Infection and the origins of apoptosis

[Guest guest]

This is one cool ass speculative article - tho kinda unclear in

places, and possibly really wrong about a couple things(?).

Whether or not you think anti-apoptosis may be the key to chronic

immunoevasion by intracellular pathogens, this contains some

FASCINATING " cosmo-biological " speculations, including the

possibility that infection may indirectly have made possible the

advent of multicellular organisms!

http://tinyurl.com/55uxf

[Guest guest]

, look up the work of Lynn Margulis. She talks all about this, and

spirochetes too.

[Guest guest]

Thanks, thats very cool - looks like shes the one that originated

the endosymbiosis view of mitochondria and chloroplasts, which is

now widely accepted. A stupendous discovery. What shes thinking

lately seems pretty weird if this web page can be believed:

http://cajal.unizar.es/eng/part/Margulis.html

Neurons are spirochetes? Hmmm. Even the other idea, that cilia and

flagella originated as sympiotic spirochetes, seems very very odd.

Its certainly not as immediately supportable asher earlier ideas.

Chloroplasts and mitochondria, after all, really act alot like

organisms - they contain their own DNA, and replicate

independently... but fortunately they have lost the ability to

spread between hosts, so their means of proliferation have converged

to ours and they behave themselves very well. Its quite odd to

consider how they became so cooperative that they lost their life

force, as it were, and became the organisms that arent - so

biologically similar to bacteria and humans alike, yet much less

alive than most viruses in the sense of having an open future.

Its extremely remarkable to think about the role infection may have

played in the emergence of multicellular organisms. Without

infection so strongly favoring apoptosis for the purpose of kin

selection, there might never have opened a stable, advanceable

disjunction between advantage to a cell and advantage to a genome -

the very disjunction that subordinates the individual cell and makes

multicellular development possible. Without infection exerting this

special effect on the evolution of unicellular organisms, we might

all still be a bunch of plankton on a pond.

If you want to really blow your mind, try pondering the emergence

and history of self-replicating macromolecules in the days before

cellular life (if you think life might have begun that way; who the

hell knows). The leading " theory " - ie guess, but a sensible guess -

is that big RNA complexes were the most sophisticated pre-cellular

forms. It seems plausible that all this happened in small pools of

water, where there was at least a sliver of shelter. With precious

little protection from one another, the evolutionary development of

such macromolecular replicons might have been incredibly

interdependant and gossamer - I guess immense progress probably must

have been rapidly shattered over and over by the emergence of

" selfish " replicon forms that rapidly consumed everything in the

little pocket world until it was all gone. Again and again till the

fragility of brewing sophistication could at last succeed in

hardening into something incredibly more robust than even the

weather-worthier, simpler forms that had ripped it apart so many

times before, during its vulnerable deviations from immediate-term

advantage.

Um... maybe.

The first quantum leaps wouldve been development of various kinds of

crude self-defense from other molecules, sophisticated and not. Then

the hydrophobic membrane was developed, and the cell, and things

started really picking up speed. Or something. Anyway we're here

now, and we got problems of our own.

" jill1313 " <jenbooks13@h...> wrote:

>

> , look up the work of Lynn Margulis. She talks all about this,

and

> spirochetes too.

[Guest guest]

> If you want to really blow your mind, try pondering the emergence

> and history of self-replicating macromolecules in the days before

> cellular life (if you think life might have begun that way; who

the

> hell knows). The leading " theory " - ie guess, but a sensible guess

-

> is that big RNA complexes were the most sophisticated pre-cellular

> forms. It seems plausible that all this happened in small pools of

> water, where there was at least a sliver of shelter. With precious

> little protection from one another, the evolutionary development

of

> such macromolecular replicons might have been incredibly

> interdependant and gossamer -

Ah, a cool thing I forgot to say about this is, one " replicon

complex " might in a sense consist of a " prime " molecule as well as

other helpful molecules manufactured by it, which would be floating

freely around in the pool. Probably some molecule types would

" belong " to multiple replicons. Its so weird. Its like one of these

little puddles is almost like a gigantic cell, lifeless in itself,

containing multiple halfway-organsims-like things, that cant be

materially separated from each other at all, or clearly materially

designated whatsoever. Amazing as the interrelationships of modern

" real " organisms are, the logics of interaction, preservation, and

change in the " RNA world " and its ancestors are maybe even another

level more crenellated. It was one weird ass little world if it

really happened; wish I could watch it all happen, the whole thing.

