The Future of Food: Genetic Improvement Meets Sustainable Agriculture

The Future of Food: Genetic Improvement Meets Sustainable Agriculture

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Good afternoon. I'm david ackerly, dean of the rouser 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 cast 9 to agriculture. Innovation, and entrepreneurship. And close ties, between. Industry, and academia. Please visit the department's, website at. 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 pnb, professor, b. Excuse me britt glassinger. As it was featured, on the berkeley concert. Berkeley, conversations. Coveted 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 rouser college community. We'll be taking live questions, via. Uh, 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 staskewitz. 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. Ryan 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, affector, gene, and the cloning and characterization. Of one of the first plant, nlr, immune receptors. Ryan 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 is 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 wagenin, university, in the netherlands. He is a member of the u.s 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 print 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, science, at berkeley's. 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 hundred most influential, people in biotechnology. By scientific, american. She is a member of the national academy of sciences. She is co-authored, with her husband. Organic, farmer raul adam check, 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. Our 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. Cam and bryan 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. Ryan 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. And welcome to everybody, um. This afternoon, it's a pleasure to join in this um panel. Um as david said. The 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 percent, increase in production. During this time period to feed the world. Unfortunately. Also that this is uh exacerbated. By climate, change. So. Being able to grow this food in an environmentally, sustainable.

Fashion. Is going to 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 in 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 in agricultural, 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, talk today. Thank you. Thanks brian. Uh pam turning to you can you elaborate, more on what it means when you think about, making, agriculture, sustainable. Locally, and globally, and into the century, ahead. What and and put that in the context, of these very fundamental, challenges that brian has laid out. Yeah i think brian, uh pointed, out. Some really important, goals. Uh for all of us that, using land and water. More, efficiently. Is is going to be critical. Most of the arable land has already been farmed, so the land. That we have we we need to use. Much more efficiently. And. Brian also. Mentioned, reducing, harmful, inputs. There are other challenges. Uh such as maintaining, soil fertility, will continue, to be really, an important goal. For. Farmers, and maintaining, farmland. 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 in the world. And uh i also like to thank you for. Including me in this conversation. And i'm, really pleased that uh, to be here and appreciate. The audience for joining in. Thank you thanks pam. Brian, i know when you're when you teach, uh, when you teach here on campus you you paint a picture of the, 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 and plant breeders, have, have worked uh, 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 reading. And 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. Um. All plants. Many people don't know this that 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. Of 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, employ, deploys. Employs. Crop genomics. But unfortunately. Plant breeding is very inefficient. And takes many years to. Introduce, these traits, into our high yielding, ergonomic, varieties, that we use today. Thus. New breeding tools that we will 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 Uh and we will definitely, circle back and talk more about the actual. Uh, the mechanisms, of what we mean by those new technologies. But pam maybe over the course of your cr if you think over the course of your career can just give us some examples, 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, uh the crops you've worked on and, and what it's meant to be a scientist, uh involved in all this work. Well, it's been um, really, fantastic. To be, uh, 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. Uh, worked with uh gerd of koosh 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. Um, and that are in our crops, have, been derived, from some of these ancient varieties. Or or. Diverse species. And so, uh. 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, uh, more recently. I. Had, the. Honor to work with david mchale. Who. Also, had, um he's at uc davis, cornell, with me but also. Spent time at the international, rice research, institute. Brought to my attention. Uh, 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 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. 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, a genetic, technique, that's not regulated. It has been really important, for developing, new varieties. So this variety. Has. Does really, fantastic. So even after, two weeks of flooding. The plants, can, survive. And, thrive. So the plants, that have. Um. This gene. Are, have about a 60. Yield advantage, and this is really. Important, for farmers. Uh, in eastern india and bangladesh. Who are able to. Harvest, grain, even in in the face, of. Of severe flooding. And last year. About six million, farmers, grew this rice which is called. Sub one. Rice. Pam if you i want to follow up briefly on, a comment you just made because 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. That as consumers, were looking for so, as, as researchers, and as plant scientists.

