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VOL. CLXIV . . . No. 56,642 © 2014 The New York Times NEW YORK, THURSDAY, OCTOBER 2, 2014
Late EditionToday, periodic clouds and sun, ashower, high 68. Tonight, partlycloudy skies, low 58. Tomorrow,some sunshine along with clouds,high 71. Weather map, Page B16.
$2.50
By MANNY FERNANDEZ and NORIMITSU ONISHI
DALLAS — The man who hasbecome the first Ebola patient todevelop symptoms in the UnitedStates told officials at TexasHealth Presbyterian Hospital lastFriday that he had just arrivedfrom West Africa but was not ad-mitted that day because that in-formation was not passed alongat the hospital, officials acknowl-edged Wednesday.
The man, Thomas E. Duncan,was sent home under the mistak-en belief that he had only a mildfever, a hospital administratorsaid; the information that he hadtraveled from Liberia, one of thenations at the heart of the Ebolaepidemic, was overlooked.
Mr. Duncan came back to Tex-as Health Presbyterian Hospitalon Sunday and was admitted fortreatment, but in those two daysin between, his contacts with anumber of people — includingfive schoolchildren and the med-ics who helped transport him tothe hospital — potentially ex-posed them to Ebola, forcing offi-cials to monitor and isolate themin their homes and to begin athorough cleaning of the schoolsthe students attended. Mr. Dun-can is now in serious but stablecondition.
Mr. Duncan’s case began withhim playing the part of good Sa-maritan on another continent.Mr. Duncan — a Liberian na-tional in his mid-40s who hadcome to America to visit relativesin Dallas — had direct contactwith a woman stricken by Ebola
in Monrovia, the Liberian capital,on Sept. 15, days before he left Li-beria for the United States, thewoman’s parents and Mr. Dun-can’s neighbors said.
The family of the woman, Mar-thalene Williams, 19, took her bytaxi to a hospital with Mr. Dun-can’s help after failing to get anambulance. Ms. Williams wasturned away for lack of space inthe hospital’s Ebola treatmentward, the family said, and theytook her back home in theevening, hours before she died.Mr. Duncan helped carry her be-cause she was no longer able towalk. In the taxi, Ms. Williams,who was seven months pregnant,had been convulsing.
Mr. Duncan flew on Sept. 19from Monrovia to Brussels,where, according to United Air-lines, he took Flight 951 to Wash-ington Dulles Airport and contin-ued to Dallas/Fort Worth onFlight 822, arriving Sept. 20. Herein Dallas, the case was being han-dled with extraordinary cautionand raised widespread concern.
There was no indication of pan-ic among residents in the largelyHispanic and African neighbor-hood where Mr. Duncan wasstaying in the Fair Oaks sectionof the city. But misinformationabout how the disease spreadswas everywhere, even as local,state and federal health officialscontinued to make clear thatEbola is not an airborne illnessand is not spread through casualcontact but through direct con-tact with the bodily fluids of asick person.
“We’re confident that it’s iso-lated and it’s being contained, buteveryone is working tirelessly todouble- and triple- and quadru-ple-check their work, to make
Scrutiny in Texas to DetectWhether Ebola Spread
Dallas Hospital Failed to Isolate Ill Liberian— Search for People Exposed to Him
Continued on Page A14
By ADAM NOSSITER
MAKENI, Sierra Leone —“Where’s the corpse?” the burial-team worker shouted, kickingopen the door of the isolationward at the government hospitalhere. The body was right in frontof him, a solidly built young mansprawled out on the floor allnight, his right hand twisted in anawkward clench.
The other patients, normallypadlocked inside, were too sick tolook up as the body was hauledaway. Nurses, some not wearinggloves and others in streetclothes, clustered by the door aspools of the patients’ bodily fluids
spread to the threshold. A workerkicked another man on the floorto see if he was still alive. Theman’s foot moved and the teamkept going. It was 1:30 in the af-ternoon.
