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nudge

CRISPR Gene editing - The Next Step in Human Evolution?

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Is anyone else following the latest developments in CRISPR/gene editing with great interest? I find the topic extremely fascinating and controversial; so many potential applications of the technology in the future, and so many possible unintended and unexpected consequences of tampering with genomes, not to mention certain ethical and safety concerns. Feels like a really good science fiction, haha. 

Do you think the technology might eventually lead to us hijacking and shaping the course of our own evolution? Could it be a major breakthrough to eradicate serious diseases and improve the quality of our lives? Or do you think that "playing God" will have inevitable catastrophic consequences for humanity? Is a Brave New World or Gattaca scenario potentially on the cards here?

 

For those who need a short overview, here's quite a good video of CRISPR in a nutshell. It's a bit out of date already with new discoveries being made almost daily, but the basics are still very nicely explained for laypersons:

 

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The one thing it will never be able to account for is intolerance. It will likely breed a different sort. 

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Some of the biggest challenges here lie with control and the ability to not let this go down the wrong path (which it will of course no one can really stop that). I think that if someone tries to police all of this it won't end nicely for anyone in the end. I do, however, like the idea that using CRISPR and CAS9 to help eradicate disease is where this all started. So many countries can't handle the kind of problems that diseases bring to the table and with recent outbreaks in recent years if the technology only takes a few weeks to build a viable solution (I think its unstable) then we could come to an era where diseases which have caused so many problems can be wiped out fast. The rest about super soldiers, etc is something I think we're far away from based on what is said about generations needing to reproduce and also due to the fact that if you had a genetically modified partner and you yourself aren't genetically modified then it probably leads to less stronger results.

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Oh I think that part of the supersoldiers and related stuff is pretty much irrelevant at any case. Man to man combat is mostly a thing of the past, modern warfare doesn't rely on it that much anymore, so I don't think any power in the world would be really interested in producing armies of superior cannon fodder. What does worry me most - other than unknown unexpected outcomes of gene manipulation in general - is the thought of big corporations owning both the rights over genetic code AND controlling the tools of modification.

As for needing generations for the genetic modification to spread successfully, there's two different options. If we're talking about genetically modifying somatic cells in an individual, then yes, in that case it will only affect the treated individual and will not be inheritable - and that's what the technology is mostly about at the moment. However, if we make DNA changes in reproductive cells (sperm, egg or one-cell embryos),  it will become permanently sealed in the germline and will be inherited by future generations, and that's by far more dangerous when it comes to long-term risks in general. Then there's also a gene drive technology which seems to make a certain gene to spread rapidly through the population by making sure that it's always inherited. Combine the two, and it's a very slippery slope. Sure, you'd still need generations for it to affect a substantial fraction of a population, but theoretically, it's already possible.

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18 hours ago, nudge said:

As for needing generations for the genetic modification to spread successfully, there's two different options. If we're talking about genetically modifying somatic cells in an individual, then yes, in that case it will only affect the treated individual and will not be inheritable - and that's what the technology is mostly about at the moment. However, if we make DNA changes in reproductive cells (sperm, egg or one-cell embryos),  it will become permanently sealed in the germline and will be inherited by future generations, and that's by far more dangerous when it comes to long-term risks in general. Then there's also a gene drive technology which seems to make a certain gene to spread rapidly through the population by making sure that it's always inherited. Combine the two, and it's a very slippery slope. Sure, you'd still need generations for it to affect a substantial fraction of a population, but theoretically, it's already possible.

I learned something new there and had to go do some reading to play catchup. I am more into prosthetic mods and bionics versus gene modification but its still very fascinating stuff. That part about gene drive in particular is fascinating because it allows modifications to impact populations over a period of time with the ramifications of changes in the host cells which no one can really control.  The day they master that we're going to be seeing some very interesting evolutionary patterns. I take the example of getting rid of something as terrible as cancer for good but with no real control on all the other factors around the mutation/mod we can't say for sure that what we're eradicating won't have an impact elsewehere in the host or their bloodline.