Whew, OK, back to work: bacteria bacteria bacteria, kill kill kill

kill kill.

[Guest guest]

Dammit, you, get out of my brain!

This is too weird. As knows, I am dealing with some of the

weirdness surrounding Lyme disease by writing a fictional account,

that plays with some of the more 'far out' ideas about where Lyme

comes from and what it's doing to us.

I was up until 3am working on a new chapter about how microbes are

key to the origin of human consciousness.

Wacky, right?

Then I read this - and sure enough, here is this woman who is a

scientist, not an author of science fiction, saying things

remarkably similar to the 'wacky' notions in my story.

Weird, weird, weird.

> >

> > , look up the work of Lynn Margulis. She talks all about

this,

> and

> > spirochetes too.

[Guest guest]

" You can reduce the study of nervous systems to physics and

chemistry but you're missing the microbiological step. It's as if

you documented the changing surface of the Earth at urban sites

using Landsat images, without knowing anything about the people.

Think of the nerve as coming from what had formerly been a

bacterium, trying but unable to rotate and swim. Thought involves

motility and communication, the connection between remnant

spirochetes. All I ask is that we compare human consciousness with

spirochete ecology. "

http://cajal.unizar.es/eng/part/Margulis.html

If that is really her writing or speech, as claimed by that website,

its just not science. What she expresses there is a poetic

comparison that illuminates the feeling of consciousness, not an

argument. Perhaps she has arguments for this somewhere else... most

scientists like to show em off at all times, but it aint illegal to

do otherwise.

<compucruz@y...> wrote:

>

> Dammit, you, get out of my brain!

>

> This is too weird. As knows, I am dealing with some of the

> weirdness surrounding Lyme disease by writing a fictional account,

> that plays with some of the more 'far out' ideas about where Lyme

> comes from and what it's doing to us.

>

> I was up until 3am working on a new chapter about how microbes are

> key to the origin of human consciousness.

>

> Wacky, right?

>

> Then I read this - and sure enough, here is this woman who is a

> scientist, not an author of science fiction, saying things

> remarkably similar to the 'wacky' notions in my story.

>

> Weird, weird, weird.

>

>

[Guest guest]

Well, , I was lucky enough to spend a few days with her, this was

pre-SLYME....what an amazing woman. A bundle of energy, up at 5:30 to

swim laps in the school pool, pick me up, take me back and make me

breakfast, send me off with a student while she rode her bike to

school, teach all day etc...

she did indeed originate that theory and it took 20 years for science

to confirm it through dna testing. she deserves a lasker if not a

nobel but women in science have a hard time of it...

she studies spirochetes in the termite gut...i can't go into all the

details here but her theory is pretty darn interesting

she had a piece in daedalus recently about syphilis, nietzsche etc.

he went mad suddenly at the end. she thinks yes, spirochetes can go

latent and then burst out all at once and his madness was a sudden

recrudescence of syphilis at the end after dormancy

if you want to blow your mind with a beautiful little book read

freeman dyson's origins of life. he's a fan of hers.

> >

> > , look up the work of Lynn Margulis. She talks all about

this,

> and

> > spirochetes too.

[Guest guest]

> > >

> > > , look up the work of Lynn Margulis. She talks all about

> this,

> > and

> > > spirochetes too.

[Guest guest]

> > >

> > > , look up the work of Lynn Margulis. She talks all about

> this,

> > and

> > > spirochetes too.

[Guest guest]

Whoops.

Krueger at Univ Washington, Spokane, believes this (microbes

origin of consciousness).

Its true too, I believe it.

Long time ago, he was a postdoc at Harvard I believe, and...darn...my

slyme memory is failing me as I interviewed him last fall...there

were bacterial cell wall proteins in the spinal fluid, I think...he

said it freaked out science too much and he's never been able to get

a grant to pursue this...they could be used by our CNS as signalling

proteins, I think...

> > >

> > > , look up the work of Lynn Margulis. She talks all about

> this,

> > and

> > > spirochetes too.

