Long Forgotten Memories

by NotWithoutEnd

Rating: teen
Tags: Tragedy, Dark, Sad, Romance, Comedy, Adventure
Length: 6776

An older pony recounts some history of Equestria, his challanges, failures, and triumphs

A very aged pony retells parts of his life, from his days as a colt onward as a series of journal entries. He lives in modern day Equestria, but almost all of the events occur long before the Mane 6 were born. I try to stay cannon as much as possible, but the story will sync back up near the end. He's a scientist and his entries reflect the use of that particular lens in viewing reality.
Give an elder pony and his cynical views on life a place in your heart.

Note: The protagonist was, at one time, an OC pony at tumblr (whathathponywrought). Unfortunately, life happened and the account started gathering dust. Lots of dust. I've chosen to no longer use Tumblr to continue his story. If you'd like proof that I own the account, I'd be more than happy to provide it.

Published 1970-01-01 00:00:00 UTC
Last updated 2012-09-10 23:04:01 UTC

My Return Home

2011/09/05

A small spell of banishment never harmed anyone. At least, I don’t feel harmed. Of that, only time will tell.

Equestria has changed so much since I last gazed on its beauty. I hardly recognize my home. I have seen so many wonderful things since my exile, but nothing so beautiful as the place of my youth.

Enough reminiscing, however. There’s much work to be done. I find it unlikely all of my equipment or libraries have been destroyed since I left. I must salvage what I can.

-W

2011/09/06

A few of the caches I’ve searched have been left untouched. Some of the more useful equipment is salvageable. Others, well…  It will take some time before I can start asking important questions again. Even longer if, in my absence, the machinations of time and rust have caused subtle damage to my creations.

That being said, good science is driven by patience, persistence, a small sprinkling of genius. It is primarily the blood, the sweat, and the tears that pushes one through complete darkness, stumbling onto the rare happy discoveries that dimly light the way. I will persevere, now, as before. I’ve not waited this long to start anew by throwing in the proverbial towel.

I am tired, however. I’m not as young a colt as I used to be. I must sleep now. I can barely keep my eyes open.

-W

2011/09/06

I overslept this morning. Perhaps it was the fresh hay or the cool night air, but for the first time in recent memory, I slept. There were dreams of course. Echoes of memories rekindled, I think, by my return home. It’s surprising how easily everything came back to me. Ponies, places, events from way back when.

But, none of that exists anymore. Lost in the sands of time, I imagine.

Enough waxing poetic about my lost home, though. I’ve made good progress in making a temporary home. Once I’m done here, I’ll see about finding something to eat. I think there’s an apple orchard nearby. I’m sure the owner won’t mind losing a few apples to a somewhat homeless, old pony.

-W

2011/09/06

There.

My temporary home is clean and order is on the way. I managed to find a nice colt kind enough to let me have some of his apples. I’m pleasantly surprised such hospitality continues to exist.

The apples were so wonderful. I must find a way to return the favor one day.

Now it’s time for this old pony to lay its head down and rest. Tomorrow, I think I’ll try to go into town and see what I can see.

Goodnight, tumblr.

-W

[h4]

2011/09/07

I spent the afternoon reviewing some of my old work journals. I’m rather surprised the papers are still intelligible. So much we hypothesized and tested and retested. I’m surprised we learned as much as we did exploring our wild ideas.

Perhaps some younger colts and fillies would find these interesting. I’ll see if I can’t compile and type out some usable story from these.

-W

The Plague

2011/09/12

I remember we were in Appleoosa one autumn. Cool winds blew across the plains and my parents made me wear an overcoat to stay warm. I was so young at the time. Still a “blank flank.” The fall harvest was in and our caravan was there to gather supplies and preserved foods to sell in larger cities over the winter.

