Human genetic modification?

[magnemoe]

I am 100% against this at the current level because of the problems it can induce. However, since it has been begun, it's going to end up something like Khan OR people from the anime Gundam Seed. Those are the two extremes I can see. How long is the question. One of those was a war the other became a civilization in space. If it can be used to cure a disease, it will either be suppressed OR insanely expensive for normal people. If it can be used for that, it can be used to enhance unborn people-and that will be priced outta reach of normal people.

I agree here, problem with current level of GM is the failure rate or rater the low success rate because the methods are crude and inaccurate. Even if the result looks good it can easy have errors.

Methods will have to be significantly improved before trying on humans, after plants we will probably do lots of improvements on animals first.

The expensive part fails: this is nano stuff, main cost is the development, the actual process is pretty cheap once nailed down, it will not take many man-hours to do. Today the problem is that you have to try a lots of time and then check if the result is good, this is time consuming and hardly relevant for animals even.

If you want to make money on something who is very expensive to develop but cheap to do you want to keep the cost down to get volume up. Computers and mobile phones is the best example here.

Various new changes might be expensive in the start, like many other products you might want to keep price high in the start to get fast money then lower it to increase volume, TV marked is an good analog, same with new features for cars. It will also be competition. One bonus benefit of keeping the price high in the start is that any errors will only hit an limited group.

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I don't understand your first sentence... at all...

I never said that this would be an evolutionary handicap, just that direct genetic modification isn't really necessary, and that progress is being made as to natural evolution.

There will be another human species within the next few hundred thousand years. Homo sapiens has only been around a few hundred thousand, and since everything is going faster nowadays... I wouldn't be surprised to see a successor in the next 200000 years.

Sorry, It was messed up, the only Natural selection pressure on humans today is protection against lethal diseases who kills in young age, how many is it who is serious killers?

In historical time this was the main driver not so much anymore.

Yes things happen faster however evolutionary changes happens slower as its little pressure.

That said i'm all for GM on humans once the process is perfected, see few downsides.

The only one might be that we might split into multiple species over time.

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This is where this stops being a good idea. What constituted a defect? More importantly, which defects deserve to be fixed - well, pre-fixed, so to speak, in this manner? Because once something is shown it can be altered, someone will offer that for a price, regardless of how necessary it is.

EDIT: That's not to say I'm against it - that would be thowing out the baby with the bath water. You just have to keep aware that this is one of those circumstances where you can't throw out the the bath water and still keep the baby.

Well aging and cancer is obvious defects, only having two set of teeth might also qualify but is more of an feature.

[Bill Phil]

Sorry, It was messed up, the only Natural selection pressure on humans today is protection against lethal diseases who kills in young age, how many is it who is serious killers?

In historical time this was the main driver not so much anymore.

Yes things happen faster however evolutionary changes happens slower as its little pressure.

That said i'm all for GM on humans once the process is perfected, see few downsides.

The only one might be that we might split into multiple species over time.

Not true, actually...

We are changing the environment, and thus whatever can adapt will adapt, including us, from a natural response. So it's like natural and artificial selection... I guess?

Things are happening faster, which means we'll change the environment quite a lot, and thus cause natural responses.

And Earth will not be the same. It's changing all the time. In 100000 years, there'll be quite a lot of world-changing events.

Once it's perfected, it's good for fixing some natural screw ups. But some things are just not meant to be dealt with.

If you want to fly, you need wings. But you need tons of other things, so many changes that it's not really human GM anymore...

[magnemoe]

Not true, actually...

We are changing the environment, and thus whatever can adapt will adapt, including us, from a natural response. So it's like natural and artificial selection... I guess?

Things are happening faster, which means we'll change the environment quite a lot, and thus cause natural responses.

And Earth will not be the same. It's changing all the time. In 100000 years, there'll be quite a lot of world-changing events.

Once it's perfected, it's good for fixing some natural screw ups. But some things are just not meant to be dealt with.

If you want to fly, you need wings. But you need tons of other things, so many changes that it's not really human GM anymore...

However we do not adapt to the environment, we use technology instead, one month ago I would be dead in an hour I was was naked outside.

Making clothes is a bit faster than waiting a 1000 generations to grow fur, humans was able to use technology to adjust to any environment on earth: polar regions, rain forest and deserts only with technology in the stone age. Variation between human races is variable disease resistance, protection against the sun and different beauty ideals.

