Trispero

by Sean Adelman

Jason walked over to the experimental group habitat. There was nothing special. They were normal-appearing mice, all huddled in one corner seemingly content. Not sure what Ed wants me to see. Doing as Ed instructed, he checked on the control habitat before speaking. What the heck? The control habitat was the same size, but there were fewer than half the mice and they all seemed much smaller. The only thing that was similar was that they were huddled in one of the corners similar to the experimental group. He then looked at the other groups and noticed that the mice in all of those habitats were scattered. They would group in small groups, but not like the trisomy population.

  “Uh, the controls clearly have not done as well, and the trisomy groups want to stay together more than the other populations.”

  “Correct. The control trisomy population typically loses 30-50% due to attrition from cardiac defects, but mostly they are somewhat ostracized. They just don’t get to the food and water and get picked on by the other mice. So before they are old enough to isolate, we typically lose a bunch of them. That’s the normal state of affairs. That’s not even the most interesting finding. Guess what I found last week when I came in.”

  “I’d say mice, but I think you may not appreciate that.”

  “You’d be correct about that. No, the trisomy experimental population was mostly gone.”

  “Someone took them, for testing or a mistake?”

  “No Jason, most of them escaped. We actually found them in a cabinet in the break area.”

  “I don’t understand. How did they get out?”

  “It’ll be easier to show you.”

  Ed walked Jason over to a terminal and sat down to log in. Jason watched intently, curious as to what Ed was up to. He became even more confused when Ed opened up security footage of the lab. Jason crept closer to watch. It was grainy but clear enough to see. The mice had formed a mouse ladder on top of each other, and the mouse on top had something in its mouth. It took a minute or two but the lid opened and remaining mice scurried up the makeshift ladder. There were only three mice left when all was said and done.

  Jason hardly knew what to say, so he simply replied, “Oh my.”

  “I know it seems hard to believe, but it gets even more interesting. As I reviewed the security footage for the previous several weeks, I noticed that the escape was calculated. They tried something different each night, finally getting to the door. It then took them the rest of the week to figure out how to get out after creating the ladder. I was so fascinated that I tested them with our maze test. Individually, they are smarter than the other mice, but not off the charts. What’s different was their ability to work together. When you team them up they far exceed the other mice in terms of problem solving.”

  “As amazing as this is, it actually fits with my theory. The proteins we have isolated don’t seem to have accomplished a whole lot in their own right as enzymes or direct mediators. I think that is because they are trans-acting proteins. They don’t code for building block genes; they code for a gene that changes the blueprint of several genes on the 21st chromosome. Trans-acting proteins could influence alternative splicing of the existing genes. We could be seeing an evolution due to the reorganization of some of the regulator proteins we’ve been measuring.”

  “So these trans-acting proteins are changing several of our genes, if only slightly. It makes sense, and since we know some of the regulatory proteins involved we can test this.”

  “Exactly.”

  “Jason, I think we have some interesting information for Gerald.”

  27

  ANN ARBOR—2015

  Debbie was good at writing programs, but better at seeing their faults and making the programs dance. It had taken a year to get this position so she was doing everything she could to make it work. Today she was reviewing the security protocols for Gibson’s research arm. She didn’t write all of the software, but she did know all of the holes, which is why she was here. Debbie spent the day in front of the computer trying to break through the company’s firewalls. It’s time to go. I need to get out of this place. I have plenty of data for the presentation tomorrow.

  She locked everything up and downloaded her data onto a removable storage device that she kept secure. She kept an isolated copy for the same reason they hired her. She didn’t trust their security. After securing everything, she grabbed her bag to leave the building. Debbie’s apartment was an easy walk and it was a pretty day so she hadn’t even put her coat on this morning. Nothing like some sun and a beautiful day to make it seem like the day wasn’t so bad. I think I might ride my bike downtown tonight. Her apartment was on the second floor and was filled with people that worked with Gibson Labs or were grad students at the university. She set down her bag and changed her clothes before taking her bike downstairs.

  Debbie had been so focused on having everything ready for tomorrow she couldn’t even remember if she’d had lunch or not. As she got close to downtown, she was sure the traffic going by her could hear her stomach growling. Debbie rounded the corner off of Plymouth that led over a bridge onto a cobblestone street that ran right by Zingermans Deli. I earned a sandwich today. She parked her bike and got into line for a sandwich. She would usually get takeout because she hated eating in a restaurant by herself, but tonight she would sit outside and enjoy herself.

  Conrad Gibson was sitting in his office with his colleague Henry Geller. He had just received another anonymous email and was furious. “We have to discover who is doing this, Henry.”

  “I suspect someone inside our system is blackmailing us, Gibson. It’s playing like a bad movie. They haven’t asked for anything, right? They’ve just been sending us information. Information that only three people in the world should know about.”

  Gibson was able to get himself under control. “We’re meeting with Erin Sydney, the security consultant you hired, tomorrow. She’s confident that she can resolve this. The information they have stolen from us so far has been problematic, but not something damning or vital to our business. Have you actually met this woman before Henry? I’ve spoken with her on many occasions but not yet met with her.”

