h a l f b a k e r yI didn't say you were on to something, I said you were on something.
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I know I'll need this eventually. My research says simplicity is best for the sufferers of dementia. This is a flat screen monitor that hangs on the wall, displays the day of the week. and one reminder. Keep it simple. Someone else has to input the data in advance of course so it will display automatically.
Today is Friday, October 16
You have an appointment with Dr. Smith at 2:00.
This is meant for an elderly person who wants to continue living independently, but has other help, such as a driver, meals prepared and nursing assistants that check in throughout the day.
I have looked online and can find only the date and time digitally available. there are also recorded messages. But a dementia patient will not likely be able to push buttons for messages.
Digital Photo Frame connected to Internet
https://www.pix-star.com/ I use this for remotely adding family photos etcetera. For my father. [AusCan531, Oct 22 2015]
Microsoft Hololens
http://www.microsof...soft-hololens/en-us Reality-augmenting devices can add virtual annotations to physical objects. [Cuit_au_Four, Oct 23 2015]
Preimplantation Genetic Diagnosis
https://en.wikipedi...n_genetic_diagnosis Fertilize in vitro and snuff out genetic defects in the test tube [Cuit_au_Four, Oct 23 2015]
[link]
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Hi [dentworth] ) remember me? |
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Wife's grandmother, who is in stage 6 of 7 and can't
remember exactly how many kids she has sometimes, would
react with 'Who is Dr. Smith, and why did he put this thing on
my wall?" |
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Yes xan of course I remember you. You're the lady who flew
the space craft to my house last night! |
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I have elderly parents, one already had the worst dementia
imaginable and true enough if I'd put this up on his wall
he'd have ask who is dr. smith. But this would best suit
early stages of memory loss.
I found a product in the UK costs about $500. Which does
this. |
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You could surely set this up using an old computer?
Just have the display on the wall, and the computer
itself somewhere out of site. |
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good suggestion Maxwell, we've been looking for a calendar app that might do the job. |
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You could, in fact, just create each day's screen using
Word or a graphics package. |
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It wouldn't have the automation of a calendar app,
but it would be a good deal more flexible. If there
was nothing scheduled for that day, you could put up
a picture that meant something to him. |
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Hi [dentworth], remember me? I'm the lady who flew a
space craft to your house last night. Ehem...not really, just
jealous. |
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Anyways, about this idea a little information that most of
you probably don't know; I now work in an Alzheimer's
Memory Center, on the evening shift. It is difficult and
challenging, but I'm where I am needed the most. Hence I
am pretty much an objective expert at this point and would
love to offer my input. |
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What you say is true. In the early stages, (1-5), this would be
an excellent adjunct to other reminding devices. Later
stages would respond very much to what [RayforSteele]
suggests. Also at that stage, things on the wall tend to get
taken off the wall, and put in strange places. |
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I'm assuming through your comments that this, then, is for
your mother who is suffering mild to moderate memory loss.
Be that the case, please accept my heartfelt concern, and
reach out to me, if there is anything I can do. |
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So good to see you here. Several old baker's have wandered
in lately. Great to see you back. |
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I like the sound of the Ementia. Especially if they have those plugin dongles because I have had it with gas pumpers; don't even wipe your windows and then stand around expecting a tip. Here's a tip - get a shave! Used to be three of them came out in sharp uniforms and they would pump up your tires too, if you needed it. Now that was worth a tip. I used to drive a Ford; a Manchego I think. Bought it cash and drove it off the lot. It had that rich leather that Spaniard from Fantasy Island liked so much - the tall one. But that midget - do they call them midgets now? - he did his part too. I think that was what made the whole thing work. They were a good team, those two. Or was that some fancy cheese, now? |
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don't limit it to the date and a reminder. old photos of the patient's past and interests could illuminate their life in more ways. |
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Beautiful addition, [po]. |
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We have an electronic picture calendar that displays today's
day and date, digitally. No reminders on it though. |
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Assuming someone has the time to update it manually (as
in [Max]'s suggestion), it might be better to use something
old and familiar like a chalk board. Maybe get a routine
where the last person to help get the person ready for
bed goes over the next day's schedule and updates the
chalk board with tomorrow's date and activities. Or do it
in the morning. I assume the person being cared for
would benefit more interacting with or at least observing
the person updating the chalk board rather than having
them spend that time sitting at the computer in the
other room updating the display. |
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Trust me, when you have an elderly parent who is no
longer the owner of a full deck, anything as
complicated, loseable and removable as a wristwatch
is not somewhere you want to go. |
