Andy_McKenzie

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Andy_McKenzie — LessWrong

When cryoprotectants are perfused through the blood vessels in the brain, they cannot cross the blood-brain barrier as fast as water can move in the opposite direction. And cryoprotectants generally have a much higher osmotic concentration than the typical blood plasma. For example, the cryoprotectant solution M22 has an osmotic concentration around 100 times higher.

As a result, in a successful cryoprotectant perfusion (without fixatives), water rushes out of the tissue into the blood vessels, the tissue dehydrates, and you end up with a shrunken brain that is visibly pulled away from the skull. The brain weight goes down by 50% or more. This is currently considered a good sign of cryoprotectant perfusion... (read 1272 more words →)

115

Why I'm not trying to freeze and revive a mouse

Andy_McKenzie

5mo

(Cross-posted from here.)

If you read even a tiny bit about brain preservation, you will pretty quickly find people saying things along the lines of “they can’t even freeze a mouse and bring it back to life” and thereby dismissing people in the field as hopelessly deluded.

It will not surprise you to hear that I think that they are wrong. The whole point of brain preservation is that while we are not able to reverse the process of long-term preservation today (trust me, if we could, you would know), we can still attempt to preserve the information in the brain so that if powerful technologies do arrive in the future (which many expect),... (read 3250 more words →)

Replying toImmortalism - A Rational Case for Solving Death

Andy_McKenzie6mo

Immortalism - A Rational Case for Solving Death

Thanks for writing this post. I completely agree that trying to fight involuntary death is a great idea.

A few thoughts:

In my view, recording an external mindfile (what I see/hear/say) is not nearly sufficient. Most of the information I value isn't what I see, but how I react to it, such as the unique patterns of neural activation, the associations my brain makes, and the subtle emotional colorings. A video of me watching a game of bridge tells you nothing about why that particular card game reminded me of my grandparents, or how it shifted my mood in ways I couldn't even articulate.

There's a huge difference between recording outputs and preserving the computational... (read more)

Replying toHow likely is brain preservation to work?

Andy_McKenzie1y

How likely is brain preservation to work?

identity is irretrievably lost when the brain activity stops

My point here is that this is a very strong claim about neuroscience -- that molecular structure doesn’t encode identity/memories.

How likely is brain preservation to work?

Andy_McKenzie

People often ask me this. It’s a good question. It seems potentially important for anyone who doesn’t want to die, or doesn’t want other people to have to die. I don’t feel like I have a good answer, which is one reason I want to do more research. But recently I think my answer has gotten a little better and I want to explain why.

A superficially similar question, “Does brain preservation work?” is also often asked, and I can see why people ask this, too — but it’s a question that can only be answered in the future. Brain preservation is not suspended animation. It’s about attempting to preserve the molecular structure... (read 1562 more words →)

Replying toScience advances one funeral at a time

Andy_McKenzie1y

Science advances one funeral at a time

The examples you provided don't actually support the "one funeral at a time" narrative in your title. Take Barbara McClintock's jumping genes or Barry Marshall's H. pylori discovery -- in both cases, many scientists changed their views based on compelling evidence while very much alive. There are plenty of other examples of this. For example, the acceptance of prions as disease agents, the role of microbiomes in health, dark energy, and mitochondria's bacterial origins all show how consensus can shift rapidly once a sufficient amount of evidence has accumulated. Scientists change their minds all. the. time.

This is not to say that there are not fads or incorrect beliefs in science -- of... (read more)

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Replying toRefactoring cryonics as structural brain preservation

Andy_McKenzie1y

Refactoring cryonics as structural brain preservation

Thanks for the clarification and your thoughts. In my view, the question is to what extent the polymer gel embedding is helpful from the perspective of maintaining morphomolecular structure, so that it is worth the trade-off of removing the lipids, which could potentially also have information content. https://brainpreservation.github.io/Biomolecules#how-lipid-biomolecules-in-cell-membranes-could-affect-ion-flow

You are in good company in thinking that clearing and embedding the tissue in a hydrogel is the best approach. Others with expertise in the area have suggested the same thing to me. I'm just not convinced, so I think that more research is required to tell whether that is the best approach.

ETA: Sorry, just saw your edit. Interesting thoughts on the interaction between preservation and reconstruction. Your perspective and goals make sense to me, although it is not exactly what we are pursuing at Oregon Brain Preservation. We are agnostic as to the potential method of revival and expect this to be relatively further away in the future, if it ever becomes possible.

