Huh? I thought there's always been an obvious answer to this...
Cat girls
edit: ahh... I love the part of HN that can't enjoy even the lightest of humor. FWIW: I have a severe chronic/borderline terminal health condition that is near certain to leave me dead quite early, not to mention the hell it's brought upon my physical body. In 10 years or so (maybe even sooner) - it will probably be something that's editable out in vitro. Also... I'm young as it is.
Let me have fun with my dreams of cat girls. Maybe you'd end up enjoying them too. :)
The hype cycle is overselling what’s possible with this tech today and in the near future. If for example you need most cells edited then that’s far less viable etc.
PS: The original comment brought a smile, but I still downvoted. Keeping most jokes and obvious comments off HN is a major long term benefit.
Sometimes it's not about what's visible to your eye...
Though, I do agree, in general, it's best practice not to have too many laughs on HN.
Also... yeah, current state of things is a bit hype. I have a lot of hope though having spoken with people doing research at places like University of Tokyo. I'm sure whether ethically or not, China has probably made some great strides we're not 100% aware of.
The thought of China creating an army of genetically modified 200 IQ super soldiers/scientists is both fascinating and horrifying. It's comparable to the technological singularity that would occur if we had chains of AI creating superior AI.
It's already been done in China.[1] That was an attempt to produce HIV immunity. Not clear if it worked, but it was done. The Master Race is a ways off, but they're starting from a population with an average IQ of 105, so they're already ahead.
so basically mutations would be introduced to humankind, not randomly but based X number of ideas controlled by a government and by this removing entropy to our genetic pool.
Virus would love that, yes why no, lets remove the only thing that has keep all living organism on this planet
for billions of years from extinction.
I think I saw that implied unexpected twist in NEO-Scavenger, actually. There are newspaper headlines from before the collapse (which was related to a supernatural force of belief being real causing fears to manifest). They mentioned a Chinese Supersoldier Rebellion that had overthrown their government creators, I guess paired hyperintelligence and courage are the last things you want in a populace as an oligarchy or dictatorship as they will see things going wrong and won't be afraid to risk their lives righting it effectively.
Yeah, this is actually ignoring how most dictatorships explicitly have an underclass. If you want total control you don't want your country to be strong and prosperous. You want a few blessed elite sectors and let the rest wallow in suffering and poverty so they neither have the ability nor will to fight back.
These are the types of things that will be fixed as we tip toe into altering our genes. But in the end, like most technology, someone will end up doing whatever is possible if the outcome gives them an advantage.
Some country will allow it as it gives them a leg up on others. And once you can do it in X country, the pressure will be strong for others to follow suit and allow it or fall behind.
This is excepting the case where it generates some near term negative effect that outweighs the gains to be had by it.
Unless I am unaware of something, CRISPR is not yet ready for medical usage. Sure, it is an amazing research tool. But every gene editing trick built on the back of this incredibly useful protein (Cas9, that is) has "off-target" effects. These mean that not only do you mutate your target, you cause a whole bunch of other mutations. The future of human genome engineering is almost certainly going to feature CRISPR genes in some capacity, but we just don't have the precision, reliability, and ability to avoid other deleterious mutations yet to do so.
Also, as someone working with CRISPR, it isn't quite as easy as it is made to sound. It is relatively easy, but still a lot of work! I guess that is a footnote when it makes the impossible, possible though. We need to keep having these ethics conversations though, so we can use this tool wisely.
For further reading I would recommend Jennifer Doudna's "A crack in creation". She is one of the founders of CRISPR as a gene editing tool, and her book is good reading on the topic.
CRISPR isn't quite enough. That's just patching. Direct synthesis of a human sized genome will probably be available at some point. The human genome is about 3 billion base pairs. Largest synthesis so far is 580,000 base pairs.
Just synthesizing a genome isn't going to get us to designer humans - frankly its already well within the reach of modern technology to synthesize 3 billion bases. You cant just bootstrap from the nucleotide sequence - even in really simple bacteria we have to pop the genome into a pre-prepared genome free cell with the machinery to start working on doing life stuff, and adding the complexity of human epigenetics and a multicellular organism makes that a nonstarter currently. Especially when just editing the genome is so much easier.
