The Future of Food: Genetic Improvement Meets Sustainable Agriculture

– Good afternoon, I’m David Ackerly, Dean of the Rausser College of Natural Resources at UC Berkeley The Department of Plant and Microbial Biology is one of the five departments in the college PMB is pleased to announce a series of events and programming in honor of the department’s 30th anniversary Like all of you, we had hoped these events would be in person, and hopefully we will come together in the future And for now, we’ll come to you virtually, and hope we can reach a really broad audience that way To commemorate its three decades of research, teaching, and service, PMB is hosting a series of online talks through 2020 that cover topics which reflect the department’s deep contributions to fields that include the basic biology of plants and microbes, applications of CRISPR-Cas9 to agriculture, innovation and entrepreneurship, and close ties between industry and academia Please visit the department’s website at pmb.berkeley.edu to watch for announcements of future events You may have heard the inaugural talk on June 12th, titled “Of Virulent Viruses and Reservoir Hosts” with PMB professor Blip, excuse me, Britt Glaunsinger, as it was featured on the Berkeley Conversations COVID-19 series The talk was recorded and can still be accessed at the Berkeley Conversations website Today’s talk is on the future of food I’m pleased to moderate today’s panel discussion with two people who are very well-known to the PMB and Rausser College community We’ll be taking live questions via Facebook Live or YouTube Live, whichever format you may be listening in, and we’ll come to those a little later in the session We’re also recording the talk, and it will go live shortly after we wrap up today Brian Staskawicz received his PhD in plant pathology here at UC Berkeley He is currently a professor in PMB and the scientific director of agricultural genomics at the Innovative Genomics Institute Brian has made many seminal contributions to the understanding of infection strategies of plant pathogens and defense mechanisms of plants These include the cloning of the first pathogen effector gene and the cloning and characterization of one of the first plant NLR immune receptors Brian and his colleagues also played a major role in establishing Arabidopsis as a model system to study the molecular basis of microbial recognition by plants and genetically dissect defense signaling pathways More recently, he’s leading an effort at the IGI in genome editing of agricultural crops for biotic and abiotic stress resistance and improved plant performance In 2013, Brian was awarded an honorary doctorate from Wageningen University in the Netherlands He is a member of the US National Academy of Sciences and a foreign member of the Royal Society In addition, he has been elected a Fellow of the American Phytopathological Society and a Fellow of the American Academy of Microbiology In 2019, Brian was awarded the International Society of Molecular Plant-Microbe Interactions Senior Investigator Award for his many contributions to the field of plant immunity Pam Ronald received her PhD from Berkeley’s PMB Department in molecular and physiological plant biology She is recognized for research in infectious disease biology and environmental stress tolerance Pam was a postdoctoral fellow in plant breeding at Cornell University and joined the faculty of UC Davis in 1992 In 2019, she was awarded an honorary doctorate from the Swedish Agricultural University She’s a faculty scientist in Berkeley Labs Environmental Genomics and Systems Biology division, and a Key Scientist at the Joint BioEnergy Institute She’s a faculty affiliate of the Center on Food Security and the Environment at Stanford university A National Geographic Innovator, Pam was named one of the world’s most influential scientific minds by Thomson Reuters, and one of the world’s 100 most influential people in biotechnology by “Scientific American” She is a member of the National Academy of Sciences She is coauthor with her husband, organic farmer, Raoul Adamchak, of “Tomorrow’s Table: Organic Farming, Genetics, and the Future of Food” Bill Gates calls the book “A fantastic piece of work and important for anyone that wants to learn about the science of seeds and challenges faced by farmers.” Her 2015 TED talk has been viewed by 1.7 million people and translated into 26 languages She founded the UC Davis Institute for Food and Agriculture Literacy to provide the next generation of scientists with the training they need to become effective communicators In 2019, Pam was awarded the American Society of Plant Biologists Leadership in Science Public Service Award

Pam and Brian are here to discuss the role of new agricultural breeding technologies in the quest to feed the world’s growing population, while enhancing the sustainability of our agricultural practices around the world In a world approaching 8 billion people, with most of the available arable land already in use for agriculture and the threat of a rapidly changing climate, this challenge has never been more pressing and immediate Brian, can you set the stage for us by describing the scope of the challenge in front of us in relation to the work you do and the topic of today’s discussion? – Great, and welcome to everybody this afternoon It’s a pleasure to join in this panel As David said, our world’s population currently is about 7.9 to 8 billion people, and it’s predicted by 2050 to reach 10 billion people And unfortunately we have to basically grow food greater, more than 70% increase in production during this time period to feed the world Unfortunately, also that this is exacerbated by climate change So being able to grow this food in an environmentally sustainable fashion is gonna be extremely important As I mentioned, climate change really will have a major impact on disease pressures in plants We already know that pandemics, such as wheat blast, are occurring in Bangladesh in India because of various jumps and hosts In addition, many plant disease-resistance genes are also temperature sensitive which, as you can imagine, as the climate increases, the temperature increases, the effectiveness of these genes will be lost So to meet these challenges, new technologies will be needed to increase food production In addition, high-input, resource-intensive farming systems, which have caused massive deforestation, water scarcities, soil depletions, and high levels of greenhouse gas emissions, cannot deliver sustainable food and agriculture production Obviously, there are no simple answers to these problems, but we have to find a way to produce food in an environmentally sustainable