Can CRISPR Save the World? The Next Green Revolution

[Music] here our first participant is an associate professor in the Department of plant science science and landscape architecture at the University of Maryland in College Park his research focuses on plant genome editing tools for plant biology and crop improvements and he has worked on many crop geo genomes including rice maize and carrots please welcome Yiping Qi our next participant is a director of the plant transformation of facility at Cornell University and a member of the Editorial Board of the CRISPR Journal a new journal about genome editing he has worked on the genome of rice apples hemp and wheat please welcome Matthew Wolman and also joining us today is a bioethicists from the Hastings Center she explores philosophical and ethical questions concerning the use of emerging technologies like genome editing tools such as CRISPR in non-human organisms for Public Health her work has appeared in nature biotech JAMA and the American Journal of bioethics please welcome Carolyn Newhouse we have a big panel here two more our next participant is a senior sustainable development officer and a UN Department for economic and social affairs he was a member of the core team that supported the UN General Assembly negotiations on the sustainable development goals joining us from the UN please welcome the friedrich zolto and last but not least also joining us is a professor of genetics at Cold Spring Harbor Laboratory whose lab finds and studies the genes that control growth and architecture primarily in maize he also works internationally and is a changing visiting professor at the hwa-jung Agricultural University in China please welcome Dave Jackson all right my first question for all of you how are each of you using CRISPR in your work and let's start with the sciences so we study genes in maize and that effect on plant growth and so we use CRISPR to to basically knock out the function of a gene you know maize has about 40,000 genes actually more than humans and we know we know some genes what they do but a lot of genes we don't we don't know what they do when you say knock out the function I might be interrupting it's not so when you say knock out a gene what you mean by that knock out AC means breaking its function so it's no longer functioning in the organism and so we want to know what the genes are doing we disrupt them we can see see how the plant growth is affected well yeah so actually I start kind of prior CRISPR life-science with genome editing which is Tucson lying at a time the technology causing finger nucleus leaf which is actually a protein and you need a protein engineering to do that which is hard only Hannifin laboratory in the u.s. lets they can do that in plants so I was lucky to be one of the lab for the training but later on quickly in 2010 that Newton or Talon which is derived from actually bacterial weapon from bacterial attack it's it's good but not as easy to make in the laboratory for other people to use yeah then you know you may have known lacking 2012 that milestone paper published in science reporting CRISPR Cass technology and after that everybody is using that including my lab so right now in the past few years my lab are really developing CRISPR Kastner you make more efficient and apply them to different crop pants for editing so you just like CRISPR classes just CRISPR what is that casts part of CRISPR well-cast actually means a lot of proteins for example when we typically I say Chris podcast we offer means CRISPR cast 9 which is system very specific system people are using us as other cast proteins for example another protein I'm using is cast 12a which can sort of do the same thing but can targeting where crisper cast 9 cannot target the protein the cast protein is actually scissor which to the cutting butter you also need RNA so the whole thing was actually plotting on the complex so the guide RNA can guide the protein to where yeah based on a DNA hybridization to target so upon binding specifically didn't cast lying or cast away nucleus activity is being activated so then that allowed us from break of DNA I run the transformation facility at Cornell and when my facility was originally envisioned the goal was that we would focus on making Trenchtown plants for researchers on campus and around the world thing is is that by the time they finally got my facility going CRISPR was on the scene and so instead of focused on making transgenic plants about 95 percent of the work I do is using CRISPR to modify the genomes of rice maize wheat Apple and now we're working on industrial hemp so we're focused on using it to modify very specific traits in some cases like what we're trying to see if we can increase yield with Apple we're trying to take very popular cultivars that you already know and like that you're used to seeing in your grocery store and say well if we know what gene is important for disease resistance that this Apple doesn't have resistance against can we take the Apple you already like and correct the broken gene so that it actually can the plant will then be resistant as well so transgenic is what people typically think of when they think of GMOs so it's it's where you take a gene from one organism and you put it into the DNA of another organism and it's passed down in every cell from there on out so if you hear about GMOs and you you're about GMO labeling it's generally talking about transgenic organisms and Carolyn and Friedrich you're both looking at this from a different perspective how is CRISPR seen in your respective fields Carolyn Juana you go first sure well I'll definitely say that I've appreciated CRISPR because it it serves as an excuse really to ask really philosophical and ethical questions that we've been asking as humans for literally thousands of years so questions about the appropriate nature the perfect relationship between humans and nature questions about even the meaning of what it means to be human when we're talking about using CRISPR for human gene editing ethical questions about appropriate risks and benefits or the appropriate balance between risks and benefits in various applications of CRISPR in different kinds of contexts so I always like to say to me CRISPR isn't the really interesting thing it's the questions that it allowed Meeta asks and gives me a platform for asking about again these really important philosophical and ethical questions that we don't have answers to and probably won't but are really important to continue batting around together from the perspective the United Nations and of course the member states are our main actors in the UN it's really a platform to bring the technology innovations like CRISPR other innovations to the service of humanity so challenge the chance of today and a particular we have in 2050 member states adopted 193 member states adopted the sustain Development Goals 17 goals targeting the main sustainable development challenges and one of them is o2 is on food security and nutrition and agriculture so trying to bring the science and the technological advances are we going to talk about today targeting them also at development so development for the poorest those who don't have access to nutritious food who are undernourished malnourished but of course also to the other sustain of development challenges that we have and we'll talk more about those hopefully that our agricultural production system imposes on the environments or trying to do things which can cope with climate change and also produce food in a way with less harmful to the environment so that is kind of the bigger picture I would say within the UN if we are successful we can try and be an entry point a platform and facilitate the the adoption of this technology help assess the risks and the benefits and bring it to the service of people around the world so as you were just saying a lot of people are really excited about CRISPR in terms of food security we've also heard for years about food security in terms of transgenic or GMOs too a lot of people have been excited about that technology but that technology has largely been used in corn and soy which is largely not entirely used for livestock feed or a processed food to have an entire other panel on whether yeah livestock is still food right in their art that is still feeding the world to a degree but the nutritional level and the effects on the environment are something to be questioned right so with CRISPR what will be different will there be what we see a lot more corn and soy or will it open it to other foods as well anyone want to take that debut work in corn what are you doing I think CRISPR will be used much broadly in in other plants as well as the croplands one one reason is because as you know GMOs are very controversial and to get a GMO approved for market it has to undergo a lot of testing so only the big multinational companies can can afford that so that's why we hear about Monsanto and Aron pioneer all the time because they're the companies