That was 100.000 years in stone age conditions, today the differences is washed out because more traveling and interactions and the technology is a bit more advanced. We have some new environments the last 100 years like underwater and space both was solved by technology and pretty much had to be.

---

Flying is hard, even the larges flying dinosaurs was lighter than humans and the oxygen level was higher, perhaps air pressure too. If you want to fly I recomend teraforming mars and bring the air pressure up its probably easier. Or you can use technology to fly in, not so fun but works for traveling

---

Just read that the Chinese had managed to do GM on human embryos, it did not affect all the embryos and some got other mutations too.

Not surprising and they could just as well continued with mice. Only reason to do this to verify that human embryos reacted the same way as the mice ones.

Edited April 24, 2015 by magnemoe

[KerikBalm]

Problem is, no one wants to donate embryos. No one wants to be a surrogate for this. Good luck having it happen anytime soon.

I could do it right now if I was motivated....

It would be breaking some sort of ethical "informed consent" idea though.

The thing is, they wouldn't know that they'd be getting modified sperm.

DNA is complicated. There's a lot of "junk" DNA, but we just don't know what it dies. Perhaps it's important. Perhaps not. You can't just change DNA for a better quality of life. You have to change a sequence little by little to see each change. That's per person. So it would take either a lot of people or a lot of generations.

Vague BS.

Junk DNA is an outdated term. Some DNA is clearly not important.

We can also make additions of DNA, that we know what it does. e.g. Photolyase, which would be a direct quality of life improvement, particularly for ligth skinned people who sun burn more readily.

Once the technology to modify our genetics exists and proliferates and advances, it's going to happen whether you like it or not. It's better to embrace it and learn to do it safely and positively. Once we actually make "Intelligent Design" come true, designing ourselves to be a civilized, united species instead of a tribal caveman species, truly wonderful possibilities can be unlocked.

We already have said technology.

I agree here, problem with current level of GM is the failure rate or rater the low success rate because the methods are crude and inaccurate. Even if the result looks good it can easy have errors.

Methods will have to be significantly improved before trying on humans, after plants we will probably do lots of improvements on animals first.

Please provide *anything* to support those assertions, because I'm calling BS.

Edited April 24, 2015 by KerikBalm

[magnemoe]

I could do it right now if I was motivated....

Please provide *anything* to support those assertions, because I'm calling BS.

Just general knowledge about the field, error rate is way to high to use on humans.

Last Chinese experiment confirms this. 86 embryos was modified, 71 survived, however just an faction had the change and many got other mutations too.

In short not ready for humans.

Note that success chances is increasing fast, this is an field with rapid improvements. in 10 years perhaps in 20 probably.

[KerikBalm]

so the embryos that don't survive don't get implanted...

Its even simpler if you modify the sperm with a viral-derived vector.

You can talk about off target effects and all that... but thats just a "drop in the bucket" when you look at what endogenous transposons and retrotransposons do, or the massive number of SNPs people have.

... way too much fear mongering about this sort of thing ...

[Guest]

It should be done.

And since it will be expensive as hell at the beginning, relatively few people can do it early, so if it will cause harmful side effects, it will not affect humanity as whole.

Also, it might lead to advanced technology, that allows reconfiguration of grown person, for purposes of healing trauma, fixing existing genetic defects, aesthetic purposes, and even new abilities - with option to revert easily.

Vacuum proof photosynthesizing Khajiit with megawatt class laser hidden in paw anyone?

[magnemoe]

so the embryos that don't survive don't get implanted...

Its even simpler if you modify the sperm with a viral-derived vector.

You can talk about off target effects and all that... but thats just a "drop in the bucket" when you look at what endogenous transposons and retrotransposons do, or the massive number of SNPs people have.

... way too much fear mongering about this sort of thing ...

http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378?WT.mc_id=TWT_NatureNews

This describe a bit more about the problems.

If you read my earlier posts you see I'm very positive about this however we need more experience before its practical to use.

[KerikBalm]

http://www.nature.com/news/chinese-scientists-genetically-modify-human-embryos-1.17378?WT.mc_id=TWT_NatureNews

This describe a bit more about the problems.

If you read my earlier posts you see I'm very positive about this however we need more experience before its practical to use.

#1) Genome editing likely had nothing to do with the 71 of 86 surviving - rather, its more likely that is simply the result of the injection itself (which could have contained absolutely nothing) causing 15 to die. Surviving such an event causes no long term damage.

We know this from cloning experiments, where there injections are even worse.

