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Use Cases
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Resources
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Pricing
April 2000
% complete
Jahrling wanted an animal model of smallpox to test drugs on that the FDA would accept
April 2000
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FDA requires drugs for human disease to be tested in humans before they're licensed for use; this not possible w/smallpox - no one infected (eradication), illegal to infect people w/lethal disease for study
April 2000
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Jahrling needed worthwhile information and someone to test the monkeys' blood, Joan Geisbert couldn't do it; Hensley working on Ebola but agreed; Jahrling worried CDC would be impressed and recruit her, decided to accompany her though she was annoyed at the idea of needing a babysitter
April 2000
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USAMRIID scientists built the Monkey Cabinet, huge portable aerosol chamber made of plastic/steel w/wheels; installed it along w/monkeys in CDC's Maximum Containment Lab, exposing them to 2 mil. doses of human infectious smallpox
April 2000
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Huggins monitoring monkeys while Jahrling went to Fort Detrick; monkeys got flush across their chest, some developed pimples and all recovered in a few days
April 2000
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no smallpox @ USAMRIID, Jahrling put together research team - flew them to Atlanta; got permission to take out smallpox freezer-removed smallpox, warmed it, and tried to infect monkeys by inhalation (resemble how it spreads among humans)
April 2000
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Peter Jahrling and John Higgins create a plan (after WHO opened 3-year time frame when smallpox could be worked on) to infect monkeys w/virus.
April 2000
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FDA passes Animal Efficacy Rule, states that for an exotic threat they would license new drug/vaccine if it could be tested in 2 different animals w/disease (and if it resembled a human disease)
May 2000
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Jahrling and Hensley leave for Atlanta; put on blue suits to enter Maximum Containment Labs, Hensley took blood samples from monkeys all day (monkeys breathed 10 mil. doses of smallpox - seemed fine)
June 2000
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Jahrling goes to Geneva to present Hensley's data to Ad Hoc Committee on Orthopoxvirus arguing it was "suggestive" - shows experiment failed, D.A. Henderson said never be able to infect monkeys w/smallpox; Jahrling pleaded and committee agreed to let him try again in another year
September 2, 2000
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Jahrling flew to Montpeiller (France) for 13th International Poxvirus Symposium, filled w/poxvirus experts
September 3, 2000
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naturally resistant to mousepox/some vaccinated,engineered virus killed 100% naturally resistant and 60% immunized; scientists added single foreign gene (IL-4) to natural mousepox virus which produces interleukin-4 acting as a signal in immune system; putting gene in created superlethal vaccine-resistant pox; one could probably be made for men
September 3, 2000
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ran into Richard Moyer (American, chairman of Dept. of Molecular Genetics @ U of FL) and they stepped aside to talk
September 3, 2000
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Moyer stops talking when sees poster by Australian govt. researchers from Co-operative Research Centre for Biological Control of Pest Animals, using viruses to cut back population of mice; Ronald J. Jackson was lead scientist, using mousepox (closely related to smallpox) which can't infect humans but is lethal to mice; injecting mice w/engineered virus to sterilize them but it wiped out the mice instead
September 4, 2000
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Ron Jackson and Ian Ramshaw talked w/Frank Fenner about inserting the IL-4 human gene into smallpox, he told them to publish it; might not work as it did w/mousepox, thought wouldn't be useful as biological weapon - kill too many people too fast, needed to be tested on humans to be sure it worked
February 2001
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Jackson-Ramshaw paper published, wanted to remind biologists problem of genetic engineering didn't exist and to start dealing with it; engineering technique became available worldwide on Internet; Jackson-Ramshaw experiment provoked uneasy reactions in American Intelligence Community
March 2001
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U.S. Army given permission by CDC officials to try a 2nd experiment to create a monkey model of smallpox; Jahrling put Hensley in charge of experiment
May 29, 2001
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8:00 P.M. Jahrling packing suitcase, put daughter to bed, in Atlanta by midnight
May 30, 2001
% complete
Peter Jahrling, John Huggins, Lisa Hensley, Lieutenant Colonel Mark Martinez (Army veterinary pathologist), James Stockman (animal caretaker), Joshua Shamblin and Sergeant Rafael Herrera (veterinary technicians)
May 31, 2001
% complete
gave monkey C099 (more inquisitive / confident / larger) telazol (anesthetic), Loise Pitt (head of Monkey Cabinet) loads liquid into a device to make a mist in aerosol cabinet, placed monkey in chamber; start blower, Harper smallpox blown around monkey's head, inhaled 100 mil. particles, monkey also given 1 bil. infective particles in bloodstream; needle put into biohazard container, repeat process 3 more times w.3 more monkeys
