[HN Gopher] Base editing: Revolutionary therapy clears girl's in...
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Base editing: Revolutionary therapy clears girl's incurable cancer
Author : sonabinu
Score : 659 points
Date : 2022-12-11 02:35 UTC (20 hours ago)
(HTM) web link (www.bbc.com)
(TXT) w3m dump (www.bbc.com)
| fastball wrote:
| In response to the multiple people asking if base editing and
| CRISPR are the same, the answer is: not quite. Same idea,
| different enzyme.
|
| The enzyme used by CRISPR is Cas9 (which is why you'll often see
| it referred to as CRISPR-Cas9), which acts like a pair of
| molecular scissors and cuts strands of DNA at a specific point in
| the genome.
|
| Base editing is a newer technique and utilizes an enzyme called
| deaminase, which can change the chemical structure of a base pair
| without doing the "cutting" part. There are specific deaminases
| based you use depending on which base pair you're trying to
| modify.
|
| To oversimplify a bit: base editing is a more precise version of
| CRISPR, which is less likely to cause more changes than actually
| desired, as is a problem with CRISPR. That doesn't make CRISPR
| obsolete though, because if your goals actually _is_ to remove
| entire portions of a genome, CRISPR is a more effective
| technique. Regardless, there is a lot of overlap between the
| methods: both usually use adenoviruses as the delivery vehicle,
| you can use both enzymes in tandem, etc.
| nine_k wrote:
| The word more understandable for the software developer crowd
| would be "patching". That is, changing a base pair in place.
| govg wrote:
| I took it to mean doing an in place patch / removal of code
| (CRISPR) vs doing a more general refactor that results in
| cleaner code (base pair editing).
| stanford_labrat wrote:
| For clarification, most base editors are a fusion protein with
| cas9 and the actual editing protein.
| [deleted]
| chrisweekly wrote:
| IMHO this is a good reminder that the word "incurable" means "as-
| yet unsolved", it's not an absolute.
| stevespang wrote:
| pkaye wrote:
| Hasn't this treatment been use for a while now?
| [deleted]
| TaupeRanger wrote:
| I'm not sure it counts as "revolutionary" if it has helped only 1
| person, and maybe as many as 10-12 per year. It's really the
| opposite of revolutionary, though I am very happy for this family
| and their daughter.
| ryangittins wrote:
| Sure, there is one airplane but that's hardly revolutionary. A
| couple of guys can fly a few dozen feet. So what?
| selimthegrim wrote:
| This is like if Larry David did an ad for the Wright brothers
| HiroProtagonist wrote:
| Pretty, pretty, pretty good.
| TulliusCicero wrote:
| This is like the ultimate form of Unimpressed Internet Guy.
|
| The article even talks about other trials also underway, so the
| parent comment doesn't even make any sense:
|
| > Dr Robert Chiesa, from the bone-marrow transplant department
| at Great Ormond Street Hospital, said: "It is extremely
| exciting. Obviously, this is a new field in medicine and it's
| fascinating that we can redirect the immune system to fight
| cancer."
|
| > The technology, though, only scratches the surface of what
| base editing could achieve.
|
| > Dr David Liu, one of the inventors of base editing at the
| Broad Institute, told me it was "a bit surreal" that people
| were being treated just six years after the technology was
| invented.
|
| > In Alyssa's therapy, each of the base edits involved breaking
| a section of genetic code so it no longer worked. But there are
| more nuanced applications where instead of switching an
| instruction off you can fix a defective one. Sickle-cell
| anaemia, for example, is caused by just one base change that
| could be corrected.
|
| > So there are already trials of base editing under way in
| sickle-cell disease, as well as high cholesterol that runs in
| families and the blood disorder beta-thalassemia.
| [deleted]
| Firmwarrior wrote:
| Haha, your comment is like something a venture capitalist would
| say when he's trying to lowball a startup founder in the show
| "Silicon Valley"
| quickthrower2 wrote:
| There is a time when every revolutionary invention had only
| helped one person, so far.
| tinktank wrote:
| It's a proof-of-concept. That's the hard bit done.
| flobosg wrote:
| > a revolutionary product, process, or idea is new and exciting
| and not like anything that has existed or been done before
|
| --https://dictionary.cambridge.org/dictionary/english/revoluti.
| ..
| 1123581321 wrote:
| The technique is new and will be adapted to other cancers and
| diseases.
| walnutclosefarm wrote:
| Actually, it's the other way around. The treatment described
| is an adaption of CAR-T (Chimeric Antigen Receptor T-cell)
| therapy, which was approved for use in the United States in
| 2017, to the patient's specific form of leukemia. It's a
| challenging adaptation because the cancer cells being
| targeted are the same type of T-cells that are used in CAR-T
| therapy, thus requiring the use of donor T-cells, and a
| number of modifications that are unnecessary when CAR-T is
| used for other cancers. Base editing makes that easier than
| earlier forms of CRISPR. But base editing isn't the therapy
| here, CAR-T is, and while CAR-T is certainly relatively, this
| patient is not the first to receive, just the first with her
| particular leukiemia.
| SalmoShalazar wrote:
| No, the parent comment is totally fine. The technique is
| indeed new and yes will be applied in the treatment of
| other diseases in the future. Don't know why you went to
| open with a contrarian tone.
| 1123581321 wrote:
| I don't see the disagreement! Good info; thanks.
| tsol wrote:
| First it had to be accomplished, then they can work on getting
| the price down
| DoreenMichele wrote:
| In layman's terms: She had a particularly vicious form of cancer
| where the very cells that are supposed to protect your health --
| your T-cells -- are the enemy. So they made three edits to donor
| cells and wiped out her compromised cells. Then gave her a bone
| marrow transplant afterwards to replenish her immune system with
| new cells.
|
| I'm squeamish about genetic research, but this looks really good
| to me. I hope she recovers fully and there are no further
| complications, though I imagine it's too early to guess what her
| prognosis might be.
