 So good evening. My name is David Spector and I'm director of research at Cold Spring Harbor Laboratory And it's my pleasure to welcome you to the laboratory this evening and to our lecture on the challenging relationship between humans and plants Cold Spring Harbor Laboratory has a very long history in plant biology Dating back to the 1900s when George Shull who was then a faculty member Here found that crossbreeding corn plants Resulted in 20% higher yields than natural pollination a phenomena that's referred to as hybrid vigor and to which some of our scientists are working on today and in particular Zach Lippman who you'll hear about tonight and of course Barbara McClintock who won the Nobel Prize in Physiology or Chemistry in 1983 and happened to be the first woman to win that prize Unshared usually the prize is shared among a number of individuals For her discovery of mobile genetic elements, which again is being followed up today in the laboratory by several of our plant scientists today's focus of the plant biology group at Cold Spring Harbor is on plant development gene regulation and agricultural and biofuel applications and tonight Our three speakers will give a joint presentation where they'll discuss how we've improved plants By domestication during the past several thousand years of human evolution and how new knowledge of genome sequence and genome manipulation tools such as a technology called CRISPR, which you might have read about In the newspapers or in magazines can be used to improve agricultural yields And sustainability of plants which of course is very important for our food supply And that's really a major focus of the efforts here at Cold Spring Harbor So our first speaker tonight will be David Jackson David is a professor at Cold Spring Harbor and his research is focused on defining the molecular and genetic pathways that control development and how they shape morphology of plants and Which has downstream applications of course to both plant productivity and to crop yields so Okay, thanks David for that nice introduction and welcome again everybody to Cold Spring Harbor lab It's great to see so many people who are interested in plants I actually came up with this title So I thought I should first of all explain where this came from So, you know, we have many relationships in our lives that we deal with on a daily basis with our friends our families our co-workers our bosses some of these hopefully are more pleasurable than others But for the next hour or so I want you to forget about those relationships we have with other humans and only consider that the relationships we have with plants and specifically with crops the plants that we eat on a daily basis and Humans have had a very intimate relationship with plants going back of course since the whole of human evolution But particularly the last few thousand years where we've actually domesticated plants So we've taken wild plants and turned them into plants that we call now called crops that can be used in agriculture and I'm gonna start off by talking about this process that we call domestication and I want you to Take a journey with me back in history We're gonna go back not not so long in the history of human evolution about about 10,000 years So just imagine what life was like on the planet 10,000 years ago So we didn't have public lectures in Grace auditorium at that time In fact, we didn't really have much in terms of civilization people back then were a nomadic which means they moved around a lot and We're basically hunter-gatherers. So we didn't we didn't have crops 10,000 years ago We didn't have agriculture and people survived on wild plants Wild barriers, maybe seeds from some wild grasses But those those wild plants have very low productivity And so in order to survive a small group of people would move around because they would soon use up all the edible material in a certain area and Then starting around 10,000 years ago humans started to Domesticate plants which means we selected them genetically and started to turn them into crops, and I'm gonna use Corn as an example It's a it's a plant that we work on a lot here at the lab And it's also a plant that we know a lot about it. It's history of domestication And in fact, we know the ancestor of corn and it's actually growing over here You'll see it later when the lights go up. This is a plant that still grows in the wild in Mexico It's called tisente and as I said starting about 10,000 years ago Humans started to select this plant and to transform it into what we now have as modern corn Now this story is not specific to corn and in fact during human recent human history we've domesticated many types of plants and animals and you see here on the left are some wild species and on the right are the corresponding domesticated species and Basically what we've done to these species over the last Few thousand years. I'm sorry. I didn't this pointers on all the time. Hope I didn't blind anyone yet Basically, we've taken wild plants and transform them into a version that we can eat more easily and We've taken wild animals and transformed into a version that cannot eat us easily Okay, so it's really fortunate that we got that one the right way around So, how did we actually do that? Well, this happens by a process of genetic selection Actually, you've probably heard of natural selection Which is something that happens in the wild where organisms that are naturally fitter than others will survive and proliferate more But this is slightly different because this selection is driven by humans and I'm using this popular children's game called Pokemon as an example of this So Pokemon is is a card game that many many children play and each of these Monsters or pocket monsters that Pokemon is shot for Come on trading cards that you can buy and children will trade these cards and collect certain versions of these of these creatures Now to as adults these all look pretty equivalent But if you ask my son or any other children in the audience They'll immediately tell you that some of these are much more valuable than others Right. So this one for example is really is really a very valuable Pokemon and over time if you're a good trader You will collect more and more of these valuable Pokemon's and some of the less valuable ones You might throw away or they might die out of the population So it's a gradual process of selection where we're picking things that we find attractive Okay, so similar thing happened with corn this was a very gradual process that happened over thousands of years Now first of all, I want to show you evidence That T. Sente actually is the ancestor of corn, right? You should never believe what a scientist tells you always ask for evidence and here's the evidence So even though these two plants have been separated by 10,000 years of evolution There are still members of the same species and we can cross them together and That the progeny the plants that come out of that cross Look somewhat intermediate between the two parents So that tells us that these two plants share many of the same genes and a mixing of those genes can Can change the form of the ear so that in this case we get more seeds We know that this process was very gradual because archaeologists have collected corn cobs from from caves in in Mexico and some of these have been carbon dated and So this cob for example, we know is about 5,000 years old This smaller cob is even older and some of these cobs are just one or two hundred years old So we know over history. This has been a gradual process of selection But what are the actual trades that were selected? So I talked about ears of course the ear is what we think of when we think about corn This is what we eat of course, but you can see the whole architecture of the plant has been remodeled So tisente for example, and again you can see it over there has these very long branches And these branches are not necessarily good for productivity in an agricultural field And so over time humans selected for these branches to get smaller and smaller and smaller So that in modern corn they pretty much disappeared Okay, good in modern corn they've disappeared altogether Except for a couple that were retained and have been transformed into these large ears The branches are actually still there if you look very carefully You will still see them, but they're but they've been selected almost to extinction But I really want to focus on the ear because this is that actually the structure that we study a lot And I want to talk about how the ear forms what what are we learned about how corn plants make ears? Now this is obviously what you think of when you think about a corn ear This is what I think of this is when the ear is first made by the plant and this is made This is a structure that's made when the plant is about knee-high. So already at that very early stage It's already making these ears and this one Filling development is about two millimeters. So it's about the thickness of a quarter, right? So obviously you can't see very much detail there, but if you if you blow this up in a special kind of microscope Called a scanning electron microscope. You can see this structure already has a lot of organization so at the tip here you have a Special group of cells and they're producing these organs these structures We call them primordia and these primordia Are making flowers which will make the seeds so already when the ear is tiny two millimeters in size It's already decided how many seeds it's going to make Right at the tip of the ear are a group of cells that are very special We call them stem cells and just like the stem cells we have in our own bodies are involved in Making our tissues and regenerating tissues these stem cells are the special cells that are building all these structures Basically, they're building the ear during development now. I want to this is a side view I want to take a slightly