Okay for our last session of the day we have an awesome panel of platform luminaries led by the amazing Courtney and Courtney will then introduce everybody else so take it away Courtney. So thanks for sticking around it's been a very long productive fantastic day filled with loads of information we've very much seen the birth of the first platform engineering day so congratulations to everybody who has put this on this is fantastic. We're going to be talking about how to navigate the path to platform engineering success everybody is doing this but we're seeing the birth of a movement here today and so we're going to kind of talk about the different things that people need to do and consider and how they can actually get their platform adopted and be successful in doing this so that in the future we're not discussing whether platform engineering is dead rather we're discussing how platform engineering has changed to the way that we're practicing and morphing into a new thing so without further ado my name is Courtney Nickerson I work for a company called Coop Shop and I'm going to let my lovely panelists introduce themselves. William? William Ritzel? Sousa? Hello folks my name is Aparna Subramanian I'm director of production engineering and I work for Shopify. Hi I'm Abby Bingser and I work for Centasso and I'm also a co-chair of the platforms working group for the CNCF. Hello I'm Areti Pano and I'm working for SAP.  I think platforms are clearly interfaces if you're here in the morning no I think platform engineering is engineering I think there was a fantastic quote earlier in the day I think by Samantha someone about how platform engineering is a software exercise yes it relies on reliability and operations but it's a software exercise to provide value to your business and that's what we're seeing with the platform as a product conversations going on all day as well as the the different implementations which value kind of day-to-operations and fleet management and APIs and all these things that we've been doing for software for years. And William I know you were very passionate about your definition and the one that you like platform engineering how do you like what's your favorite definition of it? My favorite definition it's an empathy driven and socio-technical exercise where the features and the of the platform are not necessarily at the at the core of the platform where but the interaction between the developers the stakeholders the users the platform engineers and the ultimate outcome of the platform is what is most important so that's for me a platform. Anything to add? I would like to add that a platform can be as thin and lightweight as you want or it can be as complex and heavy as your use case demands it and I'll also say that as a user of in a public clouds GCP at Shopify our platform actually evolves and marvels as the capabilities of GCP evolves so yeah I think it's a platform as a living breathing thing. And continuing with that Aparna do you think everybody needs a platform? That's a great question I mean it depends again on your use case and the scope and the complexity that you're trying to solve if it's you know two people and you know what your if your scaling plans aren't that big you know maybe you don't need a platform maybe your platform is a set of best practices on how to use certain things but if you want more repeatable control if you want more simplified management if you want predictability if you want to scale things if you want fewer sort of like you know run books and like last-minute heroics then I definitely think a platform is a good idea. And what are some of the cultural drivers because Arreti I know you service what did you tell me 30,000 developers? I cannot hear you. So you service 30,000 developers something like that as a platform engineer and product owner so what are some of the cultural reasons that people need to be considering when they're doing platform? I think many of the teams already had some layer of a platform I think it comes to the question whether we need to centralize that platform because one way or another everything had something and that's something you need first to evaluate what is the status quo what everybody is using and then try to decide what needs are covered by what teams already have because you it's not one customer there you have very diverse setups and you need to find out what all of them what are the partners that they are actually serving and then try to come up with a best compromise because the platform in the end is a compromise you can have one platform that serves every team so you have to find the best minimum viable product. William you work with a lot of customers right and consulting them so how do you see the the whole cultural aspect of platforms and how do you help people with those situations? That's there is no there is no cookie cutter solution for our situation that I mean there are several customers which do not understand the benefit of platform engineering other customers that do need to understand want to understand the benefit of platform engineering but they are scared because they can't they can't calculate an ROI I was speaking with Ebi and there are some other customers which I always ask what is the what is your ultimate goal what is the business value are you reaching your business value are you is there impediment in reaching that business value if the answer is yes to the last one then okay let's see how we can move forward and what are are you working into silos across developers or operation folks can is there already an initiative that is self self initiated by the developers normally to build something to speed up the business value or to the order development and and I approach it as a consequence to those answers. Of course I think it's a really interesting combination between what you said already and what you said William about platforms versus platform engineering because the the conversation you said here was already was that everybody has a platform it's just to what degree they're investing in it to how customized it is across the organization and how standard it is and you mentioned the conversation on whether or not people believed in platform engineering William and I think that fits really well with this maturity model that Nikki just blew us out of the water with on the last talk that we start at the provisional level not to say that you are insufficient if you are at provisional but to really call out the fact that I would argue every person in this organization in this room and in any technology organization is using a provisional platform you may not be investing in platform engineering as a practice and with like kind of concrete outcomes but you're using a platform when you need the more centralized and when you need to invest in the kind of built in security and those kinds of things that's when you need to invest in platform engineering as a practice as socio-technical practice and so I think that's an interesting conversation between platforms versus platform engineering and talking a little bit about getting buy-in from people a partner you also work a lot with getting buy-in and helping platform teams advocate for themselves. Yeah definitely I mean I think of it as more of a partnership than buy-in right because if you're really collaborating with your application development teams and you're helping them solve their problems then the buy-in part becomes you know less of a hurdle you're actually co-collaborators and you're solving the problem and I've also seen this pattern where the solution is actually created by the application development team and then as a platform team you work with them you standardize them you know you may be built in built in security and other things and then you sort of create a standardized solution for the rest of the company so yeah that's how I would approach it and we approach it at Shopify is it's like what are you solving for the application development team what are you solving for the company and for the business. Awesome so there's a lot and we've heard all day today how to put your client front and center user who are they and what things need to be considered but you go through all that process and the question begs if you build it will they actually come and when they do will they actually use it so who wants to take that one on first I want all of you to speak to this because I think it is the the question of the day. Yes I think everybody needs to answer this because everybody has a very different perspective of if you they build it first of all they need to know about it so depending on how big your organization is you have to find the right way the right channels to advertise it so just because you have a great platform doesn't mean that people know about it if it's not advertised the right way the other thing is that it needs to be interesting and it's to solve a problem that they actually have if everybody has something that is working and then you say here's our new platform nobody's gonna come because they doesn't solve anything new and I think the third thing is at the end management support if the platform is interesting and it does solve a problem to allocate the time to move to the platform because that doesn't necessarily come free and I think that blends very well with developer experience that the requirements come from developers so if there are no requirements no need for it they won't come. Absolutely next we're going down the line I'll go from maybe I agree with everything you said so I could just repeat it all but I'll come from a different angle and say also whether or not they need