[HN Gopher] Alphabet's Calico has begun trials on a molecule for...
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Alphabet's Calico has begun trials on a molecule for
neurovegetative diseases
Author : joak
Score : 124 points
Date : 2022-01-21 18:19 UTC (4 hours ago)
(HTM) web link (aspenbraininstitute.org)
(TXT) w3m dump (aspenbraininstitute.org)
| forgotmyoldacc wrote:
| No surprise, there's already a subreddit dedicated to people
| trying out this experimental molecule: https://reddit.com/r/isrib
| mtsr wrote:
| You should probably link to https://old.reddit.com/r/isrib
| instead, which doesn't block mobile users that don't use the
| official app.
| dharmaturtle wrote:
| I use Sync on Android. You can make reddit links open there
| by long pressing on the app icon and making sure the links
| are setup to open there. https://imgur.com/a/4qKCgSB
| cma wrote:
| Sharing this slows down the web 0.0 movement reddit, twitter,
| and instagram are pioneering.
| dragonwriter wrote:
| Isn't it Web 1.5-ish? E.g., we have browsers but devs
| aren't satisfied with them as app platforms, so they use
| various techniques (in "original" web 1.5, applets or
| plugins or downloading a file that would be opened by a
| native app) to use web links to trigger running an app in a
| native, or at least more-to-the-devs-liking, environment
| rather than using web-native tech?
| cma wrote:
| I assumed they just want notifcation permissions to spam
| people that don't know how to turn it off, so they can
| hijack their attention, and location permissions to make
| their ads more valuable through spying.
| cheschire wrote:
| The World Wide Dots, rather than web.
| comrh wrote:
| It's pretty shocking to me people are so willing to experiment
| on themselves with some research chemical that has mostly
| studied in mice.
| colechristensen wrote:
| Eh, people have different risk appetites and not everybody
| wants to wait for an authority figure to say something is
| safe (especially when that authority figure is always slow,
| sometimes makes mistakes, and sometimes makes decisions based
| on politics). I don't fault people with a little self-
| experimentation as long as they're given the opportunity to
| understand the risks and rewards they're facing.
| Suchos wrote:
| Desperate people will do whatever they can to improve
| themselves. Imagine you have neurogenerative disease and in
| few years you will be stuck to wheelchair forever.
| somesortofthing wrote:
| Maybe they're in particularly desperate situations? I do
| concur if these people are healthy/young though, seems insane
| to take something with side effects this concerning that
| don't even need proper trials to manifest if you're not
| working to fix a preexisting problem that hurts your
| lifespan/quality though.
| joak wrote:
| Excerpts: "the molecule was licensed by Calico Labs, the Silicon
| Valley biotech established by the founders of Google to find
| drugs based on the biology of aging"
|
| " In February, Calico announced that human safety trials had
| begun on the first drug candidate for neurodegenerative diseases
| it had developed based on the molecule, and that a study in ALS
| patients was slated to begin later this year. Other possible
| drugs for Parkinson's disease and traumatic brain injury are
| likely to follow."
| boppo1 wrote:
| Did the people dumping ice on their heads contribute in any
| material way?
| xibalba wrote:
| I imagine some number of them endured brain damage as part of
| the increasingly acrobatic nature of that "challenge". So
| maybe they will be downstream beneficiaries to the extent
| this drug's development advances the field of neural
| regeneration.
| sp332 wrote:
| $220 million, which funded research that discovered a third
| gene usable as a target for new therapies.
| https://en.wikipedia.org/wiki/Ice_Bucket_Challenge#Impact
| amatecha wrote:
| QuercusMax wrote:
| At least two, including Verily. Google Research also does a lot
| of health research - I work in a group called Health AI.
| [deleted]
| elwell wrote:
| I thought this post was good news?
| amatecha wrote:
| Yeah, the research itself sounds excellent and this is indeed
| good news. The fact the biotech firm is a subsidiary of
| possibly the premier proprietor of surveillance capitalism is
| fairly concerning to me. I don't personally want a supercorp
| that sees dystopian sci-fi as an instruction manual to be
| developing medical treatments.
| Guest42 wrote:
| I'd be concerned about the ethics they apply to health
| products given the changes that have happened over the years
| with search, email, and android.
| xvector wrote:
| It's absurd to complain about this when they are one of the
| few institutions working on fighting aging, arguably the
| most important problem humanity has ever faced.
| amatecha wrote:
| Yeah, it sounds great now. There's no way I want a
| multinational corp with unprecedented vision into our
| private lives also researching and producing medical
| treatments.
| Jensson wrote:
| Why would that be a problem? If they can user their ad-
| money to help cure people how is that a bad thing?
| Guest42 wrote:
| I think the incremental ROI they would need to involve
| themselves in a new area would be pretty high. They
| aren't going to dedicate a 9-10 digit sum to anything
| without expecting a much higher sum in return.
| Jensson wrote:
| Google started a lot of "moonshot" projects, expensive
| things that are very unlikely to produce any returns.
| This is one of those. If Google didn't fund this then
| this work wouldn't get done. Now it might look promising,
| but this is a 8 year old part of Google, they have been
| working for a while now.