In the next ward, a 4-year-oldgirl lay on the floor in urine, mo-tionless, bleeding from hermouth, her eyes open. A corpselay in the corner — a young wom-an, legs akimbo, who had diedovernight. A small child stood ona cot watching as the team tookthe body away, stepping around alittle boy lying immobile next toblack buckets of vomit. Theysprayed the body, and the littlegirl on the floor, with chlorine asthey left.
As the Ebola epidemic intensi-fies across parts of West Africa,nations and aid agencies arepledging to respond with increas-ing force. But the disease has al-ready raced far ahead of thepromises, sweeping into areasthat had been largely spared theonslaught and are not in the leastprepared for it.
The consequences in places
like Makeni, one of Sierra Le-one’s largest cities, have beendevastating.
“The whole country has beenhit by something for which it wasnot ready,” said Dr. Amara Jam-bai, director of prevention andcontrol at Sierra Leone’s healthministry.
Bombali, the district that in-cludes this city, went from oneconfirmed case on Aug. 15 tomore than 190 this weekend, withdozens more suspected. In a signof how quickly the disease hasspread, at least six dozen newcases have been confirmed in thedistrict in the past few daysalone, health officials said. The
SAMUEL ARANDA FOR THE NEW YORK TIMES
A 4-year-old girl, foreground, and another child thought to have Ebola lay amid bodily fluids at a hospital in Makeni, Sierra Leone.
Outracing Vows of Aid, Ebola Swamps a City Unprepared for It
Minimal Training andHaphazard Care in
Sierra Leone
Continued on Page A16
Federal officials plan to sharp-ly increase production of ZMapp,a promising experimental drug totreat Ebola. Page A16.
Ramping Up a Treatment
By MICHAEL D. SHEAR and MICHAEL S. SCHMIDT
WASHINGTON — Julia Pier-son resigned under pressure asdirector of the Secret Service onWednesday after failing to quell abipartisan political furor over re-peated breaches of White Housesecurity and losing the confi-dence of the president her agen-cy is charged with protecting.
Ms. Pierson’s support in theWest Wing began crumbling lateTuesday, in large part becauseshe did not tell the White Houseof a security failure in Atlantalast month when an armed manwas allowed to ride in an elevatorwith President Obama at theCenters for Disease Control andPrevention.
Despite meeting with the presi-dent last week, Ms. Pierson in-formed him about the incidentonly minutes before it was re-ported in the news media onTuesday evening, officials said.
Josh Earnest, the White Housepress secretary, said Ms. Pier-son’s delay in telling the presi-dent was a crucial part of “recentand accumulating reports aboutthe performance of the agency”that led Mr. Obama to concludethat the Secret Service needednew leadership.
After Ms. Pierson appeared ata brutal congressional hearing onTuesday, when she had to explainto a House panel how an armedintruder jumped the White Housefence on Sept. 19 and made it asfar into the mansion as the EastRoom, she woke Wednesday tomounting calls for her resigna-tion and withering criticism,some of it from Democrats.
By noon, Speaker John A.Boehner and RepresentativeNancy Pelosi of California, theHouse’s top Democrat, had bothcalled for independent inquiriesinto the security missteps, includ-ing the Secret Service’s responseto a 2011 incident in which a manshot seven high-powered bulletsinto the south facade of the WhiteHouse.
But Ms. Pierson was alreadyon her way out. In a meetingWednesday morning with Jeh C.Johnson, the secretary of the De-partment of Homeland Security— which oversees the SecretService — she offered her resig-nation, and he accepted it.
In a statement, Mr. Johnsonsaid he had appointed JosephClancy, a former Secret Serviceagent in charge of the Presiden-
CHIP SOMODEVILLA/GETTY IMAGES
Julia Pierson before testifyingin the House on Tuesday.
