<br><div><span class="gmail_quote">On 4/16/07, <b class="gmail_sendername">Brett Paatsch</b> <<a href="mailto:bpaatsch@bigpond.net.au">bpaatsch@bigpond.net.au</a>> wrote:</span>
<br><br>I know you asked Anders, but...<br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><span class="q"></span>
<div><font face="Arial" size="2"> W<font face="Arial" size="2">ould you classify yourself as a believer in cryonics? </font></font></div></div></div></blockquote><div><br>I would argue that if you cannot make a reasonable case that the information content is completely destroyed, as would be the case say with cremation, then at some point we will have the technology to recover it. Your question is unclear as to whether you want cryonics to simply preserve the information content or whether you expect it to lead to a full recovery of the original biological body with most (or all) of the original atoms or molecules where they were before undergoing cryonics.
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<div><font face="Arial" size="2">My point about the caveat against believers btw is
that believers reason differently and argue differently - by differently
I mean fundamentally dishonestly and evasively.</font></div></div></div></blockquote><div><br>I would argue that is a misstatement. I think there are probably only about a dozen people, at most a few dozen, in the world who have the depth of knowledge required for an *informed* discussion of the topic. Others aren't so much arguing dishonestly or evasively but from a simple lack of knowledge.
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<div><font face="Arial" size="2">On what basis do you </font><font face="Arial" size="2">think machine phase chemistry is "definately" thermodynamically credible?</font></div></div></div></blockquote><div><br>On the basis that *ALL* of biology is assembled molecule by small molecule. (Drexler effectively argued this in his 1981 PNAS paper that most people haven't read.) The use of the term "machine phase chemistry" is ill-defined. What are DNA polymerase, RNA polymerase and the ribosome if they are not machines conducting chemistry!?! (And if you don't know what they are and how they work go look them up in Wikipedia or Google. Go read [1], and then come back to the discussion.
<br><br>What I think you mean to take issue with is precision general purpose molecular assembly which is somewhat different from what is done in biology. And as has been pointed out elsewhere, Drexler *never* said that you could assemble anything and everything -- he said that there were a lot of things that you could assemble which cannot be assembled which could not be assembled using current methods. (And the entire history of chemistry over the last 100 years is a fairly clear demonstration of that.)
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<div><font face="Arial" size="2">I'm assuming you are aware of Smalleys </font><font face="Arial" size="2">fat and sticky fingers criticisms of Drexler.</font></div></div></div></blockquote><div><br>I assume you know that Smalley's criticisms are a decade or more old and haven't done a recent PubMed article review using the keyword "nanoassembly" or "nanoassemblies" and are unaware of [2].
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<div><font face="Arial" size="2"> Life </font><font face="Arial" size="2">molecules like proteins </font><font face="Arial" size="2">assemble in
compartments containing water. </font> <font face="Arial" size="2">Machine </font><font face="Arial" size="2">phase chemistry </font><font face="Arial" size="2">as I </font><font face="Arial" size="2">understand it </font>
<font face="Arial" size="2">is essentially watery-solution free chemistry. </font><font face="Arial" size="2">Without a watery solution </font><font face="Arial" size="2">how do you see machine phase chemistry </font><font face="Arial" size="2">
managing the folding of proteins?</font></div></div></div></blockquote><div><br>Not really. It is "free radical based" chemistry that would be difficult to do in water (or many other solutions). A primary reason "water" is undesirable other than the fact that it would interfere with free radical based chemistry is that it is a solid below 32C. There is nothing preventing one from doing mechanical assembly in say LN2 or LH2 or LHe. The lower temperatures reduce the inaccuracies due to thermal motion of the molecules.
<br><br>To quote directly from <span style="font-style: italic;">Nanosystems</span>, Section 1.2.2a:<br><ul><li style="font-style: italic;">A machine-phase system is one in which all atoms follow controlled trajectories (within a range determined in part by thermal excitation).
</li><li style="font-style: italic;">Machine-phase chemistry describes the chemical behavior of machine-phase systems, in which all potentially reactive moieties follow controlled trajectories.</li></ul>There is no problem (at least in my mind) for assembling proteins (or nucleic acids) at low temperatures in non-water based solutions (I would love to know what fraction of enzymes still function properly in cooled liquid ammonia (or how difficult it would be to evolve them)).
<br><br>If you want proteins (which are sequences of amino acids) to "fold" properly then you have to put them into the environment (water + temperature) for which they evolved. Even then some proteins will not fold properly without the assistance of other proteins such as heat shock factors and chaperonins.
