The Convergence of CRISPR and Human Stem Cells

welcome everybody my name is deepak srivastava and i'm a president of the gladstone institutes and i welcome you all to a very special conversation that we'll have the privilege of having today with two of our gladstone faculty shinya yamanaka and jennifer doudna inventors of induced pluripotent stem cells and crispr gene editing technologies these life science discoveries are arguably two of the most important broadly impactful of the 21st century i would say and they were recognized as most of you know by the 2012 nobel prize shared by dr yamanaka and john gurdon and most recently the 2020 nobel prize shared by dr doudna and her collaborator emmanuel charpentier now many of you have heard me say in recent years that we are at an inflection point in our ability to both understand and intervene in human disease in ways that really no longer force us to simply accept disease but rather gives us the opportunity to actually cure disease and the discoveries we'll talk about today are actually two of the main drivers in a very synergistic fashion of the transition that will occur in medicine in the coming years and you'll hear more details from both shinya and jennifer about their discoveries but in brief shinya's discovery was that you can take adult cells and take them back in time so they behave just like early embryonic stem cells that give rise to all the cells in the human body for the first time giving us the ability to have limitless quantities of human cells affected by disease right there in front of us and it also largely obviated the ethical debate around human embryonic stem cells that you all will recall and jennifer's crispr technology provided a very efficient and easy way to for the first time rewrite the genetic code with great precision both in a dish in cells and in the body for the first time opening up the possibility to definitively correct genetic mutations that underlie disease and so you know those two are such fundamental groundbreaking discoveries uh that uh it has captured the attention uh and been incorporated all over the world very quickly now at gladstone which uh most of you know is a non-profit independent biomedical research institute closely affiliated with ucsf here in san francisco the integration of shinya and jennifer's labs with teams of world-class scientists focus on overcoming some of humankind's most devastating diseases has really created a rich environment for disruptive discovery and and specifically we're leveraging these tools and technologies on neurodegenerative diseases like alzheimer's parkinson's huntington's and als cardiovascular diseases ranging from adult heart failure to childhood heart defects viral diseases ranging from hiv to now coven 19. and in efforts to also in an efforts to understand and engineer the immune system to fight diseases ranging from cancer to infections to diabetes and other autoimmune disorders and in each of those cases the current technology is allowing us to generate enormous volumes of data and we're therefore making major investments in data science and ai approaches which really are essential to fully harness the potential of modern biology and so with all these key pieces in place all under one roof at gladstone i'm so excited about the advances that i'm sure to come in the decade ahead and today we will have a chance to explore with shinya and jennifer how their discoveries will be driving a new era of medicine forward in partnership with scientists here and all over the world which fundamentally will change the paradigm of human disease so that's what we're going to explore today and i'm really excited to be able to do this with all of you here today so uh we have our panelists with us uh shinya and jennifer which i hope you can see and are highlighted i should say that uh if you uh on your view button at the top right if you click on speaker view it'll always be highlighting the appropriate individuals so uh let me start with uh uh you shinya uh shinya did his research training at gladstone in the 1990s and uh he returned to japan and since 2007 has been back running a laboratory at gladstone while also overseeing uh a research institute in kyoto focused on translating uh his induced pluripotent stem cell or ips technology so shinya let's maybe you could spend a few minutes describing your discovery in a little more more detail and how that transpired sure thank you very much dubak for the introduction uh but first of all jennifer many many congratulations on your award i i was so so happy and just out of curiosity where did you receive it on december 10th but in my backyard oh my god yeah not in stockholm not in stockholm oh okay that's a that must be a very special moment indeed as you know okay so so uh as deepak nicely described we have been working on new type of stem cells which we designated induced through important stem cells ips cells they are indistinguishable from embryonic stem cells es cells which you generate from human embryos but the origin is very different ips cells we can make ips cells from each of you from your like blood cells or skin cells that's all we need very small amount of like 10 ml of blood cells from you that's all we need to make ips cells now the procedure is very simple or all we need is a small experiment gene transfer this is like even high school students can do but by that very simple procedure we can reprogram the fate of cells of your blood cells or skin cells back into the embryonic state so they become like es like stem cells once again we designated these cells ips cells once once they become ips cells we can expand ips cells as much as we want and then after expansion we can convert ips cells into many types of human cells