Counting Up To Infinity

by Allen Fleishman

  Janet: Excellent Josh. We’ll have to increase and eventually vary your repertoire but that should cover right now. I know it must not feel good acting like you don’t understand things, but we have to keep our secret.

  Joshua: OK mommy.

  Sidney: Joshie, we’ll be taking you to all of our meetings and letting you sit at the table off to one side. Would you mind doing something like scribbling into a pad or pretending you’re asleep? If you need to talk to us, you can transmit a message. However, we might not be able to answer you during the meeting. We can’t multi-process like you.

  ***

  Joshua: Mommy, what do you do at work?

  Janet: Josh, we’re working of preventing a very bad syndrome called LPH deficiency or Morgan’s Disease.

  Joshua: That’s what I have.

  Janet: Yes Josh. We’re trying to make sure you never get sick from it. All the people at the company have that as their primary goal - to help you, and kids like you.

  Joshua: What happens to the kids with LPH deficiency?

  Janet: Their neurons don’t fire correctly.

  Joshua: The axon and dendrite bodies lyse?

  Janet: Yes Joshie.

  Joshua: But what does that mean?

  Janet: For kids a lot older than you, they start to lose feeling in parts of their body, they may not be able to control their movements, and they will eventually get very, very sick.

  Joshua: Will I get very, very sick?

  Janet: We’re all working so you won’t. In many ways, your computer will be able to replace many of the sick nerve cells.

  Joshua: Will the LPHase you’re working on make the kids better?

  Janet: It will prevent them from getting sicker, but once the nerve cell dies, it can’t be made better again.

  Joshua: Will you be able to cure those kids who you give LPHase to?

  Janet: No, Joshua. We hope we can greatly slow the disease, but the body will never be able to produce the protein it needs to hurt the bad protein. It doesn’t know how to.

  Joshua: Why don’t you fix the body so it knows how to?

  Janet: No one understands the genetic code yet. We’re not even sure where the gene for LPH is. The DNA chromosomes are tinier than the tiniest pinhead, but if the DNA were unraveled, it would be six feet long. There are so many, many genes in it.

  Joshua: But mommy, you need to make people better. The LPHase won’t do that. Only by fixing the DNA would make them better.

  Janet: We think we might be able to do that in 30 to 50 years, but we don’t know enough right now?

  Joshua: Will LPHase keep me alive until then?

  Janet: Josh, I need to work right now. You have to let mommy work.

  Although Joshua was in a room away from Janet and Sidney, and even though Janet had turned her microphone off, Joshua’s sensitive auditory pick-up heard his mother cry. He knew enough to realize that he was going to die. His mother and father knew they would fail. Dying was like going to sleep. ‘Why is mommy so scared?’

  Joshua read a number of case histories of kids with LPH deficiency. He also read some medical files and the comments by the attending physicians on the steady deterioration of the young patients. Joshua read his own medical history and knew that the LPH protein was temporarily absent, but the destruction of his neural pathways could start tomorrow or ten years from now. But, it would start.

  Joshua started to translate some ancient Hittite documents. He went over David’s notes on how he first translated the text. He would then work on Easter Island’s Rongo-Rongo and ancient Egyptian funerary cones. No anthropologist had been able to translate these long dead languages. Teacher, his inline computer assistant and mentor, said these would be good starting practice exercises.

  ***

  The words Joshua wasn’t supposed to hear were transmitted very well by the ‘earphones’ all the staff had been given. It was actually a speaker, microphone, and camera, but only the inner circle knew its real functions. No one ever said anything about employee’s wasted time, or personal telephone calls. However, if an employee started to go onto a wrong track, or forgot to order some vital piece of equipment, one of the Ins would ‘just happen’ to bump into them in the hallway and give a slight nudge onto the correct track on why it was important.

  The ‘earphone’ also transmitted how Joshua seemed ‘very shy’, or he was ‘pathologically introverted’, ‘autistic’, or how he was ‘not at the correct developmental stage’, no doubt due to the ‘intervention’. Joshua continued to carry a large notebook, a recycled laboratory notebook, where he scribbled. At least it appeared to be scribbles. It was actually shorthand notation of his notes.

