Cancer Reasearch

tonight, on cancer: the emperor of all maladies... unless we understand what's going on deep inside, we won't be able to get the next generation of medicines. does cancer attack from outside the body...or from within? viruses? chemicals? genes? we couldn't figure that out. the politics of cancer... look, we're dying out here... ...and a remarkable breakthrough. ...to see a 100 percent response rate was unheard of.

part two of cancer: the emperor or all maladies. next woman:when you first came to see me, you had a biopsy that was done, and that biopsy showed that there was cancer, cancer on the right side. you had your chemotherapy,so tell me how you're feeling. well, i've been really praying on it-- woman: i hope that my patients take away

that every moment that they spend with me and every step that they takewhile they're in my care that i'm completely there for them, and every moment isn't easy. the last mri, the size was 3.9 x 2.2 x 1.6. all right. she's had her chemotherapy.she's done. ok. woman: let look at that,that was just about a month ago.

woman; voice-over: my motherwas diagnosed with lung cancer just before my last year of training and general surgery residency. this is priorto chemotherapy. woman, voice-over: my role was as caretaker, friend, daughter, and the lesson that i learned from my mother was her strength, her humility, her ability to allow people to care for her. breast massbefore chemotherapy,

and this is the same areaafter chemotherapy. wow, amazing. it's all gone. and so the chemotherapywas very effective. that's great,that's great,that's great. i'm happy for you. woman, voice-over:i think that's often difficult to really depend on someone else when we are most fragile. now you have an opportunityto think about

whether breast conservation or whether mastectomy and so... man: because of what cancer is, it brings you in contact with another human being in a way that barely any relationship will. i mean, it's notan extraordinary relationship; it's the extraordinary relationship. narrator: for as longas human beings have lived, cancer has afflicted us, a disease that does not strike from outside,

but consumes from within. man: the thing that we're all concerned about is the fact that this couldvery likely be cancer. woman: what chance is there of being cured? really cured? what chance doi really have, doctor? i'm sure you realize that recovery is not a sure thing. man: there's nothing more horrifying,

nothing more extraordinary ofall human maladies as cancer. it's us killing ourselves. there's something profound,something psychological, there's something primitively terrifying about it. ok, i'm looking at your eye. woman: when she first told me i had cancer, i couldn't really comprehend what she'd just said, and after she said cancer, she kept speaking, but i couldn't hear anything; i was just in shock.

there is no archetypal response to cancer; patients have different responses. this woman's or this man's struggle, this child's struggle is his or her own. as family members,as loved ones, as physicians, we might be able to witness it, but it's not ours. it's their mechanism of trying to explain, trying to struggle with, trying to make peace with what's happening in their own bodies.

man: it's a real battle. it's an inner battle. it's painful in every way, and how are you gonna find peace, amidst the rage that's happening inside your body, and your own heart? narrator: throughout history, cancer's tenacity has inspired an even stronger will to understand it, to survive it, to cure it. man: if you could find one great theme in cancer

over the last hundred years, it's the men and women who have said, "i'm not taking this anymore.i'm gonna try something else." and that's how scienceand medicine are advanced. it's by people refusing to take the status quo. it's that willingness,that bravery, that heroism to do that, that has, i think, advanced cancer to the state we are now and hopefully will advance it far, far more

in the years to come. man: the president of the united states. richard nixon: i will also ask for an appropriation of an extra $100 million to launch an intensive campaign to find a cure for cancer. narrator: hopes were high in 1971 when the united states declared war on cancer. americans had made it to the moon. surely if they spent enough money and employed enough researchers,

they could conquer cancer. after all, new surgical and radiation techniques, and new combinations of chemicals already cured some forms of the disease. cures for others seemed sure to follow. but progress would prove maddeningly slow. no one yet understood carcinogenesis-- the mysterious process by which normal cells are transformed into cancer cells.

man: it is not known why the cells change and become abnormal. but they begin to grow andaffect those cells around them until the victim finds himself hopelessly afflicted with cancer. man: declaring waron something that you didn't understand at all was nuts. it wasn't like going to the moon. you knew how far the moon was. you knew what it took to get there. declaring war on cancer,

we didn't know what caused cancer. siddhartha mukherjee: that was the hubris, that, you know, if you put enough scientists into a room together, if you gave them enough money and you turned the wheel around and you juggled the box and you opened the door, out would pop a solution to this entire story. narrator: until the riddleof carcinogenesis was solved, the war on cancer would be based on trial and error, and the '70s and '80s would turn out to be deeply fractured

and contentious decades in oncology. scientists fought among themselves. patients demanded less punishingand more effective treatments, and basic assumptions were overturned. the war on cancer seemed attimes to be a war within cancer. man: breast cancer. it's estimated that oneof every 13 american women will develop breast cancer. narrator: if there was one cancer

that revealed the acrimonyand the promise of the era, it was breast cancer. by the 1970s, breast cancer was one ofthe leading causes of deathamong american women, but little progress had been made in its treatment. like their mothersand grandmothers before them, nearly all breast cancer patients submitted to the same extreme therapy, the radical mastectomy, pioneered by dr. william halsted at johns hopkins

at the turn of the 20th century. man: it became a dogma. and if a surgeon, for example, in a hospital were to do something other than a radical mastectomy, he could be put off the staff. there was no thought of doing anything else. narrator: in an eraof brutal cancer treatments, the radical mastectomy stood out. man: because there was dangerthat the cancerous cells

in the breast had invaded the pectoral muscles, those muscles were removed. the surgeon may leave a bandof the pectoralis major at this point, or the entire muscle may be excised. narrator: the radical mastectomy was based on the theory that cancer spreads outward from a central point. getting around it and cutting it out was the only way to save the patient.

man: the underlying principle ofthe halsted radical mastectomy is that cancer is an orderly process, that it starts in an organ and then it spreads to the lymph nodes. the longer you wait, the more likely it is to go to distant organs, and then when it hitscritical areas, it's fatal. narrator: for decades, women underwent the procedure unquestioningly. woman: we were in a "marcus welby" world back then.

you listened to your doctor.your doctor knew everything. you did not question your doctor. narrator: by 1970,nearly 40,000 american women were undergoingradical mastectomies every year. there seemed to be no alternative. man: breast cancer was the only cancer that it was felt you had to do the biopsy and the definitive treatmentwithin minutes of each other. you would go to surgery.

the woman would have to sign a consent that said "if it was found to be cancer,i would have a mastectomyright then and there." so you would go into the operating room, and you wouldn't know whether you were going to wake up with a breast or not. and you know how you found out? you looked at the clock. if it was 3 hours, it was cancer. and if it was an hour, you were benign.

it was just appalling. narrator: despite the aggressiveuse of the radical mastectomy, more than a third of patients relapsed, yet few questioned the operation. when they didn't work, instead of saying, "hmm, maybe there's something wrong with this theory," they said, "oh, we're just not cutting enough". and they would make it bigger and bigger, but actually there was something wrong with the theory.

narrator: it would take an observant surgeon from pittsburgh named bernard fisher to finally challenge the scientific assumptions on which the radical mastectomy was based. fisher had been doing the operation for years, but had seen little benefitto the women under his care. bernard fisher: i began to think, well, we really don't know much about this disease we're treating. what, you know, why are we doing this? narrator: fisher had thoughthard about how breast cancer actually spreads--

or metastasizes-- from one part of the body to another. unlike most surgeons at the time, he doubted that cancer moves like a spreading stain around the original site of the tumor. instead, fisher suspected that stray cancer cells detach from the original tumor very early and migrate through the bloodstream or lymphatic system to far-flung sites in the body,

where a surgeon's scalpel would never find them. fisher: i began to obtaininformation in the laboratory that there was no orderly patternof tumor cell dissemination. the idea that breast cancer was a local disease was not so. it was a systemic disease. that's what cancer was. narrator: if fisher was right, it meant that the radical mastectomy was not enough for women whose breast cancer had already spread

and too much for those whosecancer had remained localized. for the latter, fisher proposed a much smaller operation called a "lumpectomy," which removed the tumor but conserved the breast. fisher resolved to testhis theory with a full-scale clinical trial. he would divide breast cancer patients randomly into two groups: one to undergo the radical mastectomy; the other, the lumpectomy. the medical establishment was aghast. a randomized procedure

in which the doctor himselfand the patient had no control was totally abominable to the conscience of the doctors at that time. they were absolutely outto destroy me and my ideas. it was totally antithetical to theirs. when it's a choice between losing a breast and losing a life, i don't thinkthere's much choice really. man: he was the most hated surgeon in the history of mankind. his colleagues got to the cancerinstitute; they vilified him.

