Hello friends, myself Dr. Narendra Kartikar, Assistant Professor, Department of Mechanical Engineering, Valachandra Institute of Technology, Solapur. Today, we are going to see the particularly discussion and presentation on study of core learning outcome. At the end of this lecture or the session, student will be able to understand the different type of cores and also know where to apply it. Let us see the content of particularly presentation, introduction, we will see about the core, its type, different function, purpose of the cores, essential characteristics of dry sand core, type of cores, method of making the cores. You can see the particular diagram shown on the screen where the cross section of molding box is there. You can see the presence of core over there. The core is placed over there with the support of chaplets. Normally, the core is going to be present over there to produce the hollow geometry for the casting. Section diagram of casting mold is shown on the screen where once again a different kind of type of core and its placement can be visible over there. You can see the different parts in the section diagram of casting mold. The cope hub, drag hub and in between that particular those two cope and drag hub molds, the different kind of cavities and elements are present. The brown color part is shown over here that is a core. The core is placed over there in a vertical position. These two diagrams just I had shown to imagine how the particular cores can be placed and its importance to produce the hollow geometry in the casting. Let us go with the introduction of the core. Core is an obstruction which when positioned in the mold naturally does not permit the molten metal to fill up the space occupied by the core. In this way, a core produces hollow casting. Cores are required to create the recesses, undercuts and interior cavities that are often a part of castings. A core may be defined as a sand shape or form which makes the contour of a casting for which no provision has made in the pattern of molding. Cores may be made up of sand, metal, plaster or ceramics. Different functions are the purpose of the core that can be included in the mold itself. For hollow casting cores provide the mean of forming the main internal cavities. Not only that, but cores may be provide external undercut features. May be employed to improve the mold surfaces. May be inserted to achieve deep recesses in the casting. Another main function is to use to strengthen the molds. Cores may be used to form the gating system of large size molds also. Let us go with the essential characteristics of dry sand core. The core must possesses sufficient strength to support itself and to get handled without breaking. High permeability to let the mold gases escape through the mold walls. Smooth surface to ensure a smooth casting. High refractoriness to withstand the action of hot molten metal. High collapsibility in order to assist the free contraction of solidifying metal. Those ingredients which do not generate the mold gases. At this stage of this session, are you able to recall or share some of the casting parts where hollow geometries are present? Enlist such casted parts which you had seen earlier anywhere in real time. Just enlist few of them. Let us go with the type of cores. The cores may be classified according to the state or condition of core that is green sand, dry sand, no big sand. It can be also classified the nature of core material employed that is oil bonded, resin bonded, shell cores and sodium silicate cores. The classification depending on the type of core hardening processes that is CO2 process, the hot box process, cold set process and so on. The shape and position of the core is also another factor with which we can classify the various type of cores. Horizontal core, vertical core, hanging or cover core, balanced core, drop core or stop of core, ram up core and kiss core. Let us go on the discussion of particular type of cores with the position or the placement of cores. First one horizontal core. A horizontal core is positioned horizontally in the mold as shown in the figure. A horizontal core may have any shape circular or some of the other section depending on the shape of the cavity required in the casting. A horizontal core is supported in core seat at both its ends. Uniform sectioned horizontal cores are generally placed at the parting line. A horizontal core is very commonly used in the foundries. You can more elaboratively understood through the means of the image shown on the screen. The second type of core is a vertical core. On the cove side, a vertical core needs more taper so as not to tear the sand in the cove while assembling cove and drag half. It is positioned in the mold cavity with its axis vertical. The two ends of vertical cores are supported in core seat in cove and drag respectively. A big portion of vertical core usually remains in the drag. More understanding through the image shown on the screen. Hanging or cover core. It is known as hanging core because it hangs. It is also called cover core if it covers the mold and rest on a seat made in the drag. A simple hanging core is one which is not supported on any seat rather it hangs from the cove with the help of wires. A hanging core is provided with a hole through which the molten metal reaches the mold cavity. Hanging cores can be made up of either green or dry sand. The image shown on the screen will elaborate more for the hanging or cover core. Balanced core. A balanced core is one which is supported and balanced from its one end only. A balanced core requires a long core seat so that the core does not sag or fall into the mold. A balanced core is used when a casting does not want a through cavity. The image is further more clarify your concept. Drop or stop of core. A stop of core is employed to make a cavity in the casting which cannot be made with either type of cores. A stop of core is used when a hole recess or cavity requires in a casting is not in line with the parting surface rather it is above or below the parting line of the casting. Depending on its shape and use a stop of core may be known as tail core, saddle core, chair core etc. Ram up core. A ram up core is one which is placed in the sand along with the pattern before ramming the mold. A ram up core cannot be placed in the mold after the mold has been rammed. It is used to make internal or external surface details of the casting. It is more elaboratively self-explanatory figure shown on the screen. Key score. A key score does not require a core seat for getting supported. It is held in a position between drag and cope due to the pressure exerted by cope on the drag. A number of key score can be simultaneously positioned in order to obtain a number of holes in the casting. The image is self-explanatory more about the key score. Method of making the cores. Normally, the steps involved, cores and preparation, making the cores, baking the cores, finishing of the cores and setting the cores. The few of the figures are self-explanatory about these steps. Some of the references for these presentations are introduction to basic manufacturing processes and workshop technology by Rajinder Singh, a textbook of workshop technology manufacturing processes by Khurmi Gupta. Thank you.


Hey it's Sifu David we're going to show you the top 10 Wing Chun techniques sequence we're gonna show it to you right now and yes we are giving away these free DVDs Accelerated Wing Chun System Quick Start DVD normally retailing for 129 bucks but end of the contest all you need to do is to subscribe click the notification bell and like and comment on this video and you'll enter automatically into the draw every week we're going to give away a free video so good luck top 10 Wing Chun techniques we're going to show it to you right now here's the first three one two three what did i just do there we've got tanda tansao and da next one is ganda gansao and da next one is lapdak lapdak that's the first three techniques let's show it to you again okay so we go tanda ganda lapdak so you dominate the center line while keeping in the center line keeping his hands down that's the first three techniques so now we did technique number one two three one two three now we're going to do number four to six four to six is tixao jamsao paizan all right so what you do here we end up here lap lapdak then we go jipsao whoo then he'll break his elbow jipsao this is boom i'm just touching my fingers and he can feel the shock jipsao this left hand goes jamsao chop jamsao becomes a grapple to grab his neck boom right into the chin or the throat with my elbow paizan boom all right that's four five six number three four five six now we're going to do number seven eight nine seven is tixao eight is street punch nine is tixao all right i'll show that to you again okay so we did one four five six okay one seven eight nine okay one more time you're good this number four five then number ten my favorite move is the side kick so those are the top 10 most dangerous wing chun techniques the top 10 wing chun techniques of all time i hope you like the video practice hard train safe and if you haven't subscribed to this channel make sure you click the subscribe button click the bell so you get instant notification of all the new awesome video lessons that are coming out almost on a daily basis so i'll see you soon in the next lesson


Excuse me. Good morning and good afternoon. I am Jada McKenna, the CEO of Mercy Corps, and on behalf of the World Economic Forum, I welcome you to this session on data, digital, and innovation levers, taking place during the Sustainable Development Impact Summit. Together with the World Economic Forum, Mercy Corps has co-chaired the Lever for Change on Innovation for the UN Food Systems Summit, and we are so pleased to host this discussion ahead of the UN Food Systems Summit kicking off later this morning. This session is live-streamed with people tuning in from around the world. Simultaneous interpretation is available in English, French, Spanish, Chinese, Arabic, and Russian. Welcome to our panelists and participants. The world has an opportunity to dramatically advance the fight against food insecurity and hunger. Today's UN Food Systems Summit will bring together governments, donors, businesses, and members of civil society from around the world in an effort to transform the way the world produces, consumes, and thinks about food. It is critical that we work together with a sense of urgency to find solutions. 