different view and look from from above And it looks like this so now we can see close in this is the population of stem cells this little Dome of cells and in the background you can see the structures Making at these rows of organs that are going to make the seeds the rows of seeds as I as I said Now if we look a little bit closer You can even see individual cells here So these are the actual stem cells and you can see a little structures like here They look like little hamburgers. These are actually cells that are dividing right so these stem cells are Dividing when they divide they look like this and when they divide they make extra cells which then will make the organs Now if you wanted to ask Can we make corn that will make more seeds? Well, well, you know, how how could you do that? Well one way would be would be to ask Can we make more of these rows of seeds right? We know we have this group of cells and they're making these rows of Organs that are making the seeds can we just add more of these rows early in development and make more seeds Well, the problem is, you know, as you see they're pretty packed pretty tightly packed in there There isn't much space to fit in any more of those rows But what if we could just make this structure bigger? What if we could make more stem cells and make more rows of seeds now? That seems like a tall order to do But it turns out that we actually know the genes that control the stem cells in plants And this is work from my own lab here in Cold Spring Harbour as well as work from many labs around the world who work on on how stem cells are controlled in plants and the way we discover genes in plants is by looking at mutants So this is a mutant This is a plant or an ear from a plant where one gene has been knocked out or one gene is broken And you can see the effect of that mutation is the ear is much shorter and it looks kind of ugly I don't think any farmer or consumer would want to eat this But actually if you look again early in development It has a very interesting characteristic, which is you see that the stem cells Now are massively proliferating so that the normal corn has this nice small organized group of stem cells And this mutant the stem cells are just growing out of control This is kind of like a kind of cancer in plants where the The mechanisms that would normally control these cells have completely broken down Now can we actually use this information? I mean this is really interesting information to scientists who want to understand how plants grow But can we really use this information to improve corn for agriculture? Well, it turns out that we think we can and we came up with an idea A while ago now how we could do this so I showed you already That a corn plant will make a certain number of rows and this is a normal corn plant and this this Pool of stem cells here at the tip is making So you can count this as 1 2 3 4 5 6 7 8 9 10 10 rows Of those organs that that ear will make 10 rows of seeds Now the mutant I showed you Actually makes many more rows But as I showed you that the rows are very disorganized and the The yield of these mutants is very low, but you know, maybe we can control these genes So instead of knocking out the gene completely so that we have zero activity What if we could just reduce that the activity of that gene a little bit so that we can make this stem cell population A little bit bigger And now there's more space to make more of these rows and in fact this ear is now making 16 rows Okay, so this is what we call In genetics the the goldilocks idea or the goldilocks theory So you want to have the gene activity not too hot not too cold, but just right Where the stem cells are still organized and controlled But we can coax them into making more more seeds And it turns out we've actually been able to do this recently in the last two or three years We've been able to use techniques that the breeders commonly use to To to to introduce these genes and we can we can make Reduced activity versions of these stem cell genes and in fact when we do that we indeed make bigger Populations of stem cells at the tip of the ear And now these reduced activity versions of these genes Actually make ears that are as long as normal so that they're not shorter like the Like the the mutant that they they actually have more rows of seeds So and in fact in our breeding experiments with our lab strains of maize We've been able to increase the productivity of these plants by up to 30 percent So hopefully I've convinced you that a bit of basic knowledge simple knowledge About genetics and how the plant develops Can allow us to make predictions about how we could increase seed production And in fact I've shown you an example where we got that to work in practice But I want to just finish up with the thought that this is not the use of genetics In agriculture is not new as I as I showed you in the beginning Humans have used genetics basically selection for the past 10 000 years to domesticate crops And in fact if we hadn't done that we would still be Out in the forest gathering nuts and berries and small grains to eat So so it's been going on for thousands of years, but also as as David reminded us it's has a long history In cold spring harbour. So this is a again the example. He told us about george schull Who was a a scientist here in the early 1900s? He was doing experiments to understand How we can breed corn so that it can be more uniform So at the time farmers were growing corn and they had a lot of variability Some plants would make big ears some plants would make small ears and it was the yield was very unstable And so what he did was he would he inbred some plants And he produced these so-called inbred lines produced by cell pollination But those lines actually had very low productivity However, when he crossed two different inbred lines together He produced what we call a hybrid plant And these plants have much higher productivity much higher yield You see the plant is much bigger and the ears much bigger than the Parents and he actually did his experiments In the cornfield right next to the library. It's about 200 meters away from where we're sitting. This is his cornfield And in fact this simple genetic discovery When it was applied in agriculture about 20 years later Led to a massive increase in in yield of corn such that the the yields of corn per acre now Are five times more than they were back in the 1930s And this is in the large part due to this simple discovery by shul a basic genetic phenomenon That we call hybrid vigor or heterosis So with that that's the end of my part. I'm going to pass over to dorian Who is now going to bring us more up to speed with with genomes and how they can help this So I just wanted to introduce dorian where dorian is a senior scientist at the u.s. Department of Agriculture agricultural research service and she's based here at cold spring Harbor laboratory where she's an adjunct associate professor And so she's going to tell us a little bit a little bit about the major discoveries that Barbara McClintock made During her time here and before she came to call spring harbor and then she'll discuss Other work Regarding plant disease and yield which again are both extremely important in regards to our food supply So following up on that story of Scientific cold spring harbor working on me Mentioned earlier Barbara McClintock received her noble prize for using genetic approaches to understand Transposable elements or what we think about is jumping genes And what Barbara did is she used genetic approaches to follow pigmentation in the kernel of corns And what she looked at is when that pigmentation Would change if there was pigmentation And the seed was black she knew that the element had moved and jumped out And when she saw these spots here she understood that this was a result of the gene jumping Out at different stages and so what she was able to do is actually follow a visible marker That led her to understand that portions of the genome move in and out And the movement of these portions of the genome can cause differences in expression of genes Well, there are other other plants that you might be familiar with where this is happening as well in nature And in fact if we look at it in a caverné sauvignon if we look at the genome there and we look at the genome of chardonnay What's happened is a transposable element one of those jumping genes jumped in here It's basically cut out a little bit genome It's stopped the expression or it's modified the expression of some of the genes And then it's lead to this change that we see in the chardonnay great here And zach oh wait a minute on is going to tell you about some technologies that are now available That allow us to do some of the things that nature has been doing a while But actually do it in a much more directed approach So if you look around you're going to see many examples of these jumping genes you may not have noticed it before So with um right now with halloween you think about indian corn and we talked about the pigmentation But if you go around and you look you take a walk down your block and you see These beautiful variegated plants a lot of times these variegated plants are associated with those jumping So I I suggest to you next time you walk around take a look and Start to decide well could that have been a transpos on moving out when I see this plant come up And I get a sector of white was that a jumping gene? Well, we know that these jumping genes also contributed to genome Size differences and in plants here at the bottom. This is a log scale. So this is 10 fold different We can see that plants have this very very large range of the size of the genomes that you can have And this this size difference is predominantly associated with the jumping genes that we've been talking about Now genome sizes really are are different Depending upon if you're a bacteria fungi, you have a small genome