who can afford to invest tens of millions of dollars to deregulate or you know test a GMO with CRISPR it's been passed by the US Department of Agriculture that it's not transgenic which means it does not need to be deregulated and so the cost of bringing that to market is much less so I think that there's a much better potential that it will be used in to benefit other crops possible can I be used in any potential plant are there any restrictions on what CRISPR might be used for its principal you could use it in any plant in in practice we still need to usually put the plant through a process of Culture tissue culture which is what my theory is the expert and then not every plant is is easy to do that in but but in principle you could do it in at any plant what plant what are some of the plants that are more difficult to work with CRISPR plant too difficult to regenerate I know grass is difficult I mean people have done maize but it's not easy wheat is difficult some tropical species are difficult like bamboo rubber plants I think are very difficult to regenerate probably my few what makes it so difficult to use those or to do the tissues for those particular plants so it's yeah what's really cool about plants is essentially any cell in a plant can act as a stem cell so we have the ability to change the genome either with the transgenic technology or with CRISPR in a single cell and then we have to have the ability to take that single cell and give you back a whole plant with flowers and shoots and leaves and roots and the process for doing that is somewhat understood we know that there are a couple basic hormones that can control the transition from one stage of this development to the net the problem is is that even in the very the most easily easily regenerated plants each genotype has to have specific conditions for doing that so the levels of the hormones might have to be slightly changed the levels of the fertilizer type molecules that we include in the artificial media have to be changed it's very much dependent on each genotype and when I say genotype in this context what is often what I'm talking about in genotype I'm talking about like a gala Apple is one genotype that has a whole set of genes that is very different from a Golden Delicious apple for example you can see that in the store but there's more going on that you can't see but it's the differences across every single gene that explain what the genetic basis of that organism is so we've kind of been dancing around this idea I'll just go out and ask it is a chris bird plant a GMO my definition of GMO is actually looking at what is the word actually if you if you say what does it stand for stands for genetically modified organism so is in my mind every plant that we actually grow for food is genetically modified by humans because you go back to domesticated plants if you look at wild maize for example as opposed to domesticated maize it looks nothing like what domesticated maize is now it has a few grains to it it's called teosinte don't actually see grains that actually look like corn kernels over time in the selection process people have changed how those plants appear they have traits maybe you know people picked the tomatoes out there that were larger that we're sweeter they had these different characteristics but then over time we started using plant breeding and so where you cross two different plants together that might have different traits you're interested in and the goal is is that you combine them in in one final plan so you know that's that in my mind is also human genetic modification of plants so if that is then transgenic technology is and so is so is CRISPR usually so GMOs that's a very broad definition GMO is most people will probably be thinking of transgenic there right when they hear that term we may hear the public when they normally hear it they're thinking transgenic and therefore you know CRISPR when you're using it to create a deletion for example you're removing DNA you're moving genes you could do those same things by a random mutagenesis or you could do it by cross I mean so many people may not know that the way you get a lot of the diversity for plant breeding is if breeders actually will treat plants with the with a chemical called a mutagen that causes changes in the DNA and then they look for different traits so that's how for instance you've gotten 8 million different colors of cone flowers out there you're a gardener just random now we don't stray targeting a specific so the good thing about CRISPR is that you can actually specifically say I want to change this single gene so you could create those same mutations randomly but if I know what gene is required to actually make that orange bright orange cone flower I could do it with CRISPR so it's just another way of changing things but we could do both without using trans genes without using foreign DNA so by that definition it wouldn't be a Jew well well based on the recent the secretary of USDA recently in the end of March made a sort of statement basically anything which can be made of by conventional breeding like mutagen which then we can use the CRISPR caste to make them then those product wouldn't be regulated at GM which basically you know basically we treat the CRISPR cast as a new breeding technology just a new technology up reading so but if you're really inserting a transferring let's see if you put another bacterial gene into a plant to make it like a BT com resistant insect that would be steer no matter whether you are using Chris book has or not to wear be steer GM okay yeah so it gets complicated yes Dave what do you think she ever no yeah I said no GM I mean our genomes are really constantly in flux we think of it the genome is a static place but we're all accumulating mutations all the time sometimes in humans they cause cancer or genetic inherited diseases in plants for example you can compare two varieties of corn there is different at their DNA level as humans and chimpanzees so they they're they have one percent difference in the in their DNA so with Chris bird we're creating changes in DNA but the same sort of changes that happen in nature that are the basis of evolution so I do not consider that GMO I think what boyhood is very very useful from the scientific perspective I think is also the societal perspective that society you know has an expectation that we assess the risks and benefits of new technologies and these are new technologies and we have we look back on history of technology development we had cases where we've misjudged the benefits and over look at the risks so I think what I would argue for is always having a sound assessment society acceptable based on sound or knowledge also in information sharing with the public that assesses a risk benefit and that's something which often each society asteroids only see at the moment is a different risk perception assessment between among different countries across the world I think that's natural you know and then hopefully that's what that's at one level also I think uniformity among scientists that they are often this sort of a legal risk process but also among scientists informal standards guidelines that come through your big reports by the National Academy of Sciences on GMOs the risks reports on other on synthetic biology and so on that the scientists kind of adhere in in the laboratories and across the world to these sort of norms that guide the scientific process I think that's the second level that's important and then there's the level of social dialogue with with with governments and regulators who decide how to to do this but without holding back progress or you never see the key thing we don't want to be sort of relying on on a century superstition or all knowledge but to to you have defined as balance you know I think we haven't always found it but I think that it's a process that needs to be gone through those of us who you know who are pro pro pro sort of something want to push forward but we have to take society with us otherwise we end up a place where the technology is rejected rightly or wrongly we have a scientific perspective we have Asafa called perspective can we draw these distinct lines I don't think so so we've heard so much ambiguity and what this concept could mean just among the people on this panel which makes it really hard to pin down to answer your question is this a GMO or not because we've heard radically different conceptions of what a GMO is from literally everything to this much more narrow definition that's very much in keeping with the USDA's definition of a genetically modified organism so if I'm doing a sort of conceptual analysis one thing I might start with is what is it not and what is it not in sort of the public understanding and so I mean if you look at a grocer if you go to a grocery store you have GMO non-gmo project verified versus everything else so we might start with what sorts of things do the public under what sorts of things are our stamped non