I would be interested in reading some literature about the current problems of plopping a synthesized genome into a vertebrate ovum. Or a simpler multi-cellular species, say C. elegans.
This has more to do with the synthesis process itself, but here's a good read [0]. Youll notice most of the problems are around cost and logistics, but if we had the funding of the human genome project, that would be a non issue. I dont know if any articles discussing the epigenetics really exist since the organisms so far are ones where that's not really so much of a problem yet - I don't now of any de novo synthesized efforts in multicellular organisms but perhaps someone has a link (not counting cloning - the epigenetic information is carried along in the transfer).
I can't even imagine why you would want to synthesize and inject a replacement human chromosome (let alone the entire genome). That sounds like a huge waste of time and money, unlikely to achieve any reasonable goal, and prone to far more unintended side effects than localized patching
CRISPR is too unreliable and has too many off target effects to move the needle on height. By the time you've made a hundred CRISPR edits to a single genome, you've shot the other chromosomes full of holes. It's only useful for taking out one or two genes, for someone who knows they carry a fatal genetic disease, but still wants to have kids. True designer babies will be done with genome synthesis.
What you're describing is basically science fiction, far in the future. We have no technology to do what you're describing, nobody is planning on "repairing thousands of genes" to increase somebody's height.
Factual statement: "We have no technology to do what you're describing"
Correct. We can only assemble synthetic bacteria right now. Synthetic sperm is years away. Synthetic eggs are too complicated, I wonder if they'll ever be made. Synthetic embryos would be true sci-fi stuff, requiring heavy engineering and many breakthroughs.
Emotional statement: "nobody is planning on"
Human germline engineering inspires strong feelings. I'm sure that the advent of motorized vehicles would have inspired the same strong feelings in horses, if they could have understood what was about to happen to them. Nevertheless.
Well, I used to plan on this stuff. I mean, it was my career path for 20+ years. Then, after learning a lot more about the field, I came to the conclusion that these sorts of aggressive ideas are far beyond what we can reasonably contemplate, and it generates unrealistic expectations in the lay public when we suggest it's possible.
After He Jenkiu, genetic engineering took another huge hit because an irresponsible person ignored all advice and did a crappy job at fixing susceptibility to HIV infection.
This is not a "engines vs. horses argument". This is a "faster than light AI supership vs. horses argument".
So one thought I had just now: If an asexual organism has both a good and a bad mutation they are intrinsically tied together forever. But with sexual reproduction, chromosome crossover can produce offspring having the good mutation that are also free of the bad one.
Maybe we could clean up the off-target mutations using that.
Edit: To clarify, I mean somehow inducing crossover in a petri-dish.
> Unless I am unaware of something, CRISPR is not yet ready for medical usage.
CRISPR has been used successfully to treat Sickle Cell Anemia in at least one patient. [1]
You're spot on though that there are many obstacles to overcome (such as off target effects). CRISPR-Cas is not the answer, but rather just one more tool in the gene editing toolbox, albeit a very powerful one.
Yes, plenty of examples of gene editing in sick adult humans in the literature :) We have done the same with older techniques using zinc finger nucleases (same mechanism, but much more difficult to "program) and also infecting cells with lentivirus (modified HIV) to insert some useful genes. The problem is that none of these has been good enough to implement generally to save lives. Although, the lentivirus infection of T4 killer cells to fight late stage cancers seems to have promise.
I saw a program in which a geneticist described the gene editing precision prior to CRISPR as about 2-3% and after CRISPR as about 50%. That's a big jump, but as you say, what happens in those other 50% cases is of concern too when it comes to humans. Of course, this precision figure can't also be the single metric on which we judge it. However, it's an indicator that we aren't there yet too .. but are certainly moving in the right direction.
Supposing we can up the precision to, say, 4 9s - i.e. 99.99%, would that suffice? I don't know enough to say anything, but given the number of cells we typically deal with, the chance of a wrong application proliferating, however small, if it gains an advantage over the intended mutation, what consequences would it have?
Disclaimer: I'm curious about this space, but don't know much right now and am just learning up.
