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marcia day childress:good afternoon, and welcome to "themedical center hour." this is a program entitled "themalaria project, the secret government mission for a cure." i'm marcia day childressfrom the center for biomedical ethicsand humanities, happy to welcome youhere today to a program that is also one of our"history of the health sciences" lectures.
during world war ii, withmalaria a real threat to american troops fightingfitness, especially in the pacifictheater, us government mounted an all-out huntfor a malaria cure. the story of this endeavoris a very complicated one, with many threadsand many angles that give one ethical pause. it's also a story thatwent untold and unexamined for several decades, and thestory largely unknown still
among experts and specialistsin infectious and tropical diseases. while learning to minethe us national archives, public health journalistkaren masterson happened upon archiveddocuments that had been incorrectly boxed. what she found thereput her into this story of secret science in theservice of america's war effort, experimentation in pursuitof an anti-malaria drug that
took its cues from early 20thcentury german research models and methods and thatinvolved risky research on institutionalized andincarcerated americans. we're pleased to welcomekaren masterson, who is a lecturer at johns hopkinsuniversity in the writing seminars and publichealth studies programs. in this "history of thehealth sciences" lecture, she'll tell us the astonishing,sometimes appalling tale. this episode and thehistory of recent science
helps us to appreciate thecomplexity of research, how science andmedicine are always part and parcel of theirsocial, cultural, and political contexts, federalrules and regulations governing ethicalhuman participation in biomedical researchweren't always in place, and indeed, if they had been,much of this malaria project could not been done. it's also instructive torecognize the thorny business
of weighing competingrisks and priorities, whether we're exercisinghindsight or thinking about our own difficultchoices here and now. following ms. masterson'stalk, uva professor emeritus of medicine dick pearsonwill offer a brief response from his perspective as alongtime infectious disease and tropical medicine specialistand very interested reader of karen masterson's book. her book, the malariaproject, is available for sale
and signing by the authorjust outside the auditorium. again, we'd like to thankthe "history of the health sciences" lectureseries, a program of historical collections herein the claude moore health sciences library. and now, karen mastersonand then dick pearson. welcome. [applause] karen masterson:thank you, marcia.
and thank you, everyone,for being here today to listen to the storyof the malaria project. i became interestedin this story because i stumbled ontothe bioethics issues. but what really drew mein and kept me interested was this fascinating disease. i'm not a bioethicist. i don't know muchabout-- i didn't know much about bioethics.
i didn't know much aboutmalaria or world war ii before i found the story. i was actually apolitical reporter. i worked in the senate pressgallery in the capitol. i chased down senatorsand members of the house. i interviewed hillary clintonwhen she was a senator probably a half dozen times. and i wrote stories aboutlegislation and policy and politics for abig texas newspaper.
but i left that world for amore sane work-life balance. as a science writer-- beforei became a political reporter, i was an environmental reporterfor the philadelphia inquirer. and so my firstpoint of transition was to accept a fellowshipat johns hopkins, where i could study thehistory of medicine and infectious diseases. and it was there that i reallydid the bulk of my research for this book.
i was in the nationalarchives looking for somethingcompletely different when i stumbled onto a memo fromthe national research council to the lead health official thestate of massachusetts asking if researchers couldcome in and infect boston psychopathic patients withmalaria so that drugs could be tested on their infections. no less than the war'soutcome was at stake. i was looking forrecords on linus pauling,
and i found this. and i had no ideawhat to do with it. so i just kept pulling threads,and i worked with archivists, because the process forfinding records is convoluted. and this wonderfularchivist that i worked with found all kindsof records for me. and after about 500 boxes, ihad pieced together what i call and what casually was calledback then "the malaria project."
it was really is whatmarcia said it was. it was the us government'sresponse to this problem that they hadduring world war ii. troops were falling, firstby the thousands, then the tens of thousands, thenthe hundreds of thousands. over half a million us troopswere affected with malaria. that's just the us troops. malaria was a problem forboth sides of the war. all countries who hadcommitted troops to battle
had to deal with thisproblem, because we were fighting in areaswhere transmission rates were up to 80%. so the war departmentasked scientists to help. this is the box where ifound that initial memo when i was looking forsomething on linus pauling. i found a lot of recordsthat looked like this. they were top secret. this was a secret project.
and it was a secretproject because everybody knew that a malariadrug would be a weapon. it would be a weaponthat would give your side an advantageover the other, because nobodyhad anything good. quinine was the only known drug. it had been blockaded. it was a drug made fromcinchona tree bark, and the cinchona treeplantations were all in java,
and the japanese hadblockaded these plantations. they didn't know how to use it. they didn't knowwhat to do with it. the dutch owned plantations,but they blockaded it so nobody had accessto the quinine. hundreds of reportsthat looked like this were written bylead investigators for the americanproject, and they innumerate thenumber of bodies used
and what happenedto those bodies. so i could run atally in my head as i was going through all thesereports of how many people were used, and they were prisoners. they were statehospital patients. they were pows. they were conscientiousobjectors. and they were soldiers. to understand thebioethics of this project,
though, i feel it's importantto give you all context, too, so if you'llbear with me, i want to give you the backdropof what's happening all around, what happened beforethis project began, so when i get to theuse of these patients, you've got the fullunderstanding of why scientists crossed that line. and they seemed todo it so easily. it all started with this man,julius wagner von juaregg.