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</div><div><font face="Arial" size="2">I've frozen and thawed cells. Have you?</font></div></div></div></blockquote><div><br>I made cooked some frozen vegetables the other night, does that count? I think as a child I also may have fed frozen brine shrimp to my tropical fish. Don't know if I thawed them to bring them back to life however. (Just as an FYI, since I'm doing research on it now, there are a number of species of both plants and animals, including brine shrimp, tardigrades and rotifers which can be dessicated and/or frozen and thawed and survive quite well after such "death" events. In mammals the best example may be arctic ground squirrels which allow their temperatures to drop to near freezing for extended periods during the winter.)
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><div><font face="Arial" size="2">I've not personally frozen embryos but that can be
done too, also not reliably</font></div>
<div><font face="Arial" size="2">in the case of a single embryo, as I understand -
but that we (people, scientists)</font></div>
<div><font face="Arial" size="2">can do it at all speaks to the robustness of
life in *simple* forms and yet says</font></div>
<div><font face="Arial" size="2">nothing </font><font face="Arial" size="2">at all about
the freezing of organs like brains.</font></div></div></div></blockquote><div><br>It is unclear from any studies I've seen whether it is the freezing & thawing that destroys the embryos or whether the embryos were non-viable in the first place. You have to bear in mind that 60-70% of natural conceptions seem to result in miscarriages. Those eggs & sperm are not "perfect" in from the get-go.
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<div><font face="Arial" size="2">We
</font><font face="Arial" size="2">can't </font><font face="Arial" size="2">do organs. I
thinkI recall </font><font face="Arial" size="2">Eugen
saying Greg Fahy is interested in that (perhaps kidneys).</font></div></div></div></blockquote><div><br>I'd suggest you do a PubMed search on "Fahy GM [AU]" and read his paper from ~2003-6. <br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;">
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<div><font face="Arial" size="2">It is important to get that the brain </font><font face="Arial" size="2">is an organ of a multicellular life form. It </font><font face="Arial" size="2">grows as</font></div>
<div><font face="Arial" size="2">a result of the actions of cells </font><font face="Arial" size="2">but it isn't just a big lump of cells. </font><font face="Arial" size="2">I know you </font><font face="Arial" size="2">
know</font></div>
<div><font face="Arial" size="2">that as a neuroscience guy </font><font face="Arial" size="2">but I don't know how well you </font><font face="Arial" size="2">know that and I don't</font></div>
<div><font face="Arial" size="2">accept expertise on the part </font><font face="Arial" size="2">of others until I see </font><font face="Arial" size="2">evidence
</font><font face="Arial" size="2">of it.</font></div></div></div></blockquote><div><br>The brains of tardigrades and rotifers aren't as big as ours but they survive freezing and thawing. The caveat would be that their genomes have evolved to allow that.
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><span class="q"></span><div><font face="Arial" size="2">
Though we can grow </font><font face="Arial" size="2">cells in quantity in </font><font face="Arial" size="2">E.coli, we can't
build as opposed to</font></div>
<div><font face="Arial" size="2">growing a just a single frozen </font><font face="Arial" size="2">cell. A growing cell can preserve the
integrity</font></div>
<div><font face="Arial" size="2">of mitochondrial membranes. You can't do that
working from the outside</font></div>
<div><font face="Arial" size="2">to built the membrane. </font></div></div></div></blockquote><div><br>Actually, I've got some very large rhododendrons out in front of my house and I'm reasonably certain that in spite of the fact that their leaves all froze several times this winter that their cells (and mitochondria and chloroplasts) will be fine in a couple of weeks.
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><div><font face="Arial" size="2">We can produce in vitro cell free systems to do
research on. We can create</font></div>
<div><font face="Arial" size="2">liposomes - lipid enclosed spheres that aren't
cells. </font><font face="Arial" size="2">But we can't create a</font></div>
<div><font face="Arial" size="2">living cell as a manufacturing
process. </font></div></div></div></blockquote><div><br>Perhaps not, but there are parasites which inhabit human cells, e.g. <span style="font-style: italic;">Toxoplasma gondii </span> which have ~80 megabase genomes which is probably enough for replacing a significant part of the human genome in human cells should it become severely damaged. (No need to wait for chromallocytes when you can start building genome patches today (if one has enough imagination and $$$)) [3].
