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Biotech Medicine Science

Fixing Faulty Genes On the Cheap 105

Posted by Soulskill
from the what-if-i-like-the-worn-out-look dept.
An anonymous reader sends an article about CRISPR, a system for modifying genes and moving them from cell to cell. It's notable because the cost to do so is dropping to the point where it's becoming viable to use on a patient-by-patient basis. CRISPR is one of those interesting inventions that comes, not from scientists explicitly trying to cure a disease, but from researchers trying to understand something fundamental about nature. Jennifer Doudna's research at the University of California, Berkeley has focused on how bacteria fight the flu. It turns out bacteria don't like getting flu any more than the rest of us do. Doudna says the way bacteria fight off a flu virus gave her and her colleagues an idea. Bacteria have special enzymes that can cut open the DNA of an invading virus and make a change in the DNA at the site of the cut — essentially killing the virus. Doudna and other scientists figured out how this defense system works in bacteria; that was interesting all by itself. But then they realized that they could modify these enzymes to recognize any DNA sequence, not just the DNA sequence of viruses that infect bacteria.
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Fixing Faulty Genes On the Cheap

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  • Cheap almost certainly means "cheap enough to be on par American medicine" not any sort of actual definition of the term.

    • But I'd bet there are fans of fictional anthropomorphic animals who would be willing to pay American-medicine prices for gene therapy to look more furry.
      • Look, if there's one thing American Medicine beats the entire rest of the world yet, it's exploiting peoples' body image dysphoria to charge lots of money for unnecessary operations.

        (I'm a little scared that I'll offend some transsexual people by using the word dysphoria, but that's life, I guess)

        • by Kaenneth (82978) on Friday June 27, 2014 @12:52PM (#47334559) Homepage Journal

          As a trans-offended person, I'm offended by your reluctance to allow people to be offended.

          Some of us enjoy being shocked, offended, and triggered so stop cis-comfort-zone oppressing us.

          • Obviously, I did allow it, because I thought that any offense actually taken wouldn't actually be the justified sort.

        • by gstoddart (321705)

          it's exploiting peoples' body image dysphoria to charge lots of money for unnecessary operations.

          (I'm a little scared that I'll offend some transsexual people by using the word dysphoria

          Random pedantry, but you've conflated two different things.

          There is Body Dysmorphic Disorder [wikipedia.org], where people are really really concerned about the appearance of their pieces and parts. This is the broader one which includes why people get 30 plastic surgeries.

          There is Gender Dysphoria [dsm5.org], in which the pieces and parts don't matc

          • by PopeRatzo (965947)

            I wonder to what extent having all these disorders officially classified in the DSM is just a way for the medical profession to charge insurance companies for absolutely everything that goes wrong with someone.

            What else is really gained by these classifications, except profit for the medical industry and a hell of a lot more people walking around feeling like victims of horrible diseases.

            Oh, I guess the victimization industry also does pretty well by creating non-profit organizations that raise all sorts of

            • "Raising awareness" means informing the public that a cluster of symptoms is a distinct medical condition for which a distinct treatment or prevention exists or is being researched. For example, brushing teeth with a toothpaste is a protocol to prevent tooth decay, as is vaccination to prevent infectious disease. If a prevention or treatment exists, it's an invitation to see a professional to get screened for a condition so that one doesn't have to just suck it up and live with what had been believed to be

              • by Optali (809880)
                "Exists or is being researched". An euphemism for "We don't have a fuycking clue but will continue massaging our stats until they look a bit better and until we are able to put some substance in the market that we can sell as wonder medicine"

                Until it's proven that thee medical wonder is nothing but snake oil, Just recall the antidepressants and the infamous ritalin.

          • I haven't conflated those things. I was afraid someone would think I conflated those things. But I getchya.

      • It would just become a political mess; Biofur would get mired in a war between the sweatshop garment workers' union and the hoover lobby.

      • by Immerman (2627577)

        It's not just the furries who'd be up for animal-like body modification, I'd *love* to have a prehensile tail. How many times have you wished for an extra hand? And we've got the genetic blueprints from numerous relatively close relatives to guide us on how to add them gracefully - we may even carry many/most of the necessary genes already. Sure, it's not as dextrous as prehensile feet, but it can be used while walking. And besides I already have two hands, a third grasping appendage with a different set

        • by RockDoctor (15477)

          I'd *love* to have a prehensile tail. How many times have you wished for an extra hand?