GMO verified rightly or wrongly and we can sort of debate this at various levels but just in terms of bringing this all on the same page that those standards might shift and they prompt and maybe they should shift depending on our understanding of the science but just to get a handle on what kinds of things might be guiding this conversation I mean we we have to acknowledge that there is something that GMO that people understand that there's something that's not a genetically modified organism and getting clear maybe on what that is could help specify whether this counts and there's like various ways we could do that obviously there's a conceptual analysis but I think there is because there's a project out there called non-gmo verified that we could look to you for standards and I think that they're actively grappling with this question especially in light of USDA's recent decision to not consider this in terms of their regulatory paradigm going forward how are we going to whether this would meet the stamp of approval think that there are good arguments both ways but we have to understand it much more holistically and those stance can get complicated - I've seen those slapped on water wouldn't be GMO anyway right misleading even in that respect I'm Fredrik how about the there are different rules and the you the EU and developing countries correct how does all sort of work when you have different countries that have different ideas of whether CRISPR should be regulated if I would have to be careful I'm not an expert on the whole global regulatory regime but I think as I mentioned earlier there are there are differences in risk in risk assessment risk perception you know that the European Union the 28 countries of the opinion have followed with the so-called precautionary principle which is a principle of international environmental law and actually widely accepted but interpreted differently so they would say before we go ahead and and and deregulate we need to have a full understanding of the risks already anymore taking a precautionary approach basically most have smaller go slow approach whereas in the u.s. as I understand at the USDA is a fairly strict standard if it's not a plant pissed and you know and you can show that in that search you know and the EPI is a similar European I mean the immigration agency also regulates it they ever also a fairly narrow legal standard so if it doesn't meet it it doesn't follow those categories it's okay it doesn't have it so the u.s. abroad sort principle that they look at and of course behind that also again social perceptions you know and as I just mentioned here what is a GMO our relationship to how we change one's legitimate change to to the DNA and of plants and so on that that's behind some of these regulatory issues I think the key point looking forward is that we don't want there are benefits from this technology we're beginning to see them and hopefully we can extrapolate them not only to the commercial use in in in developed countries but to really need those pressing needs that we will face with a very much growing population and you know given that this water scarcity in many parts of the world given a climate change it's going to impact on on water availability on droughts heat stress to plants to make sure that we can take as I just said here this is opening in perhaps being able to to use this more widely and take it out of the realm of very large corporations into into using that for targeted needs that fit the needs of a certain agricultural part of Africa or Asia and not only a large commercial mark I think that's really where I think the challenge is and that requires a supportive ecosystem so yes the science on the one hand but also the bring it to markets a lot of what happens between testing it in field testing marketing it to the right farmers and making sure that that system is there you know if it's a commercial product that one center or the large multinationals have that behind them but finding a pioneering and very innovative crop for particular need in West Africa what will bring that to the farmer there I think that's the part that's often missing and that depends on a whole broader range of social interventions that go beyond the innovation in inner lab I mean that's the starting point but it's not the end point humans have always had the power to edit the environment we already talked about though about a little bit especially in plants is there something different about CRISPR in terms of how we're interacting with our environment that should we should be considering I'm gonna go on a limb and say no I don't actually think that there is anything different fundamentally about this particular technology except because we've had talons and zinc fingers and transgenesis and mutagenesis I just learned and selective breeding and all these other tools that allowed humans to intentionally change the other organisms and the environment in various ways for a really long time I think what's really different about CRISPR is that more and more people can do it and this is the sort of democratizing element of CRISPR is that the technology is implementable in labs around the world which is a really wonderful thing especially for bringing this to small farmers around the globe who can now work with local labs to create a crop that's tailored exactly to their needs rather than having to rely on a corporation and that's really exciting and I think that's what makes it different but again it's a difference now in access not necessarily that we are fundamentally intervening in the environment in different ways so there's a benefit to people it's broadening the technology allowing more people to use it I'm curious for the three scientists are using CRISPR in your lab who is going to benefit the most from your research for your respective crops Dave why don't you start oh we are very much at the the basic end of the research spectrum so we're really just investigating the genes that control plant development we were not specifically in application but some of some of the work that we do I think could be applied by other people to other crops for example we have some genes that we can edit they can make maize plants that make more seeds so they have higher yield so you can imagine other people might adopt that technology to to improve yield in in other crops another how about you a lot of the work that I'm doing is again is basic research but we have two particular projects where we're trying to use chrisberg I actually have a benefit for the farmer the one is would benefit farmers of apple growers of New York State and other other states around the country in the world where we're trying to take popular cultivars of apples and we're trying to take a disease resistance gene from crab apples a wild crabapple that makes apples about the size of the tip of your pinky finger and we're trying to take this gene that is that is functional in the wild crabapple we're using that information to try and correct the non-functional form in these popular cultivars to do that by a breeding would take many many years and you would never actually get back to that same gala Apple type so I could take your gala Apple and I could cross it to this wild crabapple and what I would get would be something probably maybe you don't want to eat probably inedible and we'd end up somewhere in the middle or even worse than either end so it's something that can actually allow us to get there much faster and that's one of the major benefits particularly for clonely propagated crops and one of the other projects we're working on is trying to work on a yield trait in wheat where there's a gene that actually is known to reduce yield of wheat so if we can go in and delete this gene we'll hopefully be able to increase yield and already in types of wheat that are already very have a lot of other positive traits so it's trying to go in and change one thing keeping everything else the same just change that one thing to bump up the quality and yield is a place where potentially we can have a lot of CRISPR can have a lot of impact what's happening now is that yes the population of the world is growing and so we do have to increase yield in some way to meet that but at the same time because of global warming and the other environmental conditions the actual yield of those types that are out there now is actually going to go down on the exact same piece of land over time because of the changing conditions so we have to meet the need for the increasing population but on top of that we have to meet the need to we have to make up for what we're losing by the change in climate and what about the projects on industrial hemp I'm really curious to hear about that so my lab is involved in the industrial hemp work that has been pioneered or been very well supported by Governor Cuomo of New York State he and some other state governors are very interested in and having their states be able to use grow industrial hemp this isn't this