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justinagana-blog · 7 years

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About the Game

Alien: Isolation is a survival horror video game developed by Creative Assembly and based on the Alien science fiction horror film series. It was published by Sega and originally released for Microsoft Windows, PlayStation 3, PlayStation 4, Xbox 360 and Xbox One on 7 October 2014. The game is set 15 years after the events of Ridley Scott's 1979 Alien film and follows Amanda Ripley, daughter of Alien protagonist Ellen Ripley, and her efforts to investigate the disappearance of her mother.

Unlike previous video game adaptations of the Alien franchise, Alien: Isolation places a strong emphasis on stealth and survival horror gameplay, requiring the player to avoid and outsmart a single alien creature over the course of the game with the help of gadgets like a motion tracker and a flamethrower. It was designed more in line with Scott's film as opposed to James Cameron's more action-oriented 1986 sequel Aliens, and features a similar lo-fi, 1970s vision of what the future would look like. The game runs on an entirely new engine that was built from scratch to accommodate technical aspects like the game's atmospheric and lighting effects as well as the alien's behavioural design. Creative Assembly originally intended to make Alien: Isolation a third-person game, but the perspective was later shifted to first-person in order to create a more intense experience.

Upon release, Alien: Isolation received generally positive reviews from video game journalists and sold over two million copies in Europe and the US as of May 2015. Critics praised the game's retro-futuristic art direction, sound design, and the alien's artificial intelligence, but criticised its story, characters, and voice acting. The game won several year-end awards, including Best Audio at the 2015 Game Developers Choice Awards and Audio Achievement at the 2015 British Academy of Film and Television Arts Awards. Several downloadable content packs that extend the game with new missions and challenges were also released.

Gameplay

Alien: Isolation is a single-player action-adventure game with heavy emphasis on stealth and survival horror features. The player controls the protagonist, Amanda Ripley, from a first-person perspective to interact with the environment. To advance through the game, the player must explore a space station and complete numerous objectives while avoiding, outsmarting and defeating enemies like human occupants or hostile androids. Objectives range from activating computers to collecting certain items or reaching a specific area in the game. The player has the ability to run, climb ladders, and sneak into vents. The player can also crouch and hide behind objects to break the line of sight with enemies, and covertly peek over or lean around to gain view. The player also has the ability to go under nearby tables or inside lockers to hide from enemies.

Unlike previous video game adaptations of the Alien franchise, Alien: Isolation features a single alien creature that pursues the player over the course of the game. The alien creature cannot be defeated, requiring the player to use stealth tactics in order to survive. Instead of following a predetermined path, the alien has the ability to actively investigate disturbances and hunt the player by sight or sound. Along the way, the player can use both a flashlight and a motion tracker to detect the alien's movements. However, using any of these increases the chance of the alien finding the player. For example, if the alien is moving and close enough, the tracker's sound will attract the alien, forcing the player to wisely use the tracker and remove it as soon as it detects motion. The motion tracker cannot detect enemies when they are not moving and cannot determine whether the alien creature is up in the ducts or on ground level.

Although the player can use certain weapons to defeat enemies, Alien: Isolation emphasises evasion over direct combat by providing the player with limited ammunition. The game features four weapons that become available as the player progresses throughout the game: a revolver, a shotgun, a bolt gun, and a flamethrower. The player can also craft several items by collecting schematics and different kind of materials throughout the game. Items range from EMP mines to noisemakers, molotov cocktails and pipe bombs, among others. These items help the player deal with enemies and the alien. For example, the noisemaker can be used to attract enemies in one particular direction. The alien is afraid of fire, so using the flamethrower or a molotov cocktail will force it to retreat into the station's ventilation system. The player has a limited amount of health which decreases when attacked by enemies. Nevertheless, the player can restore lost health using medkits, which can be crafted with materials in Amanda's inventory.

The space station is divided into multiple sections connected by trams and elevators. Each section is composed of a set of rooms and corridors separated by doors. Some doors require certain actions to be performed first before entry is allowed. For example, some doors require a keycard or a numbered entry code, while others need to be cut with a variety of welding torches or hacked using an electronic device. The player may also encounter computer terminals that can be used to access information or trigger in-game actions like disabling security cameras or manipulating the space station's air-purification mechanism. The game features an automap to help players navigate the different areas of the game. To save their progress, players need to locate a terminal in the game and manually insert Amanda's access card in it. If Amanda dies, the player will need to start the game again from the last saved point. In addition to the campaign mode, Alien: Isolation features a separate game mode, called Survivor Mode, that focuses on short, player-versus-alien scenarios. In each scenario, the player needs to complete a set of objectives while avoiding the alien under a time limit.

Plot

In 2137, 15 years after the disappearance of the Nostromo spacecraft, Amanda Ripley, daughter of Ellen Ripley, is approached by the android Christopher Samuels of the Weyland-Yutani corporation. Samuels informs her that the flight recorder of the Nostromo was recently located by a ship named the Anesidora and is being held aboard Sevastopol, a remote space station owned by the Seegson Corporation, in orbit around the gas giant KG348. He offers her a place on the Weyland-Yutani team sent to retrieve it so that she can have closure regarding the fate of her missing mother. Ripley, Samuels, and Weyland-Yutani executive Nina Taylor travel to Sevastopol on board the courier ship Torrens, owned by captain Diane Verlaine. The group arrives at Sevastopol to find the station damaged and its communications offline. Ripley, Samuels, and Taylor attempt to spacewalk over to the station to investigate, but their EVA line is severed by debris, and Ripley is separated from them and forced to enter the station on her own.

Ripley attempts to find help, but is confronted by Axel, a survivor who explains that Sevastopol is out of control due to a deadly "monster" lurking aboard, leading to fear and paranoia amongst the station's population. Ripley convinces him to help her in exchange for a ride off the station aboard the Torrens, but Axel is eventually killed by the monster in question, an alien creature. While exploring the station, Ripley finds the Nostromo's flight recorder but discovers, to her dismay, that it contains no data. After contacting Samuels and recovering medical supplies to treat an injured Taylor, Ripley reunites with the station's marshal, Waits, and his deputy, Ricardo. Waits explains that the alien was brought on board the station by Anesidora captain Henry Marlow, who is now in Waits' custody. Ripley learns from Marlow that the Anesidora crew discovered the flight recorder near the planetoid LV-426, where they also found a derelict ship previously found by the Nostromo crew and the nest of alien eggs contained within. While exploring the ship, Marlow's wife was attacked by a facehugger. Marlow then brought her aboard Sevastopol for emergency medical treatment, but an alien ultimately hatched from her. Waits convinces Ripley to contain the alien by luring it into a remote section of the station and sealing it inside. Ripley is successful, but Waits truly plotted to use Ripley as bait, and ejects the module from the station with her still inside. As the module careens into space towards KG348, Ripley space-jumps back to Sevastopol using an EVA suit.

Ripley makes her way back to Ricardo, who explains that the Working Joes, the station's service androids, abruptly started slaughtering the remaining crew, including Waits. He also tells her that Samuels is attempting to interface with the station's controlling artificial intelligence, APOLLO, to cease the rampage. However, APOLLO's defensive countermeasures electrocute Samuels shortly after he managed to open a path for Ripley into APOLLO's control core. Upon reaching APOLLO, Ripley discovers that Seegson, who has been trying to sell off Sevastopol for years, has finally found a buyer: Weyland-Yutani, who instructed APOLLO to protect the alien. When Ripley tells APOLLO that the creature is no longer aboard the station and demands to cease all activity, it refuses due to an unidentified presence within the station's reactor. Ripley arrives there and discovers that it has been converted into an alien nest. She then initiates a reactor purge to destroy the nest, but some aliens manage to escape and begin to overrun Sevastopol. Ripley learns from Ricardo that Taylor was sent by Weyland-Yutani to retrieve the alien, and that she freed Marlow in exchange for the location of LV-426. However, Marlow double-crosses her and takes her hostage aboard the Anesidora.

