A molecule called ‘Sandman’ could help solve the ‘mystery of sleep’ | Hacker News Reader

A molecule called ‘Sandman’ could help solve the ‘mystery of sleep’

washingtonpost.com

133 pointschriskanan62 comments

to some of us (ahem, yours truly) the idea that there's a "mystery of sleep" might seem a bit, well, strange. Don't we sleep because we get tired?

Quotes like this are typical of the American tendency to be pseudo-proud of being unintelligent, uneducated or apathetic. I'm surprised they included it and disappointed they did. Perhaps to help the readership identify with the columnist? But then again the readers are actually reading something scientific, so I don't get it.

I think the purpose of this device is to provide context to the problem. If you are about to provide the scientific explanation for something all of us experience every day "Why do things fall down" / "Why is sugar sweet" it helps to take a step back and remind the reader that there is a scientific explanation for the phenomenon they are so familiar with (so much so that it feels unnatural to even question it in the first place).

maybe he dislikes the "ahem, yours truly" part? Although I agree with your point, to me that phrase strongly conveys the "pseudo-proud" attitude the parent OP was referring to

It's a rhetorical device. Asking a dumb question and giving a smart answer is sort of a dielectical approach to writing that helps move a narrative along while conveying a bunch of technical information.

Frankly, I find the neuroscientist that pretends that we have no clue as to why we sleep to be far more obnoxious. While we don't know the full picture, we have plenty of knowledge of things that sleep is for.

I did a neuropsych degree in the early-mid 90s and worked as a sleep tech in the late 90s - we knew certain things then, so it's pretty obnoxious to have this guy come along 20 years later and pretend it's a great big mystery. There's definitely stuff we don't know, but plenty of stuff we do.

I agree, it's unappealing.

Quote sounds like something an editor would request, on behalf of the wider readership.

Perhaps a remnant from print newspapers where readers can't be assumed to have picked this exact article.

It would be great if this opened the door to sleep aids that activated the brain's natural sleep induction mechanisms, as opposed to today's sleep aids, which are basically just sedative/CNS depressant/muscle relaxers.

Well, this is what melatonin does and its OTC. My horrible insomnia was cured not by Ambien, but by .5mg of Walgreen's melatonin and even now I rarely take it.

Its also probably time we admitted human beings can't fit into lifestyles where they're bombareded with blue light, stress, etc right before bedtime. The Western lifestyle is fairly anti-traditional and old fashioned things like prayer/meditation/whatever before bed and calm family time of putting the children to bed or reading to them has been replaced with ipad usage/internet tomfoolery, or tv watching.

I doubt there will ever be a pill to fix this. If you're serious about fixing insomnia then you need to do the legwork of proper lifestyle change. Personally, the benefits I get from running flux on the desktop as well as daily meditation are incredible. Pharmacological solutions shouldn't be our first instinct.

FYI, I'm a chronic insomnia sufferer, and I also found melatonin was a "miracle cure". Even if/when it didn't help me get to sleep on time, I would still wake up feeling mostly rested and able to function the next day.

Flash forward a couple of years, and it started to catch up to me. In retrospect, I guess it was NOT working a lot more often than it WAS, but I was still able to get up at my normal time and slog through another day... until all of a sudden I wasn't.

I started having a really hard time concentrating, remembering things, etc. I went from being proud I had memorized the first 40 digits of pi, to not being able to remember my own damned zip code.

Frankly, I thought it was early onset Alzheimer's, and I started putting my affairs in order. Initial tests were inconclusive, but that's not necessarily surprising: the simple cognitive tests are only useful for spotting advanced decline if you are even remotely non- "neuro-typical". Fancier (and noisier) brain scans showed nothing unusual.

Anyway, long story short: on medical advice I threw away the melatonin, and practically overnight my symptoms evaporated.

This is all highly anecdotal, I know - and you would be foolish not to be skeptical. But I would suggest that if you are using melatonin regularly, and especially if you have been for a long time... You might want to casually start tracking your actual sleeping hours, and verify that you are really getting enough - and not just "compensating."

only thing that worked for me is counter intuitive 'sleep restriction'. Wake up earlier and earlier everyday until you naturally fall asleep at night. Hard part is waking yourself up in morning when you feel like sleeping more.

The problem with your "melatonin" suggestion is that there's no way to know how much melatonin you actually took, since there is no regulation on the chemical, and the "sleep pills" that are purchasable don't say on the label what concentration they're made at, and concentrations vary by brand, and could vary bottle to bottle (due to an inexact manufacturing technique, for example).

