This panel consisted of Nobel laureate James P. Allison, Nobel laureate David Baltimore, Nobel laureate Phillip Sharp, and was moderated by Andrew von Eschenbach.
If you were unable to tune in live to this panel, you can view the panel’s discussion here.
The panel’s transcript is below.
Jim: Ladies and gentlemen, and welcome to the Nixon library. My name is Jim Byron. I’m the president and CEO of the Richard Nixon Foundation. Welcome to day two of the inaugural Nixon National Cancer conference. Last night, we looked back at the history of the National Cancer Act. And this morning, we will get into its practical uses and implications today. I want to begin by thanking a few individuals here with us, starting with our conference chair, Dr. Andy von Eschenbach, former director of the National Cancer Institute and Commissioner of the FDA, and he spent three decades as a physician and is now the president of Samaritan Health Initiatives and a professor at MD Anderson Cancer Center. Thank you, Andy, for all that you’ve done. We also have 15 directors of NCI-designated cancer centers or director designees from those centers here with us who’ve come from across the country, and I wanna thank them all for being here as well. We also have several members of the Board of Directors of the Richard Nixon Foundation, Melanie Eisenhower, a child life specialist at Children’s Hospital, Philadelphia, and the youngest granddaughter, of President and Mrs. Nixon, thank you for being here. The Chairman of the Board, Dr. Jim Cavanaugh, thank you for being here, Jim. Gavin Herbert, founder and former chairman and president of Allergan, Chairman of Regenesis Bioremediation Products, and namesake of the Gavin Herbert Eye Institute at UCI, Thank you, Gavin, for being here. Maureen Drown Nunn, a teacher, passionate advocate for education, and consummate volunteer, from television host, who has served on our board for a very long time. Where’s Maureen? There she is. Thank you for being here. And Charlie Zhang, a serial entrepreneur and restauranter whose generosity made possible all of the technological innovations in this very room that we’re taking advantage of today.
Thank you for being here, Charlie. I also wanna recognize Mike Ellzey, Director of the Nixon Library for the National Archives, who I believe is here somewhere with us. Thank you, Mike. To introduce our conference chairman and set up our first panel of Nobel Laureates. It’s very much my pleasure to introduce, Marlene Malek, who helped immensely to bring this conference and the special exhibition that I hope you’ll all have a chance to see to fruition. Marlene received a presidential appointment for President George H.W. Bush to the National Cancer Advisory Board, which she served six years and then co-founded Friends of Cancer Research with her friend, Dr. Ellen Sigal. Friends as the organization is known is an advocacy organization based in Washington D.C. that drives collaboration among partners from every healthcare sector to power advances in science, policy, and regulation that speed life-saving treatments to patients. She’s now Vice-Chair of Friends and was with Ellen Sigal from day one. She’s on the board of the MD Anderson Cancer Center and Duke University Cancer Center and as chair of Marymount University in Virginia. She also played a vital role in both the conceiving of this conference and bringing it here to the Nixon Library because about two years ago, Hugh Hewitt invited Marlene to dinner, and they hatched this plan. Clearly, cancer research is near and dear to Marlene’s heart. Would you please join me in welcoming Marlene Malek?
Marlene: Thank you so much. Well, good morning, and welcome to the Nixon Library. We’re gathered here today this morning to commemorate transformative advances in medical research treatment and care. And this was brought about by the National Cancer Act over 50 years ago. Spearheaded by the Nixon administration and President Nixon personally, Democrats and Republicans came together in 1971 to transform medical research and treatment. And that’s why I can’t think of a better location for today’s conference. And it’s my fondest hope that we will come away from this conference with a renewed appreciation for what humanity can accomplish when we dedicate resources and commit to a common goal. So let’s begin the day with a discussion of how the National Cancer Act changed from observing manifestations of cancer and employing empiric interventions for treatment to one of understanding the mechanisms of cancer and employing rational targeted interventions. So, it’s important to start our conference in this way to understand the most amazing transitions. Rational medicine based on an understanding of mechanisms is now the reality for all acute and chronic diseases and may even pave the way in the not-too-distant future for regenerative medicine in which we as a society, not only eliminate disease but restore health. So, to lead this discussion, it’s my pleasure to introduce our conference chairman, Dr. Andy von Eschenbach. And he has poured his heart and soul and most importantly his mind into the planning of this conference. And we thank you, Andy. Andy has the rare distinction… Actually, there’s nobody better to have spearheaded this important 50th anniversary. Andy has the rare distinction of having served as both National Cancer Institute director and Commissioner of the FDA. He was president-elect of the American Cancer Society when President George W. Bush nominated him to lead the NCI. So, Andy has spent three decades as a physician and is now the president of Samaritan Health Initiatives. And he’s also now a professor at MD Anderson Cancer Center. So, in 2006, “Time Magazine” named him one of the 100 most influential people who will shape the world. So, ladies and gentlemen, please welcome Dr. von Eschenbach.
