[HN Gopher] FDA approves first test of CRISPR for genetic defect...
       ___________________________________________________________________
        
       FDA approves first test of CRISPR for genetic defect causing sickle
       cell disease
        
       Author : zuhayeer
       Score  : 423 points
       Date   : 2021-04-07 23:34 UTC (23 hours ago)
        
 (HTM) web link (news.berkeley.edu)
 (TXT) w3m dump (news.berkeley.edu)
        
       | vagrantJin wrote:
       | Yeah. My one and only concern is how tight regulation around
       | genetic augmentation/editing will be. When will medical use cross
       | over into cosmetic use and how do we regulate that?
        
         | f6v wrote:
         | You can already do a plastic surgery. So how is genetic editing
         | to make yourself hotter different?
        
         | faeyanpiraat wrote:
         | Well you wont be able to prevent rich people from getting their
         | regular life extension treatments.
        
       | pmlnr wrote:
       | I honestly thought my generation will not yet live through
       | Gattaca; seems like I was wrong.
        
         | corpMaverick wrote:
         | Rich people already have easy means for genetic improvements.
         | They just marry people that are more attractive, tall and
         | intelligent.
        
         | koonsolo wrote:
         | Helping people with severe diseases is still far away from
         | creating the perfect humans.
         | 
         | You turning this positive into a negative is distasteful.
        
           | saiya-jin wrote:
           | Road to hell is paved with good intentions. In this case,
           | creating super-humans that lack any weakness, sickness and
           | are just ideal of what can human being be without those is
           | putting them already way above everybody else.
           | 
           | One doesn't need an x-ray vision or flying around to be to
           | have superhuman status.
           | 
           | I understand your optimism because it sounds properly
           | awesome. But we humans always, without exceptions, fuck up
           | everything that is even theoretically fuckable and often even
           | the rest. If you don't see potential for evil with this then
           | I guess you lack a bit of imagination.
           | 
           | For every great discovery to help humanity there is always
           | some powerful idiot thinking how it can we weaponized, used
           | to gain advantage above others, the non-conforming, the
           | unknown, or simply the weak.
        
             | f6v wrote:
             | > we humans always, without exceptions, fuck up everything
             | that is even theoretically fuckable
             | 
             | Don't mean to intrude, but it reads rather negative. Maybe
             | you should seek help?
        
           | pmlnr wrote:
           | > Helping people with severe diseases is still far away from
           | creating the perfect humans.
           | 
           | Not as far as it looks. Honestly, it looks closer, than real
           | self driving cars.
           | 
           | > You turning this positive into a negative is distasteful.
           | 
           | I'm incredibly happy that we, as humanity, are advancing with
           | science - the mRNA vaccines are also incredible. The part
           | that is not incredible is that we, as society, are in most
           | cases still behave like we did in the stone age: greedy,
           | selfish, narcissistic. Because of this tech that should be
           | used to help those in need is most commonly used to "help"
           | those with enough funds or means.
           | 
           | Cheering for science advancements that are far out of reach
           | for the majority leaves a bitter taste.
           | 
           | EDIT BTW, Gattaca is a temporary time. Once it's passed - one
           | whole generation, so say ~80 years - that world would be
           | wonderful, but that limbo time, when the movie plays out, is
           | the nasty part.
        
             | maxerickson wrote:
             | Gattaca isn't just about the oppression of the natural
             | born.
             | 
             | You cheer for a world full of Anton's, calculating that it
             | isn't possible to make it to the other side, deciding not
             | to try.
        
             | boxed wrote:
             | > Cheering for science advancements that are far out of
             | reach for the majority leaves a bitter taste.
             | 
             | Yes. Damn that new fancy tech of farming that only the rich
             | can afford!
             | 
             | Seriously. Think about what you're saying for a second.
             | Tech that is only for the rich becomes affordable for the
             | masses faster and faster every year. Computers were for
             | _nation states_ in my parents life time. Today there are
             | computers more powerful than the first computers in cheap
             | _toys_.
             | 
             | We cheer for tech that only the rich can use _now_ because
             | it will be for the masses _soon_. Tech that never exists
             | for the rich, will not exist for anyone ever.
             | 
             | Check your logic.
        
               | delfinom wrote:
               | >We cheer for tech that only the rich can use now because
               | it will be for the masses soon. Tech that never exists
               | for the rich, will not exist for anyone ever.
               | 
               | Realistically however, this kind of area falls squarely
               | in the healthcare field which is increasingly becoming a
               | thing for the rich and indentured servitude for the rest.
        
               | alistairSH wrote:
               | In the US. Other high-income nations have mostly solved
               | the problem of affordable access to health care.
        
         | pitspotter wrote:
         | Curing genetic diseases is going to turn unlucky people into
         | more normal people, not privileged people into superhumans.
        
           | gomox wrote:
           | Given the history of humanity, I find this take to be
           | anywhere between optimistic and naive.
        
             | meowface wrote:
             | The parent said "curing genetic diseases", not "CRISPR".
        
           | gnulinux wrote:
           | Are you seriously arguing in 50 years super rich people won't
           | use this for e.g. cosmetic reasons?
        