  “I interviewed her briefly. She has impressive credentials and a personal reference from Gerald Wilson. She has been every bit as good as billed, which is why this is not the first time we have hired her consulting company. However, this is the first time we have had her do work on our internal servers. I thought it was about time given the recent events.”

  “I’m afraid you are correct, Henry. We shall see tomorrow.”

  With a full stomach, Debbie made her way back to the apartment. After hanging her bike up on the wall, she lay down on the couch before finishing the evening’s work. Her laptop was on the coffee table, so it didn’t take much effort to sit up and do a little work. After sending a few emails and secure messages to a few of her contacts via the secure software program she came up with, she decided she’d done enough for the evening. She lived in a one-bedroom apartment, so she could get to any room in the apartment in just a few steps. She looked in the bathroom mirror to remove her contacts. I think dark hair suits me. I certainly look younger. Even after a year she didn’t completely feel like she was looking at herself in the mirror anymore.

  After a glass of wine and her favorite book, sleep gracefully caught her. Fortunately it was after she was in bed. Waking up on the couch was rarely a good start to the day.

  Morning caught up with Debbie without incident. Usually since she worked mainly by herself in the computer room she rarely had to dress for anyone. Since Debbie was meeting with the boss today, she made sure that she looked at least remotely presentable. After getting dressed, she grabbed her coat and headed in.

  The administration building was where she was going to meet with them. The only time she had been in this building before was to have a brief meeting with a man named Geller before they hired her company. Since she was technically a consultant, she always had to jump through some extra security hoops. After giving her ID
to the security guard, he called. After what seemed like ten minutes had passed, he allowed her to go the third floor conference room. The man she knew as Geller introduced her to Gibson and she pulled up her data from the previous day’s attempts to break through their firewall.

  “Dr. Gibson, here are the results of my research into your system yesterday. I made twenty separate attempts using different entry points and different methods. I was able to gain access five times and break the encryption twice. I did not download or disturb any information as instructed and was supervised at all times.”

  “How long did it take you?” asked Gibson.

  “Two hours total.”

  Gibson’s face reddened. “You mean in two hours you launched yourself at us twenty times and got through five times?”

  “Yes, but I only broke the encryption twice.”

  He could barely control his anger as he leaned toward her and pounded his desk. “What do we need to do to fix this?”

  Debbie was ready. “In the interest of efficiency, I have typed up a proposal which is currently sitting in front of you. Given the concerns, I didn’t want to post this within your system.”

  Gibson looked over at Mr. Geller. “Give Miss Sydney whatever she wants to fix this.”

  “Thank you, Dr. Gibson. I’m confident I’ll be able to deliver on everything I’ve promised you. Mr. Geller, here is a list of what I will need from you to complete my contract. Most of these items are access issues and software that you already have. I know the software developer who created your security and have already spoken with him. With your permission, I will begin immediately.”

  “Of course, Ms. Sydney. Our security lead here will oversee everything you do when working on the firewall for our archives as a security precaution.”

  “I would have expected nothing less.”

  28

  DENVER—2015

  The remainder of the week since Jason had the meeting with Ed was a marathon in information-gathering for him, so Judy barely saw him all week. He spoke with both her and Lily about his hectic schedule, so they knew it was going to be like this until they met with Anne and Gerald on Friday.

  Judy had plenty of time to think about the lunch she had shared with Jason. It was terrible timing; she should have waited. The thoughts of what she should have done ran through her head again and again as the week wore on with almost no communication with Jason.

  Finally, it was Friday. Judy would drop Lily off at school then meet Jason, Anne, and Gerald back at the lab. Jason had spoken a little about it this week, but not enough for her to get the big picture. As she dropped Lily off at school, anxiety made it hard to work the clutch in her old car as her legs began to shake. Traffic was terrible, so she dropped off the car at the condo so she could walk to the university. Despite hurrying, she was the last person to arrive. Gerald and Anne were both having a cup of coffee when she walked up to the science building.

  Judy smiled as she walked toward the building. “Hello, Anne, Gerald. Are you guys ready to go see what Jason and Ed have for us today?”

  Just as they turned to go into the building, they almost ran into Jason who was almost bouncing with excitement. “Come on guys, I got one of my final assays in last night, so we’ve lots to talk about.” As Jason led them upstairs, Judy noticed that both Anne and Gerald looked at each other, trying to suppress their emotions as much as possible. The elevator ride was very quiet as all four of them stood in silence. As they exited the elevator, Ed was waiting for them.

  “Okay, guys, I’m going to give you my run through, then Jason will close with his data,” Ed said. “Afterwards, we can all voice our thoughts.”

  Ed led them around the corner to the animal portion of the room and began his talk.