We're moving up here with insects and birds. It's getting in a larger range And here humans the first human genome the human genome that the sequence it's about two and a half billion Letters or nucleotides The maze genome is about the same size Now it's only been the last I would say 15 years to 20 years that it's been tractable to start to get genome sequences And that's because some of the technologies are changing The first human genome sequence that was generated Costs about three billion dollars Okay I'm gonna As time has gone on the technology to Produce these genome sequences have improved. So the price of generating a genome has gone down My group was involved in the first draft of the maze genome sequence. This came out in 2009 At that time this genome sequence cost about 50 million dollars And what this genome was able to do for the first time Is it really gave us a detailed list of what I want to call the genes or the parts list? And what it was able to tell us is What are the genes or the parts in the genome? It was able to tell us a little bit of the information of maybe where those genes Might be expressed and when it is expressed But interestingly enough this 50 billion dollar sequence had a hard time with telling us about those jumping genes because This genome has 85 of the genome is those jumping genes And it was very hard to resolve the sequence with those technologies Now in the last year my group has been involved in generating another draft and that improved draft We can actually see all those jumping genes that Barbara was looking at And in fact we can start to look at the differences between different corn genomes And the cost point for that last year was about a hundred and fifty thousand And today we think we can do for about a third of the cost So what that's telling you is this cost point is really coming down and for the first time We really have an opportunity to start learning about all the parts How all the parts may be different in each one of us And then how those differences impact how a plant may look Now if we start to look at differences in these genomes It allows us to look at what's similar and what's different And what I want to show you here tell you a little bit more about this is what we think of the map Of of the maize genome. So the maize genome has 10 chromosomes And just to orient you here. This is this is where the centromere is so everywhere I show you one of those red strips. That's the centromere of the chromosome This green line here represents the genes and the darker it is means the more genes are there So what we start to see with this organization here and we had hints of this beforehand is that Most of the genes the genes are more likely to be pushed to the outside of the genome And those transposons that um Barbara McClintock was looking at there's a very high density in the center here Of of the chromosome near the centromere Now if you look at these two lines here these actually represent the Rice and sorghum genomes and wherever you see these blocks here It basically means that the genes in this region here Are in the same exact order as they are In in in corn and this means that for instance If we are able to have an idea that this portion of the genome might be associated with plant height It means and it's also true in sorghum a rice It gives us some idea of where there's common function that's been conserved Another important part of this is it turns out that not all parts of the genome are equal And when breeders are doing breeding what they're really doing is they're exchanging different parts of the genome And it turns out that up here what we've overlaid is something called recombination And everywhere where it's light and you see it lines up well with the centromere here It turns out that things don't recomb we combine very well there So it's hard to move things around in that area So what these maps are able to do it's able to tell breeders Which of the genes are in part of the genome that are kind of trapped and hard to move around So the genome sequence now allows us to know what the parts list are Kind of tells us where they may be expressed and how much And then it also tells us which parts of the genes might be harder to move around And and that's will help us with some of the engineering principles that we might want to look at later on So when you have a genome sequence you can also think about it as like opening up a book or reading a book And when we first got these sequences it was I was like to open it up and it's like I don't understand this language I had some hints I kind of knew where these gene part lists are And as you start to read more and more of these books you understand So the language the grammar and you could pick up them Well, what we learned in looking at this we can tell a little bit about the life history On here and what we found out these gray lines actually represents Where the maze had a history in the past of where it's whole genome duplicated So it doubled all of its chromosomes. It had 20 chromosomes And then it went back to 10 and where you see these gray lines It's where things shifted around and so when we look in those sequences What we find out is that That as it was losing genes it preferentially kept some genes And interestingly enough the maze the genes that it kept were associated with things called chromatin modifiers So if any of you guys have heard about epigenetics Right, this is where things that change and modify the those letters It kept two copies of that so maze is looking at different ways that it can modify itself and maintain modification Also, it turns out that the genes that were kept were probably beneficial for it It helped it adapt And so looking at the genes that were kept can tell us a little bit of a story of things that might have been useful for it to adapt But what the genome sequences are really allowing us to see is all the variations that exist in nature So if you when I talk about you're able to look at a life history of Of an individual or of a species you can see all those mutations and mutations don't necessarily mean a bad thing Some mutations can be very good. They can help you with Adaption so in the maze genome What would looking at getting that list helps us to understand letters that have changed and might be adapted It might allow us to look at um copy numbers genes duplicate and in plants It's a very very different strategy than in in in for instance humans in plants If you double Or you make another copy it gives you an opportunity to potentially Change where and when that gene might be expressed without impacting the one that already works for you And it turns out that it's a little different because in plants It gives you a fitness advantage to have these genes copy and duplicate But for instance in human disease, it's actually known that duplicating a gene could actually have a negative benefit or Negative impact on your health for instance Copy number genes have been associated with certain cancers. They've been associated with autism And in fact if you think about what I talked about in past where you had a whole genome or a whole chromosome Trisomy or down syndrome is associated with a lack of fitness in humans But in plants that doubling can be actually seen as an advantage in the population Okay, so that we have different strategies on how that works in plants But these individual corn plants Are can be very different from each other and we know at the sequence level and so these are three different May line and you can see the the flower portion of it is different The height of these are different and even the root Architecture and shape is different And it turns out if we look at these individual corn lines and we look at the genes that are actually in them It turns out that between five and 20 percent of the genes can be different If we look at the genes in you and I They'll be maybe one or two genes different Between us. That's it. Okay, so these are very very different and to me It's sometimes amazing to see how different they are at a sequence level But how similar they actually look when they're in the field And in fact, when you look at the sorghum and maize at very early stages, it's hard to tell them apart so for instance In this side here, this is this is a maze plant that has two copies of these genes here that confer tolerance to growing on acidic soil When you introduce a third copy of that gene, this is what the plant looks now So just having that one additional copy makes the difference Of of that plant being able to grow well on acidic soil Disease resistance is another example of genes that we see in plant genome Because now that we have the sequence we can actually look at this and see these things When you look at it, you see many of these clusters are duplicated here represented by the green So in great a major disease is is powdery mildew And in europe if you take all the pesticide that's put on all the agricultural plants In europe 50 percent of it is put on grade Okay, so that is a huge amount. So when you're drinking your wine That's that that might be going on Well, it turns out that if you when you think about disease There's a different ways that we can approach it. So for instance One way of approaching it is you might have natural immunity or if you think about how we work with What how we as humans deal with this in medicine? You can also take a drug and it may get rid of that like an antibiotic or You can be immunized and your your body then can Recognize it because it's had a history of seeing it before and then it can defend against it Well, it turns out in grapes they have a natural resistance to these diseases In their past history, they've experienced those diseases And they have now come up with a strategy on how to deal with it when the plant sees that Powdery mildew the wild plant sees it coming in what it does is it says, okay, you're