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Author Topic: Biologists devise invasion plan for mutations by John Bohannon
glassman
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http://www.sciencemag.org/content/347/6228/1300.full

Ok, i was gong to put this onto "the space invader" thread, but it should get it's own.

If you haven't heard of this already you will. Something just happened that is either a tempest in a teacup or it's big really friggin BIG.

It could be a tempest in a teacup because the guys (Gantz and Bier) who did it MAY NOT have done what they think they did and the folks at SCIENCE don't care. They don't care if it's a good paper because they need a bullypulpit to get some ehtics discussions.

it could alos be a tempest in a teacup because the pictures of the flies look to ME like a bust.
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A rare mosaic female fly, with a lighter left half mutated by MCR and a wild-type darker right half.UCSD, VALENTINO GANTZ AND ETHAN BIER

Mosaics tend to be non-germline transformations. If these guys are claiming to have inheritable genes that produce mosaics, then they have a genetic mess to clean up- a pretty bad one. Cleaning it up will teach us alot.

Insects do not have stem cells like us humans and oh, almost all other animals..... all invertebrate (with backbones) have stem cells. Thats' a big deal.

I suspect that SCIENCE may be setting this up as failure not just a failure but a spectacular failure so they can initiate a huge controversey just for th esake of a media frenzy and some outrage.
The researchers only did this transformation at the end of last Dec and it's being published in March? that's too soon. It was accepted march 10 and published on the 19th? that's ridiculouslously fast.

On the other end? This could be a huge step forward in gene manipulation, but it is not ready for prime time.

What they did was infect the fruit fly with a genetic tool from the bacterias viral immune system without any controls built in. CRSPR is part of the molecular machinery in bacteria that allows a bacteria to fight off "alien" (virus) DNA and RNA. By cutting out a 22 letter sequnce of the invaders code it can incorporate that 22 letter sequence into it's own machinery and produce the mirror image of that code to create antibodies that attach themselves to the foreign DNA or RNA. Mirror images of DNA and RNA are sticky to each other, it's a fundamntal fact of the chemistry, and when they stick to each other? They stop functioning. It's called transcription interference. Trascription blocking is one of hte promising pest control strategies that has yet to put to real world application. The toolkit from the bacteria is not designed to be inherited by it's offspring through sexual reprodution. Bacterias divide like the cells in our body do, not like sex cells do. There's a big difference and I'm not going to go into the differnce here. It's why our kids do not get immunity from diseases just because we have the immunity. Bacteria do get immunity from their parents, but we don't. The claim of this paper is that these guys placed this toolkit into the inheritable DNA of the fruit fly and that it was inherited. There are subtle differnces between insect reproduction and mammalian reproduction. The most important issue is that insects don't have stem cells and INHERIT RNA from their parents that mammals do not. It is highly likely that the experiment is not proof of inheritable DNA recombination, but inherited RNA machinery. Which is till very important. I can't read the actual procedures of the experiment until tomorrow, and whn i do read it i can share more.

There are many companies selling CRISPR toolkits of the shelf right now. Sigma Alldrich is a big one- google CRISPR CASS 9 and CRISPR CasCade to see who is profiting.

Keep in mind that this ethics chitstorm that these guys just started may end up with severe regulations being imposed.

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Relentless.
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What are the odds of adapting this to humans?
Furthermore, what are the odds of continuing any sort of information from elder to younger? Not just virus/bacteria but memory?

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glassman
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They are in the process of banning itin humans right now.
Even the scientists who are not speicailists in the feild are are running around saying the sky is falling.

That's why i went ahead and posted this article. The only reason i am conversant in this work is because my wife does it. More precisley she did it in mosquitoes and another fly over a decade ago and has not been allowed to followup any of her work. She has been shut out for business reasons rather than ethics reasons.

First off, i am still waiting to see the procedures, they should be available to me by late tonight. There's a strong indication that the experiment they did was not successful like they claim. The gene they wanted to "mutate" (i hate that word) is the yellow pigmetn gene. The mutant they used causues yellow to not be as intense hence the quote under the photo- ( with a lighter left half mutated by MCR).

OK so becuase this is a Negative marker, as opposed to glow in the dark genes from jelly fish which are apositive marker, these guys needed to use some complicated tests to prove they initiated a Mutagenic Chain Reaction. THEY DID NOT HAVE TIME TO CONDUCT THOSE TESTS PROPERLY. Thats' why i pointed out the dates.

Now come the second problem. CRIPR CAS9 is a protein that can actually attach itself tot eh side of DNA and casue the transcritpiton machinery to be blocked by its presence on the DNA molecule. They used the right code to block the yellow gene. So, it is possible, even likely that they have not actually made the genes "jump" around in the organism once they were inserted. My wifes designs were very carefully set up to avoid this mutagenic chain reaction as they call it now. We have called these autonomous transposable elements other things in the past, it isn't news.

