Saturday, May 7, 2016

I transplanted someone else's microbiome in(on)to my body and it was so surreal - Part II

You can follow along Here for my daily questionaire and Here there is a diary near the bottom

Tuesday Feb 16th - Antibiotics Day One, Experiment Day One
The first day I would be taking antibiotics. Didn't sleep much the night before or the night before that. Stress can induce mania in me. It doesn't take much these days to give me the adrenaline of skydiver. The strange thing is I usually have no problem falling asleep, I just end up waking up some hours later and no matter how hard I try can't go back to sleep.

The plan was to take 500mg Tetracycline and 500mg Cirpofloxacin, both broad spectrum antibiotics that target different proteins in bacteria to increase my chances of wiping out as much bacteria as possible. Tetracycline tastes like sour acrid sulfur, pretty awful. If you think the Malort face was bad the Tetracycline face is worse. I weighed out 500mg and mixed it with water and took it as a shot. I had some ciprofloxacin in pill form so it wasn't nearly as bad.

The diarrhea that came after was bad but I had expected as much. As anyone who has taken a significant dose of antibiotics before knows, you get the shits.

My chess rating on began dropping. Dahhhh, this usually happens when I am preoccupied and have a hard time focusing. It is a pretty good measure of my mental acuity. Also, because my stomach was messed up I wasn't consuming alot of calories which definitely messes with my mental acuity. In fact I only consumed 1000 calories on Feb. 16th!! Yikes. I generally need around 1800 to 2000 calories to perform well on memory tests and chess.

Wednesday Feb 17th - Antibiotics Day Two, Experiment Day Two
My stomach was pretty upset by this time I was also feeling pretty loopy. Unfortunately, it was time to go to the donor's place and pick up the samples for the transplant. I wanted them to be fresh for the transplant tomorrow. I told the donor to try and not eat anything crazy or abnormal the night before.

Fortunately, I had someone to drive me to the donor's place. By this time I was pretty out of it. The donor gave me a pretty hefty fecal sample in a plastic bag fresh from this morning. Then I made him take significant swabs of his arms, legs, mouth and nasal passages that I stored in 150mM NaCl. These would be used to inoculate my arms, legs, mouth and nasal passages. During the experiment I stored all the samples at ~4C in the fridge.

I took two doses of antibiotics today, still had diarrhea and still was having trouble eating much but better than yesterday at 1200 calories, chess score still suffering.

Because I didn't feel tired and hadn't slept much in two days I took 1mg of clonozepam to help me sleep and I accomplished an amazing 6 hours.... Usually, if I can get at least some sleep it keeps me from being manic. Mania for me is compounding, the less I sleep the more manic I become and the less I sleep. To help abate the cycle I take medication that helps me sleep. Sometimes this doesn't work and is insanely annoying

Thursday Feb 18th - Antibiotics End, Hotel Room Day One, Experiment Day Three
Still on the antibiotics but moved to the hotel room on Thursday, with my chess rating still suffering, down from 1425 before to 1393 today. The experiment has already started to become surreal but today it took it to a whole new level.

Once in the hotel room, I strip down to my boxers and put on booties, gloves and gown and start cleaning. I use disinfectant wipes and spray to clean most areas of the hotel room I would feasibly touch. I took bed sheets I purchased from amazon, still in packing and placed them over the hotel bed sheets and used pillow cases from amazon over the hotels. Anyone who entered the hotel room had to wear booties and if they planned on touching stuff, gloves. There was also a separate bed in the room that I never touched that they could sit on or lay on.

Then it was time. I went in the shower and cleaned myself and then started scrubbing myself using a sponge and antibiotics. My goal to wipe my microbiome completely off and out of my body before the transplant. For about 1 to 1.5 hours I scrubbed ever crevice and part of my body. Alot of people suggest it is impossible to remove all microbes from your body or that you would die if you did or any other number of insane hypotheses. It's possible but I didn't think likely. And though I didn't imagine I could remove every microbe I really wanted to try. Sadly, I only remembered to take microbiome samples before the cleaning and didn't really take any at all on the 19th because I was feeling so strange and out of it and just forgot.

At 1730 I took my first FMT pills and performed by first skin, mouth and nasal inoculations.

I did it again a few hours later.

I wanted the end of my antibiotics to overlap with the start of transplant so that the new bacteria had overwhelming numbers on and in my body.

I put on a white t-shirt I purchased from amazon. I put on underwear from amazon and a pair of laundered jeans while people were around. The Verge mention the laundered jeans as strange instead of just having purchased some new ones from amazon. How much different would the bacteria be on a new pair of jeans versus an old laundered pair of jeans? I don't know, maybe there would be a significant difference but I imagined not so. I also imagined not wearing pants much(I only really wore them when people came to my room).

