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Medicine Science

A Serious New Hurdle For CRISPR: Edited Cells Might Cause Cancer, Find Two Studies (statnews.com) 108

Editing cell genomes with CRISPR-Cas9 might increase the risk of developing cancer, two studies published Monday warn. From a report: Editing cells' genomes with CRISPR-Cas9 might increase the risk that the altered cells, intended to treat disease, will trigger cancer, two studies published on Monday warn -- a potential game-changer for the companies developing CRISPR-based therapies. In the studies, published in Nature Medicine, scientists found that cells whose genomes are successfully edited by CRISPR-Cas9 have the potential to seed tumors inside a patient. That could make some CRISPR'd cells ticking time bombs, according to researchers from Sweden's Karolinska Institute and, separately, Novartis. CRISPR has already dodged two potentially fatal bullets -- a 2017 claim that it causes sky-high numbers of off-target effects was retracted in March, and a report of human immunity to Cas9 was largely shrugged off as solvable. But experts are taking the cancer-risk finding seriously.

A Serious New Hurdle For CRISPR: Edited Cells Might Cause Cancer, Find Two Studies

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  • Impossible (Score:4, Funny)

    by 93 Escort Wagon ( 326346 ) on Monday June 11, 2018 @04:57PM (#56767844)

    We possess utterly complete, perfect knowledge regarding all possible aspects of DNA. Otherwise we wouldn't be doing this, right?

    • Re:Impossible (Score:4, Insightful)

      by alvinrod ( 889928 ) on Monday June 11, 2018 @05:15PM (#56767980)
      Nah. Most of human progress has been less perfect knowledge and careful action and more "hold my beer and check this shit out!"

      Anyone who's delivered software should intuitively realize this to be true.
    • by Anonymous Coward

      Which of course no one in the scientific world ever claimed. You should also note that CRISPR is still in the experimental stage.

    • Yes ha ha. But still Why would it do this? I can actually think of some ways but I wouldn't neccessarily expect cancer.

      • Pretty much everyone else would. Complex eukaryotic organisms spend enormous amounts of time and energy controlling cell replication and forcing cells to die off. An full grown organism is mostly in cellular stasis. A growing organism has cell growth tightly controlled.

        When you mess with that, you are very likely to end up with uncontrolled cell growth, i.e., cancer.

      • by mikael ( 484 )

        How do genes index or reference each other? We know that genes encode for proteins and enzymes plus epigenetic information that can cross generations. There have been cases where a slight rearrangement of one gene caused the entire chromosome to explode simply because the repair systems lost all sense of the organisation of genes. With DNA, the same gene can encode for six different possible enzymes due to the triplet arrangement of codons and the option of going forwards or backwards.

  • by Seven Spirals ( 4924941 ) on Monday June 11, 2018 @04:57PM (#56767850)
    Otherwise, we are going to have designer babies, cosmetic gene editing, and super-brain edits before anyone lifts a finger to cure cancer or fix Parkinson's etc.. Oh and not to mention designer viruses. Combo AIDS + Smallbox + Ebola that only kills black/white/asian people anyone?
    • Re: (Score:3, Insightful)

      by Nos. ( 179609 )

      Maybe not as a designer baby maker, but CRISPR is a lot more than that, being a potential cure for a huge number of genetic diseases that are devastating to those that have them.

    • Yes, let's hope for cancer! Hooray! /sarcasm

      I really don't know much about CRISPR, but I know at least one couple that was hoping for it to control the sex of their child. That couple already has a child with (pretty serious) autism and according to the dad at least, he was hoping that having a baby girl would cut the chances of having a second autistic child by a huge margin. Unfortuately, this new study doesn't sound like good news for them.

      • by dgatwood ( 11270 )

        I really don't know much about CRISPR, but I know at least one couple that was hoping for it to control the sex of their child. That couple already has a child with (pretty serious) autism and according to the dad at least, he was hoping that having a baby girl would cut the chances of having a second autistic child by a huge margin. Unfortuately, this new study doesn't sound like good news for them.

        Well, then, I have good news. You can already do that with in vitro fertilization, which is commercially ava

    • by hey! ( 33014 )

      I'm not sure that gene editing immediately leads to "designer" babies, except in the most superficial way. Sure, you can change things like hair, eye, or skin color, but most parents are going to be interested in those things; they'll be more interested in editing out genetic diseases like Huntington's. It's possible that families undergoing IVF with one or more donated gametes may wish to have the child resemble the non-contributor parents.

