Yale's James Rothman shares 2013 Nobel Prize in Physiology or Medicine

So thank you all for coming to share in this momentous occasion. I would ask that members of the media hold questions until after Dr. Rothman finishes his talk. I'm Bob Alpern, Dean of Yale School of Medicine. And I am pleased to welcome you all here for this joyous celebration. So I will make a few brief comments. There is a great tradition at Yale in cell biology. It was really started by George Pallotti, who identified a number of key vesicular structures within cells. And using electron microscopy was able to determine what those vesicles did. That tradition was passed on through a number of great cell biologists, a number of great department chairs of the cell biology. And the most recent department chair is our honoree today, Jim Rothman. What Jim did many years ago is he had this realization that to really understand how these vesicles moved around in the cell, you had to get rid of the cell. And you had to actually study the vesicles isolated. A lot of people in those days thought that that wasn't possible, that the vesicles would not function in a cell-free system. Jim had the courage to do it, and the talent to make it work, and led to really a molecular understanding of how vesicles traffic through the cell that has exploded today. And so we are delighted with the decision of the Nobel Committee to award the prize to Jim today. And it's great to be here to celebrate it. So let me now introduce the president of Yale University, Peter Salovey. Thank you, Bob. Thank you all for being here today, and congratulations, Jim. We are just delighted. And I have to admit, I personally am a little stunned. I'm not being inaugurated as Yale's president until next weekend. And I get to have the incredible honor and good fortune to introduce and celebrate with you a Nobel laureate this week. Jim Rothman represents the best of Yale in so many ways. He's an esteemed professor on our faculty and a summa cum laude graduate of Yale College. His Nobel Prize confirms, quite simply, what we all knew about him, his preeminence in his field, really his fields of cell biology and of chemistry, where his pioneering and innovative work and creative research have really taught us how cells work, and more significantly, the implications for some of the most troublesome diseases and conditions that affect humankind. You know, Jim is a pioneer in many ways. On the West Campus, Yale's West Campus, Jim's Interdisciplinary Nanobiology Institute was one of the first research centers that we set up there. It brings together researchers in fields like cell biology, molecular biophysics and biochemistry, physiology, engineering, and they're all working on nanomachines that can function within living cells. This activity also has implications for combating disease, for improving life and health of people all over the world. But for all this spectacular research, and for all that Jim Rothman is being honored for today in this Nobel Prize, for all that this represents as a pinnacle moment in a scholar and researcher's career, I have to tell you what Jim Rothman is going to do after this press conference. Is he going to go back to his lab and discover something new and important? Well, eventually, but not an hour from now. Is he going to go back to his office and bask in the congratulations of his friends and of his colleagues? Well, he'll get to do that too, but not right after this press conference. Rather, he is going to go teach not one, but his two classes this afternoon. And I think it is wonderful, and it is everything that we celebrate in a Yale professor, that after winning a Nobel Prize, after meeting all of you and spending a little time with you, that Professor Rothman will head to class to share his knowledge with Yale students. And who knows, in his class, might be a future Nobel Prize winner as well. Well, for now, it's with great pride, with great joy, with the best wishes of the entire Yale community, that we celebrate this moment. And I introduce to you James Rothman, the Fergus F. Wallace Professor of Cell Biology, Professor of Chemistry, Professor and Chair of the Department of Cell Biology, Director of the Yale Nanobiology Institute, and, of course, 2013 Nobel Prize Laureate, Jim Rothman. Well, this is absolutely overwhelming. And I thank Peter and Bob for their wonderful opening remarks. And it's so nice for me to see many of the people from my laboratory here, actually, and department. And thank you for coming and showing your support. Now, I'm not quite sure what the format here is. I guess I'm going to take some questions. Maybe I could make a brief statement or so at the very beginning. This is a great university. And this is a great country. And I've been very, very fortunate to have grown up and been educated in this fine place and taught to appreciate science and intellectual activity at its highest, to have matured and started my career as a researcher at a time when your idea was the only limit. Any risk could be taken, no matter how difficult. And I was fortunate to have taken a few of those risks. And today's Nobel Prize recognizes, I guess, the success that came out of that. It's still a little hard to believe this is all happening, I have to admit. And Bob mentioned a little bit about the process of protein trafficking in the cell. And I was reminded of the fact that endorphins are secreted. One of the themes of today's Nobel Prize is the organization of transport pathways in the cell and the storage of secretory products. And one of the less heralded but absolutely critical secretory products are the endorphins, which cause a good mood. Now, everybody has commented on how my mood has been very good today. And my wife, Joy Hirsch, has commented that I haven't yet complained today, and it's already 12.30. And I think that's because the secretory pathway that my colleagues, Randy Schechtman, Tom