buy and all of those different elements of the regulatory system channel. Or kind of winnow down the number of seeds, the number of traits, the number of varieties that we might find on the marketplace. And so in thinking about something like, "can gene editing diversify or open up the possibilities for genetic engineering of crops in new directions that are perhaps exciting that give us more opportunities for sustainability or for climate adaptation or even just for dietary improvement", we have to think about actually whether this whole system that we've set up in order to bring new varieties to market is conducive to that. And that's even before you get to the question of whether a food processing system can handle different kinds of crops, or whether supermarkets are willing to put them on the shelves or even indeed eaters becoming willing to consume them. The bottleneck is really in thinking of who's able to engage in the development of the foods we eat. And right now that is perhaps a narrower set of actors than we might wanna have.
Julia - So when it comes to having gene-edited foods on our supermarket shelves, never mind transgenic produce like the algae oil from crops. There are a lot of hoops to jump through beyond public opinion, but maybe one day in the future, we could all be checking out some produce that has been safely modified to help our health, satisfy our taste buds, protect the environment and can be grown more sustainably.