including like brain neurons heart muscle cells hepatocytes skin cells blood cells again uh bone cells battery all types of cells so now we can make a huge amount of human cells from your own tiny amount of blood cells so now we are trying to use this technology ips cells in two medical applications one is in regenerative medicine also known as cell therapy but equally important application is drug development we can use these cells to understand diseases and to overcome diseases to identify new drug candidates by using ips cells from human from patients on cells so all these two medical applications uh what we have been working for the last almost uh 20 years thanks junior and we'll get into some more details about how we can utilize this uh further so uh let me now ask uh uh jennifer uh to uh describe her crispr technology and i'm sure most of you know jennifer uh did her groundbreaking work discovery at uc berkeley and as an investigator of the howard hughes medical institute as well and she oversees the innovative genomics institute which is a joint effort between berkeley ucsf and gladstone to really maximize the impact of christopher technology in the years ahead and about three years ago she started a second laboratory at gladstone to marry the disease-focused biology that we're so well known for at gladstone with her crispr based approaches so jennifer it'd be great for the audience to hear a bit from you about how crispr works and maybe even how you came across upon the discovery thank you deepak it's a real pleasure to be here today and with you uh and shinya together it's a delight to have a chance to tell you a little bit about our science so as deepak was mentioning crispr is a technology to change the genome of cells that means to be able to precisely alter the dna sequence in ways that give scientists incredible control over genetic manipulation and in the future and even even now thinking about ways that this kind of manipulation can be useful as a clinical therapy so i'm going to show you one very short video that illustrates how the crispr technology works and share my screen here so we're looking at a this is a picture of a cell and you know that in a human or a plant or animal cell the dna is held inside the nucleus of the cell so it has a membrane around it and so as i run this video i'll show you how the crispr technology works inside the nucleus to make changes that are precise to the dna sequence so let's take a look so we're zooming into the cell and we're going inside the nucleus and there's all the blue dna that's sitting in in there and this purple blob that you see is a protein called crispr cas9 it has a little molecular zip code in it that allows this protein to grab onto a particular sequence of dna unwind it and then make a precise cut and once the dna is cut those broken ends of the dna can be handed off to repair enzymes in the cell here they come and those repair enzymes are able to find that break and fix it and in the process of repair create an edit in the example we just saw the edit is very small a small single chain very site-specific change to the dna but we can also use crispr to introduce whole new sections of dna that get inserted during the process of repair and over the last eight years this technology has been adopted globally by labs around the world who are using it to understand the function of genes and also increasingly to use it as an actual way to manipulate the dna in cells for therapeutic benefit and i'm sure we'll get into some examples of how that's actually working great thanks jennifer so i think all of you can appreciate easily the impact of both of these major discoveries what's probably harder for you to know is what amazing people both jennifer and shenya are and in terms of uh their generosity kindness and uh the way they collaborate and they're just great people to be around so we are we are so lucky to have them both and their laboratories in our community so i think if you if you step back uh and look at what's transpired this century we've gone from not really understanding the causes of human disease so much to being able to sequence the genetic code or the dna of individuals at scale that's been unprecedented and so even now and certainly in the coming years it's not unreasonable that we'll know the genetic variation that occurs in every person and the challenge will be to understand how that is actually related to human disease and what is the mechanism by which those mutations might cause disease and so uh so that'll afford the opportunity to both understand why disease occurs intervene in it and as we mentioned earlier it may be even corrected by not just reading the code but then also writing the code and so let me start by asking i'm going to ask each uh both shinya and jennifer how the others discovery has impacted the promise and the capabilities of their own discoveries because that's really what the beauty of these two is that they're so synergistic so uh shinya uh let me start with you uh how does the ability to edit the genome uh enable the ips technology well crispr has a huge huge impact so we developed ipso technology in 2006 and the crispr was uh uh developed by jennifer in 2012 so the first six year of six years of ips cell uh world technology was like a free crisper era it was kind of a dark time and after 2012 with crispr it's a post crispr era it's a whole new world actually so before crispr for example in cell therapy we need to worry about immune rejection after transplantation and i uh the best uh way to overcome immune immune rejection is to make ips cells from each individual patient and that's our ultimate goal but uh at the moment it's too expensive and it takes too long it takes almost one year so