      The really controversial eugenic manipulations are ones that invo

      • I'm not sure that gene editing immediately leads to "designer" babies, except in the most superficial way. Sure, you can change things like hair, eye, or skin color, but most parents are going to be interested in those things; they'll be more interested in editing out genetic diseases like Huntington's.

        I'm not sure that plastic surgery immediately leads to "designed" bodies, except in the most superficial way. Sure, you can change things like breast size or tummy flatness, but most patients aren't going to be interested in those things; they'll be more interested in fixing burn damage or developmental defects.

        • by hey! ( 33014 )

          So, you think plastic surgery is morally wrong?

          • So, you think plastic surgery is morally wrong?

            I don't think designer babies are morally wrong, unless they are designed by the government (or similar) and they tell you what you're having. I was poking holes in the argument. Of course people want designer babies.

            • by hey! ( 33014 )

              My "argument" was to take the emotional weight of the term "designer babies" off the table and look at how it was likely to be used. Yes, the result could be called a "designer baby", but so could surgery to correct a cleft palate.

              • I would say it all boils down to how it's used. If a rich, elite couple specifically wants a daughter, with green eyes, red hair, but say, not too many freckles, that's a designer baby and I think the elite would jump all over that.
                However I would expect that the public would view using CRISPR to prevent a child from having an abnormal condition like cleft palette or club foot as basically just medicine, in the same way that plastic surgery, when used for a medically unnecessary nose job is viewed as desig

                • by hey! ( 33014 )

                  I would think the most likely reason someone would use to alter a child's appearance would be in the case of IVF with donated eggs or sperm. But even so, even if we had the technology to edit zygote genomes, you wouldn't be able to specify an appearance to the degree of specificity you're imagining.

                  When the human genome was sequenced it turned out to be far, far smaller than anyone had expected. This is because genes and traits don't have a one-to-one correspondence; traits are the result of the intera

    • I mean, I would really love if they could fix my congenital anosmia. Not being able to smell like everyone else sucks..

      They'll never allow it if there is a good chance of cancer though. Smell isn't that important..

    • by Dog-Cow ( 21281 )

      You are so fucking stupid, it's almost amazing that you're even alive. People have been working on cancer and Parkinson's for decades. They aren't going to stop now, when something like CRISPr makes their efforts more likely to be productive.

  • If CRISPR does cause cancer, researchers might be able to use that to find causes and treatments.
    • If CRISPR does cause cancer, researchers might be able to use that to find causes and treatments.

      We know how to cause cancer. There are lots of chemicals, not to mention radiation that are known carcinogens. More importantly, we know what cancer is. Cancer is a cell that went haywire. Probably the most promising treatment for cancer involves fingerprinting the particular haywire cell you have and training your immune system to attack it directly.

    • Re:A silver lining? (Score:5, Informative)

      by im_thatoneguy ( 819432 ) on Monday June 11, 2018 @05:30PM (#56768116)

      The article addresses this. P53 is like the ECC of the DNA. It detects errors and then either self destructs the cell or fixes the 'damage'. The concern is that CRISPR weakens the p53 response and therefore the natural Error Correction processes of the cells which normally terminate tumorous dna damage.

      However, the cancer treatments using CRISPR (and several other CRISPR therapies) don't rely on p53

      CRISPR-based editing of T cells to treat cancer, as scientists at the University of Pennsylvania are studying in a clinical trial, should also not have a p53 problem. Nor should any therapy developed with CRISPR base editing, which does not make the double-stranded breaks that trigger p53.

      • What's most important about these studies is what they show us about the role of P53. Is it an underlying component of the immune system? If so, can we do a CRISPR edit and then set a new "checksum" for the P53 to guard as the valid version of this cell?

        • P53 [wikipedia.org] is well-studied [nature.com] - if not completely understood - and the "checksum" comparison is a very loose metaphor. You might also usefully compare it to a 9-1-1 dispatcher: It receives reports of things gone wrong from many different sources, and passes the message along to many different emergency responders.
  • Shocked (Score:5, Funny)

    by reanjr ( 588767 ) on Monday June 11, 2018 @04:59PM (#56767872) Homepage

    I for one am shocked that gene editing can lead to a disease caused by altered genes.

    • Re: (Score:3, Informative)

      There are apparently two methods by which CRISPR alters the genes. One is by slicing the bad parts of the gene (this is the approach I believe is being used for the First-in-human Phase 1 trials about to begin in US), and the other is by replacing the bad parts of the gene by healthy parts. The latter method is what apparently increases the risk of tumors.
  • I thought one of the things they were looking at was using it as a solution to cancer cells. Would it be approved to use if it could cure an 'incurable' form of cancer, only to risk causing another cancer? Could it be used to cure the cancer that itself caused?
    • Could it be used to cure the cancer that itself caused?