  ***

  The first study with LPHase was an unqualified success. No one died or got sick. The sick patients were given a single very low dose of LPHase to three patients and saw no pathologic laboratory values, no unexpected headaches, or other side effect. They then doubled the dose and repeated the administration to three new patients. They did this five times. No unusual problems were noticed. There was also a small, non-statistically significant, decrease in the LPH protein. With this small study, they didn’t expect to see effectiveness, only a hint of safety.

  A second study with the expected dose was now in the works. Forty children between the ages of 8 and 20 were given a slow intravenous infusion of LPHase and twenty were administered an identically appearing bag of saline – a placebo. The volunteers were given the intravenous bag of study material once every other week, each infusion lasted two hours. No one in the company or the clinics knew who was given what. It was a classic randomized placebo controlled trial. However, the doctors in the field saw some patients with no new LPH symptoms. Their old symptoms didn’t get better, but at least they weren’t getting worse, other patients continued their steady deterioration. Families traveled across continents to a hospital clinic in order to get the biweekly infusions and the check-up. The parents knew the alternative was their child would die. Even the parents whose child had increasing symptoms were staying in, because once the first six month part of the study was over, their child was assured they would receive the active drug, LPHase. It was either the treatment or inevitable death from the disease. Parents would do anything for their sons and daughters.

  ***

  Dr. Thiemann was the head of the chemistry department. He was sitting at the LPHase NDA progress meeting. The new drug application submission to the FDA was a couple of years away. His attendance was typically just a formality. He was thinking about cooking some Veal Scaloppini and what ingredients he needed to pick up at Harry’s Farmers Supermarket. Thiemann sat next to the six year old retarded boy. Joshua’s parents sat at the other end of the table. Joshua was invariably a silent little boy, immersed in his coloring or scribbling with his four crayons into the lab book that his parents had given him. Joshua was the unofficial mascot of the company. Many people rubbed his head for good luck as they past him in the halls. Joshua so quiet, and his movements so few, that by now most people completely forget he was at the meetings. As a diversion to the boring meeting, Dr. Thiemann occasionally glanced at the boy. Joshua seems to be completely absorbed by his scribbling. The only odd thing was the orderliness of many of the lines. It had almost seemed like the boy had used a ruler. Obviously it was his autism which created the perfectly up-and-down or side-to-side lines. He had read that autistic children rarely interacted with people and preferred their inner world.

  Out of the corner of his eye, Dr. Thiemann noticed a sudden twitch in the young boy. He turned to face Joshua. Rather than the invariably passive child, Joshua had a sudden and violent transformation. At first, the boy jumped from his seat. Joshua had a huge smile on his face. Thiemann turned and whispered, “What’s wrong?”

  Joshua said, “I did it. I did it. I did it. In twenty years from now.”

  Dr. Thiemann looked confused, “You figured somethin
g out in the future?”

  Joshua was about to say something, when he just said, “Oh. Being silly. Sorry.”

  Dr. Thiemann did not hear the simultaneous question from both Janet and Sidney, as they were transmitted by radio waves. Nor did he hear the reply of “Oh, nothing.” Thiemann only noticed Joshua staring at the wall lost in thought. At fourteen different places in the complex, at brilliance 84, computers were linked to focus on answering different aspects of the same question.

  ***

  Two days later, Joshua called a meeting of the Ins. Joshua had already determined that each of the six adults could talk without being interrupted.

  Joshua: I want to talk to you about something really, really important. Could you all close your office doors?

  Martin: What’s up Josh?

  Joshua: You know how David was able to translate ancient languages. Well I’ve been working on understanding a much older language, the human genome.

  Janet: Sweetheart, the Human genome is too big, even for you. There are three billion different DNA base-pairs, if you unraveled the DNA which is coiled 1/2500 of an inch across, it would be 6 feet long.