Dr. von Eschenbach: Well, good morning. Before I introduce my panel, let’s probably take a little bit more of a historical perspective as to how we arrived at this point in time. Last night, we looked at some of the history behind the formation of the National Cancer Act, but it goes back a little bit further than that. If we go back 100 years or so, to the turn of the 20th century, the preoccupation of science was to understand the fundamental nature of matter and of energy. And Nobel Laureates, brilliant scientists were probing the mysteries of the atom in its nucleus. And as they understood those mysteries, they unleashed forces that changed the course of civilization. We got everything from atomic energy to quantum mechanics to material sciences, like lasers, and even an understanding of that little thing running around the nucleus called the electron. So you’re all strapped to cell phones, iPads, etc. If we fast forward because of some of that progress around the turn of the mid-portion of the century with the discovery of DNA, science’s quest began to move from understanding the fundamental nature of matter and energy to understanding the fundamental nature of life. And brilliant scientists like those we were meeting just a few moments, began to probe the secrets of the cell and its nucleus. And as those secrets have been unraveled, once again, we’re changing the course of civilization by being able to take control of life processes. Now, the way in which that was able to come about is because scientists focused on the most egregious disorder of life, the most egregious disorder of normal life processes of growth and differentiation, and that disorder was cancer. So when we think about the impact of the National Cancer Act and what it mobilized, it enabled and mobilized brilliant basic scientists like the three you are just going to meet to use their skill talent to probe the cell and its nucleus, to probe the cancer cell and its nucleus. And they have been unraveling the secrets, the secrets of the genetic, molecular, and cellular mechanisms that drive our life processes.
It’s really a privilege among all of those scientists who have been involved in this quest to introduce three of them to you this morning to share their perspectives on their journey and the impact of the National Cancer Institute. Dr. David Baltimore, who is with me here on the stage, I love the idea that he started close to Philadelphia at Swarthmore, but of course, moved on to Rockefeller Institute, MIT, and was President for the Institute of Technology. Received his Nobel Prize in 1975, as he was probing the mysteries of reverse transcriptase and how RNA and DNA interact. We have with us virtually Dr. Phillip Sharp. Phil got his Ph.D. at the University of Illinois, was at Caltech Cold Spring Harbor and is now been an integral part of MIT. He was probing the fact that DNA had segments that did not affect, translate into gene expression, and again, to understand the diversity of how from some genes we get so many proteins, and how that coding of RNAs now led us to many other ventures that you’ll hear about. But he received his Nobel Prize for that work in 1993. Jim Allison, a fellow Texan, got his Ph.D. at the University of Texas, was at Scripps here, an employee in California, back to MD Anderson, Sloan Kettering, and then now back to MD Anderson, where he’s been unraveling the mysteries of the immune system, and how that has altered and changed our lives in profound ways, for which he received the Nobel Prize in 2018. We’re privileged to have the three of them to share their journey and to share their insights. And I’m gonna begin by asking them each briefly to comment on this evolution of revolution of science that they’ve been a part of, and particularly how they think the National Cancer Act of 1971 and the impact that that’s had may have contributed to or accelerated that process. So, I’m gonna begin David with you…well, with our virtual partners and Phil, Dr. Sharp, if you’ll begin by telling us a little bit about how you think the National Cancer Act has been impactful in this evolution of science.