What Is that balance of the traits that farmers want and the traits that consumers, want in the in the ones that have drawn, attention, in in the research community. So one thing to keep in mind is for a crop like rice, the farmer is the consumer. So. Most people that are growing rice in less developed countries, are subsistence. Farmers. So that means that they grow, uh, really only enough rice to feed themselves. And their families, so when a farmer has. The ability, to grow. Rice, even, uh under flooded conven. 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, uh to support their children's. Education, for example. And then if you're uh. If you're in a developed, country. And. Are, possibly, not concerned. With uh how farmers, are. Um. Able to grow their foods. Uh. So. You know there are there are many different types of traits that. Consumers, in in developed countries, are interested, in and and particularly, people are interested, in color, and flavor, and diversity. And. Um. Taste of course. So, um. But those are also concerns, of of farmers in the less developed. Part of the world as well, is that what you meant, yeah well, absolutely, and of course and of course, what consumers, want is of concern to what farmers are growing because this is a it's an integrated, system, and. Part of sustainability, is financial sustainability. And if there's not a more you know what does the market want and if there's not a market then. That's going to impact, of course practices, on the farm so. The food system might be one of the, you know most complex, parts of our modern society, that entire. Chain right from the soil, all the way through to the to the waste product at the other end so, lots of moving pieces. So you've been talking about rice and and brian i want to talk a little bit more about the diversity of crops so. In 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. What's the what other, i'm curious what other crops you're working on and what the motivation, is like what are the what are the crops that really, need attention. As we face the challenges of the 21st, century 21st, century. Absolutely. So um, the igi, which is the innovative, genomics, institute. Um which was started a few years ago by jennifer doudna. Um basically. Um. Since it's a lot of philanthropy. Funds our research we decided to work on crops that really impact. A lot of the developing, world. And, i think it's 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 going to be extremely, important. So we set out, a very robust. Plant transformation, dna, delivery systems 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, coaster, cote d'ivoire. And that it's subject to this really.

Important, Um virus disease called cacao swollen, shoot virus. So we are working in collaboration. With um, 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 it's a very challenging, crop we have. Very, recently, about ready to submit a, manuscript, where we've actually. Accomplished, um with myeong j cho who's the director of plant transformation, and genomics. The ability, to actually manipulate. Um cacao, plants in tissue culture so that's 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. And, um 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 it's not a cash crop so you don't find companies, working on these so we feel that an institute, such as the uh, igi. Who's got, these resources. Can apply these to crops that are important for the developing, world. Um. You know we work on some other 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. Yeah i 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, because that becomes a real staple. Uh and just it's something that's on the table in various forms, you know with every meal and something that's not part of our diet. At all in the northern hemisphere, and that kind of in that way, brian i want to i want to stay with you for a moment and because you've mentioned crispr, we've talked about crispr you mentioned gene editing.

For Our for a gener, 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 it's a it's a single term and yet it encompasses, a very wide variety of underlying. Technologies. And biological. Discoveries, so. I i think this is a, this is really an important moment just can you share from, uh especially, you work with the, igi. What how to make sense of that term gmo, and then what does this word gene editing mean like because that is of course we're hearing this much more in you know popular discourse, in the media in the media. So typically, a gmo. Is. A plant, that is created, um, by, using plant transformation. With a vector called agrobacterium. Tumofations. 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. Um, pathogens. I mean these, 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. Um essentially. What crispr, allows you to do is to, do, aggregate, 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 where 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 um. I want to just to continue at that moment one of the analogies, that you often hear is that the genome, is like the book you know a book, and. A lot what's happening in evolution, is the the letters are changing 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. So it sounds like in some cases, what these technologies, have done is like taking a whole section of someone of a different book and moving it in like just you know copying and pasting. Versus, the equivalent of a word processor, of uh you know making a correction a change here or a change there, am i pushing the analogy, too far does that, help i think, i think these analogies, have you know you can think of it as a word process 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, by a particular, mutation, and so scientists can go in now, and basically, change, the. Gene very simply, by using, a crispr, technology, to change that so we can make, precise, changes. We can change the um. That basically, correct, a bad allele, for a good allele. And the same thing could be done in plants we can do that but also. In plants, we're hopefully going to be able to and pam can talk about this later.

