ed_LabDreams Episode 1 Script as of 9-29-13 [Opening Title] LabDreams Science in a Story Antibody Evolution Machine, Episode 1 [Intro Animation] [Intro music] AI voice, software interface shows map [chill, techno/technologyish music, ambient] ‘ Origin: EB(Emerging Bio) Biotech Facility, Seattle, WA: 10.28.2020 ...international laboratory designing commercial products using gene therapy, cancer vaccines, synthetic biology and the development of improved bioinformatic techniques. Black Dawn log ************* Records of Interest Init. 2.19.2018 Arlington Group, private investors, commissions EB pathology department’s development of classified bioweapon. Weaponized agent based on rabies virus, and modified to investor’s needs. [scrolls through list of records] Record Record Record Record [stops suddenly, focuses on details] Infection Report 2.01.2019 0600 emp id #00978 …………………… infection rate %.001………………status: contained 2.02.2019 0600 emp id #00231 emp id #00233 emp id #00234 …………………… infection rate %.002………………status: contained 2.02.2019 0700 emp id #00138 emp id #00163 emp id #01534 emp id #00678 emp id #00183 emp id #00234 …………………… infection rate %.01………………status: contained 2.02.2019 0900 Subject infection rate %.2 2.02.2019 1200 Subject infection rate %2 2.02.2019 1210 Outbreak 3.01.2019 Quarantine in effect Isolated lab teams continue Black Dawn research and development EB mode and conduct shifts under radar Note sent out to EB personnel on 3.01.2019: EB asks for your patience and cooperation in solving the issue of outbreak. Termination of all infected personnel will be inappropriate, until a cure for the illness can be developed. Remaining uninfected personnel are instructed to exercise personal discretion, as to when termination is unavoidable… Observations: “Victims” of the virus are continually referred to as “zombies”, by many remaining, uninfected EB staff members. This is due to the zombie’s rabid nature and resemblance to the pop culture icons. ...Humans and their ever-present need to over-simplify and label phenomena. Perhaps sacrificing scientific terminology for that of pop-culture is fitting, for these organics. Present- Surveillance camera POV shows Emily and Derek lounging in front of lab equipment and computer monitors (eating something, the conversation pauses mid bite.) Derek: So, the other day, I was looking around the Internet at physics stuff. You know, quantum and particle physics... I started asking the obligatory, “existential” questions: (A bit mocking) “Why does anything exist”? Seriously, why are there any particles or particle interactions at all? Even if you take religion’s perspective and say that a god made everything, that still doesn’t tell you “who made God” or “why anything exists”. Of course there are questions we’re never gonna answer, but what else are we going to do… besides work, I mean. Emily: (laughs) Hmmm. . that reminds me about that book A New Kind of Science? Did you ever read that? Derek: No, but you mentioned it the other day. Emily: It really got me thinking about these “existential” questions, as you call them. It has a lot to say about existence in general, and challenges many of the basic precepts of science. Derek: OK, first of all: You don’t get to correct me! I already put “air quotes” around existential. Second: Why you gotta’ be a jerk all the time? Third: …continue. (Hands motioning forward) Emily: (Pauses and sighs at her brother’s difficult nature) Anyway, the book is written by Stephen Wolfram, who was the driving force behind Mathematica- Derek: Yeah, Wolfram/Alpha. Emily: Exactly. Anyway, in A New Kind of Science- Derek: Does Wolfram pay you a stipend, every time you mention the name of his book? Emily: (Pause) Anyway, in… Wolfram’s book. (Shoots a sharp look at a satisfied Derek) he shows how insanely complex behavior can emerge from extremely simple systems. There are literally hundreds of renderings of these cellular automata in this book, represented by black and white squares that interact with each other according to simple rules. i.e.: if you’re a square and you have two neighboring squares that are black, you turn white in the next turn step. Some rules lead to very uninteresting results, i.e.: everything is just one black square. Conversely, some rules lead to very interesting results. Some are so interesting; in fact, they have been proven to be Turing Complete. In other words- Derek: Computationally universal, yeah, unlike our friend Steve, I went to college. Emily: (through her chuckles.) Steve went to College. Derek: How many box-tops did he have to redeem for his diploma? (chuckles a bit) Seriously, has anyone actually seen it? Karl Sagan is one the references listed on my resume, you know. (Emily is still laughing, they clearly think they are smarter than Steve.) (Bringing it back) Anyway, they can perform any computation that can be computed aaand… Emily: (recovering and continuing from Derek’s “and”) Wolfram’s argument is similar to the concept of digital physics; which states that the fundamental basis of physics is not energy or matter, but information. Wolfram expounds on this concept, saying that our universe is basically one big computation. That it may be very similar to one of these cellular automata. Derek: This is seriously interesting (kind of snaps out of it) but this doesn’t answer why anything exist at all? (More genuine than before) Emily: Well, Wolfram draws a parallel between these cellular automata and universes: Maybe there are many