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Genetic Singularity Event: CRISPR editing

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#151 mag1

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Posted 04 September 2017 - 02:10 PM

https://singularityh...es-the-science/
http://www.nature.co...ature23305.html

It is time to seriously consider gene editing, now that technical hurdles have been overcome (see first url above).
But this couldn't be used for IQ enhancement because introducing novel genotypes could not be introduced with above technique (urls above).
Okkkkkkaa?


Does this not somehow neglect the fact that introducing novel genotypes is not required to increase IQ enormously?
This has been described in the posts above.

If there were 10,000 IQ SNPs, it is only necessary to change a few hundred to achieve the most extreme intelligence now observed in any human.
A typical human might have thousands of heterogeneous SNPs that either exerted positive or negative effects on IQ.
Typically if two beneficial alleles are present instead of only one, the polygenic score moves up to 2.
For example, an embryo with 1200 heterogeneous SNPs for IQ, might have their IQ increased by 12 SD simply by using this new technique
to edit to the optimal homozygous genotypes.

Human enhancement through genetic manipulation of the genome could piggyback on the insatiable drive to prevent severe childhood illnesses without the
scientific community being fully aware of this potential.

Edited by mag1, 04 September 2017 - 02:43 PM.


#152 mag1

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Posted 04 September 2017 - 04:58 PM

Other animals such as chimps, rabbits, mice, dogs, birds and others also have a g factor. These g factors should also be

highly polygenic. By using the CRISPR technique suggested above to maximize chimp IQ it should be highly possible to

optimize a chimp's IQ well past that of the maximally observed human. This is feasible today without any difficult ethical

questions.

 

If humans are uncertain about enhancing humans that is fine.

However, the consequence will be that our overlords will be big and hairy or perhaps small and hairy with a proclivity for

carrots.



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#153 mag1

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Posted 04 September 2017 - 08:00 PM

I have been criticized on the thread before for my suggestion of a Global Fertility Moratorium, though

given these current revelations I must speak my truth once again.

 

Acts intended to result in human reproduction should cease everywhere in the world.

 

Finalizing the technology which has now been developed for the realization of extreme human phenotypes needs to take place.

We also need to upgrade our state of consciousness to integrate the concept that humanoids with wondrous levels of intellect

are now imminent.

 

Humanity's goal should now be to provide all the children to be with the gifts that they will use to help us solve our many problems,

 

Others have been unsure of this suggestion in the past, though from everything that I now understand such a Moratorium 

would be highly recommended. Fortunately, today is a holiday so I should not receive an excessive amount of negative energies

right away.

 


Edited by mag1, 04 September 2017 - 08:02 PM.


#154 mag1

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Posted 09 September 2017 - 02:14 AM

I have been asking around online about the optimization of IQ. As of yet there has been no big push back concerning whether this doable. Yet, the big surprise response that I have encountered is that somehow this will be a technology reserved for the elite.

This would not seem to me to be a likely outcome. Certainly over a shortish time frame while the technology was perfected and fixed costs were recovered this might be true, though over a longer time horizon I do not see this.

There would be a network effect involved. Only having a few genetically enhanced humans would impose a large burden on those who were to look after them. There would be a range of socio-developmental issues which might need to be addressed. Having a larger generation of the enhanced would spread these costs.

There are a range of other issues. For example, will society really allow a large portion of the community live in a state of eternal dependence on social services that result from an underlying genetic condition? It is important to remember that intelligence has a contributing role to many other medical conditions.


Do others on the thread agree with the idea that genetic engineering will be for the elite?

Edited by mag1, 09 September 2017 - 02:19 AM.


#155 mag1

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Posted 09 September 2017 - 06:19 PM

Perhaps we should relaunch this thread on another thread.

The pace of change has now accelerated,

 

The Genetic Singularity is now near.

 

This is a profoundly important moment for humanity.



#156 mag1

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Posted 23 September 2017 - 09:58 PM

Admittedly, it has taken me some time to adapt to the concept of 1500 IQ people.

It is easier to do so knowing that implementing such a technology really is not feasible currently.

 

One of the main obstacles would be to actually find the variants involved.

This has been ongoing for over 10 years and I thought the research might incrementally advance over the next many years.

 

Until now. 

 

Research has now been published that in one run found all the additive heritability for height.

This explained 40% of the variance.

When the technique used (CS Lasso L1 penalized regression) is also applied to intelligence in a large sample a large amount

of the variance would likely also be detectable. In finding what will likely be a substantial portion of the genetics that drive variation

in intelligence, the ability to IQ enhance the next generation will move ever closer.     

 

https://www.biorxiv....190124.full.pdf


Edited by mag1, 23 September 2017 - 09:59 PM.


#157 beauty4eva

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Posted 05 December 2017 - 03:36 AM

The recent announcement that CRISPR technology has been used to genetically edit a human embryo has substantial implications for humanity. It would not be unfair to say that we now live in a very different world.

The endless arguments about nature versus nurture, and claims of different characteristics of different groups of people need now to be reconsidered in light of the CRISPR breakthrough. What are the social and political implications of a future society that did not have a substantial proportion of its population with medical issues? What role, if any, would government play in such a future? The future will be very different from what has happened up to this point in history.

The profound changes that genetic engineering with CRISPR (and possibly other technologies) deserves a thread on this forum. I am very excited about the possibilities in store. Anyone else interested?



I hope you're right.