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8 hours ago, Mel81x said:

I learned something new there and had to go do some reading to play catchup. I am more into prosthetic mods and bionics versus gene modification but its still very fascinating stuff. That part about gene drive in particular is fascinating because it allows modifications to impact populations over a period of time with the ramifications of changes in the host cells which no one can really control.  The day they master that we're going to be seeing some very interesting evolutionary patterns. I take the example of getting rid of something as terrible as cancer for good but with no real control on all the other factors around the mutation/mod we can't say for sure that what we're eradicating won't have an impact elsewehere in the host or their bloodline.

I've just read that clinical human trials are expected to begin (approval pending) in Europe and the US in 2018 for subjects with sickle cell disease and β thalassemia. Numerous clinical trials on cancer have been already underway in China for quite a while, I'd love to see the results, but information is obviously very scarce... Some researchers even predict that this could be a new Space Race 2.0, haha.

And yes, it is very fascinating. I'm even quite tempted to buy some stock in the industry; definitely a very speculative, volatile and high-risk investment, but I'm pretty curious to see how it works out in a long-term.

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9 minutes ago, nudge said:

The Chinese have always been ahead of everyone in the gene race. I remember reading an article years ago which stated that they do all this without having to get too much government regulation and that is what has led to a majority of breakthroughs on their side. Move over to the US and you've got all kinds of regulations that stop this, not to mention the fact that the participant has a high chance to ending up dead as well which won't sit well with clinical trials that anyone says are okay. This is where the line is drawn and is also potentially why the science as a whole has failed to mature fast enough in Western countries. The downside to the Chinese methodology is introduction of other gene related issues into the population considering no one is really controlling all this and the earliest clinical trials for this go back to 2015. I agree with some of the comments as well saying that this is all really about money and the prestige of saying we did it first. Luckily for everyone involved the only 'big' issue is an immune response problem which I am sure they will fix in the following years.

Its not really a race when there is only one horse running towards the finish line. 

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3 minutes ago, Mel81x said:

The Chinese have always been ahead of everyone in the gene race. I remember reading an article years ago which stated that they do all this without having to get too much government regulation and that is what has led to a majority of breakthroughs on their side. Move over to the US and you've got all kinds of regulations that stop this, not to mention the fact that the participant has a high chance to ending up dead as well which won't sit well with clinical trials that anyone says are okay. This is where the line is drawn and is also potentially why the science as a whole has failed to mature fast enough in Western countries. The downside to the Chinese methodology is introduction of other gene related issues into the population considering no one is really controlling all this and the earliest clinical trials for this go back to 2015. I agree with some of the comments as well saying that this is all really about money and the prestige of saying we did it first. Luckily for everyone involved the only 'big' issue is an immune response problem which I am sure they will fix in the following years.

Its not really a race when there is only one horse running towards the finish line. 

There was a great AMA thread on reddit with researchers from Doudna's lab at UC-Berkeley and The National Human Genome Research Institute recently, and one of the discussed topics was this particular immune system issue. It appears that Cas9 enzymes often used for research are originally from common bacteria and so the human body may have already formed immune responses against those proteins. Therefore modifications of the CAS enzymes or finding different enzyme from microorganisms that do not cultivate in human bodies are among the ways to get around this immune response challenge.

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4 minutes ago, nudge said:

There was a great AMA thread on reddit with researchers from Doudna's lab at UC-Berkeley and The National Human Genome Research Institute recently, and one of the discussed topics was this particular immune system issue. It appears that Cas9 enzymes often used for research are originally from common bacteria and so the human body may have already formed immune responses against those proteins. Therefore modifications of the CAS enzymes or finding different enzyme from microorganisms that do not cultivate in human bodies are among the ways to get around this immune response challenge.

Interesting. So the vehicle for introduction is something that the human body naturally defends against? Aren't there risks involved with finding other carriers that could potentially lead to mutations (long term of course) that could then potentially require some sort of control?

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16 minutes ago, Mel81x said:

Interesting. So the vehicle for introduction is something that the human body naturally defends against? Aren't there risks involved with finding other carriers that could potentially lead to mutations (long term of course) that could then potentially require some sort of control?