i used to go to the meetings and sit and listen to them tear him apart. i sometimes wonder how he survived it. what struck me was he was a tough guy. narrator: fisher responded to his critics with characteristic bluntness. "in god we trust," he said,"all others must have data." fisher: breast cancer is a scientific problem. it is not an intellectual exercise

or an emotional problem. and therefore, the data which determines what or what not should be done must be obtained and analyzed in a scientific way. mukherjee: he was thought to be a traitor, he was thought to be hacking away at the very foundations of his discipline. he was denied grant funding. he couldn't recruit surgeons to the trial. susan love: the people at the academic centers

and the people that were really hardcore, they didn't change. they had put their whole life into this, and to say that they were wrong, to themselves, i don't think they couldadmit it, even to themselves. narrator: fortunately for fisher, breast cancer patients themselves had finally begun to questionthe radical mastectomy. lover: the women by this timewere getting wind of this. the women were the ones that were finding out

maybe there was an alternative, and it was the women who really drove the change and the shift to breast conservation. narrator: at the head of that movement was a science journalist named rose kushner. at the age of 45, kushnerhad been told that she neededa radical mastectomy. as she researched the procedure, she became infuriated by how blithely physicians prescribed it. "no man is going to make another impotent without his permission," she wrote,

"but there's no hesitationif it's a woman's breast." love: she went to the medical meetings, and she berated the surgeons, and she was this little,short woman yelling at them, and they were all, you know,shaking in their boots. i think that todayis the beginning of the end of mastectomy for the routine treatment of all... all breast cancer. narrator: rallied by kushner and others,

breast cancer patients began flocking to fisher's study. the trial comparing the radical mastectomy to the lumpectomy would take a decade, but when the resultswere finally released in 1985, they were unequivocal. man: we have a report aboutbreast cancer this evening which is of vital concern to virtually every woman. man: it concludes that womenin whom the breast is removed do not live any longer an women in whom only the tumor is taken out.

man: it didn't make a difference whether you amputated the whole breast or just took the tumor out of the breast. the survival was the same. love: it wasn't the amount of surgery; it was the kind of cancer that they had, and probably that some cancers got out before you got there, before the surgeon showed up. and so you could cut all you want,

but the horse was out of the barn already. what does this mean for women with breast cancer? radical mastectomy is nowno longer a viable operation. radical mastectomy is out. narrator: although mastectomies remained common, the radical surgery pioneered by dr. halsted that also removedadjacent muscles and tissue would all but disappear in the years to come. fisher had overthrown one of the central dogmas in cancer therapy:

that cutting more meant curing more. almost as importantly, he had reminded the field of cancer medicine that treatment, without understanding the underlying mechanism of cancer, could do enormous damage. love: what happens in medicine and in science is we come up with a storyto explain our observations, and we get enamored of our story. and then we use that story to keep going on,

and it propels the research, and it propelsthe kind of treatments you do, and it's really only when youjust can't justify it anymore that we start to throw it out. but it lasts a long time, these stories. woman: i was 6 or 7when i saw the show "mash," and it was so exciting, and i felt that that wassomething that i could do, and my mom was the personwho told me that i could do anything.

my mom and dad didn't go to college, but when i said i wanted to be asurgeon at 7, they're like "ok." don't worry. don't worry. i would say that i'm the first generation sort of post-segregation. it was a time that my parentsfelt that there was opportunity, and so that they had waited a long time, and so it meant for us thatthere was a lot to accomplish. narrator: dr. lori wilson is a surgical oncologist and the director ofthe surgery residency program

at howard university. lori wilson: the fact thatyou could make a difference in someone's life that actually could save their life, and that by far i thought was one of the most dramatic things about surgical oncology. narrator: dr. wilson specializes in breast cancer-- in research as well as in her practice. right now the important thing is to make sure that you're feeling well

and that you're doing well. woman: excited. you're excited and you're nervous, and i know that we can... we can--we can do that to you. ha ha! deep breaths. wilson, voice-over: whenever we know that cancer is the diagnosis, we always want to make surethat we give all sides

and that you may not be cured, and that your cancer could progress to something that could end your life. ...that's fine. all right, i wantto get a quick look just to examine youreal quick, to see ifi can feel anything so that we can watch as we move forward. all right.all right. narrator: in july 2013,

dr. wilson herself was diagnosed with breast cancer. lori: the first personthat i called was my husband. i told him that the diagnosis was cancer, and he said, "i'll be right home." i think the thing that caught me off guard is that i not only havebreast cancer in one breast, i actually have breast cancer in both breasts, which is a very unusual wayfor patients to be diagnosed. carole riley: all right,you may go aheadand get dressed,

and we'll get you started. narrator: to complicate matters, lori has a different kind of cancer in each breast. on the right isa particularly aggressive type called triple negative. on the left, the cancer is a type that may be treatable by chemotherapy, but it has already spread to her lymph nodes. it makes it more difficult to treat and so, um, the statistics are-- are worse.

riley: are you ok?you don't looktoo happy today. lori: no, i'm just a little weepy today. it's the fear ofthe unknown and, you know, wondering when... wilson, voice-over: i thinkone of the difficult parts i am having is with the totality of the diagnosis. i can process i have breast cancer, but what the long-term impact that may be, i'm having a difficult time,sort of, processing that.

so we're going to do a right thyroid lumpectomy. she has a... narrator: soon after her diagnosis, lori shared the news withher colleagues and students. lori: this is one of the assistant chiefs that sent this to me: "why you? "i instantly asked myself. "but i soon realized that if there is anyone "who can attack the situation

"with the type of strength andfaith that is needed, it is you. "you give each and everyresident that you touch hope, "the hope that is neededto resist the urge to quit "and to just keep fighting a little more. "i know you would do anything for us, "but now the table's turned. "it's time for you to watchyour commitment pay off. "we'll be your soldiers through this battle, "from taking a greater role with mammo-day

to extra work of any sort, to becoming--" "to becoming the leader thatyou make us believe we can be, is done." man:this is the problem of cancer. why does this cell,instead of dividing intotwo normal and equal parts, divide into 3, 4, or even 5 unequal parts? narrator: thefailure of radical mastectomy, which could be traced directlyto a mistaken understanding of how cancer spreads,

had provided further proof that to make progress in treatments, oncologists had to solve the fundamental mystery of the disease: what causes healthy cellsto suddenly begin dividing without restraint? man: for many years, we hadno idea what caused cancer, why it grew, why it was as nasty and difficult as it was, and without understandingthe molecular underpinnings of cancer, we really were at a loss to develop approaches that would be much more targeted and much more effective. mukherjee: a lot of the work that was performed

up until the 1970swas an empirical approach. since cancer is a diseaseof abnormal cellular growth, let's try to use inhibitors of cellular growth to kill cancer cells. that says, "i'm not really sure what is causing, "what's driving the growth, "but let's just use thingsthat kill growing cells, "and let's hope and pray thatwe'll just kill cancer cells a little bit more than normal cells." and it was startlingly successful

in the case of childhood leukemias and some other cancers. but now, by the 1970s there's a sort of a, almost a terror in the field that unless we understandwhat's going on deep inside, we won't be able to get the next generation of medicines. man:we have made major progress. but it's important to appreciatethat most of these approaches have been made without a basic knowledge of what cancer is all about.

narrator: most researchers believed that there would turn out to be a single cause of all cancers, and therefore a single cure. beyond thatthey were hopelessly divided. there were 3 competing theories about what causes normal cells to turn bad. each was based on seemingly solid evidence, each ad zealous advocates, and each seemed utterlyincompatible with the others. man: there were meetings on viruses and cancer,

chemicals and cancer, genes and cancer... and no one went to each other's meetings. they were really silos in a field called cancer research. narrator:the most widely held theory was that cancer was caused by viruses. man: they are very small but nevertheless, viruses are responsible forcolds, influenza, measles, polio, and many other ills. and now research scientiststhink they may be involved in cancer as well.

narrator:the idea of viral carcinogenesis traced back to 1908 and a young researcher at rockefeller university named peyton rous. man: the idea was in the air in the early 1900s that viruses cause human disease, but the only human disease they'd been implicated in were so-called infectious diseases. peyton rous, a young scientist, had it in mind that maybeviruses might cause cancer,

and he was presented with anopportunity to test this idea by a long island chicken farmer. narrator: the farmer broughtrous a prized plymouth rock hen, which had developed a rare tumor in its breast. rous identified the tumor as a sarcoma-- cancer of the tissue-- and tried to understand what caused it. michael bishop:the first experiment he did was to take the tumor and disrupt it

into more or less single cells and then transplant that into another chicken, and lo and behold, that chicken would get a tumor. [crowing] narration: having provedthat he could spread cancer like an infectious disease, rous tried to identify what inside the malignant cells was responsible. he broke the cells open and filtered out their contents until he was left with something very, very small

that could still spread cancer from chicken to chicken. to rous, the likeliest explanation was a virus. bishop: he published a one-page paper in the journal of "the american medical association" announcing that he had found a filterable agent, presumably a virus, an infectious agent that could cause cancer. well, all hell broke loose. mukherjee: this had a revolutionary effect

on our understanding of cancer because it was very clear therewas an agent, there was a cause, and there was an effect. virus, cancer, and therefore,the claim was being made that cancer was a viral disease. man: time will show that viruses, or at least a virus-like process, will be found to be oneof the major causes of cancer. narrator: for several decades after rous' discovery,

virologists searched for a cancer virus in humans but found none. people were looking forother examples of the virus, and they were trying to figure out other ways to understand how the virus worked. and frankly, the toolsfor doing that weren't there. it was hard to push that concept beyond what rous didin those first experiments. narrator: then, in 1957, in a dusty field hospital in uganda, an irish surgeon named denis burkitt

observed strange oral and abdominal tumors occurring in a large numberof children in his clinic. man: these unfortunate children, usually under the age of 12, with enormous swellings of the jaws and sometimes of the abdomen. it is unfortunately invariably fatal. narrator: not only was thisa previously unknown cancer, but it seemed to spread through the population in a broad band, as if it was contagious.

