Pre-Existing Immunity to CRISPR Found in 96% of People in Study
xconomy.com
xconomy.com
"Published now in @NatureMedicine on #CRISPR & Immunity to SpCas9. 6 months has past since the preprint was online & it is a long time in the CRISPR field. Since then additional work showed how to circumvented this by modifying Cas9 protein or using Cas9 orthologs. So No panic !" [1]
[0] https://www.biorxiv.org/content/early/2018/04/04/295139
[1] https://twitter.com/GaetanBurgio/status/1057206850213441542
(This is a joke, in case that needs clarifying)
By the way, "cancer" is a class of diseases, not a single disease to treat, and many of them currently have CRISPR-derived treatments being actively developed.
Does this mean all the hype was nothing more than hype?
Should anyone with investments in CRISPR be seriously looking at dumping their stock?
Should anyone who was holding out on CRISPR to give us super powers / cure disease / etc start drinking copious amounts of alcohol instead?
Despite my tone, I seriously am asking what the implications of this are, because it's not my area of expertise.
Besides, the ethical problems with experimenting on human beings are extremely intractable.
In these cases, the presence of cas9 antibodies is a severe limit to many of the techniques that these companies were working towards.
I really dislike pandering, dismissive statements like this.
What's so inherently wrong with the entire category of genetic "enhancements" (changes for a perceived positive benefit)? You can't respond to this by just pointing out some proposed enhancements or motivations that are silly. I'm asking why you object to the very idea of any enhancements.
What about changes to make the following at some point in the future (these are just to give the general idea of positive changes, I'm not saying CRISPR could necessarily be used for them). These are things that in principle could be addressed by genetic "enhancements".
- stop people from getting diseases like celiac disease
- lessen our evolutionary desire for fatty and sugary foods (that no longer makes sense in the modern world, and which causes great harm)
- address some of the more egregious cognitive biases that cause so many problems in the world
I'm not sure how to interpret this - are you saying we should use CRISPR to make people think a certain way? If so this seems like a pretty horrific suggestion.
(Also, why do you put 'cognitive biases' in quotes, as if it's a notion of suspect legitimacy?)
Also, you're assuming it would necessarily be something people resist. Remember that this could be quite a fair way into the future. By that time our understanding of things like the human brain and how it works (and of all its limitations), and of how to change details of our bodies and brains, may be very good and well-accepted, such that it's not a big deal.
And, regarding "How are you going to enforce your eugenics program" (emphasis added), grow up.
To suggest otherwise is to ignore history.
And since you suggested it and are actively defending it in this thread, yes it is yours in the context of this thread. Own it.
Humans are, for example, very poor at making risk assessments. Evolution has "programmed" our brains to focus too much on certain things and not enough on others. These heuristics might have made sense in ancestral environments bit are quite harmful in today's world. Evolution has already "made us think a certain way". Why would it be so horrific to, for example, lessen certain of those tendencies, if they are harmful?
The examples I gave are hardly of "Changing how people fundamentally think and reason".
> Such transformative things will be met with pushback
It certainly could be. There's also what I said in my last comment, about why that's not necessarily so. Which you have ignored.
> if such a program is deemed beneficial by the powers-that-be it will be pushed upon the populace through means anywhere from marketing campaigns to outright genocide.
That is such a ridiculous argument to make in response to what I have said.
That is to assume that 1) the governments feel so strongly about it and 2) feel that they need to go to extreme lengths to make their will accepted. There is no reason to think that either of those conditions would be true in the case of DNA modifications like I have talked about. You certainly haven't attempted to argue for it.
Your argument could be used against any suggestion. "If such a program of combatting global warming through enforced tax on carbon is deemed beneficial by the powers-that-be it will be pushed upon the populace through means anywhere from marketing campaigns to outright genocide." See how ridiculous that sounds?
> And since you suggested it and are actively defending it in this thread, yes it is yours in the context of this thread.
Grow up. You said "How are you going to enforce your eugenics program". Show me where I said anything that even implied some sort of 'program' that is 'enforced' upon people, or that I had some sort of plan to do so? Don't try to make it out as if you were saying something else.
And "eugenics" is 'a set of beliefs and practices that aims at improving the genetic quality of a human population' [1], which is exactly what you're talking about here. There's a reason the term has fallen out of favor since WWII.
Who said anything about "Forcing all humans to think one specific 'rational' way, eliminating all 'cognitive biases'", either! Show me anything I wrote that even suggests this.
> And "eugenics" is 'a set of beliefs and practices that aims at improving the genetic quality of a human population' [1], which is exactly what you're talking about here.
Show me where I said it wasn't "eugenics". (but there's a big difference between forcing people into it and it being voluntary. There's also a big difference between various alternatives for what the genetic changes are, and I've been very clear about what sorts of things I'm talking about).
I'm amazed at the disconnect in this subthread between what I have actually said and what people are claiming I said!
You think simply because it implies a value judgement that you can be skeptical of it?
And I (as a scientist) really dislike having to frame everything I do as being relevant to human medicine for laymen to appreciate it.
Some things are extremely valuable even if they can't be used to treat cancer and congenital disease.
My only counterpoint is that I and many other "laymen" (as apparently we're referred to?) can't be expected to appreciate your work if you can't explain it.
