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3. Ribonucleic acid (RNA) is a polymeric molecule implicated in various biological roles in coding, decoding,
regulation, and expression of genes.
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5. the emperor of all maladies - p 343
the genesis of proteins from genes requires an intermediary step
a molecular cell .. *rna
on jumping in the middle (aka: starting ish) here:
and jumping on within the middle (aka: ending ish) here:
intrigue with Jennifer’s crispr to.. zone in on and get rid of
and/or restore mutations via rna et al
intrigue with Siddhartha’s mechanism/model/metaphor to ..
re juvenate the natural process of self-organization..
rather than kill by some med
and intermixing throughout the middle (aka: dancing ish) here:
intrigue with Vinay’s intrigue with blockchain to.. coordinate
interoperability ness
6. with a ton of other stuff in the middle.. (aka: everything is misc)
from his ted…
mechanisms, models, metaphors
so.. imagining the metaphor where the cell is a human – (ie: most efficient
repairer of fractures in our humanity) – and wondering if setting enough of
us free (in a petri dish of sorts – rat park ish) we might facilitate a
mechanism/model/metaphor – that is deep/simple/open enough to re-
grow/organize all of us toward a more natural (and less unhealthy) state.
toward systemic change ..vision versions toward self-organizing humans
p 6
cancer, we now know, is a disease caused by the uncontrolled
growth of a single cell. this growth is unleashed by mutations –
changes in dna that specifically affect genes that incite unlimited
cell growth.
in a normal cell, powerful genetic circuits regulate cell division
and cell death . in a cancer cell, these circuits have been broken,
unleashing a cell that cannot stop growing
that this seemingly simple mechanism – cell growth without
barrier – can lie at the heart of this grotesque and multifaceted
illness is a testament to the unfathomable power of cell growth.
“Cell division allows us as organisms to grow, to adapt, to
recover, to repair—to live. And distorted and unleashed, it
allows cancer cells to grow, to flourish, to adapt, to recover, and
to repair—to live at the cost of our living. Cancer cells can grow
faster, adapt better. They are more perfect versions of
ourselves”
malignant growth and normal growth are so genetically
intertwined that unbraiding the two might be one of the most
significant scientific challenges faced by our species..
or.. perhaps.. learning .. as you say.. to prevent
malignant growth.
cancer is built into our genomes: the genes that unmoor normal
cell division are not foreign to our bodies, but rather mutated,
distorted version of the very genes that perform vital cellular
functions……… if we seek immortality, then so, too, in a rather
perverse sense does the cancer cell.
p 19
the idea mesmerized farber. in the 1940s and 50s, young biologists
were galvanized by the idea of using simple models to understand
complex phenomena. complexity was best understood by building
from the ground up. single-celled organisms such as bacteria would
reveal the workings of massive, multicellular animals such as humans.
fractal thinking… toward systemic change ness.
p 27
this isolation was key to farbers’ early success.
insulated from the spotlights of public scrutiny, he
worked on a small, obscure piece of the puzzle..
minot had shown that replacing a single molecule
could restore the normalcy of blood in this complex
hematological disease.
p. 38
cancer, in contrast, is riddled with more
contemporary images. the cancer cell is a desperate
individualist, ‘in every possible sense, a
nonconformist,’ as the surgeon-writer sherwin uland
wrote. the word metastasis, used to describe the
migration of cancer from one site to another is a
curious mix of meta and stasis – beyond stillness in
latin – an unmoored, partially unstable state that
captures the peculiar instability of modernity..
if tb once killed by hollowing out lungs..
cancer kills by filling body w/too many
cells.. the pathology of excess. cancer is
an expansionist disease; it invades
through tissues, sets up colonies in
hostile landscapes, seeking sanctuary in
one organ and then immigrating to
another , it lives desperately,
inventively, fiercely, territorially,
cannily, and defensively – at times, as if
teaching us how to survive. to confront
cancer is to encounter a parallel
species, one perhaps more adapted to
survival than even we are.
learning from cancer..
cancer is phenomenally successful invader and
colonizer in part because it exploits the very features
that make us successful as a species or as an
organism.
cancer, we now know, is a clonal disease.
