Genetic Engineering and unknown consequences

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slacker
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Genetic Engineering and unknown consequences

Post by slacker »

Interesting perspective from Moises Velasquez-Manoff, with specific mention of ApoE4;

https://www.nytimes.com/2017/06/17/opin ... genes.html
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Re: Genetic Engineering and unknown consequences

Post by Stavia »

very interesting!

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Re: Genetic Engineering and unknown consequences

Post by J11 »

This is happening FAST!!!

Ten years ago few people were aware of their APOE epsilon genotype.
In fact at that time there were significant hurdles to overcome to gain such knowledge. APOE genotype is now easy and inexpensive to obtain.

The polygenic nature of AD has only been described over the last few months.

I have a feeling that we are hurdling towards a very different life.
Once the mainstream appreciates that the discussion is shifting from fixing genetic faults to optimizing human genetics, the race to our genetically engineered future will greatly accelerate.

It still does not appear to be widely understood that dementing illness is "a hardwired" feature of the human genome. It is a restriction of range problem. Those on the lower end of the polygenic distribution score should be reminded that Alzheimer pathology is universally present in those over the age of 90.

Without CRISPRing genomes this will remain true. However, CRISPRing variant APP would result in aged communities without dementing illness.

Now is the time for grown up discussion about where we are heading. The dialogue has clearly moved beyond the ban on germline editing that was proposed at the Washington meeting. Considering how fundamentally important genetic engineering will be for humanity, such a conversation would seem essential. If it were to be postponed further we would only be talking about what could be seen in our rearview mirror.
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Re: Genetic Engineering and unknown consequences

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Part of such a discussion could raise the question of how this might have bearing on the future of medicine. Without recessively inherited illnesses or dominantly inherited or polygenetically inherited after CRISPRing, what is left?

Rationalization of medical resources often involves long lags. Usually appropriate market signals are never sent within medical systems to guide people in making wise choices. Typically especially within a government administered system change is delayed for as long as possible at which point dramatic restructuring becomes necessary. When change does eventually occur, many people would then be caught out.

One suggestion that could help avoid this would be to greatly increase the wages of pediatricians. Once there is widespread uptake of genetic selection / genetic engineering, the number of newly born genetically at risk would quickly drop to zero.

This should no longer be considered to be on some distant horizon. Many on this forum have gained insights into their genomes, and wish their genotypes might have been more favorable. What is especially exciting is that with the online resources that now exist it is entirely possible to trace a genotype back 10 generations or more. This is an overwhelmingly powerful development. Once a genotype of interest were found one could go directly to an online genetics database and find other potentially family carriers. Those on the forum who have been dealt a genetic risk might Take it upon themselves to do such a search. This would be of particular importance in recessive illnesses since many of these people would be unaware that they were carriers.


Those doctors who intend to pursue a career helping these children need to be given a signal that this specialty of medicine could be impacted greatly perhaps even in the near term. Paradoxically offering a large risk premium would alert them of this risk.

There have been instances when people have been directed towards careers in medicine as a goal in itself, limited job prospects and unemployment followed.

In order to reduce the chance that this could be gamed, clear timelines could also be given for when some of these services would be delisted. In some medical systems, delisting of services to children in need has already occurred without an appropriate market signal ever being sent.
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Re: Genetic Engineering and unknown consequences

Post by hairyfairy »

If it were at all possible, I would jump at the chance to swap my apoe4 gene for a 3 or a 2, becaause from what Iv`e read, there`s no upside to apoe4 in the 21st century, it causes nothing but trouble. It may have been beneficial for our hunter gatherer ancestors, but it`s just a relic of the past & needs to be removed from the gene pool.
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Re: Genetic Engineering and unknown consequences

Post by Fiver »

J11 wrote:Now is the time for grown up discussion about where we are heading.
I agree with this but I doubt it will happen.

I'd be first in line to get a gene or two swapped out, so maybe I'm part of the problem. Though in my case, there's no chance I'm going to pass my brand new genes down to the next generation. So perhaps I'm a safer bet. :D

But I do think scientific progress is occurring faster than we can keep up, or make smart or difficult decisions as a society. I'd argue that it's already impossible to keep up and have a real understanding of it all. Even those few with great natural intelligence (lucky folks!), resources, and decades of education struggle to keep up in super-specific sub-fields of STEM. That seems to be the drive for AI, to handle the complexity that we can't.

But this sort of genetic engineering will happen, somewhere. There's too much need and profit to be had. Once successful it will confer advantages that objectors won't have and they'll be left behind. Heck, maybe genetically-engineered people will be smart enough to understand it all, or think they are anyway.