       | The_rationalist wrote:
       | If CRISPR can be bruteforced to change a significant number of
       | cells for a whole organ/body then what is stopping us from
       | rejuvenation? (store your DNA in while not too old in a safe
       | place fill this DNA in tons of virus vectors/CRIPRs and hop you
       | can be rejuvenated!)
        
         | Vecr wrote:
         | Probably not, killing off your bone marrow cells and replacing
         | them is already pretty dangerous, and other organs would be way
         | worse, because they have actual structure. Doing it with your
         | brain would be impossible, for obvious reasons.
        
       | dagurp wrote:
       | I really hope this will be successful.
       | 
       | Does anyone have an idea how much a treatment like this would
       | cost?
        
         | f6v wrote:
         | A wild guess: million+. It's supposed to be a once in a life
         | time treatment, so pharma can't milk you for life. It's not
         | that pharma is inherently bad, but rather that it costs
         | billions to get this through all the stages of clinical trials.
        
       | yarcob wrote:
       | TLDR:
       | 
       | 1) Extract bone marrow from patient
       | 
       | 2) Use CRISPR to fix broken gene in the extracted bone marrow
       | 
       | 3) Use chemo to destroy old bone marrow in patient
       | 
       | 4) Transplant fixed bone marrow from step 2 back into the patient
        
         | yarcob wrote:
         | The technique sounds promising, since it avoids the typical
         | problem of gene therapy, which is how to get CRISPR past the
         | immune system into every cell in the body. With this technique
         | you can do the CRISPR procedure in vitro.
         | 
         | A big downside to this treatment is that as far as I know this
         | kind of chemo can make male patients infertile.
        
       | codeproject wrote:
       | Two years ago, Chinese Scientist Dr.He JianKui did a very similar
       | thing. He edited the genome of twin girls so that they will be
       | immune to the HIV-virus. By all account the project is
       | successful. The announcement of this breakthrough causes a lot
       | controversies. People are shocked and dismayed. Here is the link:
       | https://www.nature.com/articles/d41586-018-07545-0
        
         | meepmorp wrote:
         | Using CRISPR to edit the genomes of human embryos because YOLO,
         | is very different to using it in a modified version of an
         | existing treatment for sickle cell anemia. Do you not see the
         | difference in ethical scale and scope?
        
           | WaitWaitWha wrote:
           | >Do you not see the difference in ethical scale and scope?
           | 
           | I agree with you that to you (and me) in this case there is a
           | difference.
           | 
           | But, who sets the scale & scope?
           | 
           | ( _I am aware that the box has been opened, it will never be
           | closed._ )
        
             | downrightmike wrote:
             | HIV is a very capable mutator, all he did was give it a
             | chance in two hosts to mutate against. and then who knows
             | the future danger of the kid's health. Dolly the sheep was
             | cloned, but had enlarged organs. So not perfect. And what
             | changes in these kids is a huge unknown and there was no
             | way to predict it, because the doc just did because he
             | could. Plus a whole eugenics program has a huge historical
             | negative example in the last century because it lead to
             | death camps.
        
             | codeproject wrote:
             | Totally Agree!!! it is the initial stage.
        
           | codeproject wrote:
           | if you read the Original Article close enough, You will see
           | the subtle point here:
           | 
           | >If this is successfully applied in young patients, it has
           | the potential to prevent irreversible complications of the
           | disease
           | 
           | How young is this going to be, One years old, 1 month old...
        
             | meepmorp wrote:
             | Bone marrow transplants as a treatment for SA are already a
             | thing. All this does is make it so you can use the
             | patient's own bone marrow instead of a donor, hopefully
             | reducing rejection. There's no subtle point to be made, the
             | question you're asking is a solved one, because it's just a
             | modification of an existing therapy.
             | 
             | Now, compare that to editing human embryos in vitro then
             | implanting them, just because you want to prove it's
             | possible to use a gene editing technique to alter the
             | genome of a person.
        
         | pitspotter wrote:
         | Trying to enhance or disable healthy genes isn't the same as
         | fixing known disease-causing mutations.
         | 
         | Moreover, identifying harmful mutations can't tell you how to
         | build superhumans. So I think the similarity is only
         | superficial.
        
           | codeproject wrote:
           | He JianKui's Project is not to build the superman. the parent
           | of the baby girls is HIV positive. He did that so that Parent
           | is not going to worry about their babies is going to get the
           | disease.
        
             | ngcc_hk wrote:
             | For now.
             | 
             | Helping China to trade is not to build a totalitarian
             | country as well. Just trade.
        
       | godmode2019 wrote:
       | Can someone answer, what is the entry method of CRISPR in adults,
       | don't it need to change all instances of a cell to be effective?
       | 
       | I don't really understand the delivery method.
        
         | konschubert wrote:
         | For blood diseases it's enough to replace all blood-producing
         | cells and their producers, I guess?
        
         | azernik wrote:
         | Brute force:
         | 
         | "...some of the patient's hematopoietic stem cells... [are]
         | harvested for gene editing outside the body. After these cells
         | are removed, the remaining bone marrow is destroyed with
         | chemotherapy to allow space for the repaired and reinfused stem
         | cells to grow."
         | 
         | EDIT: This is apparently the same procedure as conventional
         | bone marrow transplants in SCA patients. CRISPR is just slotted
         | into that workflow to synthesize a transplant, without needing
         | to find a donor.
        
