Wednesday 31 May 2017

Chemotherapy Drugs For Lung Cancer

>> welcome to the first ever facebook liveevent for lung cancer awareness month. this event is a joint effort between the nationalcancer institute or nci and lung cancer social media also known as hashtag lcsm chat. we'll be live on the nci's facebook page for30 minutes from 8 to 8:30 p.m. eastern time. at the same time, lcsm chat is conductingit's regularly scheduled hour long tweet chat from 8 to 9 p.m. eastern time. you can ask questions of myself or my gueston the nci's facebook page and we will do our best to answer those questions duringthis discussion. questions we don't answer on air will be answeredin the comments soon afterwards.

after the facebook event ends, lcsm chat willcontinue discussing tools and resources that help lung cancer patients access clinicaltrials. more information about lcsm chat is availableat lcsmchat.com. we're excited to one of the first groups ofthe use the new facebook q and a feature using two different feeds. we've worked hard to make sure you have excellentaudio and video quality but please realize this is an experiment. i'm janet freeman daily and i'm honored tobe moderating this discussion. i'm a blogger, science geek, lung cancer patientactivist, and co-founder of lcsm chat.

our topic today is immunotherapy for lungcancer, new research and clinical trials. i'm honored to be working with dr. shakunmalik, head of thoracic oncology therapeutics at the national cancer institute. welcome dr. malik. >> thank you janet and good evening. and i am honored to be here with you to talkto you and my patients about the lung cancer immunotherapy. and please call me shakun. >> oh thank you very much, shakun.

so would you please tell us a little bit aboutyour background? >> yes. so i have joined nci about four years ago. before that i worked as a clinician mainlyat the lombardi cancer center at georgetown. i led their thoracic oncology clinic wherewe saw nearly diagnosed cancer patients and made a plan for their treatment. in between georgetown and nci, i also workedat fda where it was really an eye opening experience for me to learn how fda looks atapproval of drugs and then at the nci although my main work at this time is helping investigatorsdevelop clinical trials in lung cancer, i

continue to see patients in the clinical centerat nci. >> it sounds like you're well prepared foryour position. >> thank you. >> so let's define some terms. what is immunotherapy? >> so immunotherapy is a type of treatmentthat works with your own immune system to help fight cancer cells. so instead of attacking the cancer cells directly,the drugs help your own immune system to fight cancer that it is normally supposed to do.

>> okay. and can you please explain the role that immunotherapiesare currently playing in lung cancer research and clinical trials? >> in lung cancer, the trend of approval forchemo -- for immunotherapies really started last year when fda approved first immunotherapyagent nivolumab for the second line patients with lung cancer. now these are the patients who had alreadyhad chemotherapy as a first line and then they -- when they progressed, it showed -- theclinical trial showed that nivolumab compared to chemotherapy improved survival.

since then, there -- the field has moved furtherahead and we now have actually three more drugs that are approved. and recently we had first drug approved, pambrol[phonetic], for patients in first line. this immunotherapy actually showed improvementin overall survival and progression free survival in patients against chemotherapy. it's a lot of exciting things happening inthe field of immunotherapy and lung cancer. and there are, obviously, a number of trialsthat are also ongoing looking at maintenance or looking at combinations of chemo -- immunotherapieswith chemotherapies or with other chemotherapies and immunotherapies in this field.

>> and we have several approved drugs also. okay. so last year in our google hangout, we talkedabout the lung-map trial for squamous cell lung cancer. can you explain what this trial and the rolethat immunotherapy's played in it? >> lung-map is a first trial of lung canceras a personalized therapy that was developed as a master protocol with nci and in collaborationwith pharma at fnih [phonetic]. it was a first public private partnershiptrial that started a couple of years ago. and what happened was at the time immunotherapieswere not approved for lung cancer.

so we were doing clinical trials where wewere testing patient's tissue and if they had a genetic abnormality in their tissue,they would go into one of the arms and we also were testing it against chemotherapy. we did have, at that time, an immunotherapyarm that was also experimental. so eventually, as you know, that immunotherapybecame approved was an approved therapy and improved survival in this second line lungcancer patients. we actually had to modify the trial as wedid not think that chemotherapy was a good control anymore since that was not as goodas immunotherapy. so now we actually have patients who havenever had immunotherapy that they are tested

against nivolumab that reaches a standardof care in these patients against a combination of immunotherapy. we also have a single agent drugs that arebeing tested for genetically abnormal tissue in those lung cancer patients. so immunotherapy arm has been added. we are also looking forward to another immunotherapyarm that is going to be added in a combination in patients who are going to be refractedto immunotherapy. so we had to modify this clinical trial asthe drugs became [inaudible] and we had more knowledge of what drugs and what immunotherapieswork in these patients.

>> so, trying to simplify this a little becausethere's an awful lot of arms it sounds like now. >> so the lung-map trial is for patients whohave squamous cell lung cancer and when they decide they want to enter the trial, whathappens? >> so if they want to decide to enter thetrial, if they've -- their tissue will be tested for genetic abnormalities. if they have one of the genetic abnormalityfor which we have a drug that we are testing, they will go into that arm. if they do not, they -- if they have had immunotherapy,we have a clinical trial for them which is

nivolumab versus the combination of nivolumabwith another immunotherapy. now we are going to be, in very near future,opening another trial which is for the patients who have also had immunotherapy and they havenot become refractory to that. so we have a combination of immunotherapy. so we're going to have, at least, two differenttrials amongst these arms in lung-map where patients will be able to go on immunotherapybut if they have genetic abnormality they can go into one of the arms that we have drugfor. trying to have a lot of choices. >> so for squamous cell patients, this actuallysimplifies things.

they don't have to look at all of the differenttrials that might be out there. they can be within one trial but go to thearm that seems to have the best chance of being appropriate for that. >> if they are eligible for, as you know therecould be other trials but this gives them an option that they -- this trial can -- theymay be eligible for one of the arms or an immunotherapy arm. and it gives them a broader choice of nothave to go from, you know, one trial to the other and maybe be able to -- be eligible,of course, you know, one has to see whether these patients meet all the eligibility criteriaand if we have a drug for their genetic abnormality

and if they will be eligible for immunotherapy,they can go on immunotherapy. so these patients previously were -- wouldbe one of these targeted therapies or they would be on chemo and now -- many of themhave the option to go on immunotherapy. let's talk a little bit about the side effectsthat patients experience for immunotherapy. how are those different than the side effectsthey might see for chemo? >> so chemotherapy, you know works on allgrowing cells. so that's why we have a different kind oftoxicities with chemotherapies where you know, the blood cells will drop in numbers. patients get -- got infections and sepsis.

and the -- so that -- you know it did notdifferentiate between normal cell and abnormal cell. luckily chemotherapies killed the abnormalcells so that's how we treated lung or any kind of cancer. but immunotherapies although are less toxicbut let me just take a pause, but they also have toxicities. and these toxicities may are less intensesome of the chemotherapy toxicities but they can also be annoying or they can intense. >> very intense.

>> or they can be -- you know, serious. so the more common toxicities are relatedto immune like you know, patients may have any liver toxicities. they can have lung toxicities but in general,these are thought to be different and milder than chemotherapy. so in lung cancer, most of the immunotherapiesthat we have available target individual proteins. the pd-l1 or pd 1 but there are other typesof immunotherapies that are coming down the pike. can you talk a little bit about those?

there's vaccines. >> there's -- >> there are vaccines. there are combination therapies. so they are all in early development at thistime. and it is a combination of immunotherapiesthat not only work on pd 1 or pd-l1, they work on cdla-4 and other immune checkpointsbut they are early in the development. right now what is approved for lung cancerare pd 1 and pd-l1 drugs. and [inaudible].

so there are others coming also which is great. >> there is others [inaudible]. another clinical trial we talked about lastyear was the alchemist clinical trial. is there anything new there? >> so similar changes we had to make for lung-map. we had to also make modifications of alchemistin the alchemist trial. so what alchemist is a trial for early stagelung cancer patients. these are the patients who have stage 1 to3a lung cancer that has been completely removed. and so then they will get standard of carewhich is usually chemotherapy.

and after that, patients still had a 50% chanceof relapse. so what alchemist was doing was testing patients'tissue and if they had egfr, they would go on erlotinib for two years and if they alkmutations, they would go on crizotinib for two years to test if additional targeted therapiesimproved survival in these patients beyond what we get with chemotherapy. so when immunotherapies got approved, we againhad to modify this trial because now we know that immunotherapies in metastatic settingalso help patients with lung cancer. so there were two changes we had to considerfor alchemist that happened. one was that alchemist was only for patientswith non-squamous histology because as you

know that egfr and alk mutations are in non-squamoushistology. on the other hand, immunotherapies don't onlywork with non-squamous, it also works in squamous cell histology. so we had to add another cohort of lung cancerpatients that had squamous histology as well. and we also have now a trial added which isimmunotherapy with nivolumab after they have had standard of care after surgery and versusobservation. so again, in this study we will test whetheraddition of immunotherapy after chemotherapy will improve survival in these patients. can you please explain the role of genetictesting in screening and qualifying for these

clinical trials? we've talked about identifying which drugmight match a particular patient's lung cancer. so what sort of things are you talking aboutscreening for and how do they do that? >> it depends on the clinical trial. for example, it also will depend on what kindof clinical trial or the drug in that arm is open. for example, i am talking about lung-map. so we have arms -- one of the things thatwe are able to do in these master protocols is depending on as we added immunotherapies,we can also subtract the drugs that don't

work. so if we have a target that we are tryingto block by a drug and if we see after a certain number of patients it doesn't work, we canclose that arm. so it will really depend, at the time, whena patient is newly diagnosed and then develops progression they can have their genetic testingdone even at that time. and at the time of progression can right awaygo into the lung-map trial if their genetic abnormality -- for their genetic abnormalitywe have an arm ongoing at that time. similarly for alchemist, again for alchemistwe are only testing two genetic abnormalities which is alk, alk translocation and egfr.

and if they are negative for that, then theywill be tested for pd-l1 and they will go on pd-l1 nivolumab trial. now for nivolumab trial, you don't have tobe pd-l1 positive. this is for both pd-l1 positive and negativesince we don't know at this time who are the best people who are benefited by this drug. we know that the people who are pd-l1 positivebenefit more but we also have seen that they can benefit to some extent pd-l1 negative. so both types -- so both pd-l1 positive aswell as negative can go on alchemist. so if people are interested in these trials,the trial pays for the testing if they meet

all the criteria? >> that's right. if they meet all the other criteria, the trialwould be -- it will be paid by the nci for screening. so we've been talking about clinical trialoptions for patients that have particular targets. we've talked about immunotherapy. are there any efforts looking into whetheror not patients who have egfr, alk, or ros1 benefit from combining their targeted therapywith an immunotherapy?