Aboard the Anesidora, Ripley discovers a message from her mother after her initial report of the events on the Nostromo, thus finally giving her closure. Marlow then appears with Taylor and tells Ripley that he plans to overload the Anesidora's fusion reactor and destroy the station, thus ensuring that no aliens survive. In the ensuing confrontation, Taylor kills Marlow and is herself killed by an electric discharge while Ripley is forced to escape the Anesidora shortly before it explodes. Ricardo tells Ripley that the Anesidora explosion destroyed Sevastopol's orbital stabilisers, causing the station to slowly drift into KG348's atmosphere. Ripley and Ricardo contact the Torrens for extraction, but a facehugger paralyses Ricardo, forcing Ripley to leave him. After making her way outside to help the Torrens detach from the station, Ripley is surrounded by several alien creatures and then thrown into the ship due to a blast. Aboard the Torrens, Ripley discovers that another alien has boarded the ship. Still in her EVA suit, Ripley is cornered in the airlock and left with no option but to open it, which ejects both her and the alien into space. The final shot of the game depicts Ripley adrift and unconscious in her EVA suit, then suddenly awakened by a searchlight that crosses her face.

Development

Alien: Isolation was developed by the Creative Assembly, which is best known for their work on the Total War real-time strategy video game series. The idea of developing a game based on the Alien film series from 20th Century Fox was conceived when the company finished work on their 2008 title Viking: Battle for Asgard, after publisher Sega acquired the rights to develop Alien games in December 2006. A six-person team developed a small multiplayer game to pitch the idea to Sega, a "hide and seek" prototype where one of the players had to control the alien while the others would need to conceal themselves in the environment. The game captured the attention of Sega and the project was eventually approved. Since the Creative Assembly had no experience with survival horror games, the company had to hire several people from other studios like Bizarre Creations, Black Rock, Crytek, Ubisoft, and Realtime Worlds for the project. According to director Alistair Hope, the development team grew from "a couple of guys crammed in with the Total War team" to a group of 100 people by 2014.

The Creative Assembly decided to design the game more in line with Ridley Scott's 1979 film Alien as opposed to James Cameron's more action-oriented 1986 sequel Aliens. To help the designers authentically recreate the atmosphere of the film, Fox provided them with three terabytes of original production material, including costume photography, concept art, set design, behind the scenes photos, videos, and the film's original sound effect recordings. As artist John Mckellan recalls, "It was a proper gold mine. We saw angles of things we'd never seen before." During the first stage of development, the developers deconstructed the film to find out what made its setting unique. This would allow them to build new environments that were faithful to it. Similarly, the film's original soundtrack was deconstructed so that composers could identify the main cues, which would then be used as templates to extend the soundtrack and fill in the length of the game. The developers also met Alien and Blade Runner editor Terry Rawlings, who would give them additional insight.

Rather than go for a shiny, high-tech science fiction look, the designers opted to recreate the setting and feel of the original Alien film using the work of concept artists Ron Cobb and Mœbius. As a result, the game features a lo-fi, 1970s vision of what the future would look like. For example, the game features clunky machinery like phone receivers, monochrome displays, and distorted CRT monitors. To create period authentic distortion on in-game monitors, the developers recorded their in game animations onto VHS and Betamax video recorders, then filmed those sequences playing on an "old curvy portable TV" while adjusting the tracking settings. As digital hacking was not conceived in the 1970s, the game's hacking device was built the way it would have been built on the set of the movie, and requires players to tune into a computer's signal while selecting icons on its screen. Artist Jon McKellan noted, "We had this rule: If a prop couldn't have been made in '79 with the things that they had around, then we wouldn't make it either."

The Creative Assembly wanted Alien: Isolation to have a story that was closely related to the film. As a result, the team decided to explore a story set 15 years after the events of the film which would involve Ellen Ripley's daughter and the Nostromo's flight recorder. Writer Will Porter explained that the process of creating a backstory for Amanda was "refreshing" as he felt that she was an overlooked character of the Alien universe. The derelict ship the Nostromo crew previously found in the film was also included in the game since the developers felt it was a central point in the Alien canon. Actress Sigourney Weaver agreed to reprise her role as Ellen Ripley to voice small sections throughout the game because she felt that the story was interesting and true to the film. Along with Weaver, the original Alien cast, which includes Tom Skerritt, Veronica Cartwright, Harry Dean Stanton, and Yaphet Kotto, reprised their roles for the game's separate downloadable content missions, marking the first time they were brought back together since the release of the film. All the characters were created with 3D face scans.

Alien: Isolation runs on a proprietary engine that was built from scratch by the Creative Assembly. The engine allowed the development team to accommodate technical aspects like the game's atmospheric and lighting effects as well as the alien's behavioural design. The engine's deferred rendering allowed artists to both place "hundreds of dynamic lights in the scene" and achieve great geometric detail. The alien itself was designed to look similar to H. R. Giger's original design for the creature from the film, including the skull underneath its semitransparent head. However, the designers did alter its humanoid legs with recurved ones to provide the alien a walk cycle that would hold up to scrutiny during longer encounters with the player. Between 70 and 80 different sets of animation for the alien were created. The alien's artificial intelligence was programmed with a complex set of behavioural designs that slowly unlock as it encounters the player, creating the illusion that the alien learns from each interaction and appropriately adjusts its hunting strategy. As gameplay designer Gary Napper explains, "We needed something that would be different every time you played it. You’re going to die a lot, which means restarting a lot, and if the alien was scripted, you’d see the same behaviour. That makes the alien become predictable, and a lot less scary." The save system was inspired by a scene in the film where Captain Dallas uses a key-card to access Nostromo's computer, Mother.

The developers originally planned to add a feature that would allow players to craft weapons, but the idea was ultimately discarded. According to Hope, "We thought about what people would want to do in order to survive. We explored different ideas, and one of them was fashioning weapons to defend yourself. That was quite early on, but then we realised that this game isn't really about pulling the trigger." Another cancelled feature was the alien's iconic acid blood as a game mechanic, which could melt through metal like in the film. Although the feature was implemented at one point, it was eventually removed from the game because the developers felt it would change the course of the game in a "weird" direction. In addition, the developers considered the possibility for the game to be played from a third-person perspective, but then realised that it would significantly change the experience. Hope explained that it would become "a game about jockeying the camera and looking after your avatar. But in first-person it's you that's being hunted. If you're hiding behind an object and you want to get a better view of your surroundings, you have to move." The actual development of the game took overall four years to complete after the Creative Assembly first pitched the idea to Sega. The game went gold on 9 September 2014 and is dedicated to Simon Franco, a programmer of the game, who died during its development.

Marketing and Release

Alien: Isolation was first unveiled on 12 May 2011 when UK government minister Ed Vaizey visited the Creative Assembly and revealed on his Twitter account that the studio was hiring for an Alien game. Although no gameplay details were confirmed, the Creative Assembly did confirm to CVG that the game would be released for consoles, but did not specify any format. Sega boss Mike Hayes also said that the game was going to be "very much a triple-A project. We want this to be a peer to the likes of Dead Space 2." Although the game's name was anticipated following a trademark registration in October 2013 and some screenshots of the game were leaked in December 2013, Alien: Isolation was formally announced and confirmed for the Microsoft Windows, PlayStation 3, PlayStation 4, Xbox 360, and Xbox One platforms with the release of a teaser trailer on 7 January 2014. The developers also stated that they were not worried about the fact that Sega's previous Alien game, Aliens: Colonial Marines, received a negative public reaction. According to Napper, "It did completely reaffirm to us that there was a massive Alien fanbase out there and just to see such a vocal reaction to the game, everything that they've said they want is something that we're building and we're very excited about that."

In June 2014, Alien: Isolation was presented at the Electronic Entertainment Expo (E3), where journalists had a chance to play a demonstration of the game. The game was also playable on the Oculus Rift virtual reality (VR) headset that was shown at the show. Danielle Riendeau of Polygon described the demo as "one of the most effectively terrifying slices of a game I've ever played in my life." The game was awarded Best VR Game and was nominated for Game of the Show, Best Xbox One Game, Best PlayStation 4 Game, Best PC Game, and Best Action Game at the IGN's Best of E3 2014 Awards. Similarly, at the 2014 Game Critics Awards, the game was nominated for Best of Show, Best Console Game, and Best Action/Adventure Game. In August 2014, a cinematic trailer for the game was shown at Gamescom.

Alien: Isolation was released on 7 October 2014, featuring two pre-order downloadable content missions that allow players to play two scenes from the original film. The first mission, entitled Crew Expendable, features the original crew of the Nostromo and involves the player controlling Ripley, Dallas or Parker attempting to flush the alien creature from the air vents and into the ship's airlock. The second mission, Last Survivor, is set during the film's finale and involves the player controlling Ripley as she tries to activate the Nostromo's self-destruct sequence and reach the escape shuttle. Unlike the first mission, the second mission is only available for players who pre-ordered the game at certain retailers. Upon release, five additional downloadable content packs for the game were periodically released between October 2014 and March 2015. These packs expand the game's Survivor Mode with new characters, challenges, maps, and other features. A collection featuring the game and all the downloadable content packs was released for Linux, OS X, PlayStation 4 and Xbox One in late 2015.