           | causality0 wrote:
           | But does the CRISPR method require the patient to remain on
           | anti-rejection drugs the rest of their life?
        
             | Gibbon1 wrote:
             | I would assume more likely not since they are the patients
             | own cells.
        
           | [deleted]
        
           | grapecookie wrote:
           | Bro if it actually uses chemo to destroy your marrow and then
           | grafts new youGM marrow? thats Frankenstein and evil af.
        
           | [deleted]
        
           | liamwire wrote:
           | Even with the amount of hype around CRISPR, that is...
           | incredible. Turning patients into their own donors feels
           | magical.
           | 
           | I suppose in this instance, the patients wouldn't need
           | immunosuppressants after their treatment, as I'd expect
           | standard care patients currently need for life?
        
             | rcthompson wrote:
             | I think it's an open question. After this treatment, the
             | patient's red blood cells will be producing a new protein
             | that they have never produced before. This protein only
             | differs from the previous one by one amino acid, so the
             | question becomes how sensitive the immune system is to such
             | a change. Given that the immune system has some difficulty
             | recognizing cancer cells with multiple protein-coding
             | mutations in them, I think it's likely that a single amino
             | acid change will fly under the radar and not require any
             | immune suppression, at least for the vast majority of
             | recipients of this treatment.
        
               | mschuster91 wrote:
               | Wiping out the bone marrow should also (essentially)
               | reset the immune system IIRC.
        
               | rcthompson wrote:
               | Yes, but T-cells learn to distinguish self from non-self
               | in the thymus, and I don't believe this treatment alters
               | the hemoglobin gene sequence in the thymal epithelial
               | cells. Of course, the thymus, like the rest of the body,
               | will be served by red blood cells containing the new
               | hemoglobin gene, but I'm not sure if this alone is
               | sufficient for immature T-cells in the thymus to learn it
               | as a self protein.
        
               | farfalle wrote:
               | Bone marrow transplant (BMT) recipients can still
               | experience graft versus host disease (GVHD) which is when
               | the transplanted marrow produces healthy cells that start
               | to attack the host body.
               | 
               | Besides GVHD, it is like you said. BMT patients are one
               | of the few transplant types that can eventually come off
               | of immuno-suppressants with a successful transplant. The
               | patient's original bone marrow is supposed to be wiped
               | out by chemotherapy (and sometimes some radiation) to
               | make room for the new marrow transplant.
        
               | eganist wrote:
               | Can we take a moment to appreciate the straightforward
               | naming of _graft-versus-host disease_? I couldn 't find
               | the history of its discovery beyond this (https://www.sci
               | encedirect.com/science/article/abs/pii/S03014...) and
               | even there, I couldn't find any indication of how it came
               | to receive that name specifically, but it's much better
               | than "[scientist's name]'s disease/syndrome" that we keep
               | running into because people want credits at the expense
               | of accessibility of knowledge.
        
             | quiescant_dodo wrote:
             | The fundamental idea of using the donor's own stem cells is
             | known as an Autologous Stem Cell Transplant and has existed
             | for a while. It is used as therapy for a fair number of
             | blood cancers (e.g. multiple myeloma or a few leukemias).
             | 
             | Using "something" to manipulate the donor cells has also
             | been done for these autologous HSCTs. I know of "CAR T cell
             | therapy", but there are likely others. (
             | https://www.cancer.gov/about-
             | cancer/treatment/research/car-t... )
             | 
             | I think some small number of autologous HSCT recipients
             | require immunosuppressants, but from what I remember the
             | number is very very small. (Allogenic HSCT recipients, who
             | receive cells from a different person, are _much_ more
             | likely to require lifetime immunosuppressants.)
             | 
             | It's super cool that they're able to treat genetic diseases
             | this way!
        
         | mbreese wrote:
         | Because this is a blood based disease, I'm guessing they would
         | extract blood from the patient or extract them from bone marrow
         | (more likely), treat the cells outside the body, and then
         | transfuse the modified blood cells back onto the patient to try
         | and engraftment them in the bone marrow.
         | 
         | All of the hard CRISPR stuff is likely in vitro.
         | 
         | However, I don't know anything about what the specific plans
         | are though, this is just speculation.
        
         | refurb wrote:
         | Sickle cell anemia can be "cured" by inducing expression of
         | fetal hemoglobin (fHb). You don't need to shut off the
         | defective gene and the disease is effectively "cured" if you
         | replace enough scHb with fHb.
         | 
         | So you remove bone marrow from the patient, modify the cells,
         | put them back in. The modified cells produce fHb at a high
         | enough level that symptoms of Sickle Cell go away.
         | 
         | Not that different than the already approved CAR-T therapies
         | (with the exception they don't use CRISPR for the genetic
         | modification).
        
           | maxerickson wrote:
           | This treatment modifies the adult hemoglobin gene.
        
       | keven wrote:
       | For people interested in Crispr, Rich Horgan started a non-profit
       | called Cure Rare Disease working to fast-track customized
       | therapeutics for his brother and other families with Duchenne
       | Muscular Dystrophy using in-vivo gene editing.
       | 
       | https://cureraredisease.org/
        
       | pastrami_panda wrote:
       | For those interested in CRISPR tech I'd highly suggest reading up
       | on BEAM therapeutics. It's base pair editing which makes it much
       | more precise compared to CRISPR which is editing DNA chains. They
       | don't have editors for all base pairs yet but they have a couple
       | and it looks very promising.
        
