Wednesday, 19 April 2017

Cancer Month

it is humanity's oldest enemy... its very name striking terror in those it has touched. cancer. after she said 'cancer,' she kept speaking, but i couldn't hear anything - i was just in shock. but now, after decades of research, there is new reason for hope. make no mistake, this is one of the most significant human challenges in our history.

a special three-part series explores the history of the struggle. from the pioneering surgeons, who first tried to physically remove the disease... how far could you go with your scalpel? to the first chemotherapy trials. one of the true ironies of oncology is that the very drugs that treat the cancer can themselves be cancer-causing. from the politics of healing...

look, we're dying out here and you have a medicine that could help me. to the latest breakthroughs in genetics and immune therapy. we gave that drug, and her response was...astonishing. we have the opportunity to make progress at a level that we've never seen before. from siddhartha mukherjee's pulitzer prize-winning book... if the cancer cell is evolving, then so are we. ken burns presents...a barak goodman film:

cancer: the emperor of all maladies. coming up next. man: i truthfully don't remember the drive itself. [siren] it's kind of surreal. you just don't believe that it's happening to your child. whaa! man: you know, of course you think the worst. i mean, anytime you hear "spontaneous bleeding,"

and, you know, you can't take her to the normal hospital that you would go, you need to take her to a special place, you don't know what to expect. woman: something was wrong with my daughter, and i was scared. she was not the normal, happy, running-around-playing girl. every thought went through your mind like, uh...

why? why is this happening? want to gonight-night, livy? you want to say night-night? man: it's your new reality. you know? your--your child... your child... has cancer. someday, i hope, and i'm going to pray for,

we will find a cure for cancer, and i want it done in my time. the time has come in america when the same kind of concentrated effort that split the atom and took man to the moon should be turned towardconquering this dread disease. in fact, it is now conceivable that our children's children will know the term cancer only as a constellation of stars.

for the first time in human history, we can say with some measure of confidence that the war on cancer is winnable. we will launch a new effort to conquer a disease that has touched the life of nearly every american, including me, by seeking a cure for cancer in our time. [applause] narrator: cancer is a worldwide scourge, the fastest-growing disease on earth.

by 2030, there will be as many as 22 million cases worldwide. cancer afflicts 1.7 million americans each year and kills 600,000 of them. more will die from cancer over the next two years than died in combat in all the wars the united states has ever fought--combined. one in two american men and one in three american women will be diagnosed with cancer in their lifetimes,

and nearly everyone will be close to someone who suffers from it. make no mistake, this is one of the most significant human challenges in our history. to imagine that we will find a simple solution to this, i think doesn't do service to the true complexity of the problem. cancer is part of our genetic inheritance. we will always have cancer amidst us,

within us, amongst us. narrator: cancer is not one disease. it's many. but each of them begins in the same way-- with the uncontrolled growth of a single cell. it attacks the blood, the breasts, the lungs, and every other part of the body. no one is immune to cancer, neither young nor old, rich nor poor, frail nor strong.

woman: cancer wants to live at the expense of your entire body and your entire being. it doesn't care about you. it doesn't care if you're a mother or a husband or a daughter or, you know, if you have 4 children. it doesn't care. it just cares about itself. animation: this is a struggle of life and death,

and we cannot win if we're afraid. narrator: but human beings have refused to surrender, have always struggled to understand it. was it god's curse? could you cut it out? could you burn it? could you poison it? was it a virus? did it come from the outside,

or did the enemy lie within us? in the ongoing struggle to conquer cancer, massive force has sometimes meant defeat. woman: so this will be your last cycle. tragic failure has led to remarkable success, and final victory always seems just out of reach. the struggle has reflected everyhuman strength and frailty-- resilience and terror, candor and denial,

arrogance and caring... you're doing good. blind allegiance and leaps of faith, hubris and hype and genuine hope. cancer has been called many things-- "the king of terrors," "a hidden assassin," and "the emperor of all maladies."

cancer has taken on this larger-than-life role in our culture, in our lives. it is the word that we relate to with simultaneous terror and some humility. it makes us resistance workers. it makes us historians of that empire. it makes us people who grieve about what happens when this invades our lives. it makes us soldiers.

but every year has brought a kind of clarity to our understanding of what goes wrong in a cancer cell and what can be targeted, can be prevented, can be treated. man: every field in medicine has had a moment in history that has been transforming, the moment where the knowledge that was required to change the field became available. [people cheer]

and my prediction is that the next 20 years is going to be the age of discovery for cancer and the age for new therapies. this is our time. narrator: in the winter of 1947, a 3-year-old boy dying from leukemia arrived at children's hospital in boston, massachusetts. mukherjee: he's pale, he's limping, and he has a gigantic spleen.

his spleen is so big that the child can hardly walk, and it's full of cancer cells. narrator: the boy's name was robert sandler. he'd been born to a working-class family in nearby dorchester. robert had an identical twin named elliot. man: being a duplicate, being a twin, and being your only friend, you realize quickly when things aren't right.

in the early years, probably 1947, we lived on blue hill avenue. that was a hustle-bustle time. [bell clanging] the trolley ran right in front of our house, and at night, we could stand by the living room window and watch the trolley sparks come from the wires. we could hear the animals from franklin park zoo, if the wind blew just right.

we went everywhere-- we did everything together. that's what twins do. i got sick, he got sick; what was different, though, was i got better and he didn't. narrator: even among cancers, the disease that wasravaging robert sandler's body stood out for its horror. leukemia is cancer of the blood-- the disease in liquid form,

rapidly proliferating abnormal white blood cells that crowd out healthy blood cells, ultimately leading to hemorrhage, infection, and death. like other hospitals, boston children's had a special ward for leukemic children. once consigned there, they rarely left. man: when we made ward rounds,someone would say, "leukemia," and that would be the signal

to shake your head "too bad" and move on. i remember one child, girl, she looked at me-- "i'm dying, i'm dying. "can't you save me, dr. pinkel? can't you save me?" sandler: those wards were not nice. there was a very narrow hallway, and there were rooms to the left and the right. the air was tinted with the smell of ether.

it was tinted with blood. you had kids crying, the parents standing on the sides by the walls, crying. it was not someplace that you'd want your loved one to be, not a place you'd want to be. i remember turning a corner,and my brother was in a crib, and he was crying like crazy, and i can remember putting my hand out to him. i was able to somehow keep him from crying more.

he stopped. narrator: at boston children's, robert was put under the care of a tall, imposing 44-year-old doctor named sidney farber. as the 3- year-old spiraled toward death, farber proposed a last-ditch attempt to save his life-- to poison the cancer by injecting the boy with a drug called aminopterin.

but the idea of injecting children with a rare, experimental drug was deeply alarming to farber's colleagues. mukherjee: people would say to farber, "why aren't you letting these children die in peace? "why are you performing experiments "which are going to be futile anyway? everyone knows that a chemical can't cure cancer." narrator: farber was determined to go ahead anyway,

desperate to save the lives of robert sandler and the other children whose treatment he oversaw. david nathan: if you want to talk about dread, sidney farber absolutely dreaded leukemia. that's because he did the autopsies on these children, and every single one of them died. they usually died in about 3 months, an inexorable death about which nothing could be done.

narrator: though doctors elsewhere had experimented with chemical cures, farber was the first to try aminopterin, a rare and possibly dangerous compound that starved white blood cells of crucial nutrients. on december 28, 1947, with the reluctant assent of the hospital board, farber injected robert sandler with aminopterin. no one, not even farber himself, knew what would happen. mukherjee: the question is,to what lengths would you go,

where would you go to look, how many poisons would you try, to try to cure this child-- not any child, not an abstract child, but this child-- and that was what was driving farber. narrator: sidney farber had first arrived at boston children's in 1929, becoming the hospital's first full-time pathologist. in his small basement lab over the next two decades, farber would view diseased tissue samples

from thousands of children, many of their lives cut short by leukemia. for generations, doctors had tried to devise medicines to treat leukemia. they knew that the only way to combat the disease would be to stop the runaway growth of white blood cells, and since that kind of out-of-control growth was the common feature of all malignancies, they hoped that leukemia would point the way

toward treating a whole universe of cancers. mukherjee: it is not a coincidence that cancer's history, at leastthe modern history of cancer, begins with childhood leukemia. a disease that carries 100% mortality, that occurs in children, and carries this kind of accelerated course was really a kind of reminderof the urgency of the problem. narrator: for farber,

the scientific puzzle of leukemia, coupled with its human toll,made it impossible to ignore. he was irresistibly drawn to thechildren in the wards upstairs and to the idea that he could do something to help them. man: i think that seeing the ravages of cancer impels someone like that to go on a crusade, to leave the autopsy room and to say, "i'm going to move out of my cubbyhole "and up from the basement,