|
| _So there are already trials of base editing under way in
| sickle-cell disease, as well as high cholesterol that runs in
| families and the blood disorder beta-thalassemia._
|
| That's a big deal for people with those genetic disorders.
| mcculley wrote:
| > I'm squeamish about genetic research
|
| Can you elaborate on what makes you squeamish about research?
| hotpotamus wrote:
| Have you ever tried making changes to a large, incredibly
| complex codebase with zero comments? Sometimes the changes
| you make don't have the expected results.
| dalmo3 wrote:
| Also, stateful code, no staging environment, no undo
| commit, prone to fatal runtime errors...
| svnt wrote:
| You've never made a change to such a codebase that was
| generated by a massively parallel evolutionary computer
| running for billions of years.
|
| You could just as easily make the argument that there is
| probably no body of data more stable than existing genomes.
| mcculley wrote:
| That sounds like an argument in favor of research.
| yitianjian wrote:
| Not OP, but something just feels unnatural and unsettling
| about changing humans, and especially for changing yourself.
| It feels like the uncanny valley where it just doesn't feel
| right. I'm agnostic so it's not for a particularly religious
| reasons, and it's purely an emotional response for me that's
| not grounded in logic at all, so I also just describe it as
| squeamish for no reason.
| sinenomine wrote:
| Thank you for a honest response. I think this is an
| underexplored topic - how many of our broad social policies
| were shaped mostly on the basis of sufficiently broadly
| shared visceral feeling.
|
| Should we base ultimately coercive society-wide regulatory
| framework on mere "squeamishness", appropriately
| rationalized, or should we instead embrace a non-
| discriminatory, laissez-faire approach in this domain?
| quesera wrote:
| > how many of our broad social policies were shaped
| mostly on the basis of sufficiently broadly shared
| visceral feeling
|
| All of them? I'm struggling to think of a counterexample.
| vcxy wrote:
| Yeah, I'd say the phrases "broadly shared visceral
| feelings" and "broad social policies" point to nearly the
| same concept.
| BurningFrog wrote:
| When I have these thoughts, I remind myself that typhoid is
| natural and penicillin is artificial.
|
| A big part of progress is fighting and defeating the
| natural.
|
| That said, not all genetic manipulation will end well.
| DoreenMichele wrote:
| Some people are interpreting that more broadly than I
| intended it. I'm squeamish about this kind of medical gene
| editing in specific.
|
| There is a genetic disorder that runs in my family. I used to
| be on a bunch of email lists for the condition. People with
| the condition routinely volunteer for drug studies in a
| desperate attempt to get help that current medical science
| can't provide them and/or to get free care for a condition
| that's very medically expensive.
|
| People with serious medical conditions are all too often
| treated like lab rats whose lives don't really matter.
| Treating people like me humanely isn't a real high priority.
| Quality of life is not much part of the discussion. Keeping
| us alive a little longer is the only metric that seems to
| count and horrifying things get done in the name of it.
| javajosh wrote:
| _> Can you elaborate on what makes you squeamish about
| research?_
|
| Yes, I for one can't imagine why editing the genes of humans
| would cause alarm. After all, who wouldn't want to have
| children that are smarter, more docile, and healthier? Or,
| for other people's children, who have qualities that make you
| uncomfortable and can't be edited out, like dark skin or
| homosexuality, you have the option to edit their reproductive
| ability so that such qualities can come to an end humanely,
| without violence.
|
| In the same way, I can't understand are those people against
| longevity research. Who wants to die? Not me, and certainly
| not those in power. You know, the people in power earned
| their positions, they are good at it, and mortality just
| means someone new and inexperienced will fumble around at the
| job. For continuity and safety, immortal leaders will do a
| better job and keep us safe. I don't see why anyone would
| consider this a bad thing.
|
| https://en.wikipedia.org/wiki/Satire
| mcculley wrote:
| I am, of course, aware of these tropes. If you have any
| sincere objections to research, please enlighten us.
| javajosh wrote:
| You think that sincerity is incompatible with satire?
| mcculley wrote:
| Of course not. Satire can be done very well and
| sincerely.
| rfrey wrote:
| I'm not sure how satire is relevant to this exchange.
| last_responder wrote:
| When it is mixed with the stupidity you spouted , yes.
| biophysboy wrote:
| Not the OP, but I think there are ethical concerns about
| genetic manipulation that do not amount to catastrophizing
| (e.g. 20th century eugenics is back!).
| mcculley wrote:
| Maybe the conflation is the problem for me. I don't see how
| research or even consensual application necessarily leads
| to "20th century eugenics".
| SoftTalker wrote:
| I don't see how it doesn't. Look at human history.
| mcculley wrote:
| I remain unconvinced that the inevitable existence of
| e.g., designer babies will inevitably lead to forcing
| people to have them.
| dalmo3 wrote:
| Consensual application is a huge assumption based on
| recent history.
| mcculley wrote:
| The existence on non-consensual application would not
| change my opinion on the value of research.
| kristopolous wrote:
| If we get designer babies along with curing cancer I say
| "so be it".
|
| Laws can be written to limit its use if we find it morally
| objectionable
| BurningFrog wrote:
| The problem with old school eugenics was that it wasn't
| consensual. Like forced sterilizations and abortions.
|
| If gene tech can make future generations healthier and
| smarter with informed choice by the parents, those future
| generations will look back in horror at the barbaric pro
| death & disease lobby of the 2020s.
| emmelaich wrote:
| Very interesting, because T-cells are implicated in multiple
| sclerosis.
|
| And probably other similar diseases.
| lostlogin wrote:
| The detective work going on with MS is fascinating. The blood
| work from the US military and what it has shown is really
| interesting - it's not new news but was to me when I stumbled
| on it this year.
|
| https://www.nih.gov/news-events/nih-research-
| matters/study-s...