         | jfarlow wrote:
         | The Base Editor (and Prime Editor, etc.) _is_ CRISPR (Cas9) but
         | with additional components fused to it that provide it
         | additional features allowing it to edit in a more elegant way
         | over the naked Cas9.
         | 
         | https://serotiny.bio/notes/proteins/sabe4gam/
        
           | jonplackett wrote:
           | So CRISPR now has frameworks? Cool.
        
       | o0-0o wrote:
       | Very cool. Now please, work on Myelo Fibrosis next!
        
       | mrfusion wrote:
       | So how do they get the crispr into the cell and into the cell
       | nucleus? Would fixing scd be all or nothing?
        
         | meepmorp wrote:
         | The treatment is basically a bone marrow transplant, which
         | would typically use donor cells from another person; CRISPR
         | lets you use the patient's marrow instead, hopefully reducing
         | rejection and other issues.
         | 
         | You extract marrow and CRISPR it to get rid of the problem
         | gene. Then you kill off all of the bone marrow in the patient,
         | and replace it with the new stuff. That's a cure.
        
       | stjohnswarts wrote:
       | Big if true.
        
       | nerdkid93 wrote:
       | I was super pumped for this tech to start being used in human
       | clinical trials, but a couple of years ago, there was a study[0]
       | that raised some key concerns about CRISPR therapeutics
       | increasing the risk of cancer due to some edited cells self-
       | destructing once their genomes have been modified, leaving behind
       | cells with a higher risk of cancer due to not being as sensitive
       | to genomic edits. Have these challenges been overcome yet?
       | 
       | [0]: https://www.scientificamerican.com/article/crispr-edited-
       | cel...
        
         | suifbwish wrote:
         | Woah! So the cells that accept the CRISPR modifications do so
         | because they have dysfunctional p53 gene activation. This most
         | likely means they are specifically the cells most likely to
         | become tumors if they undergo any mutations triggering
         | carcinogenesis as p53 and its helper genes are mainly
         | responsible for killing off cells that become cancerous among
         | other things.
         | 
         | This means that you can use CRISPR to selectively kill these
         | cells only since they would be the only ones that easily accept
         | and express the CRISPR modifications. This could be ground
         | breaking if it is not already tried.
        
       | DoreenMichele wrote:
       | _"We are motivated to work toward a cure that can be accessible
       | and affordable to patients worldwide,"_
       | 
       | Sickle Cell is prevalent in some populations because the gene
       | mutation is protective against malaria. (Probably only beneficial
       | if you have one copy, not two.)
       | 
       | I hope they will keep this in mind and work to eradicate malaria
       | hand-in-hand with trying to eradicate the genes that are
       | protective against it when they look to take it global.
        
         | IIAOPSW wrote:
         | "I would die for 2 brothers or 8 cousins". -JBS Haldane
         | 
         | https://en.wikipedia.org/wiki/Kin_selection
        
         | toomuchtodo wrote:
         | There is a candidate mRNA malaria vaccine in the pipeline.
         | 
         | https://blogs.sciencemag.org/pipeline/archives/2021/03/01/a-...
        
         | yarcob wrote:
         | > Probably only beneficial if you have one copy, not two.
         | 
         | One copy of the gene partially protects you from malaria; two
         | copies of the gene make you very sick.
         | 
         | That's why even in Africa only a small portion of the
         | population has the gene. The gene is an evolutionary advantage
         | as long as the prevalence in the population is low. As soon as
         | the frequency of the gene in the population goes up, it becomes
         | a disadvantage because if both you and your partner have the
         | gene your kid has a 25% chance of getting two copies.
        
         | f6v wrote:
         | That's right, but the sad truth is that those who will afford
         | gene editing and those who are at daily risk of malaria are two
         | very different groups of people.
        
         | azernik wrote:
         | This particular treatment does not affect the germ line. i.e.
         | it corrects the defect in the patient, but they can still pass
         | it on to their children, who would be (malaria-protected)
         | carriers.
        
         | maxerickson wrote:
         | It's fine if they just figure out how to cure sickle cell
         | anemia. Great even.
         | 
         | No one will force people in areas where malaria is endemic to
         | have sickle cell anemia treated, and a treatment for sickle
         | cell anemia won't slow down treatment/eradication of malaria.
        
           | DoreenMichele wrote:
           | I'm sure no one actually forced mothers in developing
           | countries to buy Nestle baby formula either. Babies died
           | anyway.
           | 
           | There are lots of sources out there. Here are just a couple.
           | 
           | https://en.wikibooks.org/wiki/Professionalism/The_Nestl%C3%A.
           | ..
           | 
           | https://www.ranker.com/list/nestle-baby-formula-
           | boycott/meli...
        
             | maxerickson wrote:
             | It's certainly not _impossible_ that governments of African
             | countries would spend thousands of dollars per person to
             | prematurely cure sickle cell anemia, but I think we can say
             | that it 's _unlikely_.
        
               | f6v wrote:
               | > thousands of dollars per person to prematurely cure
               | sickle cell anemia
               | 
               | This cure is going to cost much much more. So highly
               | unlikely.
        