to go to the platform so I think we often try and deliver a platform and people will come because it's so interesting but do they actually even have to realize they're using the platform can you build things in in a way that is kind of transparent to them I learned this lesson in the very hard way after rolling out CI CD templates to an organization of sort of 30 to 40 services so sort of pretty small scale and compares into a lot of the organizations here and then we want to change how we delivered the software to want to change from a push-based kubectl apply kind of push to a GitOps pull well that involved changing all of those pipelines and all of those pipeline templates that had been so nicely rolled out had all changed because now they were owned in the different code bases and when we were like but this is great you have better disaster recovery and it's more flexible and you'll love GitOps everyone's like I don't care and so what we realized is we needed to roll out not only to those pipelines ourselves manually and give bits to them we also had to roll out in a way that gave us as a centralized team more ownership over improving those over time because the teams didn't actually care they just wanted their stuff in production and so yeah I think sometimes we worry so much about them about users wanting to come to our platform we forget that our platform in some ways could be transparent to them and that might be the best possible solution definitely agree that migration is probably the hardest aspect of adding new features to a platform creating new platform features is actually the easy part and how how you engage with your internal customers how you bring them along how you make that process of like migration and onboarding to this new cool feature that you've built in the platform that's the hard part I'll just say that don't think of your platform users even if they are within your same company as like the captive audience right because I mean your the feature has to justify its value just like a product in the market for them to be able to like adopt it and appreciate the value and on board that new feature that you built I was I would say if if your quest if you have built a platform and then your question is now I have to get users to come on I think you shouldn't have built the platform the platform in first place so the platform is a response to a need to an agreement that you have with the developers or the developers that initiated this thing building this thing and the developer themselves or the platform team will get first we will get more developers to onboard through a developing internal developer relationship program or through just word of mouth so the platform it's so the answer is if the platform is already there you they are not gonna come they're gonna come if the platform is built in the process with them already yeah I think that's a huge huge thing that we need to talk about as well is how do you include people to make sure that they're on that journey with you so what are some steps that you've taken out at the for example to include people to make sure that they're on that on that journey with you as you built I think there was a presentation before about UX so and product management it's first to have interviews conversations with end users to try to see what they are actually doing not what they say they are doing but it was in the UX presentation it's actually letting them go through a system also what are you doing today and not what you think you're doing but what you're actually clicking on today to get something done and when you see what they're actually doing when they get stuck where's the friction then you start having what is the need and then you get to see the opportunities that might happen which might be we just need to write some documentation here we just need to improve the error message and nobody needs a platform so it comes from the product problem and facing it like this then it becomes much easier to decide also what to build and whether you need to build so this is how we are actually doing it or we try to do it at least abby anything to add I'm terrible going after already she says all the smart things but you have nicer stories no I think bringing people on the journey is as you say meeting them where they are I think again I'll maybe be contrary to what some people think but sometimes I think the interfaces we use should actually be the ones we currently use so it's not you know everybody's like oh I want to get away from ticketing platforms oh I want to create these brand new amazing web portals or CLI's and things but that's changing user behavior and if you're not gonna 10x 100x the value to that user of what they're gonna get from this brand new product that we already know we're not supposed to build completely before they we bring it to them because then they'll never come to it then we're unlikely to meet that and we've changed their behavior for not a ton of user benefit so I think where I've seen some success is when we actually put automation or better experiences behind the interfaces we're already using so they're starting to get value quickly and then they're more inclined to change their behavior towards whatever new interfaces you want to introduce because they are you've already won their interest right? You've given them some value already. Yeah I'd say that as a platform team you know you probably already own a set of applications or services that you own and you run you know be it like an inventory management system fleet management system whatever use those to actually dog food the platform that you're building right and I think that goes a long way in being able to experience those issues firsthand and gaining the trust of the development teams. Anything to add William? You want to jump in? I am very sorry I didn't understand the question. Okay we'll skip new question for you. What types of things should they be? You start there now. Yeah yeah What types of things should it so we're bringing the customer along with us we're assuming that they're always right but what types of things should we be measuring as we're looking to the adoption of people adopting our platform to ensure that we're on a path of success? I love what the speakers before us said if you can't measure it it didn't exist so what should we meet what should we be measuring everything what should we care about what brings us what brings business value forward what satisfies this business requirements we need to we need to be able to measure productivity we need to be able to measure satisfaction of the of the of the users we need to have a constant feedback of the users these are all measurements that might be numbers might be heat maps or however you want them but we need to be able to measure from the users did we need to build a roadmap did we meet that roadmap did we meet that deadline and did we satisfy that the requirement of the developer or the stakeholder of the platform that's what I think. Aparna? Yeah it's definitely a combination of like you know measuring all of the SLOs the KPIs and also what I already mentioned about like also doing like user interviews because you know this is only like part of what you can measure and what you can understand but there's also the other aspect of like that true partnership working with the customer your users understanding their pain points so I think they go hand-in-hand. I guess the only thing I'd say to that is measure everything so you can track it and change it but also understand it's okay to have measurements be short-term value so good heart's law what you measure will change behavior sometimes it makes sense to have a measurement for a period of time to track an improvement you want to introduce but a long-term version of that measurement may actually swing the behavior in a negative way and so I think yeah think about tracking what you're trying to introduce without feeling like it has to then be something you measure on a dashboard for the rest of your your career. And when I think this is a very interesting question and it's very very hard to measure when somebody says what are you measuring I I can't think because it's a very complicated thing in the sense that platforms we I'm product owner of the CI CD setup so people are not coming back to set up pipelines daily so it's not growth and they have set up one pipeline they have not set up a second one is that because it was not good enough or because it just had one service to build a pipeline on so when it comes to measurement you mostly have indicators so you try to find two three indicators that make sense and see how they're moving especially in the beginning because growth in the sense and social finite market you're not having the world you have 20 development teams so you have a very limited market and it's not really growth in this case so it's kind of looking into the indicators seeing what makes sense switch and then see if it's word of mouth in the end and qualitative data because referral is mostly what gets the platform going absolutely and just a side question so as your platform matures you kind of identify those indicators do those indicators change over time do you need to change the what what is that you're measuring or do you stick to the same measurements and indicators how to what does that maturity look like as time goes on I think also you're doing it for the usage how how is your platform used but you need to combine it with it's not used because it's not easy it's not used because it's not necessary it's not used because because because so I think the indicators with the questions change in