Full transcript of “Rare Interview with Nobel Prize Winner, Dr. Yoshinori Ohsumi on Autophagy”. Click a timestamp to open the video at that moment. Need another video? Use the YouTube transcript generator.
0:00 Dr. Ohsumi it is an absolute honor and privilege to be able to sit here with you. Thank you for taking the time to meet with me. I know how busy your schedule is and you have a large laboratory with many people working and so many of your researchers have their own autophagy laboratories today. So again, thank you very much for having me. - Thank you. I wanted to ask you a number of questions, but I wanted to begin when you were a little boy. I've read that as a child you were malnourished and you struggled in your early years to get the nourishment that you needed. Oh yep, because I was born in 1945. That was before World War II was
0:53 over - before half years before the end of their World War II. So in Japan, because it was a really hard time to get enough food. And unfortunately, my mother got to be closest to TB (tuberculosis). She should stay in bed for a long time. And so, it was a really hard time to get enough food. Oh, but in that that time almost all people were poor in Japan. So, so of course it was a difficult time, but uh
1:48 so everyone overcome those kinds. Yeah. Overcoming that at such a young age you dreamt of maybe being a scientist? Did you know about the Nobel Prize at that time? (Laughs) Yes I did. - You did, right? I knew, but I didn't think of that kind of thing. But yeah, I was not such a healthy boy and so my dream was to become a scientist when I was in elementary school. Probably because my father was working at the Kyushu University. So, it's not so
2:43 far from university side, so I wanted to be a scientist in the future. So your mind was able to sort of think about things in a different way than other scientists and that creativity, along with the science together, really brought this about and in 1988, you began your study of autophagy. Yeah, at one point I did not want to be in a competitive field working in a competitive field. - Oh interesting. Yeah, so when I started Accu, not so many people were interested in Accu.
3:32 "That's just a garbage dump in the cell." Many people saw that kind, but for me, it was probably an important organelle and not so many people were working on that subject. That was very good for me, because I'm not too interested you know in such competition, and many people are working on our autophagy field right now. So, if I were a student now, I might not work on autophagy. - Right. Right now it makes sense you know when I think about all of the great discoveries and this understanding in
4:18 the US, we talk a lot about blue ocean. So this idea of a blue ocean where there's nobody else and you have as much room to create and come up with new innovations, new science. So really it sounds to me like you were in your blue ocean and you had that in your mind, you were looking for that unique opportunity. And then had the capability to really think in a contrarian manner perhaps and begin the science. I'm very inspired by what you were saying about the amount of science from 1998 to 2016. We're going to talk about that. But before we go there, if you were to define autophagy, yourself, in today's climate, “2018," December 18th,
5:11 how would you best define it in your words? Okay for me, I want to understand how the cell is dynamic and actually life is just the current state of their agreement between the synthesis and degradation, and not so many people interested in degradation. Because yeah, science - since it looks positive but degradation a lot of people that some sort of negative passive process and not so many people work in degradation. But now we know their life is just a
6:01 good mistake: synthesis degradation. So for me, degradation must be equally important and since okay, so we should know the mechanism and the function of their degradation process. So, still we have - we should have mechanism of degradation. So and also I want to say their degradation is occurring and important as a census. That means everything almost
6:51 every function of our body is related to the degradation process not of autophagy. So now many people showing the autophagias created what many, many things. For me, probably because degradation autophagy is such a fundamental function of the cell. So yeah, I'm still working on a small tiny cells - yeast cells. But we - I always say we know about 30 percent of that total mechanism
7:43 autophagy, even in these. So still I stick on these cells. For thirty years you have been doing this research and you feel that there's about a 30 percent understanding. Yeah Yeah, if you think about memory and cell, that's a more sophisticated and complicated. So probably, we say 15 percent of their total makeup is known about autophagy. So autophagy is really - uh is not such a long history. But we are still at a quite early stage of research.
8:28 Yeah, that’s my feeling about autophagy. You speak about the number of grams of protein that we ingest in a day 70, 80, 90 grams, but then the amount that we process. Can you speak about protein synthesis and autophagy? Yeah, okay yeah. I always show there one slide our body makes 200-300 grams of protein every day. Okay but we take seventy to eighty grams of protein from food. Right.
9:14 So just two figures tells us most of them in acid for new protein, since it comes from their degradation product of our own protein. So, to understand the recycling of the protein is so important to understand cells. It's very, very interesting because I don't think a lot of people realize how much protein our body is actually using on a daily basis. -Yeah. Compared to what we're consuming and so it goes back to your point of really understanding the process.
10:01 So yeah, for me it's so it's a surprising fact that almost all our body protein is replaced every two or three months. So, we look almost the same after one year, but every two or three months all our protein is depressed. The new protein. That is the way life is maintained. - That's beautiful. Yeah. It's very beautiful. I uh - I began writing my book about four years ago while I was learning from Dr. Elizabeth Janda while I was in
10:47 Calabria, Italy and three weeks before I was meeting with the publishers, I was over the moon to learn that you had received the honor of the Nobel Prize in medicine for the work that you've done. How did you I'm curious just to know a little bit more, did you know, leading up to it that you were going to win? Did you receive a phone call in the middle of the night? How did it go? Not at night, it's at evening in Japan. Yeah, okay. Yeah, these days many, many broadcasts or TV companies or newspaper companies come.
11:43 So it's a - so many people that have allowed me. So already three or four years that’s what kind of situation happened for me. So it's hard to say but for me it's so noisy and so - I understand. - Yeah, yeah But you - were you expecting that this would happen? It's hard to say, but several people said you will have these two or three years.