               | DoreenMichele wrote:
               | The actions of African governments is not what concerns
               | me here.
        
               | maxerickson wrote:
               | What other actors are going to give people unwanted bone
               | marrow transplants?
               | 
               | I guess medical companies testing the technology might do
               | things to get people to participate in trials, but I'm
               | not real sure people with sickle cell anemia would be mad
               | about having to use modern anti-malarials instead of
               | suffering with sickle cell.
        
         | XorNot wrote:
         | We're a hair's breadth away from using genetic engineering to
         | make the mosquito extinct.
         | 
         | We have the technology (gene drive) but scientists just aren't
         | sure if we should do it.
        
           | DoreenMichele wrote:
           | They are right to have concerns.
           | 
           | There was an island where they used poison to kill all the
           | mosquitoes because it was a big problem. All the mosquitoes
           | dies and then all the things that ate the mosquitoes died.
           | 
           | And then all the things that ate things that ate mosquitoes
           | died. And it went through a few more layers of this, like
           | some modern day version of the Biblical plagues.
           | 
           | That doesn't mean we shouldn't do it. It just means it is
           | correct to not take the decision lightly.
           | 
           | (Unfortunately, I've never found a good write up of this true
           | story on the internet. I read it long ago back when dinosaurs
           | roamed the earth and I had a bright yellow rotary phone and
           | got information printed on dead trees.)
        
             | Salgat wrote:
             | Do you have a source for this? I linked below the best I
             | could find, which makes no mention of any issues with them
             | wiping it out.
             | 
             | https://www.cnn.com/2019/07/18/health/asian-tiger-
             | mosquitoes...
        
               | DoreenMichele wrote:
               | Possibly Sardinia:
               | 
               |  _The eradication of malaria helped Sardinia improve its
               | public health programs and also paved the way for socio-
               | economic development. But at a huge environmental cost
               | that is incalculable. Some farmers accused the DTT of
               | killing their livestock, bees and also fish._
               | 
               | https://totalsardinia.com/malaria/
               | 
               |  _Sheepherders, fish farmers, and beekeepers blamed their
               | dead sheep, dead fish, and dead bees on DDT spraying._
               | 
               | https://www.wanderingitaly.com/blog/article/785/sardinia-
               | and...
               | 
               | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819864/
               | 
               | Edit: Odds are good I read about it originally in
               | Reader's Digest in the late 1970s or early 1980s if you
               | want to find a dead tree copy at a library.
        
             | yardie wrote:
             | Except there are multiple species of mosquito. Only 1 of
             | them is a primary carrier for malaria. And if it disappears
             | another mosquito in the family will replace it.
        
             | est31 wrote:
             | You don't have to extinguish all mosquito species. It's
             | enough to only target those which can carry diseases.
             | Ideally one would engineer mosquitos to avoid humans
             | because of their smell.
        
               | bamboozled wrote:
               | Maybe we could also considering modifying ourselves to be
               | less susceptible to mosquitos.
               | 
               | Including helping people who live in poverty to have
               | better housing and medicine so their less susceptible to
               | Malaria ?
        
               | incompatible wrote:
               | Perhaps it would be possible to modify mosquitoes so that
               | they don't need blood to reproduce. Other insects manage
               | it somehow.
        
               | jackson1442 wrote:
               | Modifying ourselves leads into the messy territory of
               | bodily autonomy and consent. You can see this pretty well
               | in the anti-COVID-vaccine crew. I feel like it'd be much
               | more popular to modify mosquitos than apply some
               | modification to humans.
               | 
               | Not to mention the ethical (regarding equity) concerns:
               | disease from mosquitoes affects poverty-stricken areas
               | the most, yet the people with the most access to these
               | bodily modifications or procedures are going to be from
               | wealthy countries.
        
               | jcims wrote:
               | Mosquitoes are a rather distinct element in the natural
               | world and it just seems unlikely that we are capable of
               | understanding the full set of downstream effects of
               | eradicating them entirely.
        
               | bamboozled wrote:
               | I actually was talking about our behavior, not our actual
               | genetics or biology.
               | 
               | My understanding is that a lot of the diseases we want to
               | kill mosquitoes for are also more likely to affect people
               | in developing countries.
        
               | andreareina wrote:
               | There are few developed countries in the tropics.
               | Singapore is one, and dengue is a concern here. I
               | understand that the way it's mostly kept under control is
               | through a lot of spraying, which isn't exactly great.
        
               | grapecookie wrote:
               | obviously this mutation would not last.
        
               | Turing_Machine wrote:
               | Right. There are thousands of species of mosquito, most
               | of which don't carry human diseases.
               | 
               | Of the ones that do, many of are of African origin --
               | they evolved there along with us (and the diseases they
               | carry). They are thus essentially invasive species in the
               | rest of the world.
               | 
               | The nice thing about potentially using CRISPR-based gene
               | drives to extirpate (e.g.) Aedes aegypti is that it would
               | affect _only that species_ , unlike our current
               | pesticides which tend to kill insects of many different
               | species indiscriminately.
        