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[Blissmiss] Thanks for the info, I imagine you can identify the stages now just from experience. It's tough watching them fade away, some do it less sweetly and calmly than others. And no, if you've experienced this [bigsleep] you'd see changes that would convince you it's not just giving up, there are brain changes that can only be identified in an autopsy. Unfortunately. |
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Two great ideas [po] with the photos and [scad mientist] a chalk board, or a white board has also been suggested. Unfortunately [beauchamp] any addition to the body, any changes will set badly demented persons off into anxiety. I think at this point a nice happy daily reminder is best. |
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Thank you for some great suggestions! |
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//I'm still curious as to whether dementia is
caused by people giving up on a fundamental
level.// |
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No. It is true that people who enjoy life and
remain mentally active can delay the onset of
Alzheimer's, just as an athlete will remain
physically mobile longer than a couch potato if
they both have a muscle-wasting disease. |
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But Alzheimer's is primarily a disease of organic
origin. The popular theory is that it's caused by
the aggregation of a few types of protein, forming
so-called "plaques" that, in some way, are meant to
kill the cells. And some variants in the genes for
these plaque-forming proteins are protective
against Alzheimer's. However, nobody really knows
what is the primary cause - it may be just
randomly-triggered protein aggregation. It may be
oxidative stress or something else triggering the
aggregation (my wife worked on prion diseases,
and there are parallels). Or it may be something
else. It may even (just possibly) be some
unknown, virus-like thing. And nobody knows
quite how the protein aggregates kill the cells,
either. |
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It really is something that ought to be treatable
and curable. If protein aggregation really is the
key step, it ought to be possible to find small
molecules that will inhibit it (and there is some
progress in that direction). |
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Ultimately, though, the solution lies in genome
editing. We know that some natural mutations
give complete protection against Alzheimer's, so
the most direct solution is to edit the genome (of
adults; not just of embryos) to give them that
variant. |
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The same goes for many, many diseases - we know
genes that can prevent them, but at present it's
just tough shit if you don't have those genes.
(Plug: I've recently set up a biotech company to do
precisely this kind of genome editing in adult
humans.) |
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Awesome link/product [Beauchamp] not sure I wanted to have the calendar on the web unless that gets me remote access? |
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Hi [Bungston]. channeling Grandpa Simpson? |
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My 80 yo father lives by himself on the opposite side of
the
world from me. He doesn't have dementia but is
definitely
very non-technical. I've paid for his house to have WiFi
then bought a digital picture frame for him (Pixstar). It
rotates through the date and time, weather and photos. |
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All that I, or other friends and family, have to do is email
photos to a certain email address for new photo to
appear
in the rotation. I can remotely curate the photos and so
on. Dad likes the day and date function most of all as it's
easy for him to lose track otherwise. It doesn't have the
reminder function but that is a relatively small tweak.
[LINK] |
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On the good side, I recently heard somewhere that 3 cups of
coffee a day decreased the odds of Alzheimer's. (For real, this
is no reference to 2 cups, not related at all.) |
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// Could it be that the same process exists in the
brain, but the waste products don't get cleaned up
as well// It's still an open question. All we know
for sure is that some proteins aggregate to form
plaques, and the cells die. |
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We don't even know, really, whether the plaques
are (a) causing the cells to die (b) completely
irrelevant by-products of something else that _is_
causing the cells to die or (c) part of the
[ineffective] defences of a cell that has something
else wrong with it. |
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All we know for sure is that if you've got gene
variants X, Y and Z you won't get Alzheimer's.
Same goes for lots of other things, and we're
finding more all the time. Within the human
population, there are probably gene variants that
protect against most illnesses, including most
cancers. |
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The problem is that we can say "Hey, this lucky guy
won't get Alzheimer's because he has genes XYZ!",
but the guy with genes PQR is screwed. My
company wants to be able to edit PQR to XYZ, not
in cultured cells or in human embryos, but right
now and here for the poor sods whose taxes pay
for the research. |
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It's possible, but unlikely. |
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Basically, the human body is as good as it needs to be
- there's no point putting rustproofing on a WWII
fighter with a life expectancy of a few weeks. It's
only a problem now that we're no longer at war and
want to keep'em flying. |
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It's possible, but unlikely. |
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Basically, the human body is as good as it needs to be
- there's no point putting rustproofing on a WWII
fighter with a life expectancy of a few weeks. It's
only a problem now that we're no longer at war and
want to keep'em flying. |
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I didn't say I agree (at least, I don't think so).
