View Full Version : Gene Therapy and the Sickness
cmcdtv 11-28-2005, 12:34 AM "We used to think that our fate was in our stars. Now we know that, in large measure, our fate is in our genes."--Francis Crick
I posted information on the Tiberius thread here (http://www.thefuselage.com/Threaded/showpost.php?p=631251&postcount=1496) about Gene Therapy, but I know not everyone obsesses over that thread and I think this is worthy of its own discussion.
So, gene therapy is one of the more controversial scientific issues today. You can learn about it here (http://en.wikipedia.org/wiki/Gene_therapy) at Wikipedia, or interestingly enough, through this site (http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml), which is the Oak Ridge Research Lab.
One of the most experimented methods of gene therapy is using viruses to transmit the new gene information. One of the more successful types of viruses is the adenovirus (http://en.wikipedia.org/wiki/Adenovirus) in the news lately because it is the group that the avian flu belongs to.
Now, we know that the Hanso Foundation has been studying Eugenics and Life Extension, both programs which could benefit from changing and altering genes. One for the creation of a new race and one for replacing aging genes in order to extend life.
As noted by my sis, todell:
Alright, now, on thehansofoundation.com site there is a press release about a Chimp named Joop who has lived 105 years. When you click on the bottom, you can get to a secret page. That page is a fax from the GHO (kinda like the WHO) urging Hanso to allow them to inspect their Zanzibar facility to investigate an outbreak of Meningococcal meningitis. Viruses are the most common cause of meningitis. Could Dharma have been doing experiments with gene therapy using a meningitis virus as a vector, and it escaped? Causing the sickeness?
Is it possible that the sickness is tied into gene therapy/ That the virus or viruses that are used to manipulate genes have gotten out and are infecting people?
Gene therapy failure can lead to cancer as well, interesting since we have seen Diane with some form of disease, more than likely cancer, Claire's boyfriend's uncle had testicular cancer, and Sawyer's uncle had a brain tumor. Could it be that they were all some how involved with some of these experiments? For that matter, what if Cooper needed a new kidney because of some sort of genetic disorder (although this takes for granted that Cooper is Locke's dad and not connected in some other way) and Locke, as part of an experiment (at a different time from his surgery) contacted menigitis with the gene therapy but it went wrong causing his paralysis?
Also, gene therapy opens up a whole other can of worms ethically, separate from its failings and their possible outcomes. One of the more promising forms is the addition of a 47th chromosome. Repairing genes is complicated ethically, but what about fundamentally changing our structure? Controling evolution. Fascinating, scary questions abound. I'm sure there are others out there who have a better working knowledge about all of this and I'd love to hear your thoughts, as well as those of others, cause I have a feeling this may be really important.
As Francis Crick notes, our destiny seems to be in our DNA. Gene therapy, then is a form of trying to change destiny. Fate up against the will.
Todell 11-28-2005, 01:10 AM !!! Genetic Engineering (http://en.wikipedia.org/wiki/Genetic_Engineering) !!!
One of the best known applications of genetic engineering is that of the creation of genetically modified organisms (GMOs).
There are potentially momentous biotechnological applications of GM, for example oral vaccines produced naturally in fruit, at very low cost. This represents, however, a spread of genetic modification to medical purposes and opens an ethical door to other uses of the technology to directly modify human genomes.
These effects are often not traceable back to direct causes in the genome, but rather in the environment or interaction of proteins. The means by which 'genes' (in fact DNA strands that are assumed to have discrete effects) are detected and inserted are inexact, including such means as coating gold particles with DNA to be inserted and literally firing it at strands of target DNA (see gene gun), which is guaranteed to cause insertions in at least some random locations, which can on rare occasion cause unplanned characteristics.
Similar objections apply to protein engineering and molecular engineering for use as drugs. However, a single protein or a molecule is easier to examine for 'quality control' than a complete genome, and there are more limited claims made for the reliability of proteins and molecules, than for the genomes of whole organisms. While protein and molecule engineers often times acknowledge the requirement to test their products in a wide variety of environments to determine if they pose dangers to life, the position of many genetic engineers is that they do not need to do so, since the outputs of their work are 'substantially the same as' the original organism which was produced by the original genome(s).
A radical ambition of some groups is human enhancement via genetics, eventually by molecular engineering. See also: transhumanism.