Continued on Page A19
Secret Service Director ResignsUnder Pressure About Breaches
By CHRIS BUCKLEYand ALAN WONG
HONG KONG — The slightteenager with heavy rectangularglasses and a bowl cut stoodabove the ocean of protesterswho had engulfed downtownHong Kong. His deep voice wasdrowned out by cheers, but thecrowd did not mind: They knewhim and his message. It wasJoshua Wong, a 17-year-old stu-dent activist who has been at thecenter of the democracy move-ment that has rattled the Chinesegovernment’s hold on this city.
“When I heard the national an-them starting to play, I certainlydid not feel moved so much as an-gry,” Mr. Wong said a few hourslater, after a protest at a flag-raising ceremony on Wednesdaymorning to mark the Chinese Na-tional Day holiday. “When it tellsyou, ‘Arise! All those who refuseto be slaves!’ — why is our treat-ment today any different fromthe slaves?”
Mr. Wong emerged as a figurein Hong Kong’s activist circlestwo years ago, when he ralliedstudents against a governmentplan to introduce “patriotic edu-cation” in schools, attacking it asa means of Chinese CommunistParty indoctrination. He played apivotal role in setting off the dem-onstrations of the past week,leading a surprise charge on agovernment building that result-ed in his arrest and promptedthousands to take to the streetsahead of schedule. Local newspa-pers with close ties to Beijinghave sought to smear him as atool of the United States.
In reality, Mr. Wong is trou-bling confirmation for the au-thorities that the first generationin Hong Kong to grow up under
Chinese rule is by many meas-ures also the one most alienatedfrom Beijing’s influence. He wasborn less than nine months be-fore this former British colony’shandover to China in 1997, andraised here at a time when theparty has tried mightily to winover the people and shape theminto patriotic Chinese citizens.
His prominence in the protestmovement also embodies a shiftin politics here — youth angeramplified over the Internet, be-yond the orbit of traditional polit-ical parties — that has confound-ed the local government and infu-riated its Communist supervisorsin the mainland.
That shift has made somethingof a political star of Mr. Wong,who comes across as a hybrid ofa solemn politician and a bashfulteenage sensation. These days, ifhe is not surrounded by admiringsupporters, he is usually mobbed
At 17, Setting Off Protests That Roil Hong Kong
CHRIS McGRATH/GETTY IMAGES
Joshua Wong, 17, addressing demonstrators in Hong Kong onWednesday. His group has been a major force in the protests.
Continued on Page A10
THINNER CROWDS
The protests became less crowdedas the authorities appeared to beadopting a strategy of waiting outthe demonstrators. Page A10.
By KIM BARKER and KATE TAYLOR
She got to know Mr. Shaynak— “ShayShay” to his favorites —during her sophomore year,when she and a friend went to hisclassroom at lunch. He tutoredthem in geometry. He sometimesbought them lunch outsideschool. He gave one of them ciga-rettes.
Then, at one point, Sean Shay-nak, the hip aerospace teacher inhis early 40s with a flight sim-ulator in his classroom, asked thegirls if he could take pictures ofthem in the park, to inspire anude painting he wanted to do.According to a friend of one of thegirls whom she later confided in,they thought the request wasweird and put him off, sayingthey were too busy. They told noone. They thought: Why ruin ateacher’s life?
But this past June, a year afterone of the girls had dropped outof Brooklyn Technical HighSchool, Mr. Shaynak sent her apicture of his penis over Snap-chat, the app that lets peoplesend messages that disappear inseconds. Horrified, the girl took ascreenshot. The app notified Mr.Shaynak of the screenshot. Hethen sent the girl two pictures ofhis face looking angry.