I loved Appleoosa. Aside from the apple trees, the earth ponies had planted fields of wheat, barley, and corn that seemed to spread for miles. When the wind blew, it looked like spun gold rippling. It seemed so soft that you could reach out and stroke it. Since it was harvest time, we were asked if we’d be kind enough to help lighten the load. I wasn’t allowed to reap at all, but I got to pull my little wagon! That first night I was so tired and sore, but it was a good kind of sore. I wasn’t as sore the next day. Or the next. About a week after we arrived in Appleoosa, though, I remember not wanting to get out of bed anymore. Like the bed was so comfortable, I should just sleep there forever. I was so tired. And hot. Every bone in my body ached.

Sometimes I had bad dreams. It was always in the same place: our wagon. I was on a bed of straw with blankets over me. Sometimes I saw my mom, her head nestled on my stomach. I think she had been crying, trails of tears matted her face. In other dreams, she lay next to me. She looked asleep. Peaceful, except for the black splotches on her hide. Like she’d been bit by a snake, a lot. In my dream, I tried to touch her hoof with mine, but I was so tired. I could barely move a muscle.

I dreamed of my father, too. He forced me to eat and drink, but every time he was in my dreams, he looked more and more sad. I wanted to comfort him, tell him everything was going to be alright. That as long as we were together, there wasn’t a reason to be sad. And I looked down,  but my mom wasn’t there. I looked up and my dad wasn’t either. I tried to cry. To shout for my momma and pappa.

The only thing that came out of my mouth was a sad little whinny.

-W

2011/09/27

It wasn’t until many years later that I understood the full implications of the plague that ravaged Appleoosa and other villages. That my family, along with the rest of our merchant group, unknowingly carried the disease from port to towns and villages some hundred miles before we, too, succumbed. That, just as ponies were narrowing in on where the disease seemed to be spreading from, we had already packed up shop and move to the next town. The merchants that purchased goods from us, likewise, traveled to other towns.

The plague rippled through Equestria faster than any royal pegasus or incantation sent to warn the unsuspecting.

When I finally got up enough courage to read through the royal report on the disease (years later), I read that, at age of two, I was the lone survivor of the Appleoosa outbreak. I was rescued by a team of ponies tasked with containing the disease. The containment team found a mass grave where ponies were buried. Those not accounted for there could be found scattered beds across the village. As if all of Appleoosa breathed its last hacking breath and left for greener pastures as one.

All except for me. I still do not understand why a young colt survived one of the most horrific diseases ever encountered since the sealing of Discord. A disease resistant to the most potent herbs, the best efforts scientists, doctors, and unicorns Equestria over. A disease resistant to magic. That consumed magic.

Pegasi are recorded to have fallen from their lofty homes, too weak to take flight. As if the clouds themselves refused to carry their diseased hoofs. In one instance, an entire floating metropolis, unable to ignore the pull of gravity any longer, collapsed earthward. Block by terrifying block. It has been postulated that those parts of the city hit first were also the first to fall. Additionally, it’s been decided that the city did not fall in a day. According to an analysis of the debris field and the “flight path” of the city, almost a week had past from the first buildings fell to the last.

Unicorns, the wards of magic, found themselves woefully unprepared for the effects the disease inflicted on its victims. Once infected, a unicorn’s horn disintegrated at the moment of magical conjuration. The use of magic on a victim seemed to only make the plague grow ever more virulent. Though apparently immune, it is hinted that even Princess Celestia feared working her magic, lest she bring about more suffering.

Appleoosa and many other cities were razed. Cleansed by fire. Removed from all maps by royal decree. The survivors, once cleared, found themselves moved to new cities. New homes. New lives. There were so many orphans, too, myself included. So many of us had seen their entire families vanish, consumed by blistering, burning fevers. And pain. Though we still looked like young colts and fillies, all of us had lost our childhood.

It was in one of the many impromptu orphanages that I first met Candlelight Flicker. The pony that gave me a shoulder to cry on. That would become my teacher and mentor. That, along with her daughter, would eventually knit anew a family for me. A concept I was certain I’d permanently lost.

-W

2011/10/01

I realize I’m writing this history out of order, but I got my scanner working finally and I wanted to try it out.

