>> rose: welcome to our program. we begin tonight with siddhartha mukherjee and a remarkable new book called "the emperor of all maladies: a biography of cancer." >> cancer is like a car. when the car works, the cancer cell is like a car. when the car works properly, it's accelerator and brakes are very much a fundamental part of the car. you can't imagine the car without acceleration or brakes. yet if you jam the accelerator inappropriately or if you snap the brakes inappropriately, then this car-- which is adapted to accelerate and stop-- begins to become unable to accelerate and stop. >> rose: it has a life of its own. >> exactly. and you've got to admire the extraordinary mechanism that's inside every one of our cells that allows this automatic process or acceleration and braking to happen normally. the fact that we grow up as these incredible multicellular

organisms, sometimes i say to myself, it's extraordinary that we're not exploding with cancer. >> rose: we continue with a new movie called "love and other drugs" with the actors anne hathaway, jake gyllenhaal and the director ed zwick. >> one of the things that set this is film apart is that the stakes are so high and because the stakes are high you're able to get more complexity of character and, i don't know, you get to explore that between us. and delve deeper. as a result i think the film is a more enjoyable experience to watch. >> i think it was... it's very different. and it felt like a real strength that i had never really put on to film before. you know, i had never been able to be funny or have my.... >> rose: using different muscles as they say. >> yeah. i mean, it's worked in my everyday life. i don't like to take myself too seriously everyday. but for a long time i tried to in films and i think this is the better way to go. i feel that way. >> rose: it felt just the most

wonderful opportunity to talk about love and i find that the descriptions of love in movies these days are so overly simple. >> rose: yeah. >> and they've become this really reductionist genre and this was talking about the complexity of love and mistake of love and how serious it can be and how seriously funny. >> rose: siddhartha mukherjee, anne hathaway, jake gyllenhaal and ed zwick when we continue. maybe you want school kids to have more exposure to the arts. maybe you want to provide meals for the needy. or maybe you want to help when the unexpected happens. whatever you want to do, members project from american express can help you take the first step.

vote, volunteer, or donate for the causes you believe in at membersproject.com. take charge of making a difference. captioning sponsored by rose communications from our studios in new york city, this is charlie rose. >> rose: almost 40 years after president nixon declared war on cancer in 1972, the disease is more common than ever. it is now estimated that one out of three american women will get cancer during her lifetime and one out of two american men will get cancer in their lifetime.

in some countries, it has already surpassed heart disease as the leading cause of mortality. joining me now is dr. siddhartha mukherjee. he's a cancer physician and assistant professor of medicine at columbia. the new book is called "the emperor of all maladies: a biography of cancer." drawing upon his own experiences with patients, he presents a textured portrait of the disease and its 4,000 year history. i am pleased to have him here at this table for the first time. welcome. >> thank you so much. thank you. >> rose: why did cancer need a biography? >> well i started writing this as a history of cancer. the book really grew out of a question a patient had asked me. and the question was... she was a woman who had been battling abdominal cancer and she said to me "i'm willing to go on but i need to know what it is that i'm battling. i need to know what i'm fighting." so the book is a 600 page... >> rose: answer to her question. >> an answer to her question. but the word "history" which is how i originally had imagined the book, a history of cancer

which is in some ways what it is seemed too inert. because as i was writing the book i was taking in the stories of patients, my patients, the history of patients and it really seemed i was sort of looking not at something but at someone and hence the word biography. >> rose: are first-known cases of cancer? >> we know very little about the ancient history of cancer because we don't have the tissue. we only know it metaphorically from writing and we can only surmise when this history begins. the very first time the history begins goes back to the oldest surgical and medical textbooks that we possess as human beings, and one of them is the book first written about 2,500 b.c. and there's a description of what might be a case of breast cancer, but we don't know. >> rose: when do we know? >> well, we don't know until much, much later. i mean, the word "cancer" again, it's a very rich metaphorical word, comes from the greek. they call it cancer because hippocrates famously thought that the lump of cancer, the

tumor, was like a crab under the skin. it was a crab and hence the cover. and the blood vessels that were around the cancer, the tumor, were like the legs of the crab and the crab was dug underneath. much as you might find when you go to the beach you might find a crab under the sand and you can only see tim presentation of the crab, the shadow of the crab. so hence the word cancer. but even what hippocrates called caer may or may not have been cancer. again, we don't know until the 18th or early 19th century when we describe the disease in cellular terms. that's when we really know it's real cancer. >> rose: so a patient says to you "doctor, i've been diagnosed as having cancer." >> yes. >> rose: what is it? >> well, i think the fundamental thing that it is is that it's a pathological proliferation of cells, occasionally cells that don't know how to die, but certainly cells that don't know how to stop dividing. and that pathological proliferation of cells is a process that starts up typically in a single cell and it goes and multiplies over and over again