Isn't there something to do with transhumanism on your Drs. and Missing Limbs thread? (http://www.thefuselage.com/Threaded/showthread.php?p=576358&highlight=transhumansists#post576358)
bigmouth 11-28-2005, 12:47 PM cmcdtv and todell: Fascinating stuff! Did you see this post (http://www.thefuselage.com/Threaded/showpost.php?p=516724&postcount=10) re rTMS way back when by JohnnyReb? The part he quotes mentions that rTMS can produce a transient increase of CREB phosphorylation in the retina and pineal gland. Now check out this description (http://www.thefuselage.com/Threaded/showpost.php?p=516740&postcount=11) of CREB1, also by JohnnyReb:
Functions: THIS PROTEIN BINDS THE CAMP RESPONSE ELEMENT (CRE), A SEQUENCE PRESENT IN MANY VIRAL AND CELLULAR PROMOTERS. CREB STIMULATES TRANSCRIPTION ON BINDING TO THE CRE.
The science jargon is mostly beyond me, but could this talk of transcription refer to gene therapy?
Sesostris 11-28-2005, 01:10 PM Could it be that they were all some how involved with some of these experiments? For that matter, what if Cooper needed a new kidney because of some sort of genetic disorder
Or Susan - Walt's mother - die of a "blood infection"... I'd been wondering if it had been some possibly mutated form of hemophilia or anemia (caused by single-gene defects). Susan also a result of possible experiments... and through her, Walt?
Although it's interesting if Cooper and possibly Emily Locke (a schizophrenic, also a hereditary illness) have had experiments done on them... results that passed onto their son John.... how long have these experiments been going on? At least as long as Locke has existed, presumedly. Possibly his sister too (not to mention there's that weird story of the golden retriever and Locke's sister. Which have many folks speculating about the nature of Walt/Vincent's relationship. Vincent possibly part of some of those zoological/genetic experiments?).
JohnnyREB1977 11-28-2005, 02:22 PM Hey y'all!
Really interesting thread you've got here, cmcdtv! And thanks, bigmouth, for bringing up the CREB info here. I went searching and found some more information on gene therapy, rTMS and CREB. Now, I'm not at all certain about what this stuff is supposed to mean, but I find certain things interesting.
The discussion of locomotion and locomotors (Locke?) and
The talk of "novel" places and novelty in relation to the CREB quote
as well as
motor control in rTMS.
Not sure how it can be twisted into gene therapy yet, though.
First author: Alvarez-Jaimes, Lily (poster)
Poster 165 - Mon 12/07, 12:15 - Hall I
Session 081 - Intracellular signalling II
Abstract A081.2, published in FENS Forum Abstracts, vol. 2, 2004.
Ref.: FENS Abstr., vol.2, A081.2, 2004
Author(s) Alvarez-Jaimes L., Centeno M., Feliciano M. & Maldonado-Vlaar C. S.
Addresse(s) Dept. Biology, University of Puerto Rico, San Juan, Puerto Rico.
Title Phosphorylation of the cAMP response element binding protein (CREB) in the nucleus accumbens during spatial behavior.
Text Several studies have reported a role for the nucleus accumbens (NAcc) in learning and synaptic plasticity. NAcc receives afferent projections from the hippocampus and the pre-frontal cortex that seemed to be involved in mediating spatial learning and memory processes. In addition, NAcc functions as a neural bridge for the translation of cortico-limbic information to the motor system mediating locomotor learning, which is the expression of a correct locomotor response associated with exploration. Previous studies from our laboratory have shown that Protein kinase C (PKC) and Mitogen-activated protein kinases (MAPKs) are activated following training in a food search spatial learning task. In the present experiment, we are further characterizing the molecular substrates that may be subserving NAcc-dependent spatial behavior. The cAMP response element binding protein (CREB), a transcription factor implicated in the formation of Long-Term Memory, was studied in the NAcc following spatial training in the food search spatial learning task. Western blots were performed to detect the phosphorylated and total CREB protein levels. Preliminary data show that CREB is significantly phosphorylated (activated) in the NAcc 48 h after habituation and at 5 min and 1 h after the first spatial training session in comparison with the naive group. Published data has reported that CREB phosphorylation increases by exposure to a novel environment. Therefore, we conducted further control experiments in order to dissociate the effect of a single exposure (novelty), exploratory and spatial behavior in the food search apparatus on CREB activation and expression. Results showed that CREB phosphorylation is significantly increased by exposure to a novel environment. These findings suggest that novelty may contribute to the increase in CREB phosphorylation observed in habituated and spatially trained rats. Supported by NIH/NIDA 1 R29 DA11665-04 (CSMV) and RISE-SUBE R25 GM6-1151-01 (LAJ and MZF).