Since you are curious I will try to answer with a bit of a tangent :) But, in short, the real problem is the unintended edits that happen at the same time. Because if you mutate a bunch of stuff in a cell, you will probably end up giving the patient cancer. 99% efficiency is good, but not really essential for many gene therapies.
Something Cas9 does really well is find the sequence you program it to look for, and then bind super tightly to it. You can even change your Cas9 so it will no longer break the DNA. Once you do this, Cas9 cannot edit the DNA by itself, but you can add a second enzyme to it that is able to change a single base of DNA from one letter to another. In theory this means you could target a single nucleotide somewhere in the ~3 billion letters of the genome. We call this changed Cas9 "base editor". It is much more refined than the crude DNA breakage of Cas9, since base editor will initiate only one time of edit in the genome (a single letter flipped from A to G or C to T). But it will still have unintended edits! It is pretty trivial to test for these in whole genome sequencing, and it turns out you will get plenty of them.
Another problem, which might seem more important, but I think is a much easier fix in the medium term (~10 years). Is that base editor will actually target a region of about 5-6 bases around the intended target and will happily flip those bases too. So you are unlikely to get just your intended mutation. Some of your cells will also get other mutations in the same spot. The reason this is less concerning in the long term is that I think this can be fixed with optimisation of the base editor protein. The off target effects are much more difficult to prevent.
>the off target effects are much more difficult to prevent
Why is that the case? And are there any promising theories for how we might overcome that problem?
CRISPR has already been approved for some forms of gene therapy. I assume that's because, for people with crippling diseases, the benefits clearly outweigh the risk. But going forward, as we address less crippling diseases, how do you grok the known benefit/unknown costs of using CRISPR for a cure? This will be an even bigger problem once CRISPR is used for more superficial or cosmetic things. We need to create a decision model and quantify the risks as much as possible.
I have a feeling that countries will "compete" on taking risks with CRISPR. For example, China might see CRISPR as a way to increase its dominance on the world stage. If there's a risky way for CRISPR to increase intelligence, they might take the risk, because China has more to gain than America.
>Why is that the case? And are there any promising theories for how we might overcome that problem?
I am still quite new to CRISPR so I am unsure what people are doing to solve this problem. As for why, I would say that the problem is that, like most proteins, Cas9 just bounces around using brownian motion and there is always just some probability of it being near the wrong piece of DNA at the right time. There's not much that can be done about that! However, we can do something about Cas9's binding affinity to sequences that are similar, but not idetnical, to the target sequence. One could imagine Cas9 binding (with lower affinity) to a sequence of 20 bases that is incorrect on a couple of bases. Indeed, much of the off-target effects come from this. So if one could modify Cas9 to only bind to the exact sequence that should reduce off-target mutations.
If you actually know the target loci for whatever disease, it's a much more sensible prospect to just put the patient on a drug for life that inhibits whatever that mutation does. If the treatment turns out unsafe, you just take the patient off. With editing the genome you can't really go back if you find out after the fact that you screwed up. CRISPR is a great research tool, but I think in vitro fertilization is fine enough for catching congenital diseases.
This is a good point, it can be hard to predict what gene does what. Most genes that have been targetted for gene therapies tend to be the singular and known source of a genetic disease. Something like the sodium transporter mutation in cystic fibrosis. If you fix it, it is clear what will happen; you will clear out the disease. Most diseases are not so simple and we are still getting to grips with even mapping the mutations scattered across the genome and the global human population that are relevant to certain diseases. I think when you dont have a single genetic cause, but a mix of various genetic factors instead, then the drug route is optimal. For exactly the reasons you stated.
In vitro fertilization isn't anywhere close to ubiquitous let alone screening. Genetic editing isn't cheap either but it is only needed for patients with problems instead of literally everybody born.
Technically the issue may or may not be drug "additive" and inhibitable like "stop making this protein" but "start making this with your blood cells".
I suspect the only way humans will successfully colonize the solar system is with gene editing. Genetic modification can be used to reduce the life support requirements in various environments. For example, different gravities, different gas pressure, gas composition, tolerance of various chemicals, radiation, etc.
