Watch Episode Here
Listen to Episode Here
Show Notes
This is a ~1 hour conversation of Aastha Jain Simes (https://www.livelongerworld.com/,https://www.linkedin.com/in/aasthajs) and Azra Raza on her unique and passionate journey in oncology and her ideas for cancer therapy.
Azra is an amazing person, clinician, and scientist; see more of her work at:
Columbia web page: https://www.cancer.columbia.edu/profile/azra-raza-md
Personal site with poetry and much more: https://azraraza.com/video-category/poetry-and-ghalib/
Her youtube channel: https://www.youtube.com/channel/UC3VoqZUJz-bQMXnRZi7SjbQ
Her TEDtalk: https://www.youtube.com/watch?v=07rgtBzN4Qo
CHAPTERS:
(00:00) Cancer, stress, cell fusion
(11:13) Immortality, fusion, giant cells
(19:49) Personalized stent, global equity
(29:23) Stent monitoring and suffering
(39:05) Limited progress, first-cell paradigm
(54:54) Navigating a cancer diagnosis
PRODUCED BY:
SOCIAL LINKS:
Podcast Website: https://thoughtforms-life.aipodcast.ing
YouTube: https://www.youtube.com/channel/UC3pVafx6EZqXVI2V_Efu2uw
Apple Podcasts: https://podcasts.apple.com/us/podcast/thoughtforms-life/id1805908099
Spotify: https://open.spotify.com/show/7JCmtoeH53neYyZeOZ6ym5
Twitter: https://x.com/drmichaellevin
Blog: https://thoughtforms.life
The Levin Lab: https://drmichaellevin.org
Transcript
This transcript is automatically generated; we strive for accuracy, but errors in wording or speaker identification may occur. Please verify key details when needed.
[00:00] Michael Levin: I'm very happy that you two can meet each other. I think that Azra is a very inspirational person, and I want to have a chance to hear her thoughts on cancer. Ideally, we can talk about some of her other interests as well. We'll spend some time on that.
[00:16] Aastha Jain Simes: You definitely have a broad range of interests with literature and poetry and philosophy, so that's fascinating.
[00:23] Michael Levin: Yeah.
[00:24] Aastha Jain Simes: I'm excited to meet you, Dr. Raza, because I think your work is laudable: you actually treat patients with cancer. You also do research on cancer. You've authored an amazing book called "The First Cell." But your story with cancer is also deeply personal because you lost your husband to it, which is devastating. I want to start with a basic question, which I think most people take for granted. What, in your opinion, is cancer?
[01:00] Azra Raza: Thank you for having me, both of you. It's an honor to be on your podcast. And thank you for that kind introduction. Cancer, interestingly, is when some part of our body decides to rebel. The body is a confederacy of cells. It's the rebellion of oneself against the entire confederacy to simply be immortalized for itself. That is what we call cancer.
[01:44] Aastha Jain Simes: What do you think causes cancer? I know there are many different theories, many different causes of it.
[01:55] Azra Raza: I would say stress, because when you start looking at all cancers, whether they're liquid or solid, in lymphoid tissue or brain tissue, there is a convergent evolution in that some things are common to every cancer. And that's how we define it. The two things common to every cancer are, number one, that a cancer cell can ignore growth inhibitory signals. It can continue to proliferate without paying any attention to what's trying to stop it. And number two, a cancer cell stops maturing. An immature cell that proliferates or divides forever is cancer. The question is, what causes it? Because it's starting in one cell. People tend to think that there must be something wrong with the cell. But it could also be something wrong with the environment, the soil in which the seed is growing. Something goes wrong, which is forcing this cell to misbehave. What could that be? That's what I'm calling stress. Stress of something like an infection in the liver, for example, with hepatitis B virus. The infection starts; the virus starts killing lots of cells. Immediately, the body responds with an inflammatory reaction. Immune cells start coming to that site to try and remove the debris, to eat up the dying cells. All this causes a lot of stress. Cells are now getting a fight-or-flight signal: either you're going to develop a strategy to survive, or you're going to die. Cells don't have time to think this out. They have to react instantly, or they're going to die. One of the strategies they develop under this stress is fusion. Two cells will fuse. That doubles their DNA. That doubles all their internal armament that they need to withstand the stress. This fusion is a normal response to stress. It happens, for example, in the liver: two liver cells will fuse, and now they can fight better. But once in a blue moon, a liver cell can fuse with a blood cell that had come to remove it or to take away the debris of this dying cell. When that happens, that heterotropic fusion between a tissue cell and a blood cell could cause all the problems. That's where it can begin. So then what causes cancer? Is it the seed? Is it the soil? Is it everything? Is it the immune system? I'm saying that it's all of this. It is an organic disease. It's a disease where the whole body is involved because as soon as you involve the immune system, the blood, it's all over. I'd like to continue our conversation as we go forward, discussing this particular aspect of response to stress. Everyone knows that any organ which has chronic inflammation—whether the gut, the stomach, the liver, or the uterus—anywhere there is chronic inflammation, cancer is more likely to arise. And it is because of this stress-caused fusion.
