TERRY GROSS, host:

This is FRESH AIR. I'm Terry Gross.

When the, quote, "War on Cancer" started after President Nixon signed the 1971 National Cancer Act authorizing hundreds of millions of dollars for cancer research, some scientists thought cancer could be curable within a few years. There's been a lot of false hope and hype since then, no cure but a lot of progress. Where are we now in the war on cancer, and can this war even be won? Those are a couple of the questions that inspired the new book "The Emperor of All Maladies: A Biography of Cancer" by my guest Siddhartha Mukherjee.

As an oncologist immersed in the daily care of patients, he wanted to pull back and research the history of cancer to better understand the illness he was confronting and treating. Dr. Mukherjee is a cancer physician and researcher. He's an assistant professor of medicine at Columbia University and a staff physician at Columbia University Medical Center.

Dr. Mukherjee, welcome to FRESH AIR. What did you want to get out of writing this book as an oncologist yourself? Why is it important for you to have an understanding of the history of cancer and why do you want your patients to know that?

Dr. SIDDHARTHA MUKHERJEE (Physician; Assistant Professor of Medicine, Columbia University): Well part of the reason is that, you know, I think one of the themes in the book is that the past, particularly in medicine and science, is always conversing with the future. There are ways in which you don't know until you excavate the past of medicine; why we're here right now and what happens next. I mean, Terry, you know, the book really grew out of a question that a patient had asked me and she was a woman with abdominal cancer and I was treating her. She had relapsed and responded and relapsed and responded and finally she said, you know, I'm willing to go on, but before I go on I need to know what it is that I'm battling.

And it was a very humbling moment for me, because not only could I not answer her question, I couldn't point her to a book or a resource that would answer her question in the most fundamental sense. I mean there are 5,000 books in the world about cancer, you know, how, if you want to eat carrots, you can cure this kind of cancer et cetera. And I actually found those books vaguely insulting. And I also found that there was no resource, there was no history. And so I wrote this book really because it wasn't there and it was an attempt to try to write the history and to bring us up to the present such that we could understand what happens in the future.

GROSS: Before we talk about the history of cancer treatments, let's talk about some of the things you and your patients are up against and the brutality of some of the treatments. You describe your work with a patient named Carla. Would you describe the kind of cancer that she had and the incredible regimen of chemo that she had to undergo with only a 30 percent of surviving after all that.

Dr. MUKHERJEE: So Carla has acute lymphoblastic leukemia. It's a very aggressive form of cancer of the white blood cells. It usually presents in young children but it can - there's a variant of it that presents in young adults, actually even in older men and women. And Carla happened to have the older variant, obviously. She was diagnosed when she was in her 30s. And in children, this kind of cancer is highly curable, 80 percent curable, 90 percent curable, depending on the circumstances. But in adults, for reasons that we still don't understand, the cure rate sinks down to in the 30s and 40 percent range, and Carla had that variant of cancer.

The chemotherapy regimen for this cancer is extremely toxic. It is a regimen in which we go on and on and on almost without any break combining multiple drugs, seven or eight drugs, adding radiation in certain instances and in fact so much so that we actually put in chemotherapy into the spinal cord in order to prevent these white blood cells from overgrowing out in the brain. And so that's how toxic and complicated this chemo regimen is.

GROSS: So what do you tell a patient like Carla when you know that the odds of her surviving are 30 percent and that you're about to administer this incredibly toxic set of chemo drugs including injections into her spine to prevent the cancer from spreading to her brain?

Dr. MUKHERJEE: The first job you have I think is to inspire confidence in a patient and you do that actually by being humble. This is a kind of great irony of oncology is that the thing that really inspires confidence in patients is by telling them exactly what is known and exactly what is unknown and trying to lead them through that process. And in Carla's case, you know, I was a fellow in training, one of the things that I said to her is, here's what we know. Here's what we know will happen and then we'll sort of meet this blast of the unknown. We won't know whether your counts respond. We won't know what happens but when we are there we will find a way to solve that problem and we'll do it together.

And I think that, for me at least, is very reassuring to say as a doctor and I think, I hope, for patients, is very reassuring to hear.

GROSS: And she survived?

Dr. MUKHERJEE: Absolutely, she survives today.

