Immortality

[Dr. Diaphanous]

Humanity has always dreamt of immortality. Many have tried to achieve it, but all have failed. Eventually people realised that nothing in nature can last forever.

But that isn't true. The essence of life is renewal. There are many life forms that do have an essentially unlimited lifespan - from the 5000 year old trees to the immortal jellyfish that can renew themselves indefinitely. Human cells, too, have the potential for immortality. Humans are full of potentially immortal cells that continually divide to replace damaged cells. So why can't humans live forever? Because some cells cannot be replaced, but live as long as the human - most importantly, the nerve cells. These are the cells that make up our brain - essentially making us who we are - so they cannot be replaced.

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So here's my idea - to reprogramme all the cells in your body (or at least the stem cells) to continually replace damaged cells (including nerve cells) so that your body never grows old. The downside being that your memories slowly fade away irretrievably as the nerve cells in your brain are replaced.

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How realistic is this idea? Could it actually work at some point in the future?

Would you volunteer for this treatment if it had been perfected? Say for the sake of argument that your memories go back as long as the apparent age of your body. So you can stay 20 forever, but you will never have memories beyond 20 years. Alternatively, you could elect to have a weaker form of the treatment so your body will always be 80 but you can remember 80 years in the past (although the oldest memories will be faded to the same degree as an untreated person remembering 80 years ago).

What would the social implications be? For example, if someone has no memories of a century ago and possibly their personality has drifted somewhat, can they still be considered the same person? What about for legal purposes?

All those moments will be lost in time... like tears in rain... Time to live forever.

(Feel free to use this in your fiction/ medical research)

[idobox]

There is a name for cells that don't age and keep multiplying. It's cancer.

Keeping a body alive is a question of respecting many equilibriums, and messing with stem cells to change their multiplication and aging behaviour is going to be a massive headache, but nothing strictly impossible.
You probably wouldn't loose much memory. Brain tissue is highly redundant, with often a few tens to hundreds of neurons doing the job a single one could do. As some ide, the others keep the memory.

Now neurogenesis is a very complex and poorly understood thing, and some functions would be very hard to repair. Some neurons have very long and branched axons connecting many parts of the brain and cerebellum. Getting a new neuron to grow in such a way it connects to all these distant parts, with the right weights, in an already fully develloped brain, will be a nightmare.
The scenario you describe could lengthen our life expectancy by a considerable amount, but would not make us immortal. To reach true immortality, we will have to switch to a more reliable, and easier to repair, medium. It doesn't have to be a true computer simulation (a very frequent thing in SF), it could be some kind of periodic rebuild of the complete brain, be it a normal one, or a bionic one.
My opinion is that we will make more and more devices able to emulate parts of the brain, devices that can be replaced and whose data can be saved, until all the critical stuff is replaced by bio-electronic devices(bio because the brain produces, and is sensitive to a wide range of chemicals), and we have a bionic brain. The most tricky part will be to measure and copy "data" from live tissue to machines, but could be avoided by replacing the brain of new-borns by a blank bionic one.

[Dr. Diaphanous]

There is a name for cells that don't age and keep multiplying. It's cancer.

And stem cells?

Now neurogenesis is a very complex and poorly understood thing, and some functions would be very hard to repair. Some neurons have very long and branched axons connecting many parts of the brain and cerebellum. Getting a new neuron to grow in such a way it connects to all these distant parts, with the right weights, in an already fully develloped brain, will be a nightmare.

Alas! Realism!

replacing the brain of new-borns by a blank bionic one.

Isn't that the same as just making a robot, but you have to go through the bother of making the organic body? I suppose meatware has a few perks such as healing, but it's pretty easy to damage and hard to replace parts or upgrade. Also: The brain of a newborn isn't blank. What about all the genetic predispositions and intincts? (Or would you genome-sequence the parents and programme your bionic brain accordingly?)

[Izawwlgood]

And stem cells?

Can become cancerous. Have you heard of leukemia?

Isn't that the same as just making a robot, but you have to go through the bother of making the organic body?

Eh?
I think you need to learn a bit more about the biology of what you're asking, or ask some more questions about it. Also, ask yourself what you want to be immortal. The ovarian cancer cells of Henrietta Lacks will be around for a long time, but are most certainly not Henrietta Lacks. I can make some part of you immortal pretty easily; that doesn't make you immortal.