#2) "only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,â€Â"

I don't see why.... Oh no! we tried to make a GMO baby, but its a regular baby!

How is that a problem?

Sure if you are trying to correct a genetic defect, you'd like to be able to correct it all the time - this success rate make affect the economic viability, but its not an argument against trying

#3) "His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. ... The rates of such mutations were much higher than those observed in gene-editing studies of mouse embryos or human adult cells."

Perhaps a bad assumption, they may have already been there. Perhaps they used a bad guide RNA, or had contaimination of other guide RNAs.

I use CRISPR/Cas9 on adult human cells - its a self contained system that is pretty specific, it comes from a bacterial cell, but the system works in pretty much any cell, because it doesn't depend on host factors to do its DNA modification (it is a complete system by itself). There is no reason they shouldn't get the same specificity in embryo cells.

Either they weren't careful in designing their guide RNA, or the cells they used already had those mutations.

Note: "critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them."

There is absolutely no reason to suspect that it does, it doesn't make any sense for it to work any differently.

It works efficiently, specifically, and predicatbly from Eubacteria, to Archea, to Eukaryotes including plants, fungi, mice, cultured stem cells... but fertized oocytes... whoah... whole new territory here (sarcasm).

If its really a problem, they can switch to TALENs -> I also used those briefly before switching to CRISPR/Cas9. TALEN constructs are a pain in the ass to make after designing them... the CRISPR system... I order a pair of oligonuleotides for $10 each, and then once I receive them, spend half a day making the construct - super simple and easy.

4) There are many other types of genetic modification that could be done in addition to this.

[Mazon Del]

Mazon Del, your cards have already been dealt. No stacking the deck now.

I'm all for using genetics to cure diseases, such as Tay Sachs and worse. Because then a life has been saved. But changing yourself because you want to, barring th impossibility, isn't reasonable. You have to work with what you've been dealt. That's what life is about.

Completely untrue.

While maybe 30+ years ago, we couldn't do TOO much to alter ourselves, today we have an entire industry based around it. Cosmetic surgery allows the ugly to become beautiful. I can change genders, not perfectly admittedly, but well enough. I can change my race. There are other experimental modifications as well that people perform on themselves. A popular one among electrical engineering transhumanists is to numb a finger (usually the index finger), make a small incision, and then slide in a very tiny gold plated neodymium magnet (quite cheap). Let it heal over the course of a few days, and congrats! With that finger you now have the ability to detect electromagnetic fields! A brand new sense! They can tell if a wire has electricity running through it just by holding their finger near it, the charge interacts with the magnet causing it to wobble slightly which your body can feel.

The ONLY reason we cannot do anything terribly interesting like putting in (useless, but possibly good looking) wings is because most first world countries ban such experiments because....they want people to stay human.

While I am not one of the doomsayers that believes that the world is shortly going to suck, as far as being a place for humans to live is concerned, I still think it is quite important to begin experimenting into body engineering techniques quite heavily. Both because of getting rid of this irrational dislike for becoming what we currently aren't, as well as the boons for humanity as a whole. I guarantee you that if the FDA became much more accepting of body modifications that were not simply 'quality of life' improvements, that within a decade we'd have implantable vision systems (screens in your eyeballs). I could see a company existing around the idea of an implantable monitoring system that can allow for semi-real time monitoring of your bodies functions, warning you (and your doctor if desired) when it detects something is amiss.

You argue that we work with what we've been dealt and that is what life is about. I don't quite agree, but let us assume that is the case. I have been dealt a brain to utilize the technologies and abilities of my species to become something new, something I find better for whatever foolish reason that might be. As you can see, this argument is flawed and pretty much translates to "I feel uncomfortable with this concept and I would rather nobody can explore it so I don't have to be bothered by it.", which I don't hold against you. A huge portion of humanity seems to have this opinion. Slowly though, this is beginning to change. About time.

[magnemoe]

#1) Genome editing likely had nothing to do with the 71 of 86 surviving - rather, its more likely that is simply the result of the injection itself (which could have contained absolutely nothing) causing 15 to die. Surviving such an event causes no long term damage.

We know this from cloning experiments, where there injections are even worse.

#2) "only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,â€Â"

I don't see why.... Oh no! we tried to make a GMO baby, but its a regular baby!

How is that a problem?