  “I have four populations of animals with a genetic anomaly we want to look at. Each population has forty mice. Twenty of those mice are our experimental group that we inserted our gene into, and twenty of the mice have the anomaly but do not have our gene. One of our populations has a defect in T cell function, one of our populations has a gene that makes them very prone to certain cancers, one has a gene that makes them get Alzheimer’s very early in life, and one population is a model of trisomy 21, or what we call Down syndrome in humans. Each population of mice has two groups—a control and experimental group—that we have inserted the new gene we derived from Lily’s chromosome as I mentioned earlier. What makes the extra DNA from Lily now a gene is that we have inserted a starter sequence so that it is actually coded as a gene now, whereas before it was just uncoded extra DNA.

  “The first population we have here is the immunodeficiency population. We exposed each to a variety of bacteria, virus, and parasites. The control group had a 50% infection rate with each vector and a mortality of 90% which means only two of the twenty mice survived. The experimental group is over here and had a total infection rate of 25% and only two mice exhibited any symptoms whatsoever that were mild at best. The control group performed exactly as expected according to data from previous experiments, which means all of these mice survived.”

  Ed held his hand up. “Please hold questions until we are done.”

  “The next population was our cancer population. In the control group without the gene, 75% or fifteen of our mice contracted sarcomas. In contrast, no identifiable tumors were isolated in the experimental group. In the Alzheimer’s population, 10% or two of the mice in the experimental group exhibit delayed mental function with no progression of disease. In the control group without the gene, 80% or sixteen of the mice exhibited mental delay. All of the sixteen affected control mice with mental delays appear to be progressive, and eight mice have now expired.”

  Ed walked around the room and Judy caught the silent exchange between Ed and Jason. Jason looked like he could barely control his excitement at watching the others absorb the information.

  “Now the interesting part,” Ed continued. “Look at these two habitats, Anne. Tell me what you see.”

  Ann was visibly nervous. “Why me?”

  “Because I like you, and Judy already knows this part.”

  “Okay, I’ll try. This group seems normal. Nothing special, normal size. I don’t know how many are supposed to be there, but they all seem to be there. In the other group, it seems there are less than half the mice and they’re much smaller and skinnier.”

  “Yes, very astute. So the small mice are part of the control group and they don’t have the gene. Those poor things just don’t do as well. They are shunned and many don’t survive. The main thing they have in common is how they huddle together, which is why you had trouble counting, Anne. Lastly, instead of just going through my spiel, I am just going to show you the video. Jason, lights.

  On a portable screen, Ed played the same security video he had played Jason. He then played the previous weeks’ videos.

  Everyone sat in stunned silence for a moment after watching the video. Anne spoke first. “You fixed their immune system?” Judy realized she must have been thinking of young Jerry and his compromised health problems.

  “Not exactly, Anne, but I think the net effect is a better immune system. Let’s have Jason finish now.”

  “Thanks, Ed. First off, we had trouble attributing all of this to one protein that functioned as an enzyme or bonded with a receptor that could explain this, so after much research and thought, we postulated that it is a trans-acting protein. It affects alternative splicing so that a single gene can code for multiple proteins. In this case potentially more than one gene. These proteins typically work by allowing certain parts of genes to be skipped so that when the messenger RNA is made, it makes a slightly different protein.”

  “English, please,” said Gerald.

  “We believe that the protein we discovered helps edit the genes on the 21st chromosome to be slightly different. That is how one protein is affecting more than one function.”

  “Can you test, or prove this?” asked Gerald.

  “Great question, and t
he answer is, sort of. We’ve been able to isolate the T cells in both the immune-compromised mice and cancer mice from the experimental groups. They don’t express any of the receptors we see in the genetically-engineered, tumor-targeting cells already in production. By that, I mean the T cells we use now for treatment are normal T cells that we have programmed to attack certain receptors for specific cancers. We don’t see any of these very specific things in our experimental mice. These T cells are, for lack of a better word, ramped up super T cells. They certainly won’t cure all cancers or infections, but definitely make it much less likely. With the Alzheimer’s mice, the gene is inserted right next to the Mir-155 gene which is thought to decrease a protein called SNX27, a protein that the brain needs to make its neurons fire properly. This gene regulates how much SNX27 is available, so in people with Down syndrome they have extra Mir-155 which we think affects mental function and plays a role in Alzheimer’s. Our gene inhibits function of Mir-155 and actually increases the effect of SNX27 in our trisomy mice. Sooo, our experimental mice have improved mental function and better immune systems.

  “Now that I’ve told you some of what I think, I want you to tell me why you think our trisomy mice were able to do what you saw. Judy?”

  “They are clearly better problem solvers. Watching the time course over the week, they went through a trial-and-error process.”

  “Very astute, but…”

  “Oh man, there is always a but.”

  “But, even though they were clearly better problem solvers, they were not astronomically smarter, not enough to explain this leap. When you watched the final escape, what was unique about their method?”

  “They formed a ladder: a mouse ladder,” said Judy.

  “They worked together. When a group of intelligent beings works together without thought of the personal gain, only working toward a common goal, amazing things can happen. Somewhere on the 21st chromosome is the gene for empathy. The protein affects brain function and improves the immune system. The empathy factor is unique to trisomy 21. We made tough, smart mice who care about each other.”