Sudhoff, and I are credited with having understood in a new way has been stimulated. And so my endorphins are stimulated. My adrenaline, however, is not yet stimulated. I'm sure the questions will allow that to happen. Certainly, my dopamine has been stimulated as a reward system. But I'm counting on some good questions from the press to overcome the lack of sleep that came about from a call I received at 4.30 AM this morning. Shortly after that, I called the dean of the medical school, my boss, Dr. Alperin. He was a little grumpy. He didn't pick up the phone right away. But then I think something occurred to him, and he called me back. And his day has probably been about as hectic as mine has. So I want to thank all of you for coming, and I look forward to taking any questions that any of you might have. Could you raise your hand so I can see? I'm a great believer in eye contact. Thank you. Yeah, I was asleep, OK? Now, in past years, I have not been asleep on such occasions, but the calls didn't arrive. As a result, I gave up. I went to sleep very nicely. And a friendly Swedish voice began the conversation, and Professor Hansen, Jan Duran Hansen, the secretary of the Nobel Committee, was kind enough to inform me. And I tried to keep myself on the ground, that I was a recipient of this year's Nobel Prize. And he went on to tell me who I shared it with. And I expressed, as I would like to do right now, my very strong delight in sharing this prize with Randy Schechtman at the University of California Berkeley and Tom Sudhoff at Stanford University. Randy and I, in particular, go back a very long way. We've shared a number of awards together. And we started our projects, which have been complementary, some would say competitive, many, many years ago in the late 1970s. And I have found not only Professor Schechtman to be a great scientist, but we've always been very open. And the kind of openness in our, although we've never formally collaborated, the openness in the conveyance of information that we've had, we used to have actually joint research group meetings. In more recent years, as my work has taken on more of a tilt towards understanding how the brain works, I've become more familiar with Professor Sudhoff and have found him to be not only a great scientist, but a wonderful collaborator. We wrote a review article together a few years ago for Science Magazine that was a great pleasure. So that call was an other out-of-body experience. I could see that it was happening. Yes, yes, you've received the Nobel Prize and all that. But I haven't quite digested it yet, to be honest. If you have any interest in the subject tomorrow, if something good in the news doesn't come up, come back and ask me tomorrow. Yes, sir. Well, that's a very good question. I was so fortunate to start out at a time when it was possible for a young scientist to have an idea, take a risk, to seem to do the impossible. I see Dr. Jameson there in about the fourth or fifth row. Dr. Jameson and Dr. Pilati, in work that preceded mine, discovered, really, the secretory pathways. And Jim, you won't remember this, but I remember cornering you at a meeting shortly after I started at Stanford. And I asked you, I said, I'm thinking about reproducing what you've done in a cell-free extract in a test tube. And you told me I was crazy. And he hired me back many years later. Anyway, so the NIH was prepared to support me, coming from a good lab, no particular track record, going to a good lab, a good department, but with no preliminary data, no nothing. And I had five years of failure, really, before I had the first initial sign of success. And I'd like to think that that kind of support existed today, but I think there's less of it. And it's actually becoming a pressing national issue, if not an international issue. I appreciate being asked that question. Other questions? Okay, well, I'm supposed to be, so I'm going to give that a try, okay? And that's also a very, very good question. The cells in the body need to communicate with each other, right? Our bodies are very complex, and the different parts of the body need to be in sync with each other. And that principle is very fundamental. But each cell has its own boundary, or it wouldn't be its own cell. Your liver has a job, your brain has a job. Within the brain, there are many jobs that need to be done. This requires the movement of substances from one cell to another. Probably everybody here is familiar with one of the most well-understood substances of that kind, insulin, which, as you know, is very important for controlling blood sugar. And when the metabolism or production or biological handling of insulin or response to it are altered inappropriately, we can get diabetes, whether it be juvenile diabetes or adult diabetes, so-called type two diabetes. There are many other substances in the body. Neurotransmitters, for example, are stored in little packets. They're actually like little balloons. They're perhaps 500 hydrogen atoms in diameter. That's how small they are. They're very tiny little sacks. But each one contains a very potent quantity of neurotransmitter. And those neurotransmitters are released at just the right time within the brain at the right place within the brain in the right neural circuit so that we can think and act and feel. And when our feelings become out of balance, which can happen in many forms of disease, thinking about psychiatric disease, oftentimes this is the result of an imbalance of neurotransmitters. And we treat these diseases, perhaps a little more bluntly than we would like someday to be able to treat them, with drugs that modulate neurotransmitters. Prozac is a perfect example. Neurodegenerative diseases also require a provision of neurotransmitters, critical neurotransmitters. And Parkinson's disease is an example of that. So there are a great many imbalances in these pathways that I had a free moment this morning to read