Replying toRefactoring cryonics as structural brain preservation

Andy_McKenzie1y

Refactoring cryonics as structural brain preservation

Thanks for your interest!

Does OBP plan to eventually expand their services outside the USA?

In terms of our staff traveling to other locations to do the preservation procedure, unfortunately not in the immediate future. We don't have the funding for this right now.

And how much would it cost if you didn’t subsidize it?

There are so many factors. It depends a lot on where in the world we are talking about. If we are talking about someone who legally dies locally in Salem, perhaps a minimal estimated budget would be (off the top of my head, unofficial, subject to change):

Labor cost of brain preservation = ~$500-1000
Cost of chemicals, disposable equipment = ~$100-300
Cost of death

Andy_McKenzie1y

Refactoring cryonics as structural brain preservation

We discuss the possibility of fluid preservation after tissue clearing in our article:

An alternative option is to perform tissue clearing prior to long-term preservation (118). This would remove the lipids in the brain, but offer several advantages, including repeated non-invasive imaging, and potentially reduced oxidative damage over time (119).

And also in our fluid preservation article we have a whole section on it. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058410/#S7

I'm not sure why this option is much more robust that formaldehyde fixation alone. I haven't seen any strong evidence for that. I do agree that it is potentially very useful for 3D reconstruction, but reconstruction is a much different problem than preservation.

Replying toRefactoring cryonics as structural brain preservation

Andy_McKenzie1y

Refactoring cryonics as structural brain preservation

I can't speak for Adele, but here is one somewhat recent article by neuroscientists discussing memory storage mechanisms: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-016-0261-6

DNA is discussed as one possible storage mechanism in the context of epigenetic alterations to neurons. See the section by Andrii Rudenko and Li-Huei Tsai.

Replying toRefactoring cryonics as structural brain preservation

Andy_McKenzie1y

Refactoring cryonics as structural brain preservation

This is an important question. While I don't have a full answer, my impression is that yes, it seems to preserve the important information present in DNA. More information here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11058410/#S4.4

Refactoring cryonics as structural brain preservation

Andy_McKenzie

I first learned about cryonics when I read Eliezer and Robin's posts about it on Overcoming Bias years ago. I got cryopilled. Somewhat amazingly to me, I'm now a researcher in this field. So I thought this community might be interested to know that I was one of several co-authors on a paper just published in Frontiers in Medical Technology, titled "Structural brain preservation: a potential bridge to future medical technologies".

In this paper, we propose reframing cryonics as a type of structural brain preservation, focusing on maintaining the brain's physical structure that encodes memories and personality, rather than making the focus about low-temperature storage per se.

We explore what brain structures likely need... (read 798 more words →)

108

Being against involuntary death and being open to change are compatible

Andy_McKenzie

In a new post, Nostalgebraist argues that "AI doomerism has its roots in anti-deathist transhumanism", representing a break from the normal human expectation of mortality and generational change.

They argue that traditionally, each generation has accepted that they will die but that the human race as a whole will continue evolving in ways they cannot fully imagine or control.

Nostalgebraist argues that the "anti-deathist" view, however, anticipates a future where "we are all gonna die" is no longer true -- a future where the current generation doesn't have to die or cede control of the future to their descendants.

Nostalgebraist sees this desire to "strangle posterity" and "freeze time in place" by making one's own... (read 600 more words →)

Replying toCryonics p(success) estimates are only weakly associated with interest in pursuing cryonics in the LW 2023 Survey

Andy_McKenzie2y

Cryonics p(success) estimates are only weakly associated with interest in pursuing cryonics in the LW 2023 Survey

Thanks for the comment. I'm definitely not assuming that p(success) would be a monocausal explanation. I'm mostly presenting this data to give evidence against that assumption, because people frequently make statements such as "of course almost nobody wants cryonics, they don't expect it will work".

I also agree that "is being revived good in expectation / good with what probability" is another common concern. Personally, I think niplav has some good analysis of net-negative revival scenarios: https://niplav.site/considerations_on_cryonics.html

Btw, according to the author, 'Lena' is largely a critique of exploitive capitalism: https://qntm.org/uploading

Cryonics p(success) estimates are only weakly associated with interest in pursuing cryonics in the LW 2023 Survey

Andy_McKenzie

The Less Wrong 2023 survey results are out. As usual, it includes some questions about cryonics. One is about what people’s level of interest in cryonics is (not interested, considering, cryocrastinating, signed up, etc.). Another asks about people’s subjective probability of successful restoration to life in the future, conditional on there not being a global catastrophe destroying civilization before then. This is also known as p(success). I thought it might be interesting to plot these (with the subjective probability estimates on a log scale, of course):

It is true that people who are more interested tend to give higher subjective probability estimates of success (median probability estimates: signed up =... (read more)

Why wasn't preservation with the goal of potential future revival started earlier in history?

