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posted by martyb on Thursday August 03, @10:47PM   Printer-friendly
from the the-best-made-plans-of-mice-and-men... dept.

The human embryo editing study first reported by MIT Technology Review last week has been published in Nature. Scientists led by the Oregon Health & Science University's Shoukhrat Mitalipov edited human embryos to remove the MYBPC3 mutation associated with hypertrophic cardiomyopathy:

The experiment corrected the defect in nearly two-thirds of several dozen embryos, without causing potentially dangerous mutations elsewhere in the DNA.

None of the embryos were used to try to create a baby. But if future experiments confirm the techniques are safe and effective, the scientists say the same approach could be used to prevent a long list of inheritable diseases. "Potentially, we're talking about thousands of genes and thousands of patients," says Paula Amato, an associate professor of obstetrics and gynecology at Oregon Health & Science University in Portland. She was a member of the scientific team from the U.S., China and South Korea.

[...] Amato and others stress that their work is aimed at preventing terrible diseases, not creating genetically enhanced people. And they note that much more research is needed to confirm the technique is safe and effective before anyone tries to make a baby this way. But scientists hoping to continue the work in the U.S. face many regulatory obstacles. The National Institutes of Health will not fund any research involving human embryos (the new work was funded by Oregon Health & Science University). And the Food and Drug Administration is prohibited by Congress from considering any experiments that involve genetically modified human embryos.

Nevertheless, the researchers say they're hopeful about continuing the work, perhaps in Britain. The United Kingdom has permitted genetic experiments involving human embryos forbidden in the United States. "If other countries would be interested, we would be happy to work with their regulatory bodies," says Shoukhrat Mitalipov, director of the Oregon Health & Science University's Center for Embryonic Cell and Gene Therapy.

Also at NYT, MIT, BBC, Science Magazine, and Scientific American.

Correction of a pathogenic gene mutation in human embryos (open, DOI: 10.1038/nature23305) (DX)

Previously: First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success


Original Submission

Related Stories

First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success 28 comments

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


Original Submission

Scientists Question Observations of the First U.S. Human Embryo Editing Study 7 comments

Skepticism surfaces over CRISPR human embryo editing claims

When the first U.S. team to edit human embryos with CRISPR revealed their success earlier this month, the field reeled with the possibility that the gene-editing technique might soon produce children free of their parents' genetic defects. But the way CRISPR repaired the paternal mutation targeted in the embryos was also a surprise. Instead of replacing the gene defect with strands of DNA that the researchers inserted, the embryos appeared to use the mother's healthy gene as a template for repairing the cut made by CRISPR's enzyme.

But such a feat has not been observed in previous CRISPR experiments, and some scientists are now questioning whether the repairs really happened that way. In a paper published online this week on the preprint server bioRxiv, a group of six geneticists, developmental biologists, and stem cell researchers offers alternative explanations for the results. And uncertainty about exactly how the embryos' DNA changed after editing leaves many questions about the technique's safety, they argue. (The authors declined to discuss the paper while it's being reviewed for publication.)

Embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, who led the now-disputed experiments, released a statement saying that his team stands by its explanation. "We based our finding and conclusions on careful experimental design involving hundreds of human embryos," it says.

[...] Although the researchers inserted short strands of DNA as templates for repair, the cells didn't seem to take them up; those specific sequences were absent from the embryos. The cells must have relied instead on the nonmutated sequence in the egg donor's DNA when making the repairs, the team concluded.

The bioRxiv response, led by developmental biologist Maria Jasin of Memorial Sloan Kettering Cancer Center in New York City and Columbia University stem cell biologist Dieter Egli, challenges that interpretation. The authors, which also include well-known CRISPR researcher and Harvard University geneticist George Church, say that the Nature paper goes against conventional wisdom about how embryos are organized early in development. Right after an egg is fertilized, the DNA from the sperm and the egg aren't believed to be in close enough proximity to interact or share genes, they explain.

Previously: First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success
U.S. Human Embryo Editing Study Published

Study in question: Correction of a pathogenic gene mutation in human embryos (open, DOI: 10.1038/nature23305) (DX)


Original Submission

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  • (Score: 0) by Anonymous Coward on Thursday August 03, @11:31PM (2 children)

    by Anonymous Coward on Thursday August 03, @11:31PM (#548518)

    Anyone know if this is covered under the embryonic stem cell research ban of the Bush years?

