Rewriting the Rules of Medicine with Dr. Ben Ebert, President and CEO of Dana-Farber Cancer Institute
Willy Walker: Good afternoon, and welcome to another Walker Webcast. It is my great pleasure to welcome Dr. Benjamin Ebert, president and CEO of Dana-Farber Cancer Institute and director of the Dana-Farber Harvard Cancer Center. He is also the Richard and Susan Smith Professor of Medicine at Harvard Medical School. Dr. Ebert is a renowned cancer researcher whose work has shaped how we understand and treat blood cancers, particularly conditions like myelodysplastic syndromes. Did I get that right, Dr. Ebert?
Dr. Ben Ebert: Close enough.
Willy Walker: Close enough? He's received numerous honors for both his groundbreaking research and his commitment to mentorship. He serves on the boards of several major research organizations, including the Broad Institute and Break Through Cancer. Dr. Ebert earned a bachelor's degree from Williams College and was a Rhodes Scholar at Oxford University, where he completed his Ph.D. and received his MD from Harvard Medical School. He trained in internal medicine at Massachusetts General Hospital and completed a fellowship in hematology and oncology at Dana-Farber. Dr. Ebert, it is a pleasure to have you. I have lots of really smart people who join me on the Walker Webcast. I think you're probably in that top decile, if not the top 1% of really smart people, so I have to have my game on, if you will. Ben, if I can back up for a second. Walker& Dunlop’s headquarters are in Bethesda, Maryland, and you actually grew up in Bethesda when your dad was working at NIH. The easiest thing for me to ask you is, “Where did you go to high school?”
Dr. Ben Ebert: So I moved just before high school. I went to Burning Tree Elementary School in Bethesda. I went to Pyle Junior High. I would have gone to Walt Whitman, but we moved to Nashville when I was in eighth grade.
Willy Walker: And did you go to a public high school in Nashville, or did you go to a private school in Nashville?
Dr. Ben Ebert: I went to a private school called University School in Nashville, right on the Vanderbilt campus.
Willy Walker: Yeah, that's great. And then on to Williams College. You were a juggler, amongst other things, at Williams College. When I read that about you, I sat there and said, “How amazing that this incredibly gifted man also can put five pins up in the air at the same time and keep them all up in the air.” Do you find that juggling skill actually works in managing Dana-Farber?
Dr. Ben Ebert: Probably there are more than five things in the air, that's for sure. There's a lot going on. I think I got asked at an interview once, “Tell us something nobody knew about you,” and I said that, and then it sort of got a life of its own, everybody knows. But yes, juggling was one of those things. I was a math major, and it was a kind of math geek type thing to do. And it was really fun, and yes, it does feel like juggling now for sure.
Willy Walker: I was interested. You talked about being a math major; you tutored in high school; you tutored people in math. Is that what gave you the sense of giving back? Throughout your career, you've shown this incredible capability to both teach, train, and mentor people. And as I read some other interviews in preparation for this, it was very evident to me that one of your great prides is not just your family, but also those mentees who have been influenced in their lives. Did that come from that early tutoring experience, or was that from something else?
Dr. Ben Ebert: I think I've just always enjoyed it. It's so satisfying, so rewarding to teach at all levels, medical students, graduate students, college students, and high school students, and see them grow as scientists or as clinicians, and then go on to do great things. One of the most fun things every year for us is when alumni from my laboratory get back together at one of the big meetings and see each other and are now leading labs all over the world. It's really one of the most satisfying things to see people mature intellectually as scientists and as clinicians. So, just something that I've always gained great pleasure from.
Willy Walker: My understanding is that if you had not been a doctor, you wanted to be an architect. That's an odd other side to the mathematician scientist brain, is it not?
Dr. Ben Ebert: I think that is purely aspirational. I don't think I'd have any talent as an architect, but it's always seemed fun. And actually, what you do as well, the building and developing properties, has always been a fascination for mine. I love watching them go out, watching the organization and the financing, what goes into big projects. We actually have an opportunity to do that firsthand now because we're building our own inpatient hospital right now, and that's really exciting to see all of the aspects of the planning and building come together.
Willy Walker: Did that end up being 300 or 350 beds? 300 beds.
Dr. Ben Ebert: Yeah, we are capped by a local park on the muddy river in Boston, and any higher would cast too many shadows on that park. So we've basically packed as many rooms as we can in the footprint and the height that we can.
Willy Walker: When we talked about architecture, it does remind me that your mother was an artist and a photographer. You and I share mothers with a very creative side. My mother was also a photographer, and I believe, like you, I didn't inherit any of those creative skills. I'm a little bit more linear in my thinking and my expression, if you will. But I thought that was an interesting commonality amongst the two of us.
Dr. Ben Ebert: Yeah, I love looking at art as a consumer, but certainly not as a creator.