>> there are some trials that are lookingat this at the moment but as you know, that is something that we need to start with asmaller pilot trials. and if we do have a pre-clinical and clinicalbenefit then it can go into large randomized trials. there is alk plus immunotherapy trial ongoingat the moment. >> we've been using the terms pd-1 and pd-l1but we haven't really defined what those are. could you talk a little bit more about thepd-1 blockade and what that's about? >> so this is -- these are the enzymes thatare proteins that are found in tumor tissue. and so these -- if they are the ones if youblock them, then the cancer cells die.

so that's why they are called pd-l1 and pdl. and so these are expressions of the proteinin the tumor cells. and patients can be positive or negative -- >> -- in their tissue. so you can -- we can test this on the tumortissue. >> so the pd-1 as i understand it is a proteinthat's on the white cell. yes. that's correct. >> which is part of the immune system.

and pd-l1 is on the tumor cell. >> it can be on tumor cells yes. >> but not necessarily. but not necessarily correct. so there are other types of immunotherapiesalso. one of the things that a question that's comein is about adoptive transfer of t-cells. could you talk a little bit about what thatis? >> right. so you can have adoption of the t-cells whereyou can transfer the immunotherapy -- immune

cells and that can block. blocking them can help cancer cells. so those are all the things that are beingtested at this time but we don't have drugs that have either approved or have been testedin the big clinical trials at this time. >> there are some clinical trials that arelooking at it though. all right. let's see another question. so are there other types of immunotherapiesthat i'm getting a question. like cancer vaccines.

can you talk a little bit about how thosework? >> so again cancer vaccines are that you tryto make -- you give the vaccines and again, make your own immune system fight cancer. so there have been this -- vaccines have beentested many, many years ago and so far, there has not been a positive clinical trial thathas led to an fda approval of these vaccines for lung cancer. but that doesn't mean that won't happen infuture. it doesn't mean that we are not going to beable to refine these vaccines and be able to help in future but we'll see how the fieldgoes.

some patients with other cancers like melanomahave had long-term response to immunotherapies. are we seeing that in lung cancer also? >> this is -- yes. so this is an interesting question that weare looking at. so what happens is that most of these patientsmay not -- even though they benefit and have overall survival but when you look at thesurvival curves, you're going to always have a tail end which means that at the end ofthe curve there is going to be a number of patients that continue to live long. and so a lot of research at this time is beingdone and who are these patients.

i mean, as you and i talk, that these patientscould be who have pd-l1 expression but that's not the whole story because we know that itworks better in this. but there is something about those patientsthat where pd-l1 or not only pd-l1 there maybe something in their system or body. why these patients live longer than most ofthe patients what we call, you know, we have a clinical trial that we're looking at thesepatients called exceptional responders. why do they exceptionally do well. so that is a lot of interest brought by nciand other investigators to look at those patients. look at their genomics [phonetic].

look at their, you know, tumor tissue to seewhy are these patients responding and why are they doing better than other patients. and that you see a lot in immunotherapy. >> you see a lot in other targeted therapiesas well but immunotherapy it's much more pronounced that you see that big tail end. so we've talked a bit about clinical trials. are these clinical trials we're talking aboutonly for patients with advanced cancer and if a patient is interested in a clinical trialhow do they find them if their doctor is not able to help them find it?

>> so clinical trials are not only for advancedpatients as we just talked. alchemist is for patients who have early stagelung cancer. and lung-map, on the other hand, is for patientswho have advanced staged lung cancer. there are some trials that are ongoing andeven earlier stage where we are testing whether immunotherapy in new [inaudible] which meanseven before they have had surgery. whether that makes a difference in this spaceagainst studies are just being started and it will take us few more years to have ananswer to that. so it can be for any early stage or late stagepatients, we also are going to be having a trial started for maintenance that patienthas advanced stage then they respond to chemotherapy

or immunotherapy and how long we can treatthem with these drugs and maintain them. so it can be on any lung cancer patient. it is a matter of finding the right trial. now the question is how do patients find theseclinical trials? so one of the ways we are at nci looking atmaking the navigation for patients easier so that we can help them. they can try to check at trials.cancer.gov. that will help them or they can call our cancerhelp line and their physician as well can help them find the clinical trials.

>> and we will be also discussing more resourcesand ways to find clinical trials on the hashtag lcsm chat on twitter at the same time. >> yes, and -- >> so. >> so i thought -- >> go ahead. >> yeah so that you will give them that resourceas well. so we just have a little bit of time. i want to ask quickly.

how can people access clinical trials if theydon't live near a major academic cancer center? >> janet, you'll be surprised to know that60% of our sites for both lung-map and alchemist are in community based sites. so -- >> oh that's good to know. >> so -- you know it will be hard for me tosay, you know, if patient lives very far from academic center that they -- you know howfar that that community based center will be but it will be much easier for them tofind if they can go on the trials.cancer.gov or talk to their physician and find out wherecan they get on these clinical trials.

and again, i'm very happy to say that morethan 60% of our sites are in community based centers. we have another question that came in fromthe audience. can patients on immunotherapies initiallysee their cancer progress or might patients on immunotherapies take a longer time to seea response than possibly on other treatments? >> that's a very good question. an excellent question actually. we are seeing that much less happen with theseimmunotherapies but it can happen. so it takes -- when an immunotherapy is givenor these drugs given, sometimes in the beginning

we didn't know about this phenomena calledpseudoprogression, the patient's tumor may show that it is bigger but it is usually whatwe have noted is that it is from all these immune cells coming around the tumor and tryingto, you know, go around it and then eventually it will calm down and then it will start shrinking. and also sometimes these tumors may stay samesize and you know, we may be concerned oh it's not shrinking but then you see that thesepatients will live a long time with just the same size in the tumor. so the doctors know this phenomena and againit was much more seen pronounced with another type of immunotherapies called clta-4 cellsbut we do see sometimes with these immunotherapies

also and then we just follow these patientsand do another scan in a few weeks and feel better when these tumors start shrinking andthey start -- cancer patients continue to do well. well we're approaching the end of our facebooklive time. so when this event ends, please join us inthe ongoing lung cancer social media chat which we'll be discussing tools and resourcesto help patients access lung cancer clinical to participate, just search twitter for thehashtag lcsm and include the hashtag lcsm in all your tweets. if we have any questions that were postedthat we didn't get to, answers will continue

to be posted in the comments section on thenci's facebook page. you can see a recording of this video soonon the nci's website and youtube pages. so we have just a minute or two longer. do you have something you'd like to say inclosing dr. malik, shakun? >> thank you, janet. and i thank you for giving an opportunityto talk with you today. and it -- >> well, i appreciate your -- go ahead. and if you have any questions or patientshave any questions please feel free to send

us questions and i'll be more than happy torespond to those questions. >> all right. well thank you shakun for joining me. it's always a pleasure to talk with you. i appreciate your willingness to share informationwith patients. so we are closing out this facebook live evenfor lung cancer awareness month. this is janet freeman daily and -- >> this is shakun malik from nci. thank you.

signing off.

Chemotherapy Drugs For Colon Cancer

man: i truthfully don'tremember the drive itself. [siren] it's kind of surreal. you just don't believe that it'shappening to your child. whaa! man: you know, of courseyou think the worst. i mean, anytime you hear"spontaneous bleeding," and, you know,you can't take her to the normal hospitalthat you would go,

you need to take herto a special place, you don't know what to expect. woman: something was wrongwith my daughter, and i was scared. she was notthe normal, happy, running-around-playing girl. every thought went throughyour mind like, uh... why? why is this happening?

want to gonight-night, livy? you want to saynight-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 finda cure for cancer, and i want it donein my time.

the time has come in america when the same kind ofconcentrated effort that split the atomand took man to the moon should be turned towardconquering this dread disease. in fact, it is nowconceivable that our children's childrenwill know the term cancer only as a constellationof stars. for the first timein human history, we can say with somemeasure of confidence

that the war on canceris winnable. we will launch a new effortto conquer a disease that has touched the lifeof nearly every american, including me, by seeking acure for cancer in our time. [applause] narrator: cancer isa worldwide scourge, the fastest-growingdisease on earth. by 2030, there will be as many as 22 millioncases worldwide.

cancer afflicts 1.7 millionamericans each year and kills 600,000 of them. more will die from cancerover the next two years than died in combatin all the wars the united states hasever fought--combined. one in two american menand one in three american women will be diagnosed withcancer in their lifetimes, and nearly everyone willbe close to someone who suffers from it.

make no mistake,this is one of the most significant humanchallenges in our history. to imagine that we will finda simple solution to this, i think doesn't do service to the true complexityof the problem. cancer is part of ourgenetic inheritance. we will always havecancer amidst us, within us, amongst us. narrator: cancer isnot one disease.