in these cells I'm going to kill you I'm going to kill these cells and sacrifice these few cells So that then I won't get infected for the rest of And this is not that dissimilar to what our immune system might do So we know that wild grapes have this natural resistance because they've experienced some time in their in their past history And they have a way to deal with it So why don't we move it in? And why don't we well it turns out because you know They have a lot of baggage besides that disease resistance genes wild grapes. They don't taste very good It turns out that wild grapes are actually male or female and it turns out that beautiful Bundle of grapes that we see is actually a hermaphidite Right and it turns out that we don't know what the gene is for male and female for sex And then we also still don't know what all these genes are here Most importantly if we made those crosses it turns out a grape plant doesn't become mature for fruit until three or four years So we'd have to wait three or four years so you can find out If it was the sex of the plant that we wanted and so for instance now we're able to generate these genomes I can generate the grape genome at about $5,000 It's a much smaller genome. It's it's one one sixth of the size of the maze And so I can start now looking and I can use some other approaches to delve in and potentially identify some of these Genes using a combination of the sequence and genetic approaches So what that allows me to do is really cut down on the plants that I'll keep in the time it takes to breed it Here's another example rice blast So it turns out that In the four or five year loss in china from rice blast to use you could feed 60 million people Okay, well it turns out Plants when they've been exposed to this They can come up with multiple strategies on on how to defend themselves against that talk about in these wild varieties But it turns out, you know the disease or the pathogen is also smart too And it learns a way to overcome it. So if you've ever seen allison wonderland There's a scene where the red queen all you can do is keep up with The distance away from the red queen's army. You're just constantly going and that's what the plant is doing But what it turns out that we can look in wild rice varieties And it turns out that they will have found multiple ways Of defending against this and one of the ways that we can accelerate The protection is by giving it multiple ways of dealing with the disease at one time So it won't break down as rapidly And one of the ways that we've been able to do that is by looking at these wild rice varieties It turns out that there's some signatures that tell us if there's a certain confirmation And it's been conserved and selected for it probably has a use So now we can actually go into these sequences and come up with many many different strategies and mechanisms By which we can defend against that So what many of us in this room? Don't know people who are hungry I mean and so But the reality is is that in the next 25 or 30 years food security is going to be one of the major things that are going to be In really critically we need to think about for ourselves and for our children They're going to be An additional two billion people We're going to have to deal with The change in climate now all of a sudden these plants are exposed To different pathogen pressures because of the climate change, right? They're also exposed to different pathogens because normally they wouldn't get up and walk somewhere But we pick them up and put them somewhere else and they've never experienced those pressures before so they haven't had a way to deal with them So one of the things that we have to consider is how do we balance for instance feeding people? This example is just putting nitrogen on and we get an increased yield versus what happens when you have a bloom from too much excess nitrogen going into the water So these we can actually use the genome sequences and understanding these biological mechanisms To actually improve the way that we approach them So what i've been telling you about Is really about the genetic variation that exists all those mutations that have happened in nature in the adaptive ways The plants have learned to get around things, but we can also induce random mutations And i'm going to show you an example of work in my group where we've done this in sorghum now sorghum Has um is it's come out of africa. It's come out of a very drought tolerant environment Normally what you see here is when you look at the flower portions of plants It will usually only make one flower where it could be making three and three seeds but perhaps Being in a very drought nutrient starved environment A plant may only want to choose to make a few seeds but have all those seeds have a better chance in life um a nutritional quality So if you look in nature, you never ever ever ever see A natural sorghum plant that will have all three of these uh season plants But using an induced random mutation We've been able to identify a single letter change from a g to an a Which now takes us from here to here And so we can use now some of the approaches to basically be able to push that into other plants um other sorghum plants or perhaps even other grasses to increase yield And zack's going to be telling you about some of those approaches that can be used to do this So our next speaker is zack lippman zack is a professor here at cold spring harbor laboratory And his lab focuses on the tomato plant And how he can uh manipulate that plant to produce more food um He will also discuss how new genetic technologies can be useful To provide important positive traits and plans Thanks david and thanks to david doreen for letting me anchor the group Usually the anchor is the fastest I can't promise that will be the case because It may not be the best situation because that's sooner to the wine and sooner to drinking our pesticide so Maybe we'll take our time So um what i'm going to talk to you about is Work from my lab work from david's lab relating to work in doreen's lab, and it focuses on again A concept of discovering these genes using basic biology and genome sequencing that control flower fruits seed production And disease resistance So we have these genomes at our fingertips now and as doreen told you we can now read those genomes very cheaply We can find all the mutations that are existing that nature has provided And it helps us discover the genes for example that control as david told you the population of stem cells at the tips of the plant And david showed you that by manipulating the genes that control those stem cells We could make them a little bit larger and get more years that years that have more kernels rows of kernels So I work primarily on tomato and we're also interested in stem cells because these stem cells Relate to the number of flowers that are produced on the tomatoes on the vine as well as the size of the fruit So the hope is to use these genes and discover these genes by studying mutants so that we can improve crop yield So the more knowledge that we have on these genes to control these growth processes The more targets that we have and i'll use the word target later for us to be able to improve crops By manipulating these genes in ways that was never before possible So before I get into that I want to talk to you a little bit about crop production I think a lot about farming I worked on a farm as a child and I enjoyed working on the farm The crop I liked the least was tomato happened to be I won't explain why but if anybody's interested I can tell you after during the cocktail session But essentially this is what you would might think about and i'm sure many of you in the crowd have grown your own tomatoes in the garden Maybe five to ten plants your favorite varieties or heirloom tomatoes You put them in in the spring and after maybe two months if you've done a good job You have a green thumb you'll come and you'll harvest like this fellow here a nice bucket of red tomatoes But as we also know we often are a little bit lazy But we don't want to put in the effort to grow these luxurious tomatoes from our garden and we're willing to settle for those Hard rather tasteless tomatoes that come out of fields like this And this is what I want to show you about real agricultural production using tomato as an example You can think of the same for corn and for sorghum And so this is a fresh market tomato production in field Which is where most of the fresh market large-fruited tomatoes come from also from mexico And these plants are essentially grown in these very long rows Where people's will come during harvest time and put them into these bins They'll walk these bins down these very long rows And they'll collect them when they're greenish orange-ish and they'll put them in these trucks These trucks will get loaded to completion and after they're completely loaded They'll be removed from the field in this long caravan of trucks And essentially taken to storage until they'll be gassed with the hormone to cause them to turn red As much as you may not want to hear about that This is the reality of how a lot of our fresh market tomato production is generated And in order to feed this growing population We will have to realize that this is a part of an integrated system where we have large-scale production As well as what we you know would appreciate going to farmers markets and more organic sustainable Sustainability types of production. So this is fresh market tomato production and one thing I think you can see here and if you've grown tomatoes in your own garden You may know that oftentimes they become very tall and lanky and very large extremely large These are large, but they're not as large as you might see growing in your home garden from heirloom tomatoes In fact, these are a lot more compact and this is why they're staked here They won't grow much higher than that and