Dr. Sharp: Well, it’s had a large number of effects and really tremendous effects. But I wanna speak a little bit about the basic science side of cancer, how we understand the nucleus and the cell, and how the National Cancer Act impacted that. Because in the National Cancer Act, there was the acknowledgment of the need to get a greater understanding of the human cell. And that led to a number of basic cancer centers. And MIT was one of those centers and that’s where I have spent my career. But more importantly, in 1971, I left Caltech after completing a postdoctoral study and was looking for opportunities to do science, particularly focused on human cells, particularly focused on the problem related to cancer. And because of the Act and the expansion of Cold Spring Harbor with the support of a National Cancer Program Project Grant, I was able to find a position with Jim Watson, Watson and Crick at Cold Spring Harbor, and therefore launched my career into studying how viruses interact with cells to cause cancer because we could manipulate viruses at that stage. And it gave us a tool to probe these processes in a very specific way. And then a few years later, MIT established the basic Cancer Center under the guidance of Salvador Luria, another Nobel Prize winner, a great friend of a leader in science. And that led to my recruitment to MIT down the hall from Dave Baltimore, which was a major inducement for my accepting a position. And I have seen this blossoming of our knowledge of the cell due to the contributions of the enormous community. But that community was nucleated and supported by the leadership and the resources and the national effort to have impact on the lives of patients by advancing our understanding of cancer and treatment of cancer, and control of cancer. And that has been an enormous success story.
Dr. von Eschenbach: David, you started with attention to DNA, and we’re looking today and being able to do genetic engineering, and CRISPR, etc. From your perspective, what was that trajectory like, and what was the impact of having the National Cancer Act and the NCI?
Dr. Baltimore: As opposed to Phil, I started working in virology in 1960, ’61 first as a student at MIT, and then at Rockefeller. And I did that, I chose to work on viruses because they were the simplest form of life. And I thought we could make advances that took advantage of the knowledge, the centrality of nucleic acid, and the structure of nucleic acid, which had been elucidated by Watson and Crick in ’53. And it was a good choice because it was the only organism, if you call a virus an organism, that was simple enough to manipulate, that you could begin to understand its fundamental nature. By the end of that decade in the 1960s, I realized that the only thing we had left to understand in virology was how a virus caused cancer because the rest of it was gonna happen and still happening as we all know. And so I set out to understand RNA containing tumor viruses because RNA was clearly the central player in the transition of information from DNA to RNA to [inaudible 00:18:04], so we can really understand how an RNA virus exist that could cause cancer. It could permanently change the way a cell grew. And luckily, I’ve found a path to showing that the virus particle itself had an enzyme that would reverse the flow of information from RNA back to DNA, and therefore, prepare a molecule that could stably modify the behavior of a cell. And so we, at that point, suspected, although I must say we didn’t know that the way that these viruses control cells is by having genes that could be reverse transcribed into DNA, put into cells, and control the growth of the cell. And that was all before the National Cancer. In fact, I’ve always sort of wondered what impact that word had on the passing of the National Cancer Act because it was well-known that we had done that. And, of course, the major figure in that whole story that’s not here to tell is part of it is our attempt was a great scientist that had for 10 years been saying, that this was how things were gonna play on. Once the National Cancer Act was passed, there was a national commitment to taking this known knowledge that we had and expanding it out, and there was a recognition, and I must say to me, that recognition was embodied in Benno Schmidt, who was the head of the National Cancer Panel, I guess. And because he said to me, he said, “This money is not gonna go down the paths that we’ve been investigating cancer traditionally. It’s gonna go to fundamental work, so that we can understand from the bottom up what it means to be a cancer zone, what it means to drive a cancer zone to continue division.” And that’s our work.
Dr. von Eschenbach: Brilliant. And we’ll come back to some of that because originally is some interesting background history. But Jim Allison, you know, more than a century ago, Paget came up with a theory that the outcome of cancer, the outcome of a disease is the interplay between seed and soils, the seed and soil hypothesis. So it wasn’t just the cancer cell but the environment, micro-macro-environment the cancer cell finds itself in. You’ve devoted your career to understanding the micro-macro environment from the point of view of the immune system. How has the National Cancer Act transformed immunology using tumor as a model system and how has that influenced your career?