GROSS: So let me ask you an honest question here. When a patient has such a serious and hard-to-treat form of cancer and finds a doctor like you who is obviously really smart and probably very good with a bedside manner but kind of inexperienced, because you're still a fellow at this point in the story, do they get nervous that the doctor is young and inexperienced? Have you faced that a lot?

Dr. MUKHERJEE: I did. I continue to face that. I mean, as it turns out, when you're being treated at an academic medical center, the fellow is not the only person who is taking care of you. The fellow is overseen by attendings. There's a whole team of doctors and nurses and a whole variety of people come to allow you to go through this, so the fellow is one part of this.

But that said, I think the fellow is a very major part of it because it's the person whose learning curve is the most exponential. And in a sense, I always say this, you know, to my own family, it's the person who is right at the frontlines who actually knows the most about medicine.

When I was training in internal medicine we sometimes used to perform a procedure in which we would put a catheter, a centralized catheter into the heart and I would say to myself, you know, if I ever had to have it done for myself or a loved one, the person I would choose is not the senior attending, not the junior person in training but the fellow who has just come out of training because they know exactly what the risks and benefits are. They've sort of been at the frontline. They're like the soldier who has been there, who knows trench warfare. And so in some ways I think, of course, there is a whole team of experienced professionals who weigh in on the care but the fellow's experience is the most acute.

GROSS: If you're just joining us, my guest is Dr. Siddhartha Mukherjee. He's an oncologist who has written a new book called, "The Emperor of All Maladies" and it's a history of cancer.

Can you explain for us laypeople what the current understanding is of what causes a cell to become cancerous?

Dr. MUKHERJEE: We've begun to get a glimpse of this - of this event. And what we know about it is the following: There are - in cells, there are genes that are present whose normal function is to regulate the growth of the metabolism and the cell division of cells. And corruptions of these genes, mutations of these genes essentially activate or inactivate critical processes that act like accelerators and brakes. So to rephrase this: You can imagine the cell as a molecular machine and cell division is one of the activities it performs and there are accelerators and brakes on cell division.

Now if you, by mutating genes, if you jam the accelerators or if you mess up the brakes, then the cell doesn't know how to stop dividing and it begins to divide incessantly. And part of that division also creates even more mutations. Sometimes there are genes that can be mutated which can accelerate the mutations of other genes. And this process goes on and on until you've found a cell which is now capable of infinite cell division and does not know when to stop dividing, and that's what unleashes a cancer cell.

But that said, I think that's just the beginning of an understanding. Obviously cancer is not just a dividing cell. It's a complex disease. It invades, it metastasizes, it evades the immune system. And so there are many, many other features of cancer which are still in their infancy in terms of our understanding.

GROSS: Can you tell us about another feature of cancer that has recently been discovered?

Dr. MUKHERJEE: Well actually, one of the most amazing - I just recently went to a seminar, an academic seminar at Columbia in which the scientist was trying to find out how is it that cancer evades the immune system. So he has been obsessed with this idea for several years and has finally invented a mechanism by which he can reactivate the host's immune system and potentially attack the cancer.

And this is not just a kind of a fantasy but in fact one of the first such drugs recently was put into a clinical trial in metastatic melanoma and was surprisingly effective at increasing the survival of patients with metastatic melanoma. And he reminded me that, in fact, there has been no drug, no known drug in the past which has increased survival of patients with metastatic melanoma, and yet activation of the host's immune system seems to increase survival. So that just tells us how little we know about sort of the global qualities of cancer, about these new qualities that we're discovering.

GROSS: We're in an era where there are now some targeted drugs, drugs targeted to specific forms of cancer and there are many more drugs in the works. I guess the two best known targeted drugs are Herceptin and Gleevec. I'd like you to choose one of those two drugs that's easier to describe and tell us how it works as a targeted drug.

Dr. MUKHERJEE: So Gleevec is an excellent example of how one can target cancer therapy. Essentially the cells that Gleevec attacks are a form of a particular leukemia. It's called chronic myelogenous leukemia, or CML - I'll call it CML. CML cells have an activated gene and that gene is what drives them to proliferate pathologically, to keep dividing pathologically. And that gene was discovered in the 1980s and it's called BCR-ABL. And essentially what Gleevec does is that that gene makes a protein called BCR-ABL and Gleevec essentially goes in and lodges itself into the heart of this protein, this pathological driver of cell division, and inactivates it.

