
Five big mysteries about CRISPR’s origins - bcaulfield
http://www.nature.com/news/five-big-mysteries-about-crispr-s-origins-1.21294
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s_dev
I found this Kurzgesagt video a useful intro to CRISPR:
[https://www.youtube.com/watch?v=jAhjPd4uNFY](https://www.youtube.com/watch?v=jAhjPd4uNFY)

~~~
problems
Radiolab also did a very good job with it:
[http://www.radiolab.org/story/antibodies-
part-1-crispr/](http://www.radiolab.org/story/antibodies-part-1-crispr/)

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Wonnk13
Fresh Air on NPR yesterday did an hour where they discussed gene editing and
the such. Incredibly fascinating! I was recently diagnosed with colon cancer
(i'm doing great) and I'm totally rediscovering genomics. Having not given any
thought to this stuff since AP Bio in highschool so many advances have been
made!!

I'm especially curious how machine learning will play into all of this (the
broader genomics community). So much more interesting than the "cyber" stuff I
work on now :)

~~~
palamoun
I listened to this program on NPR yesterday too and was very intrigued. For
everyone else, the guest on Fresh Air was Michael Specter, who recently wrote
an article in the New Yorker about CRISPR. Here's a link:
[http://www.newyorker.com/magazine/2017/01/02/rewriting-
the-c...](http://www.newyorker.com/magazine/2017/01/02/rewriting-the-code-of-
life)

(Glad you're doing well by the way)

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sk1zzyk1d
I found the quote below from Surviving the 21st Century by Julian Cribb
similar to many attitudes I've encountered on the other end of the interest
spectrum. The warnings are worth heeding, yet how can we ignore such tech,
just as we pursue nanotechnology that has similar dangers, when such
scientific pursuits may be what allows the human race to persist long after
the Earth ceases to be habitable.

"All biowarfare laboratories - and indeed, many ordinary biotech labs – thus
represent an ongoing existential threat to humanity whose safety, like that of
nuclear materials, cannot ever be guaranteed.

"This was highlighted in early 2016 when James Clapper, U.S. director of
national intelligence, issued a warning that even gene editing (such as by the
technology known as CRISPR) should be added to the list of weapons of mass
destruction, adding that it 'increases the risk of the creation of potentially
harmful biological agents or products'. (Regalado 2016). Other scientists
warned that genetically modified lifeforms could be used to target specific
groups of humans carrying certain genes, or if released in agricultural
‘designer crops’ might result in uncontrollable plagues. They cautioned that
gene editing technology is far cheaper and easier to access than nuclear or
chemical weapons."

\- Surviving the 21st Century, Julian Cribb, Chapter 8 "The Urbanite (Homo
urbanus)"

~~~
kneel
James Clapper's job is to worry about everything, of course he would say that.

The common flu is a lot more dangerous than CRISPR/cas9.

The CRISPR/cas9 system has potential for existential threat in the same way
that AI does (not anytime soon.) This is what happens when you develop a new
set of tools.

~~~
ahazred8ta
> James Clapper's job is to worry about everything

"And Ye Shall Know the Truth and the Truth Shall Make You Free" is inscribed
in the lobby of the CIA, but informally they say "the truth will just make you
nervous". :(

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neom
Peripherally related book recommendation: [https://www.amazon.com/Vital-
Question-Evolution-Origins-Comp...](https://www.amazon.com/Vital-Question-
Evolution-Origins-Complex/dp/0393088812) Someone here on HN recommended it to
me and it was an awesome read (that I doubt I understood).

~~~
alextheparrot
In line with this, I'd also like to recommend 'The Gene'[0]. The author has
informed me of new things (Even though I studied biochemistry during college)
and also focused a lot on the ethical discussions relating to genetic
modification. It also directly discusses CRISPR as it is quite new. I'd
recommend all of Mukherjee's other books as well (Mainly Emperor of all
Maladies).

[0][https://www.amazon.com/dp/1476733503](https://www.amazon.com/dp/1476733503)

~~~
fossuser
I'd second this recommendation - currently reading it right now and it has the
nice combination of being really interesting and really easy to read.
Mukherjee's style is really clear and enjoyable.

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adventured
I'm rather obsessed with CRISPR these days. I'm considering leaving
traditional tech and self-funding a new CRISPR company. The accessibility - in
most every regard - of CRISPR has entirely changed the game in gene editing.
It's only going to accelerate and there is so much land to discover, pick a
direction and go. Cas9, Cpf1, CasX, CasY, it's all so exciting compared to
most of the things I see in tech these days (except for AI and VR).

~~~
nyolfen
do you have any suggested reading (for a layperson)?

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epberry
> often only about one bacterium in 10 million will gain a spacer that lets it
> defend itself.

Incredible... The scale and probabilities involved in these processes are mind
blowing.

In general I liked this article because it posed a few open ended research
questions and explained why they were relevant. As someone who barely knows
the difference between a bacteria and a virus I felt it was pretty
understandable.

~~~
woliveirajr
> "There are typically 40 million bacterial cells in a gram of soil" [1]

That would mean 4 in each gram of soil, if Wikipedia is correct. Bacteria
scale is so disproportional to what we deal in daily basis that I'm pretty
sure we know almost 0.01% of all existing species, families or any other kind
of grouping them you like.