it's many. but each of them beginsin the same way-- with the uncontrolledgrowth of a single cell. it attacks the blood,the breasts, the lungs, and every otherpart 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 expenseof your entire body

and your entire being. it doesn't care about you. it doesn't care if you'rea mother or a husband or a daughter or, you know, if you have 4 children. it doesn't care. it justcares about itself. animation: this is a struggleof life and death, and we cannot winif we're afraid. narrator: but human beingshave refused to surrender,

have always struggledto 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 comefrom the outside, or did the enemylie within us? in the ongoing struggleto conquer cancer,

massive force hassometimes meant defeat. woman: so this willbe your last cycle. tragic failure has ledto remarkable success, and final victory alwaysseems 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 allegianceand leaps of faith, hubris and hype and genuine hope. cancer has beencalled many things-- "the king of terrors," "a hidden assassin," and "the emperorof all maladies." cancer has taken on thislarger-than-life role in our culture,in our lives.

it is the wordthat we relate to with simultaneous terrorand some humility. it makes us resistance workers. it makes us historiansof that empire. it makes uspeople who grieve about what happens whenthis invades our lives. it makes us soldiers. but every year has broughta kind of clarity to our understanding of whatgoes wrong in a cancer cell

and what can be targeted, can be prevented,can be treated. man: every field in medicinehas had a moment in history that has been transforming, the moment where the knowledgethat was required to change the fieldbecame available. [people cheer] and my prediction isthat the next 20 years is going to be the ageof discovery for cancer

and the age for new therapies. this is our time. narrator: in the winter of 1947, a 3-year-old boy dyingfrom leukemia arrived at children's hospitalin boston, massachusetts. mukherjee: he's pale,he's limping, and he has a gigantic spleen. his spleen is so big thatthe child can hardly walk, and it's full of cancer cells.

narrator: the boy's namewas robert sandler. he'd been born to aworking-class family in nearby dorchester. robert had an identicaltwin named elliot. man: being a duplicate,being a twin, and being your only friend, you realize quicklywhen 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 rightin front of our house, and at night, we could standby the living room window and watch the trolley sparkscome from the wires. we could hear the animalsfrom 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 cancerof the blood-- the disease in liquid form, rapidly proliferatingabnormal white blood cells that crowd outhealthy blood cells,

ultimately leadingto hemorrhage, infection, and death. like other hospitals,boston children's had a special wardfor 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 wardswere not nice. there was a very narrow hallway, and there were rooms tothe left and the right. the air was tinted withthe smell of ether. it was tinted with blood. you had kids crying,

the parents standing on thesides by the walls, crying. it was not someplace that you'dwant 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 cryinglike crazy, and i can remember puttingmy hand out to him. i was able to somehowkeep him from crying more. he stopped. narrator:at boston children's,

robert was putunder the care of a tall, imposing44-year-old doctor named sidney farber. as the 3- year-old spiraledtoward death, farber proposed a last-ditchattempt to save his life-- to poison the cancer by injecting the boy witha drug called aminopterin. but the idea ofinjecting children with a rare, experimental drug

was deeply alarmingto farber's colleagues. mukherjee: people wouldsay to farber, "why aren't you lettingthese children die in peace? "why are youperforming experiments "which are going to befutile anyway? everyone knows that a chemicalcan't cure cancer." narrator: farber was determinedto go ahead anyway, desperate to save the livesof robert sandler and the other childrenwhose treatment he oversaw.

david nathan: if you wantto talk about dread, sidney farber absolutelydreaded leukemia. that's because he did theautopsies on these children, and every single oneof them died. they usually diedin about 3 months, an inexorable death about which nothingcould be done. narrator: though doctorselsewhere had experimented with chemical cures, farber wasthe first to try aminopterin,

a rare and possiblydangerous compound that starved white blood cellsof crucial nutrients. on december 28, 1947, with the reluctant assentof the hospital board, farber injected robert sandlerwith 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 abstractchild, but this child-- and that was whatwas driving farber. narrator: sidney farberhad first arrived at boston children's in 1929, becoming the hospital'sfirst full-time pathologist. in his small basement labover the next two decades, farber would viewdiseased tissue samples from thousands of children, many of their livescut short by leukemia.

for generations,doctors had tried to devise medicinesto treat leukemia. they knew that the onlyway to combat the disease would be to stop the runawaygrowth of white blood cells, and since that kind ofout-of-control growth was the common featureof all malignancies, they hoped that leukemiawould point the way toward treating a wholeuniverse of cancers. mukherjee: it is nota coincidence that

cancer's history, at leastthe modern history of cancer, begins with childhood leukemia. a disease that carries100% mortality, that occurs in children, and carries this kindof accelerated course was really a kind of reminderof the urgency of the problem. narrator: for farber, the scientific puzzleof 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 dosomething to help them. man: i think that seeingthe ravages of cancer impels someone like thatto go on a crusade, to leave the autopsy room and to say, "i'm going tomove out of my cubbyhole "and up from the basement, "and i'm going togo front and center to make a difference here."

newsreel: how many havecancer in the u.s. today? no man knows. last year, 150,000 died of it. the more science cuts downon other causes of death, the more are sparedto die of this. narrator: by the time sidneyfarber had turned his attention to helping childrenlike robert sandler, cancer had become themost feared killer in america. newsreel: asleep.

asleep, save for onemember of the family. just one week ago,mary bronson discovered that she has what may bea 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 cancerswere incurable. mary: can my familycatch 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 cancerisolated themselves-- because they were aware ofwhat it meant to some others. it was the reason thatsome people wouldn't let their children go neara relative who had cancer. when i was growing up, i hadan aunt who developed cancer, and she was hiddenin the attic.

mary: what willhappen to me? devita: people were ashamedif they had cancer. nobody wanted to be seenif they had it. mary: people don'ttell you about cancer. they don't talk about it. why not? is a cancervictim an outcast? is there no hope? no hope? nuland: we getthe word "cancer"

from the greek "crab," carcinos, which in latinbecomes "cancer," because as you look at a cancergrossly, with your naked eye, what you see is a massof tissue in the center, and it's as thoughlegs are reaching out. it's this sort of formless thing that was creeping andcrawling like a crab does. narrator: cancer is asold as human life itself. the first known writtenreference to cancer appears

in a 15-foot papyrus prepared by an egyptianphysician 4,000 years ago. he numbered all the diseasesand their treatments known to the ancient world. case number 45 refers to "swellings of the breast,large, spreading, and hard." under the sectiontitled "treatment," it reads simply,"there is none." mukherjee: there is somethinghaunting and prophetic

about that statement. in fact, it rings throughthe 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 afatal disease without cure. ancient physicians hadno real understanding of where it came fromor how it spread. nuland: they believedthat balance was

the essential thingthat 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 thefirst century a.d., the roman physicianclaudius galen

theorized that it was an excessof one of the 4 humors-- melancholia, or black bile--that gave rise to cancer. mukherjee: black bilewas mysterious. it couldn't be seen,and was therefore used to explain diseases thatlacked any other explanation. narrator: galen's theories wentunchallenged until the 1530s, when an anatomy professornamed andreas vesalius set out to createthe first detailed maps of the interiorof the human body.

man: as he was dissectinghuman beings, he found a lot of discrepancies with what he was studyingin galen's writings. and he was not outto topple galen. he had a great deal of respectand reverence for galen, but he kept finding thingsthat did not jibe with what galen was saying. narrator: bones, organs, intricate webs of nerves,arteries, veins.

vesalius published meticulouslydetailed illustrations of everything he found, but no matter how hard helooked, or where he looked, he could find no traceof black bile. nuland: from then on in, what you begin to look at is an increased recognitionby physicians that when somebody gets sick, it's because something isgoing on inside their body,

not because the humorshave gone wrong, not because god has decreed it--none of these things. something's going wronginside the body. narrator: every morning,the doctors, fellows, and residentsin the pediatric unit at johns hopkinskimmel cancer center sit down to reviewtheir patients' status. all right.who's next? woman: olivia isour 17-month-old,

previously healthy female,referred to the emergency departmentby her pediatrician. we suspected a.l.l., just lookingat the morphology. narrator: 17-month-oldolivia blair was admitted 24 hours ago. she was immediatelydiagnosed with acute lymphoblastic leukemia. doctor: so i thinkwe'll, you know,

have a little bitbetter idea of things after the procedures today, and then we can sit downagain and talk some more. man: we had been wonderingwhat was going on with her, so we were looking for somethingto make it all tie together and make it make sense. she just seemed likeshe was sick all the time. you know,you could tell, like, there was definitelysomething wrong.

this is not normal. she was a pretty healthy child,you know, up to that point. i just felt likei was giving her tylenol and advil every single day. then she startedto have that cold. it's all right,baby. don't cry. 104 fever.she scared me. we hope,and we think, that she is goingto be low risk.

man: yeah. the other thingsthat will help todetermine her risk going forward is,number one, thespinal fluid test. we need to make surethat there's noleukemia 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 enoughjust to mow the lawn. you've got to goand get the roots

of all of the weeds and getall of the leukemia cells out in order for the grassto be healthy again. take somelocal 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 treatmenthas to begin immediately, before the diseaseprogresses too far. she receives her firstdose of chemotherapy

directly into her spine. woman: she'sbreathing a littlefunny because she's sleepingso deeply, ok? so sometimes,just because she'snot fully awake-- ok. [exhales] it scares me. do you want a seaton this side? i don't like tosee her like that.

