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Comment author: Zaine 08 July 2014 03:56:24AM *  0 points [-]

I have a friend on business in San Francisco with some free time Tuesday afternoon. Do any of you have a recommendation of how they should spend that time, outside of general suggestions as might be listed here?

In response to Polling Thread
Comment author: Coscott 23 January 2014 12:42:34AM 3 points [-]

What is your opinion on the variability hypothesis that males generally have a larger biological variance than women in most traits, and that in particular this applies to intelligence, and explains in part why there is a gender imbalance in the sciences?


In response to comment by Coscott on Polling Thread
Comment author: Zaine 23 January 2014 06:31:01PM *  1 point [-]

"I believe that there is a biological variance in intelligence and insufficient information to allow for accurate qualitative analysis."

Your null hypothesis of each question assumes the difference, if present, will favour males; regardless of the theory's specifics, if you wish to gather fully rounded data on the opinions of your population, you must needs allow for that in the questions. If there's a theory that blue is finest on a Winter's day, and you wish to find out what people think of it, you must counter the inherent priming of the theory by including such options as, "Blue is finest on a Summer's day," and, "Blue is never the finest during day"; think of what the theory tries to answer. In these cases: the intersection of biology and intellectual variance between the sexes, and at what time is blue finest on Earth (you also may include, "Blue is finest on a Winter's day in Greenland, but in Madagascar finest on a Fall's day.")

Comment author: gwern 22 January 2014 07:23:23PM 1 point [-]

put morals on display for decades.

More specifically, 'Goofus and Gallant' has been running since 1948 (or 66 years now).

Comment author: Zaine 23 January 2014 06:15:48PM 2 points [-]

Ah, then the purpose for my question is rendered moot. If it was an original coining, I wished to know the thought process that went into deciding, "Yes, I shall prime thusly."

Comment author: Zaine 21 January 2014 07:05:48PM 1 point [-]

For how long did you deliberate upon whether, or what did you think whilst deciding to go with 'Gallant' and 'Goofus'?

Comment author: CellBioGuy 16 January 2014 04:12:54PM *  5 points [-]

Shortening telomeres are a red herring. You need multiple generations of a mammal not having telomerase before you get premature ageing, and all the research you've heard about where they 'reversed ageing' with telomerase was putting it back into animals that had been engineered to lack it for generations. Plus lack of telomerase in most of your somatic cells is one of your big anti-cancer defenses.

Much more of a problem is things like nuclear pores never being replaced in post-mitotic cells (they're only replaced during mitosis) and slowly oxidizing and becoming leaky, extracellular matrix proteins having a finite lifetime, and all kinds of metabolic dysregulation and protein metabolism issues.

This isn't exactly my field, but there's a few interesting actual lines of research I've seen. One is an apparent reduction in protein-folding chaperone activity with age in many animals from C. elegans to humans [people LOVE C. elegans for ageing studies because they can enter very long-lived quiescent phases in their life cycle, and there are mutations with very different lifespans]. People still aren't quite sure what that means or where it comes from.

There's lots of interest in caloric restriction still, with many organisms switching between high-fertility shorter-lifespan and loger-lifespan lower-fertility states, but with actual mechanisms quite up in the air and there being serious questions as to if it actually happens in primates at all.

That paper a year or two back where some people claimed to double mouse lifespans with buckyballs dissolved in olive oil has my attention. Nobody including me actually believes the results, not least because their experimental design and data storage/presentation was an absolute unmitigated mess, but their biological evidence of massive antioxidant effects from the buckyballs (numbers of oxidative molecules neutralized far in excess of the numbers of buckyballs) was interesting and possibly even true. You can bet there are a couple labs around Europe trying to replicate the results that we will hear back from in a few years. If it does actually have an effect I would expect far less of an effect in animals that are less metabolically frenetic than mice, which can metabolize a tenth of their body weight per day.

If I had to actually give advice though it would come from rather more prosaic sources than molecular biology. It would say get the hell up and moving fairly often, get sleep on a regular schedule and don't expose yourself to blue light after sunset, don't eat refined sugar, have friends you can rely on, and don't take strong medicines when you don't absolutely have to. And get cheap genetic tests when you can since they can tip you off about low-frequency high-impact things.

Comment author: Zaine 16 January 2014 04:51:44PM 1 point [-]

Intriguing, and thank you for the detailed reply. May I respond in the future should I have further queries?

Comment author: Benquo 13 January 2014 07:13:07PM 0 points [-]

I think the question was a practical one and "verification" should have been "vitrification."