             | bamboozled wrote:
             | Common sense must tell people that whether we like
             | mosquitos or not, they're part of the food chain. A food
             | chain which is already stressed due to climate change.
             | 
             | Scientist who are eager to take out mosquitos sound more
             | like kids who are eager to play with their new gene drive
             | rather than consider the actual impacts.
        
               | mNovak wrote:
               | While I agree it's likely, 'common sense' is also not
               | science and we shouldn't take as a given that they are an
               | integral part of the food chain. Pest species do exist.
               | 
               | Saving lives is generally a strong motivator, so it's
               | worth considering the possibilities.
        
               | tylermw wrote:
               | No, scientists who are eager to take out mosquitos want
               | to do it because it will save millions of lives. People
               | have been dying of malaria for millennia--climate change
               | has nothing to do with this particular issue/solution.
        
               | bamboozled wrote:
               | We're all very concerned, but we don't really spend very
               | much money on Malaria treatments, relief and vaccines
               | overall. Especially in the developing world. There isn't
               | even really much urgency to do anything about it.
               | 
               | No operation warp speed to help save hundreds of
               | thousands of lives a year. It's almost just like a fun
               | topic to make people feel better about themselves.
               | 
               | I've read more about how transmission of malaria works
               | and basically mosquitoes carry it from biting infected
               | humans then pass it to other humans, it's not that
               | mosquitos are evil, they don't even know what's going on.
               | 
               | I think there is a question of ethics involved
               | personally, that's because if mosquitoes had the power to
               | wipe us out, we wouldn't be that happy if they decided to
               | go ahead with the plan.
        
             | Jedd wrote:
             | This seems alarmist.
             | 
             | The citation you provided elsewhere (for Sardinia) was for
             | some DDT _spraying_ - which was obviously not targeted
             | exclusively at mosquitoes, and explains why lots of other
             | things died.
             | 
             | Targeting the very small set of mosquito species (that
             | carry malaria) with something that will wipe them out
             | within a few generations (under 12 months) seems
             | tremendously safe, because a) it's a small subset of the
             | total mosquito population, b) you can test this in isolated
             | (eg. island) environments, and c) by the very nature of
             | this, rollback is easy -- once the species has died out
             | locally, if needed you can quickly & safely re-populate
             | with non-modified specimens.
        
               | DoreenMichele wrote:
               | It's not alarmist. Not by any stretch of the imagination.
               | 
               | I'm an environmental studies major and I have a genetic
               | disorder. I'm getting healthier when that is supposed to
               | be impossible and it's in part because I'm an
               | environmental studies major and I think of the body as a
               | complex ecosystem.
               | 
               | You kill one thing or change one thing and there are
               | always myriad knock on effects. Always. Anytime you do
               | anything that's actually at all effective, there is hell
               | to pay.
               | 
               | I am getting better by trading short term costs for long
               | term gains, the exact opposite of what Western medicine
               | typically does. We monetize disease by trading short term
               | gains -- that doctors can claim credit for, justifying
               | their fees -- for long term costs which we politely admit
               | to with multi-page warning materials included with all
               | drugs and then normalize largely ignoring that stuff and
               | taking it anyway. Then when your condition gets worse,
               | they blame it on your genes instead of on the side
               | effects of the harsh drugs they have been poisoning your
               | system with for years and years.
               | 
               | It's possible to make targeted changes to an ecosystem,
               | but it's not easy and even if you get it right, there are
               | costs involved. Managing such change is hard and there
               | tends to be hidden costs that the experts want to disavow
               | responsibility for and they can generally get away with
               | it because cause and effect can be hard or impossible to
               | prove.
               | 
               | I hope they cure Sickle Cell. I hope they eradicate
               | malaria. Parasitic infections are pretty awful.
               | 
               | I hope they do it in a way that doesn't involve millions
               | of Africans being thrown under a bus so Westerners can
               | feel like heroes while hand waving off the human costs
               | for the locals which Westerners have a long history of
               | running rough shod over on the excuse that we imagine we
               | are superior to them or something.
        
               | Jedd wrote:
               | > You kill one thing or change one thing and there are
               | always myriad knock on effects. Always. Anytime you do
               | anything that's actually at all effective, there is hell
               | to pay.
               | 
               | I stand by my earlier claim.
               | 
               | While I acknowledge the potential of unintended
               | consequences, and the often surprising interconnectedness
               | of many elements within an ecosystem, I further dispute
               | the claim that any change necessitates other, exclusively
               | bad, 'hell to pay' changes.
               | 
               | Here I am, in rural Australia, and within a kilometre of
               | me these are the pests that I would be ecstatic to get
               | rid of, and that would have close to zero negative, and
               | myriad positive, knock-on effects:
               | 
               | prickly pear, tiger pear, heliotrope, pattersons curse,
               | foxes, rabbits, several species of med fruit fly &
               | mosquitoes.
               | 
               | Almost all of these are guaranteed to have no negative
               | knock-on effects simply because they were introduced here
               | in the past two centuries.
        
               | DoreenMichele wrote:
               | Australia is like the poster child for unintended
               | ecological consequences. All those introduced species you
               | cite to refute my opinion I would cite to support it.
               | 
               | Though the camel being introduced to Australia seems like
               | something of a silver lining. From what I gather,
               | Australia is now like a haven for the species.
        