Makes me think about the Sentinelese tribe They are so vulnerable to illnesses and are at the mercy of others. They just want to be left alone. In a way, they've opted out. Humanity may or may not allow them to live on one tiny island. Or, in my area, the Amish.
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Re: RE: Re: Genetic Engineering and unknown consequences

Post by Stavia »

Fiver wrote: But this sort of genetic engineering will happen, somewhere. There's too much need and profit to be had. Once successful it will confer advantages that objectors won't have and they'll be left behind.
Exactly what I think.


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Re: Genetic Engineering and unknown consequences

Post by J11 »

Thank you for replying Fiver!

"Now is the time for grown up discussion about where we are heading."

Yes, I am not sure whether I should understand your quote of my post as ironic or more as an historical counterfactual!
That was almost two years ago and the grown ups never seemed to find a moment or two to discuss the Cognitive Singularity with any amount of seriousness. The only high level discussion that I am aware of was in Washington in 2015 where an international ban on gene editing was proposed and accepted.

Even now there is a hopelessly misinformed counter-effort attempting to obstruct the emergence of smarter humans. One can hardly wait for the future to arrive. Bring on those Neanderthals I say. Current psychometric research finds that a multi-century IQ decline if continued for another few centuries could have serious consequences for our ability to maintain a so called modern lifestyle. Choosing not to upgrade our IQ for humanistic reasons would result in a humanity that was less capable of being humane.

We have had a century of:

"Hey, Hey, Ho Ho Racist Psychometric Eugenic Pseudo-Science has got to Go
Hey, Hey, Ho Ho Racist Psychometric Eugenic Pseudo-Science has got to Go
Hey, Hey, Ho Ho Racist Psychometric Eugenic Pseudo-Science has got to Go
etc.
etc.
etc.
{Repeat a few more hundred times until someone can think up a wittier primal tribal chant.}

Is it even possible that we would have to listen to this for another century?
I am praying hard that this meme can soon be retired.

However, what is approaching now is clearly of greater consequence: the Truth
{or at least some watered down version of it}.

Global mainstream media have only recently stopped with their own form of anti-rationalism dogma.
They have finally grudgingly noted that intelligence might have something to do with genetics, and some ability to control
genetics might arrive sometime when science figures all the messy details out.
This is now the minimum standard of psychometric knowledge expected of the newspaper reading audience.

If we want to take this up a notch for a discussion in a more informed scientific audience, 1 in 10 embryo selection using current GWAS SNP knowledge yields perhaps a 10 IQ point gain at a not entirely unaffordable cost for even a middle class family. A 10 IQ point gain has never occurred in any human population on such a time scale. Using pregenomic technology, increasing IQ by 1 point over the course of 10,000 years should be understood as an achievement. The new technology will overwhelm any existing psychometric differences that now might be present between and within any human population group. If given the authority, I have no doubt that I could increase human IQ by a bare minimum of 100 IQ points over the next century. Increasing IQ now should be understood as an almost trivial achievement.

Of course, the above discussion is only using a fairly mild selective force of 1 in 10 embryos. What if one were to prescreen with
population scale mate optimization? By carefully selecting couples on the basis of their existing psychometric genetic architecture it should not be unexpected that additional IQ gains could be achieved. How much is not entirely clear (currently running the mainframe on this question), though as a basic pull it out of the hat guessimate, A LOT would be consistent with my current opinion.
The prescreening of mates is completely beyond the power of government to prevent. As we all know, genotyping is freely available DTC and costs about $50. Tens of millions of people have already been genotyped. The only question now is when even more accurate PGS will arrive.

Up till now the strategy of simply choosing a smart spouse has not been an overly successful strategy to create equally smart children. In fact, this has probably been the largest commonly held psychometric myth of them all. What actually happens is that the very not so smart parents have smarter children, while the very smart parents have not so smart children. This is almost certain due to regression to the mean.

In this new era, carefully selecting spouses on the basis of their compatibility of genetic IQ architecture could completely reverse this. We are now in an era in which organizing genomes that will be resistant to regression to the mean will be possible. IQs should increase monotonically from generation to generation perhaps for centuries.

Yes, so prescreening mate selection combined with embryo selection starts to give us considerable IQ lift. One might not want to even contemplate what happens when chromosome selection is thrown into the mix. Chromosome selection was demonstrated in mice several years ago and is probably moving towards human application as substantial numbers of people are afflicted by trisomies etc. . Adding this in would increase IQ uplift probably what would best be thought of as beyond measure. At a certain
point you just run off the number scale and are reduced into the somewhat unsatisfactory descriptions of big, very big etc. .
Of course transplanted chromosomes from an optimized population scale DNA bank would bring you to scary big gains in IQ.