isn't cannabis this is industrial hemp used for fiber and for oil and for for positive medical uses such as the reduction of seizures in epileptics so we're trying to use we're developing in my lab the ability to use CRISPR to actually make changes so that we can do things like change the oil distribution in the or a change fiber amount or make the flowering time so that they all flower at the same time hemp is a crop that used to be grown in New York State it used to be grown in other states in the country but what's happened is that because it hasn't been legal to grow for many years there's not much information out there in the research community about how to actually work with it and so my lab is one of those trying to contribute to as soon as the federal government hopefully will allow it to be grown as a crop legally that will have the research tools already in hand and you think about you how how is your research on CRISPR who's not gonna benefit so well actually two aspects first of all because I'm really my lab is really focus you developed a lot of CRISPR tools to apply to different plant species and really we you know once we validate the tool we put it to a publicly repository like a gene which is NGO based on Boston there isn't the summit on rage and to other people who request so I was just checking an email from them basically they have distributed a mine region to over 100 laboratories which was kind of like you know the vector cloning vector is where you can express the caste protein as where the guide RNA in the cell right so you needed a system yeah yeah making sure yeah we have different kind of system you know for different plant so that we put all the tools which are requested by other researchers okay so all over the world that's really helping a lot of academic researcher tools it's like Amazon yeah yeah a $65 one so yeah yeah I mean I don't know whether they make some money but yeah they basically not very expensive but people can really use that to boost their research a second aspect is really I just follow Matt and Dave's you know talking about really lower the bar for every people to you know apply that to editor or kind of plant genes which is really fantastic because not like only big company can do now all the small lab can do that so with collaboration with other researchers we're actually doing that one example just I've made a few you know exactly you know cases but just briefly wrong example recently there's a paper in preparation yet what we did is we actually targeting in rice in a unit right Scotty but people are really growing eating the rice and we in that past cultivar we basically targeting simultaneous forging and the four different trader the Jing one gene can show the size of the rice seed another one can sure the weight of the rice seeds so another one basically they are like a quantitative trait but if we can now tighten them together with CRISPR one one shot and modify them all together simultaneous within one generation now we can quantitatively bring the high-yield rice so which is a success actually so using conversion of breeding and you have to cross different you know the plan together to introduce them or the trait together takes many years but now yeah yeah yeah now within two years within one year or two we can better get it another advantage of CRISPR that you can do target multiple traits at once is that something that was possible with previous technologies that's actually a Vantage of Chris podcast with Tara and zinc finger it's really very difficult CRISPR cast line you can reprogram the different guide RNA which is really easy you can targeting easily up to Tanjung at once which really we could multiplexing which really really great actually so so we've talked a little bit about how CRISPR could lower pesticides in some cases but they're also gene editing examples that could increase the use of least some pesticides I'm thinking of I think the company is siteís which last I heard was planning on using a gene editing technology to make glyphosate tolerant tolerant Fox and you could also use it for other crops to make any sort of herbicide tolerant crop right so I'm curious what your thoughts are on cases like that where we could be seeing more of the same that we've seen so far with transgenic GMOs any why don't you work on core maybe yeah I mean it's it's a complicated question complicated stories from from what I've read because we all hear that GMO crops require the use of more chemicals but there's a flip side to that which is that if you have a crop which is net which is resistant to it to a herbicide for example the farmer can choose to only spray the herbicide in the case that there's a lot of weed competition which is not not every year it depends very much on the growing conditions and on the particular local environment so so the farmers can be more selective and I think there was recently a meta-analysis of many different studies of GM versus non GM crops and that study actually showed that GM's have increased yield overall over the past 20 years that they've been growing and also have overall in decrease the amount of chemicals that they use so I think it's not so it's not such a simple relation to say that just because you're making the crop resistance of herbicide that you'll actually use more of it finally you know herbicides are actually expensive that's the reason that companies like Monsanto make them and make plants of the resistance them because they want to sell the herbicide and so farmers tend to reduce the use if they know that they can have a crop which is resistant to it and they only need to use a chemical and it's absolutely necessary was that meta-analysis looking at both insecticides and herbicides together or and basalt the total lowering or was a different from I think it was just herbicides because insecticide the insecticide GM trade that was a protein that's expressed inside the plant is not something that the farmers apply so it's it's always there there's also sometimes a societal benefit in some cases so one crop that people scientists have looked at trying to increase herbicide resistance using this CRISPR technology is cassava and cassava the interest that this lab had was that cassava is grown a lot particularly in Africa and in Africa they they are not using these pesticides as often and women and children are spending their time reading these cassava plantations and what's happening is instead of the kids actually going to school the kids are being held at home so that they can actually keep the cassava fields weeded so in this case there's actually even though you would increase the use of an herbicide a pesticide use there's actually a major societal benefit that those children may actually have a chance to actually get beyond beyond being a subsistence farmer reading is really time can see and not fun that's true so the USDA decision we talked a little bit about this already but to go to that back to that briefly that decision was based on the fact that nothing is being added in those particular uses of CRISPR right so once it is possible is it already possible to use CRISPR to insert genes or to replace genes or is that is that our people working on that now it's possible but difficult it's more difficult why is it more difficult for technical reasons in the in the regeneration process that the mother was talking about you you have to deliver the DNA that you're going to use to insert into the genome now in animals you can do that by injecting the DNA into a zygote and it's easy to to grow animals from zygotes that's what we do a for in vitro fertilization but in plants that process is very difficult so it's been done but only in the handful of laps so far so once it is easier or once we've perfected this a little bit more what are the other new possibility is that's going to broaden the use of CRISPR even more by being able to insert genes or replace genes anyone yeah I mean one of the big ones that Matthew described is introducing resistance genes from from wild wild relatives into into the into the crops that we grow so so you know plants have been domesticated and during that process a lot of genes that make plants naturally resistant to pests and pathogens have been lost and so we want to reintroduce them which you could do with CRISPR just but that one gene back in where it was naturally in the ancestral plant that has been lost during the breeding or domestication process and will scientists also use that not just to introduce genes from related or ancestral plants but other species entirely or do you see that happening with CRISPR the thing is with that is yes it's possible and I think yes people will but then you're back to a transgenic situation so if I took if I took a gene from one type of maize for resistance and I put it into another type of maize in exactly the same place where it was originally ancestrally that wouldn't be transgenic but if I then to a gene from rice and used CRISPR to insert it in that