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U.S. scientists have genetically modified human embyros using CRISPR and have apparently avoided the worst of the off-target effects that have plagued previous efforts. The results are unpublished and the team is not commenting yet:
The first known attempt at creating genetically modified human embryos in the United States has been carried out by a team of researchers in Portland, Oregon, Technology Review has learned.
The effort, led by Shoukhrat Mitalipov of Oregon Health and Science University, involved changing the DNA of a large number of one-cell embryos with the gene-editing technique CRISPR, according to people familiar with the scientific results.
Until now, American scientists have watched with a combination of awe, envy, and some alarm as scientists elsewhere were first to explore the controversial practice. To date, three previous reports of editing human embryos were all published by scientists in China.
Now Mitalipov is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating that it is possible to safely and efficiently correct defective genes that cause inherited diseases.
Although none of the embryos were allowed to develop for more than a few days—and there was never any intention of implanting them into a womb—the experiments are a milestone on what may prove to be an inevitable journey toward the birth of the first genetically modified humans.
Also at STAT News.
Previously: Chinese Scientists Have Genetically Modified Human Embryos
NIH Won't Fund Human Germline Modification
Group of Scientists and Bioethicists Back Genetic Modification of Human Embryos
The International Summit on Human Gene Editing
UK Scientist Makes the Case for Editing Human Embryos
Second Chinese Team Reports Gene Editing in Human Embryos
Scientists Keep Human Embryos Alive Longer Outside of the Womb
Francis Collins Retains Position as Director of the National Institutes of Health
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @03:52PM (16 children)
If they don't have some kind of detailed report to look at it is pointless to believe anything they are saying. Usually those reports aren't even very good anyway, but there is literally nothing to see here.
(Score: 2) by jimtheowl on Thursday July 27 2017, @04:10PM (14 children)
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @04:37PM (13 children)
Based on this phrasing, they probably used between 50 and 100 embryos consisting of 4-16 cells each. This gives a range of 200-1600 total exposed cells. How many "successful modifications" were there? Knowing mutation rates, I'd naively expect 0-16 of these cells to spontaneously gain/have a mutation at the site they were considering in the case of NEHJ (when they only see any random mutation at a given site).
Actually, is this about NEHJ or HDR (where they insert exogenous DNA)? Because that makes a huge difference. Why should we even think about this without having such basic information?
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @05:07PM (12 children)
I'd expect so close to 0 spontaneous mutations at a specific region, that I wouldn't even say 0-1. For NHEJ to occur, you need a DNA break.
Multiply the likelihood of a break at the ROI by the probability of error at the specific site and the chance of that error being the "correct" one.
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @05:34PM (2 children)
Table S2 (~0.15%):
https://www.ncbi.nlm.nih.gov/pubmed/26121415 [nih.gov]
Tables S5, S12 (~0.1%):
http://www.nature.com/nchembio/journal/v10/n8/abs/nchembio.1550.html#supplementary-information [nature.com]
Figure S1 (~1%):
http://www.nature.com/nbt/journal/v33/n11/full/nbt.3389.html#supplementary-information [nature.com]
Figure S5 (~1%):
http://advances.sciencemag.org/content/suppl/2015/08/11/1.7.e1500454.DC1 [sciencemag.org]
Similar values are found in every paper that reports on spontaneous mutation rates.
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @06:03PM (1 child)
First link:
K562 cells (a triploid leukemic cell line) were electroporated with Cas9 plasmids (mock) - doesn't sound spontaneous to me. Their results do show that guide RNA can greatly enhance indel frequency at a specific region.
https://www.atcc.org/products/all/CCL-243.aspx [atcc.org]
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @06:30PM
Sorry, but I do not see where they define "mock" in that way and your interpretation is non-standard:
http://www.protocol-online.org/biology-forums/posts/5567.html [protocol-online.org]
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @05:59PM (8 children)
Heres another:
Fig 3(1-2%)
"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/early/2015/07/21/1512503112.abstract [pnas.org]
There are more I've seen, just not finding them at the moment...
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @06:05PM (7 children)
Alright, I guess we have different definitions of spontaneous.
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @06:42PM (6 children)
I'm not sure what you are trying to insinuate. Of course mutation rates depend on cell line and conditions. By your definition of "spontaneous" there would be no interference at all (changing media, etc) and these cells would all just die.
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @07:06PM (5 children)
I thought you meant spontaneous mutations arising from the normal error rate in mammalian cells (~10^-10 per cell division). Your definition seems to be what I'd call Cas9-induced, independent of guide RNA.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761330/ [nih.gov]
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @09:24PM (4 children)
That paper gives two estimates (5e-5 and 7e-9) in fig 2 but say 10^-10 in the intro. Then the drake paper estimates 2e-8 per generation and assumes 400(!) divisions between zygote and sperm, so end up with 5e-11. They cite Drost and Lee 1995 for that 400 generations number, but that paper estimate mutations per division to be 1e^-8 (fig 1). I have seen 1e-8 mutations/cell/division as the more generally cited number, but ok.
Lets consider starting with a single cell is 400 divisions removed from its ancestor (the fertilized egg). You would have 2^400 = 2.6e120 cells produced during those 30 years (until the sperm fertilizes an egg). Apparently a sperm is ~1e-14 kg, while an average human cell is ~1e-12 kg.[1] Therefore 2.6e106 to 2.6e108 kg worth of human cells need to be produced over the course of 30 years for this scheme to work. The mass of the observable universe is estimated at 1e52 kg.[1] Why nature use such an insane scheme when it is totally unnecessary?[2]
[1] https://en.wikipedia.org/wiki/Orders_of_magnitude_%28mass%29 [wikipedia.org]
[2] https://www.ncbi.nlm.nih.gov/pubmed/25459141 [nih.gov]
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @10:13PM
Sorry, that should be "1e-8 mutations/bp/division"
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @10:52PM (2 children)
That is a very big "unless" when used in the context of cancer.