The simple cylinder of a bacteria, shown below, is Yersinia Ponis.  When Candlelight was tasked to track down the cause of the plague, no one imagined the answer would be such a tiny creature. It certainly doesn’t look like much at all of 2 micrometers (um) in length, does it?

It is not alone, however. It can duplicate itself quickly. Within days of infection, a pony’s body is teaming with the bacteria. With study, we found Y. Ponis displaying an amazing assortment of tools to attack its host. It consumes the very essence of magic we all possess. The use of magic appears to spur its growth and replication a thousand fold and the bacteria appears to prefer the magic conducting organs of a pony’s body over others.

Y. Ponis cleaves through a pony’s disease defenses like a hot knife through butter. It injects simple structures into defense cells, destroying them from the inside out. It spews other structures designed to confuse and interrupt the communication between defensive cells. Once infected, a pony is almost helpless against the onslaught.

Good nutrition, bed rest, and somepony to care for the infected will help the most while their bodies wage a very real war against a relentless invader. However, as more and more ponies become infected, these simple necessities become increasingly difficult to supply.

There are many mysteries about Y. Ponis that we still don’t understand. This disease seems so tailored to ponykind. Where did it come from? How does it know how to evade or neutralize every defense a pony has to offer? Who made it?

That last question is my own. There is a a school of thought that Y. Ponis, regardless of how perfectly tuned it seems to be to attack us, is simply that way because it evolved over time with ponies. It adapted to our defenses as we adapted to its attacks. I tend to disagree.

I doubt, however, too many of you are interested in the rantings of an old pony, so I will leave that particular bit for now. I hope some of you found this topic mildly interesting, or at least tolerable.

-W

What history can teach

2011/10/05

It is often repeated that “Those forget history are doomed to repeat it” and “History is written by the victors.” Well, perhaps they aren’t anymore. My social life continues to be in a severe state of disuse, save my occasional discussions with Ms. Derpy. It is hard to pull one’s self away from the culmination of your life’s work. I must pull away, however, if I am to complete it successfully.

I have made an acquaintance with a young unicorn, a Ms.Twilight, I believe. She runs a library from her home. She was kind enough to lend me a few books on recent (and not so recent) history. Since my return to Equestria, the world has made it painfully clear that it’s changed since I last took in its breathtaking beauty. Also, she has a new love and I never meant anything to her.

It is with some guilt that I go through her diaries. Diaries written solely by her lovers. Lovers that enjoy putting themselves in the best light possible, while putting down those they just usurped. And I believe I’ve taken that analogy quite far enough.

There are many potential explanations, but my mark on the past does not exist in any of these volumes. It is likely that my escapades were either forgotten or whitewashed. Though the conspiracy theorist in me would like to believe the latter, I believe it is far more likely that the former occurred. So much happens in a pony’s day to day life. Compound that with millions of ponies across Equestria across centuries and it is easy to see why events become lost in the shifting sands of time.

I imagined the plague that ravaged Equestria would prove to be more robust. Yet, in the volumes I borrowed, barely a footnote mentions it. There are other oddities I’ve found as well.

“Diamond Dogs”, as they are called now, are now less than they once were. Less powerful. Less intelligent. Less important. Somewhat greedy. I’m not saying the Diamond Dogs were perfect by any stretch of the imagination. Yet, we traded with them. As partners. Their abilities to sense and move the earth greatly exceeded our own. They were masters at shaping stones. At finding precious seams.

Shortly after Luna’s banishment, however, the historical accounts of Ponies interacting with Diamond Dogs practically vanishes. One century there exists thriving trade between the two groups. In the next century, it is as if the Diamond Dogs ceased to exist. No emissaries to the Palace. No new trade negotiations. Any mentions of projects and deals already in place likewise vanished. Princess Celestia commissioned a new mine to be developed for a particularly rare gem. She places substantial effort in securing the mining contract with the Diamond Dogs. Yet, a chapter or two later, the entire ordeal has faded from the historical consciousness.

The next time Diamond Dogs appear again is centuries later, as a nuisance. A band of thieving, greedy outliers that live underground. A remarkable turn, wouldn’t you agree?

Why?