May of these don't seem like binary adjustments, though. Perhaps you can increase the tolerance to radiation, but how? Perhaps by causing the body to produce a protein that shields cells from these effects, much like melanin does for UV. Assuming you do this, you immediately have to ask, what other effects does that have on the body? When these cells are destroyed by radiation, what are their breakdown products? How quickly can the body replenish them? What new nutritional requirements will be necessary to support them? The same questions can be raised for any of these "DNA feature flags."
It seems to me, viewed a certain way, the human body is almost entirely driven by emergent phenomenon. I have serious doubts about our ability to edit the source code to achieve very straight-forward single side-effect modifications.
We may very well be limited to merely adjusting "errant" DNA sequences that cause or are implicated in disease or undesired attributes. Who would choose a short child? Or one with myopia? Or one with weak muscles? Or even one with the misshapen chest and facial orifices necessary to survive lower partial pressures of oxygen?
The long term effect of custom genetic modification actually seems like it would just be used to reduce the overall genetic diversity of humans on the whole, not to improve it in drastic ways.
>The long term effect of custom genetic modification actually seems like it would just be used to reduce the overall genetic diversity of humans on the whole, not to improve it in drastic ways.
In fact, there are economic incentives to create broken clones that require daily medical attention so you can turn them into slaves that work for medicine.
Let's say we can edit the human genome (CRISPR is not approved for human use), even then, there should extremely tight limits to our genomic editing, since for the majority of the genome by sequence, expressed regions, and possibly still coding regions, has largely unknown function.
We just don't understand so much of genomic function through evolutionary time from the simple fact that we cannot easily observe it, that making anything more than a SNP change is asking for major, unfixable problems at a population level down the line. If risk is (threat x vulnerability x consequence), we need to practice the utmost caution when that vulnerability period is the rest of our species existence!
Do we have a way to measure the "resolution" accuracy of techniques like CRISPR? I feel like we don't even know the actual "resolution" of the genome to begin with...
> Cas9 cannot edit the DNA by itself, but you can add a second enzyme to it that is able to change a single base of DNA from one letter to another. In theory this means you could target a single nucleotide somewhere in the ~3 billion letters of the genome. ..A single letter flipped from A to G or C to T.
That seems like an answer to your question. The "resolution", or a single "unit", in a genome sequence is a nucleotide.
> But it will still have unintended edits!
As for the accuracy of CRISPR, two kinds of errors are mentioned. "Off-target" mutations that occur elsewhere in the sequence:
> It is pretty trivial to test for these in whole genome sequencing, and it turns out you will get plenty of them.
And mutations that occur in the same targeted location:
> ..[The] base editor will actually target a region of about 5-6 bases around the intended target and will happily flip those bases too.
On further reading, a single "unit" for double-stranded D/RNA is the base pair:
> bp = base pair(s) — one bp corresponds to approximately 3.4 Å (340 pm) of length along the strand, and to roughly 618 or 643 daltons for DNA and RNA respectively.
(A picometer, "pm", is 1×10^−12 m, or one trillionth of a meter.)
@ImaCake does mention that CRIPSR is able to "target a single nucleotide", a single base of DNA.
For single-stranded D/RNA, the nucleotide is the unit, abbreviated nt (or knt, Mnt, Gnt).
Don't underestimate this comment. Nuclear war is the expected outcome of a conflict between two intelligent species. Especially if the older species feels inadequate.
A more interesting question is how far will we go.
Based on human history, I am fairly sure the end of humanity is approaching. 100 to 150 years I'd guess. I don't mean we'll be gone, just that what we'll become will not be recognized as human by our ancestors.
If the modifications go far enough (e.g. something like completely suppressing all human emotions) I'm pretty sure it's fair to say that we'll be gone. At least I don't see any reason why we should view these potential future 'humans' as any thing more related to us than say a potential 'species' of robots.
Depending on the ancestor we may have already qualified centuries if not millenia ago - but that has more to do with them than us. If they call those who do not worship their long forgotten gods not human then we technically already lost. Let alone other specific aspects like not considering pygmy peoples human.
The point being hypothetical bigotries of the long dead is an unmeasurable metric (oxymoronic) and pretty useless.