kelly, voiceover:i started to pinch myself, like, "wake up. this isn'thappening right now. "that's not my daughter. "she's not sick. that's notmy daughter out there. "she's not going throughthis right now. this isn't happening. no." brown: for most parents,it is their worst nightmare, and our job is tohelp them recognize that while this is obviouslya shock and something that,

you know, will turntheir world upside-down, it's something that together, we have to figure outa way to work through. you know? they've got to beable to function as parents, now more than ever. yeah.that feel better? marcus, voiceover:no one has a manual for trying tofigure this all out. you're thinking that...

is my daughter gonna die? narrator:in december 1947, within days of arriving atboston children's hospital, 3-year-old robert sandlerreceived his first injection of the highly experimentaldrug aminopterin. as dr. sidney farberand his staff anxiously monitoredhis condition, robert soon beganto show results. within weeks, his blood,that had been choked with

rapidly dividingwhite blood cells, returned to normal. farber noted that sandler'sdistended belly had shrunk. his appetite had returned, and he had begun playingin the hospital corridors. sandler: when robertwent 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 cainin the apartment. i didn't have to worry about him not being therein the morning. i didn't have to worryabout him being sick. we thought it was a cure. man: the firstdemonstration of anything is an extraordinarybreakthrough, because leukemia wasconsidered to be an absolutely fatal disease,

and nobody thought thatanyone would survive. narrator: other childrenunder farber's care also showed promisingsigns of remission. perhaps aminopterin, the drug his colleagueshad so resisted, might hold the keyto a cure for leukemia. mukherjee: news ofthese remissions really spread through boston,and the idea that you could hold cancerat bay with a chemical

was suddenly in thepublic 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 potentiallyhold at bay leukemia, this could extend outto all other cancers. narrator: the dreamof a cure for cancer had long consumed some ofthe greatest minds in science, but had always founderedon a limited understanding

of what cancer actually was. in 1855, a young germanbiologist named rudolph virchow stared down the barrelof his microscope and fixed on thehoneycomb of structures that made upa sample of tissue. others had named thesestructures "cells," after the spartan roomsin which monks lived and prayed. virchow had a revolutionarytheory to explain cells-- they were not onlythe 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 healthand in sickness." nuland: as he studied cellsunder the microscope, he came to realizethat there wasn't some strange materialthat made the cells, but that every cell camefrom a previous cell.

once he pointed outthat thesis-- "omnis cellula e cellula,"he called it, "every cell from another cell"-- that changed the understandingof what cancer was. cancer cells clearly came from cells thatweren't cancerous. they clearly came from perfectly normal cellsthat had been changed. narrator: virchow's discoverypointed to surgery

as the primary treatmentfor most forms of cancer. if tumors were merelycollections of abnormal cells, it should be possible tocut them from the body. mukherjee: with theadvent of anesthesia and antisepsis, with theadvent of clean surgery, surgeons could now attackcancer with a real bravado. this was the golden ageof cancer surgery. narrator: no onechampioned surgery with more single-minded purpose

than a doctor namedwilliam halsted. halsted entered the fieldof medicine in 1868 because he did not want to work in his father'sclothing 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 reputationin new york city. narrator: from the beginning,halsted was known

for his innovativeand complex surgeries. he seemed intenton pushing himself and his patientsto the limit. mukherjee: he's addictedto perfection. he's addictedto the idea that the reason that cancer isnot being appropriately treated is because the surgeonsaren't trying hard enough. if they only tried more,if they tried better, if they were more perfect,

if they could delivera more perfect operation, then, in fact,they would cure more. cutting more meant curing more. narrator: in 1890, halstedbecame chief of surgery at the new johns hopkinshospital in baltimore, where he concentrated onpatients with breast cancer. as he operated onmore and more women, halsted confronted a puzzle thathad long mystified surgeons-- even when the breastwas removed,

cancer could still reappear in entirely new placesin the body. halsted thoughthe understood why. he believed that straycancer cells had escaped at the margins of his incisions. his answer was to cut an ever-widening arc of tissue. woman: halsted startedwith the idea that cancer startedin the breast,

and it grew centrifugally. it grew out fromthe original cancer. it had roots,it had, like, tentacles, and that if you could justget widely around it enough, you could get it all out,and you could cure it. markel: and sohalsted got the idea, what if i remove the muscleunderneath the breast and then the muscleunderneath that and then the lymph nodesbeyond that?

so he was doing this excavationin people's chests. he was really pushingthe envelope. how far could you gowith your scalpel? narrator: halsted calledhis procedure the radical mastectomy-- "radical" after the originallatin "by the root," but others took it for the morecommon meaning, "extreme." love: from a woman's standpoint,it's horrendous, because you're leftcompletely flat.

not only do younot have the breast, but you don't have yourpectoralis muscle, either, so it's just ribs,and often you don't have a nice fold in your armpitthe way you normally do because that muscleis taken, as well, and so it's really uglyand very deforming. narrator: despite thedamage they caused, halsted's radicaloperations did succeed in saving the lives ofmany of his patients

whose cancers had not yetspread beyond the breast. markel: when youthink about removing the amount of tissuehe's removing and still having decent results, this is not a hack job. people who have describedwatching halsted operate speak of it in hushed,reverential tones. it was likewatching, you know, a virtuoso violinistor a great pianist.

there were very fewpeople who could do what halsted could doback then, and so every doctor,every surgeon turned their eyes to baltimore to see whatthe great halsted was doing. narrator: before long,other surgeons around the world were not only imitatinghis operation, but taking it even further. in time, the radicalmastectomy yielded to the super radicaland then the ultra radical,

and they did not stop there. man: surgeons used thehalstedian principles of radical surgery for cancer, and they expanded itto other areas. they adopted the techniquefor cancers of other organs, so it grew widely throughoutthe specialties of surgery in the first halfof the 20th century. the common concept insurgical oncology was a big operation is more likelyto cure a big cancer.

narrator: but there wasa problem with radical surgery. whether it was for cancerin the breast, lung, prostate, or any other organ, no matter how skilled thesurgeon or bold the operation, a significant number ofpatients still relapsed with the disease elsewherein their bodies, as if the cancer had leapfroggedthe surgeons' incisions. clearly, there was a limitto 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 itwas not the full answer. and this idea--that, you know,you can take half-truths and you make full truthsout of them, and then the logicof the field closes because you say to yourself,this is the truth and therefore lies outside theboundaries of being testable. narrator: as surgeonssearched for an answer as to why some cancers hadescaped their incisions,

another therapy appearedat the turn of the 20th century that seemed to promisegreater success with far less damage. in the winter of 1896, a 21-year-old medicalstudent in chicago named emil grubbã‰began experimenting with a newly discovered form ofradiation called x-rays. the mysterious rays were ableto pass through the skin. grubb㉠wondered if theycould be focused enough

and intense enough to burn out tumorsinaccessible to surgeons. on the evening of january 29, he aimed his homemadex-ray machine at the chest of a womansuffering from breast cancer. after 18 nightly treatments, the tumor miraculouslybegan to shrink. radiation was soon heraldedas 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 wasthe invisible knife, and therefore, it couldcut into areas that the surgeoncouldn't get to. it was calledthe hot knife, as opposed to thesurgeon's cold knife. grubb㉠realizes thatirradiation is also a poison, and if we can give justthe adequate dose of poison,

perhaps by giving it locallyonly 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 discoveryspawned an industry. in the next few years,hundreds of radiation clinics opened their doorsacross the united states promising a newtreatment for cancer.

grubb㉠himself was soontreating 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 stanforduniversity scientist would even use a 6-million-voltlinear accelerator to cure a limitednumber of cancers, like hodgkin's lymphoma. but along with radiation'scurative powers,

doctors also discoveredits harmful effects. in high doses, it couldburn, scar, or blind. sometimes, it evenseemed to cause cancer. grubb㉠himself fell victimto radiation poisoning, losing his hand,forearm, and upper lip. man: all of this wastrial and error. many, many mistakes were made. some of the most tragic mistakes were the deaths of theearly investigators themselves,

who often died of leukemia,of bone and other cancers that were causedby the radiation that they didn't understandwas a very potent carcinogen. narrator: perhapsmore careful handling could mitigate thedangers of radiation, but there was a deeper problem. like halsted's radical surgery,radiation was effective only when cancerremained localized. if the cancer had spread,

radiation was as powerlessas halsted's knife. it was increasingly obviousthat what was needed was a third approachthat would attack cancer wherever it hadspread in the body-- a systemic treatment toconquer a systemic disease. woman: this isolivia blair. we have consent forbone marrow biopsy, bone marrow aspirate,lumbar puncture, administration of itc,intrathecal chemotherapy.

sison: correct. narrator: for leukemiapatients today, the standard protocolis to attack the cancer with multiple roundsof chemotherapy, but that won't be enoughfor olivia blair. after a series ofadditional tests at john hopkinskimmel cancer center, doctors have discoveredthat olivia's leukemia, a type called t-cell,

has spread to hercentral nervous system, making the disease high risk. man: the centralnervous system, which includes the brainand the spinal cord, that is actually a sanctuary orhiding site for leukemia cells. man: so obviously,the question is, what does thismean for olivia? yeah. i'm automaticallythinking that... the leukemia is in her spine.

it's in her brain. so it's more serious, then?it's high risk. what thatmeans is that her therapy willbe more intense, that she'll getextra chemotherapy, and then we are also are going to recommendthat she gets spine radiation andradiation to the brain. we don't want to doradiation.

i know. right? so we-- why...why are we doing that? sison: because weknow that radiationwill treat it. but we know that theradiation therapy could potentiallyhave effects on her cognitiveabilitiesgoing forward. i just...

come on, babe. come on.you're all right. we gave you onescenario yesterday. she's such a smart child. i know she is. she is, and she is goingto continue to be smart. she has me and youas parents. she won't see melike this, but... i need to get this out.

