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Comment by psychometry | Hacker News Reader

You misunderstand so many things.

1. There are many somatic applications of CRISPR that have no effect on the germline.

2. Even the germline applications don't necessarily "decrease genetic variability". Why would you think that?

3. Even considering off-target effects, the edits made to any particular genome are miniscule compared to its overall size, which I'm sure would astound you. There is no reason to believe these edits will make us less (or more) resistant to environmental exposures.

4. We are not talking making people more likely to contract cholera, which is easily controlled by sanitation. We're talking about preventing or curing debilitating illnesses that confer no benefit to the organism.

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I agree with points 1-3, but I would be remiss not to mention, that with respect to point 4, diseases like sickle cell anemia, which is hideously painful and fatal as a double inheritance (25% homozygous offspring in a heterozygous pairing, ss), but a wonderful defense against malaria in heterozygous offspring (Ss, 50% of said pairing). The remaining 25% homozygous wild-type (SS) are healthy, except when encountering malaria.

https://www.cdc.gov/malaria/about/biology/sickle_cell.html

I would think that a mendelian genetic disease like sickle cell might well be on our hit list for all the trouble it causes. Of course, it could be argued that mosquito nets and drugs (i.e. technology) are a better, less costly defense, than these inborn genetic mutations.

I think his point was, that in general, even the terrible mutations like sickle cell serve a purpose in ensuring the survival of our species in the face of diseases like malaria (which if it was much more potent, or our population much smaller and closer together, could wipe us out). From an "effectiveness of evolution" stand point generating those sorts of terrible diseases is a feature of the "algorithm".

We are smart enough to face the consequences of eliminating such things, of taking control of the selection function used by evolution. The question is if we are wise enough to understand that we must be prepared for the consequences, or even understand that there will be consequences.

>1. There are many somatic applications of CRISPR that have no effect on the germline.

Yes, but there are many that have.

>2. Even the germline applications don't necessarily "decrease genetic variability". Why would you think that?

Because he talked about "Unrestricted gene editing in humans" in general, and one of the goals would be designer humans and babies, which will decrease "genetic variability".

>3. Even considering off-target effects, the edits made to any particular genome are miniscule compared to its overall size, which I'm sure would astound you. There is no reason to believe these edits will make us less (or more) resistant to environmental exposures.

Tiny changes can have huge effects, especially when one doesn't fully understand what they're changing and second order effects of their meddling.

Heck, it's 2018 and we can't cure common cold or obesity, and we don't know tons of stuff about the human body, metabolism etc and how it works.

>4. We are not talking making people more likely to contract cholera, which is easily controlled by sanitation. We're talking about preventing or curing debilitating illnesses that confer no benefit to the organism.

Who is this "we" who is talking it? There's no doubt tons of state actors will be interested in making people more likely to contract all kinds of things (or be resistant to them, as long as they can spread it to the others) -- that is, weaponize the thing.

This sounds too much like the old "man playing God" trope: we don't know, therefore we should continue to revel in our ignorance instead of taking any risks. To hell with that, if I can give my children genes that prevent debilitating diseases and low intelligence and if the risks are manageable, I will take that. That possibility is decades away, but it's a worthy goal to pursue.

This is not about "designer babies" in the eye color or physical appearance sense - who knows what will be the beauty norm 50 years from now. It's about ridding humanity of what we know is deadly and, on a personal level, preventing my own bad genes getting passed on. I have a bad back, an insatiable appetite and high cholesterol, I'm balding and have a slight heart deformity. Should I pass those traits along just for the hope that someday some bald distant sibling will have immunity from a future plague? I don't think I'm really responsible for that, it's the task of future generations to keep the baldness genes in a bank or database and use it at that time if they find them useful.

The reduced genetic diversity is moot - people of all ethic groups have today a chance to reproduce instead of being wiped out like for most part of human history. We are in an explosion of genetic diversity, even very dangerous traits are being preserved in the gene pool due to the advances of medicine that made them survivable. When genetic editing will be so widespread as to threaten the genetic diversity of the human species, we will be living in a Star Trek egalitarian paradise, it's very presumptuous to think we have any foresight into such a future.

>This sounds too much like the old "man playing God" trope

Which was never much discredited in the first place.

I see: we aren't having a scientific debate, we have a political disagreement about the place of science in society.

> Decades away

Worth mentioning that Iceland has virtually eliminated Down's Syndrome from the population with genetic screening of pregnant women.

Almost all Icelandic women choose to terminate the pregnancy, if the test comes back positive for Down's Syndrome.

7 minute mini documentary:

https://youtu.be/S-X97xxw5aI

Not to counter your point, but I was referring to gene editing before implantation and inserting/replacing various traits that maximize the health of the offspring - that is still experimental. Genetic testing and selective abortion has similar end goals but is not a direct application of the ideea.

For 2, isn’t there risk that people will be influenced by association studies and seek out editing of single nucleotides thereby potentially removing ‘bad’ variants from the entire population? For example, say a gwas shows that a snp variant is associated with higher IQ. People rush to edit that nucleotide. But, they don’t understand that that snp variant may have had other beneficial effects ...

Likely, only the rich will be able to run out and get gene mods for some time.

Likely, the rich will set up charities that sponsor gene mods for the poor.

(Only a cynic would call it beta testing.)

Aren't we already doing beta-testing medicaments big scale in africa?

Given that genetic testing(+) has had twice the rate of performance-to-cost doublings as Moore’s Law since the Human Genome Project completed, “some time” may be 21 years from billionaires to subsistence farmers.

(+) yes I know that’s not the same as editing, but it’s the closest comparison I have for guestimating future improvements.

I imagine that (at least for the foreseeable future) genetic engineering will only be targeted to modifying SNPs (and other mutations) that unambiguously cause diseases.

I imagine that genetic engineering for intelligence has already happened on the downlow.

bloodlines

If we'd had the option to remove the gene that causes sickle-cell anaemia from the population, wouldn't we have taken it? Which would have meant we then didn't have the malaria-resistant population that now exists due to that same gene.

On the one hand, correct.

On the other, we’re currently exploring ways to wipe out malaria carrying mosquitoes.

On the third (genetically modified :P) hand, easy gene modification will probably lead to a similar patch-cycle as we already have for software.

On the fourth hand, thanks to the typical decade long testing cycle for medicines, the worst parts of this hypothetical future are likely to happen around the same time we get full-mind uploads.

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