combination I can't think of a good example to do that but I think it's balancing this too okay a partner add no I'll just maybe give an example that maybe if you're using rolling out a new feature measuring daily active users is great right because this is the first week and okay you want to know how many teams are even like trying it out but quickly that that doesn't become a very relevant metric to use and then it becomes like okay how many times this thing actually works what's the deployment time are we improving the deployment time are we shortening it are we actually helping to the productivity so I think it that's probably an example of a metric that would change over time anything else William I would say that because the numbers show what we want to see doesn't mean that it's a good thing so what we said measurement measuring so because people are involved I like I like the term evaluating more than measuring so when we are measuring we're measuring active users we are measuring very precise numbers when we are evaluating we are doing that but we're also associating those those numbers to the experience of the user is the developer sticking around because it is doing a lot of work or is the developer sticking around because he can get the work done or she can get the work done and it's trying it keeps trying to get it done so we need to so the number would be the same in both cases but the evaluation would be that they medically opposite in then in both cases so we need to have a way to measure the numbers but we need also to have a way to evaluate the experience and associate it to those numbers now I think you draw on a very important point which is is about the human interactions the human relationships and how people are actually relating to something as human beings because it's their day-to-day tool but they are day-to-day humans also and so the words that we're using and how we're defining these are using evaluation instead of measurement for certain aspects or promises and stuff as as a way to get people involved in the process are super important things to keep in mind we're getting close to time to wrap up so I think we should really take advantage of the fact that we have pros and ask for some pro tips so give me your best pro tip for navigating this whole process to make sure that you find success who wants to go first I'll say that as platform teams it's often tempting to put yourself which is the platform team first ahead of the application team and ahead of the company so I think it's just important to be mindful that you know the company or your business comes first and then your customers and then yourself as difficult as it may be to like sort of have that identity value what is my team doing sort of justification as platform teams it's always the best thing to put the company ahead of ourselves yeah I think I add in that it's important to realize that often we're in the position as platform engineers to keep the lights on we're doing a lot of the BAE work around an organization and it's hard to do a rewrite of something as foundational as a platform and so what we need to be looking for is ways to take the value we already have in our organization and make sure that we expose that in a more self-service way in a more operationally kind of fleet managed way and and make sure that we're building in those business requirements to make that more manageable and maintainable for our business and more valuable for our business without feeling like we need to pull in whatever brand-new tool has just come out and completely rewrite every piece of technology in our organization already William which one William William go for it I would say that the platform is nothing more than a digital screwdriver it's a tool it's something it doesn't mean to an end or a mean to multiple ends but it's just there to satisfy a goal so and that's how it should be seen and used and eventually dismissed when is is not relevant anymore and just move on to the next platform so three days treated more as that to satisfy the need of its users rather than to satisfy the ego of its creators and I think because the the people we built for our colleagues in the end so it has to do with the relationship of trust these are not random people that you will never see around but these are people you're actually sitting in the same offices with so when you have this you have to have this relationship of trust with them so that they are using something within the company and usually in the companies people talk to each other so having this relationship with the people you're building for I think it's it's a good thing and platform teams are in a privileged position to work with their end users in the same office absolutely awesome awesome insights just to wrap up a bit I know all of you are involved in different types of groups excuse me and create different resources have different communities that you're involved in we've got a list up here so that we can help everybody get involved but talk a little bit about the different groups you're involved in apart now why don't you go first yeah we'd love for more end users to join the CNCF end user developer experience thing you know in the CNCF Farlands end user means you're not selling or monetizing any of these cloud native technologies but you're using it as a user so we have the developer experience thing that meets every other Thursday and we'd love for more participants to join us and discuss the topic of all things platform and operationalizing a platform Abby yeah I think you've heard today a bit about the CNCF platforms working group underneath the tag app delivery so there's some fantastic work being done and there's a booth within the sponsor hall later where there's gonna be some fantastic conversations around how we do platform as a product in real life today so again if you're an end user that's where there's a lot of value to have those conversations and share your stories so yeah please get involved and come find us in the CNCF slack and elsewhere and I'm not in any community though but I saw now there's a platform as a product research group which I would like to be involved in and I've put in there some books that everybody wants some very basic product management skills just to see what five things to do are I've put there some resources that anybody can just live through and get an idea William yes I have recently joined the the tag app delivery work platform was working group I am I am also part of the tag environmental sustainability and please join us in either or the working group yes that's that's a that's pretty much all but it's great because like William does this all the time and he's just joined so everyone's can join it doesn't matter how advanced of us you are or not I join it I believe I believe the least advanced or whatever advanced means you are the more welcome you should be a fresher look at things it's always better from very very strong leaders they might if they're really leaders they are gonna get suggestions for somebody that just came in and sees things from another perspective so you don't need to be advanced in anything to join something absolutely something very concrete you can do this week is we're having morning coffees I know it's 715 in the morning I'm so sorry but if you're awake Le Ballon which is the hotel just across the street is hosting we have some coffees being hosted in the mornings from Sintasso my company Gitpod and Crumbware so some croissants and coffees with chats about platform engineering so please come and meet the community share your stories and it's a great way to get to know people you also do online coffee lunch session that's London yeah yeah come hang out it's online UTC it's available to a lot of Europeans then so yeah some tons of places to get involved so thank you very much I'm sure there are questions so any questions at all we've probably got time for one or two yeah just a quick sort of question here a lot of the responses of sort of why you do platform engineering we're very end-user sort of efficiency driven I usually think of like the ultimate constraint of platform engineering to tend to be your compliance yes so can you talk a little more about that can sorry I feel very passionately that today platform engineering is like the attempt to be a cool office from like 15 years ago where if you had beer in the fridge and a foosball table everyone was like this is the best work life balance we do I'm not saying you can't have those things but I feel like this talk about that the only reason we do platform engineering is for developer experience is very missing of the reason why it's invested in by organizations and when we look at that kind of cool office vibe and how we've actually transformed to realize that the best offices are the ones that provide work life balance and autonomy and the way to do your job and feel pride in your job not about the beer in the fridge I think platform engineering needs to go through that evolution as well and invest even more in the in the other side I would like to say that in my company the platform that we're building now is the old compliance tools coming together so in our case it's the other way around so we're never the cool people so but we were the compliance people we had the several tools that need didn't necessarily fit well together in an end to end process and this is what we're trying to do now with the platform so we're never the cool kids we still had the football and beer I love it and good couch but not not the cool people okay I think we've got time for one more question one more question have you spoken about delivering more value in the back end to make them come so what are some things that the platform can be 100% opinionated about in the back end that will somehow promote ROI or efficiency in any other way that's a great question so I think one place and speaking to the the point made of is this all about developer experience or some other compliance things is around cost so I think there's a lot of things you can be 100% opinionated about in your in your platform around how you size services how you shut things down that are in development environments on the weekends cube cost and other really great tools out there for the eco impact and money impact and those are the things you also start to buy in and get return on investment from your finance department and other people wanting to support your platform because they're seeing a reduction in cost I think those are one area you can do and also when you come again to the end to end processes what are the tools that the platform really supports so if you have some exotic let's say new language it doesn't necessarily mean that the platform supports it end to end the tools yes might independently do so but it's not really easy maybe end to end and that's where it's opinionated saying these five languages are supported the sixth one just pick and choose great we're done fantastic a big round of applause for our amazing panel