she... she is an extremelysmart child. how is this goingto affect her? you don't know. right? right. sison: if oliviawas 7 years old, we would not have a big problemradiating her brain. the problem is thatbecause she's 17 months, her brain is notfully developed.

it's almost there, but it'snot fully developed. so one of the things thatwe are very worried about and thinking about for olivia is the role ofradiation therapy. we know thatat the dose thatwe prescribe, there is certainlya chance of having a drop, for example, of, say, 10 iqpoints or so, but not anythingnecessarily morethan that.

that's not somethingtrivial, 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 outcometo treat very well because right now,the outcomes for kids with relapsed t-cell leukemiais not very good. it's less than 50%long-term survival. from a medical perspective,i'm willing to sacrifice

the risk toher intelligence in order to cure her disease. man: we need to havethe talk this morning and try to getthe mri this morning to really get ahandle on everythingthat's going on. i don't want to havemore talks with you guys. sison:we don't, either. man: i know this hasbeen a rollercoaster. like, when we came in,we were very optimistic,

and we still arevery optimistic about the ability to cureyour daughter. nothing isgoing to change inthis first month, so we have sometime to figurethings out. brown: what lengthsare we willing to go in the attemptto cure a child? we are quite willingto push the envelope in terms of toxicity because we knowwhat's at stake

is the restof the child's life, and that's a potentiallya very long life if they can be cured. narrator:for hundreds of years, doctors searched for a systemictreatment for cancer-- a chemical or drug thatcould find the disease wherever it hadtraveled 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 lackof any other options, scientists and physicianswere throwing all sorts of chemicalmixtures at cancer. the medieval apothecarywas full of remedies, such as boar's toothand fox's lung and crabs' legs ground up, and people,forced by desperation,

tried all of these things. narrator: but withoutunderstanding even the basic biologyof the human cell, chemical remedies werelittle more than guesswork. then, in leipzig, germany,in the 1870s, a scientist named paul ehrlichbegan to dig deeper. ehrlich experimentedwith cloth dyes from the textilefactories near his home. he noticed thatthe dyes stained

only certain parts of a cell, as if drawn to themlike a magnet. he wondered if such"selective affinity," as he called it,might mean that chemical poisons could bedirected at diseased cells, while leavinghealthy cells alone. mukherjee:paul ehrlich decides that perhaps chemicals canfit into other chemicals like locks and keyscan fit into each other,

and so the idea growswithin ehrlich that you can find specificchemicals that will kill specific organismsand spare other organisms. narrator: ehrlich calledthese hypothetical drugs "magic bullets." markel: his theory wasthat every disease has an antidote, if you will, a "magic bullet" that willfind it, root it out, bind to it,and render it harmless.

narrator: ehrlich wouldeventually create some of the first modern drugs, such as salvarsan for syphilis, for which he wonthe nobel prize. but at his death in 1915, the cancer cell, the targethe'd hoped to hit, remained stubbornlyout of reach. on a foggy night in july 1917, in the midst ofthe first world war,

a volley of german artilleryshells rained down among british troops dug innear a small belgian town. the shells carried a liquidthat quickly vaporized. it was mustard gas,and in that one battle, it caused almost8,000 casualties. its immediate effectswere horrific-- burns, blisters,blindness, death. but it had a longer-termeffect, as well, evident in the fewwho survived it.

the chemicals in the gasseemed to target only the white blood cellsin its victims. markel: doctors realizedby looking at the bone marrowof these patients that the white blood cells werewiped out of the bone marrow. it was gone.it was a ghost town. that was a very interestingobservation, but since mustard gaswasn't being used in the years after world war i,

nobody really thoughtmuch about it. narrator: in 1942,during the second world war, two yale university researchers, louis goodmanand alfred gilman, rediscovered the strangeinhibitory effect mustard gas hason white blood cells. though they understood how toxicsuch a chemical would be, the researchers set out to see if it could stopcancers of the blood.

because mustard gashad been banned by international agreement, the researchersworked in secret. they first testeda mustard gas derivative known as nitrogen mustard on a 48-year-old factory workersuffering from lymphoma. he was identified only as j.d. just as mustard gas had killed the white blood cellsof world war i soldiers,

its cousin nitrogen mustard aldo destroyed j.d.'s cancerouswhite blood cells, giving him a brief reprievefrom his disease before it eventuallyoverwhelmed him. markel: they put two and twotogether and said, "huh. maybe this isa magic bullet, "one of the magic bullets that dr. ehrlich washypothesizing about." narrator: in 1946,with wartime secrecy lifted,

the yale researchers werefinally able to publish the results of their study. markel: that startedthe ball rolling, that there were certainchemicals 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 toroot out the cancer and kill itand cure the patient. narrator:when sidney farber read

goodman and gilman's report, his reaction was that ofa doctor of dying children-- urgent, pragmatic,and insistent. nitrogen mustard had shown that chemicals could workagainst cancer. now it was timeto try others, he said. "the 325,000 patientswith cancer who are going to diethis year cannot wait." mukherjee: farber was lookingfor something less toxic.

he was worried that usingchemicals like nitrogen mustard would have such naturallimitations in sick children that he wantedother alternatives, and he wanted something thatwould attack growing blood cells with a little bitmore specificity than just anotherchemical poison. narrator: farber hoped thataminopterin would be that drug. in june 1948, robert sandler'sremarkable recovery from leukemia wasin its sixth month.

his case was featured ina report farber published on the aminopterin trial in "the new englandjournal of medicine." it announced to the world that 10 of 16 childrentreated with the drug, including robert, had experiencedsignificant remissions. as the report went to press, most of those childrenwere still alive,

filling their parents,their physicians, and the public with hope. but in the months that followed,their leukemia returned, beyond the reachof farber's drug. one by one, they succumbedto their illness. sandler: the last timei saw my brother, he was pretty sick. it was late at night. they called the ambulance.

the two gentlemenwho got out there were in their white smocks. they came upstairs,and they had lanterns-- not flashlights, but lanterns. in fact, they flashed one ofthose lanterns in my room, and then they were told itwas in the next room down, on the other side. and he was crying. out the door they went,

and that was thelast time i saw him. i don't even think he wavedto me as he was leaving. those are some of the thingsthat are just burnt in-- like you open a book,and there's the page. narrator: robert sandlerdied on april 2, 1949, not long beforehis fourth birthday. boy: is it my turn? woman:hey, luca. what?

jonathan's momwants to know, what do you want tobe when you grow up? what do you mean? entrepreneur. ha ha ha! that'swhat he told you. narrator: luca assantewas first diagnosed with rhabdomyosarcoma,a cancer of the muscles, when he was 2 years old. because his tumor wasresistant to treatment,

his doctors at johns hopkins resorted to high dosesof chemotherapy. you're going tostay with meforever, right? no. brown: luca receivedwhat we would consider just generallya salvage regimen, so these are drugs thatmight have more toxicities, so we make sure parentsunderstand that there is a small risk thatyour child will develop

a secondary cancer,a secondary leukemia, from this treatment itself. one of the true ironiesof oncology treatment as it's given today, and as it'sbeen given for several decades, is that the very drugsthat treat the cancer can themselves becancer 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 thathe had developed leukemia,

most likely the result ofhis earlier treatment. man: "doctor fees.pay 50." i have to pay 50? no. i do. you do? to meor to the bank? he also hadpositive titers... man, voiceover:one of the reasons that this weighs on me, us,is that nobody caused the rhabdomyosarcoma--it happened--

but somebody causedthe leukemia. the drugs we gave himcaused the leukemia. i told luca's familythat this wasn't good and that it wasn't curable without a bone marrowtransplant. narrator: luca received atransplant from his sister 42 days afterentering the hospital. it restored his immune system, which his doctors hadintentionally wiped out,

along with his leukemia,with high doses of chemotherapy. mother:you want to tryto eat something? i'm not eating. but you got to trytoday, so we canget the tube out. are we done? you got to oneon the other side, right there. all right.luca's next. narrator: 17 days later,

he remains underclose supervision. man:hi. good morning. hey, he's up! can we seeunder your shirt? thank you, sir. mother:is it itchy? no? brown: it's still warm. i don't feel it quiteas much as yesterday.

it doesn'tseem as raised. woman: it's reallysignificant,though, isn't it? brown: yeah. the likelycause of this rash is that as his sister's cellshave 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 lotsof 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 bounceback from and tolerate, and hopefully, he's on his wayto getting better from this. he's by no meansout of the woods, but there is a real hope that this too can betreated successfully and he can get on withthe rest of his life, and that's whatwe're shooting for.

let's go seeif you can playwith the wii. narrator: in the late 1940s,researchers still believed that cancer, no matter whereit appeared in the body, was a single disease for which there wouldsomeday be a single cure. the fleeting successof his aminopterin trial had convinced sidney farber that he was on the rightpath to finding that cure. but if chemicalswere the answer,

he'd need to try many more ofthem on his young patients, who were still dying despitehis attempts to save them. that would requirea great deal of money. farber hoped he could convincethe public to provide it. newsreel:the first lady enlists in america's fighton infantile paralysis. narrator: fortunately,there was a model for just such afundraising campaign, focused on the eradicationof a single disease.

every summer, for decades,infantile paralysis--polio-- struck down thousandsof children. sidney farber hadencountered the disease as a young residentin the 1930s. he'd also witnessed,and admired, the vast public and privateeffort to eradicate polio called the march of dimes. and i'd like a dimein change, too. are you savingthem, mickey?

