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Fixing Faulty Genes On the Cheap

Posted by Soulskill on 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.

22 of 105 comments (clear)

  1. Biofurs: the next generation of furry fandom by tepples · · Score: 2

    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.

    1. Re:Biofurs: the next generation of furry fandom by Kaenneth · · Score: 4, Funny

      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.

    2. Re:Biofurs: the next generation of furry fandom by PopeRatzo · · Score: 2

      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 money to "raise awareness" (whatever the hell that means) for their particular newly-classified disorder.

      Tell the truth, the entire in-bred confluence of people who desperately want to feel like there is a reason for their unhappiness that they can point to, and the non-profit outfits that profit from them, and the medical industry that apparently doesn't have enough really sick people to worry about that they want everybody to feel like they have some officially classified disorder seems a lot like a gigantic scan to me.

      Has the lot of people who believe they need to be better-looking at any cost really been made better by these classifications? I'm not sure.

      The only solution seems to be to stop thinking about one's self all the time and think about other peoples' welfare for a change. That does wonders for whole categories of dysphorias, I have found first-hand.

      --
      You are welcome on my lawn.
  2. How long before... by tchdab1 · · Score: 3, Interesting

    ... 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?"

    1. Re:How long before... by Wonko+the+Sane · · Score: 5, Interesting

      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.

    2. Re:How long before... by BenSchuarmer · · Score: 3, Interesting

      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.

    3. Re:How long before... by NEDHead · · Score: 3, Insightful

      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).

    4. Re:How long before... by Rigel47 · · Score: 2

      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?

    5. Re:How long before... by sideslash · · Score: 2, Informative

      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.

    6. Re:How long before... by WrongMonkey · · Score: 3, Funny

      You have the question backwards: what is the evolutionary advantage for intelligence? The smartest people certainly don't have the most kids.

    7. Re:How long before... by morgauxo · · Score: 3, Interesting

      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.

    8. Re:How long before... by radtea · · Score: 3, Interesting

      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.

      --
      Blasphemy is a human right. Blasphemophobia kills.
    9. Re:How long before... by ShanghaiBill · · Score: 3, Insightful

      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, tend to have high IQs, while the desert dwelling San Bushmen have the lowest measured. In both cases, they have adapted to the environmental conditions.

    10. Re:How long before... by dj245 · · Score: 2

      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, 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 survival.

      Evolution in the traditional sense also only affects characteristics which affect the ability to reproduce. For example, it is impossible for humans to evolve the problem of cataracts or alzheimer's out of our genetic code. By the time these problems show up, the children of those affected have already become self-sufficient. Evolution is about "reproduction of the fittest" not the more general "survival of the fittest".

      --
      Even those who arrange and design shrubberies are under considerable economic stress at this period in history.
  3. Even if it's American expensive by Anonymous Coward · · Score: 2, Informative

    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.

  4. Confused about how this works by timrod · · Score: 4, Informative

    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?

    1. Re:Confused about how this works by paskie · · Score: 4, Informative

      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!

      --
      It's not the fall that kills you. It's the sudden stop at the end. -Douglas Adams
    2. Re:Confused about how this works by rackdude · · Score: 2

      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 you wish to cut (people have worked out how to make RNA strands bind to the DNA in specific points). You then inject some of the Cas9 enzyme which binds to the "Cas section" (or in bio terms you tend to say the CRISPER promotes the enzyme) and holds it steady. This enzyme, when held near the DNA, will cause it to cut. So now you have a tool for cutting. Let's say you want to cut out a gene. You can just make two CRISPERs, one before the gene and one after. Inject the CRISPERs, inject the Cas9, and that gene is gone. But I forgot to mention the important part: you have to fix the break! You can then do genome editing by pairing this with something called Homology Directed Repair to put any sequence you want in there. There are two questions to address: why is this better than what we had before and how good is it? Before the main tools were restriction enzymes and TALENs. Restriction enzymes had a specific sequence they could cut (for example: BamHI cuts GGATCC). You can use this with some ligation (gluing back together) tools to attempt to do this stuff, but it's quite hard if you cannot specifically target an area. TALENs I haven't really used (I'm too new, my lab just started by telling me about CRISPERs) but from what I know people say they weren't reliable and were hard to make. However, CRISPERs are just an RNA sequence. There are online tools that help you design the CRISPERs as long as you know the DNA you want to target (which you hopefully do thanks to the magic of genome sequences). Making this RNA is a simple technique and once you get it, you basically have an infinite amount of the CRISPERs in case you mess up. You just take that, inject it with the Cas9 enzyme that you buy, and it works surprisingly well. Thus it has taken over in genome editing for many species. I know that in zebrafish it has become the tool to use, and from my reading it sounds like it's being used a lot in mouse, plants, and flies as well. It's just easy and reliable. Will this mean that you will use this to change your baby's eye color? I don't know, but from what I hear about its effectiveness in the zebrafish lab, although you get it working a good amount of the time, it's still not all of the time. People are okay if it doesn't correctly re-glue the DNA in 10% of your fish embryos, but would you be okay with it failing 10% on your baby? I'm not sure.

  5. Disagree with first sentiment by gurps_npc · · Score: 2
    "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.

    --
    excitingthingstodo.blogspot.com
    1. Re:Disagree with first sentiment by Alopex · · Score: 2

      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 years. My lab was trying to understand what the function of a motor protein was because we could see it, we could see processes it was involved in, but had no idea how or why it was behaving the way it did. There was no disease focus. Part of research is cataloging the natural world so that, maybe, we will one day use that knowledge for our benefit (not necessarily for disease).

      Disease is one of many applications of basic research. The amount that goes into producing chemicals through engineering bacteria and producing food through engineering plants is staggering. These applications are currently enabled by CRISPRs. I'll be interested to see how eugenics develops in the next few decades.

    2. Re:Disagree with first sentiment by radtea · · Score: 2

      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 we should.) Pure physicists are simply trying to find answers to questions; applied physicists are trying to find solutions to problems. The same is true in biology.

      --
      Blasphemy is a human right. Blasphemophobia kills.
  6. Re:Some crazy White Supremist, financed by by interkin3tic · · Score: 2

    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 planes. Watching them try to do advanced biotech would in fact be quite hilarious.