 "
To the Future or to
the Past , To
a time when humour is free...to a time when Free range Clowns exist,
and when a joke is told it cannot be untold...From the age of dystopian
copyright infringment, from the age of Mega-Corporations, from
the age of Faster Food, from the age of Double-Double-Ba©on
burgers - - Greetings!" |
A
classic dystopian vision of the future, examining
concepts of Bioinformatics, computational biology and multi-stellar
corporate copyright infringment ....
Repli©lowns --
THE CLOWNS OF TOMORROW -- their
everyware
--"They
were designed to copy Clowns in every
way except their Improvizational skills.
The designers reckoned that after a
few years they might develop their
own routines; observational humour,
political content, smut, anger, envy.
So they built in a fail-safe device
: Geengineered Obsolescence --' Excelerated
de-©lownitude"--
Actually,
The real rationale behind Excelerated
de-©lownitude
is to generate long-term sales volume
by reducing the time between repeat
purchases. Piewell
Corporation
believes that the additional sales
revenue it creates more than offsets
the additional costs of research
and development and opportunity
costs of existing product line cannibalization.
Progeria
in Scurra Syndrome-Excelerated
de-©lownitude (PiSSED)
is an Geengineered
disorder
deliberately introduced into the
major architectural proteins of
Repli-©lown ©ell
nuclei. The earliest
symptoms manifest in the ©lowns
final quadmester with a localized
scleroderma-like skin condition combined
with facial tics. As the Repli-©lown
ages beyond 1010 24 hour cycles,
additional conditions become apparent. Amyotrophic
Lateral Sclerosis (a form
of motor neuron disease) combines
with a
variety of dysplastic abnormalities
of the skin, nervous system, bones,
endocrine organs and blood vessels,
in particular smoothly
rounded or lobulated tumours surrounding
the nasal cavity, swelling of the
hands and feet leading to grotesque
overgrowth of soft tissue and bone
in limbs or around the orbit.
No treatments
have thus far been effective,
alterations to the evolvement of
an ©omedic life system have
all proved fatal. A Humorus Deoxyribonucleic
Acid (HDNA)
or 'comedy' sequence cannot be revised
once it's been established. Few Repli-©lowns
exceed 1025 24 hour cycles. At least
50% of subjects die from complications
of atherosclerosis, such as heart
attacks or strokes as their bodies
are taxed by the engorged nature
of their now oversized cartoonlike
extremities. The remaining ©lowns
die of involuntary
emotional expression disorder (IEED).
Repli-©lowns find themselves
laughing uncontrollably at things
that are only moderately funny,
being unable to stop themselves for
several minutes. There is no Neurodegeneration
associated with this, althought
the subject's sense of humor is exacerbated
(in combination with IEED the effects
are devastating ). The maturation
of these symptoms is comparable to
comedy at a rate six to eight times
faster than normal, Imagine watching
a filmed performance of a Jerry Lewis/Jim ©arrey
Hybrid as the featured performer
is slowly inflated anally with helium
and the sped up footage has been
edited by David Lynch.
Episodes are mood-incongruent : A subject will begin to laugh uncontrollably
when angry or frustrated. Near the end it's just laughter non stop...
Isolated
experimental Treatments have focused
on reducing complications, via heart
bypass surgery or low-dose aspirin.
Repli-©lowns
may also benefit from a high-calorie
diet. (But again why bother? its cheaper
to just go out and buy another one)
Growth
hormone treatment has been attempted.
EMS recombination proved a failure.
A type of anti-cancer drug, the farnesyltransferase
inhibitors (FTIs), have been proposed
by the clown rights group “Pagliacci’s
Liberation Front” (PLF),
but their use has been highly experimental.
A phase II clinical trial using the
FTI Lonafarnib began in AUG 2015.
Treatment of IEED is usually pharmacological,
using antidepressants such as fluoxetine,
citalopram, or amitriptyline in
low to moderate doses.
A combination of dextromethorphan
and a subtherapeutic dose of quinidine
is another option, but still only
a stop gap measure. If The Subject's
heart doesn't explode first, it will
eventually laugh itself to death.
Rep-©ollect
:
Abbreviation
for the Repli-©lowns
Collection (Division),
also referred to as 'the Juice
Works', a planet-wide police department
with special authorities. The primary
directive of the department is
to track and neutralise escaped/trespassing
Repli-©lowns, thus protecting
the public from the insidious scourge
of copyright infringement. Rep-©ollect is
a rather small and specialised
division, steeped in secrecy and
only vaguely acknowledged by the
HomeWorld general public. Needless
to say, Rep-©ollect and
Pie-Well
Corporation do not co-operate
very well. Rep-©ollectors are
popularly called
©lown Runners.