Dr. Allison: Well, thank you. It’s been a terrifically big influence. Actually, I was a graduate student at UT Austin when the Cancer Act was passed. I was studying biochemistry, but I got involved in some tumor projects and did some experiments that led me to show something being showed in other labs, but that we could cure mice of cancer with chemotherapy, basically, and then rechallenge them, and they were forever immune to rechallenge. And this really, at the time, really caught my eye and interested me. And about that time T cells were discovered. And not all of it was known unless there were these white blood cells that go through your body, not just through the blood of the left, but percolate through the tissues and look for viruses that are infecting or whatever. And I mean, I thought, well, maybe they can detect cancer, too. And even though that wasn’t what I was studying, but I switched to immunology for a postdoc and then got a job at MD Anderson, which I think was made possible in just about 1975 by funds from the NCI. MD Anderson was one of the original three cancer centers. And I had a project, it was more directly related to cancer in an indirect way. But I started my work there trying to understand how T cells worked but the structure of the T cell antigen receptor, which was the first key, and just had been doing that ever since. And Berkeley did some work showing… And by the way, my work was funded, even though it didn’t really on the surface of it have anything to do with cancer at all. One of my early grants was from the nationalists to allogeneic immunology but then I began getting grants from the NCI, extramural grants from the NCI. And that funded my work all the way through the discovery of inhibitory pathways in T cells, and the notion that if you can block these inhibitory signals, which serve one purpose is to protect normal cells, you can unleash the immune system to treat cancer. And after we had the fundamental work, I felt that I needed to…at Berkeley.
And again, that work was still funded, even though I was not in Cancer Center, it was still NCI funding, but did only after Sloan Kettering to really, you know, try to usher this work into the clinic and learn about the clinic myself and ended up returning to MD Anderson about eight years ago to try to expand it. And I was lucky enough to take this just fundamental research that I was doing, you know, what regulates the immune system, and every now and then venturing out from that fundamental work to do cancer experiment, learning something, and then going back to the fundamental of biology, venturing out. I still consider myself a basic immunologist. But the bottom line is that most of the clinical work we started doing was with melanoma. When we started this work and when the drug that we developed, ipilimumab was approved in 2011, the immediate survival after diagnosis of metastatic melanoma was seven months with fewer than 3% of patients alive in five years. I was telling Phil just before we started, the report came out this week, it was a six-and-a-half-year follow-up of a phase three trial of my drug plus a second-generation drug and it takes another molecule with a six-and-a-half-year survival is 58%. So, 58% of melanoma patients are now alive six-and-a-half years after they were retreated. And so, what we’re doing now is trying to extend that to other cancers, and it’s been successful. And many other types of cancers, not quite that well. And so we’ve got a ways to go and some cancers like glioblastoma, pancreatic have not responded yet. But we’ve got a ways to go. But I think as we go back and combine now what we’ve learned in immune system with some of the more classical ways of treating cancer in a way that we don’t hurt the immune system, I think we’re going to be able to get those response rates and not just response rates but I can consider the cures, I think. About 20% of people who get monotherapy with ipilimumab are alive 10 years plus after treatment. So, when I say six-and-a-half years, that’s just following it. It’s been there for a long time. It’s likely to stay there for 10 years or more. I mean, these patients basically don’t have to be looking over their shoulders any more, and worrying about a recurrence of that disease. But with more work, you know, I think that we’re gonna manage to do better and we’ve got a long way to go. But it’s a start.
