CRISPR Gene Editing In Human Embryos Wreaks Chromosomal Mayhem (nature.com) 87
A suite of experiments that use the gene-editing tool CRISPR-Cas9 to modify human embryos have revealed how the process can make large, unwanted changes to the genome at or near the target site. Nature reports: The first preprint was posted online on June 5 by developmental biologist Kathy Niakan of the Francis Crick Institute in London and her colleagues. In that study, the researchers used CRISPR-Cas9 to create mutations in the POU5F1 gene, which is important for embryonic development. Of 18 genome-edited embryos, about 22% contained unwanted changes affecting large swathes of the DNA surrounding POU5F1. They included DNA rearrangements and large deletions of several thousand DNA letters -- much greater than typically intended by researchers using this approach. Another group, led by stem-cell biologist Dieter Egli of Columbia University in New York City, studied embryos created with sperm carrying a blindness-causing mutation in a gene called EYS2. The team used CRISPR-Cas9 to try to correct that mutation, but about half of the embryos tested lost large segments of the chromosome -- and sometimes the entire chromosome -- on which EYS is situated. And a third group, led by reproductive biologist Shoukhrat Mitalipov of Oregon Health & Science University in Portland, studied embryos made using sperm with a mutation that causes a heart condition. This team also found signs that editing affected large regions of the chromosome containing the mutated gene.
The three studies offered different explanations for how the DNA changes arose. Egli and Niakan's teams attributed the bulk of the changes observed in their embryos to large deletions and rearrangements. Mitalipov's group instead said that up to 40% of the changes it found were caused by a phenomenon called gene conversion, in which DNA-repair processes copy a sequence from one chromosome in a pair to heal the other. Mitalipov and his colleagues reported similar findings in 2017, but some researchers were skeptical that frequent gene conversions could occur in embryos. They noted that the maternal and paternal chromosomes are not next to each other at the time the gene conversion is postulated to occur, and that the assays the team used to identify gene conversions could have been picking up other chromosomal changes, including deletions. Egli and his colleagues directly tested for gene conversions in their latest preprint and failed to find them, and Burgio points out that the assays used in the Mitalipov preprint are similar to those the team used in 2017. One possibility is that DNA breaks are healed differently at various positions along the chromosome, says Jin-Soo Kim, a geneticist at Seoul National University and a co-author of the Mitalipov preprint.
The three studies offered different explanations for how the DNA changes arose. Egli and Niakan's teams attributed the bulk of the changes observed in their embryos to large deletions and rearrangements. Mitalipov's group instead said that up to 40% of the changes it found were caused by a phenomenon called gene conversion, in which DNA-repair processes copy a sequence from one chromosome in a pair to heal the other. Mitalipov and his colleagues reported similar findings in 2017, but some researchers were skeptical that frequent gene conversions could occur in embryos. They noted that the maternal and paternal chromosomes are not next to each other at the time the gene conversion is postulated to occur, and that the assays the team used to identify gene conversions could have been picking up other chromosomal changes, including deletions. Egli and his colleagues directly tested for gene conversions in their latest preprint and failed to find them, and Burgio points out that the assays used in the Mitalipov preprint are similar to those the team used in 2017. One possibility is that DNA breaks are healed differently at various positions along the chromosome, says Jin-Soo Kim, a geneticist at Seoul National University and a co-author of the Mitalipov preprint.
Think of the souls! (Score:1, Funny)
I disapprove of this "research". Those aren't simple collections of cells, they're souls. Every last one of them. These scientists are going straight to hell.
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We have to start somewhere and gene editing is the most promising method to advance mankind as a whole. We've only been relying on Nature's "survival of the fittest"-strategy, because we never had a choice in the first place. Of course, having a choice always means it can be heaven or hell. Besides, nobody is asking you to do it. Just let others "go to hell" for you and you can just stay in "blissful heaven". If you ever get cancer or some other wicked disease up there on your clouds, don't worry, some devi
Re: Think of the souls! (Score:5, Interesting)
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Our first CRISPR targets would be point mutation diseases, because these require the simplest changes.