fashion, that is, we need to decrease farmer inputs, such as water, fertilizers, and pesticides I am optimistic that we are developing the tools to accomplish these goals, and this will be the subject of some of the talk today Thank you – Thanks, Brian Pam, turning to you Can you elaborate more on what means when you think about making agriculture sustainable, locally and globally, and into the century ahead? And put that in the context of these very fundamental challenges that Brian has laid out – Yeah, I think Brian pointed out some really important goals for all of us, that using land and water more efficiently is going to be critical Most of the arable land has already been farmed, So the land that we have we need to use much more efficiently And Brian also mentioned reducing harmful inputs There are other challenges, such as maintaining soil fertility, will continue to be really an important goal for farmers and maintaining farmland And we have to think about farmers themselves, how they can thrive economically not only in the United States, but in other parts of the world And finally, we really need to be sure that we can keep food affordable for even the poorest people in the world And I’d also like to thank you for including me in this conversation, and I’m really pleased to be here and appreciate the audience for joining in – Thanks, Pam Brian, I know when you teach here on campus, you paint a picture of the broad sweep of the history of agriculture for our students and putting our modern challenges in context So if you go back to the beginnings of agriculture, farmers and plant breeders have worked together and in parallel over many centuries to bring us the crops that we have today Can you share a little bit about that history of crop breeding and how it brings us to the technologies that are available to us today? – Absolutely So as we have discussed in my classes a lot, all plants, many people don’t know this, they have a geographic origin in the world For example, corn, or maize, was originated in Mexico, rice and soybean in Asia, and wheat in the Middle East So these are distinct areas Agriculture is considered to be approximately, and depending on the studies you read, between 10 to 14,000 years old And all our modern crops rose through the domestication of these wild relatives

that originated in these parts of the world As plants were domesticated, plant breeders deployed these ancient varieties as sources of traits that they introduced into modern day varieties by classical plant breeding, meaning taking pollen from parent A and putting it to parent B and getting progeny from that So just classical plant breeding, making genetic crosses In fact, plant breeding as a science was only developed in the early 1900s And as we know it today, has become extremely sophisticated and deploys modern tools of DNA marker-assisted breeding, and also employs crop genomics But unfortunately, plant breeding is very inefficient It takes many years to introduce these traits into our high-yielding agronomic varieties that we use today Thus, new breeding tools, that we’ll discuss today, will be needed to breed varieties faster and more efficiently, so we can adapt to the climate changes that are occurring throughout the world today – And we will definitely circle back and talk more about the actual, the mechanisms of what we mean by those new technologies But Pam, if you think over the course of your career, can you just give us some examples of what it means as a researcher to be on the ground, so to speak, or in the lab, applying these technologies, or the kinds of traits that you’ve worked on, the crops you’ve worked on, and what it’s meant to be a scientist involved in all this work? – Well, it’s been really fantastic to be involved in plant biology for so many years, and I had the privilege of working with scientists at the International Rice Research Institute, really from very early in my career So I was trained in Brian’s lab, lucky me, and learned a lot about disease resistance And when I began my first postdoc and first position, I worked with Gurdev Kush and others who had discovered a wild species of rice that had a really important gene for resistance And so many of the resistance genes that we use and that are in our crops have been derived from some of these ancient varieties or diverse species And so, that has been something I’ve I spent a lot of time working on, trying to understand the molecular basis of disease resistance in this wild species of rice from Mali And then, more recently, I had the honor to work with David Mackill, he’s at UC Davis Cornell with me, but also had spent time at the International Rice Research Institute, brought to my attention the challenges faced by farmers growing rice in many parts of Asia, primarily Eastern India and Bangladesh, who often lose their crops to flooding So flooding is predicted to be increasingly common as the climate changes, and most rice varieties will die if they’re completely submerged for more than three days So Dave and I were able to isolate a gene that conferred resistance, or tolerance, to this flooding And the International Rice Research Institute, led by Dave and his colleagues, were able to introduce this gene into varieties grown by farmers in Bangladesh and India using marker-assisted breeding, which Brian mentioned, which is a genetic technique that’s not regulated and has been really important for developing new varieties So this variety does really fantastic So even after two weeks of flooding, the plants can survive and thrive So the plants that have this gene have about a 60% yield advantage And this is really important for farmers in Eastern India and Bangladesh, who are able to harvest grain, even in the face of a severe flooding And last year, about 6 million farmers grew this rice, which is called Sub-1 rice – Pam, I wanna follow up briefly on a comment you just made, ’cause you talked about the traits that are important for farmers And then of course, for those of us who are on the other end, eating the food, the question is what are the traits that as consumers we’re looking for? So as researchers and as plant scientists, what is that balance of the traits that farmers want and the traits that consumers want in the ones that have drawn attention in the research community? – Just one thing to keep in mind is for a crop like rice, the farmer is a consumer, so most people that are growing rice