he was an austrianpsychiatrist who has a wonderful backstorythat i include in the book. for the purpose of this talk,because i always talk too long, and i want to make sure istay within my 30 minutes, suffice it to say thathe had figured out that a certain subset ofpsychiatric patients who had neurosyphilis, thelast stage of syphilis when the spirochetesactually got into the brain and caused damage, that thatcategory of mental health
patient could sometimes be curedand if you gave them malaria and allowed the feversto escalate to their peak a few times. and he understood it back then. he wasn't even a malariologistbut he understood it back then kind of intuitivelythat it was boosting the immune system to fightthe syphilis infection that actually helped kickit out of the system, kick it out of their brain.
and so he saw, after givingmalaria to over 1,000 patients, that if he caught thoselast-stage syphilis patients coming into thestate hospital system before they were too far gone,that he could actually cure them about 30% of the time. the british saw this andthought it was brilliant. juaregg had these strictures. you only use vivax malaria. vivax is the kindof malaria that you
get in asia, back thenin southern europe amd in the southern unitedstates, in south america. vivax is the kindof malaria that will hibernate in yourliver and launch relapses, but it's rarely deadly, versusafrican falciparum malaria, which is very deadly. and you could start showingsymptoms in the morning and be dead by theend of the day. so he said, no, youonly use vivax malaria.
and you only useblood transfusions. you don't transfuse thedisease through mosquitoes, because if you didthat, then you'd be curing syphilispatients of the syphilis, but you'd be sending themout into the community with the malariastill in their liver. so he had these rules. and he stuck by them. here you can see avery sick patient
in the background with malariaat the height of the infection. and they took blood fromhim, and they're injecting it into this patient in theforeground to give malaria to that patient. he had to keep hisstrains alive in people, because there was no wayto culture the parasites. so he always had some of hispatients infected with malaria, and he could collecthis data, and he collected his strongideals on how to use this.
the british tested his theoriesat their state hospitals, and-- it's calledmalaria therapy. they gave malariato 1,600 paretics. the late-sage syphilis patientsback then were called paretics. and of them, 36%died of the malaria during the malaria infection,25% walked away fully cured, and the rest remained unchanged. so 36% died, 25% cured, andthat was considered a success. they had a controlhospital, where
they had about 100 patientsthey were tracking, and within two years, all butthree or four of them died. i'm forgetting the exactnumbers, but most of them died within two years. so juaregg won the nobelprize, because he figured out how to treat a mental illness. and he's only one of twopsychiatrists in history to win that prize. the germans capitalizedon this idea.
bayer and company, whichwas part of the ig farben conglomerate, went into thestate hospitals and said, can we use your malariatherapy patients to test our experimentaldrugs on them? we will vet them onanimals first to make sure that they're nottoxic, but we just want to see if our drugswill work against parasites, and you've got lots of malariahere in your state hospital. will you work with us?
and they said yes. so the bayer and companywanted to displace the dutch in the malaria market. they wanted to create asynthetic version of quinine, put those slow-growing treesand that expensive process of extracting quinine fromthat bark out of business and have another blockbusterlike their bayer aspirin. because back then,malaria was everywhere, and people tookquinine like aspirin.
and so they wanted that market. and they had the goods. they were far ahead of allthe chemists in the world on creating synthetic drugs. and so they actuallyhad some leads that they got from paul erlich,actually, on where to start. and they ended upmaking two drugs, atabrine and plasmoquine. plasmoquine was the first one.
they made that aroundthe time that juaregg won his nobel prize. and in this statehospitals, it looked like it was quite activeagainst the parasites, but once they did biggerstudies in eastern europe on larger populations, theylearned that actually this drug actually destroyed bloodcells and was a real problem. and so they just kept workingat it, and in the early 1930s, they came up withatabrine, which
was based in a yellow dye. and atabrine-- its toxiceffects weren't that bad. they weren't deadly. but it wasn't a great drug,and it didn't displace quinine. it was mostly usedin the german markets and south america, whichis why this is in spanish. and it didn'treally get very far. well, fast forwardto 1930s germany, late 1930s germany and hitler'splan to prepare for war.
ig farben, this is theirheadquarters in frankfurt. it had been co-optedinto the nazi system, and their orders to bayerwere to find a better drug that german troops neededto survive these infections against malariathat they knew would be a problem in the placeswhere they planned to do battle. and so bayer got to work. and one of the scientists whowas pulled into the process was claus schilling, whoin the 1920s and '30s
was probably the leadingexpert in malaria. he did really innovative things. he milked the salivary glandsof mosquitoes to get the saliva, and he would injectit into patients and then give thepatients aspirin to suppress thefever so he could continue giving the patientsthat first stage of malaria. to understand this,malaria has several stages. i talk about three of them--the, infant the adolescent,
and the adult. dr. pearson cantalk about the technical side, but as a storyteller,these are the three most important versions. and that the infantversions, when they're in the saliva of the mosquito,the mosquito bites you, gets into your body,and it immediately goes into your liver. and one parasite turns intoabout 40,000 or 30,000. and in a week or two, theyburst out of you liver,
and they attackyour blood cells. and inside your bloodcell, one parasite will turn into 30 or 40. the cell will burst, andour pours another whole army of these parasites. so within a week or so,you've got trillions of them in your body. and at a certainstage, some of them mature into the sexualstage, the adult stage.