2020 marked the sixth year in a row where global hunger and under nutrition were on the rise. My organization, Mercy Corps, works in some of the world's most fragile places, and our global teams witness daily how the converging crises of conflict, climate, and COVID-19 are fueling hunger and food insecurity. But at Mercy Corps, we also witness a world of possibility, seeing how innovation can transform food systems that build food security, resilience, and inclusive development. We know that innovation has the potential to create more productive, efficient, and climate smart markets for healthy and nutritious food, to make systems more inclusive and to help conflict and climate-affected communities weather risk and participate in the food system. We've worked in partnership with the World Economic Forum to lead the Innovation Lever of Change, designed to make innovation a significant enabling factor for food systems transformation. The Innovation Lever identified four main innovation areas and convened experts and organizations in four working groups, which included data and digital, knowledge and technological, society and institutional, and national and regional. With the joint effort of these four groups, the Innovation Lever has identified an action agenda to guide member states and communities to fast-track food system transformation by fostering innovation. Today, we have gathered a distinguished panel representing a diverse community of public, private, and social sector innovation partners to share the role that innovation can play in transforming food systems through country-led action. Our speakers will share their insights on how we can collaborate among stakeholders and use knowledge and technology to build strong food systems that deliver healthy food for everyone, including those who live in the most fragile places. So turning to our panelists, I'd like to welcome Mr. Christian Frutiger, Assistant Director General, Swiss Agency for Development and Cooperation, Switzerland. His Excellency, the Advisory State Minister of Agriculture of the Federal Democratic Republic of Ethiopia. Her Excellents, Maryam Muhammad Said Al-Mahiri, Minister of State for Food Security, the Office of the Prime Minister of the United Arab Emirates. Mr. Sven Torre-Holster, President and Chief Executive Officer of Yara International based in Norway. And last but certainly not least, Shonda Claim, the Head of the Food Systems Initiative and a member of the Executive Committee of the World Economic Forum in Switzerland. So what I'd like, I'd like to kick off the panel asking each speaker in the order that I introduced you to give really brief remarks on two questions. Which innovation pathways offer the greatest potential to unlock and support country-led food systems transformation? And what new types of multi-stakeholder partnerships and social innovations can help realize that potential? Ambassador Frutiger, perhaps I'll start there. Thanks a lot. Thanks a lot, Jaydan. Hello to everybody. I'll sort of start with a more general, with a few more general points and then maybe we have in the second round a bit of time to go into some more in-depth examples or at least give some examples to bring this down a little bit to the concrete actions that are that are possible. So yes, we, for the first time, we will hear in today at the Food Systems Summit countries calling for a systems approach to food, to address hunger, health, climate, biodiversity and livelihood and so many other interconnected aspects that encompass food systems. So each country will express different needs and challenges to improve their food systems and they will, and this is really a novel, offer a united message that we must break silos, engage more communities and address these challenges with people, especially the most vulnerable and marginalized, as we co-design the action going forward. So these country food systems pathways have been built on inclusive national food systems dialogues that have made it possible and this is really maybe for the first time to share, listen and understand, to plan together to unleash the power of food to deliver progress on all 17 SDGs and this in our view is the first big innovation and the first big achievement of this process in the run-up to the Food Systems Summit. 147 countries engaged in these national food systems dialogues over 800 such dialogues took place all over the world, engaging more than 50,000 people all together. So that's an overwhelming result in view of the transformation of food systems, not the transition, the transformation towards sustainable food systems. This gives us a strong basic social fabric and the opportunity to understand each other better among the different stakeholders and to build trust. So these multi-stakeholder engagements also mean that we are now accountable to the thousands of people who participated in these dialogues and we are accountable to their ideas, aspirations and expectations. This means that governments and businesses must now take bold steps to change the structural imbalances of power that have distorted and pose problem to food systems over the decades. So the four innovation levers which Jada mentioned in their introduction give a series of good pathways forward and how these bold steps could be addressed, and how some of these big imbalances could be addressed. I will stop here in the interest of time and would then maybe like to come back with a few concrete examples on each of these levers later. Thank you back to you Jada. Thank you, thank you. Her Excellency Alma, Harry, would you like to go next? Thank you so much Jada, thank you so much to everyone being here at this important event and it's really exciting to know that in a few hours our food system summit is here and there to sort of pave the way for our future. And yes, we all have a role to play and the UAE also takes this responsibility very seriously in transforming its food systems. I want to share with the audience as well what the UAE is doing on a national level and also on a global level as well. So since we're discussing what are the innovation pathways, I want to share with everybody what I feel in transforming the systems here and the UAE have been really critical or see that they are really good levers to accelerate our efforts. Number one, it's harnessing the private sector and empowering them. It's really been in a way the private sector are soldiers on the ground. We need to understand their needs. We need to see what barriers are they facing. How can they develop more? How can we ensure that they take sustainable pathways as well? So we did a lot of things like accelerators, accelerators but for the ag tech sector. We did think tanks. We also just recently launched the Food Tech Valley. These are all initiatives that we've done in the country to empower the private sector to grow and develop. As you all know, the UAE is a country that has very harsh climate so we cannot do the traditional open field agriculture but we can harness technology and innovation and be able to sort of grow an ag tech sector. And this is something that excites the youth. Women are really interested in this sector too so we really want to grow this sector. So understanding the needs of the private sector is for us number one. Number two, it's creating strong links between government, academia and the private sector. Again, this is ensuring we're communicating, we're understanding needs. We just hosted last week a workshop between all these parties looking at how treated wastewater could be used as a sustainable water resource for controlled environment agriculture. We know in our climates we need a lot of water for cooling needs but why should we use desalinated water? Why not look at treated wastewater as well? So looking at how treated wastewater could be used. And then third, it's empowering a very exciting news sector which is alternative foods and in particularly alternative proteins. We really feel knowing that moving forward, hoping to have enough food for the nine billion people in future, we really need to look at more sustainable ways of how we can grow and produce our proteins. Therefore we really feel this whole sector of plant-based alternatives, cultured meat, fermentation is an industry that really needs to be looked at and empowered as well. And the UAE is taking steps in this. The Food Tech Valley will also be really looking into empowering this sector. So these are the three pathways that I'd like to share with everyone that I feel are important to accelerate in the decade of action that we're in. That's wonderful and very action packed. His Excellency Boru. Thank you, Her Excellency and the dear all participants. First, I'm very honored to participate in such a very impressive panel which will be dealt on the data and the innovation level. So currently our government through the Ministry of Agriculture and also the ATA, Agriculture Transformation Agency, collaborated to work for food systems, summit innovation level, change to help defining shared innovation principles, supporting the collaboration of actors across the sectors, meaning that from all the agricultural value chains in which we have just currently prepared the food and nutrition strategy, so that this innovation policy brief, which is prepared by this panel under the Convention of Economic Forum, will help us just in the future to transform our food system here in Ethiopia to its highest level. So through this framework, we have just stated the game-changing solutions in which the innovation technology of this data and innovation will help us. The other point here I want to just put here is regarding the data and the digital quality, including our ministry and also ATA, Jobian Agriculture Transformation Agency, the Mercy Corp, Consumers International and also World Economic Forum also produced the future marketplace playbook exploring transparent and exclusive sustainability scale models that enable all actors, meaning that along it is these value chains to from our small farmers to the producers, to the consumers, so that in order to just access and easily transform this all through this process, so that this playbook features the work for our ministry and the doing world ATA and the data hub and also transformative leverage point to drive forward the broader strategy, meaning that with that we have put in the food and the nutrition strategy, so that with this as a government and also as our ministry and also respect sectors, we are very welcome this all technologies which will be just enabling us or leveraging us to just transform our food along its value chains, so that in future with this coalition we are very honored and welcome all stakeholders or both of the government or an government participants to do participate on this all in order to realize our this strategy which have been just stated before, so that thank you very much. This is all our pointers and also back to you. Yeah, thank you, Minister Boru. Ethiopia has been on the path towards transformation for a while, so it's always great to hear about your latest efforts. And Mr. Sven Holster, please. Thank you, Teda and D.R.F.O. panelists. Yarn International is a global crop nutrition company and as a direct response to the Paris Agreement, we decided to change our mission, our vision and our strategy to embed the sustainable development goals, so our mission is to responsibly feed the world and protect the planet and in that is a promise both to help to grow food for a growing population, but also to do it in a sustainable and inclusive way. And I think in this session I'll focus on the inclusivity part of it, because sadly what we've seen in the last year is that the number of people going hungry to bed has increased for the first time in a very long time. A hundred million more people are going hungry to bed now than about a year ago, so an innovation can do something about that. And it's not to me at least only about technology, it's about the distribution of knowledge. And when we make knowledge available to everyone, we start to close the social divide that we have today. And the technologies already exist. The challenge is how do we reach the millions of farmers through user-friendly and real-time data so that they can use and let me be super concrete on this. As a response to the pandemic, we launched something called Africa Connect, where we reached out to farmers and retailers to spread agronomic competence. And in just a matter of months, we were able to get 4,000 retailers on board, 2 million farmers in Tanzania and Kenya, and with this ecosystem where we bring solutions together, we start to see real results already in the first harvest, where we see crop yields multiplying compared to where they were before. And that has a food security impact, but also from a small business point of view, we're making the farmers more profitable. And that game changer is through technology and where we can start to reward small holder farmers with additional income for better practices. And we can build on that with something that we've launched, a go to carbon lines to do carbon farming, to create additional income for the farmers, as well as we both address a climate issue, but also an income issue for the farmers. So for me, technology is a very strong solution to this, but think about it more as an enabler to spread knowledge today with the help of whether it's a smartphone like this or a normal cell phone, you can put in the palm of the small holder farmer knowledge and expertise that in the past would only be available to huge industrial scale farmers. Today, we're reaching 10 million farmers digitally by 2030. We're aiming at the connecting with 100 million farmers. I think I'll keep it there for now. That's wonderful. And those numbers are good examples of aiming for, as Mr, as Ambassador Frutiker said, aiming for transformation and not just transition. As we know, this summit is really just the beginning of an action path that we all will take to move towards transformation. So