There's a lovely phrase that someone used about this. A chemist said: Gleevec is like an arrow directed at BCR-ABL's heart. And that phrase is really memorable because essentially this little molecule goes and jams itself inside the heart of this driver protein and essentially inactivates it and that's how it makes it possible to kill these pathologically proliferating white cells and that's what makes it a targeted therapy.

GROSS: So how toxic is Gleevec compared to the kind of chemo that most people are familiar with where you lose your hair and you get nauseous and...

Dr. MUKHERJEE: It is absolutely not toxic at all. I mean, you know, there are minor side effects of Gleevec but it's not toxic. It's amazing. If you see a patient on - who is taking Gleevec for CML, the idea that they were going through chemotherapy may or may not even occur to you. I mean there are side effects of any medicine but really the non-toxicity to the rest of the body is absolutely shocking.

GROSS: And what's amazing too, isn't this form of leukemia a very deadly form of leukemia?

Dr. MUKHERJEE: It used to be.

GROSS: Right, right.

Dr. MUKHERJEE: It used to be. There is a very interesting quote in the book, you know, one of the people who I interviewed in the book is Brian Druker, who of course invented Gleevec along with a couple of other chemists at Novartis. And Brian Druker said to me at the end of his interview, he said, you know, he's achieved the perfect inversion of everything that an oncologist wants now because, because patients on Gleevec are living longer and longer and longer, the prevalence of CML is increasing.

So in other words people are living so long that you can now begin to see people alive with CML in the world sort of taking Gleevec because you take it chronically, and so Brian says he's achieved the perfect inversion of the goals of an oncologist. He's increased the prevalence of cancer in the world.

GROSS: Right, right because people aren't dying.

Dr. MUKHERJEE: People aren't dying, exactly.

GROSS: Yeah.

Dr. MUKHERJEE: They're living with cancer as opposed to dying of cancer.

GROSS: So what are the implications of Gleevec for the future of cancer treatment?

Dr. MUKHERJEE: Well the, one of the implications is that number one as Bruce Chabner, again, who I interviewed for the book, is that, you know, Gleevec is a little bit like, it's a little bit like the four-minute mile. So, you know, when Roger Bannister ran the four-minute mile, before he ran the four-minute mile people had all these theories about, you know, you can never run a four-minute mile because your lungs can just not breathe fast enough or your legs or your muscles are not designed - there's an intrinsic barrier to being able to run the four-minute mile. And of course Bannister showed that that was not true. And since then, now I don't know what the latest number is but it's something like three minutes and few seconds.

And so what that means to us, what Gleevec means to us is much like the four-minute mile, there's no intrinsic barrier to designing specific therapies. Such therapies in proof could exist. We just have to find them. And so Gleevec essentially opens an approach to running what people are calling oncology's four-minute mile, which is finding specific therapies for every form of cancer.

GROSS: And this is a kind of therapy that, unlike most chemo, doesn't kill most cells.

Dr. MUKHERJEE: Normal cells, that's right. So it has - and, you know, we'll go back to the history - but it has what would be called exquisite specificity: the idea that you would be able to kill the cancer cells while sparing normal cells. You'd find what are called Achilles' heels of cancer cells, find exactly those things that make cancer cells dependent on certain conditions for their growth and you'd be able to target those specifically such that you now would be able to kill cancer cells and spare normal cells.

(Break)

GROSS: You write in the book that when a chemo drug or the immune system attacks cancer, that then mutant clones can resist the attack and start to grow. And then the fittest cancer cells survive and they start reproducing. Is it similar to the way bacteria can become resistant to antibiotics?

Dr. MUKHERJEE: That's exactly right. That's the exact analogy. In fact that's exactly how cancer cells mutate and every round unleashes - you know, it's sort of like, I sometimes say it's like the Galapagos trapped inside your body. Every round unleashes yet another set of resistant cells and so forth until you've finally got the next evolving clone of cells.

GROSS: So that must make cancer much harder to treat because you become resistant to the treatment, no?

Dr. MUKHERJEE: That's exactly right, so you have to find the treatment that will reach that perfect balance between eliminating all cancer cells such that you ultimately are left with none. That is the ultimate cure. But sometimes you don't, again, sometimes you don't need to do that.