Basically, the way it works is: |
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(1) However fit you are, your risk of death is a few
percent per year (until a few millennia ago). |
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(2) Therefore evolution selects for people who
breed before the age of 20. |
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(3) Therefore, evolution cannot have any say in the
ageing process - once you're past 30, your body is
just coasting. |
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There are some additional complexities (such as
the possibility of grandparents helping out, which
helps to propagate genes that let you live longer),
but basically we evolved for a world where every
year could be your last. That's one of the reasons
that it's relatively easy to extend lifespan - we're
not trying to do better at something that evolution
has already tried. |
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//Several old baker's have wandered in lately.//
They were probably looking for their hearing aid
and, now that they're here, they can't remember
why they came. |
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//the human retina has evolved to last around about
80 years // That's a good point, but sadly complete
bollocks. |
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The human retina hasn't evolved to last 80 years, any
more than a Lancaster bomber was designed to last
80 years. The retina evolved to last _at least_ 30
years. If it keeps going beyond that, it's not thanks
to evolution. |
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I suppose it hinges on how you define the word
"to". |
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If you meant "in order to", then alas my testicular
verdict stands. |
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If you meant "The human retina has evolved in
such a way that, by good fortune, it lasts 80
years", then fine. |
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It's a bit like saying "The human thumb has evolved
to allow easy texting." |
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//I don't think cures for short straws sold on the open
market will lead anywhere.// |
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OK, so you're saying that, if you had a gene set that
guaranteed you'd get Alzheimer's; and if I said I could
swap out those genes for a set that was just as good
but would also protect you from Alzheimer's; you
wouldn't go for that? That's interesting. |
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My Mom is pretty much totally demented now. We have the
clock with the day of the week, time and date. I don't even
know if she knows what the clock is anymore. :( |
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Still a good idea for someone who has early stages of
dementia... |
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[xandram], My heart goes out to you. I am so sorry that you
are going through this. It must be extraordinarily hard. The
residents we have that are in stage 6, do not know what a
clock is, or a calendar. |
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We can point it out, state the time even, but the neurons in
their brain are not responding, to what we are saying and
looking at. It simply does not register. Nor does the
appearance of the room, or the people within it. |
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My boss made a pretty good analogy and it has stuck in my
head. "Every day, every hour, every moment, is similar to an
Etch-A-Sketch. Shake it, and the memories dissolve every
time. Never to return again. |
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It's a horrible disease to bear witness to for the family. The
blessing is those afflicted don't seem to know how much
they have declined, unlike some other diseases, like
Parkinson's and Lou Gehrig's. |
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//I guess if these types of cures were cheap enough. I was just
imagining people with average income faced with a bill of millions.// |
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In theory, they could be very cheap. However, as with all "drugs"
(though this won't be a regular pharmaceutical), the actual cost
doesn't depend at all on the cost of manufacturing and administering
it; it depends on how much money the company can charge for it,
until the patents run out in 25 years. Not that any of this is any help
for people with Alzheimer's today. |
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The risks aren't (or at least shouldn't) be
associated with the delivery vector. |
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The main problem with gene editing (and with
gene therapy), is off-target effects. If your system
hits the right target 99.9% of the time, that still
means trillions of cells in which it hits the wrong
target. 99.999% of the time that won't matter (the
cell either won't care, or will die), but then that
still leaves a significant risk of jump-starting a
cancer in one cell. |
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Howevertheless, it is possible. After all, most of
our cells merrily repair and replicate their own
genomes repeatedly, and this only rarely leads to
cancer. So it's not at all unreasonable to imagine
an agent that can do a spot of editing with
acceptably low risks. |
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// but then that still leaves a significant risk of jump-
starting a cancer in one cell.// |
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But we're getting pretty good at cancer. Especially if you're
deliberately watching for it. I'd say to hell with the risk.. |
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//But we're getting pretty good at cancer.// True.
