[HN Gopher] FDA approves a CRISPR-based medicine for treatment o...
___________________________________________________________________
FDA approves a CRISPR-based medicine for treatment of sickle cell
disease
Author : divbzero
Score : 503 points
Date : 2023-12-08 17:56 UTC (1 days ago)
(HTM) web link (www.statnews.com)
(TXT) w3m dump (www.statnews.com)
| trident5000 wrote:
| Pretty big news. I believe this is the first gene editing therapy
| approved by the FDA and theres a large backlog thats been in the
| works for many years. Id like to see the flood gates really open
| up for gene editing for diseases, preventative treatments, and
| even cosmetic.
| csdvrx wrote:
| > Id like to see the flood gates really open up for gene
| editing for diseases, preventative treatments, and even
| cosmetic.
|
| Me too, because it's fun to consider DNA as some code we can
| edit to get outcomes we want!
|
| However, some people are ethically opposed to that - but
| piggybacking on the preference people have for having children
| should be able to move the Overton window!
| trident5000 wrote:
| It really is inspiring. Yeah I take the opposite side,
| ethically speaking. I think its cruel to not allow people to
| fix their bodies in the ways they want and in many cases
| need. Im in the max body-editing camp. Also this should
| resolve race issues once and for all which is fun to think
| about.
| lotsofpulp wrote:
| > Also this should resolve race issues once and for all
| which is fun to think about.
|
| I doubt it. One of the root causes of "race" issues is
| humans using prior probabilities. Unless that changes, then
| the priors will simply move on from being skin tone based.
| I would suggest they already have for some portions of the
| population.
| JumpCrisscross wrote:
| > _some people are ethically opposed to that_
|
| Body autonomy may be a fundamental right requiring legal
| recognition. It curiously cuts across many protracted
| debates: abortion, vaccine requirements, transgender rights
| and now gene editing. (I suppose abortion and germ-line edits
| are a special case.)
| elektor wrote:
| Now comes the hard question, how will the US payer system afford
| it?
|
| "An August report from the nonprofit Institute for Clinical and
| Economic Review found that the treatment and similar gene-editing
| therapies for sickle cell disease would be cost-effective if
| priced between $1.35 million and $2.05 million. In the U.S.,
| patients with the condition and their insurers pay on average
| between $1.6 million and $1.7 million for disease management over
| the course of a lifetime." Source:
| https://www.politico.com/news/2023/12/08/fda-gene-editing-th...
| trident5000 wrote:
| Any new product is going to start out as expensive and this
| likely isnt a market realized price. This is the first of its
| kind. It probably still wont be cheap but its not going to be
| this absurdly priced in the future considering even the
| insurance companies likely wont pay for this.
| huytersd wrote:
| You answered your own question. The taxpayer already pays the
| same amount for lifetime treatment. This is just going to be
| the same except the person can lead a completely normal life
| after this. Also over time this will probably be much, much
| cheaper than the current lifetime treatment. There's no reason
| a lot of the process can't be easily automated.
| elektor wrote:
| No, I did not "answer my own question". These therapies are
| priced at $2.2 and $3.1 million, much greater than their
| calculated cost-effective price. And these are not small
| molecules that can be easily made generic, so not likely to
| get that much cheaper over time.
| maxerickson wrote:
| Plasmid production is pretty well industrialized. Lots of
| biotech drugs/treatments ferment plasmids as a step in
| their process (for example the Covid mRNA vaccines that
| cost $25).
|
| I imagine an expensive part of this process is incubating
| the treated stem cells to increase their numbers, and then
| just the cost of the hospital time while the new cells
| establish and the patients immune system recovers from the
| chemotherapy.
| MiddleEndian wrote:
| Lots of AI content recently (and I am working on AI-adjacent
| stuff myself lol), but I am most excited for upcoming medical
| changes. Cure every disease, then let people have designer bodies
| if they like.
| bigfishrunning wrote:
| I can't wait to grow all those extra fingers and teeth!
| evrimoztamur wrote:
| You might enjoy Cronenberg's Crimes of the Future if that idea
| is appealing to you. Very curious execution of a disease-free
| bio-tech (organ-ic-tech?) future.