the distribution of this tumor syndrome was limited to certain areasacross tropical africa. narrator:burkitt brought samples backto two virologists in london: michael anthony epstein and yvonne barr. under a microscope, the researchers discovered virusparticles in the tumor cells. the epstein-barr virus was the first definitively linked to a human cancer. the news that virusesmight transmit the disease

terrified the public. there was talk of quarantines and mass graves. but as the public bracedfor possible cancer epidemics, scientists began experimentingwith vaccines to prevent them. "the viral theory isthe most hopeful one for man," one researcher wrote. "if it is a virus, we can handle it. we can find a way to control,perhaps to prevent, cancer." man: many virus diseases can now be prevented.

polio was conquered.perhaps cancer might be too. different man: does that mean, that we can expect a vaccine against cancer? against some types of cancer, probably "yes". narrator: finding cancer-causing viruses became a consuming focus of the research community in the 1960s and 1970s. the national cancer institutepoured up to half its budget into a special cancer virus discovery program. man: hundreds of millionsof dollars were being spent

on a single idea, and that was that human cancers were caused by viruses. there was scant support for any scientist who wanted to lookat other potential causes. narrator: fort detrick, maryland, a biological weapons laboratory, was converted intoa state-of-the-art facility devoted to hunting for cancer viruses. richard nixon: i think all of us are very happy

that we have here an indication of how the genius of man, which could be used to destroy life, that same genius can betterbe used to save life. narrator: and yet, despite years of workand tens of millions of dollars, the special virus cancer programdid not discover any viruses that caused the major killers: among them, lung, colon, and breast cancer. eventually in later years,a significant number of humancancer viruses would be found, including human papillomavirus,

a major cause of cervical cancer, and hepatitis b and c,major causes of liver cancer. these discoveries would pave the way for effective vaccines. but viruses were notthe singular cause of cancer so many had been looking for. man: in the mid-1970s, the continued repeated failures to find human cancer viruses began to push cancer viruses off stage as credible agentsfor triggering human cancer.

narrator: anotherwell-established hypothesis now moved front and center: that cancer is causedby chemicals in the environment. man: but if we don't knowthe causes of most cancers, we do know what doesn't cause it. cancer is not causedby tomatoes, tight corsets, a punch on the nose, eating meat, making love, or lying on the ground in wales. on the other hand, there is evidence

that some things in our environment do seem to cause some cancers. narrator: the chemical theory was even older than the viral theory. in 1775, a london doctor named percivall pott noticed a large number of scrotal cancers among young men in his clinic. his patients had been chimney sweeps-- poor, indentured servants who spent day after day caked in ash. [bell tolls]

examining them, pott observedthat most of them had particlesof soot lodged under their skin; he suspected that it must bethe cause of their cancer. over the centuries, evidence of environmental carcinogens mounted. epidemiologists linked cancer to coal mining and to the consumption of snuff. but it wasa much more common exposure that ultimately proved the theory of chemical carcinogenesis. the link between cigarettes and lung cancer was unknownin the early 20th century.

cigarette smoking was rare, and lung cancer was nearly unheard of. i. craig henderson:if you had a patient on the ward with lung cancer in those days you made certain that all of themedical students gathered around to see this unusual disease. narrator: world war i changed everything. soldiers in the trenches were given cigarettes to relieve stress, becoming addicted.

when the soldiers returned home, they brought their habit with them. suddenly, smoking was socially acceptable. propelled by mass media, it quickly spread through the population, a symbol of status and style. man: any way you look at it, you'll feel better about smoking with a taste of kent. narrator: as more people smoked,

lung cancer claimed a greater percentage of new cancer cases. in 1900, lung cancer accountedfor less than 1% of all cancers; by 1930, it was 15%; by 1945, it was 20% and rising. still, the linkbetween smoking and cancer was little understood. man: cancerin a mother or father doesn't mean thata son or daughterwill develop cancer. it means only thatthe son or daughter should be alertfor signs of cancer,

because they may bemore likely to formcancer than others. that's most reassuring, doctor. there's so much more i want to know, i don't know where to begin. narrator: in the absence of hard evidence about cigarettes, a host of other explanations were offered to account for the rise in lung cancer. man: there was suspicionthat exposure to poison gasin the first world war was causing cancer,

that the influenza pandemic of 1918-1919 might have created scars thatwould later grow into cancer. there was the idea that roaddust from newly tarred roads was causing cancer. narrator: gradually a fewscientists began to suspect a direct link between cigarette smoking and lung cancer. mukherjee: people were thinking, "well, there must be somethingin the air," as it were, "that's causing this alteration in the behavior of a formerly rare form of cancer".

narrator: in the late 1940s, two british epidemiologists, bradford hill and richard doll, interviewed more than 150 lung cancer patients in london hospitals, asking them dozens of questions about their diet, habits, and living conditions. among them was one about smoking. after all the answers were tallied, only one common associationlinked the cancer patients: cigarettes. at the same time, in the united states,

a young german-born medicalstudent named ernest wynder became interested in the possible linkbetween smoking and cancer. with the help of one of his professors, a renowned surgeon named evarts graham, wynder embarked on his own study, interviewing hundreds of lung cancer patients, asking them if they'd ever smoked. dr. graham, a heavy smoker himself, was initially skeptical that he and wynder would find a correlation;

to his surprise, the results left little room for doubt. graham: we pursued it untilwe had made an examination of more than 600 patients, and we foundthat it was extremely rare to find anyone who was notan excessive cigarette smoker. narrator: wynder went on to conduct experiments extracting the chemicals from cigarette smoke, and found them to be potent carcinogens. this bottle contains the amount of tar

to which the average heavycigarette smoker is exposed to over a given year's period of time. the present evidence very strongly indicates that tobacco smoking, and particularly cigarette smoking, is a major cause of lung cancer. narrator: the revelation cametoo late for evarts graham. though he immediately quit smoking, he would die of lung cancer in june 1957. wynder: in medicine, as in all other phases of life,

we cannot overcome a problemby denying its existence. narrator: together, the transatlantic studies were convincing proof of a link between smoking and cancer. but cigarette companies hidthe evidence from the public behind a barrage of pseudo-science and misleading advertising. robert proctor: the tobaccoindustry really develops thisstrategy of creating doubt. it's really quite brilliant because it's not so often that they would say,

"smoking does not cause disease." they would say, "it's an open question; we need to keep an open mind." man: the industry's position is that the origin of lung cancer is complex and still obscure, and that in addition to tobacco smoke, many other factors deserve further study, such as the effects of chronicand acute lung infection, air pollution, genetic factors, stress...

proctor: this becomes thelongest running scientific fraud in the history of human civilization. man: imagine these two orange blocks as representing all thecigarettes smoked in 1910... narrator: in the years to come, the rate of smoking continued to climb. man: here are the amounts which have been smoked since then, up to 1960. narrator: ...and along with it, the rate of lung cancer. man: compare this with the numbers of deaths from lung cancer

during the same years. they're in thousands, but still going up and closely followingthe rising cigarette sales. narrator: finally, in january 1964, a blue-ribbon commission ofscientists, pharmacologists, and statisticians, appointed by president kennedy and led by the surgeon general, issued a long-awaited report evaluating the sciencebehind cigarettes and cancer. man: out of its longand exhaustive deliberations,

the committee has reached the overall judgment that cigarette smoking is a health hazard of sufficient importance to the united states to warrant remedial action. narrator: the surgeon general's report lent strong support to the theories that chemicals, such as those in cigarettesmoke, could cause cancer. further proof was added over the next decade with the discovery that factory chemicals like benzene, chloroform, and formaldehydewere also carcinogens. but though the chemical theory was gaining momentum,

it, too, would prove inadequateto fully explain carcinogenesis. the full answer would awaita deeper understanding ofthe cancer cell itself. [birds chirping] ha ha! at least he tasted it. you're a funny boy,you know that? mommy likes cherries. narrator: it's been a monthsince lori's diagnosis, and her 20-week regimenof chemotherapy has begun.

yum yum yum! i got you! yes. man:this is my wife, lori. hey, how you doing? nice to meet you. good to meet you. thank you for coming.we really appreciate it. i'll go first, yeah. lori: my husband actually isgoing to shave his head with me,

and so we will, until my hair grows back, we'll both be bald together. [hair clippers humming] lori, voice-over: he's my rock. he's been there for everything. he's looking good! y'all forgeti've been bald-headed before. 20 years ago, yeah, before lori and i got together, and the first winter when i grew my hair, and lori liked my hair,and i haven't shaved it since.