The
War on Humor:
“ There’s
nothing funny about a clown in the moonlight ”. -- Lon
Chaney
The Anti
Repli-©lown Repatriation Act of 2018 : The
now infamous 'Clowning
Around' Act - - Instigated by the Federated
Terran HomeWorld Government (formerly
McDonalds™ Corporation) declaring
Repli-©lowns illegal on the Earth, its surrounding
atmosphere and satellites. Giving official sanction for
©lown Runner Units to 'Retire with extreme prejudice'
any and all Repli-©lowns, in furtherance of the
HomeWorld government's aims or policies. Previous to
the A.R.©.R
act , terms
like 'Extraordinarily
moving'
rendition and interpretive
rendition were used to describe the OffWorld
transfer of a Repli-©lown and
other Transgenics.
©lownrunner's FutureSpeak
Lexicon :
Paint job
: Harsh
slang term in reference to a repli©lown.
Beta-©lowns
: The
original Hum-R-us phase had a
secondary title to differentiate
from Clowns proper.
This inspired
the query :
What sort of entertainer
are you?
Answer : Beta-©lown
Response : Don't mind if I do!
©lown
Juice : The
fluid resulting from punching
a ©lown.
PerformAutons
: In
an attempt to revitalise the Ron-Alt
McDonald counter-service
Model™
Franchise,
Piewell Corp instigates
Project :
Next-Fun, these repli©lowns
were referred to as the Next-us
series or PerformAutons (
©lowns designed by ©lowns
).
A re-call is issued, the PerformAuton’s
rebel. It is all the more
tragic in that they were
young. But, had they lived
very, very long lives, they
could not have expected nor
would they have wished to
see as much of the mad and
macabre as they were to see
that day. For them an idyllic
summer Mc-Happy day on Voltron
77 became a nightmare. The
Events of that day were to
lead to one of the most horrendous
acts in the annals of corporate
history. Few PerformAutons
escaped what was to become
known as the Next-us Mc-Chainstore
Massacres.
'Cancelled' performance
: To punch
a clowns ticket so to speak.
RePel-©lowns : Off
World performers refusing to except their
genetically designed
place in the universe.
Gelfs : (Genetically
Engineered Life Forms)
Bioroids : Who
many consider
to be the next
step in human
evolution.
Repli-Can'ts
: Limited
edition reproductions
of historical
figures
and deceased
celebrities.
Impossible
to replicate
effectively
using current
technology.
A
small group of RePel-©lowns
remain free and unharmed : Led
by Roy Bongo the Clowno.
--"There
was an escape from an off-world Circus. 6
Repli-©lowns,
3 male, 2 female, 1 mime. They slaughtered
23 audience members and jumped a
shuttle. An aerial patrol spotted
the ship off the coast. No crew,
no sight of them. 3 nights ago they
tried to break into the PIEWELL
CORPORATION. One of
them got fried pissing on an electrical
fence. We lost the others...."--
Suggestions
:
All the
Repli©lowns are German,
or german made, look
at Bongo ( and Rutger
for that matter )
- cold, Aryan poster
boy, flawless makeup
- sort of like the ©lone
equiv of Volvo ( possibly
speaking in german
between themselves
with subtitles trans:
Marc of course)
this would explain
why their not funny,
won't do what their
told, and the whole
extermination/genocide
thing works well
in reverse. -- Klowns
Der Zukunft --
The difference in
background themes
between Blade Runner
and Do Androids Dream
Of Electric Sheep,
Phillip K. Dick portrayed
his "andys," or
replicants, in D.A.D.O.E.S
as thinly disguised
Nazis. Powerful humans
who had absolutely
no sense of empathy
or emotional connection
with what Lincoln
refered to as ' the
better by the better
angels of our nature'.
Therefore, D.A.D.O.E.S's
replicants are dangerous.
Soulless entities
who were Mr
Dick's allusion to
what he perceived
as an out-of-control
culture drifting
towards an increasingly
selfish, heartless
society. However, Ridley Scott
viewed his replicants
in a totally different
light. refering to
them as "supermen
who couldn't fly," genuinely
superior beings who were being ruthlessly manipulated
by their genetic inferiors ( you can see how that just screams fat mcdonalds upper
management shitting on spotty teanage employees ).
Repli©lowns Rights Groups Up In
Arms Over “©lownist” Terminology :
Long upset over what they consider “second-class citizen” status,
clown advocacy organizations have begun a strong push for respect. Leading
the way is the controversial clown rights group “Pagliacci’s Liberation
Front” (PLF), which in the past has used very aggressive tactics to advocate
for fair treatment.
