📷 New York Presbyterian Hospital Journalist: Anna Yang
Interviewer: Welcome to SciSection, my name is Anna and I’m a journalist for the SciSection radio show broadcasted on CFMU 93.3 FM radio station. We are here today with Dr. Azra Raza, who is the Chan Soon-Shiong Professor of Medicine and Director of the MDS Center at Columbia University, as well as the author of the book The First Cell. Thank you for taking the time to meet with me, Dr. Raza.
Dr. Raza: Delighted to be here Anna, it’s such an honour.
Interviewer: So to begin, could you give us an overview of your career so far?
Dr. Raza: Absolutely Anna, I grew up in Karachi, Pakistan, and while growing up, I don’t know, instinctively I was always interested in nature. My earliest memories are as a four year old, I would be crawling around on the ground following ants. And imagining all sorts of their lives so I started reading about ants at a very early age, and today, I think I know more about ants than anything else. In fact, a friend of mine, who’s a poet, wrote a book of poetry dedicated to me. So that’s how much of an obsession I developed with ants. Anyway, I wanted to be a scientist, but in Pakistan, the only entry for science was through medicine. We did not have any PhD programs, and so I went into medicine thinking: good, I’m just going to finish my medical education and proceed to the west in order to acquire a PhD in natural sciences. Except, what happened in my first year of seeing patients was, that I had an encounter - my first encounter with a patient, that changed all of my scientific curiosity into a wonder about disease and the human suffering. There’s a big difference between curiosity and wonder; curiosity is something you want to know, and you find it and you’re gratified. But wonder basically stands everything on its head. Everything you’ve known so far suddenly becomes meaningless. That’s what happened to me, that all the science that I had been reading about, the evolutionary biology, paleo-anthropology, developmental psychology - all this stood on its head when I encountered a patient. And I knew from that moment as a third year medical student that I would only pursue knowledge and science that goes into the service of patients. And that’s what I did. I came to the US, I got interested in cancer at an intellectual and emotional level and that’s another story, and the cancer problem is such an intellectually challenging problem, that I was very much engaged with it. So I came to the US at 24 years of age and started working at the Roswell Park Cancer Center in Buffalo, New York before I even started my residency in medicine. But then continued my work in leukemia studies throughout my residency, fellowship, became on oncologist, and to this day, and to this day I see 30-40 cancer patients a week. And walk many of them to their deaths. But I also have a cutting edge research lab that I have been supervising for 35+ years with hundreds of original publications in high profile journals, but my most important credential, I think, is that I am also a cancer widow. My late husband, Harvey Preisler, who was born and raised in New York, at 15 years of age dedicated his life to studying cancer and treating cancer, in a cruel twist of irony got the very disease he had dedicated his life to. Our daughter was only 4 years old when he was diagnosed, and 8 when he died. So I have had to stand on both sides of the veil, as an oncologist and simultaneously as a family member. Therefore, these three credentials: being an oncologist seeing 30-40 patients, being a cutting edge laboratory supervisor and really leading some of the research in the latest multeomic technology, and finally being a cancer widow. This is the trajectory of my career.
Interviewer: Thank you, that sounds fascinating, and you have my sympathies of course, for the losses that you’ve suffered. So as you mentioned, you’re a physician scientist, so you’re on both sides of this war on cancer. So how important would you say it is for you to balance those two sides of your career, and how do you manage to maintain that balance?
Dr. Raza: I don’t know if there’s a balance, because the two are completely united in my mind. They are like two strands of DNA, they go hand in hand. What is the separation? If I’m seeing a patient and suddenly the patient has a very high blast count, that I’m encountering, that raises scientific questions, so why is there a separation? In fact, this artificial separation of “scientists you go study animals and doctors we go treat cancer,” where do we meet? It’s completely mind-boggling to me, honestly. In fact, one of the sentences in the book that you mentioned, that I wrote recently - The First Cell: And the Human Costs of Pursuing Cancer to the Last - in this book, one of the important sentences I’ve written about pointing this issue out is that cancer researchers today study a disease they never see, in animals who don’t get them. So an animal doesn’t get spontaneously myelodysplastic syndrome (MDS), but there are dozens of models of animals because they are created, and which they are calling MDS - “oh, it looks like MDS” - but of course it has nothing to do with the human disease. This is the problem. So when you ask me how do I balance the two, to me they’re one and the same thing. Sure, it requires double the amount of work, but then if you’re afraid of work, don’t come into this area, please. Just go and do something that will give you a 9-to-5 job. This is not a 9-to-5 job, and you just have to balance it as best as you can. And I’m a mother, I’m a wife - I’m a widow now, for some years - but I have a very busy social life as well. But that doesn’t mean that patients should not be front and center in everything I’m doing.