[05:37] Aastha Jain Simes: Do you see this fusion in all types of cancer?
[05:42] Azra Raza: Every single liquid or solid cancer that has been examined has found these kinds of hybrid cells, meaning the same cell expressing a blood marker and a tissue marker. We call it a cancer hybrid cell, CHC. For example, 11 years ago I started to filter the blood of my patients, filter them in a device so that the blood cells will go through, but anything larger than blood cells will get trapped on the filter. I was trying to find the first leukemia cell because I study and treat pre-leukemia and follow these patients as they develop acute leukemia. I did find leukemia cells on the filters, which are larger than normal cells. That was my idea: that a coffee filter-like technology should work. What was shocking was that I started to find these giant cells. If a blood cell is 15 microns and a blast is 20 microns, these are 100, 200, 300 micron large cells with lots of nuclei inside. This polyploid giant cancer cell, PGCC, led us to start looking everywhere about what's happening in other cancers. We were the first to find these in liquid cancers through filtration of blood, which I was doing for other reasons. Solid cancers have been studied through liquid biopsies. If there's a tumor in the pancreas, lungs, or colon, these cells can be found in the blood. Others haven't found it because they're so rare in the primary tumor. We see them once in a while when reviewing microscopic sections of tumors. Pathologists often note a very large cell and say this is a dying cell, or it's a macrophage, because they're so rare. Now that we've developed technology to look at gazillions of cells circulating in the blood through liquid biopsies and filtration technology, we have started to find these. My group has done filtration to find these in hundreds of leukemia patients. Then we looked at single-cell RNA-seq data from hundreds of colon and breast cancer patients and showed cancer hybrid cells in every single tumor. My company, First Cell Therapeutics, is trying to develop a bispecific antibody to target and take out these cells because the two antigens make it unique. A blood antigen and a tissue antigen are only present on such a hybrid cell. No other cell in the body should have these two, so we can take it out with the bispecific antibody. Through the company, we have now studied lots of different types of solid cancers — thyroid, uterus, breast, liver, everything that comes through — and we are finding these everywhere. They're rare, but they're there.
[08:57] Aastha Jain Simes: Is it always the case that when these stressed cells fuse with another type of cell it ends up being cancerous, or in some cases you might not end up with cancer.
[09:15] Azra Raza: When we look at single-cell RNA-seq data, the algorithm simply says any cell that's expressing these two markers tell us if they're there or not. Then the way we look at it is we look at the actual tumor, then the normal area surrounding the tumor. We look at cells there, and then cells from the same organ of someone completely normal who doesn't have cancer at all. So you have two controls. One is a healthy person, and the other is normal surrounding tissue around the tumor. And then we have the tumor cells. The hybrid cells are more in number within the malignant cancers, but occasionally we have seen it in the surrounding area and occasionally in healthy people. In healthy individuals, it's usually because of some infection they're having. In surrounding tissue, they're there, but very, very much fewer even than in the malignant area, except we looked at their gene expression profile because we're looking at transcriptomics data on a single-cell basis. So we look to see is there a difference between hybrid cells found in the malignant area versus normal areas? And it's an entirely different milieu. It's shockingly different. Number one, you have tons of telomerase being expressed in the malignant hybrid cells, and zero in the hybrid cells found in normal areas. Number two, the transcriptomic profile, interestingly, is totally inflammatory in the malignant hybrid cells, but not in the normal. So we can occasionally find these cells in normals, but they're very different.
[11:13] Aastha Jain Simes: Going back to something we were talking about earlier, which is what is cancer, and it's some cells rebelling against the other collective of cells, because of this stress-induced environment, why do the cells choose to respond in this manner of just being immortal and proliferating and constantly growing versus normal cells, they're not immortal? Why do you think that's the case?