Repli©lown Manifesto: “ For
centuries our forefathers the Clowns have been bringing joy and laughter to
untold billions,” said
PLF spokesman Bingo Snickerdoodle. “From
the legendary gladiatorial clown Maximus Humerus Ossis to
renowned Irish entertainer
Flowers McSoaky to Wild West legend Pogo ‘Snakebit’ Sweeney.
They gave their all to make others happy. What has their reward been? Mockery,
taunting, disrespect.”
Snickerdoodle maintains that no
other group of individuals throughout the United Star Systems (USS) has been
discriminated against to the level that ©lowns have.
“©lownism is an
enormous problem. The amount of 'Beta-©lowning' in the off-world
colonies today far exceeds the amount of discrimination faced by the next closest
group (the Mimes). Think about the language that is used in our culture: ‘I
fucked her silly’ or ‘I beat him silly’. What is that? Does
this mean that ©lowns are twisted perverts? Are we violent individuals
to be feared? This sort of language is just not funny.
However, I will say this: the
game has changed. You send one of ours to therapy, we’ll send two of yours to a noon-day viewing of
The Day the
Clown Cried. You put a whiny kid with a diaper full of chalupas
on our lap, we’ll
come back at you with an extra loud honky-horn. We ©lowns will no longer
be anybody’s… umm… ©lowns. ”
Additional
Data :
Anything,
ANYTHING that can be
done to a ©lown can
be done to a human being,
and we can do most anything
to ©lowns. This is a
hard thing to think about,
but it's the truth. It won't
go away just because we cover
our eyes.
Bio-Mc©lownics
:
Bioinformatics
and computational biology involve the use of
techniques including applied mathematics, informatics,
statistics, computer science, artificial hilarity,
chemistry, and biochemistry to solve biological
problems usually on the molecular level. Research
in computational biology often overlaps with
systems biology. Major research efforts in
the field include sequence alignment, gene
finding, genome assembly, protein structure
alignment, protein structure prediction, prediction
of gene expression and protein-protein interactions.
Bio-Mc©lownics
all began with the identification of the chromosomal
location of the 'sense of humor' (SOH) gene.
Localisation of the gene did not initially
enable amplification of the relevant genomic
sequence.
Molecular
©lowning Proper refers
to the procedure
of isolating the Humorus
Deoxyribonucleic Acid
(HDNA)
sequence ( jokingly refered
to in the industry as the
source of the funny bone
upon its discovery)
and obtaining multiple copies
of it from a pre-existing
Clown (the Templant). ©lowning is
frequently employed to amplify HDNA fragments
containing SOM genes,
an essential step in their
subsequent analysis.
©lowning
a HDNA sequence
involves
the following
5 steps :
Confirmation --
Initially, the funny fragments
must be confirmed
as 'seriously
funny' (SF)
or in extreme
cases 'funny as
fuck' (FAF).
Amplification --
Using the Polymerase
chain reaction
(PCR)
process.
Ligation --
Endonuclease digestion
of the amplfied SFHDNA with
a plasmid vector will
allow formation
of a recombinant
plasmid.
Transfection --
The recombinant
plasmid is
introduced
into a bacterial
host cell
or 'funny
shit'
(FS).
Selection --
The transfected
cell is
cultured
allowing
the recombinant SFHDNA to
replicate
and divide
along with
it. For
this electroporation
is most
commonly
employed,
although
a number
of alternative
techniques
are available,
such as
chemical
sensitivation
of cells
or tickilng
the cells
with a
feather.
The recombinant SFHDNA can
be cut
out with
the same
endonuclease
with which
is was
inserted,
and then
purified.
Further investigation
of the resulting
colonies or 'Funny Farms'
is required to confirm
that ©lowning was
successful. This
can be accomplished
by means of blue/white
screening (a-factor
complimentation)
on X-gal medium
and/or PCR,
possibly followed by DNA sequencing...
Funny
Farms are
kept metabolically
inactive and
can remain
in total stasis
for several
years while
in a dry, oxygen-free
environment,
even at temperatures
below freezing.
This characteristic
is called cryptobiosis (also
called diapause).
Once placed
in a liquid
nutrient medium
(red cordial),
the cyst-like
cell structures
begin to divide
and multiply,
and will grow
into a mature
Repli©lown
within 24 hours.
Repli©lowns
have a biological
life cycle
of 4 year.
This short
life span,
and other characteristics
such as their
ability to
remain dormant
for long periods,
have made them
invaluable
in scientific
research, including
sit-com experiments.
"live free, pie well"
"I will never forget those horrible smiling
faces as long as I live."
"If you were a ©lown, where would
you hide?" "The amusement park!"