Humans? Yes. memory? sure. we see animals do it all the time. The new project here is ants. Ants communicate using chemicals- we are trying uncode exaclty how they do it right now. Will that lead human memory? Not likely becuase insects are completely different from us. If human memory is stored on protein cassettes? We'll be able to inherit it and more.We could buld RNA for you to eat and your memeroy will be built once RNA arrives at the correct place. BTW? That's alot of research to get that done and that's not going to happen in my lifetime unless of course we figure out how to stop the epigentic aging clock.

http://www.nature.com/news/biomarkers-and-ageing-the-clock-watcher-1.15014

it could happen next week, but not if we are blocked from doing the research....

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glassman
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Hah! while i was writing the above the procedures came into my mailbox. They did the fastest simplest verification that they could. I'm not able to cut-paste copyrighted stuff like this. Science is the kind of outfit that will go after copyright infringemts just because.

They made a mess, but there's a decnt chance that did cause a chain reaction. It's not nearly as precise as it needs to be. I m sure that Scince would not have accepted this paper with this low level of proof if there was not some political agenda. The movement to ban this research can defintiley use this publication as a reason to restrict access.
Once you publish without a patent the tech is free to use by anyone -Big pharma hates that. They try to move in and shut down whoever puts the tech into the public domain.The problem is that if the bans are put in place? Only big pahrma will be able to do the work and then they get to own it all. That's what is really at stake. When these guys publish like this? Ownership of the tech. is in the public domain.

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glassman
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quote:
Originally posted by Relentless.:
What are the odds of adapting this to humans?
Furthermore, what are the odds of continuing any sort of information from elder to younger? Not just virus/bacteria but memory?



Remeber that DNA is "copied" or trancribed to RNA and RNA has about 20 "flavors". Some RNA grabs amino acids (which only plants can make) and other RNA's tell those RNA's with heir amino acids how to line up. Other RNA's give instruction on where to go within the cell and even others give isntructions on the condition of the cell to other cells nearby. This is an oversimple version of how DNA/RNA builds your body. neuroscientists are finding that certain of the proteins build up connections between brain cells which corellate to memory. perosnally i beleive cosciousness may have more than just memory but i also recognise that all animals have enough consciousness to want to stay alive so placing a value on levels of consciousness is a waste of time. Prions cause proteins to fold in ways that they are not prone to by their own chemistry. They cause mad cow disease. If prions can "erase memeory" they can also be a major protion of creating it, here's the prevailing THEORY-

For a brain cell, keeping a memory around is a lot of work. A variety of proteins need to be continually manufactured at the synapse, the small gap that interfaces one cell to another. But whereas a cell may have a multitude of synapses, the protein synthesis that grows and maintains the connection only occurs at specific ones that have been activated. Work in the sea slug Aplysia (a favorite of neuroscientists because of its large cells) showed that a protein called CPEB, for cytoplasmic polyadenylation element binding, is necessary to keep a synapse activated. Si and Kandel, working with yeast prion specialist Susan Lindquist of the Massachusetts Institute of Technology, showed in 2003 that CPEB acts as a prion.
Prions are proteins with two unusual properties: First, they can switch between two possible shapes, one that is stable on its own and an alternate conformation that can form chains. Second, the chain-forming version has to be able to trigger others to change shape and join the chain. Say that in the normal version the protein is folded so that one portion of the protein structure—call it "tab A"—fits into its own "slot B." In the alternate form, though, tab A is available to fit into its neighbor's slot B. That means the neighbor can do the same thing to the next protein to come along, forming a chain or clump that can grow indefinitely.

Once the prion's chain reaction gets started it's self-perpetuating, and thus the synapse can be maintained after the initial trigger is gone—perhaps for a lifetime. But that still doesn't explain how the first prion is triggered or why it only happens in certain synapses and not others.

http://www.scientificamerican.com/article/prions-are-key-to-preserving-long-term -memories/

not only is it a waste of time to argue about what actaully constitutes "consciousness" in my opinion, it seem obvious to me that what we call instinctual behaviour in animals is actually physically inherited memory.

Study: decapitated flatworms retain memories, transfer to new brains

Biologists that sliced off the heads of trained planarian flatworms have discovered that the regenerative creatures can retain memories and transfer these to their new, regrown brains.
http://www.wired.co.uk/news/archive/2013-08/13/worm-brains

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glassman
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OK, This just got published a few minutes ago;
the levee is breaking and this CRISPR toolkit is showing up everywhere because it wasn't patented and all the biotech firms are competing to provide the service off the shelf cheaply and efficiently...
I am thinking i might add a few chameleon colors to my crested geckoes....