    From what I can remember, scientists can't use any equipment or personal that were bought or funded and with federal money. Labs that did this kind of research had to buy two of everything as indirect federal funding of these projects would result in their grant money being taken away.

    • (Score: 3, Informative) by takyon on Thursday August 03, @11:52PM

      by takyon (881) <{takyon} {at} {soylentnews.org}> on Thursday August 03, @11:52PM (#548525) Journal

      https://en.wikipedia.org/wiki/Stem_cell_laws_and_policy_in_the_United_States [wikipedia.org]

      There was no "embryonic stem cell research ban". Federal funding was restricted to an existing number of cell lines. Bush vetoed attempts to expand this in 2006. You could still do your research, but you could not get federal funding for it. Most restrictions were lifted by Obama, but there was still this:

      Federal funding originating from current appropriations to the Department of Health and Human Services (including the National Institutes of Health) under the Omnibus Appropriations Act of 2009, remains prohibited under the Dickey Amendment for (1) the creation of a human embryo for research purposes; or (2) research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero.

      Francis Collins, who still leads NIH, will not fund germline modification [soylentnews.org], which this is. NYT confirms the funding sources:

      For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.)

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    • (Score: 4, Insightful) by driverless on Friday August 04, @02:56AM

      by driverless (4770) on Friday August 04, @02:56AM (#548570)

      "Potentially, we're talking about thousands of genes and thousands of patients,"

      To see where this is really heading, all you need to do is change one letter:

      "Potentially, we're talking about thousands of genes and thousands of patents,"

  • (Score: 1, Insightful) by Anonymous Coward on Thursday August 03, @11:37PM

    by Anonymous Coward on Thursday August 03, @11:37PM (#548521)

    Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.

    They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.

    Instead, the male gene copied the healthy sequence from the female gene. The authors don’t know why it happened.

    [...]

    The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves.

    In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cell’s mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell.

    “We were so surprised that we just couldn’t get this template that we made to be used,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. “It was very new and unusual.”

    https://www.nytimes.com/2017/08/02/science/gene-editing-human-embryos.html [nytimes.com]

    Even more remarkably, the majority of targeted blastomeres (63.6%, 35/55) resolved the DSBs by HDR using the wild-type allele, also markedly different from what was seen in iPSCs (Fig. 2d and Extended Data Fig. 2a). We did not find any evidence of HDR using exogenous ssODN, suggesting that HDR is guided exclusively by the wild-type maternal allele.

    https://www.nature.com/nature/journal/vaop/ncurrent/full/nature23305.html [nature.com]

    So they had 70 zygotes (extended data table 2) that were about 50/50 wt (wildtype) and mutant (the sperm were from a heterozygous guy). They ended up with 36/54 wt embryos (fig 2a), when they had ~35 wt zygotes to start with. Doesn't this sound like they just killed/damaged 16 of the mutant zygotes since they targeted an enzyme that damages DNA to cells with the mutant sequence? Wouldn't this also explain their strange, surprising result that the "edited" cells contained WT sequence rather than the one they injected into the cells?

    This all seems very straightforward to me with no mysteries, surprises, remarkable findings, or anything unusual other than the fact they insist that some kind of "editing" is going on...

  • (Score: 2) by MichaelDavidCrawford on Thursday August 03, @11:43PM

    Her name is French for "wings", as in Angel wings.

    Her mother was feeling her biological clock ticking, so she scouted around for a man with "good genes". To his great surprise, he became a father. To both of their great surprise, they are carriers for Recessive Polycystic Kidney Disease.

    Both of Ailes' kidneys were surgically removed when she was less than a week old. They are now in a jar of formaldehyde and on display at Stanford Medical Center.

    Ailes got her transplant when she was 3 1/2. I think she's eight years old now.

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  • (Score: 3, Interesting) by kaszz on Friday August 04, @02:46AM (15 children)

    by kaszz (4211) on Friday August 04, @02:46AM (#548564) Journal

    If a person has serious genetic faults. Maybe it's better to not make children?
    Gene editing sounds like a miracle cure but there may be side effects. And the downside risks are externalized from parents to the children. Just so they can fulfill their biological imperative.