NOTE : The name of "Bozo"
was derived from an old European word for
"Court Jester"
(Roy)-Bongo
the Clown : Appears
as a sadistic, malevolent, balloon-wielding
clown. Roys tatoos: According
to Ridley Scott quoted in Future Noir,
it was a half-developed idea they had
- another thing inspired by Jean Giraud.
So they then thought of markings that
denoted points where, say, a space war
suit would plug in to sockets. But even
that idea got left behind and we were
left with markings that are simply "A
curious detail."
So it is really up to you how you would
like to interpret them.
Zhora
character : Ventriloquist
dummy made from genegereered wood
Po-Po the Clown : Ex
keystone cop (Offworld self regulating
Repli-©lown police force).
Tinkle the Clown :
Sparkle :
Homey -27 : Party
Repli-©lown custom built for
the off-world party circuit based
on the Templant : Homey
the Clown - A
frustrated, ex-convict who performed
on the streets to make money. Homey
D. Clown (real name: Herman Simpson)
had a painted face, red hair, balding
head, and a baggy yellow and orange
clown suit with large pompom buttons
and oversized shoes. Working the
streets and occasional party, he
would asked people if they wanted
to see a trick and then say "Gimme
a dollar." This establishment
hating individual had a short temper
and hit people over the head with
a stuffed sock. He accompanied his
head bashing with the catchphrase
"Homey
don't play that!" While
visiting his parole officer Homey
claimed that his file was just
a "long
list of lies perpetrated by the "Man" to
keep a brother down." During
a children's party a child asked "Why
did you become a clown? " Homey
responded,
"I
guess its because I got so much
love to give...and its part of
my prison work release program.
I got about five more years of
this clown crap."
He ended the party by singing
the Homey the Clown song..." Homey
the clown, Don't mess around,
Even though the Man, Try to keep
him down, One day Homey will,
Break all the chains, Then he'll
fly away, But until that day,
"
Bo-Bo :
Credi-Wise
:
Che-Gue : Repli-©lown
Activist.
LaLa,
Cheezo, Bippo, Dippo, Zippo,
Mr. Giggles,
Noodles, Seesaw, Oopsie,
Flopsweat, Hoohaw, Jitters
and Sir Widebottom.
Clowns to Study
:
Krusty the Clown -Krusty
the Clown, or Herschel
Schmoikel Krustofski ( full
name: Herschel
Pinkes Remochel Krustofski
), is a fictional
character in the cartoon
The Simpsons, voiced by Dan
Castellaneta.
Krusty is the long-time
clown host of Bart and
Lisa's favourite TV show.
The TV show is a combination
of kiddie variety-television
hijinks with a sidekick,
and cartoons including
the Tom and Jerry parody Itchy
and Scratchy.
His original sidekick Sideshow
Bob has now been replaced
by Sideshow Mel. The character
of Krusty was partially
inspired by real-life clown "Rusty
Nails"
whom Simpsons creator
Matt Groening watched
as a child while growing
up in Portland, Oregon.
An illiterate, rowdy
green-haired clown on
the animated cartoon
THE SIMPSONS/FOX/1989+.
Krusty the Clown was
the favorite TV personality
of Bart Simpson (Krusty
No. 16302), a bratty
little kid who lived
in the town of Springfield,
USA. Krusty's TV show
assistants included Side-Show
Mel, Corporal Punishment,
Tina the Ballerina, his
backup band Krusty and
the Ktums and Krusty's
faithful secretary, Miss
Penny Candy. The "Krusty
the Clown"
program featured ax-throwing
stunts and cartoons like "Itchy
and Scratchy" (a
bloodier version of "Tom
and Jerry"). In
one cartoon, Itchy ran
over Scratchy with farm
harvesting equipment
and then played ball
with his decapitated
head. Despite, the gore,
kids loved Krusty. He
was so popular that Izzy's
Deli, a local eatery
honored Krusty with his
own sandwich that consisted
of "ham, sausage,
bacon with a smidge of
mayo on white bread." Krusty's
entrepreneurial spirit
once inspired a creation
of a kids summer camp.
Upon arriving at "Camp
Krusty,"
Lisa Simpson wrote a
letter home to her parents.
It read: "Dear Mom,
I no longer fear Hell
for I've been to Camp
Krusty...Save us. Save
us now!" Krusty
the Clown got his start
in showbiz in the 1960s
when he appeared on PULVER
LAWN PRODUCTS PRESENTS
THE CLOWNS OF TOMORROW.
During a 1991 episode
Krusty's real name was
revealed as Herschel
Schmoikel Krustofski,
and that he was born
to Jewish parents on
the Eastside of Springfield.