Comment author: Zaine 13 January 2014 07:59:30PM *  0 points [-]

I considered that, but the words seemed too different to result from a typo; I'm interested to learn the fact of the matter.

I've edited the grandparent to accommodate your interpretation.

Comment author: CellBioGuy 12 January 2014 10:23:46PM 6 points [-]

Biology/genetics graduate student here, studying the interaction of biological oscillations with each other in yeast, quite familiar with genetic engineering due to practical experience and familiar with molecular biology in general. Fire away.

Comment author: Zaine 13 January 2014 07:17:29PM 0 points [-]

What's the current thinking on how to prevent physiological decay over time (id est ageing)? Figure a way to recover the bits of DNA cleaved in mitosis?

Comment author: [deleted] 12 January 2014 08:27:09AM 0 points [-]

Does the waterbear experience verification and then wake up again after being thawed, or does subjective experience terminate with vitrification - subjective experience of death / oblivion - and a new waterbear with identical memories begin living?

Comment author: Zaine 13 January 2014 12:05:04AM *  0 points [-]

We need to stop and (biologically) define life and death for a moment. A human can be cryogenically frozen before or after their brain shuts down; in either case, their metabolism will cease all function. This is typically a criterion of death. However if, when reanimated, the human carries on as they would from a wee kip, does this mean they have begun a new life? resumed their old life after a sojourn to the Underworld?

You see the quandary our scenario puts to this definition of life, for the waterbear does the exact above. They will suspend their metabolism, which can be considered death, reanimate when harsh environmental conditions subside, and go about their waterbearing ways. Again, do the waterbears live a subset of multiple lives within the set of one life? Quite confusing to think about, yes?

Now let's redefine life.

A waterbear ceases all metabolic activity, resumes it, then lumbers away. In sleep, one's state pre- and post-sleep will differ; one wakes up with changed neuronal connections, yet considers themselves the same person - or not, but let's presume they do. Take, then, the scenario in which one's state pre- and post-sleep does not differ; indeed, neurophysiologically speaking, it appears they've merely paused then recommenced their brain's processes, just as the time 1:31:00 follows 1:30:59.

This suggests that biological life depends not on metabolic function, but on the presence of an organised system of (metabolic) processes. If the system maintains a pristine state, then it matters not how much time has passed since it last operated; the life of the system's organism will end only when when that system becomes so corrupted as to lose the capacity for function. Sufficient corruption might amount to one specalated synapse; it might amount to a missing ganglion. Thus cyrogenics' knottiness.

As to whether they experience verification, you'll have to query a waterbear yourself. More seriously, for any questions on waterbear experience I refer you to a waterbear, or a waterbear philosopher. As to whether and to what degree they experience sensation when undergoing cryptobiosis, we can test to find out, but any results will be interpreted through layers of extrapolation: "Ganglion A was observed inhibiting Ganglion B via neurotransmitter D binding postsynaptic alpha receptors upon tickling the watebear's belly; based on the conclusions of Researchers et. al., this suggests the waterbear experienced either mildly positive or extremely negative sensation."

Comment author: [deleted] 12 January 2014 06:54:25AM 1 point [-]

We don't know if the identity of a given waterbear pre-cyrobiosis is preserved post-reanimation. For that we'd need a more complex organism.

How would you design that experiment? I would think all you'd need is a better understanding of what identity is. But maybe we mean different things by identity.

Comment author: Zaine 12 January 2014 07:50:44AM *  0 points [-]

We'd need to have a means of differentiating the subject waterbear's behaviour from other waterbears; while not exhaustive, classically conditioning a modified reflexive reaction to stimuli (desensitisation, sensitisation) or inducing LTP or LTD on a synapse, then testing whether the adaptations were retained post-reanimation, would be a starting point.

The problem comes when you try to extrapolate success in the above experiment to mean potential for more complex organisms to survive the same procedure given x. Ideally you would image all of the subjects synapses pre-freeze or pre-cryobiosis (depending on what x turns out to be), then image them again post-reanimation, and have a program search for discrepancies. Unfortunately, the closest we are to whole-brain imaging is neuronal fluorescence imaging, which doesn't light up every synapse. Perhaps it might if we use transcranial DC or magnetic stimulation to activate every cell in the brain; doing so may explode a bunch of cells, too. I've just about bent over the conjecture tree by this point.