Willy Walker: One of the other commonalities the two of us have is either a passion for or a somewhat masochistic desire for endurance athletics. You've done a bunch of marathons. You've done a bunch of triathlons, but you also have three kids and an extremely demanding job. How do you find time for all of that?
Dr. Ben Ebert: Yeah, I think those athletic pursuits took a nosedive when we started having kids. I think I could manage a busy job being an intern and still run and exercise. Little kids were the hardest thing to keep up any exercise, but they're older now. And so I can do some of these things with them, which is great. I know you're a rider of the Pan-Mass Challenge, and I did that for a couple of years. The last two years, I did it with our eldest son. Actually, our middle child, our daughter, is gonna do one of the shorter rides this summer with my wife. We're gonna make it a family affair.
Willy Walker: It's actually interesting. I have had connectivity to Dana-Farber since my first marathon, my first Boston marathon, which I ran in 1994. My first visit to Boston was in the spring of 1994. Since I had not run a previous marathon, the only way for me to get into the marathon was to raise money for Dana-Farber, and so my first Marathon was actually on the Dana-Farber team.
Dr. Ben Ebert: That's great.
Willy Walker: Which was great. Fortunately, I then qualified the next year. I qualified in that race to then make it to the next year, so I didn't have to do that again, even though I did raise money for Dana-Farber the second year. But you mentioned the Pan-Mass challenge, which I have done a number of times. Talk for a second about that because, first of all, you have raised almost, or you went over raising, a billion dollars. To anybody who's listening to this podcast, and there are lots of them, you work for a local charity. You work for a national charity, and they talk about raising millions of dollars or hundreds of thousands of dollars. The concept that the Pan-Mass Challenge has raised $1 billion for the Dana-Farber Cancer Research Institute is just breathtaking. Talk for a moment about what the Pan Mass Challenge is and why it is so important to Dana-Farber.
Dr. Ben Ebert: Pan-Mass Challenge is just an incredible event. It's the largest athletic fundraiser in the country and started way back in 1980 by Billy Starr, who continues to lead it. And he had lost a couple of family members to cancer, was a young guy still figuring out his career, did a little bike ride to raise some money for Dana-Farber, and it just took on a life of its own. A huge part is his force of personality. So large, there are thousands of riders, something around 6,000-7,000 riders, and multiple different rides, but it turns out to be so much more meaningful than you expect. Every time you do it, if you work for Dana-Farber, to see the scale of the community support, the roads are lined with people who are supporting the riders. People who are survivors of cancer who ride are called living proof. People who are undergoing treatment for cancer, family members who have lost family members to cancer, or friends. It provides a community for people who have dealt with cancer. And it's just an incredible community of support for Dana-Farber and for raising funds for cancer research. And then the funds are enormous. Just last year, we raised $75 million, and it supports really every aspect of what we do here, from patient care through all kinds of research, really basic research to drugs that are going into the clinic.
Willy Walker: Is it challenging with something that is that successful to do standard fundraising in the sense that if you raise $75 million, when I was on the board of Children's Hospital in DC, I think we raised about $90 million a year, and that was through our annual gala and a bunch of other events. But we would kind of put all the chips in on the annual Gala, and we got fantastic sponsors and corporations to donate a lot of money, and raised a huge amount of money in our annual Gala. Everything else sort of played second fiddle to that. Does the strength and breadth of the Pan-Mass Challenge make raising money through other channels challenging?
Dr. Ben Ebert: I have not seen that at all. If anything, the opposite in that it generates so much enthusiasm. It's phenomenal exposure of what Dana-Farber is to our broader community. I think that people give in so many different ways. Some are grateful patients. Some are people who are just committed to cancer research. Some are people who don't wanna engage in athletic events. Some would be giving, whether or not they did the Pan-Mass Challenge. So it's really, really diverse. And Dana-Farber, interestingly, has kind of been a pioneering organization in that fundraising space for a long time. Dana-Farber was founded in 1947, and Sidney Farber recognized he was really generating the first treatments, responses to chemotherapy, and ultimately the first cures for leukemia. And they created this symbol of surviving pediatric cancer named Jimmy, which became the Jimmy Fund. And he was a fictional character, but representative of an actual boy who was a cancer survivor. They did events like, at Red Sox games, people would put coins in the jars for Jimmy. And so the Jimmy Fund has remained part of Dana-Farber today. And then an incredible part of that story is that the boy grew up, survived his childhood cancer, lived in Maine, and in the ‘90s as a middle-aged man, identified himself as Jimmy. His name is Einar Gustafsson and he came back, met Sidney Farber, met Ted Williams who was a huge supporter of Dana-Farber. And actually, you can't quite see it, but in the background, I have a Ted Williams-signed baseball from the moment when Jimmy met Sidney Fiber and Ted Williams in the 1990s.