Idobox handled most of these ideas pretty well, but for 'neat ways to improve longevity' there are a variety of cool sci fi ways that handle it pretty well. I liked Red Mars by Kim Stanley Robinsons take on it. Basically, some kind of gene therapy that replaces damaged genes (with magic!) and elongates telomeres (swoosh!) that people can undergo every 10 years or so.

I'm studying mechanisms neurodegenerative disorders, and honestly, I don't think cancer is really what you have to worry about. Our nervous systems and brains are pretty terribly designed for anything beyond 50 years.

[WarDaft]

You might not have your original memories for more than 20 years, but when you remember things, you often build new memories of them. In fact, you can re-fabricate the memory to be totally different given sufficient coercion - for example, being showed a photo-shopped picture where the change is something that you think makes sense.


So you wouldn't be limited to remembering only things from the last 20 years, you'd just forget things that you tended not to think about often. Which is rather like what actually happens.

[gmalivuk]

Yeah, human memory isn't that fantastic to begin with.

[Dr. Diaphanous]

Idobox handled most of these ideas pretty well, but for 'neat ways to improve longevity' there are a variety of cool sci fi ways that handle it pretty well. I liked Red Mars by Kim Stanley Robinsons take on it. Basically, some kind of gene therapy that replaces damaged genes (with magic!) and elongates telomeres (swoosh!) that people can undergo every 10 years or so.

But elongating the telomeres is the same thing as removing the Hayflick limit so the cells can divide any number of times. And there is a name for cells that don't age and keep multiplying. It's cancer (idobox, 2012).

So you wouldn't be limited to remembering only things from the last 20 years, you'd just forget things that you tended not to think about often. Which is rather like what actually happens.

That seems more plausible.

I'm studying mechanisms neurodegenerative disorders, and honestly, I don't think cancer is really what you have to worry about. Our nervous systems and brains are pretty terribly designed for anything beyond 50 years.

But surely biological healing is the only way to get brains to last longer? And surely it's "easier" than "downloading" "all the information" in the brain onto an electronic computer?

[Soralin]

Idobox handled most of these ideas pretty well, but for 'neat ways to improve longevity' there are a variety of cool sci fi ways that handle it pretty well. I liked Red Mars by Kim Stanley Robinsons take on it. Basically, some kind of gene therapy that replaces damaged genes (with magic!) and elongates telomeres (swoosh!) that people can undergo every 10 years or so.

But elongating the telomeres is the same thing as removing the Hayflick limit so the cells can divide any number of times. And there is a name for cells that don't age and keep multiplying. It's cancer (idobox, 2012).

Well it's only cancer if it's multiplying when it shouldn't. I mean, normal cells will replicate to replace lost cells, otherwise you'd have a hard time healing injuries or even just dealing with general wear and tear, but then they'll stop replicating since there are mechanisms and conditions in place which control that. telomeres being lost is not the primary limiting factor on cells replicating.

[Izawwlgood]

Idobox handled most of these ideas pretty well, but for 'neat ways to improve longevity' there are a variety of cool sci fi ways that handle it pretty well. I liked Red Mars by Kim Stanley Robinsons take on it. Basically, some kind of gene therapy that replaces damaged genes (with magic!) and elongates telomeres (swoosh!) that people can undergo every 10 years or so.

But elongating the telomeres is the same thing as removing the Hayflick limit so the cells can divide any number of times. And there is a name for cells that don't age and keep multiplying. It's cancer (idobox, 2012).

Well it's only cancer if it's multiplying when it shouldn't. I mean, normal cells will replicate to replace lost cells, otherwise you'd have a hard time healing injuries or even just dealing with general wear and tear, but then they'll stop replicating since there are mechanisms and conditions in place which control that. telomeres being lost is not the primary limiting factor on cells replicating.

That, and the fact that not all cells divide. Kidney cells and neurons are a good example of non-regenerative tissues, so improving the hayflick limit of those cells isn't going to do anything.

But surely biological healing is the only way to get brains to last longer? And surely it's "easier" than "downloading" "all the information" in the brain onto an electronic computer?