| xvector wrote:
| This kind of armchair criticism is really frustrating to
| see. Here, you have a company tackling arguably the most
| important and devastating problem humanity has ever
| faced. At least they are doing _something_ that helps
| humanity solve aging, where almost no one else is.
|
| Who cares if it's capitalist-driven? It's not like
| governments don't, or never, had the opportunity to
| attempt to tackle the same problem - they simply never
| took it, focusing on the trivial day-to-day issues, while
| overwhelmed with bureaucratic tape. And it's not like
| nonprofits attempting to solve the same problem don't
| exist either (https://www.sens.org/,
| https://www.lifespan.io/), with limited success. A
| massive financial juggernaut backing this initiative is
| exactly what it needs.
|
| What other solution do you propose?
| formvoltron wrote:
| According to the Huberman podcast, simply elevating your legs at
| night can improve the glymphatic system's ability to clear out
| junk from our brains. I haven't been able to find any links to
| actual studies on that though.
| theunixbeard wrote:
| Wouldn't it be elevating your head, rather than your legs? Most
| sources I've seen[1] that discuss inclining your bed have your
| head be higher up than your legs.
|
| [1]: https://www.google.com/search?q=incline+your+bed
| jmcgough wrote:
| I think you mean neurodegenerative diseases, not neurovegetative?
| joak wrote:
| Oops, yes, you are right. I failed to notice a wrong
| "autocorrection" from the virtual keyboard on my phone.
|
| It is neurodegenerative disease... But now the title is locked:
| I cannot edit it anymore.
|
| Thanks
| darawk wrote:
| Feel like I was just reading a comment on here today, in another
| thread, about how those stupid Google billionaires wasted all
| their money on this dumb Calico thing that will never amount to
| anything.
| transitory_pce wrote:
| Jaw dropping molecule supremacy breakthrough
| vmception wrote:
| neurovegetative? is that what we're doing now?
|
| its like something I would say in my comedy skit before doing a
| Bill Burr style impression of someone on life support before
| insulting the audience for laughing. and then complain that
| everyone's too sensitive.
| joak wrote:
| My mistake... I meant neurodegenerative.
| bostonsre wrote:
| Why is the word so bad? Not sure if it's a real word or not,
| but it seems apt. Someone that is brain dead is referred to as
| someone in a vegetative state and someone that has some neurons
| that ceased to function could maybe be referred as
| neurovegetative. But that kind of makes it sound like the
| person is completely brain dead. Maybe partial neurovegatative
| state would be better?
| vmception wrote:
| Only because its made up when we already have a word for it.
| Its not toooo bad since it conveys a particular state of
| neurodegeneration.
| pvarangot wrote:
| This is the molecule: https://en.wikipedia.org/wiki/ISRIB
| dekhn wrote:
| Nice symmetry.
| paxys wrote:
| I'm curious why it is referred to as "molecule" everywhere. It
| may be a molecule, but...so is everything else. This is the first
| time I have seen this term used to describe a drug or treatment.
| mft_ wrote:
| It's standard terminology in the pharma world.
| ozzy6009 wrote:
| There is a distinction in drug development between the
| biologics (large proteins, e.g.
| https://en.wikipedia.org/wiki/Adalimumab, molecular weight
| ~144kDa), and small molecules
|
| https://www.nuventra.com/resources/blog/small-molecules-vers...
| ALittleLight wrote:
| Atoms aren't molecules.
| engineer_22 wrote:
| I laughed out loud.
| CoastalCoder wrote:
| I'm curious as well. Maybe it's only a "drug" after they've
| combined the active ingredient with specific fillers, buffers,
| etc.?
| xiphias2 wrote:
| Calico has a very strange pipeline of drugs that don't have much
| in common. The last paper about Yamamaca factors looked quite
| interesting, but Altos is much more focused on understanding just
| that one technology. Other successful new companies are platform
| companies, which Calico isn't.
| sangnoir wrote:
| > Calico has a very strange pipeline of drugs that don't have
| much in common
|
| Aren't they all related to fighting the effects of aging, which
| is the company mission?
|
| I've observed that when some people have solved their money
| problems, the next challenge they face is their own aging and
| mortality - so they try to solve for that too.
| wantsanagent wrote:
| *Yamanaka
|
| https://en.wikipedia.org/wiki/Shinya_Yamanaka
| manmal wrote:
| ISRIB (the molecule discussed in the article) seems _very_
| promising for brain health. But people who (recklessly?) self-
| experimented with it had strange cardiac issues. A study on dogs
| discovered heart anomalies. It's nicely summarized here:
| https://forums.phoenixrising.me/threads/isrib-to-treat-me-cf...
| bpodgursky wrote:
| If we pair ISRIB with pig heart transplants it's a side-effect
| free way to boost cognitive function though.
| sdenton4 wrote:
| Open heart surgery - let alone replacement - isn't likely to
| be side effect free in our lifetime. A detached sternum is
| also a side effect, after all, requiring a couple months to
| recover to basic function...
