Shinya Yamanaka: 2017 Breakthrough Prize Symposium

so good morning everybody but it is a great honor to be here today so before starting my own talk I want to know general background of the audience so how many of you are working on live science or fire refrigerator hand oh 90% I see had physics or space ah I say how many mathematicians are there oh I see it's very very good to know thank you thank you so could I have my first slide please anyway so I I started my career as a physician surgeon thirty years ago in 18 1987 I'm not that old and actually it was my father who talked me into medicine I expected him a lot however as soon as I became a doctor within a year my father passed away he suffered from hepatitis C after transfusion so you know as a young doctor I was not able to do anything to my own father I couldn't help him that was the biggest reason why I decided to become a scientist I wanted to become a scientist who overcomes diseases so as you know science has overcome hepatitis C we now have a cure for hepatitis C however there are many other diseases that science still need to overcome if it's just a few example like Parkinson disease blindness heart failure these are all very serious conditions terrible however if you think about the cause of these diseases and injuries it's rather simple they are caused by a loss of function of just one type of cell or maybe to one or just a few type of cells for example Parkinson disease is caused by a loss of function of dopaminergic neuron brightness is caused by loss of function retinal / corneal cells heart failure is caused by the sub function of cardiac myocytes it's only one type if we find this can prepare this type of cells in a large quantity and if we can transplant these cells into patients we should be able to help patients we should be able to bring functional recovery to those patients however as we know it is extreme possible to obtain a large amount of human cells but now we can do it at risk in selling we can do it by using this new type of stem cells induced pluripotent stem cells iPS cells iPS cells have two important properties first oh I'm sorry IPS cells we generated this technology 10 years ago 2006 first in mice and then in 2007 in humans it's very simple all we need is a combination of four transcription factors by 13 these four factors all together into your own skin cells or blood cells we can make your own IPS cells from each of you IPS cells can grow infinitely we can expand as much as we want furthermore from IPS cells we can make many types of cells that exist in your body like brain cells heart cells liver cells in a large quantity by using this technology now we can prepare a large amount of dopaminergic neuron retinal cells heart cells for that we can help many patients many scientists vision scientists all over the world have been working on this application of IPS cells for example dr. muscle Takahashi a good friend of mine in Japan she has already studied clinical trial using human iPS cells two years ago for patient suffering from age-related macular degeneration it's a blindness caused by a loss of function of just one type of cells in retina she can now make that type of retinal cells from human iPS cells and she depressed patients on injured aged cells with newly developed retinal cells from IPS cells it's been 2 years and the patient has been doing very well dr. jung Takahashi he happens to be the husband of Nasser Takashi just coincidence but he has been working on Parkinson disease he can now make a very pure functional dopaminergic neuron from human iPS cells he's not testing this strategy in monkey and we're hoping that he can bring this finding to human as early as next year another friend of mine colleague dr. Coach Ito can make functional flight rates as well as a ratio fights from human iPS cells you know countries like Japan we are aging society we are going to have more and more elderly people who need blood transfusion that we are going to have less and rest students who can donate their blood so only after like in five years we will be in huge trouble we won't have enough blood donors so we need to do something alternative this IPS soap based method is a good alternative to blood transfusion this is also very close to clinical trial because in cans of safeness it's very safe no red red arrow sides they don't have they don't grow they don't have nucleus so we don't have to what we don't need to worry about Kimura janeski in this application so this is very safe also we are fighting with cancers with IPS cells by combining IPS cell technology with cancer immunotherapy we can make T cells from IPS cells and in IPS cells by using CRISPR we can modify the genome of IPS cells to whatever we want for example we can introduce t-cell receptor gene that can recognize cancer specific antigen and from those modified IPS cells we can prepare a large quantity of cancer attacking t-cells in this way we hope that we can overcome cancer at least some forms of cancers well at least initially we can make IPS cells from each individual patient autologous transplantation that indiana t it takes very long and more importantly it's very expensive we helped muscle takahashi in her first clinical trial we did genome analysis just for one patient we spent almost a half million u.s. dollar so it's just too expensive in order to overcome this practical issue we have been working on so-called IPS cell stocks so we are now making IPS cells from healthy volunteers instead of each individual patient however it's not autologous so we need to overcome immune rejection the best way to minimize immune rejection is too much yesterday however HLA is so diverse none of you in this audience has the same today unless we have identical twin in this room so here I saw all the HCA haplotype of ten individuals by color none of these can individual all our cells have the same color combination so if we want to prepare IPS cell stock that can match these ten patients with actually we need to prepare all ten HCL combination if thousands we need to prepare thousand IPS of stocks it's too much but if we can identify this kind of HCA homozygous donor the situation is very different because just making one good IPS align from this ETA homozygous donor this one donor we can cover full out of ten individuals shown by arrows because these four individuals had read and something else as long as he was he received read from the HCA homozygous donor they cannot distinguish transplanted cells from their own cells based on this model we had we and others had calculated how many ETA homozygous donors are required to cover large population this is just some examples in Japan we have calculated 140 HCA homozygous donors can cover up to 90% of all the Japanese population that means 140 cell lines can cover 100 million Japanese people in the States it's a bit more diverse but still 100 super donors HCA homozygous donors can cover 78% of European Americans 63 Asians 50 to Hispanics 45 African Americans in UK it's very similar to to Japan so many countries including us are now working on this I see a stock project I have 20 seconds okay so so today I only talk about cell therapy but there is another important medical application of this technology we can use these cells from patients like brain cells from Parkinson disease patient or heart cells from heart disease patient in order to understand in order to make disease models and in order to perform drug screening so cell therapy and disease modeling drug screenings are the two important medical applications of this technology I really hope that in next decade 10 years we can realize many of these applications so that we can overcome many more diseases so thank you very much again thank you very much and there's time for some questions anybody from the audience we have time for some questions so we should use it oh yes sorry you mentioned clinical trials in Japan are you familiar with clinical trials here in the states involving some of these applications yes in the States as you know or clinical trial using human ES cells I've already set it and we have been talking to them so that we can collaborate with each other and maybe some of their applications may move from es to IPS cell another question yes oh that that's a very important point so I don't think we can eliminate even rejection just by using Excel a mosaic of donors as you said natural killer cells should recognize those felt because they don't have one HCA haplotype so even using ET a homozygous donor we still need to use some immunosuppressants but we hope we can decrease the dosage and kinds of immunosuppressants alright that's the last question then they're over there is there any prospect that the regulatory agencies will see the wisdom of this particular model and instead of testing drugs on rats apes etc we'll use this as a screening process to eliminate its efficacy or non toxicity yes especially took 50 you know pharmaceutical companies has been using like dogs or other animals or cancer cells in predicting cardiac statistics but now we can make beating cardiac myocytes so actually many pharmaceutical companies have been working on how to use these cells in their own safety tests but we still need to talk about regulatory body because it's a huge change from conventional tests so you know in order to test in order to change that kind of stereotypic conventional test it's it's been very difficult but but I hope we can depress in in the near future in next 10 years all right well thank you very much I thank you very much [Applause]

Channel: Breakthrough

Views: 23,194

Rating: 4.9572191 out of 5

Keywords: Shinya Yamanaka, Stem Cells, Breakthrough Prize

Id: mpwWnPrAJEg

Length: 16min 31sec (991 seconds)

Published: Tue Feb 21 2017