May 31, 2001
% complete
8:00 A.M. Huggins retrieved Smallpox Key and opens freezer, removes 5 vials containing smallpox seeds, returns key, puts seeds in water @ 98.6 degrees F (temp of blood); Jahrling enters, goes to check on Hensley; Huggins removes seed vials, seeds melted to pink/milky substance, strain called Harper; sucked up Harber and put it into 4 syringes (feeling nervous, felt the danger of syringes), loaded additional 4 vials w/Harper seed liquid, carried it all into animal room
June 1, 2001
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inoculate 4 more monkeys but w/Dumbell 7124 strain of smallpox (India strain); used a higher dose than original experiment and put it into bloodstream; kept monkeys under observation not knowing what to expect, if became sick no one knew what it would look like
June 2, 2001
% complete
8 monkeys exposed to smallpox, no outward signs of illness; C099 gentler than others, gave him treats; every day gave monkeys anesthetics to examine them and take blood samples, Hensley tested them to try to find any changes; on day 2 she found smallpox DNA in blood, virus growing
June 2, 2001
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Jahrling and Huggins leave for Maryland after monkeys inoculated, left Hensley in charge assisted by Martinez, Stockman and Shamblin supported them and team fell into routine
June 4, 2001
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dead monkeys hunched up and covered w/spotty, starlike red spots all over skin and tiny pinpoint hemorrhages dense across eyelids/flanks/inner thighs - flat rash, no pustules; 2 dead monkeys had India, 1st time any strain fatal to species besides humans
June 4, 2001
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people calling from CDC, Jahrling and Huggins kept calling from Fort Detrick, Pierre Rollin volunteered to help and brought compounds to help prepare tissues for electron microscope
June 4, 2001
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Hensley went to necropsy w/out checking on other monkeys, Martinez already started when she arrived; abdominal cavity wide and puddled w/free hemorrhages, hemmorhagic spots covering internal organs (especially intestines); Martines began filling bags w/samples of organs very quickly, stomach bloody, lungs bloody and speckled by hemorrhage, liver and spleen mostly dead,took hours; finished 2nd at 3:00 P.M., went back to find 3rd monkey dead (1st of Harper) and continued on w/3rd necropsy until around 8:00 P.M.
June 4, 2001
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Martinez poked them w/pole to make sure they were dead - C171 in rigor mortis, wanted to do posts, fast, eyes normal w/out signs of blood; decided to do necropsy on C115 (heavier), brought him into room and closed door behind (prohibited to perform necropsy in front of animals of same species)
June 4, 2001
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day 4 of exposure for Harper, day 3 for India; just before 8:00 A.M. phone in hallway rings - Hensley answers, it was Stockman in MCL West - 2 monkeys dead and one on the way
June 6, 2001
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C099 had small pimples across thighs, found pustules on palate and inside lips; developed classical ordinary smallpox; as putstules enlarged and spread found dimples in them (centrifugal smallpox rash like humans); pustules clumped around extremities, scientists felt sorry for him and named him Harper; had 150 pustules, not dying - experiencing agony of human heritage
June 7, 2001
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obviously sicker,pustules erupted on hands; becoming dehydrated since he could barely swallow, Stockman bought him grape Pedialyte,Martinez brought him fruit from breakfast bar
June 10, 2001
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Harper went semiconfluent across face, began to reach stage of early crust (most dangerous, cytokine goes out of control); crusted, put whole red grape into mouth, seemed better
June 20, 2001
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Hensley had been phoning Jahrling and team sent him pics of Harper's face; brought pics to meeting in Washington for National Academy of Sciences, ran into D.A. Henderson, showed him pics, Henderson said it looked like smallpox, Jahrling told him it was, Henderson walked away (says it never happened)
July 2001
% complete
Harper scabbed over and health returned; kept feeding him treats, knew he couldn't live by regulation; on day he was to be executed Stockman and Shamblin said they had to fly home; team visited him that night and left him more food than he could eat, had no scars (healed almost completely); Hensley and Martinex put him to sleep next morning, gave him anesthetic, didn't know difference, Martinez placed him on table and watched him go, Hensley turned away
August 2001
% complete
of 8 monkeys given Harper or India 6 died of hemorrhagic smallpox, 1 of classical smallpox, Harper survived; next round they infected 6 animals, 5 died, 1 of pustular, 1 had red eyes of human blackpox victims; 3rd round infected 9 monkeys and lowered dose, none got sick at all; overall successful, next step is to try to cure monkeys w/antiviral drug cidofovir
September 11, 2001
% complete
9:00 A.M. Stockman checking monkeys, Inger Damon taking care of equipment, Rafael Herrera working in his suit listening to radio, Martinez doing necropsy; Herrera came in and told Martinez plane crashed into World Trade Center (WTC), later comes back to say another crashed into WTC and in PA headed for Pentagon; Martinez kept working, everyone told to evacuate, possible target of attack; locked smallpox frezzer, couldn't do anything to dead monkey on table, all shared showers; told to leave MCL immediately, stopped shower, left building