"and i'm going to go front and center to make a difference here." newsreel: how many have cancer in the u.s. today? no man knows. last year, 150,000 died of it. the more science cuts down on other causes of death, the more are spared to die of this. narrator: by the time sidney farber had turned his attention to helping children like robert sandler,

cancer had become themost feared killer in america. newsreel: asleep. asleep, save for one member of the family. just one week ago, mary bronson discovered that she has what may be a symptom of cancer. mary: cancer. cancer. it can start, they say, almost unnoticeably, and then it grows and grows, a horror that never stops.

man: most cancers were incurable. mary: can my family catch it? my friends? man: but not only incurable; it was thought of, cancer was, as a contamination. that was one of the reasons some people with cancer isolated themselves-- because they were aware ofwhat it meant to some others. it was the reason that some people wouldn't let their children go near a relative who had cancer.

when i was growing up, i hadan aunt who developed cancer, and she was hidden in the attic. mary: what will happen to me? devita: people were ashamed if they had cancer. nobody wanted to be seen if they had it. mary: people don't tell you about cancer. they don't talk about it. why not? is a cancer victim an outcast? is there no hope?

no hope? nuland: we get the word "cancer" from the greek "crab," carcinos, which in latin becomes "cancer," because as you look at a cancer grossly, with your naked eye, what you see is a mass of tissue in the center, and it's as though legs are reaching out. it's this sort of formless thing that was creeping and crawling like a crab does.

narrator: cancer is as old as human life itself. the first known written reference to cancer appears in a 15-foot papyrus prepared by an egyptian physician 4,000 years ago. he numbered all the diseases and their treatments known to the ancient world. case number 45 refers to "swellings of the breast, large, spreading, and hard." under the section titled "treatment,"

it reads simply, "there is none." mukherjee: there is something haunting and prophetic about that statement. in fact, it rings through the history of cancer over and over again-- "there is no treatment, there is no treatment, there is no treatment." narrator: for centuries, cancer was considered a fatal disease without cure. ancient physicians had no real understanding

of where it came from or how it spread. nuland: they believed that balance was the essential thing that kept us healthy. and what was in balance? 4 different fluids, or humors, as they called them. they attributed diseases to either too much of one of these humors or too little.

narrator: in the first century a.d., the roman physician claudius galen theorized that it was an excess of one of the 4 humors-- melancholia, or black bile-- that gave rise to cancer. mukherjee: black bile was mysterious. it couldn't be seen, and was therefore used to explain diseases thatlacked any other explanation. narrator: galen's theories went unchallenged until the 1530s, when an anatomy professor named andreas vesalius

set out to create the first detailed maps of the interior of the human body. man: as he was dissecting human beings, he found a lot of discrepancies with what he was studying in galen's writings. and he was not out to topple galen. he had a great deal of respect and reverence for galen, but he kept finding things that did not jibe with what galen was saying.

narrator: bones, organs, intricate webs of nerves, arteries, veins. vesalius published meticulously detailed illustrations of everything he found, but no matter how hard he looked, or where he looked, he could find no trace of black bile. nuland: from then on in, what you begin to look at is an increased recognition by physicians

that when somebody gets sick, it's because something is going on inside their body, not because the humors have gone wrong, not because god has decreed it-- none of these things. something's going wrong inside the body. narrator: every morning, the doctors, fellows, and residents in the pediatric unit at johns hopkins kimmel cancer center sit down to review their patients' status.

all right. who's next? woman: olivia is our 17-month-old, previously healthy female, referred to the emergency department by her pediatrician. we suspected a.l.l., just looking at the morphology. narrator: 17-month-old olivia blair was admitted 24 hours ago. she was immediately diagnosed with

acute lymphoblastic leukemia. doctor: so i think we'll, you know, have a little bit better idea of things after the procedures today, and then we can sit down again and talk some more. man: we had been wondering what was going on with her, so we were looking for something to make it all tie together and make it make sense. she just seemed like she was sick all the time.

you know, you could tell, like, there was definitely something wrong. this is not normal. she was a pretty healthy child, you know, up to that point. i just felt like i was giving her tylenol and advil every single day. then she started to have that cold. it's all right, baby. don't cry. 104 fever. she scared me.

we hope, and we think, that she is going to be low risk. man: yeah. the other things that will help to determine her risk going forward is, number one, the spinal fluid test. we need to make sure that there's no leukemia in there. man: the bone marrow,where we normally produce blood, is kind of like your lawn, and leukemia is like weeds, so leukemia can overtakethe normal grass and kill it.

so, it's not enough just to mow the lawn. you've got to go and get the roots of all of the weeds and getall of the leukemia cells out in order for the grass to be healthy again. take some local anesthesia. it's not a perfect scenario. the treatment is tough. it's a long treatment. it's tough treatment. ok. phase two. narrator: olivia's treatment has to begin immediately,

before the disease progresses too far. she receives her first dose of chemotherapy directly into her spine. woman: she's breathing a little funny because she's sleeping so deeply, ok? so sometimes, just because she's not fully awake-- ok. [exhales] it scares me.

do you want a seat on this side? i don't like tosee her like that. kelly, voiceover: i started to pinch myself, like, "wake up. this isn't happening right now. "that's not my daughter. "she's not sick. that's not my daughter out there. "she's not going through this right now. this isn't happening. no." brown: for most parents, it is their worst nightmare,

and our job is to help them recognize that while this is obviously a shock and something that, you know, will turn their world upside-down, it's something that together, we have to figure out a way to work through. you know? they've got to be able to function as parents, now more than ever. yeah.that feel better? marcus, voiceover: no one has a manual

for trying to figure this all out. you're thinking that... is my daughter gonna die? narrator: in december 1947, within days of arriving at boston children's hospital, 3-year-old robert sandler received his first injection of the highly experimental drug aminopterin. as dr. sidney farber and his staff anxiously monitored his condition,

robert soon began to show results. within weeks, his blood, that had been choked with rapidly dividing white blood cells, returned to normal. farber noted that sandler's distended belly had shrunk. his appetite had returned, and he had begun playing in the hospital corridors. sandler: when robert went into remission-- what we now know is remission-- to me, he just got better.

he just was my brother again. it was a happy time. we were raising cain in the apartment. i didn't have to worry about him not being there in the morning. i didn't have to worry about him being sick. we thought it was a cure. man: the first demonstration of anything is an extraordinary breakthrough,

because leukemia was considered to be an absolutely fatal disease, and nobody thought that anyone would survive. narrator: other children under farber's care also showed promising signs of remission. perhaps aminopterin, the drug his colleagues had so resisted, might hold the key to a cure for leukemia. mukherjee: news of these remissions

really spread through boston, and the idea that you could hold cancer at bay with a chemical was suddenly in the public consciousness. this is a time whenpeople thought about cancer really as one kind of disease, and so the idea was that if you could cure or even potentially hold at bay leukemia, this could extend out to all other cancers. narrator: the dream of a cure for cancer

had long consumed some ofthe greatest minds in science, but had always foundered on a limited understanding of what cancer actually was. in 1855, a young german biologist named rudolph virchow stared down the barrel of his microscope and fixed on the honeycomb of structures that made up a sample of tissue. others had named these structures "cells," after the spartan roomsin which monks lived and prayed.

virchow had a revolutionary theory to explain cells-- they were not only the basis of healthy life, but of disease. a cell, he wrote, is"the ultimate irreducible form "of every living element, and from it emanate "all the activities of life, both in health and in sickness." nuland: as he studied cells under the microscope, he came to realize that there wasn't

some strange material that made the cells, but that every cell came from a previous cell. once he pointed out that thesis-- "omnis cellula e cellula," he called it, "every cell from another cell"-- that changed the understanding of what cancer was. cancer cells clearly came from cells that weren't cancerous. they clearly came from

perfectly normal cells that had been changed. narrator: virchow's discovery pointed to surgery as the primary treatment for most forms of cancer. if tumors were merelycollections of abnormal cells, it should be possible to cut them from the body. mukherjee: with the advent of anesthesia and antisepsis, with the advent of clean surgery, surgeons could now attack cancer with a real bravado. this was the golden age of cancer surgery.