If we don't go far enough, someone else will. Whether Iran or China or North Korea, someone else will eventually start producing superintelligent children that will outshine all western scientists and engineers[1]. If we don't start doing it too, we will become irrelevant, prehistoric tribes that have no place in the modern world.
If we decide to allow genetic enchancements, though, we need to ensure the society won't split into classes. Some parents will probably want the freedom to choose if their child is enchanced or not, but the unenchanced children will have no chance at anything in life. The only way forward is to require genetic enchancement, no matter the opposition from religious or other groups.
I am still shaken by that conclusion, but it seems inevitable. Irrelevance, inequality or force. Choose one, or they will choose for you.
[1] assuming science allows us to do this eventually
Your way of thinking is kind of how the world economy is already saving people from poverty. Plenty of folks have managed to evade plugging into the rat wheel so far, such as the amish and hasidic jewish communities. Do you take modernity seriously enough to patch their genes like Windows 10?
Gene editing is the surest path to dystopia that I can currently imagine. And I don’t see any way to avoid the inevitable arms race. If North Korea is engineering super intelligent kids it is almost certain that South Korea and/or China will do the same. Then it will just cascade from there.
Engineered vs not engineered could easily become the new class system where the rich-ish are able to produce “better” children and exponentially widen the gap.
Could also lose all semblance of uniqueness. Want your child to be a redhead with a 170 IQ? Okay, pay enough and it’s yours.
So I think the real question is not how far SHOULD we go, but instead how far WILL we go. And how quickly will we go there.
70 comments
[ 4.5 ms ] story [ 138 ms ] threadCat girls
edit: ahh... I love the part of HN that can't enjoy even the lightest of humor. FWIW: I have a severe chronic/borderline terminal health condition that is near certain to leave me dead quite early, not to mention the hell it's brought upon my physical body. In 10 years or so (maybe even sooner) - it will probably be something that's editable out in vitro. Also... I'm young as it is.
Let me have fun with my dreams of cat girls. Maybe you'd end up enjoying them too. :)
PS: The original comment brought a smile, but I still downvoted. Keeping most jokes and obvious comments off HN is a major long term benefit.
Sometimes it's not about what's visible to your eye...
Though, I do agree, in general, it's best practice not to have too many laughs on HN.
Also... yeah, current state of things is a bit hype. I have a lot of hope though having spoken with people doing research at places like University of Tokyo. I'm sure whether ethically or not, China has probably made some great strides we're not 100% aware of.
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724388/
Virus would love that, yes why no, lets remove the only thing that has keep all living organism on this planet for billions of years from extinction.
Some country will allow it as it gives them a leg up on others. And once you can do it in X country, the pressure will be strong for others to follow suit and allow it or fall behind.
This is excepting the case where it generates some near term negative effect that outweighs the gains to be had by it.
Also, as someone working with CRISPR, it isn't quite as easy as it is made to sound. It is relatively easy, but still a lot of work! I guess that is a footnote when it makes the impossible, possible though. We need to keep having these ethics conversations though, so we can use this tool wisely.
For further reading I would recommend Jennifer Doudna's "A crack in creation". She is one of the founders of CRISPR as a gene editing tool, and her book is good reading on the topic.
Then we'll need CAD tools. Really good CAD tools.
[0] https://www.nature.com/articles/d41586-020-00511-9
CRISPR is too unreliable and has too many off target effects to move the needle on height. By the time you've made a hundred CRISPR edits to a single genome, you've shot the other chromosomes full of holes. It's only useful for taking out one or two genes, for someone who knows they carry a fatal genetic disease, but still wants to have kids. True designer babies will be done with genome synthesis.
I understand it's fun to speculate about this.
Correct. We can only assemble synthetic bacteria right now. Synthetic sperm is years away. Synthetic eggs are too complicated, I wonder if they'll ever be made. Synthetic embryos would be true sci-fi stuff, requiring heavy engineering and many breakthroughs.
Emotional statement: "nobody is planning on"
Human germline engineering inspires strong feelings. I'm sure that the advent of motorized vehicles would have inspired the same strong feelings in horses, if they could have understood what was about to happen to them. Nevertheless.