She told friends and eventuallyher parents, and her father re-ported it to the authorities. Theexistence of that photograph be-gan the unraveling of Mr. Shay-nak, 44, a commercial pilot whobecame a Brooklyn Tech teacher
Teacher Known As Cool Friend, Until His Arrest
Continued on Page A29
As rescuers assess the toll in Japan, sur-vivors of Mount Ontake’s eruption de-scribe what started as a perfect day forhiking, before a thundering wall of ashraced down the slope at them. PAGE A6
INTERNATIONAL A6-16
Shock and Terror in Japan The Alexander McQueen show, with ki-mono silks swirling around floral sculp-tures, was a highlight as Paris FashionWeek came to an end. A review byVanessa Friedman. PAGE A22
FASHION A22
Scenes From the EastGail Collins PAGE A31
EDITORIAL, OP-ED A30-31
Defense Secretary Chuck Hagel gaveunderperforming military hospitals fourto six weeks to show how they will ad-dress shortcomings. PAGE A20
NATIONAL A4, A18-21
Orders on Military Care Investors in India, and not just thewealthy, see American residential realestate as a safe bet. PAGE B1
BUSINESS DAY B1-11
U.S. Homes for Buyers in India
In a second trial, a Florida man whoshot a youth in a dispute over loud mu-sic was convicted of murder. PAGE A18
Self-Defense Claim Rejected
Amtrak officials said they would have tocurtail use of tubes leading to New YorkCity to fix hurricane damage. PAGE A4
NEW YORK A4, 24-29
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With a new novel, Marlon James arrivesas a powerful literary voice. PAGE C1
ARTS C1-8
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HOME D1-8
Escaping the Grid in Maine
U(D54G1D)y+&!"
as the team took the body away, stepping around a little boy lying immobile next to black buckets of vomit. They sprayed the body, and the little girl on the floor, with chlorine as they left.
As the Ebola epidemic intensifies across parts of West Africa, nations and aid agencies are pledging to respond with increasing force. But the disease has already raced far ahead of the promises, sweeping into areas that had been largely spared the onslaught and are not in the least prepared for it.
The consequences in places like Makeni, one of Sierra Leone’s largest cities, have been devastating.
“The whole country has been hit by some-thing for which it was not ready,” said Dr. Ama-ra Jambai, director of prevention and control at Sierra Leone’s health ministry.
Bombali, the district that includes this city, went from one confirmed case on Aug. 15 to more than 190 this weekend, with dozens more suspected. In a sign of how quickly the disease has spread, at least six dozen new cases have been confirmed in the district in the past few days alone, health of-ficials said. The government put this district, 120 miles northeast of the capital, Freetown, under quarantine late last week, making official what was already estab-lished on the ground. Ebola patients are dying under trees at holding centers or in foul-smell-ing hospital wards surrounded by pools of infec-tious waste, cared for as best they can by lightly trained and minimally protected nurses, some wearing merely bluejeans.
“There’s no training for the staff here,” said Dr. Mohammed Bah, the director of the govern-ment hospital here. “The training is just Power-Point. It is very difficult to manage Ebola here.”
In recent weeks, the world has vowed to step up its response to the epidemic, which has been spreading for more than six months. The United States has sent a military team to neigh-boring Liberia with plans to build 18 treatment centers to prop up the broken health system. The British have promised to build field hos-pitals in four urban areas in Sierra Leone, in-cluding this one. The French are setting up a treatment center and a laboratory in Guinea. The Chinese have sent scores of medical per-sonnel to the region and have converted a hos-
pital they built outside Freetown into a hold-ing center for Ebola patients. The Cubans have pledged to send more than 400 doctors to help battle the disease in the region.
But little of that help has reached this city. The dead, the gravely ill, those who are vomit-ing or have diarrhea, are placed among patients who have not yet been confirmed as Ebola vic-tims — there is not even a laboratory here to test them. At one of the three holding centers in Makeni, dazed Ebola patients linger outside, close to health workers and soldiers guarding them. The risk of infection is high, the precau-tions minimal. Patients are kept at the hold-ing centers, receiving a minimum of care, until space opens up at a distant treatment center.
“We encourage them not to have contact with body fluids,” said the district medical of-ficer, Dr. Tom Sesay.