narrator: no one championed surgery with more single-minded purpose than a doctor named william halsted. halsted entered the field of medicine in 1868 because he did not want to work in his father's clothing business. once he'd found surgery, though, he'd found his calling. nuland: he was a dashing, exciting surgeon because of how quick he was.

he developed a great reputation in new york city. narrator: from the beginning, halsted was known for his innovative and complex surgeries. he seemed intent on pushing himself and his patients to the limit. mukherjee: he's addicted to perfection. he's addicted to the idea that the reason that cancer is not being appropriately treated is because the surgeons aren't trying hard enough.

if they only tried more, if they tried better, if they were more perfect, if they could deliver a more perfect operation, then, in fact, they would cure more. cutting more meant curing more. narrator: in 1890, halsted became chief of surgery at the new johns hopkins hospital in baltimore, where he concentrated on patients with breast cancer. as he operated on more and more women,

halsted confronted a puzzle thathad long mystified surgeons-- even when the breast was removed, cancer could still reappear in entirely new places in the body. halsted thought he understood why. he believed that stray cancer cells had escaped at the margins of his incisions. his answer was to cut an ever-widening arc of tissue.

woman: halsted started with the idea that cancer started in the breast, and it grew centrifugally. it grew out from the original cancer. it had roots, it had, like, tentacles, and that if you could just get widely around it enough, you could get it all out, and you could cure it. markel: and so halsted got the idea, what if i remove the muscle underneath the breast

and then the muscle underneath that and then the lymph nodes beyond that? so he was doing this excavation in people's chests. he was really pushing the envelope. how far could you go with your scalpel? narrator: halsted called his procedure the radical mastectomy-- "radical" after the original latin "by the root," but others took it for the more common meaning, "extreme."

love: from a woman's standpoint, it's horrendous, because you're left completely flat. not only do you not have the breast, but you don't have your pectoralis muscle, either, so it's just ribs, and often you don't have a nice fold in your armpit the way you normally do because that muscle is taken, as well, and so it's really ugly and very deforming. narrator: despite the damage they caused,

halsted's radical operations did succeed in saving the lives of many of his patients whose cancers had not yet spread beyond the breast. markel: when you think about removing the amount of tissue he's removing and still having decent results, this is not a hack job. people who have described watching halsted operate speak of it in hushed, reverential tones.

it was like watching, you know, a virtuoso violinist or a great pianist. there were very few people who could do what halsted could do back then, and so every doctor, every surgeon turned their eyes to baltimore to see what the great halsted was doing. narrator: before long, other surgeons around the world were not only imitating his operation, but taking it even further.

in time, the radical mastectomy yielded to the super radical and then the ultra radical, and they did not stop there. man: surgeons used the halstedian principles of radical surgery for cancer, and they expanded it to other areas. they adopted the technique for cancers of other organs, so it grew widely throughout the specialties of surgery in the first half of the 20th century.

the common concept in surgical oncology was a big operation is more likely to cure a big cancer. narrator: but there was a problem with radical surgery. whether it was for cancer in the breast, lung, prostate, or any other organ, no matter how skilled thesurgeon or bold the operation, a significant number of patients still relapsed with the disease elsewhere in their bodies, as if the cancer had leapfrogged the surgeons' incisions.

clearly, there was a limit to what surgery could do. once the cancer had spread, it was too late. mukherjee: halsted's approachdid work for some patients. it was almost right, but it was not the full answer. and this idea--that, you know, you can take half-truths and you make full truths out of them, and then the logic of the field closes because you say to yourself, this is the truth and therefore lies outside the boundaries of being testable.

narrator: as surgeons searched for an answer as to why some cancers had escaped their incisions, another therapy appeared at the turn of the 20th century that seemed to promise greater success with far less damage. in the winter of 1896, a 21-year-old medical student in chicago named emil grubb㉠began experimenting with a newly discovered form of radiation called x-rays.

the mysterious rays were ableto pass through the skin. grubb㉠wondered if they could be focused enough and intense enough to burn out tumorsinaccessible to surgeons. on the evening of january 29, he aimed his homemade x-ray machine at the chest of a womansuffering from breast cancer. after 18 nightly treatments, the tumor miraculously began to shrink.

radiation was soon heralded as a miracle treatment. "i believe this is an absolutecure for all forms of cancer," one chicago physician exclaimed. "i do not know its limitations." mukherjee: radiation was the invisible knife, and therefore, it could cut into areas that the surgeon couldn't get to. it was called the hot knife, as opposed to the surgeon's cold knife.

grubb㉠realizes thatirradiation is also a poison, and if we can give just the adequate dose of poison, perhaps by giving it locally only where the cancer is, then we could kill the cancerand spare the human body. narrator: in the early 1900s, polish-born scientistmarie curie isolated radium, a highly radioactive element. alongside x-rays, her discovery spawned an industry. in the next few years,hundreds of radiation clinics

opened their doors across the united states promising a new treatment for cancer. grubb㉠himself was soon treating some 75 patients a day with a primitive apparatus. over the years, his gadget gave way to ever more powerful machines. by the 1950s, a stanford university scientist would even use a 6-million-volt linear accelerator to cure a limited number of cancers,

like hodgkin's lymphoma. but along with radiation's curative powers, doctors also discovered its harmful effects. in high doses, it could burn, scar, or blind. sometimes, it even seemed to cause cancer. grubb㉠himself fell victim to radiation poisoning, losing his hand, forearm, and upper lip. man: all of this was trial and error. many, many mistakes were made.

some of the most tragic mistakes were the deaths of the early investigators themselves, who often died of leukemia, of bone and other cancers that were caused by the radiation that they didn't understandwas a very potent carcinogen. narrator: perhaps more careful handling could mitigate the dangers of radiation, but there was a deeper problem. like halsted's radical surgery, radiation was effective

only when cancer remained localized. if the cancer had spread, radiation was as powerless as halsted's knife. it was increasingly obvious that what was needed was a third approach that would attack cancer wherever it had spread in the body-- a systemic treatment to conquer a systemic disease. woman: this is olivia blair. we have consent forbone marrow biopsy,

bone marrow aspirate,lumbar puncture, administration of itc,intrathecal chemotherapy. sison: correct. narrator: for leukemia patients today, the standard protocol is to attack the cancer with multiple rounds of chemotherapy, but that won't be enough for olivia blair. after a series of additional tests at john hopkins kimmel cancer center,

doctors have discovered that olivia's leukemia, a type called t-cell, has spread to her central nervous system, making the disease high risk. man: the central nervous system, which includes the brain and the spinal cord, that is actually a sanctuary or hiding site for leukemia cells. man: so obviously, the question is, what does this mean for olivia?

yeah. i'm automatically thinking that... the leukemia is in her spine. it's in her brain. so it's more serious, then? it's high risk. what that means is that her therapy will be more intense, that she'll getextra chemotherapy, and then we are also are going to recommend that she gets

spine radiation and radiation to the brain. we don't want to do radiation. i know. right? so we-- why...why are we doing that? sison: because we know that radiation will treat it. but we know that the radiation therapy could potentially have effects

on her cognitive abilities going forward. i just... come on, babe. come on. you're all right. we gave you one scenario yesterday. she's such a smart child. i know she is. she is, and she is going to continue to be smart. she has me and you as parents.

she won't see melike this, but... i know. i need to get this out. ok. she... she is an extremely smart child. how is this goingto affect her? you don't know. right? right.

sison: if olivia was 7 years old, we would not have a big problem radiating her brain. the problem is that because she's 17 months, her brain is not fully developed. it's almost there, but it's not fully developed. so one of the things that we are very worried about and thinking about for olivia is the role of radiation therapy. we know that at the dose that we prescribe,

there is certainly a chance of having a drop, for example, of, say, 10 iq points or so, but not anything necessarily more than that. that's not something trivial, though. we understand. sison, voiceover: the way that i'm looking at her case, frankly, is that we get one shot at this to get a good outcome to treat very well

because right now, the outcomes for kids with relapsed t-cell leukemia is not very good. it's less than 50% long-term survival. from a medical perspective, i'm willing to sacrifice the risk to her intelligence in order to cure her disease. man: we need to have the talk this morning and try to get the mri this morning to really get a handle on everything that's going on.

