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HEFFNER: I’m Alexander Heffner, your host on The Open Mind. My guest today, Charles Graeber is an award winning science journalist and contributor to myriad publications including the New Yorker, National Geographic, MIT Technology Review and Wired for which he is a contributing editor. His new book, “The Breakthrough: Immunotherapy and the Race to Cure Cancer” probes the treatment that aspires to make cancer chronic instead of fatal and ultimately to beat it forever. Dr. James Gulley, director of medical oncology, chief of immunology at the National Cancer Institute and National Institutes of Health calls “The Breakthrough” a must read. “It not only provides good background and good understanding for patients, but it’s also a wonderful read, easily picked up but not easily put down. I’d recommend it for any patient interested in immunotherapy of cancer.” In Graeber’s own words, “Immunotherapy is the only approach to cancer that could actually curate it: a mutating answer to a mutating problem.”
Welcome my friend. Thank you for being here. Congratulations on the book.
GRAEBER: Thanks. Thanks for having me.
HEFFNER: With the environmental hazards that surround us and of course the biology, which is sometimes predisposing us to cancer, it is not a one-track problem and it never will be a one-track disease. But I wanted to start out for our viewers who watched our episode with Dr Laurie Glimcher of Dana Farber now, formerly of Weill Cornell, what has changed just in the years since we hosted her, which was 2016.
GRAEBER: This is a remarkable field in that the book had to come out at some point but it’s continuing to evolve. It continues to change. And so during that period was really, a moment where concept was proven and drugs that could reach patients were first coming out. Since then, we’ve only expanded the types of cancers that those drugs can reach, and begun to look at thousands of other candidates. There are right now, two of the main type of most familiar types of immunotherapy, which we may get into later called checkpoint inhibitors. We’re now looking at literally some 3,500 different targets and candidates. And we’ve had you know, only within the last week we had an approval for an immunotherapy treatment for triple negative breast cancer. So that changes, there’s a new article in The New England Journal of Medicine every week and those developments, the shoring up of this new concept and the expansion of the circle of responders, people that are actually getting what’s a functional cure for cancers is widening. So that’s been really the big development sense since then and it’s profound. It’s reaching thousands of people.
HEFFNER: You were saying to me off camera to begin, you’ve heard astounding feedback from patients who’ve read the book. And I want to ask you about that, but first I want to give you an opportunity just to lay out your central thesis when it comes to the genesis of immunotherapy and the story here. How did we arrive at immunotherapy as a means to combat cancer?
GRAEBER: Right. This is a fascinating story. The reason I wrote this book and felt that I had to was because when I learned about this breakthrough four and a half years ago, no one else I spoke to knew about it, including most doctors and it yet it seemed to be the most profound thing. It seemed perhaps to be also Nobel worthy, which it ended up being, just this last November. The central thesis is this, it was something that had never really occurred to me before, which is you always know when you’ve got the cold, when a flu or something like that, you have symptoms, you have fever, sniffles, at the very least, you sound like I sound.
GRAEBER: But for the most part, you need to test to know if you have cancer. And the question is why. And it’s because it seems like the immune system is not doing anything about cancer. It doesn’t seem to be waging any sort of battle. The immune system’s really good at recognizing what’s not supposed to be in our bodies, what is not us and getting rid of it. But with cancer, it wasn’t doing that. And for 130 years at the very least, the question has been why and most of science, most scientists had accepted as fact that the immune system couldn’t recognize cancer. It was too similar to us. Cancer is us, mutated, and that there was no way we were going to end up curing cancer with the immune system and those that thought otherwise, were considered really fringe scientists.
And we have discovered that that’s absolutely not true. That in fact cancer has what I call a secret handshake that it uses with the immune system, basically saying, hey, I’m okay. I’m a regular body cell. It’s a handshake that, for instance, the developing fetus uses because the fetus is also different than the, than the mother’s immune system. And that handshake shuts down or down-regulates immune response. It keeps the immune system from killing cancer the way it does the cold. We can now block that secret handshake and cure a subset of cancers. And perhaps more importantly, we now know it’s real. We know immunotherapy is possible. We know there are these tricks that cancer has evolved to turn off the immune system. And now we know where to look for the cure. I compare it to having lost your car keys, you know, the cure for cancer I know it’s much more profound, but you’ve lost your car keys somewhere over the course of the last 24 hours. They could be anywhere. And this was our search for the cure for cancer. We now know that the, that we lost our keys in this one room because it’s only the immune system really that is nimble enough, flexible enough, adaptive enough to be able to recognize and track down and kill cancer in all of its forms and including what we now know as remissions. So that’s the central thesis.