it's not practical so uh as an alternative way before crispr before 2012 we were trying to make a kind of a bank of ips cells from like 100 or 200 uh healthy donors so even making 100 to 200 ipso lines from uh 100 donors 200 donors is a it's still a lot of work we can make only like five good lines each year so making 100 is uh actually very difficult but thanks to jenny jennifer we have another strategy we can modify our gene we can modify our genes involved in immuno immuno reactivity so that we can only have we can uh make one or a very small number of like super ip ipso lines which can be transplanted into virtually all human patients in the world so it was a a huge huge uh moment for us just for that and another example of uh uh crispr how crisper changed our thinking is now we can correct gene mutation in ips cells so as you know many diseases are caused by gene mutation so we can decapitate disease caused by gene mutation by making ips cells from patients but before crispr we could not correct that particular gene mutation so as a control we had to use another ipso line from another people from healthy people but those are not ideal or control because in addition to that particular thing each of us uh patient and control healthy volunteer they have huge differences in their genome so as a control those healthy ipso line is not ideal but thanks to jennifer we can now collect just one particular gene mutation so that we can make we can generate so-called isogenic control line so those are just two examples of how crispr how jennifer's discovery has changed our own field so i really appreciate the emperor's development thank you so much thank you shinya and as shinya mentioned there was the pre-crisper period of ips and post-crispr and i know in my own lab we had been trying to understand the genetics of a heart disease for years struggling with ips cells and there's too much noise in the system and it wasn't until we were able to to use crispr technology uh that the all the biology of the system unfolded itself and and we could understand the disease uh in that way uh so uh jennifer let me turn to you and uh oppose the same question how do you see the ips presence of ips technology really enabling uh your vision of where crispr will head well i hope i hope everyone can appreciate how powerful ips technology really is i still remember when that discovery when your first paper on this was published in yeah and this was far from my field but nonetheless it was so impactful it was so exciting that we were all you know aware of it and um you know just incredibly um enthusiastic about the possibilities now that it seemed you know in the hands of scientists to control the fate of self it's quite extraordinary and i think that you know with with crispr these two technologies together offer just extraordinary opportunities you already heard the the perspective from the you know from from the standpoint itself i think you know thinking about using crispr as a technology to both understand fundamental biology but also to ultimately use it as a clinical therapy stem cells are absolutely front and center that's what that's the the type of cell that we're going to want to be manipulating with genome editing and uh certainly i think you know in terms of understanding the fundamentals of cell development and differentiation so how does a cell which has you know every cell in our body has the same dna but some cells our brain cells other cells are muscle cells how does that you know how how do those decisions get made i think this is where this is still uh you know it's been a question that's been around for a long time in biology and is still being sorted out so i think that you know with these two uh the crispr and ips cell technologies coming together we're now at a point where that question can be addressed at a level that wasn't previously possible so i think there are both opportunities on the fundamental science of cell and tissue development as well as figuring out how we take that fundamental understanding and use it to manipulate cells in patients in ways that will have incredible therapeutic benefits thanks jennifer uh and uh jennifer i i know that uh there one one important thing that we think about uh in our field both with your discovery and shinya's is how uh serendipity is sometimes involved and uh when we're just trying to understand how uh our body and our cells work uh and even other organisms that it leads to these sort of breakthroughs that can actually affect human disease even if that wasn't the starting point can you say a bit about how you came to your discovery that i'm sure would be interesting to some folks and how important the you know it's just studying basic sciences well let's start with the fact that crispr in biology is a bacterial immune system it's a strategy that bacteria use to find and destroy viruses so i started working on this over a dozen years ago when a colleague of mine jill banfield at berkeley had discovered in dna sequences for bacteria evidence of this crispr system and at that time it was a hypothesis that it might be involved in immune you know sort of an acquired immune response that was occurring in bacteria so i was fascinated by this as well as the fact that it seemed to involve fundamentally molecules of rna so that my research in my pre-crisper years was focused around the way that rna molecules can control the flow of genetic information and cells control how and when proteins are made whether it's from the cellular dna or from a virus so i was fascinated that rna might be used in this bacterial immune system called crispr and we started investigating the mechanics of that process and that's how we got involved in ultimately a collaboration with emmanuel