| jac241 wrote:
| Totally side effect free if we ignore the risk of stroke from
| cardiopulmonary bypass (at least 0.5%), infection of the
| chest cavity (0.5-3% incidence of mediastinitis after median
| sternotomy), anesthesia complications, post op pulmonary
| embolism, pneumonia, UTI, etc.
| meowface wrote:
| I think that's the joke.
| bostonsre wrote:
| I guess it depends on how long the bad effects on the heart
| last after taking ISRIB. If it keeps lingering, you may need
| new pig hearts over time. Or.. Just keep taking ISRIB and
| just schedule a yearly pig heart transplant.
| redisman wrote:
| Sounds very cyber punk.
| manmal wrote:
| Perhaps a similar molecule can be found instead which does
| not have this problem. Or another compound can be added to
| prevent heart damage.
| bpodgursky wrote:
| It's probably going to be interpreted as cynical b/c it's
| HN but I do honestly believe that solving heart function
| will be lot easier than solving cognitive decline, and a
| win on cognitive decline is huge news (hopefully not paired
| with not pig hearts, but it's a reasonable proof of
| concept).
| PragmaticPulp wrote:
| I was debating whether or not to post some of those self-
| experiments.
|
| I'm aware of a couple more forums where people tried ISRIB and
| still claim to have lasting problems from it. One group was led
| by professional chemists who seemed like they knew what they
| were doing when it comes to testing and validating the product
| was pure.
|
| It's amazing what people can access now, but self-
| experimentation with these compounds is a terrible idea.
| meowface wrote:
| Reminds me a bit of cerebrolysin self-experiments I've read.
| It can either permanently make you smarter or permanently
| give you brain damage. Or both, perhaps.
|
| (For anyone unaware, it's a bunch of neuropeptides harvested
| from pig brains that you typically either inject or -
| fittingly, due to the source - snort directly into your brain
| through your nose.)
| treeman79 wrote:
| Developed a weird dementia at 39. Doctors Spent 2 years
| trying every prescription drug they could think of. Almost
| everything made matters worse. In some cases drastically.
| Complete nightmare. Those are with approved ones. Scary to
| try experiential.
|
| Eventually learned it was a blood disorder and a simple blood
| thinner was the answer.
| tomComb wrote:
| > It's amazing what people can access now, but self-
| experimentation with these compounds is a terrible idea.
|
| I think it depends what the alternative is. If you have
| something like Alzheimer's and no other alternatives, maybe
| self-experimentation is not such a bad idea.
| meowface wrote:
| Wow, that sounds pretty incredible. Part of what makes it sound
| promising to me is the extent of the "no free lunch" aspect:
| anecdotal reports of not just cardiac issues in humans and dogs
| but increased brain fog (mitigated with feed consumption...?),
| blunted emotions, inability to get drunk (maybe a plus?),
| accelerated cell death, psychosis and hallucinations - in
| exchange for, allegedly, reversing Alzheimer's and repairing
| lifelong brain damage:
|
| >One report of a person who gave ISRIB to their grandmother who
| had terminal stage Alzheimer's. She began to remember everyone.
| But died after 4 months (this may have been from old age and
| her type 1 diabetes).
|
| >One anecdotal report of a short course of ISRIB permanently
| fixing some prefrontal cortex brain damage in a Russian guy,
| caused by a car crash when he was a child. The repair to the
| brain was confirmed by MRI scans taken before and after the
| ISRIB treatment.
|
| Plus a pretty clear mechanism of action. Definitely sounds like
| it's worth significant study.
| joak wrote:
| Excerpt : "The molecule has restored memory formation in mice
| months after traumatic brain injuries and shown potential in
| treating neurodegenerative diseases, including Alzheimer's,
| Parkinson's, and Lou Gehrig's disease (also known as amyotrophic
| lateral sclerosis, or ALS)."
| whatshisface wrote:
| "In the 1980s and 1990s, Walter demonstrated that when too many
| unfolded or misfolded proteins--which are characteristic of
| neurodegenerative diseases--were detected inside a cell, it
| triggered the equivalent of an emergency shutoff switch that
| halted all protein construction until the problem was solved. The
| action, which Walter dubbed the "unfolded protein response," was
| akin to a blaring red alert at a busy worksite, stopping work;
| cellular repair crews would then converge on the site, attempt to
| fix the problem, and if all else failed, eventually order the
| cell to commit suicide."
|
| So... if the body will naturally restart protein production when
| the problem is resolved, and if ISRIB forces it to restart
| without solving the problem...
|
| Is this going to result in a few months of improved performance
| followed by a collapse as cells start dying for good?
| dpratt wrote:
| I'm sure that a biotech company infused with the same ethics and
| sense of stewardship and social responsibility as Google can only
| work out perfectly.
| all2 wrote:
| This is fair commentary for any under-regulated industry. I say
| that as a staunch "stay out of my business" conservative.
| Proper regulation ensures that companies are financially vested
| in the well-being of those they affect.
|
| Whether or not pharma in the US is properly regulated to ensure
| the well-being of their consumers is... debatable.
| ryan93 wrote:
| Are they forcibly injecting you? This is for people with
| desperate symptoms who are willing to take on more risk. I have
| no opinion on its efficacy fwiw.
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