Comment author: V_V 11 January 2014 04:22:17PM *  29 points [-]

Cryonics success is an highly conjunctive event, depending on a number of different, roughly independent, events to happen.

Consider this list:

  • The cryorpreservation process as performed by current cryo companies, when executed perfectly, preserves enough information to reconstruct your personal identity. Neurobiologists and cryobiologists generally believe this is improbable, for the reasons explained in the links you cited.
  • Cryocompanies actually implement the cryorpreservation process susbstantially as advertised, without botching or faking it, or generally behaving incompetently. I think there is a significant (>= 50%) probability that they don't: there have been anecdotal allegations of mis-behavior, at least one company (the Cryonics Institute) has policies that betray gross incompetence or disregard for the success of the procedure ( such as keeping certain cryopatients on dry ice for two weeks ), and more generally, since cryocompanies operate without public oversight and without any mean to assess the quality of their work, they have every incentive to hide mistakes, take cost-saving shortcuts, use sub-par materials, equipment, unqualified staff, or even outright defraud you.

  • Assuming that the process has actually preserved the relevant information, technology for recover it and revive you in some way must be developed. Guessing about future technology is difficult. Historically, predicted technological advances that seemed quite obvious at some point (AGI, nuclear fusion power, space colonization, or even flying cars and jetpacks) failed to materialize, while actual technological improvements were often not widely predicted many years in advance (personal computers, cellphones, the Internet, etc.). The probability that technology many years from now goes along a trajectory we can predict is low.

  • Assuming that the tech is eventually developed, it must be sufficiently cheap, and future people must have an incentive to use it to revive you. It's unclear what such an incentive could be. Revival of a few people for scientific purposes, even at a considerable cost, seems plausible, but mass revival of >thousands frozen primitives?

  • Your cryocompany must not suffer financial failure, or some other significant local disruption, before the tech becomes available and economically affordable. Very few organizations survive more than one century, and those which do, often radically alter their mission. Even worse, it is plausible that before revival tech becomes available, radical life extension becomes available, and therefore people stop signing up for cryonics. Cryocompanies might be required to go on for many decades or centuries without new customers. It's unclear that they could remain financially viable and motivated in this condition. The further in the future revival tech becomes available, the lower the chances that your cryocompany will still exist.

  • Regional or planetary disasters, either natural (earthquake, flood, hurricane, volcanic eruption, asteroid strike, etc.) or human-made (war, economic crisis, demographic crisis due to environmental collapse, etc.) must not disrupt your preservation. Some of these disaster are exceptional, other hit with a certain regularity over the course of a few centuries. Again, the further in the future revival tech becomes available, the lower the chances that a disaster will destroy your frozen remains before.

You can play with assigning probabilities to these events and multiplying them. I don't recommend trusting too much any such estimate due to the fact that it is easy to fool yourself into a sense of false precision while picking numbers that suit whatever you already wanted to believe.
But the takeaway point is that in order to cryonics to succeed, many things have to happen or be true in succession, and the failure of only one of them would make cryonics ultimately fail at reviving you. Therefore, I think, cryonics success is so improbable that it is not worth the cost.

Comment author: Zaine 12 January 2014 12:25:23AM *  2 points [-]

To keep the information all in one place, I'll reply here.

Cryogenic preservation exists in the proof of tardigrades - also called waterbears - which can reanimate from temperatures as low as 0.15 K, and have sufficient neurophysiological complexity to enable analysis of neuronal structural damage.

We don't know if the identity of a given waterbear pre-cyrobiosis is preserved post-reanimation. For that we'd need a more complex organism. However, the waterbear is idiosyncratic in its capacity for preservation; while it proves the possibility for cyrogenic preservation exists, we ourselves do not have the traits of the waterbear that facilitate its capacity for preservation.

In the human brain, there are billions of synapses - to what neurones other neurones connect, we call the connectome: this informs who you are. According to our current theoretical and practical understanding of how memories work, if synapses degrade even the slightest amount your connectome will change dramatically, and will thus represent a different person - perhaps even a lesser human (fewer memories, etcetera).

Now, let's assume uploading becomes commonplace and you mainly care about preserving your genetic self rather than your developed self (you without most of your memories and different thought processes vs. the person you've endeavoured to become), so any synaptic degradation of subsistence brain areas becomes irrelevant. What will the computer upload? Into what kind of person will your synapses reorganise? Even assuming they will reorganise might ask too much of the hypothetical.

Ask yourself who - or what - you would like to cyropreserve; the more particular your answer, the more science needed to accommodate the possibility.

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