Insert. Blocks, of genes into plants to actually, um. That pam has done for um. With vitamin, a we can she can talk about that maybe too, so i think it's a very, those those are good analogies, for people so we're able it's really the precision, that we're able to do with this and, at the end of the day we can actually, um. Tell people these are the precise, modifications. That we've made as opposed to gmo. You're you're kind of, don't know where it goes into the plan. And then i suppose the other important difference is gene, sequencing, is now so powerful that after making the change. You can verify, right we can we you can verify what actually changed and know, that the background, is more stable i mean, i know pam and your um. Pam in your book you, you just leave the anecdote, of something that cost millions of dollars just 15 years ago the genome sequencing, is now you know just a thousand dollars or a few thousand dollars that, the pace of change in this area has been truly breathtaking. Now pam when you talk about the rice. You, you mentioned bringing a gene from wild rice, so. Clearly, in some cases, you know. We need to know where these 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're we, we are we really depend. On the maintenance of those wild varieties, as well as trying to develop you know more uh. More productive crops. So can you, 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, you know our cropping systems. And i'm going to 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, because the other part of the diversity, question, is the role of diversity, on farms, and. Ques, you know serious questions we've been addressing for decades, but, the vulner the potential vulnerability, of monoculture, is. The, the value of diversity, within a farming system. So. I'm just. A couple 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 in the sense that you don't want to, just plant one variety, on massive, acreage. Um. And it's nice to sometimes, put in different species. Uh intercropping. And so there's a lot of examples. Like that, and then for genesis. Often biological, diversity, means, uh bringing in uh different, genetic, materials. So to make your. Um, your line more diverse more resistant to disease, and. We. Scientists, for many years have been bringing in uh. Genes from wild species, so there is transfer. Between, species. Um. That's been going on. For, for many years, in in breeding so that, 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. Biological. Diversity, that you can bring in from, outside, the plant kingdom and so the the best, 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 we go forward. Uh genome editing is obviously, very very exciting, and an important tool but i think we're going to continue to see, more conventional, methods of genetic, improvement. To be used by farmers. Widely. Yeah there's, quite a few facets i mean 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 the. Far from the truth that it's a highly collaborative, enterprise. And in that, on that note i'm i want to step back for a moment and. Uh just let the two you two of you be in conversation, a bit so, pam why don't you kick it off to uh a, lot your longtime, colleague. Okay, and mentor. Uh 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 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, um, developing, new varieties. Um. Sort of this idea of 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 um, so we talked about um, taking, traits from wild species, of plants, and plant breeders. Have then genetically, crossed these into plants. Unfortunately. We usually take one trait at a time, and so you, have a 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 any time 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 for mutations. That it 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 their previously, disease resistant, plant and 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 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. That the chance that a pathogen, can, you'll select for a 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-resistant. Genes, we hope to be able to actually, make more durable resistance. Great. Thanks. Brian as you've watched. I, wanted to let you, toss the question back to pam as you watch. Your own proteges, rise and. Flourish, in her career. It's always great to have students like pam. Um. I think a question i'd like to have you um. Ask, to you is that, you know we talked about gmos, we talked about gene editing and i think one of your more recent publications. Is, a great um. Experiment. Where you actually. Made um. Plant rice plants that actually would help 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. Okay, thanks. Um. So. For the. Carotenoid, rice, so maybe just to to go back a little bit um the audience may be familiar, with golden rice which is a really tremendous. Uh exciting, breakthrough, by peter bayer, and. Endo. Ingo petricus. 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, uh, 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 a very, serious, um. Situation. It's. Especially, prevalent. In areas where. Uh, 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. Um, carotenoids. Which are the precursor. Of vitamin a into rice and they they've been very successful. And there is. A rice variety that's, 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 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 because it's a very important, for, socio-economic. Reasons, but also. Um. It's 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 the major, uh 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, he was able to come up with. These. Golden, uh golden rice so they're golden they have high levels of, of carotenoids. So it's sort of a proof of concept, that we will be able to use genome editing. To intro, introduce. Uh agronomically. Important traits, uh two specific, regions. Of the genome. Um pam just quickly. Some of some of our listeners, remember a cassette as something you put into a sony walkman and some have no idea what we're talking about, what what does a cassette, mean in uh in gene. In genetics. Okay, so a cassette. So back in the day we'd put a single, gene, into a plant, and we'd study. Um how that plant grows. And. You know how it resists disease. But now, scientists, are able to in a sense reconstruct. Biosynthetic. Pathways. So. The the endosperm. The rice grain that we eat, does not produce, any, uh vitamin, a, and. Um. 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 um. Two to three genes, that, you can insert, as a unit. Uh into the genome. Thank you thank you so um, since we're talking about rice. Another follow-up, uh 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 and i'll just say up front we don't get to all of them. Um, but we will uh, do do, as many as we can. So there's a very broad question here pam and it's so 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, how much is, what role does the do the social equity questions, play for you about, you know who would benefit from this for, work. Uh what need is it addressing, in a broader societal context, and then the specific, follow-up, from that is. Let's you know 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 is it affordable and once you get to the other end is that an affordable product that really can be used widely around the world. Yeah thanks. Social equity, really drove my interest, um. From the start. And. You know my father's, uh, immigrant, mother grew up in the depression so we really grew up with this idea, of. Um, trying to trying to give back and and i was attracted to brian's, lab because he worked on disease resistance, and very very. Um, excited, about the idea that farmers can plant. A a, seed a genetically, improved seed, and then may not need to spray, any insecticides. Or fungicides. So that whole. Um, environmental. Aspect. Social equity aspect, really. I would say, has driven my work and i. Um. You're 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, a model organism. At that time about. 30 years ago now i think i think i got my phd, right when pmb, was was coming together. Um. And so then, picking, what diseases. And traits to work on. It was obvious to start working on disease resistance, because of the training, and i had in brian's, lab but then. Um, a colleague, uh introduced, to me the. The very serious. Um, effects of environmental, stress, so that's, that's why i started working, on. Uh the submergence, tolerance. And. I would say that. Um it is really, critical to have sort of a pipeline, so if, if you're able to do something useful, and you know we all try. To do our best and you don't really know what's what's going to work and what's not going to work. But to build that pipeline. Early, so for this emergency. Tolerance, work it was really brought to. The attention, of scientists, from farmers i mean they were losing their crops, in in flooding. And the international, rice research, institute, is part of. A. A very important, international. Non-profit. 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. Um. Very quickly. With, dave mckill'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 networks, so in, in many less developed countries, including bangladesh, and india, rice farmers, will go to. Their national. National germplasm. Centers, and they will get the seed from those centers. So in the case of submersion, tolerance, rice there was no. Need to develop, any kind of new distribution. System. And because the seeds are not regulated. Um. Uh marker assisted breeding is not a regulated, technology. It, was really quite. Um that part was, was quite, easy well i shouldn't say easy because 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 qatak, rice research, institute, in india. And the international, rice research, institute. To help breeders, bulk the seed, and distribute, to, farmers. Um. In those areas, and then i should say um you know kyle emerick. And other colleagues. Um, in in your college, did a really important study. Showing that, um the benefits, of planting, sub one rice. Accrued, to the um, the, most disadvantaged. Farmers, in the world. And, that was a really fascinating. Study, um. 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. Uh, 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 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, of a fairly important rice growing region as well, so that an. Important connection to, across to other parts of the world where it becomes the main staple. Um. Brian you've. I'm going to switch gears a little bit again picking up from our listeners.