I've spoken to several microbiologists and phd candidates that are convinced that the human body is far too complex to make profound changes in via just crispr.

Regardless I'm hopeful, definitely following the developments closely.

#158 Believer

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Posted 13 December 2017 - 12:25 PM

Many things that increase iq  also cause serious pathology. Delete gaba receptors and you may get extremely good memory (savant autism) with epilepsy and potential neurodegeneration. Delete or reduce the function of the tumor suppressor genes active in the brain and you may have more growth of the brain, so a higher iq, but also an increased risk of tumors growing.

 

It seems to me that to increase iq substantially it's as simple as:

enhance the activity of BDNF and NGF (the downstream genes activated are highly linked with iq),

increase intracranial volume,

increase glutamate receptor expression maximally,

use one specific variant of the dopamine D2 receptor gene (to increase motivation).

And that's about all you'd need to get a genius.

 

As for making people taller, people don't seem to fathom that height is not a good thing. Anything over 180cm causes serious pathology. The correct height for optimal health is probably around 160-170cm with a short torso and long limbs as seen in Africans. I'm 207cm and I can attest to the issues with the increased height. I'd love to be 160-170cm except for the negative social effects but who really cares when it comes to health.

 

People who are overly interested in social life should have no saying on what's appropriate to do with genetic therapy because they will end up encouraging the most useless changes that only confer a benefit to sexual and social activity in their childish fantasy world. Last time I checked it does not make a difference that you are 20-30cm taller than people, you still get shit on by everyone. Actually maybe even more so. And even if it did make a difference, so what? Social and sexual activity exist as a means to an end, not as an end in of itself. If you are not going to have children you might as well not have sexual organs or a sexual desire. People simply lack mental development to be mature enough to understand that these things are not important whatsoever.

 

As for gene therapies being used to enhance the population. GOOD LUCK lol. It would be easy I bet to make super intelligent and disease free humans, but our liberal governments don't approve of it. They say it causes "ethics problems" but they don't believe in objective morality so I don't understand how they can even talk about ethics. If ethics is a social construct in their fantasy world then why not socially construct it to be appropriate to use gene therapy to enhance populations? If anyone is of low intelligence it's probably these libtard politicians. What's worse is that they are actively encouraging every single self-evident moral evil and they are doing it with pride, and then they have the nerve to talk about the ethics issues of designer babies?

They are importing millions of low iq third worlders into their states which only harms the states' economy and everything. They could EASILY remove the third worlders again but these braindeads don't care. Maybe it's even intentional.

So no, we will not have designer babies or enhanced humans, not in liberal states at least. Although China I am certain will allow it.


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#159 mag1

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Posted 15 December 2017 - 02:36 AM

Believer, thank you very much for posting!

I am very impressed that you could produce such a compelling suggestion for how intelligence might be genetically enhanced.

 

It has been difficult for me to try and adjust to a future where 1500 IQ humans are possible.

The future is rapidly approaching and we seem so ill-prepared for it.

 

2018 could be the year in which the IQome completely unlocks!  

Having the ability to drastically change human IQ would upend society. 



#160 enharmonics

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Posted 24 December 2017 - 07:07 PM

[...]

As for making people taller, people don't seem to fathom that height is not a good thing. Anything over 180cm causes serious pathology. The correct height for optimal health is probably around 160-170cm with a short torso and long limbs as seen in Africans. I'm 207cm and I can attest to the issues with the increased height. I'd love to be 160-170cm except for the negative social effects but who really cares when it comes to health.

 

People who are overly interested in social life should have no saying on what's appropriate to do with genetic therapy because they will end up encouraging the most useless changes that only confer a benefit to sexual and social activity in their childish fantasy world. Last time I checked it does not make a difference that you are 20-30cm taller than people, you still get shit on by everyone. Actually maybe even more so. And even if it did make a difference, so what? Social and sexual activity exist as a means to an end, not as an end in of itself. If you are not going to have children you might as well not have sexual organs or a sexual desire. People simply lack mental development to be mature enough to understand that these things are not important whatsoever.

 

What utter garbage. I've never seen someone spew such ignorant, biased idiocy with such an arrogant tone.

 

"Who really cares"? Try growing up as a short male and being picked on, humiliated, mistreated, beaten up by taller kids, try living as a short adult male and suffering microaggressions in the workplace, being paid less than taller peers, men being dismissive and snarky toward you because they feel you won't fight back. Try developing and coping with crippling depression because of your stature, so that just getting out of bed every morning becomes a challenge. Try seeing your short statured male friends descend into alcoholism, avoidance, and suicide. 

 

Do all of that and then see if you want to ask "who really cares".

 

Last you checked it doesn't make a difference that you're 30 cm taller than everyone else? Last you checked, did people beat the **** out of you, make fun of your stature, deny you promotions based on it? Get real. You don't know what you're talking about.

 

It's funny how you try to act "above it all". "Social activity is a means to an end", yet here you are posting on a message board, a social outlet. The only one living in a "childish fantasy world" is you. Narcissists with a superiority complex shouldn't have a say in what's appropriate to do with genetic therapy either, because they'll solipsitically assume only their experience matters and what they say should go in all circumstances, like you.


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#161 pone11

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Posted 08 January 2018 - 07:32 AM

The implications for the IQ divide are also profound. Even though it is now clear that we have been fighting a futile fight on an ant hill over what in the overall scheme of things are very small absolute differences in IQ this does not mean people will or should stop such a struggle.

