
We can now edit the human genome – how far should we go? [video] - colinhb
https://www.pbs.org/wgbh/nova/video/human-nature/
======
ImaCake
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.

~~~
Animats
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.

Then we'll need CAD tools. Really good CAD tools.

~~~
vikramkr
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.

~~~
adrianN
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.

~~~
vikramkr
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).

[0]
[https://www.nature.com/articles/d41586-020-00511-9](https://www.nature.com/articles/d41586-020-00511-9)

------
WalterBright
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.

~~~
akira2501
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.

~~~
imtringued
>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.

------
LostTrackHowM
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.

~~~
ImprobableTruth
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.

------
s5300
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. :)

~~~
xeromal
There's one comment replying to you and it's not complaining

~~~
s5300
I got like 10 downvotes in three minutes ;)

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.

~~~
tuesdayrain
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.

~~~
Nasrudith
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.

~~~
imtringued
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.

------
drivingmenuts
Well, I, personally, would much enjoy having my T-2 Diabetes fixed. Also, my
hearing and eyesight.

~~~
nathanyz
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.

------
miki123211
> How far should we go?

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

~~~
jart
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?

------
msie
I really enjoyed the video. I guess I could have read about CRISPR and CAS9
but the video was more engaging.

------
wespiser_2018
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!

------
alhasaniq
Is the video hosting down? "We're sorry, but this video is not available."

~~~
stephenroller
Perhaps you are outside the United States? PBS is the public television
channel, so perhaps they geolock :(

~~~
dekhn
Huh, I was surprised to learn PBS is geolocked.
[https://help.pbs.org/support/solutions/articles/5000673797-i...](https://help.pbs.org/support/solutions/articles/5000673797-i-live-
outside-the-united-states-why-can-t-i-stream-pbs-video-content-from-pbs-org-)

------
radium3d
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...

~~~
lioeters
From @ImaCake's comment¹ above, I learned that:

> 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](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](https://en.wikipedia.org/wiki/Base_pair#Length_measurements)

------
stephc_int13
How far should we go? The science might not be ready yet, but it seems likely
that progress in field will enable us to change our own species.

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.

~~~
majkinetor
Strange thing you say you are an atheist but here you are optimistic about
intelligent design.

~~~
stephc_int13
I am not talking about intelligent design.

The beauty of evolution is that this is a process without designers. There is
simply no need for them.

------
imtringued
Go far enough that the new humans are so different and superior that they
think of themselves as a different species.

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.

------
dusted
How far?
[https://www.youtube.com/watch?v=fe8jJBoEmuY](https://www.youtube.com/watch?v=fe8jJBoEmuY)

------
valgor
We should go as far as possible assuming proper safety guidelines. To do
otherwise is an injustice to the future.

------
Jemm
As someone with genetic illness, please do what you can to eliminate genetic
diseases.

------
vmception
revert the original sin commit and make us perfect

godtoshi's vision

------
cwhiz
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.