awwww. what a story. oh, that's sweet. [indistinct chatter] yay! let's see. you can take itall off. you're okay. yeah, i'll be okay.

lori, voice-over: i don't buy into the "why me?" because so much of cancer is not predictable. it is not set on family history or any feature, and so absolutely, it could be me. hey, nene, you recognize mommy? oh! lori, voice-over: i have a 19-month-old, and i wanna see my son grow up, see my son get married and go to grad school

and all the good stuff that we expect for family, and with this diagnosis, that's a more difficult thing to see. [sighs] man: cancer strikes nearly everyliving thing on this planet. it cannot be fully cured until we understand it. and to understand it, we may have to solve the most complex puzzle of all: the nature of life itself. different man: the difficulty with handling cancer

is that it's a cellular disease. it's a disease which is of a different type than any disease we have solved thus far. narrator: by the mid-1970s, scientists had made littleprogress towards solving themystery of what causes cancer. arnold levine: we only knew3 facts about cancer. the first fact was that viruses could cause cancer. but we also knew that chemicals could cause cancer. now what viruses and chemicalshad to do with each other

in causing cancer we didn't know, but here were two independent causes. and then we had a clue that genes might be involved in causing cancer. man: these tiny structures seen under the microscope are called chromosomes. in each cell of the body is a fixed and constant number of these chromosomes consisting of a fixed andorderly arrangement of genes.

arnold bishop: there were clues that would involve genes, and there were cluesthat were largely ignored. first clue would be simply that the cancer cell gives rise to more cancer cells whichgives rise to more cancer cells. that doesn't happenunless there are genes involved. clue two was that some cancers are inherited in a limited number of cases. that screams genes. the idea that cancer is a disease of the genome

is actually a pretty old idea. you go back to the verybeginning of the 20th century, and it was proposed by a scientist, boveri, that cancer was reallydue to chromosomal defects. now, that really didn't have a lot of traction then because we didn't know anything about the structure of dna. but the idea of chromosomesgetting broken in different ways could be the basis of cancer was an old notion. narrator: the genetic theoryhad largely been forgotten

until 1967 when a biochemist at the university of california at berkeley named bruce ames made what proved to be a momentous discovery. man: i was thinking a littledifferently than other people because i was trained as a biochemist and also as a geneticist. narrator: ames had set out to invent a test to determine which chemicalshad the ability to mutate genes. one day i was reading too many labels on potato chip packages, or whatever it was,

and about this chemical additive, that chemical additive, and then i thought, "gee,we ought to have an easy test for testing thingsto see if they're mutagens." narrator: ames tested a variety of chemicals and came to an important conclusion, those agents that showed thegreatest power to mutate genes were the same ones known to cause cancer. i always kind of knew in my bones that mutation had to havesomething to do with cancer.

you were taking a normal cell and mutating it and making it different. what ames discovered is that in fact, things that cause cancer are connected by a single common property, and that is that they cause mutations in genes. so, viruses...chemicals...genes? we couldn't figure that out. we believed in every one of them, but what the relationship wasbetween these, we had no idea.

mukherjee: the most important thing is that everyone thinksthere has to be a resolution. so in other words, these 3 theories have to have a central explanation, sort of this grand, unified theory of cancer. narrator: the final piece tothe puzzle of carcinogenesis came from another west coast lab at the university of california at san francisco, run by a young virologist named michael bishop. michael bishop: when i arrivedat ucsf in february 1968,

there was no clear, single theory about what makes a cancer cell. and in fact,nothing all that tangible. it was a black box. i was working on polio virus at the time, and then i was introduced to therous sarcoma virus of chickens and overnightbecame a cancer scientist. narrator: bishop was soon joined in his lab by a young researcher named harold varmus.

harold varmus: i was a young doc who had actually had spent moretime studying english literature than science. but i started talking with mike, who had been trained much as i had as a doc and then had learned something about new technologies by working with polio virus. the two of us realized we hadthe same objective in mind. it took about 10 minutesfor me to recognize that hehad a laser-like intelligence and that we could work together and probably have a good time doing it.

narrator: together, bishopand varmus decided to tacklethe riddle of carcinogenesis by studying the strange virus first found in chicken tumorcells; the rous-sarcoma virus. bishop: the remarkable thing about this virus was that you could infect cells in a test tube, and then the next day thosecells would all be cancer cells. it was an extraordinary transformation. and how that worked, how that happened, was absolute mystery. man: the nascent discipline of molecular biology was developing. and so for the first time,

there werethe experimental instruments with which one could attack this problem: look inside cancer cells, peer into the nuclei of these cells and peer inside the genes that these cells carried in their dna. narrator: the rous sarcoma viruspresented a rare opportunity to watch carcinogenesis up close. we weren't studying virusesas a cause of cancer;

we were studying viruses as a way to find out how cancer arises, what's the mechanism of the disease. viruses are usually very simple. this particular virus has only 4 genes. we have tens of thousands of them. to understand how just 4 genescan give rise to cancer really simplified the problem immensely. narrator: through a process of elimination, a few labs,including bishop and varmus',

zeroed inon one of the virus' genes. levine: this virus that causes cancer has 4 genes, and they find that a closely related virus that doesn't cause cancer has 3 genes. and that'sa very interesting difference. what's this extra gene? and then the evidence begins to mount. this gene that got carried by the virus, the extra gene, can cause the cancer.

it was called an oncogene, a cancer-causing gene in the virus. bishop: and then we began to think about a puzzle, and the puzzle was: why doesthe virus have this cancer gene? this gene we called "src," the only thing it does is to convert the cell to a cancerous state. so the cancer gene seemed almost superfluous. well, if the virus doesn'tactually need the gene, why does it have it? where did it come from?

narrator: maybe, they thought,the cancer-causing gene did not originate in the virus at all; maybe it originated in the chicken. bishop: to my astonishment, when we looked in normal chicken cells, we found somethingthat resembled the src cancergene and rous sarcoma virus. it was a riveting moment. everybody expected that the src gene, the src oncogene, the cancer gene, was a natural resident

within the genome of rous sarcoma virus. but in fact the profound discovery they made was that rous sarcoma virus had actually stolen, had kidnapped that gene from the repertoire of normal genes that are normally stored in thegenome of a normal chicken cell. narrator: if the src oncogene had actually descended from a normal gene in chickens, where else might it be found? bishop: we looked at ducks,we looked at emus and rheas,

which are the most primitive birds living, and then eventually by fiddling with the technology, we could show that it was even in humans. mukherjee: the fact that srcexisted in all organisms, not just in viruses but in chickens and geese and in humans, that fact gave a very crucial clue because that meant that genes that are capable of causing cancer are already existing inside animal genomes.

i mean, imagine how excitingthat would have been. now, all of a sudden, you begin to see through the darkness a glimpse of whatthe clear theory of cancer is. there are genes in your body that control normal cellular growth, and if you disrupt these genes you essentially begin to unleash cancer. narrator: finally, the mystery of carcinogenesis had a single, explanation: the oncogene. mukherjee: the important thing is that the viral theory was not wrong, the environmental theory was not wrong,

the hereditary theory was not wrong. they were just insufficient. it was like the blind men and the elephant. they were catching parts of the whole. and then all of a sudden, if you stepped back, you saw the whole elephant. narrator: the discovery of the src oncogene by bishop and varmus electrified the field and would win them the nobel prize. but there was another mystery left to solve.

so far, the only actual oncogene discovered was in a virusthat caused cancer in a chicken. no one had yet found one in a human. lander: but the tantalizing suggestion from bishop and varmus' work was that there were human genes that could cause cancer. it was a great suggestion. it was a cool idea. it kinda had to be right, but to know that it really was right

required findinga human cancer-causing gene in a human cell. narrator: by the late 1970s, a worldwide hunt was on for a human oncogene. one of those joining the search was robert weinberg, a young cancer researcherat the massachusetts institute of technology. though only 36, weinberg had spent many fruitful and frustrating years in the trenches of cancer research. robert weinberg: science is aprofession for manic-depressives

because there's occasional highs where we make a discovery and then 90% or 95% of the time there's frustrating difficulties and nothing happens. what drives one is one's ongoing curiosity and the optimism that if you push hard enough and you look under enough stones, you're going to turn up some really interesting things. narrator: in february 1978,the worst blizzard in boston'shistory struck the city, unleashing hurricane-force windsand more than 30 inches of snow.

but weinberg was determinedto get to his lab at m.i.t. as he trudged through the driftsacross the longfellow bridge, he thought aboutthe elusive human oncogene. "isolating such a gene," he'd once written, "would be like walking outof a cave of shadows." weinberg: many believed that even though the varmus/bishop work was interesting in its own right, somehow it did not shed any light on what happens inside the human body. and that's what provoked my own research

starting in 1978to try to find such genes. when bob went lookingto find the human cancer gene in what was then an almostinfinite seeming human genome, it was incredibly hard. narrator: there are tens of thousands of genes in a human cell. finding one that caused cancer would be like findinga particular snowflakein the midst of a blizzard. the idea of how to do that came to weinberg as he crossed the longfellow bridge

on that snowy february day. he could isolate the individual genes in a human cancer cell and sprinkle them one by one onto normal cells in a petri dish until one of the genesturned the cells malignant. it would take a year, but it worked. man: so if you had a normal cell and you introduced that oncogene, that cell became cancer. that's very powerful.