with that, I just have a few follow up questions to kind of get us all inspired about the actions that you all are taking and to help us think about pragmatic steps we can take ourselves. I'd like to start with you, Her Excellency Almaheri. You've spoken about how the UAE is advancing innovative agricultural technology to deal with your specific climate. And can you share, and while also creating a more inclusive workforce, and I think you mentioned you specifically, can you share how you see the new ideas and practices being formed in the UAE, like can help other arid countries? Sure, sure. Thanks, Jada. And yeah, I totally agree with what Sven says. It's the innovation and technology, but ensuring that so once we know and we have this technology and innovation and expertise, we need to share this. It's our duty to do so. So the UAE being a country that has very low annual rainfall, less than 5% arable land. We really had to look into how we can innovate when looking at what we could grow in the UAE and still be sustainable. So not everything makes sense to grow here in the UAE, but because of technology advancements, there are a lot of food types that we can grow now using closed environment agricultural systems. And really for us, when you look now what you can find locally, we've got all the vegetables you can think of, leafy greens, we've got blueberries, raspberries, quinoa, salmon. These are all foods that just in the last two, three years, you're actually seeing in the market. So also making sure that the people here are aware that this is made locally and this is made sustainably. So so that people now start thinking about where food comes from because we're a country that all the last years have been very much used to importing a lot of food. Everyone was used to having food coming from abroad. But now it's kind of like this mindset change where like, no, actually you can find this locally and try to support your local producers as well. And including also the local farmers and making sure that they also know what technologies they could use, ensuring they have access to financing, access to land, access to insurance. So so we're really going through a transformation and changing the blueprint of the country and looking at what we could produce here sustainably. Just to mention that the UAE has basically a plan, a national plan. We have the UAE national food security strategy. I think it's really important for countries to ensure that they have targets to work towards. They have they have a plan and that all the authorities know the bigger umbrella to to where they're so they know where they're working towards. I think this is really important. And we have that here in the UAE. And this plan is all about transforming our food systems and also taking that knowledge, which we will hopefully then develop or are developing and sharing that with others who also have hot arid climates like we do. So we don't want to just become or we are a hub of food trade, but we want to now become also a hub of knowledge, technology for hot arid climates too. So taking this taking this up and of course, any new technology that you're looking at, there is a there's usually a high cost coming with it. But once you start fine tuning it and looking how you can down or put down the costs and really make it something that's accessible for for all is really important here as well. So yeah, so in a nutshell, what we want to do is we want to look at technology and innovation ensure we're reaching everyone ensure the community is also taking a part in this and is demanding the right foods and looking at foods locally as well. And then, of course, taking that knowledge as well to others who have the same kind of environment that we have. Thank you. I love that creation of a new blueprint and then spreading that and sharing. That's wonderful. Minister Borough, you talked about the work of the data in digital coalition and the market book playbook that emerged for that is very impressive. And we're at Mercy Corps have been really proud to be part of these efforts. Can you talk a little bit more about your vision and ambitions for advancing and scaling data and digital solutions after the summit and particularly ensuring that these solutions enable these transformations to reach the last mile. Thank you, Madam Tajeda. As you know, Ethiopia is currently just expanding her internet penetration to all, especially for these rural areas. Through that, but we started before some, as I told you, ATE data hub, the Agile Transformation Data Hub currently just giving service for small farmers, extension services by using some technologies, just SMS, the short method, and also others. So for future, our ambition with this data coalition, after we expand all this, the internet penetration to all our 80 percent of small farmers in the future, you are highly in need of just also we have just designed the strategy, the Ethiopian digital strategy, in that our country just framed into five thematic areas in which agriculture is one of its, in which we are just the future promoting the digital agriculture economy so that in that we highly need of this data coalition, the digital data, so that for that we have just expanding our infrastructures to services. So, ATE, Agile Transformation and other old international and also local developers could help us, we believe, and also when to just call for them on this special panel in the future, we have the ambition of this transforming our society. So this data revolution, okay. I get some point is very impressive point is from UAE and also other my speakers from YARA and also you and also this is very impressive from the side of this coalition, this data coalition, so that we are very, very welcome and also have revised our new policy in which it is very incited to work with this digital agriculture in the future. So we are very welcome and also Herta, we also presented our this strategy in the room, pre-submit, pre-submit, our Excellency Minister, everyone also presented there and also we have much institutionalizing and forming in the issue of this climate smart market for our food and nutrition. So this to conclude we are very welcome and also because it's your passion to have a well-conduced agroecology and also we have conducive environment and also ample large of large agricultural land use to feed ours and also the globe. Thank you very much. Back to you. Thank you. Thank you, Mr. Bohr. Kristen, I know one of the you talked about food system innovation and I know one of the things that SDC has really been a pioneer around the food innovation hubs supporting this ecosystem of food transformation at a country level. What can you talk about to us a little bit about the unique opportunities you see in those for addressing food insecurity and for ensuring innovations really reach those who have been historically excluded from the system? Absolutely, thanks a lot. It's really breaking this down then to the local level and so I'd like to just make four points on the four areas of the of the policy brief. You know on knowledge and technological solutions Switzerland has taken leadership in the food systems pre-summit to launch the coalition on agroecology together with nine other member states you and organizations and farmers associations among others. Agroecology is often you know believed as a bit of an outdated concept but we are really convinced that it's dynamic and innovative and that it can help avoid some of the clashes and dead ends in the current food systems particularly it will help these millions of small holder farmers who are at the basis of the food systems particularly in the global south and the high level panel of experts on food security and nutrition has outlined these 13 principles which clearly point into that direction. Tomorrow SDC will co-organize the launch of a citizen science initiative which reaches out to farmers and food consumers around the world and of all generations to really look at innovative ways of transiting to agroecological food systems. Second institutional innovation addressing some of the financing gaps again at local level. Governments can give the regulatory framework and the policy environment but we also need smart ways of risk sharing with the private sector and we need to find the right mix of blended finance instruments. Here an initiative just as an example in Africa looking at the missing middle so funding financing small and medium-sized enterprises in agricultural transformation so they connect basically small holder farmers to local markets. Huge financing gap there we're looking to raise with 50 million Swiss francs or US dollars in grant funding about 700 million dollars in private funding providing first loss guarantees and technical assistance out of these 50 million and raising the other 700 million. Thirdly more from a hub perspective national regional innovation ecosystems but also looking at cities. Cities are food systems ecosystems in themselves they have a powerful leverage they're also slightly more manageable than national level or regional level level systems and we have been working with cities we're also supporting a nutrition in city ecosystems initiative in Bangladesh Kenya and Rwanda to really approach towards that and last but not least data and digital I'm not going to go into details this is the whole universe but just a pitch in a bit more than two weeks time the UN World Data Forum will be taking place in Switzerland and we'll certainly continue the discussion on food systems and innovation hubs there. Thank you that's wonderful lots of exciting stuff coming on spend Yara's commitment to nature positive production and reaching farmers is and has been impressive for a long time and love to hearing about the data and digital intake that you're pushing can you talk about what continued support you see needed from governments and civil society to reach your goal of 100 million and to continue to spread to spread these innovations. Thanks Karan I'll be super short in interest of time here but if I could have a wish it would be that we could all get together and create a standardized open farm and field data exchange because if we get that in place globally we have something to build on then we can get scale we can incentivize based on that we can measure we can de-risk and through that we will be able to to also simplify the life of farmers because imagine if everyone is trying to do this in his or hers proprietary way to measure how are we then going to be able to help the everyday life of the farmers but if you have a standard in place we would be able to get that done and I'm certainly committed to that from from the other we are working with several players in the in the food system as well to to try to create this neutral system that could be a standalone system but that would enable the collection of data and also to create the incentives so that we could reach 100 million farmers this is doable but let's try to do it as simple as possible. Yes yes yes I I love that it's doable and we can do it with minimal complexity. This has been an illuminating discussion on how innovation can play a role in transforming food systems and particularly critical in understanding how innovation can work in practice to deliver results to help us advance the fight against food insecurity and hunger and and I want to give a tremendous thank you to our panelists and I sincerely hope that everyone watching this has been inspired or thought about other ways that they can move the agenda forward. I want to thank the World Economic Forum and all of you for sharing your vision I will hand it over to Sean DeClaim for closing remarks. Wonderful thank you Jada and it's just lovely to hear the panel and you know the leadership that's coming through from from all of you I think what was clear today was a real focus around people centered innovation and how innovation pardon me is a key accelerator and but also an enabler for food systems transformation and we stress that word transformation but also how it's been critical when you're looking at innovation to adopt a much wider more holistic view of innovation that includes you know local knowledge that brings in you know very strongly the whole local agenda it's a