HEFFNER: Is this the consensus now? Is everyone on board?
GRAEBER: Oh yeah. There really aren’t any doubters any longer. However, there still are a lot of people that don’t really know about it. They don’t understand, for instance, that this is fundamentally different than everything that’s come before; the cut poison and burn approaches that always attack the tumor, attack cancer.
Cancer is the monster we go after that. We poisoned essentially the body hoping that we kill cancer before we kill ourselves. And this is different. This actually unleashes the immune system to do the job that it has been evolving for 500 million years to do. And that fundamental difference, if you don’t know about it, if your oncologist doesn’t know about it, if you’re a medical center that’s not completely up on it, if you’ve received a lung cancer diagnosis and you’re still under the impression as some 50 to 60 percent of Americans are, that once you get that diagnosis, the best thing to do is to just go home and get your affairs in order and not seek further treatment because there’s really nothing that can be done. That’s no longer true. And so if you don’t know that things have changed and you don’t understand the fundamental difference between this approach and the old approaches, there’s no way you’re going to have access to it.
HEFFNER: And are you suggesting that it’s not been standardized because of a lack of resources in some communities or a lack of expertise in some communities that don’t possess the knowledge or the capacity to perform immunotherapies?
GRAEBER: Look, the a diagnosis of cancer is such a devastating event and the world, you know, really goes away or narrows down to that one, one moment. And people tend to go to ground. They seek community; they seek the comfort of familiars. And sometimes that is a local doctor who really perhaps doesn’t fully understand all the changes that have happened. And sometimes it’s a hospital that really has a chemotherapy based model, billing model, treatment model, everything else model, and also would be staffed by doctors who very rightly, were trained that immunotherapy doesn’t work, because it didn’t until very, very recently. We cured cancer in mice thousands of times, but it didn’t work consistently in people, and so in those cases which are more common than you’d think you do end up with being, being sent home, being told there no other options. And I start my book with an example of a patient named Jeff Schwartz who was told exactly that: stage four kidney cancer, was essentially sent home and only because he happened to ask somebody else who told him, you should try that to get into this clinical trial. And clinical trials are where a lot of the good stuff, the new, there’s so much new stuff coming out that there isn’t, there isn’t room. So they’re being tried everywhere. You need to get into one of those. And because he had done that, he lived, and after I published that, you know, he was Chapter One, he’s, he wanted to talk to me because of that, to get that word out. I’m hearing from all sorts of patients by email and in person who say, I’m Jeff Schwartz too. They told me the same thing. I did the same thing.
And in the book, Jeff tells a friend, or really an acquaintance that she who in a similar situation that she should do the same thing. She does this, it happens to work for her as well, and she wants to be done with cancer and she wants to leave it all behind her and he says, no, you have to pass this information on. You’ve, you’ve received it, you need to spread this word. So that’s a big message of “The Breakthrough” is trying to do that same work.
HEFFNER: Sure. Is a doctor or a hospital’s advice dependent upon the variable of how advanced your cancer is, so in his case, stage four? Is immunotherapy viewed as a potential cure or antidote for cancers that are that advanced, is that part of the conflict here between the recommendations of the medical community and the innovation that you’re describing?
GRAEBER: It’s interesting … the short answer is no. The stage four cancer, stage one cancer, it doesn’t really matter. Stage four cancer, you’ve definitely noticed it. Stage four cancer, you may have already gone through all the other options, because we can treat about half of the cancers that are diagnosed every year. That still leaves some 600,000 people in the United States alone who die of the disease. So for those patients, usually they would be of course stage four and those were the first patients for whom immunotherapy was approved by the FDA because those are the first that it was tried on. It’s really a matter of approvals, but it really doesn’t matter what stage the cancer is caught at. If it responds, it responds. And it often responds profoundly. So stage four cancers that, those are cancers that have metastasized, and moved throughout the body, they will go away if they, just they’re melted away, is the description often, if that patient is responsive to immunotherapies, that’s, we’re probably most familiar with Jimmy Carter who responded in just such a way. But so it really doesn’t even at the stage …
GRAEBER: If, and it’s a really important important note.