you have 20,000 genes and youjust introduce one into a cell and that cell will change, and that cell that isa normal cell, a good citizen, good behavior,will become a full cancer. narrator: weinberg had discovered the first human oncogene. it was called ras. weinberg: it was and it remains a detective story. can we find all the genes that are responsible for the abnormal behavior of cancer cells?

doing so, with the faith that some of our findings may eventually prove useful for those who are interested indeveloping new kinds of therapy. narrator: in the years that followed, labs around the world discovered dozens of other genes, simply awaiting a mutation totransform them into oncogenes. man: it is a discovery of great proportions-- the idea that a gene can be switched on to produce abnormal proteins and thus cancer.

it could mean that all thingswe associate with cancer-- radiation, hereditary defects, chemicals, rare viruses, smoking-- all work by touching the same trigger, the oncogene. jose baselga: i think for the first time there was a mechanistic explanation on why cancer was occurring,and it was a total revolution. the promise that perhaps ifthe oncogenes were responsiblefor the development of cancer, then if we were smart enough, we ought to be able to attack them and then to turn and cure that cancer.

we all had a feeling that everything was about to change, that we were playing out the era of trial and error, of empiricism, and we were beginning to moveto a new era of design, where we understood enoughof the science about cancer that we could imaginethe discovery and development of drugs that would selectively target what was wrong, what was different about a cancer cell than a normal cell. it was a very heady and hopeful time.

narrator: but even in the midst of their euphoria, those who had discovered the oncogene were aware of the challenges that lay ahead. "we have not slain our enemy, the cancer cell," harold varmus would say whenhe received the nobel prize. "we have only seen our monster more clearly and in new ways, ways that reveal a cancer cellto be a distorted versionof our normal selves." the vulnerability is already within us. the very genes that make you grow,

the very genes that keep you alive, will, under different circumstances kill you. narrator: dr. lori wilsonhas been undergoing chemotherapy for 5 months. because of the type and size of her cancers, she has chosen to have a double mastectomy, though not the kind of radicalsurgery done in the past. hi, lori.it's nice to see you.how are you? woman: we see less invasive surgeries today. when i started my training,

i would still see occasionally a woman who had a radical mastectomy. today i can't even think ofthe last time i've seen that. have you been operating? i have, i have. but i've been good. so in generalwhen we went aheadwith mastectomies... lori, voice-over: because of the size and type of breast cancer that i have, mastectomy is my choice on both sides.

right now i absolutely want to be better. i want not to have it come back, and so if that means mastectomy and that means not doing a lumpectomy and breast conservation, i'm ok with that. on the left side, it is soft, but still a little... vered stearns: the main concern when one is diagnosed with cancer is to try and estimate whatthe risk of recurrence is

in other parts of the body. when we initially met, her risk of cancer coming back was more than 50%. so we're definitely attacking the cancer from every possible direction. we've decided that the best approach would be to start chemotherapy first to try and shrink the cancer as much as possible before proceeding with surgery. loir, voice-over: my fearis that the chemotherapy's not as effective,

that it doesn't treat the cancer completely, that the cancer grows during treatment... which would not be a good prognosis for me. stearns: if the cells continue to be present despite the treatment, they can grow in other parts of the body, and that's when cancer becomes life threatening. say goodbye to your last chemotherapy. yay! yay! lori, voice-over:the biggest risk after surgery

would be having lymphedemaor swelling of my arm. if i had lymphedema, i probably wouldn't be a surgeon any longer. of course, that makes me sad, because there's some things that you just are. i just think that being a surgical oncologist, that's one of the things that i am. let me hug you. stearns: when the patient is a physician herself, someone who is in the field

and has seen women struggle and die of their breast cancer, you know how the story can end. man: 14 years agopresident nixon signed a bill declaring an official war on cancer. we're spending about a billion dollars a year on cancer research in this country. and what are we getting for it? americans are losing the war against cancer. narrator: in 1986, the waron cancer had been going on for 15 years.

billions of dollars had been spent, and great progress had been made in the basic science of the disease. man: how close does this bring us to a cure, which the whole world is waiting for? that's an imponderable at the moment. man: it was an incredible time scientifically, but there was this deep chasmbetween the lab and the clinic that nobody had bridged. people began to become somewhat disillusioned.

we are understanding much more about cancer, but where are the treatments? a new study says that yourchances of dying from cancer are greater todaythan they were 30 years ago. narrator: a 1986 study appeared which for the first time systematically analyzed how patients were faring in the war on cancer. one of the co-authors of the study was a respected statistician named john bailar.

woman: dr. bailar,are we being misled by so-calledsurvival statistics? well, for years and years, we'vebeen hearing marvelous stories about progress against cancer, and at the same time, many people aren't aware that mortality rates are going up every year. some 8,000, 10,000 more people die of cancer than died the year before. it's up to 450,000 this year.

how do we match this up with these stories about wonderful progress? man: that was the first shot across the bow, where credible numbers-based scientists stood up and said, "what have we really accomplished and are we on the right track?" john bailar: there was first a sense that this can't be right, and then, i must say, it was asense of rage in some places that anybody would dare to say these things.

anytime in the last 20 or 30 years we could have gone to the leaders of the war against cancer and heard the same story about how successis just around the corner. i don't, i simply don't believe it anymore. the american cancer society disputed this study's conclusion. a spokesman said, and i quote,"we're making great progress." he said, "cancer is really a lot of different types of diseases. if you lump them together,you get a distorted picture."

unquote. i think there wasa general sense in the public, certainly a general sense in congress that controlled a lot ofthe money for cancer research, a general sense even among some of the leaders in the cancer effort that things must be getting better, and we had then this solid documentation that that was not the case. narrator: bailar had a solution,

to shift priorities in the war on cancer from new treatments to prevention. man: advice to people watching, dr. bailar, this morning? bailar: stop smoking,stop smoking, stop smoking. that is the first and most important thing we can tell people today. narrator: but not many in the cancer community were paying attention to bailar's pleas for cancer prevention. those who had doled out billionsof dollars in taxpayer money, expecting new cures to be discovered,

now demanded to know where the money had gone. man: i mean, you're not running some little kiddy game here; you're running a billion dollar a year, very important project, and it worries me that you kind of don't understand the difference between how important it is to manage, and how important it is to reach the final results. narrator: without new treatments to try, doctors had few optionsfor their sickest patients. some decided to raise the doses of their drugs to higher and higher levels.

just as radical surgeonsonce pushed their disciplineto terrifying limits, now radical chemotherapists did the same. in the late summer of 1981, a doctor named william petersarrived at dana farber cancer institute in boston. peters had come to the hospital to work under tom frei, one of the pioneers of high-dose chemotherapy. man: tom frei is sort of a remarkable individual. he was affectionately knownby everybody as big bird-- tall, lanky man

with an incredible encyclopedic knowledge of the disease, an approach to treatment that drove everybody to think outside the box. narrator: frei believed he couldtranslate the success he'd had with high-dose chemotherapyin childhood leukemia to solid tumors,especially to breast cancer. man: breast cancer had begunto capture the mindsetof the community. people were looking for a way in which you would revolutionize this disease, make the war on cancer finally successful.

and it became a real rallying-point for getting treatments done. narrator: together, frei and peters decided that the way to attack breast cancer was to vastly increase the doses of chemotherapy drugs. man: the fact is thatif a two-fold difference in dose makes a difference,a 5-fold difference in dose made possibleby bone-marrow transplantation might be expectedto make a bigger difference.

narrator: bone marrow had always been the limiting factor for chemotherapy. as the source of white blood cells that protect the body from infection, bone marrow was essential. if you destroyed it, the patient would die. william peters: you had to figure out a trick to get around the bone marrow. and the concept became, why not takesome of the bone marrow out, freeze it in the laboratory,

treat the patient with as high a dose as you could tolerate, and then put the marrow back, and like seed on a new lawn,the marrow would repopulate. narrator: the procedure had been tried with some success in children with advanced leukemia, but no one knew how adult women with breast cancer would tolerate it. in the summer of 1983, petersand frei began a clinical trial, which they namedthe "solid tumor autologousmarrow program," or stamp.

peters: i said, "tom, if we're doing this, we're going to push the doses to the limit. we're going to do it once. i don't want, at the end of it, somebody to come back and say, "if you only had done a little bit more, you'd gotten the right answer." narrator: the researchers infused patients with doses of drugs5 times higher than normal, bringing them to the brink of death,

before saving them withtheir own bone marrow cells. almost immediately, they sawa response in a patient. peters: she had a remarkable response. the tumor, within a week, began to regress away such that it was almost nothingby the end of a week to two. narrator: though the stamp trial was still years away from completion, word of dramatic remissionsbegan leaking out to desperate patients and their families. woman: patients were demanding access to it. they were lobbying insurance companies

and doing a lot of pressto shame insurance companies into paying forthis unproven intervention. and it got to the point where we couldn't get people to come into the clinical trials to prove whetherthey were effective or not because they wanted access to it regardless. different woman: if somebody told you that you probably were onlygoing to live two more years and you had no ideahow you were going to die--

it might be easyor it might be really lousy-- i mean, i think you would say, you would reach for anythingthat seemed promising. narrator: many doctors were as eager to try the procedure as their patients. not only wasthe bone marrow transplant scientifically exciting, it was extremely lucrative. peters: transplants became a business. hospitals found that if they used this type of treatment approach, it could significantly improve the bottom line.