Okay, good morning everyone. I think we're gonna go ahead and get started with this second session. I'm Bobby Robbins. I'm the director of the Cardiovascular Institute here at Stanford and I'm also the chair of the department of cardiothoracic surgery. So my day job is a heart surgeon and it's wonderful to have you all here. It's been a very exciting week here at Stanford, launching our campaign for the medical center. It's beautiful weather this week, great day today.  Exercise, yes. We were just two as I just talking with, Dr. Hanopy. Yeah, not only is exercise good in Howard, not only is exercise good for your heart, it's good for your brain too. I hear Dr. Longo, so how many people went to Dr. Longo's talk earlier? Wow, what about Dr. Abuse? Yeah, yeah, okay. I kinda want to give my time to Dr. Abuse because he was so incredible. But anyway, so I'll get started here today. We're gonna talk about stem cells, but before we get started, I just wanna give a happy Mother's Day to all of you mothers here in the audience and thank you for being here today. Yeah, big round of applause. Because it is the hardest job in the world and sometimes the most thankless job. So happy Mother's Day to everybody here today who's a mother. So I'm gonna talk about the possibility of using stem cells to repair a damaged heart. The Cardiovascular Institute at Stanford, there are several institutes, there's a Cancer Institute, there's a Neurosciences Stem Cell Institute and the Cardiovascular Institute seeks to bring together everyone across the entire university who has an interest in cardiovascular science and health with the goal to translate discoveries to improve the health of our patients and people in the entire world from the cardiovascular standpoint. So I'm gonna start with a story about what I think is one of the greatest translational discovery stories ever and that's heart transplant. This is the first animal of any type, first living thing as Dr. Shumway used to say. This is unfortunately, I wanna walk around but I'm being videoed and I don't have a laser pointer so I'm gonna stand here so the camera can see me. But this is Dr. Shumway and this is Ralphie the dog who is the first living thing, first living being to survive one year following the heart transplant. This was done over 10 years of dedicated, multidisciplinary collaborative work in the labs here at Stanford and it resulted in the first successful, this is Dr. Shumway doing the first successful heart transplant in the United States here at Stanford in January of 1968. This followed quickly after with the idea that not only could the heart be replaced but also both the heart and both lungs in an operation called a heart lung transplant, the first ever done in the world. You can see Dr. Bruce Wright's here who pioneered this operation and Dr. Wright's and Dr. Shumway doing the operation. So this is what we're talking about when you hear the word translational research. There was a problem at the bedside. People were dying from heart failure. There were no drugs, there was no other option and heart transplant was the only option to save a person's life. It required going from the bedside to the bench 10 years of hard work of discovery and then coming back to the bedside to translate that discovery and now as they say the rest is history with heart transplantation. This doesn't happen overnight and one of the great things that Dr. Shumway did then and we continue to have a culture here at Stanford today is one of collaboration. As Dean Pisa always says, we're a small research intensive school of medicine and we're very close to our colleagues and it forces us to be collaborative because we don't have thousands of people in a big university. We've got the great advantage of being on the campus of one of the world's greatest universities but it requires us to work as teams and I think all of the major discoveries, all of the things that are gonna change healthcare are gonna come from collaborative teamwork and this is just a picture of our heart transplant team that was taken around the time of the 40th anniversary of that first heart transplant that Dr. Shumway performed here at Stanford in 1968. So today I'm gonna just briefly touch on cardiac transplantation, talk a little bit about artificial hearts, left ventricular assist devices and then the most important thing is to tell you that we've built 10 years, a great internationally recognized team of cardiac stem cell researchers and a program that we're going to translate into humans we hope very soon. So the problem of congestive heart failure, it's the leading cause of death, just not just cardiovascular death but all death, all the deaths in the United States.  If you look at the economics of it, $40 billion a year in US healthcare dollars are spent to treat patients with heart failure and it represents about 5% of the total healthcare budget that's expended in the nation every year. So this is another story that I think you'll find instructive and entertaining. So this is a young man who calls himself English Joe. His name is Joe Matthews and several years ago, I was sitting in my office and I got a call from the cath lab to come over. Joe Matthews was a 21 year old gentleman who was a professional rugby player. He's from the UK and he came over to the United States to play rugby and he noticed that some of the players were actually older than him and as you can see from the picture on the left with the baseball bat on, he was in incredible shape, strapping, good looking, very athletic guy and he noticed that some of his older teammates were outperforming him. When he tried to run, he was short of breath, didn't quite keep up so he's finally made his way to his local doctor who took an X-ray and his heart was massively enlarged. He was referred here to Stanford because people who have heart failure, whose heart doesn't work very well, are at great risk of sudden death. So he was transferred here to Stanford to get an internal cardiac fibula. And that's a device that is really quite remarkable in that it can sense when the heart is failing from an arrhythmia, either ventricular tachycardia or ventricular fibrillation and it can shock you like on TV when you see the paddles in the hospital and get shocked. This is all done in-planet and does the shock internally. Well, in order for that to work, you have to check whether the device is actually in the right settings and it'll work. So you have to induce one of these malignant arrhythmias, ventricular fibrillation or tachycardia. So in the cath lab that day, they induced Joe Matthews' heart to fibrillate, to stop so that they could test to see if the device was gonna work. Well, it didn't work and they couldn't defibrillate him. And so they called me and I ran over and we rushed him to the operating room and you can see him lying in the bed in one of these pictures there because he needed an artificial heart to keep him alive. There was nothing we could do. There was no other conventional operation we could do. So we put an artificial heart in and luckily because he was strong, he survived and went on to make it through his operation. A month later, he got a donor that was suitable for him and he got a heart transplant. He's now going on to be, you can see him here in this picture, a great outspoken advocate. You can go back to his website, EnglishJoe.net and you can read his whole story and he's quite the marketeer for organ transplantation and for Stanford by the way. He's a great ambassador. So he's now the fastest human in the world that's ever received any kind of transplant. He's blowing by even the guys who merely got a kidney transplant. And that's a great inspiring story. But it doesn't stop there. Why did this 21 year old strapping man's heart fail? There are two reasons why we do transplants. One is from coronary artery disease and I'll show you a picture later and hopefully not too close to lunch that it'll upset you too much of what heart attack looks like, a real picture. So that's about half of the people who get cardiac transplants have heart attacks. And we know the things that we should do to try to prevent coronary artery disease. The second group is called idiopathic dilated cardiomyopathy. Idiopathic means we have no idea why the heart fails. So in