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Yes. The future is bright for cystic fibrosis, sickle cell, Tay-Sachs and uh... a few other mostly super rare diseases. Provided we can actually improve gene-editing (much more difficult than gene-deletion) techniques to provide the required precision, of course.
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Rarity of the disease doesn't matter at this early stage of applying the technology. Cure a rare disease and you prove the concept. Besides, sickle cell is rare in white people. CRISPR has a chance to be a real hero at exactly the right time with this one.
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https://ghr.nlm.nih.gov/condit... [nih.gov]
Type I diabetes - also rare:
"Prevalence: In 2018, 34.2 million Americans, or 10.5% of the population, had diabetes."
https://www.diabetes.org/resou... [diabetes.org].
so - we are discussing a disease that will impact 0.2% of the black population. That seems to be the definition of rare.
Should it be fixed? Certainly. But lets not pretend it's not a rare blood disorder. Typ
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That's 0.5%.
From wikipedia
That's sickle cell anemia, which is just a subset of sickle cell disease.
Re: Think of the souls! (Score:4, Informative)
I didn't say sickle cell was rare. I suppose I should have put a comma after "other" to make it super clear.
The point is that there are very few single mutation diseases. This discovery ended the "OMG decoding the genome will cure everything!" hype from the late 90s. It turns out that most diseases are complicated and any genetic component they have depends on many genes, and usually also interacts with the environment.
It's difficult to see where germ line or embryonic gene editing would be practically useful. In sickle cell, for example, it's more practical just to inspect embryos and select ones that don't have it. We can, and do, do that now, no problem. The only real case for gene editing would be if both parents were homozygous and just *had* to have a baby that was genetically theirs. So a solution for a specific type of rich person.
Gene editing is *far* more useful as a tool for modifying extracted adult cells, then implanting them. Since you're going to grow the cells externally anyway, it doesn't matter if CRISPR screws up 90%, you just pick out some good ones and go to town. This technique is currently used for treating a few diseases using modified autologous white blood cells, and could potentially be a miracle for all kinds of things including cancer and diabetes.
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I'm not sure who you are replying to. If it's to my comment then you're misreading me. I'm saying gene editing is a start, and I'm not just referring to CRISP or a editing a few genes. I do mean the entire DNA. Some may not think it's going to happen, but they're just the ones who get left behind when advances are being made. The complexity won't stop us from trying. At first will it only be changes for purely humanitarian needs, then we'll see changes to make us more resistant, but we'll also see questiona
Re: Think of the souls! (Score:2)
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This is just what you believe. When has this ever stopped somebody?
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We have to start somewhere...
Have to start what? And, why?
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Have to start what? And, why?
To start making choices over our own destiny and because we can.
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Who is this "we" you're taking about? Who is making the choices? Humanity isn't a thing, it's a category.
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Mankind. And don't worry about it. Nobody will come to your door and demand from you make a choice.
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Isn't banning this sort of thing exactly one of these "choices over our own destiny" that we can make "because we can"?
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You can certainly try, but how do you enforce it? China is already mixing pigs with monkeys. Are you willing to go to war over this with another country, because you find war is reasonable and because DNA manipulation is not?
We've then ripped open the earth for its resources, we've polluted the air relentlessly, shredded huge rain forests, spilled oil in the oceans, tested countless nukes and even dropped two on entire cities, made large areas uninhabitable with radioactive materials, enslaved other people,
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I agree that mankind has to make choices over his own desitny, but how do you propose that we go about that? Currently mankind is overrun with it's desires, and is a slave to them. My efforts along these lines consist of meditation. I follow this practice [heartfulness.org]. However, regardless how I feel about the results of meditation, it doesn't seem to be for everyone. What other options are valid, in your opinion? And I'm seriously asking.