If you're willing to accept 'download consciousness onto a computer' as a hand wavy solution, I suppose you should also be willing to accept 'biological healing to get brains to last longer'.
Basically, it's complicated. Neurons are pretty impressive biological machines, but they also don't seem to last very long. A lot goes wrong, and because they don't regenerate, once it goes wrong, the brain is screwed.

A good approximation is the Martian Rovers. They built them as brilliantly as they could, with a handful of redundancies. However, once they launch off that pad, ain't nothing you can do to fix something that goes wrong. So a wheel locks, and from now on, all movement has to be done with a locked wheel. A circuit fries, and well, we didn't need that camera anyway. Brains are like that; truthfully, I feel that in our lifetime we'll see cures for all but the most aggressive of cancers, stuff that wrecks your system so fast there's nothing they can do. Caring for the life support system is going to be something we get pretty good at in the next 50 years. Now, fixing the brain... That I think, will be a challenge. Growing a new kidney from iPSCs and transplanting it into a patient? Sure! Inducing damaged neurons to divide, reconnect appropriately, and clear the plaques causing further tissue toxicity? You're getting into nanotech level precision here. Although, to be fair, I think by the time Alzheimers or ALS could be setting in for me, we'll have some therapies out. A lot of progress has been made in the last 10 years.

[Dr. Diaphanous]

Tortoises have been known to live up to 188 years, there is some evidence that Bowhead Whales can reach 150-200 years, and there is a koi carp that supposedly lived to 226.

I wonder how their brains manage? How would you even study something that outlives the researchers' grandchildren, when subtle changes over time are the thing you are studying?

[ikrase]

The brain had to be generated while operational during embryonic and childhood development.

What I think needs to be done is to add to the human body an intelligent (silicon or flesh) control system to co-ordinate the non-cancerous perpetual repair of all areas. Your head was a lot smaller when you were two and you were somewhat functional then. And it developed. It should be able to redevelop.

[Copper Bezel]

Again, that's really a sort of equivocation. We can make steno books and write down notes in them. We can't restore an individual steno book full of notes when someone sets it on fire.

[Thesh]

In the future, we may have further understanding of the brain, how to keep track of it, and repair it. Maybe even how to boost our capacity for memory storage with neural implants. Once that happens, the key to keeping us alive is nanobots that repair our cells, DNA, etc. to allow us to keep healthy for eternity. Without nanobots, I don't think the human body is capable of regenerating itself indefinitely, even with biochemical modification. We are just significantly more complex than a jellyfish.

Without interstellar travel and settlement, I don't think it's practical for humans to live forever. So if you are looking to write fiction on the subject, I would make sure that's a prerequisite.

[Dr. Diaphanous]

Cells are nanobots aren't they? Highly complex nanobots optimised for life support, repairing the body, and surviving in the environment inside the body.

[Thesh]

They are the best we get from millions of years of random mutations, but they do make mistales (see cancer). If we design something specifically for the task, it is likely we can make something much more effective at making repairs.

[Izawwlgood]

Also, our neurons evolved to only be neccesary for about 40 years.

[moiraemachy]

Without nanobots, I don't think the human body is capable of regenerating itself indefinitely, even with biochemical modification.

DNA computing is a thing. I suggest implementing data correction during DNA replication: adding some variation of the Hamming code to artificial stem cells' DNA and checking it during replication.

I'm studying mechanisms neurodegenerative disorders, and honestly, I don't think cancer is really what you have to worry about. Our nervous systems and brains are pretty terribly designed for anything beyond 50 years.

Could you elaborate? I always believed that the greatest reason why human brains lose performance when we get old was, basically, neurons getting slower, less reliable and less able to form new connections. This seems to fixable by replacing neurons by new ones. Is there a, how do I put this?, "structural" reason why human brains don't work so well when old?

[Izawwlgood]

DNA computing is a thing. I suggest implementing data correction during DNA replication: adding some variation of the Hamming code to artificial stem cells' DNA and checking it during replication.

These two things are not as related as you may believe them to be. Can you elaborate on what you are saying?

Could you elaborate? I always believed that the greatest reason why human brains lose performance when we get old was, basically, neurons getting slower, less reliable and less able to form new connections. This seems to fixable by replacing neurons by new ones. Is there a, how do I put this?, "structural" reason why human brains don't work so well when old?