| foco_tubi wrote:
| I just wanna be able to digest plastic
| numtel wrote:
| I was wondering about new digestive capabilities recently
| and wrote this blurb:
|
| https://clonk.me/nft/137/0x8abd8d9fab3f711b16d15ce48747db49
| 6...
|
| If we could eat different things, we could give up
| agriculture and save a bunch of land and energy.
| MiddleEndian wrote:
| Speaking of digesting random things, I found myself bored
| in the shoe section of some store (I wanna say Nordstroms),
| and I was curious if I could eat the leather shoes. Beef is
| beef, right? Apparently you cannot digest leather due to
| the chemicals involved in the curing process.
| selcuka wrote:
| > I was curious if I could eat the leather shoes. Beef is
| beef, right?
|
| This was a recurring theme in Lucky Luke [1]. The titular
| hero cooks and eats his boots when he faces starvation,
| usually when he gets lost in the desert.
|
| [1] https://en.wikipedia.org/wiki/Lucky_Luke
| huppeldepup wrote:
| why digest plastic if you can photosynthesise
| MiddleEndian wrote:
| I'm a big Cronenberg fan but I haven't seen this one (these
| ones? as there seem to be two). Would you recommend the 1970
| or the 2022 version?
| evrimoztamur wrote:
| Sorry, I wasn't even aware of 1970.
|
| They are apparently unrelated, it is 2022 that I was
| referring to.
| MiddleEndian wrote:
| Excellent, thanks!
| z7 wrote:
| Why stop there?
|
| https://en.wikipedia.org/wiki/Eradication_of_suffering
| AmericanChopper wrote:
| Why stop there?
|
| https://en.m.wikipedia.org/wiki/Gattaca
| __loam wrote:
| I think we're pretty far away from designer bodies. We might
| solve a lot of cancer in our lifetimes though.
| neverrroot wrote:
| Yet another first. Approved, looking forward to more such
| products, in spite of everything and all the short-term issues,
| long term is an absolute game changer across the board.
| KyleSanderson wrote:
| Lyfgenia's approval came with a black box warning about the
| possibility that patients who receive the therapy might later
| develop blood cancer and should be monitored for that risk. Two
| patients in trials of the drug died of blood cancers, and studies
| concluded that the cancers were caused by the chemotherapy
| conditioning regimen for the treatment, not Lyfgenia itself.
| confused_boner wrote:
| >the cancers were caused by the chemotherapy conditioning
| regimen for the treatment, not Lyfgenia itself.
|
| I am certain some media group is going to conveniently leave
| this part out of the title of their article, and surely no one
| is gonna waste time reading the actual article and the rumors
| will take off.
| jorlow wrote:
| The article says "patients must undergo a preparatory
| treatment with a chemotherapy drug to remove any native stem
| cells that might remain in their bone marrow." It doesn't
| make much difference to the patient if it's the Lyfgenia
| itself or the chemo drug, if the chemo drug is a requirement.
| Right?
| eszed wrote:
| Fair enough, but there remains the possibility of finding
| an alternate, safer chemotherapy drug.
|
| Does anyone know if changing the drug would require a new
| FDA approval for the entire regimen, or could the protocol
| be easily changed?
| firejake308 wrote:
| It's reasonable to expect small improvements in the risk
| profile, but I think blood cancer is going to be a side
| effect for any drug following this basic idea. You will
| always need some chemo to destroy the defective blood-
| making stem cells before replacing them with the
| genetically-modified blood-making stem cells, and any
| chemo that is strong enough to kill all of the blood-
| making stem cells in your body is necessarily going to
| have a risk of damaging healthy cells and turning them
| into pre-cancer cells. So the risk can be reduced but
| probably not eliminated.
| eszed wrote:
| That makes sense. Thank you.
|
| In theory, could a separate gene therapy target and knock
| out the stem cells that carry the mutation?
| skissane wrote:
| > Does anyone know if changing the drug would require a
| new FDA approval for the entire regimen, or could the
| protocol be easily changed?
|
| The FDA-approved prescribing information will recommend a
| particular chemotherapy regimen, but clinicians will be
| free to substitute alternatives if they believe those are
| clinically superior. They won't need permission from the
| FDA or the manufacturer to do that; clinicians deviate
| from the FDA-approved manufacturer recommendations all
| the time ("off-label prescribing").