There is no Ebola treatment center here and the patients, some of them critically ill, must be taken eight hours over bad dirt roads to the one operated by Doctors Without Borders
in Kailahun — that is, when space is available there. Some die on the way. At least 90 people already have died in the district, health of-ficials say — a figure far in excess of what the government in the capital has reported for Bombali.
Yet the World health Organization and others are still relying on Sierra Leone government statistics that appear to seriously undercount the number of victims.
Outside the district medical officer’s head-quarters at the edge of Makeni — a mining hub in better days — ambulances race off constantly for new bodies. reports of new cases poured in all weekend.
“We’re fighting to see how we can con-trol it,” Dr. Sesay said. “But we’re not being helped by the fact that we have nowhere to take our patients.”
The survival rate in Bombali district is “low,” Dr. Sesay noted.
Indeed, the holding centers appear to be little more than stiflingly hot places to die. At one of the three in Makeni, known as the “Arab hospital” because it was built with money from Gulf states, five had died overnight and into the morning one day last week; four more were ex-pected to go by that night.
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
One of them, a small boy, lay curled up un-der a wooden bed frame, and a nurse explained that he was “in the last stage, vomiting blood.” Outside the building, a boy of around 10 propped himself up as best he could against a wall, blood around his eyes, defecating.
“A lot of babies are dying here,” said Mo-hammed Kamara, a soldier guarding the facility.
Three patients lay prostrate under a mango tree in the dirt courtyard, one of them motionless with his arms and legs fully extended, crosslike.
“When they start bleeding, they go inside, and they will not come back out,” said Evelyn
Bangura, the nurse running the holding center. Close to 30 have died since the center opened on Sept. 20.
“I don’t want them to be outside,” Ms. Ban-gura complained. “We want to minimize the spread.” But some of the healthier patients are aggressive and have tried to break out of the fa-cility; Mr. Kamara, the soldier, had to cock his gun, he said. Indeed, three men shouted from one end of the courtyard, demanding to be re-leased: “So healthy for us!”
Some patients who ultimately tested nega-tive for Ebola have been let out of the holding centers, prompting a large crowd to pour into the streets to celebrate this week, thinking it meant that Ebola had been defeated. The gov-ernment quickly issued a statement saying that, to the contrary, the disease “is still with us and spreading fast.”
For many patients, the prognosis is bleak. “They are deteriorating day by day; even to
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
A16 N INTERNATIONALTHE NEW YORK TIMES THURSDAY, OCTOBER 2, 2014
can control it,” Dr. Sesay said.“But we’re not being helped bythe fact that we have nowhere totake our patients.”
The survival rate in Bombalidistrict is “low,” Dr. Sesay noted.
Indeed, the holding centers ap-pear to be little more than sti-flingly hot places to die. At one ofthe three in Makeni, known asthe “Arab Hospital” because itwas built with money from Gulfstates, five had died overnight
government put this district, 120miles northeast of the capital,Freetown, under quarantine latelast week, making official whatwas already established on theground. Ebola patients are dyingunder trees at holding centers orin foul-smelling hospital wardssurrounded by pools of infectiouswaste, cared for as best they canby lightly trained and minimallyprotected nurses, some wearingmerely bluejeans.
“There’s no training for thestaff here,” said Dr. MohammedBah, the director of the govern-ment hospital here. “The trainingis just PowerPoint. It is very diffi-cult to manage Ebola here.”
In recent weeks, the world hasvowed to step up its response tothe epidemic, which has beenspreading for more than sixmonths. The United States hassent a military team to neigh-boring Liberia with plans to build18 treatment centers to prop upthe broken health system. TheBritish have promised to buildfield hospitals in four urban areas
in Sierra Leone, including thisone. The French are setting up atreatment center and a laborato-ry in Guinea. The Chinese havesent scores of medical personnelto the region and have converteda hospital they built outside Free-town into a holding center forEbola patients. The Cubans havepledged to send more than 400doctors to help battle the diseasein the region.