Well, sort of; the terms 'lose performance', 'get slower', 'less reliable' and 'less able to form new connections' are symptoms of neurons that are undergoing neurodegeneration. For example, Parkinson's is neurodegeneration of certain motor neurons, and a body has a steadily increasing risk of developing this degeneration up to about 70 years of age. However, if you make it to 70 without developing Parkinson's, your chance of developing Parkinson's goes down. So clearly some issue is leading to the 'reduced performance' of these neurons, something that is gradual over time, and if absent, well, absent.

Furthermore, only two small parts of the brain contain neurons that are still dividing; this notion of 'just replace neurons with new ones' is, as pointed out already, basically science fiction. We have no way of delivering new neurons to the right place. We have no way of making them form the same connections as the ones they are replacing. We have no way of inducing unhealthy neurons to divide into healthy ones to replace them. Keep in mind, the longest neurons in your body go from your brain to your foot; that axon has grown over the course of your entire life. It's entirely possible that the technology required to replace the motorneuron bundle and induce axonal growth all the way to it's target is, at this level of medical technology, indistinguishable from magic.

So is there a structural reason why human brains don't work so well in these neurodegenerative disorders? Yeah; specific neurons are dying, and the brain itself is becoming riddled with failing cells.

You know how your body is constantly clearing mis-dividing cells in the body? How every day, the immune system clears, I dunno, say, 10,000 precancerous cells that would go on to develop full blown tumors? The body, you could say, is in a constant state of falling apart and being repaired. This equilibrium is vital to the normal function of the body. Well the brain is in a similar boat; the brain is constantly producing and clearing these toxic elements that lead to neurodegeneration, and, in the case of disease, lost the battle of clearance.

[moiraemachy]

Well, the idea was to stick some parity bases or parity codons in our DNA, (well, not exactly, parity only allows for error detection, I want error correction, but it's basically the same idea) and then somehow go through the the whole thing, verifying if sections are corrupted and correcting them (or triggering apoptosis if things are really messed up). This way cells could keep on duplicating without the risk of mutation.

Yeah, "going through the DNA storing it's parity and correcting errors" is still pretty damn hard and maybe could only be done with nanobots... but at least now the task the nanobots have to perform is much more straightforward. What I'd be really excited for, however, is the use of the techniques learned with DNA computing to engineer some biological modification that'd perform this task. Unfortunately, it appears that you are correct: the current state of DNA computing appears to go into another direction: benefiting from parallel computing, requiring assistance at every step and not being able to do sequential statements... nothing like ribosomes going through DNA tapes like heads of turing machines .

I remember reading speculation about that, though. Something about being able to replace some DNA sequences, making a tape that'd modify itself as the program runs... I'll try to dig it up.

[Izawwlgood]

What you just described is the biological equivalent of magic. What decides what the 'correct' sequence is? What about epigenetic factors? What about non-dividing cells?

[moiraemachy]

After a wiki walk, I can see that you're right. I thought of the control mechanism of gene expression as being something like some DNA-polymerase-like thing traversing DNA and seeking for "start" and "end" tags, and thought that with this mechanism(the ability to read and interpret DNA, for some very limited values of interpret), along with DNA-modifying enzymes, we wouldn't be THAT far away from implementing what I said... apparently, I'm completely wrong . I also grossly overestimated what DNA-modifying enzymes can do.

Still, I like the idea of data correction on DNA. Maybe if DNA had more nitrogenous bases per codon(does anything suggest that this would not be viable? After all alternative codon tables for some creatures exist. It seems to be merely a matter of adapting the tRNA), data correction could be implemented in each individual codon by specific enzymes that fit the incorrect codon, (IANAB, as you've noticed, so in case I'm in doubt, enzymes it is).

This however ignores the elephant in the room that you mentioned: epigenetics.

[Dr. Diaphanous]

Still, I like the idea of data correction on DNA. Maybe if DNA had more nitrogenous bases per codon. Does anything suggest that this would not be viable?

If each codon was 4 nucleotides long, you would need 4^4 = 256 different types of tRNA (rather than the current 64 types). Also codon usage bias would suggest that it matters which codons are used (in fast-replicating organisms), so replacing them with completely different codons could cause problems such as slowing down transcription and DNA replication. It could still work though (although rewiring the whole Genome as well as the transcriptional/translational machinery would be a major undertaking (look at all the fuss they made when they put a mycobacterium genome into a mycobacterium)).