Willy Walker: That's so neat. It makes me think of identifying themselves that maybe one day Carly Simon actually tells us who “You're So Vain” is in that classic song, and we might actually all find out. That's a neat story. In talking about fundraising for Dana-Farber and how prolific you all are, your operating budget is a little bit over $3 billion, and I wanna use this as sort of a segue into, the fact that cancer has touched the lives of pretty much all of us, whether we've lost a family member or a friend. It's so prevalent in our society and the amount of time and effort and resources we're dedicating to finding a cure for cancer and trying to figure out how we as human beings can live with it is something that is undeniably a belief that's held across humankind and in the United States across Americans. And yet we're also dealing with some very significant cutbacks right now on funding for research due to some broader political movements in the country. The relationship between Dana-Farber and Harvard is extremely tight. Talk for a moment about, and I know you wrote a memorandum to everyone inside as it relates to, what I read that to say was, “Let's keep our head down. We know what we have to do. Let's keep going and we'll see how all this plays out.” But talk for a moment about how much of your funding comes from the fundraising side versus, if you will, revenues that come from people who are engaging with Dana-Farber, versus research grants, and where you see things headed as it relates to the research side of things.
Dr. Ben Ebert: That's a great question. So that $3 billion budget, $3.5 billion budget? Much of that is the clinical budget, but the research budget is still very substantial. As you said, this is an unbelievably exciting time for cancer research and new therapeutics. I don't think there's ever been a time with greater promise for new therapeutics for cancer. We have developed in the last decade and more a whole set of just tremendously powerful new drugs for cancer that are absolutely transforming the lives of patients who would have otherwise had a fatal disease, and now may be cured. So there are many breakthroughs happening. There is a lot of interest in cancer research from many different communities. About one-third of all of our research funding comes from the federal government, mainly from the National Institutes of Health and the National Cancer Institute, which is part of the NIH. A little more than a third comes from philanthropy of various sources and that is incredibly powerful because with grants, you have to write the grant and have to wait nine months to find out whether it's gonna be funded. At the National Cancer Institute, less than 10 percent of the grants that we submit are actually funded. So there are a lot of times people write grants and they're not funded. The philanthropic funds are able to get things started really quickly before the big grants come in. Then another chunk of the funding comes from the private sector. There are interests often aligned with companies that may be pharmaceutical companies that have a drug, and we're doing clinical trials, and those are funded by pharmaceutical companies. They may be even venture capital or biotech companies that want to develop cancer drugs. We have expertise there and we collaborate. We do part of the research; they do part of the research. Our goal is to make new drugs that treat patients and make them better. Often, those collaborations are the most efficient way to really achieve that goal. So, our research funding is split between those sources. Finally, in terms of the money from the government and a relationship to Harvard to date as of the date of this podcast, the focus of the funds that have been frozen from the federal government has been to Harvard University and Harvard Medical School, but not to the affiliate hospitals. Our hospital has independent governance and independent finances unrelated to Harvard University. So, those affiliate hospitals have not yet had any funding cut. We're monitoring this. We're preparing for various scenarios, but we have not suffered any cuts in funding to date.
Willy Walker: When you talk about the partnerships that you have, it makes me think about why Boston is Boston. Michael Porter, whom I was fortunate enough to study under at Harvard Business School, had a great five forces analysis, but he also had this cluster analysis, where there were these economies that basically were created in Boston out of the mutual fund industry and out of the life sciences industry. New York finance, for instance, Denver, Colorado was natural resources, etc. He would sit there and look at these hubs, these centers of excellence where the most creative minds as well as the capital, as well the jobs, just sort of built this incredible compounding effect on making these cities, these centers of excellence. It's very clear that Harvard University kind of sits at the core, Harvard and MIT, I should say, at the corner of why Boston is Boston. As the federal government sort of prosecutes what I would call this dispute with Harvard, do you have any concern that Boston as a city ends up getting impacted negatively by any cut of funding to Harvard, which then, if you will, has derivative effects out into other institutions?
Dr. Ben Ebert: I absolutely subscribe to the idea that larger communities of people drive discovery and advances in a way that a single institution or single individuals just don't do. The Boston ecosystem—with Harvard University, all the Harvard hospitals, MIT, the Broad Institute, the venture capital community, the biotech community, the pharma community all together—an ecosystem that doesn't exist anywhere else in the world at that level. It's just an extraordinary engine of biomedical research and discovery and drug development, and it is absolutely thrilling to be part of that community. I've interacted with every one of those institutions in my laboratory, and as an institutional leader, we've interacted with countless companies in this space that employ a huge percentage of the Massachusetts workforce, a huge percentage of the Boston and Massachusetts economy. So it is definitely a great concern. I've had meetings with the governor to discuss, and meetings with other members of the state government, and the city government. So everybody recognizes the importance of this endeavor for our economy, but also the importance of what goes on here for people with cancer and people with diseases everywhere: that these discoveries ultimately lead to drug development that benefits people all over the world. So we are very worried about it, but want to do everything that we can to maintain this incredibly special and powerful community of people that drive discovery here.
