CRISPR Editing in Primates
blogs.sciencemag.org
blogs.sciencemag.org
Here is the thing, this is probably moot. The genie is probably already out of the bottle.
I doubt that an average person with CF would want testing on primates to be done in their name.
Justifying your ethical position by name-checking a disability group is kind of gross, especially given that animal testing is not a mechanism which typically results in improved treatment.
I’m sure you’ll find people who don’t feel that way. But I can’t overstate enough how horrible it is to go from being a functional adult with all the joys and sorrows that brings to being a much less functional person in pain every day. That is reality for millions of people. I don’t feel that what GP did was gross. I think it reflects reality for people who suffer on a daily basis, and whose loved ones do.
It's your choice to support that; but there are only about four million non-human primates on the Earth/or, 400,000 great apes.
A good percentage of them are already being tested on.
And I’d have any number of them tested on if it meant progress toward a cure for any number of conditions afflicting human beings. I don’t think that’s “gross.”
Most animal research doesn't have therapeutic benefit as a goal or any prospects of contributing to any therapy. Pretty much none is successful on these terms.
e.g. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1781970/
Even so, animal research as a whole is still justified and gets public funds on these terms, without any evidence of results.
Can you name one therapy, confidently, perhaps even without searching, that has clearly come out of animal testing?
[To answer my own question, the only example that I'm immediately aware of is: thalidomide.]
Why, in any other circumstance, would we want to spend a precious resource in unlimited quantity on something that is expensive, unethical, and doesn't work?
However, to claim that animal research hasn't had a massive positive impact on the advancement of biological knowledge and healthcare is not based in reality.
Animal testing has found hundreds of vaccines against HIV that work in primates, but none of them have worked in humans.
How is that a useful thing to spend time on? You have a model, and it's proven that your model doesn't work: I would expect you to throw away the model.
You could spend those excellent researchers and science budget on anything else, and expect better results.
(I get that all drugs have been tested on animals out of legislative requirement, but I hope it's clear we are talking about using animal models for de novo drug discovery).
For a business-oriented forum, I find it hard to understand why people see this as valuable.
Arguing that someone with a disability should support this because they might benefit, without reason or evidence for that, is an appeal (only) to emotion.
I find it ableist, to use disabled people as an abstract hypothetical grouping in this way, only to support a point that is indefensible any other way.
If you don't want me to have an emotional reaction, don't set up an emotive point.
Your point in the other comment was that you would cause suffering to and sacrifice "hundreds of billions" of primates for a small chance to heal yourself.
That's clearly not balanced. I personally don't think that animal testing as it exists today, and given the complete lack of direct results that it has to show us, is balanced either.
Do you really value yourself, as a human, trillions of times higher than a chimpanzee? I don't and won't respect that. You saying that, out loud, only makes me wonder how much you internally value other humans.
The technique described in the article absolutely could result in not just "improved treatment", but an actual cure. We know what causes CF. We know what causes many other genetic diseases. Right down to the individual bad DNA segment.
And there is absolutely no way those treatments are ever going to be approved without animal testing. Sorry, they just aren't.
Also note that in the study linked in the main post, the gene itself is being base edited in the liver, not globally.
By the way, I would like to point out that your ilk have killed a great many people. For decades you have cracked people over the head with the idea that cholesterol is a health outcome and that saturated fat is bad for you. It turns out that cholesterol is a heuristic and that it’s been read wrong to boot. And it turns out saturated fat isn’t just not bad for you, it’s an important part of a healthy diet.
https://www.sciencedirect.com/science/article/pii/S073510972...
Dr. Shawn Baker and Dr. Paul Saladino ate nothing but red meat and saturated animal fat for two years and they had CAC scores of zero. There is testimony that someone’s CAC score went down after cutting out sugar and adding beef tallow.
Can you blame me for resenting the medical establishment?
Getting to your assertions about cholesterol, there is a chasm between "dietary recommendations for cholesterol" and "genetic and therapeutic modification of lipoproteins."