what the Nobel Committee wrote. And in their description, they point out the many, many ways in which imbalances in these secretory and transport pathways are very commonly found in diabetes and in certain immunological disorders, and certainly in neurological disorders. And the fundamental understanding of these pathways opens the way to assess new drugs, to better develop personalized medicine based on a better molecular understanding, and therefore a better prescription of the drugs that we have available today. So I hope that at least begins to answer your question. Okay, so I don't know if everybody could hear the question. The question was, how did I hear about the award? And how did it make me feel? Well, I mean, I heard about it in a phone call that came at 4.30 a.m. from the Secretary of the Nobel Committee. And I have to say, it made me feel awake. And rather good, rather good. Thank you. Well, I wish there were a short answer to that. I'll try to give you one. You know, I think the real answer is there is usually not one moment, okay? Because the work that was recognized today, whether it was the work that came from my laboratory or the other two laureates, represented a cumulative effort of research in depth in a topic that went on for, in my case, 25 years, and which I certainly hope will continue. I met with my group today and I said, hey, guys, it's not over yet, okay? You may think we can slack off, but no, no, no, okay? But seriously, these are, to address very profound questions in nature, these are complex questions. Now, there are certain high points along the way that one can point to, and they're certainly an inspiration to get started. Mine came, actually, when I was a first-year medical student at Harvard. And when I was at Yale, my background, I studied physics, primarily, and mathematics, and so I was oriented towards machinery, so to speak, and a simplifying physical view of the world. And I was exposed as a medical student for the first time to some limited understanding of the complexities that occur within a cell in the way that a young doctor would see it. And actually, I'll always remember the lecture in histology where, actually, Jamison and Pallotti's work was being shown. It was very fresh then, okay? And I thought, my goodness, how could those vesicles form from that membrane and know where to go? And it was a complete mystery how that could happen at a molecular level. And so, when I had the opportunity and was prepared to take the risk, that's what I decided to focus on. And it was really that inspiration. Well, in what respect? Well, I think it's well under, thank you for asking that. It's well understood that, of course, right now, the entire federal budget is under restriction because of sequester, and I'm not referring to sequester. That's bad enough. But even before sequester, over the last, especially five to seven years, the NIH budget, which we all rely on, and has made America the great engine of biomedical discovery and also biomedical and medical innovation, not to mention the generator of our very important biotechnology and pharmaceutical industries, this budget has not really grown appreciably. In fact, in real terms, accounting for inflation, it's actually fallen significantly. I don't have the exact number, but I believe it's in double digits. And in addition to that, the NIH has adjusted the way that it spends money, or at least reviews money. And again, I'm not an expert on this, but the end result of it is that a much smaller percentage of the grant applications are getting funded. And it really depends on what part of the NIH and so on. And frankly, I don't have the exact numbers, so I can't be quoted on them. But it's much, much more difficult, qualitatively more difficult, for young scientists to get started today. Whereas we would expect a young scientist to be on their own and taking a risky project within about a year of their starting their labs, maybe 10 or 15 years ago. Today, if they're fortunate to get an NIH grant, it will take several years, three, four years. And the level of funding that they receive is, I believe, in relative terms, less than one might have received, certainly I received when I was started. So I sometimes, on occasions like this, when I have the opportunity to reflect, would I have been able to do and initiate, take the risk? I really am very concerned that I would not have been. And I don't mean to personalize that because I'm just one example of many people. And I see today the enormous opportunities and yet the discouragement that young scientists in this country feel. And it's something that we do need to pay attention to if we want to maintain this country as the great competitive world leader that it has been. But I have a hard time giving such advice today. I would say there's always room, to be quite honest, there's always room for brilliant young people to be successful. But you really have to be prepared to make a sacrifice to do that. I'm hopeful the situation will turn around, but I have to say I'm more measured. I'm very sad to say I'm more measured in my view than I would have been five years ago. And I hope five years from now, as a result of honest statements, such as the one that I'm making right now, that there might be some greater opportunity than there is today. Sorry to pour cold water on a great press conference. I should really finish that by saying that I do have a lot of faith in the United States of America. This is the greatest country in the world. We will, if we all pay attention, enough attention, in an honest way, we will find a way through this crisis. And we have to. Thank you. Once again, we congratulate Jim Rothman. We thank you all for coming. And you see now the charmed life that the Yale president leads. A member of our faculty, who is also an alumnus of Yale College, wins the Nobel Prize. And our football team is 3-0. Thank you all for coming.