mm-hmm. i'm gonnagive mine topresident roosevelt. the president?why, mickey! yes. you see, judy,i've got my envelopemade 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 helpof hollywood celebrities, the march of dimesmobilized the public,

who sent in coinsby the tens of millions. roosevelt: i wish to express heartfelt thanksto all of you who have contributedyour dimes and your dollars to further the fightagainst a cruel disease. narrator: within a decade, the campaign had raisedmore than $200 million, funding the research thatled to the salk vaccine. the march of dimeshad inspired many

to join the fightagainst other diseases. among them were the leaders of the variety clubof new england, who came to visit bostonchildren's hospital in may 1947, just as farber was in the midstof his aminopterin trial. nathan: my uncleand his partner started to go around boston lookingfor a place to put money, and they found, sitting inthe little dirty old basement of the children's hospital,

sidney farberin his white coat. narrator: farber seizedthe opportunity to lay out his grand vision fora new kind of hospital, dedicated to childhood cancer. nathan: sidney hadenormous ideas. he had already startedthis treatment program in childhood leukemia, and he was going tobuild a new hospital. he presented themwith his idea that

he could manage childhoodcancer on the first floor, and then there would bea tower of laboratories that would cure these patientsand find the answers. well, it was for them, exactly whatthey were looking for. they wanted something big,and he gave it to them. radio: now,in a few moments, we will bring to ourmicrophone the winner of the jane doe contest,but first...

narrator: on the eveningof may 22, 1948, ralph edwards,the popular host of the radio show"truth or consequences," interrupted his usualbroadcast from california and linked to a room atboston 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 hospitalsall over the country.

jimmy is suffering from cancer, but he doesn'tknow he has it. narrator: "jimmy" wasactually a 12-year-old boy named einar gustafson. farber had changed his nameto protect his identity and broaden his appeal so that he couldbecome the mascot for his new cancer-fightingorganization, 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? 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 aroundthe conversation. cancer was not some abstractionthat we couldn't talk about, we were too worriedto talk about. cancer was jimmy.

here was a real childwith real cancer. they weren't donating tosidney farber's fund for cancer. they weren't donating to children's hospitalfund for cancer. they were sending moneydirectly to jimmy. narrator: donations poured in, many in envelopesaddressed simply to "jimmy, boston, massachusetts." the "truth or consequences"radio broadcast,

which had hopedto raise $20,000, raised 200,000. soon, red-and-whitejimmy fund cans seemed to be everywhere-- in movie theaters, next to the cash registersin grocery stores, posted outsidebaseball stadiums. man: the variety clubof new england presents thegreat heart award

to dr. sidney farber,medical statesman. his vision extendsbeyond his laboratory. may i takethis opportunity... narrator: with the jimmy fund, the scientist sidney farberhad also become a public figure by offeringthe hope for a cure. man: now, thanks to you,there's a new and beautifully equippedjimmy fund building, where more than200 children with cancer

are given careand treatment every day. narrator:on january 7, 1952, farber opened the cancerhospital he'd dreamed of, a modernist5-story building called the jimmy fund clinic. woman: it was justa wonderful place, full of toys and trains, and the clinic,the jimmy fund clinic, made everybody just ascomfortable as could be.

woman: these childrenwere special. it was a very open,free atmosphere. the children could mixfrom one room to another, from one bed to another. narrator: farber wasdeeply moved by the plight of thechildren under his care, though he rarely showed it. evans: sometimes in the eveningbefore he was leaving, when everything was quiet,dr. farber would just go

into a room and lookat a sleeping child and stand maybe atthe 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 certaintythat a cure would be found helped keep despair at bay. the jimmy fund clinic,one visitor wrote,

"seemed suspendedbetween two poles, "both wonderful and tragic, unspeakably depressingand indescribably hopeful." man: my father nevertalked about his work in terms of failure. he was engaged in hope. hope really washis driving element. in order to keep childrenalive through chemotherapy, often, the treatments were goingto be enormously punishing,

and you just had to believe, you had to have a faith thatthere was a reason for this and that thingswould improve. luca. narrator:it's been 3 weeks since 6-year-oldluca assante received a bone marrow transplant, but complicationsare 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 isactually my first time

i come upand 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-hostdisease.

the immune systemtransplanted from his sister has begun to attackhis own cells as if they were foreign,like an infection. the big issuesince last week was the developmentof rash that progressedon friday. narrator: the doctors' hope isthat luca's new immune system will attack onlyhis cancer cells, a beneficial effect calledgraft-versus-tumor,

but if it goes beyondthe cancer cells and begins to attackhis organs, it could threaten his life. good morning. uh-oh.somebody's hiding. where's luca? mother:how do you feel? narrator: luca's doctorsare concerned because his liver isshowing signs of distress,

but they don't know what thesource of the problem is-- a viral infection or his new immune systemturning against him. loeb, voiceover: the thingsthat have been challenging about taking care of luca--it has been hard to come up with clear diagnoses forwhat's been happening. narrator: there is verylittle margin for error in luca's therapy. the dilemma is thatthe treatment for

graft-versus-host disease--to suppress the immune system-- could actually makea viral infection worse. to try to find out what'sgoing on inside luca's liver, his doctors mustperform a biopsy. mother:she's giving you pain meds rightnow, sweetie. i hurt! i want tosee exactlywhere it hurts. narrator: luca's liveris so weakened

by his cancer treatment that the operation pitches himinto yet another crisis. his blood cannot clot, and he is hemorrhaginginternally. your stomach hurts? man: it's going to besore, buddy. i'm sorry. mother, voiceover:i don't think anybody would thinkthis would happen. i don't think we thought itwas going to turn that bad.

narrator: luca willbe taken to the pediatricintensive care unit, where his condition canbe closely monitored. lucy, voiceover: when youhear that someone is going to the picu, you knowthat it's super serious, so the picu scares me. it really does. but i would stay herefor months. i would stay here for years,

if that's what wouldmake his body better. film: youngsters fromall over the world are being cared forby doctors and nurses backed by teams ofscientists and researchers at the jimmy fund building with just one goal--the cure of cancer. narrator: at the new clinicin the early 1950s, sidney farber was doingeverything he possibly could to cure the childrenunder his care,

but he was making little clinical progressagainst leukemia. within the cheerful wardsof the hospital, he tried new drugsat ever-higher doses, but in the end,the children always died. the scope of the problem wastoo big and too expensive for any one manor any one clinic. farber knew he neededstill more help if he was ever going tocreate a research program

big enoughto conquer cancer. he needed an ally. mrs. albert d. lasker is a woman of manyand varied interests-- flowers and philanthropy, cancer researchand community welfare. mary, are you happywith what is being done in the wholearea of financing medical researchin this country?

oh, i'm not a bithappy about it. the amount of money that'savailable for research is totally inadequatein the united states. you won't believe this-- less is spenton cancer research than we spend on chewing gum! narrator: mary laskerwas not a scientist, not a doctor. newsreel: america's foremostmedical scientists

and administrators received the american public healthassociation's lasker awards. narrator: she wasa wealthy socialite and a prodigious fundraiser with a passionate interestin eradicating disease. newsreel: mrs. mary laskerand dr. george bayer, head of new york academyof medicine, present the medical oscarsin boston. narrator: "i amopposed to illness,"

she once told a reporter,"the way one is opposed to sin." woman: i often asked marywhy this had become such a consuming passionand conviction, and she said, "well,i suppose it started that i suffered illnessand pain when i was a child." narrator: born in a smallwisconsin town in 1900, mary woodard suffered fromlife-threatening infections, which left her,as she would later say, "deeply resentful"of medicine's limits

and acutely sensitive tothe suffering of others. blair: one day,her mother took her to see the family laundress, who hadhad double mastectomies, and mary said,"why were they cut off?" and her mother said,"to try to save her life." she was outragedby disease and illness. narrator: after movingto new york, mary became a successfulbusiness owner, selling high-societydress patterns to working women.

there, she met hersecond husband in 1939, a wealthy advertising executive20 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 fortunepromoting products like lucky strike cigarettes. ad: â™Âª yes, for smokingthat you're bound to like â™Âª

â™Âª you just can't beata lucky strike â™Âª man: on their wedding night,albert says to mary, "what do you want todo with your life?" mary said, "i want to dosomething for human health, "the major diseases and crippling diseasesof mankind." narrator: above all,mary wanted to cure the disease that had long ago disfiguredher family's laundress. before long, albert hadenlisted in mary's cause.

there was limitless moneyout there, he told her, and he would show herhow to get it. the couple heldlavish fundraisers in their east side apartment. mary lasker: i have somepictures here by cezanne and manet and renoir,van gogh. gutterman: she felt thatyou had to have money to get peopleworking on a problem. she once called money"frozen energy,"

and i think it'san apt description. it's perfect. "what's the money doing?" i mean, she would complainabout this all the time. narrator: in 1944, the laskerstook over a small charity called the american societyfor the control of cancer. man: strike backat cancer! give to the americancancer society. they renamed it theamerican cancer society

and stacked its board with advertising executives. they not only wantedto raise money, they wanted to removethe stigma around cancer, with the help of madisonavenue salesmanship. did you know that cancerkills more children between the agesof 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 laskerbrought 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 forcearound cancer by deployingall 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 vastpublic 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 vocalabout them, and i urge everybodyto give more to the voluntaryagencies like the american cancersociety and others, and i urge them... narrator: mary laskerbattled cancer every day in the public eye, but she lostthe battle at home. on the morningof may 30, 1952,

albert lasker diedof colon cancer. mary lasker redoubledher efforts against the hated disease. she knew she could only getso far with private funds. she had to tap the vast coffersof the federal government. for this, she would needa bona-fide scientist to validate her evangelicalbelief in a cure. there was only one possibleman for the job. groopman: mary laskersaw in sidney farber

someone who could bepresented as a believer that this can change and thatwe can find the answer and that we will cure cancer. narrator: farber had beensearching for that cure for almost a decade. he and lasker concludedthat what was needed was an all-out coordinatedattack on cancer, undertaken by the largestprivate and public partnership in the historyof health care.