[Guest guest]

eric, its not just poetic. okay. she studies spirochetes in termite

guts, where they exist in all 3 stages of evolution according to her.

they swim around freely. tehy attach to the cell membrane where

unless you have a really high powered microscope they look JUST LIKE

CILIA. they also exist inside.

she figures a long time ago spirochetes attached to thermapholis a

sulfur loving bacteria, as the earth was going more toward

02/aerobic. spirochetes, by attaching to thermophilus which spewed

sulfur (if i remember this correctly from years ago), were protected

a bit from the 02. meanwhile thermiophilus got a friend who would

squiggle its flagella and helpl it move, avoiding prey and finding

food. eventually she thinks, the spirochete began to burrow in, and

the head became the nucleus of a eukaryotic cell (our cells--bacteria

are prokaryotes). this is where everyone thinks she's nuts and she's

still trying to prove it for many years.

even so, have you ever wondered why spirochetes have an affinity for

our nervous system (syphilis, borrelia). and the idea of a nerve cell

as a sort of paralyzed flagella--carrying electrical impulses--is

kind of neat. ovf course, evolution is convergent. it keeps making

the same smart things over and over in different places, it evolves

eyes all over the place for instance. so tails (sperm, cilia,

borrelia etc) are a good idea.

> >

> > Dammit, you, get out of my brain!

> >

> > This is too weird. As knows, I am dealing with some of the

> > weirdness surrounding Lyme disease by writing a fictional

account,

> > that plays with some of the more 'far out' ideas about where

Lyme

> > comes from and what it's doing to us.

> >

> > I was up until 3am working on a new chapter about how microbes

are

> > key to the origin of human consciousness.

> >

> > Wacky, right?

> >

> > Then I read this - and sure enough, here is this woman who is a

> > scientist, not an author of science fiction, saying things

> > remarkably similar to the 'wacky' notions in my story.

> >

> > Weird, weird, weird.

> >

> >

[Guest guest]

" jill1313 " <jenbooks13@h...> wrote:

> she did indeed originate that theory and it took 20 years for

> science to confirm it through dna testing. she deserves a lasker

> if not a nobel but women in science have a hard time of it...

Are you kiddin me? It seems like biologists have gone to Stockholm

for a heck of alot less. Youd think that discovery would be worth

like 3 Nobels.

The presence of bacterial cell envelope proteins in cerebrospinal

fluid could be due to sub-pathogenic colonization. I know there are

many studies finding that the healthy human body is not at all

sterile - I havent combed thru em but I'm inclined to figure theyre

probably correct.

I still dont see the other arguments for a symbiotic origin of the

neuron. Some spirochetes are neurotropic, but so are herpes viruses.

Neurons are long, but so are muscle cells - they are so long they

have to have multiple nuclei.

The cilia/flagella symbiosis theories involving spirochetes will be

alot harder to demonstrate than the symbiotic nature of mitochondria

and chloroplasts, since cilia lack DNA, and the cilia are now (known

to be, I assume) generated from eucaryote DNA. Perhaps she thinks

that when the penetrating tip of the spirochete became the eucaryote

nucleus, the cilia-coding DNA was transfered... well its all very

weird, but I keep an open mind. Its just that its relatively easier

to imagine proto-eucaryotes developing nuclear membranes and

cilia/flagella on their own. Even the humble procaryote has myriad

transcription factor proteins etc that interact with its chromosome,

as well as replication and transcription enzymes etc - I dono how

much these molecules vary between procaryote taxa, but if there is

any incompatibility the nucleic-material-mergation of a spirochete

and a proto-eucaryote in this way could be a very fumbling

courtship.

I'd *love* to blow my mind on the Freeman Dyson book one day but

alas, I havent even read any Heraclitus in months, I just dont have

the sap to read anything for interests sake - I'm so depressed and

nervous that only working on stuff in the realm of anti-bacteria

therapy can sustain morale. Except when it keeps on being cloudy all

week like this, I virtually cant do anything at all. Just take

baths, watch TV, groan, etc.

[Guest guest]

Lo, I have yammered in vain - what a shock, not

This page says there is some possible direct evidence of gene

transfer from endosymbionts into the host genome:

http://opbs.okstate.edu/~melcher/MG/MGW1/MG1378.html

Far *out* man! It even has a name, horizontal gene transfer. These

concepts are all over the articles on apoptosis in this issue:

http://www.nature.com/nrm/focus/apoptosis/articles_cdd_mf.html

.....of which several are very interesting, not just the one I posted

originally.