Again if you come back to Gleevec; Gleevec doesn't really eliminate cancer from your body. What it does is it sends the cancer cells into a kind of state of deep hibernation. It kills all the actively proliferating ones. But interestingly, when you stop taking Gleevec you can relapse with cancer cells that are somehow hidden somewhere in your body. It's a process we don't understand fully.

GROSS: Why is it that breast cancer cells are different than leukemia cells and they're different than colon cancer cells. Now, as you point out in the book, the original idea for the War on Cancer was that cancer cells are cancer cells. We'll figure out a way to kill all the cancer cells and therefore we will vanquish cancer. But it turned out to not be that simple because all the cancers have different cells.

Dr. MUKHERJEE: That's correct. I mean this is a very common question, you know, why is it that breast cancer cells are different from leukemia cells? The simplest answer to that question of course is that it's partly because breast cells are different from blood cells. Our body has evolved exquisitely detailed instructions that allow a nose cell to become a nose and that allow a blood cell to become blood and a breast cell to become a breast cell and they are all performing functions that are requisite for the survival of a multi-cellular organism called a human being.

Now that's part of the reason, of course, then that is that when a breast cell becomes a breast cancer cell, it evolves along a particular pathway but it still retains some of the characteristics of its original precursor or ancestral breast cell. And therefore every single tissue, every single tissue that bears cells that divide, therefore there's a diversity of cancers that is produced.

Now that said, there are commonalities as well and one of the most amazing things about modern or contemporary cancer genetics is that it is reorganizing the universe of cancer in terms of peculiar and unexpected organizations. I'll give you a good example of that. We talked a little bit about this kind of leukemia called chronic myelogenous leukemia, or CML, and we said that there's a mutation in a particular gene which drives this leukemia - this gene happens to be called BCR-ABL. They're actually two genes fused together, BCR and ABL, which create this mutant gene, BCR-ABL.

Now it turns out that there is a cousin gene which is active in a completely different kind of cancer, a solid tumor that grows typically in the abdomen called a gastrointestinal sarcoma, or a GIST. You would say well there's no relationship between a leukemia, which grows in the blood and chokes the spleen, and a solid tumor that grows in the abdomen and doesn't resemble it anatomically or physiologically at all. But it turns out if you lift up the covers there are common genes, there are cousin genes that drive both of them.

Now if you hadn't uncovered the underlying genetics and reorganized the world of cancer, you'd never imagined that these are connected. And this is what's happening overall in oncology. So in other words, a breast cancer might turn out to have a very close resemblance with a gastric cancer, but not every breast cancer. And this kind of reorganization of cancer in terms of its internal genetic anatomy has really changed the way we treat and approach cancer in general.

GROSS: Is our genetic system programmed to get cancer?

Dr. MUKHERJEE: Well, you know, it's always hard to answer questions which are -which speculate about evolution, but this much is for sure: The very genes that allow cells to proliferate, to survive, to move, to adapt to circumstances, to resist poisons, those very genes, when they become corrupted, are genes that are co-opted by cancer cells to become cancer.

So there is of course a deep link, and as the book suggests, if there's a seminal discovery in oncology in the last 20 years, it's exactly that. It's the idea that cancer genes are often, this is not always true, but are often mutated versions of normal genes. And that moment, the arrival of that moment really chilled the world of cancer biology. The book describes that moment. It really sent a kind of a chill down the spine of cancer biology. Because here we were hoping that cancer would turn out to be some exogenous event, a virus or something that could be then removed from our environment or removed from our bodies and therefore we would be rid of it.

But the idea that cancer genes are sitting inside each and every one of our chromosomes, just waiting to be corrupted or inactivated and thereby unleashing cancer is of course one of the seminal ideas of oncology. But it also, it's a -as you can imagine - a deep philosophical idea about what it means to be a human being and how sort of the seeds of cancer are sort of already inlaid into our chromosomes.

(Break)

GROSS: You write about how horrible cancer treatment was in the '70s and how difficult cancer wards were and the intensity of nausea caused by the chemo drugs. Why is it that chemo drugs - many chemo drugs don't produce that intensity of nausea any longer?