wilde… most people are other people
p 46
A patient, long before he becomes the subject of
medical scrutiny, is, at first, simply a storyteller, a
narrator of suffering—a traveler who has visited the
kingdom of the ill. To relieve an illness, one must
begin, then, by unburdening its story.”
self-talk as data
p 48
Depression and cancer, the psychic and physical
diseases of black bile, were thus intrinsically
intertwined.)
depression – also something we often treat w/in
silence and shame
so.. story is part (perhaps first step) to curing
illnesses .. and one’s we can’t seem to cure have
been silenced by shame..
hippocrates siad once … that cancer was best left
untreated, since patients live longer that way.
the problem w/treating cancer surgically, galen
suggested, was that black bile was everywhere, as
inevitable and pervasive as any fluid. you could cut
cancer out, but the bile would flow right back, like
sap seeping through the limbs of a tree.
the surgical removal of tumors – a local solution so
a systemic problem – was thus perceived as a fool’s
operation.
deep enough ness…
p. 68
the ultimate survival from breast cancer, in short,
had little to do with how extensively a surgeon
operated on the breast; it depended on how
extensively the cancer had spread before surgery.
as george crile, one of the most fervent critics of
radical surgery, later put it, if the disease was so
advanced that one had to get rid of the muscles in
order to get rid of the tumor, then it had already
spread through the system – making the whole
operation *moot.
huge… irrelevant ness
p 87
with cancer it was the similarity of the cancer cell to
the normal human cell that made it nearly
impossible to target.
p 140
what we needed was quite the opposite of a
systematic approach – an intuitive and inspired leap
of faith into the deadly abyss of deadly drugs..
leap frog – for (blank)’s sake…
p 143
doctors are men who prescribe medicines of which
they know little, to cure disease of which they know
less, in human beings of whom they know nothing. –
voltaire
p 238
Since the illness was man-made, its
solution could also be man-made.
p 305
my task was to repossess imagination
from death.
(after.. if a man die.. it is because death
has first possessed his imagination.. –
william carlos williams
easy to repossess imagination w/false
promises; much harder to do so with
nuanced truths.
p 343
in late 50s..from paris and caltech and cambridge..
discovered the genesis of proteins from genes requires
an intermediary step – a molecular cell .. *rna
or perhaps chip as aa/ai/?
rna
RNA is the working copy of the genetic blueprint. It is
through RNA that a gene is translated into a protein.
This intermediary RNA copy of a gene is called a gene’s
“message.” Genetic information is transmitted from a
cell to its progeny through a series of discrete and
coordinated steps.
first, genes located in chromosomes, are duplicated
when a cell divides and are transmitted into progeny
cells. next, a gene, in the form of dna, is converted into
its rna copy. finally, this rna message is translated into
a protein.
This unidirectional flow of genetic
information—DNA → RNA → protein—
was found to be universal in living
organisms, from bacteria to slime molds
to fruit flies to humans. In the mid-1950s,
biologists termed this the “central
dogma” of molecular biology.
Siddhartha Mukherjee’s mechanism
7. p 347
mutants.. from copying error.. during cell division..
link between x rays and mutations..radiation causes
cancer.. since x rays also cause mutations.. could
cancer be a disease of mutations..
p 348
what caused mitosis to turn so abruptly from such an
exquisitely regulated process to chaos…. what had
failed was a kind of biological imagination...
p 351
temin imagined creating cancer in a
petri dish… in 1958 .. succeeded…
(previous could only look at rous’s
because only way you could see.. like
looking for keys..lost in house.. under
street corner lampstand..)
temin’s imagination that allowed him to
look… and re imagine
temin believed that the cell and its
interaction with the virus, had all the
biological components necessary to
drive the malignant process. the ghost
was out of the organism.
biological info, the dogma proposed,
only travels down a one way street from
dna to rna to proteins.. how on earth,
temin wondered, could rna turn around
acrobatically and make a dna copy of
itself, driving wrong way
Temin made a leap of faith; if the data
did not fit the dogma, then the dogma—
not the data—needed to be changed.
from documentary – episode 2
52 min – the fact that sarc existed in all –
birds, chickens, emu, people… see through the
darkness a glimpse. of clear theory of cancer.
ie: there are genes in your body that control
normal cellular growth and if you disrupt
these genes.. you essentially begin to
unleash cancer..