and every generation produces kind of a little evolutionary cycle such that you get more and more evolved cells. that's what cancer is. but that said, i would immediately stop them and say "but every different cancer has a different face." so although there's a deep commonalty between this very different kind of cancer, prostate cancer, breast cancer, leukemia, although they're connected at the cellular level, i would also say that they're very, very different faces and, again, hence the term "biography." this is an object with many faces and it's an attempt to try to reconcile these very different kinds of faces of cancer. >> rose: and many causes for each cancer. >> absolutely. >> rose: many genetic causes for each cancer. >> genetic and environmental causes for each cancer, absolutely. >> rose: and you believe that we will find prevention? cure? >> i'm optimistic about the fact that we will find preventative mechanisms and cures for some cancers. i don't think that there will be a single magic bullet. again, remember, in the 1970s there was this idea-- actually

it's an old idea from the 19th century-- that there would be a single magic bullet, the so-called penicillin for cancer. this phrase was bandied about a lot and it's really been laid to rest, i think. we will never find a penicillin for cancer. that said, we will convert some cancers into chronic diseases during our lifetimes. we already have, actually, to some extent. >> rose: part of your technique here is to personalize it. >> yes. part of the writing of the book for me... for me, the book would only be written if it became a journey of my own discovery. and part of that discovery always was who's the patient? where is the story of the first patient? the first man? the first woman? and let me tell you one very quick story, which is sort of a metaphorical story, very central to the book. i became obsessed with finding the very first patient that sydney farber treated with chemotherapy. actually, one of the first patients in the history of medicine to be treated with chemotherapy. and all i knew was his name was r.s. i knew nothing about him. i knew he was in boston and he

had leukemia, he was two years old. and i began to look for r.s. because i needed his story to write this book. and i tried to send out e-mails through list serves, nothing. so i got dejected and i took to delhi, to india, where my parents live and someone said "this famous medical biographer of cancer lives a few doors down from where i live in india, this is, again, a thousand miles away from boston. and i went to him and i said i'm interested in this story and he said oh, i went to sydney farber's clinic 1950 and i have a roster of these patients treated in 1950, would you like that roster. so here i was a thousand miles away from where i thought i would find something and i found the name, i ran back... i mean i flew back, but i sort of ran back to boston and i could then find r.s., his name turned out to be robert sandler, and i could find a picture of him in the saturday evening post from boston and i could find his house. and about 15 minutes later i was

standing in robert sandler's house. so for me that was... became metaphorical for writing the book. it became a... because i today myself, well, the only way this book is going to be written is if i find story upon story of these first patients. where are where were they? where did they live? and i had to go to those places in order to write the book. >> rose: it also gives you a narrative. >> it gives you a narrative. in fact, the book is dedicated to robert sandler who lived for three years. and it says "to robert sandler and those who came before and after him." because he begins the journey. >> rose: you went to oxford you're a rhodes scholar. >> uh-huh. >> rose: how did you go from oxford to medicine? >> actually, i had already applied to be in medicine before i went to england, actually. the rhodes came as a benign and very welcome boon of lightning to me and so i decided to take a detour and medical school was militia than happy to oblige. >> rose: were you better off because you had that addition to your own liberal arts education?

>> i was. at oxford... i went to oxford initially thinking i'd study philosophy but then i studied cancer biology, cancer immunology. so already, you know, in some ways i came to medicine in the opposite direction. i didn't start medicine with patients, i started medicine with cells. and that actually inform this is book in very complex ways. the idea that you could begin from the microcosm and expand out to the macrocome, from cells to patients, literally, is an important element to this book. so i thought my own journey from oxford to studying cells under the microscope to being struck by seeing the first patient in medical school was an important personal journey. >> rose: that that the book is finished, what's your obsession? >> (laughs) i'm back in the laboratory. the nice thing about being a draw doctor, being in a laboratory, is it keeps you humble. i was telling someone the other day, i'm on the book tour but on the 23rd i open the book somewhere and then i fly back and i'm immediately on call for

being at columbia because it's thanksgiving weekend. so, as you know, medicine doesn't wait for anyone. and it's a very good reality check before you get too crazy about your own book. there's always the patient waiting for help and opinions. >> rose: is there something really remarkable about cancer cells? >> it is an astoningly adaptive moment that allows a cancer cell to come out of our bodies. you know, the seminal discovery which i noted in the book, the seminal discovery of cancer biology is that typically-- though not always-- typically cancer is caused by the activation of genes that are already in each and every one of our cells. now, when that discovery occurred... >> rose: the activation? >> the activation or inactivation of genes that are already present in every cell. so it's not as if cancer occurs because some virus... typically. there are cases that are certainly that. but not as if cancer occurs because... >> rose: go ahead.

because something turns on? a cell... >> inappropriately, or turns off inappropriately inside every cell. but the things that are turning on and turning off are genes that have profound normal functions in every cell. so in other words, it's, again, the analogy has been made the that cancer is like a car. when the car works... the cancer cell is like a car. when the car works properly its accelerator and brakes are very much a fundamental part of the car. you can't imagine the car without acceleration and brakes. yet if you jam the accelerator inappropriately, or if you snap the brakes inappropriately, then this car-- which is adapted to accelerate and stop-- begins to become unable to accelerate and stop. and that's of course... >> rose: and has a life of its own. >> exactly. and you've got to admire the extraordinary mechanism that's inside every one of our cells that allows this automatic process of acceleration and braking happen normally. the fact that we grow up as these incredible multicellular organisms.