But little of that help hasreached this city. The dead, thegravely ill, those who are vom-iting or have diarrhea, are placedamong patients who have not yetbeen confirmed as Ebola victims— there is not even a laboratoryhere to test them. At one of thethree holding centers in Makeni,dazed Ebola patients linger out-side, close to health workers andsoldiers guarding them. The riskof infection is high, the precau-tions minimal. Patients are keptat the holding centers, receivinga minimum of care, until spaceopens up at a distant treatmentcenter.
“We encourage them not tohave contact with body fluids,”said the district medical officer,Dr. Tom Sesay.
There is no Ebola treatmentcenter here and the patients,some of them critically ill, mustbe taken eight hours over baddirt roads to the one operated byDoctors Without Borders in Kai-lahun — that is, when space isavailable there. Some die on theway. At least 90 people alreadyhave died in the district, healthofficials say — a figure far in ex-cess of what the government inthe capital has reported for Bom-bali. Yet the World Health Or-
ganization and others are still re-lying on Sierra Leone govern-ment statistics that appear to se-riously undercount the number ofvictims.
Outside the district medical of-ficer’s headquarters at the edgeof Makeni — a mining hub in bet-ter days — ambulances race offconstantly for new bodies. Re-ports of new cases poured in allweekend.
“We’re fighting to see how we
and into the morning one day lastweek; four more were expectedto go by that night.
One of them, a small boy, laycurled up under a wooden bedframe, and a nurse explained thathe was “in the last stage, vom-iting blood.” Outside the building,a boy of around 10 propped him-self up as best he could against awall, blood around his eyes, defe-cating.
“A lot of babies are dying here,”
said Mohammed Kamara, a sol-dier guarding the facility.
Three patients lay prostrateunder a mango tree in the dirtcourtyard, one of them motion-less with his arms and legs fullyextended, crosslike.
“When they start bleeding,they go inside, and they will notcome back out,” said Evelyn Ban-gura, the nurse running the hold-ing center. Close to 30 have diedsince the center opened on Sept.20.
“I don’t want them to be out-side,” Ms. Bangura complained.“We want to minimize thespread.” But some of the healthi-er patients are aggressive andhave tried to break out of the fa-cility; Mr. Kamara, the soldier,had to cock his gun, he said. In-deed, three men shouted fromone end of the courtyard, de-manding to be released: “Sohealthy for us!”
Some patients who ultimatelytested negative for Ebola havebeen let out of the holding cen-ters, prompting a large crowd topour into the streets to celebratethis week, thinking it meant thatEbola had been defeated. Thegovernment quickly issued astatement saying that, to the con-trary, the disease “is still with usand spreading fast.”
For many patients, the progno-sis is bleak. “They are deteriorat-ing day by day; even to swallowfor them is a problem,” Ms. Ban-gura said, adding that the con-stant flow of bodies, and the hos-pital’s inability to help, were tak-ing a toll on the beleaguered staff.
“To watch people like this de-teriorating, deteriorating, it islike a psychological trauma forus,” she said. “Very painful forus.”
The nurses do what they can,dispensing anti-malarial medica-tion, deworming the patients, giv-ing them analgesics. But virtu-ally all of those not already coma-tose appeared glassy-eyed andlistless.
Down the road, an ambulancepulled up, delivering eight newpatients to the third holding cen-ter; two were too far advanced towalk into the low-rise concretefacility at the edge of Makeni.
“The problem we are having isthe little children,” said the chiefhealth officer there, Unisa Kanu.
Unicef said Tuesday that theEbola epidemic had orphaned atleast 3,700 children in the region.
“Their mothers are alreadydead; we have seven orphansnow,” Mr. Kanu said. “That is theproblem we are having now.”
PHOTOGRAPHS BY SAMUEL ARANDA FOR THE NEW YORK TIMES
Above, a woman and her child, each believed to be infectedwith Ebola, in Makeni, Sierra Leone. Left, a patient in a looselysegregated ward at another hospital in the city.