Re: dietary recommendations, which seems to be what you are referring to, I think that the evidence for or against specific dietary recommendations for many types of nutrient intake is hardly compelling. But it's also not an area of my expertise.
Re: therapeutic reduction of cholesterol, the results over decades are totally unambiguous: reducing LDL-cholesterol via statins and PCSK9 inhibition reduces cardiovascular disease and prolongs life. And those benefits are also conferred to people who have lower cholesterol throughout their life due to genetics.
I disagree about LDL. It’s not as simple as LDL. There are different kinds of LDL and some are worse than others as is pointed out in that link, I think. Medications that reduce LDL do other things too and it’s not clear that their effect on LDL is the real vector for their efficacy. And people with elevated LDL sometimes don’t develop the diseases that high LDL supposedly causes. It’s a broken model based on an overly intuitive interpretation of legitimate data.
I read a biochemistry textbook. The same one you guys read. The only time it mentioned ketosis, it was a brief footnote in effect saying “ketosis is a dangerous abnormality and results in diabetic ketoacidosis.” It was literally a sentence or two for the whole metabolic phenomenon of ketosis. A widespread textbook printed in the last 5 years if I recall. That’s when my eyes were opened to the possibility that the doctors have been making oversights. How could you blame a doctor for believing his textbook?
But if you look outside of the mainstream literature, it appears that that high LDL is protective. Also statins appear to cause more problems than they solve ( So has Aseem Malhotra been screaming about for nothing?). While I cannot quote 'studies' ( I do believe that you can find some if you searched ) , there are compelling anecdotes ( like that of Dr. Shawn Baker) which to me proves consensus on a topic need not necessarily mean that the view is correct. Ofcourse people quickly remind you that anecdotes are not data...
Ok I know what you mean, what you mean is that we don't have a formal definition. But I'd like to believe that a perceptive physician does know when people are unhealthy, i.e they observe the person physically, not merely look at numbers. Such physicians are a dying breed though.
If I'm interpreting the article correctly, though, it sounds like in their trials they think they may have edited nearly all the targeted cells.
Using the single-cell sequencing we’ve learned that disease is sometimes driven by a very small sub-population of cells(e.g. cancer treatment resistance). There’s no way of knowing how the organism will respond to a perturbation even in 1% of the cells.
Most of the targeting today is happening through antibodies, but the majority of LNP delivery at this point is done passively without targeting mechanisms on the LNP (Needle injection point aside).
That's actually one advantage of CRISPR over just injecting mRNA - you can target specific cell-lines (Even if you change the genome of many cell types) by using cell-specific promoters for the edits you make instead of relying on surface affinity based targeting of the LNP.
Interesting resources:
[0]: https://www.nature.com/articles/nrd.2017.243 (General review 1)
[1]: https://www.frontiersin.org/articles/10.3389/fmolb.2020.5879... (General review 2)
[2]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5498813/ (PCSK9 target again, but via siRNA actuator)
[3]: https://genomebiology.biomedcentral.com/articles/10.1186/s13... (Example of cell-specific CRISPR integration)
Not a book, but the News Features in Nature have a similar flavor, eg [1]. And for following up with the motivating article... well, there's sci-hub, for now.
[1] "The mysterious microbes that gave rise to complex life" https://www.nature.com/articles/d41586-021-01316-0 in https://www.nature.com/nature/volumes/593/issues/7859 .
* mRNA and lipid nano particles to get the mRNA into cells
* 2 pieces of mRNA. One codes for the change to break the gene for the protein being targeted and another to create a enzyme to edit the first piece into the genome
* both bits of mRNA need to be in the cell, then the enzyme and gene are created and the enzyme edits in the gene
So any cell where this works correctly (and its descendents) no longer produces the protein. It appears that about 60% of cells get hit successfully (based on a 60% drop on the protein level).