|
| If the manufacturer wants to update the official
| recommendations in the prescribing information, then
| they'll need FDA approval for that. But it is possible
| for clinicians to publish their own treatment guidelines
| (e.g. in medical journal articles), independent of the
| manufacturer, and the FDA has no control over those.
| eszed wrote:
| What a weird system: there's something better, but the
| manufacturer _isn 't allowed to tell you about it_. What
| if they, like, slide the journal article across the desk,
| whilst holding their finger alongside their nose and
| winking?
| skissane wrote:
| > What a weird system: there's something better, but the
| manufacturer isn't allowed to tell you about it.
|
| It is the way medicine works - not just in the US, in
| most countries worldwide. Not just about gene therapy,
| about all drugs and devices.
|
| The FDA and its international equivalents (the EMA in the
| EU, the TGA in Australia, etc) regulate the
| manufacturers, not the clinicians. They control what the
| manufacturers sell and even what the manufacturers are
| allowed to say about their products (in product
| packaging, prescribing information, advertisements and
| marketing collateral). They don't control what the
| treating clinicians do with those products - to the
| extent that is regulated, it is the job of other
| regulatory agencies (e.g. professional licensing boards,
| civil courts hearing medical malpractice claims, etc)
|
| > What if they, like, slide the journal article across
| the desk, whilst holding their finger alongside their
| nose and winking?
|
| What they'll do instead: there will be a conference where
| (among other things) the journal article author will
| present their findings/recommendations, and the
| manufacturer will sponsor (and hence help pay for) the
| conference. They never actually said anything, they just
| made sure you were there to hear about it.
|
| I'm not a doctor but my mother is. When I was a teenager,
| she'd be invited to these free dinners at fancy
| restaurants paid for by pharmaceutical companies, and a
| couple of times they allowed her to take me along (she
| was allowed to bring her spouse/partner to some of them,
| so she just asked "can I bring my teenage son instead"?).
| During the dinner, some academic would do a presentation
| on their research into how wonderful one of the company's
| drugs was, and also do some Q&A. So the manufacturer
| wasn't technically saying anything, everything was said
| by some academic (whose research they were funding). I
| didn't understand it all, but I found it rather
| interesting. Still didn't follow her footsteps into
| medicine though (although my younger brother has).
|
| But, she tells me the regulators have cracked down on
| free perks from pharmaceutical companies, so they are
| forced to be a lot less generous nowadays than they were
| back in the 1990s. (This is not the US though, this is
| Australia.)
| confused_boner wrote:
| I was thinking more that it could poison the reputation of
| gene therapy by causing folks to falsely associate cancer
| with gene therapy. And that false stigma could carry on
| even if one day chemo was no longer needed.
| skissane wrote:
| There is active research on doing gene therapy without
| requiring chemotherapy (or radiation) first. It has been
| shown to work in mice, and they may eventually get it
| working in humans too. It would likely require a
| significant modification to these gene therapies though,
| since one approach is to alter the method of growing the
| stem cells to produce a significantly higher number, and
| then transplant that, with the hope that the transplanted
| edited cells outnumber and outnumber the original unedited
| ones. So very likely the FDA would treat that as a new
| therapy requiring a new approval process.
|
| https://med.stanford.edu/news/all-news/2019/05/radiation-
| fre...
|
| There is also ongoing research into immunotherapy for
| killing stem cells, as an alternative to the existing
| methods of chemotherapy and radiation. Potentially,
| immunotherapy could have significantly reduced secondary
| cancer risk.
|
| https://jhoonline.biomedcentral.com/articles/10.1186/s13045
| -...
| SamBam wrote:
| > Vertex set the price of Casgevy at $2.2 million
|
| > Patients must spend weeks, even months, in the hospital before
| and after the therapy is administered.
|
| Yoiks. So how many actual people are going to be able to get this
| treatment?
