Shhh…don’t tell Peter Thiel


I wish I weren’t so pessimistic, but it’s my nature to doubt this paper in Nature that purports to have found a substance that improves learning in in old mice. Maybe it’s true, but I’d want to see it replicated multiple times and with other parameters examined. There have been way too many examples of magical infusions to improve this or that — I immediately think of John Brinkley, who transplanted goat testicles into human patients, but don’t carry the comparison too far. I don’t think the people doing this experiment are unethical quacks like Brinkley at all. It’s a reasonable preliminary experiment.

They’re infusing cerebrospinal fluid (CSF) from young mice to old mice, and seeing improvements in a memory test.

The first step for Iram and her team was to give ageing mice an experience they would remember. The team gave 20-month-old mice three small electric shocks on their foot in tandem with several flashes of light and sound, to create an association between the lights and the shock. The researchers then infused the brains of one group of 8 mice with CSF from 10-week-old mice, while a control group of 10 mice were given artificial CSF.

After three weeks the mice faced the same sounds and lights, but this time without a shock — recreating the context of the fear without the actual fear-inducing action. Mice that receive young CSF remembered the shock and froze in fear almost 40% of the time, but that happened only around 18% of the time in mice given artificial CSF. The findings suggest that young CSF can restore some declines in ageing-brain abilities. “The broader implication is that the brain is still malleable and there are ways to improve its function,” says co-author Tony Wyss-Coray, a neuroscientist at Stanford. “It’s not all lost.”

Cool. I know I’m not as good at remembering stuff as I was when young, a common experience in us older folk. A little special fluid that would brighten up my brain would be nice — for me, that fluid is coffee, but if someone has a better brain juice, I’d try it.

Except…it might just be me, but I’m a little leery of behavioral tests done in mice, because mice are complicated and there’s this so-called replication crisis in just these kinds of experiments. Also, CSF? You’re going to have to squeeze a lot of mice to get a human-sized dose. It would be better if they isolated something specific in CSF…oh, they did. That’s promising.

The researchers also isolated a protein from the CSF cocktail that another analysis had suggested was a compelling candidate for improving memory: fibroblast growth factor 17 (Fgf17). Infusion of Fgf17 had a similar memory-restoring effect to infusing CSF. Furthermore, giving the mice an antibody that blocked Fgf17’s function impaired the rodents’ memory ability. Wyss-Coray and Iram have applied for a patent on their findings around Fgf17.

Why did they have to ruin it by taking out a patent on it? Suddenly I’m seeing a whole lot of potential bias introduced into their studies. I know it’s a capitalist planet, but on the one hand a scientist should be working to disprove their hypothesis, and on the other hand a patent-holder is going to see the promise of a lot of money fading if they disprove it.

They’ve also seen an effect of blood plasma on memory.

The work on CSF is inspired by Wyss-Coray’s past work showing that plasma from young mice could restore memory function in older rodents. A start-up co-founded by Wyss-Coray, Alkahest in San Carlos, California, has conducted small trials suggesting some cognitive benefits in mice and people with dementia given the company’s plasma-derived products. Other groups are exploring different methods for using young plasma, but the field is still in its infancy.

Who is funding this? Somehow it seems like something that would appeal to a ghoulish venture capitalist in California.

Also, I’m sorry, but you’d have to get a reverse spinal tap to reap the benefits of Fgf17 which kills a lot of the appeal.

It took more than a year for Iram to perfect the process of collecting CSF and infusing it into another brain. Collection is extremely challenging, she says, and has to be done with precision. Any blood contamination will ruin the fluid. Pressure in the brain is a delicate balance, so infusion must be slow and in a specific location within the brain: the cerebral ventricle. The delicate procedure might pose challenges for use in people, says Julie Andersen, who studies Alzheimer’s and Parkinson’s disease at the Buck Institute for Research on Aging in Novato, California.

might pose challenges”? My memory isn’t that bad yet that I’d risk blowing out my ventricles to get a slight enhancement. I’m also curious to know how antibodies against Fgf17 are having an effect, since antibodies have an extremely limited ability to cross the blood-brain barrier.