charpentier which led to us figuring out how the crispr cas9 protein works as an rna guided protein to cut dna and once we made that discovery it was possible very quickly to see how it could be harnessed as a technology for genome editing because it takes advantage of the cell's own repair mechanisms to repair double-stranded dna breaks so it was a you know a process that began with fundamental a fundamental question in biology a curiosity driven project i like to say it was small science you know not big science but it led in in directions that none of us could have predicted in the beginning yeah i think it's really quite remarkable when you think about the origins of that and it just highlights how important it is just to solve nature's problems and and you can lead to this uh shinya uh i know that in your training when you were a fellow training at the gladstone institutes in the 1990s you had initiated a project that in a very securities circuitous way ultimately uh contributed to you being on a path to make the ips discovery i'm sure it'd be really interesting for folks to hear how that all transpired yes i did my postdoc training at gladstone uh 25 years ago i i hope i haven't changed although i had a bit more hair at that time so as a postdoc naturally i worked very hard and i was lucky to identify one new gene so but i didn't have a clue what that gene was doing and i went back to japan and i continued working on that gene which i discovered at gladstone and i found that gene was very important in mouse embryonic stem cells i didn't expect at all but it was just coincidence so that's how and why i got very very interested in es cells the biology of es cells and i uh since then it was like year 2000 so 20 years ago and since then i have been working on uh year cells pre-important stem cells and that work uh went to all the way to the discovery of ips cells so it started 25 years ago at gladstone but i didn't expect i would work on es or ips cells in the rest of my life at that time so because science is so unpredictable yeah yeah and i think one of the beautiful things that uh really allowed your both of your discoveries to spread so quickly is that in both cases it was really easy as jennifer said a high school student can do gene editing and in shenya's case within a year every lab in the world studying these sorts of things was was able were able to make ips cells because it was simple and so that oftentimes in discoveries or interventions the simplicity is really key to really democratize uh these discoveries and allow them to have the greatest impact so uh maybe let's turn to uh how what do you what are some of the first areas where you think uh your discoveries can have a clinical impact uh maybe uh let's let's start with you uh uh jennifer to see you know where do you think crispr technologies will first have an impact well you know it's amazing we're already seeing the results of clinical trials with crispr for blood diseases that include sickle cell anemia and thalassemia and so several patients have already been treated and it's been you know they're well into their you know second year of uh since the initial crispr therapy was delivered and um they're doing very well so it's it's been an amazing journey of seeing this fundamental biology turned into a technology and now using using it in these initial clinical trials was success so that's that's been very exciting i think in the near future we'll see obviously expanded use of the crispr technology to treat other blood disorders as well as many more patients that are suffering from sickle cell disease and and then pretty close on the heels of that are applications in in the eye and in the liver because those are both tissues where delivering the crispr molecules into the cells that need editing is relatively straightforward and so i think over the next couple of years we'll be seeing increasing applications in those tissues and very likely results of initial clinical trials both from academic groups and from companies that are doing that work and then i think the the third tier will be diseases that are also resulting from a single genetic mutation in the human genome as those as sickle cell disease is an example of and i'm thinking here of muscular dystrophy which is a very well known disease that affects mostly young boys and is a defect in a single gene that results in muscle deterioration and right now there are very active efforts to use crispr as a treatment for muscular dystrophy and again early studies at least in animals are looking very promising the challenge there is delivery so how do we how do we get the crispr molecules into muscle cells in a patient to get enough editing so that that there's a therapeutic benefit so that's kind of where that challenge is right now but you know it's just extraordinary to see that in less than a decade the crispr technology has gone from the stage of a fundamental discovery to you know an actual application that's being used in patients in the clinic yeah it's it's remarkable the initial discussion initial paper describing crispr uh was in 2012 only eight eight to nine years ago so it's really a remarkable path let's stay on this topic for a moment jennifer you you mentioned that uh delivery is an important hurdle in getting things uh in various to address race diseases um it might be worthwhile for people to hear what is it that made you want to come and start a second laboratory at gladstone some years ago and how do you see that that effort helping you achieve the full potential of your discovery well as you know deepak i've i've always been um you know a scientist who's done fundamental research and i you know like many of us i always i was hoped that my work would have a