| coldpie wrote:
| Indeed. The good news is, it actually turns out to be about the
| same or cheaper than ongoing treatment of a untreated sickle
| cell:
|
| """Each treatment is an individualized "one-off" treatment. For
| this reason, a single treatment for a single patient is
| expensive. At present it is estimated that in the UK treatment
| will cost PS1 million or more. In the US the estimated cost is
| $2 million.
|
| That may seem prohibitive, but we need to consider the overall
| cost-effectiveness of the treatment, which means comparing the
| cost of treatment to the cost of managing each disease without
| the treatment. Sickle cell patient require frequent
| hospitalization, which can be very expensive. One analysis
| found that Casgevy can be cost effective at PS1.5 million or
| $1.9 million. This is in range of the estimated cost. Also, the
| longer the treatment benefits last, the more cost effective the
| treatment becomes. A lifetime of transfusions or hospital
| admissions adds up."""
|
| https://sciencebasedmedicine.org/first-crispr-treatment-appr...
| BurningFrog wrote:
| Not quite true: Identical twins/triplets/etc, can reuse the
| same cure.
| thereisnospork wrote:
| > it actually turns out to be about the same or cheaper than
| ongoing treatment of a untreated sickle cell
|
| If I were a betting man I'd wager the house that the above is
| exactly why it costs what it does. 'Pay 2 million now, or pay
| 2 million over the rest of the patient's life as they suffer'
| is a pretty inarguable value proposition.
|
| Of course once patents expire and processes refine prices
| will come down. The wheel of progress rolls on (more of less)
| as intended.
| ericmay wrote:
| This is Day 1 so the price and how well it works _today_ is
| almost certainly the worst it will ever be. Insurance will
| likely cover the cost. It 's a very bad, painful, and outright
| deadly genetic mutation and $2.2 million is practically
| _nothing_ compared to doubling someone 's lifespan or giving
| them an extra 10 years.
|
| More info I found relevant regarding cost for typical treatment
| and out of pocket estimated costs:
| https://www.hematology.org/newsroom/press-releases/2022/the-...
| ponector wrote:
| I don't agree that it is nothing. 2 millions, if applied
| properly, could do good for many people. Take ten children
| from poverty, give ten children chance to get a good
| education, etc.
|
| There is always a some kind of moral dilemma: should you
| spent millions to try to extend extremely I'll person or help
| with that money to some healthy poor children?
| dopa42365 wrote:
| It's possible to do both :)
| lotsofpulp wrote:
| How? Society does not have unlimited resources.
|
| Especially the one that extremely ill people need,
| humans.
| huytersd wrote:
| People with sickle cell already cost the taxpayer _a lot_
| of money over their lifetimes. I wouldn't be surprised if
| it cost more than this treatment.
| lotsofpulp wrote:
| Of course, in that case it is simple. I imagine dopa42365
| was referring to a scenario where there was an
| alternative way to spend the money.
| ponector wrote:
| Possible in theory. But real life shows neither will be
| done in enough quantities.
| esturk wrote:
| Such a crass statement. What if you're the patient? Would
| you spend 2 million to live 30-40 more years? It's so easy
| to step back and weight the lives of other as if you're
| making the decision for others.
| lotsofpulp wrote:
| The $2M represents a certain portion of society's
| productivity, which is not unlimited.
| dragonwriter wrote:
| Yes, but spending it preventing debilitating disease that
| would cost about the same amount over the lifetime of the
| sufferer is a no-brainer, even in net econonic output,
| terms.
| ponector wrote:
| But it is so only for few countries with ridiculously
| high costs of medical services. What about other? If we
| are talking about someone from south America?
|
| 2m is much higher that either costs or economical output
| the treated person could deliver through lifetime.
| soulbadguy wrote:
| > What if you're the patient?
|
| What if you are on those 10 poor kids he mentioned ?
|
| I don't agree that OP statement is "crass". It's a very
| pragmatic and important question we have wrestle with.
| esturk wrote:
| Except those 10 poor kids aren't spending their own money
| to save themselves. The patient is though which is the
| point.
| soulbadguy wrote:
| if it's their own money sure.
|
| But almost all care services end benefiting from some
| sort of subsidies. Even if just by increasing the cost of
| inssurance for the rest of the population
| arcanemachiner wrote:
| The median income in America is a little under $40000 per
| person[1], so that $2.2 million pretty much represents
| the entire financial income of the average American over
| a working lifetime (55-60 years).