[1]
[https://en.wikipedia.org/wiki/Bacteria](https://en.wikipedia.org/wiki/Bacteria)

~~~
problems
The amount of knowledge we lack with regards to species still surprises me. We
can do pretty well with plants and animals, but we don't even have good
genetic analysis on types of mushrooms that grow on the surface, picking up
any field guide often results in "this looks quite like it, but the ones from
this part of the world make people sick and we don't actually know if they're
related".

~~~
toufka
We really don't have a good grasp even on the _variety_ of plants and animals.
We do know a lot about the _foundations_ of each organism's genetics, but
we're just now peeking into their variation. And that is precisely why you see
biotech starting to get interesting and useful above and beyond basic
discovery. When we start looking not just for 'how life works', but for 'how
does it glow', 'how does it climb', 'how does it live so long', we start
getting pretty cool answers. But we're JUST starting.

Much of what know comes from a short list of organisms (that can grown in lab
conditions). There is a 'model organism' [1] for the simplest organism (that
can grown in lab) for each step up the ladder of biological complexity
(towards humans).

\- bacteria : E coli

\- eukaryote : yeast

\- multi-cellular : nematode

\- plant : arabidopsis

\- nervous system : fruit fly

\- spinal cord : zebrafish

\- mammal : mouse

\- primate : monkey

There are definitely others (sorry for leaving out your favorite model...),
but in general, we know a lot about these model organisms. And that covers a
wide gamut, but still we know very little specifics about everything in
between.

Further, because we've been so focused on (funding) human health, we know a
lot about how humans work. But what we've missed is all the ancillary tech
that could be used to support human health, or human
society/technology/industry at large. CRISPR proteins (and its similar tech)
which will end up revolutionizing our biological tehcnology come from non-
human-like, and otherwise unfundable hobby research. PCR/GFP all came from
looking at weird things and saying, "that's cool, how does that work?" not "I
want to cure cancer". It's hard to get funding to study how various bacteria
battle each other in the soil when you cannot know how it might affect human
health...

[1]
[https://en.wikipedia.org/wiki/Model_organism](https://en.wikipedia.org/wiki/Model_organism)

~~~
spynxic
> that's cool, how does that work?" not "I want to cure cancer"

With regards to your final note: [https://en.wikipedia.org/wiki/Top-
down_and_bottom-up_design](https://en.wikipedia.org/wiki/Top-down_and_bottom-
up_design)

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takinola
Can someone ELI5 how gene editing works? I understand that CRISPR can target
specific genes to make changes but how does that work in practice?

Suppose we identified the gene for Huntington's disease and wanted to design a
therapy to snip it out and put a benign replacement in its place. Given the
human body contains trillions of cells, each carrying the complete set of
genes, which cells would be targeted by the therapy? If the CRISPR therapy
targeted only cells in a certain organ or region, does this mean the person
would have different sets of genes in different parts of their body? What does
this mean for any children born post-treatment? Do they inherit the new genes
or are they stuck with the old crappy version?

~~~
yellow_viper
CRISPR is a newly adopted technology that allows the bacteria in the cell to
fight against the Viruses that affects the Human cells. It also allows making
some specific changes in the DNA of the Human Being and some other organisms.

Clustered Regularly Interspaced Short Palindromic Repeat is the acronym for
CRISPR. It is an RNA gene-guided editing platform, which is helping to break a
double-stranded DNA at a specific location within the genome by making use of
a Protein Coat (Cas9) and a synthetic RNA guide.

In the simple life forms like bacteria and another organism, a simple sequence
of CRISPR acts as a crucial component of the Immune System for protecting the
organisms health. Viruses are the small infectious agents that invade the
bacteria in the cells and attack the bacteria. If viral infection threatens
this invaded bacteria, then the CRISPR immune system can attack and destroy
the genome of the invading virus. The genome of the virus contains the genetic
material for its replication. By destroying the genome, the CRISPR immune
system protects the bacteria from viral infections.

Source:[http://www.whitedust.net/what-is-crispr-and-how-can-it-
edit-...](http://www.whitedust.net/what-is-crispr-and-how-can-it-edit-your-
dna/)

you can learn more about it and watch the video about CRISPR/Cas9's mechanism
and function.

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dankohn1
I love this quote from the article: "Viruses outnumber prokaryotes by ten to
one and are said to kill half of the world's bacteria every two days."

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hyperpallium
> _when viruses infiltrate a bacterial ecosystem, often only about one
> bacterium in 10 million will gain a spacer that lets it defend itself._

Sounds like, when under mortal threat, grab some DNA. Even if it mostly causes
cellular suicide by grabbing its own DNA, if just one bacterium acquires
immunity, the group as a whole benefits.

Of course, group selection doesn't seem to work... but maybe the very high
probability of death means this low probability last-ditch attempt is worth it
for the individual - which then passes on the CRISPA machinery and the
specific immunity to its "progeny"... which then have a nicely cleared out
environment all to themselves... like eucalyptus after a bushfire.

Desparate times call for desparate measures; and high risk/high reward.