[11:40] Azra Raza: That basically is asking the question, why don't normal cells become immortal? Or how do normal cells die that cancer cells have overcome that step? There may be 1,000 different strategies that are being followed by these cells. I'm just picking up on one, which is fusion. I don't know how many others there are that are successful and working all the time. That's why cancer is rare. Science is forever a self-correcting enterprise. We never say anything dogmatically because we know tomorrow we may be proved wrong and we have to be prepared to accept it because we are not religious leaders, we are scientists. The difference between science and religion Carl Sagan described best. He said that religion is all about preserving the exact text that came, even if it was thousands of years ago. You have to preserve everything. Science is constantly a changing expedition. You have to keep correcting. I feel that there are tons of strategies cells follow under stress. One of them seems to be present here. Why am I so interested in it? Independent investigators have been noticing that when you remove every microscopic sign of a solid cancer, recurrence or relapse begins first with the appearance of these giant cells. People have shown in thousands of cases that if you remove someone's lung cancer, and after all the treatment—surgery followed by radiation and chemo—you now, post-therapy, perform a liquid biopsy. If you find a single giant cell after this treatment, relapse is imminent. If you don't find any giant cells, there's a straight line of survival followed for several years now. These studies have been going on for over 10 years, but no one wants to think about them because everyone's so obsessed with genetics. Genetics—one gene, one magic bullet is going to cure cancer. We can't think beyond that. Biology has taken a backseat to the microbiologists.
[14:13] Aastha Jain Simes: So in terms of being diagnostic, you could, in theory, just test whether there are some of these large cells and figure out a patient's risk for relapse, right?
[14:24] Azra Raza: I think we have done better than that. Henry Ford in 1909 said, "If I had asked my customers what they want, they would have said a faster horse. I gave them an automobile instead." So what I'm going to show you as our solution to this problem is a jet plane in the days of horse carriages. We are so far ahead of the game. This is the cure for cancer I'm holding in my hand. It's a syringe and a needle. And the cure for cancer is not in the syringe some medication. It is in the needle. What is in the needle? In the needle is a coronary stent. Stents that are put into open heart vessels. Millions of people are walking around with these coronary stents. And stents are put in the bile duct, in kidneys, in the heart, everywhere stents can be put. Well, we have a stent inside this needle, which has electronic circuitry that is shown here. I've spread it out. This is the work of biomedical engineers at Columbia University, Sam Sia and Ken Shepherd. I've been working with them for 10 years on this device. The electronics is such that we can inject this stent—it's an implantable device—into one of the large blood vessels in your arm. And this stent will go and sit there forever. It can stay from birth to death, we think. Then it creates an electrical current so anything that passes through will cause impedance. And by picking up electrochemical impedance spectroscopy, you can tell a small cell from a large cell. So the first thing we can do is any time a cell larger than an expected normal blood cell passes through this stent in your arm, it's going to immediately send a signal. There is a chip that is built in here that will record it, and it's going to the data cloud. It's being recorded and continuously AI monitored. So the idea is here that we can program the stent, Astha, so that if it sees a cell bigger than this size, it will be electrocuted.
[17:06] Aastha Jain Simes: I have so many questions. Mike, this ties into your work with bioelectrics, because you've been looking at the bioelectrics of cancer. I'm curious, what are your thoughts on this?
[17:18] Michael Levin: I love it. It's super creative and interesting. Just one question I had on the basics of it. What do you think for this fusion? Do you think that the ability to do this or the tendency for cells to do this under stress is an innovation of multicellular body plans, or do you think this is something that unicellular organisms would do under stress anyway? How ancient do you think this is?
[17:46] Azra Raza: We see this all the time. Look in fungi, you see unicellular fungi that actually start sticking together and forming groups and colonies. They make literally termite-like branches out like that. So no, it is common to our most primitive life forms. What do you think, Michael?
[18:14] Michael Levin: As we've discussed before, thinking about how the system responds to stress is critical, absolutely critical. Your focus outside of the genetic causes is, again, super important. What we study is the disconnection of cells by stress and a number of other mechanisms that induce them to disconnect from the rest of the tissue. At that point, my story about this is that the larger group cell collectives can have very large cognitive light cones, meaning that their goals are large. They build and maintain organs and all this. And then, as stress causes them progressively to disconnect electrically, all of their goal states shrink to very small things. Survival, migration, proliferation, ancient unicellular things. And so it's very interesting to me that during that process, as they are leaving the large collective of which they are part. I've been part of this, it was great, but now life is not so good. The stress — I'm leaving this organization, I'm out of here. Yet they're interested in fusing with something else on their scale. They'll merge with something else and see how life is that way.
