As The Toast searches for its one true Gal Scientist, we will be running a ton of wonderful one-off pieces by female scientists of all shapes and sizes and fields and education levels, which we are sure you will enjoy. They’ll live here, so you can always find them. Most recently: How to Build a Galaxy and Fight an Army.
Hi, Toast! As a brief instroduction, my own research is focused in the areas of infectious disease and cancer, and using organic chemistry and enzymology to discover new drugs. Specifically, I design and synthesize molecules to inhibit enzymes that are integral for the progression of various disease states, and I love it because it lies on the interface of chemistry and biology. But I also have a great deal of excitement about other really cool, new research findings outside the area I specialize in. Stuff like sleep, and why we do it and what it means.
I would venture to guess that most of us have suffered from sleep deprivation at some point in our lives, whether mildly self-induced as a consequence of some current stressor or as part of a larger, more widespread pattern. What’s interesting about it is that pretty much everyone has the same uncomfortable experience in the lack-of-sleep situation: inability to concentrate, incompetence when it comes to decision making, forgetfulness, general non-retention of information. So why does sleep deprivation universally make us all feel like we’ve just crawled out of the primordial sludge? And why is sleep so important?
It’s an interesting question seeing as pretty much every living species on the planet Earth sleeps (well, at least all vertebrates). There’s this disease called fatal familial insomnia (FFI), in which people suffering from it are physically unable to sleep. It starts sometime in adulthood when they begin to experience progressively worsening insomnia, which persists throughout the course of the disease. They suffer from panic attacks, paranoia, etc. Then, after about four months of insomnia, they start hallucinating. This lasts for about five months until they lose a ton of weight, disintegrate into dementia, become unresponsive to environmental stimuli and die. In one instance, doctors tried to alleviate the symptoms of an FFI sufferer by using sedatives to induce a coma, but even this was unsuccessful. These people simply cannot sleep. You know what causes this disease? Misfolded proteins in the FFI sufferer’s brain. The same type of thing that causes mad cow disease. But I digress…the point is that sleep is crucial. Crucial enough that lack of it will kill you. So crucial that hibernating bears wake up from hibernation to sleep. So what is the science behind sleep? What is this crazy phenomenon where we lie dormant, in dark places, snoring and drooling and mumbling without any outward semblance of self-awareness?
It’s generally pretty well accepted that the purpose of sleep is to allow for the rejuvenation of various systems in the body (immune, nervous, etc.). For instance, rats that have suffered skin burns have a retarded rate of healing when sleep deprived. Sleep is also intimately related to memory and brain function. But that is only part of the story and our understanding of the subject is incomplete at best.
An article published recently in Science by a team of researchers from the Center for Translational Neuromedicine at the University of Rochester Medical Center illuminates one of the crucial functions of sleep (DOI: 10.1126/science.1241224.) From their research, Xie and coworkers have concluded that during sleep, the toxic products of brain metabolism (yes, our brains create waste just like the other organs in our bodies) are evacuated from the interstitial (in-between) space among brain cells. Here’s the thing: our brains do not have a lymphatic system (a system that transports stuff that needs to get moved.) So this interstitial space among brain cells serves the purpose of a lymphatic system in the brain – removing toxic metabolites produced by normal brain functioning. The interstitial space holds the brain waste until it is washed away by the flow of cerebrospinal fluid (CSF), which is filtered out of the blood and pumped into the brain. After percolating around the brain a bit, the flow of CSF (and the waste products it picks up) is eventually pumped back out into the blood stream around the brain, where it can ultimately be removed from the body by other means. Now, how does sleep affect this?
So usually, this interstitial space occupies about 14% of the total volume of the brain. Xie and researchers monitored both anesthetized and naturally sleeping mice and found that the interstitial space increases by over 60% to occupy 23% of the total volume of the brain when the mice were in both the anesthetized and sleeping states. This allows for an increase in the flow of the CSF and the toxic brain metabolites transported by it. These researchers found that when the mice were awake, the CSF flow was limited only to the surface of their brains – occluding the transport of toxic metabolites from deeper in the brain tissues. While in the waking state, the CSF flow was limited to just 5% of the flow found when the brain was in a sleep state. When the mice were asleep, the interstitial space was found to expand, allowing the CSF to flow into the deeper tissues of the brain and more effectively carry away harmful products of brain metabolism.
Bottom line: the increased flow of CSF through the interstitial space during sleep allows for the more effective removal of toxic brain metabolites. One of those toxic metabolites is a peptide known as β-amyloid (Aβ). This peptide is intimately related to the progression of Alzheimer’s disease (it forms plaques in the brain). Xie and researchers put radiolabeled Aβ (basically put a tag on it so they could monitor its whereabouts in the brain) and found that when the mice were sleeping, the radiolabeled Aβ was evacuated from the brain two times faster than when the mice were awake.
These findings by Xie and coworkers shed some light on the symptoms experienced by sufferers of FFI, right? Because of their inability to sleep, the toxic waste products of brain metabolism build up in the interstitial space of their brains, and they experience panic attacks, paranoia, hallucinations, and eventually dementia and death.