|
| So in essence, you'd be trading the equivalent of one
| person's entire lifetime of productivity in exchange for
| the first generation of a radical new medicine whose
| outcome is unknowable.
|
| I don't think it's crass to err on the side of caution
| for such a scenario.
|
| [1] https://en.m.wikipedia.org/wiki/Per_capita_personal_i
| ncome_i...
| vidarh wrote:
| These people mostly do get treatment now, for decades,
| involving regular expensive long term hospital stays. So
| you're trading already expensive treatments that cut
| their earnings potential drastically both by cutting
| number of productive years but also due to extensive sick
| leave.
|
| So if there even is an increase in the total cost of
| treatments, it's not at all a given it's a a net increase
| once account for decades of additional working life.
| imtringued wrote:
| I see you are a fan of the MAiD program in Canada.
| ponector wrote:
| Of course I will do anything to prolong life of myself
| and my family, like any human being.
|
| But as a society with limited resources we need to set
| priorities. I hope everyone will be able to receive
| treatment.
|
| However, such treatment is only for rich people, or from
| rich countries.
|
| Even some countries in Europe are not reach enough to pay
| for such medicine. Like Zolgensma, which also costs
| around 2 millions USD to cure SMA.
| ben_w wrote:
| Crass, sure.
|
| Not sure it's really easier though, economics and
| emotional affect are often at odds. Ask people if a
| hospital administrator should spend 100k on either a
| single liver transplant for an 11 year old girl, or
| spread over 100 less expensive life saving interventions
| for 50 year olds, most people will say save the girl _and
| demand the administrator be fired for even needing to
| think about it_.
|
| (Half remembered but apparently real scenario, though I'm
| not sure where from)
| imtringued wrote:
| Why? The way health insurance works, all of those are
| profitable treatments. There is no "choose one or the
| other". Sick children/adults becoming healthy adults that
| can pay for health insurance is not a moral dilemma.
| ben_w wrote:
| What are you asking "why" about, exactly?
| dragonwriter wrote:
| > 2 millions, if applied properly, could do good for many
| people.
|
| Its very close to the lifetime average financial cost of
| medical services related to sickle cell disease for those
| with it, from things posted elsewhere in the thread. So its
| literally just paying the same (loosely) financial cost up
| front and then _not_ having them suffer through the
| disease.
|
| An incentive structure that encourages mostly making the
| wrong decisions on things like this when it comes to
| cost/quality-of-life is why the US has the most expensive
| healthcare system in the developed world on a per capita or
| per GDP basis, and doesn't have better-than-typical general
| outcomes to show for it.
| twoodfin wrote:
| To be fair, those incentive structures also encourage the
| development of what everyone knows going in will be--
| initially--absurdly expensive treatments.
|
| Over-under on when the NHS agrees to pay for this?
| monero-xmr wrote:
| This is the effective altruism / utilitarianism insanity.
| If we only thought about "what the best use of $2 million
| is" we would still be living in huts.
| refactor_master wrote:
| Actually, utilitarianism and capitalism have been the
| strongest growth factors for human prosperity and welfare
| since forever.
|
| Many societies with excessively strong opinions on morals
| however are literally living in huts.
| krapp wrote:
| >Many societies with excessively strong opinions on
| morals however are literally living in huts.
|
| Setting aside that the US government is deeply influenced
| by Christian conservatism and the culture by Puritan
| ideals, to the point that no American President can be
| elected without vocally professing faith in God, Christ,
| or being seen with a Bible in hand, and thus is the most
| moralizing culture within Western civilization by far
| (particularly where sex and gender are concerned,) which
| hut-dwelling societies are you talking about,
| specifically?
| refactor_master wrote:
| Here's a graph showing the negative correlation between
| "hut-dwelling" and "utilitarianism":
|
| https://www.pewresearch.org/short-reads/2019/05/01/with-
| high...
|
| The US can be said to be both. E.g. you won't find many
| "huts" along the northeastern coast, but search and
| you'll find them elsewhere:
|
| https://en.wikipedia.org/wiki/List_of_U.S._states_and_ter
| rit...