position then technically it would be a transgenic plant and then you deal with all of those other regulatory issues this is why the USDA deciding that CRISPR is not going to be regulated that there are a lot of caveats to what wouldn't be regulated this that example would be regulated almost certainly so scientists might not avoid that because it's technically difficult they might avoid it just because it's harder to deal with the regulation and the perception from society so sometimes you have anyways seen in media reports that CRISPR is very easy you can just order up the parts online and anyone with you know a basic lab can do it at home or in their kitchen is it that easy you've already talked about some of the difficult some of the challenges and for example putting a new gene and but is it really that easy to do I can I do it no sorry [Music] easy for plant because you have to go to regeneration process which is not to set up in your kitchen when you garage right so or certainly for other microbe you you know bacteria let's say may it's usually bacteria may be easier but you know still you need some setup so when you see the kits online it's really to do bacteria or something people aren't making corn in their kitchen there is one plant called Arabidopsis which is sort of the fruit fly of the plant kingdom it's the model main model system and to transform that plant is extremely easy you we use a bacteria called agro bacterium and normally we have to go through this very elaborate tissue culture to get that to work which you know you wouldn't be able to do at home for a rubber topsis you just dip the plant into the bacteria and it becomes transgenic so i think anybody with the reagents that you can get from a gene for $65 forever top succeeds for much less than that i think you could do it it's not why that's a model no no that that was that process was discovered after it was adopted as a model it was it adopted the model because it's small and has a small genome so it's easy and it's rocket cycle so we can go from sea to sea in about six weeks okay so I'm curious how collaboration helps realize the potential for CRISPR in each of your work collaborating with other groups all my publication recently about CRISPR castes are involving other laboratories almost more than two other laboratories usually like so I think it's very collaborative so sometimes because of the competition everybody want to make two or better for me I want to publish peer-reviewed paper I want to have to work harder to rather collaborating with people it really easy way to in mixings happen quickly so and sometimes we share same goal to develop a better crop so we collaborate because they have germ plasm I don't have but I have the tool to make that happen so they don't know so my name I don't know how so much know how about make it to work but but regardless I mean we only have seeing so many applications in calm soy being rice out of drops I suppose there's so many hundreds of other pass species which we haven't tapping with Chris podcast yet so which is something people are constantly searching carburation for exams this morning I was counted by a scientist from Africa I talked about possible correlation CRISPR editing banana for making banana disease resistance on fungal pathogen which is big big problem in Africa so so maybe another way to talk about collaboration is collaboration with industry so that has sort of caused a lot of the fears and suspicions about GMOs for those of you that do collaborate with industry is it different when we're talking about Chris Barrie and what are some of the benefits of working with these large companies are you thing you work with some companies can you talk about what that's like what key was company to me is that so as long as we find the same karana for example they are so interesting developing CRISPR to make it better more efficient so the company can apply making that pipeline move faster to develop product but for me is I also wanna that kind of tour to help other researchers are the farmers other people who don't have the resource to also apply them to those kind of applications so so we have same ground that's why I'm kind of very positive involving involving those kind of collaboration and if you work with is a pioneer yeah we work with pioneer one of the biggest maize breeders in the world and we work with them to bring to try to bring that the basic discoveries that we make in our lab to the farmer so we do not work with the elite varieties that farmers in the Midwest would normally grow just because we have our own lab strains that we work with but pioneer have the resources and the technology to take our discoveries and transfer them using CRISPR into these elite lines that they sell and potentially could bring benefits for the farmer of increased increase yield and now there you do a lot of work with breeders on a state funded initiative so what's that process like so the the state funded initiative I'm working on is this industrial hemp so actually all of my work is collaborative when I'm working with a breeder we talk about what traits they're particularly interested in I give them advice I'm I'm the technical end for those collaborations the person who can tell them how to actually use the CRISPR tools give them back their regenerated plants and that have the edits in them do the advice and then they do a lot of the phenotyping which is the process of saying does the change that we made actually have a positive or negative effect on how the plant behaves and who are the other main funders for this kind of work like we talked about industry we talked a little bit about state funded stuff what what other funders are involved in CRISPR with agriculture most of our funding is from federal funding agencies of the National Science Foundation and US Department of Agriculture anyone else any other pots of money we don't know about other foundations or other foundations okay another thing I'll say about collaboration is this technology is moving incredibly quickly so for us to do a CRISPR experiment and get the result may take six months or one year in that time the technology has changed so almost as soon as we start an experiment we're out of date and so we go to a lot of conferences to hear that the newest advances that certainly I was generating and that that becomes a collaboration when we share share those resources is that exciting or frustrating when you started an experiment you're like wow and Carolyn speaking and collaboration what do you think about the need for collaboration with scientists working with public outreach and with IO a thesis to sort of introduce these technologies in a way to the communities they'll exist in yeah I think it's super important so when we're thinking about collaborations I suppose we could think more broadly about collaborations I'll remind everyone that taxpayers are paying those federal grants so that's one way in which we're all collaborating in the development of this technology whether you like it or not but then when you're actually developing a technology I think it's really important to have this public engagement in public outreach effort which is involves scientists who are willing to communicate their work like these guys are and able to do it in a way that helps people understand what they're doing so as a bioethicist I think it's it's super important to have cross this and disciplinary collaborations between humanists and scientists between bioethicists and scientists and to think about what questions there are so in these really technical matters different kinds of questions different different ways of assessing risks and benefits come to the fore and I think that we can work collaboratively sort of in more academic partnerships to figure that out but then in moving the conversation more to the public it sort of draws on a different skill set with communicating and and being open and willing to listen to the public and the public is not just one homogeneous whole but many different kinds of publics that are out there to bring those bring lots of concerns into the fold and and even change and redevelop technology with that in mind so I think for thinking think talking about research River at large and the public's role in that there's definitely a role to bring the public's values concerns motivations and needs and desires into the research process so that the products that are developed are ultimately responsive to the end-user whether that's a farmer who's planting it or eaters who are buying the product at what point in the research does that need to happen how early and do all of you have bioethicists and other humanists in your lab saying don't do that people won't like it well that would be a marketing professional well I probably do work with bioethicists and your labs no no what are you think about that this is this engagement that's kind of full information to the public and what some could potentially call the science policy interface