So here’s the proposal for the purpose of sleep: during the day, the brain accumulates toxic metabolites in the interstitial space. When the accumulation of these metabolites hits some concentration, we start to feel tired. The accumulation of metabolic waste flips a switch in our brains, indicating that we need to go to sleep so they waste can be more effectively cleared from our brains. The result is the cycle of wake and sleep states that we all experience. So get some sleep – it’s a beautiful thing.
Tags: chemistry, gal science, sarah st. john, science, sleep
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This lasts for about five months until they lose a ton of weight, disintegrate into dementia, become unresponsive to environmental stimuli and die.
HOLY FUCK.
Welp, time to add this to the List of Things I Will Be Unreasonably Terrified Of Getting, along with Hiccups That Won’t Go Away for Years.
I am so frightened of Those Hiccups that the ordinary kind of hiccups can tip me into a panic attack. No joke. Brrr.
Holy shit, I had no idea those even existed.
Don’t worry! If no one in your family had it, you are not going to get it. The number of people in the world with FFI is in the low hundreds, and they’re all concentrated in a small number of families.
Hi, Sarah! Great little review! I’m also an enzymologist from Indiana! If I still lived there, I’d offer to screen your inhibitors for you!
That’s awesome! I actually got my Ph.D. in organic synthesis and have moved on as a post-doc in an enzymology lab. It’s like a whole new world!
This is fascinating, Sarah! Thanks!
So, question: since starting full-time work 18 months ago, I’ve been getting tired much earlier than I used to in high school/college/grad school/whatnot. Is this because my brain is doing more stuff and accumulating more brain junk, hitting the go-the-fuck-to-sleep point sooner?
(Also, who else wants a nap right now?)
Question seconded! Also: can this brain-waste make you anxious? No matter how good my day was, I’m always at least a little (sometimes a lot) anxious at night, but wake up completely fine. Even when I’m super-anxious by bedtime, my mornings are always a million times better.
Sleep is definitely a Thing but there is also a pretty strong connection between circadian rhythms and mood disorders, which is also cool / fascinating.
Thanks for reading!
I do not know the answers to these questions, but they are good questions. It is plausible that more thought leads to more brain waste and ultimately to getting tired faster…
It’s also plausible that brain-waste leads to anxiety in some people…
THESE ARE GREAT HYPOTHESES THAT DESERVE INVESTIGATION!
I volunteer to nap heavily. For science.
(Also, thank you for writing about science in a way that is interesting and understandable. It’s not something everyone can do.)
if you’re getting up earlier for work than you used to (regularly) for school, that could be it–I was always a late sleeper/night owl but enough time on the standard workday schedule has turned me into one of those people who routinely wakes up before 9am on weekends.
it’s also a getting-older thing, I think–I could regularly get by on 4ish hours of sleep a night when I was younger & feel mostly fine (particularly if I could binge-sleep after a few days) but now I’m 30 & just can.not.
“For instance, rats that have suffered skin burns have a retarded rate of healing when sleep deprived.”
Did anyone else have to take a moment and think about that study? Because I did, and now I can’t stop, and in spite of my meat-eating-and-leather-shoe-wearing-and-generally-pro-research stances, I am horrified.
I didn’t (see above, I was still seriously freaked out by the idea of not-sleeping myself to death) but NOW I did and… yeah. That’s… that’s really fucking horrific. Even knowing the valuable things science can learn from it, that’s just awful
Yeah, it’s pretty fucking terrible. Do you know they cut the vocal cords of Beagles so that they can’t cry out in pain when being experimented on? Poor dogs live in cages their whole lives and never see the sun or the grass.
See also: http://www.beaglefreedomproject.org/
D: D: D:
jesus
Whoa. I wonder if this could have anything to do with how much more alert I feel after meditating! (I generally only do it at work, in the afternoons,when I’d kill for a nap).
Seconded! Is it like a speed wash cycle for our brains?
Eyes in the dark. One moon circles.
That episode frightened me as a child.. so thumbs up to you for that somewhat obscure ST:TNG reference!
uh, that episode frightened me as an ADULT, to the point that thinking about it (even now, in my un-spooky apartment) gives me the willies.
I haven’t revisited it as an adult. Not sure if I want to. Spiritual (or mental) possession is another one of those things that also gives me the creeps, and being the unwitting conduit of a dying person is waaaaay to close to that.
Loved this, so well-explained. Forwarding to my 5-month-old, who is currently the PI of a sleep-deprivation study with her parents as research subjects.
Hahah. I just moved my kid into her own room after over a year of shitty sleep. I am A DIFFERENT PERSON. It is glorious. You will get here too. I shudder to think how I’ve stayed employed this last year after noting the uptick in productivity.
I’m so glad that my daughter’s funding ran out right after her first birthday.
You know, if she didn’t have you sign consent forms, you could probably report her to an IRB and get some kind of compensation.