clinical impact someday and you know help somebody somewhere but i didn't have a it wasn't really a clear you know concrete idea of how that might happen until crispr for me and so with this technology it was immediately clear how this could have ultimately a real tangible you know in outcome in people that are suffering from a genetic disease and maybe maybe ultimately from other other diseases as well such as cancer i see a question in the chat about that and so um the question for me was how do i how do i make sure that my efforts in my fundamental research are going to be funneled directly into the hands of people that are you know clinically connected and are able to work with patient derived samples and ultimately with patients and so the gladstone was the very obvious place to to do that it was really my top choice and i was so fortunate to have the opportunity to open a lab at gladstone where i now have a group of people working side by side with clinical immunologists with people that have expertise in a whole range of fields including your own work deepak in cardiovascular disease and development where we have an opportunity to take the crispr technology and develop it very specifically for particular clinical indications and so that's been very exciting and i have no doubt that in the coming years we're going to see real tangible impacts from that work yeah well thank you and that i'm certain we will be able to do that together and we are certainly committed to that at gladstone in fact many of the folks in our audience are committed to that as well with us on that journey in your case uh with ips cells and with the combined use of crispr as you described how do you use what what areas do you see impacting first uh so once again uh there are two major medical applications cell therapy and drug discovery and in both areas many applications are already in clinical trials for cell therapy for example or diseases like parkinson's disease heart failure some blood disorders like flat threat deficiency and cartridge dysfunction and also for cancer those are already in clinical trials and i think cancer immunotherapy using ips cells is very promising like car t therapy is already available and it's very effective but it's one disadvantage is that it takes some time and it's too expensive but by using ipso technology we can lower the price and time for preparation uh so i think one what i interested in the most is right now is cancer immunotherapy using ips cells but many other applications are equally important for drug discovery we have been using ipsos from patient suffering from various rare diseases and intractable diseases and many drug companies have already studied clinical trial one example is als amyotrophic lateral sclerosis so multiple drug candidates have been identified using patient ips cells and some of them are already in clinical trial and i have an access to some unpublished data and they are really promising so i hope some of them will turn out effective on human patients as well as you know in als research for the last 100 years we have developed many effective drugs on mice mouse model but unfortunately they are not effective on human patients but now we are using human ips cells from patients i really hope they will be effective on human patients as well yeah thanks shiny and i know there are clinical trials started with ips cells for parkinson's disease also and eye disorders and other areas so those things are all moving and so i think over the next five years we'll see the readouts of those and i think there's a lot of promise in many of those areas we had a question about cancer treatment in the chat room and you touched on both of you touched on that and i think we see that as an enormous potential and for that very reason just less than a year ago we started a new institute at gladstone around genomic immunology to really uh harness the potential to marry both ips and crispr technologies to create immune cells that are engineered just right so they can go find and target cancer cells in new and better ways to get rid of them and also for many other diseases so i think that these technology both of these technologies really have uh give us a lot of hope for being able to manipulate the immune system for lots of lots of different human diseases so as as we go along and make these have these advances initial trials or sometimes in the academic setting but also many times have been in the commercial setting and so ultimately if we want to get therapies to people and scale them they need to move out of the academic centers and into the commercial sector where they can be really developed as a therapeutic and marketed and and spread widely um each of you have taken a little bit different approaches i think to that so jennifer uh we even have some questions in the chat but i was planning to ask you about how how do you view that step and commercialization and your role in it also well you're right deepak i think for technologies to be actually brought to bear on diseases in a broad sense they really have to move into a commercial setting typically because of the financial requirements to do that kind of development and the need for a large team to you know develop the the um clinically indicated molecules that are required and move through the regulatory process as well as of course conducting clinical trials so i've been a you know i've been a a big proponent of um you know helping new companies to get started in the crisper space and i'm involved in a few of them you know myself and most of those are companies that have actually been founded by former students of mine who are now at those companies and developing them so for me as an educator you know i think one of my primary