| lebuffon wrote:
| I have long suspected that viruses are the underlying cause
| of most of the diseases that have eluded us for the last 50
| years. HIV gave us insights into a novel way that viruses
| can operate. It makes sense to think that there are more
| ways than we imagined.
|
| E/B virus is suspect in Type 1 Diabetes too. E/B
| Vaccination could eradicate a group of diseases
| potentially.
| inglor_cz wrote:
| Resetting the immune system can be already done and it seems to
| help against auto-immune diseases such as lupus, but it is very
| dangerous. Once you destroy the immune system of the patient,
| and before it grows back from donor cells, the patient is
| fatally vulnerable even to normally banal pathogens such as the
| common cold. Keeping the patient isolated and alive in a
| hospital full of germs is a major challenge.
|
| That is why this kind of therapy is only used when the patient
| faces death anyway.
| sinenomine wrote:
| >I'm squeamish about genetic research
|
| And I'm sad about millions upon millions of mostly well-meaning
| people, who died of ultimately preventable causes - if only we
| could push the research from the lab to clinic faster.
|
| Everybody is prone to ageing, and very soon it will be our
| turn.
| lettergram wrote:
| The challenge with genetics research is it could also result
| in the death of every human on the planet.
|
| It's an amazing power for good and bad.
| sinenomine wrote:
| You don't need to ban, say, clinical trials of gene therapy
| (especially with inert lipid nanoparticle carriers which do
| not replicate), to ban a quite narrow and not really
| clinically useful subfield called "gain of function
| research".
|
| Why can't our legal system deter the obvious high-level
| publicly visible perpetrators of the recent "gain-of-
| function" fiasco is really some food for thought.
| shadowgovt wrote:
| As a general rule, we don't arrest people for things that
| aren't illegal.
|
| ... Unless by "deter" you just meant "make it illegal,"
| in which case, agreed.
| lettergram wrote:
| It's more than broad weaponization of viruses that are a
| danger though.
|
| Take for instance what we're doing with plants. We make
| designer plants that provide food, and are immune from
| particular pesticides. We then spray the fields and all
| the other plants and bugs die (besides the immune
| plants).
|
| What happens when it turns out some genetic inserts in
| the corn creates something like mad cow disease (but in
| humans) 3-5 years later? Turns out some protein the corn
| produced we thought was harmless caused massive issues.
|
| Genetics has massive implications even if well meaning.
|
| I think the ability to eliminate disease is massively
| powerful and a net good. That said, I'm concerned about
| the long term tail end risks of such work.
|
| I don't think you can ban it, because someone will do the
| work. And those that do the work will get a competitive
| advantage (eventually letting them "win"). I think it's
| about mitigating risks by reducing / limiting mass
| adoption of genetic based technology without a very long
| window of analysis.
| filoeleven wrote:
| > I think the ability to eliminate disease is massively
| powerful and a net good.
|
| One real-world example of this is genetically modifying
| the American Chestnut by splicing in genes of the
| Japanese Chestnut, which is resistant to the blight since
| it co-evolved with it. The resistance comes from how
| Japanese Chestnut trees respond to oxalis acid by walling
| it off, preventing the fungus from spreading.
|
| > That said, I'm concerned about the long term tail end
| risks of such work.
|
| One bleak science fiction novel that takes place in this
| kind of future, specifically an amped-up version of the
| corporate GMO food crop meddling you referenced, is The
| Windup Girl by Paolo Bacigalupi.
| BurningFrog wrote:
| How could genetics research kill all humans?
|
| Asking for a friend.
| [deleted]
| PicassoCTs wrote:
| Eh, life forms can have a exponential growth curve, so
| virologist and bacterial genetic research can easily kill
| a large part of the population. But then we are well on
| the way for that, so who cares?
| BurningFrog wrote:
| Developing a virus that kills a certain ethnic group
| seems like it could be possible.
| PicassoCTs wrote:
| One could even craft a virus that is targeting a certain
| behavioral anomaly like sociopathy, if its genetically
| clearly identify-able. All one would need is a proof-able
| potent carrier virus and once could reign in the
| destructive potential of humanity.
|
| "No more bad boy behavior, or the bad boys vanish from
| the surface of the earth." behavioral deterrence via a
| biologic weapon.
|
| What a fascinating nash equilibrium, the unsocial
| monsters, forced to be social, including applying gentle
| pressure, so they do not become history like there
| victims of the past. What a concept..
|
| Then it mutates and kills us all..
| meowface wrote:
| >One could even craft a virus that is targeting a certain
| behavioral anomaly like sociopathy, if its genetically
| clearly identify-able.
|
| It isn't, and I'd be surprised if it ever could be. There
| will always be statistical correlations (especially when
| looking at multiple genes in combination) but you can't
| conclude what a person's brain and mind are like just
| from their genome.
| shadowgovt wrote:
| Probably not. Genetics isn't nearly as clean a people
| imagine it to be.
|
| Much easier to target one individual (and their whole
| host of genetic factors) than to target one genetic
| factor that can be associated with an ethnic group and
| pray that it doesn't either also express itself in an
| undiscovered way in other ethnic groups or have knock-on
| effects or the potential to mutate.
|
| We aren't as genetically different as people imagine, and
| this sort of approach would be absolutely playing with
| fire.
| epgui wrote:
| That's wildly over-apocalyptic for such a general
| statement. (biochemist)
| hoseja wrote:
| Nonono that would be lovely, finally some evolutionary
| pressure. What's the real threat is breeding obligately
| obedient citizenry and immortal leaders. Which is the first
| thing practical genetic engineering will probably be used
| for.
| [deleted]
| GenerocUsername wrote:
| I feel like this type of medicine is more like a research study
| waiting for a perfect match patient than it is highly
| personalized treatment...