Reception

Critical reception for Alien: Isolation was divided but generally positive, with review scores ranging from IGN's 5.9 out of 10 to The Guardian's 5 out of 5 stars. Josh Harmon of Electronic Gaming Monthly felt that Alien: Isolation "succeeds as a genuine effort to capture the spirit of the film franchise in playable form, rather than a lazy attempt to use it as an easy backdrop for a cash-in with an ill-fitting genre." Writing for GameSpot, Kevin VanOrd credited the game for its tense and frightening gameplay, stating that "when all mechanics are working as intended, alien-evasion is dread distilled into its purest, simplest form." However, he criticised the game's "trial and error" progression and frustrating distances between save points. Jeff Marchiafava of Game Informer stated similar pros, but criticised the story and poor acting from the voice actors.

The game's visuals and atmosphere were highlighted positively. Polygon editor Arthur Gies felt that Alien: Isolation is "a beautiful game, full of deep shadows and mystery around every corner," while Dan Whitehead of Eurogamer praised the lighting and unusually compelling environment design. IGN's Ryan McCaffrey gave high marks to the game's retro-futuristic art direction and sound design, commenting: "From wisps of smoke that billow out of air vents to clouds of white mist that obscure your vision when you rewire an area's life-support systems in order to aid your stealthy objectives, Isolation certainly looks and sounds like a part of the Alien universe." Similarly, PC Gamer reviewer Andy Kelly said that the game's art design sets Alien: Isolation apart from the likes of System Shock or Dead Space and creates a "convincing science-fiction world, with machines and environments that are functional and utilitarian, rather than overtly futuristic."

The story and characters were generally criticised, with Game Informer stating that "Amanda exhibits little growth or personality, other than concern for her fellow humans and a desire not to die gruesomely." Similarly, Blake Peterson of Game Revolution noted that none of characters are fully developed. According to him, "we never spend enough time with them to build the emotional bond necessary for their inevitable deaths to mean anything." GameTrailers said that most of the computer terminals found in the game contain unoriginal logs to describe predictable events, but also remarked that reading reports from different computer terminals "grounds Sevastopol in an appreciable way."

Writing for GamesRadar, David Houghton highlighted the alien's advanced artificial intelligence, stating that "progress becomes a case of 'if' and 'how', not 'when'. Movement is measured in inches and feet rather than metres, and simply remaining alive becomes more exhilarating than any objective achieved." Peterson praised the gameplay for being tense, scary and effective, commenting that Alien: Isolation is "a solid, incredibly striking example of the survival horror genre that uses its first person perspective to greater personalize the horror." PC Gamer credited the crafting system for giving the game "a lot of unexpected depth", allowing players to outsmart enemies in multiple ways. The game's Survivor Mode was praised by Chris Carter of Destructoid, who felt it offered players different feelings and experiences each time they played it.

Although the gameplay was praised by several reviewers, some found the game to be unnecessarily long, repetitive and unforgiving. In a mixed review, McCaffrey felt that the game does not offer many options of survival, requiring players to spend most of their time hiding in lockers "staring at the motion tracker". Polygon criticised the overexposure to the alien creature, turning Alien: Isolation into an irritating experience. As Gies explained, "Every time I thought I heard the monster, every blip on my motion tracker, was a cause for a tightness in my chest at first. By the 300th time I dived under a table or into a locker, I wasn't scared anymore — I was annoyed." Despite the criticism, Alien: Isolation was considered a "brave" title due to its difficult and unforgiving gameplay, a feature that is uncommon in games with large development costs. As of January 2015, Alien: Isolation has sold over one million copies worldwide according to Sega. As of March 2015, the game has sold over 2.1 million copies in Europe and the US.

Accolades

Alien: Isolation received several year-end awards, including PC Gamer's Game of the Year 2014, Audio Achievement at the 11th British Academy Games Awards, Best Audio at the 15th Game Developers Choice Awards, and four awards at the 14th National Academy of Video Game Trade Reviewers. The game also appeared on several year-end lists of the best games of 2014. It was ranked 1st in The Daily Telegraph's the 25 best video games of 2014, 2nd in Empire's the 10 Best Games Of The Year, 2nd in Time's Top 10 Video Games of 2014,[61] 4th in The Guardian's Top 25 Games of 2014, 3rd in Reader's top 50 games of 2014 by Eurogamer, and in Daily Mirror's the 10 best games of 2014. In 2015, Alien: Isolation was ranked 7th in Kotaku's list of the 10 Best Horror Games.

Possible Sequel

In October 2015, Creative Assembly studio director Tim Heaton stated that, while Sega was disappointed with the sales of the game, a sequel was "not out of the question" and that "there was more to be said". However, he also highlighted significant obstacles in creating a sequel, commenting: "Spending very significant amounts of money, and getting close to break-even or just about in the black? That’s not where Sega wants to be, when we have a brilliant portfolio of other games that do great business". Sega later confirmed that a sequel is still being considered, but the question of whether or not a sequel would be profitable will eventually decide the fate of the project.

On 24 April 2017, rumours of Creative Assembly producing a sequel were published by PSU.com. However, Eurogamer later pointed out that the rumour is likely false, as much of the original design team behind Alien: Isolation were no longer with Creative Assembly.

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smoke-eyes-fic · 7 years

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April Fool’s Drabble

Sorry folks cucu and I are still working on the new chapter. Getting schedules and brain meats lined up in the proper times to get stuff done has been a rather insane venture. So as a sort of apology, and in observation of April Fool’s I give you an old drabble from my folders of long ago. It sadly doesn’t have an end cause I was never sure where to cut it off. Feel free to create the rest yourself. Timeline wise - this is after all the whatever-goes-down in the fic. A happy ending with a house and a dog. And hi-jinks ensue. This is based on an old joke I made ages back. Many apologies to those who don’t get the gag.

It had been an uneventful dusty summer day. The few chores around the farm had been done in the early morning before the Texas sun started beating down. There was some minor maintenance work that needed to be done on Sam's tractor. But Engineer would get to that when the sun wasn't so high. In the mean time he'd been dozing on the couch watching a Western on the television with Fleabag the hound asleep on his feet. Spy had declared he'd seen enough John Wayne in his lifetime and was in some other part of the house reading. The Spook was getting restless again, soon he'd start insisting they leave the farm and go traveling.

The doorbell rang startling the Texan awake, Fleabag bayed loudly running to greet whoever was at the door. "Better not be another salesman" he muttered darkly as he slowly rose from the couch, he had hoped they would have learned after the last time. "Just a minute" he called stomping to the door. "Dangit Flea!" he grunted grabbing the dog by the collar dragging him back so he could open the door. "Can ah hel-" he froze as he squinted at the figure through the screen door.

It was a young girl in a red dress and a beat up red sun hat that threatened to slip over her eyes. "Hullo" she said quietly pushing her hat back to peer up at him. She looked to be no older than six he guessed, too young to be out by herself. Something about her made him doubt she was here to sell cookies. Girl scouts didn't usually bring suitcases with them. He wasn't sure why, but he had a sinking suspicion he knew who to blame for this.

His suspicions were confirmed as she finally added "I'm looking for my Papa."

This was a bad dream, he tried to tell himself, closing his eyes for a moment. He would open them and he'd still be on the couch with his movie. He opened his eyes and the girl and her red hat and suitcase were still standing on the doorstep with no sign of disappearing into thin air."Spah!" he yelled into the house "Git out here!"

Unable in good conscience to leave the child on the doorstep he opened the screen door and gestured for her to come in. Quietly she stepped inside, she turned to her suit case but the Texan had already picked it up. He noticed it was battered but well made, labels from all over the world covered the scuffed leather.

"Who was at the door?" Spy asked walking into the room."Relative of yours?" he asked glancing at the girl, his eyes seemed to avoid looking at the suitcase.

"Actually-"

"Papa!" the girl cut the Texan off walking towards the Frenchman.

A choked sound emitted from Spy's mouth instead of words as he stood rigid in the doorway.

"-She says she's one of yours." Engineer finished lamely.

The child stopped in front of him oblivious to the fact the man was turning a rather unpleasant shade of gray. She placed her chubby hand into her dress pocket and pulled out a small sealed envelope and held it out to him. Quickly regaining composure Spy accepted the letter, ripping it open. His eyes darted across the papers, narrowing with every line before his hand lowered and glowered at the girl.