Perhaps the Diamond Dogs found something in their mines that forever altered them. As fantastic as that sounds, there are a number of instances where things better left forgotten are suddenly, and terrifyingly, brought back into reality. The joys of Discord being the most recent of these.

Perhaps their society collapsed. Famine. Strife. Civil War. Political Coups. Any of those possibilities and more, either by themselves or combined, can scatter even the greatest of civilizations into mere relics of their former glory. While I cannot imagine why ponies would allow such an important ally to fall, sometimes it is inevitable.

There are a myriad of other explanations that could account for the change, but few that explain their complete absence in these written histories.

Perhaps the information is still out there. It might exist in another tome or perhaps even the Diamond Dogs themselves have an idea. Or, sadly, what occurred may never be known.

How sad. So many questions.

So little time.

-W

A winter wrap up to remember

2011/10/07

I am vaguely closer to my goal than last week. With so much in disarray, much of my time is spent just getting back what I’d lost.

I ended my work for the day as the rains came. I find the constant patter against the roof almost soothing. When I still lived with my parents, the caravans would have to stop at the side of the trails during rain storms. Loaded with so much cargo, the wagons would easily become stuck in the mud. You also had to consider the ponies pulling the wagons.

I remember the whole caravan, my one big family, would come together and tell stories. Tall tails and rumors. Stories of mighty mares and valiant stallions. Of true love and destiny. Romance and tragedy.

My mom would tell the story of how she met my dad. How he literally swept her off her hooves. At the speeds he must have been going, I doubt she saw what hit her.

During a winter wrap up, dad took a dare to use his skates and break the ice covering a river. A river several miles in length whose starting point was half way up a mountain. The way dad told it, his ride on the way down was as smooth as silk and he meant to show off to the mares cutting up the lake next to their town. He tripped and ‘accidentally’ slid next to my mother, where she fell just so into his hooves

Mom’s side of the story was filled with blood curdling screams coming from this tiny orange streak as it rocketed down the mountain, followed closely by a small avalanche. Said streak, upon reaching the mostly cut lake, tripped and started rolling. All flailing legs, he clobbered half the lake team before the avalanche arrived and put a stop to the whole ordeal. Three of his skates were found several days later, embedded in various rooftops across town. They never found his fourth skate.

Dad always turned interesting shades of embarrassed when mom told her version. They promised that, one day, they’d take me to see their home. Though they’re gone now, I wonder if I can find the town they grew up in. See if there are any legends of orange streaks that haunt the mountainside on cold winter nights…

-W

Time, I find, is not on my side

2011/10/09

I explored some of the countryside, today. I don’t think I was looking for anything in particular. It was enough just to be there.

The rain last night brought with it a cold wind and I awoke to crisp morning air. The wet earth squished under my hooves as I made my way to gather water. All around me, the once green trees sported leaves of gold, yellow, and red. Such beauty. The colors swirled all around me whenever the wind blew. It was like being enveloped by a sunbeam. A cold and windy sunbeam, but a sunbeam nonetheless.

Above me I could see thousands of birds. Probably more. I think I saw some pegasi flitting about here and there, as well. The birds flew in great squadrons or swarms, sometimes landing in the trees or a nearby field. Their chatter was so loud while they rested and looked for food. And then, just like that, they were off again. With glee, they took to the skies again as one. Oh, if I could soar like that just once in the time I have left.

I drank from the cool spring near my home. No, I give it too much credit. The spring was downright cold. As warm the hike to the spring made me, the water was ice to my lips. I drank a long, deep pull. The feeling of satisfaction surprised me as if, for that one moment, I was perfect. As if I could be - no - was content for the rest of my life with the satisfaction this morning, alone.

I just looked at icy spring water. An old stallion looked back. His muzzle is etched in grey. His once vibrant green coat now so worn and dull. The remnants of a once favored toy left to rot in the sun. And eyes. I just couldn’t get over his eyes. They seemed so tired. Not physically tired, as if after an all nighter or a long gallop. Weary. Exhausted. Of what? I do not know.