Joe Matthews' case, his coronary arteries look great, perfectly normal. His heart muscle looked fine. His electrical system was fine. His valves looked okay, but his heart failed. The muscle just didn't squeeze. It's true that your heart is about the size of your fist and your chest. And Joe Matthews' heart, because I put my hands around his heart, was the size of a basketball, this big, and it was failing. And how can that be that just six months before that this gentleman was playing professional rugby but his heart failed? So that's one of the great challenges and one of the things that the Cardiovascular Institute has really focused it on. Try to understand the mechanism of why the heart fails and come up with novel and innovative therapies to treat heart failure. One of which is gonna be stem cells. So in 2000, there was a paper published by these two gentlemen, Pira and Versa, who are now in Boston, and Don Orlik, who is at the National Institutes of Health. And they published a paper that really received a lot of attention and a lot of press about how cardiovascular diseases, particularly heart attacks and heart failure, were gonna be transformed by this work. This was work in rodents and rats that showed that if you take adult bone marrow cells and you inject into the heart, magically these bone marrow cells turn into cardiac muscle and the heart beats and that's gonna be the cure for all heart failure. So we've been working on this for about three or four years. Irv Weissman, who I'm sure is a familiar name to many in the audience, he directs the Stem Cell Institute here at Stanford. He discovered the markers for both mouse and human stem cells, hemopoietic stem cells. And if the world is fair, he'll win the Nobel Prize for this work. Well, Irv and I had been working in this area and I'd been pushing him and we'd been using skeletal myblast and bone marrow cells to try to treat heart failure and rats and when this paper came out and Irv and I live about a block from each other on the campus here, I could walk to my house in about 15 minutes. And so this paper came out on a Friday, Saturday morning I'm at home and the phone rings and Irv calls me and said, did you see that article in Nature? I said, yeah, isn't it exciting?  We were almost there.  Cannot be possible that a bone marrow cell, an adult bone marrow cell can magically differentiate in a heart cell. So we began working, trying to re-duplicate this work. And in Nature in 2004, we published a paper that was published at the same time. This is a picture of Irv and one of my postdocs, Eric Balsam, who did this work. We published this work in Nature along with a group in Seattle led by Chuck Murray that confirmed what Irv said, that adult cells cannot magically turn into other types of cells. The only cells that we know that can do that are embryonic stem cells and now IPS cells, inducible pluripotent stem cells. And I'll talk about that in just a second. So that really changed the world because in that intervening three to four years when Inversa and Orly could publish their paper, it became rampant that people all over the world were taking cells and they were claiming that any kind of cell with a catheter injected into the heart would heal heart failure. I think Don, what was the guy from Hawaii? Don Ho went and claimed that he was magically cured. And so an important thing happened. Once our paper was published, I think it stopped all of this unrealistic hype about what biology could do. And also importantly, the FDA stepped in. And for the first time, a biologic cell was regulated by the FDA. And so now you have to apply for what's called an IND and an investigational new drug permit to be able to do stem cell injections into humans. So when we think about injecting cells into the heart, there are a couple of factors that one must consider. One is the patient population. They're basically two. One is the Joe Matthews heart failure needs a transplant. The other population are those patients that have an acute heart attack, acute myocardial infarction that cells going into the heart hopefully can prevent damage. There are different cell types that can be used. I'll go over a few of those. Cell survival factors. A lot of the work that I'll talk about today is in collaboration with Irv Weissman and Joe Wu. Joe Wu is really one of the leading stem cell, cardiac stem cell biologists in the world. And we're very fortunate to have him here at Stanford. One of the things that we have a tremendous advantage over all the competition is our imaging facilities here. Sam Gambier is speaking in the next room and luckily we get to watch our colleagues in their talks because these are being filmed. But Sam brought Joe here with him from UCLA and we really have an incredible advantage because we have a molecular imaging core in the Clark Center that is second to none in the world that allows us to follow the fate of these stem cells. And it turns out that most of the cells that are injected in the heart within the first week or so have died. So that's gonna be an important thing. Are there things that we can do to make the cells survive longer? Then the imaging I talked about and then what the mechanism of action is. There is some controversy about, well, can some of these adult cells cause the heart to improve transiently? But the mechanism of action that we seek is really growing new heart muscle and having that heart muscle, this new heart muscle, connect to the heart muscle that's still in the heart that works well, the viable muscle that's not been damaged. And so that's gonna be an important mechanism of action for us. So here's sort of a current list of the type of cells that can be used. We've covered bone marrow cells and there's still people who are injecting bone marrow cells. I'm not really sure why they're doing that but they're modifying these bone marrow cells but just to be clear about it, everyone realizes from the work we did originally here that bone marrow cells will not turn into new heart muscle. Then their skeletal myoblasts, even though we started with these cells, I never quite understood how that was gonna work. What we were thinking is that the skeletal muscle would grow and prevent the heart from dilating and maybe that would help. It turns out that it caused arrhythmias in the heart and that's basically been abandoned. Then there are so-called mesenchymal stem cells that are adult cells. Again, some people think that there's a possibility that these cells could differentiate into a heart muscle cell but there's no great evidence for that. There is a new area. I'll talk mostly about embryonic stem cells and IPS cells but there is some new interest in is it possible that in our heart there are cells, a small number of cells that are able to divide. We're taught in medical school that the brain and the heart, the cells in both of those organs don't divide. You're born with X number of cells and they don't divide. We're beginning to realize, certainly for the brain, I know Irv and some of the neuroscientists have discovered that there are cells that divide. The heart is still controversial but it's possible that there are cells at least in the heart that would be capable if treated with the right genes to differentiate into new cardiac cells and I'll talk a little bit about that at the end. And then there's embryonic stem cells and inducible pluripotent stem cells. So this is where we've done a lot of our work here at Stanford is using the mouse here with the green ears and all the cells in this mouse express a green fluorescent protein which is a marker for us to be able to use the molecular imaging I talked about to follow the mice and it's been a very valuable tool for us to gain new knowledge into whether these cells stay where they're injected and what the fate of them are. So embryonic stem cells, when an egg is fertilized, there's one cell and then that cell divides into two cells and those cells divide into four, eight, 16 and at a certain point, up to the time of about 64 cells, all of these cells, if you take a cell from this inner cell mass of this blastocyst which is at about the 64 cell state, these are embryonic stem cells. So the question is why does one of these cells, let's say cell A, become skeletal muscle and cell B become heart muscle? Unknown, there are certainly genes that we're beginning to understand how to differentiate these cells. So the embryonic stem cells can develop into any cell in the body and will but at some point they go down a path of differentiation and there are certain signals that are turned on and certain signals turned on that causes the cells to either become a heart cell or a brain cell or a liver cell. So that's an important point. The second is that if you take these cells that are undifferentiated, then put them into a human that will try to become every cell in the body and the problem with that is that there are tumors that are formed called teratomas. That's why there have only been five people in the world ever that have gotten embryonic stem cells, three for spinal cord injury, two of which were done here by Gary Steinberg in collaboration with a clinical study that Geron sponsored. Unfortunately, Geron stopped that trial and got out of the stem cell business and then there were two patients who received embryonic stem cells to treat macular degeneration, but that's it. We believe our group has an application in and we've been given a lot of positive feedback and we learn next month whether the California Institute of Regenerative Medicine are gonna award us $20 million that if we win that grant it'll allow our group to be the first group in the world