His father, Rabbi Hyman
Krustofski (voice of
Jackie Mason) disapproved
of his son aspiring to
be a clown. In a parody
right out of The Jazz
Singer (1927), Krusty
told his father "I
wanna make people laugh." Unfortunately,
his father responded "Selzer
is for drinking, pies
is for eating." When
the Rabbi discovered
his son performing at
a Rabbi Convention in
the Catskill Mountains,
(twisting balloons into
images of the Star of
David and Menoras), he
refused to ever speak
with his son again. However,
with the assistance of
Bart and Lisa Simpson,
their twenty-five years
of silence ended and
the two were happily
reunited. Some Krusty
Stats: Krusty's family
arrived on Ellis Island
in 1902. Krusty lived
in a large mansion called “Shtickfair” until
he lost it to the IRS,
Krusty is chain smoker
and suffered a heart
attack that forced him
to wear a pacemaker.
Krusty has a vertical
scar on his chest from
the heart surgery and
a superfluous third nipple.
During the Gulf War Krusty
entertained the troops
at a USO program and
met a shy soldier with
chestnut brown hair and
22 confirmed kills. They
had a short fling that
produced a cute little
girl named Sophie [she
plays the violin].
Original
Script Source - BladeRunner (with
Voice over)
Planned Scene BreakDown - for ©lownRunner
short Film.
Back
Story :
Possible
Toon assassinations as well or at least
implied. (cross over link with Krusty
the Clown being killed).
The 21st Century's Clowns,
Repli-©lowns & Performers
(C.R.A.P) Union is
based on 2 universal truths :
1. Professional
Humor is hard.
2. Clowns
scare the fuck out of people. Coulrophobia-
Fear of clowns.
“ To
me, clowns aren't funny. In fact, they're
kind of scary.
I've wondered where
this started and I think it goes back
to the time I went to the circus,
and
a clown killed my dad. ” --Jack
Handey
C.R.A.P started
with a few Clowns at the Concerned
Unicyclists Negotiating Tolerance Service with
a dream for a Union that would focus
on promoting tolerance and understanding
of amusing performers throughout the
galaxy, standardised education withinin
the Clown arts and spreading Clownery
around the known universe. Unfortunatley C.R.A.P has
devolved into is a miserable place, due
to stringent restrictions put in place
by The Repli-©lown
Registration Act of 2018, and
the represive roll played by the near
omnipresent Multi-Global
Hyper-Mc-Mega-Cola™Corp (formly
McDonalds™ Corporation) (upon
its purchase of all existing
Clown related patents & and
related ACME products).
Old jokes and comedy routines are taught
by rote and new humour and performances
are vetoed or disallowed for audience
viewing until they have been tested for
decades under controlled conditions.
Multi-Global
Hyper-Mc-Mega-Cola™Corp > Pie-Well
Corporation : Mega-Corporation
and main manufacturer of Repli-©lowns,
named after Eldon Pie-Well or
perhaps a whole corporate dynasty. A
multi-national and obviously multi-galactic
enterprise, employing hundreds of thousands
or perhaps even millions of people. If
one follows the cyberpunk tradition with
mega-corporations, it is an implicit
fact that the corporation basically has
its own government, police force, code
of laws etc. The Pie-well
Corporation may or may not be
the sole Repli-©lowns
manufacturer, there are indications
that the corporate language might
be French.
Multi-Global
Hyper-Mc-Mega-Cola™Corp > ACME
Corporation : Wile
E. Coyote often obtains
complex and ludicrous devices from
a mail-order company, the ACME Corporation,
which he hopes will help him catch
the Road Runner. The devices invariably
backfire in improbable and spectacular
ways (see Rube Goldberg machine).
Whether this is result of operator
error or faulty merchandise is debatable.
The coyote usually ends up burnt
to a crisp, squashed flat, or at
the bottom of a canyon. (Some
cartoons show him suffering a combination
of these fates.) How the coyote
acquires these products without any
money is not explained until the
2003 movie Looney Tunes:
Back in Action, in which
he is shown to be an employee of
Acme. In a Tiny Toon Adventures episode,
Wile makes mention of his protege
Calamity Coyote possessing an unlimited ACME credit
card account, which might serve as
another possible explanation. Wile
E. being a "beta tester"
for ACME has been another
suggested explanation. Wile E. also uses
war equipment such as cannons, grenades,
and bayonets.
The company name was likely chosen for
its irony (acme means the highest point,
as of achievement or development).
The common expansion A (or American) Company
that Makes (or Making) Everything is a
backronym. The origin of the name might
also be related to the ACME company
that built a fine line of animation stands
and optical printers.
Among the products
by the ACME Corporation are :
ACME portable holes ACME catapults ACME earthquake
pills ACME rocket sled
kits ACME Burmese tiger
trap kit (thus nailing a Burmese tiger
(Stop, Look, and Hasten; Surprisibus!