[Izawwlgood]

Codon bias isn't really a way to assess what 'should be there'. You can make claims about how a particular base pairing may be more prevalent in certain portions of certain sequences, but in humans, you aren't going to be able to reliably say 'well GC is more enriched in introns so clearly if you're going along DNA and you have ATs, it MUST be an exon'. Also, I think it's always kind of amusing when someone says "Well you could make nanobots that store information about what DNA should be there, and then when they reread it, replace mutated DNA". Think of the sizes involved here; DNA is virtually as information dense as you can get. Storing binary bits on single atoms is only about 10 times more dense than storing quarternary bits on nucleotides, so your nanobots are going to have to have some pretty impressive things going for them.

But yeah, if you could magically fill the body with nanobots that had a copy of your entire genome, corrected for all potential errors, and perpetually read the DNA in all your replicating cells and corrected it (better/faster than the correction machinery you already have!), you still aren't solving the problem of epigenetics, and you still aren't correcting for any of the host of non-cancerous disorders caused by genetic abnormalities.

Also, eukaryotic gene expression is way more complex than 'read along until you find a start codon, crank out a protein'. I don't mean for that to sound rude, but it's an insanely complex process with multiple factors binding to multiple DNA domains and recruiting multiple components.

[WarDaft]

We have no way of delivering new neurons to the right place. We have no way of making them form the same connections as the ones they are replacing.

Is that actually necessary though? As long as they are introduced and grown in a typical manner related to human learning, they don't have to be the same, or even in the same place. Old skills and memories you don't use or think about would fade away, but they do anyway. No particular neuron is terribly important, considering how many there are in the brain. Replacing every neuron in your head over 30 or so years would require introducing 100 new neurons every second which - spread out over your whole brain - is not such a huge difference. There are always axons growing in the brain, if we put it in a renewal process, there would just be more growing at any given time.

Of course this still doesn't bring it within a thousand miles of easy.

[Izawwlgood]

There are always axons growing in the brain, if we put it in a renewal process, there would just be more growing at any given time.

I don't think this is as true as you think it is.

I remember reading that simply injecting stem cells into someone's CNS was sufficient to stave off neurodegeneration, but I'll have to find the article. I wouldn't be surprised if developing neurons were capable of directing their own growth in an adult human being, but, I wouldn't be surprised if they weren't either.

[idobox]

There are always axons growing in the brain, if we put it in a renewal process, there would just be more growing at any given time.

I don't think this is as true as you think it is.

I remember reading that simply injecting stem cells into someone's CNS was sufficient to stave off neurodegeneration, but I'll have to find the article. I wouldn't be surprised if developing neurons were capable of directing their own growth in an adult human being, but, I wouldn't be surprised if they weren't either.

They don't grow much in the adult brain. Synaptic weights can change a lot though.
There are growth factors that can stimulate and lead the growth of axons, but it's a slow and random process. For example, when a nerve is cut, it can grow again, but the axons will connect randomly, so the neuron that used to connect to this muscle, will connect to another one, and you won't really be able to control what you do.

You also have to keep in mind that there hundreds of different types of neurons, with different receptors, different transmitters, different electrical dynamic properties and different morphologies. Putting new neurons in a brain would be comparable to throwing transistors in a computer case and hoping it repairs it.

Downloading the brain might not be as difficult as it seems. Most of the stuff that gives our personnality and memories happens in the neocortex, the outer layer, that is only 6 cells thick. The deeper structures are less specific, and wouldn't need to be copied exactly, except for some critical stuff, like the hypothalamus.
The amount of data to collect is still enormous, and difficult to capture, but we can do it on a small scale, and if IT technology keeps following Moore's law, it should be feasible someday. The most difficult part is measuring stuff, and nanotechnology will be necessary to implant billions of electrodes.

[WarDaft]

I don't think this is as true as you think it is.

I remember reading that simply injecting stem cells into someone's CNS was sufficient to stave off neurodegeneration, but I'll have to find the article. I wouldn't be surprised if developing neurons were capable of directing their own growth in an adult human being, but, I wouldn't be surprised if they weren't either.

