Perfect Pathogen; Fatal Flaws in the Human Immune System

As my faithful readers may know, only about a dozen of which exist (what an exclusive club!) I am an evil mad scientist femboy supervillain. I have weekly battles against superheroes, all of which I have lost because good guys always win (never get discouraged though! 87th time’s the charm!).

But how would you know? As of yet, I’ve just used this blog to explain obscure science concepts. Until I inevitably conquer the planet and make my autobiography required reading, my loyal followers will have no way to know of my glorious exploits. 

No longer! I will give you an account of my misadventures through my completely objective narrative lens. In doing so, I will also both entertain and inform you as that’s the whole point of this blog.

Story:

“MWAHAHAHA! BEHOLD my perfect pathogen! The greatest bio weapon ever devised by man!” I said dramatically, wildly gesticulating towards a petri dish in a biosafety level 3 cabinet.

“Okay.” My lab assistant, Igorevich Ivanovsky, said.

Numerous times in history a disease brought humanity to its knees. And those were just weird mistakes of evolution. Well evolved diseases are more like the common cold. Parasites don’t want to kill everyone, they need us. So if nature can cause a pandemic by mistake, imagine what a disease could do if it were actually designed to do that?

“In my studies I’ve found flaws in the human immune system and created a germ to exploit every one of them! Then the WHO will have no choice but to call for another global lockdown!”

“But why?”

“I don’t like leaving the house, y’know?”

“So, how does it work?” Igorevich asked.

Igor is some kind of Eastern European going to university in America. He works as my lab assistant, and for free no less! I’ve always wanted a lab assistant named Igor. He thinks he’s here as a graduate student intern and I’m a professor that can get him a PhD. Of course, neither of these are true in any capacity, but university degrees are mostly for bragging rights and are not an accurate measure of anyone’s capacity for scientific evil. Though it does mean I have to mentor and explain things to him, which is a great excuse for exposition dumps.

“Well, for one, symptoms don’t show up until after a week of being infectious. That seems to have worked pretty well with SARS-CoV-19.”

SCIENCE!

A lot of the innate immune system works by detecting molecules that most bacteria, fungi, parasites, or viruses tend to have. There are about a thousand of them, plus mannose which has an entire system dedicated to it for some reason. So I just made sure that my pathogen uses none of those. 

The immune system can still notice it, but has way fewer ways to do that. There are Toll Like Receptors (TLRs) inside of cells that can detect viral RNA, but only one type of cell actually uses them so that’s not a huge problem.

The secondary immune response is a lot better. It can destroy basically anything, including you. To avoid that, it needs to develop special targeting molecules called antibodies that can tell the immune cells exactly what needs destroying.

“Blin, I know this. You think Igor sleep through basic immunology?” He doesn’t actually talk with that thick of an accent, I just like writing him like that.

“Silence, Igor!”

So the innate immune system depends on having molecules able to bind to and mark things that are expected to be on pathogens. Such as peptidoglycan which is found in the cell wall of most bacteria. But we only have about a thousand of these, which isn’t enough to cover all possible pathogens. So the adaptive immune system has a way of making new markers modularly so they can bind to practically anything. These are antibodies.

But the way these antibodies are made is very stupid. Basically, special cells called B Cells are made in the hundreds of millions every day in your body. They have numerous genes for slight variations of every part of the antibody. Mathematically speaking, there are about 1×10¹⁶ different combinations by combining these parts in different ways. That’s a 1 with 16 zeros after it.

The B cells design antibodies through somatic recombination, where they cut out huge swaths of their own DNA in order to bring the correct combination of genes together. The problem is that in the process of cutting out parts of the DNA to bring these together, you lose the genes in between. Because of this, that original 1×10¹⁶ goes down to just 1×10⁹, which is still a lot more than 1000, but not as good. 

Also, because they are changing their own DNA, if the cell makes an antibody that happens to also bind to your own cells, there aren’t many chances for it to ever make an antibody which doesn’t do that. So your body just kills all the ones that didn’t turn out, which is usually around 75%. And that’s after 50% of them die during the process of them editing their own DNA. Antibody development is a monstrously inefficient process and is a big part of why you get so tired when you’re sick.

“So why don’t the B-Cells just do that with RNA so they don’t lose so much DNA?”