i mean, sometimes i say to myself it's extraordinary that we're not exploding with cancer. it's an extraordinary adaptive moment in our evolving as multicellular organisms that these accelerateors and brakes don't get broken all the time. and therefore you have to admire what an extraordinary thing it is when this event does occur inside a human body and eventually a cancer cell does grow out. >> rose: what's the key to finding a cure and/or treatment? >> well, the key, really, is to go back into the fundamental biology of the cell. it's to return back to the mechanistic understanding of what cancer is and to find out, well, what are the mechanisms? what are the accelerateors and what are the brakes and how do those accelerators and brakes, to use this nalg, differ from breast cancer cells to leukemia cells. so to find the exact alterations. >> rose: have we found it in any particular cancer? >> well, we've found in the many cancers. the pictures is still incomplete but we found in the many

cancers. we know, in fact, the cancer genome project, which is really the on verse of the normal human genome project is precisely directed to asking this question. just to remind you, the cancer genome project is, of course, a catalog of... producing a catalog of all the mutations that occur in the cancer cell compared to a normal cell. so when you have that entire catalog laid out, you can say well, this breast cancer haass mutations in gene x, y, z and a. this other breast cancer cells may have mutations in genes p, q x, and z. and thereby recategorize the entire universe of cancers in terms of these fundamental genetic changes to genetic mutations. >> rose: so what happens when you have something like gleevec? >> amazing things when you have a discovery like gleevec. you have this targeted drug and that goes in and kills every single tumor cell but happens to spare every normal cell in the body. there's a lovely analogy made in the book with roger banister's

running of the four-minute mile. four generations people would say you can't run a four-minute mile. that's not because you're not running fast enough it's because the human lung is fundamentally designed such that you can't run faster than four minutes. or the human muscle is fundamentally designed, sets a natural limit. of course the same thing would be said about cancer. they would say you never find any specific therapy for cancer, you have to use these poisons because cancer cells are too similar to normal cells. and into this world bursts a drug called gleevec. and gleevec is exactly that. it's a drug that can go and target that mutated cell and kill it while sparing every normal cell. >> rose: if we do it one time, why can't we do it... >> well, that picture i just painted is a little bit simple because in some cancers, like c.m.l., leukemia, the leukemia that happens to be targeted by gleevec, in fact, the driving

gene, the driving mutation, the accelerator, if you will, is well known, well characterized. in other cancers it might be much more complex. it might be several accelerateors that are broken and several brakes that are missing. and if that's the case then imagine finding a drug to each one of them. that gets pretty complex. >> rose: everybody says early detection is important. what makes it important? >> well, what makes it important is that cancer is a disease that metastasizes and it's actually typically... not always but typically metastasis that kills patients. it's metastatic cancer that kills patients. if you can track the cancer in its earliest form before it moved elsewhere in the body. if you can get the crab while it's still locally under the sand and you can remove it, you essentially have the capacity of being cured. >> rose: and that's what happens? >> that's what happens when an early tumor is detected by a mammogram, for instance. what you're trying to do in a mammogram is you're trying to say that's a very early stage cancer, let's take it out before

it spreads. the reason that doesn't work all the sometime that even small tumors can spread. so size makes a difference. early stage tumors can be detected by mammograms but not every small tumor is in an early stage. it may have spread and therefore metastasized outside the breast. >> rose: where are we in still cell therapy? >> well, the answer with stem cell therapy is one of the things that's very striking about the new biology of cancer is the analogy between cancer cells and stem cells. by that i mean the genes that happen to drive many forms of cancer happen to be also active in certain adult and embryonic stem cells. so so there's an analogy here. and it's this analogy that's being deeply explored in the laboratory to try to find out could we take the insights that are coming out from stem cells and apply them to cancer cells? >> rose: and? >> and the answer is well, yes. yes they are. i can give you a couple of examples.

there are genes that actually very active part of our laboratory and other laboratories explores the gene that actually is very fundamentally involved in fruit fly embryo genesis. and when you look at that gene and what happens in cancer... it's highly active in cancer cells. so it's a reminder, not only a biological reminder but a political reminder that evolution is connected. and what's worthwhile in fruit flies is very important in a cancer cell. we're trying to find mechanisms to attack those genes right now. >> rose: if you look back over the next 20 years, could we have done things that were obvious and didn't do beyond spending more money to have brought it to... brought us to a much better place? >> absolutely. well, let's just talk about the question of money for one second. so, you know, the ens eye budget is $5 billion give or take a little change. now some people think that's... think that's an enormous amount of money. just to give you a contrast, we spend $900 billion on the war. so the war on cancer is a pittance compared to several

military campaigns that the country has run and is continuing to run. so let's put that into perspective. >> rose: and how many people does cancer kill in 2009? >> 600,000 men and women in america alone. >> rose: 600,000. >> right there. you have the number. could we have done something different in hindsight? the answer is yes and no. we could have been... the 1972 war on cancer was launched with a lot of optimism. the slogan was "let's find a cure for america for its 200th birthday. what a great gift that would be." there's a kind of hubris in that statement. there's a kind of optimism in that statement, of course, but also hubris in that statement. and i think that hubrisic quality was the problem. scientists withdrew from the battle front because they thought that they had somehow... that the implication was that this was a cytotoxic war, a war