Figure 2 is looking at adult mouse tissue (some of which are heavily exposed to the external environment or have a very different internal environment), so it makes sense that the estimates exceed the ideal error rate of DNA polymerase and the error correction machinery of the cell.
The paper probably isn't the best for an estimate, but I came across it while I was looking for the maximum tolerated mutation rate for mammals. If you're interested: It seems that ~100x is tolerated (though the mice die around 3 months compared to 27), while 10000X is embryonically lethal (some random citation that I came across) for mice.
(Score: 0) by Anonymous Coward on Friday July 28 2017, @03:46AM (1 child)
He goes into carcinogenesis later, and discusses how the "multi-stage" theory requires much higher mutation rates. If you get epidemiological data from seer and plot age specific incidence, there is a "turnover" for many cancers where they become less common. This also requires many more divisions and/or much higher mutation rates than usually assumed.
Anyway, the best would be if they take a sample of cells before doing any of this "gene modification", and see how many are "modified", then send the rest on to be treated, but that doesn't seem to be a thing. So all we have are their controls. Apparently when someone publishes a paper about this, its is usually 0.1% to 1% are mutated at the target site either before anything happens or due to environmental factors. I couldn't find it earlier, but there is a paper that reports for one situation it was as high as 10%, and low as .001% for another.
(Score: 0) by Anonymous Coward on Friday July 28 2017, @11:55AM
Yes, I've always found it frustrating that lots of studies skip controls or have few biological and technical replicates. This is more true for expensive techniques (whole genome/transcriptions, ChIP-seq, IP-MS, micro-array, animal models, etc.) as there is little incentive to produce good quality data at the expense of novel, positive data.
Since most quantifications in biology are relative and the systems and techniques can be extremely noisy, most baseline numbers reflect the noise and error instead of being an accurate value (excepting studies that set out to specifically determine this).
(Score: 2) by takyon on Thursday July 27 2017, @07:47PM
The answer is no.
Obviously, someone leaked the existence of this research. It is big news regardless of whether it worked or not.
[SIG] 10/28/2017: Soylent Upgrade v14 [soylentnews.org]
(Score: 2) by kaszz on Thursday July 27 2017, @04:22PM (2 children)
Official embryos that are not implanted into a womb. And unofficial that are.
Now we just need big muscles, slight psychopathy, order eager and aggressive mods. //DoD
(Score: 2) by DannyB on Thursday July 27 2017, @04:32PM (1 child)
Strong psychopathy for those destined for management or higher position. It has been correlated to CEOs. But probably applies to lesser management positions within an organization.
Bigger other endowments.
Things you left out that the future will want:
* ability to work long hours without complaining
* loyalty to the Dear Leader
* not asking too many questions
The lower I set my standards the more accomplishments I have.
(Score: 2, Funny) by realDonaldTrump on Thursday July 27 2017, @05:24PM
Don't make rocket scientists, make really beautiful women. Make them like Marla: nice tits, no brains. A woman who is very flat-chested is very hard to be a 10. Would you go out with Marcia Cross or would you turn gay, DannyB? Make them like Princess Diana. She had the height, she had the beauty, she had the skin. I'd do her. If she hadn't been dead so long, I'd definitely do her. Thank you. 🇺🇸
(Score: 3, Funny) by DannyB on Thursday July 27 2017, @04:34PM (5 children)
What I really want to know when it comes to gene editing: vi or emacs
The lower I set my standards the more accomplishments I have.
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @04:47PM (4 children)
I do all my genome editing with sed, you insensitive clod!
(Score: 0) by Anonymous Coward on Thursday July 27 2017, @05:12PM (3 children)
Lazy punks, if you aren't manually coding the bits you're a slacker just like your old man!
(Score: 2) by Unixnut on Thursday July 27 2017, @06:06PM (2 children)
Nah, real men just bone the woman directly, and the DNA arranges itself. :-)
(Score: 2) by DannyB on Friday July 28 2017, @01:09PM (1 child)
If you are up on current news, you would know sperm counts are dropping. Thus it would take more boning sessions in order to achieve conception. Due to the increased effort, it is simply not worth doing. So no more boning women.
The lower I set my standards the more accomplishments I have.
(Score: 2) by Unixnut on Friday July 28 2017, @01:33PM
> Thus it would take more boning sessions in order to achieve conception. Due to the increased effort, it is simply not worth doing. So no more boning women.
I can't vouch for others, but I very much enjoy boning women. Having more boning sessions is a-ok with me! The increased effort just means I get fitter from all the exercise. Indeed I have boned women where there was no chance at all of pregnancy, but still found it very moreish!
Also, sperm counts are dropping in "feminised societies", the rest of the world (euphemistically named as " high machismo" in TFA ) are more than willing and able to take up the slack. Assuming we even have to keep the accelerated pace of human population growth, which I don't think is necessary.
(Score: 2) by Oakenshield on Thursday July 27 2017, @04:52PM
Khaaaaaaaaaaaan!
(Score: 0, Redundant) by nnet on Thursday July 27 2017, @07:17PM
Kha-a-a-a-aaaaaaaaaaaaaaan