It's very likely that the delivery of Cas9 from any bacteria will always elicit some sort of immune response, but the strength of it can probably be tested in advance and controlled. I think potential mutations is not the biggest issue here (it could be avoided by the use of naturally occurring anti-CRISPR proteins, a sort of an off-switch which would turn-off the gene editor and thus remove the danger of any potential future mutations), it's rather antibodies and T-cells rendering the therapy ineffective and triggering a widespread attack on the body's own tissues that would be extremely dangerous. To avoid immune reactions, some researchers take a different approach where they only use CRISPR/Cas9 outside of the host body to edit the genes in the lab and then return the edited, Cas9-free cells back to the host (that's the approach in current clinical trials too). This is definitely limiting though, as it wouldn't work in treating many genetic diseases. However, if you introduce an alternative carrier that doesn't trigger any (or just insignificant) immune response AND then use the off-switch so it doesn't stick around in the body anymore, both problems could be solved, potentially?

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Gene editing and supersoldiers?

All we need are nuclear equipped walking battle tanks called Metal Gear and we're well on our way.

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3 minutes ago, Bluebird Hewitt said:

Gene editing and supersoldiers?

All we need are nuclear equipped walking battle tanks called Metal Gear and we're well on our way.

I wouldn't take supersoldier and designer-baby stuff  too seriously, it's nothing more than a sensationalist utopian (or dystopian, rather) fantasy. At this point, at least :ph34r:

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Well you can put me down for the Youth Gene right off the bat and I am fairly sure Deadlinesman is putting his hand up high for the extra hair... 

On a more serious note this is where science fiction becomes science fact and only our imaginations limit progress.. When you think of the potential to do good then you would suggest that we push on but always there must be some caution involved.

I couldn't imagine for example many years further down the road having the potential to live thousands of years because we have eradicated old age and disease, We are over populated as a planet as it is without having people live well beyond what the planet would be capable of sustaining. It would force us out into space looking for sustainable planets to colonize... Living for so long would make deep space travel more realistic. Whats 15 years getting to a planet when you can live for thousands?? On the plus side never getting old or dying would mean that any knowledge learned would stay with us rather than being lost when someone passed away for example and this would allow us to continue building rather than starting over with each new generation. 

Crippling diseases I could understand eliminating if possible that could only be a good thing for peoples quality of life like the Cancer theory but where would you stop? We are all unique and yet if parents could pick just the best bits to have some sort of ideal model human being then we would all become almost the same and I cant decide if that's a good thing or not? 

One of the most important things for me is that being able to live for so long ( if they ever actually achieve that ) takes away a massive part of what makes us human. The feelings of losing a loved one for example, Cherishing what time you have because you know that it could gone at any time, All these sorts of things is what makes you the person you are.. I might think that with never dying or living forever there might be a danger we could become a little bit robotic if you like, lose those feelings that give us great joy or great sadness... We might take things for granted perhaps.. 

So much to discuss on this subject really... so many things to take into account

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11 hours ago, nudge said:

It's very likely that the delivery of Cas9 from any bacteria will always elicit some sort of immune response, but the strength of it can probably be tested in advance and controlled. I think potential mutations is not the biggest issue here (it could be avoided by the use of naturally occurring anti-CRISPR proteins, a sort of an off-switch which would turn-off the gene editor and thus remove the danger of any potential future mutations), it's rather antibodies and T-cells rendering the therapy ineffective and triggering a widespread attack on the body's own tissues that would be extremely dangerous. To avoid immune reactions, some researchers take a different approach where they only use CRISPR/Cas9 outside of the host body to edit the genes in the lab and then return the edited, Cas9-free cells back to the host (that's the approach in current clinical trials too). This is definitely limiting though, as it wouldn't work in treating many genetic diseases. However, if you introduce an alternative carrier that doesn't trigger any (or just insignificant) immune response AND then use the off-switch so it doesn't stick around in the body anymore, both problems could be solved, potentially?

Learned something new there. when you say that they use CRISPR/Cas9 from outside the body isn't that the same as cell invasion and doesn't body try and fight that? I can't imagine them being able to shut all auto-immune responses?

9 hours ago, Bluebird Hewitt said:

All we need are nuclear equipped walking battle tanks called Metal Gear and we're well on our way.

One day we'll see a gene-therapy bottle with Solid Snake on it. Then ... O.M.G.