      Infinite recursion detected.

      Though if you tell that to the pharmaceutical companies, they'll fund the fuck out of it.

  • by Wycliffe ( 116160 ) on Monday June 11, 2018 @05:19PM (#56768008) Homepage

    Cancer is basically cells that went rogue. You telling me that slicing and dicing DNA (sometimes accidentally in non-target locations) can sometimes cause a cell to not do what it was suppose to? CRISPR is more targetted than say getting hit with a blast of radiation which causes random mutations but you are still changing the programming of a highly complex instruction set written in obfuscated code that we barely understand.

    • by Anonymous Coward

      Cancer is basically cells that went rogue. You telling me that slicing and dicing DNA (sometimes accidentally in non-target locations) can sometimes cause a cell to not do what it was suppose to? CRISPR is more targetted than say getting hit with a blast of radiation which causes random mutations but you are still changing the programming of a highly complex instruction set written in obfuscated code that we barely understand.

      What's more, DNA in body cells gets reordered all the time. Most changes have no effect. Some cause the cell to die. Rarely it causes cancer. The point being, the code isn't the same in every cell, so some cells might be more vulnerable than others. There are a lot of cells. Yes, it is a very complex problem.

    • by kackle ( 910159 )
      Brainfuck?
  • Why would it be a surprise that 3.2 billion years of evolution has produced a system you can't just twiddle with? How can you understand a system which has iterated so long and so profoundly?

  • by fahrbot-bot ( 874524 ) on Monday June 11, 2018 @05:27PM (#56768094)

    Scientists found that cells whose genomes are successfully edited by CRISPR-Cas9 have the potential to seed tumors inside a patient.

    Regular cells, that haven't been edited by CRISPR, have the potential to seed tumors inside a patient -- that's how people usually get cancer.

  • by Anonymous Coward

    This is an obvious and expected issue. Only the particulars are new science. Seems to be solid work, and gives us something else to "tune" in order to make gene editing a reality.

  • It would seem that those in the fledgling field of genetic engineering are making the same mistakes that those in the then fledgling AI field made in the 60s, to wit: 1. Problems that seemed to be difficult are spectacularly solved. 2. Extravagant forecasts are made on the basis of those successes. 3. The next batch of problems are tackled, and they prove to be much more difficult than the previous batch. 4. The discipline becomes a scientific laughing stock. AI has yet to leave stage 4 completely behind.
  • by Rick Schumann ( 4662797 ) on Monday June 11, 2018 @06:08PM (#56768372) Journal
    Wow, you mean mucking about in our DNA with an editor when we don't really know how everything works might give us a fatal disease? Shocking, I tell you, shocking!
  • by Anonymous Coward

    For literally years, I have been keeping untold trillions or quadrillions of cells that I subsequently integrated into my own body, mostly from leafy green plants called lettuces, in a CRISPER! I could get CANCER from that?!? Shit... I thought the biggest danger was E. Coli...

    • For literally years, I have been keeping untold trillions or quadrillions of cells that I subsequently integrated into my own body, mostly from leafy green plants called lettuces, in a CRISPER! I could get CANCER from that?!? Shit... I thought the biggest danger was E. Coli...

      I'm still hanging onto hope your post was made with sarcasm but I can't tell because I know people that would say something like this. Regardless, there is so much wrong in this statement I'm having trouble figuring out where to begin. I'll give it a shot.

      1. You don't "integrate" entire cells into your body like you're describing
      2. There is no DNA transfer when you eat food to your body, at best (even though unlikely) it might DNA transfer might occur with the bacteria in your gut
      3. This article is all about CR
  • I really like your post because it will be useful for readers so thanks for writing such useful information. Large Garbage Bags Online India [arawindapolybag.com]
  • Sounds like this editor is incompatible with DNA.

    Probably the old End Of Line issue, so...

    1. Edit with CRISPR-Cas9
    2. dos2unix
    3. Profit

  • So in very related news, that might render this problem void:
    CRISPR-Cas9 Improved 10,000-Fold by Synthetic Nucleotides
    "Scientists at the University of Alberta in Canada have developed a technology that can dramatically improve the specificity of CRISPR-Cas9 gene editing. The approach uses synthetic guide molecules known as bridged nucleic acids (BNAs) in place of the system’s native guide RNAs (gRNAs) to direct the Cas9 enzyme to its target DNA sequence, and so reduce off-target DNA cleavage."
    https://www.genengnews.com/gen... [genengnews.com]

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