in which you put lots of poisons in and thereby find the penicillins for cancer. and that was not the case. that is not the case for today. so in hindsight i think the hubristic optimism would have been dampened and people's expectations could have been more adjusted. >> rose: were there ever steps in which people were on the wrong track and had to come scampering back to the right direction? >> absolutely. the book is about many such steps. i'll give you one example. the famous radical mastectomy arises from the notion if something is good than more has to be better. >> rose: right. >> so in the 19th century the idea was that if you could take... if a breast tumor was discovered, then you would do the most radical surgery possible, excavating not just the breast but the tissues around it, the muscles, actually in some cases the collarbone to try to stave off cancer. it took 90 years to disprove that theory. 90 years and hundreds of thousands of women's bodies to disprove that theory. part of the reason was who would opt for non-radical surgely.

the word itself became a conceptual trap. if you were given the option, well, mr. rose, we're going to do the option of radical surgery versus nonradical surgery for cancer, which would you choose? >> rose: radical. >> exactly. >> rose: make sure you get it. >> exactly. but it was actually patient advocates who began to question and say why haven't we run a trial of this? why is it that we're just sort of saying this must be the right approach? why haven't we run a tribal. betty rollins famously said wait a second, this is a radical procedure occurring on women's bodies. why don't we go back and revisit and put it to a clinical test. and the clinical tests were done and it was absolutely negative. there was no difference between a local mastectomy, between that and radical mastectomy or lumpectomy, the radiation and even less radical surgery. >> rose: relapse happens. >> yes. >> rose: why does it happen? >> the quick answer is we're not sure. it happens because of several mechanisms. one of them is, of course, the hall said the meckism?

which is that the tumor hasn't been exa separated enough. we haven't taken it out. that's local relapse. the second is that cancer cell grow resistance to drugs. so that's relapse of resistance. perhaps the most controversial and most interesting idea being advanced and i've written about this a little in the book is that cancers also possess stem-like cells. so these are cells sort of like the roots... >> rose: smoking is a cause? >> absolutely smoking is a cause. >> rose: every doctor says that. >> yeah. >> rose: not that there's a question about it. their reaction is exactly like yours. >> yes. yes. someone recently asked me, well, what preventative things should i do in order to... what five preventative things should i do in order to not get cancer. i said stop smoking, stop smoking, stop smoking, stop smoking, stop smoking. >> rose: and there are certain stories about that. if you have not smoked for ten or 15 years then... >> well, there appears to be the situation where if you stop smoking for several years, you actually revert back your risk

somewhat to the normal range. in fact, even if you are smoking it's important not to be nihilistic about it and say well there's more to come and that's stopping, quitting, can make a difference to your prognosis. i mean, the story of how smoking got discovered ooze a... how tobacco smoke got discovered as a carcinogen as told in this book is an amazing story. >> rose: what's the story? >> well, the story is that smoking had become so common at one point of time that you couldn't discern a link between smoking and cancer. it was like as richard pito, the epidemiologist said to me, it was like asking is there a link between sitting and cancer? every sits and some people get cancer so how could you run a study to discern the link between sitting and cancer? so it was the two scientists... actually, two pairs of scientists, winder and graham in america, and dole and hill in england who really uncovered this link. winder and graham are very interesting characters. graham was an important surgeon. he actually had devised a

mechanism. he invented the removal of the lobe of the lung for lung cancer. and when ernst winder, a student went up to him and said "do you think there's a link between smoking..." you know? know, smokeing is going up, lung cancer is going up. could there be a link? and graham said "so has the use of nylon stockings." how could there possibly be a? it's become invisible. and it was through these careful epidemiological studies in which they followed doctors-- a group of doctors-- prospectively over time that they began to discern the link that those who smoked died of lung cancer while those who didn't smoke didn't die of lung cancer. so it was an incredibly careful epidemiological study. >> rose: what's the most deadly cancer? >> well, the list of culprits is quite nasty. but, you know, among the big ones these days, pancreatic cancer. >> rose: why is that? >> well, again, we're not sure we know. part of the reason we think is that for some reason

chemotherapies or even other drugs don't seem to get into these tumors very easily. so one reason has to do with that. but that's not the only reason. there are other reasons as well. the genetics of this tumor are probably quite complex. many, many different accelerateors and brakes broken, as it were. so getting therapy against this tumor is another problem. the third reason is it's very insidious. it often doesn't get detected. there's no easy detection test. it's not like you have a mammogram for pancreatic cancer so it prevents in advanced stages. >> rose: is there any hope we will have some kind of detection system? >> well, absolutely there are hopes that you can have detection systems and they already abound. there's colonoscopy for colon cancer, mammograms we talked about. as recently as very, very tantalizing study which was halted early because it was so strikingly positive from the national cancer institute which looked at high-risk smokers and asked the question if you do cat scans in these smokers can you