and they circulateinto your surface cells and emit a chemicalthat makes you 100% more attractive to mosquitoes. it's actually amosquito attractant. and a mosquito is going to biteyou, drink in that adult stage, and in the mosquito's gut, theyfuse into a oocyst, or an egg sack, and a week or two later,based on air temperature, those sacks burstwith these new infant versions, these stick-likeversions in the saliva.
and so what schillingwanted to do was boost the immune systemagainst that first version of the parasite so that yourimmune system would recognize it quickly andstop the infection, never get into your liver,you'd never had an infection. and he was actuallymaking some progress, but war started, and so hehad to go to heinrich himmler and ask for anopportunity to study this. and himmler said,sure, i'll give you
the dachau concentration camp. and so schilling was sent there,and he infected about 1,000 prisoners with malaria. actually, in hiswing of the hospital, they had clean sheets. they were given anextra ration of food. they had to berelatively healthy, otherwise he couldn't take them. you can't give malariatherapy to people
who are already dying. and so from some perspectives,his patients actually lived longer beingin his hospital ward as part of his studiesthan the inmates who were exposed totyphus and the ss cruelty. when the americans liberated theconcentration camps, he stayed. the ss all fled, right? he stayed to tell thejags, the army lawyers who were overseeing the hearings,that he had this great data,
that he had studiedmalaria, that he found some great results,and that his colleagues, who looked up to him before thewar, would want the data. and here he is trying toexplain, yes, yes, yes, i infected inmates,and i kept them sick, and their feverswent-- yes, yes, yes. but you don't understand. this is what we do. we're malariologists.
this is a part of what we do. army lawyers didn'tknow anything about juaregg or malariatherapy or the direction that all thisresearch was going in. and so he was convicted,and he was hanged. and that much was theend of germany's lead in malaria research. on the american side, thingswent very differently. this lowell coggeshall in thesuit amid all the white coats.
after the war, hebecame the dean of the university ofchicago's medical school. he was vice presidentof the university. he advised president eisenhoweron medical policy, especially medical education policy. he said we arefocusing on body parts too much, that specialties arethe wrong direction to go in. we're pumping outway too many students who are specialistsand not enough who
understand the whole body. we should be working with nursesassociations and public health associations. this is a whole body approach. and in the 1950s, he was calleda communist in washington, and so he retreated back tothe university of chicago and continued his good work. but i found him a relief. so that i found what i thoughtwas a man who was a good man.
he was actually anice man who was the lead thinker on theamericans creating this model based on the germans' work. and so i use himto tell my story. and i start with when hewas just a cub graduate student in the swampsof leesburg, georgia, studying malaria for therockefeller foundation. the rockefeller foundation thenwas what the gates foundation is today.
they invested $100 millioninto getting rid of malaria in the us south, whichis about $1.5 billion in today's dollars. so they were a big part of it. and he was very fortunate,an interesting guy, came from nothing,was a poor farm boy. and he wanted toget out of farming, so he decided to study biology. and he ended up,through a series
of good luck andhard work, ending up at the rockefeller foundation. and they turned himinto a malaria expert so that by the timethe war started, he was the lead thinkeron how to tackle this problem before we committedany troops to the ground. here he is in one of thefirst meetings of the malaria project, talkingto other experts about how they weregoing to convince the war
department that the wardepartment needed this. well, the war departmentwasn't ready to listen. and as they wereformulating their ideas, coggeshall got pulledaway from washington, because the us was secretlyarming and supplying the british, whohad been cornered in egypt by rommel's forces. and the way we weredoing it was we were running-- pan am airlineswere the front for the army air
command, runningsupplies from miami down to the elbow of brazil,across to the hump of africa, and then across the saharainto egypt to help brits. and everything wasstopped right there at the hump of africabecause of malaria. the gold coast is whatghana was called back then, and liberia, whereour airships were, were nearly 100% infectionrate for malaria. so juan trippe,the head of pan am,
begged coggeshall to comeand help, and he did. so he went overseas, andthis is what he found. he found the jungles justtorn up to move supplies and to build airstrips. so when you tearup the landscape, you create more breedinggrounds for mosquitoes. and so what he saw was aproliferation of mosquitoes. and he quickly realized, wait aminute-- our problem might not be just the drugs.
our problem mightbe mosquitoes, too. so he said, we're goingto screen everything. the british royal air forcesaid, we've been here forever. back off. we know how todeal with malaria. screens aren't going to do it. you need the quinine. and so coggeshallsaid, well, all right, let's create a study.
so he had 100 royal airforce pilots on one campsite, and 67 pan am pilotson the other campsite. he wrapped the panam folks in screen. all the barracks were screened. they had to use bed nets ifthey weren't in a screened area. they had to wear theirclothes rolled down, their pants rolled down,their sleeves rolled down. so there was a very strictcontrol of their behaviors. and then the british justhad quinine, no screens.
and of the 100 britishpilots, 78 of them came down with malaria andlosing over 1,000 man days. and of 67 that werewrapped in screens, only one came down withmalaria, and it was because he snuck out for sex. [laughter] and so what coggeshallfigured out was that, ok, then you have to sanitize thesex villages of mosquitoes as well.
there's a bigbackstory on liberia and how we used that countryand what transpired there while we were getting rubberfrom the river plantations and using that as an entrywayto the war to the north. but i don't havetime to get into it, but it's very fascinating. and so cogeshall cameback from the war with a different,more informed approach that he brought tothe war department.