in less developed countries are subsistence farmers So that means that they grow really only enough rice to feed themselves and their families So when a farmer has the ability to grow rice, even under flooded conditions, that means that they’re able to feed their families and sometimes even sell some of that rice to bring in some income that they can use to support their children’s education, for example And then, if you’re in a developed country and are possibly not concerned with how farmers are able to grow their foods So there are many different types of traits that consumers in developed countries are interested in And particularly, people are interested in color, and flavor, and diversity, and taste, of course But those are also concerns of farmers in the less developed part of the world as well Is that what you meant? – No, well, absolutely And of course, what consumers want is of concern to what farmers are growing Because it’s an integrated system, and part of sustainability is financial sustainability And if there’s not market What does the market want? And if there’s not a market, then that’s gonna impact, of course, practices on the farm So the food system might be one of the most complex parts of our modern society, that entire chain, right from the soil, all the way through to the waste product at the other end So lots of moving pieces So you’ve been talking about rice And Brian, I wanna talk a little bit more about the diversity of crops So in the Northern Hemisphere, or perhaps almost across the entire globe, a huge majority of the calories that we all eat, come from just a few crops, and corn, and soy, and wheat, and rice I think top that list But of course, around the world, people eat a whole lot of different things And of course, we all enjoy diversity in our diet So in your work, in the Innovative Genomics Institute, I’m curious what other crops you’re working on, and what the motivation is? What are the crops that really need attention as we face the challenges of the 21st century? – Absolutely So the IGI, which is the Innovative Genomics Institute, which was started a few years ago by Jennifer Doudna Basically, since it’s a lot of philanthropy that funds our research, we decided to work on crops that really impact a lot of the developing world And I think it’s fair to say that CRISPR technologies, or gene-editing technologies, will probably have a greater effect on billions of people in the world, where in medicine, maybe hundreds of thousands So I think it’s quite evident that I think that using gene-editing technologies in agriculture is gonna be extremely important So we set out a very robust plant transformation DNA delivery system, and we establish crops such as wheat and rice as being important, and we’re able to actually regenerate plants And not just the model plants, but the ones that farmers actually use in the field But I think a couple of other examples that we’re currently working on is that we work on cacao People that like chocolate are interested in cacao What you should realize is that 50% of the world’s chocolate is produced in the Ivory Coast, or Cote d’Ivoire, and that it’s subject to this really important virus disease called cacao swollen shoot virus So we are working in collaboration with Mars Corporation who gave us a nice gift to actually study how we could actually use gene editing to alleviate this particular pathogen from cacao So very important, and it’s a very challenging crop We have, very recently, about ready to submit a manuscript where we’ve actually accomplished, with Myeong-Je Cho, who’s the director of plant transformation in genomics, the ability to actually manipulate cacao plants in tissue culture So that’s a great advancement Another crop that we work on that companies don’t work on is we work on cassava And cassava is a plant that originated in South America, but it’s grown a lot in Africa, so smallholder farmers And one of the major problems with cassava is that a lot of the roots produce cyanide, and they’re very toxic to the people that eat this, and they can cause various diseases in the smallholder farmers when they eat these various crops So we have developed systems now where we have identified the genes that are involved in making cyanide in cassava, and preliminary results suggest that we have eliminated cyanide production from these plants So this is a great accomplishment We hope to be able to field trial these in the near future So cassava is a plant that many people, as I said

But it’s not a cash crop So you don’t find companies working on these So we feel that an institute such as the IGI, who’s got these resources, can apply these to crops that are important for the developing world We work on tomatoes also where there’s some diseases that we’re involved with But major crops are wheat, rice, cacao, and cassava that we talked about – Early in my career, I had the great opportunity to spend quite a bit of time living in Brazil and working in the Amazon and ate a lot of cassava, ’cause that becomes a real staple And just, it’s something that’s on the table in various forms with every meal, and something that’s not part of our diet at all in the Northern Hemisphere in that way Brian, I wanna stay with you for a moment, because you’ve mentioned CRISPR We talked about CRISPR, you’ve mentioned gene editing For our broad, public audience out there, most people just know the term GMO, and it’s just this one word, and it’s a single term, and yet it encompasses a very wide variety of underlying technologies and biological discovery So I think this is really an important moment Just can you share from, especially in your work with the IGI, how to make sense of that term GMO? And then, what does this word gene editing mean? Because that is, of course, we’re hearing this much more in popular discourse in the media – So typically, a GMO is a plant that is created by using plant transformation with a vector called Agrobacterium tumefaciens, which is a natural soil bacterium that transfers its DNA to plants, and scientists in the 1970s, early ’80s, found a way to disarm these particular plasmids and insert genes of interest, and then put them into plants Now, one of the criticisms people have had about GMOs is that when you insert DNA into plants, it goes into a random part of the genome, so we can’t control that Now, gene editing is an invention that, actually it’s a natural system that bacteria have used to fight bacteriophages, or viruses, that infect pathogens I mean, these phages that come in, these bacteriophages And the bacterium can actually eliminate them by recognizing the DNA, and then cutting it into small bits And so, essentially, what CRISPR allows you to do is to do more precise gene insertions into the place So we can now direct and target genes into the plant in a very precise way that we couldn’t do with GMOs And that, in fact, in the United States, APHIS, which