detect lung cancer? and the study was strikefully positive. you can detect early stage lung cancers and increase survival. you don't need a tissue, just a scan. >> rose: and where are we on understanding how frequent you can take scans and how frequently you can't and what's the radiation impact? >> the radiation impact is sizable. it's worthwhile thinking about it. if you go to the national cancer institute web site, which describe this is study, it raises the question, how often should we be doing these scans because there's a real risk of radiation so like any other story in this book it has to be balanced against what the risk factors are. >> rose: are we looking at some possible technological break through that we're working towards that may happen which will give us a leg up? >> absolutely. we're looking for those technologies. but that rirdz... let's talk about the substructure of technology. the substructure of technology is getting people interested in science. the substructure of technology

is how do you create technologies that will allow us to battle cancer in the future? that's a challenge facing us as a nation. one last point is that technology can be more complex than a c.a.t. scan or it can more complex than a new medicine. very famously i profile cecily saunders, the woman who invented... i would say invented palliative care. palliative care is also a technology. it didn't exist and a british nurse turned physician had to launch a movement because again the 1960s the hubristic optimism about curing cancer was so dense that someone had to say wait a second, who's going to take care of patients? who's going to take care of pain? how are we going to take care of men and women who have no hope in terms of cure and make them live dignified lives through the end? that, too is technology, right? and so one of the things that we learned from this book is that

technology comes in many, many different forms and each one of those forms has to be invented. >> rose: as you may know from the brain series that we do here we always ask this question. >> i love that series. >> rose: (laughs) thank you. what is the one question you most want to find the answer to? >> well, the one question that i think is really burning right now is how one converts the wealth of genetic information that's slowly coming out of these cancer genome projects into therapy and prevention mechanisms. how does one do that and what is the best way to engage a new generation of which xheplists to make new drugs. can we invent new mechanisms which we can find early signs so that we can prevent cancers? can we essentially create preventative mechanisms that live in a petri dish that we don't to launch norm mouse epidemiological studies until the cancers come out in the population to say, oh, my goodness, it must have been asbestos, or oh, my goodness, it

must have been smoking. so i think in every direction prevention and therapeutic direction we need to try to find out how to connect the wealth of information from this project towards finding prevention and therapy. >> rose: "the emperor of all maladies: a biography of cancer," siddhartha mukherjee, thank you. >> thank you for having me on the show. >> rose: extraordinary book. >> rose: "love and other drugs" is ed zwick's new movie. it's loosely based on the book "hard sell: the evolution of a vagary salesman" by jamie ready. set against the backdrop of the pharmaceutical industry of the late 1990s, it's the story of a drug salesman who falls in love unexpectedly with a woman with early onset parkinson's. here is the trailer for the film. >> hay, lisa. her >> her name's not lisa. but if every time i say hey lisa she'll think i dated a girl who looked just like her. she'll develop this unconscious need to win my approval and from

then on it's cake. >> damn. >> why would you want to be a pharmaceutical rep? >> it pays over a hundred grand a year, that's why. >> hello, ladies. hello, gorgeous. wait, there's another one. >> if the patient asks, your name is turn. >> i'm dr. knife. >> and who are you? >> jamie randall, internal. >> let's have a look. >> you let me take my shirt off! >> wait! okay, i apologize. let me take you out for a cup of coffee. >> strong eye contact, implied intimacy. you're good. >> are you always this mean? >> actually, this is me being nice. >> you have beautiful eyes. >> that's it? that's the best you got? this isn't about connection for you. this even about sex for you. this is about finding an hour or two of release from the pain of being you. and that's fine with me because all i want is the exact same thing. ♪ show me how you do that... >> why don't you have a boyfriend he? >> i just keep it simple. >> i could do that.

>> hello? >> i like hearing the sound of your voice. >> you like hearing the sound of her voice? were you abducted by aliens? >> i hear we're coming out with a new sex drug, viagra. i want it. >> this is a revolution. >> i've already sold 2,000 prescription this is month alone. >> hard to believe, isn't it? hard to believe. (laughs) you're a good man but you're on the fast track. can't do that with me holding you back. >> she rejected you! that's why you wanted her. >> i need you. >> i need you more. ♪ stay with me beautiful girl stay with me ♪ beautiful girl

>> i'm sorry, i know it's so late. >> oh, my god. >> oh, my god! >> whoa! get her out! >> rose: joining me now is the director ed zwick and co-stars anne hathaway and jake gyllenhaal. i am pleased to have them here to talk about this movie. so tell me about just sort of organizing this movie. what made you want to make it? what was the book that turned you on about this book? >> it felt just the most wonderful opportunity to talk about love and i find that the descriptions of love in movies these days are so overly simple. >> rose: yeah. >> and they've become this really reductionist genre and this was talking about the complexity of love and mistakes of love and how serious it can be and how seriously funny. >> rose: and what's the complexity of love in this film? >> oh, so you're going to start off with the softball one for me. (laughter) >> gosh, we've been talking about it so much lately. and i think that... >> rose: about the complexity of

love? >> the complexity of love. yes. but we've also been talking about the nature of the film and how a lot of people have been called it a rom-com. but i don't know it expands upon the idea of what a rom-com would be... >> rose: that's short for romantic comedy? >> yes, sorry, i should have... i will not use any more abbreviations for the rest of the interview, charlie. >> rose: (laughs) >> and one of the things that set this is film apart is that the stakes are so high and because the stakes are high you're able to get more complexity of character and you get the explore the free form between us and delve deeper and as a result i think the film is a more enjoyable experience to watch. >> rose: what's the magic of their relationship? >> huh. i think actually it's resistance that creates the magic of their rerelationship. it's their denying or wanting to deny any type of intimacy.