bottom up agenda that looks at institutional and institutional innovation but also of social innovation so I think what we were hearing today was particularly a focus around we we heard really clearly some of the wonderful leadership examples that are coming out from countries who are really looking to build those ecosystems at the at the country level to really focus on those whether it's food valleys or whether it's building out in in UAE or whether it's building on the the wonderful work of the agricultural transformation agency in Ethiopia and Christian talked about the the role of looking at ecosystems but also not just nationally but including cities and so so how you would build out these these food innovation hubs and what what that would mean and I think then also just the how we break the silos we heard about agroecology and regenerative food and you know what that means and you know with the food innovation with the innovation lever it's been interesting to to really focus on we we heard the farmers voice come through very strongly and it was talked about a lot today and the whole creation of a hundred million farmer platform promoting solutions towards net zero nature positive food system transformation and then finally yes we did hear about digital but what we heard was this is not the whole thing and and some really exciting discussions there around the this idea of a digital data coalition that's coming out of the innovation lever and also things like the the marketplace playbook the digital data marketplace playbook and just some of the the great examples that are coming out and some and that was really born out of a conversation between consumers and consume led by consumer international and farmer organizations you know organizations like mercy book or playing such a key role and we've just seen a a terrific lot of examples of where we can really start to look at inclusive use of of data to actually improve food systems to make sure that we're reducing waste that we're we're actually doing this in a much more inclusive way so I hope if you've taken nothing away from this you've taken away a much broader view of innovation than simply one that's just focused on digital or technology but actually this much more inclusive holistic view of innovation so thank you to the panel really exciting to hear all this leadership that's coming through in in UAE and Ethiopia the role that you know countries like switzerland are playing both in their own country but also globally and then you know organizations like mercy call the leadership there and companies like Yarra thank you very much


Hi everyone, Joe for Jaspy's CaseBreaks.com, coming at you with 2022 Gold Rush, Autograph Jerseys. It's a multi-sport break, six boxes, which is a whole case, random letter break. We're going by the first letter of their first name. And actually, let's go back to the one we... So the next break is already loaded up. So it's a 19-spot break, so for example, if you pull an each row, and you have a letter I, you get each row. For example, I think most of these are going to be custom jerseys. You may see some officially licensed ones as well. But it looks like it's a multi-sport, including some soccer. Those are all the letters right there. Also, the Eagles multi... The QB multi-signed jersey will go to letter E, and the University of Kentucky jersey will go to letter U. I'm not sure if there's an example of that over here, but just keep that in mind. All right. So this is break number one. You can see that the next case is already in the store. Big thanks to this group for making it happen. Let's randomize you a letter. Let's roll it, randomize it, five and a one, six times, one, two, three, four, five, and a one, six and final time. After six, we've got Tana down to Chad. Five and a one, six times for the letters. After six times, we've got ZU down to P. All right, Tana with Z and U, Chad with C, Jim with T, Chad with E, Adam with NV, James FH, Tana with B, Chad MS, Andy IK, Nancy L, Chad WY, and J, Jake with R, Ben with A, Chad with G, Tana with D, and Chad with P. So let's sort alphabetically, and remember going first letter of their first name. Now we're going to pause the video. When we come back, we're going to see if there's any trades, and then we'll have the break. Stick around. We've got the case right here. Stick around. We'll be right back. All right. Welcome back, everyone. Oh, I forgot to write TWC in the chat. TWC trade window closed. Big thanks to everybody here. We're going first letter of their first name. That should make this break pretty easy. We've got six jerseys in here, the gold rush seal right there. Dropping my knife, I thought I was going to stab myself. If it's Pelle, it'll go to P. We'll just make that easy on ourselves. All right. Good luck, everybody. Oh, man. Rex, I wish I had Stormtrooper gear to wear while I watched those shows, but that's not in the budget. I'm going to turn off that top camera right over here just for a second because I'm going to take a look over here. We don't want to reveal it too early. Who are you? Do they have the names on them? Do they have a name on here? Oh, I know who this is. All right. We can play a quick, some quick rounds of who am I? Nothing else is sold out after this, right? Was everyone going to let me leave early without doing the double header? I hope so. It's my Friday. I'm Jason with the double header tomorrow. Brian. Oh, sorry. Brian is his name. So B. Tana, you'll get it. But Brian who? Played for two teams mine, two NFL teams my entire career. A former second round overall pig. Four-time first team all-pro. Second-time all-pro. Nine-time pro bowl or part of the NFL 2000s all-decade team. A PFWA all-rookie team. Ended my career with 1,147 tackles. 26 sacks. 36 forced fumbles. 19 fumble recoveries. 37 interceptions and four total touchdowns. I'm in the pro football hall of fame. It is not Brian Urlocker. Gilo's got it. It's Brian Dawkins. That goes to Tana in the letter B. Got a cool order. So these are custom jerseys. I think I'm just going to leave them inside this. Yeah, you can tell that these are just custom jerseys. I'll leave it nicely folded in here. Ah, Carl's going to make me work tonight. So this is what I'm going to do now. This is going to be a great game for Aaron Judge Cut-In. Like, you can put that one in. Does he always do it on his own runs? I know. That's when we need the Aaron Judge Cut-Ins. All right. So I guess Carl's going to make me do the double header tonight on my Friday. Just trying to get out of here. But no, Carl's like, you got to work, Joe. All right. Oh, next you saw those colors right there, but who are you? I'm a pitcher. Starting pitcher. I bat left, but I throw right. Think of a different Mets pitcher. Grizzle Bees. Played for the Mets my entire career. Four-time All-Star, two-time MLB first team. They do that now. Two-time NL Cy Young and NL Rookie of the Year and NL ERA leader and a two-time NL Strikeout leader. He's pretty darn good. He's going to be a free agent at the end of the season, too. Through 2022, 82 wins. 57 losses. 252 ERA. 1600 strikeouts already. A whip of 1.00. That's right. Degote says Grizzle Bees. Degrom says Nate. Both of you got it. There's some officially licensed jerseys mixed in there. That's awesome. There's his auto there. Chad with the letter J. There you go, Chad. Should we take a look at this? These are pretty cool. It even has the Nike Retail tag still attached to it. Nike tag on the bottom as well. I'll get this folded up nicely before it goes anywhere. Third one. That's got to be this player, right? All right. I am a right fielder. 25 years old, bats left, throws right. There's a lot of bats left, throws right here. Lifetime 268 batting average. 73 home runs. 256 runs batted in. I wasn't all star this year, actually. And the AL Triples leader in 2020. Not Ben and Tendi. Not Cedric Mullins. He's with the Astros. I'll give that away, because it's not a letter break, not a team break. Let me take one more guess. That's right, Kevin M. Kyle Tucker. There's his autograph right there. Pretty highly-tied prospect. Beckett card, Beckett sticker. It's right over there. Custom jersey. Andy with the letter K. All right, we've got a basketball player. 24-year-old basketball player from Nolans, born in New Orleans, Louisiana. 6-3-185 point guard in the NBA. Went to high school in Texas. Went to college in Kentucky. And was a fifth overall pick. I'm still with this team. Was first team all SEC. SEC, all freshman team. SEC tournament MVP. McDonald's All American. And what did he do last year? Average about 23 points a game. 3.9 rebounds a game. 5.6 assists per game. Not Tyler Hero. John Wall is not 24 years old. John Wall says not play for one team his entire career. He was the fifth overall pick in the 2017 NBA draft. Not a manual quickly. There you go, Kevin. It's a fox in the box. De'Aaron Fox. There's the Beckett infill right there. There's his autograph right in the middle of the five. Another custom jersey. No, no, like NBA logo man up there. Letter D. More Tana with the De'Aaron Fox. Oh. I know who you are. Alright, I'm a retired basketball player. Born in Milwaukee, Wisconsin. I'm 52 years old now. 6'5", 195. Was a, well, yeah. Was shooting guard. Small forward. Went to high school in Milwaukee, Wisconsin. Went to college at Three Rivers. Three Rivers College. A public community college in Poplar Bluffs, Missouri. And then transferred to Alabama. Played there in the early 90s. And was a first round pick, 24th overall by the Golden State Warriors. Played for the Warriors, the Knicks, and the Timberwolves. A four-time NBA All-Star and All-MBA First Team. NBA All-Defensive Second Team. All-MBA Rookie Second Team. Second Team All-SEC. SEC All-Defensive Team. Ended up averaging about 18.3 points per game. Four assists. And about a steal and a half per game. I also have a legal issues section in here. And there was a bit of a choking incident with a coach. That was unfortunate. No? Thought the choking the coach would... Pretty well. Another custom jersey here. You got the JSA card and all that information. There's his autograph right there. All right, letter L. That'll be for Nancy, the letter L. All right, final one. Good luck, everybody. All right, we're going to end with a retired football player. We're going to end with a retired football player retired a long time ago. Got to listen to the clues first, Carl. Who am I? I'm 71 years old. Born in South River, New Jersey. 6'2", 12". A wide receiver. Played with one team my entire career. Went to college in Tulsa. Went undrafted. And then ended up in the Pro Football Hall of Fame. A Super Bowl champion. A three-time first team all-pro. A three-time pro bowler and an FL receiving yards leader. Part of the NFL 1970s all-decade team and part of this team's ring of honor. Played 156 games with just one team my entire career. Played 10 years in the NFL. Ended up with 489 receptions for 7,822 receiving yards and 48 touchdowns. That's a lot when you're playing in the 70s. Cowboy. So think about Dallas Cowboys number 88s in the 70s. Not Largin, not Blitnikov. Well, what else is there? He did a little bit of coaching with the Cowboys in 85, the Dallas Texans in 91. Was an executive for an AFL team for a year. And then for another couple years another champions indoor football executive there as well. Not to pre. You'll know his name when I say it. Dorset is a running back I want to say this is a wide receiver number 88. And this was still the days when numbers meant something when you played a football position chat. In April 28th, 2017 I was selected to announce a pick in the 2017 NFL draft which took place in Philadelphia. It missed booze from Eagles fans and intents he led out a dramatic speech and announced Shadobe Awuzier as a 60th pick for the Cowboys. Cowboys Hall of Fame wide receivers in the 70s. Oh, no one's getting it, huh? This goes to Tana and the letter D. It's Drew Pearson. There's Drew's autograph right there. There's the Beckett sticker right there. And that goes to Tana once again and the letter D. That's it folks. Thanks for watching. Thanks for breaking with us. Thanks for playing Who Am I. I'll see you next. There's another case loaded up so I'll see you next time for the next one. Thank you.