"What's it say?" the Texan asked but neither the girl or Frenchman offered any explanation.

Brushing past the girl he took the letter from Spy's slack grip. It was elegant stationary, the message itself was French written in neat flowery feminine hand writing.

"This is a trick." Spy insisted loudly to no one in particular. "Putain de menteur,"

"Don't use language like that with kids present." Engineer scolded him as he tried to translate the letter but was having trouble concentrating, his mind reeling through too many things at once. Who was this girl? Where was her mother? Who was her mother? How did she come to be here in the middle of Texas?

"Merde! -I'll use whatever language I feel lik-" the Frenchman found himself silenced by one of the Texan's hands over his mouth.

"Hush." he hissed, looking at the ceiling and began slowly counting to ten, trying to organize his thoughts.

He never doubted that Spy had children. From his understanding of the man and his past misadventures, he was willing to guess the snake had fathered at least three or four. Though that was a rather conservative guess he told himself. He never expected to meet any of them. Let alone for one to end up on his doorstep.

He hoped this wasn't the start of a trend.

Finally reaching ten he lowered his hand from Spy's mouth hoping the idiot would have the sense to stay quiet for the time being. Looking back down at the girl he noted the resemblance between her and Spy. The same eyes, dark hair, thankfully she seemed to have been spared the man's nose.

"Where's your Mama sweetie?" he asked kneeling down to look her in the eye.

"Dunno, she dropped me off at the gate." the girl informed him simply as if this was the most normal thing in the world ."She told me I was staying here for a while with my Papa and his friend while she worked." Well that explained the suitcase, and why he hadn't heard a car drive up. Or why the girl didn't seem confused to see him in addition to her father.

"She's not staying here!" Spy insisted to no one who was listening.

"What's your name?"

The girl's eyes darted up at Spy and back to him, "Carmen" she responded, not the least bit shy.

"Ah tell yah what, Carmen. Let's go to the kitchen, get you some cookies and milk while your Papa and I talk. Would you like that?"

The girl eagerly nodded and followed him into the small kitchen. He sat her down at the table and pulled a couple of cookies out of the cookie jar. He nervously bit into one of the cookies, hardly tasting it as he chewed into dust, before putting the entire ceramic jar in front of the girl. Glaring at Spy who had tried to palm a cookie for himself, he poured the child a large mug of milk and left the jug out where she could hopefully reach it.

"Now you stay here, while we talk in the other room. Alright?" Carmen was too occupied with her mouth full of crumbs to do much more than nod. With a wide forced smile for the girl's benefit he grabbed Spy's arm before he could slip away and dragged the protesting man out of the kitchen to the other end of the house, hopefully out of ear shot.

"That girl and her putain mère are liars!" Spy insisted to Engineer who leaned on the door that was only escape from the room.

"Who's her mother?" he asked irritably.

"It was a long time ago." the Frenchman answered defensively. "Years - before you and I-"

"-That's obvious. So who is she?"

"I was trailing her for BLU, they suspected she was courier for an exchange of Austrailium from a black market source. Then one thing led to another and-" the man shrugged pulling his cigarette case out of his pocket.

"So who is she?"

"She was an agent for Reliable Excavation. One of their spies, our paths had never crossed before. Never crossed after. It was a- one night tryst."

"Yah slept with an enemy Spy?!"

"I slept with you!" Spy pointed out. "Still do," he added.

"T-that's-" the Texan sputtered. "t-that's neither here nor there!" he insisted feeling his ears burn. "B-but an enemy spy?" He shouldn't be surprised that the man had affairs with others from RED. He'd known that the Frenchman had little regard for rules or boundaries. At least that explained how the woman had tracked Spy down here. He imagined that only another person in the same line of work could manage that. He held the letter over his face and skimmed the letter haphazardly translating the French writing in his head.

Dear [what the hell does she call him - his name - his alias? Spy? Shithead? Idiot?]

I see you and your pet cowboy have settled down for now. You do like to make yourself difficult to find don't you?

You've had your fun, now it's time to take responsibility for past mistakes. I'm sure you don't remember much of me or that night we fought in Las Vegas. Or what came after. I wouldn't have thought much of it myself, if it wasn't for the end results. Her name is Carmen by the way.

I've been called away to a job - I'll be away for an unknown amount of time and it seemed it was high time the two of you got to know each other. I'm sure you'd agree with me that a child should know their parents. If only to see what poor life choices look like.

Before you start calling me a liar I have included some lab work you should see. My Medic owed me a couple of favors-.

Curious Engineer flipped to the next page. It looked like some sort of lab chart, "She included a paternity test." he said quietly.

"What?" the chart was yanked out of Engineers hands roughly. "How did she even…" Spy trailed off muttering profanity darkly under his breath.

The Texan sighed and went back to reading the letter.

- I expect you to take good care of her since she is your own flesh and blood. I will be back to collect her. Do not think you can dump her in an orphanage for your convenience. If you do, or if anything else happens to her be assured I will hunt you and every alias you ever used down and make you suffer. The same threat applies to your pudgy companion as well.

"Pudgy?" he repeated - rubbing the back of his neck.

"This has got to be a fake!" Spy fumed on, the floorboards creaking as he paced, "Where the hell would she even get a sample?"

Engineer sighed, half an hour ago he had been dozing on the couch, planning repairs to a tractor not worrying about some kid that got dumped on his doorstep. "Spook" he pinched the bridge of his nose. "Spook" he repeated again "Could'ya- Could'ya stop pacin' for a sec?"

#Team Fortress 2 #carmen sandiego #spy #engie #spyxengie #drabble #sorry this goes nowhere #did this for the lolz #april fools

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bountyofbeads · 4 years

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How Scientists Could Stop the Next Pandemic Before It Starts https://nyti.ms/2ysmlBg

How Scientists Could Stop the Next Pandemic Before It Starts

Researchers believe they could pre-emptively create vaccines and drugs to fight a wide range of viral threats — if they can get sufficient funding.

By Jennifer Kahn | Published Published April 21, 2020 Updated April 22, 2020 | New York Times Magazine | Posted April 23, 2020 |

On a cold morning in February 2018, a group of 30 microbiologists, zoologists and public-health experts from around the world met at the headquarters of the World Health Organization in Geneva. The group was established by the W.H.O. in 2015 to create a priority list of dangerous viruses — specifically, those for which no vaccines or drugs were already in development. The consensus, at least among those in the room, was that as populations and global travel continued to grow and development increasingly pushed into wild areas, it was almost inevitable that once-containable local outbreaks, like SARS or Ebola, could become global disasters.

“The meeting was in a big room, with all the tables arranged around the edge, facing each other,” one of the group’s members, Peter Daszak, recalled recently. “It was a very formal process. Each person was asked to present the case for including a particular disease on the list of top threats. And everything you say is being taken down, and checked factually, and recorded.”

Daszak, who directs the pandemic-prevention group EcoHealth Alliance and is also chairman of the Forum on Microbial Threats at the National Academies of Sciences, Engineering and Medicine, had been given the task of presenting on SARS, a lethal coronavirus that killed roughly 800 people after it emerged in 2002. (SARS stands for Severe Acute Respiratory Syndrome and is officially known as SARS-CoV-1.) “We’d done a lot of research on coronaviruses, so we knew they were a clear and present danger,” he told me. “High mortality, no drugs or vaccines in the pipeline, with new variants that could still be emerging.”

The discussion, he said, was intense. “Everyone else in the room knows the facts already — they’ve read all the research,” Daszak said. But for each pathogen, the speaker had to convince the room that it presented a significant threat — “that this disease really could take off, and that we should concentrate on it rather than on Lassa fever or something else. So, you argue the case, and then people vote. And sometimes it gets quite heated. I remember that monkey pox was an issue, because there are outbreaks, but there’s really nothing we can do about them. It was a really rigorous, really excellent debate — and then afterward, we went and had fondue.”

The final list — which did contain SARS and MERS, along with seven other respiratory, hemorrhagic or otherwise-lethal viruses — also included something the W.H.O. dubbed “Disease X”: a stand-in for all the unknown pathogens, or devastating variations on existing pathogens, that had yet to emerge. Daszak describes Covid-19, the disease caused by the virus SARS-CoV-2, as exactly the kind of threat that Disease X was meant to represent: a novel, highly infectious coronavirus, with a high mortality rate, and no existing treatment or prevention. “The problem isn’t that prevention was impossible,” Daszak told me. “It was very possible. But we didn’t do it. Governments thought it was too expensive. Pharmaceutical companies operate for profit.” And the W.H.O., for the most part, had neither the funding nor the power to enforce the large-scale global collaboration necessary to combat it.