               | Jedd wrote:
               | I'm interested in how you defend (if I'm reading that
               | correctly) retaining those pests in Australia.
               | 
               | Further afield from my humble abode, yes, Phytophthora,
               | lantana, black rats, blackberry, feral goats / pigs /
               | deer, cane toads, camels, etc.
               | 
               | The reason we can export camels to the middle east is
               | that when we imported them from there, we didn't import
               | the various parasites that are now rampant in that part
               | of the world.
               | 
               | Perversely this gives us an export trade _and_ a
               | massively out of control population of highly destructive
               | and resilient beasts.
               | 
               | If we could remove all wild camels from Australia over
               | the space of 10 years you'd be hard-pressed to identify
               | any net negatives, and certainly it'd be impossible to
               | identify any negatives that were detectable when mapped
               | onto a graph of the positive effects.
        
               | DoreenMichele wrote:
               | No, you are not reading that correctly.
               | 
               | They are invasive species that exploded in Australia due
               | to a lack of natural predators. How you can cite their
               | existence as a refutation of anything I've said baffles
               | me.
               | 
               | I've been up excessively long. With any luck, I'll be
               | asleep soon.
               | 
               | Ciao.
        
               | danmaz74 wrote:
               | > Always. Anytime you do anything that's actually at all
               | effective, there is hell to pay.
               | 
               | Just the first counter examples that comes to my mind:
               | "Western medicine" eradicated smallpox and polio; what
               | was the hell price for those?
               | 
               | "Western medicine" really only means medicine based on
               | the scientific method, and shouldn't be conflated with
               | the profit maximisation mechanisms which are so prevalent
               | in the US medical system.
        
               | DoreenMichele wrote:
               | Overpopulation is one of the consequences of actually
               | solving problems. Birth rates fall after mortality rates
               | fall. The result is a bump in population size.
               | 
               | This is a known phenomenon. It's very well documented.
               | 
               | It's not a reason to keep letting people die, but the
               | transition comes with costs.
               | 
               | That's just reality.
               | 
               | Antibiotics were supposed to be the end of disease. Now
               | we are brewing antibiotic resistant infections.
               | 
               | It's common for diseases to jump species when adequately
               | threatened. Organisms don't like being eradicated and
               | will fight back.
               | 
               | You see more genetic mutations in diseases, fomenting
               | resistance, when they are under pressure.
               | 
               | We've lost some of the medical best practices I grew up
               | with. I have no idea if that's directly related to the
               | eradication of small pox or polio. I haven't specifically
               | studied those cases.
               | 
               | Change comes at a cost. That doesn't mean it isn't worth
               | pursuing. It does mean that cavalier attitudes about how,
               | _clearly_ , this is all upside have a tendency to be
               | dangerous.
        
               | danmaz74 wrote:
               | There are cavalier attitudes on one side, and alarmist
               | attitudes on the other side, and in my humble opinion
               | saying that "Anytime you do anything that's actually at
               | all effective, there is hell to pay" falls in the latter.
               | 
               | What's the hellish consequence of eyeglasses?
        
               | DoreenMichele wrote:
               | _What 's the hellish consequence of eyeglasses?_
               | 
               | That's a misreading of my statement that talks about
               | killing a thing in an ecosystem and thereby upsetting the
               | balance of the ecosystem.
        
               | zo1 wrote:
               | > _We 've lost some of the medical best practices I grew
               | up with._
               | 
               | Which practices are you referring to here?
        
               | DoreenMichele wrote:
               | When I was growing up, medicine was more focused on
               | social elements. It more explicitly recognized that
               | people spread disease from person to person.
               | 
               | At one time, the way we stopped STDs was we took the
               | names of all your recent hookups, contacted them and let
               | them know they had been with someone who had just tested
               | positive for a particular STD and offered them testing
               | and treatment.
               | 
               | In my teens, the AIDS crisis hit. In the US, it was
               | mostly associated with gay men and IV drug users. These
               | populations had reasonable concerns about giving a list
               | of contacts to authorities and pushed for drug research
               | and stronger privacy policies.
               | 
               | My understanding is we largely no longer use this proven
               | method of stopping the spread of most STDs.
               | 
               | I can also remember going to a doctor with a sibling and
               | a couple of cousins and all of us getting treated so that
               | the issue wouldn't just go round and round through the
               | family. I feel like that was a fairly common practice at
               | the time and we mostly don't do stuff like that anymore.
               | 
               | Historically, doctors did house calls and were one of the
               | smartest, best educated people in town and towns were
               | relatively small. They could address issues that helped
               | contribute to your medical problem beyond just
               | prescribing drugs and surgeries.
               | 
               | Now we act like human beings are specimens in a petri
               | dish and like their physical health is unrelated to their
               | lifestyle or the fabric of their life.
               | 
               | I think this is a big problem. The phrase "We've thrown
               | out the baby with the bathwater" comes to mind but
               | doesn't quite fit.
               | 
               | What we've done is tossed aside wisdom and context to
               | worship at the alter of ooh shiny diagnostics. The high
               | tech diagnostics are useful but the largely unnoticed
               | loss of wisdom and context is a serious problem and we
               | aren't even trying to solve it because we mostly haven't
               | noticed that it matters.
        
           | Dig1t wrote:
           | I think about this a lot.
           | 
           | What's to stop some random, non-scientist, group of people
           | from just doing this? Mosquitos are pretty evil..
        