In the current context a couple both with 3 SD IQs would expect their offspring to regress to the average. There is a continual force attracting everyone back to average. The obvious prediction would be that likely is now no longer true. Now that the GWAS have found reliable SNPs for IQ, selection can begin. This means that if those with above average IQs were to take advantage of e.g. PGD their offspring would never regress to the average again. The IQ divide could widen out into the distant

future. The 3 SD couple could have their 7 SD offspring who parented their 11 SD children...

 

@mag1 the problem with this thread is that you have waxed poetic about standard deviations in post after post after post after post, but never do you clearly state what your actual idea is.   

 

You say that a couple with three standard deviation intelligence could have children with seven standard deviation intelligence by using Preimplantation Genetic Diagnosis (PGD).    What are you proposing?  This couple is going to have 5000 abortions in order to produce a super child?   Could you actually try to connect the dots of the words you are using and propose a real idea?   The mother does not have enough embryos to harvest to make random selection meaningful if we need to wait for random selection to turn on 10K SNPs.
 
If the idea is to use CRISPR technology in order to turn on all 10K SNPs associated with high intelligence, then why would that idea require a 3 SNP couple at all?  You could take the embryo of a child that would otherwise be below average intelligence and - after turning on the 10K SNPs - that child is now a super genius.   
 
And I think it is clear that this approach will never benefit most of us.  The only people who will attempt this will be rogue scientists or nations, and in any modern democracy, such experiments would be forbidden on ethical grounds.


#162 mag1

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Posted 08 January 2018 - 10:39 PM

Hi, pone11 thank you for stopping by the thread.

 

Very exciting news about the next generation of 3-BP.

Looks like cancer will be toast.

 

I have been totally startled by the developments that have been ongoing with GWAS and genetic enhancement possibilities.

My main concern is that there will be an attempt to endlessly delay rolling out the technology.

 

This is why I have been more focused on the selection technology.

Embryo selection is already a mature technology.

Adding in polygenic selection will not be a large step from current methods.

CRISPR might be stoppable, though stopping selection is much less plausible.

 

In fact, a company has already launched a service for selection.

http://genomicprediction.com/

 

This is only the first generation of the technology.

What happens when it is optimized?

For example, selecting the optimal sperm and the optimal egg would require no ethical issues involving

the right of an embryo to life. Could anyone plausibly that a sperm is a life? or even an unfertilized egg?

Choosing the best combination out of the 2^23*2^23 possibilities would result in a massively accelerated

timescale for evolution. Each generation might represent tens of millions of evolutionary time. 

As a guess, using this fairly low tech approach might add 10 SD per generation.

This would result in overwhelming social change.

 

We are now embarking on a radical reengineering of humanity.

Virtually all human traits/diseases are polygenic.

Being polygenic means that extreme phenotypes can be created.

This would apply to IQ, Educational Attainment, height, resistance to illness, etc. .

 

Merely selecting the highest IQ embryo results in a 1 SD increase in IQ. Regression to the mean can no longer be assumed.

In fact those with the highest IQ in our community will have a substantial amount to gain if they select offspring of even higher

IQ than themselves. Animal breeders have been doing such intensive selective breeding with farm animals for over a century.

 

A generation without risk of genetic disease is no longer a question of empty speculation; it is apparently already unfolding.

It should be no great surprise that China has recently surpassed the US in PGD capacity.

The race is on.


Edited by mag1, 08 January 2018 - 10:47 PM.


#163 pone11

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Posted 09 January 2018 - 04:38 AM

This is why I have been more focused on the selection technology.

Embryo selection is already a mature technology.

Adding in polygenic selection will not be a large step from current methods.

CRISPR might be stoppable, though stopping selection is much less plausible.

 

In fact, a company has already launched a service for selection.

http://genomicprediction.com/

 

This is only the first generation of the technology.

What happens when it is optimized?

For example, selecting the optimal sperm and the optimal egg would require no ethical issues involving

the right of an embryo to life. Could anyone plausibly that a sperm is a life? or even an unfertilized egg?

Choosing the best combination out of the 2^23*2^23 possibilities would result in a massively accelerated

timescale for evolution. Each generation might represent tens of millions of evolutionary time. 

As a guess, using this fairly low tech approach might add 10 SD per generation.

This would result in overwhelming social change.

 

All of these genomic services currently test an embryo.  Given that your hypothesis was that we need to turn on thousands of SNPs to move the needle on IQ much higher, that approach gets us nowhere.   You would need many thousands of fertilized eggs in order to observe a fortuitous arrangement of SNPs and allow that egg to proceed to a birth.   No human female could provide enough eggs.   

 

The current technology is used to identify a fetus with a potential disease condition.   Is any couple going to abort 10 fetuses hoping to wait for one fetus that is a standard deviation beyond their own intelligence?  I don't think it is realistic.

I very much like the technical idea of examining millions of sperm and then selecting the one that would provide the best SNP outcome with a given egg.  That technology does not exist.  It would require partial sequencing of half a genome on a vast scale and then would have all kinds of issues about how to get the specific sperm to the egg in time.  That isn't going to happen for a long time.

 

What probably will happen - illegally - is that someone will start to use CRISPR to engineer embryos early on.  Even that would require decades of illegal - and immoral - human experimentation in which many of those children would be born with horrible defects.   