[19:49] Azra Raza: I wanted to add to it that I think of it like a somatic cell pregnancy. Because that literally when these two weird cells, completely different lineages fuse their genome, what emerges is something that has thrown its program back, its differentiation program, back to the zygote level. And that's where it gets stuck. So it's now immortal because it has the zygotic ability to continue to form from one cell a huge adult eventually. But on the other hand, it has become immortal because it has continuous power to proliferate. It's so interesting to think about what electronics are playing, what role here. That's why, Michael, I've always been interested in trying to develop a common program with you, because I think that if we combine our strengths and have an implantable device, the biomedical engineers Sam Sia and Ken Shepherd have named it the stentinel. I love that name. It's a stent and sentinel. It can detect biomarkers like pieces of protein, RNA, DNA by this very tiny molecular signaling that can be detected. This is all being done in vitro already so that when we get the device inserted, all this is ready. The last thing I want to say is that, Michael, you know that I started my career in this country when I was 24. I had come here and wanted to start my residency in medicine. I arrived here in January, and my residency wasn't going to begin until July. So I panicked. I thought, in these six months, somebody is going to cure cancer, and I'm going to be left behind. So I showed up at Roswell Park Cancer Center, where I was in Buffalo, and said, please take me, make me do anything. I'm ready to start. They put me in. They had a fellowship available for six months. They gave me pediatric oncology. So I began in pediatric oncology. But within three months, they sent me off, not because I was doing something wrong, but because I was crying the whole time. I can't sit on babies and two-year-olds and push bone marrow needles into them and spinal taps and all the horrible things we used to do to them. When I got to the adult service as a result of these crying fits, they sent me off. The first thing I noticed was that the same three drugs we were using successfully to cure acute lymphoblastic leukemia in children had no effect in adults.
[22:49] Azra Raza: The disease was exactly the same. So what was different? Obviously, the rest of the cells in a two-year-old are nascent virgin cells, whereas in a 70-year-old, every other cell in the body has received 1,000 cuts. So it's going to metabolize the same drug very differently than a two-year-old's body. We could even have the best curative treatments, but they won't work. They'll work in one and not in another situation. Secondly, I realized that even if a little version of ourselves cannot serve as a model for the adult self, then how are we using animal models to try and develop drugs or try to understand cancer when that animal does not get that cancer spontaneously? We produce something in it, we immunocompromise the mouse, and then give it some cancer cells and claim, oh, it has developed lung cancer. This occurred to me when I was in my 20s, that you can't use any model to study. You have to use human cells. And also, what Norbert Wiener, the god of cybernetics at Harvard, said, "the best model for a cat is another cat, preferably the same one." Which means the only way to really look for a cure is to personalize. What we are finding in you, Asta, or in Michael may not work for me because my lifestyle is completely different than yours. I eat masalas and chicken tikkas all the time. You are surviving on hot dogs and hamburgers. The idea is that in order to personalize, you have to go to the individual. But cancer is a silent killer. It doesn't announce its appearance. It can be stage four before you detect it. No age is immune from cancer. So then, ultimately, you need a technology which can start at birth, continue till death, and continuously monitor for wellness-to-illness transition. That's what you need. This is so logical. But I'm treated as the pariah in the field for saying this. I'm the one who's treated as if I've written the satanic verses of medicine.
[25:52] Aastha Jain Simes: It makes a lot of sense to me. If you can monitor it from the start and then nip it in the bud just when it's beginning to form, that's obviously the best way instead of letting it progress. Do you think the sentinel could be applied universally, or would that also have to be personalized in many ways?
[26:19] Azra Raza: The same stent, the same coronary stent, works for everyone. Aastha, I come from Pakistan. The entire budget of Pakistan, which is a country of 230 million people, is $34 billion. Last year in America, phase one clinical trials of cancer, 86.7% of which completely bombed, cost $60 billion. $60 billion thrown away in phase one trials. Why? Because the preclinical testing platforms were all these artificial models on the basis of which drugs were assessed as extremely powerful and curative and brought to the bedside. We haven't learned that 95% of these things are failing today. The 5% that succeed are not curative. For a fraction of 20% of patients, they can improve survival. I'm talking about advanced cancer. Those that appear in early stage one or two can still be treated with those paleolithic therapies of slash, poison, and burn. Nobody should be living through any of that caveman stuff. We should have patient-centric, compassionate solutions. That only means revolutionize early detection. That's where we should be focusing. Instead, we constantly focus on the last cell and developing more and more toxic, more and more elaborate therapies that can be given to 10 patients in America, and the rest of the world can go to hell. This is the way to democratize medicine. This is the way to take it to populations of underserved communities in this country who have no access to screening measures and personalized treatments. I think this is the only way.