Willy Walker: When you talk about driving discovery and partnerships, there's a sense that the discoveries that you all come up with and the therapies that you will invent and create can impact the global population and save lives and make a huge difference in lives. You're also in a competitive world. You're not isolated in Boston, saying, “We've got everything and we don't have to worry about it.” You've got MD Anderson in Texas and you've got Sloan Kettering in New York, which are two phenomenal cancer research centers and hospitals. How do you manage friend and foe, if you will, in your seat?
Dr. Ben Ebert: That's a really great question. In fact, I was at a board meeting this week for Break Through Cancer, one of the organizations you mentioned, which involves five institutions, including MD Anderson, Memorial Sloan Kettering, and Dana-Farber, as well as MIT and Johns Hopkins. The whole concept is about collaboration, that every project has scientists from all those five institutions that work together, that share data without any reserve, without trying to hold anything back. The funding is really contingent on demonstrating that those teams are working together in a frictionless way and are generating discoveries. So I think from a scientific standpoint, generally, people are very eager to collaborate. Science has become so complex, and the technical expertise to execute on really ambitious projects often requires many different types of scientists from different institutions to execute at the very highest level. I would say the trainees grow up embracing that concept. I would say that competition has its role as well, and that the lab's full on the weekend. There are people here on a Sunday night or on a Saturday night in my lab. To some degree, they want to be the first to make a discovery. That thrill of discovery is unbelievably high. It's really exciting. People do want to drive that forward as fast as they possibly can. A little bit of competition, as always, drives human nature, and drives people to work really hard. But I would say my lab and our Institute are extremely collaborative. If you look at any of our papers, there are usually 20 authors from multiple institutions, shared first authorship, and shared senior authorship on the papers. When patents are filed, they're often filed by multiple institutions that work together. So we definitely feel that collaboration advances the field faster than working in isolation. And we encourage and try to create the systems, the funding mechanisms to encourage that as much as we can.
Willy Walker: You're constantly in a competition as it relates to talent. You want, well, you want Dr. Ben Ebert coming to Dana-Farber and not going to MD Anderson if you do well. We as the public, if I, heaven forbid, get cancer, I'll want to go to one of the best hospitals there is with the very most advanced cancer research for whatever condition I have. But for you, it's to get the greatest minds. When a doctor is making a decision or a researcher is making a decision to go to MD Anderson versus Dana-Farber, what are the variables that they're looking at in the sense of, Dana-Farber vis-a-vis MD Anderson is a little bit further down the road on therapeutics in this line of research that I'm going after. They've got a better lab. They're gonna pay me more. There's a chance for me to publish more. What are the defining characteristics as you go to meet with the world's very best doctors and researchers to try and attract them to Dana-Farber?
Dr. Ben Ebert: That's a great question. I certainly spent a lot of my time on the recruitment side and dealing with these questions. There's certainly a portion of it that is the standard stuff for any kind of job, what resources you might have, what your salary might be, that type of thing. But overall, I've found that that is less important for people coming to Dana-Farber. We need to be reasonably competitive on those. But the environment, the intellectual environment, both for the practice of medicine and for doing science, tends to be the most important aspect of both productivity and job satisfaction and enjoyment of being here or elsewhere. Dana-Farber has always been based on a foundation of equal emphasis on research and clinical medicine, and that is very attractive to some people. The people who come to Dana-Farber want to advance the field. If they are a full-time clinician, they still think like scientists. They can talk to laboratory-based scientists to understand their language and think about how those findings can be translated, or to articulate to a scientist the clinical challenge that they're facing that needs to be addressed. Our scientists, even if they have no clinical training, tend to know cancer, the therapies, and the opportunities extremely well. So I think creating the culture, creating the environment that is best for that type of discovery, is what attracts people, and then the broader ecosystem that we were talking about in Boston is also a major draw. Similarly, for clinical medicine, taking care of patients is also extremely collaborative. You work with a medical oncologist. We'll work with the radiation oncologist, a surgeon, nurses, geneticists, nutritionists, and a wide range of pharmacists, so many different professions. Working with really outstanding people who are absolutely dedicated to their job, who feel the mission of the institution, makes it a pleasure to come to work every day, rewarding to come to work every day. From my perspective, creating that culture and maintaining and growing that culture is the most important thing to ultimately attract the best talent.