From Page A1
Outracing Pledges of Aid, Ebola Is Swamping a City Unprepared for It
The dead are oftenkept among patientswithout a diagnosis.
By ANDREW POLLACK
Federal officials are planningto sharply increase production ofZMapp, which is viewed by manyexperts as the most promisingexperimental drug for treatingpeople infected with Ebola inWest Africa.
The Department of Health andHuman Services is in advanceddiscussions to enlist CaliberBiotherapeutics, a Texas compa-ny that can produce the drug inmillions of tobacco plants, ac-cording to federal officials andpharmaceutical industry execu-tives.
Federal officials, along withtwo of the world’s biggest char-ities — the Bill & Melinda GatesFoundation and the WellcomeTrust — are also looking at ar-ranging for production of ZMappin animal cells, the more conven-tional method used by the bio-technology industry. Althoughthat would take longer, it wouldallow for greater output by tap-ping into the biotechnology in-dustry’s huge production capaci-ty.
“We’re going with multiplemanufacturers,” a federal officialsaid, speaking on condition of an-onymity because contracts havenot yet been signed. “Caliber iscertainly one we’re considering.”
Despite the new efforts, sup-plies of the drug are expected tobe limited to hundreds or thou-sands of treatment courses byearly next year, which would notbe nearly enough if the epidemiccontinues to spiral out of control.
“The biology just doesn’t allowyou to do it tomorrow,” said AlanMagill, who heads the malariaprogram at the Gates Foundationand is trying to arrange for moreZMapp production.
ZMapp was able to protectmonkeys from Ebola even whenadministered five days after in-fection. And it may have helped afew people infected during the
current outbreak, including twoAmerican aid workers who gotEbola in Liberia and recovered atEmory University Hospital in At-lanta.
Still, there was only enoughZMapp for seven patients, two ofwhom subsequently died.
Experts say it is impossible totell from such limited experiencehow well ZMapp works. Andthere are other experimentaldrugs that have shown promisein animal testing, and productionof those might also be increased.
But for now, ZMapp may offerthe best shot because it consistsof proteins called monoclonalantibodies, widely used as drugsin the biotechnology industry,which latch onto the virus andneutralize it. “It’s extremely ra-tional that an antibody againstEbola would be effective,” saidDr. Susan Desmond-Hellmann,chief executive of the GatesFoundation and a former biotech-nology industry executive. “It isextremely rational that it wouldbe safe.”
ZMapp, which is actually acocktail of three different anti-bodies, is being developed byMapp Biopharmaceutical, a tinySan Diego company, with fundingfrom the United States and Cana-dian governments.
The doses used to treat theAmerican aid workers were pro-duced in tobacco leaves at a facil-ity in Owensboro, Ky., that isowned by Reynolds American,the tobacco company.
That facility has now resumedproduction, but the federal offi-cial said it was expected toproduce only about 10 to 20 treat-ment courses by the end of theyear, and the same amount everymonth going forward.
So the Biomedical AdvancedResearch and Development Au-thority, a branch of the Depart-ment of Health and Human Serv-ices, is considering additional
production from Caliber, which isbased in Bryan, Tex., and co-operates on projects with TexasA&M University.
Caliber also produces proteins,including antibodies, in hydro-ponically grown tobacco plantsbut has a larger production ca-pacity than the Kentucky facility.
No official contract has beensigned, so plans could stillchange. But federal officials havevisited Caliber regularly.
“They are actively engaged,pretty much on a daily basis,working with Caliber and A&M,”Dr. Brett P. Giroir, the chief exec-utive of the Texas A&M HealthScience Center, said Wednesday.Executives at Caliber and Mappdeclined to comment for this arti-cle.
Both Caliber and the Kentuckyfacility sprang from a projectsponsored by the Defense Ad-
vanced Research Projects Agen-cy, which was looking for a wayto quickly produce vaccines ortherapeutic proteins in the eventof an emergency like a flu pan-demic.