Dr. MUKHERJEE: Well, to some extent it's because the drugs themselves have changed and we've found ways to create variants - chemical variants of those that don't cause that much nausea. But really, really the real secret is that we found better, newer anti-nausea medicines. The kind of anti-nausea medicines that are deployed in the wards today are fundamentally different from the ones that were available.

And you know, one of the things that gets ignored in the history of cancer is the enormous role that taking care of symptoms, that palliative care has had in this disease. Anti-nausea drugs, anti-pain medicines, psychological and psychiatric help; antidepressants have played an enormous role in taking care of the cancer patient, not as kind of a site of a single disease, but as a human being in totality.

And I actually wanted to return to that history in this book and I paid a separate tribute to Cicely Saunders, this nurse from England, who sort of launched the palliative care movement. And Cicely Saunders had something very evocative to say about it. She said two things. One thing is she says - well, first of all, I want to emphasize the fact that palliation is not the negative of treatment. It's not the antimatter of chemotherapy. It's essentially part of the same problem-solving. You can't take care - even if patients who have a treatable or curable form of cancer, you can't take care of them without paying attention to the palliative aspects of their care. And the second thing she said, and it's not soft medicine. This is medicine as hard-edged, as real, as central to the care of patients.

So I think again, to come back to your question, anti-nausea medicines are just one of several different ways that we've learned to take care of patients who are undergoing chemotherapy.

GROSS: One of the forms of chemotherapy is the megadose form, where you harvest your own stem cells from your bone marrow. Stop me when I'm getting this wrong.

Dr. MUKHERJEE: Yes. Absolutely.

GROSS: And then once those stem cells are out of your system and aren't in danger of being killed by the chemo, you administer massive doses of chemo in the hopes of killing the cancer cells, and then when the megadoses of chemo are done you reintroduce the person's stem cells and, you know, hope for the best. What's the status of that treatment now? Is that still being used a lot? What kind of cancers is it considered most effective for?

Dr. MUKHERJEE: The major trials were run in breast cancer and then the trials were negative. And this was a - it's a very sad episode in oncology. You know, this episode actually is a recapitulation of the past in some ways. And it goes back to this old theory which is that if something is good then more of that something must be better.

And so the idea was that especially in the 1980s, the idea was that for breast cancer we just weren't trying hard enough. If we could increase the doses of chemotherapy, if we could muscle them up even further then we would finally eliminate breast cancer from the body. And, of course, the reason we couldn't do that so simply was essentially, the bone marrow of patients would give way and the patients would die of bone marrow failure.

And so the idea that grew out of that was well, what if we just took the bone marrow out, froze it, gave maximum dose of chemotherapy to breast cancer patients and then reintroduce the bone marrow back. Well, now we have a perfect solution. We can maximize chemotherapy and we can now also protect the bone marrow.

Unfortunately, of course, it didn't work and that story is told in the book. And it's a tragic, tragic story because there was a point of time when women and doctors were so convinced that this would work that they almost wouldn't participate in clinical trials. They said well, how can we possibly run a trial on something that we know has got to work? This story carries the memory of the kind of optimism that very quickly tips into hubris, which is so much part of the story of cancer.

GROSS: And one of the horrible parts about this story is that there is so much suffering involved with that treatment, because you basically have killed the person's immune system.

Dr. MUKHERJEE: That's right.

GROSS: So what did we learn from that experiment with the megadoses of chemo and the stem cell transplants for breast cancer patients?

Dr. MUKHERJEE: Well...

GROSS: Like, what were the positive results of that? Or were there any?

Dr. MUKHERJEE: Well, we learned that it didn't work and, you know, in medicine learning the negative is just as important as learning the positive, otherwise, you know, our field would be strewn with - we'd only report positive results and we'd never know what doesn't work, so that's the one thing that we learned.

I mean what else have we learned? We learned an enormous amount about the tolerability of chemotherapies, how much can and cannot be given to the human body. And also, I think philosophically or I think more sort of in the history of medicine, it represents a really important break because there's a point of time when doctors and scientists and patients have to tell themselves, you know, this strategy has reached a certain limit. That although these are important drugs, there is no denying that the drugs that were discovered during the 1960s and 1970s still play and will play an important role in the future of cancer. And yet, what we do learn from them is that these strategies have a limit and that it's really a call to us to invent new medicines to tackle this disease.