Sure if you are trying to correct a genetic defect, you'd like to be able to correct it all the time - this success rate make affect the economic viability, but its not an argument against trying

#3) "His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. ... The rates of such mutations were much higher than those observed in gene-editing studies of mouse embryos or human adult cells."

Perhaps a bad assumption, they may have already been there. Perhaps they used a bad guide RNA, or had contaimination of other guide RNAs.

I use CRISPR/Cas9 on adult human cells - its a self contained system that is pretty specific, it comes from a bacterial cell, but the system works in pretty much any cell, because it doesn't depend on host factors to do its DNA modification (it is a complete system by itself). There is no reason they shouldn't get the same specificity in embryo cells.

Either they weren't careful in designing their guide RNA, or the cells they used already had those mutations.

Note: "critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them."

There is absolutely no reason to suspect that it does, it doesn't make any sense for it to work any differently.

It works efficiently, specifically, and predicatbly from Eubacteria, to Archea, to Eukaryotes including plants, fungi, mice, cultured stem cells... but fertized oocytes... whoah... whole new territory here (sarcasm).

If its really a problem, they can switch to TALENs -> I also used those briefly before switching to CRISPR/Cas9. TALEN constructs are a pain in the ass to make after designing them... the CRISPR system... I order a pair of oligonuleotides for $10 each, and then once I receive them, spend half a day making the construct - super simple and easy.

4) There are many other types of genetic modification that could be done in addition to this.

Looks like you know that you are talking about

So the Chinese team messed it up, not unlikely it smelled a bit sensationalist to me.

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Completely untrue.

The ONLY reason we cannot do anything terribly interesting like putting in (useless, but possibly good looking) wings is because most first world countries ban such experiments because....they want people to stay human.

Well that would be very hard, tails on the other hand would be pretty easy, an rare mutation has cause some kids to be born with real tails so it might just be one gen who switch it on or off.

Would require some more extra work as you would like it a bit longer and prehensile but not impossible

[Mazon Del]

Well that would be very hard, tails on the other hand would be pretty easy, an rare mutation has cause some kids to be born with real tails so it might just be one gen who switch it on or off.

Would require some more extra work as you would like it a bit longer and prehensile but not impossible

Oh yes, wings would indeed be MUCH harder than a tail. The internet holds rumors of some people that have had internal prosthetic extensions added to their tailbones that allow for lightweight 'clip-on' tails that attach via magnets. Not prehensile by any means, but still something 'attached'. That said, I'm not certain how much I believe those rumors. I feel the magnetic attachment system is likely to be too weak for such an application, too much lever action from whatever tail you might add there. If the magnets were strong enough to overcome it there would likely be an uncomfortable amount of pressure on the skin.

But of course, if we allowed research into such modifications (genetic or prosthetic), I'm sure we'd come up with a much better system. >

[Robotengineer]

Note: I haven't read this whole thread, but I've skimmed it.

I am not against genetically modifying humans if it can be possible, but I also think that progress should be slow and well-thought out. Human Genome Modification has the potential to allow us to accelerate our own evolution and prevent disease, but it also has the potential for many, many, many terrible uses. HGM technology is not unlike others, in the fact that it can be used for good and bad, and that it has an inherent danger to it. By danger I mean, if a country, organization or individual can use this technology, what level of havoc could he/she/it let loose on the world an species? Atomic technology has a high danger level on national levels, but a much lower danger with organizations and individuals, (assuming they would have to make their own weapon that is). HGM could be much more beneficial than atomic energy, but could have worse repercussions than atomic technology, if one assumes that all changes are final, and could enter the general population.

All of this leads to some obvious questions.

• There is also the issue of rights, what rights does a heavily genetically modified person have?
  
• Are they still human?
  
• Can 'new' genes be patented?
  
• What if they decide they don't want to be an experiment anymore?
  
• How would you stop an experiment?

[-Velocity-]

All of this leads to some obvious questions.

• There is also the issue of rights, what rights does a heavily genetically modified person have?
  
• Are they still human?
  
• Can 'new' genes be patented?
  
• What if they decide they don't want to be an experiment anymore?
  
• How would you stop an experiment?

How are the first two of these even valid questions? Why should their "humanity" or "lack" thereof be in any way relevant? In a world where people exist that are non-human, would you be in favor of a N a z i-like (stupid censor) regime that oppressed these non-humans in favor of some twisted and baseless concept of human species superiority and purity? Would you round up the people that are "non-humans" and send them to concentration camps to be exterminated?