of career that has bridged both academic and industrial research. Currently, Dr. Corn is the founding scientific director of Innovative Genomics Institute, which is a unique collaboration between UC Berkeley and UC San Francisco. Additionally, he is an assistant professor of molecular biology and bio-physics, oh, molecular and cell biology at the University of California, Berkeley. Previously to this, he was a group leader at Gen and Tech, noted for incorporating multiple fields in the development of new therapeutics. The current aim of his research is to end genetic disease, such as sickle cell disease, through the development of next generation genome editing technologies. These tools, such as CRISPR-Cas9, have allowed novel discoveries about the fundamental workings of cells and also the mechanisms of diseases. Additionally, Dr. Corn has publicly spoken about potential ethical challenges posed by widespread applications of these technologies. Please welcome Dr. Corn to the stage. Thanks very much for having me here today. Good afternoon. This conference has been really fantastic. I think this is one of the wonderful things about a liberal arts education. I did, my undergraduate at a small liberal arts college, University of Puget Sound in the Northwest, and this is one of the things that I think is so great about these environments, you know, merging both questions about science with questions about how do we think about these things? You know, not just what can we do, but what should we do? I'm gonna start by getting a poll from the audience. I didn't warn anyone in advance I would do this so there's no clicker or anything like that that you can do. But this is an easy poll. How many of you have read a book or seen a movie that incorporates genetic engineering? Right, Jurassic Park or anything like that, Gattaca, right, did it end well? So, typically this is the way we think about genetic engineering, right? In popular culture it's very often this warning sign, scientists go off into a lab, they do something crazy, they make dinosaurs and those dinosaurs end up eating the scientists and it's not great, right? But there's another side to new possibilities in genetic engineering and that's potentially someday to be able to cure genetic diseases. That's one of the things that I'm very passionate about. Genetic diseases are caused by mutations that are in people's DNA. You can treat genetic diseases right now, but it's so-called palliative care. So you treat symptoms, but the underlying cause remains the same and what the hope is for genetic diseases to give people the possibility if they want to be able to treat the mutation in their genome. So that's what I'm gonna talk about, where are we? And not in some sort of science fiction way, but really like where is the technology? What's actually realistic? What can we do today? What might we do in the future? And I promise no dinosaurs. So let's start off by talking about what are we really talking about? We're talking about genes and genes are things inside all organisms that really shape life. So bacteria have genes and in fact the rise of resistance to antibiotics is caused by mutations in genes that are in the bacteria that allow them to process those antibiotics. Whenever you look at your favorite furry friend you can see genes at work. So all dogs are related to each other and just small changes in a couple of genes give the huge diversity between dogs. And of course, if you look at your neighbor you can look left, look right and try to figure out are their ears attached or are they separate? That's a genetic trait, okay? But genes can also go wrong. So mutations in genes can cause genetic disease. This is a picture of the so-called bubble boy. This person was born with severe combined immunodeficiency or SKID. The end result of SKID is that people are born with no functioning immune system. And so they need to be isolated from the environment because they get sick very, very, very easily and very, very badly. The thing about SKID is that there are many, many, many different mutations that can lead to this and all of them result in having no functional immune system. Now there are other types of genetic diseases where there's a single mutation that can cause that disease. An example of that would be sickle cell disease. So everyone with sickle cell disease has the same mutation, okay? And it's in a protein called hemoglobin that normally carries oxygen. And that mutation instead causes the hemoglobin protein to clog up capillaries. So it makes your red blood cells form this weird shape, clogs up capillaries, and it leads to very, very severe pain, okay? That capillary clogging also leads to a greatly decreased lifespan. So in the developing world, people live until maybe they're around 45. In Sub-Saharan Africa, where the trade is most prevalent, people usually die around age five, okay? So this is a genetic disease. Sickle cell disease is very prevalent in tropical or other countries where malaria is quite present. And so in the US, the trade is most often found in individuals of African descent. But it also pops up all throughout the world. So like I said, there are plenty of people in the US that have it, but there are millions of people in Africa. So what we're really talking about here is a huge amount of genetic information in someone's body, okay? So if you think about your body as sort of a, each cell contains a library of genetic information, and that information gets read out. Most of the time when you have mutations, those mutations cause a typo, but you can still figure out what the sentence says. So you can think about maybe you're reading through a book and there's something that changes a word a little bit, you can still figure out what that means, and that would be a neutral mutation. And actually between you and the person sitting next to you, there are thousands of neutral mutations, and they're basically benign. They don't really do anything. But every once in a while, there's a mutation that changes the meaning of a word, and it can change the meaning of the word very, very, very seriously. So simple example might be, if you think about the word dancer, that's one letter away, a C from the word cancer. So you can imagine that in the entire book, if the word dancer gets changed to cancer in just the right way and just the wrong place, that can be really bad. So what do we hope in terms of genetic engineering, the hope is really to be able to take this huge amount of genetic information and to flip things back, to be able to take mutations that have arisen and put them back into a state that does not cause disease. One of the reasons why people are really excited about genetic engineering research right now is because in the last couple of years, we've now understood much more about our own genomes. So when it comes to reading genomes, sequencing genomes, sequencing people, understanding what mutations are out there, there have been huge, huge strides over the last decade. It's now actually possible for individual patients to have their genomes completely sequenced, the procedure is totally non-invasive and it really only costs about $1,000 when you get down to it. So it's actually quite cheap and it gets done on a relatively routine basis. The problem is what you do with all that information because what I told you is that if you take any two individuals and you sequence them, there are going to be thousands of changes and most of them don't really do anything. So there's a big question about how do you know what mutations cause problems, but then of course, once you figure out which one causes the problem, you need to be able to do something about it and that's where genome engineering comes in, gene editing. The problem is we're much better at reading than we are at writing. So we've had tools to be able to change genomes for about 20 years. Things are starting to accelerate. CRISPR-Cas9 is one example of that acceleration, but we're still very new at this. So like I said, gene editing has been around for about 20 years. So that might be a little bit of a surprise to people in the audience, why am I only hearing about this now when it comes to science? Why isn't it that I heard about this 20 years ago? And in part, it's because it was pretty hard to do. So the first gene editing tools were called zinc finger nucleases, and it might surprise you to know that these are actually in the clinic right now. There is a company that is using zinc finger nucleases to try to cure diseases, and in fact, they have pretty promising results to try to cure HIV. So the idea here is that HIV attacks a certain cell in your blood, and it does so by binding onto a certain thing that's on the surface of that cell. And that thing that's on the surface of the cell doesn't seem to do much else. So what do these gene editors do? They delete the thing on the surface of the cell, and now the HIV has nowhere to go, and you can eventually clear it out. So this is actually in phase two clinical trials for HIV and has been shown to cure people of HIV. But again, zinc finger nucleases are hard to use. They're slow to deploy. You really have to be a specialist in the art to use them. So what has really changed gene editing research is the development of so-called CRISPR-Cas9. And the fundamental advance here is not the idea of gene editing in and of itself, but the democratization of gene editing for research and hopefully, eventually, for therapy. So what is Cas9? Let's take a sort of geek out moments, talk about how does this thing actually work. I'm going to present a little blob. In this blob, you have Cas9, which is the protein, and it's recognizing a piece of DNA and opening up that piece of DNA. Cas9 then uses a piece of RNA, which is another piece of so-called nucleic acid in the body to recognize that. So when I talk about DNA and RNA, just think back to ATGC, that kind of thing, which hopefully you've heard about before. One thing you might remember about DNA is that you have pairs of these bases, these nucleic acids. And the way that works is A always goes with T and G always goes with C. That's really the fundamental thing that's transformative about CRISPR-Cas9. If you know that A goes with T, G goes with C, which I just told you, that's it. That's all you need to know to design a genome editing region. So you no longer have to spend decades figuring out how does ink fingers work and what cases do they work and what cases don't they work. If you know that A goes with T and G goes with C, you can design a genome editing region. And that allows people to, instead of focusing on the ins and outs of the tools, they instead can focus on just making the tools, reprogramming those tools and using them. It also means that reprogramming this is simple and easy, and as you'll hear in a bit, that means that you can access many more problems. You can access many more different diseases and ask many different questions that you couldn't get to before. So the way genome editing actually works is you make that program change on the RNA, the ATGC part, and that brings Cas9 to a certain area of the genome. And then Cas9 cuts that part of the genome. And that might sound surprising, right? We're talking about editing. Why are we suddenly doing cutting when we wanna be doing editing? And the reason this works is that all organisms that are out there have evolved great ways to protect their genomes.  