In several EU countries, you can buy melatonin pills made by an actual pharmaceutical companies (which also manufacture prescription drugs) OTC. You could order it online. Note there's a difference between unregulated supplement and an OTC drug.

Although I think your worry about quality excessive, it's not like making pills is rocket science. The supplement companies most likely get the powder in bulk from biochemical factories that also manufacture prescription drugs.

In the US, the supplement industry is much less regulated than the pharmaceutical industry.

The concern is not excessive, at least in the US. Consider https://consumerist.com/2016/07/27/anyone-can-make-market-a-... :

> While real drugs — prescription or over-the-counter — must demonstrate levels of safety and effectiveness before hitting store shelves, dietary supplements are effectively regulated like food products.

https://consumerist.com/2016/01/20/7-things-you-need-to-know... gives a summary of a Frontline episode on the topic; Frontline does documentaries on public affairs topics.

Or, from 2001, http://ajcn.nutrition.org/content/73/6/1101.full - "All plant products were correctly identified by botanical plant species (ie, Panax species or E. senticosus); however, concentrations of marker compounds differed significantly from labeled amounts. There was also significant product-to-product variability: concentrations of ginsenosides varied by 15- and 36-fold in capsules and liquids, respectively, and concentrations of eleutherosides varied by 43- and 200-fold in capsules and liquids, respectively."

Or from the 1990s, http://www.sportsci.org/jour/0003/lmb.html :

> Analysis of 16 commercial DHEA products revealed that only half the products contained the amount of DHEA stated on the product label; content varied from 0 to 150% of the stated content (Parasrampuria et al., 1998).

> Melatonin supplements have failed to meet quality claims or delivery profiles stated on their labels (Hahm et al., 1999).

It lists others as well.

Mine was cured by establishing a consistent sleep schedule, a change in diet, and not doing anything interactive for at least an hour or so before bed (no programming, no video games, etc.).

I concur with several others on this thread that in my experience, after years of trying different things, the only thing that worked was consistently waking up early everyday (~6am).

I also read in bed until I'm sleepy (usually within 30 minutes). The common literature on this subject says not to do that so I avoided for a long time. But one day I decided to try and it worked!

http://www.consumerreports.org/vitamins-supplements/does-mel...

Note that this does not address quality of sleep or effect on circadian rhythm, both of which are the primary action of melatonin supplements.

Is there some study to indicate that it does?

> but by .5mg of Walgreen's melatonin and even now I rarely take it

Does that require a prescription?

You can buy melatonin in a variety of doses over the counter. Its normally near the vitamins and supplements part of the store.

OTC melatonin has fairly unpredictable quality though. The amount of melatonin in the entire bottle might be correct, but the amount in each pill may vary wildly. You can get prescription melatonin that's actually controlled so each pill has the same amount in it.

Or you can get it in pure powder form and make your own dose (like http://www.powdercity.com/products/melatonin-powder )

Note higher dosing is NOT better...most OTC melatonin supplements give too much. 0.5 to 1.0 mg should be used 1-3 hours before bedtime.

1-3 hours? Do you have a source for that advice? Everything I've read, and my personal experience with it, suggests taking it (as you say, .5 to 1mg) 30 minutes before you want to fall asleep.

http://www.mayoclinic.org/drugs-supplements/melatonin/dosing...

http://www.talkaboutsleep.com/how-to-use-melatonin-correctly...

Number of hours are all over the map. Hey, if you feel its effects within 30 minutes, then that's what you should use...

Personally I take it 45 minutes before expected bedtime (irregularly, only if I feel I need it).

I use a liquid form of melatonin. A dropper is included in the one I use. I found I could measure my dose way more accurately than breaking tiny 3mg pills haphazardly.

Well, this ended on quite the cliffhanger. Incredibly curious what is next discovered about this "sandman" ion channel and what it interacts with and responds to.

Additional links:

Oxford write-up which sticks more prosaicLly to the science (I imply no pejorative connotation to "prosaic", I simply mean there are fewer flourishes and asides): http://www.ox.ac.uk/news/2016-08-03-researchers-discover-san...

Paper in Nature: http://www.nature.com/nature/journal/vaop/ncurrent/full/natu...