          Have the sensual / sexual implications and possibilities not begun to dawn on you?

          And besides I already have two hands, a third grasping appendage with a different set of strengths and weaknesses would add more options.

          OK, maybe they have.

          • by Immerman (2627577)

            Obviously - if you can name an external appendage without extensive erotic potential I'd accuse you of a lack of imagination. What's your point? Personally, if I were modifying my genes for erotic potential there are far more... interesting options available, if not quite so closely related. Dolphins for example - why settle for a prehensile *tail*? Biology is after all a many-splendored thing.

  • How long before... (Score:4, Interesting)

    by tchdab1 (164848) on Friday June 27, 2014 @12:31PM (#47334387) Homepage

    ... you can go to a local independent chop shop and tell them "my phone says I have an extra guanine in my 14 chromosome and it's causing my food allergy to modified mangoes - can you get it out this afternoon?"

    • by Wonko the Sane (25252) * on Friday June 27, 2014 @12:34PM (#47334415) Journal

      Did you know human livers are a single broken gene away from maufacturing vitamin C from glucose, just like almost every other mammal?

      The liver perform every step in the process except the final one, because of a single transacription error that was introduced into the germline back in ancient times

      It would be cool to see what happens when they fix that.

      • by BenSchuarmer (922752) on Friday June 27, 2014 @12:47PM (#47334523)
        It's more efficient to get Vitamin C from food. If it wasn't, that mutation would have been selected out of existence a long time ago.
        • by gstoddart (321705)

          If it wasn't, that mutation would have been selected out of existence a long time ago.

          OK, smartass, what is the evolutionary advantage for stupidity?

          Because you'd think we'd have selected that away a long time ago as well.

          Hell, we have an appendix. Why do we have an appendix? Why hasn't evolution made that go away?

          Evolution is awesome, but it can do some silly things that stick around.

          • by NEDHead (1651195) on Friday June 27, 2014 @01:02PM (#47334645)

            There is some evidence that the appendix acts as a reservoir of the gut biota to repopulate when the need arises due to illness (or excessive antibiotics, etc).

          • Re: (Score:3, Informative)

            by sideslash (1865434)

            OK, smartass, what is the evolutionary advantage for stupidity?

            I suggest you ask evolutionary biologists. Specifically, go ask that group of evolutionary biologists standing over there lamenting their inability to connect with females, who somehow prefer muscularly ripped albeit less cranially endowed surfer dudes.

            Am I kidding? I'm not sure.

            • by radtea (464814)

              I suggest you ask evolutionary biologists.

              And evolutionary biologists will ask, "What is the evolutionary advantage of intelligence?"

              What we think of as "intelligence"--the specifically human abilities to build complex machines and to use anything to represent anything else and to create unbounded chains of logical inference--is almost certainly an epiphenomenon of having a brain big enough to engage in the kind of complex social and cultural behaviour that developed due to sexual selection in our evolutionary history.

              The human brain is like the pe

              • by Immerman (2627577)

                > probably because we could be more entertaining and interesting to women with big brains

                Hell, if you actually focus on it big brains can help you attract pretty much anyone that doesn't actively prefer stupidity - and that's pretty rare. Give up math, science, comics, etc, etc, etc and instead focus all that brainpower on actually observing and analyzing the behavior of people around you, and experimentally modifying your own behavior to test your hypotheses on social interaction in a rigorous manner -

          • Re: (Score:2, Informative)

            by tepples (727027)

            OK, smartass, what is the evolutionary advantage for stupidity?

            A complex brain uses energy that could be used elsewhere to propagate the species. Humans are extreme K-strategists [wikipedia.org], which make few babies but put more effort into raising them. So-called "lower" animals may be r-strategists, which make lots of babies in hopes that some survive.

          • by WrongMonkey (1027334) on Friday June 27, 2014 @01:45PM (#47335029)
            You have the question backwards: what is the evolutionary advantage for intelligence? The smartest people certainly don't have the most kids.
          • by morgauxo (974071) on Friday June 27, 2014 @01:55PM (#47335123)

            In developed countries stupid people tend to have more children.
            Running a brain takes a lot of calories. In places where people have to worry about starvation I wonder if IQ might even be a liability.
            We are really lucky that humanity ever even achieved inteligence. It will be extremely lucky if we actually manage to keep it.

            • by radtea (464814)

              In places where people have to worry about starvation I wonder if IQ might even be a liability.