|
| Is this technique broadly applicable? Or limited to very
| specific cases
| christkv wrote:
| Its coming within the decade for cancer vaccines. The trick
| is to be able to scale production and lower the turnaround
| time.
| DoreenMichele wrote:
| It looks to me like a somewhat unique opportunity to risk it
| because without this treatment, she was dead anyway and in
| fairly short order. So it was a means for them to learn
| something with very little potential downside. Worst case
| scenario: The treatment kills her. And she was dying anyway.
|
| From the article:
|
| _In Alyssa 's therapy, each of the base edits involved
| breaking a section of genetic code so it no longer worked.
| But there are more nuanced applications where instead of
| switching an instruction off you can fix a defective one.
| Sickle-cell anaemia, for example, is caused by just one base
| change that could be corrected._
|
| And I already quoted (in my previous comment) the next
| paragraph that indicates they are already doing trials. This
| is potentially a big deal and they seem to be pursuing it in
| a very reasonable and conservative fashion, which is always
| something that concerns me with this type thing. There's a
| lot of potential for terrible and horrifying abuse and that
| is not what I am seeing described here.
| runnerup wrote:
| Seems like this particular version of gene editing only
| works with blood/marrow disorders? If someone had a single
| mutation affecting their colon or eye, would the same
| technique be appropriate?
| markus92 wrote:
| Blood/bone marrow is relatively easy as you have a very
| clear delivery vehicle for your modified genes. Actually
| getting to the colon cells or retina is a lot harder,
| can't just inject it into the blood and expect it to end
| up in the right place.
| pbronez wrote:
| Yeah, those are valuable opportunities. You have to take
| risks to learn, but human life is to valuable to risk.
|
| I remember looking into the state of the art around in
| utero and neonatal health when we got pregnant. I was
| astonished at how limited the knowledge is. I quickly
| realized the big gaps are just because it's too risky to
| study. You can't morally experiment on pregnant people and
| infants.
| gizmo686 wrote:
| A "problem" with this treatment is that, for most patients,
| the current standard of care works. To the extent that this
| treatment is effective, it is likely effective for most
| leukaemia patients, including those who would respond well to
| current treatments. It is very plausible that this treatment
| (or a refined version of it) will eventually be shown to be
| superior to the current standard of care, in which case it
| would become the standard of care, and the current treatment
| will be relegated to the niche patient that does not respond
| to gene edited t-cells.
|
| More broadly, the technique of precisely editing DNA of
| select cells to perform specific engineered tasks is very
| broadly applicable. But that is a technique for developing
| treatments, not a treatment itself.
| noobermin wrote:
| Remember what "works" means in this case. Chemotherapy, or
| for other cancers, radiation, surgery that removes large,
| healthy parts of organs that might have a tumor.
| Chemotherapy has hosts of side effects, of course (hair
| loss, nausea, ruined immunity, CIPN, etc) some permanent
| for some people. It "works" when you look at what KPIs
| oncologists like, very reductionist things like "5-year
| overall survival" whilst you ignore things like quality of
| life both in the short term and long term.
|
| We should be moving away from chemotherapy. It really is
| poison (cytotoxin) that has "treatment" of cancer as a side
| effect, just because it will readily kill cancer cells more
| than healthy cells whilst also taking a lot of the healthy
| cells with it. But, it's the "established" standard of
| care, which many doctors built their careers on, so I
| suppose it won't go away soon.
| wholinator2 wrote:
| Surgery to remove part of an organ, followed by
| chemotherapy gave my mother a few more years of life. Are
| you suggesting there is some other alternative, currently
| accepted and understood, that would've worked better?
| Because while those side effects are terrible they are
| usually more temporary than the extension of life that
| they afford people. Face the question, would you rather
| chemo for a couple months and then live a couple years,
| or die in a couple weeks?
| tpm wrote:
| No, they are suggesting we should strive for better
| therapies.
| walkerbrown wrote:
| > will eventually be shown to be superior to the current
| standard of care, in which case it would become the
| standard of care
|
| How does this overturning occur? Do care providers agitate
| for change? Or is it typically a response to headstrong
| patients and families?
| Someone wrote:
| It starts with researchers convincing their ethical
| review board that they should be given the opportunity to
| experiment with the different approach.
|
| That's why new procedures almost always are done on
| patients who are as good as dead (gene editing to change
| one's hair color won't soon get past ethical review, for
| example, but if gene editing gets used in mainstream
| medicine, enough data may be collected to make a review
| board say it's acceptable to give it a try)
|
| The first experiments typically only prove the medicine
| or procedure works. Long term survival of the patient the
| exception. From there, it's step by step towards treating
| healthier and healthier patients.
|
| If it turns out the approach is better for the typical
| patient, patient groups (who may even have paid for part
| of the research) start lobbying for its use. If the new
| procedure is both better and cheaper, insurers also will
| lobby for it.
| throwuwu wrote:
| Isn't this treatment simply accomplishing the same thing
| that the current treatment does but in a targeted way with
| hopefully much fewer side effects? When you have cancerous
| T cells the only option is to eradicate all of them and
| start over with a bone marrow transplant. Normally that
| would mean frying them with radiation or poisoning with
| chemo which also effects a lot of other tissue. This
| treatment is supposed to only kill the T cells.
| specialist wrote:
| That's my noob understanding too. This is a more precise
| form of autologous transplant.
|
| I assume quick adoption of base editing for trickier
| cases, eg for T-cell acute lymphoblastic leukemia, like
| this patient had. Note that she had a previous
| transplant, using the more conventional treatment of her
| T cells. Just starting with base editing will be much
| less onerous to future patients.
|
| This is one tough person. Surviving chemo then two
| transplants is amazing. Just thinking about it crushes my
| heart.
|
| Source: Had bone marrow transplant 30+ years ago. My then
| experimental treatment became the default option (as
| applicable). Don't know much about biology or medicine,
| but I can repeat what I've heard and read.