As Covid-19 has spread around the world, overwhelming hospitals and even mortuaries, there has been widespread consternation over how we could have been caught so flat-footed by a virus. Given all the shining advances of high-tech medicine — computer-controlled surgery, unprecedented immunotherapies, artificial-intelligence programs for assessing heart-disease risk — this failure feels utterly baffling. How could the entire world remain so powerless? More important, what could be different next time?

According to some infectious-disease experts, the scientific tools already exist to create a kind of viral-defense department — one that would allow us to pursue a broad range of vital global projects, from developing vaccines and drugs that work against a wide range of pathogens to monitoring disease hot spots and identifying potential high-risk viruses, both known and unknown. What’s lacking is resources. “We really did miss the wake-up call,” Daszak says. “The alarm went off with SARS, and we hit the snooze button. And then we hit it again with Ebola, with MERS, with Zika. Now that we’re awake, we should think about where to go from here.”

In late March, Vincent Racaniello, host of the podcast “This Week in Virology” and a professor at Columbia University, conducted an interview with the pediatric infectious-disease expert Mark Denison. Denison, who teaches at Vanderbilt University Medical Center, led a team that developed one of the most promising current treatments for Covid-19: the drug remdesivir, currently being tested by the pharmaceutical company Gilead Sciences.

On the show, Denison noted that because it is almost impossible to predict which virus might cause the next pandemic, researchers had long argued that it was essential to design panviral drugs and vaccines that would be effective against a wide range of strains: all types of influenza, for instance, or a substantial group of coronaviruses rather than just one. When his lab was first applying for a grant to study remdesivir, Denison recalled, that was already the goal. “We don’t want to work with a compound unless it inhibits every coronavirus we test,” Denison said. “Because we’re worried about MERS, we’re worried about SARS-1, but they’re not really our problem. The future is the problem.”

Panviral drugs — ones that work broadly within or across virus families — are harder to make than broad-spectrum antibiotics, largely because viruses work by hijacking the machinery of our cells, harnessing their key functions in order to replicate. A drug that blocks one of those functions (e.g., the production of a particular protein) is often also disrupting something that our own cells need to survive. Researchers have begun to find ways around that problem, in part by refining which process a drug targets. But they’ve also begun to test existing drugs against a wider array of viruses. It was in just such a follow-up screen that Gilead discovered that remdesivir, originally developed to treat hepatitis C and later tried against Ebola, might be effective against coronaviruses. (Favipiravir, an influenza drug developed in Japan, is another broad-spectrum candidate.) The reason drugs sometimes work in extremely different diseases — in, say, Ebola and coronaviruses and flu — is that they block some common mechanism. Remdesivir and favipiravir, for instance, each mimics a key building block in a virus’s RNA, which, when inserted, keeps the virus from replicating. “It’s definitely possible to make a drug that would work across a good range of coronaviruses,” Racaniello says. “We honestly should have had one long ago, since SARS in 2003. It would have taken care of this outbreak in China before it got out. And the only reason we didn’t is because there wasn’t enough financial backing.”

Panviral vaccines are also becoming a real possibility. In recent years, a number of prospective universal flu vaccines have been developed that work by targeting not the virus’s globular head, which mutates easily, but its stalk, which barely mutates at all. (As Daszak noted, if this outbreak had been a flu rather than a coronavirus, we’d be in much better shape.) Another new approach, mRNA vaccines, works by exploiting messenger RNA — a kind of courier that communicates the genetic instructions for making proteins — to drive an immune response. The advantages of mRNA vaccines are potentially enormous, in part because they can be made very quickly (one month instead of six for a known strain; two to three months for a novel virus) but also because they can be made on a vast scale (billions of doses, compared with the 100,000 doses that were needed for the Ebola epidemic). They’re extremely adaptable too: If a researcher can develop a platform that works with this coronavirus, it’s easy to redesign it for the next one. (One mRNA start-up, Moderna, set a drug-industry record by creating a prospective Covid-19 vaccine, mRNA-1273, in just 42 days, using the virus’s genetic sequence. The drug is currently in Phase 1 clinical trials to be safety-tested on healthy volunteers.) And while no mRNA vaccines have yet received F.D.A. approval, Covid-19 will almost certainly change that.

But for years, Racaniello notes, the real obstacle to making panviral drugs or vaccines has been that no one was willing to pay for their development. For pharmaceutical companies, he points out, panviral vaccines are simply a terrible business proposition: Companies have to spend hundreds of millions of dollars to develop a shot that people will get once a year at most — and not at all in years when no particular disease is ascendant.

Panviral drug treatments are unprofitable for similar reasons. For one, the course of treatment is short, usually just a few weeks; for chronic diseases (diabetes, high blood pressure), patients take regimens of pills daily, often for years. (One person noted that Gilead’s stock price actually dropped after the company produced a revolutionary hepatitis C drug. Because the treatment completely cured patients, the market for it started to shrink, undermining the company’s bottom line.)

The other problem is that there’s currently no way to quickly test for most viruses, which is essential if a doctor wants to establish a diagnosis and prescribe the right drug. As a result, Racaniello says, it’s “a chicken-and-egg situation: No one is developing drugs for these viruses because there’s no way to test for them. And no one is developing tests, because there aren’t any drugs to prescribe.”

Governments, meanwhile, have been reluctant to fund panviral development — both because it’s expensive and because the rewards can feel remote, especially as many diseases originate in other countries. “We don’t prevent well; we respond well,” Daszak notes. “Remember when Obama got $5 billion for the Ebola outbreak in West Africa, and U.S. troops went to help fix the problem? That’s heroic. How heroic is it, three years before Ebola, to say, ‘We’re going to fund a massive program in West Africa to help these poor countries get ready in case an outbreak happens?’ He’d be laughed out of the room!”

Global nonprofits like the Gates Foundation have tried to step into this funding void. The foundation has supported GAVI, an international alliance that helps vaccinate children in poor countries and spearheaded a fund to fight H.I.V., tuberculosis and malaria worldwide. Mark Suzman, the chief executive of the Gates Foundation, says that when governments and companies do pull together, the focus is often on projects like these rather than “forward-looking” issues like pandemics or climate change. One exception, he says, has been CEPI, the Coalition for Epidemic Preparedness Innovations, an NGO that was founded in 2017 to coordinate and finance the development of new vaccines for diseases that might lead to a pandemic. When it started, Suzman told me, CEPI was a low-profile project: “It was really a response to the Ebola epidemic of 2014 and 2015. Now, of course, it looks incredibly farsighted.”

CEPI works by identifying the most promising research, and then connecting it to industry and government resources, in order to bring multiple sets of “candidate” vaccines through initial clinical trials. The goal is to create a stockpile of potential treatments for known coronaviruses, hemorrhagic fevers and other global threats that could quickly go into production in the event of an epidemic. Daszak noted that CEPI is running a trial for a vaccine against Nipah virus, a zoonotic virus — one that exists in animals but can infect people — which can cause acute respiratory illness and fatal encephalitis. “This is the classic example,” Daszak says. “So far, there have been only a few outbreaks, so the market is minuscule: a few thousand people a year get it, in Malaysia or Bangladesh. But it infects a wide range of animals, and that means it’s likely to keep crossing over into people. And if it ever broke out, it could be a pandemic with very lethal consequences.”

The group also funds technologies aimed at “Disease X” (the potentially pandemic viruses that we have yet to discover) with the goal of faster vaccine development should a totally new threat emerge. As Jake Glanville, whose company, Distributed Bio, received a grant from Gates Foundation to create a universal flu vaccine, told me, “This is how we win the forever war, and not just battles against these pathogens.”

CEPI isn’t the only group trying to find solutions to the drug and vaccine problems. In the United States, a federally funded university collective called the Antiviral Drug Discovery and Development Center (AD3C) was created in 2014, with the goal of developing drugs for influenza, flaviviruses (including West Nile), coronaviruses and alphaviruses. Like CEPI, AD3C partners with pharmaceutical companies but focuses on salvaging and reformulating promising drugs that might be valuable but that the company isn’t interested in pursuing. (When Gilead discovered that remdesivir worked on coronaviruses, for instance, the treatment was routed to AD3C, which enlisted scientists at Vanderbilt University and the University of North Carolina to repurpose it.)