First author: Doyle, Karen (poster)
Poster 49 - Wed 14/07, 12:15 - Hall I
Session 214 - Regeneration
Abstract A214.4, published in FENS Forum Abstracts, vol. 2, 2004.
Ref.: FENS Abstr., vol.2, A214.4, 2004
Author(s) Doyle K. (1), Barrett L. B. (1), Stevenson M. (2), Mautner V. (3), Seymour L. (2), Berry M. (1) & Logan A. (1)
Addresse(s) (1) Mol. Neurosci. Group, Birmingham, Uk; (2) Dept. Clin. Pharm., Oxford, Uk; (3) Inst. Cancer Studies, Birmingham, UK
Title Neuron specific adenoviral gene therapy for neurotrophin delivery after CNS injury.
Text Adenoviruses (Ad) are promising vectors for gene therapies for CNS injury, however, their use is limited by the widespread expression of CAR. Studies show that the surface of type 5 Ad can be masked by chemical modification with poly[N-(2-hydroxypropyl) methacrylamide] to ablate native viral tropism. We investigated whether polymer-coated viruses (PCV) preferentially infect pinocytotic DRGN (dorsal root ganglion neurons) and RGC (retinal ganglion cells) as a gene therapy approach for neurotrophin stimulated axon regeneration.
Texas Red labelled PCVs were preferentially taken up by DRGN and RGC in mixed cultures. The surface charge of neurons; assessed with polylysine-FITC, indicated that 50% of DRGN and 80% of RGC were positively charged. By contrast, 100% of glia were negatively charged. The surface charge of PVCs was -30mV. This suggests that preferential uptake of PCVs was due both to the highly pinocytotic nature of neurons, and to their cell surface charge. However, infection of neurons using PCVs resulted in poor transgene expression, which may be due to the inability of unmodified PCVs to unpackage in the cytoplasm.
PCVs were retargeted with NGF or FGF-2 to promote gene expression. RGC mixed cultures infected with FGF-2 retargeted PCVs gave higher levels of expression in neurons than glia. Immunohistochemical studies indicated higher expression of the FGF-2 receptor in RGC compared to glia. The results suggest that the atopic Ad strategy is untenable for neurons and that Ad retargeting may be useful with a neuron specific ligand.
Glover et al. (2002) produced an Ad using the promoter Synapsin-1 and the woodchuck posttranscriptional regulatory element (WPRE) resulting in neuron specificity and high transgene expression. We are currently evaluating the strategy of neuronal targeting of neurotrophin genes using this promoter in our CNS models.
Theme Development
Transplantation and regeneration / Regeneration
First author: Paulson, Olaf B. (poster)
Poster 438 - Mon 12/07, 16:00 - Hall II
Session 131 - Control of posture and movement
Abstract A131.4, published in FENS Forum Abstracts, vol. 2, 2004.
Ref.: FENS Abstr., vol.2, A131.4, 2004
Author(s) Paulson O. B. (1), Balslev D. (2), Christensen L. O. D. (3), Law I. (2) & Miall R. C. (3).
Addresse(s) (1) Danish Centre for Magnetic Resonance, Hvidovre, Copenhagen, Denmark; (2) Neurobiology Research Unit, Copenhagen, Denmark; (3) University Laboratory of Physiology, Oxford, United Kingdom.
Title Enhanced accuracy of mirror tracing during rTMS-induced proprioceptive deafferentation.
Text Objective: to test whether a “virtual lesion” induced with transcranial magnetic stimulation (rTMS) over the primary somatosensory cortex improves performance in a mirror tracing task.
Background: in novel situations in which the visual feedback is rotated relative to the movement of the hand - e. g. in a mirror – movement error correlates positively with the activity in muscle spindle afferents and deafferented patients outperform healthy controls. This suggests that proprioception is disadvantageous for motor control when there is a visuoproprioceptive conflict.
Methods: rTMS 15 minutes 1Hz TMS pulses at 110% motor threshold were delivered 3 cm posterior to the motor hotspot of the left hemisphere, at the putative location of the primary somatosensory cortex. This decreases cortical excitability for several minutes after the pulse train.