i don't want to havemore talks with you guys. sison: we don't, either. man: i know this has been a rollercoaster. like, when we came in, we were very optimistic, and we still are very optimistic about the ability to cure your daughter. nothing is going to change in this first month, so we have some time to figure things out. brown: what lengths are we willing to go

in the attempt to cure a child? we are quite willing to push the envelope in terms of toxicity because we know what's at stake is the rest of the child's life, and that's a potentially a very long life if they can be cured. narrator: for hundreds of years, doctors searched for a systemic treatment for cancer--

a chemical or drug that could find the disease wherever it had traveled in the body and destroy it. mukherjee: chemotherapy, the idea of using a chemical against cancer, actually has ancient roots. for a long time, forced by the lack of any other options, scientists and physicians were throwing all sorts of chemical mixtures at cancer.

the medieval apothecary was full of remedies, such as boar's tooth and fox's lung and crabs' legs ground up, and people, forced by desperation, tried all of these things. narrator: but without understanding even the basic biology of the human cell, chemical remedies were little more than guesswork. then, in leipzig, germany, in the 1870s,

a scientist named paul ehrlich began to dig deeper. ehrlich experimented with cloth dyes from the textile factories near his home. he noticed that the dyes stained only certain parts of a cell, as if drawn to them like a magnet. he wondered if such "selective affinity," as he called it, might mean that chemical poisons could be directed at diseased cells,

while leaving healthy cells alone. mukherjee: paul ehrlich decides that perhaps chemicals can fit into other chemicals like locks and keys can fit into each other, and so the idea grows within ehrlich that you can find specific chemicals that will kill specific organisms and spare other organisms. narrator: ehrlich called these hypothetical drugs "magic bullets."

markel: his theory was that every disease has an antidote, if you will, a "magic bullet" that will find it, root it out, bind to it, and render it harmless. narrator: ehrlich would eventually create some of the first modern drugs, such as salvarsan for syphilis, for which he won the nobel prize. but at his death in 1915,

the cancer cell, the target he'd hoped to hit, remained stubbornly out of reach. on a foggy night in july 1917, in the midst of the first world war, a volley of german artillery shells rained down among british troops dug in near a small belgian town. the shells carried a liquid that quickly vaporized. it was mustard gas, and in that one battle, it caused almost 8,000 casualties.

its immediate effects were horrific-- burns, blisters, blindness, death. but it had a longer-term effect, as well, evident in the few who survived it. the chemicals in the gas seemed to target only the white blood cells in its victims. markel: doctors realized by looking at the bone marrow of these patients that the white blood cells were wiped out of the bone marrow.

it was gone. it was a ghost town. that was a very interesting observation, but since mustard gas wasn't being used in the years after world war i, nobody really thought much about it. narrator: in 1942, during the second world war, two yale university researchers, louis goodman and alfred gilman, rediscovered the strange inhibitory effect

mustard gas has on white blood cells. though they understood how toxic such a chemical would be, the researchers set out to see if it could stop cancers of the blood. because mustard gas had been banned by international agreement, the researchers worked in secret. they first tested a mustard gas derivative known as nitrogen mustard

on a 48-year-old factory worker suffering from lymphoma. he was identified only as j.d. just as mustard gas had killed the white blood cells of world war i soldiers, its cousin nitrogen mustard aldo destroyed j.d.'s cancerous white blood cells, giving him a brief reprieve from his disease before it eventually overwhelmed him. markel: they put two and two together and said,

"huh. maybe this is a magic bullet, "one of the magic bullets that dr. ehrlich was hypothesizing about." narrator: in 1946, with wartime secrecy lifted, the yale researchers were finally able to publish the results of their study. markel: that started the ball rolling, that there were certain chemicals that were far more active againstcancer cells than normal cells

and that if you could use itin a controlled, measured way, you could use that to root out the cancer and kill it and cure the patient. narrator: when sidney farber read goodman and gilman's report, his reaction was that of a doctor of dying children-- urgent, pragmatic, and insistent. nitrogen mustard had shown that chemicals could work against cancer.

now it was time to try others, he said. "the 325,000 patients with cancer who are going to die this year cannot wait." mukherjee: farber was lookingfor something less toxic. he was worried that using chemicals like nitrogen mustard would have such natural limitations in sick children that he wanted other alternatives, and he wanted something thatwould attack growing blood cells with a little bit more specificity

than just another chemical poison. narrator: farber hoped that aminopterin would be that drug. in june 1948, robert sandler's remarkable recovery from leukemia was in its sixth month. his case was featured in a report farber published on the aminopterin trial in "the new england journal of medicine." it announced to the world that 10 of 16 children treated with the drug,

including robert, had experienced significant remissions. as the report went to press, most of those children were still alive, filling their parents, their physicians, and the public with hope. but in the months that followed, their leukemia returned, beyond the reach of farber's drug. one by one, they succumbed to their illness.

sandler: the last time i saw my brother, he was pretty sick. it was late at night. they called the ambulance. the two gentlemen who got out there were in their white smocks. they came upstairs, and they had lanterns-- not flashlights, but lanterns. in fact, they flashed one of those lanterns in my room,

and then they were told it was in the next room down, on the other side. and he was crying. out the door they went, and that was the last time i saw him. i don't even think he waved to me as he was leaving. those are some of the things that are just burnt in-- like you open a book, and there's the page. narrator: robert sandler died on april 2, 1949,

not long before his fourth birthday. boy: is it my turn? woman: hey, luca. what? jonathan's mom wants to know, what do you want to be when you grow up? what do you mean? entrepreneur. ha ha ha! that's what he told you.

narrator: luca assante was first diagnosed with rhabdomyosarcoma, a cancer of the muscles, when he was 2 years old. because his tumor was resistant to treatment, his doctors at johns hopkins resorted to high doses of chemotherapy. you're going to stay with me forever, right? no. brown: luca received what we would consider

just generally a salvage regimen, so these are drugs that might have more toxicities, so we make sure parents understand that there is a small risk that your child will develop a secondary cancer, a secondary leukemia, from this treatment itself. one of the true ironies of oncology treatment as it's given today, and as it's been given for several decades, is that the very drugs that treat the cancer

can themselves be cancer causing. narrator: luca was inremission for 2 and 1/2 years, but in the spring of 2013,during a routine follow-up exam, blood tests showed that he had developed leukemia, most likely the result of his earlier treatment. man: "doctor fees.pay 50." i have to pay 50? no. i do. you do? to meor to the bank?

he also had positive titers... man, voiceover: one of the reasons that this weighs on me, us, is that nobody caused the rhabdomyosarcoma-- it happened-- but somebody caused the leukemia. the drugs we gave him caused the leukemia. i told luca's family that this wasn't good and that it wasn't curable without a bone marrow transplant.

narrator: luca received a transplant from his sister 42 days after entering the hospital. it restored his immune system, which his doctors had intentionally wiped out, along with his leukemia,with high doses of chemotherapy. mother: you want to try to eat something? i'm not eating. but you got to try today, so we can get the tube out. are we done?

you got to one on the other side, right there. all right. luca's next. narrator: 17 days later, he remains under close supervision. man:hi. good morning. hey, he's up! can we see under your shirt? thank you, sir.

mother:is it itchy? no. no? brown: it's still warm. i don't feel it quite as much as yesterday. it doesn'tseem as raised. woman: it's really significant, though, isn't it? brown: yeah. the likely cause of this rash is that as his sister's cells have now started to take

and make their own blood. woman: his sister'sgrowing inside of him. mother: but it's notlike you test his blood, and it wouldchange or anything,because it's-- brown: oh, it does. mother: kind ofcool, right? kind of cool. brown, voiceover: what we hope to see is that there's very little of luca leftin his blood and bone marrow

and lots and lots of his sister there. brown: i think we'restill on track. nothing that's happenedhas put us off track for you guys gettingout of here real soon. mother: ok. that's what matters. cool. brown, voiceover: it's unbelievable what these kids can bounce back from and tolerate, and hopefully, he's on his wayto getting better from this.

he's by no means out of the woods, but there is a real hope that this too can be treated successfully and he can get on with the rest of his life, and that's what we're shooting for. let's go see if you can play with the wii. narrator: in the late 1940s, researchers still believed that cancer, no matter where it appeared in the body, was a single disease

for which there would someday be a single cure. the fleeting success of his aminopterin trial had convinced sidney farber that he was on the right path to finding that cure. but if chemicals were the answer, he'd need to try many more ofthem on his young patients, who were still dying despite his attempts to save them. that would require a great deal of money. farber hoped he could convince the public to provide it.