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<div><font face="Arial" size="2">So talk to me like a cell biologist. Tell me your
protocol or point me to a peer reviewed paper.</font></div></div></div></blockquote><div><br>I don't understand the emphasis on creating a "synthetic cell". Why is this necessary? Its much simpler to reprogram existing cells and deliver them where needed (
e.g. enhanced genome stem cell therapy). More importantly if you are going to develop "real" cryonic suspension reanimation methods one probably wants precision delivery of proteins and genetic materials so one is talking complex forms of gene therapy -- not synethetic cell therapy.
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><span class="q"><div> </div>
<div>> See it as a ridiculously detailed form of 3D printing, where you
want</div>
<div>> to write prepared molecules into a matrix of frozen water. </div>
<div><font face="Arial" size="2"></font> </div></span>
<div><font face="Arial" size="2">Handwaving. Show me a paper or a protocol.</font></div></div></div></blockquote><div><br>There are a number of published peer reviewed papers on 3D printing of cells onto various matrices and having them grow into functional biological systems. I believe one of the more recent involved the growing of heart valves. The printing of molecules is more complex and we do not yet have print heads capable of that level of resolution. AFMs have the positioning accuracy required and there is no reason to believe we can't produce tips (or ink jets) capable of spitting out a few molecules at a time. There is no financial driver at this time to produce these methods. In part because organ transplants are still expensive and risky propositions. Even if you were able to manufacture (print) or grow new organs they are not an ideal solution.
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With current technology, cryo EM one can't scan a
single cell. You scan</font></div>
<div><font face="Arial" size="2">lots </font><font face="Arial" size="2">of them and get
an aggregated averaged out picture. Fair warning </font></div>
<div><font face="Arial" size="2">handwaving about future </font><font face="Arial" size="2">technology will prompt me to want to see what you</font></div>
<div><font face="Arial" size="2">know about the relevant </font><font face="Arial" size="2">small scale physics.</font></div></div></div></blockquote><div><br> I'd suggest you might want to review [4-7].<br></div><br>
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<div><font face="Arial" size="2">I even
think it is impossible. Because you have to get your manufacturing fingers around
the cell clusters whilst the cells in the centre of the cluster have to be
at the right temperature to act like</font></div>
<div><font face="Arial" size="2">cells and bind to the other cells. And once they
are like that they will start to die faster than your manufacturing fingers can
build more cells onto the seed cells. </font></div></div></div></blockquote><div><br>Do you think we can't get fingers around something 10 microns in size? Hell we are patterning hundreds of millions of devices at 45nm in microelectronics (and planning to go below 30nm). Do you think hydrogen bonds stop working if you are using them at -190C? Putting a frozen water cell down on a cube of other frozen cells at -190C and getting it to stay where you put it does not sound like a problem to me. Putting a cell filled with liquid N2 down on a cube of cells filled with liquid N2 doesn't sound like a problem either. The tricky part will be replacing the
<span style="font-style: italic;">l</span>N2 with <span style="font-style: italic;">l</span>H2O. You might be able to go from N2 to NH4 to H2O but the liquid phases don't overlap unless you subject them to some pressure I would suspect (some I guess some work needs to be done here...).
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><div><font face="Arial" size="2">But we are getting ahead of ourselves. Putting
</font><font face="Arial" size="2">together any old cell, (assembling</font></div>
<div><font face="Arial" size="2">it like a manufacturing process not growing it like
in cell culture) rebuilding </font><font face="Arial" size="2">a </font></div>
<div><font face="Arial" size="2">single celled </font><font face="Arial" size="2">organism say that functions </font><font face="Arial" size="2">like a single
celled organism, </font><font face="Arial" size="2">(eats,</font></div>
<div><font face="Arial" size="2">moves, divides to replicate) - that would
be </font><font face="Arial" size="2">the Science or Nature paper of
the</font></div>
<div><font face="Arial" size="2">year in which it was done.</font></div></div></div></blockquote><div><br>Its also way beyond the technology we need to have. I would say assembling a eukaryotic cell from scratch would normally come *after* you have assembled the first nanorobot from scratch.
<br><br></div><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><span class="q"><div><font face="Arial" size="2">Biological or theoretical? What nanoscale
dissassemblers are you talking about?</font></div></span></div></div></blockquote><div><br>The biological ones clearly exist. In your stomach, you intestines, certain soil bacteria and particularly fungi have lots of them.