But we're still not great at it. |
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Howevertheless, genome editing is where I'm heading
for the next few years. Keep 'em crossed. |
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"Keep 'em crossed?" Mine's in a double helix already, and my
thanks to you not to unravel 'em. |
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Is there some specific chemical that is produced during sleep that causes individuals to forget their dreams shortly after they wake up? Maybe dementia patients are constantly over-producing that chemical. |
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//How do you magically rewrite DNA in all existing
cells without a teleportation system that has on-
the-fly editing ?// |
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It's not easy. The actual editing system is hard
enough, but the problem you're thinking about is
how to get that system into every cell. |
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There are virus-like systems (ie, you package your
components into empty viral shells). You can also
do it using lipid vesicles (basically, tiny droplets
surrounded by what looks like a cell membrane) -
these can fuse with the cell membranes to deliver
their contents. Even naked DNA can get into cells
(assuming that your editing system is a DNA
machine). None of these is easy (especially for
brain cells - the brain is pretty well isolated), but
it's doable. |
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The general aim (Alzheimer's aside) is to be able to
make your genome a read/write system as opposed
to the read-only system which it is at the moment. |
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//How do you magically rewrite DNA in all existing
cells without a teleportation system that has on-
the-fly editing ?// |
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It's not easy. The actual editing system is hard
enough, but the problem you're thinking about is
how to get that system into every cell. |
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There are virus-like systems (ie, you package your
components into empty viral shells). You can also
do it using lipid vesicles (basically, tiny droplets
surrounded by what looks like a cell membrane) -
these can fuse with the cell membranes to deliver
their contents. Even naked DNA can get into cells
(assuming that your editing system is a DNA
machine). None of these is easy (especially for
brain cells - the brain is pretty well isolated), but
it's doable. |
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The general aim (Alzheimer's aside) is to be able to
make your genome a read/write system as opposed
to the read-only system which it is at the moment. |
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So... you can't actually change a cell, but you can change its offspring... ? |
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//alterations, possibly permanent and even
heritable, through radio penetration.// No. At
least not by any means that we can even think of
imagining to begin to start to conceive of at
present. |
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//you can't actually change a cell, but you can
change its offspring... ?// No, you can change the
cell itself. There's one caveat: if the cell has
irrevocably committed to something (like
differentiation to form, say, a muscle cell), you
won't really be able to change it into something
else. Or if it has already made plaques of
aggregated protein, it may not be easy to disrupt
those plaques. But if the cell is making, say, a
protein which _will_ eventually form plaques,
you'll be able to replace the gene for that protein
with one which makes a non-plaque-forming
variant. |
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(sorry - bit of a tangent here). Despite all the hoo-
ha over genomics, there's not much we can
actually do, directly. You can figure out that
certain gene variants cause certain problems, and
then maybe try to find fixes (downstream of the
genes) for those problems, but it's very difficult.
And you can edit an oocyte to produce a person
free of those problems, but that doesn't help you
or I. Genomics at the moment is a read-only
technology - it's a bit like a spell checker that only
tells you where you need to apply the Tippex. |
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In 10 years time, all of current genomics will be
seen as just a minor pre-amble; actually fixing
things at the genomic level will be the important
stuff. |
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In my lab[1] we have some experience with genomic editing of bacteria. If I may, I'll give you a quick overview: |
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The way we do it is to first create a copy of the region we want to change with the alteration in the middle. This is placed in a special vector (a plasmid) which we can select for (with antibiotics) and against (it produces an enzyme which kills the cell in the presence of sugar). Setting this up takes at least a few weeks.
We describe the plasmid as a 'suicide vector', because it carries the DNA we want into the cell, but can't reproduce inside the cell. (We grow it up inside other cells where it can replicate.) So we introduce the plasmid to the bacteria we want to change and select for it. What we're hoping for is 'homologous recombination' which integrates the vector into the genome at the place we're targetting. After making sure it's in (by killing off the other cells), and checking it's in the right place, we grow up many cells and select for excision (by plating on sugar, which kills cells which still express -make protein from- the sacB gene).
What we're hoping for is a second homologous recombination which removes the vector. The result is either a strain with the change we want, or a revertant which is the same as the parent strain. Or, something else which we don't want, like a random deletion which happens to remove the sacB gene. So we screen the resultant colonies for what we want, and then can move on, and try to remember why we were doing this in the first place. |
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So this takes _ages_, and there's a lot of checking involved. It does have the advantage that we can make large alterations (big insertions or deletions), but remember that we're doing this to individual cells in large populations. There are other methods which can make very minor changes (like changing one base to another in a specific sequence - and that's largely what changing human alleles would be about) and can even be run in parallel, but again they need a population and screening for the result (and IIRC the process in a paper I read introduced more mutations than deliberate changes). |
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Of course eukaryotes have vastly larger genomes - which are typically in two copies to complicate matters. Maybe there are tools to be had from retroviruses, but my expectation is that in the medium term the best we can hope for is the ability to modify germ-line cell's genomes (egg or sperm essentially). Culturing and modifying spermatogonia (which become sperm) might be a basic approach, because they grow and divide. (I haven't looked; I assume people are working on that.) We can of course screen and select embryos already. The main issue is the legal aspect of doing so. |
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[1] In the sense of the one I work in; I'm not the boss. |
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" We've already tried it -- ethyl methane sulfonate is an alkylating
agent and a potent mutagen -- it
created a virus so lethal the
subject was destroyed before we
left the table." |
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" Then a repressor protein that
blocks the operating cells." |
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" Wouldn't obstruct replication,
but it does give rise to an error
in replication so that the newly
formed DNA strand carries a
mutation and you've got a virus
again... but all this is academic...