this compact determinate plant is one trait that I want you to focus on this term called Determinate which makes essentially this very compact plant which allows it to grow in three to four months to completion In which case you come in after the three months You're harvesting your yield you're out You're turning over the soil and you're putting in a whole new crop after that Okay, so this determinant growth was a major change from the heirloom tomatoes and also the wild ancestor The wild form that was domesticated. We heard about corn domestication Tomato also had a wild ancestor that was an indeterminate form that would become very large in the field much like a tree Now that's for fresh market tomato production the need for having these compact determinate plants The same is true for production for processing. This is ketchup sauces soups juices Tomato processing production depends on having these determinate plants these compact plants Because you can harvest them in rows on a combine This is a machine known as a combine and this machine is coming through the field cutting the plants from the field Separating the green parts of the plant the vegetative parts from the fruits You have mechanical annually grading the quality in the fruits They're then loaded onto these large 18 wheelers and this is my favorite part looks like it's puking here. This is great There it is. Yeah, so And so this is a massive production and and again It's all because of this determinant compact growth habit and one other trait one other mutation that i'll tell you about So I will tell you a story of two genes of how did we achieve this? Can we do a better job and using tomato as an example? I hope to convince you that we can So how did this compact plant growth habit come about? Well, it came from a natural mutation and this natural mutation was first published in a journal in 1927 It had been discovered a few years earlier in a farmers field in florida And he was growing the typical indeterminate Plants that would continue to grow from the stem cells up here much taller much higher And he found randomly one plant a single plant That he called self pruning And the name speaks for itself This plant was a rare mutant that self pruned So obviously he didn't know the gene that was involved. He didn't know the specific Change in the dna code that occurred But he knew that this was a rare mutant plant And when this was donated to a researcher eager he essentially said Appropriately that selections from this cross population should give us a valuable new race of early tomatoes Why early tomatoes because instead of continuously producing These flower and fruit clusters over a long period of time and having progressive fruit set and ripening now these Compact determinant plants have a burst of flower production a burst of fruit set and essentially uniform fruit ripening Which allows you to go in and harvest in one go after three months And this is a better reflection of what the difference is This is the kind of cultivation that goes in greenhouses or glass houses You might buy tomatoes on the vine from europe that come from holland or perhaps from canada Where you prune the plants to one main shoot and these plants will grow for 10 to 12 months And you'll successively collect these high value expensive tomatoes Over the course of that 10 to 12 month growth period Here is that bushy determinant growth where you have this about probably 20 pounds of fruit on this plant In a three month period allowing you to have this burst of fruit production and yield that can now be harvested in florida and california In those processing ways Now the second trait that was critical was discovered by the father of tomato genetics Who I happened to have a pedigree with through the history of my training over the last 15 years Dr. Charlie rick who passed away sadly in 2002 used to visit South and central america to collect wild relatives of tomato including defining the true wild ancestor of tomato And one close relative came from the galapagos islands This species here known as selenum cheese mani eye He was walking through the fields and he he wasn't sitting here all the time on the turtle like this but He had a good sense of humor But basically behind him are these tomatoes that are growing these rocky outcrops And he happened to find a rare natural mutant Where it's a little hard to see it'll become more apparent in the next slide This stem leading to the fruit doesn't have what's called a joint or an elbow now next time you go to the grocery store You'll never look at tomatoes or corn or or grapes the same way after this In this case, I think you'll you'll you'll really remember this one when you go and look at tomatoes on the vine You'll see something like this either it has this swollen part What we call loosely a knuckle or a joint Versus not having it and so what that happened what happens when you have this knuckle And this is what you see in wild plants and also the heirloom tomatoes Is that when the fruit is pulled from the plant it separates right from that knuckle? That's a natural what we call Obsession zone a separation zone because the fruit naturally wants to fall to the ground rot and then spread its progeny seed for the next generation Now this natural mutation that dr. Rick found Completely eliminates That knuckle and that joint and so what happens now when you harvest the fruit you completely separate from the stem Why is that important? Well, if you're loading these into your bins you have to manually remove them You might say well, why do I have to remove them in the first place? Because as the fruits ripen especially in the california processing production They poke the neighboring fruits and you have post harvest fruit damage It's a major problem with processing and all processing tomatoes and now many fresh market tomatoes Have this Jointless trait this second mutation and here's a real summary of you just go back to the moon I showed you from california the jointless trait allowed this and the self pruning trait mutation allowed this Okay So we know that these two examples are mutations that nature has provided nature has provided thousands of mutations For domestication and for breeders to be using in crop improvement. We heard that from doreen We saw examples from day But what I would like to argue and it's a nice time for us to then sit up here after and perhaps have a discussion Is that nature hasn't given us enough? So all of those sequence genomes that we have from corn and from tomato and from grape is revealing The base changes it's revealing the jumping gene differences and where they've moved from one to another place In the different genomes of corn or tomato But the problem is is that even though we have thousands of these mutations Perhaps these good mutations are not in the genes that we want them to be in And what if there are no mutations in those particular genes? Or what if we want to have different mutations in genes that we know when they have mutation a did a good thing But maybe if they had a different mutation that gene it would do that same good thing even better Okay, so here's an example From my lab in tomato. These are cartoons of plant architecture This is you can imagine just a cartoon of the self pruning mutation or the mutant plant Which again itself prunes and what we had Early on in my work. It was a theory or hypothesis that perhaps we could find Second mutations in other genes that would relieve or partially suppress The compactness of this plant now. Why would that be useful? Because if you have a slight relief of the self pruning effect Maybe you would get a few more shoots a few more flowers and a few more fruits Before the self pruning kicked in in other words a slightly larger plant More flowers more fruits more yield. Okay. Now, how did we go about doing this? Well before we had the technology that doreen mentioned before and and also david called crisper Which I will explain in a few slides We didn't have the ability to say well I want to mutate this specific gene to get this suppression or relieving of the Determinate compact growth habit So instead we had to use techniques that breeders have used for more than a century to induce new variation New mutations in the genome, but this is occurring randomly Now, how do we go about doing this? I can't give you the details I'll give you a little snippet. You can take seeds of tomato You can take pollen of corn and you can treat them with certain chemicals that obviously you wouldn't spend too much time around yourself Because they essentially modify the dna to cause problems during the duplication of the dna that lead to randomly Accumulating mutations now that's a good thing in terms of creating new variation But it could be a bad thing for the plant because if you create too many mutations the vigor of the plant will go down Maybe you won't even get any fruits because there might be sterility But if you hit the sweet spot in terms of creating the new mutations You can do an experiment like this where you have this cartoon showing you mutations And then you can walk through a field and this is a field from out east where we grow some of our fields every year And you can scan not from the sky walking the rose You can look through the rose and find like in 1923 when they discovered that rare mutant in the florida field We can now find the rare mutants that we induce that might suppress the compact habit and give us more yield So we did this but it's very inefficient It worked it took us about four years to get to the point that i'm about to show you Where we have a toolkit of new mutations A whole collection of mutations in the same genes and also new genes that when we combine them by making hybrids as dave talked about We can have this vigor effect where we can go from the traditional yield from the original The shorthand name is sp for the self pruning mutant We can have