Interviewer: Yes, thank you for pointing that out, I think that’s a very unique and important perspective to have, and so thank you for sharing that. So, you’ve had a lot of successes throughout your career so far, what would you say you’ve done differently compared to your peers throughout the years to help you become who you are today and achieve the kind of success that you’ve had?
Dr. Raza: I think the thing that helped me to begin with is that I’m an immigrant. I’m a Muslim. I’m a woman. At 24 years of age I arrived in this country with the grand design of curing cancer. So I have an outsider’s perspective. The culture I come from is an interesting blend of Athens and Jerusalem: passion and reason, spirituality and science. There is a seamlessness which blends them. The way we are raised is to realize that if you climb a mountain in pursuit of zen, the only zen you will find on top of the mountain is the zen you bring with yourself. What does that mean? It means that in a way, the moment of gratification, the ultimate goal, if you achieve it can never measure up to the vastness of your dreams and desires. Because what provides a force to your life and to your engagement with the deep questions in life are your dreams, your visions, your wanting to do something different. All the time knowing full well that there may never be a calm of consummation. Because life is an enigma into incompletion. So while my goal and my dream is to cure cancer, I also am fully practical and understanding I may never achieve that dream, but that doesn’t mean that I should stop trying to find my zen. And I don’t set little goals for myself, because we are allowed to dream big dreams and have a big vision, and do our very best to try and reach it. So I think it’s a very cultural thing to begin with, and this is why when I came to this country, one of big important lessons was never get involved emotionally with your patients, don’t get too close to them. Why? Because emotions cloud judgement and you may not be able to provide them with the best care. To me, that’s the exact opposite of what you should be doing; unless you are engaged with a patient emotionally, how are you going to understand what’s bothering them? What is their 3 AM agenda that keeps them up at night, what should you really be trying to help them with in a holistic way? How do you heal them rather than just cure them with an antibiotic for an infection? You know, that kind of thing. So I think my trajectory, my background, my immigrant status, my being outside the box allowed me to depend on instinct rather than the tradition and custom of this country. And so, when I decided to study acute myeloid leukemia, then I would have made a mouse model for it if I had been studying in this country. But coming from Pakistan, I was a young, naive person. It never even occurred to me to make an animal model. So I would say that these life experiences, the context in which you are raised, the education you get, and also - I was the child of immigrants who had moved from India to Pakistan, at the time of the partition of the subcontinent. My parents had the immigrant’s obsession with their children having to somehow do better than they did, and they were colonized by the British. They realized, if you can’t fight them, join them, and beat them at their own game. And the best thing that the west brought to the east was the age of reason, thinking, modern science, the industrial revolution, education, and my parents, for all seven of my siblings, insisted that we get the highest possible education and really gain knowledge for the sake of knowledge. Not for the sake of monetizing it. That would be crude and crass in our culture.
Interviewer: So you mentioned that you study acute myeloid leukemia, and your research focus is acute leukemia and preleukemia. Could you tell us a bit about how you chose those two diseases as your area of focus, both in research and in clinical practice?
Dr. Raza: Very simple, Anna. I became infatuated with the intellectual challenge of cancer, after seeing my first patient, which is etched on my brain of course, but the whole idea was that when I came to this country and wanted to do research in the area, it was very clear that studying a solid tumour poses certain problems: you can only remove the tumour once, you have to disaggregate the cells to study them. Liquid tumours, they are flowing all the time, you can sample as much as you want: before, during, after treatment. It’s so much easier to study, they’re in single cell suspension. So I started studying acute myeloid leukemia and treating patients, but within eight years or so, it became very clear to me that within my lifetime this disease is so malevolent, so vicious, that it will not be cured in my lifetime. And unfortunately I was right, that the same two drugs I was using in 1977 to treat acute myeloid leukemia - these two drugs are popularly called seven and three because it’s seven days of one, three days of another - are the same two drugs I’m giving in 2020. So I was unfortunately right. But many of my patients gave the story that a few months before, sometimes years before they were diagnosed with leukemia, their counts were low. Anemia, things like that. And that’s called pre-leukemia and myelodysplastic syndrome, so I said “wow, this is great! Now I can just study patients in the earlier form of pre-leukemia, follow them as they develop leukemia, and unravel the whole transformative journey of the cell.” And that’s how I started, by studying acute myeloid leukemia and then moving to pre-leukemia following that.
Interviewer: That’s lovely, and so your work in pre-leukemia and acute leukemia, as well as your belief that we should work on treating cancer and targeting it at its earliest stages as opposed to the later ones as we currently do, are some of the main ideas in your book The First Cell: And the Human Costs of Pursuing Cancer to the Last, so for those of us who aren’t familiar, could you give a brief summary of the book and share some of your reasons for writing it?