HEFFNER: Right. So, so far, what percent of immunotherapy is in the clinical stage versus in the practice of hospitals and doctors?
GRAEBER: That’s a great question. There’s so much, in the preclinical pipeline, so many drugs being developed that, so few drugs being used that it’s really a very, very small percentage.
HEFFNER: In other words, my question is, what percent is accessible if you’re in a major city anywhere in the country?
GRAEBER: Oh, right. Immunotherapy is not the first go-to for most cancers at this point. However, it’s becoming increasingly frontline for lung cancer, certain types of small cell lung cancers, it’s certain childhood leukemias and melanomas, it really, right now the way the approvals work is, it’s they’re very specific for either a genetic mutation that’s a new type of designation, but they’re very specific for a phase of cancer and whether or not you’ve tried everything else and it didn’t work. But that’s broadening. I mean, I compare this in the book; or rather the scientists and researchers I spoke to compare this to our penicillin moment with cancer, which is to say penicillin was a big deal. Penicillin saved millions of lives and it saved hundreds of thousands of people right away. That was an overnight success. But the real breakthrough of penicillin was the concept of the antibiotic. Very few people are taking, you know, going to their drive-through pharmacy and getting penicillin. They’re getting a host of other, you know, doxycyclin or something else.
And that has had a profound effect on humanity. And that’s where we’re at right now with cancer immunotherapy. We now for the first time know it exists, know it’s real, and we’re expanding the circle of responders and types of cancer that can respond.
HEFFNER: So it was built as a last resort, but often the things that we think of as being built for the last resort are the ones that arrive at the solution, right, I mean that, we’ve gone from layers of treatment to thinking about immunotherapy as have you tried X, Y, Z,
HEFFNER: Z is now potentially the beginning of curing cancer as opposed to the last stage of a patient’s experience
GRAEBER: Oh, absolutely. We’re talking now about cancer vaccines, which is a science fiction sounding thing,
GRAEBER: It’s very personalized.
HEFFNER: It’s a real thing. Tell us about that. But so how is that connected to the immunology?
GRAEBER: Right, so, you know, the, because we never considered or most of science didn’t consider that the immune system was involved with cancer at all. That the immune system couldn’t see cancer, couldn’t kill cancer vaccines, which we use to introduce our bodies, our immune systems to diseases, weakened forms of diseases. It’s sort of like, it’s like giving a, well, I don’t want to use a kitten with a wounded bird type of thing to teach it to be a hunter, but it’s, it’s almost like that. Or like distributing wanted posters. This is what the bad guy’s going to look like. These are little fragments, distinct fragments of this bad guy disease. We build up a clone army of, of cells specialized against that disease. And then if that disease does come, we’re ready for it.
That never worked with cancer. But now that we understand that it could work with cancer, we can actually take the steps to take someone’s tumor, or understand what exactly, you know, the, the tumor cell are cells, they, they look different, which is to say that they’re sort of studded with proteins like a Christmas ham. And those proteins are distinct to the type of cell. We can recognize our proteins from foreign proteins. If we could find the proteins that are unique to your cancer that are not found on normal body cells, we can create a vaccine against that cancer. And now that we also realize that, that cancer is using those secret handshakes or putting the brakes on the immune system, we take the brakes off, block the secret handshakes and introduce the vaccine, and it should work as well as a measles vaccine.
HEFFNER: So let me just understand this, so the immunotherapies are cultivated to create, can be cultivated in time to create the vaccine. Is that?
GRAEBER: That’s right. Immunotherapy really, it covers a broad range of treatments and they’re really anything that addresses the immune system and not the tumor, specifically. So there are, there are various types. They are types of immunotherapies that take the brakes off of the immune system that block those secret handshakes. There types of immunotherapies where we take, you know, the killer cells, the t cell, and we make specialized versions of those that are designed just to see your cancer,
GRAEBER: We build them up in a lab and they become these hunter killer Robocop cells. And then there the vaccines, there are types of immunotherapies that are able to link an immune cell and they bind on one side to an immune cell and on the other side to a cancer cell.