Your cells have defenses against DNA damage. And in your cells, this happens in one of two ways. On the one hand, you have error-prone repair, which leads to deletions and insertions at a region. And on the other hand, you have the opportunity to put in extra information, which the cell will then copy off of and incorporate that information. So what does that mean? When you get the insertions and deletions, that will disrupt whatever's there. So if there was information that was doing something, let's say something said dancer, now it might say DA, XQ, blah, blah, blah, right, all kinds of weird stuff. It breaks whatever was there, okay? That's useful from a research point of view, because the way we do research in biology is taking something that works already, say in a cultured cell or in a model organism, and we try to break it in very precise ways and ask, how does breaking this thing in this precise way change the outcome? That's the way we learn things about the world around us. That's important because the world around us is very complicated. And so instead of trying to say build a car engine just from a whole bunch of parts laying around, we start with already working car engines and take out one piece at a time and ask what does this do? So Cas9 on the one hand is a way to ask fundamental questions about how the engines that are ourselves actually work. From an editing point of view, the sort of more surgical way of doing things, we can swap mutations in and out in a very precise way. So instead of putting in that weird, crazy, ex-QZ in the middle of Dancer, we can take the sequence that says Cancer and change it back into Dancer. So it's very precise and very surgical. So there's uses for fundamental research and there's potential to curing genetic disease. But one of the things is that context really matters. Turns out that not every cell in your body has the same types of repair mechanisms as every other cell. So one of the things that people are trying to figure out right now is when you try to make these fixes in, say, a brain cell versus a blood cell, how do we better control and get the outcomes that we want? So I really wanna stress that we're not at the science fiction future now where we're just able to put these kinds of changes into cells in patients right away. We're still in the, we have new tools, we need to understand how they work and we need to understand how they intersect with our own bodies. So let's zoom in a little bit more from the blob. What I'm showing you here is a 3D model of Cas9. So this is actually what Cas9 looks like. This is based on a so-called crystal structure that was solved relatively recently. So this is actually physically what Cas9 looks like. Cas9 is the protein that's in white. The gene that it's recognizing is in blue and the guide RNA which gets used to pair to the gene, the ATGC pair, that's in orange. We can pop away part of Cas9 and you can see that what happens is the guide RNA wraps around the target gene and when it does so, it leads to these breaks. Once those breaks get put in, that's the signal for the cell to say up, I have a break in the genome and I need to repair it, I need to do something with that. So really Cas9 is a little genome editing machine. I'm not gonna get into the details of how Cas9 and CRISPR systems were discovered other than to take a quick aside to say, CRISPR-Cas9 is one of the really amazing stories of how fundamental research can have huge implications for application and potentially treating therapy. Cas9 and CRISPR are actually bacterial systems, the bacterial machines, they were discovered by people not looking for genome editing machines, there were people who were just trying to ask, how is it that bacterial work? And it turns out they have huge implications for treating disease. So I think one of the lessons that we have is, it's important to, maybe a better way to put it is, fortune favors the prepared mind, you need to go out and ask good questions about the world, but it helps to just be curious and to ask those questions without saying, I wanna find a genome editing machine to just ask generally, how does the world around me work? So let me come back to the idea of democratization. I told you there's this easy way of doing the retargeting, what that does is it really changes the way we think about using these genome editing tools. It used to be that a whole bunch of people would have a whole lot of different questions. And if you wanted to ask those questions using genome editing, you'd have to go to your one genome editing expert, and then everything would bottleneck around there. And so things slowed down a lot. And actually they ended up being quite expensive. And with Cas9 what happens instead is that everybody now can use these tools themselves. And so that's one of the things that I wanna put out there is, using Cas9 and CRISPR systems to cure genetic disease is very, very exciting. But one of the huge possibilities here in general for therapy is the ability to ask and answer questions that are more fundamental, much more rapidly. And that's really I think sort of the snowball effect that will have an effect in our lives. So curing genetic disease is a really important part of CRISPR-Cas9, but now being able to ask the hundreds of questions that people might have and not have all that research bottlenecked in one little area, I think is gonna lead to a huge acceleration in fundamental understanding which will eventually lead to more cures for even non-genetic diseases. To give you an idea of how quickly things are moving, this is a chart showing how many publications mention genome editing. I told you that genome editing was around for about 20 years, so it was in the 90s, but the mentions of genome editing in the literature, in scientific literature were so small before the invention of Cas9 you can't even see them on this graph. So a few people were working in Cas9 right when Cas9 got discovered and CRISPR systems got discovered and deployed, the mentions of genome editing just absolutely exploded. So at this point, there are about 4,000 Cas9 publications in the past four years alone. There are about four papers published every single day. The field is moving at an incredible pace. And I think that just gives you an idea of how exciting people find this. So the use of CRISPR-Cas9 is really transforming biology by letting people ask these kinds of democratized questions. So it's useful in a variety of model organisms. It turns out that it works in non-human primates to ask questions that might be even closer to human health. It works in agricultural species such as wheat, corn, things like that. In my lab, we tend to use it in human cells. So this means, like I said, not only can we use it to ask fundamental questions for research, but we can potentially have hope to apply it towards genetic disease. But as a quick aside, it could even have impacts beyond that. So people have also shown that genome editing using Cas9 works in agricultural species, goats, cows, chickens, et cetera. And people have shown that it works in mosquitoes and the malaria parasite. So people are starting to think about ways of potentially eradicating malaria using genome editing tools. That's a topic for another day because I think we wanna focus on the possibility for, say, genome editing and reproduction. So let's give a concrete example of how genome editing might change the way people treat diseases. Let's focus this on sickle cell disease. Sickle cell disease is a blood disorder. So it's caused by sickling of red blood cells, but that eventually comes all the way back to bone marrow. Your bone marrow is the source of all the blood components that you have. Now, sickle cell disease can be cured permanently through a so-called allogeneic transplant. And allogeneic means you take the bone marrow from a healthy individual and you transplant it into someone with sickle cell disease. And that then renders them healthy, right? They no longer have the bone marrow with the mutation. They have the healthy bone marrow and that cures them. But there are a lot of problems with this. Number one, it can be very hard to find a donor. Number two, the act of doing this bone marrow transplant, you have to ablate the bone marrow and that renders the person who gets the bone marrow transplant infertile. And number three, there is a small chance, about a 1% chance, that people who get this bone marrow transplant will reject the graft. They may have to get another bone marrow transplant to replace their own bone marrow, giving them the disease back again. Or there's a possibility they may never wake up from the operating table. From a gene editing point of view, what we want to do is instead turn this to an autologous transplant. And the easy way of thinking about this is we want to make people their own bone marrow donors. So we want to take someone's bone marrow, which has the sickle cell mutation, take it out, edit the gene to put it back into wild type and then transplant it back into that person. So in this way, rather than taking bone marrow from a healthy person, putting it into someone with a disease, we take someone's own bone marrow where they have the disease and turn it healthy and put it back in. Sickle cell disease is just one example of this. So there are about 100,000 people in the US that have sickle cell disease, which is actually a pretty large number. But worldwide, there are about 350 million people that have some form of genetic disease, at least that have been identified. There are 7,000 different monogenic disorders. That means diseases that are caused by mutations in a single gene, that we know of. And part of the reason people are very excited about CRISPR-Cas9 for genome editing is exactly what I told you previously, which is that it's very easy to make neuroagents. So if it's very hard to make a different genome editing agent, say it takes a year for each one, you can imagine if there are 7,000 different diseases and it takes a long time to make each one, it's gonna take forever to do this, even leaving aside all of the challenges around doing regulation and safety and things like that. Even just finding the first agent to do the editing is gonna take forever. But Cas9 is very fast, it's very easy, and so at least on paper, it could be possible to make a different genome editing agent for each individual mutation, which brings up the idea of personal cures. And the reason I think this is so powerful is something that is actually not private to genetic disease, but it's the idea of something called the long tail. So the long tail may be recognizable to you in the context of something like Amazon or doing Google searches or things like that. And the idea here is that when most people go out, they look for, say, two or three things, two or three products, and that covers a lot of space. Maybe 50% of things are covered by two or three products. So think about this in the context of genetic disease, a bunch of patients have two or three different genetic diseases. And the rest of the 50% is covered up by a huge smattering of a whole bunch of different stuff. That's the long tail, okay? So two or three things capture the first 50%, and the last 50% is covered by thousands. So that's a problem. If you have a tool or reagent to make a cure that is very slow to develop, you'd only be able to do something for the two to three, for 50% of people, for the people who have the two to three diseases. But to really affect the long tail, the other 50%, you need something that's fast and easy. And so the hope that we're not there yet is that Cas9 might be able to address the long tail. Now, there are a lot of challenges here beyond just making these reagents. When you start thinking about personal cures, you have to start thinking about, how do you show that this is safe? How do you run a clinical trial if there are only five people in the world that have this disease? I'm not going to address that because you could probably do an hour-long discussion about just that one issue. I'm gonna focus on just the, I'm gonna say it's potentially there. And so I think one of the things we need to do is start talking about what does the regulation landscape look like now that the possibility is there for the long tail. So I've been talking about gene editing in sort of generic terms. I'm now gonna make a split between so-called somatic gene editing and germline gene editing. Somatic editing means that you make a mutation that has not passed down to different generations. So an example would be this bone marrow transplant that I talked about.  