[28:18] Michael Levin: The personalized aspect is really critical. We're starting to look at. We make these anthrobots out of specific patient samples. We're starting to look at how these things interact with cancer cells, for example, and how they're going to behave under stress, how they're going to interact. We can think about some very specific things based on what you were saying today. These kinds of personalized models are going to be very important.
[28:50] Azra Raza: What Aastha asked is, is this stent going to work for everyone, or do you have to personalize it? I'm saying you don't have to personalize a stent, but the data that you collect and how you're going to deal with the problem it poses has to be personalized. That's where, Michael, what you're saying is spot on. We need the help of people like you who are in a completely different discipline, who can think about it very differently than I am, or the biomedical engineers are.
[29:23] Michael Levin: Yeah, we all...
[29:25] Aastha Jain Simes: Please go ahead, Mike. I was going to ask on the sentinel point. I think it would be amazing for people if you could elaborate on how it would work in terms of detection. I know you mentioned the electrical current of the large cell versus small cell would be different, but a little more detail on how it would work would be amazing.
[29:47] Azra Raza: I'm not a biomedical engineer, so I don't want to go into detail, but roughly speaking, to put it in terms laypeople can understand, if there is an electrical field that is created, then anything passing through that electrical field will cause a disturbance of the field. If the thing passing through is small, the signal it gives is small. If it's large, it's going to be a large signal. That's all we are picking up. That's about the size of the cell. Let's say that I put this stent in my arm, and it detects a first cell. It will relay the signal to the chip that is on it, and that signal will be read and relayed immediately to the cloud where the data are gathered and analyzed by AI. A warning is sent to my iPhone through an app to say some trouble is brewing. Then you go in and look — it's detecting. This little stent can scrutinize, monitor, and analyze the entire five liters of blood in an adult every 18 days. How different is that than doing a periodic 10 ccs of blood for detecting some biomarker once a year? This thing, every 18 days, is going through all your entire five liters of blood. So let's say it detects that there are giant cells. What does it mean for me as a patient now? What should I do? Should I go in and ask for a bone marrow transplant? What should be done with this cell? I don't think we should rely on any one parameter to make these kinds of decisions. I think a stage is set for this first cell to arise. If we detect the first cell, we should immediately think, what is the stage that is being set? Is there inflammation going on? How can we detect these markers? This is why we go to biomarker detection. I realized the importance of the environment, the microenvironment, way back 40-plus years ago. I started to save samples on my patients. Not just blood, serum, plasma, saliva, bone marrow aspirate, but I started freezing bone marrow biopsies in DMSO, which are completely intact geographically; everything is in place. It's not like you are suctioning something and mixing up oranges and apples. That is all preserved.
[32:40] Azra Raza: I have all these samples going back to 1984: 60,000 samples from thousands of patients longitudinally obtained in my tissue repository. Not one cell comes from another oncologist. And what's more, I have taken care of every single patient with my own hands. I have—every biopsy means something to me. This is not some game for me because I see 30 to 40 cancer patients a week. I'm answerable to them. I'm giving them the same horrid news of 40-plus years. It's shameful. So that's one tissue repository that we can go to, do multiomics, and find out what biomarkers were associated when this cell first appeared. Second, I'm studying pre-leukemia and trying to see what biomarkers and what cells change when acute leukemia occurs. But what about solid tumors? I said we should be studying people who are at risk of getting a solid tumor, start following them when they're at risk until they develop it to see: can we catch the first cell? Can we catch what I call the first-cell stage of cancer, which is very different than stage one? This precedes stage one sometimes by years, when the inflammatory environment is being produced. Who's at risk of cancer? The highest risk is in cancer survivors. People listening to this podcast: any of you who have had cancer, or who have family with cancer, or some loved one who has had cancer—don't get anxious. The individual risk for a cancer survivor to develop a new second cancer—not recurrence, a new second cancer—is only 13% higher than normal. But if you look at the population as a whole that is getting cancer, 20% of all new cancers in the US occur in a cancer survivor. So I started to collect their samples. I have a whole repository of cancer survivor samples in which many have developed new cancers. Some have developed recurrence. Now I have all this right now trapped on filters. In the future, it will be trapped and sent here. I know the science sounds like science fiction. What Michael does also sounds like science fiction. People don't believe me, Michael. They think it's pie in the sky and I'm just imagining these things. That is not true.