You've Uh i think it's fair to say you've been in this business for a long time, um. You've had. Students, many generations, of students and. Again to paraphrase, from the question that came in what. The question is what advice do you give students entering the field now about both the technical skills they need as well as like what we call the soft skills and and how has that advice, changed, how, how has your mentoring had to change, as the science has changed over the decades. It's a good question um i think. The way way i have always approached science, is really to ask biological. Questions, and then. Basically, try to. Find technologies. That will help me save, um 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. Being able to because 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 be able to bring those two. Systems together. Also i think it's important for students what i find today most interesting, most students. Really want to make a difference in the world. So they want to, do basic research, they want to translate, that basic, research into solving, problems, that have an impact on humanity. And i think. Instilling, those um particular, um. Traits into students has been important, as as we've gone along. Um again i think having a passion. You know show people how you have a passion for science. And how important that is in, accomplishing. Your task. And um. Those are probably, the most important things. So brian you you you may not be able to see this, we knew that we had a slightly unstable, web connection, to pam, and i think she um, 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 um. So. Uh, going back to going back to the traits, you talked about how climate change, will impact, disease, which is the area you've spent. You know your career in, can you say a little bit more about. Traits maybe non-disease, traits just since you're you know in these discussions, widely. What are um. 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. Or nicholas, carravolius. As a graduate student of mine. And with support, from the open philanthropy. Project. We're studying, um. Stomatal. Density. In rice, with the. With the idea that we can regulate. A particular, master regulator, called stomagin. Where we can have, an expression, of, from almost. Very few stomates, to over expression of stomachs, 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 drought resistant. So, you can use not only is crispr important for inserting things it's a research, tool you can actually make allelic, 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 of the important genes, in these quantitative, tr. Loci. So, lots of lots of things to do and. A lot of challenges, out there but we think that, making drought resistance, is going to be really important. So we've so we've focused, so far mostly. On the drought issue and well the flooding, drought. And disease. But in terms of the discussion about sustainability. One of the key, um. Challenges, is the 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, uh wi-fi. Drop out but you're back, so, um tell us a little bit about, the current status of research and the and and the role of genetic. Genetic technologies.