| phkahler wrote:
| Wiping out your immune system and replacing it has something
| like a 50/50 survival rate even if you use your own cells.
| It's a hail Mary than usually either kills or cures.
|
| I knew a guy with cancer that had this done. He survived the
| process, but unfortunately the cells they restored him with
| were not cancer free like they thought. He died anyway.
|
| I think increasing the survival rate for these things could
| be very useful.
| l33tman wrote:
| Wiping out the recipients immune system and transplanting a
| donor system is in itself a common (advanced) practice since
| long, so the new part here is the tweaking of the donor
| system. Very interesting.
| maxerickson wrote:
| The edited cells did not replace her immune system. They
| were used to destroy it.
|
| Then after that a bone marrow transplant was done to
| restore it.
| namaria wrote:
| We are at the "assembly" stage of genetic tinkering. Manually
| changing over the 'machine code' of the cell, the linear sequence
| of physically bound instructions. I wonder what the future might
| bring in terms of higher level programming of cells.
| cactusplant7374 wrote:
| This is CRISPR, right? Or is base editing different?
| jghn wrote:
| Similar but not the same [1]
|
| [1] https://www.nature.com/articles/d41586-019-03536-x
| greesil wrote:
| Sounds like the crispr "grep" part is the same, but the
| payload does a base pair swap instead of cleaving.
| once_inc wrote:
| When is the head of the department going to do a televised
| interview?
|
| > https://youtu.be/B3xY6Ffy_wE?t=68
| smeej wrote:
| Tangential, but I wonder how long it'll be before we start
| combining these recent advances in AI with a dataset like
| Medikanren and identifying really custom treatments.
| lebuffon wrote:
| This is a wonderful outcome and amazing science and all involved
| are to be commended for saving this girl's life.
|
| However would it not make more sense to try and prevent the
| disease in society, since there is a viral component to it? It is
| a retro-virus and was first discovered in 1977. Is there even
| research on a vaccine? We have one for cervical cancer. (Hit's a
| nerve since I have a child with Lymphoma)
|
| https://www.who.int/news-room/fact-sheets/detail/human-t-lym...
| [deleted]
| MontagFTB wrote:
| It sounds like this is a continuation of work that was tested as
| far back as 2015: https://www.businessinsider.com/r-gene-edited-
| cells-keep-can...
| dossy wrote:
| Finally, debugging human software - this is the inevitable future
| we've been waiting for.
| janalsncm wrote:
| Huge news. This will save tons of people as the cost comes down.
| We are truly living in the future.
| nullish_signal wrote:
| hughes wrote:
| Are you saying Alyssa's rare form of leukemia should not have
| a cure because she and her friends in oncology might
| quadruple the planet's population?
| subroutine wrote:
| Would you trade (a) total cure for all cancer for (b) the
| human population to go from 8 to 16 billion?
|
| Yes, absolutely. Surely population growth can be dealt with
| more humanely than killing people off with cancer.
| nullish_signal wrote:
| I disagree with the notion of benevolent DOCTORS "Killing
| people off with cancer".
|
| Was the patient body full of DOW Chemical or DDT or Big
| Gulps or Pharmaceuticals[0]? industrial Society and Old Age
| are what "kill people by means of cancer"
|
| [0] USA being the only country I know of to allow public
| Advertisement of Controlled medicines
| subroutine wrote:
| I'm not sure what you're talking about. Choosing to not
| cure cancer is killing people off with cancer. The little
| girl in the article had leukemia. It sounds like you
| would prefer to let children die of cancer because of
| your weariness of population growth.
| ryanwaggoner wrote:
| I believe the world population is expected to peak this
| century, not because of people dying or starving at higher
| rates, but because when countries become more developed,
| their birth rates plummet. I don't think there's any reason
| to think curing _all_ diseases and ensuring no one ever
| starved again would change that.
| tsujamin wrote:
| Echoing a response to a nearly invisible comment above, why
| did make this comment?
|
| These sorts of articles are a weird attractor on this site...
| unlikelymordant wrote:
| You arent anti-natalist, so your view is that people should
| be born and die from preventable disease or starvation
| ("medicine and agriculture saved them")? Isnt anti-natalism
| preferable to that?
| SapporoChris wrote:
| The idea that we should not progress because we might have
| more populace is repulsive. A simple reversal of the idea is
| insightful. Should we minimalize the human population? Seems
| absurd.
| nullish_signal wrote:
| Homeostasis.
|
| I propose the DEFAULT be no growth or no decay. Of course
| it's natural for animals to spread and be fertile. Of
| course. But we already conquered and inhabited everywhere
| with land and water.
|
| Obviously Technology will advance or stall (or collapse)
| regardless of my small whims -\o/-
| FpUser wrote:
| >"What happens when there are 16 or 32 Billion people?"
|
| Not sure about other part but in the western world birth rate
| is gong down and is not enough to offset decrease of the
| population. Having people leave longer will not change it in
| any way. If we ever grow to this number it will not be
| because of curing cancer.
|
| >"Even the idea that "GDP should rise 2% every year" makes me
| nauseous."
|
| You think anybody responsible for GDP growth gives a hoot
| about what "makes you nauseous"?
| Tade0 wrote:
| Past projections of human population growth were generally
| overblown, because nobody expected e.g. China's population to
| (officially) peak this year.
|
| Meanwhile world population growth peaked in the late 60s and
| has been in decline ever since. The 21st century will likely
| see the global population reaching its limit at less than
| 11bln.
|
| That's still a lot, but not nearly as much as 16bln.
| PaulDavisThe1st wrote:
| Still, it could be like saying "Falling from the 8th floor
| is nothing like falling from the 20th", despite the fact
| that both of them are fatal.
| nullish_signal wrote:
| If 8 or more story-falls are fatal... 8-Town limits hi-
| rises to 8-Stories 20-Town limits hi-rises to 20-Stories
|
| Which Town and what Height of Buildings would you rather
| be a tenant of?