              Brain size and IQ are not particularly correlated, and I've seen at least some research suggesting that people with high IQs or more education are actually more efficient at using their brains, to the extent that there is some thinning of the grey matter in such individuals in their late teens or early 20's.

              Thinking does take more energy than not, but this isn't a big effect compared to brain size: http://www.scientificamerican.... [scientificamerican.com]

          • by ShanghaiBill (739463) on Friday June 27, 2014 @02:18PM (#47335327)

            OK, smartass, what is the evolutionary advantage for stupidity?

            Smart people innovate. Dumb people follow routines because "we have always done it that way." So in a desert dwelling hunter-gather tribe enduring a drought, the smart guy innovates by digging for water and building a still. It comes up dry, and he dies of thirst. The dumb people follow the trail through the desert that their grandmother showed them decades ago, and find a waterhole.

            In an urbanized society, innovation has limited risk, and generous rewards. In a primitive society, innovation has big risks and limited reward. So people that have a long history of urbanization, such as the Chinese and Ashkenazi Jews [slashdot.org], tend to have high IQs, while the desert dwelling San Bushmen [slashdot.org] have the lowest measured. In both cases, they have adapted to the environmental conditions.

          • by dj245 (732906)

            If it wasn't, that mutation would have been selected out of existence a long time ago.

            OK, smartass, what is the evolutionary advantage for stupidity?

            Because you'd think we'd have selected that away a long time ago as well.

            Hell, we have an appendix. Why do we have an appendix? Why hasn't evolution made that go away?

            Evolution is awesome, but it can do some silly things that stick around.

            Most people think of evolution as "survival of the fittest", but this is a gross simplification. In a population bottleneck [wikipedia.org], genetic diversity can shrink rapidly if a large portion of the population dies out. Imagine what would happen if everyone in the world died except a small and distinct group- lets say the Vietnamese people just for example. If the population recovered and repopulated the world, humans would have lost a tremendous amount of genetic diversity which may or may not be beneficial to sur

            • by Immerman (2627577)

              Alternately, survival of the fittest is about *genes*, not individuals - and given mortal organisms, their reproduction usually correlates very closely to the survival of their genes.

              Interestingly, in many hive organisms this correlation fails in favor of the super-organism. Among honeybees for example the workers (female) are fertile, but share far more genes with their siblings than they would with their own children, and so survival of the fittest (genes) leads them to promote the health and reproductio

        • by Rigel47 (2991727)
          The error in your statement is that you believe evolution only accumulates the good and never the bad. Why is there a whole raft of genetic diseases in the human population now? Shouldn't they have been "selected out" a long time ago?
          • by radtea (464814) on Friday June 27, 2014 @02:05PM (#47335207)

            Why is there a whole raft of genetic diseases in the human population now? Shouldn't they have been "selected out" a long time ago?

            Many genetic diseases are the result of optimizations for other things (anemia is related to malaria resistance, there is some problematic gene in a Jewish sub-population that is related to plague resistance, etc.)

            Evolution is continuously running an extremely complex multi-dimensional optimization problem with a time-varying objective function. Local minima abound, and it's easy for organisms to get trapped in them.

            Furthermore, kin selection and possibly group selection play a role in human evolution, which makes the whole thing even more complex and non-linear. So looking at specific genes and saying, "That doesn't make sense!" as if there was some obligation for the universe to "make sense" to our naive pre-scientific intuition is fairly silly.

            The human genome is a Rube Goldberg apparatus that manages to make hundreds of thousands of products out of 40,000 strongly interacting templates plus a bunch of ridiculously inefficient secondary control mechanisms like micro-RNAs (which in some typically degrade already-transcribed mRNA). Pointing to one step as if it can be considered in isolation from everything else is not a good move.

            Loss of vitamin C manufacture could well have to do with the development of some other pathway that was more important at the time, and may well continue to be more important today. The only way to really find out is to either a) understand the genetic trade-offs in detail or b) ask some volunteer to have their vitamin C production turned back on by a technique like this. Personally, I'd recommend the former.

            Given how weird humans are developmentally, some things like this may be important when we're young and not so much when we're older, so in the fullness of time we may find we can turn on vitamin C production only after people mature, for example. The possible range of futures, given how little we know now, is large.

            In the meantime, we have plenty of people with genetic diseases that we know the cure will not significantly disrupt their cellular machinery, because we have lots of examples of people without those diseases who are just fine.