goals with these companies is actually to you know to not only establish a place where commercialization can take place but to do it in a way that gives opportunities to young entrepreneurs who are you know inclined towards the business world or the biotech world and are passionate and very deeply knowledgeable about the science that will be necessary for success and that's been really rewarding it's been really exciting to see these young entrepreneurs taking off and you know getting getting the kind of support that they need and i've learned a huge amount along the way and i have to say i really enjoy the you know kind of you know i love running an academic lab and working in the nonprofit world but it's also been very interesting and certainly very rewarding to help these young companies to get started and now to start seeing the incredible advances that they're making and as we discuss you know these are uh companies that are starting to run clinical trials i i definitely think over the next three to five years we'll see the the fruits of those trials coming to the fore and um and not only that but you know creating jobs here in california and elsewhere that are important for pushing forward the whole biotechnology sector and and jennifer as these things move more commercially what do you see as the biggest threats to this success of this what are the obstacles that you see that still need to be solved we talked about delivery that's one but what are the others well i think another there are a couple of comments in the chat about this you know the the challenge of you know kind of the ethics of genome editing how do we think about the uh and i i put in that bucket i define that fairly broadly it's not only the ethics of the editing that you're doing but it's also affordability accessibility you know for me you know this will be rewarding only if it ultimately becomes available to everybody that can benefit from it not just to to a few and so that's a you know that's a taller how do we how do we achieve that and again i do feel that it's going to be through public-private partnerships you know companies of course have to be thinking about the bottom line and how to make a profit and reward their their investors whereas non-profits and academic organizations can can often take a longer view and tackle very you know long-term kinds of problems that will require you know a lot of fortitude and maybe a lot of clever students to you know invest their energies in it over time so i think that's that's a big challenge going forward is just getting that that balance right and and figuring out how to communicate about this technology so that as it becomes more widely available to treat different types of diseases and even to do other things such as working as a diagnostic for example that um you know that people understand that crispr is a technology that brings very broad benefits and and that its risks are being appropriately managed by the scientific community yeah and i know you've been an international leader in uh getting the whole world to think about the ethics of crispr technology uh and uh with the pitch johnson support we've you know been able to focus some on that more and uh what about there's in the chat room uh the the concerns about off-target effects i know a lot of people think about that maybe you could comment on how you think about that yeah well i again i i take sort of a broad view of that i think you know we can define off target effects as edits that occur at an undesired or unintended place in the dna but it could also be edits that are made intentionally but then have unintended or undesirable results and so you know that that is it all comes under the realm of what where the technology is today in terms of understanding how it works and how accurately it works and then continuing to make it even better and the good news is that right now i think you know the the um there's been so much work that's been done to understand the accuracy of crispr to develop forms of these proteins that are even more accurate than they are naturally that i don't currently see the accuracy of editing as a bottleneck in applying it even clinically i do think it's critical to understand the outcome of edits and and to have the you know the right tools to be able to assess the accuracy of editing and fortunately again there's been a huge amount of work in that area so that we do increasingly have very sophisticated tools for assessing the outcomes of editing so um yeah i mean i guess the summary is it's uh you know we have tools to assess it and um and it currently isn't really the bottleneck in the field i would say yeah and another as an example of another intersect being able to put the machinery into human ips cells of the desired cell type that you want to edit allows one at least in as a test to see what other changes might be made even before you do it yeah in the person in the patient so that's another example of how the two uh leverage one another um shinya in uh going to the same kind of line of thinking with you what uh what do you see as the some of the ethical issues around ips obviously it solved in part one ethical issue around the human destruction of human embryos for human embryonic stem cells but i know you you realize it rages raises other ethical issues yeah exactly for example we can make like sperm and x from ips cells in mouse we can already generate a new mouse in life from ips cells by making sperm and x so the question is how well can we do it we may be able to overcome uh infertility issue but uh it's a huge esco question there is a huge ask question how much we can do we should do the other esco potentially important issue is to make organs by using ips cells in large animals