|
| ...I don't know about Human Population, but I know that
| "more code" is certainly not "better code", just as "more
| sub-systems" does not mean "more quality of code"
| d_tr wrote:
| Stop embarrassing yourself. You started by talking about
| population growth in a post about a kid's cancer, and now
| you are continuing with making stupid analogies that
| barely make sense.
|
| Getting rid of cancer will alleviate a huge source of
| suffering and despair and it will do nothing of
| consequence to the population. Even if it did we should
| not care.
| dools wrote:
| There will only be 11b people
| zamfi wrote:
| Don't worry, there's no shortage of ways to prevent getting
| to 16 or 32 billion people.
|
| First among those is that very few countries have birth rates
| that exceed replacement rates! And the others are on a very
| strong trend to follow over the next 10-20 years.
| gizmo686 wrote:
| A) We have already largely solved infant mortality in the
| developed world, and are making progress on the issue
| globally. Societies seem to adapt over time by decreasing
| birthrates to compensate [0]. In fact, in most of the
| developed world, birth rates are below replacement rate.
|
| B) Despite all of the medical advances we have made, we have
| hardly put a dent in old age. Medical science has made great
| progress in stopping people from dieing young, which has
| pushed up the average lifespan. But a 100 year old today is
| still likely to die within a few years even with the most
| advanced medical treatment.
|
| Having said that, at some point, we are likely to start
| making breakthroughs in maximum lifespan, which could very
| quickly put us back into rapid population growth. Eventually,
| we would probably see society adjust to the point that having
| _any_ children is no longer expected of a typical human, but
| that could be a painful transition depending on how quickly
| we we go from a lifespan of ~100 to unbounded.
|
| [0] Although it is not clear if this is directly related to
| infant mortality, or a response to broader economic changes,
| tluyben2 wrote:
| Where I live in the EU, people get old; 100 here is not so
| rare and there are many 90+. Most of them are healthy;
| walking the mountain for shopping daily and going to the
| bar for a shot or two in the morning. 0 of them want to
| live longer. Not because physical but because the mental
| agony of yet more time, see more horror. Think people who
| don't have this issue underestimate how bored and 'done'
| most older people are. My grandparents (all 4) made close
| to 100 in good health and wanted out since 70. When you are
| young you want to live forever, when older I don't think
| many people do.
| Aeolun wrote:
| I seem to remember reading that there is some limit to the
| age of the brain, separate from the mortality of the body.
| So even if you were to not die from any cause you'd be
| pretty much done after 150-170 years.
| delecti wrote:
| I think it's a stretch to assume we know much about what
| happens to brains after just 120, let alone 150-170.
| gizmo686 wrote:
| Setting aside any specific mechanism, the overall point
| still seems plausible. Assuming we can prevent the
| primary causes of aging (e.g. telomer shortening), we
| will likely start to find other parts of human biology
| that start to fail, either because of additional aging
| mechanisms, or just limitations of the body's self-repair
| mechanisms.
|
| Human biology is incredibly complex, and there has been
| no evolutionary pressure for it to sustain itself beyond
| its natural biological clock. These problems are probably
| solvable eventually, but not until we live long enough to
| see them. Which problems means we will have at least a
| few generations of people die after the initial old-age
| cure.
| nullish_signal wrote:
| The guesses at what culture might look like in a fully-
| populated planet, beyond the reduction of birth rates, is a
| very interesting consideration.
| nullish_signal wrote:
| I must add, a reply to my moaning about limitless
| exponential human growth that starts off with
|
| "We have already largely solved infant mortality in the
| developed world, and are making progress on the issue
| globally."
|
| ...certainly makes me feel feelings about population
| growth!!
| Dylan16807 wrote:
| The immediate feelings you had before you read the second
| sentence are not good conversational material.
| tluyben2 wrote:
| You have a lot of feelings about stuff that is. As I get
| older, that seems incredibly unproductive and I stopped
| doing that.
| bglazer wrote:
| You first
| ekianjo wrote:
| Better to have more people than to be on the down slope of
| demography where the world world ages faster and faster
| mmsc wrote:
| I thought the same thing initially, then I realized that rare
| forms of cancer are... rare. Not that many people die from
| them to cause a significant increase (or lack of decrease) in
| the population.
| tptacek wrote:
| You can't simultaneously be pro-natalist and anti-
| exponentialist, at least not without being a Bond villain.
| daniloalmeida wrote:
| I just read the title to get hopeful. Now I'm in the comments to
| be realistically disappointed.
| klipt wrote:
| > The team at Great Ormond Street used a technology called base
| editing, which was invented only six years ago.
|
| Fun fact: J M Barrie who wrote Peter Pan donated the copyright of
| both the book and play in perpetuity to Ormond Street children's
| hospital. It's been a significant source of funding for them over
| the years.
| Semaphor wrote:
| > It's been a significant source of funding for them over the
| years.
|
| TFA:
|
| > Still, best estimates are that it's not a hugely important
| part of the hospital's budget.
|
| which links to The Guardian [0]:
|
| > The hospital has abided by Barrie's wishes expressed in his
| will and always kept the proceeds from Peter Pan a closely
| guarded secret. With copyright expiry looming, De Poortere is
| at pains to point out the revenues are "significant", but not
| as great as many suspect.
|
| > "People who talk about millions a year have a strange idea of
| what a character is worth," she says. "On the whole, it's been
| significant but I wouldn't call it huge. I am on my own doing
| the Peter Pan administration, but I am part of a charity that
| has 100 people."
|
| > If the newspapers of 1929 were right about proceeds of
| PS2,000 a year, that would be PS90,000 a year in today's money,
| according to the Office for National Statistics.