ever to put embryonic stem cells into a heart. And I think that is a great translational story just like heart transplantation. This is an example of how big thoughts and big ideas can be accomplished at a place like Stanford. I just wanted to put this slide in because this shows you what a human embryonic stem cell transplanted in the heart developed into cardiac tissue. This is exactly what a cardiac muscle looks like. It was an embryonic stem cell, a human embryonic stem cell that was injected into a mouse heart that had a heart attack. You can see the striated bands that look just like cardiac muscle. These red areas are expressing protein called connexin 43, which means that this new cardiac muscle is connecting to other viable cardiac muscle that's left into the heart. And that's gonna be an important part of any therapeutic approach for treating heart failure. Now, there are problems with embryonic stem cells. I covered with you the problem of teratomas. So the way we get around that is that we know these protocols that we can give genes to these cells and differentiate them until this embryonic stem cell develop into a heart cell. And then we purify those cells and put into the heart. The problem with embryonic stem cells is that they come from embryos. So there are certain ethical and moral issues that have been well publicized. The second thing is that the embryo has a genetic code. Now we heard a tool butte talk in the last session, those of you who were in that session about the genetic code. But suffices to say that the embryo has a certain group of antigens that are different if I'm getting those cells from an embryo and my immune system will try to reject those cells. So that's the second problem with embryonic stem cells and then the teratoma is the third. So there's a new type of cell that was discovered in 2005 called inducible pluripotent stem cells, IPS cells. And so these are cells that the way that this works is you can take any adult cell in the body. The easiest thing to do is to take a biopsy from the skin called a fibroblast. And then there are four important genes that can reprogram these cells into pluripotent stem cells. They're just like embryonic stem cells except they're your cells. And then those can be used to go on to differentiate into cardiac cells or neuro cells and then they can be used for therapeutic approaches to treat heart failure or Parkinson's disease or diabetes. Moreover, every drug that you consume is tested by regulation by the FDA, but it's tested for toxicity in a very rudimentary hamster cell model called the choce cell. And it's simply whether the calcium channel works, yes or no. There was a drug called sysopride back in the 90s that was given for gastric motility. If you had reflux esophagitis or reflux disease, you were given sysopride and your GI system moved forward. It was a multi-billion dollar drug. It was screened through these choce cells and deemed to not have any cardiac toxicity. However, that drug had to be pulled from the market because there were over 80 deaths from a condition known as prolonged QT syndrome. If you look at the QRS complex from an EKG, it's a prolongation that causes these deadly arrhythmias to the ventricular tachycardia fibrillation. Just imagine, and what we're doing here at Stanford, we're developing 1,000 IPS lines from people that have a variety of different cardiac diseases. Artery disease, dilated cardiomyopathy, atrial fibrillation from all ages, all ethnicities. And just imagine that before you take a drug to market, you could test in a petri dish whether this drug had an effect on the QRS complex because these IPS cells in a dish can be beating, you can measure an electrocardiogram, and you can determine whether that drug would have toxicity and produce this disease called prolonged QT syndrome. So those are three areas that I think IPS cells will be used, one for therapy, one for drug screening, and then to understand mechanisms. Think about, we just had a major publication about mechanisms of how aortic aneurysms form in Marfan's patients. And to be able to test this, instead of doing a big clinical trial that costs a lot of money and can be dangerous, you could develop IPS cells, cardiac cells from patients with Marfan's disease, and basically do clinical trials in a petri dish. Think about that, and we can get to that in the question and answer session. So coming back to the forms of heart failure, I think that stem cells hold great promise for treating certainly both dilated and ischemic cardiomyopathy. Here at Stamp, we've got the great fortune to have not only great basic scientists, engineers, imaging experts, but also clinicians and patients that have heart failure. Because of that worldwide recognition and heart transplantation, we get patients from all over the world with heart failure. And we're able to come back to this idea of translational research, having problems in the clinic, taking them to our labs, working together in teams, and coming up with innovative therapies that we take back and treat our patients with. So this is a picture from the inside in the operating room of what a heart attack looks like. This is the inside of the left-sided pumping chamber, the left ventricle. This is normal muscle. This is the mitral valve. Blood flows through the mitral valve into the left pumping chamber. The left ventricle comes through the aortic valve, which you can't see, and it's pumped out to the heart. It took from the heart to the body. So this white area is scar tissue from a large myocardial infarction or a heart attack. One of the coronary arteries was blocked. And so the idea is, how do we treat this? Today, we have some conventional operations that I'll show you here in just a second. But the other is transplantation. Our idea is that we would replace the scar tissue. We would convert this damaged heart muscle that doesn't beat anymore. We could replace that with stem cells and reproduce and regenerate new cardiac tissue and cause the heart to beat stronger and more normally. And I believe it won't be just injection of cells. It'll be a tissue engineering approach. And this just shows you an example of a cardiac tissue on a matrix to produce what's called artificial myocardial tissue that could be re-implanted. In an operation, first, this is how we treat this area of heart attack. You can see this is thinned out. This is the picture I showed you from the inside. This is all thinned out, non-functioning heart muscle. And we simply go in and cut that out and put a Dachron patch.  But it's rigid and doesn't beat. Think about that artificial myocardium that I showed you. And could we make a patch to treat this area of the heart such that these cells would be beating? Just like we're doing in the lab today and we've treated many mice in this way. I think that this is the hope of the future that first we'll do it by surgical approach. But I believe that eventually we'll have a tissue engineering approach that would be used through a catheter in the cath lab to be able to repopulate this area of damaged heart muscle and restore cardiac function. Just in the last couple of minutes, I wanted to just show you another pioneering effort and tell you a little bit about heart failure, treat official hearts, LVADs. In 1984, Phil Orrier, who's cardiac surgeon here at Stanford, implanted this device which was developed in our labs called the Novacor device. It's a left ventricular assist device, a heart pump, into this gentleman. It was the first time that any person had been kept alive with an artificial heart and survived to get a transplant. It's what's even more remarkable to me about this is that this gentleman, the first person ever in the world survived for over 20 years with his transplant, all work done here at Stanford. So I think that it's gonna be a combination of both transplantation, stem cell therapies and artificial heart therapies. We're to the point now where these devices can last for up to five, seven years. The devices are getting smaller, much easier to implant. This is the size of about a D battery that's placed right into the left ventricle, sucks blood out of the ventricle and then pumps it out to the aorta and to the body to support our patients. And indeed, if we get this CERM grant, our is gonna be patients that require these left ventricular assist devices to get them to a transplant. We're gonna inject the embryonic stem cells. We think it's a safe model because we can mitigate the possibility of these cells going out to the body and having teratomas. More, this is a chance when we take the heart out to do a transplant, we can look under the microscope and look and see how many of these cells survived and if indeed they turned into new heart muscle. So I'm incredibly excited about that. I just put this last slide in here to show that not only does cardiomyopathy happen in 21 year olds and 80 year olds, but it also can happen in newborns. And this is a child that Bruce Wrights and I put an artificial heart in and about two weeks later got a transplant and is alive and doing well. So just in summary, I think that transplants have been remarkable over the last 40 years. We've saved thousands of lives. That effort started here at Stanford and is now spread around the world. Additionally, the first successful left ventricular assist device was done here at Stanford. And I believe that will be the first place in the world to inject embryonic stem cells and demonstrate to the world that stem cell therapy can also be a novel and innovative treatment for heart failure. Thank you for your attention and I look forward for your questions. No questions. Wow, okay, there