he said, ok, wedo need the drugs, but you need to have peoplein those combat zones who understand malariadoing anti-mosquito work, because you can't killall the mosquitoes. and by the way, only about40 of them carry malaria, and they're all anopheles,so you do targeted studies and anti-mosquito work. and the war department said,no, too much, too much. you've got more than 500 campstraining men to go to war.
wait in line. and that's pretty much theway it was until bataan, when the japanesebombed pearl harbor. they next went tothe philippines, and they attackedmacarthur's troops. and macarthur's troops were allforced out of manila and down onto the bataan peninsula, whichthe rockefeller foundation had already studied and knew that30% to 80% of the local people were seeded with malaria.
fortunately, his troopshad a supply of quinine that lasted them about a month. and when that quinine supplyran out, they started falling. and they fell by thousandsso that by the time of the surrender,80% of the troops were infected with malaria. the commanders allwrote back saying, we had plenty ofmunitions, we had plenty of big guns and rifles,but we had nobody to man them.
everybody was sick. that woke up the war department. and they called cogeshallin and his colleagues. and they said, we'reopening the spigot. tell us how much you need,set up whatever infrastructure you need for this. it was folded under theoffice of scientific research and development,which we are all the wartime science projectswere contained and organized.
it was a secretwhite house office that got funding thatwasn't approved by congress. it's where the manhattanproject was housed. so now the project is going. and in the next months,over 400 scientists were brought into the fold,50 universities, and most of the largepharmaceutical companies and a half dozen statehospitals and, to start with, three prisons to dothe clinical work.
all this was gettingpulled together while we were landing 10,000marines on guadalcanal, ripping up the landscape,the waters pooled and created perfect mosquito habitat. the camps became mud holes. the shelling and just the totaldestruction of the landscape, again, produced prolificnumbers of mosquitoes. and one of themedical corpsmen said to one of the battle commanders,i see a problem here,
because we know the localpeople are seeded with malaria, and now we have alot more mosquitoes than when we first arrived. and the men are all gettingeaten alive at night. we're going to have aproblem with malaria. and the command is recorded. it was sent back to dcto the headquarters. the commander said,we're here to kill japs, and to hell with mosquitoes.
that month, the same timethat that report came in, the first cases ofmalaria started filling the makeshift hospitals. and on guadalcanal on newguinea, by the end of 1942, the infection rate was3,000 per 1,000 men. so they were gettingit repeatedly. the only option thatthe war department had-- because the malaria projectwas just getting underway; it was just comingtogether-- with this drug
that i mentionedearlier, this yellow dug, atabrine, that thegermans had made. and it was toxic. we didn't know howto make it properly, so it was also inconsistent. our drug companiesdid their best, but they didn't do that well. and we also didn'tunderstand the dosing. so actually whenthe orders went out
to put all troopson this drug, we overdosed them so that by thethird pill, twice a week-- by that third pill, reportswere coming in of troops doubling over withcramps, soiling themselves with uncontrolled diarrhea,throwing up, already meager rations in these battle zones. in tunisia, historianshave recorded this, and there's a battlefor hill 609, where it was hand-to-handcombat, and our men
had to stop fighting becausethey were soiling their pants. it was just-- itwas a nightmare. and then a rumor went aroundthat it caused impotence. and that was it. men weren't going to take it. they were not goingto take this drug. the sands ofguadalcanal were made yellow by 10,000marines spitting out their atabrine pill.
they were supposed to takeit in their mess tent. they'd step outside, andthey'd just spit it out. the sands were yellow. so the war department turned ontheir propaganda machine, which contained theodore geisel. he was in the office. and so he drew thesewonderful posters, and they became ubiquitous. they were everywhere.
they were out in the field. they were on the bumperstickers of all of the jeeps. they were included inthe trailers of movies. i don't know if you knowanything about world war ii, but going to see a filmwas really big deal. and so theseposters and cartoons that were produced by thelooney tunes-- after the war produced the looneytunes series, they created these cartoons.
these were so ubiquitos thatthe troops started calling mosquitoes ann for anopheline. they were slowly beingindoctrinated into this notion that you had to avoid theseanopheline mosquitoes if you wanted to avoid malaria. billboards went up. they tried to get sex to getthe attention of the men. take atabrine! this [inaudible] one says,atabrine keeps me going.
and then the war departmentstarted training units, malaria units that were trainedin identifying and dealing with malaria that thenattached to the combat units. they were trained in--they have dipsticks they're dipping into thepond to collect larva so that the larva could bestudied so they could learn to see the differencebetween an anopheline larva and a regular mosquito. because this is allabout targeting.
you can't kill allmosquitoes, right? there are just too many of them. so if you target the species,then you can control malaria. so here they are learning. this is in a campin new orleans. this is before they shipped out. general patton actuallyhad units in place after the alliedtroops took tunisia and were ready to launchthe attack on sicily
and then get to italy. and remember this isall before normandy. so the approach to hitlerwas through his underbelly, going north africa,sicily, italy, and then up through the alps. and patton didn'tunderstand these guys. because they didn'tcarry rifles. they carried dipsticks. and he called themdipshit units.