Surprisibus!) ACME jet-propelled
roller skates Acme (triple strength fortified)
leg muscle vitamins ACME Giant
Rubber Band (For Tripping Roadrunners) ACME Dehydrated
Boulders ACME Hi-Speed
Tonic ACME Batman suit ACME Bumble
Bees ACME Wild Cat and
- a wide selection of explosives: TNT,
dynamite, nitroglycerin ...
|
The
Anti Repli-©lown Repatriation
Act of 2018 : The now infamous 'Clowning
Around' Act - - by
the World
Government (formly
McDonalds™ Corporation) declaring
Repli-©lowns illegal on the Earth,
surrounding atmosphere and satellites.
Giving official sanction for
©lown Runner Units to 'Retire with
extreme prejudice' any and all Repli-©lowns,
in furtherance of the government's aims
or policies.
Geoffrey Guliano,
one of McDonald's Ronalds in the late
1970s, admitted on a 1991 installment
of the on-air magazine A CURRENT AFFAIR
that he no longer wanted to
"participate in the violence
and bloodshed of innocent animals." His
association with the religion of
Hinduism and his attempt to atone
for his actions inspired him to open
a ten-acre cow protection facility
(a Dama Shala) with the hopes of
keeping some cows from the beef-hungry
jaws of Americans. Instead of billions
served...he wanted billions saved.
He concluded
"I was
the personification of the meat eating
for the planet. I am guilty as charged.
If I can save one cow from your table,
my mission will be accomplished."
Earlier in his acting career, Mr.
Guilliano was crowned the mascot
for Burger King "the marvelous
magical Burger King who can do most
anything."
Chew: |
(Chinese,
screams) |
Roy: |
Buffology,
longevity, incept dates. |
Chew: |
Don't know -- I,
I don't know such stuff. I just do
noses. Just noses -- genetic design
-- just big red shiny noses. You
Humorus, huh? I design your nose. |
Roy: |
Chew, if only you
could smell what I've smelt with
your nose. Questions. |
Chew: |
I don't know answers. |
Roy: |
Who does? |
Chew: |
Piewell. He --
He knows everything. |
Roy: |
Piewell corporation? |
Chew: |
He's big boss.
Big genius. He, he design your mind,
your sense of humor. |
Roy: |
Ah,
smart. funny. |
Chew: |
Cold. |
Roy: |
Not an easy man
to sniff out -- |
Chew: |
Me cold. |
Roy: |
I guess... |
Chew: |
Se-, Sebastian
he take-- take you there, he take
you there. |
Roy: |
Sebastian who? |
Chew: |
J. -- J. F. Sebastian--
Sebas... Sebas... |
Roy: |
Now--where... would
we find this.... J. F. Sebastian? |
|
|
Point mutation
: A mutation due to an intramolecular
reorganization of a gene.
Dr. Eldon
PieWell : The
facts of life. To make an alteration
in the evolvement of an comedic life
system is fatal. A comedy sequence cannot
be revised once it's been established.
Bongo : Why
not?
Dr. Eldon PieWell : Because
by the second day of incubation,
any cells that have undergone reversion
mutations give rise to revertant
colonies like patrons walking out
on a crap routine. its just not funny
anymore.
Bongo : What
about EMS recombination?
Dr. Eldon PieWell : We've
already tried it. Hydro
Dimethyl Sulfonate as
an alkylating agent, a potent
mutagen It created a virus
so lethal the test ©lown
exploded before he left the
operating table.
Bongo : Then
a repressive protein
that blocks the comedic
cells.
Dr. Eldon Piwell
: Wouldn't
obstruct replication,
but it does give
rise to an error
in replication so
that the newly formed SFHDNA strand
carries the mutation
and you've got a
virus again. But,
uh, this-- all of
this is academic.
You were made as
funny as we could
make you. |
The portion
of the original blade runner script
pertaining to the repair of accelerated decrepitude,
as written is total gobbledygook. For instance, EMS is
commonly used as a mutagen, but it doesn't
create viruses; the contrived rule about coding
sequences being incapable of revision doesn't
make sense; the stuff about repressors causing
replication errors is just babble. He
should have just said his lifespan was in part
an ontogenetic consequence, and it couldn't
be corrected short of rewinding his entire
life history back to fertilization, and replaying
his development. (but why argue with an enduring
classic, the dialogue works.)
Ethyl
Methane Sulfonate :
Is a mutagenic, teratogenic, and
possibly carcinogenic organic compound
with formula C3H8O3S
and CAS number 62-50-0. It produces
random mutations in genetic material
by nucleotide substitution; specifically
by guanine alkylation. This typically
produces only point mutations. It
can induce mutations at a rate of
5x10-4 to 5x10-2 per
gene without substantial killing.