like pigs so potentially we can overcome the shortage of donors or organ transplantation but once again the question is how much we can do how much we should do so those are new esco issues that we have uh uh facing right now yeah thank you uh i think uh boy the time is going by fast uh we've got ten more minutes i'm sure we could all do this for an extra hour but let me come to um uh a few more maybe more fun questions rather than someone so much to science but uh we've got a great question um from the chat room that i wanted and i'm sorry i won't be able to read all of these from the chat but i'll try to address them later and that is what makes someone a great scientist rather than a very good one jennifer let's start with you oh dear okay i was hoping to hear shin it's right well we can start with chin yeah okay no i'll give i'll give it a second um i think it's i think it's a combination of things i think uh i think you have to be kind of stubborn um you have to be very very persistent and kind of driven um and partly this is you know i've now been running my academic lab for almost three decades and so i've seen a lot of you know a lot of very smart very talented students and post-docs go through the laboratory over that period of time and i think you know consistently so it's not it's not intrinsic intelligence you know all these people are are very very smart they're very talented in that way but i think what separates the very good ones from the really the absolutely off-scale uh people who i say wow they could they should have my job um are those that are just you know really driven they're passionate about an idea nothing's going to dissuade them from it uh they're gonna figure out a way to find an answer or get this idea to to work or to decide that you know it's not going to and they're gonna you know pivot to something else that turns out to be interesting in its own right so it's really that kind of persistence and and passion um somehow that i think really separates uh people that i've seen you know the really the very the very best ones but i don't know how you would what you would say shenya well well i i agree i agree but in addition to that i have to say uh unexpected results uh are a really a big chance yes so whenever you do every graduate student every postdoc they must have had some unexpected result and you can have two reactions one is being excited about unexpected result and the other one is being disappointed by unexpected results if you can enjoy unexpected result there may be a huge chance in it so that happened probably only twice or three times in my life in my uh 30 years as a scientist but it does happen and it please consider it a huge chance so that that's my message yeah i think that's great advice and i know in your occasion when you're training a gladstone you were trying to address cholesterol levels in the liver by affecting the liver and you ended up creating a liver cancer and in you could have been disappointed and moved on but instead it led you to studying why cells divide more than they should and and ultimately do your stem cell work so it's great yeah i i got excited but very important thing is that my boss my mentor tom minority he got very excited too so it meant a lot yeah to us a young scientist yeah yeah and it happened it happened to my very first experiment in my graduate school my very first experiment i got very unexpected result i got excited but my mentor he got very excited too so oh yes i i was very lucky yeah the only thing i would add to that is you have to know which unexpected results to be very excited about right yeah good good taste yeah you have to have good taste important that's right well it speaks to importance of mentoring which is as you all know is so important to us at gladstone it's part of our in our mission statement you're a great example of the product of that uh jennifer uh uh you know that i have uh two daughters who are interested in science they look up to you you're their role model and i know that you think a lot about women in science and i'd love to hear your thoughts about how what this means to you know two women getting a chemistry prize for the first time ever nobel prize it's really really quite remarkable the first of many i hope yes i expect um yeah i think it really you know it really uh is is is something that speaks to to a lot of younger scientists and especially young girls and women who are going into the stem fields i can't tell you how many countless students i heard from especially girls and women after the announcement about the nobel prize who were just so touched you know and they just i i didn't expect it honestly i it would surprise me but it really was so interesting that for many people it was kind of personal you know they felt a personal joy about about this this particular prize and i think for many women it made them feel empowered enabled um you know supported and and uh you know it was sort of a real uh shot in the arm of encouragement for for girls who might be going into this field so that's amazing and um i i certainly consider myself uh incredibly fortunate it's not the kind of thing that i don't think anybody goes into science imagining winning a nobel prize i certainly didn't and that wasn't something i was you know thinking about or working towards but um but i think uh you know it does sort of now give all of us and especially for for women in the field i think a feeling that uh you know women's work can be um can be appreciated as it would be if they were a man and i think that's you know it's a really important message yeah i see i tell you i see it firsthand it makes a huge difference so thank you for that um shinya uh you attended the received a nobel prize in 2012 as