different mutations on top the codes and the names don't matter you can ignore them But essentially lead to a new higher yielding tomato plant mutations upon mutations So this worked but we would really like to have a faster and easier way to achieve this This is where we start talking about the concept or the technology known as crisper gene editing And for this I need to have everybody forget about plants for the moment and think about something that's decidedly not at all related to plants And that has to deal with bacteria So many years ago it was discovered that bacteria have an immune system It's not the same type of immune system that you and I have It's a different kind of immune system to protect them from being infected by viruses. Yes, bacteria can be infected by viruses These are called bacteriophage. They literally look like these little moon landers Where they sit on top of the surface of the bacterial cell and they'll inject their dna They'll replicate their dna and then they'll essentially kill the bacteria Okay, so what bacteria have evolved are molecular scissors to be able to recognize The first infection chop up with these molecular machines, which we call enzymes The dna from the virus into little snippets Then it takes those snippets and I believe me when I tell you this it inserts those snippets into its own dna And so the next time it's infected It's constantly reading off of its own dna and providing a surveillance system to say Oh, does that snippet that I put in my dna from the old virus? Does it match the new one I'm being infected with if it does it then matches up? And it will cut with the molecular scissors the virus coming in now Why does this have to do with plants and our complex relationship from Dave's title? And here and and why we're here tonight talking about how we can improve crop yields using research Well, it has to do with some very smart scientists who said let me take this immune system And engineer it in a way so that I can use these molecular scissors in any organism I want To create cuts in dna in any dna that I want Now you might think well, why do I want to do this? Well, we've been talking about mutations and how there are good mutations So now we know that there are genes that might have an increase in the stem cells Okay, so maybe we want to mutate that gene to get more stem cell Now you can use this crisper gene editing system to create breaks in dna This dsb start stands for double strand break because dna is double stranded and so you create a break now Once the break is made say well, what happens the cell doesn't want that break it will repair that break But when it repairs the break It's not that efficient and so you end up creating mutations during the repair process You can think of it as the equivalent of a scar Now that mutation now can effectively eliminate the activity of a gene And so here's an example of using this technology just in the last two years To create disease resistance by creating targeted mutations in plants and the example has to do with wheat Where some scientists in china had published An example of using the crisper gene editing technology To mutate a gene that is essentially like a lock and key mechanism when it's infected with this powdery mildew We heard about powdery mildew in grapes wheat also is infected with powdery mildew You end up with these yellow spots. You have dramatic yield losses The lock and key mechanism is that you have a key that is a lock that is Recognized by the key coming in from the pathogen or the disease and if you create mutations in the lock The key cannot infect essentially that's what's happening here And so you can create targeted mutations in the genes that they believed would create resistance And they were able to create resistance in one step What does that mean one step essentially one generation one generation is about a year And so in one year they achieved What would have taken thousands of years of breeding in domestication or in breeding in the last You know hundred years if the mutations even existed it would have taken probably 10 to 15 years Here's an example that we've done in our lab in tomato Let's bring you back to the knuckle and the joint and the jointless trait Here we have a cartoon of a normal gene right here. These are the controlling dna pieces that turn the gene on and off during growth You have normal gene normal activity We can now Molecularly cut with the scissors and the crisper technology the jointless gene And this is a variety of tomato that we work on a plum tomato where we've now in one generation Eliminated the joint so this can be done in any variety and so you may ask well I already have the jointless mutant. I already got it from nature. That's right But now you don't have to cross between varieties to bring that desired trait in mutation Into other varieties over many years of breeding now in one generation you have the trait that you want So that's a very black and white change What about the fact that in breeding there are often examples in fact many of the examples involve less Damaging mutations to genes that have much more subtle effects on growth These were essentially major players in domestication and in breeding why because often you want to have just a little tweak You can think about The volume on a radio you don't want to go too low You don't want to go too high you want to be at the goalie lock state where your ears aren't hurting So in often case oftentimes these traits that you see here For example the number of rows that you have in barley or the number of pods on soybean or the clusters Of flowers and fruits and grapes are based on not major changes in genes and the mutations But more subtle changes in in the genes through subtle mutations So then we started to ask can we create using the molecular scissors A range of changes in yield traits in other words Perhaps we can create a continuum of changes from very weak effects to moderate effects to stronger effects So in this case we don't want to create mutations in the gene itself because when you make the break and you repair That essentially kills the gene. It's done. It's not going to work anymore But I mentioned earlier that these little lines here represent the dna that control when the gene is turned on and off during growth So what about if we use the molecular scissors to mutate these regions? And so we can now create a range of mutations a collection of mutations, if you will In the controlling dna without hurting the gene itself Just the level of activity of the gene like you saw from dave, but in a much more directed way You can create a range of reduced activity and here we can in fact only recreate The kind of yield gains that I showed you from our random mutagenesis But now even though i'm showing you the same picture, trust me, it works the same way We can in fact change the activity in this case of just the self pruning gene so that we hit a sweet spot Where you have more flowers and more fruits Okay, so we have the ability to fine tune these traits in a very directed way because of this new adapted bacterial immune system that can create mutations in essentially any organism of of your liking So final slide is that crisper has the power to enhance breeding by rapidly customizing and optimizing productivity And this customization and optimization is something i'd like you to leave Here with in your minds is that with these technologies you can now go into sorghum You can go into corn you can tweak the stem cell numbers so you have more rows and any variety you want You can mutate the gene that increases the number of kernels from two to three or four in the sorghum And any sorghum variety you want and you can do the same in tomato So we're at the precipice of a basically a revolution in crop breeding because this gene editing And with that i'll say thanks very much. Thanks to my colleagues for setting the stage And if you'd like more information you can get it here Okay, i'll invite uh, dave doreen and sack uh up to the table and they'll be more than happy to entertain questions from you I get that question every talk i give Every talk, um, I have a colleague in florida at the university of florida. His name is harry clea And he's been working on flavor and fruit quality traits for the better part of 25 years And he is doing exactly the kinds of things that we were talking about today But going after genes that essentially Were lost during breeding the flavor genes and he's trying or in this case They were bad mutations and he's trying to correct those mutations to bring back those genes that give you the volatiles that you smell And of course the sugars in the acidity that you taste um When you get yields from plants in a field and you're getting larger yields like from corn or tomatoes What is the detriment is there less soil uh, is soil depleted more or is it all just plus plus Well, if the plant is yielding more it will be taking up more nutrients from the soil But on the positive side we can produce more yield from a smaller land area And so overall We can devote less land to agriculture use more land for natural resources or So you you essentially need more fertilizer to promote the Well, so fertilizer is a complicated issue as dorian brought up. I mean that There are other scientists are working on on that issue. So some plants actually don't need much fertilizer so legumes for example naturally fixed nitrogen from the air through associations we have with with bacteria And people are actually working on ways to try and introduce that Process into other crops. So maybe in the future we can use less fertilizers. So a larger plant yield product Is not as detrimental in other words if you get a hundred percent better yield in corn, you don't lose a hundred percent Neutriment in the soil Yeah, that's right. I mean basically Part of the issue with yield is the plant deciding how much of its biomass to