and so he left hisbehind in tunisia. he didn't take themto sicily with him. and so he didn't know-- hedidn't have anyone there advising him on what to dowith 30% of his troop strength was eroded by sickmen with fevers. he went into two hospitals--this is pretty famous. he went into twohospitals, not just one. i mean, this one hospitalis the most famous, but he went into twohospitals and slapped soldiers
because they were sick. and historians now lookat those two cases, and they believe thatboth men had malaria. eisenhower almost fired him. but he was just not programmedto deal with malaria. it had to be forced on him. whereas macarthurwas the opposite. macarthur totally got it. after what happened tohis troops in bataan,
he all on board. he ordered more units than thetraining camps could provide. he had his units hiringlocal men by the thousands to clear the debrisout of the rivers so that the water wouldrun, because running water kills larvae. he had them spraying tiretracks with [inaudible] because these islands wereripped up by these trucks and by shells.
and he also hadunits just studying the larva and the mosquitoesand the local populations to see how seeded theywere with malaria so that targeted controlscould be put in place. all the doctors had togo to malaria school so that they could learnthe difference between you falciparum and vivax. there's actually four kindsof malaria that humans get. but really, the two bigones were these two, vivax
and falciparum. they had to understand thedifference between a relapse and recrudescence andthey had to understand what blackwater fever was,which was an overuse of quinine and then the infection causingblack blood in the urine, and it usually led toreally uncomfortable death. macarthur, as you cansee here on the right, even went to school. this is in australia.
he really wanted tolearn about malaria. there is an interestingbackstory about a captain engberg who was innew guinea trying to tell the services ofsupply that he had no vd rate. they kept asking him. sos kept saying, sendus your vd rates. and he would say, idon't have vd rates. i don't have venereal disease. we don't even haveany women here.
we have malaria. please send me malaria supplies. and they wouldwrite back and say, you are about to be disciplinedbecause you haven't sent us your vd rates. so he sent back arather colorful letter using an f bomb to saythat they had sheep, and if they wanted him toinvestigate sex with sheep, he would do it, butthere were no women.
and so the mps weresent out to arrest him. and macarthur's malariaexperts stepped in. they did a study. and they just provided thedata that the sos command needed to recognize thatthere was a malaria problem. and macarthur, tohis credit, then so admired this guyfor being direct, hired him as hispersonal physician. macarthur was on it.
the army air command jumped in. this is italy. when the germans startedto retreat from italy, they destroyed all thedikes and pump systems that had kept the countrysidefrom being flooded, knowing that the flooding wouldcreate anopheline mosquitoes. and so when the fifth armyand the british forces were coming through in may, itwould be about malaria season, and they expected thatit would slow them down.
so this was an actof germ warfare. this was all going on overseas,while the malaria project back home was coming together. james shannon, who wasthe future nih director, ended up being the headof the clinical studies. he worked on what was thencalled welfare island. it is now roosevelt island. he had written thestate officials to ask that all ofthe appropriately
healthy mental healthpatients throughout the state be collected here on thisisland at goldwater state hospital and manhattan statehospital so they could be used, so they could be given malariaand used in these studies. now we're not talkingabout paretics anymore. we're not talking aboutjust neurosyphilitics. we're talking aboutschizophrenics, people with bipolar disorder. anybody who was healthy enoughto withstand the malaria
therapy was sent to him. and this was hisclinical material. this was his biologicalthinking dialed way up. and it was theexigencies of war, and he stepped upand met the demand and figured out a way to collectas many bodies as he could. he used prisoners at sing sing. this is sing sing prison. he also used rahwayin new jersey.
this is a picture ofboston psychopathic. the project got up and runningthere, led by alan butler. saint elizabeth's hospital in dcwith 6,000 beds was also used. this is g. robert coatney. he was a parasitologist. he wasn't even a doctor. but he led the clinicalstudies in the south. his prisoners were inatlanta penitentiary, the us penitentiaryin atlanta, which
was not a high security prison. he used state hospitalpatients in milledgeville, the milledgeville statehospital in georgia, at the south carolinastate hospital. and by now, it's well into1943, and they've been at it, and they're notfinding anything. they're testing thousandsof compounds on bird malaria and hundreds on people. most of them are sulfa drugs.
they're not reallyhaving any breakthroughs on novel compounds. everybody is mad at each other. the chemists who areworking on bird malaria are frustrated because theclinical researchers want to take drugs to thepatients far sooner than they think they should. and besides, birdmalaria doesn't really
extrapolate to human malaria. your model is all wrong. and they're fightingone another. coatney is complainingbecause the military keeps taking not onlyhis lab assistants and sending them overseas,but also the inmates. so inmates aregetting early release. if they're not highsecurity inmates, they're getting early release.
and so they're in themiddle of the study, and they're getting dragged out. as the leaders in this projectare having little meltdowns, they have a breakthrough. during the liberationof tunis in tunisia, a french doctor comesforward, corners an americaninfantryman, and says, i have the cure for malaria. i have a drug that ismade by the germans.
bayer made this drug. they made me test it in theadobe villages of tunisia right before you all arrivedto start this battle. i collected thisdata on them, and i can show you that itnot only cures it, but it prevents malaria. and i want you tohave it, because i don't like thebritish and french, i don't want thefrench to have it.