Andy_McKenzie

Cross-posted from my blog, Neurobiology Notes.

John Hunter (1728–1793) did not have an especially promising start to his academic life. He was born the youngest of 10 children to a family living in the countryside near Glasgow. They lived in a two bedroom cottage and the children slept in box beds that were pulled out of the walls every night. He was stubborn, hated school, did not like to be taught reading or writing, would skip classes whenever he could, and quit formal education altogether at 13, the same year his father died. He said that he “totally rejected books,” instead preferring to gain practical knowledge first hand. He spent his time helping... (read 1771 more words →)

Replying toOn the future of language models

Andy_McKenzie2y

On the future of language models

Very high-effort, comprehensive post. Any interest in making some of your predictions into markets on Manifold or some other prediction market website? Might help get some quantifications.

Transcript of Sam Altman's interview touching on AI safety

Andy_McKenzie

Sam Altman, CEO of OpenAI, was interviewed by Connie Loizos last week and the video was posted two days ago. Here are some AI safety-relevant parts of the discussion, with light editing by me for clarity, based on this automated transcript:

[starting in part two of the interview, which is where the discussion about AI safety is]

Connie: So moving on to AI which is where you've obviously spent the bulk of your time since I saw you when we sat here three years ago. You were telling us what was coming and we all thought you were being sort of hyperbolic and you were dead serious. Why do you think that ChatGPT and... (read 2829 more words →)

121

Brain preservation to prevent involuntary death: a possible cause area

Andy_McKenzie

(Cross-posted at the Effective Altruism Forum)

Previous EA discussions of this topic: here, here, here, and here. Note that these primarily focus on cryonics, although I prefer the term brain preservation because it is also compatible with non-cryogenic methods and anchors the discussion around the preservation quality of the brain. See here for more discussion of terminology.

This post is split up into two sections:

(a) Technical aspects, which discusses why I think preserving brains with methods available today may allow for revival in the future with long-term memories and personality traits intact.

(b) Ethical aspects, which discusses why I think the field may be among the most cost-effective ways to convert money into long-term QALYs,... (read 2900 more words →)

A review of cryonics/brain preservation in 2016

Andy_McKenzie

Relevance to Less Wrong: Whether you think it is for better or worse, users on LW are about 50,000x more likely to be signed up for cryonics than the average person.

Disclaimer: I volunteer at the Brain Preservation Foundation, but I speak for myself in this post and I'm only writing about publicly available information.

In 2016, cryonics remains a fringe operation. When it is discussed in the news or on social media, many express surprise that cryonics is a "real thing" outside of science fiction. Many others who do know about cryonics tend to label it a pseudoscience. Brain preservation (BP) through non-conventional cryonics methods such as those using aldehyde fixation is even

... (read 619 more words →)

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Transcript of Sam Altman's interview touching on AI safety

Honey, I shrunk the brain

Refactoring cryonics as structural brain preservation

Why I'm not trying to freeze and revive a mouse

Andy_McKenzie

Andy_McKenzie

Honey, I shrunk the brain

Why I'm not trying to freeze and revive a mouse

How likely is brain preservation to work?

Refactoring cryonics as structural brain preservation

Being against involuntary death and being open to change are compatible

Cryonics p(success) estimates are only weakly associated with interest in pursuing cryonics in the LW 2023 Survey

Why wasn't preservation with the goal of potential future revival started earlier in history?

Andy_McKenzie

Transcript of Sam Altman's interview touching on AI safety

Honey, I shrunk the brain

Refactoring cryonics as structural brain preservation

Why I'm not trying to freeze and revive a mouse

Andy_McKenzie

Andy_McKenzie

Honey, I shrunk the brain

Why I'm not trying to freeze and revive a mouse

How likely is brain preservation to work?

Refactoring cryonics as structural brain preservation

Being against involuntary death and being open to change are compatible

Cryonics p(success) estimates are only weakly associated with interest in pursuing cryonics in the LW 2023 Survey

Why wasn't preservation with the goal of potential future revival started earlier in history?