There are 100 billion odd neurons in the brain. To have all of them simultaneously not growing an axon more than a small fraction of the time requires that each neuron grown an axon at a rate of less than 1 per (ten thousand years * N), where N is the average number of seconds it takes for an axon to grow (I imagine it's a lot more than 1.)

[Izawwlgood]

Most axonal pathfinding growth happens during development. During maturation, elongation of axons is what's happening in motor neurons. Brain plasticity I'm less familiar with, but the changing around if connections is pretty new I believe.

But motor neurons are distinctly not dividing, and distinctly not making new connections past development. The same can be said for the vast majority of neurons, presumably because neurodegeneration in alzheimers.

[Copper Bezel]

For example, when a nerve is cut, it can grow again, but the axons will connect randomly, so the neuron that used to connect to this muscle, will connect to another one, and you won't really be able to control what you do.

I'm still very solidly in the "this is not easy, or likely even possible" camp, but it should be pointed out that the brain does often manage to relearn the new connections, because it's a plastic and self-correcting system. Like Izzawlgood said, it really is sometimes as simple as squirting in some stem cells (and sometimes not at all.)

[idobox]

For example, when a nerve is cut, it can grow again, but the axons will connect randomly, so the neuron that used to connect to this muscle, will connect to another one, and you won't really be able to control what you do.

I'm still very solidly in the "this is not easy, or likely even possible" camp, but it should be pointed out that the brain does often manage to relearn the new connections, because it's a plastic and self-correcting system. Like Izzawlgood said, it really is sometimes as simple as squirting in some stem cells (and sometimes not at all.)

Warning, all of what follows is exagerated to make things simpler. There is still much we don't know, and even more I don't know.

That's mostly in the cortex, and it is able to do so because there is a high level of interconnection in the cortex, ie you don't need to grow new neurons or axons to compensate for destructed tissue, you can "just" use a different part of the cortex that used to receive the same inputs and used to ignore them.
The level of plasticity in the stem and other deeper structures is much less important, and when things go wrong, you never really get better, because the small cluster of highly specialized cells that connected to a few other very specialzed nuclei cannot be replaced.
If we want to replace them, we first need to be able to grow the right kind of neurons, and then to direct the growth of the axons to targets that are mm scale, hundreds of mm away, without connecting randomly to everything's that's in the middle. Not strictly impossible, but it's going to require some serious technology. In many case, it will probably be easier to replace the defective parts with engineered devices, using wires or RF links rather than axons, carefully positionned by a trained surgeon; rather than getting a modified/artificial biological system to have the same accuracy. The engineered devices can be pure electro-mechanical systems, and be very resilient; or partly biological, using neurons for example, and be more adaptable and self repairing to some extant.

[Izawwlgood]

it will probably be easier to replace the defective parts with engineered devices, using wires or RF links rather than axons, carefully positionned by a trained surgeon; rather than getting a modified/artificial biological system to have the same accuracy.

Out of curiosity, are you saying this from a perspective of clinical/biological knowledge, or assumption?

The engineered devices can be pure electro-mechanical systems, and be very resilient; or partly biological, using neurons for example, and be more adaptable and self repairing to some extant.

I'm not sure what makes you think this to be true; you're describing components that have yet to be invented, being implemented into a system that has yet to be fully understood, all of which are microscopic. While I dig the idea of replacing neurons with RF transmitters, and synapses with RF receivers, you also forget that one hurdle to be overcome is that the actual exchange of information is chemical in nature; this component you're describing is pretty complicated.

[idobox]

Out of curiosity, are you saying this from a perspective of clinical/biological knowledge, or assumption?

I don't claim to be an expert, but I jsut started a PhD in computational neuroscience, and I'm currently reading a lot of neuroanatomy right now. The complexity and range of connections is awesome.

I'm not sure what makes you think this to be true; you're describing components that have yet to be invented, being implemented into a system that has yet to be fully understood, all of which are microscopic. While I dig the idea of replacing neurons with RF transmitters, and synapses with RF receivers, you also forget that one hurdle to be overcome is that the actual exchange of information is chemical in nature; this component you're describing is pretty complicated.