put into the The corn or the tomato the fruit In nature wild plants Want to tend to hang on to a lot of their nutrients and they put a small amount into a small number of seeds Right, they want to survive for a long time But that's not what we want in agriculture. We want plants that will produce All of the yield at the end of the season so that can be harvested Easily as as Zach mentioned for the tomatoes There's some there's some other strategies as well. There's a difference between an annual plant and a perennial plant So for instance, if you we could make corn a perennial plant Then all of the investment it makes into the root structure can be reused again And so as as Dave was saying, there's Several strategies that we can think about applying and we can learn from for instance, soybean that's able to fix and we can think about Can we apply that could we perennialize plants and save that way as well? So there's several strategies to improve that Hi, I have a question that may have some political implication also, but how much of your research And work being done on a genetic level qualifies as creating genetically modified Plants now and the reason I'm asking is I had the opportunity this summer to visit A large corn manufacturing pioneer hybrid out in iowan We toured the research facilities and at the end of the tour, which was actually walking through the cornfield labs They were very proud to say that none of the products of the none of the hybrid corn that they have is genetically modified It's purely hybrid a hybrid which is Very much different that what you're talking about. So my question is how much of the research That's groundbreaking that's you're doing ends up in our plate essentially with you know, how much of our tomatoes now Are genetically modified based on the work that's being done Does that make sense what I asked Does your does all of your research qualifies creating genetically modified plants now? Because I know that essentially a lot of what we are eating nowadays Is genetically modified whether we like it or not for the better or the worse So I can I can speak to some of those items. So The example of those randomly induced Approaches to create novel mutations is not considered genetically modified. So in fact If you looked at I'm not sure seeds that were generated in the 60s to get those mutations they used multiple approaches including a radiation Chemical and those weren't considered genetically modified and still are not considered genetically modified with regard to our research Right now the concept of crisper as far as as the united states department of agriculture And what's happening right now as far as policy Is they're making decisions on on basically the size of the mutation may actually contribute to whether it's defined as as A gmo or not because is um in my talk I hope it came across that in nature we normally see Very very large rearrangements happening all the time Very small rearrangements. So much of the work that we do to understand biological mechanisms And then approaches to deploy them for instance is crisper at this point in time would not be considered gmo's It also is it should um, there's been a lot of discussion and this could be this is politically You can think about this Many of you are familiar with Um Being a drug to market Costs a lot of money to bring a drug to market not all drugs are brought to market There are a lot of drugs that are dealing with orphaned diseases that are never brought to market because the cost of bringing to market is very high The cost of bringing a gmo plant to market Is in the range of bringing a drug to market Which means that there has to be enough value or money to To push that forward and usually that That value chain a return on investment happens for the farmer Not you as a consumer What's really exciting to me as a research Is some of those things we're talking about like flavor changes for instance Are now tractable to bring to market In a way that we couldn't bring to market before using other technologies because we can now bring these to market with a very um with the Licensing and things will be very very different. So the potential to bring to market to you Beneficial items like that flavor, right Is now tractable in a way that was never ever tractable under our existing policies And regulations for how a germplasm is introduced to the market The same thing is true for dealing with for instance disease as we were talking about You know, if you had a choice of modifying the plant so you no longer had to put pesticide on it or Continue to treat that That plant with a lot of pesticide Which choices would you want to make but the regulatory policies over introducing them now using Um traditional gmo approaches is very costly. So we would continue to use pesticides Does that does that help um Yes, just just a second that nothing that any of us talked about this evening is gmo. So it's um, there's a strict definition of gmo's is as we understand it is Where people have taken a gene from a different species say from a bacteria And put that into the plant genome So none of this is Is that technique we are just modifying plant genomes in a very similar way to which humans have modified plant genomes Over the last few thousand years to to domesticate plants So this is not yeah, this is not gmo I uh wanted to ask about uh the plasticity of uh the genomes You were talking a little bit about the corn having a great deal of plasticity over more than the uh Um grape I believe so you I was wondering about like the uh potato and tomato and the rice as uh their genomes have About the same amount of plasticity So so if we look at the existing rice genomes We don't see as much changes as we see in maize maize seems to be almost like on steroids with regard to its its plasticity, but The other way we can think about it is We've only had an opportunity to look at a few genomes Right, so so this is a real time for discovery to see um How frequently we do see things like that. I mean most of our genome sequences so far have been on domesticated plants which have been under specific selection That we've put it under so I think I think what we're gonna find there are a lot of differences But every every organism has a slightly different strategy on on on how it may adapt It's it's genome architecture will also Allow it to have different ways to adapt as I said in in humans It's it's not a successful strategy for us to double chromosome That leads to cancer It's not a successful strategy for us to To double a gene number because that could offset how how different components in the genome work together Yes, it does Many plants are wind pollinated including Corn and sorghum So how do you prevent the spread of the CRISPR modification going to the neighbor's field? And the second question is uh, what is the story with patenting? I'm assuming the modified seeds are patented What does it mean to the farmer who wants to grow his corn organically? So two excellent questions so coming back to this question of Whether it's a GM or not so you can think about the CRISPR technology As a hit and run So you you use the scissors to create the hit and then you get rid of the scissors they run away You can do this through traditional crossing and so you're left with the equivalent of what a mutation would look like through natural processes so what I would say is that That's now one new mutation in a collection of many naturally occurring mutations Which in and of themselves you can put on the same plate in terms of whether there's a concern about them spreading And and it really attests to the fact that the CRISPR technology Is not about bringing in foreign dna and worrying about that foreign dna then spreading through wind pollination It's more about just working with the dna that the plant has already provided and enhancing the natural processes so um indeed With wind pollination if there are wild relatives nearby The CRISPR edited scar if it can cross pollinate with that wild relative the mutation among the thousands of mutation that are already there Will spread and cross but so will the thousands of other mutations So I guess what i'm trying to Impress upon you is that the CRISPR edit mutations should be No of no more concern than the naturally occurring mutations. They don't really create anything foreign in the plant As to the patent side of that we need an hour To discuss what's going on So i'm not sure how much people have followed and i'll try to sum it up in 30 seconds There was a co-discovery made of the re-engineering of the bacterial immune system from uc berkeley and mit and The two had discovered it essentially around the same time the uc berkeley team had filed for the patent first The mit team filed for its second, but they took an accelerated track You can pay to have a faster review of the patent application And they were awarded the patent before Now the berkeley side has contested that And we're all waiting and there's big big big money behind this and it will go on for years One very interesting thing is that since then there have been other Molecular scissors that have been discovered versions of those molecular scissors We heard from doreen about Different genes and how they can come for example our genes resistance gene families Well the molecular scissors are encoded by genes and they come in related gene families and those have since been patented And so those may now come into play and how the original patent situation works out So the question about when it gets to a farmer is going to take some time But there's a lot of money behind this And i think for a very good reason because as i said it will be transformative to agriculture And it should be added to the toolkit So i'll just add to that. Is that talked about the patent on crisper? But i think maybe your question is more about patents on actual seeds that companies generate So so a lot of seeds