The ethyl group of EMS reacts
with guanine in DNA,
forming the abnormal base O-6-ethylguanine.
During DNA replication, DNA polymerases
that catalyze the process frequently
place thymine, instead of cytosine,
opposite O-6-ethylguanine. Following
subsequent rounds of replication,
the original G:C base pair can become
an A:T pair. This changes the genetic
information, is often harmful to
cells, and can result in disease.
Many mutagens cause a wide variety
of cancers in humans.
EMS is often used in genetics as
a mutagen. Mutations induced by EMS
can then be studied in genetic screens
or other assays.
Biotechnology: “The
use of biological systems to create
goods & services"
Restriction enzymes [Nobel Prize 1978]
-- DNA sequencing [Nobel Prize 1980]
-- Polymerase Chain Reaction (PCR) [Nobel
Prize 1993]
Principles
of Genetic Engineering & Biotechnology
Genetic
Engineering involves the
laboratory manipulation of
DNA
This may involve isolation
of a "gene of interest"
in vivo or in vitro "©loning"
of the gene
analysis of the ©loned
gene
gel electrophoresis
Southern nucleic acid "blotting"
DNA sequencing
Genetic ©loning
:
©loning a cell means to derive a
(©lonal) population of
cells from a single cell. This is an
important in vitro procedure when the
expansion of a single cell with certain
characteristics is desired, for example
in the production of gene-targeted ES
cells. Most individuals began as a single
cell and are therefore the result of
clonal expansion in vivo.
Organism
( Asexual
reproduction ) :
©loning means to create a new
organism with the same genetic information
as a cell from an existing one ( identical ).
It is an asexual method of reproduction,
where fertilization or inter-gamete
contact does not take place. Asexual
reproduction ( also known as agamogenesis )
is a form of reproduction which does
not involve meiosis, gamete formation,
or fertilization. This form of reproduction
is common among simple organisms such
as amoeba and other single-celled organisms,
although most plants reproduce asexually
as well (see vegetative reproduction).
Animals
:
©loning exists in nature in some
animal species and is referred to as
parthenogenesis. An example is the "Little
Fire Ant" (Wasmannia auropunctata),
which is native to Central and South
America but has spread throughout many
tropical environments.
Reproductive
©loning :
Reproductive ©loning is a technology
used to generate an animal that has
the same nuclear DNA as another currently
or previously existing animal. Deuschy
Dolly the sheep, was created by reproductive
©loning technology. In a process
called
"somatic cell nuclear transfer"
(SCNT), scientists transfer
genetic material from the nucleus of
a donor adult cell to an egg whose
nucleus, and thus its genetic material,
has been removed. The reconstructed
egg containing the DNA from a donor
cell must be treated with chemicals
or electric current in order to stimulate
cell division. Once the ©loned
embryo reaches a suitable stage, it
is transferred to the uterus of a female
host where it continues to develop
until birth.
Deuschy Dolly or any other animal created
using nuclear transfer technology is
not truly an identical ©lone of
the donor animal. Only the ©lone's
chromosomal or nuclear DNA is the same
as the donor. Some of the ©lone's
genetic materials come from the mitochondria
in the cytoplasm of the enucleated
egg. Mitochondria, which are organelles
that serve as power sources to the
cell, contain their own short segments
of DNA, although this is only 0.01%
of the total DNA.
Acquired
mutations in mitochondrial DNA are
believed to play an important role
in the aging process.
Also mutations occur with every cell
division so no two cells in an individual
are identical, nor are ©lones.
Thus, nuclear transfer ©lones
from different maternal lineages are
not ©lones in the strictest sense
because the mitochondrial genome is
not the same as that of the nucleus
donor cell from which it was produced.
This may have important implications
for cross-species nuclear transfer
in which nuclear-mitochondrial incompatibilities
may lead to inviability.
Health
aspects :
The
success rate of ©loning
has been low :
Dolly the sheep was
born after 277 eggs were
used to create 29 embryos,
which only produced three
lambs at birth, only one
of which lived, Dolly.
Seventy calves have been
created from 9,000 attempts
and one third of them died
young; Prometea took 328
attempts, and, more recently,
Paris Texas was created
after 400 attempts. Notably,
although the first ©lones
were frogs, no adult ©loned
frog has yet been produced
from a somatic adult nucleus
donor cell.
There were early claims
that Dolly the Sheep had
accelerated aging. Aging
of this type is thought
to be due to shortening
of telomeres, regions at
the tips of chromosomes
which prevent genetic threads
fraying every time a cell
divides. Over time telomeres
get worn down until cell-division
is no longer possible — this
is thought to be a cause
of aging. However, subsequent
studies showed that, if
anything, Dolly's telomere
were longer than normal.