I think in probabilities and some people think in exactitudes. What would the probability be that an old laundered pair of pants would effect the outcome versus a new pair of pants. In my opinion it was very small to none. I call it reason.

Friday Feb 19th - Hotel Room Day Two, Experiment Day Three
I ordered some take-out and chilled. I had heartburn all day but was refraining from taking an antacids because I didn't want them to mess with my gut. I actually was starting to relax and regain some of my normalcy as can be seen by my chess rating increasing and my calorie intake was also up. I enjoy staying in hotels because I don't have cable or network TV at home and it is great to watch old movies.

Saturday Feb 20th - Hotel Room Day Three, Experiment Day Four
I haven't taken a shower since he transplant started and I have been rubbing bacteria all over my body. Heartburn was getting to me and sitting in the same bed and not really leaving the hotel room was really getting to me. I was mentally and physically exhausted.

Sunday Feb 21st - Hotel Room Day Four, Experiment Day Five
I finally get to go home. When I arrived home I cleaned the apartment and put new sheets on the bed and the coverings on the couch were laundered. I rubbed my skin all over the bed and the couch to try and populate them with my new microbiome and then I took a shower.

Friday, May 6, 2016

I transplanted someone else's microbiome in(on)to my body and it was so surreal - Part I

This is the story of a Speculative Science experiment. The data and results are meant to be a guide and not meant to withstand rigorous peer review (though I did my best to be as rigorous as possible). The experiment has an 'N' of 1, as Scientists say, meaning it was only done once on one person and therefore the results cannot be statistically generalized.

This is a story of how I challenged myself mentally, physically and intellectually to push the boundaries of what I think human beings are capable of in terms of Science exploration.
And this is story of me, about my need for self-reliance after all the shit I have been through in my life, my hope to inspire others and my reckless pursuit of Science Fiction.

This is a long story.

And it starts with medical issues.

I have suffered from gastrointenstinal problems, so do other members of my family. In college I began to have serious GI issues and an MD told me that it might be IBS. This was around 2004 there was no test for IBS. Ever since then when I talk to a GP I have received the generic MD advice, "Don't be stressed, eat healthy, exercise." all to no avail. I pooped alot or felt like I had to, maybe 3+ times a day on a normal day. I always thought it was just something I needed to deal with until it became much worse in the past few years. I was ovo-vegan for a year, vegetarian for the preceding year. My diet in the past 15 years has fluctuated between mostly chicken nuggets (first year of graduate school) to mostly vegetarian (near the end of graduate school). My diet now consists mostly of chicken, rice and vegetables.

Post-nasal drip is brutal. I have had it for about 5 years. I finally went and was tested for allergies and such 6 months ago and the tests came back negative. Spent thousands of dollars in deductibles, tried a bunch of different medication anyway that the MD was prescribing. They kept giving me stronger and stronger nasal sprays, none worked (LOL). Then I had a CT scan for polyps but the MDs responses were not clear on the results, really vague about maybe something. 

You may not know or maybe you do but I suffer from Bipolar Disorder. It's actually not much like what you see in the movies or TV much more boring and painful. Days or even a week without sleep, depression, anxiety and a hint of crazy. Medication with rough side effects(I didn't even know akathisia was a thing or how painful it could be, until I took seroquel). MDs who want to charge you $200+ per session and all seem disinterested in really helping you. A therapist who would fall asleep during our early morning sessions, a therapist who would answer emails during our sessions, a therapists who thought I was his rival and would try and get the group against me during sessions (super fucked up). Mental illnesses are diseases that giving hugs or being loving doesn't fix.

Great Odin, I sound like a mess.

Besides these things I would probably be considered by many to be healthy. Resting pulse rate of ~60 bpm, very little sugar with small amounts of fat in my diet. Weight around 170 lbs at the time of the experiment. My exercising has fluctuated, in the past 15 years but I have probably averaged 1-2 days a week of rock climbing or soccer(some weeks 5, some weeks none).  

Gastrointenstinal issues, obesity and many other things have been linked or suggested to be linked to each individuals microbiome. There have even been suggestions that your microbiome can influence your mood or play a role in mental illness(don't know enough to agree and to link any of those papers) Interestingly, the Fecal Microbiota Transplant(FMT) company(organization?) Open Biome screens for mental health issues in potential donors!

So it began with the question, Could a microbiome transplant cure me of some or all the things that ail me?