you go. With a large area of infarct and injecting stem cells, there must be a time frame before they can become active. Are you working on what's the right size area to put the stem cells in and at what point you really can't wait for the stem cells to take over those logistic plans going on? So that's a very good question. The question had to do with how big an area and how you target the area and can you wait for the stem cells to start taking effect. That's a very good question. It turns out that this first study that we've planned would be a safety study. So if you or someone who needed an artificial heart and we came to you and said, in addition to the artificial heart, we're gonna put these embryonic stem cells in because it gives us an opportunity to study the biology of them, to see if they're gonna be safe and then we take them out and look at them under the microscope, as I said. But one of the things that we've thought about and we can't make any problems, but as the patient is recovering, it's usually about three months from the time that you get an artificial heart until you find a suitable donor that's found for you to do a transplant. So after about a month, our plan is to turn the pump down and look under echo guidance and we know the area we're gonna inject those cells to see if the heart's functioning well with the idea one day that someone who's in an emergent situation needs an LVAD, we can put the cells in at the same time and then slowly wean the LVAD away as the cells start to take over new function. Now for people that aren't in that dire strait, I believe that earlier on, so there's a spectrum of heart failure that at one end is an LVAD in a transplant, but there are signs and I think genetics are gonna be able to help us predict who has headed down the pathway of failure and we wanna start to inject those cells earlier so that they can start to divide and incorporate. So we don't know how much time that'll take but we think it's probably gonna be several months. But it's a good question, yes. Yeah, so what I've described to you so far would be sort of a proof of concept in first step and you would need a big operation for the direct injection or to put this tissue engineering patch in. But I certainly believe that these therapies will be done through a catheter. You'll come in, you'll have a catheter go into your heart, we've got sophisticated imaging and locating devices that allow us to find the area of damage and inject cells now. This has been done with these bone marrow, adult bone marrow cells. Now there hasn't been much utility because as I outlined before they don't really work to form new heart muscle but we believe that embryonic stem cells and I think more importantly IPS cells because we can take your own cells and use those. So I think that this is all gonna be done minimally invasively. Whether we can do it to prevent damage is still up in the air but that's the idea behind a big heart attack so that you have your artery closed and instead of having a big scar and damaged area that results from a big heart attack then at the time you're having chest pain you come into the hospital, this goes on now and usually in less than an hour if you come into the hospital your artery's opened up in our cath lab and there's a stint in your artery and then to use stem cells at that point to prevent damage. The areas of the infarct that occurred acutely if you get the stem cells out to try to prevent damage and mitigate any scar and damage to the heart muscle because it's a spectrum. You get the cells die and then the heart starts to thin and the heart gets bigger because it's failing. So acutely the idea would be to try to prevent any further damage by injecting those cells down the coronary arteries or directly into the heart muscle at the time of a heart attack or earlier on in this spectrum of heart failure but it'll be less invasive for sure, okay? Those are the bone marrow cells. Those are adult bone marrow cells. And then the other question was related to, you mentioned the FDA and I'm in the biotech industry and a lot of the issues, I mean, the FDA deals with small molecules and has not come around to cell therapy. So how do you see them kind of getting to a point where they understand what? Well, for us to do this for us to do this cell therapy study we have to have an investigator initiated IND today with the FDA. So we've got four years. We find out in June from CIRM, if we get the grant we've got four years to get to humans and there are tranches of money that come to us depending on the benchmarks that we hit but one of the early benchmarks is and as part of our application we've had to have pre-pre-IND meetings with the FDA. So they're regulating cell therapy today. Certainly if you, because we believe that I didn't have time to cover all this and this gets into a little more detail but we believe that because these cells most of which don't survive we're gonna need to genetically modify the cells to cause them to differentiate but also to help them to survive because you put them into an environment where it's sort of hostile. There's inflammation, it's in an area where there's not enough blood flow. So you're gonna have to have gene therapy in addition to cell therapy and the FDA gets really concerned about that. So they're definitely regulating them and the CD34 cells are these adult bone marrow cells that we used in that first study. I will say that there is some, there's some suggestion that there's certain paracrine factors, not that the cells will develop into new heart cells but that there are some factors that can help to grow new blood vessels into an area so that the area around that heart attack there's a rim of tissue called the transition zone and to help that area function better by growing new blood cells. So that's why people continue to use adult bone marrow cells inject into the heart. Ann? Do you envision the stem cell therapy being more useful for one of the types of cardiomyopathy versus the other? The ischemic cardiomyopathy obviously blood supply is the problem. So when you put new cells in the blood supply may not be optimized but with an ischemic, with an idiopathic cardiomyopathy it's a much larger area. Do you envision one being better than the other and more useful than the other? Yeah, that's a veteran question there from Ann who's our chief of staff by the way and one of the best doctors I've ever known.  So that's a good point. I think that everybody has gone and that's when I said at the patient selection side acute myocardial infarction done in the cath lab down the coronaries, chronic disease which is either ischemic from a heart attack or idiopathic cardiomyopathy that Joe Matthews. I see that cell therapy is gonna be directed toward the ischemic first because that's a defined area that we can see on this device called a Noga device in the cath lab. You can test and see the area that's not moving and using echo. We can direct cells into that infarcted area. You're right. I think that's why it's gonna be a tissue engineering play with pro angiogenic factors and pro survival factors, anti-apoptotic genes. But I believe that's gonna be the first place. Now, I didn't have time to really talk about the resident cardiac cells and whether there are gene therapy strategies that can convert those cells into new cells.  I think the dilated cardiomyopathy's though the real thing, we're clearly, and you've probably heard this across this week, we're clearly moving from an era of diagnose and treat to one of predict and prevent. Predict through the genetic code and try to prevent these diseases. And we really don't know, there's been some suggestion that these dilated cardiomyopathy's have to do with viruses, coxsacky B virus. And so just imagine if you could find a gene that said that one person was more susceptible to a cardiomyopathy, a dilated cardiomyopathy, if they got coxsacky B virus and you could develop a vaccine, you could basically eradicate that disease. But for the dilated cardiomyopathy's, a stem cell play, I think it's gonna have to be resident stem cells that are stimulated to grow new cells. So I'm getting the time's up. I'll be happy to stay around. We have 15 minutes before we go back to the plenary session again. Again, thank you all for being here today. I really enjoyed being with you and I'll stick around and answer any questions you may have. Thank you. The preceding program is copyrighted by the Board of Trustees of the Leland-Stanford Junior University. Please visit us at med.stanford.edu.