I shrugged. “I dunno. The DNA thing happened to evolve first I guess. Evolution doesn’t select for what works best, it selects for whatever’s good enough.”

So basically, I just made sure to design my pathogen such that the antibodies that would bind to it the best are the impossible ones. So even when it does have an antibody out, it won’t stick very well. And most of the possible ones would also bind to your own cells meaning a lot more B-cells will have to die than normal.

NOT SCIENCE!

There are many other faults in the immune system, but I don’t have the time to mention them here. Believe me, there are a lot of them.

“I thought you want to take over world? How can you do that if everyone is dead?”

“Oh, no! This will only kill superheros and conservative-voting 65 to 72 year olds. Everyone else will just get a bad cough.”

Suddenly, I got a call from the front desk. “One moment, I gotta take this.” 

“Boss!” My evil minion receptionist cried, gunshots and screams of anguish clearly audible in the background. 

“Oh, hi Samanda! How are things?” I asked, winding the phone wire around my finger.

“Terrible, Boss! We’re under attack by a hero! They’ve broken through the first three lines of defense faster than we can fall back! Boss, what are we gonna do?”

I calmly told Samanda that it depends on which hero it is. I wasn’t worried. We’ve got contingency plans for all of them except Superguy. She said they were moving so quickly she couldn’t even recognize the costume.

“Don’t worry Samanda, just hold the line as long as you can. Fight valiantly! Never surrender, never give in!”

“I don’t get paid enough for this, you f-” She said before I dramatically hung up the phone. 

I commanded Igor to bring up the front lobby security camera. Freeze frame on the hero. Enhance.

He tells me to wait for a moment, then spends several moments connecting to the site ethernet on the shitty laptop we keep in the lab. He brings up the live security footage and pauses it revealing Superguy casually walking through my henchmen.

Superguy is Earth’s mightiest good guy. The icon of hope, or whatever. Despite looking exactly like a human and even being able to interbreed with humans, he’s actually an alien from the planet Neon. For whatever reason, this makes him completely indestructible and infinitely strong. He has no known weaknesses except for a deadly peanut allergy. (also colorful fragments of his home planet called neonite, but those mostly just make him gay.) 

“And today we had tater tots deep fried in peanut oil, peanut butter and tomato soup, PB&J sandwiches, and a peanut brittle dessert at the cafeteria, so we’re all out of peanuts.”

“Your American food makes no sense.”

Then I heard the distinct sound of a tall white man speed walking through the solid steel blast doors at mach three. “Oh, sounds like Samanda wasn’t able to hold the line. I’ll just have to deal with him myself.” 

“Earlier today, you need my help to open jelly jar.” Igor gave me a snide smile, his elbow on the back of his chair.

“Silence, Igor! I have a plan. By the way, I forgot to give you the vaccine/antidote so you should probably hold your breath.” I opened the fume hood and grabbed a petri dish of the prototype prefect virus.

Igor’s eyes went wide. He covered his mouth while trying to crawl into a vacant fume hood, muffling a string of words in his native language which I assumed were compliments of my tactical genius.

Suddenly, Superguy burst through the door to the cleanroom in his particularly insufferable way, both violating biosafety procedures and ruining a perfectly good door. It wasn’t even locked.

“Alright, villain. We both know how this is going to end. So why don’t you put an end to your sick deeds and turn yourself-” I threw the petri dish at his face, splashing him with agar and cell colonies. He immediately started coughing and spitting.

“HA! You’re like those asshats who thought they didn’t need the Covid vaccine just because they’re young and do cardio. Physical strength has nothing to do with the strength of your immune system! You get sick just like the rest of us, Neonian! MWAHAHAHA!”

Superguy walked up to me and gently tapped me on the face with such force that I flew backward into a rack of glassware.

“You ne’er-do-well, it…it just got in my mouth! I’ve never gotten sick before, and your little science experiment isn’t about to change that.”

Just ‘science experiment’. Not epicdemic. Not an outbleak. Not even Outyerendza or plangue. Even I can quip better than these heroes. I thought aliens were supposed to be smart? 

I groan on the floor. “Oh, yeah… You’re an alien, so I guess that would make sense. Your immune system has a completely different set of flaws. Oh, maybe that’s why you get allergies? Your immune system overreacts because it’s never been challenged before!”