Willy Walker: As you think about various cancers, I'm curious to know where the research dollars are going. Is it to the most prevalent cancers, the most challenging cancers, or the cancers where Dana-Farber has made so much progress that there's the ability to get to a therapeutic that actually changes lives in a much bigger way than some other cancers that are more challenging to address, as you sit there and think about, in my world, it's all capital allocation, right? I get asked by analysts all the time, “Okay, Willy, where are you allocating capital at Walker & Dunlop?”, which then reflects upon where we see growth. When you think about resource allocation at Dana-Farber, is it that you wanna go after the cancers that are most commonly held, if you will? Or the illness level, is it such a level that you want to go try and impact the most people? Is it the most challenging cancer? Because if we can crack the most challenging cancers, we can get the, if you will, nothing's easy in your world, but the easier ones, or is it finally that there are certain research methodologies and therapeutics that you all have developed, that there's this flywheel that will get you further down the path, or is it something that I have not put out there as a potential path?
Dr. Ben Ebert: No, that's such an interesting question, too. I think research is extremely entrepreneurial. So each of the faculty members who run a lab is kind of like a small business owner themselves. They fund their own lab; they write their grants; and they look for their opportunities. So we have hundreds and hundreds of individual people constantly surveying the environment and looking for that opportunity. Often, just like in business, you're looking to zig when everybody else is zagging. When I started my lab, I realized that there was a disease that you worked on pronouncing at the beginning, myelodysplastic syndrome, that had almost nobody working on it scientifically, whereas very similar diseases, other blood cancers, had tons of people working on them. There's often a self-reinforcing loop where people train in a particular disease, and they keep working on that disease. I realized nobody was working on this one disease, and there was an opportunity with new tools to make progress in understanding that type of blood cancer. So I focused my attention initially on that. When it came time for somebody to give a talk about that disease, I didn't have any competition. In other diseases, if there were a hundred people are more senior than I, I never get on the podium. So, it was the way.
Willy Walker: By the way, I have to tell you, I listened to one of your speeches on that, and it's some pretty dense stuff, Dr. Ebert. I have to tell you. I sat there and struggled to try and keep the thread throughout it. But anyway, go ahead. It was fun to listen to your presentation.
Dr. Ben Ebert: Sorry to put you through that. I think people look for those opportunities, and sometimes it's by disease type. Often, it's by a target or a mutation that may be present in multiple different cancers. It may be a therapeutic modality like “How does the immune system get unleashed to target cancer?” which then ends up benefiting many different types of cancer. Then there are cancers that are rare, and we probably over allocate resources to them because otherwise, nobody else will. Pediatric cancer is at the top of that list. It is difficult to impossible for many drug companies to invest a large amount of money in a rare cancer or pediatric cancer where there's no way they could ever recoup their investment. So, we need to work on that. We have examples where we have been able to work out the biology, test a therapeutic, and really de-risk it. Then, once we've really shown efficacy, the private sector can take it up and run with it, which we ultimately need for the drug to become available. So we do look, and there are some fields that are going to run by themselves that are super well-funded, very high profile. Then, there are some fields where we give it a little extra push because if we don't, nobody else will.
Willy Walker: So there's a lot in that response that I want to kind of dive a little bit deeper into. You mentioned immunotherapy. Immunotherapy, from what I gathered, and again, I have to put massive disclaimers, I am such a neophyte to all this stuff, and I am so thankful to you for spending time with such a neophyte on these issues. I am far from an educated questioner of you on the intricacies and the specifics of your field. With that said, on immunotherapy, my take was that we haven't really been that successful at, if you will, stimulating immunotherapy to have your own body go and attack the cancer, whereas we have been very successful in using T-cell therapies to go and attack cancers. Can you explain the difference between those two and whether I'm correct in saying that immunotherapy hasn't gotten to a point where we can sort of unleash that on ourselves?