Genetic engineering for human treatments took a 20+ year hit because one guy died in a trial at UPenn https://en.wikipedia.org/wiki/Jesse_Gelsinger
After He Jenkiu, genetic engineering took another huge hit because an irresponsible person ignored all advice and did a crappy job at fixing susceptibility to HIV infection.
This is not a "engines vs. horses argument". This is a "faster than light AI supership vs. horses argument".
Maybe we could clean up the off-target mutations using that.
Edit: To clarify, I mean somehow inducing crossover in a petri-dish.
CRISPR has been used successfully to treat Sickle Cell Anemia in at least one patient. [1]
You're spot on though that there are many obstacles to overcome (such as off target effects). CRISPR-Cas is not the answer, but rather just one more tool in the gene editing toolbox, albeit a very powerful one.
https://www.npr.org/sections/health-shots/2020/06/23/8775436...
Supposing we can up the precision to, say, 4 9s - i.e. 99.99%, would that suffice? I don't know enough to say anything, but given the number of cells we typically deal with, the chance of a wrong application proliferating, however small, if it gains an advantage over the intended mutation, what consequences would it have?
Disclaimer: I'm curious about this space, but don't know much right now and am just learning up.
Something Cas9 does really well is find the sequence you program it to look for, and then bind super tightly to it. You can even change your Cas9 so it will no longer break the DNA. Once you do this, Cas9 cannot edit the DNA by itself, but you can add a second enzyme to it that is able to change a single base of DNA from one letter to another. In theory this means you could target a single nucleotide somewhere in the ~3 billion letters of the genome. We call this changed Cas9 "base editor". It is much more refined than the crude DNA breakage of Cas9, since base editor will initiate only one time of edit in the genome (a single letter flipped from A to G or C to T). But it will still have unintended edits! It is pretty trivial to test for these in whole genome sequencing, and it turns out you will get plenty of them.
Another problem, which might seem more important, but I think is a much easier fix in the medium term (~10 years). Is that base editor will actually target a region of about 5-6 bases around the intended target and will happily flip those bases too. So you are unlikely to get just your intended mutation. Some of your cells will also get other mutations in the same spot. The reason this is less concerning in the long term is that I think this can be fixed with optimisation of the base editor protein. The off target effects are much more difficult to prevent.
>the off target effects are much more difficult to prevent
Why is that the case? And are there any promising theories for how we might overcome that problem?
CRISPR has already been approved for some forms of gene therapy. I assume that's because, for people with crippling diseases, the benefits clearly outweigh the risk. But going forward, as we address less crippling diseases, how do you grok the known benefit/unknown costs of using CRISPR for a cure? This will be an even bigger problem once CRISPR is used for more superficial or cosmetic things. We need to create a decision model and quantify the risks as much as possible.
I have a feeling that countries will "compete" on taking risks with CRISPR. For example, China might see CRISPR as a way to increase its dominance on the world stage. If there's a risky way for CRISPR to increase intelligence, they might take the risk, because China has more to gain than America.
I am still quite new to CRISPR so I am unsure what people are doing to solve this problem. As for why, I would say that the problem is that, like most proteins, Cas9 just bounces around using brownian motion and there is always just some probability of it being near the wrong piece of DNA at the right time. There's not much that can be done about that! However, we can do something about Cas9's binding affinity to sequences that are similar, but not idetnical, to the target sequence. One could imagine Cas9 binding (with lower affinity) to a sequence of 20 bases that is incorrect on a couple of bases. Indeed, much of the off-target effects come from this. So if one could modify Cas9 to only bind to the exact sequence that should reduce off-target mutations.
Technically the issue may or may not be drug "additive" and inhibitable like "stop making this protein" but "start making this with your blood cells".
* Make all women 4.5-5.5 foot
* Remove balding from men
* Alter jews so they have long nose ,black hair and blue skin
It seems to me, viewed a certain way, the human body is almost entirely driven by emergent phenomenon. I have serious doubts about our ability to edit the source code to achieve very straight-forward single side-effect modifications.