Dr. von Eschenbach: Great testimonies to the critical importance of basic research and the need to continue to foster that you can’t solve a problem you don’t understand. You’re right, David. Prior to the National Cancer Act, Congress had allocated $250,000 for a study on cancer that came forth as what has been called the Harbor report. And it said that based on the work you’re alluding to and others, that the science was emerging, and the timing was right for the commitment, so that if we could understand cancer, we then might be able to do something about it. And a lot of what you’ve alluded to, and Phil brought this out, a lot of this occurred in the context of this interplay between basic research, and clinical research, and the observation of the clinical realities. I had a conversation with Josh Lederberg at one point who started out as a medical student, decided then he didn’t wanna be a physician. He wanted to be a basic researcher, scientist, but he said he doesn’t think he would have ever gotten his Nobel Prize if he added those clinical perspectives and insights. You’ve mentioned, Phil, the relationship with the Cancer Centre. And one of the big parts of the National Cancer Act was immediately funding 15 more cancer centers and now we have 71 plus, etc. Talk a little bit about that interplay between basic research and the clinical reality, the clinical research, and particularly from the point of view of your exposure to cancer centers. How has that made a difference? Phil, you wanna start with that?
Dr. Sharp: It’s made an enormous difference and it can… It made an enormous difference at various levels. So, for example, in the mid-’70s when I made the discovery of split genes, that as you mentioned early in the introduction, the gene comes in pieces and it’s spliced together to make the functional protein. Right down the hall between David and my lab was Bob Weinberg, who was struggling to isolate a gene that he had identified in human cancers that showed tumor type activity in cells and culture. And understanding the gene structure and this chromatin around it and other features of basic science, he was able to isolate the first human mutant gene, the RAS gene from a cancer and show that cancer is a genetic disease. But all of that depended on having clinical cells, tumor cells in an environment in which this interest of bringing genes to understanding the basic science of cancer was essential. But then as a cancer center, it participates in the National Cancer Institute processes. As a director of the Cancer Center at MIT for eight years, and I became a director in the mid-’80s, you participate in policymaking issues, you participate in review committees, you participate in meetings sponsored by the National Cancer Institute, you participate in bringing people together to form grants, and you participate in sharing of knowledge with everyone, all the way from the most clinical people to people who are more directly involved in the interface between clinical and the basic cell and the cell activities. And that community, which is beyond the university, it’s beyond the lab, it’s a larger national and international community, brings progress very rapidly from one site across the country and it instills a vision of people working together to really impact on the lives of patients. And so when innovations such as the immune blocking therapy that Jim was beginning to develop, that has become a part of the National Cancer research community and trying, as Jim just described, to find ways of expanding the activity of this immuno blocking therapy to other types of cancer.
But it’s a very dynamic community, bringing young people and training them, providing them resources around the country, and then developing with his focus on how to better understand and treat cancer. But I will say, it also has allowed us to see a lot of other diseases, in terms of new understandings of cell interactions and others that are critical for all medical care. So the National Cancer Act not only impacted on cancer, it impacted across the whole biomedical science and biomedical treatment now, and was the seed in large part for the whole biotech community that is now very strong in this country.
Dr. von Eschenbach: We will come back to that. But Jim, I know you personally from the point of view of both when you were at Sloan Kettering, and now at MD Anderson, you love hanging out with clinicians like Chris Peters, etc. How has that interplay between you as a basic scientist and clinicians who are dealing with the reality of cancer in the clinic, how’s that influenced or impacted your hypothesis generation, your trajectory of research?
Dr. Allison: On several ways, I mean, one of them is just learning from them the sense of urgency about the need that patients with lethal kinds of cancer, you know, need help and how we need to, you know, move our work along as quickly as we can. But also, particularly when I moved to Sloan Kettering, I learned about some of the hurdles you have to get through, just showing something in a tissue culture or showing something in an animal model does not necessarily, you know, mean it’s gonna work. You have to be able to go that extra distance to go into humans because there is no perfect animal model for human immune system or anything else that you’ve got to actually try it and people and you’ve got to realize that you’re dealing with things that could actually harm the patient as well. And there’s a balance between those two, you know, moving the drug fast enough to help people but not doing it so fast, you become reckless and causing a lot of harm. And I also learned that you can also from a number of clinicians, including Chris but Pam Sharma about to devalue doing trials in small numbers of patients and analyzing and much in the way we would a mouse experiment, you know, dissecting down to the cellular and molecular level, what the impact of whatever the treatment we did was, so that even if you don’t hit a good home run and see a clinical outcome, you can see from learning enough about the signatures associated with good outcome. If you try something new, are you on the right path? And if you add two things together that give you individual components, you can begin to do a lot more good or have a lot more effective therapist than if you just try a single one. And, you know, you can learn a little bit about that in the laboratory in mice. But there’s no substitute for doing clinical trials, not big ones, where you’re looking for a statistically significant difference in survival or anything like that but just data seeking trials, where you treat patients with a drug where there’s a chance of helping them but you get biopsies and really study, you try to learn from every patient.