Dr. Ben Ebert: No, I would say that it has been quite successful and maybe part of how we define success. We had decades upon decades of immunology research trying to understand how you could use the immune system to attack cancer, with no progress. And almost to the extent that people had said, this is a fool's errand. We're never gonna get the immune system to attack a cancer cell because cancer cells are our normal cells, and the whole challenge for the immune system is to recognize what's your own self and what is foreign. So you can attack a bacteria or a virus, but not attack your own cells, which is what causes autoimmune disease. Discoveries that were made in part at Dana-Farber by an investigator named Gordon Freeman identified what we call checkpoints. It was holding those T cells, holding the immune system back from attacking cancer cells and from attacking our own cells. It turns out that those drugs targeting those checkpoints, which are called checkpoint blockade, have been phenomenally successful. So, for metastatic melanoma, when I trained, metastatic melanoma had a 100 percent fatality rate. It was not a survivable disease. Now, on the order of 40 to 50 percent of those patients with checkpoint blockade are either cured or have very long-term survival, 10 years out, with no evidence of their cancer whatsoever. And that's just from the immune system. Another example of the immune system that works is a bone marrow transplant. Bone marrow transplant cures people not just because of the chemotherapy you get before the transplant, but because the transplanted immune system recognizes the leukemia or cancer cells and eliminates them. So the cures from transplant are ultimately an immunotherapy as well. So those have been very widespread. Very active lung cancers as well, and immunotherapy has had huge success in treating lung cancer. There's another type of therapy that you talked about, which is called cellular therapy. And that is, instead of modifying the immune system with a drug, you remove T cells from the patient, re-engineer those T cells to target cancer cells, and re-infuse them back into patients. The fact that we can do that still boggles the mind, and to do that at scale, hundreds and thousands of patients take their individual cells, re-engineer them with a virus, grow them up, re-infuse them, and have them attack the cancer cell. It’s just stunning. And that field is burgeoning as well. It's so creative. New types of cellular therapies are being developed constantly, and some of those are also curative. There are some patients with blood cancers who get phenomenal responses and even cures. And so it speaks to (1) the creativity of what's going on now, designing all sorts of engineered products that have such great efficacy, but (2) it also demonstrates the essential basic science that enabled those discoveries. The immunotherapies that work would not have been possible without decades of hard research, much of which is unproductive, but ultimately led to the fundamental discoveries that led to these super-powerful drugs. I think at a moment when we're talking about the financial return and the investment of the federal government's investment at the NIH, it has led to just transformative therapies that have benefited and cured patients everywhere in the country and all over the world. It's important to note that these basic discoveries that didn't know where they were heading often end up leading to the most transformative therapies.
Willy Walker: When you talk about the immunotherapy on the metastatic melanoma and people living with it for 10, 15 years or the rest of their lives, do they require to be on drugs for that entire period of time to have the immune system continue to act the way that you have prompted it to or does the immune kick in and keep doing it in perpetuity once you've gotten it going?
Dr. Ben Ebert: Yeah, that's the amazing thing—that you activate the immune system, and that immune system creates its own memory and continues to provide surveillance for any cancer cells coming back. It's kind of like, if you get exposure to a virus when you're young, you don't get it 20 years later because your immune system remembers that virus and attacks it again. So that priming of the immune system to the cancer cells can be maintained for a long time, and with the immunotherapies, they don't tend to get treated for years and years and years. On the other hand, there are therapies that we use for a long time in remission to keep cancers from coming back or to keep it at bay, often called maintenance therapy. In some cancer types, that is very effective in keeping the low-level therapy. But if you're gonna treat it for the long-term, you obviously need to have a treatment with very low toxicity.
Willy Walker: I'm assuming there isn't a specific number to this, Dr. Ebert, but how much of cancer is inherited and how much cancer is, if you will, due to life and behavior in life that then brings on the cancer? Clearly, there are certain cancers that you all have identified as genetically linked, and then there are others that all of us, whether it's the conditions you're in, whether you're close to Roundup, and I know there've been huge lawsuits about that. And I actually just saw a news flash this morning about a state that wants to stop the lawsuits as it relates to that, but smoking, and there are all sorts of other things that we know are things that we do to ourselves that very much increase the incidence of cancer. What's that breakdown in the world?
Dr. Ben Ebert: That's a great question. And then the other thing is just bad luck. The mutations happen all the time, and a huge percent, probably the majority of cancer, just bad luck. Even lung cancer happens in non-smokers, and things. So, then the percentage of cases that have a really powerful genetic predisposition is increasing, as we've done genetic testing on more and more patients. It's getting toward about 15 percent of our general adult oncology patients have some genetic predisposition. It's even higher in children who have cancer. As we recognize that more, people will often say, “Oh, I had two members of my family that had breast cancer” or something. We do genetic testing, and we know which family members have that inherited risk. Then, we can really customize the early detection plans for that person. So if somebody has a BRCA mutation, they have a high risk of breast and ovarian cancer. There are other mutations that increase the risk of colon cancer or leukemia. In those individuals, we would have a different plan for surveillance to make sure that we detect cancers early. And so that's real. One of the vanguards of our field is identifying who's at greatest risk. It could be because of an inherited risk. It could be because of a known exposure. It could be because of prior cancer. A prior cancer is a huge predisposing factor to a new cancer. We really are working hard on early detection and intercepting cancers early, based on their genetic predisposition in large part.
Willy Walker: You're as good an expert on the face of the planet as there is as it relates to those early detection tests that are going on. Let's put it this way. You know a lot more about it than I do. I go to my annual physical, I get annual blood work from my doctor, and I go about having my doctor come back to me and say you're extremely healthy, and on you go. What they do as it relates to the annual testing on making sure that any markers that you may have are being detected early.
Dr. Ben Ebert: Yeah, you mean what do I do for myself?
Willy Walker: Yeah. What do you do for yourself? Or if you don't think that you're best, if you don't think you're in best practice, what do you see other people doing that you think is practice?