newsreel: the first lady enlists in america's fight on infantile paralysis. narrator: fortunately, there was a model for just such a fundraising campaign, focused on the eradication of a single disease. every summer, for decades, infantile paralysis--polio-- struck down thousands of children. sidney farber had encountered the disease as a young resident in the 1930s.

he'd also witnessed, and admired, the vast public and private effort to eradicate polio called the march of dimes. and i'd like a dime in change, too. are you saving them, mickey? mm-hmm. i'm gonna give mine to president roosevelt. the president?why, mickey! yes. you see, judy, i've got my envelope made out right here. it's all ready to go. see for yourself.

oh, i know. that's themarch of dimes, the infantileparalysis fund. that's right. narrator: with the help of hollywood celebrities, the march of dimes mobilized the public, who sent in coins by the tens of millions. roosevelt: i wish to express heartfelt thanks to all of you who have contributed your dimes and your dollars

to further the fight against a cruel disease. narrator: within a decade, the campaign had raised more than $200 million, funding the research that led to the salk vaccine. the march of dimes had inspired many to join the fight against other diseases. among them were the leaders of the variety club of new england, who came to visit bostonchildren's hospital in may 1947,

just as farber was in the midst of his aminopterin trial. nathan: my uncle and his partner started to go around boston looking for a place to put money, and they found, sitting inthe little dirty old basement of the children's hospital, sidney farber in his white coat. narrator: farber seized the opportunity to lay out his grand vision for a new kind of hospital, dedicated to childhood cancer.

nathan: sidney had enormous ideas. he had already started this treatment program in childhood leukemia, and he was going to build a new hospital. he presented them with his idea that he could manage childhood cancer on the first floor, and then there would be a tower of laboratories that would cure these patients and find the answers. well, it was for them,

exactly what they were looking for. they wanted something big, and he gave it to them. radio: now, in a few moments, we will bring to our microphone the winner of the jane doe contest, but first... narrator: on the evening of may 22, 1948, ralph edwards, the popular host of the radio show "truth or consequences," interrupted his usual broadcast from california

and linked to a room at boston children's hospital, where a little boy lay ill. edwards: well, we're not goingto give you his last name, because he's just like thousandsof other young fellows and girls in private homes and hospitals all over the country. jimmy is suffering from cancer, but he doesn't know he has it. narrator: "jimmy" was actually a 12-year-old boy named einar gustafson.

farber had changed his name to protect his identity and broaden his appeal so that he could become the mascot for his new cancer-fighting organization, the jimmy fund. edwards:hello, jimmy! jimmy: hi. who do you think is going to winthe pennant this year?

the boston braves, i hope. ha ha!who's the catcher? phil masi. that's right. have youever met phil masi? no. man: hi, jimmy. my name is phil masi. who is that, jimmy? phil masi! well, where is he?

in my room. mukherjee: this was a way of really turning around the conversation. cancer was not some abstraction that we couldn't talk about, we were too worried to talk about. cancer was jimmy. here was a real child with real cancer. they weren't donating tosidney farber's fund for cancer. they weren't donating

to children's hospital fund for cancer. they were sending money directly to jimmy. narrator: donations poured in, many in envelopes addressed simply to "jimmy, boston, massachusetts." the "truth or consequences" radio broadcast, which had hoped to raise $20,000, raised 200,000. soon, red-and-white jimmy fund cans

seemed to be everywhere-- in movie theaters, next to the cash registers in grocery stores, posted outside baseball stadiums. man: the variety clubof new england presents thegreat heart award to dr. sidney farber,medical statesman. his vision extendsbeyond his laboratory. may i take this opportunity...

narrator: with the jimmy fund, the scientist sidney farber had also become a public figure by offering the hope for a cure. man: now, thanks to you, there's a new and beautifully equipped jimmy fund building, where more than 200 children with cancer are given care and treatment every day. narrator: on january 7, 1952, farber opened the cancer hospital he'd dreamed of,

a modernist 5-story building called the jimmy fund clinic. woman: it was just a wonderful place, full of toys and trains, and the clinic, the jimmy fund clinic, made everybody just as comfortable as could be. woman: these children were special. it was a very open, free atmosphere. the children could mix from one room to another,

from one bed to another. narrator: farber was deeply moved by the plight of the children under his care, though he rarely showed it. evans: sometimes in the evening before he was leaving, when everything was quiet, dr. farber would just go into a room and look at a sleeping child and stand maybe at the foot of the bed or just inside the door,

and he had a deep humanity. these were his children. he talked about it-- sort of his children. narrator: farber's certainty that a cure would be found helped keep despair at bay. the jimmy fund clinic, one visitor wrote, "seemed suspended between two poles, "both wonderful and tragic, unspeakably depressing and indescribably hopeful."

man: my father never talked about his work in terms of failure. he was engaged in hope. hope really was his driving element. in order to keep children alive through chemotherapy, often, the treatments were going to be enormously punishing, and you just had to believe, you had to have a faith that there was a reason for this and that things would improve.

luca. narrator: it's been 3 weeks since 6-year-old luca assante received a bone marrow transplant, but complications are setting in. mother: luca feelinglike this is crappy. he's been sleepinghalf the day. yes. so his fever went up.

i mean, just notbeen feeling good. you know? oh, boy. wake him up. let himknow you're here. i tried. luca. man, voiceover: this is actually my first time i come up and he's sleeping. he's always awake. so...he's tired.

luca, you wantto eat something? hmm? does your back itch? huh? narrator: luca is suffering from graft-versus-host disease. the immune system transplanted from his sister has begun to attack his own cells as if they were foreign, like an infection.

the big issue since last week was the development of rash that progressed on friday. narrator: the doctors' hope is that luca's new immune system will attack only his cancer cells, a beneficial effect called graft-versus-tumor, but if it goes beyond the cancer cells and begins to attack his organs, it could threaten his life.

good morning. good morning. uh-oh.somebody's hiding. where's luca? mother:how do you feel? narrator: luca's doctors are concerned because his liver is showing signs of distress, but they don't know what the source of the problem is-- a viral infection

or his new immune system turning against him. loeb, voiceover: the things that have been challenging about taking care of luca-- it has been hard to come up with clear diagnoses for what's been happening. narrator: there is very little margin for error in luca's therapy. the dilemma is that the treatment for graft-versus-host disease-- to suppress the immune system-- could actually make a viral infection worse.

to try to find out what'sgoing on inside luca's liver, his doctors must perform a biopsy. mother: she's giving you pain meds right now, sweetie. i hurt! i want to see exactly where it hurts. narrator: luca's liver is so weakened by his cancer treatment that the operation pitches him into yet another crisis.

his blood cannot clot, and he is hemorrhaging internally. your stomach hurts? man: it's going to be sore, buddy. i'm sorry. mother, voiceover: i don't think anybody would think this would happen. i don't think we thought it was going to turn that bad. narrator: luca will be taken to the pediatric intensive care unit,

where his condition can be closely monitored. lucy, voiceover: when you hear that someone is going to the picu, you know that it's super serious, so the picu scares me. it really does. but i would stay here for months. i would stay here for years, if that's what would make his body better. film: youngsters from all over the world

are being cared for by doctors and nurses backed by teams of scientists and researchers at the jimmy fund building with just one goal-- the cure of cancer. narrator: at the new clinic in the early 1950s, sidney farber was doing everything he possibly could to cure the children under his care, but he was making little clinical progress against leukemia.

within the cheerful wards of the hospital, he tried new drugs at ever-higher doses, but in the end, the children always died. the scope of the problem was too big and too expensive for any one man or any one clinic. farber knew he needed still more help if he was ever going to create a research program big enough to conquer cancer. he needed an ally.

mrs. albert d. lasker is a woman of many and varied interests-- flowers and philanthropy, cancer research and community welfare. mary, are you happywith what is being done in the wholearea of financing medical researchin this country? oh, i'm not a bit happy about it. the amount of money that's available for research

is totally inadequate in the united states. you won't believe this-- less is spent on cancer research than we spend on chewing gum! narrator: mary lasker was not a scientist, not a doctor. newsreel: america's foremost medical scientists and administrators received the american public health association's lasker awards.