The only way I can see in which a person's humanness or non-humanness would actually matter could be in reproductive matters. For example, certain couplings between different artificial species of persons could be genetically similar enough to conceive a child, but not genetically similar enough to have healthy, non-deformed offspring. You could thereby make a case that it might be wise to illegalize natural reproduction between these species. (It might still be possible to take and combine shared genes from the two parents and still produce healthy, viable biological offspring for the couple- it's just that conception would have to occur artificially, in a lab.)

Edited April 24, 2015 by |Velocity|

[Mazon Del]

I think more the point with bringing up the question of "are they still human" is that in a lot of ways our current legal systems actually spell out precisely what a human is for the purpose of providing 'basic human rights' to them. So if someone were to go full furry or something and pop out right today, in a legal sense it is technically possible that one could argue (with no certainty of defeat) that those laws no longer apply to them. Of course, it is a little 'easier' if the person in question started as your basic human, but lets say they also have a child with them that was born this way. The legal waters get more murky.

Questions 1 and 2 are currently murky at best. But only because of the way we've accidentally set up our legal system.

Question 3, it depends.

In the USA, we recently had a pretty great situation happen a year or two ago where the Supreme Court declared that you may NOT patent genes that you snagged from a living creature. You may patent the procedure you used to GET those genes, but the genes themselves are effectively open source. So while someone might patent a specific process to provide someone with the hearing of a dog, the specific genes to do so are free to use for anyone who wants to use them.

Question 4: This depends on what Robotengineer means by this question.

-If the person wants to drop out of the experimental trial for having the gene conversion, then this depends on the agreement they created with the group running the experiment. These agreements by the way ARE governed by ethics boards, as well as the standard laws and protections of the country you are in. Considering you cannot actually sign away your right to freedom, and that no ethics board would allow it, you cannot actually be 'caged' for the length of the experiment. Now, there ARE exceptions to this, but those again would be controlled by the laws and ethics boards. For example, if you are testing out the vaccine to some virus, you DO consent to being in quarantine for a period of time, but these would of course be spelled out, plus any candidates would be screened to attempt to limit the possibility of someone insisting on attempting to leave at this time.

-If you mean the person wants their modifications to be undone at some later point, this ends up being a question of technical feasibility more than anything else. If the tech exists, and you were changed as part of the experiment, then maybe part of your agreement is to be able to have the change undone. But maybe not. This leads into Question 5.

Question 5: You just might not be able to. And that isn't a bad thing.

There is plenty of precedent for people undergoing irreversible experimental procedures. Brain surgery, amputations (at one time), transplants, etc. You would flat out be unable to enter into an agreement to be the volunteer WITHOUT being fully aware that you cannot go back once things have started. If you end up regretting it later, that is nobodies fault but your own. This again is another throwback to those ethics committees, you CANNOT run an experiment that permanently changes another human being without informing them in no uncertain terms that what is happening cannot be undone. In triplicate.

Now, if you are choosing to participate in these experiments in North Korea as they try to make the ultimate super soldier and it turns out their ethics committees are less willing to adhere to international guidelines on this topic...well, whatever argument we might have is moot, because if they are willing to break those ethics guidelines, chances are they are going to break the ban on the research anyway. So I am assuming we are discussing participating in these experiments somewhere that will attempt to do everything above board and by the book.

As far as Robotengineer's concerns for the individual's ability are concerned...I hate to tell you this, but it's pretty much too late to stop that. There are open source kits you can download that are instructions on how to set up pretty much every piece of lab equipment you might need to genetically engineer whatever you might want to attempt. Last I heard, the only 'missing piece' to the list was an actual gene sequencer, the device that lets you 'print' out the DNA strand/segment of your choice. That said though, it is a matter of time before this is solved, plus this isn't the largest stumbling block. As of 20-30 years ago, there were coupons in scientific magazines (official ones, not populace stuff like Scientific American) where for about $20, not including shipping, and the data file, you could get two 5 milliliter vials of your DNA strand (I forget how many base pairs it was limited to at the time though, several thousand I believe, these days we are MUCH better) in about a week. Not really a whole lot of oversight on what was done with this material, mostly because it is too easy to lie. They don't have the ability to check what this strand will/could do, so they don't know you are trying to provide someone with venomous fangs.

While many Synth-Bio (civilian genetic engineers) people tend to keep things official (getting their garage labs registered as a GE lab, going through the process of getting it checked out and confirmed by the government, etc) there really is nothing keeping you from setting this up in your basement and not telling anybody. Best I remember, none of the parts for the kits are anything that would be on a watch list. Just motors, ras-pis, various things like test tubes, etc.