It's not like genetics is the only field that struggles with this. I'm primarily a web developer and still remember the 10+ years of trying to explain to people why "The Web" was an important technology that would radically impact all of our lives. I still remember the bubble. I still remember being told this was a dead field. Where are those people now?
I remember how dismissive people were about mobile apps, too.
The same challenge applies to AI, blockchain, virtual/augmented reality, etc.
As a non-scientist, I struggle to explain to people why it's important that we increase our funding and support for all of the sciences. It's hard to appreciate how seemingly "useless" discoveries combine with other "useless" discoveries to give us the amazing advances in technology and medicine that we have today.
BUT, we have to try.
And when some "layman" dares to ask about the meaning of such-and-such a discovery, maybe take a deep breath, recognize we don't all have you incredible knowledge about this topic, and appreciate that someone is expressing interest in what you do, in the only terms they have available to them.
All of which was a long-winded way of saying: All I know about CRISPR is what I read in relatively mainstream publications. Help me out. Or don't. Your call, really.
Of course, absolutely, explaining what we do is hugely important. Actually I think that bringing new knowledge to the rest of humanity is the second most important thing after actually generating said knowledge.
> can't be expected to appreciate your work if you can't explain it.
The frustration is that people only seem capable of appreciating science when it has direct and tangible benefits for humans. (and that's why i posted the previous post, not cause you dared ask a reasonable question)
"Why do you do this?" "What can we use this for in humans?"
Basic research is vitally important, and has contributed so much to society. Yet by its very nature you can't predict if how any specific piece of basic research will provide benefit.
It's a fundamental misunderstanding of basic research and scientific and technological development to expect to be able to know, and thus say, what the benefits might be.
Rather than expecting to be able to predict the benefits, we have to have a more 'statistical' set of expectations. That, on aggregate, and over time, basic research will provide substantial benefits.
And it's not just the general public who don't appreciate this. I find that many people working in applied research don't appreciate it either.
(And no apology needed... I shouldn't take things so personally.)
What about making them harmless instead? Surviving on donuts (plus perhaps supplements) and staying perfectly healthy... Think about it! :D
Fly immune systems obviously are quite different. But the technique still holds a lot of promise. Like any cutting edge technology there are potential problems in developing it into useful therapies, and there is a chance something better will come along and displace it.
It is very difficult to edit all the dna of living organism as each cell has a copy. Easier to do as an organism develops.
https://labiotech.eu/medical/crispr-therapy-cancer-risk/
CRISPR is definitely going to go through the "hype cycle" - as in the hype will die out long before we can prove it can be safely used in humans, and these achievements will likely happen in the background over several decades time span.
You’re right that there’s a certain amount of hype surrounding CRISPR, especially when it comes to potential medical application (whether this works remains to be seen, although I and most people in the field remain optimistic). But until something even better comes along I don’t think interest in CRISPR will die down soon.
And the comment that I replied to implies that it is talking about certain applications of genetic engineering which have to happen in the germ line. So I disagree that what it says is “plain wrong”, it’s just incomplete.
We have no idea what the impact would be for modifying germ line cells in a developing human being.
Does that mean it could be used when young, before the immune system is primed?
There's a bit more nuance than this, but this makes it significantly more difficult to pull off gene editing in a human.
The major problem is still how do you target cancer cells? If you can find something that makes them unique, say a cell surface receptor, or an unusual metabolic process, there are lots of ways to target them for removal. It's just hard to uniquely identify cancer cells. Right now, most chemotherapy drugs target the phenotype of "fast replication" which really isn't too selective.
How about performing whole-genome sequencing on a tumor, and then targeting the differences with the patient's natural genome?
There are a companies that currently focus on this area specifically by leveraging the ever dropping costs and capabilities of gene sequencing by developing targeted immunotherapy solutions that can target the specific genetic makeup of a tumor from a biopsy.
Other cancers there may be a mutation in one of these genes that makes it more or less effective and lead to cell cycle deregulation. Those are good targets for T cell killing.
In any case, it is probably a more effective approach in cases where we understand potential epitope targets to directly expand T cells that can do the killing rather than having some intermediary in the mix.
The difference is more likely to be in the expression level or epigenetic (de)repression of a particular gene than the presence or absence of that gene. Organisms don't tend to keep around genes that only serve to form tumors.
A slightly better approach would be to use RNA-sequencing to look for mRNA signatures in tumor vs normal cells.
Get a construct into the cell that is only transcribed if specific pathways are overly active, effectively testing that cells "cancer status". This is the hard part.....
Then have it translate something pathogenic-looking that gets presented on the surface.
So now the question is, how do you design some kind of promoter sequence that looks for, say, tp53 mutations or something similar?
This is perhaps not surprising, but still very disheartening news
Hammers don't also fundamentally change the course of evolution.
It's like comparing a slingshot with a nuclear missile
If we modify harmless bacteria to build the enzyme for us, then sure, the modification could well end up on harmful bacteria.
Also you could argue that the title is misleading, as stating that CRISPR evokes an immune response is inaccurate; CRISPR from a bacterium that frequently comes into contact with most humans evokes it, and not all CRISPRs are the same.