Amesh Adalja, a senior scholar who specializes in infectious-disease and pandemic preparedness at the Johns Hopkins University Center for Health Security, told me that approaches like these are going to be “instrumental” in preventing whatever comes after Covid-19. “In the wake of this pandemic, people are going to realize that spending money on organizations like CEPI is a good investment — especially when you realize how much having a vaccine against the coronavirus would have offset the damage and destruction and disruption that we’ve seen.”

Despite these efforts, there is still one overarching problem: how little is known about the planet’s viral threats. Viruses make up roughly two-thirds of all newly discovered human pathogens — far more than either bacteria or fungi. Over the course of human evolution, we’ve been exposed to so many that about 8 percent of the human genome is made up of retroviral DNA sequences that have inserted themselves into the human germ line, often to our benefit. (An ancient virus is thought to be responsible for the development of the human placenta, for example.)

Perversely, viruses get no advantage from making people seriously ill; it’s simply a byproduct of the encounter. Over the years, or sometimes centuries, viruses and hosts usually reach an accommodation: They coexist. Typically, the most dangerous viruses are those that have jumped into humans from other species, as happened with Covid-19. That’s partly because the disease is new, so our immune system hasn’t had a chance to create antibodies. But it’s also because an unfamiliar virus is more likely to throw our immune system into overdrive, potentially fatally.

For anyone hoping to identify where the next pandemic is coming from, the difficulty is that there are literally millions of viruses to analyze. One paper recently estimated that there were 1.6 million potentially zoonotic viruses, of which fewer than 1 percent have even been identified. “One thing we definitely need is better diagnostic testing where we’re actually looking for these emerging pathogens in people,” Adalja says. “Because there are already many, many one-off cases that no one ever diagnoses, but which could be the first sign of a new virus jumping into a human species.” While influenza and coronaviruses are known pandemic threats, they’re far from the only ones. Nipah and Hendra viruses are deadly paramyxoviruses that have emerged from bats within the past three decades. Marburg is a highly lethal hemorrhagic fever like Ebola, but without any vaccine or treatment in the pipeline. (Dozens of other hemorrhagic viruses also exist, but so far haven’t made the jump to humans.)

One argument against doing this kind of work has been that the risk of any single virus’s causing a pandemic is low. Most viruses simply aren’t equipped to make the jump from animals to humans — and even when they do, most aren’t able to replicate in ways that become dangerous or spread from person to person. The problem, Daszak says, is that when you multiply a 10-million-to-one event by the total number of animal-human interactions, the probability isn’t that low after all. “It’s really easy to scientifically demonstrate that these are rare events and we shouldn’t bother,” he added. H.I.V., for instance, was originally present in primates, and spilled over into the human population only about 10 times in the span of a century; each time, it quickly died out — until it didn’t. “Statistically, when you look at the likelihood that a virus will, first, be able get into a person, and then be able to replicate, and then get transmitted through sex, the probability seems like it should be minuscule! But what we failed to appreciate was both the adaptability of viruses, and the dimensions of the human-wildlife interface.”

Hoping to get a more accurate estimate of which viruses could be a threat, Daszak recently traveled to a rural part of Yunnan province, in China, and took blood samples from people who live there, looking for antibodies that would show how often they had been exposed to bat coronaviruses. (Detectable antibodies typically last two to three years after an infection.) “This was bat coronaviruses alone — not all the other stuff that’s out there,” Daszak said. “And we found that 3 percent of the population had been exposed — which tells me that these things are spilling over at an incredible rate, as part of everyday business in rural China.”

Which means, Daszak says, that between one million and seven million people a year in Southeast Asia pick up bat coronaviruses. “For most of them, it probably doesn’t even cause illness. There may have been some little outbreaks that never got noticed, or cases where people even die, and it gets put down to influenza or something.” He paused. “But that is a huge level of spillover. It’s not difficult to imagine one of those infections mutating a bit and becoming Covid-19.”

Policing points of potential spillover is challenging — and the effort needed to rigorously track and test wildlife even more so. As Racaniello observed, “We’ve known since SARS that bats harbor dangerous coronaviruses. So bats are an obvious place to look. But even then it’s not easy to do. You have to crawl into a bat cave, you have to catch them somehow. It’s tedious, costly work.”

In the United States, for example, some species of mice harbor hantavirus, which periodically infects people, most often when they inhale aerosolized mouse droppings — say, when sweeping out a dusty cabin or garage. Because the infection, which starts like a flu but is fatal in 38 percent of cases, doesn’t spread from person to person (yet), the pandemic risk is currently low, Racaniello says. “A good question is, what would have to happen for that virus to become human-to-human transmissible? And also, what else do mice have that might be a threat to people? But the mice of the United States have barely been sampled, in terms of the viruses they carry.”

During the Obama administration, a U.S.A.I.D. program called PREDICT was created to fill that gap, by using biological surveillance and predictive modeling to identify the most likely sources of zoonotic disease. During the 10 years the program existed, researchers found more than a thousand new potential zoonotic viruses, including an unknown Ebola strain. (Daszak, whose group received financial support from PREDICT, called the project “visionary.”) After the program’s funding ended in September, shortly before the coronavirus outbreak began, the Trump administration authorized two successive six-month extensions. A U.S.A.I.D. spokesperson said that in September, there will be “a planned transition” to a new prevention program, Stop Spillover, with a proposed budget of between $50 million and $100 million over five years. “For these sorts of programs to work, you have to be patient,” Racaniello told me. “But these projects also cost money, and they don’t necessarily seem like they’re producing much in the short term, so they’re the easiest things to cut when you want to cut a budget.”

One challenge for pandemic hunters is understanding which animals are most likely to be the source of viruses. Bats, the original carriers for many zoonotic viruses, rarely pass those diseases to humans directly. (One study found that bats in China harbor more than 500 different coronaviruses, but they also carry paramyxoviruses, influenza and hemorrhagic viruses like Ebola.) More often, Daszak explained, bats infect another animal, which then infects us. “About a fifth of all mammals are bats,” Daszak points out. “And they’re all over the globe. We just don’t realize that, because they fly at night. But they’re out there, pooping all over the place — just like deer and birds, except we don’t see it.” (It’s worth noting that, of the thousands of bat species, only a few — such as the fruit bat and horseshoe bat — are currently thought to be the major reservoirs of zoonotic disease.)

Bats also fly, can live for a long time and thrive across a huge range of habitats, which means that we, and other animals, are more likely to come in contact with them than with other species. Racaniello pointed to an outbreak in Australia in the 1990s that was caused when bats began frequenting a racehorse stable, infecting the horses, which then passed the disease on to their human trainers. In Malaysia, Nipah virus emerged from pigs, on farms in an area that harbored fruit bats. In the Middle East, the MERS coronavirus — which most likely originated in a bat — became endemic in camels, who at some point started passing it on to people.

“Before that outbreak, it wouldn’t have occurred to anyone to look in camels for a pandemic virus,” Racaniello said. “The same is true for a lot of things. For instance, we knew that bats carried SARS-like coronaviruses, but it was only when they started looking for the cause of the first SARS outbreak that they found it had jumped from bats to civet cats, which is how we got it. But as to all the other animals in the world, we pretty much have no idea! So, I think you just need to cast a very wide net.”

To do that, Daszak helped found an ambitious project called the Global Virome Project, which seeks to identify 70 percent of the estimated 1.6 million potentially zoonotic viruses over 10 years, at a cost of $1.2 billion. “We found the closest relative to the current SARS-CoV-2 in a bat in China in 2013,” Daszak told me. “We sequenced a bit of the genome, and then it went in the freezer; because it didn’t look like SARS, we thought it was at a lower risk of emerging. With the Virome project, we could have sequenced the whole genome, discovered that it binds to human cells and upgraded the risk. And maybe then when we were designing vaccines for SARS, those could have targeted this one too, and we would have had something in the freezer ready to go if it emerged.”

Racaniello supports this strategy — “I like the test-every-creature-on-Earth approach, personally” — but acknowledged that there were also ways to narrow the field. Risky zoonotic viruses, he noted, are more likely to be found in mammals or birds; anything else is just too big a genetic jump. Within that group, animals that are evolutionarily closer to us are also higher-risk, because we share more of the receptors that viruses use when they infect a cell.

Another risk factor is simply how likely we are to come into contact with a particular animal, whether from activities like logging, through the wildlife trade or through farming. (Measles is thought to have arisen out of the domestication of cattle, while pigs and chickens carry swine flu and bird flu.) But while vaccines exist for some domesticated animals — there’s a successful one for coronavirus in chickens, and researchers recently created a MERS vaccine for camels — there’s no way to vaccinate wildlife, or even urban animals like mice.