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I personally see meditation as idleness. Whatever one can learn from mediation cannot be as much as what one can achieve by being active. If that's working in a soup kitchen or building a house, being active seems more beneficial than meditation. Perhaps think about this the next time you meditate. Might be you're really just meditating for selfish reasons.
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It was impossible for you to post to slashdot without meditating on what you wanted to say first. Meditation steers action, but that's not it's only use.
A simple example of meditation...
Sit there and think of the person that you love most in your life (mom, dad, siblings, spouse, god, etc...) and why you love them so much. Do that for 60 seconds. Afterwards, how do you feel?
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"Survival of the fittest" is a misnomer and often misunderstood. There is no "advance" in any sense other than "different than it used to be". Evolution is not at all about which organism is the best adapted to their environment, but which organisms manage to pass along their genes to later generations. For example, the very bright and gaudy plumage in some male birds that makes them much more visible to predators. These aren't optimizations for survival but techniques to attract picky females.
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It still is survival of the fittest, or to clarify, of the fittest genes. It doesn't just apply for a species as a whole, it also applies for individuals. Making yourself look better to attract a partner still means you're trying to beat the competition.
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"...and gene editing is the most promising method to advance mankind as a whole."
Is it? Citations please.
"We've only been relying on Nature's "survival of the fittest"-strategy..."
How are we "relying" on it? Seems clear we've been defeating it for quite a while now.
"Of course, having a choice always means it can be heaven or hell."
Choice means two fictitious places?
"Besides, nobody is asking you to do it."
Nobody is asking anyone to do it. The concern is whether it is ethical for anyone to do it. No one'
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You seem quite self-righteous for a dumbaas.
That's only in your head. Progress won't stop for you or for me. I'm only more accepting of the fact than you are and got a thicker skin.
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Good that corn has no soul, so even Republicans can continue to eat GM crops, where someone has tinkered with the creation of god.
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Good that corn has no soul, so even Republicans can continue to eat GM crops, where someone has tinkered with the creation of god.
But Democrats will not, because chickfear.
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Considering that just as many pregnancies end is miscarriage as they do in abortion, I presume that means everyone who has a miscarriage is also going to hell.
Silver lining (Score:4, Interesting)
The good news is that this should disuade the unscrupulous from editing humans for spurious reasons like making super soldiers - because it won't work. Unfortunately it also means that fixing genetic defects in the germ line is no closer today than it was yesterday.
Re:Silver lining (Score:5, Insightful)
I don't know, if unscrupulous people are doing this to make super soldiers, I don't think even something like a 75% failure rate would desuade them...
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I don't know, if unscrupulous people are doing this to make super soldiers, I don't think even something like a 75% failure rate would desuade them...
Hail No Bra [youtube.com] (30 seconds in).
More realistically : GODZILLA !!one (Score:1)
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A lot of those germ line defects could be 'fixed' just through simple PGD techniques, no new tech needed. But that is expensive, and makes the anti-abortion lobby angry. Mostly it's just expensive.
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You don't really know what evolution is, nevermind how it works, do you?
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OK, I'm genuinely interested.
I cannot fathom what misunderstanding of evolution would lead to such a comment. Would you care to explain your understanding of what evolution is?
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CRISPR has the net equivalent effect of causing mutations, in this case intended -planned- ones. Should be much more effective than random ones.
The one thing doesn't speak to the other even if you're right that it should be more effective because the mutations caused are planned. Only you aren't. CRISPR causes both planned and unplanned ones.
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Doesn't exactly lend any credibility to evolution. Quite the opposite.
Natural selection got us to where we are today. Are you satisfied with the human species as it stands?
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Natural selection got us to where we are today. Are you satisfied with the human species as it stands?
Natural selection currently seems to be trying to remove from the gene pool those that are susceptible to COVID-19 but most everyone is trying to stop that happening. Do you think that is the right thing to do?
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The right thing to do, from the standpoint of species survival, is to do everything we can to kill off the virus. As Randall Monroe pointed out recently, the biological immune system is only the first line of defense for humans. Our civilization, with its ability to organize cooperative labor to solve large-scale problems, is the most important part.
