Sunday, February 12, 2012

Gene Therapy For Inherited Blindness And The Allegory of the Cave

Another victory for genetic therapy, restoring sight to the blind. Certain genetic disorders rob individuals of sight. Imagine trying to navigate the world without being able to see. This article describes how genetic therapy is being used to reverse a type of genetic blindness.

I wonder what the impact technology like this would have on a person who has spent their entire life in darkness. I am reminded of the Allegory Of The Cave.
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The Allegory of the Cave

  1. Plato realizes that the general run of humankind can think, and speak, etc., without (so far as they acknowledge) any awareness of his realm of Forms.
  2. The allegory of the cave is supposed to explain this.
  3. In the allegory, Plato likens people untutored in the Theory of Forms to prisoners chained in a cave, unable to turn their heads. All they can see is the wall of the cave. Behind them burns a fire.  Between the fire and the prisoners there is a parapet, along which puppeteers can walk. The puppeteers, who are behind the prisoners, hold up puppets that cast shadows on the wall of the cave. The prisoners are unable to see these puppets, the real objects, that pass behind them. What the prisoners see and hear are shadows and echoes cast by objects that they do not see. Here is an illustration of Plato’s Cave:


    From Great Dialogues of Plato (Warmington and Rouse, eds.) New York, Signet Classics: 1999. p. 316.
  4. Such prisoners would mistake appearance for reality. They would think the things they see on the wall (the shadows) were real; they would know nothing of the real causes of the shadows.
  5. So when the prisoners talk, what are they talking about? If an object (a book, let us say) is carried past behind them, and it casts a shadow on the wall, and a prisoner says “I see a book,” what is he talking about?He thinks he is talking about a book, but he is really talking about a shadow. But he uses the word “book.” What does that refer to?
  6. Plato gives his answer at line (515b2). The text here has puzzled many editors, and it has been frequently emended. The translation in Grube/Reeve gets the point correctly:
    And if they could talk to one another, don’t you think they’d suppose that the names they used applied to the things they see passing before them?”
  7. Plato’s point is that the prisoners would be mistaken. For they would be taking the terms in their language to refer to the shadows that pass before their eyes, rather than (as is correct, in Plato’s view) to the real things that cast the shadows.If a prisoner says “That’s a book” he thinks that the word “book” refers to the very thing he is looking at. But he would be wrong. He’s only looking at a shadow. The real referent of the word “book” he cannot see. To see it, he would have to turn his head around.
  8. Plato’s point: the general terms of our language are not “names” of the physical objects that we can see. They are actually names of things that we cannot see, things that we can only grasp with the mind.
  9. When the prisoners are released, they can turn their heads and see the real objects. Then they realize their error. What can we do that is analogous to turning our heads and seeing the causes of the shadows? We can come to grasp the Forms with our minds.
  10. Plato’s aim in the Republic is to describe what is necessary for us to achieve this reflective understanding. But even without it, it remains true that our very ability to think and to speak depends on the Forms. For the terms of the language we use get their meaning by “naming” the Forms that the objects we perceive participate in.
  11. The prisoners may learn what a book is by their experience with shadows of books. But they would be mistaken if they thought that the word “book” refers to something that any of them has ever seen.
  12. Likewise, we may acquire concepts by our perceptual experience of physical objects. But we would be mistaken if we thought that the concepts that we grasp were on the same level as the things we perceive.

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People in darkness their entire lives would not be unlike the prisoners from Plato's cave. They grew up hearing things described to them. And now are granted sight for the first time their entire perceptions of reality would be changed. When humanity crosses the threshold into singularity will it be similar to these patients?

Humanity itself could be seen as blind and the concepts of what will come post singularity are earth shattering. Reality changes around us all the time. These patients that are going to be able to see for the first time have a unique chance to look at the world through innocent eyes. Will they like what they see?