And so they sort of force them together, sort of a, you know, like a forced dance. And then in that proximity you’ve got a greater chance of killing them. There’s this wide range of, of treatments all called immunotherapy.
HEFFNER: Is it conceivable that in the next decade we could have cancer vaccines and booster shots?
GRAEBER: I want to be careful because everyone I speak to is cautious. They are, not cautious about using the c word about using cure as, as a, as a word that there’s a word out there. Preventative cancer vaccines are sort of a different matter because you don’t really know what cancer’s always going to look like. But there are certain hallmarks of cancer. There are certain red flags that some cancers have that we can prevent against in that respect. Or we can do things, you know, the vaccine against HPV, that’s a different thing. The virus, HPV virus gives you a predisposition and an increased chance of developing a certain types of cancer.
GRAEBER: And the way I think of it, cancer is like rolling the dice. You’re constantly replenishing the cells in your body. You, we run through a full body’s weight of cells every year. That’s why your apartment is so dusty, perhaps, or mine is, it’s, we get rid of that many cells,
GRAEBER: We replenish them constantly. And as you do that, each time you make a new cell, a daughter cell, there’s a chance you do it wrong. It’s sort of a messier process than you’d think. Partially because we’re evolved, messiness is baked into us and the dice are rolled. It’s incredibly improbable that you’re going to end up with a cell that’s a mistake that also happens to work and be greedy and can get its own blood supply and become cancer. But it’s incredibly improbable. But the dice rolled over and over and over again.
GRAEBER: Things like genetic predispositions or vaccines, they basically take half of the dice and already stick them on here for you trying to turn roll six. They’re already all sixes, now you’re only rolling half of the number of dice. So we will increasingly now that we really understand how cancer works so much better, we can actually; we can work to prevent that too. But the real thrust I think is in the personalized, personalized answers to cancer, personalized vaccines, personalized treatments, because your unique cancer, your unique. I say roll of the dice, but it, the dice have to have a lot more sides than we’re familiar with. Your cancer, whatever it looks like, whatever it’s specific traits are, it’s specific proteins, fingerprint is, that’s what we will be able to develop and, and the future of AI and, and our computing capacity and that technology really factors in. So that’s why it’s a science fiction thing that’s actually, it’s very difficult to do, time consuming and expensive, but there are clinical trials going on right now with it and we should expect those results I would say within the year for the first ones.
HEFFNER: You analogize this to a penicillin moment.
GRAEBER: Uh huh.
HEFFNER: So is the idea of these scientists ultimately that we will safeguard our cells and our bodies through the vaccines from birth, or that these immunotherapies will be available like the multiplicity of antibiotics that you described, penicillin being the founding invention and then all the others that are tailored to particular symptoms. Which of those models do the scientists studying say is more likely to materialize.
GRAEBER: Well it’s, it’s really in theory, both are possible. What’s more likely is that you prevent the disease or that rather that you treat the disease when you have it, but you don’t think of it in the same way that we think of cancer right now.
HEFFNER: You think of it like strep throat.
GRAEBER: Just think of it like something you can treat treat.
GRAEBER: Because you, because you can, and those technologies just, there’s a broad array of cancers that respond immediately to taking the brakes off. So finding more brakes, finding more discovering what makes some cancers respond in what makes others not respond. Combinations. So you’re still going to probably there, there won’t be a magic bullet.
There won’t be one single silver bullet that kills all cancer and prevent, because cancer is a host of diseases. We say it’s 200 some diseases, but really it’s, it’s an infinite
HEFFNER: So, let’s roll our sleeves up and getting there.
HEFFNER: When we had Laurie Glimcher or Maria Freire here to discuss the same subject, it was the expense, always the funds to build the innovation to build these innovative solutions. Is that where we are today or is it more complex in terms of answering this question of how in 10 years we have those available treatments and cancer is truly chronic if not defeatable entirely?
GRAEBER: It’s a great question and something that needs to be addressed now. You can’t simply pour money on it and know that you’ll, you’ll have the solution. We don’t have all the answers. We don’t fully understand the immune system.