universes and they all follow different, simple rules. Some of these universes would be very uninteresting and even die out, forcing the pattern to stop computation. Conversely, (a bit proud of her parallel) some of these universes are so interesting, that intricate, complex and beautiful behavior emerge. Derek: That’s some serious sentencing you did there. Let’s see if I am tracking you. So, there are as many sets of these rules as there are universes? Emily: Correct. Derek: Yes. With my help, even Steve could understand your scientific tirades! Steve: (Voice crackling over the computer speakers) Yeah, I got it. Derek: (Beat, then as fast as he can compose his shock) Steeeeeeeeve! We were just talking about you! Steve: (Still deadpan) the channel’s open... (Physically uncomfortable reactions from Emily and Derek) ...and I’ve reached the target point. Derek: (Trying to make up for getting caught, being an asshole) Zombies cause you any trouble? You alright? Steve: I managed. (Audible pounding and racket is heard over the com) Derek: Wait, are they in there with you?! (A bit panicked) Steve: Relax, Cupcake, they are on the other side of the door. The AEM looks OK, and I have the vile. Someone wanna tell me what I’m supposed to do with it? Derek: Didn’t Jeff tell you, when he gave you the vile? Steve: Not all of us have time to sit and chat about physics, Ladies. Just tell me what goes where and we can be done with this. Claire: (Enters the computer room with Derek and Emily during Steve’s last line. Leaning over the top on Derek, to get closer to the com) Steve! You made it! Steve: (Getting a tad frustrated about not getting an answer, but instead another person to waste his time.) Yeah, what do I do with the vile? Claire: Well, I’ll fill you in. In the room you’re in, is the Antibody Evolution Machine, or AEM. It’s still in working order, right? Steve: (grumbly man noise) Looks OK. Claire: (small sigh of relief) Good. This device allows you to insert any protein, antigen or virus into the machine, and it will produce an antibody that binds to it. Steve: I’m a little rusty on my immunology. Can you clarify a bit, so I know what to do with this thing? Claire: Yes, certainly. (Moving Derek out of his seat, and sitting in it, almost reflexively. Derek obliges and is used to this type of behavior from Claire, by now, but not altogether happy about it. He then leans against some of the equipment, so as not to look unimportant. Emily smiles at this.) Your body usually produces antibodies to target antigens in a virus or bacteria already. That’s how vaccines work. You can inject a person with a protein or virus, and their immune system will go through a process of rearrangement, mutation, and selection to produce an antibody that can bind to the target and neutralize harmful pathogens. Steve: Ok, so- Claire: But, before you know what antibodies do, you have to know what they are. Antibodies have different components. They have two heavy chains connected to two light chains through disulphide bonds. The whole molecule forms sort of a “Y” shape. Like two limbs coming out of a trunk. The tips of the limbs contain the part that actually binds to antigens. This segment contains a “hyper-variable” region. The genes that code for this “hyper-variable” region are the genes that undergo a lot of the rearrangement, mutation and selection, to produce different structures that can bind to different antigens. Steve: What abou- Claire: There are three main segments to the “hyper-variable” region on the heavy chain: the V, D, and J segments. (CS) There are many variants in each lettered segment, so when the segments combine, they form a different antibody with each variant combination. These variants can also be mutated to produce a whole new variant. But the light chain just has a V and a J segment with no D segment. Steve: Um look- Anyway, normally your body just rearranges, mutates and simulates all of these segments with many different cells that produce antibodies-sometimes called B cells-to find an antibody that (CS)has the right “lock” to fit the pathogens “key”. The AEM is used when a patient can’t produce their own antibody. For example, if there is a snake bite the venom will affect the patient much faster than they could ever produce an antibody to save their lives. In these situations you can produce antibodies against the snake venom in another animal and then inject this into the human. We’ve tried to weaken our zombie virus and inject it into animals to produce the antibody, but the virus weakens the immune system of the victims too quickly for us to get anything useful. Our human zombies are also not producing any antibodies or recovering either. Therefore, we use this machine to do what the human body would normally do. We have it produce the antibodies against the zombie virus artificially, and then inject our “Vaccine” into some of the zombies to see if we can cure them. Steve: So the- Claire: We’re not entirely sure, of course, if it will cure them, but you should know how it works-if it does. It produces artificial arrangements, mutations and selections of V, D, and J DNA. Then it translates this into protein in vitro. The final antibody product is then screened against the protein using SPR which stands for Surface Plasmon Resonance. SPR is really complicated and I don’t have time to delve into too much detail, but basically, when something binds to the protein which is on a surface, this change of mass can be detected. It can also