[35:35] Michael Levin: Yeah, science fiction just means you have a slow Gantt chart. People who think this is science fiction—I think it's really important that everybody hear what you're saying as somebody who actually takes care of these patients, especially the pediatric patients, because I'm not even a clinician and I receive all kinds of emails saying, "Why do you do this research with the frogs and the worms?" They say, "You shouldn't do these things. It's too much. It's too far. We shouldn't be doing these things. It's scary." It blows my mind because anybody with the slightest exposure to the amazing patient populations out there, the suffering is incredible. And there's a huge segment of healthy people who are not seeing it. They don't understand that this is what's at stake. Every time you either suppress or fail to support the efforts to understand what's going on and help people, you are complicit in this suffering. We have to get this stuff under control. And I hope everybody's hearing what you're saying, what it's like to do this on a day-in and day-out basis to tell people what their experience is going to be. I don't have the words for it.
[36:59] Azra Raza: It's heartbreaking. My book is full of just patient stories because I'm looking at everything to do with cancer through the prism of human anguish. What is it we are doing to the patient, to the families, the psychic violations we are visiting on them? It's just not for one individual. I'll give you one example, Michael. When my own husband died, my daughter was very little. First, he was diagnosed when she was only four. She was very tiny, poor thing. But she grew up the next four years, practically five years. She was eight when he died. Four weeks after he died, she got a very bad flu. Of course, everything was being given to her. Her asthma acted up. But one week later, she was getting better. I was sitting in my living room one morning, and she came out of a room crying inconsolably. As a mother, my heart sank — she's feeling much worse. Something's happened. I said, "What is it, Sherzad?" And she couldn't answer. When she controlled herself, this is what she said. She said, "No, Mom. I feel fine now. But now I know how horrible it is to feel that sick and how good it is to feel better. And my dad never got better." This is the sensitivity of an eight-year-old who's empathizing with her father, who never got better. What kind of society are we living in that we are tolerating the suffering of millions of people and giving ourselves gold medals constantly for game-changing therapies? They're all technologies, for God's sake. They're doing very little to help our patients.
[39:05] Michael Levin: What is your current assessment, as far as you know, from where we were 50 years ago? You pick a time, but how are we doing? Is there any sector of patients that are getting help, and what does that look like in general?
[39:24] Azra Raza: There are subgroups, little islands of responses, but they're so little. I'll give you an example, everyone talks about CAR-T therapies. The immune therapy where you engineer immune cells from the same individual to go and target their cancers. Let me just give you the statistics on that. Last 10 years, 27,000 people received this treatment in 10 years. In 10 years, what was the incidence of actual cancers? 2 million, 20 million, 2 million a year, so nearly 20 million cancers. So first of all, out of 20 million in 10 years, you have treated 27,000. How many patients, what percentage is it good for? What is the treatment cost? Minimum $1,000,000 for each patient. That's the financial toxicity. What about physical toxicity? CAR-T cannot make a difference between what is a normal B lymphocyte versus a malignant B lymphocyte. So it's going to kill every B lymphocyte in the patient's body. And now how do you replace those immunoglobulins for the rest of their lives? They have to get immunoglobulin replacements. Go and see some people's brains just liquidated in the presence of these CAR-Ts. What is the outcome? The median survival for these 27,000 patients is 14 months. Meaning half of those people are dead within 14 months. There is a longer tail going out, the second half has a longer tail. But that— you are developing a treatment that is costing this country to come on the verge of a financial collapse in the health sector. You're developing that kind of treatment for a small percentage of patients, which is not too much better than chemotherapy for at least half of them, because they're dead within 14 months like they would be with any other treatment. I just gave you this extreme example because, as you asked me, some people must be doing better. There are cancers. Lymphomas and malignant melanoma have lots of good antibodies and immune therapies. What about multiple myeloma? At one time, median survival was five years. Today, so many people live a median of 10 years, if not longer, with multiple treatments that have been developed. But taken together, these are very few cancer patients. The vast majority are brain cancer, lung cancers, GI cancers, bone marrow cancers. You asked me what is the difference? I say not 50 years ago, 100 years ago. If somebody presented with a glioblastoma stage four 100 years ago, the outcome is no different today for a glioblastoma stage four than it was 100 years ago. What about pancreatic stage four? No different. Take any of these cancers once it's advanced—all bets are off. For my cancer that I've been treating, acute myeloid leukemia, you won't believe this. In 1977, when I started, we were treating the disease with two drugs, popularly called seven and three, because seven days of one, three days of another. Today, in 2025, same two drugs, seven and three. In 1977, five-year survival was 26%. Today, it's 28%. And that 2% increase is not because we have better drugs, it's because we have better supportive therapy, better antibiotics, better antifungals. This is the state of affairs, Michael.