so i want you to haveit and send it home. and it took several months. i found a report in this box. it took several months for itto be translated from french into english. and by the time ithit the project, the project had veryfew bodies left. they had so used their bodies,their state hospital patients and their prisonersthat they needed
to open up a whole newwing of their effort. and this man led theeffort, alf alving . he's a university ofchicago professor, swedish. he was a real expert. and he reluctantly,almost by force, took over a triangleeffort that included the university of chicago,nantino state hospital. it was about 30 milessouth of chicago and then 20 miles to the west.
this is where hegrew the malaria. so by now, they'reusing the state hospital patients to grow parasites. they're takingparasites from troops from both sides of the war. they're giving falciparum,vivax, different strains of both, ovale if they have it,malariae, the two other ones. anything that they're takingfrom the soldiers' blood, they're injecting into thesestate hospital patients
and growing the parasitesthere and then driving them to the prisons. this is stateville prison,which was where alf was. now, alf wasinnovative because he decided that he wasn'tgoing to worry about-- this is a high securityprison, so they're not going to be released. the inmates aren'tgoing to be released. and he decided he was going touse the smartest ones there.
he was going to canvasthe guards and the warden and figure out who thesmartest inmates were and was going to use themas his lab technicians. and his most productivewas nathan leopold, who is looking straight at youin the middles of the photo. does anybody remember theleopold and loeb murder case from 1924? richard loeb, nathanleopold, brilliant, rich sons of business titans inchicago, picked up a neighbor
off their mansion-linedstreet and killed him just to see if they couldget away with it. and then they helped thejournalists and the police with their investigationbecause they were so confident that they were so smart thatthey were going to just get away with this murder. and they weren't that smart,and they did get caught. and so this is clarence darrowin the foreground, who came up with a very cleverprecedent-setting
in the annals of criminal law,the history of criminal law. he saved them and gotthem life plus 99 years. richard loeb died ina shower stall fight, but nathan leopold lived on tokind of run his little fiefdom at the prison. and went alf alvingarrived there, alving needed to use him. alving couldn't stand him,but he needed to use him. and so he became one of themost productive lab technicians.
he was even usedin the experiments and then was releasedlater because of it. he actually earned hisrelease from prison because of this malaria work. what they made from thisgerman compound that was captured into thisis the drug chloroquine, which after the warwas used like aspirin in the tropics in theworld health organization's first-ever attemptat eradicating
an infectious disease. and it is creditedwith saving more lives than any other synthetic diseasemade for infectious diseases. but by 1950 in asia,resistance cropped up. and then by the 1970s,that parasitic resistance to the drug had spreadthroughout the world, throughout the malarious world. and that's pretty much thestory of every drug that's even been made against malaria.
most of drugs, almost alldrugs that we use today and we know of today came fromthis world war ii project, except the artemisinins,which is a chinese herb. and even the artemisinins noware following this pattern. so for me, we're stilllooking for that pill. all that work, and we'restill looking for a pill. i came away from thisresearch thinking that cogeshallactually had it right, that drugs maynot be the answer.
they can be helpful,but you need to work with theconditions on the ground. and so in the contextof the 21st century, that is working on healthsystems first and drugs second. and the biggest lesson forme in thinking about this is that most of our money,most of the money going towards malaria researchnow actually comes back into our labs for drugand vaccine development, and a minority of it,a very, very little
of it when it comes to malariaresearch, although more if we're talkingabout aids research, goes into building healthsystems on the ground. on the bioethicsside of this, which is i know what you'remostly interested in, william bynum reviewed my bookfor the wall street journal and said, "mastersonallows her readers to make up their own mindsabout whether war could be good for science and medicine.
i came away thinkingthat even if it, the price is frightfully high." so with that, i'dlike to stop talking, and i know dr. pearsonis going to come up and probably has--he might correct me on the technical stuffthat i perhaps got wrong. richard pearson: [inaudible] karen masterson: butthank you very much. richard pearson: itis a tremendous honor
to participate today. and i have a number of comments. let's see. here we go. i'll get my equipment together. i was trying to thinkof a notable quote that might capture a little bit ofthe impact of this book on me as i read it. there were many, manypoints of connection,
but i went back to isaacnewton. "if i have seen further, it is by standing on theshoulders of giants." and i think indeed we'veseen a lot further today through karen's outstandingtalk and her masterpiece, "the malaria project." and i want toemphasize the mission to find a miraculous cure. janet, my wife, is here. and the two of us in 1977were in monrovia, liberia.
we'd landed at robertsfield-- and we actually saw a picture of that-- theside of an army air force base constructed during world warii and plagued by malaria. i remember the franticknock on our door late one hot, steamy evening. it was weird to havean unannounced visitor at that time of day,as janet will tell you. and as i opened thedoor, i was confronted by our watchman, who isholding this limp young child,
approximately of theage of two years. and it was immediatelyapparent she was very sick. and i put my hand onher, and she clearly had a high temperature. so we had an old toyota. the battery didn't work. it was parked ontop of the hill. he helped me push it down. it started, and wemade a hurried run
to the john f. kennedymedical center, where i was servingon the faculty. i don't have thatpatient's blood smear, but i've brought onefrom the literature. and it would have lookedsomething like this. you can see the red blood cells. this is a normal one. it has little nucleus. and here you can seemalaria ring worms
within those erythrocytes. approximately 40% ofthese cells were infected. and falciparum malariainfects cells of all ages and can be fatalwithin 24 to 48 hours. at that time in west africa,25% to 50% of children die before they reachedthe age of five years. malaria was the principalcause of that death. by the year 2000, there weremore than a million deaths annually around theworld from malaria.