The article doesn't spell it out, but it seems that's how dopaminergic stimulants make it hard to sleep. Dopamine deactivates the sleep circuit. This opens the way to stimulants that doesn't impair sleep and the reverse. That could explain (partially unknown) modafinil's mode of action - a dri that works preferentially on the sleep neurons.

It's not a molecule though - it's an ion channel. There is no compound called sandman as I understand this.

The authors refer to the CG8713 gene product as Sandman, which is a single molecule. Flybase associates this gene with a single polypeptide, predicted to be 395 amino acids long [1].

My research skills are rusty, but I found a paper which makes it sound like this channel is probably a heteromer [2].

So yeah, the ion channel is almost certainly composed of more than one subunit (and thus more than one polypeptide, and more than one molecule), but the researchers are focusing on this subunit.

[1] http://flybase.org/reports/FBpp0087858.html [2] http://www.ncbi.nlm.nih.gov/pubmed/17074048

A channel is made of molecules. But I see you point.

I have my own theory.

We sleep because that's when we are logged out of the virtual game that this world is.

I'm only semi-serious.

But let's work with it. What if we research sleep right until there is nothing left to find out, and we since can't figure out any reason at all for it?

Could we use that to postulate for a reason that is non-physical? Spiritual? Virtual reality? Something else?

All is one; during sleep the undistracted soul is absorbed into this unity; in the waking state, being distracted, it distinguishes diverse beings. (Chuang Tzu)

When you're logged out of a virtual game, nobody can force you to log back in. But you can wake up someone who's sleeping.

Some people are hard to wake up.

Have you never set a game with alerts that make noise if something interesting is happening, so you rush back and play?

The delay in waking up is how long it takes the "player" to get back to his chair.

If the player did not go back that would be seen by us as fainting, or in longer situations, a coma.

That's just the simulation mixing it up. If I am going to use a simulation as an escape it sure as hell is going to be single player.

Hey Hiro, you want to try some Snow Crash?..

So why do we dream "programming"? I'm sure many others here too suffer from problem-solving in their sleep.

Maybe it's just refactoring and caching, and we are full biological systems with no hidden variables in the macroscale.

> So why do we dream "programming"?

Because the "you" that is conscious is actually your game player in another world. So it's that "person" that is actually programming. Your body here is basically a robot.

This would also explain why we can't figure out what consciousness actually is - if it's not physically in this world that would make it hard to figure out.

This theory makes the need to logout/sleep even more puzzling: if the need to logout is not attached to the robot then why did it biologically evolve on the robot in the first place?

That's the whole point - it's not the robot sleeping. For example people in a coma don't sleep.

> biologically evolve on the robot

I'm not aware of any multi-cellular organisms at all that don't sleep. None.

So if it did evolve it must have done so in a single celled organism that doesn't sleep, which of course makes no sense. (Why evolve the need for something you'll only need when multi-cellular?)

" ... and future research will explore what affects sleep quality once asleep ..." :)

"Sleeping animals are incredibly vulnerable to attacks, with no obvious benefit to make up for it — at best, they waste precious hours that could be used finding food or seducing a mate; at worst, they could get eaten."

It seems pretty obvious that sleep had an evolutionary advantage to conserve energy when the species couldn't be productive. For example, human sleep during the night because we can't forage / hunt / find a mate during the night because our vision requires light.

"Pretty obvious" answers never hold up much to scrutiny, or the questions wouldn't be actively studied.

Many animals are nocturnal. They eat and mate during the night, and sleep during the day. From your theory, what reason do they have to sleep during the day? They could be doing all sorts of productive things in the light -- more mating, making homes, defending themselves and their babies from predators, migrating, etc etc.

Yet they need to sleep during the day. Why?

It looks like some pretty heavy optimizations are needed if you want to be successful in one of those environments (daytime vs nighttime). Visual perception has to be fine-tuned for one of those environments. Perhaps thermal regulation is different too.

So I guess one possible explanation is that too many fine-tunings are required to work well in one environment, to allow the organism to be a good performer in both. So the logical choice is to withdraw from the other environment - just don't participate.

The parent comment only mentioned humans being diurnal, not other animals.

There's a number of strong evolutionary forces that explain nocturnality: niche differentiation, crypsis, a predation arms-race, water conservation, etc.

https://en.wikipedia.org/wiki/Nocturnality#Survival_adaptati...

I'm not sure your point about humans vs other animals.