then determine the affinity, which is how tightly the antibody binds.The antibodies with the highest affinities are the ones that are most evolutionarily fit and they are chosen as the basis of the next round of rearrangement, mutation, and selection. Steve: (Waits a beat) So the virus is in the vial Jeff gave me, we put it into the AEM and a vaccine comes out? Claire: Essentially, yes. Steve: (calm, but a bit irritated) Next time, say that. You know, if I die, and you have to train a new “Pathology Go-fer”. That’s what you called me yesterday, right, Derek? Derek: (Claire shoots him a look, as Emily looks quite uncomfortable) Yah…(awkwardly laughing) weh-uh Lots-I got lots of jokes. You should hear what I call myself. Steve: (deadpan, challenging) What do you call yourself, Derek? Claire: Boys. We don’t know how long the virus will stay intact without proper preservation techniques. Let’s get the AEM operational and get you, Steve, to safety then you two can compare the length of your respective manhood in person. End of part one Steve: So what do I have to do? I’m sure the AEM doesn’t just fire up. Emily: Well, uh, no. There are some preliminary power output protocols you can run, by flipping the three switches underneath the main LCD, on your right side. You should then be able to follow the instructions on the screen, (her voice begins to gradually trail off.) until it asks you for a password. Steve: What’s that? You say password? Emily: Y-yes. I did. Steve: (Knowing the answer, already based on Emily’s behavior.) Well Emily, what’s the password. (Waits a beat) You don’t know the password, do you? (Waits another beat) Emily, you got 10 seconds to give me somethin’, before I lose it and just drink the damn vile. Emily: (Typing at a feverish pace on her computer, stammering a bit) A-alright, I know that Osaka, set the password to be the sequence of the restriction enzyme site for the SfiI enzyme, in a plasmid sequence. SfiI sites have a pattern like: GGCCNNNNNGGCC where, unfortunately, the Ns can be any DNA base pair at all. We need to find out what these Ns are, in that plasmid sequence Osaka was working with. Steve: Who’s this Osaka guy, and why don’t we just ask him? Claire: Osaka Muramaki was the lead engineer on the AEM project, and currently a zombie sooo… Emily: (Muttering to herself while working seriously at the computer) Ok, so I can’t just do a search for “GGCC” in the text file, because there are too many GGCC sequences throughout the whole plasmid that I would have to search through. So I’ll need to use a regular expression to find the sequence you’re looking for. Steve: (Sarcastically.) Sounds great Emily. Emily: (Uncomfortably jabbering) Uh, yeah... a regular expression is just a more sophisticated form of search. It's special because it matches patterns instead of exact text strings like normal. Steve: That’s riveting stuff, Lady. Emily: (Uncomfortable silence. Looks to Derek, Derek shrugs, then more muttering) What I’ll need to do is open up the text file with the plasmid sequence stored on the cloud, Then copy and paste that into the text box of a website called regexr. Okaaaay… done. Now, I just search for the string “ggcc\w{5}ggcc”. The “\w” regular expression token matches any word character, and the “{5}” designates how many times the previous token needs to be matched. When you put it all together this should match the site we’re looking for. Got it! Its “ggcccagccggcc” Steve: (Pause to indicate the password being entered) ‘Kay, I entered the password. Oh good, it’s loading. It looks like more quality time with the gang. Derek: (Emily turns back over to Derek) (long pause, then exhales) So, Wolfram? Emily: Well, I did have a few more things to say on the matter. Claire: Ughhh. Are you two having another one of your pointless conversations again? Matt: They’re not pointless. They’re interesting and enlightening. (chuckles) Claire: Whatever you say. I'm going for coffee. Anyone want anything? Derek: Nope. Thanks. Matt: Sure. Steve: Black. Claire: (Laughs like a dork, but genuinely, she just laughs like a dork) Good one, Steve. (Continues to chuckle a bit, out the door.) Derek: (A bit Irritated that Steve made Claire laugh. HE is supposed to be the funny guy. Derek switches the com feed off.) So what did you want to say? Emily: (to Derek) Oh yeah. (deep breath, and begins) Since we know that things do exist, once we accept that, we have to decide what they should exist for. For example: what should we be doing? What is the purpose of our lives? There are many different people, who say myriad things on this matter, but I find it most interesting when people say that the purpose of life is to maintain life or to create more life. Think about that. (Pauses for effect) Humans want to be as happy as it is possible, for the longest amount of time possible, correct? However, in order to experience happiness you have to be alive and capable of experiencing an entire gradient of emotion. Derek: Wait, why do you have to be able to experience the negatives? What if I want to be happy forever!? I should be able to do that. Emily: You should, however improbable that may be to execute, but you’re forgetting that it is not even possible to experience happiness unless there is also some level of an alternative. Some level of resistance. Life is in a constant state of flux; a state of non-equilibrium that is trying to maintain itself away from some of the more homogeneous equilibrium states in the universe. I. e.: a room full of