Really what has long been the fear is not actually someone who will try to do something 'evil' like make a zombie plague (check out "Under a Graveyard Sky" by John Ringo. <3 ), but someone who is trying to 'help' humanity. Let me paint you a pretty picture. Most people tend to agree smoking is bad for you. You, a brilliant Synth-Bio guy have decided to tackle this problem. So you snag a sample of flu virus or something similar, you couple it with a nicotine molecule (or something near enough to fool the immune system) and you breed this virus. If everything goes well, once someone has been infected with it, they will go through standard flu symptoms before being done with it, no more aware of anything special having occurred than a standard flu. But now lets have that person pop a cigarette to celebrate their health (hah). What happens? Their immune system has identified the nicotine molecule as a major identifying feature of the flu! So now that it detects the nicotine molecule back in your system, it goes on full alert. Suddenly you've got a fever, sore throat, etc. Slowly over time either through conscious or subconscious training, you will stop using tobacco products. In a way, they have helped you. Yay. But now what about the people whose immune systems overreact? Their next puff sends them into an anaphylactic shock. What about a non-smoker that caught a whiff of second hand smoke? Very indirect, but that 'helpful' person has quite likely caused several people to die.

So that is what we can deal with when someone is trying to be 'sensibly nice'. But now what if they are a little less...sensible. Clearly dogs are a worse choice than cats. They go around, they bark at you, they growl, the bite. Terrible. But you can't convince anyone else to see this. Clearly for the safety of children and people everywhere, it would be best to discourage them at the biological level from being interested in dogs. Extrapolate.

Now, are we actually anywhere near these two scenarios occurring? Most certainly not. Will we be? Within about two decades? Possibly. Can we stop this? Not really. All we can really do is try to be as well equipped to deal with the consequences of such people as possible.

[magnemoe]

Note: I haven't read this whole thread, but I've skimmed it.

I am not against genetically modifying humans if it can be possible, but I also think that progress should be slow and well-thought out. Human Genome Modification has the potential to allow us to accelerate our own evolution and prevent disease, but it also has the potential for many, many, many terrible uses. HGM technology is not unlike others, in the fact that it can be used for good and bad, and that it has an inherent danger to it. By danger I mean, if a country, organization or individual can use this technology, what level of havoc could he/she/it let loose on the world an species? Atomic technology has a high danger level on national levels, but a much lower danger with organizations and individuals, (assuming they would have to make their own weapon that is). HGM could be much more beneficial than atomic energy, but could have worse repercussions than atomic technology, if one assumes that all changes are final, and could enter the general population.

All of this leads to some obvious questions.

• There is also the issue of rights, what rights does a heavily genetically modified person have?
  
• Are they still human?
  
• Can 'new' genes be patented?
  
• What if they decide they don't want to be an experiment anymore?
  
• How would you stop an experiment?

Well we don't have an clear definition of human as its no need. Mongoloids has an extra chromosome and I don't think they are fertile but they are still human.

They are also mentally disabled but that is outside the issue expect talking against them.

All sci-fi around this is after an good story not realism, if you want slaves use AI or uplifted animals, here you are into muddy water, also practical: how smart can you make an dog before it is an citizen and not an animal.

More fun, what if human 3.11 or human 4.0 decides they don't want to be humans anymore.

Genes can be copyrighted in the US but not in Europe I believe. More practical to use the patent rules on the actual GM operation not the gene.

Also pretty irrelevant for humans, patent duration is 20 years, few have kids before they are 18, add 9 months for mother and 9 on kid.

Last two don't make sense, its not an experiment its an finished product.

More relevant, what is the GM company responsibility if you get secondary effects late in life.

Edited April 24, 2015 by magnemoe

[KerikBalm]

Looks like you know that you are talking about

So the Chinese team messed it up, not unlikely it smelled a bit sensationalist to me.

Well, maybe, maybe not.

They were using embryos with chromosomal abnormalities. That typically leads to problems by itself. These other mutations may have had nothing to do with the CRISPR/Cas9 system. They only used such abnormal embryos because they had to because of regulations stopping them from using viable embryos.

Furthermore, if off target effects are really a problem in this case... its a problem that has already been solved.