“That’s why we need to be studying these things,” Daszak says. “We’ve shown repeatedly that any disease, once it gets into human-to-human-transmission mode, it’s going to come to the U.S. We’re always in the top five every time we do that analysis. We said, about Ebola, because it’s not respiratory, it’s never going to break out of a village, or a country. And it did! And if you get a version with a longer asymptomatic incubation time, like we have with Covid-19, imagine what that could look like.”

In the wake of the Covid-19 pandemic, more systems of global cooperation and investment have started to emerge. In late March, the Gates Foundation set up a Covid-19 Therapeutic Accelerator to screen a vast number of existing drugs and compounds that hadn’t made it to market, in order to test whether they might work on other diseases.

The screening, done by the Rega Institute in Belgium, will scan and test 14,000 compounds in a Scripps Research Institute library, as well as the proprietary libraries of 15 pharmaceutical companies, including Bristol-Myers Squibb, Eli Lilly, Merck, Novartis and Pfizer, for possible crossover treatments. Because most of the drugs have already been tested for safety, they need to be tested only for efficacy, speeding up the process.

The willingness to share proprietary compounds, says Suzman of the Gates Foundation, is “pretty unprecedented.” And while that collaboration is currently focused on Covid-19, the hope is that, after the current crisis has passed, that same collection could be screened for more ambitious projects — like a broad-spectrum anti-coronavirus drug. “I am optimistic — cautiously optimistic — that this is a kind of precedent,” Suzman said. “And that it will lead to more and better global health collaboration.”

Monalisa Chatterji, a microbiologist who is part of the Gates Foundation’s drug-discovery arm, agrees. “The conversation has started” for future pandemics, she told me. “Should there be a standing shared library of unused drugs that research labs can test? Should similar things be done around diagnostics? Should there at least be an agreement where every company has already agreed to provide access to its library in a pandemic situation?” She added, “That sounds small, but it’s these small things that eat up time when it matters.”

The big question, according to nearly everyone I spoke with, is whether we’ll manage to maintain this political and financial will over time. Racaniello and Daszak both remember being sure that after SARS and Ebola, pandemic prevention would be a priority; instead, each outbreak was quickly forgotten. And while it’s hard to imagine forgetting the current disaster, researchers worry that funding and attention will once again fade in the face of competing pressures. As Rancaniello observed, the combined 2019 budgets for the National Institutes of Health and the National Science Foundation was $47 billion — less than 7 percent of the $686 billion allocated to defense. “I would argue that viruses are just as much a threat as a bad nation would be to the military,” Racaniello said.

Or as Daszak put it: “We don’t think twice about the cost of protecting against terrorism. We go out there, we listen to the whispers, we send out the drones — we have a whole array of approaches. We need to start thinking about pandemics the same way.”

*********

Coronavirus Is Forcing Medical Research to Speed Up

By Kim Tinley | Published April 21, 2020 | New York Times Magazine | Posted April 23, 2020 |

As scientists race to understand the coronavirus, the process of designing experiments, collecting data and submitting studies to journals for expert review is being compressed drastically. What typically takes many months is happening in weeks, even as some journals are receiving double their normal number of submissions. Science, one of the world’s most selective research outlets, published the structure of the spiky protein that the virus uses to enter host cells — crucial knowledge for designing a vaccine and antiviral drugs — nine days after receiving it, according to Holden Thorp, the journal’s editor in chief. “It’s the same process going extremely fast,” he says. Is there precedent in Science’s 140-year history? “Not that anybody can remember.”

For both experts and laypeople, being able to access dependable health advice has never felt more important, or challenging. The World Health Organization has described a “massive ‘infodemic’ — an overabundance of information, some accurate and some not — that makes it hard for people to find trustworthy sources and reliable guidance when they need it.” Indeed, in recent weeks, new research has emerged that complicates such basic questions as who should wear face masks and when; what degree of physical separation is safe; and how the virus primarily spreads.

As a practice, science continuously interrogates and refines our understanding. “The answer is never so simple as ‘Masks work or masks don’t.’ It’s going to be ‘Under what conditions do masks have an effect?’ and ‘How much of an effect do they have?’ ” says Brian Nosek, executive director of the Center for Open Science. “The questions that we want answers to are much more complicated than the evidence that we have at any one moment.” The problem is that now we want those answers to be definitive and fast.

That demand for conclusiveness highlights longstanding tensions over the role of a scientific journal. Should it be an arbiter of facts or a generator of new ideas? A keeper of the historical record or a predictor of the future? A private channel for scientists to communicate with one another or a megaphone with which they can reach the public? Or all of the above? “I think this whole pandemic has very much changed our view of ourselves,” says Richard Horton, the editor in chief of the British medical journal The Lancet. “We feel very much that we are publishing research that is literally day by day guiding the national and global response to this virus. And that is both daunting and full of considerable responsibility, because if we make a mistake in judgment about what we publish, that could have a dangerous impact on the course of the pandemic.”

The strength of traditional academic journals, compared with other means of broadcasting scientific knowledge, is that they have the expertise to interrogate the validity of highly specialized experimental methods and the accuracy of the resulting data — and also make the importance of new findings clearer in context. That means getting relevant experts to review papers, which is especially difficult when dealing with a novel pathogen. Many of those who have gained expertise in Covid-19 are also in the thick of trying to stop it. “What we can say with confidence is the best available evidence is what’s coming through the journals,” Nosek says. “But the best available evidence is far, far short of certainty,” he adds — and the decisions that we make about the evidence have “to embrace the uncertainty.”

To make potentially life-or-death research available as quickly as possible, many publishers of elite journals with hefty paywalls, including Science, The Lancet, JAMA and The New England Journal of Medicine, have made coronavirus content free online. Thorp says he and others have also encouraged researchers to post their submissions to so-called preprint servers, where anyone can access them, before review. “Then, we’re not deciding whether the world should or should not have the information,” he says. “What we’re deciding is whether this is an important part of the scientific record that should have the endorsement of our peer-review process.”

By definition, however, it’s difficult to say whether a preprint is “reliable and dependable and true,” says Peter Drotman, the editor in chief of Emerging Infectious Diseases, a journal published by, but editorially independent from, the Centers for Disease Control and Prevention. (It has always been open access.) On the other hand, researchers sharing preliminary work may be helping the scientific community as a whole collaborate more efficiently and effectively — for instance, by enabling researchers to rapidly confirm and build on one another’s findings rather than unnecessarily duplicating experiments.

Scientific journals consider their audience to be other scientists, not the general public. But the scientific journal as we know it was actually born because of popular demand for information during a pandemic.

In the early 1820s, a smallpox outbreak struck Paris and other French cities. A new vaccine was in existence at the time, but reports varied about how effective it was. A powerful medical institution in Paris, the Académie de Médecine, gathered its members to discuss what advice it should issue to the nation. Historically, such meetings were held privately, but the French Revolution had ushered in a new era of government accountability, and journalists were allowed to attend. The scientific debate they relayed upset some members of the Académie, which had hoped to make a clear, unified statement, says Alex Csiszar, an associate professor of the history of science at Harvard University. In response, the Académie sought to regain control of its message by publishing its own weekly accounts of its discussions, which evolved into the academic journals we know today.

Now those same journals tend to be too specialized for general readers to grasp easily, making the concept of “open access,” as far as the public is concerned, “more of an idea than a reality,” Csiszar says. Nevertheless, the current pandemic has certainly increased both the readership of scientific journals and their citations in the press. Before January, the most-read article in Emerging Infectious Diseases, a 2006 study, had 20,000 views. The current most-viewed article, also from 2006, has more than 480,000 views: It gives instructions for making your own “simple respiratory mask” from a T-shirt.

What this sudden growth in scientific engagement will mean over the long term is an open question. Thorp worries about a backlash if people perceive scientists to have overpromised solutions to the pandemic. “It is difficult to share progress with adequate caveats about how long things might take or whether they will work at all,” he wrote in a March editorial. “This is not just fixing a plane while it’s flying — it’s fixing a plane that’s flying while its blueprints are still being drawn.”

Then again, if government officials had heeded available science sooner, we might not be on that plane at all. On Jan. 31, The Lancet published a paper forecasting a global pandemic and asserting that “preparedness plans should be readied for deployment at short notice, including securing supply chains of pharmaceuticals, personal protective equipment, hospital supplies and the necessary human resources to deal with the consequences of a global outbreak of this magnitude.” Britain’s National Health Service “didn’t take any of those actions,” Horton has written. U.S. health agencies and the White House didn’t, either.