and i think they're both into purely sex. and then ultimately... you know, think about complexity of love and i couldn't help but look at you. (laughter) just watching the trailer, she's watching herself and it's as if she's going play by play watching the monitor on set or something. she was mimicking her own facial expressions. >> i just want to go back to the pleasure of pittsburgh. >> rose: are you rethinking how you did it? every time you see it are you judging yourself harshly? >> can't i do both? (laughter) i don't know. i just think it kind of... it's a sense memory thing. i mean the other day we had the premier in los angeles and there was a scene and i couldn't tell... and i was crying during the scene and i couldn't tell if i was crying because i was moved or because i was crying actually on screen at that moment. i don't know. >> rose: so tell me more about your character and then we'll come back to this. >> he starts off as a... what did we call him at the beginning

of this? he's really a womanizer. callow. >> rose: a seducer. >> a callow seducer. and little does he know that's a skill in the pharmaceutical world. (laughter) and so he becomes a viagra rep. >> rose: not a quality, a skill. >> yes. and he becomes a pharmaceutical rep and then he happens to be there right at the invention of viagra and he becomes... >> rose: so it's set in the 1990s. >> '96, right. and he happens upon this girl mag ghi a doctor's office while he is doing what they call a percentorship which is essentially bribing a doctor to get in to sell him drugs. he meet this is girl. >> rose: pick up on that and who your character is and why she's in the doctor's office. >> the reason my character is in the doctor's office, my character is maggie murdoch. she has stage one early onset parkinson's. and she just had her apartment burglarized so she's out of midz and she needs a prescription really fast so he goes to see

the first doctor who will basically see her. >> rose: take a look at this. this is jake who plays jamie tells maggie-- anne-- that he loves her. here it is. >> are you okay? your heart's beating really fast! jamie, jamie, jamie, talk to me! >> oh, i... i love you. >> what? >> oh, god. >> no, no you don't. >> don't touch me! okay, up, do you want a glass of water? >> i'm sorry. >> it's fine, water, water. >> oh, yeah. >> okay, see, here you go. here you go. >> i love you.

>> stop saying that, okay. >> i can't. i love you. >> um... >> you don't understand. i've never said that to anyone before. >> up... i once said it to a cat. >> okay. you can hold me now. >> rose: is this your first romantic comedy? >> yes. yes. >> rose: is it different? timing and all of that stuff? >> yeah. i think the humor. in terms of rhythm i think what i discovered... what i knew when annie and i first worked together on "brokeback mountain" was that we were both sort of musical actors. we were both really rhythmic. and i think we just... ed sort of shined a light on that so this seedling between us grew into a large tree. (laughter) comedic, romantic exceed dick tree. but i think it was very different. and it felt like a real strength that i had never put on to film before. i had never been able to be funny.

>> rose: using different muscles as they say. >> yeah, it's worked everyday in my everyday life. i don't like to take myself too seriously everyday but for a long time i tried to in films and i think this is the better try go. i feel that way, at least. >> rose: why him? when you decided to cast this? >> i think i had a privileged view. >> rose: what was the? >> i think i got to know him. i saw things that maybe he had not yet had opportunity or been inhibited to reveal and part of it had to do with that charm and those comedy bones and self-deprecating humor and all the things that sometimes actors are i think so concerned. i find male actors most of all so concerned with demonstrating just how serious and intense they can be. and to take his craft and apply it to something of himself which is that innate sort of charm. that is really what i was looking for. >> when i think about it, too. i grew up watching dan any kaye

was one of my favorite actors to watch. my mom would always... he was... i would mimic him and when you watch fred astair on... with these types of... hepburn and tracey, those are things i grew up with. those are movies that my parents played so i think it just sort of brought me back to the things i love. what acting was and i neat like we moved away from a little bit this sense of comedy even within the drama and it's hard to play and it's found play and it's real acting. >> but the difference is more of the rhythm you were talking about in terms of you have to have a certain rhythmic sense because comedy demands time. >> yes. yes. when we... even in our interchange even as people she and i kind of get off-- for lack of a better phrase--. >> rose: (laughs) i like that one. >> ...on each other intellectually. >> i like to get off on jake intellectually. (laughter)