Comments

  1. answersingenitals says

    If this is truly successful, couldn’t we expect the creation of genetically modified microbes to produce the Fgf17 by the buttload (uhh, the brainload) as is now done for insulin?

    As far as the patent application, IANAL, but it is my understanding that patents are only granted for inventions, not discoveries. Iram, et. al. discovered the Fgf17, they did’t invent it. They might be able to get a patent for for inventing an extraction or purification procedure. I might be wrong about this – there’s a first for everything (I might be wrong about that also).

  2. Akira MacKenzie says

    They’re infusing cerebrospinal fluid (CSF) from young mice to old mice, and seeing improvements in a memory test.

    Oh joy. Just wait until Alex Jones and Q Anon cultists hear about this. If you believed the blood libel and “adrenochrome” you’re going to fall hard for this.

  3. EvoMonkey says

    The “memory test” that the researchers use in the mice is a very specific type of fear conditioning. The effects of CSF from young mice or Fgf17 may not translate to other forms of learning or memory loss.

  4. PaulBC says

    Heh. I don’t know if this is “Great minds think alike.” or “Everyone knows Peter Thiel is a psychopath.” but last week when this came out an NYT article, my first thought (which I posted to my small group of FB friends) was “Don’t tell Elon Musk or Peter Thiel. They’ll probably want to ‘harvest’ youthful spinal fluid for personal use.”

  5. birgerjohansson says

    Ageing and death.
    .
    Vangelis -who made the music for films like Blade Runner- has just died.

  6. moarscienceplz says

    What EvoMonkey said. Also ISTM that running a maze is both a better model for the kind of memories we’d want to enhance in humans AND would be more humane towards the mice.

  7. birgerjohansson says

    A more pragmatic approach would be to eat lots of cranberries. Recent research shows this gives significant improvement of blood flow in the brain.

  8. PaulBC says

    birgerjohansson@7

    A more pragmatic approach would be to eat lots of cranberries.

    What am I a farmer? We’re talking about the future, man, the future! Don’t give me your hippie granolahead advice when I am looking for a sciency technological solution!

  9. birgerjohansson says

    The late comedian and musician Powel Ramel would have been 100 years May 28th.

  10. birgerjohansson says

    PaulBC @9 try uploading bowhead whale DNA. You will live 150 years, and maybe be able to eat plankton.

  11. PaulBC says

    birgerjohansson@11 I thought you meant Ramel could have benefitted from the spinal infusion. It made total sense to me.

  12. PaulBC says

    birgerjohansson@12 Now we’re talkin’! Where do I sign up?

    (OK, I should shut up and do some work.)

  13. Snidely W says

    Great. Now where can I get me some CSF?
    Which pool of expendable humans won’t be missed by civilized folks?
    Aha! Republicans!
    Pretty soon I’ll have all the learning ability of Republi-….
    Crap. Never mind.

  14. seachange says

    Ms Vander Pluym has an Abattoir thread. Maybe we can require some donors of CS fluid from there.

  15. birgerjohansson says

    Can we look forward to a Simpsons episode where Monty Burns harvests plasma from orphans? The reverse spinal tap would not deter him, as his weekly health regimen is already so drastic Homer once thought he was a space alien when meeting him afterwards.

  16. Wharrrrrrgarbl says

    There is a device called an Ommaya reservoir which exists for just this kind of infusion of intraventricular medications. That being said, the surgery to implant one involves exactly as much drilling holes in your skull as you might expect, so I don’t think mild cognitive impairment is going to be the kind of condition where the benefits outweigh the risks.

  17. birgerjohansson says

    Since we are already drilling holes in the skull, can we go one step further with some cyborg parts?

  18. birgerjohansson says

    Saving brains?
    Washington University School of Medicine has discovered that an epilepsy drug stops nervous system tumor growth in mice.
    .
    OT
    This is totally off-topic, but Brandon Tenold has dug up a 1999 Japanese film that would have been a perfect fit for the “Mock The Movie” stuff we did a decade ago.
    https://youtu.be/dR8haOuVERs
    Rock’n Roll, guns, zombies, an alien invasion.. this is the best film ever made.