narrator: she was a wealthy socialite and a prodigious fundraiser with a passionate interest in eradicating disease. newsreel: mrs. mary lasker and dr. george bayer, head of new york academy of medicine, present the medical oscars in boston. narrator: "i am opposed to illness," she once told a reporter,"the way one is opposed to sin." woman: i often asked mary why this had become

such a consuming passion and conviction, and she said, "well, i suppose it started that i suffered illnessand pain when i was a child." narrator: born in a small wisconsin town in 1900, mary woodard suffered from life-threatening infections, which left her, as she would later say, "deeply resentful" of medicine's limits and acutely sensitive to the suffering of others. blair: one day, her mother took her to see

the family laundress, who had had double mastectomies, and mary said, "why were they cut off?" and her mother said, "to try to save her life." she was outraged by disease and illness. narrator: after moving to new york, mary became a successful business owner, selling high-societydress patterns to working women. there, she met her second husband in 1939, a wealthy advertising executive 20 years her senior

named albert lasker. advertisement: places all! all join hands. circle left. narrator: one of the mostinfluential admen of his time, albert had made a fortune promoting products like lucky strike cigarettes. ad: ⶠyes, for smoking that you're bound to like ⶠⶠyou just can't beat a lucky strike ⶠman: on their wedding night, albert says to mary,

"what do you want to do with your life?" mary said, "i want to do something for human health, "the major diseases and crippling diseases of mankind." narrator: above all, mary wanted to cure the disease that had long ago disfigured her family's laundress. before long, albert had enlisted in mary's cause. there was limitless money out there, he told her, and he would show her how to get it.

the couple held lavish fundraisers in their east side apartment. mary lasker: i have some pictures here by cezanne and manet and renoir, van gogh. gutterman: she felt that you had to have money to get people working on a problem. she once called money "frozen energy," and i think it's an apt description. it's perfect.

"what's the money doing?" i mean, she would complain about this all the time. narrator: in 1944, the laskers took over a small charity called the american society for the control of cancer. man: strike backat cancer! give to the americancancer society. they renamed it the american cancer society and stacked its board with advertising executives.

they not only wanted to raise money, they wanted to remove the stigma around cancer, with the help of madison avenue salesmanship. did you know that cancer kills more children between the ages of 3 and 15 than any other disease? give generously to theamerican cancer society. it's really very simple--just mail your gift in an envelope,addressed like this.

mukherjee: mary lasker brought a kind of energy, a kind of dynamism, a kind of vision that had never existed before. she began to create a kind of public force around cancer by deploying all her wealthy friends, but reaching deeply into theminds of the american public, and in doing so, cancer could make that leap away from, you know, the back wards,

the shunned-away, the pariahs of medicine into becoming a vast public phenomenon. mary lasker, as aperson of some means and great interest,you can devote much of your timeto medical research. how do you go about enlisting supportfor your views? well, i'm very vocal about them, and i urge everybody to give more

to the voluntary agencies like the american cancer society and others, and i urge them... narrator: mary lasker battled cancer every day in the public eye, but she lost the battle at home. on may 30, 1952, albert lasker died of colon cancer. mary lasker redoubled her efforts

against the hated disease. she knew she could only get so far with private funds. she had to tap the vast coffers of the federal government. for this, she would need a bona-fide scientist to validate her evangelical belief in a cure. there was only one possible man for the job. groopman: mary lasker saw in sidney farber someone who could be presented as a believer that this can change and that we can find the answer

and that we will cure cancer. narrator: farber had been searching for that cure for almost a decade. he and lasker concluded that what was needed was an all-out coordinated attack on cancer, undertaken by the largestprivate and public partnership in the history of health care. groopman: mary lasker had the political smarts and the connections,

and sidney farber had the gravitas, and together, they formed a formidable force that really couldn't be stopped. man: dr. farber has been called the father of chemotherapy in the treatment of cancer. narrator: while lasker workedher contacts in congress, farber did his part, proselytizing for the coming revolution in chemotherapy. dr. farber, will youmake a prediction

as to how long it may take before cancer can becalled conquered? i don't believe that's possible, sir. i think the answer is that there is more activity and research today in the field of cancer than ever in the history of science and medicine, and with this tremendous amount of activity, i think we have the right to expect that great progress

and rapid progress will be made. narrator: farber and lasker concentrated their efforts on a small, poorly funded government agency, the national cancer institute--the nci. they hoped to focus its mission and provide the means to eradicate all forms of the disease. by 1955, lasker and farber's efforts had succeeded. with new appropriations from congress,

the nci would quickly become the center of the cancer world, and at its center was its scientific director-- a bold, brilliant specialist in infectious diseases named gordon zubrod. during world war ii, zubrod had helped lead the federal government's massive effort to combat malaria, which had ravaged american forces in the pacific. he employed some of the first randomized clinical trials ever conducted.

zubrod brought the same military precision and gung-ho spirit to the nci, recruiting a new generation of researchers willing to try almost anything to defeat cancer. one of zubrod's first recruits was a 28-year-old specialist in blood disease named emil freireich. man: we dumped my 3-month-old baby and my pregnant wife and my broken-down car

and took everything i owned, and we drove to washington, and i went to his office-- dr. zubrod--and i said, "i'm reporting for active duty." and he said, "freireich, what do you do?" i said, "well, i'm a trained hematologist. i made a great discovery in mechanism of inflammation." "you should cure leukemia." "yes, sir." narrator: zubrod paired emil freireich

with another young researcher, coincidentally named emil frei. to tell frei and freireich apart, their colleagues began calling them tom and jay. mukherjee: they were both named emil, but they couldn't have been more different characters. frei was composed, reserved. he was cool. jay freireich was the opposite.

he was loud. he was passionate. he was charged. narrator: zubrod fostered a try-anything approach, which was especially appealing to frei and freireich, who already had reputations as daring and innovative researchers. with their colleagues, they began to scour the natural world for chemicals to try against cancer.

no location was too far away, no compound too exotic. film: the search is worldwide. there are 10 million natural products that might contain an anti-cancer compound. near nairobi, botanists gatherleaves and the bark of trees to process and test against cancer. mukherjee: there were tens of thousands of drugs that entered the nci pipeline. we are talking about an enormous,

extremely sophisticated for its time, extremely dedicated process, which creates a vast library of chemicals from the natural world, from the unnatural world, and each chemical asked the question, does it kill a cancer cell? what kind of cancer cell? at what dose? does it spare a normal cell? nothing of this sort hadoccurred in the world before.

narrator: following sidney farber's example, frei and freireich began testing the most promising chemicals on children with leukemia. parents flocked to the nci clinic to enroll their sick children in the trials. freireich: they were there for only one reason-- not to figure out why they were sick, not to figure out how they got sick, but to get better. they came to the clinical center like you go to lourdes.

they came seeking some relief from the horror that they had to face. if you can imagine... your children, 6, 8, 10 years old, and they're bleeding to death, and they have lumps all over, and they have headaches, and they're vomiting, and they hurt. i mean, it's horrible. all these parents, just hounding me,

"you've got to do something, freireich." well, we had to do something. narrator: the researchers did all they could, but progress was agonizingly slow. no sooner would a drug begin to work than the cancer would adapt a defense to it. nathan: the problem was resistance, that cancer is a complicated illness that can find a way to bypass

the very action of the drug that you're trying to give. narrator: but the nci researchers believed they knew how to overcome the problem of resistance. freireich: zubrod came from infectious disease, and the infectious disease guys had learned an important principle-- that is, if you gave two drugs at the same time, the emergence of resistance was prevented, and it was more effective.

nathan: but how much of each drug should you give? should you give a full dose or cut the dose? how many doses a day or a week? it was all unknown. narrator: unlike sidney farber, who favored giving one drug at a time, frei and freireich experimented with two-drug combinations. each time, the remissions grew longer,

but still the children relapsed, or simply succumbed to the brutal side effects of the treatment itself. freireich: at the time,80% of the children who died, died just from bleeding to death. leukemia didn't have a chance to kill them. there's blood on the sheets. there's blood on the uniforms. the nurses are covered in blood from head to toe.

the trials really crept ahead, month by month by month, often increasing survivalby 2 months, 4 months, 8 months, and you could say to yourself,"why am i doing all of this? "am i really doing all of this to increase "the lifespan of a child by 3 months? is it really worth it?" narrator: david nathan arrivedat the nci's clinical center as a young researcher assignedto the leukemia division. nathan: i have to say,

it didn't look likebiomedical research to me. it looked just like a death warrant. these kids would come in; of course they were going to die of their disease, but we were making them much worse. i felt it very, very keenly. it was hard. i felt so badly about what i was doing that i went to see dr. zubrod,

and he wanted me very much to continue, and i had to tell him that i just didn't think i could do it. his answer to me has always stayed with me. he said, "i understand you completely. "i know what this is like. "i know what's going on there, but we're committed. "we're going to do something about childhood leukemia, and the only way we can do it is to push ahead."