GROSS: The main character, so to speak, in your book is Dr. Sidney Farber, for whom the Dana-Farber Cancer Institute in Boston is named after. What was his role in discovering anticancer treatment?

Dr. MUKHERJEE: Sidney Farber was a pathologist. He, in the 1940s, he was called a doctor of the dead. He was - became particularly interested in childhood leukemia because he was diagnosing childhood leukemia, but he had no treatment for it. Children with childhood leukemia would live for about a week or two weeks, then they would die. It was a uniformly lethal disease. And so Farber became interested in an idea which he had known from other scientists, and the idea was that the growth of normal white blood cells is dependent on a vitamin called folic acid - a vitamin found in vegetables. And Farber began to wonder well, if normal white cells depend on the growth of folic acid, then the leukemia cells - leukemia is a cancer of white blood cells - the leukemia cells become even more dependent on folic acid? And so could he use an anti-folic acid, an antagonist of folic acid, to get remissions?

And so, a friend of his, an Indian chemist called Yella Subbarao, had a chemical like this. And so essentially Farber got some of these chemicals and he began to inject kids with these anti-folates and he found remarkable, although short, remissions. And in doing so, he sort of launched the history of chemotherapy and the idea that he could cure cancer with chemicals alone, and that's why he plays a central role in the book.

GROSS: Now he also plays a central role because he hooked up with a wealthy woman named Mary Lasker and together they helped get Congress to pass, and helped get Nixon to sign, a bill creating and funding the National Cancer Institute. This was in 1971. You reprint an ad they took out in the Washington Post in 1969 - December of 1969 that was headlined: Mr. Nixon, you can cure cancer.

Dr. MUKHERJEE: Yes.

(Soundbite of laughter)

GROSS: So this started the official War on Cancer. And yet, the medical community as you describe it was pretty divided about whether this war on cancer was a good idea. Why would you think it wasn't?

Dr. MUKHERJEE: Well, the medical community was divided in part because they - a lot of people, particularly the basic scientists thought that it was too premature to launch a war on cancer. That if you hyped up the nation and said well, we're going to launch - you know, one of the subtitles in that advertisement was: Why don't we cure cancer by America's 200th birthday? What a gift that would be. So you can imagine, there was a kind of an optimism, a kind of a hubristic quality about this advertisement. And the medical community, many scientists said it's just too premature. We don't know enough about the cancer cell. It's like launching a rocket on the moon without knowing Newton's laws.

GROSS: But didn't that money help scientists figure out what they needed to know to start progressing?

Dr. MUKHERJEE: Absolutely. Absolutely.

GROSS: I mean you have to start someplace.

Dr. MUKHERJEE: Absolutely.

GROSS: And so wasn't that infusion of money really helpful or was it not?

Dr. MUKHERJEE: It was very helpful. But again, the money had to be directed appropriately. And for a long time there was a big question about whether the money should be directed towards finding more of these poisonous drugs that basically killed cancer cells or should the money be directed more appropriately towards basic investigations to uncover the mechanism by which cancer became - cancer emerges - what's the right balance between those two ideas or those two mechanisms of funding? And I think eventually that right balance was found and the - it's the mechanistic understanding of cancer that's really transformed our understanding of cancer today.

(Break)

GROSS: Now you write about the infighting that was taking place in the '70s between therapists using radiation and chemotherapists. What was the fight about?

Dr. MUKHERJEE: The fight about - was what - you know, everyone was trying to find the best solution to cancer. And the surgeons, the chemotherapists and the radiotherapists all thought they had the right answer. Now as it turned out, none of them had the right answer, and also as it turns out, all of them needed to collaborate with each other to treat cancer. Or to give you an example, today breast cancer, particularly, is treated with every single one of those modes. You have surgery followed by radiation followed by chemotherapy followed by targeted therapy and that's what has allowed breast cancer to change from a very lethal disease to, in some cases, a chronic disease, which is much less lethal than it was 50 or 100 years ago. But it depends on an incredible collaboration between every single discipline or every single subdiscipline within oncology.

GROSS: Speaking of breast cancer, there was a period when radical mastectomies had become the preferred method of treatment. And I want you to describe like what a super-radical mastectomy was like in, would this be the '70s or the '80s?