Dr. Raza: Thank you Anna, that is a subject most close to my heart. So I’ll begin by just quoting you one statistic: in 2020 - this year - the age-adjusted mortality from cancer is the same as it was in 1930. I can’t make up such statistics. Because they are so bad. Sure, there has been a 1% annual decline in cancer mortality in America in the last 30 years, which means that 26% fewer people are dying of cancer. But that decline follows a steep incline in the preceding 30 years, and both the up and down swings parallel the rise and fall in smoking. So it isn’t that this 1% decrease in mortality is coming from something new we have developed as a strategy. In fact, we are curing 68% of patients diagnosed with cancer today. But curing with what? Slash, poison, burn. The same treatments we were using in the 1950s, and 60s. The 32% that we are not curing? Their outcome is no different than it was in 1930, because they’re diagnosed with advanced disease. So basically the only reason we have been able to cure 68% of patients - with a few exceptions here and there that account for less than 10% of non-slash-poison-burn treatments - the vast majority, especially the common cancers that are killing 90% of cancer patients, we have made very few advances. So the question comes out: okay, where have the 250 billion dollars in research gone, that have produced over 4 million publications in cancer, why is nothing improving the bedside problem? This is my issue! And the reasons I point out in the book is - I call it CRUSH. Cancer is a highly complex disease. Yet we are trying to deal with it with a reductionist conceit - oh, we’ll find one gene that causes one cancer, and then we are going to cure it with one magic bullet. So the complexity, the reductionist conceit, the ultra hype of small little gains - you know, you see these big headlines: new cure found for lung cancer, and in fine print it will say “in mice.” But you see, most of the public gets fooled into thinking, “wow, they found a lung cancer cure, now if I get lung cancer, I can go into such and such hospital and be cured.” This is the smoke and mirror approach that has created a sense in the public that great advances have been made. I’m sorry! Very few advances have really helped patients. Then the next thing is the simplistic clinical trials we are doing based on animal studies. You create an artificial tumour in a mouse, you treat it with a drug, the mouse gets cured, now you bring the drug to the patient’s bedside. When you bring it to the patient, it has no meaning! 95% - again, I can’t make up such statistics - 95% of experimental trials in cancer today fail entirely. The 5% that succeed only improve survival of a fraction of patients - 20-30% benefit for maybe five months at most. Usually it’s two months. And the patient is financially ruined because the price of these drugs is like 20,000 dollars a month. And that is the final thing, the high financial cost. So the CRUSH of cancer, why I wrote the book, it’s the complexity of the disease, the reductionist conceit, the ultra hype, the simplistic clinical trials based on animal studies, and the terrible high financial cost. Which is killing the country; we have a 3.5 trillion dollar healthcare budget, the whole healthcare system is on the verge of collapse, and no one is being cured. My patients are dying at the same rate and I’m using the same drugs that I was using in 1977, this is what made me write it. No one is thinking of patients. Everyone is thinking of their next paper in Nature, the next grant they have to write, what about the suffering of humans? So the very title of my book is: The First Cell and the Human Costs of Pursuing Cancer to the Last. Because basically 90% of the current budget of the government goes to support research on end-stage disease. Only 5% on early detection and prevention. It is mind boggling.
Interviewer: Now something else that you mention throughout your book at multiple points is a tissue bank that you’ve created, and it’s a very unique tissue bank, so could you tell us a bit more about that.
Dr. Raza: Everything in my professional life is mediated by patient experience, really. And so I had an experience with a patient named JC in the early 1980s, which really changed me forever as a young person. And I realized that I should study pre-leukemia, and try to intercept the disease before it becomes a leukemia like JC was suffering from. And when that thought came to me, I said “well then, I have to study cancer cells. So I better start saving them.” It never occurred to me to make a mouse model. So I started just taking blood, marrow, biopsies, whatever I was getting and putting them in the freezers. And this created the tissue bank in 1984 which today is the world’s largest for this disease. I have 60,000 samples from thousands of patients, serially collected as they progressed through their disease from pre-leukemia to acute leukemia. And do you know, of the 60,000 samples in dozens of freezers, not one cell comes from another physician. So every vial in these freezers is a poignant story to tell for me. These are too personal because to this day I do the bone marrows with my own hands. In clinic on Monday I did six bone marrows, and you feel so humble when someone whose hemoglobin is five grams, who cannot breathe properly, tells you “Dr. Raza, take as much marrow as you want from me. Even if it doesn’t help me but will help someone else.” And this is what makes the tissue bank so precious. And of course I have not been lazy, I’ve used samples from the tissue bank, published hundreds of papers, but is that what I need? Another paper in Nature? No, for God’s sake, so the idea I have is that we need to study the entire tissue repository, the serial samples, with every sophisticated, latest technology available. Proteomics, genomics, transcriptomics, metabolomics, everything we need to study, on patients, multiple times. Use AI, big data analysis, to come up with: how do we trace the disease back to its very start, and then ask the question “why does some healthy person even get pre-leukemia?” What made them susceptible? What were the polymorphisms they were born with, they inherited, or they were exposed to, or what is their microbiome like, that made them get this, and that’s the only way we’ll go back to the earliest stage and then learn how we prevent this disease.