Experiment 1: 12 healthy volunteers received either real and sham rTMS. Trials of normal tracing were performed before (20 trials) and immediately after rTMS (2 trials) followed by 6 trials of mirror tracing. Each trial lasted 10 seconds with an intertrial interval of 10 seconds.
Experiment 2: 10 healthy volunteers received both real and sham rTMS on two separate days, 2 days apart. Proprioception was measured using a finger position-matching paradigm.
Results: experiment 1: mirror tracing error was smaller following real-rTMS than following sham-rTMS (Mann-Whitney U-test, p<0.05). No difference was found across intervention groups in the speed of mirror tracing (p=0.180), speed of post-rTMS tracing (p=0.937), in the average error over post-rTMS tracing trials (p= 0.485) or in learning speed (p= 0.485).
Experiment 2: proprioceptive mismatch error was larger following real-rTMS than sham-rTMS (paired t-test, p<0.05).
Conclusion: it is possible to enhance mirror drawing accuracy in healthy people, presumably by reducing the excitability of cortical areas that contribute to the sense of hand position.
Theme Motor systems
Control of posture and movement / Kinematics
http://fens2004.neurosciences.asso.fr/posters/Mcle/McleA1.html
Todell 11-28-2005, 06:19 PM Gene therapy failure can lead to cancer as well, interesting since we have seen Diane with some form of disease, more than likely cancer, Claire's boyfriend's uncle had testicular cancer, and Sawyer's uncle had a brain tumor. Could it be that they were all some how involved with some of these experiments? For that matter, what if Cooper needed a new kidney because of some sort of genetic disorder (although this takes for granted that Cooper is Locke's dad and not connected in some other way) and Locke, as part of an experiment (at a different time from his surgery) contacted menigitis with the gene therapy but it went wrong causing his paralysis?
cmcd: Diane is dying of cancer. From "Born to Run"
TOM: (surprised) Holy -- Katie. Wh-what are you doing here?
KATE: Diane's dying of cancer. Thought I owed it to her to come see her.
Also, note this exchange between Locke and Helen in "Orientation"
[Locke outside trying to light a cigarette but can't. A woman from the meeting approaches.]
HELEN: Probably a good idea. You know if you get kidney cancer you've only got one.
TabbyRasa 11-29-2005, 01:29 AM cmcdtv...I mentioned your thread (GMOs....juice) on the Juice theory thread...
http://www.thefuselage.com/Threaded/showpost.php?p=632967&postcount=265
Sam G 11-29-2005, 02:47 AM !!! Genetic Engineering (http://en.wikipedia.org/wiki/Genetic_Engineering) !!!
Isn't there something to do with transhumanism on your Drs. and Missing Limbs thread? (http://www.thefuselage.com/Threaded/showthread.php?p=576358&highlight=transhumansists#post576358)
I think I'm on this thread but if I'm not i want to be.
Sam G 11-29-2005, 03:20 AM Joop wasn't a chimp. Joop was an Orangutan. Orangutan's have 98% the same DNA as Human's do. They have "long calls" very similiar to sounds we've heard on the isalnd. They are extremely strong, live in the treetops.
HIV was passed on through chimps.....oh heck going looking.
http://www.wired.com/news/medtech/0,1286,63424,00.html?tw=wn_tophead_3
Bingo.
Hooper charges that during Koprowski's vaccination campaign, kidneys from chimpanzees infected with SIV were used to grow the virus. The film cites a historical precedent: Another anti-polio campaign in the 1950s injected millions of people with vaccines containing the monkey virus SV40.
http://www.thebody.com/whatis/origins.html
ChiefTanLost 12-05-2005, 10:07 PM Meningococcal disease can lead to the loss of limbs. :)
Todell 01-21-2006, 08:32 PM Gene therapy failure can lead to cancer as well, interesting since we have seen Diane with some form of disease, more than likely cancer, Claire's boyfriend's uncle had testicular cancer, and Sawyer's uncle had a brain tumor. Could it be that they were all some how involved with some of these experiments? For that matter, what if Cooper needed a new kidney because of some sort of genetic disorder (although this takes for granted that Cooper is Locke's dad and not connected in some other way) and Locke, as part of an experiment (at a different time from his surgery) contacted menigitis with the gene therapy but it went wrong causing his paralysis?
Dragging this back up. Interesting that Angelo had a tumor on his spine, no? Is Angelo another failed Hanso gene therapy experiment?