    • (Score: 1, Interesting) by Anonymous Coward on Friday August 04, @03:19AM (2 children)

      by Anonymous Coward on Friday August 04, @03:19AM (#548586)
      That's the thing, most of the people who are OK with this sort of research and tech are the same people who are OK with abortion.

      Detection of genetic diseases is much easier than repairing them. So abort the embryos with the diseases and let the ones without survive. You're going to have to detect the diseases before any such repairs anyway.

      And if the defect-ridden people keep shooting duds too bad. There are already 7+ billion people on this planet, many without genes that are that crap.
      • (Score: 2) by takyon on Friday August 04, @03:37AM

        by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @03:37AM (#548592) Journal

        It's true that you can screen embryos for diseases before using them in IVF. In fact, that is one criticism of the study noted in the NPR article:

        Darnovsky and some scientists argue that many couples who carry genetic diseases already have safer alternatives to this sort of gene editing. Couples carrying genetic diseases can go through in vitro fertilization (IVF) and have their embryos tested before being implanted in the womb.

        "I will admit to experiencing a sense of puzzlement," says Fyodor Urnov, an associate director at the Altius Institute for Biomedical Sciences, a nonprofit research institute in Seattle.

        "The question I have is: 'Why did you folks bother, given that there is a safe, effective, approved and ethical way to attain exactly the goal you have set out to do without any of the significant logical and ethic hurdles of having to edit a human embryo?" Urnov says.

        If two people would have a defective child 100% of the time, good luck banning them from procreating, or from doing the slightly better thing by correcting diseased embryos.

        The real story is that while the researchers say this is for correcting genetic diseases, they will polish all of the techniques necessary to create a designer baby. It doesn't matter if a rich couple are duds or studs, they will be able to pick and choose the "best" (or favored) genes, with more control and overwhelming results than carefully picking the "best" two people on the planet. Gay and lesbian couples will be able to create biological children [time.com] that are a mix of the genes from the couple with designer-picked genes added for good measure. Money makes the world go round (pregnant), baby.

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      • (Score: 2) by kaszz on Friday August 04, @03:54AM

        by kaszz (4211) on Friday August 04, @03:54AM (#548604) Journal

        The detection techniques for natural genetic problems may miss one-off genetic defects caused by gene editing. Some people will have genetically defect offspring no matter how much in-vitro, detection and abortion they try. That's where this technique comes in. And a big bag of ethical and incentives questions show up.

        And of course, once it's possible to remove diseases. Why not add some other qualities? the R&D is already paid and rich people will pay even more. If a line of edited genes contains defects it may result in mass deaths, hospitalization or hoards of psychopaths. Seems people just can't resist the fingers in the jar and will suffer the consequences. This time others will suffer too.

    • (Score: 2) by takyon on Friday August 04, @03:26AM (11 children)

      by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @03:26AM (#548588) Journal

      That argument won't work on parents. They want children and nobody can tell them no if they can get a hold of the cash or have the right health insurance policy.

      Germline editing has much more use than just correcting a few diseases. It can also be used to make children "artificially" smarter, more attractive, or whatever. There are people who will pay 6-7 figures to produce one genetically enhanced kid.

      As for side effects, they seem to have found a way around unwanted mutations. If there are other side effects, they will be apparent early in life or probably even before the baby is born. And that's why we need research in the first place, to figure out how this stuff works. You can't make an omelette without cracking a few eggs.

      Having a kid the normal way risks creating a suffering deformed mutant. If editing can be done in a way that routinely produces healthy offspring, it will be done. Banning it because "fulfilling their biological imperative" is an unworthy reason doesn't make sense. You might as well ban sex or have a One Child Policy or whatever. Oh, you don't want that? Then get out of the way.

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      • (Score: 2) by kaszz on Friday August 04, @03:59AM (8 children)

        by kaszz (4211) on Friday August 04, @03:59AM (#548607) Journal

        Implement true genetic heritage policy? or make clinics strictly liable for genetic side effects?

        On the societal scale. What happens when these super enhanced persons is supposed compete with others on "equal" terms seems like a blood bath in the queue.

        • (Score: 2) by takyon on Friday August 04, @04:07AM (3 children)

          by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @04:07AM (#548610) Journal

          On the societal scale. What happens when these super enhanced persons is supposed compete with others on "equal" terms seems like a blood bath in the queue.