I’ve learned that if you do a trial where you don’t learn something from every patient, you’ve really wasted a bunch of patients and wasted time, and really done harm, I think. So, that’s the main thing I’ve learned is this take credit hardly, know what you’re looking for, and then go in and get the tissue in the blood and look at the changes and try to see the impact, so that you can learn the next time, are you blocking this particular pathway and not another one? And, you know, how do you put all these together because that’s how we’re going to move from now. Having melanoma as an example of two blockers together. But it’s gonna be a lot more than that combining, as mentioned earlier, more conventional therapies, like chemotherapies and tyrosine kinase inhibitors in ways that can prime immune responses to get us over the top. And anyways, clinical trials are obviously an essential part of that.
Dr. von Eschenbach: Well, it’s a beautiful model of, you know, we used to think of bench to bedside, but what I hear you describing and what you wanna do is it’s now a circular process that we started with discovery, development, and we get delivered. The delivery reinforms us in terms of some of the basic discovery that needs to occur. And David, you were kind enough with other Nobel laureates and basic science to come to be at NCI and meet with me, and help inform the agenda. And I remember one session, you made the comment that there’s so much more we need to learn about cancer, but there’s also the opportunity to use what we already know in a more strategic way to intervene in those critical steps in the process, whether it’s metastasis, or initiation, etc. Speak a little bit more about your continued effort to go beyond your own work to really drive that strategic approach to dealing with the clinical reality of cancer by understanding these fundamental mechanisms.
Dr. Baltimore: I’m a basic scientist and I love working on basic mechanisms. And I think it’s important that there be a cadre of people who actually don’t respond to the urgency of the cancer patient and drive knowledge deeper and deeper into the nature of the normal cell processes and how those get bastardized in a way by cancer cells. But I also have always thought it important that we test our knowledge by trying to apply it because it may be too early. It may be that we don’t know enough, it may be that we don’t have a right context for treatment, but it may be that we do know enough. It may be that at least for some cancers, and I think Jim Allison’s focus on melanoma is really interesting in that regard because that was a cancer that was, in a sense, easiest to handle immunologically and most responsive, where you could make the greatest difference. But there are still cancers for which we simply don’t have an umbrella. And again, Jim mentioned pancreatic and glioblastoma, but there are plenty of others. In fact, there are melanomas that are still killing people. So we don’t have a complete solution to any cancer problems. And so we have to go back to the basic sciences and say, “Well, there’s something we’re missing. What is it?” And often we don’t know. We have no idea. I mean, if I go back to 1960, when I started in basic science, we literally had no idea what was going on in cancer. We didn’t know about oncogenes. We didn’t know about suppressor genes. We didn’t know about reverse transcription. We didn’t know about anything. We’ve had to learn all that. The amazing thing is that in those 60 years, we’ve learned all of this. We’ve gotten to the point where, for some patients, we can say, “We have the materials to allow you to live a normal lifespan.” But for so many others, we don’t, and we have to keep the focus on basic knowledge. I will point out that you have three people on this panel, all of whom have Ph.D.s, none of whom have an MD, none of whom are actually trained in medicine, and that shows you where the knowledge comes from that allows an advance something as totally challenging as the cancer problem.