What is happening? Magsize so We're gonna watch the flash together.  You know me so I'm gonna watch this and You get to experience it by the way the surprise I had for y'all did come let me know for the next few days If you figure out what it is. All right Let's get this in You're the best thing to do by the way if you want to watch it with me Find it on Netflix or if you haven't recorded on your own DVRs And you just watch it along with me. I got it on DVR. So I'll be skipping ahead, you know When the commercials Last episode was crazy I'm really digging the brighter red suit and the white on the ceiling. That's dope. Wait a second Suppose we now choose the color on your suit. Will it be because we got the idea from this picture? No, that's crazy. I mean, we're living in a causal nexus. Wow This is so trippy like Marty and the Polaroid trippy Not as trippy as anyone Oh Oh Founding member of the Justice League I Operating system is Wow, that's interesting.  Yeah, baby No, that reminded me of that terminator to think you have to do what I say I just wanted a virus around What do you want to talk to me? Um, so listen What's everything going on? Investigating Wells and hanging out about Barry. You cannot tell Iris about Barry. This isn't about Barry Now the timing might seem off, you know, everything that's going on, but I want to propose to Iris I don't like your blessing He need a blessing on that hairline is I knew that Magnet sights. Let me know when it's too late Let me know When my hairline gets to here to know my head if I'm living in doubt, you know Wow, this is crazy I will do it I mean, excuse me one of the two speedsters in Barry's house tonight his mother died was Barry I mean the flash he was there, which means that one day in the future Barry will travel back in time to that night Okay, actually I wasn't talking about that. I kind of Already time traveled by accident I was running to try and stop a tsunami from hitting the city a few weeks ago Right before you started getting those dreams Oh, you mean the ones where Wells uses his super speeding hand to shed a part of my heart does yes, right, right?  What else could they be memories? What if that day Cisco found out that Wells is reverse flash and then Wells killed him But when I ran back into I changed the timeline so that event never happened if it never happened How can Cisco remember it? I don't know.  I think I've got Really bad I think Mary's iris I Well, it's an interesting enough my facility is a very place I would like to take him I'm not gonna try and convince you with promises, but detective Give me a chance. I think we already know what you're capable of doctor. You heard a lot of people at night So those doctors in there they're good enough That's in the city That's in the country look at them They have no clue what's going on there baffled and the reason for that is what's happening inside Barry is a mystery and they don't have the tools to solve it, but he do that's right Millions of people used to look in my lab And what did they see they saw the future? Well, let me take that technology Let me your son actually does have a future This goes memory somehow somewhere in his subconscious is the key the key what now getting my dad out of person And how are we going to do that? Now the hell they gonna get through these dimensions Wells is a scary motherfucker Amy Into history They think you can be used to help people suffering from post-traumatic stress disorder Check and check the theory is that it will allow people to objectively enter their dreams and face their fears Still working on the talking part. You're sure this thing isn't gonna, you know mess with my brain The amount of electricity required to trigger lucid dreaming is harmless probably With all of the metahumans in central city people have been seeing some strange things Things that they don't understand and it's really just a matter of time before psychological issues develop And lucid dreaming will help the doctors better understand their fears and treating of course You still need to guide the patient from the outside right directing the specific aspects of that dream We're still working on a communications interface when we dream The middle brain lights up with electrical activity. Where as the higher brain Remains dormant once we find a way to make both parts of the brain active manages to matter find the frequency That will stimulate the language center. Then the dreamer could speak he could describe history exactly Dream I could use anyone right to my gender specific I would try a frequency.  It's it's really important. Yeah She said oh wait you still haven't said that you haven't asked her yet, or you did ask her and she said I was gonna propose tonight I went to Joe to ask for his blessing. He said no Repeatedly weird. I need to talk to him find out why Look, I know me ask you like this. It's a little awkward. Yeah, but you know how hard But she's gonna be she finds out that Joe's not on the board Yeah You put the glasses on fall asleep and start dreaming not that hard If I go back into it, am I gonna die in real life? I mean, what are we talking about here? Is this inception or dreamscape here? Drink this What am I five? Just drink it. Okay.  Let's just go Now I'm adding a low level delta wave which should help you fall asleep Okay, I gotta warn you though. Usually it takes me a long time I mean I'm not saying I'm like an insomnia I'm right to sleep So that's how you get him to shut up. He's entering ramp. It's working already. Jesus Can you hear me?  I think he might have tampered with my work I need to try He reminds me of somebody I know Okay, okay. I can't I can't figure out.  We both knew we had to move faster. I know my science y'all They suffocated everybody else in there because the vacuum god damn it. Everybody passed out Right, wouldn't that happen? There is Anything that I have learned in our time together very is that The only thing standing in the way of you achieving every goal that you set for yourself Is you how strong you will get in our thing that you need Glass is very powerful When he really wants to be It's cop in spanks Don't do that I mean he thinks of Cisco as a son. Barry was getting um That's what some I trust neckel. I'm not sure what that means. I'm waiting for it. You see that No, I never should have let Wells take you from that hospital none of this would have ever happened If you hadn't let him take me I would be dead for sure. But even then I knew something wasn't right Everything my gut was telling me not to trust him But I did because I was so desperate to see you. Okay. Yo, this isn't your fault It's not your fault Look at me. I'm bad at that thing that has happened to us all of it. It was him And now he's gonna pay for it This is so well set up a fake showdown with a fake opponent It was never really there. He figured if we saw both of them together, it would prove that it wasn't the man in yellow This all just keeps getting crazier and crazier I just talked to dr. Wells. He's attending a lecture downtown. We'll be back You know when he gets here you need to be working on the trap so you see as yourself the hologram Hold on isn't that in your dream when everything went old calling ma temple of doom. Yeah Yeah, I'm ready for him I originally designed the force field to keep a speedster from getting out But I've reversed it now It won't let one in there you try it.   I don't want to see this Uh Well, I so agree with that and I and I and I know that we have a lot going on right now And I should definitely be the last person taking Eddie's case, but I don't get it. Joe. Why did you say no? Because if Eddie proposes to iris, she's gonna get caught up in the moment and the romance and she's gonna say yes What's wrong with that? Again, I don't know why I'm saying this because one day she's gonna wake up and realize she married the wrong guy But she'll stay anyway because she made a promise I don't want that kind of life for her or him She's got feelings for you Barry. She may not know how to deal with those feelings right now Always have been You know that too speaking of iris. Just I mean, I don't know in text By the way, I am a fan of the old flashes Sound effects. I like this one It never seems to be your time, but I need you to listen to me right now like the really listen to me What do you want to say baby? Of course, yeah Whatever you need to tell me I'm listening Hey, I mean, I know this is gonna sound really crazy at first Like what's up crazy girl? Everything's strange. It's been going on in central city. It all goes back to that night Every bit of information that I've collected since I changed sighting nothing predates the explosion Whatever was released into the atmosphere that night.  Yeah, it's interesting. It's there's there's just Recall in your theory. Um, you know, I was affected by whatever was released by the explosion and I don't have any powers Yeah, look, I mean, I know that it's it's really mind-blowing.  How are, um, everything's okay with you and eddie? Sure, sure you have a great, why? Yeah, okay, I'm okay. I'm gonna Let me read over all of the information and we'll definitely talk about it later. I promise. You just It's crazy. Yeah, okay. Just let me just go through it and uh, we'll talk later I'm here for the reason and you came to live with us. It's not it looked like he's playing sleep We made he playing comal right now. How was your lecture? Placitude in this? I said I better myself Um, where's Cisco? Uh, he is in the bunker thinks he finally figured out what went wrong at christmas You know when we were trying to catch the He's found. Nope. Just that it was important Picks, mrs.    We know you're not Harrison Wells. Just tell us who you are the confession An anticipate as difficult as the past 15 years have been for me how much Looks like this is the last commercial break y'all. It's everything that is crazy all this time This stroke We needed a good stroke Actually, though, would you mind if we park here for a second at this week when I was arrested and look me happy Is that what you need me to propose? I was west Sometimes just feel it.  I know it's you Wells Is he a bard? That is funny and the reason for that as those guest lists are concerned I haven't been born yet Not a chance insurance I really do hate Wells in a way.   This is crazy It's a totally different. This is a new chapter now because Everything's out the bag.  Iris knows now thorn I don't know if that's his dad or not, but They're definitely related glad y'all told me to check this out Post your comments down below. Let me know what you all think If you enjoyed my reaction hit the like button share and subscribe if you did not Hit the like button should share and subscribe One of these subscribers well