The exchange of information is often ionic more than chemical. We can record the activity of neurons and stimulate or inhibate them with simple electrodes. This won't be able to reproduce some effects, that's why I suggest hybrid systems.
I wasn't thinking of single pseudo-neurons having RF transmitters, rather of bigger circuits communicating between each other this way to avoid the need of cables.

And yes, we're far from understanding everything, and even further from being able to replicate it, but it's not as difficult as it might seem, and electronics are the easiest way. Work on hippocampal prosthesis is pretty fascinating in that it will probably be able to replace a very central and imporant of the brain in the foreseable future.

[gmalivuk]

And yes, we're far from understanding everything, and even further from being able to replicate it

Actually, I think we'll be able to replicate it long before we understand everything.

[Izawwlgood]

I don't claim to be an expert, but I jsut started a PhD in computational neuroscience, and I'm currently reading a lot of neuroanatomy right now. The complexity and range of connections is awesome.

Ahhhha...

The exchange of information is often ionic more than chemical.

Half right- potentiation is determined by ion transport, but neuronal firing is the release of neurotransmitters. Your RF circuit idea is neat, but would be circuventing the ion flux aspect, not the neurotransmitter aspect.

but it's not as difficult as it might seem

Not to be a dick, but I always kind of scoff when people say this about fields they don't work directly in. This is like when physicists say about, say, the cytoskeleton, 'why don't you just model it as a series of self-assembling monomers?'. Why? Because it's more complicated than that.

[idobox]

Half right- potentiation is determined by ion transport, but neuronal firing is the release of neurotransmitters. Your RF circuit idea is neat, but would be circuventing the ion flux aspect, not the neurotransmitter aspect.

For most cortical neurons, as much as we understand, currents can do the same job as neurotransmitters.
Real neurotransmitters will be needed to replace stuff like the dopaminergic or serotonic system because they don't only cause ionic currents, but a number of other changes in the postsynaptic cell. I still think it's easier to build a microfluidic system than to get stem cells to specialize in the right kind of neuron and grow axons and dendrites the right way, in the right places, and connect with the right neurons.

Not to be a dick, but I always kind of scoff when people say this about fields they don't work directly in. This is like when physicists say about, say, the cytoskeleton, 'why don't you just model it as a series of self-assembling monomers?'. Why? Because it's more complicated than that.

I have to clarify. A few years ago, I thought it was absurdly complex, year 3000 type of complex.
It's not as difficult as it seemed to me, since people are actually pretty close (still one or two decades from implantation in humans,a t least) to make working implants that replace central parts of the brain.

Replacing parts of the cortex will probably be the most difficult. Current microelectronic technology can fit a reasonable amount of artificial neurons per unit of surface, but we are lightyears away from being to able to reproduce the level of interconnection. Also the individual differences are huge and important to reproduce, so you will need a way to measure them, which is total science fiction right now, while most parts of the mesencephalon, at least those we understand best, are simpler to reproduce, being basically control or regulation systems.

[Izawwlgood]

I'm fairly new to neurobiology, so can you linky me to an example of a neuron that potentiates and fires solely with the use of ions? It is my understanding that channels (which allow the flow of ions for potentiation) are entirely predicated on neurotransmitter binding (or in some cases, other stimuli like pressure, heat/cold and various other compounds), which can raise the action potential of the neuron such that it fires. Firing produces a wave of depolarization, and at the synapse, causes the release of neurotransmitters.

AFAIK, there is no neuron that releases ions which somehow directly potentiate the recieving neuron.

It's not as difficult as it seemed to me, since people are actually pretty close (still one or two decades from implantation in humans,a t least) to make working implants that replace central parts of the brain.

There are implants that deliver metronomic current to different parts of the brain, kind of like a pacemaker, but they're pretty radical and only for things like non-drug responsive epilipsy. Sticking a few electrodes in a brain and pulsing a small current is vastly different from claiming we can rewire or replace parts of the brain.

Again, I think you're understanding the level of complexity involved here on every level; from the organization of the network to the molecular diversity each component of the network responds to and outputs.

[Frenetic Pony]

This isn't "fictional" at all. From the standpoint of physics there's no reason humans can't be immortal. To explain: From a chemical/molecular level ageing has been identified primarily as a gradual degradation of dna. The primary cause of this appears to be the reduction of the size of telomeres.