 

What are you doing is engaging in a kind of fantasy where you play in your mind with the idea of turning on all of the high-IQ SNPs.   In theory it is possible.   Getting from here to there is highly non trivial, and I'm skeptical that it will happen rapidly.



#164 mag1

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Posted 10 January 2018 - 03:40 AM

pone11, I greatly appreciate your restarting this thread so that I can more clearly communicate what is now underdevelopment.

Your firm demand for precise and accurate details is very much in order.

Happy New Year!

 

I have now gotten over the initial shock of 1500 IQ people and can be more coherent.

 

Firstly, even the low grade embryo selection technique has substantial potential to greatly change phenotypes in the community.

This is an important point to clarify. Ball parking IQ genetics: there might be 10,000 SNPs involved, with 500 per chromosome,

current evidence suggests that the effect distribution is normal and centered at zero, with most of the minor allele frequencies in

the range of 20-50%.  A typical person might have 5,000 beneficial SNPs with 250 per chromosome (0 SD IQ) . A supreme genius such

as John von Neumann would have 5,500 beneficial SNPs (+5 SD IQ).

 

A simulation came up with 100 SNPs per SD, and 100 SDs in total.

Thousands of embryos would not be needed to substantially select for IQ or any other highly polygenic trait.

It is currently thought that merely selecting 1 embryo in 10 would result in a 1 SD increase in IQ.

 

This would be true for any randomly mating couple.

The polygenic nature of IQ and the implications for IQ enhancement through genetic selection is a universal truth.

 

This will have extremely profound social implications.

There is currently no nation that has a reported IQ even 1 SD above Greenwich mean.

For example, Japan's national IQ is typically reported as 105.

 

It is now possible for anyone to move the next generation in their family's IQ by 1 SD at a fairly modest expense.

 

To go back to the numbers: Each chromosome might have roughly 250 good SNPs on average, though for any comparison

there would be expected to be some variation, let's guess an average variation of +20 SNPs. Over 46 chromosomes this would be

a difference of a possible difference of +900. This would be a 10 SD enhancement of IQ. If you could completely extract all the gain,

there would be a new average IQ in the community of 10 SD or 250. No human has ever had 250 IQ. Farm breeders have enhanced

phenotypes for over a century and gains are still occurring. The same would be true for humans. Simply selecting the best embryo will

result in ongoing increases in human phenotypes including IQ.

 

This is a minimally complex technology that is already well entrenched across fertility clinics. It has recently been noted that China has

done a massive build out with this technology and is now already ahead of the US in this area.

 

There is no aborting of fetuses involved here. There is no fetus. One implementation of this would be selecting among embryos of perhaps

only a few cells of maturity.

 

This is true that the current technology is typically about selecting against a monogenic disease. Such technology has been in use in the community

for almost 50 years. For many, existing technology has not resulted in a perceptibly different humanoid life form. Polygenics clearly will result in

such a change. The main difference will be that everyone will reproduce through fertility clinics. Clearly it will seem quite odd if some would choose

any other form of reproduction. It will no longer be seen as ethically acceptable to allow a randomly recombined life to be brought into the world.

Would someone think it rational to go to a casino to select the genotypes of their children. I think not. Then why would they allow a completely random

genetic process to select their children's genetics? The horrific genetic mistakes that are all too common today will soon be a thing of the past.

 

Ideally for sperm selection, one would only need perhaps 100 sperm to have a wide range of recombinations for each chromosome. Perhaps instead of +20 per chromosome

one could move to +50. This would more than double the top end of optimal IQ with a very simple technology. Of course, one might then always look for a chromosome donor

who had been highly selected to have an extremely unique chromosome perhaps with a rating of +100. This would again double the top end phenotype.

Large scale sperm sequencing would never be needed. All that would be required would be to sequence the parents once and then use FISH to find which chromosomes recombined. Perhaps 5 Fish probes per Chromosome would be enough.

 

Going to sperm and egg genotyping would entirely eliminate ethical questions associated with this technology.

 

I have avoided focusing on CRISPR because this is the high end route and there was almost immediate resistance expressed to enhancing IQ or improving

humanity. The first international response was to declare an international moratorium. Genetic selection sidesteps the high tech end entirely. Profound disruption of

human society can occur without the approval of government: Increasing human IQ by even an average of 1 SD would have extremely significant implications.  

 

Moving the conversation away from CRISPR also allows us to talk about what can be done now and not in decades. The selection technology is already widely

accessible in the community. What is of particular note from the url I provided above is that this company stated that they would not be specifically selecting for

enhanced IQ. This is especially interesting because they stated that it was not that they could not provide such a service, but that they felt that the social issues

surrounding such technology have yet to be fully resolved. This interpretation of what is and is not socially acceptable might be different in other regions of the world 

(including for example China).

 

Whatever horrible birth defects that might arise in the future will almost certainly occur in those who have been genetically engineered by the casino protocol.

It is quite startling how flawed human reproduction can be in this respect.

 

One only has to look to some of the universe's most affluent communities to see what happens when randomness is allowed to design the genetics of children.

Silicon Valley is experiencing an extreme autism epidemic. This is obviously not a great surprise. Surely everyone can think back on those class members who

were clearly intellectually gifted and yet somehow not entirely socially normal. Perhaps shadow autism? And they then migrated to Silicon Valley, met, married

and mated other highly selected people who also were somewhat autistic. They then rolled the genetic dice and, as is now widely acknowledged, have created

a generation with more than a quirky personality. For those who have been paying even the slightest attention, we are now confronting a very large autism

challenge not only in the Valley but across most of our communities. It is not difficult to imagine that once the roll out of the next generation of genetic services

finally moves into stride there could be scenes similar to Thanksgiving sales that one can view on their television sets. Namely ordinary citizens fighting over the

last half priced wide screen TV set.