Dr. von Eschenbach: Yeah, you were three major in the seats, we just planted you in the right soil, which was the Cancer Center. You’ve alluded to something I wanna touch upon and get all three of you to just converse about this. The progress that’s been made in cancer and our understanding of cancer, and understanding some of these fundamental underlying mechanisms is now applicable across all diseases, acute and chronic. We can see that things are now cancer-led and not cancer-centric, and that science is becoming, if you will, horizontal across these. And it’s a little difficult. I don’t wanna go too far with this. But we’ve been trapped in the old model of observing manifestations of disease phenotypically, lump in a woman’s breast, the shadow on an x-ray, and we designed and organized accordingly. But now we’re seeing that when we get down below the macroscopic and microscopic to the molecular level, there are similarities that transcend diseases. We’re looking at SARS-coV-2 right now and more RNA vaccines, etc. Talk a little bit about your perspective on how our understanding of cancer is now impacting our ability to understand and manage a whole host of other diseases. Jim, you’re in tumor immunology, but yet we have immunology that’s affecting autoimmune disease, we have infectious disease. If all of you could share with us and converse with each other as to where you think we are in the integration of science and where it could lead us using cancer as that discovery system. Jim, I pointed you out. You wanna start with how you…?
Dr. Allison: I’ll say that, very early in our studies, what I realized we wanted to get a really aggressive immune system response to cancer. And so one of the things we did was studied autoimmunity to try to understand how it works and ways of making it worse to [inaudible 00:43:44] with the reasoning that if we could do that, and you do the same thing in the context of cancer. But now we’re trying to go the other way and figure out how to use those same lessons to turn it off, the ones we were trying to show before and making some progress. They’re not enough yet, but some drugs have come out of our cancer work that are now in use in treating some kinds of autoimmune disease. But one of the things that we began to realize lately is that things are not quite as simple as we think they are because a postdoc in my lab has some very early information but very intriguing data showing the neurotransmitters and neurophysiological sensors and products of nerve cells that can influence the activity of T cells within a tumor. And so, you know, we haven’t linked that up to the nervous system is larger thing but I think that it’s gonna lead us into perhaps interaction with immune system with the nervous system both in causing neurological diseases but perhaps also in neurological regulation immune responses in some cases. So it’s just speculation at this point. I don’t know. We’ve just got the early molecular fingerprints that suggest this is going on.
Dr. von Eschenbach: And moving us into areas of neurodegeneration in Alzheimer’s, etc. Phil, you were talking about RNA and that we have mRNA vaccines. What do you see as the horizontal dispersion of what we’ve learned in cancer to other diseases?
Dr. Sharp: It’s been absolutely enormous. I was involved in starting Biogen and a biotech company, and a large biotech company, the oldest freestanding biotech company in the country. In 1978, we saw the interest in interferons becoming a treatment for cancer and others. But let’s look at the CoV- SARS-2 situation. We now have RNA vaccines, where we can redesign a vaccine in two months and show it safe in patients and move it into treatment. And this has really changed how we are responding to this challenge. And if you look at our understanding of the virus, and how the virus has evolved, and how our immune system and our monoclonal antibodies, which we now make to treat this virus, how it can evade that immune response, all that information, is a product of this lateral engagement of breakthroughs. But I just wanna mock something David said, this venture is not even close to being over. We’re seeing an integration of engineering and the high throughput computation and large databases in their understanding of cancer, how to predict who’s going to develop cancer, how to find it early, and how to then intervene more effectively. So, we are not close to the end of the journal occurrence. We will be making enormous progress over the next 20, 30 years, all the time improving the outcome of the lives of patients.
Dr. Baltimore. Well, as Phil has just said, the impact of the knowledge that was generated through the National Cancer Act and through the focus on cancer as a problem has permeated the way we deal with every disease. When you think about what disease is, a large part of it is infectious disease. And that has certainly been an area of the application of the knowledge that has come out of cancer. But a lot of is genetic disease. And there is no question that the way we approach cancer, a genetic disease, has influenced the way we approach all inherited disease. Inherited the level of the transmission through generations, as well as inherited as a consequence of mutations in the body. And we’re now using genetics as a probe for almost all diseases because there is a genetic component, there’s inherited component in the way we respond to diseases, the way we respond to infectious diseases, as well as others. So it’s all mixed up together. And I think it’s worth spending just a moment thinking about training because new generations come up every decade, let us say, to take over from us who have done our part. Where are they trained? They’re trained in basic research laboratories. MD, Ph.D.s are getting Ph.D.s because they need the approach that is taken in a basic research laboratory. And then it’s possible to move into disease-focused institutions and to bring institutions that have a basic source like the MIT Cancer Center or Caltech, or the Broad Institute, take a more recent edition to focus on the disease elements that we don’t understand and that we can illuminate life by a basic investigation.