>> rose: if they get off on each other, you've got a lot going, don't you? >> you bet, you bet. >> rose: (laughs) >> and you can't fake it. what is chemistry? it's a word everybody uses but nobody can create. >> rose: it's getting off on eacheer intellectually. (laughter) >> i now have a definition which i can use in other interviews. >> rose: but this is a real subject. the idea of whether... can two actors really make it happen if it's not something from? >> i think they can create a semblance of it, but i think there's something on the part of an audience when they intuit the real thing and i think it's some... seeing some inner life in each other. some fascination, some utter excitement and even something vaguely competitive. something competitive internally and with each other that is pushing each other. almost like playing tennis with you. >> i've seen actors sabotage each other, that's for sure. and i've been involved in that. >> me, too. >> and i think... with us that sense of competition is always a

oneupsmanship. and once one person takes the next one to the level it's exciting and we want to go higher. >> the one upsmanship is a positive thing because i don't know if i can go higher than this but if you can that gives me a reason to try. one of the great things about working with jake is i just enjoy listening to you. it's captivating. that's the intellectual getting off on each other. >> i like listening to myself, too. >> we took two very intense weeks and just really got to know each other. it was on the word and off the word. >> rose: doing what? just hanging together and itself ising around a table doing readings or... >> a lot of takeout food. a lot of talk about our lives. looking at films. >> explore that for me. directors i know are people who do just that. mix nichols told me he has people reveal themselves in some way. >> and i think that's a perfect description of what it was. >> we talked a lot about very intimate things it's hard to say but it finds itself in the

d.n.a. of the film. that trust and comfort. >> trust is what it creates. >> we talked about what turned us on sexually. >> rose: (laughs) are you serious? >> yes. what didn't turn us on. >> it's an interesting idea and i think people who teach leadership talk about things like this. >> i once heard the most wonderful story about mike nichols that he wanted to learn to watch by... neil simon wanted to learn to directly watching mike nichols but all he talked about was their children and where they ate for dinner and yet somehow the play got better. >> so. >> rose: what does a director do to make sure that you will be able to hopefully make the movie in your head? >> boy, i think it's really about trying to create some circumstance to carve away, push away the entropy of life and create a sacred space in which these magical creature cans do what they do and facilitate that and sometimes it means a goad

here and a push there and i used to be much more overdetermined in that but i think it's really now about... gee, it's... it's so inneffable. it's really about an exchange. it's an exchange between my intentions and my ability to let go of all those intentions and try to see what's really happen and try to just mold that in some way. >> rose: you made us face embarrassment over and over again in the process. you have to be game to open like that. when you're working with someone like ed, you... the list of leading actors he's worked with is kind of extraordinary. and so the performance he's gotten from them is pretty extraordinary, too. so to know that you have... you're going to be pushed and you have to be game to be pushed. you have to be an actor to be ready. i keep saying be embarrassed but

it's very important to go beyond what you know and he somehow... >> rose: gets you out of your comfort zone. >> every single time. we were in rehearsal once and i remember him making me sing a line. because i wasn't getting it. the music from the line wasn't happening and he said... >> rose: this is in this film? >> this this film. he just said "i don't feel the history in the line. i don't feel like you've... it's something that you have heard since you were a kid" because it's a line where i say i can recite the six pernicious anemia... medical jargon. he said, i don't believe your character, he said sing it. and it was me and annie and ed and i remember annie just looking at me and i said "i'm fine, i'll take it home and work on it." and he said sing it. and we sat there for 15 minutes and i didn't sang it for 15 minutes and it was utter embarrassment until i did sing it. and the singing of it was nowhere near as embarrassing as

i thought it would be. but it was a torturous 15 minutes. >> rose: did it get the line that you wanted with a sense of the authenticity of the family? >> absolutely. absolutely. but it's about... it's not even about the line. it's actually about fleeing yourself of the inhibition and, yeah, he did. >> what kind of directing maximizes your performance? >> well, ed did something extraordinary, he said it really beautiful about creating the entropy of life. oh, my goodness. poet. (laughter) but one of the things that ed does that was remarkable on this film in particular because we were working at such a clip and we had to delve into some really big feelings working at a pace, he removed all sense of time. and one thing that really helps me is just we talked about that trust and what i learned on this film was that really establish that trust and it's okay to

fail. it was okay that each scene wasn't perfectly as i had intended it. sometimes it became something more because it had no... took a left turn somewhere. and we wind up in a different place and it was more beautiful because jake and i shared it because ed believed in it. and as a result i wasn't what i intended but it's just its own thing that was wonderful. i had that experience with ed and i had that experience jonathan demi on "rachel getting married" with where the film had... there was so much respect surrounding the film and so much respect surrounding the process of what it is to be an actor that it was its own world that was fluid and safe and creative and it winds up feeling like a really intense form of make believe which i suppose is exactly what it is. but sometimes it doesn't feel like that. sometimes it can just become a job. >> apart from this film as your latest film, was "rachel getting

married" was that the best... did you think of that as the best performance anybody had ever gotten out of you? >> personally, i think "ella enchanted" is pretty up there. (laughter) the day i finished work on "rachel getting married" i was with the wonderful actor bill erwin and we were heading back... the house we shot in was probably... a mile away from the trailers so we were in the car on the way back, a big bus... van where everybody goes together. and he said "how do you feel?" and i said "satisfied." and that was the first time i've ever been able to say that about my work. >> rose: the first time? >> uh-huh. so i think... i don't know if it was... it's too hard to be so objective about your work and say best, worst, middle, whatever. >> rose: i appreciate that. >> but i knew i was satisfied. >> rose: do you know what you did that made you satisfyd? >> i had a career to create the character so that was a huge part of it. but it was also i had absolute