 

I do not have $1 billion. If I were to have such a sum dropped from a passing pigeon or something, then I would not find it unreasonable to spend 10% of my 

net worth on genetically engineering each of my children. Some might find such spending excessive and perhaps even objectionable, though by doing so

I would be building out the technology and allowing a reduction in price so that everyone else in the community would eventually gain access to such technology.

Of course, if I were to put $100 million on the table for optimized genetic engineering for my child the results, even given today's technology would without question be

quite stunning. The phase transition behavior of different traits has now been discovered. This means that it is now understood that about 1 million DNA samples

would essentially completely unlock the IQ genome and most any other human trait/condition.

 

There is simply no reasonable chance that the future will be even remotely similar to the present.

The technology that could start us on this journey does not need to be overly hi tech.

 

 

 

 

 

 

 

 


Edited by mag1, 10 January 2018 - 04:16 AM.


#165 pone11

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Posted 10 January 2018 - 04:56 AM

@mag1 so you are identifying three different approaches to increasing IQ:

 

1) Allow natural combination of sperm and egg, and then use genetic testing to select the embryo most likely to be the smartest

 

2) Try to find a technology that allows genetic identification of very large numbers of sperm, to select the sperm most likely to produce a good combination with a given egg.

 

3) CRISPR technology, which implies direct genetic manipulation of a fertilized cell

 

Regarding 1), I think you should try to clarify what exactly your proposal is.   For example, do we collect 10 eggs from a female?   Do we fertilize all 10 eggs at once, test all the fertilized eggs for their genetics, and then select the most promising fertilized egg?   Practically speaking, who is going to do that?  No organization exists to do that.

 

To select for intelligence based on our current understanding of intelligence SNPs is also likely just guesswork.  I'm not sure we have the foundation in research and understanding the interactions between SNPs to make these decisions.

 

Regarding 2), how does FISH help identify genetics of a sperm?  I thought FISH denatured the sample, and then FISH also involves some kind of genetic recombination to do its identification?  In other words, it is not a totally passive approach, which is what you probably need since the sperm only contains 23 chromosomes?   You can't mess up your original sample or you have destroyed the potential for that sperm to do its work.

 

I see lots of technical problems with this approach, but I also think this is by far the way the best way to tackle this problem.   If you could get financing to start a company to do this, and if you could invent novel solutions that would let you genetically profile very large numbers of sperm, you could then select the best candidate for a given target egg.   This approach would avoid objections from religious organizations that you are discarding a fertilized cell, since you would select the best sperm and hope to only fertilize one egg.

 

Regarding 3), I fear that CRISPR is going to start a eugenics arms race.   At first it will be rogue researchers doing illegal work.   At some point governments will realize that unless they participate that a competing government that creates 100K genius children might simply be able to outcompete everyone else.   In any case, this isn't something we have any chance to stop at this point.  The genie is out of the bottle.


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#166 mag1

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Posted 11 January 2018 - 03:45 AM

Yes, I wanted to suggest a range of possibilities.

Another one would be that one could select the optimal chromosomes from 100 sperm and 100 eggs.  

Given the nature of gametogenesis one could genotype the complementary sperm/egg and would then know the genetics of

the ungenotyped gamete. 

 

My intention was to signal that once this moves into the mainstream and becomes big business there would be a wide range of

low hanging fruit that would then be available for further development.

 

The url that I provided above is now already offering a service that will select the optimal embryo for a range of traits.

Polygenic risk scores now exist for a wide range of traits/diseases. So, with this currently existing service one could now

select am embryo with a very low risk of Alzheimer's, or diabetes, or schizophrenia or many many other traits.

 

This should give readers of this thread something to think about. We are now entering an era in which typical parents to be

might reasonably consider selecting a particular future for their offspring. Until now only a small group of parents who carried

or were affected by various conditions would become customers of fertility clinics with the purpose of choosing the genetics of

their children. With the current state of the technology, there is no reason to expect that genetic selection will not go mainstream.

 

It is only when you start looking through your genome that you realize that there are many genetic edits that would probably

be for the best. I have genotypes for cannabis induced psychosis, potential alcohol and drug seeking tendencies, dyslexia,

and many many others. Anyone with a background in genetics would comment that these are not causally related to those conditions

which is true. Yet, removing such risk enhancers would be a wonderful gift to give the next generation. In an optimized version of

genetic selection, the next generation would be profoundly different from what humans have been up till this point in time.

 

A big problem in this discussion is that there is a substantial knowledge gap concerning where the technology currently stands.

There is this impression that we are talking about science fiction. This is largely incorrect.

 

The science fiction that has shaped the conversation simply did not prepare us for what is now science fact.

Brave New World will never happen.

There will be no generation with alphas and gammas.

The next generation will all be alphas; we will be the gammas.

 

The alphas that were portrayed in Brave New World really did not seem that overly smart.

We have been accustomed to a genetic overclass that was perhaps only 1 SD IQ over the average in the community.

A 1 SD increase is now easily within the reach of anyone interested.

We are now likely beginning a long term journey in which there will be at least 1 SD increases in IQ per generation possibly for centuries.