more than 90% of thosewere in equatorial africa. and of those, thevast majority were in children under five years. in fact, most wereunder three years. so our watchman's daughterwas infected with a killer. and it was clear that herlife hung in the balance. as i read the malariaproject, i was captivated by thefascinating accounts of the giants responsiblefor the prevention of malaria
and the development ofthis miraculous cure chloroquine in the firstpart of the 20th century. and they were giants indeed. they risked their livesin the swamps of georgia to the battlefieldsof guadalcanal. and as karen pointed out, manywere flawed, some terribly so, using patients inpsychiatric hospitals, prisoners inconcentration camps, convicts in american prisonswithout informed consent
and human safeguards. but at the end, the objectiveof that project was achieved. several days after thatfirst knock came a second. this time our watchman was back. in one arm, he was holdinghis alert daughter, who had recovered from her malaria. his other arm was holdinga chicken, a live chicken. janet could tell you the rest ofthe chicken side of the story, but i was left with thewonderful memory of what
it is to stand on theshoulders of giants and use this miraculous drug,chloroquine, to save her life. parenthetically, it's importantto add that janet and i were taking weekly doses ofchloroquine to prevent malaria, as were other expatriates. and we remained healthythroughout our year and a half in west africa,which at one point was known as the whiteman's graveyard because of the risk of themalaria to those
of us who do not have immunity. so what is the current statusof malaria in the year 2016? here are the most recent data. half of the world's populationremains at risk of malaria. 214 million casesoccur each year. that would be more than 90%of the american population. the bad news isthat 438,000 people die each year from malaria. the good news is that'sdown from a million a year
in the year 2000. much of this relates toroll back malaria program, with 500 partners, includingthe world health organization, the us government, the gatesfoundation, which overall has seen a 60% decreasein malaria deaths, i think in large part using theinfrastructure and developing infrastructure. this is attributed to theinsecticide-impregnated bed nets, field-applicable rapiddiagnostic tests identifying
patients with malaria,and artemisinin-containing medications thatkaren has discussed. here in the united states, wehave approximately 1,500 cases of malaria each year. we see them at uva. we have several cases a year. i was called aboutone just two weeks ago and some had beenreturned from east africa. the victims are typicallyimmigrants or travelers
coming from africa,india, southeast asia, and occasionally latin america. we have excellentrapid diagnostic tests and effectivetreatments of malaria now in the united states. our greatest challenge isto think of the diagnosis. so here's a take-homepoint for you. and you're all responsible nowthat no one that you know well dies of malaria in this country.
the first is feverin the returning international traveler ismalaria until proven otherwise. so you need to say this with me. so are you ready? now, i'm not kidding. all: fever in the returninginternational traveler is malaria untilproven otherwise. richard pearson: i'mgoing to say it again, because it's really important.
fever in the returninginternational traveler point number two, you usemedications to prevent malaria when you travelinternationally to sites where it is transmitted. think about that. don't take a chance. we're very fortunate at uvato have a wonderful traveler's clinic staffed by doctorserik hewlett, tania thomas, and shannon moonah.
but it's a greatsource of information if you have questions. today the war on malariacontinues on many fronts, led by giants here and abroad. at uva, we are extremelyfortunate to have dr. jennifer guler, who is here today--jenny-- who has been studying the mechanisms of drugsusceptibility and resistance in plasmodium falciparum,which is the killer, and dr. [inaudible]who is developing
new ways of rapid diagnosis. so in conclusion, let me thankkaren for an outstanding talk and her stimulatingaccount of the malaria project in her book. you all need to read it. looking into thefuture, i envision karen returning to discussa new book, which i think will be entitledvictory in the war on malaria, therest of the story.
so karen, i can'twait to read that book and hear your discussion. thank you. marcia day childress:thank you both so much. this is, again, a very rich andcomplicated story that moves in many different directions. we have a good number ofminutes for your comments and questions. and we'll have a coupleof mics available.
if you have a question,please identify yourself before you ask your questionor make your comment. but we look forward toa good conversation. audience: my name is karen, andi work in the health sciences library. i thought your talkwas incredible. and you're such agood storyteller. my father was a medicalentymologist straight out of his phd programgoing into the war
and was in the firstmalaria control unit embedded in a combat zone. so i grew up hearingthese stories. but you've provided such arich, much more complete picture of all-- karen masterson:what was his name? audience: kenneth knight. he was part of theskeeter beaters. there's a book aboutthe skeeter beaters.
but i grew up knowing thatmalaria killed more soldiers than the japanese at the time,is what they always said. so it makes me just reallyappreciate the whole story. thank you so much. definitely share yourbook with my brothers. karen masterson: oh, great. thank you, yeah. audience: hi. i'm a retired physician.
i'm 92 years old. i was a technologist in newguinea for a year, malaria technologist. i went to schoolthinking i was going to get a six-month course inmalaria as a pharmacist's [?]. and they sent me out witha microscope and a rifle. karen masterson: it couldhave been you under that tent. audience: --for six weeks. and your pictureswere fascinating.