|
| Just to expand ;)
|
| [0]:
| https://www.theguardian.com/business/2007/dec/28/gtormondst
| monero-xmr wrote:
| ShamelessC wrote:
| what in the actual fuck
| sgc wrote:
| You need to avoid spending the principal + inflation, which
| is significantly harder to do.
| hilbertseries wrote:
| Why did you make this comment?
| monero-xmr wrote:
| Regarding donations - you should donate assets that will
| produce cash for infinite time. Pure cash donations that
| are unencumbered are foolish, IMO.
| jacobriis wrote:
| AI that filters insane non-sequitur personal anecdotes from
| HN comments cannot come soon enough.
| sph wrote:
| Leave AI out of forums for humans, please. They are not
| welcome here.
| guiambros wrote:
| ChatGPT?
| hn_throwaway_99 wrote:
| Thanks very much for posting this tidbit, very interesting!
|
| After seeing your comment I did a little googling, and
| fascinating to me is that a special law was passed in the UK
| specifically to make one of the Peter Pan copyrights held by
| Great Ormandy Street never expire:
| https://www.plagiarismtoday.com/2015/10/21/peter-pan-and-the...
| jv22222 wrote:
| Huh, very cool. I had never imagined there would be a
| scenario where I was genuinely happy about a never ending
| copyright!
| Dylan16807 wrote:
| Keeping some stories out of the public domain forever is a
| pretty terrible way to fund something.
| [deleted]
| eyelidlessness wrote:
| Don't worry, Pan never wanted to grow up.
| sph wrote:
| I dunno, if it saves some children's lives, instead of
| Disney trying to make it another blockbuster franchise,
| that's perfectly fine by me.
| bambax wrote:
| Taking away freedom is always about "saving children's
| lives". It's so common in fact that the instant one hears
| about "saving children's lives" we can be certain
| something very bad is going to happen.
| johngalt_ wrote:
| I am not a big fan of copyright myself, but calling being
| unable to use someone else's story for yourself "taking
| away your freedom" is a bit too much.
| bambax wrote:
| Isn't it obvious where this could be going? Let's save
| more children's lives by making all copyright infinite.
| foldr wrote:
| I mean, no? There is absolutely no indication that that
| particular slippery slope is being slid down. Can you
| even point to anyone advocating for infinite copyright on
| all works on the basis of the Great Ormond Street
| example?
| Dylan16807 wrote:
| Not if you really believe in the concept of public
| domain. Old stories should belong to everyone, not
| "someone else".
| pastacacioepepe wrote:
| The proper solution would have been for the state to fund
| the hospital as needed, while freeing everyone else to
| create content based on Peter Pan if they wished so.
| namaria wrote:
| Civilization is made of unsavory compromises... Funding
| by taxation and committee spending, or by fetishisation
| of conspicuous consumption are also pretty bad and yet
| quite prevalent.
| jonsen wrote:
| Agree, there should be other ways in a modern society.
| [deleted]
| musicale wrote:
| In this case the copyright seems to have expired
| essentially everywhere, but a special UK extension for
| Peter Pan allows for royalty collection for performances or
| adaptations of the play there in spite of the copyright's
| expiry.
| jordanbeiber wrote:
| I've started watching star-trek (as it makes me fall asleep
| immediately) - this stuff sounds like a star-trek episode!
|
| Something Dr Crusher would come up with.
|
| It makes a distant future where we quickly engineer a fix and
| inject it seem almost plausible.
| rmak wrote:
| Closer to star gate sg1 episode than star trek, I love that
| series.
| unsupp0rted wrote:
| It is something Dr. Crusher came up with:
|
| > Barclay's Protomorphosis Syndrome
|
| > Attempting to cure Lieutenant Reginald Barclay of his
| Urodelan flu, Dr. Crusher used synthetic T-cells to activate
| the gene that would fight off the infection. However, an
| anomaly in Barclay's genetic structure caused the T-cell to
| mutate and activate all of Barclay's dormant genes, including
| his introns. The T-cells then became airborne, spreading
| throughout the ship like a virus and causing the crew to "de-
| evolve."
|
| https://memory-alpha.fandom.com/wiki/Barclay%27s_Protomorpho...
| yread wrote:
| wow it goes from ok to completely nuts within one sentence.
| Activated introns hahaha
| namaria wrote:
| Oh man I love getting high and watching the original Star Trek.
| All the imagined analogue computer technology makes me
| wonder...
| system2 wrote:
| Dr. McCoy would've given green alcohol.
| ars wrote:
| Is there any worry/chance that the modified T-cells will survive
| and multiply in the body instead of dying out?
| gizmo686 wrote:
| I'm talking well beyond my competency, but short of one of
| those T-cells spontaneously becoming cancerous itself, I don't
| see how. T-cells do not duplicate themselves. Instead, new
| T-cells are creates in bone marrow. Since they are not editing
| the genes in the bone marrow, there is no mechanism within the
| body to create new cells using the modified DNA.
| hliyan wrote:
| Great to see medical techniques slowly starting to resemble
| engineering design:
|
| 1. Donor T-cells added with receptors to destroy the recipient's
| cancerous T-cells.
|
| 2. Donor T-cells' markers removed to prevent them from attacking
| each other.
|
| 3. Donor T-cells' existing receptors removed to prevent them from
| attacking the recipient's other cells (since the donor T-cell
| will see them as 'foreign').
|
| 4. Donor T-cells altered to resist chemotherapy.
|
| It seems each of these changes were achieved by editing specific
| base pairs to _break_ the relevant gene, except perhaps for (1)
| adamredwoods wrote:
| To even have something like this actually respond, in the way
| they planned it, is a marvel. I know they have worked with
| T-Cells before, but this is putting it to precise use.
|
| Sadly, cancer is vicious. It only takes one rogue cell to keep
| building, about 2-years for it to surface again. Luckily, this
| process seems repeatable.
|
| I can't imagine the euphoria that family feels right now.
| beaned wrote:
| Do people with base-edited DNA pass their modified genes on to
| their offspring?