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<div> <font face="Arial" size="2">Inside cells, biomolecules, proteins assemble
and fold into the right shapes</font></div>
<div><font face="Arial" size="2">in water. </font><font face="Arial" size="2">Proteins won't fold </font><font face="Arial" size="2">the way they do out of
water.</font></div></div></div></blockquote><div><br>That isn't clear. So long as you have a solvent which will form hydrogen bonds I strongly suspect that at least some proteins will fold properly (there's a PhD thesis or several idea for you...). If you have a folded protein and cool it down it doesn't become "unfolded" (they unfold on heating because the increased atomic motion disrupts the hydrogen bonding which holds them together). Proteins (or membranes) primarily become disrupted on cooling due to crystal growth in the liquids (primarily ice) disrupting the physical structures, potentially in some cases causing covalent bond breakage (but I know most of those covalent bonds aren't broken otherwise my vegetables would have turned to mush when I boiled them on the stove).
<br><br>It is interesting that one of the primary methods used by organisms to resist desiccation is to produce trehalose which appears to form lots of hydrogen bonds with the biological molecules and sheltering them and perhaps allowing them to resist structural distortions during from the removal of the water.
<br></div><br><blockquote class="gmail_quote" style="border-left: 1px solid rgb(204, 204, 204); margin: 0pt 0pt 0pt 0.8ex; padding-left: 1ex;"><div bgcolor="#ffffff"><div><br><span class="q"><div><font face="Arial" size="2">
Dunno what you mean. Only working
nanoSYSTEMS I know of are biological</font></div></span>
<div><font face="Arial" size="2">ones the others are purely speculative (fanciful
even).</font></div></div></div></blockquote><div><br>The nanoSYSTEMS of antarctic bacteria work down to at least -4C. Though they probably work a bit more slowly than those we commonly encounter. <br><br>[BIG SNIP -- because I've got limited time to critique emails to the ExICh list]
<br><br>Brett, I am glad that you are studying Cell Biology. Its one of the fields people will need to know to contribute to these efforts in the future. But I think it is reasonable to assume that Anders has studied it as well (as well as god knows how many other subjects). Its only when one has a good grasp of one field that one begins to understand what is required to integrate it with others of equal complexity. That is why
<span style="font-style: italic;">Nanosystems</span> will always go down in my book as one of the most brilliant books ever written. Chapter 12 I could easily understand because it was my field of expertise but its taken me more than a decade to begin to understand some of the other areas and the kind of research that went into them. So one can argue against cryonics for a few more decades, perhaps you have the time and energy to do so. Or you can simply ask whether people like Eric D., Marvin M., Ralph M. and Robert F. might be able to connect some insights together better than people who seem to have focused in very narrow areas much of their lives (
e.g. Dr. Smalley).<br><br>Robert<br><br>1. Kornberg, A., "DNA Replication" (2005)<br>
<a href="http://www.amazon.com/Dna-Replication-Arthur-Kornberg/dp/1891389440">http://www.amazon.com/Dna-Replication-Arthur-Kornberg/dp/1891389440</a><br>2. Hickenboth, C. R. <span style="font-style: italic;">et al</span>
, "<a href="http://www.nature.com/nature/journal/v446/n7134/abs/nature05681.html">Biasing reaction pathways with mechanical force</a>," <span style="font-style: italic;">Nature</span> <span style="font-weight: bold;">
466</span>:423-427 (22 Mar 2007).<br>3. Note, I am not suggesting patches onto <span style="font-style: italic;">T. gondii</span>, I am suggesting assembly lines that produce <span style="font-style: italic;">T. gondii</span>
packages that deliver largely human genome subsets. If one assumes only
2-2.5% of the 3 gigabase human genome codes for useful sequence
(particularly if one is delivering "organ" specific genome subsets),
then <span style="font-style: italic;">T. gondii</span> could carry a complete human genome set of genes.<br>4. "New light microscope sharpens scientists' focus" (10 Aug 2006)<br>
<a href="http://www.physorg.com/news74439510.html">http://www.physorg.com/news74439510.html</a><br>5. Betzig, E. <span style="font-style: italic;">et al</span>, "<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16902090&itool=pubmed_docsum">
Imaging intracellular fluorescent proteins at nanometer resolution</a>," Science 313:1642-5 (15 Sep 2006).<br>6. "Imaging Transparent Brains" (3 Apr 2007).<br>
<a href="http://neurophilosophy.wordpress.com/2007/04/03/imaging-transparent-brains/">http://neurophilosophy.wordpress.com/2007/04/03/imaging-transparent-brains/</a><br>7 .Dodt HU <span style="font-style: italic;">et al</span>
, "<a href="http://http//www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17384643&itool=pubmed_docsum">Ultramicroscopy: three-dimensional visualization of neuronal networks in the whole mouse brain
</a>," <span style="font-style: italic;">Nat. Meth</span> <span style="font-weight: bold;">4</span>(4):331-6 (Apr 2007).<br>
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