6 hours ago, Bluewolf said:

I couldn't imagine for example many years further down the road having the potential to live thousands of years because we have eradicated old age and disease, We are over populated as a planet as it is without having people live well beyond what the planet would be capable of sustaining. It would force us out into space looking for sustainable planets to colonize... Living for so long would make deep space travel more realistic. Whats 15 years getting to a planet when you can live for thousands?? On the plus side never getting old or dying would mean that any knowledge learned would stay with us rather than being lost when someone passed away for example and this would allow us to continue building rather than starting over with each new generation. 

This one fascinates me for other reasons and more importantly the point that you mention about knowledge never being lost. Today, our brains are so limited in their actual use by us eventhough a lot of stuff happens automatically and in more cases involuntarily. Imagine a longer lifespan teaching us as  a race to harness that power. 

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2 hours ago, Mel81x said:

Learned something new there. when you say that they use CRISPR/Cas9 from outside the body isn't that the same as cell invasion and doesn't body try and fight that? I can't imagine them being able to shut all auto-immune responses? 

No no, I mean editing ex vivo as opposed to in vivo CRISPR delivery methods. As in, they take certain cells from your body (e.g bone marrow, blood cells etc), apply CRISPR/Cas9 to edit it as desired, culture edited cells in the lab, and then infuse it back into your body. So there's no immune response as it's your own (modified, but Cas9-free so it doesn't trigger immune reaction to a certain enzyme) cells. 

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9 hours ago, Bluewolf said:

Well you can put me down for the Youth Gene right off the bat and I am fairly sure Deadlinesman is putting his hand up high for the extra hair... 

On a more serious note this is where science fiction becomes science fact and only our imaginations limit progress.. When you think of the potential to do good then you would suggest that we push on but always there must be some caution involved.

I couldn't imagine for example many years further down the road having the potential to live thousands of years because we have eradicated old age and disease, We are over populated as a planet as it is without having people live well beyond what the planet would be capable of sustaining. It would force us out into space looking for sustainable planets to colonize... Living for so long would make deep space travel more realistic. Whats 15 years getting to a planet when you can live for thousands?? On the plus side never getting old or dying would mean that any knowledge learned would stay with us rather than being lost when someone passed away for example and this would allow us to continue building rather than starting over with each new generation. 

Crippling diseases I could understand eliminating if possible that could only be a good thing for peoples quality of life like the Cancer theory but where would you stop? We are all unique and yet if parents could pick just the best bits to have some sort of ideal model human being then we would all become almost the same and I cant decide if that's a good thing or not? 

One of the most important things for me is that being able to live for so long ( if they ever actually achieve that ) takes away a massive part of what makes us human. The feelings of losing a loved one for example, Cherishing what time you have because you know that it could gone at any time, All these sorts of things is what makes you the person you are.. I might think that with never dying or living forever there might be a danger we could become a little bit robotic if you like, lose those feelings that give us great joy or great sadness... We might take things for granted perhaps.. 

So much to discuss on this subject really... so many things to take into account

The thing is, even if it became reality, it would only be accessible for the rich while the poor would still die of old age and diseases... And we're just too good in killing each other, that you can't eradicate either, haha. This actually reminds me of the setting of Gattaca, a movie where the society consists of those who are genetically modified (aka superior) and those who are not (aka inferior), thus leading to genotype profiling and genetic discrimination. 

Aging (and biological immortality) is a very interesting topic on its own!

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3 hours ago, nudge said:

The thing is, even if it became reality, it would only be accessible for the rich while the poor would still die of old age and diseases... And we're just too good in killing each other, that you can't eradicate either, haha. This actually reminds me of the setting of Gattaca, a movie where the society consists of those who are genetically modified (aka superior) and those who are not (aka inferior), thus leading to genotype profiling and genetic discrimination. 

Aging (and biological immortality) is a very interesting topic on its own!

Very true... I was going to touch on that a bit in my original post but thought I was straying dangerously close to a Sir Balon type length reply so cut it short.

You are of course right, Whatever way they try to sell this so they can secure it as an on going investment it would only be a matter of time before people less well off were being denied it or being told that it would cost so much money that they would never be able to afford it. Then of course only the elite members of society would benefit and then where would we be??? The other aspect you touched on is also true.. making a few changes to DNA does not stop you getting crushed in a car accident or smoke inhalation from a burning building so death is still a factor regardless of how well we live... 