| elektrontamer wrote:
| Germ cells need to be edited for that. The edited T cells can't
| get inherited.
| gizmo686 wrote:
| No. The only DNA that gets passed to offspring is what is in
| the sperm/eggs. Collectively these are referred to as the
| "germline". Research into germline editing is illegal in the
| US, and frowned upon internationally.
|
| The most famous case is from 2018, when Chinese researcher He
| Jiankui created the first genome-edited babies. Using CRISPR to
| give the babies resistance to HIV-1. [0]. This change will
| propagate to the decedents of the subjects [1]. The Chinese
| Academy of Science, along with the global medical community,
| denounced this experiment; and He Jiankui was arrested.
|
| [0] The necessary mutation, while rare in humans, is naturally
| occurring, and generally thought to confer HIV-1 resistance.
|
| [1] Subject to normal genetics that arrises from sexual
| reproduction, where a given parent is responsible for only half
| of a child's genes.
| NaturalPhallacy wrote:
| > _Research into germline editing is illegal in the US, and
| frowned upon internationally._
|
| I would bet money someone's doing it anyway.
| hooloovoo_zoo wrote:
| Marvelous! I wonder why she needs a second transplant though.
| Izikiel43 wrote:
| The base therapy basically removed her immune system, the
| second transplant recreated it.
|
| In software terms, they did a clean install of the immune
| system after formatting it.
| uwagar wrote:
| treating biology as software isnt gonna end well.
| t-3 wrote:
| It's explained in the article that the second transplant is
| necessary to replace the white blood cells which should have
| been fully wiped out by the first transplant of modified cells.
| b800h wrote:
| But her body ought to start manufacturing her original
| T-cells at some point, right? Or are the stem cells producing
| them cancerous too? Doesn't say that in the article, and it
| doesn't seem like a reasonable inference, so there's a bit of
| detail missing there.
| sowbug wrote:
| Even if the self-manufactured cells were healthy, the
| patient is vulnerable to infection with a compromised
| immune system, and adding more white blood cells reduces
| that vulnerability.
|
| Tangent: before undergoing some kinds of chemotherapy,
| patients are injected with drugs that stimulate white-
| blood-cell production. Most of your body's WBC production
| happens in the long bones of your body, and the sudden
| burst of "factory" activity makes your legs ache, the way
| growing pains hurt in children.
| hooloovoo_zoo wrote:
| But why can't the modified cells function as regular T cells
| in addition to the modifications?
| zaroth wrote:
| I think they don't usually last that long. The body won't
| keep producing the modified cells.
|
| Plus I think the modification made them basically only good
| for killing the native (cancerous) T cells
| hooloovoo_zoo wrote:
| Could be. It would be nice if you could maintain the
| modification though because then you don't have to worry
| about some cancerous cells surviving the first wave.
| frontierkodiak wrote:
| The article states "The first base edit disabled the
| T-cells targeting mechanism so they would not assault
| Alyssa's body". Not an expert but I presume the 'targeting
| mechanism' is the T-cell receptor, whose activation is
| necessary (but not sufficient) to trigger immune response.
| hooloovoo_zoo wrote:
| Maybe, but the second transplant also needs to not
| assault Alyssa.
| Narretz wrote:
| The second transplant is a stem cell (bone marrow)
| transplant, i.e. it replaces the cells that produce the
| t-cells.
|
| This is how leukemia therapy is normally finished after
| chemotherapy / radiation therapy kills the cancer cells.
| ggm wrote:
| In heroic medical science history fiction it's a bit of a trope
| to write "the operation was a success but the patient died"
|
| I sincerely hope she survives at least 5 years, and significantly
| more. If she gets only a single year of treatment -free high
| quality life outside of respite care, that would be a bitter pill
| outcome but might still be held a success. Sometimes giving
| people a year of quality life at end-of-life is a good outcome.
|
| The article as written is light on for data and time info. She's
| had at least 3 post treatment checks one of which was 3 months,
| the other 2 not stated but 6monthly might not be unusual.
|
| Recurrences in blood borne diseases are not unheard of. She had
| some signs of recurrence at 3 months but it went away. Maybe
| fragment traces? Non viable remainders flushing out of the
| marrow? (I don't know if this is even plausible. I'm not in
| medicine)
|
| It's great news, but so was Christian Barnard's first transplant.
| In modern terms the survival wasn't very long. (200 days in the
| first 4)
|
| A better outcome would be like Steptoe's work on assisted
| conception and birth. (IVF) and I certainly hope she and future
| patients have that.
| ausbah wrote:
| is there any specific reason to think this disease could come
| "roaring back" aside from general unknowns of a new treatment?
| epgui wrote:
| The fact that she developed cancer in the first place means
| that she is more likely to continue developing cancer, via a
| plethora of mechanisms. Cancer is always just a matter of
| time, for all of us. Subtle mutations accelerate the
| timeline, and they accumulate over time.
| uwagar wrote:
| thdespou wrote:
| Noone is forcing you to accept anything. If else the girl and
| parents had to make that decision and accept the risks. They
| would probably had to sign a legal document as well. Maybe you
| need to chill out of the conspiracy mindset.
| uwagar wrote:
| lol. said the same thing about covid vaccine and then brought
| in the mandates.
| Doorstep2077 wrote:
| This looks pretty great, hopefully a huge step forward for the
| medical industry and finding cures for cancer. Unfortunately
| don't know too much about it; wish there was something that
| allowed me to learn about medical problems easily, without
| needing to understand the jargon
| ricardobeat wrote:
| Very similar report by the same author from 2015:
| https://www.bbc.com/news/health-34731498
|
| It doesn't explain what "designer immune cells" were, so it's
| hard to tell what's different in this more recent treatment.
| Duller-Finite wrote:
| that study used TALENs; this one used CRISPR base editors
| thewatcher23 wrote:
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