
Can a molecule that makes mice smarter heal a human brain? - fraqed
https://www.statnews.com/2016/09/28/memory-isrib-peter-walter/
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unimpressive
FTA:

"To Walter’s dismay, some are buying ISRIB online and ingesting it, long
before it’s been extensively tested...

Some outside scientists remain skeptical. They warn that interfering with
vital cellular mechanisms, as ISRIB seems to do, could lead to a host of
dangerous side effects. They caution that it will be years, or possibly
decades, before it’s ready for testing in humans."

Cause, meet effect.

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iconjack
Isn't _Flowers for Algernon_ required 7th-grade reading anymore? This isn't
going to end well, people.

~~~
philipkglass
I would guess that you are right simply because most drugs that initially show
promise in mice fail during clinical trials in humans.

But it's also worth remembering that the trope in fiction of
_$REALLY_GOOD_THING_ turning out to be _$BAD_THING_ in disguise is just that,
dramatically convenient fiction. There's no natural "game balance" to the
universe. Yet popular entertainment is very small-c conservative about human
improvement; if vaccines were still the stuff of fiction rather than daily
life, a TV drama would show that universal prevention of smallpox has some
terrible side effect that turns out to be worse than just letting people get
infected and die. Fortunately we know that to be false but it won't stop
dramatists and those shaped by them for immediately looking at newer
biomedical advances with the most crushing cynicism.

(Not _really_ directed at you, since I take it you're joking a bit, but this
was the comment that prompted my thoughts...)

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beambot
> I would guess that you are right simply because most drugs that initially
> show promise in mice fail during clinical trials in humans.

What about the contrapositive... How many substances fail in mouse studies
(and are discarded), yet would have been viable in humans? Any known examples
of this?

~~~
philipkglass
I don't know off the top of my head of any drugs that work in humans but have
intolerable problems in mice. I do know that some substances are much more
toxic to other mammals than to us. For example, acetaminophen is very toxic to
cats. Theobromine is much more toxic to dogs and cats than to humans.
2,3,7,8-Tetrachlorodibenzo-p-dioxin is rapidly lethal to guinea pigs at a
level that might only cause skin problems and/or reproductive defects in
humans.

~~~
blackbagboys
Minoxidil, the active ingredient in Rogaine, is lethal to cats.

~~~
eth0up
Curiously, felines are apparently among the most resistant mammals to prions,
maybe second to pigs.

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KlaudijLikon
The fact that you can patent a molecule blows my mind.

~~~
leemailll
This is how big pharma works.

~~~
phkahler
Yep, isolate lovastatin from red yeast, patent it, market it, and then try to
make the supplements take it out since they're not FDA regulated.

BTW, red yeast rice did wonders for my blood work.

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zafka
I am curious. Does anyone know someone who has tried this on themselves yet?

~~~
RankingMember
Some "life extension" site forum had a group buy for the stuff apparently.
People posted some of their results:

[http://www.longecity.org/forum/topic/68589-isrib-group-
buy-n...](http://www.longecity.org/forum/topic/68589-isrib-group-buy-new/)

One quote: _So far I 'm very much surprised about the effect on the overall
cognition. My personal experiences are, that ISRIB definitely has it's effects
on memory consolidation, but in my experience it doesn't only influence the
long term memory formation (as JPC suggested), but the short term memory as
well. It mens practicaly, that while reading a text, it is way much easier to
remember the words, expression, and contexts as well (after 1-2 days). For
instance currently I'm studying medicine basics again (I will enter a
residency program soon), the subjects floaded with unique expressions related
to molecular biology, basics of anatomy etc.. meaning, they are not very easy
to link while memorizing even for a medical professional (they are meant to be
boring..), and so far, after two days (meaning the text I read on friday) I
can still remember a lot sharper on the names of for example cellular
proteins, special basic physiological mechanisms than before, it is very
obvious to me. I have to add, that I would value my memory above the average
(as far as I can asses), but lately I somehow got slower by memorisation (I
think it is an aging effect, and that was one of the reasons, why I started to
search for some chemical hacking of my brain..)._

~~~
AstralStorm
Sample size of 1, no blinding, no verification of the substance received.
Quite worthless.