  Joshua: There are many letters, I know that, but they spell words, codons – many of them are used to give the body instructions on how to do things. Nevertheless, the instructions were done poorly. Any mutation that just repeats a code, without harming the person, is passed on. All the obsolete code, like having gills and a tail are passed on. Many sections have no real purpose. Other sections are repeated over, and over, and over many times. The parts that do work often have really bad code, like going from New York City to Boston by first stopping at Washington, Dallas, Washington, Dallas, Tokyo, Washington, Dallas, and Mexico City. It was kept because it worked. Sort of. Mommy, it was a very poor program written by ‘millions of blind drunken programmers’ over billions of years, it can be made much, much simpler. It’s never been proofread. It was never optimized. When you get rid of the useless code, it’s no larger than the code for Microsoft Word. I can make it more foolproof. I can make it so it fixes LPH Deficiency.

  David: Go on Josh.

  Sidney: Joshie, are you sure about this?

  Joshua: As sure as I’ve ever been dad. I’m positive dad. I’ve never been more certain of this than anything I’ve ever done.

  Sidney: It sounds like the proofread DNA would be very different from normal human DNA, shorter.

  Joshua: Actually about 1200 times shorter dad. And much faster to replicate too.

  Sidney: This is scary stuff. How would you change the DNA? Would you do it for only the nerve cells? I’m more concerned about all the details.

  Joshua: I’d have to change all DNA by having a DNA snipping machine attached to a retro-virus. We could also splice in some red blood cells so it would not get attacked by the body’s natural defenses. The virus would only have a life span of 2 days, by changing the Hayflick Limit to 28. The virus would also immediately die in the presence of light, especially ultra-violet light. I’ve worked it all out. The DNA snipping machine and the virus would only be merged in the very last phase of the manufacturing process. The virus can be killed in eleven different ways.

  Phyllis: Hayflick limit?

  Martin: Leonard Hayflick determined that many cells, like the lung cells have a limit of the number of times they can replicate. For lung cells, it’s 50. After that, well, the cell just ages. Sid, Janet, I’ve learned a long time ago to listen to David. This could be the biggest breakthrough in human history, if it works. If it fails, it could exterminate humanity and perhaps all life just as easily. I think we’re going to need to look at this VERY, VERY carefully.

  David: Let me check out Joshes assumptions.

  Janet: I have one and only one stipulation, before I’ll even think about thinking about it. Joshua you will not try it on yourself. I will not even consider it unless you promise this first Joshua.

  Joshua: Uh … But mommy, I won’t die. I can’t.

  Janet: YOU WILL NOT BE THE FIRST GUINEA PIG ON THIS. I’ve been in research too long to imagine the first attempt at anything, especially something this complex, could work the first time. I know how smart you are, but the experimental basic science was never done. You’d be guessing about most of it. If we consider this, it will be tested first on other people, terminal patients, who have no other hope. None! I will veto this otherwise. I want your solemn word here.

  Joshua: If it works then?

  Janet: Yes, maybe, just maybe, then. And only when I say so. Only then.

  Sidney: I agree with your mother on this. I also won’t consider it otherwise.

  Martin: Me too. Joshua give me your word of honor that we will experiment on only those that we unanimously agree on.

  Joshua: But Uncle Martin, it will work. I promise. OK

  Corey: I think we’re getting too far ahead of ourselves here. The first step is to see what Josh has done. What the new human genome actually does. We also must guarantee that the virus can be killed and dies very, very quickly, and the DNA machine can be killed and dies very, very quickly.

  David: I just checked out the snipping machine and virus. It’s like Joshua said, it looks like he had all things covered. It doesn’t just have redundancy to make sure it dies, it has eleven simultaneous independent systems to guarantee inactivation and destruction. Each one alone is at least 99.9999% fail-safe. Even factoring in all the viruses that would be created and all the cells affected, I’m completely satisfied that they would not replicate out of hand.