I examined my rippling reflection in the waters closely. Was that everything I’d become? Just an old pony whose best days were behind him? Whose only wish was to enjoy the mornings in peace? Eat some greens and fruit and just live the life of leisure until this old body goes to sleep for the last time?

To let everything I’d worked for go to waste? The painful sacrifices and difficult choices? The time I lost. No! The time stolen from me.

I glared down at the aged pony beneath me. So helpless. So undeserving. I crushed him under my hoof and watched as the resulting ripples traveled downstream.

This flesh may be weak, but my soul? My soul is willing.

-W

A unicorn's gaze

2011/10/18

After much TLC (read: delicately beating it into submission with a hammer, among other things), I finally finished putting back together my power generator. It’s just a small little fuel cell. You give it water, some food, and a bit of sunlight and it produces an electric current. A current harnessed to drive work in other machines.

Why go through all of this work? Why not use magic?

For one thing, magic can be unreliable. Its strength depends on the season, the current orientation of the moon, stars, sun, and other celestial bodies, what you’ve eaten this morning, what your neighbor’s eaten this morning, the mood of the nearest unicorn, if you’ve paid your taxes, how many times you begged for luck in last night’s card game, among other things. And that’s just for magical items.

Unicorn magic can be even more temperamental. As nice as an individual unicorn may be, they usually have a mean streak the distance to the moon and back if you so so much as hint that their last spell is almost-but-not-quite-perfect-you’re-so-close-you-just-need-to-tweak-this-spell-like-this-Promise!LastTime!

Especially when you follow it up with I’m-sorry-I-was-wrong-can-you-tweak-it-justeversoslightlythatway.

The gaze from a frustrated unicorn have been known to level cities.

On Depression & Suicide

Perhaps some of you will humor an old pony.

It has been apparent since I first logged on to ponynet, not so long ago, that more than a few ponies know little to nothing about depression. Even more have a misunderstanding on what someone who’s suicidal goes through. Though I doubt many ponies will read this, I feel it is important that I at least try to help correct this.

Having the blues or being depressed for a short time is normal for everypony. Perhaps your friends have kept secrets from you and this made you sad? Perhaps you messed up on a task everypony else thinks is easy? Maybe you got yelled at for something that wasn’t your fault or was an accident. You feel bad for a while and then, a little later, you move on.

Being depressed from time to time is normal. Having depression is something completely different. It is a long term/chronic disease. A depressed pony is not thinking normally - they react to events differently. Events that might cause a regular pony to just feel down or upset can cause a pony with depression to spiral into depths unknown of self loathing. Some days are better than others, but over time the entire experience destroys a pony. It eats you from the inside out. Makes you think things that aren’t true.

The result… the result is a pony that lives under a rain cloud. No, that is wrong. A raincloud does not suffocate. A raincloud does not color every action with fear or sadness. A raincloud does not drain the energy from you, making the prospect of just getting out of bed a torturous action. A raincloud doesn’t convince you that you just want to be alone. That it’s better to be by yourself, ruminating in your own thoughts. You’re a burden. No one cares, anyway.

Don’t let anypony know that you’re depressed, because that would just cause them to worry about you. Don’t tell anypony about the feelings you have, they won’t understand and it’s obvious that they have more important things on their mind. You are the most useless, Celestia-damned pony to ever exist and you will never, ever, do anything right. Fuck you, you waste of space. Equestria is better without you.

How do I know this? The thoughts above? Those are mine. They replay again and again and again. Sometimes, even now. Every mistake is a tragedy. Every missed opportunity is the end of your life. Friends and family only put up with you because they have to. You are an embarrassment. A mistake. A failure. A burden. That no matter what you do or how hard you try you will never be good enough for anything or anyone.

When I first met Candlelight, I tried so very hard to make her like me. I was funny and cute and please just anything so you’ll take me from my daily hell at the orphanage. She did, eventually, but not until I did something so incredibly stupid.