suddenly, the doors opened. community hospitals,doctors in private practice, every academic institution now had to have its own high-dose chemotherapy program. narrator: 43-year-old anne grant was one of those womenwho underwent the treatment outside of a clinical trial. diagnosed with metastatic breast cancer, she felt she had little choice.

almost all the doctors we interviewed suggested that we considerhigh-dose chemotherapy with a stem cell transplant. the treatment was presented as, "this is the way it's done, "this is the gold standard of treatment, and this is what we do." i was there, i believe, 21 days, and it was just every day blended into another. i never knew if it was day or night.

everything was painful, and you're so sick you can't do anything. you're dying. i mean, you're feeling yourself dying. narrator: peters was seeingthe same horrific side effects within his clinical trial. one in 5 women were dying from the treatment. peters: you had to sit and ask yourself, can we go on? are you really a madmandoing this type of approach? are you really outside the bounds of what you should ethically be doing?

and we worried about it. i'd be a liar if i didn't say that i didn't think long and hard about the difficultiesthat we had in those settings. narrator: after a decade of study, peters own clinical trial revealed that the procedurehad been no more beneficial than regular doses of chemotherapy. in 1999, he presented his findings

to a shocked and disappointed cancer community. love: the randomized controlled trial showed that there wasno difference in the survival, but the people who got the transplants had a higher chance of dyingfrom the transplants. and so the idea that this wasthe answer to breast cancer just didn't work. that more wasn't better. it wasn't better in surgery,and it wasn't better in chemo.

peters: every patient died of their disease. and if we could change that, we needed to do it. if it worked, we'd be famous, ok? if it doesn't work-- well, all right,you've made a contribution, and that's the way medicine moves forward. narrator:before high-dose chemotherapy for breast cancer was finally abandoned, it had been performed on thousands of women.

follow-up studies confirmedthat these patients had received little or no benefit, and many had lost their livesas a result of the procedure. we did this in the united states for 15 years, transplanted more than 15,000 women, did it without clinical trials to actually show that it was beneficial. this is an example of howmedical oncology and medicine just got totally out of hand. jerome groopman: there are times when you do everything to the maximum

and you have a scientificfoundation to justify that, but then there are times whenyou need to step back and say, "am i really doing what is best for the person "and how do i balancethis effort to extend life "versus the impact that your therapies have in worsening that life?" narrator: in the end, even those who survivedpaid a terrible pricefor high dose chemotherapy. anne grant, voice-over: i have tremendous cognitive problems

that cause a lot of frustration in my life, and i'm not bitter. i just get frustratedwhen i can't do something. and i wish i could get my words all the time, and i wish i could remembershort-term memory things, and i wish that i...um... didn't have these pauses. narrator: the failure of high dose chemotherapy marked the end of an era in cancer treatment, in which the guiding principlehad been "more is better." few doubted that a new, morerational strategy was needed,

one that would bring theinsights gained in the lab to patients in the clinic. mukherjee: this was a crisis of faith. it was a time when all of a sudden the discipline had to look back on its own history, on itself and to ask questionsabout where it was going, where had it come from, and what was going to happen next? narrator: dr. lori wilson and her family have come to los angeles, tothe cedars-sinai medical center,

where she will have her surgery performed. ok, no mischief. yeah, you're ok. bye-bye. can you say bye-bye to mommy? i love you! i'll see you later. lori, voice-over: ultimately,we are going to find out from the surgery the final results from going through thechemotherapy regimen that i had.

and then making decisions about my life from there. ok, now i am going to weigh you. if you could step on the scale and then we will put your earrings here, and then we could give it to your husband. can i call you by your first name, lori? i would prefer that. or you want doctor? i would preferyou call me lori.

can you tell me what surgery we are doing for you today? i am having mastectomieson both sides. mm-hmm. i'm having my lymph nodesdone completely on the left, and a sentinel nodedone on the right. uh-huh. and who is going to be your surgeon for that? dr. giuliano. man: good morning, where's lori?

woman: right there.good morning, doctor. narrator: armando giuliano isthe doctor lori trained under as a fellow 13 years ago. i didn't expect to be workingtogether again like this. no, no, not like this. man: we say in surgery once a fellow, always a fellow. that relationship doesn't change, and here was this young womani remember in her early 30s, who now comeswith bilateral breast cancer.

we'll take good care of you. lori: i know you will. thank you. appreciate it. ok, we'llget things rolling, as we say in surgery. armando giuliano: we all loved lori as a fellow. she was very hard working,very smart, fun to be with. totally reliable and very inquisitive. you could see that she had a certain spark,

that lori would do something with her life and with her career. giuliano: ok. are you ready? we only need one set up. we're going to do the right side first. ok, let me have a marking pen. raise the table a bit for me, lorraine. giuliano, voice-over: lori hastwo cancers, one in each breast, both of which are very disturbing to me for different reasons. so on this side her nodes were negative.

we'll see if they are negative today. how's that look? pretty good, huh? and then we'll put the central node incision here. narrator: dr. giuliano will begin the surgery by removing the sentinel lymph node, which will be immediately biopsied. if it tests positive, it will signal that lori's cancer has spread beyond her breast.

giuliano: ok, blue dye please, eileen. you can identify the first lymph nodethat's been hit by the cancer and therefore the one mostlikely to have malignancy, and if you take that outand there's no cancer in it, then there's not going to becancer in any other lymph nodes, and what happened is we decided that, "well, why remove negative lymph nodes?" narrator: giuliano is one of the doctors who pioneered this procedure 20 years ago as part of the movement to save women from unnecessary surgery. giuliano: people didn't believe it, of course.

initially, surgeons would see itand say, "it doesn't make sense. we've created a magic lymph node." there's nothing magic about it. it was just recognizingthe anatomy of the lymphatics. so that's the lymphatic that is taking the cancer cells and the blue dye from the breast right to that lymph node. frozen section, please, for me. giuliano: it was a eureka moment, the first time we saw a blue lymph node,

and we would take that out,and it invariably predicted whether the cancer had spread or not. so you can now doa much less radical operation. man: again,it's lori wilson, lori wilson. [telephone rings] woman: pathology is on the phone. do you want it on speaker? giuliano: please. woman: regardingfrozen section results on patient lori wilson.

woman: ok, go ahead. woman, over phone:no carcinoma seen. giuliano: all right, thank you. thank you very much. giuliano: good news,she gets a break. narrator: lori's doctors see no sign of her cancer having spread, but they will have to wait for the results of a more thorough pathology to know for sure. giuliano: i think when you treat cancer

it's important to know your limitations and understand what you can be sure of and what you are not sure of. so much of what we do is uncertain. we can't predict the future. giuliano: hey, lori,you awake? it went great. everything went very well. the sentinel node wasnegative on the right.

i really am very pleased. giuliano, voice-over: and that's very hard for patients. all right,see you later. i think uncertainty is part of treating cancer. woman: hope is a funny thing. you have to base hope on something. so when my cancer came back, and i really, you know, when youhave 16 tumors in your lungs, you're not thinking survival.

so i didn't have hope at that point. narrator: barbara bradfield was just 48 when her breast cancer relapsed in 1992. already, she'd endured a mastectomy and round after roundof radiation and chemotherapy. barbara bradfield: the oncologist says, "well, we're gonna hit it with the stronger chemo." i said, "no, we're not. "if it didn't work the first time,

"it's not gonna work this time. "i'm not doing that. if i'm gonna die, i don't want to die bald and throwing up." the doctor said, "well, i know this doctor over at ucla "who is doing studies of oncogenes, can i send your slides over to him?" and i said, "i don't care. sure. fine. whatever you want." this one is resistant. this one is resistant.

narrator: bradfield's slides were sent to dr. dennis slamon, an oncologist workingat the ucla medical center. the son ofa west virginia coal miner, slamon had grown up watching lung cancer ravage his community, developing what he called, "a murderous resolve" to find a cure. he was the first in his family to go to college and then medical school, completing his training the same year as bishop and varmus' groundbreaking discovery of the oncogene. like many other researchers of his generation,

slamon believed thatthe discovery of the oncogene offered an opportunity to attack the disease in new ways, by creating smarter drugs that could discriminate between healthy cells and cancer cells. can we understand what's broken in a normal cell that makes it a cancer cell? and if we understand what's broken, target that specifically. and if we're able to successfully do that,

in theory, we should have treatments that are: a) more effective, and b) less toxic, and by no means was i alone in that observation. man: we always were lookingfor things that could target the cancer cell, leave the normal cells alone, and try to separate the normalbody from this, as it were, this distorted version of thebody, the cancer in the body. narrator: already, the first targeted therapy against cancer had been discovered. in the early 1970s, a drug called tamoxifen

was shown to arrest the progress of certain types of breast cancer by starving them of the hormone estrogen. dennis slamonand other younger researchers wanted to refine targeted therapies still further by going after the specific oncogenes that give rise to specific cancers. mukherjee: scientists like slamon came of age at a time when the oncogene was discovered. so their question was no longer, "what is the oncogene?"