In May 2015, I wrote an article titled The Future of Microbiome Forensics tldr; it discussed recent advances in using the human microbiome as a tool to identify individuals. Being a hacker it started me thinking about how one could obfuscate the microbiome or maybe even replace their own microbiome with someone else's to circumvent the ability of people to use the microbiome for surveillance.

I applied for an Art grant to explore these things because no one would fund a Science grant to do this stuff. Check the Video part of the application out here I didn't, however, receive the grant.

I wanted to replace my whole microbiome. Replace my mouth and nasal bacteria with a healthy donors and maybe cure my post nasal drip. Replace my GI bacteria and maybe cure my GI illness, and replace my skin bacteria because we are a whole ecosystem and and maybe all the bacteria contribute to mental health and maybe I would reinfect myself with my old bacteria.

I had to two reason to perform this experiment

1. Health
2. Is it possible to replace my whole microbiome

So the next question was, How to do it?

Obviously, I didn't just want to do the experiment and be like "Hmmm, I feel better, #WINNER!". So, I needed a way to track how my body and mind function on a daily basis to help me better understand how I am functioning. I created a questionaire that tracked the things I thought would be effected by the experiment, everything from working out to sexual libido to caffeine and alcohol consumption. Check out daily data here. 

I also wanted to take samples that could have the bacteria in them sequenced eventually using 16s metagenomic sequencing. List of samples taken over the course of the experiment here

Then I needed to figure out how this thing worked. How do I store donor samples? How do I inoculate myself with poop samples, from above or below? What about skin inoculation, nasal inoculation, mouth?

I read up on some stuff and decided to create a short protocol.This document also has a more detailed diary from during the experiment (but don't cheat and read ahead).

Well, (un?)fortunately this was something that had been in my mind for a long time and it was going to happen. I decided that I needed to set some dates. I knew March 2016 and April 2016 would be busy months with traveling and such so I figured February would be a great time.

The weird thing about this experiment is that many people I talked with thought it was super cool, scary, but cool. Pain, C. diff, hospital, all awaited me many warned.

Scary. I mean the experiment came with risks but as it became closer to the date of the experiment it seemed that others were more scared for my safety than myself. So much so that it scared me alot. Was I being completely reckless, so much so that I would regret it? I would be sitting contemplating the experiment and see myself 10 years in the future completely regretting my decision to not plan better or chose a better donor.

I wish I could I say I had a rigorous process of choosing a donor but instead very few people were actually willing to participate. Maybe it was the thought that if something went wrong they would feel responsible. I don't really know, I never really asked. It is a weird conversation to have to begin with. Imagine receiving a text from your friend that says "Hey I was wondering if you have any illnesses that can be transferred by blood or poop or if you have any history of gastrointestinal problems, post-nasal drip or allergies or mental illness." HAH. Then being like "Well why don't you want to help?"

It took me a while but I finally found someone within driving distance(I wanted fresh samples) that was a healthy, male. Someone I have trusted with my life before, we have Rock Climbed alot together, so I figured I could trust him with my life again. People have asked me if I was against having someone who was female donate, I wasn't against it if needed, in fact when I was having trouble finding a healthy male donor I seriously considered it. My goal, however, was to reduce the variables that would lead to a negative health outcome. Some studies have shown sex differences in the microbiota of individuals.

One of the toughest decisions I had to make was whether to test the donor for diseases that could be transmitted. It was a really interested conundrum and had me thinking alot about how much we really trust each other in life but we really don't. Do you trust someone enough to be your friend but not enough to take their word that they don't have any health issues because you are going to ingest their poop? How does this relate to the Hacker mentality? If someone wants to replicate this study should they feel the need to to test their donor? Am I being reckless and.or promoting reckless behaviour?

Most of the illnesses that are tested for and possible to transmit through poop are obvious. No one walks around with a pathogenic E. coli infection and doesn't know it(though maybe some might argue). The main issues is hepatitis, especially because it is suggested that viral hepatitis can lie dormant for 10 years. There are many types of Viral Hepatitis but A, B and C are the most common. From what I have read acute infections of Viral Hepatitis can clear on their own for A, B and C. Even so A is usually cleared by the body on it's own and for C there is medication that can cure you. Generally, poop is also tested for HIV.

What is my goal? That was my question. My goal was to create something that was accessible. I believe that the more difficult a technology is to access the less impact it can have. Getting tested for Hepatitis can only be done through a medical professionals orders as with most blood tests, which makes the process even more complicated and expensive.

I constantly have a battle within myself.

