The Villain of CRISPR • Hacker News Board

Re: The Villain of CRISPR

#41

Post by [deleted] » Mon, Jan 25, 2016, 5:31 PM UTC

Blahah wrote: post #8

Q6T46nT668w6i3m wrote: post #3

Earlier quoted context omitted.

> Michael Eisen is a professor at Berkeley and friend and colleague of Jennifer Doudna. What’s the path forward? Is labeling Lander a “villain” useful?

It's 'useful' in countering an image that people who only read Lander's paper might come away with, and useful in drawing attention to the problem he (Mike) perceives. Whether any of this is useful in a broader sense is unclear, but we are almost certainly seeing the most important story in history of biology for this generation unfolding before us.

[deleted]

Re: The Villain of CRISPR

#42

Post by kauffj » Mon, Jan 25, 2016, 5:32 PM UTC

junto wrote: post #20

I hate the fact that breakthroughs like this are patentable. People need to follow Alexander Flemings lead: The pharmacist Sir Alexander Fleming is revered not just because of his discovery of penicillin – the antibiotic that has saved millions of lives – but also due to his efforts to ensure that it was freely available to as much of the world’s population as possible. Fleming could have become a hugely wealthy man…

I think the notion that one can own facts will one day be viewed as archaic as the notion that one can own people.

Re: The Villain of CRISPR

#43

Post by nycticorax » Mon, Jan 25, 2016, 5:33 PM UTC

I thought this article was interesting because it was that first think I've read that actually lays out a seemingly plausible case for why Doudna et al. deserve primary credit rather than Feng at al. The "Whig History of CRISPR" article was interesting, but it left me wanting to hear more about the biology.

Re: The Villain of CRISPR

#44

Post by nonbel » Mon, Jan 25, 2016, 5:40 PM UTC

daughart wrote: post #36

nonbel wrote: post #15

I have never seen a paper on CRISPR that can distinguish between selecting pre-existing mutants and actually modifying genes. I have read probably a dozen or so at this point, and it is amazing that they always fail to address this either in citations or actual data. At first I thought it was an honest mistake, but now it would not surprise me if some of the main players know that their experiments with CRISPR have b…

It's not clear to me what you are saying. Cas9/CRISPR unambiguously cuts the genome at a target site determined by the guide RNA sequence. In the presence of a DNA oligo with partial complementarity to the cut site, the DNA repair mechanism will sometimes incorporate the "payload" oligo, causing the genetic locus to be engineered from one sequence to another, predetermined sequence.

Start with 10^6 cells. Say 0.1% (1 in 1000) are already mutants at that site. Then add something that kills 100% the non-mutants and you will be left with 10^3 mutants without any gene editing. Say it kills 50% of the non-mutants and renders the rest quiescent due to DNA damage (not dividing), then you are left with 10^3 mutants and 5 x 10^5 non-mutants at time t0. After eg 7 divisions you will have 10^3 x 2^7 = 1.28 x 10^5 mutants, corresponding to 25% of the total.

It depends on the initial number of cells, initial proportion of mutants, division rates, and toxicity. I have also noted that the initial number of cells is usually reported without any uncertainty, which makes me think those numbers may be rather unreliable.

Re: The Villain of CRISPR

#45

Post by cowsandmilk » Mon, Jan 25, 2016, 5:40 PM UTC

nonbel wrote: post #31

daemonk wrote: post #17

Earlier quoted context omitted.

But there are plenty of knock-in experiments where foreign DNA was put into the cut site. Are you saying a pre-existing mutant with the foreign DNA was used in those cases too?

Please link to one/some of the papers you are referring to. From what I have seen, they always detect edits in the controls or fail to report enough information to say either way, eg: "Although rare (∼1–2%), edits were detected with Cas9-only control treatment, including at the predicted CXCR4 cut site, potentially indicating trace amounts of experimental contamination of the Cas9 RNPs." http://www.pnas.org/content/1…

What other controls do you expect to see? Dataset S1 seems complete to me. There is a similar background level of indels both at the CXCR4 site and off-target 1 and off-target 2 sites. The experiment increases indels at the CXCR4 site, but not at the off-target sites.