important thing.. viral/chemical.. weren’t
wrong. just not sufficient.. like blind men and
elephant… siddhartha –
1:16 – a crisis of faith – siddhartha
when you treat cancer important to know what you can/can’t
be sure of – juliano – uncertainty is part of treating cancer
vepisode 3 -
pointed out genes are much more complex.. –
sidd
abnormalities not oncogenes but tumor
suppressor gene – fail to stop cells from
dividing.. oncogene like an accelerator.. tumor
suppressor like breaks.. all cells have both
defects
dealing w/tip of iceberg.. push cures even
further away.. could see more clearly .. but
chaotic.. like rubix cube.. one side can be fine..
but rest are now toxic – ldk
work for a while.. then stop working… because
of: resistance…. cancer cells are constantly
mutating.. so genetic diversity of cancer
grows… transforms idea of treatment from
static idea to dynamic idea – sidd
may not be the same disease in anyone.. a
moving target.. cancer becomes resistant to
whatever drug we are using
1:11 – immune system:
cancer is literally evolution in a bottle. all
forces.. all history in life.. that plays out at
billion times speed of evolution.
if cancer exploits the power of evolution to
survive.. perhaps only a commensurate
weapon can overcome it.. the human immune
system.. an extraordinary set of defenses…
first explored 19th cent surgeon … william
coley.. tumor seemed to vanish of own accord
after serious infection.. birth of cancer
immunotherapy.. hoping to trigger fever that
would overwhelm the cancer.. steven
rosenberg since 1970s… self-cure.. answer had
to lay in patients own immune system….
sooo..
1:16 try to identify cells that were attacking
the cancer and use them to develop a cancer
treatment..
1:17 – could you educate to attack cancer cell and not
normal cell. sidd
remove tumor.. find t cells fighting tumor… take cells
out.. grow them out.. turn a few cancer fighting sells
into an army.. then put them back in
1:22 – immune system might be holding itself back
from attacking cancer cells – allison – can remove
breaks.. free immune system to attack cancer..
on being attacked for saying such things as.. i think
immune system might solve this..
for many decades we’ve concentrated on the tumor..
rather than the host immune response… ie: patient and
tumor..
1:25 – another novel approach.. immune
system as surveillance… but often blind..
and miss them… so we have to redirect
that t cell.. a new gene forces it to see..
ie: taking off blindfold.. re engineering t
cells..
let the cells do the work they were
designed to do..
on educating immune system to see/kill
cancer
immune system is there for whole trip..
patience that respond to it will respond
for a long time..
intro’d to Jennifer via wef 2016 panel…
staying human
[i was intrigued when she talked of the
ability to zone in on and get rid of
mutations.. thinking.. great.. but won’t
help.. if we don’t also get rid of mutant
living.. that produced them in the first
place. and perhaps in similar
way..thinkings/ponderings from
siddhartha et al.. placebo rna – toward a
nother way to live]
crisper tech
when viruses infect a cell they inject their dna.. in a bacterium..
the crispr system allows that dna to be plucked out of the virus
and inserted in little bits into the chromosome dna of bacterium..
these integrated bits get inserted at a site called crispr…
crispr – a mechanims that allows cells to record over time the
viruses the have been exposed to… those bits of dna are passed on
to the cell’s progeny…
blockchain ness
1:05 – this coordination problem
43 min – turning governance into degovernance systems is kind of
radical.. but over and over again find possible once to loop… so no
need for governance.. policy evaporate..
begs systemic change.. where the b ness becomes irrelevant..
what if the only governance/b we need is getting us out of the
mess/mistrust/mutations.. we’ve accumulated over the years of
ie: manufactured consent et al..
a nother way
this allows cells to keep a record of infection… a
genetic vaccination card…
once bits of dna inserted into dna chromosome..
makes copy … exact replicate.. of viral rna.. a
chemical cousin of dna…
little bits of rna from crispr bind to protein..
called cas9 and form a complex that functions
like a sentinal.. searches to find match… when
sites found… this complex associates and allows
cas9 to cut up the dna..
so like a pair of scissors that can cut dna… and
importantly.. this is programmable… to make
break in dna at that site…
could be harnessed for genome engineering…
analogous to way we use word processing to fix
typing in document
cells have ability to detect broken dna and repair
it… by pasting together or integrating new…
we can trigger cells to repair breaks by disruption
or incorporation of new…
crispr is like software.. can re program
clinical application w/in next 10 yrs
Jennifer Doudna’s crispr
8. intro’d to blockchain thinking beyond.. mostly via vinay
37 min – hub and spoke efficient for moneys… but not autonomy….