Dr. Ben Ebert: That's a great question. I just do the standard stuff, struggle through my colonoscopies, and stuff like everybody else. But I think there is a frontier right now that we're just working out where there are new technologies coming along, and we're trying to figure out where they fit in. I haven't taken any yet, but the question is, there are these blood biopsies that can be done where you can detect little bits of tumor DNA in the blood. It's an incredibly attractive idea that you get a blood test that tells you if you have cancer anywhere in your body. That's a seductive idea. What we need to prove in our kind of standard of proof in the field is, if you detected that cancer early with that new test, would you prevent any morbidity or any mortality from that cancer? Would you live longer? At a population level, people got tested for that, and those studies are just ongoing for these new tests. They're not yet proven. For that reason, they're not covered by insurance because insurance wants that piece of evidence. Some of these tests are getting approved for direct-to-consumer marketing, but they're not yet covered by insurance. So that's a really exciting area. It's possible some of these blood biopsy tests could detect cancers early and would lead to intervening and preventing deaths from those types of cancers. It's also possible that those tests detect cancers that would eventually be detected through other means, and it wouldn't change the outcome at all. So that's what we need to really figure out and prove, and those studies are huge and expensive. Tens of thousands of individuals have to be followed over the years, but those studies are ongoing and there's a lot of promise. Then, if you layer on artificial intelligence, there's a whole lot of additional sides to early detection that will come into clinical practice, I think, in the coming years.
Willy Walker: I want to dive into that AI thing in a moment, just one quick thing on your early detection piece. Breast cancer and breast cancer awareness in my lifetime have gone from something that people didn't really talk about to incredible awareness, and then women getting mammograms on both a very consistent basis and probably earlier in their lives than they typically would. The mortality rate of breast cancer has come down dramatically as both research dollars have gone to it, as well as more awareness of it. There's been massive capital invested in therapeutics and in treatment, and that's what's brought the mortality level down versus the early detection of it and mammograms as being a much bigger reason why the mortality levels have gone down, because we're picking it up earlier.
Dr. Ben Ebert: Yeah, they're both incredibly important. There's clearly an impact of our new therapies on overall mortality from cancer. And if you think about the really transformative effects on mortality from cancer, a lot of it is early detection. Suppose you think about cervical cancer as a major type of cancer that is almost completely eliminated by pap smears, by the HPV vaccines. That is an enormous triumph of early detection. Colonoscopies are incredibly effective at detecting and preventing colon cancers. Mammograms have been great. The PSA has been a challenging test for prostate cancer. I think everybody has a conversation with their physician to sort of decide on how to use PSA. Advances in early detection have been among the biggest impacts in overall mortality from cancer, and then identifying the most powerful carcinogens and decreasing exposure is the other thing that has had a huge impact, and decreasing smoking rates is the highest on that list.
Willy Walker: I've listened to you and read some things as it relates to the promise of AI. I was back at Harvard Business School a couple of weeks ago and they gave us a presentation on how they're teaching AI to MBA students. It was fascinating and I won't take any time on this webcast to talk about that, but it was really an eye-opening. Most important to me was it sort of took the, I don't wanna say theoretically because AI is far more than theoretical, but what it took was the power of AI and it brought it down into a practical use case where everyone in the room could sort of sit there and say, “Wow, that's eye-opening. I now see the impact that could have on how an MBA student dreams up a business plan and then gets the business plan sort of turned into an actual business.” And again, I won't bore you with all the different steps. As it relates to cancer research and what's going on at Dana-Farber, has AI and the promise of AI come to the point where you sat there and said, “We've got a research project that we thought was gonna take five years with X amount of testing and X amount of big computer work. And now all of a sudden, we've been able to use the power and harness AI to make it so that we can condense that period from five years to three years or two years, or to three days,” as you've been using these massive models?
Dr. Ben Ebert: There are specific examples where that is true right now, and then many more where we can see it being true in the future. In the pure research realm, one of the areas that has been a spectacular breakthrough is the structure of proteins. This won the Nobel Prize last year, where an algorithm called AlphaFold can take the string of amino acids that make up a protein. It was completely impossible, at the level of unthinkable, to take that string and then understand the three-dimensional structure of that protein without doing crystal structures, which are very time-consuming and challenging. They take years to complete. But Alpha-fold takes all of that information, every structure that's ever been solved, and can now take that string of amino acids and produce a three-dimensional structure of that protein. At the beginning of that, structural biologists would say, “Oh, no, that prediction's never going to be right.” Now they are good predictions. So, I can have a first-year graduate student in the lab, with no experience in structural biology at all, who is making predicted structures for the proteins and how proteins interact, which is the basis of a lot of the science that we're in and be able to inform that in a way that they would have taken years to get that structure. So that's enormously powerful. That's enormously powerful for drug discovery as well, to be able to test small-molecule possible drugs binding to a protein completely in silico on the computer and not doing thousands of tests or millions of tests of candidate drugs binding to the protein, when that could be done with billions of molecules by the computer. That's an example that's here today; it's operational every day of the week in my lab and all over the Institute and all over the world. That's an unquestionable breakthrough. There are algorithms in clinical practice, reading mammograms, chest CTs, and CAT scans of the lungs, where the AI highlights areas where the radiologist should look. So it doesn't do the job entirely for the radiologists, but it says to look at this lesion really hard and make a judgment and that combination of the AI focusing the attention of the radiology on the most critical area with the expertise of the women is now part of clinical practice and radiology. We are sure that the same will happen in pathology as well. The basis of cancer diagnosis remains a tissue biopsy, putting that on a glass slide, and looking at it by a trained pathologist. But pathologists can benefit enormously from AI algorithms that help predict cancer from normal tissue.