They only targeted liver cells. That's good because the liver tends to soak up foreign materials from blood. But edits were found at low levels in other organs (spleen etc). That shouldn't make much difference as the protein in question is only produced in the liver. But beware I guess as a multi-use protein could be altered in multiple organs.
Also, it looks like the edit was very accurate and didn't break other genes at anything like the rate it broke the target.
This is pretty incredible stuff. The biochemical equivalent of keyhole surgery.
Yikes there is a lot of important information being glossed over here
This is mind blowing stuff. I wish our best and brightest put their mind on this rather than working on online ads
Yeah, I'll get a job instead, lol.
Bruh
If you shoot for 5 it might take six. If you shoot for 6 it will take 8. I know you can't read too much into such a short comment, but do some serious introspection. You're setting off like every alarm bell for someone that's about to get absolutely hosed by a doc program.
I'm all for doing serious introspection before (and during!) a PhD, but the comment is way too short to set off many alarm bells for me.
How about one could opt-in to be taxed in state so that money goes out to science. (Where I live there is a tax for a de-facto church if one belongs to that church)
Vote for science.
Earmarked taxes are exactly how we get funds favoring religion. Let your representative represent, but choose them wisely.
As an individual after I've voted, and I still want to contribute some of the earnings I've made, how do I go about that? Is it the best just to start political influencing. Why not directly give money to specific areas of science. Making science a little bit transparent to general public might give motivation for people spend some money that is not distributed similarly as tax payers.
Currently people are supporting e.g. musicians through patron-like systems, why not scientist. I think there could be a risk in that scientist would need to start wasting their time managing some kind of public display of what they do.
There definitely should be a really solid financing from tax only, and it would be horrible if a system was created to undermine that so that you would need public collection of money for projects. I'm not saying that.
The Royal Society funds basic research, and is funded by donations. It's been running since 1660.
Jerry Pournelle, the late science fiction author, mentioned on his own blog that there was a period of time as a psychology PhD student when he, too, lived on monkey chow. However, he did it out of poverty, not out of a spirit of scientific inquiry.
It was unbearable - we later discovered it's what they use to feed prisoners and some zoo animals.
Honestly, vegetables and legumes aren't much more expensive and vastly superior.
While I don't philosophically agree with the sentiment what someone making actual policy will tell you is that scientists are, in average, already being payed way more than the "value" they add to "the economy" in their lifetime. There doesn't seem to be a supply crunch for people wanting to pursue a career as a biomedical researcher and the field is highly competitive, as most people on it can tell you.
To change that, being completely blunt and with no nuance, I think three things can help:
- As a society scientists get "moved out of the market". They kinda already are "out of the market" if you think that most of the money they make comes from strategic government grants backed by monetary emission or by discretionary allocation by "illuminated" boards that are sitting on a stash of money that patents from a very small percentage of previous "science" makes.
- We low the barrier for someone to be able to do the "science" we need. Like with music production. A lot of people will be able to self-finance. This is happening with lab equipment but it will likely never happen with research trials and human experimentation.
- More money is thrown to whatever "science" we want in general. Like what happened with space exploration or AI.
I hope a little bit of the three keep on slowly happening and maybe eventually we will reach a breaking point where everyone has access to personalized cutting edge medicine/diet/exercise plans. I don't find it likely but I hope we make progress torwards that in my lifetime.
I bet that we will see some form of this. In some way we already do in the form of recreation drug users, body modification hobbiests, fetishists, and nutropics users.
Due to the way Academia is structured there simply aren't enough jobs, and the more senior people can get stuck just writing grant applications instead of doing actual science.
I'd massively expand the number of National Labs and research institutes so it isn't such a pyramid scheme - and allow budget for some sort of "scrum master" figure to deal with the non-science bureaucratic stuff.
Expanding the grants budget would also help make it less desperate so scientists can focus on doing science and not begging for funds.
Doesn't seem like that would solve any huge health problem, but the proof of concept that you can edit DNA in the liver fairly freely should be enormously fruitful