If the person who got that somatic edit now has a child, their child may still have the mutation passed down to them. The difference in germline editing is that you edit, when you edit the so-called germline, you might be editing the eggs or sperm or even the embryo. And that change would be then passed down through generations.  So let's talk first about what issues there might be. I've talked a lot about the promise and how excited people are about this. Some of these concerns came up in the previous discussion and I think were really well covered, but I just wanted to go over them really quickly. The first off being access to treatment. Now, I want to point out this is not a private problem to genetic disease treatment. In fact, the graphic that I'm showing here that shows their problems with stigma, drugs cost too much, there's no confidentiality. All of these things apply to the treatment of genetic disease, but this is a graphic from a WHO handbook, the World Health Organization handbook on treatment for HIV and AIDS. And every single one of these problems, access to clinics that can do gene editing, problems of confidentiality, how do you protect someone did get an edit, did not get an edit, how much is it really gonna cost? All of this applies to a new technology like genome editing. There's another problem which I think has not been covered yet but is no less important, which is part of the challenges of these genetic diseases that they occur in minority populations. And especially when it comes to sickle cell disease, these populations have not been treated well by the medical establishment. And so when I go out and I talk to patients with sickle cell, half of them are excited because they say it's really great that you are focusing on a disease that affects us, who happens to be a minority population. And the other half says, why are you giving us this experimental medicine that you don't actually know is not gonna have some terrible side effect? And I think that's a really important message to take home and one which I don't have a very good answer for. Like we talked about during the discussion, I'm trying to provide options for people but I think that we do have to think hard about where do we test these medicines, how do we show that they're safe and how do we do so in a way that's very responsible to the populations that we're trying to treat. And this especially becomes the case when we start moving into context where these genetic diseases are so rare that say 10 people in the world have the disease and so how do you actually run a trial when running a trial means affecting everyone? The third challenge even with somatic editing is that public acceptance of this is relatively modest. So this is a poll done by Pew Research which I think finished just a couple months ago and they asked people, would you want somatic editing? Not germline editing, but somatic editing. Remember not passed down. Would you want it for your baby if it had a chance of improving that baby's health? And you can see that it's about 50-50 split, okay? So these are people that say my baby is in trouble but I would not want to have editing done and I think it's very telling that in fact there's a split between whether or not people have kids or not and it goes at least to me it went opposite the way that I thought it would. If people have a child, they're actually less likely to think that somatic editing would be a good choice for that child. Now this is in contrast to something that I see a lot when I work with patients who have children with genetic disease. I work with a couple of different patient groups. Some of those patient groups are vehemently for somatic editing. I mean, they want to abolish the FDA and say I don't really want safety trials, I don't want any of that, give me the medicine right now because their children are suffering. And so I think this is another one of those things that would be really interesting to discuss in the future is to what extent do we empower patients to give them access to things when we cannot guarantee that they will be safe. So now let's talk about germline editing. I think people talk a lot about germline editing when it comes to genetic disease but I actually want to start off by talking about the research applications. So this picture is of Kathy Nyakin. She recently had a paper come out in which she asked a very fundamental question using germline editing. And the question she wanted to know is why is it that pregnancies sometimes fail? And you might ask yourself, well, this is surely we must know this by now. The answer is no, we know almost nothing about it. And part of the reason is we have had no tools to be able to ask anything about developing embryos in humans and there's been very little appetite to try to do that research. So Kathy in the UK did a very nice set of experiments trying to ask one part of this fundamental question. And I think that's one of the things that we want to make sure that we do when we talk about germline editing, we don't want to throw the baby out with the bathwater. We want to enable people to answer fundamental questions that will affect a lot of people's lives even in cases that do not impact genetic disease. Now there are cases where germline editing might be useful for therapy. So cases where not just editing the person who's afflicted with the particular disease but making sure that if they don't want to, they don't pass that treat down to their children, there are cases where that might be applicable. And one example of that would be Huntington's disease. Huntington's disease is a so-called repeat expansion disease. You have certain repeats in the gene and for reasons I won't go into, over time over generations they expand out. And what that means is that if the parent is a little bit affected, the child might be more affected, the grandchild will be more affected than that and the great grandchild might be affected most of all. So patients say, look, I'm gonna get a cure for myself but my kid I know is gonna have this disease and they're in fact gonna have it even worse than I do. Why can't I do germline editing to just stop this disease where it starts? And so I think again, this discussion needs to be a little bit more subtle than just like a somatic good germline bad or vice versa. I think we need to talk about these things in terms of specific diseases, specific patients and specific applications. I think we have a little bit of time to do this because it turns out that germline therapy, even if we had all agreed that it would be fine, it's not yet ready for the clinic. So number one, there's a concept of safety. How do you know that you're hitting just what you wanna hit, editing just what you wanna edit and not something else? It turns out that these editing agents can have pleiotropic effects, that means they can hit where you wanna go but they can also hit somewhere else. And until we get very good at only hitting what we wanna hit, you obviously would not wanna chain, you would not wanna pass these off targets on through generations. There's a more subtle problem which is one called mosaicism but actually maybe even more fundamental and harder to get over. Mosaicism is when different cells in the body receive different traits and this can happen in humans. It happens actually, everyone in the audience is familiar with a case of mosaicism which would be a tortoise shell cat. If you see a tortoise shell cat, all those different colors come because those cats are mosaic. Each cell in the coat has a slightly different trait. When you go in and you do germline editing, even in a model organism, such as in these mice which are a real life example, you can see that in these mice, some of the mice are white, some of the mice are black and some of them are modeled. And that's because not all of the cells in that initial mouse, in the initial mouse embryo got the same edit. And this has been the case with germline editing since people started to use it. It's a severe problem and again, we need to understand more about why mosaicism happens to be able to figure out a way around this. A third and possibly the biggest reason to not yet put germline editing in the clinic is really just do we really want to do this? And I think this is actually the biggest barrier. And I think for good reason. When we think about the previous thing, safety mosaicism, these are technical hurdles and those are things that could be overcome probably if we wanted to do it. Public sentiment, that's not something to be overcome, that's something to be discussed, right? That's a question of do we really want to do this? How far do we want to go? What's appropriate, what's not? And I think that it's telling that in this same pure research study, people asked would you be more or less likely to be in favor of gene editing if something was passed on to kids or not passed on to kids? And you can see that if someone made an edit that would be passed on to the whole population, very, very few people find that acceptable. So I think that's something that we need to talk about and I think we need to as societies decide is this something that we want to allow and if it is something we want to allow are there specific cases that we want to allow it in? Why do people even consider this? There's the disease point of view. There's also the question of enhancement. So I want to bring this spectra up in the room because I think this is something that we want to talk about because if we just talk about gene editing for genetic disease, the question becomes relatively easy. Okay, someone has a disease and we want to cure them. There are a lot of subtleties there that we did discuss just a bit ago but it's a little bit easier than saying, well, what about prevention of disease? So for example, there are genes that you can edit in the body that will prevent heart attacks, basically. So there are people that are naturally born that have these mutations and their cholesterol is basically zero. They're incredibly healthy. And the question is, should everybody get this? Rather than taking statins all the time, should everybody get this? There are mutations you can make that can make people more muscular. Like I said