you are made as well as we could
make you." |
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//in the medium term the best we can hope for is
the ability to modify germ-line cell's genomes// |
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I disagree. It has already been shown, for
example, that the approach I'm following can
cause modification of a large percentage (not all,
yet) of cells in a whole, intact, living and
breathing mouse. The tools that they used to do
that are _not_ precise enough (there are off-target
effects), but there are closely related tools which
_are_ precise enough already. (I'm being a bit
cagey here because this is what my company is
doing.) |
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As for timescale and complexity, what you describe
is the whole process of setting up an homologous
recombination (ie, from planning to making the
constructs, to actually applying it to bugs and
validating the result). In the case of, say,
replacing a beta-amyloid gene in humans to
prevent Alzheimer's, we are talking about creating
a single construct (or, to account for existing
variants, a handful of constructs), once and for all.
This will be a little like the development of any
pharmaceutical, with the important difference
that treatments for other diseases can follow a
very similar model (whereas pharmaceuticals tend
to be one-offs). |
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The actual treatment involves a series of either
injections or infusions, at most requiring a few
very short appointments. It's not going to be
tablet-izeable, but it's about as simple as it can
get. |
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Damn. That's fascinating stuff. You can certainly see the risk/rewards model the company has to deal with. |
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For my investor pitches I wear a tie. |
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The last one went badly, though. I may have to add
trousers and a shirt. |
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Never ask me if I'm sure. I'm always sure. |
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//As for timescale and complexity, what you describe is
the whole process of setting up an homologous
recombination (ie, from planning to making the
constructs, to actually applying it to bugs and validating
the result). In the case of, say, replacing a beta-amyloid
gene in humans to prevent Alzheimer's, we are
talking about creating a single construct (or, to account
for existing variants, a handful of constructs),
once and for all.// |
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Sure - I was just trying to explain the whole process for
other people. The immediate bladerunner
response suggests it was a wasted effort, but still, the
intent was there. |
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//... The tools that they used to do that are _not_
precise enough (there are off-target effects), but
there are closely related tools which _are_ precise
enough already. (I'm being a bit cagey here because
this is what my company is doing.)// |
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If you have a better strategy then get on and patent it
already, then licence for molecular work ASAP. I neeeed
it!
Of course, if you're trying to make medical treatments,
there are other problems (which I mentioned,
obliquely). If you had a treatment ready to go *today*
then what's the earliest point at which it would be
through clinical trials and cleared for widespread use? I'd
be rather surprised if you're already at that
stage but keeping it quiet[1], but I would be astounded if
your first treatment was for Alzheimer's, rather
than, say, cystic fibrosis.
So you can see the science barely gets a look-in before I
think we're looking at treatments for future
generations - even if you're highly optimistic overall. |
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[1] Quite apart from the Miracle Breakthrough, where the
hell did you -as a small company- get funding
for clinical trials without leaving stealth mode?[2] |
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[2] ...Perhaps you mortgaged Buchanan palace? |
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No, I'm nowhere near even testing this in anger.
And
yes, it'll take as long as (or longer than) any other
treatment. But hey, gotta start somewhere. |
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Also, there's no guarantee that the current system
of clinical trials will continue indefinitely. If I have
a treatment, and if someone doomed to
Alzheimer's is willing to take the risk, who's to stop
me? |
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And yes, CF would be a better target, given that
CF
would be a treatment of active and life-
threatening
illness rather than a prevention. |
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// CF would be a better target, given that CF would be a treatment of
active and life-threatening illness rather than a prevention.// |
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And it's got a known and clear-cut mutation causing disease.
And the primary target is in an easily accessible tissue.
And it's recessive, so you have two targets per cell, of which you only need
to hit one.
And you don't even need to modify every target cell, maybe even one in
ten would do it. |
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That just makes it merely very difficult. |
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This is almost certainly a stupid idea, but until
a cure is found, aren't we just trapping patients
into our memory-based society, and we get
distressed by their inability to fit in with our
system. How about a time-free place, with
patients of similar condition get to live free of
us? |
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Yes, but that depends on how you do things. |
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