their question is,"how do we kill a cancer cell "by understanding what an oncogene is? so what isan oncogene specific therapy?" narrator: by the 1990s, dozens of these new cancer-causing genes had been discovered. one in particular intrigued slamon. it was called her-2. in its regular form, the her-2 gene is vital to normal cell division. it creates antennae-likestructures called receptors

that send and receive signalstelling the cell to divide. but in its malignant form, the her-2 oncogene copies itself over and over, and these duplicate genes createa dense forest of receptors. jose baselga: the cell goes crazy because there are so many receptors that the only thing the cellcan do and knows to do is to grow in a totally uncontrolled fashion. it is not dissimilar to having a very powerful car, a porsche, a ferrari,that has the gas pedal stuck.

that thing is going to continue to go very, very fast until it crashes. narrator: her-2 was alreadybeing studied by researchers at the san franciscobiotech company genentech. using the oncogene, the genentech scientistshad induced cancer in mice. but they had no idea if it was responsible for any human cancers. the only way to find out would be to search for it in hundreds of different types of tumor samples. they asked slamon to help.

dennis slamon: we had a bank, it sounds strange, but a bank of tumor tissues that had been removed for therapeutic purposes for patients. and as we were working our way through our tumor bank with all the various cancers, we were looking for the gene called her-2, when we got to the breast cancer part of the bank, we found a pretty gross alteration that was occurring in about 20% to 25% of the patients' tumors.

there are tumors that havemultiple copies of the gene and they have much higher signals, and so they have much moreintense bands here. so this band represents what the gene looks like in this analysis. if this is a breast cancer cell, some breast cancer cells wouldn't have any her-2 poking through the surface,or maybe they'd have one or two. but there were breast cancer cells where the surface of the cellswas stuffed with her-2,

tons of it. what really became exciting is when we went back and looked at the clinical data. we found that those women whose tumors contained this alteration had a much different outcome. they were among the women whohad the very worst outcomes. so they would have recurrences much more quickly, and that was the first areawhere we started to seethere was smoke here. there was a genetic alterationthat was associated with

the most aggressivehuman breast malignancies. so now you have two pieces ofinformation that are critical. one: that oncogene is present, and if it's present, the tumoris very, very aggressive. and the next question is: how to target this? narrator: both slamonand some genentech scientists believed there was already a weapon available with which to target the oncogene. it was called an antibody,

and it exists within the human immune system. mukherjee: you could thinkof antibodies as intensely,exquisitely targeted missiles made in the body to target viruses, bacteria, or other cells. narrator: scientists already knew how to genetically engineer antibodies outside the human body. the trick would be to find one that could target the her-2 oncogene. within a couple of years, genentech researchers had developed a number of custom antibodies they thought might work.

slamon: so we took antibodiesthat genentech had made, and found that there were several of them that could inhibit the growth of these human breast cancer cells in culture if they had the her-2 alteration. and if they didn't have the her-2 alteration, the antibodies had absolutely no effect on them. so now we had something that wasmore even than a smoking gun. narrator: the most promising of these new antibodies was named herceptin. slamon was eager to try itin her-2 positive patients,

but genentech executives were wary. man: at the time, we were a small company, resources were extremely precious, and there were certain people that thought this was just nonsensical, even after that proof of concept was demonstrated. and other people thought that this could be the future of cancer therapy. and it was that core of scientists who kept the project alive,

who really believedthat the data meant something. i would go up a lot and tryto lobby the non-believers that this was something that was real, in fact i sort of got a moniker within genentech, and that was being called dennis the menace. narrator: slamon buttonholed company executives in the hallway, begging them to fund a small clinical trial. finally, genentech agreed. he immediately set about recruiting women with late-stage breast cancer.

barbara bradfield's slidesarrived just in time. slamon: we tested her tumor, and it turned out to be one ofthe most positive we'd seen. she probably would not have survived more than 3 or 4 months. i was hoping i could die with dignity. that was really where i was at that point. and i got this call from dr. slamon at ucla. he said that i could qualify. he'd love to have me in the study.

and i said "well, is there chemo?" and he said, "yes, it will bechemo and then this drug." and i said, "no thank you,i'm not doing that." so we said goodbye and goodnight. the next morning, very early,he called me back and he said, "i've been thinking about you all night." slamon: i said, "i realizeyou may have made a decision, "and i don't want to try to unduly influence you, "but i want to tell you--

i really think this is something you should reconsider." barbara bradfield: by the timehe was halfway through it, i was thinking "i don't have anything to lose." so that was the start of the herceptin trials. narrator: bradfield joined slamon's trial in october 1992, along with 14 other women. all of them had exhausted every standard treatment for breast cancer. slamon: they wereas much a part of the story and, in fact, colleagues,as anybody who was involved in the science.

we were excited about the science coming from the laboratory. they had a bigger dog in this fight. mukherjee: it's a verypeculiarly intimate setting. they actually get to know each other's stories. there's a young womanwho's undergone a very toughbone marrow transplant. there's a chinese woman who'sbrought in a stash of herbs. she says,"i'll take the latest drug if you let me take the oldest drugs." we had one gal that came all the way from boston.

her name was bev, and she wasa lot of fun, very raucous. she brought this lovely cakethat had breasts on it, and it said "breast wishes, dr. slamon." my tumor in my neck wasthe touchstone of the study, because from the very beginning, it was the only tumor that could be felt. you could see it. it was right here. and so every week everybodywould come in and feel it. well, within the firsttwo weeks, it got smaller,

and so that was the most exciting thing. everybody would come in and feel it and go, "if yours is getting smaller,that means mine is, too." narrator: but for many of the women, the therapy wasn't working. one by one, they began to drop out of the trial, too ill to continue. halfway through the trial, there were only 5 patients left, including bradfield. mukherjee: it's like a sisterhood of hopefuls.

everyone's watching everyone else. and there is a desperation. and yet only some people are responding and some people are not. narrator: as slamon anxiously awaited the trial results of herceptin, other researchers began looking for new oncogenes to target. one of them was brian druker, a young doctor who had leftthe dana-farber cancer institute for a research lab in oregon. brian druker: when i was doing my oncology training,

learning how to take care of cancer patients, it was like they had put me into a room with a light bulb that was stuck on and gave me a baseball bat, and they said to me,"knock out that light bulb. "and here's your baseball bat. "and if that doesn't work,we're going to use a bigger bat, high dose chemotherapy." and i said, "why don't we figureout why the light's stuck on

and fix it that way?" narrator: druker had becomeinterested in a rare and fatalblood cancer called cml: chronic myeloid leukemia. in 1973, a researcher at the university of chicago named janet rowley had identified the specificgenetic mutation in cml cells: the ends of two different chromosomesaccidentally switch places. in this new form, the gene suddenly triggershyperactive growth of cells. druker: i was in medical school in the late 70s. we knew about janet rowley's pioneering work

identifying exchange of material between the ends of two chromosomes. but it wasn't until i actuallygot back into the laboratory that we really could understand what the consequences of thatswap of chromosome material was. and it actually was an oncogene that caused the unrestrained growth of white blood cells in this leukemia called chronic myeloid leukemia. narrator: it happened that chemists at the swiss pharmaceutical company ciba-geigy,

later named novartis,were looking at a class of drugs that seemed active against the kind of oncogene that causes cml. hearing of this, brian druker and his colleague charles sawyers approached the company and askedif they could test the compounds in their labs. man: this was not a project that had a timeline and a planwhen it was first hatched. neither one of us expectedthe drug to really work at the level that it ended up working. there was this one compound that stood out

head and shoulders above theothers at killing leukemia cells and not harming normal cells. narrator: druker called his drug imatinib, later known by its trade name gleevec. first in a petri dish, then in mice, the drug seemed to wipe outany trace of cml cells. druker: now, we had a lot more experiments to do, but it was really excitingto actually see a compound that was doing what i had hoped a compound could do.

that was almost too good to be true. charles sawyers: brian and itook it upon ourselves to convince novartis thatthis drug had to be tested in patients. druker: that was two or 3 years hammering at getting this drug into clinical trials, and it was an uphill battle. i had something that might beable to work for them; it needed to get a try. if it doesn't work, fine. i'll go away, you'll never hear from me again,

but give it a chance. narrator: brian druker and dennis slamon were in the vanguard of a newgeneration of doctor-researchers whose persistence brokethe barrier between research and treatment. slamon: being involved in those early studies showed us that you could take this really basic science research and translate it from the lab into the clinic and take clinical questionsand bring them to the lab and get answers was really the whole promise of this new approach.