Re: The Villain of CRISPR

#46

Post by daughart » Mon, Jan 25, 2016, 5:42 PM UTC

jedberg wrote: post #34

daughart wrote: post #32

Earlier quoted context omitted.

It will take millions of dollars of research to turn this basic bioengineering technique into an approved (safe and effective) human therapy. How do you motivate investors to fund this research without the safety net of a patent to protect that investment from free-loaders?

The way it was done before patents -- government funded research institutions whose only motivation was to provide scientific breakthroughs so they could continue to receive government funding.

There's a huge gap between the scientific breakthrough and the work needed to create a safe and effective therapy. It's not academically interesting, and academic scientists won't do it. It's optimization, not discovery. And what about the cost of the clinical trial, which could be $500m?

Government funded research institutions will continue to provide BREAKTHROUGHS to receive funding.

Re: The Villain of CRISPR

#47

Post by onetwotree » Mon, Jan 25, 2016, 5:44 PM UTC

RyanShook wrote: post #18

Can someone share a tl;dr version of this?

CRISPR is a mechanism by which some species of bacteria and archea can edit a virus out of their genome -- it's essentially a small immune system. CRISPR is "hot" right now because of the potential to use it to edit arbitrary genomes. Bear in mind that the technique has a long way to go. It's more or less impossible to do it right now without causing a lot of side effects elsewhere in the genome.

As with most science, this has taken a long time and been the result of work by many, many scientists. Some scientists have big egos and are fighting about who the "real genius" is. Furthermore, it's widely thought that there's going to be a lot of money in this technique, if you can get a patent on it.

TL;DR; cool and potentially very useful science happened, now big egos, big greed, and people who would rather get rich and win a Nobel prize than share the discovery and its benefits with the world are having a fight about it.

Re: The Villain of CRISPR

#48

Post by daughart » Mon, Jan 25, 2016, 5:45 PM UTC

nonbel wrote: post #44

daughart wrote: post #36

Earlier quoted context omitted.

It's not clear to me what you are saying. Cas9/CRISPR unambiguously cuts the genome at a target site determined by the guide RNA sequence. In the presence of a DNA oligo with partial complementarity to the cut site, the DNA repair mechanism will sometimes incorporate the "payload" oligo, causing the genetic locus to be engineered from one sequence to another, predetermined sequence.

Start with 10^6 cells. Say 0.1% (1 in 1000) are already mutants at that site. Then add something that kills 100% the non-mutants and you will be left with 10^3 mutants without any gene editing. Say it kills 50% of the non-mutants and renders the rest quiescent due to DNA damage (not dividing), then you are left with 10^3 mutants and 5 x 10^5 non-mutants at time t0. After eg 7 divisions you will have 10^3 x 2^7 = 1.28…

No pre-existing cells have the mutation at the site you're trying to engineer. It just doesn't happen. Otherwise selection alone would be good enough. But mice cells don't have that much intrinsic variation. Plus a lot of time they're inserting whole genes or larger payloads. The statistical probability of that arising from chance is zero.

Re: The Villain of CRISPR

#49

Post by onetwotree » Mon, Jan 25, 2016, 5:45 PM UTC

junto wrote: post #20

I hate the fact that breakthroughs like this are patentable. People need to follow Alexander Flemings lead: The pharmacist Sir Alexander Fleming is revered not just because of his discovery of penicillin – the antibiotic that has saved millions of lives – but also due to his efforts to ensure that it was freely available to as much of the world’s population as possible. Fleming could have become a hugely wealthy man…

Also Banting, the discoverer of insulin (or at least its potential to treat diabetes).

Re: The Villain of CRISPR

#50

Post by epistasis » Mon, Jan 25, 2016, 5:46 PM UTC

junto wrote: post #20

I hate the fact that breakthroughs like this are patentable. People need to follow Alexander Flemings lead: The pharmacist Sir Alexander Fleming is revered not just because of his discovery of penicillin – the antibiotic that has saved millions of lives – but also due to his efforts to ensure that it was freely available to as much of the world’s population as possible. Fleming could have become a hugely wealthy man…

The inventions of scientists in academia, like employees in the private sector, are owned by their employers. Universities and research institutes typically have a policy to profit from these inventions via patents in order to fund more research.

The people that need to change this are at the administrative level: laws via congress, and then chancellors of universities.