Dolly died in the year
of 2003. Ian Wilmut said
that Dolly's early death
had nothing to do with ©loning
but with a respiratory
infection common to lambs
raised indoors like Dolly.
Consistent with Deuschy
Dolly's telomeres being
longer, analysis of the
telomeres from ©loned
cows showed that they were
also longer. This suggests ©lones
could live longer life
spans although many died
young after excessive growth.
Researchers think that
this could eventually be
developed to reverse aging
in humans, provided that
this is based chiefly on
the shortening of telomeres.
Although some work has
been performed on telomeres
and aging in nuclear transfer ©lones,
the evidence is at an early
stage.
Timeline
of Species
©loned :
The
modern ©loning techniques
involving nuclear transfer
have been successfully performed
on several species.
Landmark experiments in
chronological order :
Tadpole: (1952) Many scientists questioned
whether ©loning had
actually occurred and unpublished
experiments by other labs
were not able to reproduce
the reported results.
Carp: (1963)
In China, embryologist Tong
Dizhou ©loned a fish.
He published the findings
in an obscure Chinese science
journal which was never translated
into English.
Mice: (1986)
was the first successfully ©loned
mammal; Soviet scientists
Chaylakhyan, Veprencev, Sviridova,
Nikitin had mice "Masha"
©loned. Research was
published in the magazine "Biofizika"
volume ???II, issue 5 of
1987.
Sheep: (1996) From early embryonic
cells by Steen Willadsen.
Megan and Morag ©loned
from differentiated embryonic
cells in June 1995 and Dolly
the sheep* in 1997.
Rhesus Monkey: Tetra (female, January 2000)
from embryo splitting.
Cattle: Alpha and Beta (males, 2001)
and (2005) Brazil.
Cat: CopyCat "CC"
(female, late 2001), Little
Nicky, 2004, was the first
cat ©loned for commercial
reasons.
Mule: Idaho Gem, a john mule
born 2003-05-04, was the
first horse-family ©lone.
Horse: Prometea, a Haflinger female
born 2003-05-28, was the
first horse ©lone.
For a complete list see:
List of animals that have
been ©loned. During
the first several divisions
of a fertilized egg, no
differentiation occurs
and the cells can be separated
without harm, but each
will grow into an identical
individual. This process
has been used on cattle
for decades to produce
hundreds of identical individuals
in some cases. This process
is not considered ©loning,
but is called budding.
The new individual is not
derived from a differentiated
cell, but from an undifferentiated
egg. There is no way to
determine which are the ©lones
and which is the original.
*Deuschy Dolly the
Sheep
Dolly (05-07-1996 -
14-02-2003), an ewe,
was the first mammal to
have been successfully ©loned
from an adult cell (while
the mice in USSR was ©loned
from embryo cell back in
1986). She was ©loned
at the Roslin Institute
in Scotland and lived there
until her death when she
was 6. Her birth was announced
on 22-02-1997.
The name "Deuschy" came
from a suggestion by Jesse
Haase who helped with her
birth, in honor of Dolly
Parton, because it was
a mammary cell that was
©loned ( in
the XXI Century the 'Dolly II' -a hybrid
of "Deuschy" and
her namesake- would be marketed to
NU-Zealand in an attempt to lure out
males of a reproductive age after a
large percentage of the islands populations
was rendered sterile by the 'guerrier
d'arc-en-ciel deux' incident ). The
technique that was made famous by her
birth is somatic cell nuclear transfer,
in which a non-reproductive cell containing
a nucleus is placed in a de-nucleated
ovum (which then
develops into a fetus). When
Dolly was ©loned in
1996 from a cell taken
from a six-year-old ewe,
she became the center of
much controversy that still
exists today.
Dolly's success is truly
remarkable because it proved
that the genetic material
from a specialized adult
cell, such as an udder
cell programmed to express
only those genes needed
by udder cells, could be
reprogrammed to generate
an entire new organism.
Before this demonstration,
scientists believed that
once a cell became specialized
as a liver, heart, udder,
bone, or any other type
of cell, the change was
permanent and other unneeded
genes in the cell would
become inactive. Some scientists
believe that errors or
incompleteness in the reprogramming
process cause the high
rates of death, deformity,
and disability observed
among animal ©lones.
Embryonic
©loning :
Somatic cell nuclear
transfer
Somatic cell nuclear
transfer can also be used
to create a clonal embryo.
The most likely scenario
for this is to produce embryos
for use in research, particularly
stem cell research. This
process is also called "research
©loning" or "therapeutic ©loning."
Therapeutic ©loning, also called "embryo
©loning," is the | | | |