Are you suggesting sleep evolved for a different reason in humans than it did for our ancestors and the millions of other species that sleep?

That doesn't seem obvious at all, it presumes sleeping is about conserving energy and that's an unwarranted assumption and baseless assumption. Sleep very well could be a requirement for brains to work they way they do. If you are deprived of sleep you will shortly go crazy; sleep isn't about saving energy.

If you see anything that seems obvious, you can bet science already checked that out and moved past it and that it's more complicated than that.

Anytime your beliefs conflict with science, you should immediately question your beliefs, not the science. The odds are absurdly high, near a virtual certainty, that your beliefs are wrong; never assume science is missing the obvious (unless you're a scientist and it's your field of study, then you might be onto something but you're still probably wrong).

Yeah. For starters, there is a whole bunch of toxins that build up when you don't sleep enough. But it can't be the whole story, as why wouldn't we have mechanisms to remove those and keep the brain functioning?

It can't be all about memory retention. There are some fascinating studies on how some groups of neurons repeat the same patterns they did when the organism was awake, presumedly for long-term storage. But why can't storage happen while awake?

There must be a reason why these "brain batch processes" run while most of the brain is shutdown.

I've found that it's best to not think that evolution optimizes for the best thing but rather that it optimizes for "good enough". Sometimes they are one and the same but they don't have to be.

Sleep could have started as a rudimentary adaptation to one thing and ended up being refined and coopted for other things.

Evolution is diverse, if all living things need sleep then I think its A: something that is absolutely needed, without it you wont survive [guaranteed] B: A left over from our common ancestor

    > why wouldn't we have mechanisms to remove those and keep the brain functioning?

I don't know if it's in the links below, but I remember hearing a talk that the flushing required physical changes inside the brain: Widening of channels (by neurons getting smaller and making room, if I remember that correctly?). So normal function can't go on while the flushing process is being performed.

https://www.nih.gov/news-events/news-releases/brain-may-flus...

https://www.nih.gov/news-events/nih-research-matters/how-sle...

Since we have distinct sleep phases we may not have just one "sleep", (very) different things going on at different phases.

Science can often be helped by some questioning, esp. from scientists outside the field of study.

>If you see anything that seems obvious, you can bet science already checked that out and moved past it and that it's more complicated than that.

Science doesn't do anything. Even if it did, you should be able to look the obvious results up and figure out where current research has taken your question.

Many nocturnal animals have eyes and utilize vision of light. Also, many animals who wake during the day and utilize vision of light also frequently hunt at night (eg see lions during hotter seasons).

It may well be that specializing systems such that they perform well during daylight only could lead to greater advantage than maintaining additional mechanisms for performing well at night also (or vice versa), and that sleeping during the downtime in order to conserve energy might confer supplemental advantage in this scheme. But we don't know if this explains all sleep, in all species.

Even if we did, then sleep in animals which perform reasonably well at any time of day would still be unexplained. Common ancestry wherein sleep evolved earlier may explain that, but we don't have that evidence as far as I know.

As such, it doesn't seem this is quite so easy to conclude about, let alone obviously so.

> For example, human sleep during the night because we can't forage / hunt / find a mate during the night because our vision requires light.

What makes you think the causality is in that direction? This is clearly a teleological argument (read: assumes that everything has a function, which is contradictory to the way evolution works, where the only function is to help your genes propagate).

Taken on its own, unconsciousness is a massive evolutionary setback--an explanation like "conserves energy" doesn't cut it, when there are plenty of nocturnal predators around. Why didn't humans evolve to lie down at night, with their heartrate and breathing slow, but remain fully aware of their surroundings? That would make survival to reproduction age a lot simpler.

No, there is animals that sleep during the day and can see perfectly good during the night.

As other commenters has said it's not that obvious.

I suspect it's more that sleep is a necessary requirement for consciousness, but it's not clear why. Maybe recalculating weights for the neural net based on new input data requires 'downtime'.

There was some earlier evidence that 'cleanup' is happening the brain or some chemical pathways were being reversed. Either way behavioral speculation based on evolution isn't very good science.

> because our vision requires light

Even on a new moon, there's plenty of starlight. Nocturnal animals are able to take advantage of that.

>because our vision requires light.

doesn't that assume that requiring light came before sleeping at night. It could be the opposite, our vision requires light because we sleep at night?

Optical vision does not seem to require sleep:

https://en.wikipedia.org/wiki/Sleep_in_fish

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