I grew up poor on a farm in the middle of nowhere in Valparaiso, Indiana and my single mother worked as a babysitter and bookkeeper to pay the bills. Both my Mom's first and second husbands were physically abusive and we always struggled through poverty. Evictions, repossessions and writing checks at the grocery store that my parents knew were going to bounce. We regularly had utilities shut off, electricity and phone disconnected. This was no fault of my mother's as she worked as hard as she could, ended up obtaining her college degree in accounting after 40 and sacrificed to give me and my brothers many opportunities.

Now I am not poor. I went to the University of Chicago for graduate school, a private school and generally considered one of the top ten in the world. Most people I interact with would be considered upper-middle class. I worked at NASA for two years under a prestigious fellowship.

I left NASA because I was tired of how fucked up Science had become, how it was classist and wasteful. I paid around $4,500 to sequence samples for this project out of pocket so the results wouldn't be dismissed. I teach Science classes for free at local BioHackerspaces and I teach Science classes for Money at local BioHackerspaces. I run a company that is trying to make Science inexpensive and accessible but I also run a _company_ that is trying to make Science inexpensive and accessible.

I just want people to be able to be free. Free to explore this reality. I think all other freedoms come from this one. Freedom to have access to information and tools and resources. It is hard to oppress people without controlling what information they possess.

If knowledge is outlawed then I will have and disseminate knowledge.

This is the thesis of this experiment. A fuck you to everyone who puts journal articles behind paywalls, who has rules so we can't explore, who tells us what is and isn't worthy of being published and who charge outrageous prices for everything Science because they are profiteering gluttons. I want to give back for the opportunities I have had and I want to show that even though you might be poor financial there is so much you can contribute through Science.

Ok back to the experiment.

It's December 2015 and I decide that I am going to reserve a hotel room in February 2016. Our homes are covered in our microbiomes. Papers have shown that within a few days of moving into a new place we colonize it with our bacteria. This would make it difficult to transplant a completely new microbiome onto my full-body so I thought that I should stay in a hotel room for a few days. I would clean and sterilize the room as best I could.

My GI had been bothering me a shit ton in Jan. I was co-chairing the GRS Photosensory conference and spent half the time in my hotel room trying not to poop in the bathroom. It was the worst. Probably one of the worst attacks I have had.

I couldn't wait for the experiment to start. I actually wanted to start it early I was suffering so much. But I knew other people were invested in documenting it. So I waited.

I decided to take antibiotics for this experiment. It was rough. If I had to do this again solely for health reasons I would probably forgo the antibiotics.

Understand, most all studies of FMTs are in relation to C. diff infections of which I did not have nor was I trying to cure. Could I have used the exact same protocol for a C. diff infection? Maybe, but instead of attempting a maybe I wanted to do my best to make sure this experiment was successful.

This experiment was more than just an FMT.

Normally, FMTs are done without antibiotics but I figured since I was trying to do a transplant across my whole body it might be required. Also, I wanted to have a complete replacement and not just a few species. My work at NASA was around microbial communities and plastic degradation and my Master's degree from Appalachian State was in studying microbial biofilms and signaling. In ecosystems, microorganisms don't function alone, through quorom sensing and many other methods they communicate and share resources and space. I wanted a new community not just a few new species and to accomplish that I thought the best way was by using antibiotics. In theory populating a community with a few species of bacteria is done much easier than replacing the whole community due to competition and the reason that the old bacteria might not have a reason to go away. Antibiotics I imagined would help so that the new bacteria had much less to compete against and many of the old bacteria were gone.

There have been many studies to show that FMTs work well with glycerol treated frozen feces but again these studies are usually all in relation to treatment outcomes of C. diff infections. I wanted my samples to be fresh. I did not want to risk the bacterial communities in the samples being disturbed from the original donor communities.

One of the reasons FMTs are difficult to replicate with a designer community(i.e. a human putting quantities of bacteria in a designer pill) is that we don't know how much or how little importance each species plays in the process. I had no reason to risk using frozen poop.

There was also the choice of inoculation orally or through enema or both. Most(all?) FMTs are done using a gelatin capsule inside an "acid resistant" capsules as it should help the bacteria survive the traverse through the stomach acids. I used only gelatin capsules. There are no papers that I can find that use solely gelatin capsules, so this isn't to say that it shouldn't have worked just that I was probably better off using the acid resistant capsules. The original plan was also to do both enema and oral but I read research that oral dosages are just as efficient so I went with just that. This could have compromised the experiment but in the end it worked out. Why did it work out? It could be a couple of reasons, I ended up not diluting down the samples or adulterating them in anyway(removing particulates adding saline, glycerol or freezing) and I took antibiotics. It could just be that the acid in the stomach is not as big a worry as suggested but these are just hypotheses with not much evidence to back them up.

Feb 16th 2016, the first real day of the experiment and the first day I would start taking antibiotics.