            • by Rigel47 (2991727)
              You have a good command of biology. My fundamental objection is with this statement:

              Loss of vitamin C manufacture could well have to do with the development of some other pathway that was more important at the time, and may well continue to be more important today.

              What if there was a co-occurring mutation that was, at that time, more advantageous than the loss of vitamin C production? What if the loss of vitamin C production happened to a population living in an area with abundant ascorbic acid in their food? Maybe they killed off their less-lucky neighbours? The notion that something is because it's got to be optimal is false. There's a lot of flexibility to life even within a

        • I always figured we lost that gene because our ancestors lived in trees and largely fed on fruit making the gene useless, in that context anyway.
        • Unless there was no reason to select against it, like if foods containing vitamin C had been available to an extent that there was rarely a shortage of it when there was an excess of glucose.
        • by Anonymous Coward

          It's more efficient to get Vitamin C from food. If it wasn't, that mutation would have been selected out of existence a long time ago.

          That argument doesn't even apply because the liver goes through all but the last step. It might apply if all the prerequisite steps didn't happen, but really cutting out that last step just means more junk floating around that cost energy to make with no useful result whatsoever (completely disregarding the fact that in most climates it isn't more efficient to get vitamin c from food).

        • It's more efficient to get Vitamin C from food. If it wasn't, that mutation would have been selected out of existence a long time ago.

          Not necessarily. It probably WAS more efficient, when our primate ancestors lived in the rainforest, and munched on fruit all day. Most primates can't synthesize vitamin c either. But once the ability to synthesize vitamin C was lost, it was no longer part of our gene pool. So when we left the tropics, and switched to a diet based more on grain and meat, it was too late to adapt.

      • by spacemky (236551) *

        ...people start crapping out citrus fruits?

        • by gstoddart (321705)

          ...people start crapping out citrus fruits?

          As always, I will invoke rule #34.

          I'm sure it's been done. ;-)

      • It's amazing how much functionality the liver has. At times, it feels more accurate to claim that a human is a parasite attached to a liver.
        • by Immerman (2627577)

          Symbiote, please. Have you ever seen a liver try to acquire and ingest food? Not a pretty picture.

      • by morgauxo (974071)

        Well, maybe in some third-world places people get healthier. That is, if they ever even get access to this modification. Everybody else just pees more. Given that so many are already drinking pop, coffee and beer when their bodies need water we might actually see health go down in the first world due to dehydration.

    • It is hard to predict the progress of technology, so - NO: I won't tell you "how long before...." But I'll try to explain why CRISPR is special enough to be exciting in my experience and what technological/engineering hurdles need to be overcome in order to reach your objective.
      At the moment, variations of the CRISPR-CAS system can only edit the genome of individual cells in vitro with varying efficiency. This is assuming you can culture the cells to begin with. For example, I work with human embryon
  • a crazy Arab, will try to weaponize it.

    Hilarity will not ensue...

    • No. That's nonsense. Crispr needs to get into a cell in order to do anything. These things aren't self-replicating either.

      Say a terrorist has a crispr combo that mutates several of your anti-cancer genes. He's got nothing: he'd need to get that into at least one of your cells in order to have any chance of giving you cancer. If he has a means to introduce it into one of your cells... he doesn't need crispr. He could just use a poison or some normal carcinogen.

      Terrorists kill with pipe bombs and
      • by Nutria (679911)

        Crispr needs to get into a cell in order to do anything. These things aren't self-replicating either.

        If we've got to do this one cell at a time, then what's the point, even if it's "only" several hours per cell? Working 24x365, it would take 342 years to rewire a measly 1 million cells.

        No, the medical goal has to be to get this working automatically at the nano-scale.

        • Again, nonsense. One can do quite a bit with a single stem cell or embryo. Furthermore, you can work in parallel: you don't need to do one cell at a time. You can do a bunch of cells in a dish, make a new organ, then implant it.

          And, again, any method of introducing crispr to a large amount of cells in the body would still be harder than just injecting someone with poison. There's no need to make it self-replicating like a virus.
          • by Nutria (679911)

            There's no need to make it self-replicating like a virus.

            Sure there is: to kill $your_hated_minority automatically and discriminately. Which was the point of my original post.

            (Not that it would work. Too many whites, African-Americans and Jews share too much DNA.)