          I don't think it will be much different than the income inequality problem. If your parents are multi-millionaires or billionaires (maybe trillionaires in a few decades?) and if they don't live a humble lifestyle or withhold money from their kids like Warren Buffett does, then you have it made in life. You have probably interacted with some of these people. They have the opportunity to have better educations, get good jobs without needing to do work, can control industries to keep small businesses small, bribe cops and politicians, and get away with murder in some cases. Having kids that are 10% smarter or a bit more attractive could aid in preserving the dynasty and increase the wealth pile, but it's just adding a little insult to injury at that point. Super enhanced persons are not needed for a blood bath since that could already be coming if automation kills jobs but universal basic income is slow to follow.

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          • (Score: 2) by kaszz on Friday August 04, @04:24AM (2 children)

            by kaszz (4211) on Friday August 04, @04:24AM (#548614) Journal

            Bloody riots can be quick. And if those are enhanced with smart middle class people that can turn nasty.

            • (Score: 2) by takyon on Friday August 04, @04:45AM (1 child)

              by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @04:45AM (#548618) Journal

              Income inequality and unemployment will be what sparks riots, not mere genetic enhancements.

              IQ genetic enhancement is estimated to only have a modest impact of a few points (environmental factors also matter, which are already in favor of the rich) based on the "intelligence genes" that are currently known (or suspected). It won't create a middle class Sun Tzu tactical genius that leads the poor and downtrodden to victory (oh man, that's kind of like Code Geass hahah). I'm not sure if the poor would defeat the rich with sheer numbers or if the rich will stave off resistance with a combination of bread 'n' circuses, captive government, superior firepower, or creating distance between themselves and the riffraff (think of seasteads, the film Elysium, or just rich hoods and cities with police under their thumb and additional private security).

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              • (Score: 2) by kaszz on Friday August 04, @11:41AM

                by kaszz (4211) on Friday August 04, @11:41AM (#548689) Journal

                The point is that sufficient inequality will spark riots. And automation, AI and genetic enhancement may be what pushes the inequality enough to have never before seen riots. And people that go hungry or have no hope will have too little to loose.

        • (Score: 2) by takyon on Friday August 04, @04:17AM (1 child)

          by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @04:17AM (#548612) Journal

          Implement true genetic heritage policy? or make clinics strictly liable for genetic side effects?

          Heritage policy won't work. People will shop around and find a place to have their edited kids. China will be happy to take some of our rich people, and give them special privileges as well. Many countries will let clinics operate with impunity. Maybe you want to go overseas and come back to the U.S. with your edited kid. Who will prove that the kid is edited when the genomes of the parents are covered by genetic privacy laws. Not to mention that the rich people are likely to get their way in the first place, preventing any such inconvenient policies.

          You keep coming back to this point of side effects. Once the technology is worked out, which is the point of research like this, side effects will be rare or non-existent. Baby designers may not even end up using the household name CRISPR/Cas9 if other enzymes or nanobots prove to be more efficient. But if it's just today's technology, this study shows that you can have a seemingly high success rate (we almost always have an Anonymous Coward throwing shade at every biology study) and you can select a correctly edited embryo from the pile of 50+ you created. Kind of like IVF but with an extra step.

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          • (Score: 0) by Anonymous Coward on Friday August 04, @11:13AM

            by Anonymous Coward on Friday August 04, @11:13AM (#548680)

            I have had the exact same issue with every crispr study since the first paper I read on the topic. My story has never changed. But in this case their error is particulary egregious since it isn't some small percent of initial cells that come "pre-edited", but 50%. The quality of these studies is getting worse and worse as the hype gets louder and louder.

        • (Score: 2) by Bobs on Friday August 04, @03:35PM (1 child)

          by Bobs (1462) on Friday August 04, @03:35PM (#548764)

          As a 9-year old asked me - "what happens when the (genetically enhanced) want to compete in the Olympics?"

          Or compete for scholarships?

          And what happens when their kids or grand-kids who are 'partially enhanced' want to compete?

          This will be a big issue, and we will need to make rules to address it.