Chromosomal mayhem is a bit overblown (Score:1)
Of 18 genome-edited embryos, about 22% contained unwanted changes
Embryos can easily be tested for unwanted DNA (changed or not), so these 22% can be discarded.
Youâ(TM)d think genes have a check sum (Score:2)
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In a sense it does! Nature has given you a brain, hasn't it? And brains think about stuff. When you're scratching your head right now then that's Nature doing a checksum.
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If they were intelligently designed, they would.
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If they were intelligently designed, they would.
If stupidly designed maybe.
Intelligently designed, they wouldn't want to give up the whole random mutations and survival of the fittest parts of evolution.
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Depends on their purpose. If they were intelligently designed, they wouldn't need to evolve.
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Not really but there are many correction mechanisms.
They do (Score:3)
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... Nothing as simple as a checksum.
Doing a checksum means that you trust the checksum mechanism more than you trust the data. For instance when data has to travel through an insecure environment, but then can be verified in a secure environment, does one use a checksum.
However in nature is there no such thing as a secure environment. It would render an ordinary checksum mechanism as we know it to be a single point of failure. Any organism could just attack the checksum mechanism and not only destroy the purpose of the checksum, but disable
The Earth is a bitch... (Score:1)
Homo Sapiens have outgrown their use
All the strangers came today
And it looks as though they're here...
Try, try and try again. (Score:1)
So CRISPR doesn't work.
Let's remember that...
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In other news (Score:2)
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Monkeys with keyboards discover preprint servers and proceed to write articled based on non peer reviwed discoveries.Thanks COVID..
preprint servers are way to get that peer review. unscrupulous media outlets turn them into headlines. thanks, schooling system.
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He did?
Re: A bit creepy (Score:1)
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Way to be bothered with using human embryos for clear science, and not be bothered when people murder them.
I am also pro-abortion - all the way up to and let's say a few months after birth. Why? That baby doesn't really know what's going on. If there's a good reason not to have it, don't.
But I also see how *most* people think that would be murder.
What I don't see, is how people don't understand the *other* group just thinks murder is a few months before the *other* group. And you would probably stand up
Re: A bit creepy (Score:1)
I don't think first 6 months abortion is murder but I don't cheer it on either. After 6 months does bother me. The abortions that are right there where it could survive outside the womb with minimal care are wrong, IMO.
Spot the typo in this gene (Score:2)
GACTAGCSMALLPEEPEECTGATCG
Misleading subject (Score:2)
I'm confused by the subject: "CRISPR Gene Editing In Human Embryos Wreaks Chromosomal Mayhem". That headline makes me think that the CRISPR is a good thing in that prevents (wreaks) chromosomal mayhem. Or it that CRISPR causes chromosomal mayhem?
Help get me an editor!
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Sault's law (Score:2)
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Sault is an idiot. His laws seem incorrect. Also he uses a fuzzy weasel word "more complex" .. which can be arbitrarily defined to always be true.
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Sault is an idiot. His laws seem incorrect. Also he uses a fuzzy weasel word "more complex" .. which can be arbitrarily defined to always be true.
Ah, but even you can feel the truth in it I suspect (you use the word "seem"). And you are angry. You just don't like the truth. We don't have a future of infinite advance before us in which we genetically improve man. And people like you think 4.5 billion years of evolution makes nature, well, an idiot we are going to improve upon in, what, a few thousand years? And "more complex" with regard to the genome is pretty obvious: add more DNA to add more abilities or enhance already existing ones. Not really ha
Did they go overboard to get overboard results? (Score:2)
Not being anything resembling a specialist on this, I'd want to know if this shares or avoids the issue that the last study show this type of result had.
Namely that they used a way overaggressive method that didn't match with recommended practices.
Lotto (Score:1)
Never use cannon to catch a mosquito (Score:2)
And CRISPR is roughly equivalent to the Death Star.
Yeeaaah, ... (Score:1)