6 hours ago, Mel81x said:

Learned something new there. when you say that they use CRISPR/Cas9 from outside the body isn't that the same as cell invasion and doesn't body try and fight that? I can't imagine them being able to shut all auto-immune responses?

One day we'll see a gene-therapy bottle with Solid Snake on it. Then ... O.M.G.

This one fascinates me for other reasons and more importantly the point that you mention about knowledge never being lost. Today, our brains are so limited in their actual use by us eventhough a lot of stuff happens automatically and in more cases involuntarily. Imagine a longer lifespan teaching us as  a race to harness that power. 

Good point... If we were given hundreds of years to learn then it stands to reason that as long as we kept learning or were willing to learn that we could tap into other parts of the brain that we currently don't use... Then where will that take us?

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Latest breakthrough:

Quote

 

Cancer cells engineered with CRISPR slay their own kin

Using gene editing, scientists have hoodwinked tumor cells into turning against their own kind.

Cancer cells circulating in the bloodstream have something of a homing instinct, able to find and return to the tumor where they originated. To capitalize on that ability, researchers engineered these roving tumor cells to secrete a protein that triggers a death switch in resident tumor cells they encounter. The cancer-fighting cancer cells also have a built-in suicide switch — so the weaponized cells self-destruct before they can start tumors of their own, the team reports in the July 11 Science Translational Medicine.

The new study isn’t the first attempt to fight cancer with cancer. Previous research has used circulating tumor cells to deliver cancer-killing viruses to noncirculating tumor cells, for example. But the new approach uses a gene-editing technology called CRISPR/Cas9 to manipulate the offensive-line cancer cells and give them more sophisticated properties, such as the ability to self-destruct once no longer needed.  

“The new twist here is the use of CRISPR-based technology to add resistance or sensitivity features to the parental cells,” says Renata Pasqualini, a cancer biologist at Rutgers Cancer Institute of New Jersey in Newark.  

Getting the technique to work took several steps. First, researchers hunted for a protein that could trigger cell death in many types of cancer cells. The winning candidate, a protein called S-TRAIL, killed off a variety of cancer cells and wasn’t particularly toxic to healthy cells.

Then, the team tested two different approaches. The first used glioblastoma (a kind of aggressive brain cancer) cells that were resistant to the effects of S-TRAIL. Researchers used CRISPR to edit genes in these tumor cells to make them produce lots of S-TRAIL, and then set the cells loose on cancer cells that were sensitive to the deadly protein.

In another approach, scientists took glioblastoma cells that were sensitive to S-TRAIL’s effects, and cut out the genes that impart that sensitivity before giving the cells the genes to produce the protein.

Both kinds of engineered cells reduced the size of tumors in mice compared with mice who didn’t get the treatment, the researchers found. Mice given the treatment lived longer, too.

Each approach has pros and cons, says study coauthor Khalid Shah, a stem cell researcher at Brigham and Women’s Hospital in Boston.

In a clinical setting — still a long way off for this research — using cells that aren’t yet resistant to S-TRAIL could be “a little bit cumbersome,” Shah says. It would enable doctors to collect patients’ own cancer cells, and then turn them into a weapon targeted against people’s specific cancer. But the wait time for that special cellular engineering might make the option a no-go for very sick patients.

The other approach, built with standard cells that are already resistant to S-TRAIL, could be stockpiled in hospitals for quick and easy access. But because those cells would be foreign to a patient, there would be a greater risk that the body would reject them.

https://www.sciencenews.org/article/cancer-cells-engineered-crispr-slay-their-own-kin

 

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On 7/13/2018 at 19:09, nudge said:

Latest breakthrough:

All I could think of when I read that was "Et tu, Brute?". It's quite cool that you can use the same genetic traits of the offspring of a cell to kill the parent system considering how they always like to track back to home. The one thing that doesn't get explained in the article even though there are self-destructive properties on these cells is how much of the destroyed cell is left behind? If history has taught us anything its that evolution finds a way to make things stronger so what are the chances of these cells to spawn new cancers which are then not only harder to eliminate but also, godforbid, faster and more lethal due to evolution?