|
| I'll leave it as an exercise for the reader to determine
| where the most "huts" are found.
|
| So it's flat out wrong to claim that some sort of
| perceived moral bankruptcy with regards to the value of
| human life has left our society in the stone ages, when
| all evidence points to the contrary.
|
| Under utilitarian capitalism people are expendable, but
| in the meantime they are less likely to dwell in huts
| than morally superior societies.
|
| Note that I've blatantly equated religion with moral
| here.
| ponector wrote:
| What about real people who are living in huts right now?
| With few million you can drastically improve thousands of
| lives.
|
| Are they not worth saving? Because they are far away and
| have small purchasing power there is small sense to help
| them.
| ericmay wrote:
| I understand the dilemma, but many of those same children
| you are thinking of live in poverty in places such as
| Africa _and_ with the misfortune of sickle cell disease.
|
| If we prevented treatment because the money could be used
| elsewhere, we likely wouldn't/won't develop a drug that we
| could eventually[1] make cheap enough to cure these kids
| and give them longer lives too. We can do better!
|
| [1] There is a cynical take here about drug costs,
| geopolitics, etc. but I am rejecting that cynicism.
| robwwilliams wrote:
| As mentioned above--this is day 1.
|
| How much did the first human genome sequence cost?
| (Effectively several billion dollars--now $1000.) How
| much did the first organ transplant cost? How much did
| the first electronic computer cost?
|
| Yes, cost will slow widespread use but it will spur the.
| next wave of innovation---some motivated by profit, some
| motivated by social altruism.
| ericmay wrote:
| I wrote the OP :) I agree with you. What I was trying to
| highlight is that many of the people the person who
| originally responded to me was concerned about have the
| exact disease! And we need continued development with
| initial high costs to hopefully bring the costs down.
| imtringued wrote:
| I'm sorry but the "cure" for that requires political change
| involving the stepping over of some people's corpses. You
| can only do that once people are sufficiently angry.
|
| Healthcare? People pay to be and stay healthy. The money
| was earmarked specifically for this purpose. Also, in the
| long run, you will be able to cure diseases even those
| "healthy" children have.
| _qua wrote:
| Sadly, unlike tech, the price of drugs doesn't always go down
| over time.
| jimbob45 wrote:
| The Hep C cure was 100k USD when it released in 2014. 10 years
| later, it's 25k USD max before insurance.
|
| The price you see now will likely shrink in the coming years.
| Pretty good opportunity for an analysis on CRISPR pricing if
| you have a well-trafficked blog and are willing to track this
| for the next five years.
| biomcgary wrote:
| And much better than a liver transplant.
| chimeracoder wrote:
| > And much better than a liver transplant.
|
| There are a lot of steps in between "acute HCV infection"
| and "requiring a liver transplant", and many insurers, even
| today, will require you to go through some or all of them
| before considering paying for HCV antivirals.
| chimeracoder wrote:
| > The Hep C cure was 100k USD when it released in 2014. 10
| years later, it's 25k USD max before insurance.
|
| That's not a great comparison. There was a previous cure for
| hepatitis C before the first antiviral-based cure 2013, and
| the initial treatment regiment for the antiviral based
| regimen was a hybrid of the two, before they settled on a
| fully antiviral-based treatment.
|
| The reason that the antivirals came down in price so quickly
| was because so many nearly-identical ones came on the market
| within a couple of years. That's due to the discovery of a
| particular protein and corresponding class of inhibitors some
| years earlier, which was not patented, opening the door for a
| flood of drugs which are all functionally identical in
| purpose and mechanism of action, but chemically distinct and
| eligible for separate patent protections.
|
| That came at a time when political and other pressures made
| some private insurers more willing to approve treatment
| (usually after a few rounds of denials and appeals) - but
| again, with an emphasis on _some_ , because there are large
| classes of people for whom it is difficult or impossible to
| get treated for HCV today. (They're just not the ones likely
| to comment on HN).
|
| Contrast to this treatment, which is for a congenital
| condition that does not have the same political pressure to
| address, and for which a significant financial barrier to
| access is not merely the costs of the drug, but the cost of
| the associated care (chemotherapy, etc.) which is _not_
| included in the quoted price. In addition the patent laws
| function differently in this case, to the detriment of
| patients.
