Curing Sleep: My Experiences Doing Cowboy Science
Epistemic status: Subjective report describing youthful exuberance. The actual experimentation part of this was very badly executed.
In light of the recent homemade peptide vaccine, this is a writeup of my experiences in insufflating internet chemicals.
This happened during a period of my life when I was very bored, kinda rich, and getting really into darknet libertarian culture. This is cowboy science, and upon reflection, I was insufficiently concerned about either of legal troubles or brain damage.
Background
Orexin (aka hypocretin-α) is a neuropeptide which promotes wakefulness, weight loss, and happiness. Damage to the orexinergic system seems to cause Type 1 Narcolepsy—comorbid with sleepfulness, obesity, and depression.
Deadwyler et al attempted to prove a causal relationship, by sleep-depriving rhesus monkeys and having them insufflate orexin. It appears that sleep-deprived monkeys snorting orexin perform as well on cognitive tests as the non-sleep-deprived monkeys.
So there I was, a graduate student reading through this paper, and you can hear the gears in my head turning.
Orexin insufflation appears to promote wakefulness in sleep-deprived primates.
I am a sleep-deprived primate.
...
Transhuman Greed
Will this cause some kind of...anti-narcolepsy? Have I found a cure for sleep itself??
I was properly embracing More Dakka. But this Kerbal Space Program-tier science thought wasn’t as nuts as it seemed. This was 2012, the orexin research was fresh, and my neuroscience professors were still touting the party line of “perhaps the only purpose of sleep is to keep humans indoors and conserving calories during the night, because their comparative advantage is day. We don’t even know why, or even if, we really need sleep!”
(We didn’t know about sleep-as-memory-post-processing, or that, during sleep, the brain lobes spread apart to let the CSF pressure-wash away all of the metabolite byproducts. We just thought sleep was one of those no-longer-adaptive biological quirks inflicted by evolution, which, in defense of past neuroscientists, happen all the time.)
And so, at the thought of no longer needing to sleep, I was filled with a transhuman greed...
The Experiment
So I ordered a vial of primate-brain orexin from the internet, and got to snortin’.
(Did you know that places selling chemicals “for research purposes only” don’t check to make sure you’re a real researcher? As far as I can tell, it’s just enough verification for them to maintain defensibility when you do something stupid with their chemicals. This has problematic implications for biosecurity and should be patched immediately, but is great when you want to do something stupid with chemicals.)
I asked my friends which of them were willing to go on this journey of discovery with me. Perhaps predictably, most of them took issue with deliberately putting a little-researched internet chemical into their brains, “to see what happens”.
But I did find one volunteer. And so we began to do science. Or, at least, SCIENCE!!
Our experimental design was as such:
We will establish baseline tests for our subjects—reaction speed, serial sevens, short-term memory recall, and whatever else comes up when you google “cognitive test online”. We will establish baselines for ourselves both in sleep-deprived states, and non-sleep-deprived states.
I will unfreeze and measure out the appropriate doses of this powder into some distilled water, and put it in insufflation syringes.
We will give the orexin syringe to our sleep-deprived subject, and they will SNIFFF
Results
Our scores on the tests during conditions of sleep deprivation improved to be commensurate with baseline.
We still felt sleepy, though.
However, the reason why I didn’t take to the streets shouting about my cure for sleep was because the experiment was so sloppy that I didn’t even trust those results. See below.
Experimental Design Flaws, Any One Of Which Would Get It Thrown Out, tbh
Although my confederate experimenter/subject was blinded to whether the spray was orexin or placebo, I was not. I guess I intended to compensate for the placebo effect by “trying real hard”.
Because orexin was expensive, I only bought enough for four doses, which put an upper limit on how many trials we could run.
n=2, y’all.
Now, Take to the Streets and Do A Science
Thus concludes my tale. And although for a few years afterwards I puttered about trying to recreate this experiment, I got distracted by life and romance and cryptocurrency, as is always the case.
If you feel like studying this area and perhaps curing sleep, I am cheerfully available as a consultant.
Whatever happened to orexin and the sleep peptide research, anyway? This feels like the first time I’ve heard about it since 2014, but I didn’t hear about any crippling side-effects or big failure to replicates (of the sort that have seriously hampered interest in oxytocin). Did DARPA just stop funding it and no one else stepped in?
How did the feeling compare to modafinil, if you’ve tried all-nighters with that? With modafinil, I always characterized it as not so much that you felt sleepy as that you felt irritated, like “butter scraped over too much bread”, in Bilbo Baggins’s phrase.
From my email exchange with Deadwyler, I took away that DARPA lost interest, and Deadwyler himself disappeared to go work for tobacco companies. And because orexin occurs naturally in the brain, it can’t be patented, which means that it’s hard to make money on it.
(I would expect a snortable cure for sleep would be worth something regardless, but I’m not a pharma company, so what do I know.)
Felt very different from modafinil; on a moda all-nighter I feel just mostly normal, kinda headachey, and a numbed fatigue. On orexin I still felt like I hadn’t slept; let me paste in my journal entry from that day (which is, to my great consternation, literally the only note which remains from this experiment).
“Feel spacey and out of it. More so than I did earlier, though that might just be that I’m interacting with people now.
Also hungry. More hungry than warranted? Not sure. Had a mealsquare around… 9? 10?
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Some people are willing to pay a premium for the ability to buy something legally.
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I’m confused why your lab didn’t know about sleep as memory post-processing. My high school psych class in 2005 taught that.
Made me laugh out loud twice, I enjoyed this post 😊
I’m not sure it’s actually useful, but I feel like I should introduce myself as an individual with Type 1 Narcolepsy. I might dispute the claim that depression and obesity are “symptoms” of narcolepsy (understanding, of course, that this was not the focus of your post) because I think it would be more accurate to call them comorbid conditions.
The use of the term “symptom” is not necessarily incorrect, it could be justified by some definitions, but it tends to refer to sensations subjectively experienced by an individual. For example, if you get the flu, your symptoms may include a headache, chills, and a runny nose. On the other hand, it’s rather unlikely that you may tell your doctor that you are experiencing the symptom of obesity, you’d say you’re experiencing weight gain. Comorbid conditions, on the other hand, refer to conditions (with symptoms of their own) that often occur alongside the primary condition. The term “comorbid” is the one I find most often in the scientific literature about narcolepsy and other disorders and conditions.
Why am I writing an entire comment about this semantic dispute? Well, firstly, given the goals of this website, it seems that correcting an error (no matter how small) seems unlikely to have an unwanted result. Secondly, I think that the way we talk about an illness, especially a chronic illness, can significantly affect the mindsets of people who have that illness. The message of “narcolepsy can cause obesity” seems less encouraging to an obese narcoleptic than “Narcolepsy increases the chance of becoming obese”. That might just be me, though, so it’s inconclusive.
I hope this comment hasn’t been too pointless to read. What do you think about the proposed change? Do you think that there’s a difference between calling something a symptom and calling it a comorbid condition? Oh, and if anyone wants to know anything about my experiences with type 1 narcolepsy, ask away.
Fair critique! Changed.
This article is amazing, I appreciate a good laugh.