creating both professional through regular free bodies where you have scientists you know and talking to policymakers and trying to make sense with each other and outreach efforts like this you know talking to the public things like the New York Times which publishes a very good supper on Tuesdays on science issues which really put the science in a credible way out to the public so that outreach and and I really think I've learned a lot first needs because you can read about these things but having and hearing it from scientists makes a tremendous difference so that's that effort but also institutionalizing that you know to find I think sort of sometimes anti science buyers or this knee-jerk reaction about things like or GMOs are all bad you know and having this much more nuanced explanation of what GMO is could be how we can understand them and and shift the sign of the perception and make sure that old misperceptions aren't repeated because we don't wanna repeat the errors of yesterday because I think this technology clearly has so much promise that we can't be tethered to those past those or misperceptions you know we have to be clear-eyed and open about any risks there may be but we do want we don't want to be tethered to the old misperceptions and and and sort of help us and not get gittery where we want to be so I think that that's really really important and I think this kind of dialogue is super important but it also needs to take place within universities and I think also the heads up because in some ways what we're saying I think the trimmer' sounds maps of a general and scientist have the advantage of being there right at the coalface on very concrete questions but going back a little bit the sort of the drawing the lens back a little bit further and taking the time out to be here and that's also hear us in some ways is useful as well because it it informs and can make maker the whole enterprise more successful I think so we need that cutting-edge research but has to have a dialogue with it sort of interdisciplinarity as well you know which of course is time-consuming and sometimes frustrating but for the bigger enterprise as was mentioned it is the public it's the taxpayers it's the public's that will ultimately determine the overall public acceptance of this technology no matter how advanced we are in the lab it will only fulfill its full potential if they if the public's that were mentioned really buy in and accept I think that's the end of the day yeah just say - I think it shouldn't be surprising when publics bring lots of various concerns so I think there's a tendency especially in the GMO non GMO debate to think that anyone who's anti GMO is also anti science and I think that that's the wrong inference to make there can be people who completely understand it but for different kinds of reasons just don't feel comfortable with it or think that it sort of approves my life too much so an example is something like how different farmers farming practices might change communities and the labor practices within that community how different farmers bring their skills and knowledge and and cultural and familial traditions to working the land and how has that changed by CRISPR and that's it's not about science so it's not being anti science it's recognizing that this technology and all technologies actually shape how we interact with the world and how we interact with each other and changes in that sense really change who we are as people and how we relate to each other so I think farming is actually a really good example of something that at a local level has its own value system and its own approach and I think it shouldn't be lost on us in this conversation that people who are resistant to give that up or who see a sacrifice and giving up that kind of approach to working with the land might experience that as a loss and it has nothing to do with misunderstanding the science and everything to do with what they perceive as something of a an assault to their cultural and familial traditions and the same goes with what we eat so well I don't want to go on and on but the idea that what we eat is very much rooted in our cultural and familial traditions as well and when they're seemingly is an attempt to change that to radically change what's on your plate that's perceived as something that's deeply personal and and something that would change in a sense who you are and how you engage at the dinner table with your family so again that that's not an anti-science sentiment but it is one that we should that should be on the table so to speak when we're having these conversations about whether crisper can save the world it's going to change it and we should back at least acknowledge the ways in which it will change how we relate to each other as in our labor and even as we just have dinner so a common criticism against genetic engineering in general and I'm sure the scientists might roll their eyes a little bit at this is that scientists are playing God but this is really powerful technology and in some ways it's unprecedented so let's talk a little bit about the risks and about what could go wrong with the tech so for example could CRISPR be used to create new pathogens and pests how do you model for unforeseen circumstances in your research to protect us against these things if a plant becomes resistant to natural pests or blight what's to prevent it from you from becoming invasive and so on and so forth so how do you think about risk in your labs and in thinking down the road to what might happen eventually with the technologies that you're working with do you think do you want to start yeah sure so so I think I often see just like technology is technology just like the knife was knife we can cut it in oak and you have can have a kitchen or you can own somebody right just depending how you you know you know car can sometimes cause accident but we have to come here to his car so first podcast definitely is a lot of advantage you know we use that as a as a tool and so but really how can really be used for really bad purpose bad outcome I haven't really seen much beside the dream Drive you know we don't really want to get too much about wiping up about species like you know yeah I I don't want to do that right so it's so but but really was thinking about how you know applying as a codenvy teen sort of next generation pattern or a new reading technology right so to really speed up the breeding process we have been practicing the farmers or breeders or scientists or a society are practicing this southern the years to make the call as today the Communist oi being you never sing that the same thing before right so we we are constantly making this kind of without changing the genome but CRISPR just a tool allow us to make it happen so I really never think about something really bad last thing I would say so if people are think about oak it's a scissor which were cut here you wanna cut in a literary just gene but you know giving less remitting three billion base pair maize genome or human genome how can you make sure it is only gonna make the change at your intended target right so that will be a issue of of targeting so there's actually a little too controversial in making animal sorry luckily you know recently we actually got a paper accepted a publishing genome biology kind of coming soon next months probably which we did a various sort of a comprehensive study and we CRISPR cast genome modified there are many many plants in rice and then we sequence that you know entire genome of every plant we modified and then we compare that to our parent of plants which has been has not been modified and then we found actually we indeed the founder mutations and we actually find about 200 mutations across every single plant so but that mutation was sort of arise during tissue culture why are you making a sir induced that from Cali to make her plant so not because Chris podcasts we even found adjuster if you have a cedar from the parent of plants the seed already the next generation already contains 40 mutations compared to parents so that's a lot of mutation but Chris podcast with only very very bad press for castrate and we made one out of 15 that one only make a few like three to five additional mutation which is unintended so that level of targeting is really minimum so audience understands what we're talking about with off targeting this is the idea that you have the magic scissors and it's gonna go to this one gene you want to turn off but what if it goes to a different gene that's very similar and it just goes to Don cuts the wrong thing this is the idea right yeah yeah just like a metaphor people say CRISPR kasia's Amissah missile targeting a missile may be fine somewhere else it's dangerous right so how can you make sure it's not fly over to other sites right so so we actually are starting show it is very safe it's really good to the psyche only touch so your study was showing that there are mutations that happen even with no CRISPR that