narrator: despite the children's deaths, frei and freireich had seen pronounced declines in white blood cell counts, a clear sign that the toxic chemicals were having an effect on the disease. encouraged, they pushed even harder. if two drugs were better than one, then four must be better than two. in 1962, they launched a trial called vamp. mukherjee: vamp was an acronym

for 4 individual chemotherapy drugs, and they had all been chosen because the theory was that each of them had a different pattern of attacking cellular growth. it would be synergistic, and it would therefore kill all cancer cells, drive the cancer cells down to zero, and therefore completely cure the cancer. narrator: on september 24, 1962,

frei and freireich began treating the first group of children in the vamp trial. there were 16 of them-- 10 girls and 6 boys. researchers at the nci were deeply divided. some believed that vamp was going too far. if two drug combinations had caused children to bleed to death, what would four drugs do? freireich: we're a bunch ofyoung bucks who know nothing. everybody thinks we're experimenting on the kids.

they're worried about buchenwald and horrors... but when you understand something, you understand it, no matter what people say, you know? i was looking at it. i understood it. i counted the cells.i took care of the children. i knew it was right. "you're wrong, freireich." well, i mean, how the hell do you know i'm wrong?

i mean, i know what i'm doing. tinkle, tinkle! there you go, darling. narrator: olivia blair has responded extremely well to her first month of chemotherapy, and she is now in remission. bye! say thank you. blow kisses? you're welcome.

do you see the difference in her since the beginning? kelly, voiceover: she's just so strong and so resilient. it's just amazing. if i had been through half of the stuff that she's been through, i would be in bed, like, "don't talk to me. please don't talk to me." man: hi, guys. how you doing? narrator: although olivia's doctors are encouraged by her early response,

they remain concerned withthe possibility of a relapse. what's he doing? marcus, voiceover: when you hear that word remission, you think that that means she's cured, and so that's a common misconception. do you like this light? it just means that they can't see it. narrator: the doctors are recommending olivia be enrolled in a clinical trial

of yet another chemotherapy drug, called nelarabine. there you go! sison: a lot of people know that leukemia in kids is curable. when we present the idea of a clinical trial to parents, they understand that this is how we got to where we are today. they understand we're not necessarily "experimenting" on their child, that we're actually taking

the best-known treatmentand trying to make it better. man: so, at this point, olivia is in the category of intermediate risk. what's mrd? sison: mrd is minimal residual disease, so that's the amount of leukemia that we could detect or not detect at her day 29 bone marrow from monday, so her mrd is 0.0. it's the absolute best result we could have hoped for. ok?

great. wonderful. all right. now where do we go? we know that patients, even when they're mrd negative, have leukemia somewhere in their body, and if we don't continue treatment with an intense regimen like we're planning, then it will come back.

and the question is, does she receive nelarabine? ok? we don't know if it helps, and even if it helps, we don't know if it's worth the side effects that you could potentially have from nelarabine-- nausea, tiredness, fever, decreased counts, and then, less likely, fast heartbeat, blurred vision, pain in the eye, pain in the abdomen,

sores in the lining of the throat... sison, voiceover: so, all of the treatments that we give have significant and severe side effects... increases in bilirubin, infection... but again, it's one of those decisions of balancing a patient's life versus the side effectsthat the treatment will give. muscle damage that also can then damage the kidney, problems with breaking down carbohydrates, also,

that would cause inflammation in the pancreas. [olivia crying] as you can see, the list is long. this is probably the hardest decision along the way that you guys have to make. how do we find out ifthey get the nelarabine? how do youfind that out? it's random--it's randomized, right? sison: there's a formula that spits out,

"ok, the next patient that consents is gonna get it, and this one's not going to get it." that's like... i don't...i don't... i don't feelcomfortable with that. the thought of your child's treatment being left up to a computer is a very hard concept to take. marcus, voiceover: when you're making

those type of decisions, of course you want it to be the right thing for her. and it's ok if you decide not to be in the study. marcus: so you just try the best you can as a parent to learn as much as you can to make an informed decision, but you never know. it's 1-10% on the... on the highest.

i know we all want to do what's best for livy. yeah. i don't know what to say. [clears throat] lord, what we ask for youright now, father, is just to kind ofnudge us in the rightdirection, lord, and put us at easeand at peace with the decisionthat's ultimately made, and we just humbly askfor your guidance in makingthis decision, lord.

um...amen. in jesus' name. amen. amen. woman: 1963. that's when i first felt sick. i was in junior high school, and we were living on eastern avenue, and we were walking down to the beach, my sister and my friends, and, um...i was tired. i really felt tired.

you know? it wasn't like the measles or, you know, chickenpox. usually that would go away, but this just didn't go away. it just got worse. narrator: karen lord was 13 years old when she was diagnosed with acute lymphoblastic leukemia. in june, 1964, with her health declining,

she was taken to a hospital in boston, where she was quickly put on the 4-drug vamp regimen first tried at the nci by tom frei and jay freireich. lord: my doctor just decided that i would not know. they just didn't talk about it. they just would say,"here's your daily cocktail," but they wouldn't say the word chemotherapy. i called the treatment my martini time with the iv. yeah. we'd joke about it, the nurses and i.

"oh, it's martini time again." when i had first entered the hospital, i was 108, and i went down to 50 pounds. for a year, i was mostly in bed, and i just would be in afetal position most of the time. narrator: the chemotherapy caused severe nerve damage and made karen so delirious at times that she had to be forcibly restrained. she became addicted to morphine

and for months hovered near death. lord: i remember the priest coming in, and he had this purple scarf around his neck, and he had this little cross, and he would pray, and he didn't tell me i hadthe last rites of the church, but i knew it, and i had it 3 times, so... sometimes the pain was so bad, it would have been better if i did go to the other side. narrator: gradually, though, the drugs began to work.

lord slowly recovered. after 12 months of treatment, she was ready to return to school and a normal life, one of the first children ever cured of leukemia. lord: when i went back to the high school, they all thought i died, and they says, "ooh, we thought you were dead," but i says, "no, i'm not dead. i'm here, and i'm back in school."

narrator: other children in the vamp study also began to see the tide of white blood cells created by their leukemia slowly recede. mukherjee: incredibly, some of the children actually began to recover, and when they did bone marrow biopsies, they began to find that in fact, the cancer had gone into a profound remission-- a remission so profound, so deep in leukemia

that you couldn't finda single abnormal cancer cell inside any of these bone marrows. narrator: though still the minority of cases, these were not the fleetingremissions of farber's trials. these lasted. freireich: the breakthrough of vamp was, number one, the concept that a systemic cancer could be cured. from that point forward, cancer research was totally transformed,

because now, people who said, "you can't cure cancer. you're finished." we can cure cancer,at least childhood leukemia. narrator: despite its intense toxicity, the success of combination chemotherapy suggested that it might be possible to use the same strategy against much more common varieties, such as breast and lung cancer, even after they had spread.

dr. farber, how do you think cancer will eventually be controlled? i think that cancerwill be controlled, eventually,by chemical means. narrator: from his office at the jimmy fund clinic, sidney farber had followedthe multi-drug trials at the nci with a mixture of pride and apprehension. his experiments with aminopterin had inspired frei and freireich's work,

yet for farber, the suffering inflicted on children by these trials crossed a line beyond which he would not go. younger scientists did not share farber's apprehension. even david nathan, once a skeptic, was now converted to high-dosecombination chemotherapy. nathan: by that time, about 30% or so of the children were surviving with combination chemotherapy, and as far as i could tell, there were no survivors

in patients with the chemotherapy that sidney wanted to do. narrator: in 1968, after leaving the nci for boston children's hospital, nathan made the trip to the jimmy fund building to confront farber. nathan: i go into the room, and there he is in his white coat, and i start right away and say, "you know, i really feel "so strongly about combination chemotherapy,

"and i feel as a physician "that i cannot refer the patients to you if you won't adopt it." well, he absolutely flew into a rage. he really shouted at me and simply said, "get out of here. i'll never see you again," and i realized i never would see him again. he really hated to hurt a child, and that dominated him.

i had to say to him, "look, isn't it better to try to cure one out of three?" and i can still hear him saying, "i will not injure two children to save one." narrator: it's been 40 days since luca assante's transplant, and the latest results from his bone marrow biopsy have just come in. so how was his bone marrow test? they did a good job?

