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Cloning instead of WILTing?


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#1 Florin

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Posted 22 March 2011 - 08:08 PM


Instead of using WILT to cure cancer, would there be any advantages in periodically transplanting the brain into a cloned body, and would this procedure even be practical? For rapid development of cloned bodies, organ printing techniques might make it possible to "print" entire bodies. The problem of reconnecting the brain with the rest of a cloned body's nervous system will also have to be overcome. Barring mature nanotech, how tractable are these issues? Are there any showstoppers? Would this procedure be better than WILT at preventing and curing cancer?

#2 Michael

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Posted 07 April 2011 - 08:26 PM

[Crosspost from SENSF Forums; some links and formatting lost, names scrubbed]
[quote name='Florin Clapa' timestamp='1300824498' post='457157']Instead of using WILT to cure cancer, would there be any advantages in periodically transplanting the brain into a cloned body, and would this procedure even be practical? For rapid development of cloned bodies, organ printing techniques might make it possible to "print" entire bodies. The problem of reconnecting the brain with the rest of a cloned body's nervous system will also have to be overcome. Barring mature nanotech, how tractable are these issues? Are there any showstoppers? Would this procedure be better than WILT at preventing and curing cancer?[/quote]
First and foremost, I think that in a practical sense, the question is ultimately moot. Tissue engineering and cell therapy are already one of the 7 planks in the SENS platform, and I can think of no tissue for which there would not be a need for some replacements; and, of course, organ printing is one of the methods by which tissue engineering, at least for simpler organs, is under pursuit today. Indeed, tissue engineering is and likely will be for some time the single strand of SENS where academic and conventional biotech resources are being poured most aggressively Once you can tissue engineer the individual tissues and organs, it will become progressively easier to increase the scale thereof, and eventually the ease of replacing (say) whole kidneys, or kidneys plus much of the surrounding vasculature, etc, than to do isolated patches. If this turns out to work faster than WILT, we can just do it.

But I don't think it would be wise to dispense with aggressive pursuit of WILT and try to double-down instead on tissue engineering (including whole-anencephalic-body tissue engineering), in case the latter proves infeasible, or (as I suspect) proves to take far too long, especially if (as I expect -- and see below in reply to John) cancer starts rearing its head uglier than ever if we clean up everything else first and have nothing better than even the best tech forecast from conventional cancer therapies in the relevant timescale.

I think that challenging as WILT is, it is a much simpler solution -- and, importantly, can be rolled out in stages, and conveniently the tissues that are easiest to WILT (epithelia) are the same ones that are most vulnerable to cancer (and the progress vs. risk seems to roll out fairly evenly from there).

But, I could be wrong. Solvitur ambulando!

As an additional barrier, I do think that a lot of people (and to lay my cards on the table, I'm one of them) would simply rather hang on to their "existing matrix," even if it is being turned over on a faster and larger scale than that which we are already biologically equipped to do, than to replace it wholescale.

[quote name='Florin Clapa' timestamp='1300824498' post='457157'][quotename='Anon 1']I never heard that brain tumors, even limited to aggressive ones, do not develop out of brain tissue and that WILT is intended not to be applied to brain tissue. Could you provide sources?[/quote]
Primary brain cancer, which can be further divided into gliomas, meningiomas, and other rarer kinds of tumors, is classified as originating from the brain, but it doesn't seem to really develop from neurons and supporting cells such as mature glia which make up the structure of the brain itself. Instead, gliomas might originate from oligodendrocyte precursor cells that retain their ability to divide. If this is the case, these cells would probably have to be destroyed before transplanting the brain into a cloned body. The meninges, from where meningiomas arise, would also have to be removed before transplanting the brain. Since the meninges have capillaries which feed the brain, I'm not sure if it would be possible to remove it though. As for the rarer kinds of primary brain tumors, I don't know where those originate from, but I don't see how they can develop from the brain's post-mitotic tissues which is the only kind of tissue that we'd be interested in transplanting.[/quote]
Ye-e-e-ah. Dude, that's just messy ;) . It's going to be hard enough to do stem cell therapy in the brain, without having to preemptively wipe out and replace large chunks of it. And of course, those new, pristine precursor cells (and, actually, mature cells -- below) will still be vulnerable to developing cancer, unless they're WILTed. ISTM that we're gonna have to WILT everything anyway, and may as well get on with it.

[quote name='Florin Clapa' timestamp='1300824498' post='457157']According to Aubrey, WILT itself targets only mitotic competent tissue:

[quote] WILT (Whole-body Interdiction of Lengthening of Telomeres), first suggested in 2004, is a radical proposal that seeks to address this feature of cancer head-on, by pre-emptively altering as many as possible of our mitotically competent [emphasis mine] cells in such a way that the capacity for indefinite cell division could not be achieved even by the high degree of mutagenesis and selection that a tumour harbours.[/quote] [/quote]
In a sense, this is all relative. All tissues with genes encoding telomere-lengthening machinery are mitotically competent, when it comes right down to it. In muscle, there's satellite cells; in the brain, there's neurogenesis per se, and not just turnover of astrocytes, glia, etc. And of course, as long as there are genes encoding telomere-lengthening machinery lurking in even "postmitotic" cell types, that status is contingent. As it stands already, one of the earliest aberrations to plague the AD brain is the appearance of unscheduled cell-cycle events in those “postmitotic” adult neurons.

[quote name='Anon 2']cancer peaks by mid-old-age, and then declines dramatically in advanced old age. So does Alzheimer's (albeit later) and some kinds of stroke.

I'd really like to know what's going on here. [/quote]
I'm sure that a survivor bias is part of it, as Anon 1 suggests: the oldest-old are, almost by definition, a population enriched with people unusually resistant to the diseases of aging, and we see early protection against such diseases in offspring of centenarians, etc. But another thing, which has significant direct and indirect evidence in its favor, is that old tissues are inherently less capable of getting new cancers going, because they're running out of viable stem cells from which (most) cancers might occur. ISTM that this is also consistent with the fact that the decline in the rate of the age-related rise in cancer incidence occurs substantially earlier than that for AD, CVD, influenza hospitalizations, etc (see eg. Fig 1 in (1)).

References

1: Rae MJ, Butler RN, Campisi J, de Grey AD, Finch CE, Gough M, Martin GM, Vijg J, Perrott KM, Logan BJ. The demographic and biomedical case for late-life interventions in aging. Sci Transl Med. 2010 Jul 14;2(40):40cm21. PubMed PMID: 20630854.
http://www.lifestari....org/site/paper

#3 Florin

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Posted 08 April 2011 - 12:33 AM

To view most of the replies about this topic and avoid crossposting, visit the SENSF's forum at http://www.sens.org/...s/oncosens/1963. Currently, registration is required to access the SENSF's forum.

Edited by Florin Clapa, 08 April 2011 - 12:37 AM.





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