that's where i was. and i was attachedto a naval sea unit, so you're in dutch newguinea then another year in the philippines. but this was '43, '44, '45. my kids know the story. karen masterson:yeah, i came away from this story a littlebiased, because there were all kinds of politicalreasons for wanting
to say that one thing or anotherbrought the malaria rates down. but really, by 1944,those malaria rates were tumbling, especiallyin the pacific. and i think it comesthrough in my book that i was very biased towardsthe malaria group units, because i think they madethe biggest difference. it wasn't the atabrine. they figured out how to useatabrine, and it helped, but i really think itwas the malaria units.
audience: it wasreally ok to be yellow. and we were all yellow. karen masterson: yeah. but thank you. i'm justin mutter, afellow in geriatrics here and a wannabe historian. and i wanted to go back towhat you have been saying here at the end about thistension-- and i'm going to give it asort of category here--
between vertical approachesand horizontal approaches to eradicating orcontrolling disease. because i think it's atension that we still very much live with today. and i wanted to just seewhat your comments would be about that. i think there are the bioethicsof human experimentation, very powerful in what you'veuncovered here in this story, but also the bioethics of how wedistribute resources and think
about how we use those veryimportant and scarce resources in controlling andpreventing disease. so i wonder, are there anykey other take-home points in that debate that informwhat we're doing today? karen masterson: well,from my perspective, what you know informs me. i actually thoughtabout the bioethics of making these choiceson where the resources go, but they're so real, right?
so when ebola wasexploding in west africa, i was asked to write apiece for time magazine that linked malaria, whatcan we learn from malaria to inform what wedo about ebola? and in that context,i really felt strongly that the lesson coming outof this book that i learned is the lesson that everybodyneeds to take from it, and that is if youdon't have basic health care on the ground, you don'thave basic health services
on the ground, we willsee again and again-- it might not be ebola next time. we probably will seeanother ebola outbreak, but it might besomething even scarier. and there's very littlewe can do to tamp it down if we don't have trainedpeople on the ground in these countries identifying,isolating, and preventing the spread of the disease. so for me, preventionhas to be the answer.
the drugs, i don't criticizethe gates foundation or any of the pharmaceuticalcompanies who have created nonprofitarms so that they can work on these drugs andthe vaccine that may or may not comes out, probablynot going to come out. all that is great work, andi think our scientists learn so much from that money here. but i do wonder whatwould happen on the ground if the balance wereshifted a little or a lot,
and we saw more basic healthservices created and sustained in places like liberia. we should try it. we've been on this drugtrail since the war. really the warshifted that paradigm. before the war, we got ridof malaria through economics. the us south outgrew malaria. the dams created electricity. electricity brought industry.
industry created jobsthat got people out of shacks and intohomes with closed eaves. and they could afford screes,and those who could afford fans could blow the mosquitoes away. and those who couldafford air conditioning could keep the mosquitoes out. i mean, it was thisconfluence of things, but it was economic development. we outgrew malaria.
and that is prettymuch the story of every country thathas eradicated malaria. they economically outgrew it. so while i appreciateall the hard work that goes into makingpills and vaccines, i just really feel liketrying a different course might produce differentresults, longer-term results. i mean, the reductionin infection rates is temporary, right?
we pull out of there, andthose rates go right back up, like they did in 1970after the world health organization pulled out oftheir eradication effort. sri lanka andindia's malaria rates got down to close to zero. and when resistance spreadand we could no longer use the drugs, and wecouldn't use ddt, which was anotherproduct of world war ii-- mosquitoes developed resistanceto that, we recoiled.
the west recoiled. the world healthorganization pulled out, and those rates went upeven higher in india. and the death rates werehigher because people had lost their acquired immunity to it. i don't know if thatanswers your question, but i'm not an expert, so ikind of quietly feel that way. i feel like it's people whoare on the ground really doing the work needto come to that moment
where they decide what's better. i have several thoughts. i think that we needto pay great attention to the injustices,social and economic around the world, that underliemany of these diseases, including malaria. i also think it'snot an either/or. it's a both/and. we have varioustools in our hands,
some of them now artemisinins,which are for this moment effective, butlikely they'll lose their effectiveness in time. so that clock is ticking. we tried ddt, and themosquitoes became resistant and we did greatenvironmental damage. we now are thinking aboutgenetically altered mosquitoes. and we have models of healthcare like paul farmer's outreach for hiv thatneed to be expanded
into a more comprehensivecommunity health care system. so i think it'sboth/and, and we need to use all ofthese opportunities as quickly as we can to getour fingers around the problem. marcia day childress: we'repretty much out of time, but i'd like to mentionlast week's program was on mosquitoes andzika, and certainly some of these same pointscame up about the challenges, not only on the front oftrying to find a vaccine
or something like that,but simply of the mosquito control in a lot of areas,that those mosquitoes can breed in water in a bottle cap andthe difficulties of working in challengingenvironments to do that. karen masterson: and zikamosquitoes were most plentiful and are most plentifulin the really poor areas, so this is anothereconomic issue. and there's been some talkof it in that context, but it is an economic disease.
marcia day childress: yeah. very much, very much. so again, thank youboth for these programs. actually, next week, we do nothave a "medical center hour." we've had to cancel becauseof unforeseen circumstances with the speaker whowas to have come. so no "medical centerhour" on october 26. the next program is wednesday,the 2nd of november, highlighting ethicsconsultation at uva, resources
for negotiating tight spaces. and we'll have five folks here,clinicians talking about ethics consultation here at uva. and i'll hope to see you then. thank you all so much. thank you, karen mastersonand dick peterson.