 

To put this into further perspective, only 1 million genotype files would be necessary to unlock human IQ.

This is a calculation based on theory from phase transition research.

It has already been validated in human height.

As soon as we reach somewhere near 1 million DNA files, we would then have ALL the IQ SNPs that exist.

However, Ancestry.com already has 8 million such files and will likely surpass 10 million within the next month or two,

other genomics companies have many millions more of these files. A million file Educational Attainment GWAS is

expected at any time. It is no longer reasonable to suggest that the human genome cannot be deciphered. Such statements

were made only a year or two ago. However, with current technology it is now understood to be incorrect.

 

The SNPs involved in IQ have such minimal effect sizes that interactions probably only explain a fairly small fraction of the

heritability. 

 

The sperm suggestion was merely to point to the next step up with the technology and to rebut the idea that an overwhelming and completely

unmanageable amount of sequencing would be needed. All you would need to do is sequence the parents once. From there it would only be a

question of determining where the gametes recombined. Avoiding sequencing every gamete and only genotyping a few locations on each chromosome

reduces the workload by a factor near 1 billion. 

 

   

This technology is already being constrained more by social/political factors than by what can now be achieved. Clearly the technology could be used to select

for IQ. However, this is thought to be too sensitive. Yet, almost everything in life leads back to psychometric g. Did the same people who passed an international

moratorium on gene editing also intend to doom those with schizophrenia, or autism or Alzheimer's or other cognitive impairments ... to debilitating and unfixable

medical problems. Intelligence is a prominent feature in all of these conditions and many more. Intelligence is the central node of a range of neuro-psychiatric behavioral

metabolic conditions. When will a mature discussion begin in which it clearly stated that enhancing intelligence is necessary to fully address a range of medical problems.

 

How is it ethically acceptable that enhancing intelligence has been characterized as a step toward a morally repugnant eugenic future?  

Where is the humanity of those who have assumed such authority?

 

The political interference that has already emerged to try and stop the future has greatly motivated me to avoid a hi tech approach.

Selection does not require CRISPR.

It does not require anything that would not be available to an even medium-low technology environment.

There is no reason to think that this technology is not now doable in many developing nations.

   

Of course once we have increased IQ by 1-2 SD, then most of the social obstructionism will vanish.

With human IQs of around 100, we are not far from the line of only being able to get by.

Many people in this IQ range need a range of professionals to cope with their lives.

As IQ is enhanced, the social requirement for social classes of "helpers" and "helped"

would no longer be needed. A big part of the resistance of actually making a fantastic

eugenically designed world is that there are likely those who might be interested in

preserving the current hierarchy. Once the wave of IQ enhancement begins, people

will wonder how anyone could have thought in such a way.

 

 

 

 


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#167 mag1

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Posted 12 January 2018 - 12:13 AM

Thank you Mr. Agreer!

Not sure what you are agreeing with, though I'll take the credit and run with it.

 

We really need to have a mature conversation about what is about to happen.

The mainstream perception of where the science currently stands is woefully outdated.

It does not seem entirely unlikely that if this continues we will all wake up one morning in the not too distant future and have super super smart kids and have no idea how to manage them.

 

It is critically important that we start thinking about this now.

There could be substantial security risks if we don't.

 

 

 

 

 


Edited by mag1, 12 January 2018 - 12:14 AM.


#168 sensei

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Posted 12 January 2018 - 12:44 AM

Hi, pone11 thank you for stopping by the thread.

 

Very exciting news about the next generation of 3-BP.

Looks like cancer will be toast.

 

I have been totally startled by the developments that have been ongoing with GWAS and genetic enhancement possibilities.

My main concern is that there will be an attempt to endlessly delay rolling out the technology.

 

This is why I have been more focused on the selection technology.

Embryo selection is already a mature technology.

Adding in polygenic selection will not be a large step from current methods.

CRISPR might be stoppable, though stopping selection is much less plausible.

 

 

 

Single base pair editing is now a reality A-T to C-G in DNA 

 

http://www.sciencema...ng-new-ways-fix


Edited by sensei, 12 January 2018 - 12:45 AM.


#169 mag1

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Posted 12 January 2018 - 03:05 AM

Thank you sensei for this update.

 

My concern is that with CRISPR endless roadblocks will crop up as we move closer to the clinic.

It will become another mirage in which the future CRISPRed world is always a step ahead of us, though eternally is never any closer.

https://www.biorxiv....18/01/05/243345

 

Of course, CRISPR might not actually be entirely helpful until we actually know what the exact causal SNPs are.

With polygenic traits having extremely small effect sizes identifying these causal variants could be a time consuming search.

Selecting at the level of the chromosome might help avoid such concerns.

 



#170 pone11

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Posted 12 January 2018 - 07:47 AM

Thank you sensei for this update.

 

My concern is that with CRISPR endless roadblocks will crop up as we move closer to the clinic.

It will become another mirage in which the future CRISPRed world is always a step ahead of us, though eternally is never any closer.

https://www.biorxiv....18/01/05/243345

 

Of course, CRISPR might not actually be entirely helpful until we actually know what the exact causal SNPs are.

With polygenic traits having extremely small effect sizes identifying these causal variants could be a time consuming search.

Selecting at the level of the chromosome might help avoid such concerns.

 

We know exact genetic mutations in specific genes that cause many specific diseases.  I guess even for these cases CRISPR is a long way off from being therapeutic because there is still no way to force the change into all of the tissues of the body?