  • by Anonymous Coward

    It could be worth it. This could be huge. Besides sickle cell, there's cystic fibrosis and a bunch of others. Not to mention high vulnerability to cancer caused by faulty genes. Angelina Jolie could still have her breasts. I could stop taking medication for gout.

  • This technology has been advertised everywhere in my institute... and now its on Slashdot... I wonder if there is someone behind their marketing campaign?
  • by Joe Gillian (3683399) on Friday June 27, 2014 @12:54PM (#47334569)

    From the Wikipedia article, it seems like CRISPR works by injecting a strand of "neutral" genetic material into a genome and cause genes to not be transcribed - so you can "turn off" an improperly expressed gene, but can't actually replace it with a normal one. The NPR article, however, has people mentioning the idea of replacing improperly expressed genes with normal ones.

    From what I understand, the difference between the two is that if Wikipedia is correct, CRISPR would only be useful in humans (once they get it to be accurate) to cure diseases that arise from a gene being expressed when it shouldn't be, for things like sickle cell or Huntington's. However, if NPR is correct, CRISPR can also cure diseases that arise from a gene not being expressed when it should, such as hemophilia.

    Which one of these is correct? What is CRISPR actually good for?

    • by paskie (539112) <pasky@ucw.PLANCKcz minus physicist> on Friday June 27, 2014 @01:24PM (#47334813) Homepage

      CRISPR is a tool that allows you to cut the DNA in two disjoint pieces at a specific point (specification of this point is a parameter of a particular CRISPR instance). What happens then depends on your setup; bacteria will just insert some junk at that break point, or you can pack your custom DNA sequences along the CRISPRs and they will be spliced in, connecting to each of the two disjoint pieces by one end. Thanks to this, at that specific point, you can disable a gene or modify or add an extra sequence.

      We had tools to do this before - restriction enzymes or TALENs. They weren't really usable for therapeutic purposes, though, due to much less reliable targetting, more laborous engineering (parametrizing your instance for a specific sequence) and low effectivity (the break happens only in a a few percents of cases). CRISPRs are easily parametrized, can be precisely taretted, and have effectivity in tens of percents (in general; can vary organism by organism). It's still a work in progress, but looks pretty promising!

      • To add onto that (since I was reading up on this), the cell itself splices in the new DNA sequence very rapidly and efficiently, since it's a mechanism the cell uses to avoid cancer.

        In the double helix, when one strand of the DNA is broken, the string of DNA is held together by the other strand, it's an easy fix. Both strands broken at the same place means the DNA has come completely apart, has sustained some serious damage. The cell detects that pretty rapidly. The cleaner way is to find the sequence
    • CRISPER works via the connection between the CRISPER and the enzyme Cas9 (that's why it's actually called CRISPER-Cas). I will simply talk about the synthetic bio version, not the naturally occurring. So let's say you want to do a targeted genome edit at a specific point in the genome. To do this, you need to make your CRISPER RNA as follows: you have the "Cas section" (crRNA) and "localization" section (tracrRNA). The way it works is that you design the localization section to be complimentary to the DNA y
  • by gurps_npc (621217) on Friday June 27, 2014 @01:12PM (#47334723) Homepage
    "CRISPR is one of those interesting inventions that comes, not from scientists explicitly trying to cure a disease, but from researchers trying to understand something fundamental about nature."

    There is no such thing as a researcher trying to understand something fundamental about biology that is not trying to cure disease.

    As for not trying to cure a specific disease, no real innovations come from trying to cure a specific disease. All the really cool stuff comes from doctors trying to figure out how something works, in the hope that some day their knowledge will cure a disease.

    • by Alopex (1973486)

      This is patently false. There is a whole swath of biological research under the banner of "basic science" which, while it may purport to address a far-off disease application (for the sake of grant $$$), is only aimed at understanding how life functions at the most fundamental levels. Thousands upon thousands of researchers in this country are funded by the NSF and NIH (among others) precisely to figure out things we know that we don't understand.

      For an anecdote, I did this kind of research for a few year

      • by radtea (464814)

        There is a whole swath of biological research under the banner of "basic science"...

        Absolutely. I've worked both with pure biologists and physicians (and biologists in a medical context) and they have dramatically different outlooks and mindsets. Many, many biologists are deeply interested in understanding what is going on, while physicians and medical-focused biologists are much more interested in finding stuff that works to solve this problem.

        The divide is very similar to that between pure and applied physicists, although for some reason we don't talk about "applied biologists" (perhaps

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