are right natural your nature have mutation otherwise we wouldn't evolve as human right and that in general there weren't that many off-target effects but there were some did I understand that right yeah we intended a design a very sort of warp batter guide RNA which already had one yeah it's just just to show how it can happen right because you know the things then we learn actually if you can limiter the mismatch of base base so 2 2 and then you can actually avoid that so that's a worst-case scenario scientist makes a really terrible magic scissors we're just like what might happen right right most of you aren't gonna make bad magic scissors right even is that the compared to natural occurring mutation rate is very very small okay so it's very safe all right Matthew what do you think about risks with this particular technology how do you plan for these sorts I I think the risks are fairly limited in the plant biology realm they're much greater if you're talking about medical purposes trying to do this in human beings the fear is that if the scissors did cut in the wrong place you know like if you're trying to you know people are looking at can you actually remove HIV from the genome and may and cure someone of HIV by taking the scissors and cutting the HIV virus out of the genome but what if they actually cut out another gene and when you cut that gene out you actually induce cancer you know if if you induce cancer in my plant yeah I might be sad but I think I think we'll all survive different stakes there there are very different stakes and so that's that's one thing to keep in mind and you know the other thing is to say you know the goals that I have in my lab the final goals for the final final products that I'm making are not any different than what they were before I want something that's high yielding in his disease resistant and is giving fruit that you that you would want to eat etc etc etc I'm using a different way of doing it and so you wouldn't evaluate the final product differently you you're still going to go through the same sorts of evaluations if you're doing something that is transgenic technology then you have to bring those other sets of concerns about but the risks that that you're thinking of are not that great and are there ways to test for example if you cut a gene and it for some reason makes the plant have a toxin that it didn't have before have an allergen it didn't have before what's the process for detecting something like that for example so there are there are so many tools now that we can possibly use for doing this there there's full genome sequencing you can check every gene in the genome make sure you had the the edits occur only in the genes you want them to occur and you can use these techniques called metabolomics where you actually take all the metabolites and you figure out what is in them and you compare your final edited version versus the original version and you say you know are there any toxins that that have appeared in your edited version that you didn't have in your original you know there are there are a number of these tools now thanks to where we are in science today that we can do screening to actually check for those things what do you think about risks yes so you know as humans were completely dependent on agriculture for our for our existence like ten thousand years ago we would not be sitting in this room having this discussion we would be hunter-gathering you know finding whatever what wild fruits or berries we could find to eat so you know we have two most heavy crops and now those crops are completely dependent on others for their survival right have you ever seen a corn plant growing in the wild it just does not exist that hunts have been bred so much that they do not exist in the wild anymore they cannot compete with with wild plants so I think the risks of editing agricultural crops are non-existent or at least minuscule now if you were to edit an invasive species or wild species it's possible you could make it more invasive we'd actually don't understand how certain crops are more invasive in others or certain plants should say so but currently I don't know anybody working on those planets and if if people were to welcome to my show they would take appropriate risk so I'd certainly need to I mean there were a lot of concerns originally with transgenic technology that you make corn resistant to herbicides and then you'd get corn going off everywhere and you wouldn't be able to but it actually doesn't happen you know the corn stays where you planted it and you harvest it you bring it back and it hasn't taken over the world other than where farmers have actually purposely planted it and so I think that's why for domesticated crops there's really limited risk so we have about five more minutes and we're gonna open it up to an audience Q&A so my last question for all of you before we do that what are you most excited to see happen next with CRISPR in agriculture and how long down the road do you think we are to getting there do you want to go through first and we'll go down the line I think adding new genes so new traits into crops is very is a promising new area as we talked about earlier it's still very challenging to add new genes using CRISPR but for example you can imagine making crops more nutritious better health properties so that's I think that will happen might be at five years or ten years from now but it's settled so it will come and could make our food more more healthy for us magic I think to see that the the basic research being done moved to the Applied Research and targeting it at where we need it in terms of more trough resistant crops crops dealing with heat stress with water scarcity and actually having real examples I think the story with the GMO as we heard this promise and I think it under under delivered in terms of the kind of things we need to deal with with hunger and food security in developing country to see that come through if CRISPR can really deliver that part and come with the ecosystems around that in terms of research in developing countries technology transfer we haven't talked about licensing because CRISPR is licensed for commercial purpose has to be licensed so find ways to make sure that part of developing technology doesn't hold back the promise not just in full-scale commercial use but actually for for developmental purposes and actually is an age of sustained all developed I think there's enormous potential we've learned lessons about applying technologies and getting that's that that sort of push behind them they're the sort of backdrop but you're getting that right with Krista because I think the technology itself nothing we've heard is really promising we need to get the other parts of the puzzle together to get the full picture Carolyn I'm gonna agree very much with what Frederick just said which is I hope CRISPR really is the catalyst for thinking about the delivery system right that we're gonna create high yield crops that are fantastic and drought resistant and could help with some lots of ways but we need to think about the political systems that would actually be capable of delivering that to the people who need it the economic systems and the social and cultural understanding and dialogue and and to a certain extent change that would actually be necessary for CRISPR to to save the world which I suppose is that we all hope it will do this tall order what do you think I agree with David that you know if we can actually make these more complex changes where we actually can more easily readily correct a gene that is broken for instance replace a functional copy a non-functional copy with a functional copy that's one thing the other thing and this is coming more from my perspective as a tissue culture person is we really need to be able to have more efficient tissue culture technology so that we can make these sorts of edits possible in a larger variety of crop plants anything well because well they've set us so basically I think to ask ya to two aspects first of all is really I'm very very excited alike about the possibility like all the I mean the the bias so low that all the people can practically not in your garage but in the laboratory can really in a modify engineer making better reading better crops I mean not only limited in a price but many many other plant species people never imagined they can modify the genome or now it's possible like Wyatt well I mean like like besides Apple I have collaborated with working with pear and orange and you know you just a week ago people in a modified a watermelon and is that just a lot of plant you can sing about then people are thinking about coffee tree disease you know and all kind of like banana disease now if you can modify making the clock more resistant that's awesome right I think now it's possible to use a tool but again you needed people to be able to use a license you know the CRISPR technology you know to be able to do that and you needed a you know the transformation