 

One thing I do not understand:  what happens in a case where CRISPR makes x% of your tissues "fixed" but y% remain unfixed?   The body would live in a state of partial defect, with the two different cell lines co-existing side by side?   I guess in this case the CRISPR therapy would continue to be applied repeatedly, hoping to get enough cells converted over time to fix the underlying disease sufficiently well?



#171 Kalliste

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Posted 12 January 2018 - 11:29 AM

Very bad results for CRISPR. Most humans seem naturally immune to the therapy.



#172 pone11

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Posted 12 January 2018 - 12:09 PM

Very bad results for CRISPR. Most humans seem naturally immune to the therapy.

 

That is just a bump in the road.   They just need to work on a delivery vehicle.

 

The first generation of RNA therapies had similar issues, with lots of immune responses and problems getting the RNA into places where it could be used.   Newer generations of RNA therapies use custom molecules to bypass immunity and deliver replacement RNA where it is needed.   This approach is working in animal studies for metabolic diseases like urea cycle disorders and some of the fatty acid oxidation disorders.

 

I think they will overcome the immunity issue.  I still have no concept of how they will manage to change more than a very small percentage of the whole body DNA.



#173 sensei

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Posted 12 January 2018 - 12:49 PM

 

Very bad results for CRISPR. Most humans seem naturally immune to the therapy.

 

That is just a bump in the road.   They just need to work on a delivery vehicle.

 

The first generation of RNA therapies had similar issues, with lots of immune responses and problems getting the RNA into places where it could be used.   Newer generations of RNA therapies use custom molecules to bypass immunity and deliver replacement RNA where it is needed.   This approach is working in animal studies for metabolic diseases like urea cycle disorders and some of the fatty acid oxidation disorders.

 

I think they will overcome the immunity issue.  I still have no concept of how they will manage to change more than a very small percentage of the whole body DNA.

 

 

CRISPR CAS 13 works much better

 

And it is not an actually correct statement to say humans are immune to CRISPR CAS 9 -- in a very small cohort (40 or so people) 79% had antibodies to Staph CAS 9 -- duh staph is in 90% of peoples noses, a species wide subclinical infection -- I bet it's close to 100% for p.acnes based CAS9

 

But when they looked at T cell immunity -- only 46% had antibodies to Staph CAS 9, and ZERO had immunity to strep CAS 9 -- and there are literally THOUSANDS of CAS 9 enzymes to choose from.

 

https://www.theatlan...-system/549974/

 

And just because you have antibodies that can bind to something does not mean there are enough to work. Everyone who becomes infected with HIV develops antibodies to HIV -- yet almost all 99.997% die from complications of HIV without anti-retroviral therapy.


Edited by sensei, 12 January 2018 - 12:52 PM.


#174 mag1

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Posted 12 January 2018 - 02:09 PM

Of course, from the point of view of genetic engineering of an embryo anti-CRISPR antibodies are of no

importance.



#175 dalack

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Posted 05 March 2018 - 06:14 AM

I think George Church's  anti aging research will be leading the way. This guy's a genius and i'd bet money that several of his patents will be key to reversing aging.  He's already shown he can correct mitochondrial aging with Crisper plus they are working on a full body Crispr delivery system. 

 

https://www.nextbigf...st-comments-362



#176 mag1

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Posted 22 April 2018 - 04:39 PM

The recent ssgac results in which they found 3,000 SNPs for EA have finally moved genetic enhancement in the spot light.

It is no longer reasonable to expect that this will not happen, the only question that remains is when.

Apparently, in China the answer to this question might have been yesterday.



#177 mag1

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Posted 21 May 2018 - 02:21 AM

I have only recently become aware that an even more dramatic possibility exists for IQ uplift.

 

Duf1220.

 

These CNVs can add 3 IQ points each for some of these small segments of DNA.

Humans typically have around 30 of a particular type of these genetic variants, creating a variation

of possibly 20 points from those with the most to those with the least.

 

There is a very noticeable increase in their number as you move up from average mammals to average primates and then to humans.

It is possible that gene editing in many of these CNVs could greatly enhance human IQ, while at the same time possibly introducing concerns

about autism and schizophrenia risk.

 

These CNVs open up the potential of creating an entirely new humanoid genius species not in centuries, but within a single generation.  

Adding in 100 might result in 300+ IQ humans. Up till this point this thread has been focused mostly on low end embryo selection technology. Such technology might perhaps only give 20 IQ point average enhancement per generation; adding Duf1220 elements possibly could go well beyond that. 


Edited by mag1, 21 May 2018 - 02:32 AM.


#178 mag1

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Posted 25 July 2018 - 08:14 PM

1.1 million person Educational Attainment GWAS has been published in Nature Genetics.

This article reveals 1271 SNPs for EA that if optimized would give ~17 SD of EA or roughly 200 IQ.

Hundreds of more IQ points should be uncovered as the sample size moves up to 2-3 million.

 

https://www.nature.c..._referer=nature

 

Embryo selection is already a widely available reproductive technology.

Now that the SNPs have been published there is no longer any reason for IQ uplift not to begin.

The first generation of IQ enhanced humans could be born starting April 23, 2019.

Get ready!


Edited by mag1, 25 July 2018 - 08:42 PM.


#179 mag1

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Posted 28 July 2018 - 09:56 PM

I have reread the thread and it surprises me that the idea about embryo selection was introduced less than a year ago. The implications of having very small effect sizes did not register with me.

