[avinashv]

While the author is pretty clear that "only a passing knowledge of modern microbiology" is necessary, I think that understates some of the technical language in here. I really laughed at the line, "Silencing a gene with CRISPR/Cas is incredibly simple." Still, I learned a lot. This is the closest I've come to feeling like I know what's going on in CRISPR.

CRISPR has got to be one of the most important scientific achievements of the past few decades, right?

[DaveWalk]

Absolutely. The movement from discovery (from the unsexiest of all fields, bacteriology!) to a reliable tool is unprecedented[1] in the scientific realm. For my money it is easily on track for a Nobel Prize: it allows mankind to examine with precision unknown just years before.

[1] I see a parallel to short hairpin RNA gene silencing (shRNA, a.k.a. RNA interference, RNAi). A breakthrough discovery, at use at the bench in less then a decade, and an easy clinch for the Nobel Prize. CRISPR has gone even faster.

[dnautics]

> The movement from discovery (from the unsexiest of all fields, bacteriology!) to a reliable tool is unprecedented.

Uhm, restriction enzymes?

for the uninitiated: https://en.wikipedia.org/wiki/Restriction_enzyme

(basically, restriction enzymes are what CRISPR is basically set to replace for complex systems/organisms where restriction enzymes are too weak; although for simple systems restriction enzymes are waaay simpler)

[dluan]

I really wonder if it's just a matter of time before you get clans of technology in bio. Akin to the PHP vs Ruby vs Node vs Go evolution.

At the end of the day, they are just tools, and tools however technically shiny, don't by themselves deliver better end products.

[dnautics]

That's already happened with NG DNA assembly. PIPES cloning vs. Gibson Assembly vs. ColdFusion, etc.

In the case of restriction enzymes, though, they've been around in continuous use since something like the 70s, they're very well characterized, NEB has had a continuous research program where they've been optimized out the wazoo.

Technically speaking they are fundamentally simpler than CRISPR (one component, vs. 2). They also are more generally useful when your genetic manipulation is done outside the cell. So there's a clear tooling difference in CRISPR/RE. Most people who use CRISPR, will use REs in the process of make the DNA piece they're putting in alongside the CRISPR. You'd be a fool to use CRISPR in E. Coli or Yeast.

So 'clan'ing ain't gonna really happen here.

[neuronic]

Yes. The next time some "What is the most promising technology?" thread pops up on reddit, you can safely post CRISPR.

Depending on how things go with the patent stuff and the technology itself, sooner or later this will absolutely transform our lives. We are looking at the incubation of a technology that may easily save millions of lives (over a long time frame).

Potential for misuse is near infinite though - imagine a privatized CRISPR inaccessible to the sub-$50 million/ year crowd.

The limitations of CRISPR really do appear to be few though. Lots of techniques and methods will be developed and figured out in the next years. It allows us near complete control over the most essential biology. And all that in vivo.

The road ahead is rough but I am confident that CRISPR can become the magic tool I just described. It will be black and white magic. Question is which will dominate?

[zardo]

Potential for misuse is near infinite though - imagine a privatized CRISPR inaccessible to the sub-$50 million/ year crowd.

I can imagine a lot worse than that. Imagine genetic engineering gets dirt cheap, and that does seem to be the direction we're headed. Novel pathogens are going to be a lot easier to design than treatments and preventative measures to protect against them. How do you stop the proliferation of bio-weapons? I'm thinking that would be about as easy as stopping the proliferation of malware.

[ethbro]

> I can imagine a lot worse than that.

From the RadioLab podcast linked above (excellent, btw), far more frightening in the long run: introduce genetic changes to the reproductive cells.

... which then automatically become part of any offspring.

... which are then automatically inherited by any subsequent generations.

And, new species.

[ChuckMcM]

I totally want the gene to control metallic objects :-) But I agree with you, at some point you will have to ask what species is this? Are you human or something else? I expect CRISPR to show up in athletes first, high risk/high gain and difficult to claim cheating.

[technotony]

One major difference is that you have to order your DNA typically from a third party provider and they can screen for pathogenic sequences. We could probably stop malware if we could screen all the code before anyone was allowed to run it. I think the current system is reasonably robust for stopping novel syn bio pathogens.

In my mind the big risk comes with home based DNA printers. There are several close to getting to market (eg http://www.kilobaser.com/), at that point we lose control over what gets printed and then maybe there are concerns... though I do think creating a pathogen is really hard and most likely to end up killing the creator before anyone else.

[kanzure]

> at that point we lose control over what gets printed and then maybe there are concerns

You have never had control. Perhaps instead you are more worried about our biological weaknesses; there are many! People die all the time from various diseases and even aging. I suggest fixing this before you outlaw DNA manipulation. All of life is a manipulation of DNA in one way or another, and is in fact essential to the maintenance of life... But vulnerabilities should be patched, not swept under the carpet.

[mbreese]

It's very hard to Figure out what a random piece of DNA will do just from the sequence. Combine that with other molecular biology techniques for combining, slicing, and dicing DNA, and there would be very little hope to do any sort of prospective screen.

[jashephe]

> It's very hard to Figure out what a random piece of DNA will do just from the sequence.

While it's certainly true that it's hard to determine the function of a DNA sequence from scratch, it's considerably easier to compare that sequence (or the sequence of the translated polypeptide) to other homologous sequences to see if it matches something dangerous.

I previously worked in a lab that studied Bacillus anthracis, and we had a bit of trouble getting a major gene synthesis company [1] to produce a plasmid with a variant of atxA [2], and atxA isn't even a toxin, it's just a transcriptional regulator. We presumed that they just BLASTed [3] the sequence we gave them and threw up a red flag when it matched anthracis. So this sort of sequence-checking already occurs.

[1] https://www.dna20.com/

[2] http://www.ncbi.nlm.nih.gov/pubmed/8577251

[3] http://blast.ncbi.nlm.nih.gov/

[avinashv]

> Potential for misuse is near infinite though

Fully agree, though I see the potential for good to be more.