trust in myself in my decisions and i had trust in the whole makeup of the film and it just felt like theater. and i had moments like that in our film, too, where jake was the most extraordinary partner you could ask for because each take wasn't a rigid thing we had to strive for. we were allowed to listen and play each time and ed was fine with that. of course you had in the back of your head some worry about matching shots with each other or continuity. but you really allowed us to play the intentions however spontaneous they were in that moment. >> speaking of all this, back to our earlier point, there was this thing i read about you getting everybody comfortable with removing your clothes or smeg? what was... >> rose: (laughs) >> this has been somewhat exaggerated. >> clear the record on charlie rose, would you? >> rose: this is the place to do it, wouldn't you think?

>> charlie, i couldn't agree with you more. >> i was asking and demanding them day after day after day to put themselves in this situation of being naked in front of the crew, in front of... >> rose: a delightful bunch of people. >> majority men. >> majority men. is this. >> rose: if you were going to get naked in front of a crew... >> this is the crew to get naked. >> they said "you're making us get naked again?" i said "fine, i'll just get in bed with you." >> rose: and what happened then? >> i did. i don't remember what happened after that. (laughter) >> he took pictures. >> rose: that's right, there was a picture. what was the picture element? there is film somewhere with you naked with your actors? >> i'm not naked. >> you are naked! we're all naked and under pillows. >> there are strategically placed pillows. >> what was so disturbing to me was how sort of enthusiastic he was about taking off his own clothes. (laughter) but that was sort of made... you

were... maybe you just didn't want to waste time. >> that was that's what it was. >> a director always worries about time. >> rose: is comedy harder? >> i find everything hard. (laughs) i find everything difficult. i think comedy on film is really difficult because, gosh, it's so hard to make it qont white housely spontaneous and everybody... eventually everybody know it is joke and so much about comedy is just enjoying the laugh and eventually people have heard it so often it's just not funny anymore and... but i find both hard. (laughs) >> rose: this is someone who really takes this job seriously. >> (laughs) >> rose: this is someone who really wants to be as good as she can be. this is not someone who just wants to be a star but wants to be one hell of a professional. that's what i meant. >> thank you very much. >> rose: i'm serious. that's what i feel. >> yes. every time she takes the lead. i think if you looked at... it

takes some cohones to do shakespeare in the park as a hollywood actor and do as well as she did. >> i try. >> this can seem like a crude example but i bring this up whenever i talk about her. there's a moment in the movie where ed was shooting the two of us in bed with two different cameras and i was supposed to sit up into a closeup and then there was another closeup on annie in bed. and as i got up into my shot i passed through her shot and by mistake i pulled the sheet away from her so her top was exposed. she turned to continue the dialogue in the scene but her top was exposed. and there was this moment where i don't know any other actress who would have kept going. she kept... she kept the scene going. and there was... it was what was happening in the moment. >> rose: understood the moment. >> it was not about watching herself or what people might think. it was about being with me in that moment. and it's in the movie as a

result because it's so alive and real. is. >> rose: so what were you thinking? what, if anything. >> i did take a moment to nyse think "oh, god, i know this is going to be the one he's going to use." (laughter) i gave myself that moment then i thought "but it's going very well." it will be okay. >> rose: did you learn something from that? >> hmm. um... >> rose: trust your instincts would be one. >> trust your instincts is one and the nudity will most likely wind up in the film. no, no, honor the scene. it was just about honoring the scene. we had a great take going and i'm happy that was the one that got in the scene because that happened to be the best one. >> rose: what's the best advice you ever got act acting? >> i think working with meryl streep really changed me as a performer because i was... i had been doing it for a few years but i was really... i was still very young and still very wide-eyed about the whole thing. my personal journey was a lot like my character's journey in

"the devil wears prada." although i knew exactly who i was working with. and i... i just watched her get it done. it wasn't about what she was experiencing, her feelings, it had nothing to do with what was going on in her personal life. she just showed up with the... with an absolute deep to her core understanding of the character and played it. and it was like watching a queen rule because she was able to just transform the energy and the air around her. she could drop the temperature or raise the temperature on the set and it was... watching that kind of power in front of me and getting to just be around that i think all of a sudden i just became aware of... that something greater was possible and it kind of made me want to... i became also aware that i could probably never, ever, ever hope to achieve it because merrill is just a one... i think she's a one in a century actress

possibly even more. but that was possible and that was a bar to strive for. >> rose: and you? >> i remember chris cooper saying to me... we did a movie called "october sky" when i was 16 years old. and i remember asking that... i remember asking chris what advice would you give me? i just want some advice and he said "have no regrets." and i think that has to do with preparation. >> rose: it has to do with life. thank you all very much. great to see you. "love and other drugs" opens on november 24. captioning sponsored by rose communications captioned by media access group at wgbh access.wgbh.org