It had seemed to me to be such a defeat for the potential for IQ enhancement. I had thought that CRISPR would be the technology needed to realize IQ uplift. However with CRISPR it will probably take decades to finally reach the clinic. Yet, here we are now just 3 years after the thread launched and genetic enhancement with existing infrastructure is now feasible. Simple IVF embryo selection will bring us to a world of health, prosperity and wisdom. The entire conception of a genetically stratified life can fade.

 

The Age of IQ uplift has begun.

 

A big concern that I have had right from the start was that there would be endless opposition and regulatory friction to moving IQ enhancement forward.

Yet with IVF clinics, patients already are faced with the question of choosing embryos for implantation. It might not be especially easy to know what

the exact motivation that might exist for choosing any specific embryo. If parents chose an embryo with a 1 SD higher genetic IQ potential, then this might not be 

entirely conspicuous. It would be simply a private choice decided by parents to be and the clinic. Such an arrangement begins to push aside the interference

of the broader community and the government.

 

This is such an exciting journey and I feel so blessed that I can watch as a new chapter in human history begins.

 



Click HERE to rent this GENETICS advertising spot to support LongeCity (this will replace the google ad above).

#180 Kalliste

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Posted 30 July 2018 - 05:24 PM

There was another round of very bad news regarding CRISPR induced mutational load recently.

 

http://www.foxnews.c...study-says.html

 

 

Gene-editing tool CRISPR-Cas9 has garnered significant amounts of positive press in recent months, as the promise of gene editing could help with medicine and alter DNA for the better. But a new study suggests that CRISPR isn't all it's cracked up to be.

The study, published July 16 in Nature, makes the case that instead of CRISPR being thought of as a pair of "molecular scissors" (as it has been previously called), making surgical precise cuts, it may actually be "blunt" and cause more damage than previously thought.

"This is the first systematic assessment of unexpected events resulting from CRISPR/Cas9 editing in therapeutically relevant cells, and we found that changes in the DNA have been seriously underestimated before now," said Allan Bradley, one of the authors of the study, in a statement. "It is important that anyone thinking of using this technology for gene therapy proceeds with caution, and looks very carefully to check for possible harmful effects."

FUTURISTIC GENE EDITING TECHNOLOGY MAY CAUSE CANCER

The study was co-authored by Michael Kosicki, Kärt Tomberg and Bradley, all of the Wellcome Sanger Institute in Hinxton, U.K.

According to the study, some CRISPR (short for Clustered Regularly Interspaced Short Palindromic Repeats) edits may actually produce indels (known as deletions) at a scale of thousands of bases, or significantly more expansive than previously thought. This affects adjacent genes and could interfere or disrupt certain genetic operations that have been deemed normal.

“The cell will try to stitch things back together,” said Bradley, a mouse geneticst in an interview published to coincide with with the study. “But it doesn’t really know what bits of DNA lie adjacent to each other.”

Kosicki, Tomberg and Bradley's findings conclude that the reason this type of damage has not been encountered before in previous studies is because damage at this scale was never allowed to occur. In effect, the cell itself is not doing what it is supposed to and that's causing alarm for some researchers in the field.

“I do think this has been underappreciated by the field,” said Patrick Hsu, a bioengineer at the Salk Institute in La Jolla, Calif.

The results of the study hit the stock prices of some companies associated with CRISPR, according to a report in The Wall Street Journal.

Prof. Maria Jasin, who was not involved in the study, said the research shows that more work is needed. "This study is the first to assess the repertoire of genomic damage arising at a CRISPR/Cas9 cleavage site," Jasin said in a statement. "While it is not known if genomic sites in other cell lines will be affected in the same way, this study shows that further research and specific testing is needed before CRISPR/Cas9 is used clinically."

Fox News has reached out to George Church, professor of genetics at Harvard Medical School and one of the inventors of CRISPR-Cas9 with a request for comment.

CRISPR COULD ONE DAY HELP CONSERVATIONISTS SAVE OUR OCEAN'S CORAL

Previous studies often used many copies of the same thousand-pair sequence, TechCrunch reports, which allowed CRISPR to function properly and the threat of any damage was negligible. It's only when longer strands of DNA are introduced does the level of danger rise.

"We speculate that current assessments may have missed a substantial proportion of potential genotypes generated by on-target Cas9 cutting and repair, some of which may have potential pathogenic con-sequences following somatic editing of large populations of mitoti-cally active cells," the authors wrote in the paper.

Despite the genetic damage seen on longer DNA strands, it's unlikely to stop or halt CRISPR's use when it comes to gene editing, James Haber, a molecular biologist at Brandeis University in Waltham, Ma. told Nature.

“It means that when people use it, they need to do a more thorough analysis,” Haber said in the article published in Nature. “It’s generally important to know whether your mutations are as you think they are.”

NEW CRISPR TECHNIGUE COULD ACCELERATE A CURE FOR HUNTINGTON'S DISEASE AND ALS

CRISPR has been credited with several biological and scientific achievements in recent months, including eliminating viruses in pigs that could be harmful to people, which could lay the foundations for pig-to-human organ transplants.

The gene-editing tool has also been used to correct a disease-causing gene mutation in human embryos, preventing the mutation from passing to future generations.

Fox News' James Rogers contributed to this story. Follow Chris Ciaccia on Twitter @Chris_Ciaccia

 


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