Mammoth step forward? Scientists splice Woolly DNA into elephant cells
Published time: March 23, 2015 04:43
The introduction of the genes was done through a new developed technique CRISPR (clustered regularly interspaced short palindromic repeat), that allows for precise editing of DNA taking out parts of modern elephant DNA and replacing them the prehistoric genes.

http://rt.com/news/243097-dna-mammoth-cloning-progress/

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Relentless.
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I don't get a bad feeling from this.. I'm not sure why but I suspect we're supposed to be smart enough to have this ability. Moral enough? Kind of doubt that, but perhaps it comes from ability.

Interesting thought that morality comes from the misdeeds of ability..

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Relentless.
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There's a chance I should say the exploration of ability?

Interesting either way.

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glassman
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mistakes will be made. nature has a way of selecting them out and dealing with them. hopefully they won't be too serious.
The part that annoys me is that i wasn't joking when i said that aging processes could be better controlled or manipulated, and the longer we wait to do it the more people lose the chance at benefiting from it. Say people could live for 200 healthy years instead of 80? Alot of things would probably change, and mostly for the better. Peopel could be more patient and you'd have a higher percentage of people with a great deal more wisdom.

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Relentless.
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Oh absolutely. Imagine if the base population age was 105 instead of what it is now at what? 30?

Imagine their inability to sway opinion with their bs.

I suspect that would be cause enough to not allow it.

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Relentless.
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Honestly I suspect it is already happening. Not sure about you but I know for a fact that I am far more youthful at 41 than my father or either grandfather was at this age.

I also notice that friends of mine who are my age and 20 years more look vastly more young than similar age groups did 20 or 30 years ago. Could be perception I suppose but I doubt it.

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glassman
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quote:
Originally posted by Relentless.:
Honestly I suspect it is already happening. Not sure about you but I know for a fact that I am far more youthful at 41 than my father or either grandfather was at this age.

I also notice that friends of mine who are my age and 20 years more look vastly more young than similar age groups did 20 or 30 years ago. Could be perception I suppose but I doubt it.

I have noticed. I assume it's got to do with year-round availability of fresh fruits and vegetables and good refrigeration and storage of all food.
There is a clear and unambiguous set gene of markers that define life stages. Embryonic stem cells can become any other cell. Whne the stem cells "decide" which set of cells they are going to organise into, a step called methylation occurs. The methylation causes that part of the gene to be blocked from transcribing. It usually allows another area of the gene to become active in response. We are learning right now how to DEmethylate. Of course this methyaltion and demethylation occurs at many sites at the same time and also in specific sequences along the timeline. You have to remember that it will take alot of trial and error to get it right. Science imporves incrementally and steadily toward goals until somebody makes a break through and then progress can be overwhelming. CRISPR is major breakthrough but so many people have become paranoid about GMO that linear scientific progress is being interrupted and breakthroughs will be even fewer and far between.

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glassman
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I keep mentioning stem cells for a good reason. The fly D.mellanogaster that was "tranformed" (or not) in the above mentioned article has no methylation markers in it's genome. The fruit fly has been a 'model organism" in genetics for decades but it doesn't have stem cells. Insects don't have stem cells. It's a bad model organism. When my wife decided to get into this game she chose insects because insects tend to be ignored by PETA and other anti-research groups. Beleive me they are actively meddling and interfering even at major research facilities. The ants and wasps and bees do have a homologue to stem cell activity though. When a bee or ant is born the colony feeds it specific molecules made by other members of the colony that determine whether it will become a "sexual" (queen) or a "worker". Queens live ten times or more longer than the workers. A worker European honey bee lives about 60 days, and queen bees live for three or more years (this is variable). The differences are remarkable and people have known this since Egytptina times or earlier. My Great Granma maternal-paternal ate comb honey every day of her life and swore that it made her live longer. She died at 89 and was pretty healthy until the year she died. If you go online you can find thousands of nutritioanl supplement preparations from Royal jelly which is the food that bees feed their larvae. The queen gets a full diet of it for many days while the workers get it for only three days. Ants are still a big question mark. The research hasn't been done yet. Nobody knows the analog for Royalactin (the most intersting protein in Roayl Jelly) in ants yet. So you can guess where we are headed right?
Anyway in ants and bees, methylation starts to occur in the workers and the queens (but in drosophilla there is no methylation) right away. It causes a visible difference in the ants and bees queens and workers. So we have a roadmap with visible signposts to lay out which sites methylate and why at different stages. Will it lead direclty to human longevity? prolly not. if published to teh public domain, it could lead another researcher, if they are where they need to be, to make that breakthrough that we need.

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