             | maxerickson wrote:
             | If you make a gene drive you are a scientist.
             | 
             | Hopefully whoever decides to just go do it has the sense to
             | only target mosquitoes that preferentially feed on humans.
             | Much less ecosystem impact that way.
        
               | danielheath wrote:
               | > If you make a gene drive you are a scientist.
               | 
               | These days, introducing a known mutation via a CRISPR
               | gene drive is engineering. The hard part is scaling it so
               | your mutation doesn't die out, testing to ensure that it
               | is actually propagating, etc.
               | 
               | > Hopefully whoever decides to just go do it has the
               | sense to only target mosquitoes that preferentially feed
               | on humans.
               | 
               | You have to repeat a considerable amount work for every
               | single target species. I highly doubt they'd target more
               | than one.
        
               | maxerickson wrote:
               | There's several species that preferentially feed on
               | humans and we've done a banger spreading them around.
        
           | grishka wrote:
           | The frogs gotta eat something.
        
             | XorNot wrote:
             | The general consensus at the moment is that there's no
             | apparent food chain where mosquitos are the primary source.
        
               | AlotOfReading wrote:
               | Except for places like the arctic, where they're
               | basically primary pollinators and a food of choice for
               | most predatory insects.
        
               | learc83 wrote:
               | Do all the species of mosquitoes your talking about feed
               | on humans, and do they carry malaria?
        
               | AlotOfReading wrote:
               | Yes and yes?
        
               | Turing_Machine wrote:
               | No, they don't.
               | 
               | The (many) species of mosquito found in the Arctic do not
               | carry malaria. Malaria is largely a tropical and
               | subtropical disease.
        
               | AlotOfReading wrote:
               | Avian malaria is endemic to Alaska, and both Finland, and
               | Siberia formerly had endemic human malaria, especially
               | the more southern regions. Something up there is
               | definitely capable of being a vector for it.
        
               | learc83 wrote:
               | But is malaria a big enough problem in the arctic to
               | bother targeting the mosquito species there that _could_
               | carry malaria? From a quick Google search, I 'm guessing
               | no.
        
           | BurningFrog wrote:
           | What's talked about is only making the 30-40 of the 3500
           | mosquito species that carry malaria extinct.
           | 
           | Ecologically, they can normally be replaced by some of the
           | 3460 others.
        
       | jostmey wrote:
       | I've learned a lot about gene therapy. The immune system is a
       | major bottleneck to wide spread gene therapy. If you modify the
       | genetic makeup of cells in your body, the immune system will
       | recognize the new antigens being presented by these cells and
       | attack. Many gene therapy target point mutations that don't
       | require significant alterations to correct that would alarm the
       | immune system.
        
         | amelius wrote:
         | Don't point mutations cause proteins to fold differently? And
         | thus causing the proteins to become globally different rather
         | than locally different?
        
           | jostmey wrote:
           | 1. Most point mutations won't result in significant changes,
           | but if we are talking about gene therapy, the specific point
           | mutation probably did effect protein folding or function 2.
           | Proteins in each cell are broken down into unfolded fragments
           | and presented on major histocompatibility complexes as
           | antigen.
        
         | f6v wrote:
         | It's also that we don't have organism-scale models of how
         | change in one gene will affect other body functions. We don't
         | know how to build these kind of models and we don't have even
         | 1% of the data to do that. Organoids are just emerging, but
         | they aren't 1:1 representation of what happens in real human.
        
       | doubtfuluser wrote:
       | For my understanding: crisper works by cutting the dna at
       | specific points surrounding the relevant part and then
       | exchanging, right? How likely is it, that in the whole DNA string
       | there are other instances this "surrounding" matches and would be
       | cut? How is this prevented / not causing side effects?
        
         | yarcob wrote:
         | The nice thing about CRISPR is that you can use pretty long
         | sequences for matching, so in theory you can just pick a
         | sequence that doesn't occur anywhere else and cut there.
         | 
         | (Before CRISPR, you would use restriction enzymes with a short,
         | fixed recognition sequence, typically 4-6 base pairs [1]. In
         | that case it was a bit tricky to find the right enzyme that
         | cuts the DNA in the right place, and not in an unwanted place.
         | And you couldn't just cut the DNA in any place you want.)
         | 
         | [1]:
         | https://en.wikipedia.org/wiki/List_of_restriction_enzyme_cut...
        
         | julienreszka wrote:
         | DNA has something like "Bytes"
         | 
         | Clustered Regularly Interspaced Short Palindromic Repeats
        
       | doggodaddo78 wrote:
       | Is there more than one cause of sickle cell?
        
       | [deleted]
        
       | xiphias2 wrote:
       | Hasn't Vertex already run an experiment on people and cured
       | sickle cell disease using CRISPR last year? What's new here
       | (except that the organizations are different)?
       | 
       | https://sicklecellanemianews.com/ctx001-sickle-cell-disease
        
         | maxerickson wrote:
         | That trial deactivated a gene (causing a different one to be
         | more active).
         | 
         | This trial is inserting/editing a gene.
        
           | xiphias2 wrote:
           | Thanks!
        
       ___________________________________________________________________
       (page generated 2021-04-08 23:02 UTC)