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Article Taken From http://www.kurzweilai.net

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Gene therapy for inherited blindness succeeds in patients’ other eye

February 12, 2012


Retina photo of a patient with Leber congenital amaurosis (credit: National Eye Institute, NIH)
Retinal gene therapy for congenital blindness has taken another step forward, as research further improved vision in three adult patients previously treated in one eye.
After receiving the same treatment in their other eye, the patients became better able to see in dim light, and two were able to navigate obstacles in low-light situations, according to researchers at The Children’s Hospital of Philadelphia and the University of Pennsylvania . No adverse effects occurred.
Neither the first treatment nor the readministered treatment triggered an immune reaction that cancelled the benefits of the inserted genes, as has occurred in human trials of gene therapy for other diseases. The current research targeted Leber congenital amaurosis (LCA), a retinal disease that progresses to total blindness by adulthood.
“Patients have told us how their lives have changed since receiving gene therapy,” said study co-leader Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at Penn. “They are able to walk around at night, go shopping for groceries and recognize people’s faces — all things they couldn’t do before. At the same time, we were able to objectively measure improvements in light sensitivity, side vision and other visual functions.”
Other objective results came from brain signals seen in neuroimaging. When a dimly flickering checkerboard pattern flashed in front of a patient’s recently treated eye, an area in the brain responsible for vision lit up during functional magnetic resonance imaging (fMRI).“This finding is telling us that the brain is responding to the eye’s sensitivity to dim light,” said radiology researcher Manzar Ashtari, Ph.D., of The Children’s Hospital of Philadelphia, the study’s co-leader.
LCA is a group of hereditary retinal diseases in which a gene mutation impairs production of an enzyme essential to light receptors in the retina. The study team injected patients with a vector, a genetically engineered adeno-associated virus, which carried a normal version of a gene called RPE65 that is mutated in one form of LCA.
Previous clinical trial with one eye
The researchers in the current study previously carried out a clinical trial of this gene therapy in 12 patients with LCA, four of them children aged 11 and younger when they were treated. Exercising caution, the researchers treated only one eye — the one with worse vision. This trial, reported in October of 2009, achieved sustained and notable results, with six subjects improving enough to no longer be classified as legally blind.
The Center for Cellular and Molecular Therapeutics (CCMT) at The Children’s Hospital of Philadelphia sponsored both the initial clinical trial and the current study, and manufactured the vector used to carry the corrective gene. Katherine A. High, M.D., a co-author of both studies, is the director of the CCMT, and a pioneering gene therapy researcher.
The research team’s experiments in animals had showed that readministering treatment in a second eye was safe and effective. While these results were encouraging, the researchers were concerned that readministering the vector in the untreated eye of the patients might stimulate an inflammatory response that could reduce the initial benefits in the untreated eye.
“Our concern was that the first treatment might cause a vaccine-like immune response that could prime the individual’s immune system to react against a repeat exposure,” said Bennett. Because the eye is “immune-privileged” — relatively isolated from the body’s immune system — such a response was considered less likely than in other parts of the body, but the idea needed to be tested in practice.
As in the first study, retina specialist Albert M. Maguire, M.D., a study co-author, injected the vector into the untreated eyes of the three subjects at The Children’s Hospital of Philadelphia. The patients had been treated one and a half to three years previously.
The researchers continued to follow the three patients for six months after readministration. They found the most significant improvements were in light sensitivity, such as the pupil’s response to light over a range of intensities. Two of the three subjects were able to navigate an obstacle course in dim light, as captured in videos that accompanied the published study.
No safety problems found
There were no safety problems and no significant immune responses. There was even an unexpected benefit — the fMRI results showed improved brain responses not just in the newly injected eye, but in the first one as well, possibly because the eyes were better able to coordinate with each other in fixating on objects.
The researchers caution that follow-up studies must be done over a longer period and with additional subjects before they can definitively state that readministering gene therapy for retinal disease is safe in humans. However, said Bennett, the findings bode well for treating the second eye in the remaining patients from the first trial, including children, who may have better results because their retinas have not degenerated as much as those of the adults.
Furthermore, Bennett added, the research holds promise for using a similar gene therapy approach for other retinal diseases. Ashtari said that fMRI may play a future role in helping to predict patients more likely to benefit from gene therapy for retinal disease.
Ref.: Jean Bennett and Manzar Ashtari et al. AAV2 Gene Therapy Readministration in Three Adults with Congenital BlindnessScience Translational Medicine, Feb. 8, 2012 DOI: 10.1126/scitranslmed.3002865.
Ref.: Gene Therapy for Leber Congenital Amaurosis, National Eye Institute

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