Dr. von Eschenbach: That’s a perfect lead-in. So the idea of the young mind and training. So here’s what we’re gonna do. We’re gonna make the three of you 50 years younger, we’re gonna take away your Nobel prize, and you’re now reflecting on this 50 years of progress. So you’re starting right now, what would you wanna study right now? What would you focus your career on the mystery that you would like to solve, given the 50 years of progress, given the fact that we have stem cell biology, we have computational biology, we’re moving from an era of experimental biology to theoretical biology, etc.? You’re now in 2021, 50 years younger and you don’t yet have your Nobel Prize, well, what are you gonna do? And you’re all smiling but nobody is answering.
Dr. Allison: I’ll tell you what interests me lately is something that we found in others, it’s not unique to us but just a surprising mutability plasticity of cells. We used to think there’s given states and we have textbooks that says, you got this state, this state, this state, this state. And after they differentiate, they’re immutable. And my friend, that’s just not true. Immune cells, in particular, have the ability to take on a lot of the characteristics of the cells around them and to respond to signals of change that complete transcription patterns and even look like different kinds of cells. It’s just understanding that, you know, the mechanisms that are involved in that is something I can cope with. I am too old to do it now but I think if I was a little bit younger, that’s what I would start thinking about.
Dr. Sharp: So, I will follow up on that because if I were starting now, I’d try and approach the thought processes. But life science is informational science. It’s informational that has been with us for 3 billion years as organisms that divide. And now we see our tools to understand the nature of that information and a cell and the whole explosion of IT, machine learning large capacity computing. And I think that integration over the decades in front of us is going to reveal some remarkable, deep understanding of both cancer and all of life science. And I would try to be in the middle of that mix if I was young and doing it again.
Dr. Baltimore: You know, there are two ways that you think about what you’re gonna do at the outset of your career. One is to sort of follow your nose. A guy like Ed Wilson cared about ants. And he went and tried to find every ant in his community, and to give it a name, and to understand its properties. And he became a central figure in ecological science. But others of us, like I was interested in viruses. It doesn’t matter where you start. It matters what you do. And that is to really investigate at a fundamental level what’s going on in whatever it is you care about. The other way to decide what to do is to kind of look globally at science to say, “Where are the big open questions?” Evolution is a big open question, but the brain is a big open question. And that’s one that will benefit from all the things Phil was just talking about and lots else because it is so complex, evolving, you know, numbers that I can’t even remember how many zeros are involved in them, scallions and trillions and whatever of synapses. So there’s no question that’s a challenge to anybody who is looking for a way to go into science and to find a big question. Where’s this dark energy and dark matter? And you can go after that. But I don’t even understand the words and the way to go after it.
Dr. von Eschenbach: Well, if we can keep some of your progress going with stem cells, we’ll get you those 50 years back pretty easily. You know, we’re in the midst of a pandemic, of infectious disease nature, Alzheimer’s is in many ways a pandemic affecting us globally. And in 1971, cancer was a pandemic. There was not one family that was not touched by this disease. The work that the three of you and your colleagues in basic research have helped us come to grips with being able to solve that pandemic. There’s more work yet to be done but we know how far we’ve come. You’ve opened the doors for us to be able to solve the pandemic of today with SARS-CoV-2 and you’ll help us solve the pandemic of tomorrow, neurodegenerative diseases. So we are grateful to you, not only for your participation on this celebration of the 50th anniversary of the National Cancer Act but grateful to you as basic scientists and your colleagues for helping us understand and deal with a disease that was virtually a death sentence 50 years ago when this all began. Thank you. God bless you for your work, and we’re looking forward to the next 50 years of your contributions. Thank you.