I wonder if the endosymbiont organelles were " enslaved " into their

current cooperative condition, or instead were such successful

parasites/commensalists that they ran out of uninfected hosts to

exploit, and hence had to start " sucking up " to the hosts as host

and parasite interests converged.

This area of inquiry could be helpful in the anti-infective

manipulation/restoration of apoptotic function - if such a thing is

indeed called for, powerful, and possible.

> The cilia/flagella symbiosis theories involving spirochetes will

be

> alot harder to demonstrate than the symbiotic nature of

mitochondria

> and chloroplasts, since cilia lack DNA, and the cilia are now

(known

> to be, I assume) generated from eucaryote DNA. Perhaps she thinks

> that when the penetrating tip of the spirochete became the

eucaryote

> nucleus, the cilia-coding DNA was transfered... well its all very

> weird, but I keep an open mind. Its just that its relatively

easier

> to imagine proto-eucaryotes developing nuclear membranes and

> cilia/flagella on their own. Even the humble procaryote has myriad

> transcription factor proteins etc that interact with its

chromosome,

> as well as replication and transcription enzymes etc - I dono how

> much these molecules vary between procaryote taxa, but if there is

> any incompatibility the nucleic-material-mergation of a spirochete

> and a proto-eucaryote in this way could be a very fumbling

> courtship.

[Guest guest]

I think its fascinating, Jill. I will try to get a copy of the Dyson

book. And your description of Lynn makes me want to learn about her

as well.

Thanks for sharing this,

> > > >

> > > > , look up the work of Lynn Margulis. She talks all about

> > this,

> > > and

> > > > spirochetes too.

[Guest guest]

...there was some study with algae and bacteria I think? Anyway

they did run a study in the lab, where the bacteria parasitize the

algae or visa versa I really can't remember, anyone one parasitizes

the other and MOST Of the algae die but because of random variation, a

few adapt. THen over generations, the adaptation gets better and

better (nature conserves energy) until they become a unified complex

different " better " organism.

SOmetimes its environmental pressure that leads to

symbiosis...sometimes perhaps accident.

Freeman Dyson said something to me in a brief email interview once,

about symbiosis being an infection that was almost fatal...but not.

[Guest guest]

TNF--tumor necrosis factor--we discovered it originally I guess

because of tumors...and we know its involved in inflammation--also

found in the brain involved in sleep......

That's one example.

So the bacterial cell wall protein--eric might be right, maybe it is

subclinical infeciton in all humans--but it could also be that over

time our bodies adapted and began to use these as signalling chemicals.

>

> I think its fascinating, Jill. I will try to get a copy of the Dyson

> book. And your description of Lynn makes me want to learn about her

> as well.

>

> Thanks for sharing this,

>

>

>

..

[Guest guest]

That is one rad experiemnt.

Ive read there is one known eucaryote that lacks mitochondria - and,

no surprise, it has bacteria as an analogous endosymbiont.

Finding out about this cross-*kingdom* horizontal gene transfer

thing opens alot of possibilities. It makes the superfunky

endosymbioses proposed in Margulis' new ideas seem significantly

more workable. Who knows.

It also may be kinda discouraging, in that intracellular parasites

can perhaps capture our genes, giving them an ultimately powerful

way to manipulate our cells. Hopefully this hasnt happened broadly.

It appears Rickettsia conorii may have captured a vertebrate gene

for a protein containing an apoptosis-linked domain, as addressed in

" Origin and evolution of eukaryotic apoptosis: the bacterial

connection " , found at:

http://www.nature.com/cgi-taf/DynaPage.taf?file=/cdd/journal/v9/n4/full/4400991a\

..html

" jill1313 " <jenbooks13@h...> wrote:

>

> ...there was some study with algae and bacteria I think?

Anyway

> they did run a study in the lab, where the bacteria parasitize the

> algae or visa versa I really can't remember, anyone one

parasitizes

> the other and MOST Of the algae die but because of random

variation, a

> few adapt. THen over generations, the adaptation gets better and

> better (nature conserves energy) until they become a unified

complex

> different " better " organism.

>

> SOmetimes its environmental pressure that leads to

> symbiosis...sometimes perhaps accident.

>

> Freeman Dyson said something to me in a brief email interview

once,

> about symbiosis being an infection that was almost fatal...but

not.