Dr. MUKHERJEE: A little bit before that, super-radical mastectomies were beginning to be performed. So to remind ourselves, radical mastectomy is yet another theory of cancer in which, again, follows the dictum of if something is good then more must be better. Radical mastectomy was invented by several people, most notably William Halsted, on the theory that we weren't cutting enough. That somehow or the other, little minute remnants of tissue were being left behind, and that if we cut more, we would cure more. And so Halsted began to excavate deeper and deeper into the breast, to cut large amounts of the breast and the associated lymph nodes out.

And this edged further and further until you reached the super-radical, the ultra-radical mastectomy in which not only the breast but parts of, you know, parts of the collarbone or parts of the tissue under the arm would all be excised. It was like a macabre race to take out as much of the cancerous body as possible so as to cure women.

GROSS: And why was that discontinued?

Dr. MUKHERJEE: Well, it was discontinued because ultimately, trials showed that it didn't really help. In fact, as it turned out, even small tumors could metastasize elsewhere in the body and therefore, cutting more locally didn't save any extra lives. And it took - I mean this is an amazing thing, Terry. It took 90 years to reach that conclusion. It took 90 years before surgeons and chemotherapists and oncologists could collaborate with each other to launch the kind of trials that finally showed that radical mastectomies didn't improve survival by a month compared to a lumpectomy plus radiation or a local mastectomy.

GROSS: But people still have - oh a local mastectomy. Okay.

Dr. MUKHERJEE: That's correct. Yes.

GROSS: A lot of people still have local mastectomies.

Dr. MUKHERJEE: That's correct. People have local mastectomies. That's a, you know, perfectly reasonable decision, depending on the surgeons. But the radical mastectomy was not a local mastectomy. It involved a wide excavation of tissues, a removal of many of the chest muscles. A removal of many nodes, sometimes even more, as I said, sometimes more super-radical forms.

GROSS: Now breast cancer is one of the cancers that we know there's a gene, the BRCA gene. Actually, there's a couple of BRCA genes, right?

Dr. MUKHERJEE: That's correct.

GROSS: So how does that advance the possibility of treating breast cancer?

Dr. MUKHERJEE: Well, it advances in several different ways. But before we go into the advancements you have to recognize an important fact and I, you know, I just was recently reminded about this by Bruce Ponder, who came here from Cambridge to talk about the BRCA genes. You know, if you take all the known genes that we've identified which are responsible for breast cancer, we don't even get to 50 percent of familial breast cancer. In other words, if you take every known gene that's been identified as a risk factor for breast cancer, we are only scratching the surface of the number of genes that are involved in breast cancer. So BRCA1 and BRCA2 are just the beginnings of a story.

GROSS: Right. And is it helping to treat breast cancer?

Dr. MUKHERJEE: Absolutely, in two or three different ways. Number one is that if you happen to have BRCA1 or BRCA2, your siblings and your female children can also - and your male children - can also be found out whether they carry this risk factor, this mutation or not, and they can undergo a variety of things. They can be screened more intensively for the possible development of breast cancer. Or, in more extreme circumstances, women have chosen to undergo prophylactic mastectomies or prophylactic ovarian removals to prevent breast cancer. And both strat-- all those strategies work.

The final piece of it is that for the first time we're beginning to see targeted therapies that particularly attack breast cancers that are mutated in the BRCA genes. So this is - this takes advantage of the fact that if you have a mutation in the BRCA gene, then your breast cancer has certain proclivities that normal cells don't. And, in fact, there have been therapies that are directed against those proclivities, such that they now exploit the biology of the BRCA gene.

GROSS: If you're just joining us, my guest is Dr. Siddhartha Mukherjee. He's an oncologist who's the author of the new book "The Emperor of All Maladies: A Biography of Cancer."

You've just completed a biography of cancer looking at the history of cancer. I'm going to ask you to look ahead now a little bit...

Dr. MUKHERJEE: Mm-hmm.

GROSS: ...where your book ends. What are some of the strategies or medicines that you are most hopeful about?

Dr. MUKHERJEE: The few things that I'm extremely hopeful about is that I think the wealth of information that's coming out of the human genome and the cancer genome will eventually lead to a whole new host of new medicines. That's already started. I talked a little bit about Gleevec. We talked a little bit about the drugs that particularly attack cells that are mutated in BRCA1, for instance, and so forth. I think those are where the treatment is going.