is the Animal Plant Health Inspection Agency, the new rules and regulations say that plants, that when we make simple insertions or deletions are not regulated as a GMO, and they don’t pose any greater risk than would naturally be done – So just to continue with that moment, one of the analogies that you often hear is that the genome is like a book, and what’s happening in evolution is the letters are changing, and the words are changing, and some of those mutations, or, it’s like a typo, have no meaning at all And then, some are quite important So it sounds like in some cases what these technologies have done is like taking a whole section of of a different book and moving it in, like just copying and pasting versus the equivalent of a word processor of making a correction, a change here, a change there Am I pushing the analogy too far? Does that help? – No, I think these analogies, you can think of it as a word processor So for people in the audience that aren’t familiar with this, that some of the applications that are being done in biomedicine So for instance, they’ve been very successful now There are trials out there right now where sickle cell anemia has been identified for a particular mutation And so, scientists can go in now and basically change the gene very simply by using CRISPR technology to change that So we can make precise changes They basically correct a bad leo for a good leo and the same thing could be done in plants We could do that But also, in plants, we’re hopefully gonna be able to, and Pam can talk about this later, insert blocks of genes into plants to actually, that Pam has done with vitamin A She can talk about that maybe too So I think it’s a very Those are good analogies for people It’s really the precision that we’re able to do with this And at the end of the day, we can actually tell people these are the precise modifications that we’ve made as opposed to GMO, you kind of don’t know where it goes into the plant – And then, I suppose the other important difference is gene sequencing is not so powerful that after making the change, you can verify, right You can verify what actually changed and know that the background is more stable I mean, I know, Pam, in your book,

you just moved the anecdote of something that costs millions of dollars just 15 years ago, the genome sequencing is now just $1000, or a few thousand dollars The pace of change in this area has been truly breathtaking Now, Pam, when you talked about the rice, you mentioned bringing a gene from wild rice So clearly, in some cases, we need to know Where can we find these traits is an important question And I think there’s a lot of recognition that the wild relatives of our crops are incredibly important sources of material So we really depend on the maintenance of those wild varieties, as well as trying to develop more productive crops That’s a specific question, but maybe if you can just think about that? But also, just put in broader context, what’s the role of biological diversity in developing our cropping systems? And I’m gonna feed you a second part to this question Your husband’s an organic farmer Some people might find that a bit unusual to have an organic farmer and a plant breeder It’s working side-by-side, and you’ve written a book together ‘Cause the other part of the diversity question is the role of diversity on farms And of course, series of questions we’ve been addressing for decades about the potential vulnerability of monocultures, the value of diversity within a farming system So just a couple of different questions about the nature of biological diversity and the role it plays in agriculture – Yeah, well, as you pointed out, there’s biological diversity on farms in the sense that you don’t want to just plant one variety on massive acreage, and it’s nice to sometimes put in different species, intercropping, and so there’s a lot of examples like that And then for geneticists, often biological diversity means bringing in different genetic materials So to make your line more diverse, more resistant to disease, and we scientists for many years have been bringing in genes from wild species So there is transfer between species that’s been going on for many years in breeding So that’s very, very, very important, because if you can bring in a diverse set of genes, then you’re going to be less vulnerable to epidemics There’s also a biological diversity that you can bring in from outside the plant kingdom And so the most famous example of that is the BT gene from bacteria, which has been very, very important to farmers globally So this is a genetic engineering technique where you isolate a gene from a bacteria that confirms resistance to an insect So farmers have been able to massively reduce insecticide spraying So that type of genetic diversity, I think, will continue to be very important as we go forward Genome editing is obviously very, very exciting and an important tool But I think we’re gonna continue to see more conventional methods of genetic improvement to be used by farmers widely – Yeah, there’s many, many different facets there that come together Now, a lot of people think of science as a scientist alone in the lab, and everyone in science knows that’s far from the truth, that it’s a highly collaborative enterprise And on that note, I wanna step back for a moment and just let the two of you be in conversation a bit So Pam, why don’t you kick it off to your long-time colleague – Okay, and mentor So, Brian, you first taught me about selection pressure, which I think is a really important concept for people that are not in the agricultural community to understand So I’d like to ask you to talk about selection pressure Kind of explain why farmers can’t just get one variety and forget about developing new varieties Sort of this idea that the ability of pathogens to overcome resistance, how important that is And also, what kind of efforts you and IGI are doing to try to engineer durable resistance – Great, it’s something I’ve been studying my entire life, I guess, or academic life And so, we talked about taking traits from wild species of plants and plant breeders, and then genetically cross these into plants Unfortunately, we usually take one trait at a time And so, think of a field where every plant is genetically identical out there And it turns out that pathogens are quite tricky, and that they’re able to actually make mutations And that’s due to selection pressure So anytime in biology, when you put pressure, whether it be antibiotic resistance, whether it be disease resistance, it’s a matter of time before the pathogen will, you’ll select from mutations that can overcome that resistance I don’t want to go into the details of that,