Like depression, suicide is misunderstood by most ponies. Suicide is a terrible thing and any pony contemplating ending everything isn’t making an ‘easy’ decision. It is almost never considered lightly or quickly, though head traumas can cause forms of insanity where suicide is the end result. In the case of depression, it is the accumulation of months or years of torment, both internal and external.

My torment at the orphanage was daily, through the bullies that abused me and my own internalized hatred for myself. Candlelight had been worried about me for some time. She kept trying to tell me “Everything would be all right.” To just try to hang on, there’s always tomorrow. That she loved me and I was a wonderful colt. As I look back on it now, I think she was trying to adopt me at the time.

I’d come up with a plan. I’d managed to steal, in small amounts over time, a bunch of medicines and herbs. I don’t even know what half of it was. I’d heard from some of the older colts that a pony could overdose and die if they took enough. I hid my collection from everyone. I didn’t want anyone to know what I had in mind.

One day, I accepted my plan as the only logical course of action. This made me cry. I sobbed uncontrollably for hours, a typhoon of emotions frothing in my head. Sadness, joy, anger, frustration, pleasure, release. I thought about all the things I wanted to do with my life and, one by one, let them go. I let Candlelight go. I let Ferris go. I let my few friends at the orphanage go. I let my parents go. I don’t know about now, but suicide was considered a mortal sin back in those days. I would never see my parents in the green pastures.

And that. That was ok. It felt like a mountain of rubble had been lifted from my small shoulders. I didn’t know the when or where, but nothing anyone could do to me mattered anymore. I would be free soon.

I was happy! I smiled! I laughed! For the first time in months, I actually laughed. Not just kindof laughed or fake laughed. Really laughed. And that, above all, should have worried everypony. When somepony who has struggled with long-term depression or a mental illness suddenly makes a sustained 180 in terms of their mood and outlook, it often means that pony has made their decision. It’s damn near like waiting for your favorite holiday or your birthday. There’s a present waiting for you! Nothing else matters!

It was spring. One day, not long after I’d made my decision, my tormentors came to pay me a visit. Something I’d done had made them look ‘bad.’ I don’t remember much of the beating. I only remember how I came around to deciding that, yes, this would be the day. I didn’t fight. I just waited for it to be over.

When I was alone, I snuck to the place I hid my collection. Heh, I was so scared. Just because I’d made my choice didn’t make the prospect of death any easier. But what was a single death compared to looking forward to a lifetime of pain and suffering? My hooves shook as I took the medicines. Ate the bitter herbs. Some of them made me gag, so I had to take them with water.

I made my way back to my cot and pulled out the nature book Candlelight had given me. Equestria is so beautiful. I flipped through and admired the pictures. Mountains so high they touched the clouds. Forests so dense you couldn’t distinguish one tree from another. The moon smiling down on the world amidst a starry sky. I think the last picture I remember seeing before I fell asleep was a beautiful sunsets over a rolling ocean. The water looked like it was on fire.

The next few days are a blur. I don’t remember the doctors pumping my stomach. Or forcing magical ingredients down my throat. I have whispers of dreams. Candlelight lay a hoof to comfort me. Some faces from the orphanage. Ferris. It was days later that I fully came to.

Heh. I put more of myself out there than I expected I would.

Depression is nothing so simple as unhappiness. It is a pony’s mind on the offensive against itself. Though there is often some external stimuli to kick things off, there doesn’t have to be. By their very nature, Depression and Suicide are not things anypony can handle by themselves. The game is rigged, from the beginning. It’s not fair. It’s not even something family or friends can handle. Regardless of their good intentions, they do not having the training necessary to help a pony in this battle.

A trained and licensed psychiatrist is best. They will be able to determine the causes of the depression. To give a pony options in the ways their depression can be treated. Certain herbs and magic can quiet the mind. Therapy, especially Cognitive Behavioral Therapy, can give a pony the tools necessary to defuse the sickness at its root. With work, some ponies can be mostly cured of their depressive symptoms.

If a pony is suicidal, the best thing anypony can do is provide them with help immediately. A pony who’s decided, really decided, to take their own life will not tell you. In general, they won’t make a big deal out of it. To them, it’s just one more thing to do. At this point, they should be classified as insane (they are not thinking normally). You cannot fix them. You cannot help them by yourself. Get help immediately.