that’s why people were so excited about bitcoin.. didn’t go through
hub…
so best of hub & spoke (cheapness of interoperability) and p2p
(autonomy)…. in single unit
io dance ness
43 min – turning governance into degovernance systems is kind of
radical.. but over and over again find possible once to loop… so no
need for governance.. policy evaporate..
begs systemic change.. where the b ness becomes irrelevant.. what if
the only governance/b we need is getting us out of the
mess/mistrust/mutations. (jennifer/siddhartha) … we’ve
accumulated over the years of ie: manufactured consent et al.
back to – 1:05 – this coordination problem
and letting go of thinking we have to control the coordination…
rather.. we have to get rid of the things blocking the natural
coordination. perhaps blockchains biggest purpose is as a placebo ish
rna.. yes.. helpful beyond that… but we may need it less the more we
are us (as opposed to what we are today – not us)
51 min
since no real order (physics/relativeity)… we
sequence in arbitrary and take order an publish as
block.. if everyone ok.. move to next block… not
magic..
the magic is the selection mech by which we pick
the person to order the blocks that is fair and
incentivized that people would do it.. such a tiny
sliver of magic…
:05
that’s where we were… computer science had given up on this
coordination problem… relativity says no.. the reason you need
bitcoin is relativity… you get rid of the mining by using: proof of
stake.. people prove serious about doing this stuff.. by betting
reputation on the fact they’ll do it.. a trust and verify system…
but not finished yet…
1:07 – on technical back end.. it looks like a web site..
or rna..?
who verifies data is accurate in first place… 1/ take names… if lying ..
prosecute.. solve trust problems w/ big stick 2 use lots of software
mech’s ie: have to sign each transaction… so can identify you
blockchain… via seth
http://sethgodin.typepad.com/seths_blog/2016/01/3-
d-printers-the-blockchain-and-drones.html
Most of the stories of Bitcoin haven’t been about the
blockchain. They’ve been about speculators, winning
and losing fortunes. And most of the stories of 3-D
printers have been about printing small, useless toys,
including little pink cacti. And most of the stories
about home drones have been about peeping toms
and cool videos you can watch after other people
make them.
Choose your stories carefully.
.. et al ad infinitum
Vinay Gupta and bockchain
9. so thinking..
if rna is link/message between dna and protein… and it is where the
mutation resides, ie: if copy from dna gets mutated.. then fixing.. that
rna.. by deleting/removing mutants… or waking rna up.. to noticing the
mutants… will kickstart the system back into its natural order of
things…self-organizing to immune itself.. regenerate itself.. in health..
again..
and
if self-talk (chip) is link/message between heart and world… and it is
where the mutation resides, ie: if copy/representation of person gets
mutated.. then fixing.. that self-talk.. by deleting/removing mutants.. or
waking self-talk up.. to noticing the mutants.. will kickstat the system
back into its natural order of things… self-organizing to immune itself..
regenerate itself… in health.. again..
10. perhaps rna-ish/self-talk will get us back to eudaimonia..
a ginormously smaller us, that uses less energy, is less mutant, … more alive.
11. if rna is a copy of our dna.. and can carry mutations that
cause ie: cancer.. the emperor of all maladies..
and we could augment/uncover natural ness (close
enough rna copy to kill/restore mutants) restoring
synthesis
so that the dance (dna via rna to protein) can dance..
imagine self-talk as a copy of our being.. and how that
convo could carry/perpetuate mutations that cause.. ie:
not us ness.. the emperor of the emperor of all maladies…
and we could augment/uncover natural ness (quiet
enough to heart) restoring conversation
so that the dance (eudaimoniative surplus/oneness via
whimsy/curiosity) can dance..
12. perhaps giving a jumpstart (ie: replacing a turtle’s shell)..
and most of all.. trusting the natural process of
self-organizing ness
(so either from the get go.. or helping with detox/mutation removal first..)
we can wake up our listening.. to the rhythm..
already in each one of us.
13. to get to the root of everyone’s problem/cancer/mutation/desire
searching..