The most common TALEN system consists of a pair of "TALENs", which contain 18 TAL "modules" fused to the FokI nuclease. The TAL modules each recognize 1 base pair. So if you want to cut at a location, you make a TALEN reccognizing 18 bp upstream on the 5' strand, and a TALEN recognizing 18 bp downstream on the 3' strand.

The FokI nuclease only functions as a dimer, when the two talens bind to each side of the DNA, the FokI nuclease domains are put together, and they cut...

So you need 36 basepairs to specifically match... its pretty easy to select a unique sequence of 36 nucleotides.

If you only targeted 4, like ATAT... well, you'd find that all over the genome, and cut all over the place. If you used a sequence that targets 8 nucelotides, it would start to get pretty specific, but you'd find ones that match for say.. 7 out of 8, and you'd have a chance of cutting that target that is a match for 7 out of 8.

Obviously, going from 8 to 18 increases specificity.

TALENs are protein only, and sort of coil around the DNA helix, and don't tolerate mismatches very well. Also, by using a pair, both parts would have to have off target binding at the same location to cut. If one binds off target on its own, there is no FokI dimer, and nothing happens.

CRISPRs on the other hand are a RNA-protein complex, where the RNA basepairs with the DNA and provides the target recognition for the associated protein. The guide RNA is 20 nt long (they tried longer ones, but it didn't help, and they were processed down to 20 nt anyway).

IIRC from the papers, it won't cut if there is a single mismatch in the first 11 base pairs, but it does tolerate some mismatches in base pairs 12-20 -> so ideally you pick sequences where the first 11 basepairs don't occur anywhere else in the genome. Otherwise, you have to pick sequences where maybe the 1st 11 occur somewhere else, but the next 9 don't match well. If there is another sequence in the genome that mateches in the first 11, and for 19 out of 20 of the base pairs... you'll probably get some off target cutting there.

The Cas9 nuclease only cuts when the RNA binds its target well (which induces a conformational change) - it cuts both strands...

So CRISPRs, as they occur in nature, and as first adapted by humans are less specific than TALENs (TALENs being an artificial addition of a nuclease to the DNA binding modules of TAL Effector proteins)

However, taking a lesson from the TALEN system, last year (or was it 2 years ago, I forget). They developed Cas9 mutants that did not cut both strands.

You thus needed a pair of CRISPRs to perform a double strand break (repair of single strand breaks is error free in theory and observation).

On targeting the forward strang, and one the reverse.

This basically "squares" the specificity.

If out of a 3 billion bais pair genome, you get ~100 off target events on average... how many of those off target events also get a 2nd off target event for the 2nd CRISPR needed to perform the double strand cut?

Do the math.

The Chinese team used the easiest, simple CRISPR-Cas9 system. They didn't use the more complex CRISPR pair, or the pain in the ass to make TALEN pair.

They did a proof of concept, and it worked. If you're really worried about those off target effects, we've already got systems to deal with those - its just more effort - and I'm guessing the team thought it was more effort than it was worth for a proof of concept that doesn't even lead to viable embryos.

Edited April 24, 2015 by KerikBalm

[Mazon Del]

Fascinating! Thanks for the info KerikBalm!

Just out of curiosity, when you say ~100 off target events, is that number based off of real experiments, or just sort of an example number? Quite curious.

[Robotengineer]

How are the first two of these even valid questions? Why should their "humanity" or "lack" thereof be in any way relevant? In a world where people exist that are non-human, would you be in favor of a N a z i-like (stupid censor) regime that oppressed these non-humans in favor of some twisted and baseless concept of human species superiority and purity? Would you round up the people that are "non-humans" and send them to concentration camps to be exterminated?

I want to clarify that no, I would not be in favor of a regime that holds 'natural' humans above genetically modified ones.

[KerikBalm]

Fascinating! Thanks for the info KerikBalm!

Just out of curiosity, when you say ~100 off target events, is that number based off of real experiments, or just sort of an example number? Quite curious.

Its just some sort of example number. Its not like we have the funds to do whole genome sequencing everytime I do a gene knockout or addition. But I can look at some other papers... use bioinformatics to see how similar other regions of the genome are to my 20 nt base pair (If you want, I can put a screenshot of some search results where it shows the next closest sequences, and how many/what the mismatches are, where those sequences are, etc - most of the tiem there are so many mismatches that its very unlikely to cut there, other times I may actually look and see where that is (typically, its a non-coding region, which is very tolerant of small indel mutations - they're not like coding regions where deletion of one basepair causes a frameshift that screws up an entire protein).