Any pony that announces their intentions to commit suicide is begging for help. They are at the edge and know of no other way to ask. Again, they need help. It is not acceptable to antagonize them with “If you were serious, you’d have done it.” They will.

If you are suicidal, there are so many options available to you. I implore you to contact your local suicide prevention hotline. If the internet is more your thing, please look up http://www.reddit.com/r/suicidewatch

I’ve never asked my followers to reblog anything of mine, but if you can, please do so now. Perhaps my story will help make a difference in somepony’s life.

-W

((And yes, this happened. I’ve changed almost all of the details to fit this rp character, but the core is true. The attempt was mine.))

Author's Note: This was posted in response to several Tumblr users running into problems with depression and attempting suicide. I wanted to share my own experiences and help how I could.

Current Science: Cancer Research

I hope my followers will, again, indulge me in a long post. Very long. Nothing depression, but it could be educational. I apologize for that in advance.

Leukemia - Painful suck death

Like most cancers, Leukemia is a disease that sucks mightily. There are many different types, causes and survival rates that depend on any number of factors. Basically, your immune system goes haywire in a variety of ways and causes uncontrolled cell replication.

You die from leukemia because there are white blood cells EVERYWHERE. They completely take over your bone marrow, preventing functional red blood cell, platelet, and (ironically) white blood cell production. This leads to, in order, anemia, hemophilia, and a compromised immune system, not dissimilar to AIDS. And that’s just the bone marrow. Your other organs get piled high with them, too. Damage to spleen and liver aren’t uncommon.

Why do they do this? Don’t your white blood cells protect you from invaders? Yes, they do. However, sometimes things can go horribly wrong. First, however, some basics.

Immune System - The many. The proud.

Your body has two different types of immune response. Innate (i.e. you are bad therefore I eat you) and specific (think America’s Most Wanted - tracking down known fugitives). Your specific immune response is comprised of two types of cells: B Cells and T Cells.

B cells recognize a pathogen (intruder) based off of an antigen. An antigen is something specific that only a particular pathogen has. A bit like an identifying tattoo or beard, except much much more specific. Once an antigen is recognized, B Cells will replicate and begin spewing antibodies. Antibodies, once bound to a pathogen, target the pathogen for destruction or, in the case of toxins, can neutralize the toxin by itself.

T cells come in two different types. Killer and Helper. Killer T cells target those cells in your body that are already infected by a virus and destroy them.

Helper T cells are like the generals on a battlefield. They coordinate the innate and specific immune responses and can signal other cells (via cytokines) to do specific tasks.

Your B cells and helper T cells work together. One can activate the other, a bit like the Wonder Twins or DBZ characters fusion, combining their powers.

They don’t actually merge, but the effect is the same. Upon activation, the shit has hit the fan. There’s an intense reaction that puts your body on the offensive. Have you ever had the flu and felt those aches and pains in your bones? Your bones contain marrow, one of the primary sites for immune cell development. The aches are likely the result of your body bringing all of its offensive and defensive capabilities to bare.

A Fatal Misstep

In Leukemia, some of either the B or T cells have sustained damage to their DNA, the instruction molecule of cells. DNA, along with the epigenetic molecules that sit atop DNA, contain all of the instructions a cell needs to perform its duties. While every cell in your body contains the exact same instructions, different cells have different instructions active depending on their task and the current stimuli (either internal or external).

As with all cancers, this damage to DNA causes a sustained, uncontrollable replication of these damaged cells. Each damaged cell creates more damaged cells.

Cancer Research, So Far

To combat cancer, scientists have developed different treatments to try and kill of the cells with varying degrees of success. A joke in the scientific community is that, if clinicians could just get the cancer onto a petri dish, they’d be able to cure all cancer. Often, promising cures in vitro (on a dish or a test tube) fail miserably in actual living subjects. Your body is extremely chemically active. Finding a compound that is only active inside cancer cells, while ignores other cells and isn’t accidentally transformed by some normal chemical reaction in your body is extremely difficult.