but we now understand the mechanisms, how this actually works But what happens is that a farmer plants a crop, and it’s usually only a matter of several years when the pathogen will mutate and overcome that resistance, and now cause disease on that previously disease-resistant plant Then, the whole process has to start over again, where you have to try to find new genes for disease resistance, and then breed those into the agronomic varieties that you need So it’s a constant biological warfare between the plant and the pathogen, going back and forth So to try to counteract this effect, there are many theories in which people are trying to do for a durable resistance One approach that we’re trying to do at the IGI is to actually identify multiple disease-resistance genes And so instead of actually inserting, or genetically crossing, one gene at a time, we want to bring these genes in as a block So for instance, if we can bring six disease-resistance genes in at one time, the chance that you’ll select for pathogen that will overcome all six of these genes is greatly reduced Not only that, you can start mixing and matching disease-resistance genes such that you can distribute them within the field and not have all the plants genetically uniform So this is the power of gene editing, or CRISPR technology, is that we can introduce genes that we can’t do by classical breeding into plants And so making these novel combinations of disease-resistance genes, we hope to be able to actually make more durable resistance – All right, thanks – Brian, as you’ve watched I wanted to let you toss a question back to Pam as you watched your own protege rise and flourish in her career – It’s always great to have students like Pam I think the question that I’d like to have you, ask to you is that We talked about GMOs, we talked about gene editing And I think one of your more recent publications is a great experiment where you actually made rice plants that are actually, would hope cure blindness So if you could compare and contrast your efforts with GMOs, with those of gene editing, for traits that you’re interested in developing? And maybe, draw upon your book, which I think is something that people should read I’ll give you a plug for your book also – (laughs) Okay, thanks So for the carotenoid rice So maybe just to go back a little bit, the audience may be familiar with golden rice, which is a really tremendous, exciting breakthrough by Peter Beyer and Ingo Potrykus a number of years ago now And so the Rockefeller Foundation supported them to develop rice that had higher amounts of, ultimately, vitamin A And the reason is that vitamin A deficiency is a very serious problem in many parts of the world It’s estimated that 500,000 children go blind every year and half of the children die So this is obviously a very serious situation It’s especially prevalent in areas where families don’t have a diverse diet They’re eating rice three times a day They don’t have access to other types of foods that are nutrient-rich And so the idea was to engineer carotenoids, which are the precursor of vitamin A into rice, and they’ve been very successful, and there is a rice variety that’s been approved for food consumption in many countries now, including Bangladesh, as well as developed countries, New Zealand, United States, Canada, and I think it’s the last regulatory hurdle And hopefully, it’ll be in the hands of farmers soon But we got very interested in this and thought it would be a nice pilot test to try to use genome editing to introduce this particular cassette into rice And we chose it, obviously, ’cause it’s very important for socio-economic reasons, but also it gave us a nice example So it’s big, it’s like 5.2 KB So Oliver Dong in my lab really, who carried out most of the experiments, was able to identify what we call landing pads So a region of the rice genome that when you insert a new gene will not disrupt other essential gene function And so he was able to identify a number of landing pads and was able to insert this carotenoid cassette

into two regions of the genome And he was able to come up with these golden rice So they’re golden, they have high levels of carotenoids So it’s sort of a proof of concept that we will be able to use genome editing to introduce agronomically important traits to specific regions of the genome – Pam, just quickly, some of our listeners remember a cassette as something you put into a Sony Walkman They seem to have no idea what we’re talking about What does a cassette mean in genetics? – Okay, so a cassette So back in the day, we’d put a single gene into a plant, and we’d study how that plant grows and how it resists disease, but now scientists are able to, in a sense, reconstruct biosynthetic pathways So the endosperm, the rice grain that we eat, does not produce any vitamin A And colleagues over the years were able to identify really just two genes that needed to be added So in this sense, a cassette is a cassette of two to three genes that you can insert as a unit into the genome – Thank you, thank you So since we’re talking about rice, another follow up, and in fact, we’ll turn now to some questions coming from the audience So thank you all very much And if you are listening, YouTube live and Facebook live, you have a chat window there, you can put in questions And I’ll just say upfront, we don’t get to all of them But we will do as many as we can So there’s a very broad question here, Pam, and it’s also kind of two part One is, as you pick problems to work on, and I’m paraphrasing, as you pick problems to work on, what role does the do the social equity questions play for you about who would benefit from this sort of work? What need is it addressing in a broader societal context? And then, the specific followup from that is once you’ve done your work, like with the rice example, how does it get from that research lab out to a subsistence farmer? And what’s that pathway? And once you get to the other end, is that an affordable product that really can be used widely around the world? – Yeah, thanks I think social equity really drove my interest from the start My father’s an immigrant, mother grew up in the Depression So we really grew up with this idea of trying to give back And I was attracted to Brian’s lab, because he worked on disease-resistance and very, very excited about the idea that farmers can plant a seed, a genetically-improved seed, and they may not need to spray any insecticides or fungicides So that whole environmental aspect, social equity aspect, really, I would say, has driven my work And working on tomato and pepper in Brian’s lab was really