We may very well be limited to merely adjusting "errant" DNA sequences that cause or are implicated in disease or undesired attributes. Who would choose a short child? Or one with myopia? Or one with weak muscles? Or even one with the misshapen chest and facial orifices necessary to survive lower partial pressures of oxygen?
The long term effect of custom genetic modification actually seems like it would just be used to reduce the overall genetic diversity of humans on the whole, not to improve it in drastic ways.
In fact, there are economic incentives to create broken clones that require daily medical attention so you can turn them into slaves that work for medicine.
We just don't understand so much of genomic function through evolutionary time from the simple fact that we cannot easily observe it, that making anything more than a SNP change is asking for major, unfixable problems at a population level down the line. If risk is (threat x vulnerability x consequence), we need to practice the utmost caution when that vulnerability period is the rest of our species existence!
> Cas9 cannot edit the DNA by itself, but you can add a second enzyme to it that is able to change a single base of DNA from one letter to another. In theory this means you could target a single nucleotide somewhere in the ~3 billion letters of the genome. ..A single letter flipped from A to G or C to T.
That seems like an answer to your question. The "resolution", or a single "unit", in a genome sequence is a nucleotide.
> But it will still have unintended edits!
As for the accuracy of CRISPR, two kinds of errors are mentioned. "Off-target" mutations that occur elsewhere in the sequence:
> It is pretty trivial to test for these in whole genome sequencing, and it turns out you will get plenty of them.
And mutations that occur in the same targeted location:
> ..[The] base editor will actually target a region of about 5-6 bases around the intended target and will happily flip those bases too.
¹ https://news.ycombinator.com/item?id=24459427
---
On further reading, a single "unit" for double-stranded D/RNA is the base pair:
> bp = base pair(s) — one bp corresponds to approximately 3.4 Å (340 pm) of length along the strand, and to roughly 618 or 643 daltons for DNA and RNA respectively.
(A picometer, "pm", is 1×10^−12 m, or one trillionth of a meter.)
@ImaCake does mention that CRIPSR is able to "target a single nucleotide", a single base of DNA.
For single-stranded D/RNA, the nucleotide is the unit, abbreviated nt (or knt, Mnt, Gnt).
https://en.wikipedia.org/wiki/Base_pair#Length_measurements
We can't predict the outcome, even in out wildest dreams or worst nightmare, we'll always be wrong.
Are we afraid of uncertainties? Of course we are, evolution taught us to be.
Not doing everything we can would be in total contradiction with the behavior of humankind since the dawn of ages.
I am both an optimist and an atheist, there is no God and nothing is sacred.
The beauty of evolution is that this is a process without designers. There is simply no need for them.
Based on human history, I am fairly sure the end of humanity is approaching. 100 to 150 years I'd guess. I don't mean we'll be gone, just that what we'll become will not be recognized as human by our ancestors.
The point being hypothetical bigotries of the long dead is an unmeasurable metric (oxymoronic) and pretty useless.
If we don't go far enough, someone else will. Whether Iran or China or North Korea, someone else will eventually start producing superintelligent children that will outshine all western scientists and engineers[1]. If we don't start doing it too, we will become irrelevant, prehistoric tribes that have no place in the modern world.
If we decide to allow genetic enchancements, though, we need to ensure the society won't split into classes. Some parents will probably want the freedom to choose if their child is enchanced or not, but the unenchanced children will have no chance at anything in life. The only way forward is to require genetic enchancement, no matter the opposition from religious or other groups.
I am still shaken by that conclusion, but it seems inevitable. Irrelevance, inequality or force. Choose one, or they will choose for you.
[1] assuming science allows us to do this eventually
godtoshi's vision
Engineered vs not engineered could easily become the new class system where the rich-ish are able to produce “better” children and exponentially widen the gap.
Could also lose all semblance of uniqueness. Want your child to be a redhead with a 170 IQ? Okay, pay enough and it’s yours.
So I think the real question is not how far SHOULD we go, but instead how far WILL we go. And how quickly will we go there.
Go far enough that parents sue companies because their child doesn't match the designer baby form they have filled out.
Go far enough that there will be racial violence between the "natural" and genetically engineered humans.
Too much ambition will bring severe consequences... Please don't go beyond what is absolutely necessary.