Telomeres are functionally useless areas of your dna chain at both ends. These ends don't get transcripted into proteins, in fact they don't directly affect you at all. However as cells divide errors do occur, usually this results in apoptis, triggered cell death. Now, usually these errors in replication occur at the ends. This is where telomeres become useful.

Imagine an error occurring in a telomere, the cell still ends up fine, energy is not wasted, cancer doesn't form, something else doesn't go wrong, etc. However that cell, should it be responsible for further replication in the future, will now replicate that shortened telomere. Now, as every cell in your body (except theoretically the neurons responsible for long term memory, and perhaps/probably a lot other neurons, go argue about it) get replaced many times, any errors, like telomere shortening, will get compounded. Thus over time this compounding of error results in ageing and death through any number of secondary affects of dna replication error. (See incorrectly transcripted (bent) protiens and etc.)

However, there is no fundamental physical reason humans can't have perfect dna replication until the physical resources are no longer left due to entropy in billions of years (assuming this is, in fact, the inevitable fate of the universe). Point is, is there a fundamental physics reason for ageing? Nope, none whatsoever. So now we have to deal with this just in terms of engineering practicality.

To which I would point to any number of studies and currently in development medicines that are examining this dna replication error and engineering. For example, an organism has recently been proven to replicate itself perfectly, again and again, essentially making it immortal. Even more impressive, a drug enhancing certain already active mechanisms for preserving telomeres has already been tested on live mice, extending their life by as much as one and a half times (assuming death by ageing). Mean time to market from lab in terms of a proven medicine is 13 years by the way.

The summation of all this is a seemingly startling but never the less probable truth: there are going to be significant life extending drugs available on the market within two decades if not significantly less time. If you are below the age of 40, if not older, there is a not insignificant chance, assuming historical trends of economic growth and technological progression continue (I.E. we don't all die from an asteroid/nano bot von neumann machines/whatever); Anyway, assuming historical trends there is an not insignificant chance that you yourself will live to become immortal (in the not ageing sense).

In abstract terms, this seems totally amazing. In practical terms, I'm wondering where I'm going to invest my money and ride the wave towards however many hundreds of millions to hundreds of billions this sort of thing could make.

[Izawwlgood]

FP, you should read the thread. Telomere's are only a portion of what accounts for aging. Some species of vertebrates actually lengthen telomeres with each replication. Furthermore, I'm not sure you understand what telomeres are actually doing from your description of them; errors in telomere replication aren't what amounts for reduced cellular replication in terms of telomeres involvement in cellular replication.

[Frenetic Pony]

Most axonal pathfinding growth happens during development. During maturation, elongation of axons is what's happening in motor neurons. Brain plasticity I'm less familiar with, but the changing around if connections is pretty new I believe.

But motor neurons are distinctly not dividing, and distinctly not making new connections past development. The same can be said for the vast majority of neurons, presumably because neurodegeneration in alzheimers.

I've problems with this "definitely not" thing. It was not so long ago that neurogenesis was "definitely not happening at all" after development in the womb. Now it's "oh, it only happens in migrating to the olfactory bulb and hippocampus". From what I understand, it may be better to say overall that "we aren't totally sure how neurons and axons and etc. work, but we're getting a lot better at finding out."

I wouldn't rule out replacing so called "specialized" neurons and other things until such time as we stop making startling and unexpected discoveries about how everything functions on a regular basis. That's certainly not saying stop hypothesizing, nor that current conclusions are incorrect. But, if I wasn't tired and in class, I'd go back and find papers that have just now described how long terms memory neuronal connections are strengthened among various other important roles. Point being that being confident of a lot of conclusions at the moment feels a tiny bit reminiscent of Max Plank's physics professor telling him that physics was a "dead field" and that "pretty much everything has been figured out".

[Frenetic Pony]

FP, you should read the thread. Telomere's are only a portion of what accounts for aging. Some species of vertebrates actually lengthen telomeres with each replication. Furthermore, I'm not sure you understand what telomeres are actually doing from your description of them; errors in telomere replication aren't what amounts for reduced cellular replication in terms of telomeres involvement in cellular replication.

Part of the papers I've read suggest that they are, though I'd love to see other papers. I don't claim to be an expert on the subject at all, just very interested. Thanks for the suggestion.