So, that's how things stand 100 days before the start of the era of IQ enhancement.
I am so glad that we finally had this grown up discussion, because if we had waited any longer we would have had 1000 IQ people running around and have had absolutely no clue what was happening. As it is we have 100 days, so at least we can start training at endurance running. For whatever reason, there is still a notable absence of other grown ups (correction: best call them adult children) engaged in this discussion. One can only hope that leadership will eventually emerge on this issue.

Yet, for those who might still be unsure how the 21st Century will unfold, I can predict with almost 100% certainty that the Cognitive Singularity will materialize during this century and create pervasive and profound social disruption.

Do you want to know where we are heading?
Look up!
Look straight up!
Last edited by J11 on Mon Nov 26, 2018 6:05 pm, edited 2 times in total.
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Re: Genetic Engineering and unknown consequences

Post by Fiver »

J11, you’ve given this a lot of thought! I was serious when I said that I’m sure genetic engineering will happen someday soon, somewhere. Actually, technically it alteady has....they replaced a muscular dystrophy gene, I think, right?

For me, I just want to fix an apoe gene then retire to a quiet farm somewhere. I barely have the IQ to keep up now!
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Re: Genetic Engineering and unknown consequences

Post by J11 »

Fiver, when I first posted about this I even wondered myself: Is it realistic that IQ uplift will help the apoe4 community?
It did seem somewhat ... out there.

Yet, here we are and those who are informed up to the level of reading a mass circulation newspaper are aware-- to at least some degree of consciousness-- that intelligence enhancement is on the way. Media is waving the white flag. They must be as worried about this as I am. It is only months away now; they wouldn't have blinked if it were any further away. The logic being well if it isn't in this quarter's financials then don't worry about it. Planning your future by looking one step ahead does not sound like wise advice to me. As I am sure you are aware, once scientists can move the needle even somewhat on some experimental variable, it is foolish to bet against an exponential curve emerging tout de suite.

I think there should no longer be any doubt that this is approaching. My inclination would be to expect more than the minimum.
It is simply too important for our economy, our security, our future to believe that this will all just blow over.
The millions of people with apoe4 genotype, their advocates and the entire broader dementia community and other health
challenged communities should reasonably be expected to become engaged and perhaps directly participate in humanity's IQ uplift
as a strategic means of advancing their self-interests.

This is what has sparked the current media capitulation.
https://www.nature.com/articles/s41588-018-0147-3

Those on the forum interested in their rough genoIQ could consult the supplementary file for the variants.
The results from this article were actually originally disclosed many months earlier, so a wave of cognitively enhanced children
might already have been born. Clearly the transition to the new era over the next few months might seem under-whelming perhaps even non-existant, though through time we can expect Singularity scale disruption to emerge. A 10 point IQ upgrade which is thought to be doable within a reasonable budget would create a gale force technological storm. At a minimum the next generation would amplify this by another factor of 10. All of our current problems would then be easily solved; I suppose then the question might become how do we fix all of our new problems?

There are some nations in the world where maximal use of these results for cognitive enhancement should not be a total surprise. China has not so long ago become the world leader in preimplantation genetic diagnosis (overtaking the US). They have not hidden their intention to use genetics to enhance the competitiveness of their people. They have also been notably silent about their own research into cognitive genetics even though they would also be considered the world leader in sequencing. It should also not be a total surprise if they were to announce at some not too far distant date that mass IQ enhancement was already producing a generation of high IQ children. The economic value to world capitalist markets would be massive. Someone with an IQ of 200 can generate roughly $100 million per year of wealth generation.

The one big question that I am still unsure about is how high? Increasing IQ by a mere 10 points would accelerate technological progress by a factor of 10. 100 points would give 10 to the power of 10. Are we actually ready for a 10 billion fold increase in technological change? Um, Fiver if you have an extra pile of hay on your farm, I'm in! What I am worried about is that others on the forum look like they might have better agricultural aptitude than I possess, though I could read up on it on the net. It is amazing how muchand fast one can learn if one has to!

The date to keep in mind is April 8, 2019. This will be 9 months after the Ahead of Press posting of the Nature Genetics article.
This would be the logical date to declare as the start of a new era of human existence. For this forum it should also be thought of as a milestone: the date when a cognitively enhanced supergenius humanoid species makes its first tentative debut in our world and likely will help us solve our dementia crisis. Thus, working through the details of how much enhancement and how fast might become an ever increasingly relevant question for our forum to quantify.
Last edited by J11 on Mon Nov 26, 2018 6:10 pm, edited 1 time in total.
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