Note I made some changes to my previous post, I typed it too fast and made some errors. CRISPRS are a RNA-Protein complex, not a RNA-DNA complex.

The natural system has 2 RNAs(the "tracer" RNA and the "guide" RNA) and a protein.

The modified system we use in the lab fuses the tracer and guide RNA into one RNA so it can be expressed from one standard vector we use (as to why the natural system has them separate: 1 tracer RNA can work for many guide RNAs, which are expressed by bacteria against foreign DNA, as an antiviral defense - we don't need or want to have a plethora of guide RNAs, and its simpler to have them as 1 unit)

This RNA is basepairs withthe DNA as normal, and provides the target recognition... I was thinking about writing that basepairing with DNA sentance and had "DNA" in my mind when I wrote the RNA-DNA complex thing instead of RNA-Protein.... also there are many examples of RNA-DNA complexes... and I sort of automatically typed them (a sort of stupid biological autocorrect in my brain)

Anyway, before CRISPRs, we had TALENs, before that we had Zinc-Finger Nucleases.

TALENs aren't completely obsolute because they are more specific, but the paired CRISPR system is so specific, I doubt there will be a reason to use TALENs.

TALENs also have the advantage of not using RNA, because in some cases, its hard to get the RNA where you want it, but protein import signal sequences may work fine: ie mitochondria genome editing for example - mitochondria genome editing is a whole different story, and its pretty much the last genome we can't manipulate in a useful way (you need to cross 3 membranes, inbetween the inner two is a very low pH region with H+ ions, and in mammals, and any rupture to this membrane releases CytC which triggers apoptosis - although this isn't the case in yeast, and we can manipulate yeast... my lab is working on this problem with mammalian mitochondria now as a side project)

Before TALENs, which have had a very short run because the CRISPR system was discovered shortly after the TAL module code was discovered, people use zinc finger nucleases.

Conceptually, they were similar to talens - protein only. Also, again fused with a FokI nuclease domain, and used in pairs. They were also constructed by joining together DNA recognition "modules" to target the sequence you want -> only (IIRC, its an older system I never actually used) these modules recognized 3 base pairs at a time, with some tolerance if only 2 out of 3 matched, and we couldn't find modules that corresponded to every possible combination of 3 base pairs, so for some sequences, there was no corresponding combination of known modules to recognize the sequence.

[WinkAllKerb'']

(https://www.nasa.gov/content/twins-study/#.VT5qZyHtlBc)

+

procreation and aging

+

(http://en.wikipedia.org/wiki/Termite#Reproductives)

+

cretaceous (66 to 145 million years ago old species)

=

!?!

the right question is: where would you want to be when the sun become a red star giant and when orion black hole eat the galaxy ... i do believe in thoose times i'd like to be very very far away also i want to be sure that at this time we're still able to reproduce ... the space environnement genetic repercutions is "one" of the real mindbugging concern and matter to care about [(traps)] regarding distance and travel time so on regarding current "results and observations" it require more inquiries (feel free to search and browse non hoax official results logs from nasa,esa,etc.) ...

(a yeah oops it's already in my sig, sometime i tend to repeat sorry ; )

Edited April 29, 2015 by WinkAllKerb''
(and yup the 0 to 130 life span way to think is infinetely% unrelated regarding thoose kind of serious concern(s) )

[magnemoe]

http://www.hervekabla.com/wordpress/wp-content/uploads/2014/12/kelly-astronautes-1024x576.jpg

+

http://upload.wikimedia.org/wikipedia/commons/thumb/d/d3/Coptotermes_formosanus_shiraki_USGov_k8204-7.jpg/220px-Coptotermes_formosanus_shiraki_USGov_k8204-7.jpg

+

cretaceous (66 to 145 million years ago)

=

http://www.fhwa.dot.gov/context/practitionersguide/images/2_2_html_34bb4fb0.gif

!?!

I do not get this at all.

[WinkAllKerb'']

edited a lot anyway what i mean is i m kinda " " " " curious " " " " about a(^n) 9 months gestation(s) " " " " result " " " " in space ...

as relevant is what R&D responsabilities on single individual when testing and trying to solve such things ...

Edited April 29, 2015 by WinkAllKerb''
delayed posting

[musicpenguin]

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[magnemoe]

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http://nextbigfuture.com/2015/04/complete-woolly-mammoth-genome-sequenced.html

Raise you with a mammoth.