We’ve really only just begun to realize that, ah we should be looking over there. We should be studying the immune system in terms of cancer treatment. We now understand how cancer blocks the immune system, the difference between 2016 and 2019 – light years of understanding. There were aspects that we thought were going to perhaps be part of the answer that have proven not to work out so far. There are other aspects that have other factors, thousands of others that have shown up and given us greater promise and we’ve doubled the number of responders, but the money is important. Every single one of the breakthrough elements that I talk about in the book came at some point in some way through the National Institutes of Health, National Cancer Institute. All that fundamental research, basic research is absolutely essential. And right now we’ve just, the newest budget proposal slashes that budget by 12 to 15 percent for the NIH and the NCI respectively.
And if you, I can tell you what’s definite. I mean it’s difficult to speculate on the future.
GRAEBER: That most people feel that we will actually arrive there and arrive there within that timeframe. It’s not one of those things that’s forever on the horizon we actually are closing in. But if we don’t fund the work and we don’t look for the answer, we definitely won’t find it.
HEFFNER: Are there factors besides funding, how about the deployment of that funding? How about the restrictions imposed on the funding? How about the mental acumen and personalities that are in the room. What are the other factors besides the funding itself?
GRAEBER: The immune system itself, the immune system is,
HEFFNER: So not those other things, the deployment of the money or the efficiencies or the regulation.
GRAEBER: I think the efficiencies are growing. There were blocks between, you know, that you’ve got every pharmaceutical company in the world now they’re either in immunotherapy or they want to be, there’s only two types of pharmaceutical companies right now. They’re pouring enormous amounts of money into this. A lot of that money unfortunately is going towards making slightly different versions, you could say knock off versions, but it’s slightly different versions of the same effective immunotherapy that’s working right now. That PD one anti PD, one anti PDL one we’re making and maybe a dozen of those being made, that redundancy is a waste of money from the standpoint of pure research. It’s because, it’s like everyone making their own version of cola because we now know, well that definitely works and whatever other treatment you make, you’re going to want to pair it with that. So if you have intellectual property over here that wasn’t working well, maybe you suddenly realize, ah, it wasn’t working well because we had cancer was putting the brakes on the immune system the whole time, we need our own version of that. That redundancy is a waste. There are also other aspects of intellectual property that that had been a concern and our inability to share information. We would like, we’d love to believe that everybody involved in cancer research and everyone treating cancer is constantly updated on exactly what the front edge is …and that’s
HEFFNER: There’s no central storage house.
GRAEBER: There’s not one central storage house. It’s getting much better. Places like the Parker Institute, CRI, a number of other institutes are actually pouring huge amounts of money into forcing people together, getting rid of the incentives for hoarding information. But that’s still; it’s still a problem.
HEFFNER: We have a minute left. Charles, tell me the most poignant story you heard from a reader in your numerous book talks over these last months.
GRAEBER: Oh Gosh;
HEFFNER: Or a sense of the spectrum…
GRAEBER: Just a recent one, I got yesterday, was someone who wrote saying that they had been a stage four diagnosed, were not going to seek further treatment that seemed like the wrong thing to do. They’d heard me speak. And they didn’t, they didn’t even want to go. They were brought by a friend and they realized that that wasn’t the right way. So the most hopeful thing I’ve heard, the most exciting and gratifying thing, was really that it restored hope to people and justified hope. And so they’re actually asking for better answers because if you don’t feel entitled to ask good questions, you don’t feel empowered to ask questions of your doctor if you don’t understand the field, cancer is complicated, immunotherapy is complicated. I tried to write it so that everyone can understand it. And hearing that that is working and making a difference in human lives, that’s been enormously gratifying.
HEFFNER: Your message to the viewers, no matter where you live geographically, no matter where you’re from, seek out this advice and you can hopefully find, if you need it, immunotherapy near you.
GRAEBER: That’s right. Make sure that you’re at a cancer center, a comprehensive cancer center, a university cancer center, somewhere where they’re not afraid to go outside of outside of their old system of billing, that they have answers for you and don’t be afraid to ask for a second opinion.
HEFFNER: Thank you Charles.
GRAEBER: Thank you, sir
HEFFNER: And thanks to you in the audience. I hope you join us again next time for thoughtful excursion into the world of ideas. Until then, please keep an open mind visit The Open Mind website at Thirteen.org/OpenMind to view this program online or to access over 1,500 other interviews and do check us out on Twitter and Facebook @OpenMindTV for updates on future programming.