Willy Walker: That AlphaFold technology on the protein sequencing was done by Google, was it not? And that's actually freely accessible by any research institution on the face of the planet. So I'm correct on that, am I not?
Dr. Ben Ebert: You're correct. Absolutely. We use it all the time and we're not paying for it.
Willy Walker: I do find it to be interesting. Every once in a while, we sit around and read newspaper articles that say that big tech is A, too big and B, you can pick whatever social issue you want to go after and say that they're not doing something good in that area. But I would say that, from my understanding of what they've done there, having developed the technology and then turned it over for therapy research has really been quite an incredibly valuable tool that has been shared with the entire world.
Dr. Ben Ebert: Couldn't agree more.
Willy Walker: The next frontier to wrap things up. If we'd had this conversation five years ago, and how far Dana-Farber and cancer research have gone over the last five years, and you project forward for the next five years. Is your assumption that we have moved much, much more rapidly in the next five years on many of the things that your teams are working on right now and that there really is some incredibly breakthrough work that will be done in the five years that could really change the incidence and the impact of cancer on Americans, on the citizens of the world?
Dr. Ben Ebert: I'm an absolute believer that this is the most promising time for cancer research and for new therapeutics for cancer that we've ever had. The fun part of the question is that those most exciting breakthroughs are the least expected. So, that's always exciting—that things come out of nowhere that you least expected. There are so many different types of new therapies that are being worked on, really different modalities that there's enormous promise from so many directions, so much research going on in academic labs and companies that are gonna make these breakthroughs. One huge class that we've been very involved in is undruggable proteins. So there are targets in cancer that were thought to be just hopelessly difficult to ever make a drug against. One of the biggest examples is a protein called KRAS, which is mutated in almost 100 percent of pancreatic cancers, about 50 percent of colon cancers, and about 25 percent of lung cancers. In just recent years, there have been tremendous breakthroughs in the chemistry and being able to make drugs against KRAS. It’s now showing just amazing clinical efficacy. That idea that you can take a problem that was thought to be unsolvable to solve it, and now show clinical benefit is inspiring, particularly in a disease like pancreatic cancer, where it's been one of the most difficult types of cancer to treat. So, it’s those seemingly intractable problems that we then come up with a solution for that I think are most exciting, and then we talked about earlier, advances in early detection and early interception are a massive, massive opportunity. I really hope that in five years, we will be doing new tests to detect cancer. We'll have new algorithms on how to work those up and to intervene, develop therapies on earlier-stage cancers that have not spread or are not as advanced, not as genetically complicated, that have real efficacy and prevent the development of full-blown cancers.
Willy Walker: I am incredibly thankful for, (A) all that you do every day to help us as a nation and a world get more insightful and more capable of dealing with this awful disease that impacts so many people. And (B) I'm also super grateful for you taking an hour to talk about everything that you're doing at Dana-Farber. To anyone who's listened today, I would just say, as someone who, as I said at the top of the call, raises money for Dana-Farber. Cancer research back in 1994, and have done it subsequently from there. Dr. Ebert didn't ask me to say this, but I'm going to do a public service announcement to say that if you feel like being generous to one of the very best cancer research medical institutes in the country, go to DanaFarber.com. Is it EDU or is it COM? I don't even know. That clearly shows everyone this was not a prepared solicitation.
Dr. Ben Ebert: It's a dot org.
Willy Walker: Okay, DanaFarber.org. Or go out and participate in the Pan-Mass Challenge. And if you do participate in The Pan-mass Challenge, I will see you there because it's an incredible event that brings so many people in this community together to support the incredible work at Dana-Farber, as well as allow for people who are either suffering from cancer who have been thankfully cured from cancer or who have unfortunately lost a loved one to cancer. It is an incredible community event that really pulls people together to share both the hope, the excitement, and the grief of what this disease has done to our society. So Ben, thank you so much. I'm super appreciative of all that you do.
Dr. Ben Ebert: Thank you, Willy, and I look forward to seeing you at the Pan-Mass Challenge.
Willy Walker: Yeah, so do I. Thanks. Have a great weekend. Appreciate it. Take care.