This is the best comment thread.
This is my favorite Gal Scientist yet.
This is so interesting! It also makes me think of the meme that Margaret Thatcher got by on four hours’ sleep a night, which is like YES UNTIL SHE HAD DEMENTIA FOR THE LAST 15 YEARS OF HER LIFE
Right?! I don’t think the 20 hr day is worth the 15 YEARS OF DEMENTIA! Interesting aside, Margaret Thatcher was originally a chemist.
Aren’t there rumors that Thatcher some genetic help with that?
FATAL FAMILIAL INSOMNIA!! I am morbidly obsessed with that disease. Did you know that there’s a version that occasionally strikes people who have no family history of it? And sedatives/sleeping pills just make it worse? Or that it was partly discovered by an Italian man looking through a church’s records on local families to figure out why everyone in his wife’s family was dying so young?
All those facts are horrifying, except for the bit about the Italian man, which is mostly just interesting.
This motivated me to write a stern email to my terrifying landlord about the INCESSANT BANGING of my radiators which ruin my sleep and cause me to wake up bleary-eyed and angry and, apparently, full of uncleared brain-toxins.
Fully open all of the valves on the base of the radiator to ensure that they drain properly. It might take a day to drain but it will help
You can also buy a doohickey at a hardware store to bleed the radiators and make them quiet and lovely again.
The NY Times has published a couple of articles recently about the link between insomnia and depression and the efficacy of sleep therapy for treating depression. Makes a lot of sense, and more so in light of the above.
This is excellent!! I am a cancer prevention researcher and sleep is a very hot topic right now in chronic disease prevention– there is a very cool emerging area of research around the importance of sleep hygiene, especially in correlation with obesity. So far my reading on the subject has been limited to the connection between poor sleep hygiene and chronic disease (shift work and being awake at night is also linked to breast cancer), so it was very interesting to learn more of the functions of sleep and how weird our brains are. You go, girl scientist!
You can also buy a doohickey at a hardware store to bleed the radiators and make them quiet and lovely again.
But I digress…the point is that sleep is crucial.
No, no, the point is–the point always is–that prions are fucking terrifying.
PRIONS ARE FUCKING INTENSE.
That’s the most important fact I learned from a degree in Biology.
This is a nice explanation of this study. It also makes me feel less guilty about my patented NOPE response to life choices that require prolonged sleep deprivation.
Hi Sarah! Fascinating piece. I really enjoyed your writing style, and how you made complex science-fact-things applicable and interesting to anybody reading. The Toast did a great job running your article! Hope to see more from you!
Sleep is definitely a Thing but there is also a pretty strong connection between circadian rhythms and mood disorders, which is also cool / fascinating.
This was fascinating
I have a question in relation to the build-up of waste brain due to lack of sleep, and seeking professional help for insomnia.
I have a friend who has the worst insomnia of anyone I’ve ever met. She even is able to take an entire Ambien, after being awake for over 48 hours, and STILL not be able to sleep. Sometimes she CANNOT SLEEP FOR DAYS, and eventually only sleeps because she has literally passes out. The longest she went without sleep was over a WEEK, and afterwards she slept for almost 24 hours. Even after a night without sleep, she appears relatively normal, just a bit tired. But when she hasn’t slept for days, I have witnessed her having very brief hallucinations (“whoa it just got all purple in here”, she once said), and she becomes unable to stay awake in class, and also is more easily confused and mentally overwhelmed . She also has terrible headaches almost daily, and sometimes has migraines so bad she cannot stand up. She connects these to sinus problems (which she does have), but I also think lack of sleep is a contributor. She also has some anxiety (as do I along with many people, let’s be honest), but she deals with it very well.
She’s lucky to get two hours of sleep at night, and half the time sleeps less than an hour or not at all.
Despite her “I’ll-just-deal-with-it” attitude, I am worried for her mental health, even more so after reading this article.
I’m not worried about FFI, but I wasn’t aware that mental illnesses later in life could be connected to lack of sleep. She has seen her doctor for this, but I wonder how effective he really is, since he apparently instructed her to take only half an Ambien tablet, and to not take it every night. But if even a whole Ambien combined with a lack of sleep for days can STILL not make her sleep, I worry that she should have it more looked into. But knowing her, she will most likely just suffer in silence rather than seek further help.
Basically, I’m wondering if anyone here would have any suggestions regarding my friend.
Many people have sleep problems, but I think that not being able to sleep for days is a whole other level. I don’t think she should have to suffer like this, and should seek some better help, but I have no idea who would be able to help (and how other than just give her more Ambien). Especially concerning how her insomnia could hurt her later in life, maybe even more than it does now, is worrying.
Does anyone have any advice?
That sounds terrible. I think your friend needs to see a doctor, other than the one she has already seen, who specializes in sleep – or at least one that could point her in the direction of a specialist. Maybe you could offer to go with her?
sstjohn2013, thank you!
Great article Sarah, all has been said in comments. I don’t have any more words to appreciate your efforts in this writing 🙂