groopman: mary laskerhad the political smarts and the connections, and sidney farberhad the gravitas, and together, they formeda formidable force that reallycouldn't be stopped. man: dr. farberhas been called the father of chemotherapyin the treatment of cancer. narrator: while lasker workedher contacts in congress, farber did his part,

proselytizing for the comingrevolution in chemotherapy. dr. farber, will youmake a prediction as to how long it may take before cancer can becalled conquered? i don't believethat's possible, sir. i think the answer is that there is more activityand research today in the field of cancer than ever in the historyof science and medicine,

and with this tremendousamount of activity, i think we have the right toexpect that great progress and rapid progresswill be made. narrator: farber and laskerconcentrated their efforts on a small, poorly fundedgovernment agency, the national cancerinstitute--the nci. they hoped to focusits mission and provide the means to eradicate all formsof the disease.

by 1955, lasker and farber'sefforts had succeeded. with new appropriationsfrom congress, the nci would quickly becomethe center of the cancer world, and at its center wasits scientific director-- a bold, brilliant specialistin infectious diseases named gordon zubrod. during world war ii,zubrod had helped lead the federal government's massiveeffort to combat malaria, which had ravaged americanforces in the pacific.

he employed some of the first randomized clinicaltrials ever conducted. zubrod brought thesame military precision and gung-ho spiritto the nci, recruiting a new generationof researchers willing to try almostanything to defeat cancer. one of zubrod'sfirst recruits was a 28-year-old specialistin blood disease named emil freireich.

man: we dumpedmy 3-month-old baby and my pregnant wifeand 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 reportingfor active duty." and he said, "freireich,what do you do?" i said, "well, i'm atrained hematologist. i made a great discovery inmechanism of inflammation." "you should cure leukemia."

"yes, sir." narrator: zubrodpaired emil freireich with anotheryoung researcher, coincidentally namedemil frei. to tell freiand freireich apart, their colleagues begancalling them tom and jay. mukherjee: they wereboth named emil, but they couldn't have beenmore different characters. frei was composed, reserved.

he was cool. jay freireich wasthe opposite. he was loud.he was passionate. he was charged. narrator: zubrod fostereda try-anything approach, which was especially appealingto frei and freireich, who already had reputations as daring and innovativeresearchers. with their colleagues,

they began to scourthe natural world for chemicals to tryagainst cancer. no location was too far away,no compound too exotic. film: the searchis worldwide. there are 10 millionnatural products that might containan anti-cancer compound. near nairobi, botanists gatherleaves and the bark of trees to process and testagainst cancer. mukherjee: there weretens of thousands of drugs

that enteredthe nci pipeline. we are talkingabout an enormous, extremely sophisticatedfor its time, extremely dedicated process, which creates a vastlibrary of chemicals from the natural world,from the unnatural world, and each chemicalasked 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: followingsidney farber's example, frei and freireich began testing the most promising chemicalson children with leukemia. parents flockedto the nci clinic to enroll their sickchildren in the trials. freireich: they were therefor only one reason-- not to figure outwhy they were sick,

not to figure out how theygot sick, but to get better. they came to the clinical centerlike you go to lourdes. they came seeking somerelief 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 dosomething, freireich." well, we had to do something. narrator: the researchersdid all they could, but progress wasagonizingly slow. no sooner woulda drug begin to work than the cancer wouldadapt a defense to it. nathan: the problemwas resistance,

that cancer isa complicated illness that can finda way to bypass the very action of the drugthat you're trying to give. narrator: but the nciresearchers believed they knew how to overcomethe problem of resistance. freireich: zubrod camefrom infectious disease, and the infectious disease guys had learned animportant principle-- that is, if you gavetwo drugs at the same time,

the emergence of resistancewas prevented, and it was more effective. nathan: but how much ofeach drug should you give? should you give a full doseor cut the dose? how many dosesa day or a week? it was all unknown. narrator:unlike sidney farber, who favored givingone drug at a time, frei and freireichexperimented

with two-drug combinations. each time, the remissionsgrew longer, but still the children relapsed, or simply succumbed tothe brutal side effects of the treatment itself. freireich: at the time,80% of the children who died, died just frombleeding to death. leukemia didn't havea chance to kill them. there's blood on the sheets.

there's bloodon the uniforms. the nurses are coveredin 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 allof this to increase "the lifespan of a childby 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 likea death warrant. these kids would come in; of course they were goingto die of their disease, but we weremaking them much worse. i felt it very, very keenly. it was hard.

i felt so badlyabout what i was doing that i went to see dr. zubrod, and he wanted mevery much to continue, and i had to tell him that i just didn't thinki could do it. his answer to me hasalways stayed with me. he said, "i understandyou completely. "i know what this is like. "i know what's going on there,but we're committed.

"we're going to do somethingabout childhood leukemia, and the only way we can do itis to push ahead." narrator: despite thechildren's deaths, frei and freireich hadseen pronounced declines in white blood cell counts,a clear sign that the toxic chemicals were havingan effect on the disease. encouraged, they pushedeven harder. if two drugs werebetter than one, then four mustbe better than two.

in 1962, they launcheda trial called vamp. mukherjee:vamp was an acronym for 4 individualchemotherapy drugs, and they had all been chosen because the theory was that each of them hada different pattern of attacking cellular growth. it would be synergistic,and it would therefore kill all cancer cells, drive thecancer cells down to zero,

and therefore completelycure the cancer. narrator: on september 24, 1962, frei and freireichbegan treating the first group of childrenin the vamp trial. there were 16 of them--10 girls and 6 boys. researchers at the nciwere deeply divided. some believed that vampwas going too far. if two drug combinationshad caused children to bleed to death,what would four drugs do?

freireich: we're a bunch ofyoung bucks who know nothing. everybody thinks we'reexperimenting on the kids. they're worried aboutbuchenwald and horrors... but when youunderstand something, you understand it, no matterwhat 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 helldo you know i'm wrong? i mean, i know what i'm doing. tinkle, tinkle! there you go,darling. narrator: olivia blair hasresponded extremely well to her first monthof chemotherapy, and she is nowin remission. bye!

say thank you.blow kisses? you're welcome. do you see thedifference in hersince the beginning? kelly, voiceover: she's justso strong and so resilient. it's just amazing.if i had been through half of the stuff thatshe'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'sdoctors are encouraged by her early response, they remain concerned withthe possibility of a relapse. what's he doing? marcus, voiceover: when youhear that word remission, you think thatthat means she's cured, and so that's a commonmisconception. do youlike this light? it just means thatthey can't see it.

narrator: the doctors arerecommending olivia be enrolled in a clinical trial of yet another chemotherapydrug, called nelarabine. there you go! sison: a lot of people know that leukemiain kids is curable. when we present the idea ofa clinical trial to parents, they understand that this is how we got to wherewe are today.

they understand we're notnecessarily "experimenting" on their child, that we'reactually taking the best-known treatmentand trying to make it better. man: so, at thispoint, olivia is in the category ofintermediate risk. what's mrd? sison: mrd isminimal residual disease, so that's the amount of leukemiathat we could detect or not detect at herday 29 bone marrow

from monday,so her mrd is 0.0. it's the absolutebest result we couldhave hoped for. ok? great. wonderful. all right. now where do we go? we knowthat patients, even when they'remrd negative, have leukemiasomewherein their body, and if we don'tcontinue treatment

with an intenseregimen likewe're planning, then it willcome back. and the question is, does she receivenelarabine? ok? we don't know ifit helps, and evenif it helps, we don't knowif it's worth theside effects that you couldpotentially havefrom 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 liningof the throat... sison, voiceover: so, all ofthe treatments that we give have significantand severe side effects... increasesin bilirubin,infection... but again, it's oneof those decisions of balancinga patient's life versus the side effectsthat the treatment will give.

muscle damagethat also can thendamage the kidney, problemswith breaking downcarbohydrates, also, that wouldcause inflammationin the pancreas. [olivia crying] as you can see,the list is long. this is probablythe hardest decisionalong the way that you guyshave 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 formulathat spits out, "ok, the next patient thatconsents is gonna get it, and this one's notgoing to get it." that's like... i don't...i don't... i don't feelcomfortable with that. the thought ofyour child's treatment being left up to a computer

is a very hardconcept to take. marcus, voiceover:when you're making those type of decisions, of course you want it tobe the right thing for her. and it's ok ifyou decide not tobe in the study. marcus: so you just trythe best you can as a parent to learn as much as you can to make aninformed decision, but you never know.

it's 1-10% on the... on the highest. i know we allwant to do what'sbest for livy. yeah. i don't knowwhat 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. woman: 1963. that's wheni first felt sick. i was in junior high school, and we were livingon eastern avenue, and we were walkingdown to the beach,

my sister and my friends,and, um...i was tired. i really felt tired. you know? it wasn'tlike the measles or, you know, chickenpox. usually that would go away, but this justdidn't go away. it just got worse. narrator: karen lordwas 13 years old when she was diagnosed

with acutelymphoblastic leukemia. in june, 1964, with herhealth declining, she was taken toa hospital in boston, where she was quickly puton the 4-drug vamp regimen first tried at the nci bytom frei and jay freireich. lord: my doctor just decidedthat i would not know. they just didn't talk about it. they just would say,"here's your daily cocktail," but they wouldn't saythe word chemotherapy.