i mentioned jennifer is just a few months into that process i know that changed your life a lot and i was wondering if what you might uh offer to jennifer in terms of advice on a post nobel period and what lessons you might have learned that might be helpful well so uh the you know receiving the nobel prize uh was a start of many good things i i have been very enjoying uh having many good opportunities like this but at the same time it was a beginning of many bad things as well so i got many phrases but i got many criticisms as well so uh you have to be tough and you have to have people or protecting it for example or in many cases you have to say no to some offer if you say no directly from you some people may understand that many people may get upset so if you have somebody to say no instead of you i think deepak i think in that sense a great song is a huge help in protecting you because we want to spend as much time as possible on science not on non-scientific issue so we we do need a protection and uh i'm sure gratitude will be a huge uh has a huge role in that deepak is very good at saying no in a very gentle way for others at least i need to be better for myself yeah i tried to play gatekeeper for a bit virginia which is helpful so um we're unfortunately coming up on the hour uh there's so much more we could talk about they're great questions in the chat room i'll try it for those that put in questions i'll actually try to respond to those later with you directly but let me uh end uh with uh hearing from each of you what do you v in your what do you envision 2030 looking like with respect to your discoveries maybe we'll start with you jennifer i think we'll see by by 2030 i think we'll see multiple therapies that are available for for patients with crispr not only for sickle cell disease but my hope by then is that you see it for muscular dystrophy and probably a few other genetic disorders as well i think a lot of it again depends on other kind of you know coordinating technology such as in delivery and sequencing that will be essential to validate those uh you know the editing that will be necessary in those to treat those diseases so i think that's one thing and i want to just also mention that we focused on biomedical applications today for christopher but you know crispr is a technology that also works in you know many other types of cells including plants and microbes and one of the things that i'm working on right now at the innovative genomics institute in partnership with a number of scientists including folks at the gladstone is to address some of the challenges of climate change using using crispr and there what we're doing is manipulating the microbial communities that live in the soil or even in together with plant roots to do things like increase carbon fixation carbon storage and also to increase the output in agricultural products things that will be necessary i think over the next 10 years in particular as we deal with those challenges for climate change yeah i think that's going to be it's going to be a really fascinating decade to see it unfold uh shenya what about you what what do you see 2030 looking like so of course i i hope many applications like parkinson's disease cancer therapy they are in clinics not in clinical trials in 10 years from now but in addition to that we are now trying to generate tissues 3d tissues and even 3d organs and i hope uh by 2030 they will be in clinical trial and more important is i think many people working in young people working in ipso like at grubs or our institute in kyoto i hope they will be doing something very different their own science one good example is a mrna vaccination for kobe 19 the founder of moderna he was 10 years ago in 2010 he was making ips cells by using mrna that's right and the same scientist went to harvard and he started a company and that company modena is leading the world by making mrna vaccination so that's a very good example of how we can change in just 10 years so yes i hope many many uh same kind of examples will happen from this audience yeah hopefully yes in my own life as well that's right you have a lot more a lot more to go that's a great point though because that derek rossi who used mrna for the first time in making ips cells uh that technology is what religions are modern in modern as you mentioned but it's a great example that may not be obvious to everybody is that science is basically like building a building a structure it's one layer on top of the other and you really don't know where it's going to end up when you start laying that first brick but as scientists we all build upon the discoveries of our peers and people who came before us and that's really the fun of the beauty of science it's like art it's like creating something that nobody's seen before and it's just a beautiful thing uh well uh let me thank all those in the audience who are with us today it was wonderful to be with you thank you all for your interest and many of you for your support but you really drive a lot of our science and i'm sure we'll be in the coming years and we're we're so grateful uh shinya and jennifer for your uh time today and for your as great science uh that you do and i'm very confident that the visions that you both laid out for 2030 will come to fruition and we'll do everything we can to make that a reality thank you all so much and uh have a wonderful evening thank you very much everybody you

Channel: Gladstone Institutes

Views: 1,308

Rating: 4.8222222 out of 5

Keywords: Science, Research, Stem Cell, Cardiac, Neuro, Virology, Immunology, UCSF, Gladstone Institutes, Data Science, Biotechnology, Biomedical Science, Biotech

Id: Gt1UTLmMMCM

Length: 60min 20sec (3620 seconds)

Published: Wed Jan 20 2021