fantastic, but I decided that I wanted to work on a food staple So that’s why I switched over to start working on rice, which was also becoming a model organism at that time about 30 years ago now I think I got my PhD right when PMB was coming together And so then, picking what diseases and traits to work on, it was obvious to start working on disease resistance because of the training that I had in Brian’s lab But then, a colleague introduced me the very serious effects of environmental stress, so that’s why I started working on the submergence tolerance And I would say that it is really critical to have sort of a pipeline So if you’re able to do something useful, and we all try to do our best, and you don’t really know what’s gonna work and what’s not gonna work, but to build that pipeline early So for the submergence tolerance work, it was really brought to the attention of scientists from farmers I mean, they were losing their crops in flooding And the International Rice Research Institute is part of a very important international, nonprofit program that is focused on putting improved seed in the hands of farmers So the International Rice Research Institute already had a whole set of collaborators in Bangladesh and India that were able to trial very quickly, with Dave Mackill’s leadership, trial the new varieties that were being developed And then, the seeds then are just put in the hands of farmers through the normal network So in many less developed countries, including Bangladesh and India, rice farmers will go to their national germplasm centers, and they will get the seed from those centers So in the case of submergence-tolerance rice,

there was no need to develop any kind of new distribution system And because the seeds are not regulated, marker-assisted breeding is not a regulated technology, it was really quite, that part was quite easy Well, I shouldn’t say easy, ’cause they still had to bulk up a lot of seed The Bill and Melinda Gates Foundation did provide funding to the Bangladeshi Rice Research Institute, the Cuttack Rice Research Institute in India, and the International Rice Research Institute to help breeders bulk the seed and distribute to farmers in those areas And then, I should say, Kyle Emmerich and other colleagues in your college did a really important study showing that the benefits of planting Sub-1 rice accrued to the most disadvantaged farmers in the world And that was a really fascinating study And it’s because in India, there’s a caste system And historically, for hundreds of years, the lower caste farmers have had the most flood-prone land, and so they’re really seeing the major benefits – Oh, that’s a fascinating connection And also, many of our listeners will know that California does not produce vast quantities of wheat and corn, but we do have flooded farmland and a significant rice industry So right there in Davis, you’re in the heart of a fairly important rice growing region as well So an important connection to across the other parts of the world where it becomes the main staple Brian, I’m gonna switch gears a little bit, again, picking up from our listeners I think it’s fair to say you’ve been in this business for a long time (laughs) You’ve had students, many generations of students And again, to paraphrase from the question that came in The question is: what advice do you give students entering the field now about both the technical skills they need, as well as what we call the soft skills, and how has that advice changed? How has your mentoring had to change as the science has changed over the decades? – It’s a good question I think the way I’ve always approached science is really to ask biological questions, and then basically try to find technologies that will help me to basically solve those problems I think the best advice I can do today for students is that the interface of computational biology and molecular biology are more paramount than ever ‘Cause what’s happening is that there’s a massive revolution in gene-sequencing technologies, and we’ve created these massive databases And students have to be able to manipulate these databases and to be able to write code and scripts, to be able to deal with these large databases So I really encourage students to get trained in computational biology and being able to bring those two systems together Also, I think it’s important for students, what I find today most interesting, most students really wanna make a difference in the world So they wanna do basic research, they wanna translate that basic research into solving problems that have an impact on humanity And I think instilling those particular traits into student have been important as we’ve gone along Again, I think having a passion, show people how you have a passion for science and how important that is in accomplishing your task And those are probably the most important things – So Brian, you may not be able to see this We knew that we had a slightly unstable web connection to Pam, and I think she may have dropped off for a moment So we’ll hope she drops right back in So let’s just continue the two of us So going back to going back to the traits, you talked about how climate change will impact disease, which is the area you’ve spent your career in Can you say a little bit more about traits, maybe non-disease traits, just since you’re in these discussions widely? What are key traits that gene editing might be able to help with, specifically in relation to our now very focused attention on climate change as a challenge for agriculture? – Right, I give an example from work in my laboratory, where Nicholas Karavolias is a graduate student of mine, and with support from the Open Philanthropy Project, we’re studying stomatal density in rice with the idea that we can regulate a particular master regulator called stomagen, where we can have an expression of from almost very few stomates to overexpression of stomates And it’s well been established in the literature that if you find this sweet spot of stomatal density,