previously, there are mutations that can render people HIV resistant. So you might ask yourself, there are questions about enhancement where people talk about hair color and intelligence. Those are not really on the table right now. We don't understand what makes someone more intelligent or taller or anything like that. We do know single genes that could be edited that would render someone HIV resistant. Are those things that should be on the table? So I want to bring that up because I think that's one of those things where if we say yes to one, the question is how do we keep people from doing the other? One of the things that people have actually started to talk about is making edits that will enable people to go to space. So this is something that I think is, this sounds very science fiction, but is one of those things that people are thinking about for the long run. So it turns out humans are not adapted well to space at all. They get osteoporosis. They have, I'm not talking about the breathing in space. No amount of gene editing is going to fix the breathing in space problem. But for example, you develop heart problems, things like that. And so some people have said, look, if we are really, really serious about long-term space travel, sending someone to Mars, we don't want them to arrive on Mars and everybody on the craft has had a heart attack and has brittle bones, right? We need to do something about this. So I think this is one of those things that you would think would only come up in a science fiction book, but people are starting to talk about this and people are starting to say, look, if we're really serious about this as a program, we need to be having these discussions. So I bring this up sort of in the idea of vigorous debate for the further flung future. Finally, why would you consider germline editing? I think the fundamental reason that that is actually the hardest to argue about and comes up the most often with patients is patients say, look, you could do somatic editing and it's gonna affect, but just me. But I want my kids to have a better life than I had. And I think that's something that, personally, I find it very hard to argue with patients about that. How do you tell someone, no, that's not right. You want your kids to have a better life than you did. So I think that's something that we need to really grapple with and I think it's something that we really need to involve patients in. So what is genome editing gonna look like? I've told you a little bit about how the science works and what some of the technical and ethical problems are. Where are we today? Well, right now we can do a lot of research. We can figure out what genes do and we can use that to understand more about how we work and how the world around us works. And that really makes research much faster and much better. In the medium term, I think that we're gonna see really the rise of so-called synthetic biology. People are gonna be able to use genome editing tools to say make better fuels, to make better medicines. And in the medium term, we're actually going to see therapies for these blood disorders. So for example, sickle cell disease. There are several groups, my lab included, but also several companies that are working on cures for sickle cell disease. And several of them have gone on paper to say, we're gonna be in the clinic by 2018 to 2019. Not available for sale, but starting trial. So I think in the medium term, we will start to see somatic therapies for some of these blood disorders. And then in the long term dreams, here I really think the question is, what do we want? I learned a while ago that it's very dangerous to prognosticate about what's gonna happen in 20 years because everything is gonna be different in 20 years. But you might say, well maybe there's a way to do therapies completely in vivo. You don't take bone marrow out and put it back in, you just do an injection and treat sickle cell disease that way. There's this possibility that I brought up of personal cures where say two people in the world have a genetic disease or one individual person has a genetic disease. You could develop something that cures just that one person. So this is really the kind of disruptive science fiction that I think we really need to start talking about. Part of the reason we need to start talking about it is that even though things are early days and everything is kind of chaotic and we're sort of building this car while we're driving, the car really is a race car. Things are moving really, really fast. So we have to consider how are we gonna use this new ability? We're on the brink of these cures for diseases. We could use it for things like designer babies. I get asked questions about designer babies all the time. And there are these bombastic headlines about the end of life as we know it from just editing all the things. Because of these kinds of headlines, the scientific community together with you know, ethicists and sociologists got together and had a meeting in the National Academy of Sciences. You're gonna hear actually from some of the people who are at this meeting. I think to really summarize the outcome of this meeting it was a big yellow light. So what they basically said was germline editing is okay in some restricted sets of things. And I think that is an interesting, it's an interesting distinction to draw. Germline editing is okay, but it's only okay in some situations. When is it not okay? When is it okay? I think our moving targets, at least for me. Things are moving really quickly. I wanna give you an idea of how quickly things are moving, especially on the germline editing front. So just in the last month, three papers came out on editing in human embryos to either correct mutations to reverse potentially pathogenic mutations, or to just learn more about fundamental research. So there was this lull. People were trying to figure out, is this okay? The decision came down that yes, this might be okay in some situations and things are starting to go really fast. Like I said, there are a lot of technical hurdles, but there are also, I think that it's possible those will be overcome. And so the next question for us is just what do we want to do? So I'm gonna leave with just a couple of questions. Really what do you think in the audience? Some things to spark discussion, hopefully in the panel session and in general throughout the day. Just to ask yourself, if you had a genetic disease, would you edit yourself to cure that disease? Somatically, right? Knowing that that would be changing your DNA. Would you edit to prevent a disease? So let's say you didn't have a genetic disease but you had a mutation that predisposed you to something that would happen later in life. Would you edit yourself to prevent that disease? And would you undergo germline editing in either case? If you either had a genetic disease, would you undergo germline editing to prevent from passing it down to your kids? Or if that mutation just gave you a higher chance of getting something, would you get preventative germline editing to avoid passing that down to your children? And finally, how would you balance your own personal family priorities, right? Your own sense of self and your own sense of your own health and control of your own health and your desire to have your kids have a better life versus societal acceptance? I ask this because in several of the patient populations that I've talked to, they've said, look, I know this is not accepted. I frankly don't care. My kids in a wheelchair, they're just getting worse.  I want this to go forward right now. So I'm not gonna say that I come down on one side or the other. It's a very complicated question but I would encourage everybody in the audience, those particular patients have come down on one side but I've also talked to patients that say, look, even though I have this disease, it's a scary thing. I don't want this type of editing at all. So I encourage you to think for yourself, what would you do if you were in that situation and let's hopefully talk about that over the day. That, I'm gonna finish up. Thanks very much for your attention. And now I think we go to the panel discussion. Oh, no.


I want to make a heart-shaped steak for Valentine's Day. Let me show you how. I think Cupid sent that. Set it on its side and we go right down the middle. Get it butterflied perfectly just like that for your sweetheart. We're going to hit it with some soy sauce and some yellow mustard.  Mix it all around. Next up get your danos original. Danos is low sodium so you can use more of it. Just going to poke it in around the entire steak. Poke that flavor in. A little bit more soy sauce. Now we got our hose coat and we'll let that sit five to ten minutes. Then we'll flip it and hit the other side. Sprinkle generously. So now we're just going to rotate it. Give it a flip. Oh yeah. Now we let it rest for about 15 minutes. How'd he do? Wow. If they don't love you yet, they're going to love you after this. That's Bussin'.


Hey there Zwifters, welcome to another episode of how to run on Zwift. Today we're going to be looking at keyboard shortcuts. Now most of the things that you do on Zwift can be accessed from the menu system with your mouse. So let's have a look at the main Zwift screen here. If we click on menu at the bottom, you can see that most things you can click on with your mouse there and you can get to with your mouse. So pairing for example. Okay, however, you can access most of those things via a keyboard shortcut. For example, the pairing screen. If you press A on your keyboard, the pairing screen comes up.  Again, if you want to customize your avatar, you press T on the keyboard and the customization screen comes up. And again, get out of that by pressing escape. Those are the things that you can access with your mouse and with the keyboard. There are some things though that you can only access from this screen with a keyboard shortcut. For example, if you decided at this point that you wanted to do a workout so you'd kind of missed it when you first logged on, you might think the only thing you can do is log back out and log back in again. But if you press E on your keyboard, the letter E brings up the workout screen. You can choose a workout from there. Or again, you can press escape and you're out of it. If you want to message people, say you're in a group run, for example, and you want to say hi to people, you want to just give some instructions out or say something to somebody, press M on your keyboard, start typing, hi guys, and press enter. And you'll see on the right hand side there where my name is, hi guys pops up. And that will appear to people in the locality of you on Zwift. So not the entire 4,000 people that are running or riding on Zwift at any one time, but just the people in your local vicinity in the virtual world. And that's about it. Maybe the P key brings up the promo code. If you've got a promotional code for some new kit or something like that, you can tap that in there. And it used to be the case that you could press U and it would change the units from kilometers to miles, miles to kilometers. Now I'm pressing U and nothing seems to be happening. But I'm sure that used to be the case. If anybody does know, do let me know. And that is it guys. That's keyboard shortcuts for you on Zwift. Do take care. We'll see you again for another episode of how to run on Zwift very soon. Bye bye.