12:37 Yeah, so of course I'm not too seriously thinking about that situation. For me, is just like I said. - Right. So yeah. So let's talk a little about the science and where it was in 1998. Maybe we can even show the graph. Yeah. I'd love to show the graph that we were talking about, but tell us so in 1998, when you began your research, how many - how long did it take for the first paper to be published? Yeah, it took three years. - Three years. Yeah, because one day I wanted to publish two papers, two separate papers,
13:29 but that was not a good way. So, we should outline the paper that one was decent, but it took a long time. It took a long time for me, but it’s quite usual if you start something new. - Then if we fast forward to 2016, over six or seven thousand papers per year are being published. And now certainly after the Nobel Prize in medicine, there's probably so many more that are getting published. - Yeah I think so.
14:15 And so, this effect of it's just overwhelming to think about the millions of people now in the world that are able to benefit from the work that you began in 1998, or even before. - Mm-hmm yup. Probably as I said, autophagy or protein devaluation is such a basic of a function of the cells. So, to understand these cells for our body, autophagy must be involved. So many things. It's quite, it's not - naturally
15:13 we can say autophagy might be related to so many things that might not be found. So... The reason that my work was inference in just finding mobile autophagy in the Yeast cell, tiny cell. But that allowed me to dissect the autophagy process. That means that we could get autophagy related genes. And fortunately, we could get almost – the most important genes at the first screen
16:06 and that was very good for us to understand the mechanism of autophagy. And I move to there to IBB (Institute). My colleague started autophagy genes in mammals in France and we showed their autophagy genes that were conserved from yeast, to mammals or France and that was their most important thing for the autophagy field. Before ATG genes, every analysis of autophagy
16:55 was just their morphological studies by EM. And as you know, the rest is not so easy to analyze biochemically, so my chemistry was very difficult. Still, but now, still it’s very difficult. So, once we got there, ATG genes changed the landscape of the autophagy research. You can analyze their autophagy by using ATG genes manipulation. So that completely changed their autophagy
17:49 research all over the world, and many people suddenly started now autophagy with various kinds of organisms and various kinds of cell kinds of cell types and tissue organs. So finding the discovery of ATG was so important for that kind of work. What are you most excited about when you sort of look at these spikes and the important findings around the field, what are you most excited about in today's climate, as it relates to the field of autophagy, and maybe the
18:41 applications to humans? Sorry? What gets you the most excited about the field now as it relates to our human health? Hmm. Yeah, still okay. Now many people are interested in their autophagy with the various kinds of disease and also health problems. And I think that these are quite reasonable, because our cell is just maintained. As I
19:28 said, the census and degradation are so important. So, our cell should be maintained, clear, clean every time. So that is a very important process. So, autophagy is also one function about the autophagies or just recycling and the important function of autophagy is their elimination of harmful or
20:14 unwanted material activation in the cell. Those kinds of clearance must be very important to understand the health and some sort of diseases. So, so yeah, we’re probably still waiting. We still we don't have a specific medicine to regulate autophagy. That might be a good way to apply autophagic research.
21:02 Do you think that medication, that area will be coming forth sooner than later? - Yeah, yeah, I think so. That's really good to hear. Let's just see, I had a couple more questions. I was curious to know with the senolytic therapies, are you familiar with these therapies at all? The Senolytic Therapies like it's called with Fisetin or Quercetin. Basically, these therapies- I'm not sure if you're familiar with them, but no problem if you're not. - Probably not.
21:49 Okay, no problem. Okay, let me just see. So, when we see how much research is coming forth and how you as one individual, chose to take this path where other people were not- the millions and millions and millions of lives that will be truly, hopefully transformed, so the cell is healthier and lives better is something that is completely and totally humbling. And I can say from my point of view, but also from so many others, just such gratitude and thankfulness to you for making that choice. It's remarkable and I am so incredibly honored to
22:40 be sitting across the table from you. Okay, yeah - for me yeah so... Oh, what should I say? Yeah, they serve - of course we have many serious problems about the food. Some people stop and people even ditch- people have their
23:30 own serious problems. So, it is very important to handle our own life- just a mutation condition. So still we should learn a lot about how our body is working. Still we have information about how our whole body is organized and so a very important question. For me, each cell is quite simple because they need just one cell.
24:18 Still, we have so many problems to be solved. Our body cells - in our body is so organized and so every cell has its own function - a different function. So it is very important to know how those cells are harmonic and communicate with each other. With that, so autophagy - every cell has its their autophagy function. But the problem is just their enhancement about autophagy, and will it enhance all
25:08 cells of autophagy. That might have the problem, so we need to understand how cells communicate and how a different cell has different functions. And finally, we need to manipulate the other autophagy in every type of cell that might be important for medical application. So, some simply autophagy inhibition of all autophagy might not help the health because some cells are required of the
25:54 autophagy. Some cells should be helping autophagy, so still we need more works on how autophagy is regulated in every cell type and the same time. My future hope is to understand the mechanism of autophagy in our body. - Very, very interesting. So the questions that you ask yourself around your area or your life's work are tied to like you said - what your hope is. And what it is your dream, what is your dream around your work?
26:42 - Okay yeah. I'm already quite old, so I don't know how long I will continue my work in the present - my hope is that I want to have a very good quantitative method to measure result of autophagy activity and we need to have a good mess of the two. What is degraded, how much, and how much of the extent of the autophagy degrades every component in ourselves. So yeah, I want to have a biochemical system.
27:39 And it’s difficult to show those kinds of things - just using these cells will help to improve some analytical methods in our body’s autophagy. That’s my dream at this moment. Yeah - That’s beautiful.