breeding of seeds for farmers is done by companies And they patent the lines that they breed to protect their product, right? I mean like any product if a company makes something they want to have protection so that if they develop something somebody else could just come along and Propagate those seeds and sell them for half the price whereas that company You know spends millions of dollars in in the breeding process. So there is a patent on the seeds. I think those patents last about 20 years after that No, there are Not gmo's just just regular lines that companies are breeding Plasm germ plasm variety they have variety releases and they have certain identifiers associated with them Oh, so So germ plasm when a germ plasm variety is released It will get a certain identification and it will have a certain amount of time where that variety Is The equivalent of patent it but it's it's with the germ plasm variety release that happens with that What's What's the nutritional difference when you have such an increase in yield? um Are you seeing less nutritional value in the plant because you're pushing it so hard In the actual for itself. Yeah So We the question is whether there's a nutritional hit when you have increases in yield and what that hit is And also quality traits That often depends on the mutation that has been created to increase that yield And also this is a question about the overall physiology of the plant So the leaves are essentially the machines that are making the factories of sugar And then that sugar gets pumped into a sink. We call this a source The leaves are the source of the sugars and the sinks or the fruits and the seeds are also a sink And so you have this relationship where you don't want to have this pendulum swung too far to the sink side Because now you're spreading a limited pool of sugar to a larger sink So it relates to dave's goldilocks and and also why I talk about customization as opposed to optimization Um Those two are related you want to customize and then optimize to that right balance of growth And in our own data, we do know that there can be a hit in terms of flavor Sweetness sugars if you go too far with the yield And so with the crisper technology We can create mutations that are at the right sweet spot in terms of their activity So we haven't swung the pendulum that far Who I just wanted to that was great what you said earlier About she asked can you bring back the flavor of tomatoes? So that necessitates that there once was a flavor and that it was there and I'm curious when did that disappear? and and who Is responsible for that And and And and is that worldwide or is it just the tomatoes that we get here in the united states because I I've spoken to a lot of You know immigrants people immigrated here over the years And a lot of the commentary that I get is that you know back home on in the fields on the farm It's jam packed with flavor And we have these dead You know dead tasting plants here. So so this happened Over the course of domestication. There was a selection for yield traits ripening traits that essentially Without getting to do too much detail. They purged the flavor versions of the genes The ones that are most flavorful if you will providing the most flavor They've been able to now go back and look at the the molecular pathways That control those flavors and they're able to discover key genes That the versions of those were lost and they know the versions they want and the hope is to bring them back This is all within the last probably 150 200 years of breeding But I think in many ways it was a necessity because as you start to play with flavor You're connected to ripening and when you're connected to ripening and flavor you're you're connecting to shelf life And so the need to perhaps remove those was was occurring because There was that kind of production that I showed you in florida, right? So you may not like that as a flavorful, you know, it's not a very flavorful tomato But there may be now a way to put in step by step to find the sweet spot No pun intended Where you get a little bit more flavor in or even more to the point where we're satisfied Without compromising the types of large-scale production that needs to to have So this is kind of a two-part question The first one is that I recently read a paper on the use of the crisper cast 9 system For the evaluation of off-target effects And so do you guys think that within a few years scientifically we would be able to Quote unquote prove or get very close to definitively proving that there are no Unwanted side effects and GMOs So and then the second part of the question is assuming that is true It's very clear that the public is not going to absolve their fear of GMOs overnight So what can scientists do and the scientifically literate public do to help educate and remove such a fear? I can try to address that so Just to explain the question so He was referring to something called off-target effects So Zach described this very precise molecular scissors that goes to one gene in the genome And cuts it and makes a mutation that except through the spot You want to mutate or change? But you know nothing is perfect And so there are there is a phenomenon of off-target effects, which is Sometimes those scissors can end up in a different part of the genome And make a cut in a different place This is really a big issue in the idea of using this in humans Right potentially we could use crisper to fix genetic diseases a lot of diseases We suffer from a genetic and if you have these off-targeted effects where the scissors go to a different gene and like that That's a big problem. It seems that implants off-targeted effects are much lower. So we don't Generally people are not too concerned about them people have sequenced The whole genomes of crisper Modified plants and have not found that off-target effects are very Extremely low frequency. So it's not really an issue Coming back to whether there's a concern about GMO is again to echo what Zach said and Dorian as well It's considered that crisper is not a GMO, right? So we're using this To modify the genome but in a similar way to which breeding or natural selection could modify it So it's not not a GMO in that the defined sense where we brought in a gene for another organism because that gene is taken away Right. So making a GMO are there off-target effects. Could you affect something in the genome? When you introduce this other gene? So, yeah, this is something that's very heavily regulated and in fact The reason why there are so few GMOs on the market right now Mostly only corn and soybean are GMO most of the crops we eat most of the plants we eat are not GMO And that's because any GMO goes through very extensive testing similar to What a new drug that was would be coming to market? So it goes through FDA testing goes through environmental ecological testing. So so yeah, so generally You know those tests don't come up with any off-target effects or unexpected effects In fact, some companies actually Have a way of targeting the transgender one position in the genome And they know that that position doesn't have any genes that could cause a harmful effect if modified I wanted to thank you for the education this evening And I wanted to return to a framing principle of the dialogue related to food security Some hard numbers nine and a half billion people to feed by in 33 years And diminished arable land and increased challenges on the arable land that we have And then you you brought up diseases blast rust and others that challenge the growers of the food that we eat today and perhaps in more exposed areas where Small holders are serving small villages or themselves Without capacity to put to work The innovations that you're pioneering here to relieve them of the threat of starvation I think the job ahead is overwhelming how Can you and colleagues of yours Get these life-saving technologies To communities that are far and dispersed on the planet To prevent them from losing crops We saw in china 60 million people in a year's worth of of crop loss There Clearly if that happened in small villages in africa that would be Catastrophic in terms of lives lost What is the strategy to proliferate your work in the work of your colleagues elsewhere To make sure that this doesn't happen We're sitting here tonight talking to communities as an example. I think what we really As scientists often were guilty Of not speaking in a language that's so easy for others to understand I can tell you that This is the first time that I had practiced for a talk in a long time And and I don't know about david orine, but we all practice together um One of the real challenges that we have is educating the public we we want these questions We want to be able to explain in the simplest terms the kinds of techniques and technologies that we're using And the hope is that we can dispel myths And also at the same time elevate the knowledge Across the divides so that others can feel more comfortable asking those questions that that Don't surround myths and and I don't want to get into discussions of myths We touched a little bit about it on the tonight, but it's really about education and communication On the scientific sense. We're always collaborating with people outside cold spring harbor to do our research Dave and I collaborate together doreen and I have collaborated together and we collaborate with outside institutions And we also collaborate with industry in the hopes that we can translate our discoveries to industry And not necessarily the big corporations that are probably running through your minds right now Also some smaller companies that are starting up that are trying to take this technology and educate the public in the right way So we really feel it's a lot about education and communication So let's thank that doreen and dade for some great insight Can please join us. There's a coffee reception out in the lobby