          • (Score: 2) by takyon on Saturday August 05, @03:51AM

            by takyon (881) <{takyon} {at} {soylentnews.org}> on Saturday August 05, @03:51AM (#548996) Journal

            I have written [soylentnews.org] on this [soylentnews.org] topic before [soylentnews.org].

            Athletics is already very lopsided and in some cases it is just a search for the best genes or the person who can get away with the best doping. Think of the individual sports where the winners and losers are separated by seconds or milliseconds.

            There is no scheme that would allow you to deny gene therapy, microchip implants, anti-aging, etc. to athletes without it creating an "unprotected class" of athletes that you allow to suffer more harm than normal folks. Denying these technologies to people will be the equivalent of using them as gladiators, since you'll be allowing them to sustain brain and whole body cellular damage. I mention microchips because those could have a dual use of greatly enhancing personal intelligence while allowing the user to optimize their movements unnaturally. Imagine a computer implant doing physics calculations and using data from your eyes in order to let you automatically move on any surface with the least amount of effort, or use parkour moves, etc.

            You could try to create a separate Olympics for these people. A Regular Olympics, the existing Paralympics for the disabled, and an Enhanced Olympics. Already you have the problem I mentioned of denying medical advances to the Regular Olympics athletes. We have seen controversial crossovers from one pile to another like Oscar Pistorius. He didn't win an olympic medal, but he did compete in the 2011 World Championships in Athletics against non-disabled people and won a medal then. You will have people with stealth advancements including "gene doping" competing in the Regular Olympics even if an Enhanced Olympics exists. We already have a blurring of the lines on gender divisions in these competitions with athletes accusing other athletes of being intersex with an unfair advantage. That will only get worse as technology allows even more control over hormone levels and muscle growth (to the point of hypertrophy).

            Within an Enhanced Olympics, or regular Olympics, or any sort of sporting events, you will face the issue of genetic inequality, as you mentioned. The rich will be able to create designer offspring who are not only optimized for athletic prowess, but grow up to be sexy enough to put on the box of Wheaties with no hesitation whatsoever from General Mills.

            I don't find this human germline editing unethical at all. But I do find it unethical to deny medicine or medical advances to athletes, harming their overall health and subjecting them to aging diseases in order to maintain the purity of competitive spirit or whatever bullshit the IOC and other orgs want to call it. This conflict could end sporting as we know it. And you know what? That might be a good thing. Once you break down all the doping, drug, and enhancement rules, and pull out a lot of the advertising money because people are jaded about superhuman freaks going to toe to toe with people who trained hard to compete, we could be left with something that better explores the competitive spirit and celebrates human achievement. Sure, it is easier to climb Mt. Everest than ever before, but people still do it and engage in supermarathons and other feats. Instead we currently have sob stories with slick editing from CBS/NBC/FOX, a very unequal playing field (can you afford personal trainers, the most optimized equipment, and supercomputer simulations of your body?), and a lot of people pretending that there is no doping (it just gets more sophisticated every time they are caught). Don't forget the NFL, which is pretty much proven to cause brain damage [soylentnews.org] the way the game is currently played since they hit each other more violently than they did decades ago and no amount of concussions is safe for the human brain. If regenerative medicine can cure that damage before it can destroy minds and lead people to suicide, it needs to be done, regardless of whether or not it leads to players competing in their 60s without retiring. Or if you can't accept that you need to go ahead and ban the sport.

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      • (Score: 0) by Anonymous Coward on Friday August 04, @07:56PM (1 child)

        by Anonymous Coward on Friday August 04, @07:56PM (#548847)

        It can also be used to make children "artificially" smarter, more attractive, or whatever. There are people who will pay 6-7 figures to produce one genetically enhanced kid.

        How about they pay me 6 figures to fuck the wife? The child is likely to be smarter, more attractive etc. ;)

        The child might grow up to be a smart-ass asshole like me but that's not a fatal genetic disease. Might even be advantageous in some scenarios...

        • (Score: 2) by takyon on Friday August 04, @09:19PM

          by takyon (881) <{takyon} {at} {soylentnews.org}> on Friday August 04, @09:19PM (#548866) Journal

          Unfortunately your paternal DNA will be targeted by DNA-scanning kill drones. They'll use XKeyscore to find out that you want privacy, and then collect your DNA from the trash and put you on the To-Do list for when martial law is implemented.

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