Now that said, I think there's an equally important role of prevention and the book talks about this. I think even in prevention, we are moving in a direction in which we are integrating the insights of the genome into prevention. And by that, I mean instead of looking for carcinogens just in the environment using large epidemiological studies, we're beginning to look using more innovative ways to find carcinogens in the world. How do various chemicals affect genes? And you can all - you can do this in a petri dish. You can essentially ask this question: Do these chemicals mutate genes that are important in the development of cancer? And you can make more sophisticated variations of this. You can say well, okay, even if they don't mutate genes, do they activate certain genes? And all of this is occurring, remember, in a petri dish before this chemical gets released into the real world.

So this kind of questioning I think can be - is really beneficial because you could then potentially prevent putative carcinogens from appearing in the world. So I think those are among the most exciting things that are happening; targeted therapies, novel directions in prevention, and, you know, the incredible insights from the human and the cancer genomes.

GROSS: What kind of cancer breakthrough would you most like to see in your lifetime?

Dr. MUKHERJEE: Well, I'd like to see important breakthroughs in cancers that are tough to treat: pancreatic cancer, esophageal cancer, some variants of brain cancers. Those are, you know, if you think about cancer as a march of progress, as a kind of the Pied Piper, as sort of leading out into Hamelin, there are many cancers that have been left behind in that march. They're sort of frozen in time and metastatic pancreatic cancer, metastatic melanoma, some brain cancers are those. So I'd love to see those - at least something happen in those directions.

GROSS: You describe a scene that I found so interesting. You know, you talk about how your patients live in cancer world but you kind of live in cancer world too because you're so obsessed with treating your patients and with understanding how the treatments work, with learning the history of cancer for your book. So there you are with your wife in the delivery room. She's delivering her first baby.

(Soundbite of laughter)

Dr. MUKHERJEE: Yeah.

GROSS: You've got your scrubs on, you're asked to like cut the umbilical cord and what goes through your mind?

Dr. MUKHERJEE: Well...

(Soundbite of laughter)

Dr. MUKHERJEE: ...I'm trying to cut the umbilical cord, but on the flipside of my mind, it's almost a split of my right brain and my left brain, and here I am in sort of the most glorious moment of my life, the birth of my child, and on one side of my brain I'm saying to myself, I have got to harvest her umbilical cord blood cells because these cells are useful in transplantations for kids who have leukemia. So here I am, as I said, it's literally experiencing a split brain syndrome in which I'm trying to be present emotionally in the birth of my child and yet cancer is flitting on - back and forth in my mind and I'm trying to harvest her umbilical cord blood cells in case, you know, I can bank them for a future transplant for other kids with leukemia.

GROSS: Now what happens typically to the umbilical cord blood cells?

Dr. MUKHERJEE: You know, it's often, and this is the tragedy of it, it's often flushed down the sink and often not collected all. I think, you know, we absolutely need to have better centralized banking facilities free of charge which allow us to bank these cells because kids with leukemia can benefit from cord blood transplantation and they need these - these are very precious cells.

GROSS: Why are they so precious?

Dr. MUKHERJEE: Well, because they contain blood-forming stem cells that can go into the blood and create new blood. And they are so precious because they can be transplanted into another child and give rise to the blood system of the child and you can therefore eliminate the leukemia. And if you eliminate leukemia you can often eliminate the normal - the child's blood stem cells and you can replace it with the cord blood from another child, and that's why they're incredibly precious.

GROSS: So were you able to harvest the blood stem cells from the umbilical cord of your baby?

Dr. MUKHERJEE: I was able to harvest the cord blood cells. But I was also able, thankfully, at the end of it all to enjoy the moment of childbirth.

GROSS: Thank you so much for talking with us.

Dr. MUKHERJEE: Thank you so much. It's a real pleasure.

GROSS: Dr. Siddhartha Mukherjee is the author of the new book "The Emperor of All Maladies: A Biography of Cancer." You can read an excerpt on our website, freshair.npr.org, where you can also download podcasts of our show.

Coming up, the controversy over whether Jane Austen's syntax and punctuation are really hers or an editor's. Our linguist Geoff Nunberg weighs in.

This is FRESH AIR.

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