[44:02] Aastha Jain Simes: This brings me to a more fundamental question. Why do you think we haven't made that much progress?
[44:09] Azra Raza: I think about this. It's on my 3 A.M. agenda. I stay awake thinking about why is it that other people are blind? There's a complex battery of reasons, but one of the most important reasons is that as doctors, we enter a profession to treat disease and help our patients. We never think of prevention. The entire focus is always on treatment. The first problem is doctors themselves. Second problem is that doctors who are seeing patients don't do research. Researchers who are studying cancer in their labs don't see patients. This is a crazy kind of thing. It should never happen like this. There is no crosstalk between them. They hate each other most of the time. Number three: the way the system has evolved. The whole field has been hijacked by money trails. The government agencies that put out grant requests ask for proposals in certain areas. If you don't apply in that area, you get no funding. You have to channel yourselves; even if you're thinking differently, in the end you have to do those things on mice. For example, in the 40-plus years I've had my tissue repository, nobody supports it. There's no mechanism to support this. I hold fundraisers. Who helps me the most is my patients. They try to give me personal money. I say, no, I don't need it; please give to my tissue repository. They give us support. This is how I'm running the tissue repository and groveling and begging in front of everybody, because the whole system is that academics apply for these government grants, they use models that are so abnormal, they develop these things, and then they have to hand them to industry to develop it further. Industry's stated reason for existence is to make money for their shareholders. They're not going to worry about what patients are dying or what we are doing. Their thing is how much money can we make out of it? At least they're honest about it. But think of the academics who are handing these horrible drug targets to the industry to develop. Now you tell me who's responsible. I don't know whether it's doctors, PhD researchers, government agencies, or all of us, inclusive.
[46:51] Michael Levin: I think you're at the epicenter of just state-of-the-art cell biology, bioengineering, and the clinical side of things. So I think what you're doing is incredibly important. And that's the synthesis of those three branches, as you said, is not common. It's not common that people do this. And I think it's a very powerful set of new ideas.
[47:15] Azra Raza: But this is why I've become an old woman and constantly disregarded, disrespected, and ignored. So why? Because nobody else is doing what I'm doing. Around this Sentinel, the four biomedical engineers, myself, and my scientific colleague, we have made a company, because that's the only way people are even willing to give money to invest in something. Columbia, because we are an academic center, owns most of the equity. They own the intellectual property rights, etc. We made a company. We said if we get $6 million — what is $6 million? It's nothing. $6 million, we promise you that we will have this device plus the tissue repositories, cancer survivors, and our own examined by multi-omics to deliver the biomarkers we need, plus the cells we already know, plus the Sentinel in 18 months, ready for discussion with FDA for IDE (Investigational Device Exemption) and implantation. We shouldn't have a problem because this has been implanted, this is getting implanted all the time, stent. So it's not really different. We are not doing anything with it except to detect certain things. So it shouldn't be a problem with the FDA. We are ready to deliver in 18 months all of this for $6 million. The last big investor I had a meeting with — you won't believe what I was told. He said, "Yes, Dr. Azza, we believe that you are a credible person. You've been interested in this area and you've done all this." As I pointed out, $50 million has gone into developing this device. And what I have in the tissue repository, you can't even put a dollar figure on its value. He goes, "Yeah, I understand all that, and you are likely going to succeed and get this device in. But in order for me to invest with you, you have to do a study of doctors' behaviors, that once you have this approved and ready for implantation, doctors will actually do this. So please do a study first to show me that you can change their behavior. And then I'll think about investing." Oh my God, this is what I'm dealing with. I asked him, do you ask this question when you are investing in drugs developed in mice? What kind of accountability is there for others that isn't there for me? I don't know. Is it because I'm colored? I have an accent? What is it? What am I saying that's wrong? Eleven years ago, I gave a TED Talk saying all of this. My first slide on the TED Talk was a picture of a mouse. I said, "This is the real elephant in the room." What effect have I had on the world? Nothing. And patients are dying. That's the horrible thing.
[50:34] Aastha Jain Simes: The good thing about something like this Tentinel is that consumers will ask for it because they'll want early detection and prevention. If you can go even the private consumer route, that's going to be very high demand for that.
[50:53] Azra Raza: Very good point.
[50:55] Aastha Jain Simes: What do you mean by the first cell stage of cancer? You said this is very different from stage one cancer.