Around, 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 the the bt trade has been. Really, uh phenomenally, important for farmers, in reducing their insecticide. Use so just for an example. Uh, eggplant. Uh 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 are not really controlled, or regulated, and so it's very very harmful, often. Um, to farmers, and their families, especially, when they don't have, a 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, we need to keep in mind, the the importance. Of, reducing, insecticide. Use um and, sometimes i, i i hear, sort of a little bit of confusion. In. 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 uh, traits like bt will continue to be important. There's a lot of, scientists, that are working on. Nitrogen, use efficiency. And, and phosphate use deficiency, 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 the general ideas. That if. Plants are able to use these, uh really important, fertilizers. More efficiently, there will be less runoff. Into streams, into our ecosystems. And and into the gulf of mexico, which, 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 is important as well, um to try to use, um, add those inputs, sparingly. So it's really a combination, of farmer practices. And genetically, improved. Crops that are that are going to be critical, for addressing, these important problems. So, i have there's a question here which, it follows in part on that and that is that. One of the. Um. One of the, really. Novel. Novelties, that arose 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, and, which is. 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. Of crop reading and, so my question, and i'll start with brian but maybe i'm interested in both of you is. Um. Especially, when you're thinking about these. Things like these equity issues. Where does the, intellectual, property side come in in terms of who what does it mean to own these discoveries. Uh of course there's a lot at stake and potentially, a lot of, financial consequences, in stake in terms of the. Both the. Inventions, and also those who are the downstream, users. And is is gene editing, changing, at all. The. Landscape, in terms of intellectual, property. And, agriculture. You know that's a great question, and it's a very complex, issue as you could um well imagine. Um, obviously, there are. Traits that you can gene edit and you can patent these, it's really depends, on what. The. The patent. Holders, of this. What they want to do with licensing, these, particular, technologies. I pushed at the igi. That, we would not. Take any of our discoveries. And would not exclusively. License, them to any everybody so they would be widely available, and furthermore. If therefore, 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, um, 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. Um there's. Lots of, intellectual, property out there and it's it's, even the whole crispr. Patent situation, is still being debated. And. Resolved. Hasn't been resolved totally yet. Pam anything to add from your perspective. Yeah i think um. You know, there are specific, examples, so for example, gold and rocks which was developed, it was funded by a non-profit, rockefeller, consortium. But they, um, borrowed. Different, you know, tools, and parts, from. Um syngenta. And. What what ended up happening is agenda, released, all their, um, their rights and so golden rice that is now being.