  19. birgerjohansson says

    Brains and nerves:
    The Washington University School of Medicine has discovered that an epilepsy drug stops nervous system tumor growth.
    .
    This is completely off-topic, but the “brains” thing reminds me of the latest film dug up by Brandon Tenold.
    It would have been perfect for the “Mock The Movie” blogging we did a decade ago.
    https://youtu.be/dR8haOuVERs
    Rock’n Roll, guns, zombies, invading aliens.. this is the best film ever made.

  20. birgerjohansson says

    When I pressed “post” the system gobbled up the comments without anything showing up in the thread. If It fixes itself, there may be some doublets I posted before understanding wha was going on. Or maybe I included some word that the programs automatically reject, thinking I am trolling.

  21. addiepray says

    The great 1922 Buster Keaton short film has a gag alluding to a “goat gland specialist” and I was never sure what it was referring to… I guess now that I’ve clicked your link I know, though I’m not sure my world is improved by knowing about Brinkley.

  22. John Morales says

    It probably says something about me that I had to look up who Peter Thiel might be.

    Anyway, this post title would be clickbait, except I read all the posts anyway.
    So it isn’t, for me.

  23. Ridana says

    Was there a control group that got no treatment at all? How many of them forgot (or would have forgotten) to be afraid of the lights? Injecting anything seems like it could be damaging, so they compared CSF to fake-CSF. But how do they know the ones that got real CSF were better than doing nothing at all?

  24. says

    @1: In the US, one can’t get a patent for discovering or isolating a “composition of matter” found in nature — but could get a patent for:
    • Synthesizing that compound from other chemicals (the method of synthesis would be patentable, the output not)
    • Or, as is much more likely, establishing a therapeutic method, usually including doseage parameters (“A process consisting of transcranial injection within 3cm of the subject’s dominant-hand-associated audio cortex of Wonderflonium into an adult human subject over the age of 45 with between 1.75mcg and 2.10mcg per kilogram of the subject’s body mass in a single does repeated every 18-24 months”)

    In general, I think we absolutely should tell Thiel about CSF. Then, with enhanced memory, he might remember how to be human… oops, that sort of assumes that he’s ever been human† or capable of learning to be human, so that CSF would actually have a benefit.

    † Thiel is one of the lizard people. Pass it on.

  25. dictyostelium says

    What’s the applicability on humans? Barely 2 years versus 60 years or something, are the mechanisms still the same?

  26. cvoinescu says

    What Ridana said. It would make sense to compare 20-month-old mice that got CSF from 10-week-old mice to 20-week-old mice that got CSF from other 20-week-old mice. That way, both cohorts get foreign, natural CSF, so that controls for the trauma of the procedure and for possible reactions to infusing foreign CSF, and does not add the confusing factor of comparing natural to synthetic CSF. How do we know synthetic CSF does not make the mice dumber?

  27. chrislawson says

    Seems like the wrong control to me. Artificial CSF is an electrolyte buffer solution with a bit of glucose and zero protein or lipids. Artificial CSF is mostly used in tissue-level experiments to keep neurons alive long enough to study their electrophysiology, and we know that artificial CSF can effect physiological function in unexpected ways (this paper found that rhythmic patterns of neuron activity were “completely controlled” by the rate of aCSF flow over the tissue sample).

    The appropriate control would be CSF collected from older mice and another control group of untreated mice. Even if the finding is repeatable, it could well be that young CSF does nothing while artificial CSF impairs memory function.

  28. PaulBC says

    John Morales@28 Thiel shows up in Ashlee Vance’s biography of Elon Musk. They were both involved in early PayPal. Thiel is also notorious for using his money to destroy Gawker, an internet media company that outed him. He founded Palantir, an evil company with an appropriately evil name, that mostly contracts out to government spook agencies (or, apparently they have now diversified). Honestly, what pissed me off was when they started hogging all the office space in downtown Palo Alto, driving out the smaller startups that had traditionally occupied it. (Resulting if indirectly in a time consuming commute for me to SF for a couple years. Yes, it’s personal.)

    Thiel is also a big financial supporter of Amy Chua’s Tiger Baby JD Hillbilly Vance who will be the next junior senator from Ohio if they’re the dumbasses I expect them to be.

    Hope this helps.

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