Some promising work has been performed in trying to convince your body’s immune system to take out the cancer. Again, in vitro the idea works. In your body, however, the effect is less than adequate.

Cancer Research, Now

This changed in August of this year. In August, a group of researchers published in the New England Journal of Medicine some amazing results. The researchers were successful in ‘convincing’ a patient’s immune system to go on an all out offensive against their late stage leukemia. Of the three patients that received this treatment, two are in complete remission, even 10 months later. The third had a 70% reduction in the leukemia in their blood.

To explain how they did this, I need to go a little bit farther into biology than your high school biology book probably went.

All cells have a collection of proteins floating around on their cell membranes. These proteins allow the cell to interact with other cells, take up food and oxygen, expel wastes, and receive signals that would cause a change in behavior.

B cells, and only B cells, have a protein on their cell membranes called CD19. In the particular leukemia the researchers were trying to attack, the B cells were the culprits. The researchers modified the helper T cells (using modified HIV as a vector to deliver new instructions) such that the T cells would recognize CD19 as something it needed to destroy. Not only that, but to replicate so that it could appropriately marshal a response from the body.

The modified T cells did the job. A week or so after infusion, the patients started to show symptoms of a defensive response. Two weeks in, the patients’ bodies were taking part in a major onslaught. They’d developed what was called ‘tumor lysis syndrome,’ which is a term used to describe what a body goes through when cells (cancer or otherwise) die en masse. Your body has difficult cleaning up so many dead and dying cells all at once. In this case, it meant B cells were being shredded everywhere they could be found.

Shortly thereafter, the patients returned to normal. No leukemia could be found in the blood, in the bone marrow, or in the lymph nodes. Every B cell, damaged or not, had been wiped from the patients’ bodies. Even after 6 months, this was the case as the modified T cells were still present and on the lookout. In one patient, over 2 pounds worth of leukemia had been destroyed.

Cautious Optimism is Warranted

One draw back of this technique is that any cell with the particular protein you’re targeting will be annihilated. Since B cells target pathogens they’ve seen before, any viral or bacterial immunity the patients’ had once been ready to use is now gone. There is a very real chance these patients will have difficulties dealing with infectious diseases. Then again, they won’t shortly die from having their organs clog up with white blood cells.

Many more tests are required to ensure safety of the treatment, improve its effectiveness, etc…, but this is a huge step in teaching the body to recognize cancer as something to be killed off.

The raw paper can be viewed here.

When Dinoponies Ruled the Equestria

2011/09/10

Before I get into the more interesting aspects of my life, I thought it might be important to describe who I am. Or perhaps I just like hearing the sounds of my hooves hitting the keyboard. Probably the latter.

When I was young colt, sometime during the late Triassic, I remember the world was filled with new and exciting places to explore. The regal sisters brought out the sun and moon and life was at harmony. My parents traveled Equestria with a merchant group, moving goods from town to town. We never stayed in any place for long. Maybe a few days. We were there to buy low, sell high, and then on to the next town. Lather, rinse, repeat.

I remember my childhood mostly as a blur. New towns or cities, new fillies and colts to play with, and lots of different food to try. Every village, town, or city had its own unique flavor. I think crêpes are still my favorite. Filled with apples or strawberries or peaches? mmmm…

I think it’s the differences in cultures ponies from different places put together that stuck with me the most. You could start in one city, where, unless you were “high class”, no pony would give you the time of day. A day or so travel later, you could arrive in a village whose ponies had almost nothing, but you were the honored guest. What little food they had was yours.

In my colt years, I learned to buy and sell goods, how to haggle, how to count money and make bartering exchanges. How to pay taxes (yuk). How to avoid taxes (on occasion). How to smuggle goods and ponies(rare, but exciting). All the things a young, merchant-pony-in-training should learn. When we were in a town, I’d help mind the stall and try to sell. While traveling, my parents and some of our friends in the caravan would help teach me new skills or make me practice what I’d already learned.

-W