perhaps from being established otherwise you know you wouldn't be able to deliver and make it happen so I think everything has to come together things are going well but I just feel very excited about that so great alright let's open it up to audience questions but before that let's say thank you to our wonderful panel [Applause] could you explain our CRISPR works I thought we did a little bit with the metaphor does anyone want to take that like using that metaphor of the word processor I'll give it a go so let me tell you how it was discovered so you know we we get diseases bacteria infect our body as we get sick bacteria believe it or not also get diseases they get infected by viruses and they get sick or they die so what scientists discovered started starting 15 years ago is that bacteria can protect themselves against viruses what they do is they have this little machine called CRISPR they snip out a part of the virus DNA when they get infected put that into their own genome from then on they have an immune system so that whenever they're infected by that virus they can recognize it and they can cut the virus DNA and they use it using these molecular scissors the caste 9 which is a protein that cuts DNA and a piece of RNA which is the guide that takes it to the part of the genome that it has to cut so it's basically a molecular machine that can find a region of DNA and and cut it that was really good did that answer your question so the part that he's leaving out though is that the edits that we're talking about all happened downstream so the body you know a human body a plant has the ability to fix these cuts almost perfect perfectly in most cases but at a certain percentage of time it's not fixed perfectly so for instance instead of putting my hands right back together perfectly maybe it would make a small deletion and suddenly I lose one of my hands or maybe you lose the key noun in the sentence so it no longer makes sense and if you do that then the gene doesn't work so you've essentially taken a piece out you can also though take out a larger piece like take out both of my hands and replace them with your hands for instance so that's like taking out my version of the gene and putting his version of the gene right back in place so the cassadine does the cutting and then you're taking advantage of the normal repair mechanisms for fixing DNA which work most of the time but not all of the time and it's only because of the the chance of it not working properly that we're able to do the edits that we do question I'm curious to know if when you've made your edits let's say in hemp or in maize as the result ever been what you something unexpected did it adversely affect some other gene in the genome that you were working on so the first CRISPR experiment we did we expected that we would get corn plants with bigger ears that was our hypothesis what we got was dead confluence and you know death science right you don't know what's could already expect took us about a year to figure out and now we've figured out that the gene we were tinkering with not only affects plant development but it also affects the plan immune system so how plants protect themselves against pathogens and we actually got funded by the USDA to study this process because it's really cool science yeah so you don't always get what do you what do you expect any other unexpected things in the lab perfect science so far well to me unexpected thing isn't really the efficiency is not 100% you have to scream like Tony Paz get a few of them have to edit but even that is only one chromosome is edited the other one the same genes not being edited you have to go to the next generation look at the homozygous solo edits so that's the efficiency we have been constant what will make it more efficient so you'll do CRISPR and many different plants but it won't be every single one no no it's your lucky than if you everything so efficiencies way low so who is next so does somebody own CRISPR or how is it made available how is it controlled what what's the that aspect of it I didn't quite get there's actually a really interesting patent fight over that I don't know if anyone's expert in that I'm not sure the answer though anyone know well technology just like you know something in your iPhone can be patented by the people who discover it even in biology and so yes as she alluded to there is a patent fight between UC Berkeley and the Broad Institute in Boston over who discovered it so and it's a matter of you know going through people's notebooks and saying you know did you really make that discovery on that day and were you were the first person to make that discovery you know and it's it's a very complicated process because you know scientists are very competitive and they want to publish first and they also want to get the race to it and this technology is worth billions of dollars so there is you know a lot of lawyers are getting very rich right now just debating it but but having said that it is free to use for researchers in the public in the public to mate so i can reuse CRISPR for easily you could also if you wanted to commercialize it make a product with it you would have to pay licensing fees and you would have to pay figure out I guess we're to pay those two because we don't know if so barring the example of the dead corn plants do these genetic modifications always carry down to subsequent generations or their cases where that does not happen yes and no and so ideally we want changes that will be inherited but depending on how you generate them you can get what we call somatic mutations so UK could get a mutation in the leaf for example which does not pass through the germline through the flowers of the next generation but we have ways to control that and we you know we try to direct it so that it is inherited in the germline because otherwise it's very difficult to study it we probably have one time for one more okay thank you very much do you think that scientists should buy the controversy in the society that exists about CRISPR and genetically modified organisms did you say should they fight the conference yes so should they be doing should they be engaging with the public or should they just be in their lap in any way in any way maybe like using I don't know even social media maybe are you out on Twitter occasionally so there are a remarkable number of scientists running for Congress this year which is a very exciting tune of event imagine why US political system so there's scientists fighting the fight on all levels including perhaps one of the highest ones in this country so the short answer is yes and I think it's really encouraging I think we're seeing more and more of it so that's awesome yeah when I when I took started my position two and a half years ago I said that I saw my position a little more broadly than they did which was partially in the lab and partially out there with the public trying to communicate about the technology my goal when I when I go out there is I'm not trying to tell people what to think I just want them to understand the science of how we do it and then you know let them using the information about how we make these things to give them a more informed base some witch to make their decisions so I think it's I think it's very important for scientists to be out there because there are as you said there are some people who are coming at some of these discussions from a more personal position where they feel like it's changing their lives or their farming or things like that but there are other people with some serious misconceptions about what's actually happening number one there are also some misplaced there are some negative thoughts about certain things like huge huge agrochemical companies that are then affecting their view across the board on all genetic engineering or CRISPR technology and they're making it sound like all all CRISPR or all GMOs are bad because they're focused on the company and the money so my goal is to go out there and show these are the ways that we can do it I'm not working for a company and I'm trying to do it I'm trying to get things out they're trying to do things you know just to try and share with you guys and everyone else I come in contact you know what kinds of things are we thinking about and how are we trying to make things better alright great on that note thank you for coming here we're out of time we're out of time but we can talk [Applause] [Music]

Channel: World Science Festival

Views: 29,419

Keywords: Is a CRISPR-altered Plant a GMO?, GMO, Genetically modified organism, genetic engineering techniques, Genetic engineers, What are the risks of using CRISPR in plants?, CRISPR discovered or invented, CRISPR, What is CRISPR, crisper DNA, DNA, edit your DNA, custom DNA, Genome Editing with CRISPR-Cas9, CAS 9, RNA, vaccine coronavirus, coronavirus, COVID-19, pandemic, World, Science, festival, NYC, New York City, 2020

Id: d_v1RPN3AoM

Length: 75min 26sec (4526 seconds)

Published: Sat Mar 14 2020