air which is not really hard to maintain, because it’s already reached equilibrium. But, there’s a problem: the ordered state that life tries to maintain is delicate, even tenuous. When you attempt to input order into anything that is constantly changing and shifting, it is going to be quite difficult to do and can even end in complete failure. In this case, failure would result in death. A finite game is playing to win, but an infinite game is continuing to play. But, I- Derek: Hold on. Did you just paraphrase Kevin Kelly? Don’t take credit for that, Sis! Thought you could slip one past your dolt of a brother, huh? Ugh. Stop being too on top of it! Anyway, I think, the resistance of this death, the pursuit of maintaining life, making more life and progressing, this whole process of evolution that we are fighting through, is what life is really about. That’s what resonates most with me. This pursuit is our only chance at experiencing happiness. Derek: Wow. That is astonishingly one-sided of you, Sis. (Claire walks back into the room with the coffee. Derek immediately flips the com back on. Claire Gives Emily her cup.) Emily: We’ll finish this later (narrows her eyes at her brother.) Claire: Has the AEM come online, yet? Steve: Still loading. Claire (to Emily and Derek): I can’t believe you two can spend so much time talking about physics and philosophy in situations like this. You know that Steve is in a room surrounded by violent infected virus victims, right? Derek: Oh come on Claire. Steve can take care of himself, he’s more than capable. (Claire makes a face like “Your probably right,”)We’ve been dealing with this zombie outbreak for about a year and a half now. There isn’t much we haven’t seen, Claire. Plus, you have Emily and me to keep everything in working order and running smoothly. (Knowing where Steve’s talents really lie, but downplaying them for comic effect.) Plus, I guess Steve. Steve: (More deadpan sarcasm) I feel pretty safe, with you two around. Claire: (pushing past those comments) Wait, what exactly happened, a year and a half ago, Derek? Derek: That’s right you transferred here a couple of months ago. They probably weren’t really big on orientation when you got here. I know they aren’t now. Well, come, sit down and I’ll tell you the whole story: (like he is telling a fairy tale to a child.) Once upon a time, there was a bio-weapons department of a tiny, little science company in Seattle, called Emerging Bio, and- Claire: (laughing) Stop it, you fool! Just tell me what happened. Derek: The pathology (Don’t know what department would be working on this.) department, was working on a job for The Arlington Group, and they wanted a bio-weapon with a few specific abilities. Basically, they took the rabies virus and then modified it a bit. The virus could infect people, but they wouldn’t have any adverse affects from the disease or any symptoms until they received a certain chemical compound, from another source. It could be in the water supply, or an air purification system; however you want to get the final viral component of the disease, to the victims. Once the virus was activated the people would become something out of a George A. Romero flick. Hence, everyone calling them zombies. Whoever transferred fluids with the victims, would contract the virus as well. From what I understand, Pathology was also trying to make the virus very addressable so that it could target very specific tissues or race groups based on something unique about their genome. The idea was to eventually hone the virus to be capable of targeting individuals for assassination. I don’t think they got very far with the “addressable” part of the virus, though. You know, before something went horribly wrong and there was an outbreak in our facility. Claire: Interesting. I wonder how addressable they would have been able to make the virus. Targeting a specific genome seems like a very complicated process. Derek: Don’t know. You’re right though, that is super-sega-mega complicated. Maybe it has something to do with the specific virus they chose. At any rate, it doesn’t much matter, now. I think we can label the experiment a failure. Claire: But think of the opportunities for the future of immunology! If we can target a specific genome to infect someone, then we can probably also perform targeted gene therapy to cure virtually, anything! Derek: How about we start with the zombie virus we made out of depravity and negligence! Claire: (Laughs) Deal. Steve: (Almost under his breath) Damnit. Emily: Oh no, what’s wrong? Derek: (Starting to panic again.) Is there a zombie in there?! Steve: Jesus, Derek, stop trying to kill me off, already. I’m fine, but once it booted, and I loaded the vial, an error message tells me there’s a broken compressor. Emily: Are you serious?! Is there a contract someone signed that says NOTHING WILL WORK IN THIS FACILITY!? Derek: Settle Down, Em. (Looking around mock nervously) It will hear you. (Leaves joke, and moves on to more important matters) Steve, I think there’s a stockpile of instrument parts in the D wing. There might be a compressor that fits the AEM there, buuut… Steve: Yeah, D wing. Opposite end of the facility, got it. (Starts packing his things and getting ready to venture outside again.) Aren’t you guys closer to the D wing? One of you want to go risk your neck, for a change? Derek: Sorry Steve, your breakin’ up. Steve: (lightly chuckles) Keep coms open, in case I need anything. Claire: We’ll be here, good luck!