Placebo effect is strong enough children recognised as more intelligent by
chance do act and measure smarter.

~~~
beambot
Many major innovations occurred from individuals experimenting on themselves.
In fact, it's one of the few ways to make progress when you have overbearing
regulatory agencies.

You should be glad that many enterprising "sample sizes of one" are willing to
become anecdata for everyone else. They push the boundaries so that maybe,
just maybe, we get the benefits of these advances within our lifetimes rather
than after many generations of careful study (ie. too late for me).

Carry on, intrepid experimenters! Some of us appreciate your reckless abandon.

~~~
goatlover
But we can't know from a sample of one whether the placebo effect was in play,
or whether the individual's response was atypical.

~~~
beambot
How do you think humanity learned about new medicines before clinical studies?
A journey of a thousand miles starts with a single step; or in this case, a
single experimenter.

~~~
crooked-v
This is also how people learn about the dangers of fan death, how carrots help
improve your night vision, and that bulls are enraged by the color red.

~~~
beambot
Those examples seem _super_ consequential compared to all the medical
advancements that we got... I would gladly keep the medical advancements in
exchange for turning off fans inside, eating more carrots, and avoiding red
around bulls (or just avoiding bulls altogether; they stink).

Thankfully, humans like to try new things and then apply cause-and-effect
reasoning to create good, new hypothesis (based by early citizen science
evidence). I suspect that trait has massive benefits in our evolution. I hope
people don't get put off by calls for "rigorous science" and keep
experimenting on their own... and that the scientific establishment latches on
to good ideas to do more rigorous studies! [The two aren't mutually exclusive!
It's not zero sum!]

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applecore
How does this now-patented "ISRIB" molecule compare to Leonard Guarente's
research[1][2] on nicotinamide riboside and pterostilbene supplementation?

[1]: [http://nymag.com/scienceofus/2016/08/is-elysium-healths-
basi...](http://nymag.com/scienceofus/2016/08/is-elysium-healths-basis-the-
fountain-of-youth.html)

[2]:
[https://news.ycombinator.com/item?id=12345526](https://news.ycombinator.com/item?id=12345526)

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AstralStorm
An interesting new approach. Let's wait for the studies to follow.

He is mistaken about "nothing" in case of brain trauma. Racetams have been
shown to be mildly effective.

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quickmouse
What if the drug only makes mice be more nervous or active and that's why they
found the submerged platform more quickly?

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criddell
What's the difference between healing a brain and just generally improving a
brain?

~~~
blacksmith_tb
A semi-facetious question, perhaps? Healing at least is a return to a
baseline, "generally improving" is more subjective. I would tend to expect
that changing any system as complex as the human brain would have the
potential for improving some things, while impairing others. Not that it would
impossible to find a compound that only produced changes we considered
positive, without any we considered negative - just unlikely.

~~~
criddell
Not facetious at all.

If I take that molecule and find that I can acquire perfect pitch as an adult
or easily learn a new language, was my brain "damaged" prior to taking the
drug?

~~~
blacksmith_tb
Different, clearly, but the 'damage' (or 'healing') would be subjective,
wouldn't it? Since most of our organ systems return to the mean, I still
suspect it's more likely that taking it when you have no reason to would be
more likely to cause negative changes, rather than positive ones - but brave
people are apparently willing to make that gamble.

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SubiculumCode
The article's title on statnews.com bugs me, I admit I have not investigated
this case, but...

I suspect it wasn't that graying old man that discovered that molecule, but
that man's brilliant but underpaid post-doc that discovered that molecule.

~~~
zafka
Walter (Main Investigator), gave credit to Carmela Sidrauski his Post-Doc. He
said if it were not for her, they would not have looked at it. The chemical
itself was kicked out by a massive screening of small molecules, but
originally not looked at because it was not very soluble.