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I finally decided to bite the bullet and bought some stock in three biotech companies that specialise in CRISPR... if this works out, the drinks are on me. In like 15 years maybe xD 

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27 minutes ago, nudge said:

I finally decided to bite the bullet and bought some stock in three biotech companies that specialise in CRISPR... if this works out, the drinks are on me. In like 15 years maybe xD 

Hope it all works out well.... 

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21 hours ago, nudge said:

I finally decided to bite the bullet and bought some stock in three biotech companies that specialise in CRISPR... if this works out, the drinks are on me. In like 15 years maybe xD 

You should take some money now and ask someone to age a bottle for you on the off-chance you actually make money :)

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17 hours ago, Mel81x said:

You should take some money now and ask someone to age a bottle for you on the off-chance you actually make money :)

High risk, high volatility; I know it's a complete gamble hehe. I just been following it for a long time and have a good feeling about this; at those stock prices it's well worth a bet anyway!

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A Chinese researcher has just reported the birth of world's first genetically modified babies (twin girls whose embryo DNA had been edited with the use of CRISPR to prevent HIV infection); a dubious an unverified claim at this point as China launches investigation amid a global outrage, but this will be huge if it can be verified; and there are some very interesting clinical trials documents published online that appear to support the claim that Southern University of Science and Technology in Shenzhen has been recruiting couples in 2017 in an effort to create the first gene-edited babies by eliminating a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera. This has started a huge shitstorm in China now, as there are reports that the approval of the ethics committee has been faked in order to run the experiment, and all institutions are denying their involvement. 

 

More infos: 

https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/

 

This might be a big bluff (very likely), but if it's not, then it's going to be HUGE. 

@Mel81x

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54 minutes ago, nudge said:

A Chinese researcher has just reported the birth of world's first genetically modified babies (twin girls whose embryo DNA had been edited with the use of CRISPR to prevent HIV infection); a dubious an unverified claim at this point as China launches investigation amid a global outrage, but this will be huge if it can be verified; and there are some very interesting clinical trials documents published online that appear to support the claim that Southern University of Science and Technology in Shenzhen has been recruiting couples in 2017 in an effort to create the first gene-edited babies by eliminating a gene called CCR5 in hopes of rendering the offspring resistant to HIV, smallpox, and cholera. This has started a huge shitstorm in China now, as there are reports that the approval of the ethics committee has been faked in order to run the experiment, and all institutions are denying their involvement. 

More infos: 

https://www.technologyreview.com/s/612458/exclusive-chinese-scientists-are-creating-crispr-babies/

 

This might be a big bluff (very likely), but if it's not, then it's going to be HUGE. 

@Mel81x

The one thing I am 100% sure I can't call a bluff on is the fact that there is no ethics committee of any fucking kind in China when it comes to this kind of experimentation. I'd be embracing this as a nation and telling everyone else to take their ethics and shove it because they've just made one of the biggest if not the biggest leap we will see in our lifetimes with genetic engineering. An embryo with natural resistance to existing diseases (whatever form they are in) is a huge step for science and if it is proven true I am willing to even bet on the fact that a lot of geneticists will be making their way to the far-east for work rather than stay in the caged cells they have right now due to the human rights. This is not to say of course that we don't need some curtailing of the process but if its to do what they are doing in Asia right now then I'd be in favor of them continuing their work and even finding proper cures to these diseases with further genetic research.

Edited by Mel81x
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10 minutes ago, Mel81x said:

The one thing I am 100% sure I can't call a bluff on is the fact that there is ethics committee of any fucking kind in China when it comes to this kind of experimentation. I'd be embracing this as a nation and telling everyone else to take their ethics and shove it because they've just made one of the biggest if not the biggest leap we will see in our lifetimes with genetic engineering. An embryo with natural resistance to existing diseases (whatever form they are in) is a huge step for science and if it is proven true I am willing to even bet on the fact that a lot of geneticists will be making their way to the far-east for work rather than stay in the caged cells they have right now due to the human rights. This is not to say of course that we don't need some curtailing of the process but if its to do what they are doing in Asia right now then I'd be in favor of them continuing their work and even finding proper cures to these diseases with further genetic research.

I think the denials and reports of "fake" approvals are just the reaction to the public outcry it caused; as you said, China normally has no qualms with stuff like this and see ethical concerns as a hurdle to taking the lead in an area of such importance. 

It does open Pandora's box though...

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