Now these facilities are likelyto get their first big test.
“It’s not been tested, live-fire,”the federal official said. “And nowwe’re doing it.”
The system involves infectingtobacco with a genetically engi-neered virus that contains the in-structions to make the antibody.
“Every time the virus tries toreplicate, it spins out a copy of amonoclonal antibody,” saidCharles J. Arntzen, a professor atArizona State University who haslong worked on such systems.The leaves are ground up to ex-tract the antibody.
The federal official said thatCaliber and other facilities that
will be brought on line couldproduce 40 to 100 treatmentcourses per month.
But Dr. Giroir of Texas A&Mand a biotechnology industry ex-ecutive familiar with Caliber saidCaliber could potentially producehundreds of treatment courses amonth.
Researchers say the dose usedin the monkey experiments,which was also used to treat thepatients in Africa, is probablymore than needed. If monkeytesting can confirm that a lowerdose is sufficient, then manymore human treatment coursescan be made.
There are also efforts under-way to increase the amount ofprotein produced by each plant.Mapp is said to be working withanother small company, NoviciBiotech, which has a method oftweaking the genetic instructions
for the antibodies in a way thatcould boost production.
Monoclonal antibodies used fordrugs — like Herceptin and Avas-tin for cancer, and Humira andRemicade for rheumatoid arthri-tis — are typically produced ingenetically engineered Chinesehamster ovary cells, or CHOcells, which are grown in giantstainless steel vats.
While production in tobacco issaid to be faster and cheaper toget started, there is only limitedtobacco capacity, while there is ahuge capacity in the biotechnol-ogy industry to produce antibod-ies in CHO cells.
The Gates Foundation and theWellcome Trust, as well as fed-eral officials, are helping to scoutsome of this capacity for ZMappproduction. However, it wouldtake months to genetically engi-neer CHO cells to produce theantibodies and to scale up pro-duction. Meaningful productionwould not come until next year.
And officials say new monkeytesting might be needed to showthe antibodies produced in CHOcells are as effective as those pro-duced in tobacco. At least oneearlier study suggested this wasnot the case.
Federal officials said some ofthe early doses of ZMapp will betested for safety in healthy volun-teers. That is controversial be-cause it means the scarce drugwould be diverted from patientsin Africa.
Dr. Jeremy Farrar, director ofthe Wellcome Trust, said it wasnecessary to establish basic safe-ty, particularly in light of mistrustof Western medicine by somepeople in the outbreak area. “Thereality is,” he added, that suchsafety testing “will happen quick-er in the U.S. or the U.K.” But theWellcome Trust has given a grantof about $5.2 million to a consor-tium that will move quickly totest ZMapp and other drugs insick patients in Africa.
U.S. to Increase Production of Drug to Treat Ebola, but May Not Meet Demand
SEAN GALLUP/GETTY IMAGES
Proteins glowing under ultraviolet light on a plant used to produce the Ebola drug ZMapp.
C M Y K Nxxx,2014-10-02,A,016,Bs-4C,E1
swallow for them is a problem,” Ms. Bangura said, adding that the constant flow of bodies, and the hospital’s inability to help, were taking a toll on the beleaguered staff.
“To watch people like this deteriorating, de-teriorating, it is like a psychological trauma for us,” she said. “Very painful for us.”
The nurses do what they can, dispensing anti-malarial medication, deworming the pa-tients, giving them analgesics. But virtually all of those not already comatose appeared glassy-eyed and listless.
Down the road, an ambulance pulled up,
delivering eight new patients to the third holding center; two were too far advanced to walk into the low-rise concrete facility at the edge of Makeni.
“The problem we are having is the little children,” said the chief health officer there, Unisa Kanu.
Unicef said Tuesday that the Ebola epi-demic had orphaned at least 3,700 children in the region.
“Their mothers are already dead; we have seven orphans now,” Mr. Kanu said. “That is the problem we are having now.” n