narrator: by the spring of 1993, the initial trial ofthe breast cancer drug herceptin had ended, and slamon was ready to share barbara bradfield's results with her. bradfield: the door suddenly flew open, and he and his assistant come walking in with the biggest grins on their faces and said, "there is no more cancer". my husband and i lookedat each other and we said,"there's no more cancer?" and dennis said, "come on, i'll take you down to radiology

and you can look at the slides." so we went down and we looked at the screens and he pointed out, "here's the 16 tumors in your lungs. now look over here, not there." we didn't quite know what to do with that information and neither did dr. slamon. he said,"this is new ground for us. "we don't know if your cancerwill be back in 3 months. "we don't know if it's really cured.

just go home and enjoy life." narrator:barbara bradfield's remission was the first in the history of cancer therapy. never before had a cancer-causing oncogene been identifiedand successfully targeted, but this was only a first step, a small stage one clinical trial. genentech and slamonwould need to try herceptin in many more patients before they could be sure it was working.

slamon: course you always worry, is this sort of the one-off example and it won't be repeated when you go to larger phase-two trials. narrator: as slamon and genetech prepared for a wider clinical trial news of herceptin's early success had already leaked out. doctors are calling it a breakthrough. man: a promising, but still unproven drug. woman: a drug that could mean a stay for some women facing a possible death sentence.

narrator: soon genentech wasinundated with calls and letters from women who wanted the drug. woman: this was absolutely a valid question, which is, "look, we're dying out here. "this is a serious illness, and you have a medicine that could help me." the drug raises hopes for the future, but helps only a handfulof the women who need it now. narrator: because they neededto do a wider trial first,

the company refused. susan desmond-hellmann:the company wanted to focuson the clinical trials, and they wanted patients to enroll in the trials, not to get the drug outside of the trials. if you don't carry out thatvery careful clinical process, you can't look back at the endand say with any confidence that, "i know this drug works." it's a terrible reality that medicine, which is the most human of all the sciences,

is caught performing the leasthuman of all experiments which is to deny patients medicines even when they seem to besuccessful in small trials, but it's the reality, andthat is that there has beenso many false leads, that doing something too early is always a formula for disaster. narrator: the issue came to a head after a young gynecologistnamed marti nelson relapsed with breast cancer. nelson wanted to enrollin the wider clinical trial of herceptin, but she was repeatedly denied.

man: we kept getting the run-around, getting one person blaming another. time was going on. she was getting sicker and sicker. but we continued to ask for the drug, and then marti died withoutour ever getting an answer. narrator: the death of marti nelson galvanizedthe breast cancer community. in 1994, dozens of activistsconverged on genentech's campus. [chanting, horns honking]

mukherjee: they decide thatas a part of their protest they're going to hold a funeral procession for marti nelson. robert erwin: it absolutelytook genentech by surprise. if they didn't know who we were before and what the breadth of our willingness to engage in this issue was, they certainly knew it after that. narrator: the activism that had begun with rose kushner's opposition to radical mastectomy, and continued in the stamp trials,

now reached a boiling point. fran visco: for the first time, you had a company that wasengaged in cancer research having to deal with people chaining themselves to cars in the parking lot and demanding access and being in front of the nightly news. that just had not happened in cancer. [sirens] narrator: desperate to resolve this impasse,

genentech executives sat downwith breast cancer activists in 1995. the negotiation ended with a compromise. the company agreed to providesmall amounts of herceptin to women outside their trialon the basis of a lottery. it wasn't a perfect solution, but it brought an end to the protests. in 1997, the trials were finally complete. susan desmond-hellmann was one of the first genentech executives to hear the results.

susan desmond-hellmann: i hung up the phone and literally ran as fast as i could down the hill to the building where art's office was. ran up the stairs, ran inhis office, closed the door, and i got on the board. he had a whiteboard in his office, and i drew the survival curveof the patients in the trial and showed him the data that patients had lived longer. narrator: in fact, herceptin hadextended the lives of women

who had taken the drug by an average of 50% over those who had not, with hardly any side effects. it was one of the most significant results in the history of cancer medicine. slamon: what gets you through the work is the data. we talk about how do you fightwhat may be an uphill battle or look like an uphill battle, and it's just anunflagging belief in the data, and i think you have to beyour own worst critic, but if the data keeps comingback telling you, "this is real.

this is right. this is the way to go," then you have to believe it. bradfield: the next year we did tests again, and my cancer was still all gone, and it's never come back. cancer is a funny thing because once you have it, it sits like a little monkey on your shoulder. it never goes away. it's been 20 years, and it'sstill part of my psyche.

and it changes who you are. there's a little element of fear that never goes away. woman: so this is your first visit since surgery, right? lori: yes. you can come on upon the bed here. somebody is asleep! so go aheadand remove everythingfrom the waist up off. put the gown that's behind you on opening towards the front,

and then dr. giuliano will be right in. narrator: a week after her surgery, lori is meeting with dr. giuliano to receive the pathology results. they will show whetherthe chemotherapy and surgery have completely eradicated the cancer from her body. giuliano: i was chompingat the bit to get the pathology, and i called the pathologist, and he was very excited and told me that we had a complete response. giuliano: on the right, no tumor at all.

lori: oh my gosh! and on the left, all the lymph nodes were free and that big, giant tumor was down to 3 millimeters. oh, my goodness. lori, voice-over:the thought that it would work for all of the breast cancerthat i had on both sides, and that we'd have no residual disease on one side and minimal residual disease

only in the breast on the other side, making it a success. this was notin any of the scenarios that i had sort ofthought out in my mind. that i could havea complete response or... it's fantastic! all the lymph nodes were free. thank you,thank you so much! i appreciate it. come on out, get dressed.

ok. thank you. yay! it's not what i expected, but i will take it. ha ha! i will absolutely take great news like that. once i had my surgery and had my pathology, then that helped me sort ofsolidify sort of a prognosis. but in all that, there are no guarantees.

and--so that's the grey area for me. each time i have somethingthat may pop up that-- that probably wouldn't have been an issue a year ago, i'll think about, "well, is thisthe moment that i find out? is this the moment that i potentially could have recurred?" narrator: in june 1998, brian druker was finally given the go-ahead to begin clinical trials on a drug for chronic myloid leukemia. druker: every single patientwe enrolled had their bloodcounts return to normal. in the context of the history of cancer,

we expect a 10% or 20% response rate. to see a 100% response rate was unheard of. absolutely unheard of. at that point i knew we had something that was fundamentally different than any other drug for this leukemia because it was treating somebody that no other drug was able to control and it did it rapidlyand without side effectsand it was a once-a-day pill. that was absolutely amazing to see. mukherjee: there's a lovelydescription of herceptin andgleevec as the 4-minute mile.

[gunshot, cheering] before roger bannister ran the 4-minute mile, there was a group of people who said, "it's not possible to run the 4-minute mile because human physiologyjust isn't built that way." announcer: and banister has done it! the mile in 3 minutes, 59.4 seconds. mukherjee: what happens whenyou break a record like that is not that you break the limit,

it's that you break the idea of a limit. and in oncology the idea of the limit was you could not design a drug that was specific for a cancer cell. levine: in the end, thisvalidates the 25-year search. it's the beginning of targeted therapy. it's the beginning of changing therapy completely in cancer. and it says that all thatresearch that was done for25 years on hamsters and mice and in tissue culture cells and then transitioned to humans and all the information we gotis now being used to make drugs,

is now being used to help people. it was a proof of principle that"yes, this is going to work." targeting oncogenes is working and will make a disease that is lethal to a disease that is curable. announcer: 4, 3, 2, happy 2000! narrator: as the 20th century came to an end, great strides have been madein the centuries-old struggle against cancer. the new drugs herceptin and gleevec

showed that the disease might be stopped by targeting specific oncogenes. researchers also now knew thatdifferent types of cancer were caused by genetic mutations, and it seemed possible a curecould be found for each. and there was still another reason for hope. scientists from around the worldwere already collaborating on what would become one of the largest scientific projects in history with major implications for cancer research--

the mapping of all the genes in the human body. but limited success did notguarantee ultimate triumph. mukherjee: in medicinethere's always self delusion. this is its greatest strength and its oldest sin. you always want to believe. if you become too inuredto the possibility of success, then you loose all your passion and you become a robot. on the other hand if you believe too much, you know, you become a monster, right?

and somewhere in between lies the real wisdom of clinical medicine. narrator: scientists hoped they had finally found the road to victory, but no one could imagine the number of twists and turns that still lay ahead. next time, on cancer: the emperor of all maladies... we have the opportunity to make progress at a level that we've never seen before. new treatments bring new hope. you're holding the cells in your hand that might save your life.

the cost of cancer... getting cancer is one of the worst economic things that can happen to you... ...and the future of the fight. if the cancer cell is evolving, then so are we. the conclusion of cancer: the emperor of all maladies. announcer: for web-exclusive content, more about the film, and to watch the entire show, visit

pbs.org/emperorofallmaladies and join the conversation on twitter using #cancerfilm. "cancer: the emperor of all "maladies" is available on blu-ray and dvd. the companion book is also available. to order, visit shoppbs.org

or call 1-800-play-pbs. also available for download on itunes.