i called the treatmentmy martini time with the iv. yeah. we'd joke about it,the nurses and i. "oh, it's martinitime again." when i had first enteredthe 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 chemotherapycaused severe nerve damage and made karenso delirious at times

that she had to beforcibly restrained. she became addicted to morphine and for monthshovered near death. lord: i rememberthe priest coming in, and he had this purplescarf 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 ihad it 3 times, so... sometimes the pain was so bad,

it would have been better ifi did go to the other side. narrator: gradually, though,the drugs began to work. lord slowly recovered. after 12 monthsof treatment, she was ready to returnto school and a normal life, one of the first childrenever cured of leukemia. lord: when i went backto 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 backin school." narrator: other childrenin the vamp study also began to see the tideof white blood cells created by their leukemiaslowly recede. mukherjee: incredibly,some of the children actually began to recover, and when they didbone marrow biopsies, they began to find thatin 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 thesebone marrows. narrator: though stillthe minority of cases, these were not the fleetingremissions of farber's trials. these lasted. freireich: the breakthroughof vamp was, number one, the concept that a systemiccancer could be cured.

from that point forward, cancer research wastotally transformed, because now, people who said,"you can't cure cancer. you're finished." we can cure cancer,at least childhood leukemia. narrator: despite itsintense toxicity, the success of combinationchemotherapy suggested that it might be possibleto use the same strategy against much morecommon varieties,

such as breastand lung cancer, even after they had spread. dr. farber, how doyou think cancer will eventuallybe controlled? i think that cancerwill be controlled, eventually,by chemical means. narrator: from his officeat the jimmy fund clinic, sidney farber had followedthe multi-drug trials at the nci with a mixture of prideand apprehension.

his experiments with aminopterin had inspired freiand freireich's work, yet for farber, the sufferinginflicted on children by these trialscrossed a line beyond which he would not go. younger scientists did notshare 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 withcombination chemotherapy, and as far as i could tell,there were no survivors in patients withthe 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 buildingto confront farber. nathan: i go into the room, and there he isin his white coat,

and i start right away and say,"you know, i really feel "so strongly aboutcombination chemotherapy, "and i feel as a physician "that i cannot referthe patients to you if you won't adopt it." well, he absolutelyflew 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 neverwould 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 cureone out of three?" and i can stillhear him saying, "i will not injuretwo children to save one." narrator:it's been 40 days since luca assante's transplant,and the latest results from his bone marrow biopsyhave just come in.

so how was hisbone 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 newimmune system, transplanted from his sister,has taken over and is producinghealthy blood cells

that have driven hiscancer into remission. what about the restof the things? i mean,the bilirubin went up. yeah. so the onlynegative thing is that the bilirubinwent up some. narrator: but the newimmune cells are continuing to attackluca's liver in what is now a full-blown case ofgraft-versus-host disease. i can't spin thatinto a positive thing.

oh, my god.something else? we don't needanything else, ok? we've had enough. the virus piece is better,but he's not all better. so we have norecommendations for any changes today--just more of the same. more ofthe same is good. loeb: i thinkthat the reason that he's not all betteris because of

the graft-versus-host disease, so hopefully, we'll makethat piece better, too. narrator: after 20 days in the pediatricintensive care unit, luca has become critically ill. lucy: the worst feeling isnot 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 ableto go play soccer? you want to go play soccerwhen you get back home? lucy, voiceover: i hadn't heardmy kid talk in 20 days. so i haven't heard himsay "mommy" in 20 days. that's pretty tough. but i have my husbandhere with me, and we don't leave luca at all,so he knows we're there. sometimes people thinkyou're stronger than what you really are,but i feel strong

because i'm fighting with luca, and i'm not going tolet him fight alone. good job! you want to put thison the side? you play later?or you want to play? narrator: luca's doctorswere 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 kidstreatment to fix one tumor, and it has the chanceof causing another. i don't regretgiving him those drugs because if we hadn'tgiven him those drugs, he would have diedat age 2 instead of 6, but it's still bothersometo know that the drugs that we gave him to treathis first tumor

ultimately caused himto die as a child. there are stillparts of his case that none of us reallyunderstand very well. i'm sure that we're goingto spend a lot of time trying to understandwhat happened, because if we canunderstand what happened, then maybe we can do somethingdifferent next time, and the next kid won'thave this happen. dr. farber,it gives me great joy

to give you the americancancer society's high honor, its gold sword. narrator: by the late 1960s, sidney farber and mary lasker'scampaign to cure cancer seemed more urgentthan ever. lasker continued to takeher fight to congress and to lobby her close friendin the white house, lyndon johnson. gutterman: one time, a yearbefore johnson left office,

mary went to the white housebecause she wanted an additional$100 million appropriated for cancer research, and so she's inthe oval office, and lyndon's complainingabout everything. the vietnam waris 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 ofa flirt, as we all know, and he put his handon her knee and said, "mary, how badly do you wantthat hundred million?" and she not so gently liftedhis hand off her knee and said, "lady bird is my bestfriend in the world. now, am i going to getthat 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 walkedon the moon. national faithin science soared. roger. the eva isprogressing beautifully. they're setting upthe flag now. narrator: the moon landingwas the result of a close partnership betweenscience and government.

if such a partnershipcould conquer space, farber and lasker wondered, why could it notconquer cancer? i, richardmilhous nixon,do solemnly swear... narrator: there was a newpresident in office now, and they set out to enlist himand the american public in a campaignfar more massive than had everbeen seen before-- a conquest, as mary laskerput it, of inner space.

mukherjee:in december 1969, if you woke up and you opened"the new york times," you would find a very differentkind of advertisement-- not for a productthat you could buy, but for something thatthe nation should buy, and that was fora war on cancer. groopman: the advertisingwas a juggernaut. they said, here it is. many people won'tutter the word.

we're saying it in"the new york times," we're saying it to the presidentof the united states, and we are going to mobilizea national effort with a promise thatthis horrific disease will be eradicated." narrator: on march 9, 1971, senators edward kennedy,a democrat, and jacob javits,a republican, introduced a bill callingfor $400 million

in federal fundsto fight cancer. lasker lobbied her manyfriends on capitol hill, refusing to take nofor an answer. gutterman: mary's skillswhen she went to congress were a sight to behold. there was no timefor small talk. she would say, "i'm justhere on one issue." many of them would complain,look at their watches-- "i know what you want,

but, you know, we gotall these bills." and she said, "but whatabout your wife? i understand your wifehas cancer." "yeah, that's unfortunate." "well, how do you thinkshe's going to get better? can i count on you?" narrator: "the iron is hot,"farber had written lasker. "this is the time topound without cessation." lasker turned to her friend,

the newspaper columnistann landers, to urge her readers towrite their congressmen. landers' column ran on april 20. within days, mountainsof mail were piling up in capitol hill mailrooms. blair: the outpouringwas beyond imagination. hubert humphreycalled up mary and said, "you've got to give meanother secretary. i have 60,000 lettersin my office."

narrator: thanks tofarber and lasker, cancer was no longer a diseaseto be hushed up or hidden. "to oppose big spendingagainst 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 signingthe cancer act of 1971, and i hope thatin the years ahead that we may look backon this day and this action as being the mostsignificant action taken during this administration. thank you. narrator: the passageof the act provided funding for cancerprevention and research

that dwarfed anything thathad been raised before-- $1.6 billionin 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 governmentfor the kinds of sums which would bevery hard to raise even with the most generousof philanthropists, but also to create an entitybased on a promise,

and that wasthe cure of cancer. narrator: today, more thanhalf a century after sidney farber'sfirst chemotherapy trials, childhood leukemia has asurvival rate of nearly 90%. the era of bold andceaseless experimentation, borne mostly by children, led to the most elusiveof achievements--a cure. brown: every time you can chipoff a little bit of uncertainty and make the right answersmore clear,

in any aspect of theclinical care that we give, it's gratifying. if you look 50 years ago,it was all uncertainty. now there are certain thingsthat we know are effective, where the right thingto do is so clear. the more that we canchip those things away and put them into that category, the less humbled we'reall going to feel. olivia!

what do you think? oh, i know.this is cute. narrator:for olivia blair, almost a year afterher diagnosis, her cancer remainsin full remission. i love you. kelly, voiceover: we don'twant her to know that something's reallywrong with her, because she has no ideawhat's going on right now.

where's livy? she's so young. she's notgoing to remember this. boo! boo! peek-a-boo! there you go. kelly, voiceover:she's going to beat this. she's going to be32 years old, and she's going to be proudto show her port scar and say "look at me."

where's petey? i... just don't want to thinkthe worst anymore. i just want to thinkthe best, and... just enjoy the timethat we have with her. where youwant to go? come on. narrator: in the lateafternoon of march 30, 1973, an emergency signal sounded

throughout the jimmy fundclinic in boston. doctors and nurses raced toward the director'seighth-floor office. they found sidney farber withhis face resting on his desk, dead from a massiveheart attack. farber: in some ways,my father was remarkably lucky to be able to workuntil 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 usedthis language, maybe, but i would sayhe was blessed. narrator: farber was survivedby a handful of the children he had treated atthe jimmy fund clinic, including "jimmy" himself,einar gustafson, who would liveto the age of 65. farber himself hadnot lived to see how the war on cancer he had helpedbring about was waged, but his friend and partnermary lasker believed

victory might now be lessthan a decade away, and she had reasonsfor her optimism. she and farber hadhelped turn cancer from a subject no onewanted to talk about into a national priority. the full force ofthe american government was now enlistedin the struggle. nixon: it will not failbecause of lack of money. if $100 million this yearis not enough,

we will provide more money. narrator: new techniquesin surgery and radiation were now beingused effectively against a variety of cancers, and researchers had discoveredchemicals that could kill malignant cellsno matter where they spread. to some in the cancer community,the challenge now seemed simply to find the rightcombination of chemicals to combat each kind of cancer.

but despite theseinitial triumphs, the war on cancerwould stretch on for 3 decades and more, and those who fought itwould find themselves engaged on a thousand battlefields against an elusiveand resilient enemy-- the cancer cell itself, whose true nature no oneyet fully understood. until that mysterywas solved,

victory could never be won.