Hopefully, Will soon be grown in bangladesh, philippines, and other parts of the world, is will be completely, in the public domain, which is really, um 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 this emergence, tolerance, gene. Um. We. Made the decision, to. Be sure that that gene was publicly, available, so there's no. We published it so there's no patent. You see there's no uc davis patent, on that gene so that means. Um, if anyone wanted to use it in genetic, engineering, they could use it but also. Um, if you're just using marker assisted breeding, and not using any of our you know genetic, sequence, that, that also would be in the public domain so i think, it's very clear in less developed countries, that, um, there has been and there will continue, to be. A lot of push, um to be sure those tools are are in the public. Uh domain, and and it's a different story, in the united states in europe, where, um, almost all farming, is for-profit. Whether you're an organic farmer or a, conventional, farmer. Um so the so the landscape's, a little bit uh difficult, there, i think one thing. Maybe we, can talk about if we have time. Is this idea that it's, the gene itself, is is really where the patent, is, held but, it's actually often the germplasm. So corn. Breeding. Um 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 are very very valuable, even independent, of any new genes that are being. Added. And so there's, uh, a lot of interest. In, and concern, about the the, the genetic, background itself, being patented, and i don't know if, brian, um or david have anything, to add to that but it's it's certainly an ongoing, debate. No brian anything to, follow up on that. No i just like i said it is an ongoing, debate, and um. You know hopefully, that. Um. Good rationale. Will prevail, and trying to make these technologies, move forward. Um, and so, yeah, i don't have anything more to say about it sorry.

So Um so one thing i mean one thing i really hear you saying is that it matters where the funding comes from foundation, funding has really been important here and. Um. Now pmb, has had a long history, of very close collaboration, with some private sector players in in, biotechnology. So. As you've watched this unfold over several decades, i'll ask brian. Have you, is that relationship, really changing do you see a shift in the nature of the relationship, between the 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 uh cacao, where, um, mars corporation. Is not interested, in holding any intellectual, property, their their major. Motivation. Is to actually. Have a supply of chocolate so they're willing to, give the tech. Gift 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 um. It's um it's it's definitely but but a lot of the companies i know that, if they have intellectual, property like corteva, which used to be pioneer, hybrid. They have actually. Allowed their technologies. To be used the 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. Uh, that. Actually, i mean that's an important incredibly important sentiment there and also just the idea that there are 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 each case on its on you know on its own merits i would say. In the last few moments i'm going to turn it a little bit more, um, maybe a little lighter and a little bit, uh. I'm going to say a personal question it's not very personal, it's a great question from the audience for each of you, who are your scientific, heroes. Brian, brian, of course says there's the obvious, answer. It's the only answer, in this setting, uh well that was a setup but brian, how about you who's. You know i would say that um. My professor, my phd, professor, was a real intellectual. Um. He's still around nicholas panopoulos, 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 question one thing he always says if you can think of an experiment. And if it's not an 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 panopoulos, for me, well and and brian that speaks to something that again people are not inside. The scientific research community may not, fully realize, how powerful, that mentor, student relationship, is and it and it shapes our entire careers and i think, all of us could tell that story, of the influence, of our, advisors. And, and, what a difference it made. Uh in the club in the i want to give you each, opportunity, for some closing. Thoughts, and specifically. Um, this is a 30th anniversary, event, and. Uh, those who know our history at berkeley pmb came together in, a merger and reorganization. It wasn't the invention of biology, it was just the uh 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, 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 um. Brian. Brian go ahead and start, okay i can just start it so i think that, obviously, i've been at berkeley before the pmb, department, started. And um, i think. What's really been important for me um. As as a faculty member in pmb. Is the great colleagues, that we've had that really form. Um, berkeley, is again a great place that has attracted, amazingly. Good graduate students in postdocs, and have, benefited, from being able to attract those students in post-docs. But also, i would generally, say, across, campus that i've developed, collaborations. With people outside, 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. Used cryo-em. Technology, to really get an important, complex, of disease resistance, immune receptor, out, and that's with the collaboration, with the ava nagalas's. 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 sciences, at davis, at stanford. Uh ucsf. So i think as you go forward, berkeley. Is in a great place because you have these four major institutions. You've got you know ucsf, stanford. Berkeley davis. And it's all within a 70-mile. Radius, or 100-mile, radius of each other so it's really.

Berkeley's, A great place to come to do science. Thank you and pam some, closing, thoughts. Yeah, well i really, um, appreciate, being invited, back uh being a graduate student at berkeley was really a fantastic. Experience. You know i i, i gained, um, 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. Lou feldman dick malkin steve linda patty zambrisky. John taylor, i mean we bob buchanan, we had a really fantastic. Group of professors, that were mentoring, us, um, and and so it's been. Uh a really excellent. Uh, to be back. And, you know i i concur, really with, what brian said you know as you go forward in your career. You continue, to meet uh, 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, because you're always. Learning. And um, 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.

2020-09-16 02:40

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