None of that, of course, is within our individual control. So in addition to following public-health guidelines, how can nonscientists engage with studies, or news that cites studies, to help them protect their health? Checking sources is important: Heed information that comes from respected journals. But also remember that even the best peer-reviewed advice is likely to change — and change again. That’s how science works, and now it’s working faster than ever. If we put our faith in a single conclusion, it’s easy to feel distressed when it’s amended. If we trust the process, imperfect though it is, we’re better prepared to change with it, which is the most we can hope to do.

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Sadness’ and Disbelief From a World Missing American Leadership

The coronavirus pandemic is shaking bedrock assumptions about U.S. exceptionalism. This is perhaps the first global crisis in more than a century where no one is even looking for Washington to lead.

By Katrin Bennhold | Published April 23, 2020 Updated 5:06 a.m. ET | New York Times | Posted 23, 2020 |

BERLIN — As images of America’s overwhelmed hospital wards and snaking jobless lines have flickered across the world, people on the European side of the Atlantic are looking at the richest and most powerful nation in the world with disbelief.

“When people see these pictures of New York City they say, ‘How can this happen? How is this possible?’” said Henrik Enderlein, president of the Berlin-based Hertie School, a university focused on public policy. “We are all stunned. Look at the jobless lines. Twenty-two million,” he added.

“I feel a desperate sadness,” said Timothy Garton Ash, a professor of European history at Oxford University and a lifelong and ardent Atlanticist.

The pandemic sweeping the globe has done more than take lives and livelihoods from New Delhi to New York. It is shaking fundamental assumptions about American exceptionalism — the special role the United States played for decades after World War II as the reach of its values and power made it a global leader and example to the world.

Today it is leading in a different way: More than 840,000 Americans have been diagnosed with Covid-19 and at least 46,784 have died from it, more than anywhere else in the world.

As the calamity unfolds, President Trump and state governors are not only arguing over what to do, but also over who has the authority to do it. Mr. Trump has fomented protests against the safety measures urged by scientific advisers, misrepresented facts about the virus and the government response nearly daily, and this week used the virus to cut off the issuing of green cards to people seeking to emigrate to the United States.

“America has not done badly, it has done exceptionally badly,” said Dominique Moïsi, a political scientist and senior adviser at the Paris-based Institut Montaigne.

The pandemic has exposed the strengths and weaknesses of just about every society, Mr. Moïsi noted. It has demonstrated the strength of, and suppression of information by, an authoritarian Chinese state as it imposed a lockdown in the city of Wuhan. It has shown the value of Germany’s deep well of public trust and collective spirit, even as it has underscored the country’s reluctance to step up forcefully and lead Europe.

And in the United States, it has exposed two great weaknesses that, in the eyes of many Europeans, have compounded one another: the erratic leadership of Mr. Trump, who has devalued expertise and often refused to follow the advice of his scientific advisers, and the absence of a robust public health care system and social safety net.

“America prepared for the wrong kind of war,” Mr. Moïsi said. “It prepared for a new 9/11, but instead a virus came.”

“It raises the question: Has America become the wrong kind of power with the wrong kind of priorities?” he asked.

Ever since Mr. Trump moved into the White House and turned America First into his administration’s guiding mantra, Europeans have had to get used to the president’s casual willingness to risk decades-old alliances and rip up international agreements. Early on, he called NATO “obsolete” and withdrew U.S. support from the Paris climate agreement and the Iran nuclear deal.

But this is perhaps the first global crisis in more than a century where no one is even looking to the United States for leadership.

In Berlin, Germany’s foreign minister, Heiko Maas, has said as much.

China took “very authoritarian measures, while in the U.S., the virus was played down for a long time,” Mr. Maas recently told Der Spiegel magazine.

“These are two extremes, neither of which can be a model for Europe,” Mr. Maas said.

America once told a story of hope, and not just to Americans. West Germans like Mr. Maas, who grew up on the front line of the Cold War, knew that story by heart, and like many others in the world, believed it.

But nearly three decades later, America’s story is in trouble.

The country that defeated fascism in Europe 75 years ago next month, and defended democracy on the continent in the decades that followed, is doing a worse job of protecting its own citizens than many autocracies and democracies.

There is a special irony: Germany and South Korea, both products of enlightened postwar American leadership, have become potent examples of best practices in the coronavirus crisis.

But critics now see America failing not only to lead the world’s response, but letting down its own people as well.

“There is not only no global leadership, there is no national and no federal leadership in the United States,” said Ricardo Hausmann, director of the Growth Lab at Harvard’s Center for International Development. “In some sense this is the failure of leadership of the U.S. in the U.S.”

Of course, some countries in Europe have also been overwhelmed by the virus, with the number of dead from Covid-19 much higher as a percentage of the population in Italy, Spain and France than in the United States. But they were struck sooner and had less time to prepare and react.

The contrast between how the United States and Germany responded to the virus is particularly striking.

While Chancellor Angela Merkel has been criticized for not taking a forceful enough leadership role in Europe, Germany is being praised for a near-textbook response to the pandemic, at least by Western standards. That is thanks to a robust public health care system, but also a strategy of mass testing and trusted and effective political leadership.

Ms. Merkel has done what Mr. Trump has not. She has been clear and honest about the risks with voters and swift in her response. She has rallied all 16 state governors behind her. A trained physicist, she has followed scientific advice and learned from best practice elsewhere.

Not long ago, Ms. Merkel was considered a spent force, having announced that this would be her last term. Now her approval ratings are at 80 percent.

“She has the mind of a scientist and the heart of a pastor’s daughter,” Mr. Garton Ash said.

Mr. Trump, in a hurry to restart the economy in an election year, has appointed a panel of business executives to chart a course out of the lockdown.

Ms. Merkel, like everyone, would like to find a way out, too, but this week she warned Germans to remain cautious. She is listening to the advice of a multidisciplinary panel of 26 academics from Germany’s national academy of science. The panel includes not just medical experts and economists but also behavioral psychologists, education experts, sociologists, philosophers and constitutional experts.

“You need a holistic approach to this crisis,” said Gerald Haug, the academy’s president, who chairs the German panel. “Our politicians get that.”

A climatologist, Mr. Haug used to do research at Columbia University in New York.

The United States has some of the world’s best and brightest minds in science, he said. “The difference is, they’re not being listened to.”

“It’s a tragedy,” he added.

Some cautioned that the final history of how countries fare after the pandemic is still a long way from being written.

A pandemic is a very specific kind of stress test for political systems, said Mr. Garton Ash, the history professor. The military balance of power has not shifted at all. The United States remains the world’s largest economy. And it was entirely unclear what global region would be best equipped to kick-start growth after a deep recession.

“All of our economies are going to face a terrible test,” he said. “No one knows who will come out stronger at the end.”

Benjamin Haddad, a French researcher at the Atlantic Council, wrote that while the pandemic was testing U.S. leadership, it is “too soon to tell” if it would do long-term damage.

“It is possible that the United States will resort to unexpected resources, and at the same time find a form of national unity in its foreign policy regarding the strategic rivalry with China, which it has been lacking until now,” Mr. Haddad wrote.

There is another wild card in the short term, Mr. Moïsi pointed out. The United States has an election in November. That, and the aftermath of the deepest economic crisis since the 1930s, might also affect the course of history.

The Great Depression gave rise to America’s New Deal. Maybe the coronavirus will lead the United States to embrace a stronger public safety net and develop a national consensus for more accessible health care, Mr. Moïsi suggested.

“Europe’s social democratic systems are not only more human, they leave us better prepared and fit to deal with a crisis like this than the more brutal capitalistic system in the United States,” Mr. Moïsi said.

The current crisis, some fear, could act like an accelerator of history, speeding up a decline in influence of both the United States and Europe.

“Sometime in 2021 we come out of this crisis and we will be in 2030,” said Mr. Moïsi. “There will be more Asia in the world and less West.”

Mr. Garton Ash said that the United States should take an urgent warning from a long line of empires that rose and fell.

“To a historian it’s nothing new, that’s what happens,” said Mr. Garton Ash. “It’s a very familiar story in world history that after a certain amount of time a power declines.”

“You accumulate problems, and because you’re such a strong player, you can carry these dysfunctionalities for a long time,” he said. “Until something happens and you can’t anymore.”

_____

Christopher F. Schuetze contributed reporting from Berlin and Constant Méheut from Paris.

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