Interviewer: Yeah, that’s wonderful. Now looking forward, you have a vision for an institution called the First Cell Center, could you tell us a bit more about that?
Dr. Raza: Yes, thank you, because that is a futuristic vision, and it’s coming to fruition now, actually. I don’t want to scare any of your audience. Listeners, if you are hearing this, please don’t be scared. But the statistics are that one in five new cancers in America, one in five, is diagnosed in a cancer survivor. And the most important person to me is my own late husband, Harvey. He had his first cancer at 34 years of age. He survived it. He got his second cancer at 57 and he died from it. The two cancers were completely unrelated, there was no relationship between the two. Completely different tumours. So why is it that one in five cancers appear in cancer survivors? Because one: they already have some predisposition to get cancer which we haven’t fixed, so they get a second one. And number two is that the treatments we are giving them make them susceptible by damaging other cells, stem cells, to get these kinds of cancers. So let’s do the math: if there’s 1.7 million new cancer patients being diagnosed in America, it means 340,000 of them are happening in cancer survivors. Those are the people at highest risk of getting cancer, why aren’t we studying those people who have survived one cancer, follow them aggressively for the appearance of the first cell? Why is no one thinking of doing this? So the Center I have imagined, the First Cell Center, is a center around cancer survivors and this is not a new idea for me, because I had this idea in 1996, and I established a TIME center - therapy-induced malignancy evaluation - at Rush University in Chicago. I tell this story in my book, that as I was leaving Chicago with all my samples, some unrelated, low clerical person came and made the movers unload the research charts from thousands of patients who were cancer survivors who had given me their serial samples, although all the paperwork was complete. So anyway, I tell that story in the book. So as a result, today I have thousands of samples rotting in my freezers, and they have thousands of research charts rotting in some warehouse in Chicago. But the universities cannot come to plan, because patients don’t mean anything to institutions, they’re only interested in protecting themselves. So my idea of the First Cell Center is - and you know there are 16 million cancer survivors today in America. Even if one million of them just gives to the center ten dollars a month for one year, I’ll have enough money to do all of the studies I need to do. I would start saving, simply blood samples, every 4-6 months on anyone who has a history of cancer or has been diagnosed and treated for it. That’s it. We just keep saving the samples. And then, when we have enough samples, we go in and examine them with all the multeomics, latest technology, and figure out if we are seeing any disease-related perturbations that are early harbingers of coming crises for one of those patients. That’s the idea.
Interviewer: Yeah, that’s a very special vision that you have, and so thank you for taking that on. I just have one last question to end the interview, and you’ve alluded to this throughout the interview but as a summary, could you tell us what you think the scientific community right now, particularly the portion of the community that’s concerned with cancer research and cancer care, needs right now?
Dr. Raza: Only one thing. Which is: think of the patients, first and last. Any experiments, scientists, you are designing on your lab bench, ask yourself: what does it mean? How will it help the patients? How many thousands of years will it take before it can be converted and translated into improved treatment? And if it’s not, give it up! And oncologists, stop trusting other people to do your work. Stop standing outside the patient’s room on your rounds discussing balancing electrolytes for 45 minutes and spend five minutes saying hello to the patient and thinking about what’s killing the patient - it’s the cancer, not the electrolyte imbalance. I think all of us are really guilty of not thinking of the patient. All the time, everything should be motivated by one thing and one thing alone: the person who’s suffering. And it is horrible suffering. And this is what I see on a daily basis, and this is what I describe in the book, over and over. And so, this is your last question, let me end with a short poem from Emily Dickinson, which really conveys my feelings very clearly.
I measure every Grief I meet
With analytic eyes -
I wonder if It weighs like Mine -
Or has a Different size.
I wonder if They had it long -
Or did it just begin -
I cannot find the Date of Mine -
It’s been so long a pain -
I wonder if it hurts to live -
And if They have to try -
And whether - could They choose between -
They would not - rather die -
Interviewer: Yes, that’s a beautiful poem, thank you for leaving off with that, I think it’s a very powerful message. And that brings us to the end of the interview Dr. Raza, thank you again for joining us today, and for everything that you’re doing in the battle against cancer, both as a doctor and a scientist, it’s been a pleasure to speak with you.
Dr. Raza: Thank you so much, Anna. Good luck to you.
Interviewer: And for everyone listening, that’s it for this week of SciSection. Make sure to check out our podcast available on global platforms for all of our latest interviews.