TabbyRasa 02-02-2006, 08:08 PM OK, I picked this thread of many where this could go, but did not re-read the whole thread. I happened upon this screencap of the crib (http://www.lost-tv.com/pictures/displayimage.php?album=38&pos=18) that Michael and Susan were looking at in a flashback in S1/Special.
Check out the signs above the shelves...they say "ATS" "CARRIERS" "TRAVEL". Carriers travel...as in "carriers of disease travel" to other locations on the Island, and/or around the world? Remember the "Quarantine" signs. Or, "carriers within DNA travel" through to the progeny? The "ATS" is the end of "CARSEATS" (seen in lost-media screencap)...extraneous info?
If this is a clue, what does it mean? Michael is standing with open arms in front of these signs. And he was so happy in that scene. After Walt's birth (age 2 or so), Susan took Walt and travelled to Italy (was Michael in Australia?). Susan died of a virus within one week of getting sick, according to Brian, in this epi. And we know (some of) the rest.
Possibly related, but maybe not: here is a link to some info on the polio vaccine (http://longlostlist.kazorum.com/longlostlist-about237.html) that I posted on the LLL after viewing S2/The 23rd Psalm (Eko's priest brother was going to buy polio vaccine). Note: you will need to register at the LLL to post there, and possibly to view, as well. If needed, I can quote some of it here.
cmcdtv 02-03-2006, 12:36 AM tabby, let me just say, when you aren't where to post something, post it either here, the Drs. and missing limbs, or now the mMm thread. Either myself or todell will be able to connect it.
For example. Was Eko born to kill, and the consequence of the experiment in designing a 'killer' there was a disporportionate number of children who fell victim to polio?
To Michael and Walt. It's also the scene where they decide to name Walt after Michael's father right? If his dad was involved in some sort of experiment, Walt would be the third generation. And as todell has suggested, is it possible that Susan learned something about Michael and Walt that caused her to flee? That she was debating in that scene, and she reconciled naming the child after Michael's dad with taking him out of Michael's life?
Always post on some thread that I've started tabby. I love your posts and they make me think of things I hadn't even considered.
TabbyRasa 02-03-2006, 02:12 AM Always post on some thread that I've started tabby. I love your posts and they make me think of things I hadn't even considered.
Thanks:) ...that's what I hope when I find something that seems important but I can't see the light...I searched and found some "sickness" and "2 months" threads, but realized it needed to go to you. I always figure if I dump the info somewhere, it might make sense to someone!
I still think it was cruel of Susan to take Walt AND Michael's rights away...he was so happy in that scene, never saw him that happy again...it really took a toll on him when he lost Walt. Because he was the stay-at-home dad while Susan worked, so he really bonded with him. But maybe it wasn't her choice and she was forced.
And yeah, I think there is something about the polio vaccine and Eko...maybe because his brother was shot and killed, the vaccine was never acquired or distributed, and thus the children fell victim, as you say?
Doc Bushwell 02-04-2006, 11:41 AM First, I love the gene therapy speculation, folks, and I am intrigued by the whole infection theme which is interwoven into the "Lost" mythology. Just as there is a "Science of Star Trek" (sci-fi with a nod to real science) so there is an emerging "Science of 'Lost'."
Just a point of clarification in the gene therapy discussion:
Adenoviruses, the vector most often used for gene therapy experiments, are distinct from the influenza virus, i.e. they're in two different families. Adenoviridae use linear double stranded DNA as their genetic material whereas Orthomyxoviridae (the viral family which encompasses influenza viruses A, B & C) use single stranded RNA as their genetic complement. Adenoviruses and influenza/orthomyxoviruses have other differing morphological features.
With that said, carry on!
Todell 02-04-2006, 03:50 PM Grazie, Doc! And welcome to the Fuselage! Anything else you can add to the discussion is most welcome--
cmcdtv 09-01-2006, 05:49 PM In light of recent news (http://www.cbsnews.com/stories/2006/08/31/health/main1955526.shtml?source=RSS&attr=HOME_1955526): I thought I would bring back this old thread.
Makes me wonder if whatever cured Rose was a naturally occuring virus, rather than the large magnet. And that's what the vaccine is for, for people who are not sick, to protect them from a virus that has been experimented on by THF for general use. If they are trying to spread a worldwide pandemic, like some have suggested, what if it is worldwide pandemic to save us? A virus that can kill whatever malevolent disease the world is due?
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