[51:12] Azra Raza: What we are calling the first cell stage is when we can detect the biomarkers, the pieces of protein, DNA, RNA that are associated with whatever chronic inflammation is going on, setting up the stage and then the appearance of the first cell, which is the appearance of these hybrid cells. If these two are together, we think this is the first cell stage of cancer. At this point, Astha, reversing with even lifestyle changes could work. Or even drugs like metformin or Ozempic could work. Just finding it and reversing inflammation is much easier than trying to deal with that end-stage monstrosity that is impossible to control. This test will be useful eventually and very quickly, not just for cancer, but for early detection of all chronic diseases like dementia. It can pick up the wellness-to-illness transition all the time. And yet, look at the difficulty I'm having raising $6 million. It drives me nuts.
[52:25] Aastha Jain Simes: I'm curious if the stent has been used in the past, and it sounds like the novel technologies and the actual detection and figuring out what's a cancer cell and the biomarkers. Why hasn't this been tried before? Because it seems like such an important thing to work on, to have early detection for all sorts of diseases right from the start.
[52:50] Azra Raza: This is the question I keep asking. Why is no one looking at the inception of cancer? Why is everyone trying to develop treatment of established cancers? Because the mentality of doctors is to treat. This is how we grew up being doctors. We don't think of prevention or early detection at all. People who have thought of early detection have tried periodic liquid biopsies, and they've all had their problems. Because the ultimate solution is that it has to be continuous detection. And it has to involve more than one thing, not just cell-free DNA looked at for methylation patterns. You have to combine multi-omics to come up with the right signatures that are unbeatable, that are really very strong, and prove the presence of abnormality. Why haven't people done it? Because they're focused on the last cell. If only we would focus on the first cell, we would be making such rapid progress. Because think of all the intellectual assets that are being lost right now in those useless studies. Think if we reversed them and forgot about the money; it's the intellectual input that's so badly needed. No one has tried this concept in cancer, absolutely. But there are stents like this for other things, CardioMEM, exactly the same stent we are using. It measures pulmonary pressure. That's very important. That has the same electronic circuit as here. So these things have been implanted. It was approved and eventually bought by Abbott for $427 million. So these are working constantly. 20,000 people a year have that stent placed in them. So it's not that a cancer stent hasn't been developed or placed; others have.
[54:54] Michael Levin: Do you have anything to say for people? If somebody has been given a diagnosis at this point, what should their first step be to educate themselves on what is actually useful, what is worth doing, how to navigate this thing? What do you recommend people do?
[55:20] Azra Raza: Listen, I deal with this all the time, Michael. The only good news we can give our patients when we are diagnosing cancer is to say it was diagnosed early. That's the only good news, because that's at a curable stage. So the first thing when somebody is diagnosed is to figure out where their disease is, whether it's curable or not. And if it's curable, then what are the strategies that would be followed? Is there just surgery that will remove it or chemo or radiation or immunotherapy or combination of all, what steps? And if the patients can't do so much because there's so much psychic trauma that goes with it that your mind becomes foggy. You're getting constant information from doctors and trying to manage appointments, and there's a big difference between the kingdom of the living and the kingdom of the dead where you get moved with that diagnosis until you come out of it. It's a very confusing and complex situation. That's why cancer involves not just the individual patient, but the family and even the community. Half my patients come with access issues because they're on social security and they just can't travel or access a ride. Community services or church services bring them over. I think it's so important for patients. The wealthy ones with lots of resources available to them can have all this at the tip of their fingers. But for people who are not so fortunate as having that much money, there is the internet. There are young people around you. If you're not at home with using these electronic devices, get as much information as you can. The most important thing I'd say, Michael, is find a doctor that you think is communicating with you well and is sympathetic enough to not just try to cure you, but actually is concerned about healing you. The violations that are going to be visited on your body and your mind are so profound that you do need some partner in this journey who you feel comfortable with. That's where Emily Dickinson says beautifully, "Surgeons must be very careful when they test their knife; for underneath their fine incisions rests the culprit life." In other words, a surgeon can use a knife to remove a wart or a tumor. But the problem is underneath their fine incision rests the culprit life, which is a far more inclusive and complex situation than just curing the disease. You have to heal the person.
[58:30] Michael Levin: Maybe we can do another session. I'd love to hear your thoughts on the prevention side and the stress and the link to psychology and to other aspects of life that might go beyond the traditional thoughts of chemical stresses. Thank you so much for today. I think this is just super important for people to hear and thank you for your amazing work. I love your approach. The technology is very promising. Thank you for that.
[59:03] Aastha Jain Simes: Thank you so much. I'm looking forward to you curing cancer.
[59:09] Michael Levin: Yeah.
[59:10] Azra Raza: Through early detection.