  Martin: OK, let’s do some preliminary work and see if the virus is feasible and if the DNA snipper can be produced. Josh, could you identify where in the DNA the LPH disease gene is located. I’ll arrange to get the DNA of a number of patients sampled to confirm you’re correct.

  Joshua: Mommy, can you give DeGrassi from Bacteriology/Virology the instructions on getting a sample of the retrovirus I found, something that is benign and dies easily. And also give him instruction on how to splice in the human red blood cell binding points. I’ll also create a process to mass produce the DNA snipper.

  ***

  Three months later another meeting was called.

  Corey: I did all the in-vitro work. I checked the virus that DeGrassi devised based on Joshua’s manipulations. The virus is a benign subspecies of the GVB-A virus. It would also die in the presence of any light greater than 20 lumen light at two feet. It was especially sensitive to the ultra-violet spectrum of 0.2 lumen. The virus is also very sensitive to any form of alcohol and oxygen. Oxygen concentrations greater than 1.12% would kill it. An alcohol concentration of 0.006% would bond to the virus and lyse it. I confirmed that inside the host, the virus divides 28 times. At the end of the 28th division, it completely stops dividing and can’t reproduce any more. Each cell division takes about 10 minutes, so it only becomes active at the end of 47 hours, give or take six hours. At the end of the 28th replication, the virus invades a cellular nucleus and activates the DNA replication process. In order to invade the nuclear boundary, the virus must shed its own sheath. The virus disintegrates at this point. From the seven-sided head of the virus with its left-handed flange and the shape of the DNA snipper machine, the snipper is designed to ‘ride’ this and only this virus. It cannot fit any other virus. David ran simulations with other virii and we tested the best candidates. None worked. The body lets the virus invade it and doesn’t offer any defensive reactions, no doubt due to the red blood cell shell. It replicates with the virus.

  The snipper is actually 23 machines, one specifically designed for each human chromosome. I took tissue samples and mixed them in a Petri dish. I tried it in other animals and in each case, it failed to activate, even with other primates. On insertion into a nucleus, it takes each part of the divided DNA and cuts, then bonds, a segment. Otherwise, in various places it replaces either one or more than one DNA sequence. I di
d this experiment with DNA from 900 different human cells. I even repeated the results with different races, and got identical results. The machine always cut the same sequence or inserted a single gene. The only exception was when I tried non-human species, where it failed to activate.

  I recommend that on the day of administration, the room be kept constantly bright. The patient should be covered in a light opaque covering, for example tin foil. All hospital personnel would wear type A hazmat suits and have a single glass of wine prior to coming in contact with the patient or the virus. All of the patient’s wastes should be mixed with alcohol prior to sterilization.

  The only negative I can come up with is that that I have no idea what the machine is doing. None at all. But whatever it does, it seems to work in 100% of the cases I tried it in.

  Martin: Both Sid and I tried to tackle the DNA aspect of things. We were able to confirm the DNA sequence. Five patients with LPH Deficiency had the faulty gene and ten normal patients didn’t. With the samples that Corey ran, it did not change the gene Josh identified in cell samples taken from normal patients, but only replaced the gene in patients who have LPH deficiency with a normal sequence. What else it’s doing, I have no idea.

  Janet: Josh, are you doing anything else besides treating LPH Deficiency?

  Joshua: Well, yes mom

  Janet: What else?

  Joshua: I’m also correcting the gene for hemophilia, sickle-cell anemia, Tay-sacks disease, Lou Gehrig’s Disease, Hunter’s disease, Gaucher disease, and a bunch of other inherited abnormalities?

  Martin: What? Are you crazy? Is that a good idea, to mix one treatment for many, many diseases?

  Joshua: Actually I thought it would be the best idea. One of the things that Natalie from the Regulatory department said was, ‘Once you get a product, the thing that slows you down the most is when you tinker with it. Never change anything in the manufacturing process; otherwise you’ll spend years redoing all your original studies.’ I’m just following her advice. We only will need to do the Phase I and II studies once.