that you can actually make plants more drug-resistant So you can use, not only is CRISPR important for inserting things, it’s a research tool You can actually make a lead with diversity of genes to be able to study traits You can also, as many people may or may not know, that many genetic traits in plants aren’t single genes They’re what are called quantitative trait loci We don’t need to go into the details of that But needless to say, there are many genes that contribute to a trait and using CRISPR technology, you can dissect out which these genes that are really important So there are many of these QTLs for drought tolerance And so we’re trying to actually think about ways in which we can use CRISPR to identify which are the important genes in these quantitative trait loci So lots of things to do, and a lot of challenges out there But we think that making drought resistance is gonna be really important – So we focused so far, mostly on the drought issue, well, the flooding, drought, and disease But in terms of the discussion about sustainability, one of the key challenges is the inputs into agriculture, and two of those inputs are, of course, fertilizer and pesticides And I believe Pam is back Pam, we noted your brief wifi dropout, but you’re back So tell us a little bit about the current status of research and the role of gene editing and genetic technologies, specifically addressing this issue of the inputs to agriculture and the problems that arise from both high-nutrient inputs, as well as pesticide use – Yeah, as I mentioned earlier, that the BT trade has been really, phenomenally important for farmers in reducing their insecticide use So just for an example, eggplant, which is the most important vegetable in India and Bangladesh, is also very susceptible to insect pests And farmers in Bangladesh were spraying their crops three times a week, sometimes even every day, to try to control this particular pest And especially in less developed countries, sometimes the insecticides are not really controlled or regulated And so it’s very, very harmful, often to farmers and their families, especially when they don’t have proper protection So scientists at the Bangladeshi Rice Research Institute in Cornell were able to engineer eggplant to carry this BT gene and were able to dramatically reduce insecticide use, often down to zero And so I think we need to keep in mind the importance of reducing insecticide use And sometimes I hear sort of a little bit of confusion in the public that don’t fully understand that the idea of the BT trade is to reduce the use of insecticides, some of them which can be really quite toxic So that’s why traits like BT will continue to be important There’s a lot of scientists that are working on nitrogen-use efficiency and phosphate-use efficiency I think these will be very important I don’t know, maybe Brian knows, but I don’t think any of these traits are out really in the field in the hands of farmers But the general idea is that if plants are able to use these really important fertilizers more efficiently, there will be less runoff into streams, into our ecosystems, and into the Gulf of Mexico, and many other areas, which are, there’s a lot of nutrient runoff and pollution So I think genetic technologies will be important Of course, management is important as well to try to add those inputs sparingly So it’s really a combination of farmer practices and genetically-improved crops that are gonna be critical for addressing these important problems – So there’s a question here which, it follows in part on that And that is that one of the really novelties that erode us, frankly, in the last 30 years, is the idea that that living organisms and genes can be patented and that they have intellectual property around them Not a lot of us wouldn’t be intuitive if we think of a lot of this as sort of products of nature, but these are very much an intersection of a natural product and the ingenuity of crop breeding So my question, and I’ll start with Brian, but maybe I’d be interested in both of you is, especially when you’re thinking about these things like these equity issues, where does the intellectual property side come in, in terms of what does it mean to own these discoveries? Of course, there’s a lot at stake, and potentially a lot of financial consequences at stake, in terms of both the inventions and also those who are the downstream users

And is gene editing changing at all the landscape in terms of intellectual property and agriculture? – That’s a great question, and it’s a very complex issue as you could well imagine Obviously, there are traits that you can gene edit, and you can patent these It really depends on what the patent holders of this, what they wanna do with licensing these particular technologies I’ve pushed at the IGI that we would not take any of our discoveries and would not exclusively license them to everybody So they would be widely available And furthermore, if they are for developing countries, they would be given freely to those countries And many companies actually have made that pledge that they would actually give their intellectual property to developing countries That’s important So maybe the developed country, which they might be able to afford to acquire these licenses But in the developing world where they can’t, I think, would be very important So it’s a complicated matter There’s lots of intellectual property out there, and even the whole CRISPR patent situation is still being debated and resolved It hasn’t been resolved totally yet – Pam, anything to add from your perspective? – Yeah, I think, there are specific examples So for example, golden rice, which was developed, it was funded by a nonprofit Rockefeller consortium, but they borrowed different tools and parts from Syngenta, and what ended up happening is Syngenta released all their rights And so golden rice, hopefully will soon be grown in Bangladesh, Philippines, and other parts of the world, will be completely in the public domain, which is really very important if you’re talking about very poor farmers So they’ll be able to plant the plants, harvest the seed, and replant So there’s no intellectual property restrictions And I think that is critically important in the less developed parts of the world The same with the submergence-tolerance gene We made the decision to be sure that that gene was publicly available We published it, so there’s no patent There’s no UC Davis patent on that gene So that means if anyone wanted to use it in genetic engineering, they could use it But also, if you’re just using marker-assisted breeding and not using any of our genetic sequence, that that also would be in the public domain So I think it’s very clear in less developed countries that there has been, and there will continue to be, a lot of push to be sure those tools are in the public domain And it’s a different story in the United States In Europe, where almost all farming is for-profit, whether you’re an organic farmer or a conventional farmer So the landscape’s a little bit difficult there I think one thing, maybe, we can talk about if we have time, is this idea that the gene itself is really where the patent is held, but it’s actually often the germplasm So corn breeding has been developed for 70 years, so there’s very valuable, what we call germplasm, which