they didn't seeany leukemia cells. that's great news. you deserve some goodnews once in a while. yes, we do. that is good news. narrator: luca's new immune system, transplanted from his sister, has taken over and is producing healthy blood cells that have driven his cancer into remission. what about the rest of the things?

i mean, the bilirubin went up. yeah. so the onlynegative thing is that the bilirubinwent up some. narrator: but the new immune cells are continuing to attack luca's liver in what is now a full-blown case of graft-versus-host disease. i can't spin thatinto a positive thing. oh, my god. something else? we don't need anything else, ok?

we've had enough. the virus piece is better, but he's not all better. so we have no recommendations for any changes today-- just more of the same. more ofthe same is good. loeb: i think that the reason that he's not all better is because of the graft-versus-host disease, so hopefully, we'll make that piece better, too.

narrator: after 20 days in the pediatric intensive care unit, luca has become critically ill. lucy: the worst feeling is not being able to hold him. you can't physically, like, hug him the way you want to. luca, look.your soccer coach just emailed mommyabout you. he wants to know,are you gonna be able to go play soccer? you want to go play soccerwhen you get back home?

lucy, voiceover: i hadn't heard my kid talk in 20 days. so i haven't heard him say "mommy" in 20 days. that's pretty tough. but i have my husband here with me, and we don't leave luca at all, so he knows we're there. sometimes people think you're stronger than what you really are, but i feel strong because i'm fighting with luca, and i'm not going to let him fight alone.

good job! you want to put thison the side? you play later?or you want to play? narrator: luca's doctors were not able to reverse the course of his disease. two months later, he died at home, surrounded by his family. luca was 6 years old. loeb: we're still in an era

where we give kids treatment to fix one tumor, and it has the chance of causing another. i don't regret giving him those drugs because if we hadn't given him those drugs, he would have died at age 2 instead of 6, but it's still bothersome to know that the drugs that we gave him to treat his first tumor ultimately caused him to die as a child. there are still parts of his case

that none of us really understand very well. i'm sure that we're going to spend a lot of time trying to understand what happened, because if we can understand what happened, then maybe we can do something different next time, and the next kid won't have this happen. dr. farber, it gives me great joy to give you the american cancer society's high honor, its gold sword.

narrator: by the late 1960s, sidney farber and mary lasker's campaign to cure cancer seemed more urgent than ever. lasker continued to take her fight to congress and to lobby her close friend in the white house, lyndon johnson. gutterman: one time, a year before johnson left office, mary went to the white house because she wanted an additional $100 million appropriated

for cancer research, and so she's in the oval office, and lyndon's complaining about everything. the vietnam war is still raging. "mary, i just can't do it. $100 million!" and she said, "lyndon you have to. we're getting progress now." and lyndon was a bit of a flirt, as we all know,

and he put his hand on her knee and said, "mary, how badly do you want that hundred million?" and she not so gently lifted his hand off her knee and said, "lady bird is my best friend in the world. now, am i going to get that hundred million?" and he said, "you got it mary." man: hello, "eagle."houston. we're standing by.over. [beep]

narrator: in the summer of 1969, americans walked on the moon. national faith in science soared. roger. the eva isprogressing beautifully. they're setting upthe flag now. narrator: the moon landing was the result of a close partnership between science and government. if such a partnership could conquer space, farber and lasker wondered,

why could it not conquer cancer? i, richard milhous nixon, do solemnly swear... narrator: there was a new president in office now, and they set out to enlist him and the american public in a campaign far more massive than had ever been seen before-- a conquest, as mary lasker put it, of inner space. mukherjee: in december 1969, if you woke up and you opened "the new york times,"

you would find a very different kind of advertisement-- not for a product that you could buy, but for something that the nation should buy, and that was for a war on cancer. groopman: the advertising was a juggernaut. they said, here it is. many people won't utter the word. we're saying it in "the new york times," we're saying it to the president of the united states,

and we are going to mobilize a national effort with a promise that this horrific disease will be eradicated." narrator: on march 9, 1971, senators edward kennedy, a democrat, and jacob javits, a republican, introduced a bill calling for $400 million in federal funds to fight cancer. lasker lobbied her many friends on capitol hill,

refusing to take no for an answer. gutterman: mary's skills when she went to congress were a sight to behold. there was no time for small talk. she would say, "i'm just here on one issue." many of them would complain, look at their watches-- "i know what you want, but, you know, we got all these bills." and she said, "but what about your wife?

i understand your wife has cancer." "yeah, that's unfortunate." "well, how do you think she's going to get better? can i count on you?" narrator: "the iron is hot," farber had written lasker. "this is the time to pound without cessation." lasker turned to her friend, the newspaper columnist ann landers, to urge her readers to write their congressmen.

landers' column ran on april 20. within days, mountains of mail were piling up in capitol hill mailrooms. blair: the outpouring was beyond imagination. hubert humphrey called up mary and said, "you've got to give me another secretary. i have 60,000 letters in my office." narrator: thanks to farber and lasker, cancer was no longer a diseaseto be hushed up or hidden.

"to oppose big spending against cancer," one observer said, was now to "oppose mom, apple pie, and the flag." with this groundswell, the senate passedthe national cancer act, 79-1; the house, 350-5. members of the senate, members of the house, ladies and gentleman, we are here today for the purpose of signing the cancer act of 1971,

and i hope that in the years ahead that we may look back on this day and this action as being the most significant action taken during this administration. thank you. narrator: the passage of the act provided funding for cancer prevention and research that dwarfed anything that had been raised before-- $1.6 billion in the first 3 years alone.

groopman: the national cancer act was a paradigm change. it was the selling of a dream, to not only look to government for the kinds of sums which would be very hard to raise even with the most generous of philanthropists, but also to create an entity based on a promise, and that was the cure of cancer. narrator: today, more than half a century

after sidney farber's first chemotherapy trials, childhood leukemia has a survival rate of nearly 90%. the era of bold and ceaseless experimentation, borne mostly by children, led to the most elusive of achievements--a cure. brown: every time you can chip off a little bit of uncertainty and make the right answers more clear, in any aspect of the clinical care that we give, it's gratifying.

if you look 50 years ago, it was all uncertainty. now there are certain things that we know are effective, where the right thing to do is so clear. the more that we can chip those things away and put them into that category, the less humbled we're all going to feel. olivia! what do you think? oh, i know. this is cute.

narrator: for olivia blair, almost a year after her diagnosis, her cancer remains in full remission. i love you. kelly, voiceover: we don't want her to know that something's really wrong with her, because she has no idea what's going on right now. where's livy? she's so young. she's not going to remember this.

boo! boo! peek-a-boo! there you go. kelly, voiceover: she's going to beat this. she's going to be 32 years old, and she's going to be proud to show her port scar and say "look at me." where's petey? i...

just don't want to think the worst anymore. i just want to think the best, and... just enjoy the time that we have with her. where you want to go? come on. narrator: in the late afternoon of march 30, 1973, an emergency signal sounded throughout the jimmy fund clinic in boston. doctors and nurses raced

toward the director's eighth-floor office. they found sidney farber withhis face resting on his desk, dead from a massive heart attack. farber: in some ways,my father was remarkably lucky to be able to work until the moment he died. to be in that environment, to still be pursuing his dream, he was a very fortunate man. he wouldn't have used this language, maybe, but i would say he was blessed.

narrator: farber was survivedby a handful of the children he had treated at the jimmy fund clinic, including "jimmy" himself, einar gustafson, who would live to the age of 65. farber himself had not lived to see how the war on cancer he had helped bring about was waged, but his friend and partner mary lasker believed victory might now be less than a decade away, and she had reasons for her optimism.

she and farber had helped turn cancer from a subject no one wanted to talk about into a national priority. the full force of the american government was now enlisted in the struggle. nixon: it will not fail because of lack of money. if $100 million this year is not enough, we will provide more money. narrator: new techniques in surgery and radiation

were now being used effectively against a variety of cancers, and researchers had discovered chemicals that could kill malignant cellsno matter where they spread. to some in the cancer community, the challenge now seemed simply to find the right combination of chemicals to combat each kind of cancer. but despite these initial triumphs, the war on cancer would stretch on

for 3 decades and more, and those who fought itwould find themselves engaged on a thousand battlefields against an elusive and resilient enemy-- the cancer cell itself, whose true nature no one yet fully understood. until that mystery was solved, victory could never be won. tomorrow night, 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.

tomorrow night 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.

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