is just the genetic background that’s used to make hybrids, and those are very, very valuable, even independent of any new genes that are being added And so there’s a lot of interest in, and concern about, the genetic background itself being patented And I don’t know if Brian, or David, have anything to add to that But it’s certainly an ongoing debate – Brian, anything to follow up on that? – No, like I said, it is an ongoing debate, and hopefully that good rationale will prevail in trying to make these technologies move forward I don’t have anything more to say about it, sorry – One thing I really hear you saying is that it matters where the funding comes from Foundation funding has really been important here Now, PMB has a long history of very close collaboration with some private sector players in biotechnology So as you’ve watched this unfold over several decades, I’ll ask Brian, is that relationship really changing? Do you see a shift in the nature of the relationship between university researchers and private researchers, and then this interface to making things available around the world? – It’s interesting I gave you the example of cacao where Mars Corporation is not interested in holding any intellectual property Their major motivation is to actually have a supply of chocolate So they’re willing to give funding to develop technology,

so farmers can produce the chocolate that they can use So I’m not sure all the other companies have the same rationale behind that But a lot of the companies I know, that if they have intellectual property, like Corteva, which used to be Pioneer Hi-Bred, they have actually allowed their technologies to be used in a developing country They will give the rights to those in developing countries So I think, on a case-by -case basis, hopefully we’ll be able to accomplish this I think it’s important that we democratize these technologies – Actually, and that’s an incredibly important sentiment there And also, just the idea that there are no some single, silver-bullet statements or answers across all these things That it is very much case-by-case And we need to look at each case on its own merits, I would say In the last few moments, I’m gonna turn it a little bit more, maybe a little lighter and a little bit I’m gonna say a personal question It’s not very personal There’s a great question from the audience for each of you Who are your scientific heroes? – Brian, Brian, of course! There’s the obvious answer It’s the only answer in this setting – Well, that was a setup But Brian, how about you? – I would say that my professor, my PhD professor, was a real intellectual He’s still around Nicholas Panapolis was his name And he really taught me how to think in testable hypotheses, and this really has stuck with me my entire career And he was a great mentor And I can’t say enough what an influence he had on me, how to approach science and ask important questions And one thing he always says: “If you can think of an experiment, and if it’s not that expensive, just do it Don’t talk yourself out of it, because you’ll often find that it may not work the way you want, but serendipity comes into play, and you will find something totally new.” So I would say Nick Panapolis for me – Well, and Brian, that speaks to something that, again, people who are not inside the scientific research community may not fully realize how powerful that mentor-student relationship is, and it shapes our entire careers And I think all of us could tell that story of the influence of our advisors and what a difference it made I wanna give you each an opportunity for some closing thoughts And specifically, this is a 30th anniversary event And those who know our history at Berkeley, PMB came together in a merger, in reorganization It wasn’t the invention of biology It was just the founding of the PMB Department in its current form But what about the future? If you could look ahead to the next 30 years of plant biology, plant breeding here at Berkeley Davis, what’s on the horizon? And of course, this is one of the questions for students entering the field, thinking what their career might look like Well, Brian, go ahead and start – Okay, I can start it So I think that, obviously, I’ve been at Berkeley before the PMB Department started, and I think what’s really been important for me as a faculty member in PMB is the great colleagues that we’ve had that really form Berkeley is again a great place that has attracted amazingly good graduate students and postdocs, and I’ve benefited from being able to attract those students and postdocs But also, generally, I’d say across campus I have developed collaborations with people outside of the department So I think as you move forward, you just can’t work with just a few people in your own department, you have to reach out, because there are new technologies I’ll give you an example We’ve just recently use cryo-EM technology to really get an important complex of disease-resistance immune receptor out And that’s where the collaboration with the Eva Nogales Lab and Raoul Martin who’s the graduate student So being able to go out and to really interact with other members, not only on this campus, but UC Davis We have a lot of close relationships with the great plant scientists at Davis, at Stanford, UCSF So I think, as you go forward, Berkeley is in a great place Because you have these four major institutions, you’ve got UCSF, Stanford, Berkeley Davis, and it’s all within a 70 mile radius or 100 mile radius of each other So Berkeley’s a great place to come to do science – Thank you And Pam, some closing thoughts? – Well, I really appreciate being invited back Being a graduate student at Berkeley was really a fantastic experience I gained from Brian’s mentorship and also Nick’s mentorship who was there when I was there, and also so many fantastic faculty in the program I know many of them are retired: Lew Feldman, Dick Malkan, Steve Lindale, Patty Zabriskie, John Taylor, Bob Buchanan We had a really fantastic group of professors

that were mentoring us, and so it’s been really excellent to be back And I concur really with what Brian said As you go forward in your career, you continue to meet fabulous scientists, and many scientists that are willing to help you in an area that you’re completely unfamiliar with And that’s one of the great things about being a scientist ‘Cause you’re always learning And so thanks very much for giving me the opportunity to join you today – Well, thank you, Pam Thank you, Brian Thank you to everyone who’s listening for joining us today We hope you’ll come back for future events as part of PMB’s 30th anniversary In the meantime, stay safe and best wishes