|
| The history of hepatitis C and its treatment is fairly
| idiosyncratic and it would be a mistake to use the price
| trajectory of HCV antivirals as a predictor for any other
| treatment.
| ajross wrote:
| Collectively paying for rare but expensive treatments is
| literally the problem that insurance solves. This isn't wildly
| out of the expected range for this sort of thing. And it will
| surely get cheaper as it evolves.
| lotsofpulp wrote:
| Since the collective probability of rare, but expensive
| health issues is basically 100%, I would describe it less as
| insurance and more as wealth redistribution. Hence the
| (typical) requirement to purchase insurance and lack of
| ability to price it based on risk.
|
| Of course, insurance and taxation can be viewed as similar
| things anyway, but it is different from things like term life
| insurance or motor vehicle insurance or home owners
| insurance.
| soulbadguy wrote:
| > Since the collective probability of rare, but expensive
| health issues is basically 100%, I would describe it less
| as insurance and more as wealth redistribution.
|
| Humm no... It's just risk amortization...
| lotsofpulp wrote:
| If it was just that (in the US), then there would be no
| need to prevent insurers from pricing based on health of
| the insured. Or legislating a 3x cap on premiums between
| highest and lowest premium. Or legislating out of pocket
| maximums.
|
| The premiums are very explicitly a subsidy from young to
| old, which I view as a tax by a different name. Except
| instead of it being based on one's income/wealth, it is
| based on age.
| BurningFrog wrote:
| What we in the US call "health insurance" is today very
| different from the textbook definition of insurance.
| lotsofpulp wrote:
| I don't think any developed country in the world has an
| alternative "health insurance" model. I believe
| Switzerland and Germany require people to purchase health
| insurance and it is not priced based on health risk.
|
| Health risks in general are very predictable and very
| high, especially as one ages.
| soulbadguy wrote:
| > If it was just that (in the US), then there would be
| non need to prevent insurers from pricing based on health
| of the insured. Or legislating a 3x cap on premiums
| between highest and lowest premium. Or legislating out of
| pocket maximums.
|
| I do not follow the point you are making here. The
| regulation and legislation around health insurance do not
| change the nature of it.
|
| I think you are assuming that insurers have perfect risk
| assessments power and thus regulating them should be
| unnecessary. But they don't and we have to.
|
| > The premiums are very explicitly a subsidy from young
| to old
|
| You are just repeating your assertions here. I would love
| some arguments.
|
| > which I view as a tax by a different name. Except
| instead of it being based on one's income/wealth, it is
| based on age.
|
| Sure, as long as we agree that is just your point view
| and nothing rooted in reality.
| lotsofpulp wrote:
| Sorry, I don't really know how else I can explain it. The
| age rating factor itself is pretty self explanatory.
|
| Instead of charging a sicker or older person $10,000 per
| month and healthier or younger people $100 per month
| because that is close to the expected loss in the
| calendar year for the insurer, they are mandated to
| charge younger/healthier people $1,000 per month so the
| older person can only be charged $3,000 per month.
|
| Imagine a similar law for motor vehicles. The car
| insurance companies can only charge the worst and
| riskiest drivers 3x what the safest driver pays.
| Basically, you can keep getting into collisions and at
| some point your premium will stop increasing. Where will
| the money to pay for all the damages come?
|
| > I think you are assuming that insurers have perfect
| risk assessments power and thus regulating them should be
| unnecessary.
|
| I do not assume this. Insurance and tax/wealth
| redistribution is a spectrum.
| soulbadguy wrote:
| Here what i am understanding of the point you are making
| :
|
| When we offer a service to a group of person, and somehow
| mandate a flat price for that service. The people using
| the service less are subsidizing the cost for the people
| who use the service less.?
| lotsofpulp wrote:
| Yes, although I think you meant to type
|
| > The people using the service less are subsidizing the
| cost for the people who use the service more.?
|
| Also, it is not a flat price, it is a capped price.
|
| As an aside, think about how the optics would have been
| if the politicians were transparent that a significant
| portion of the tax liability to pay for the healthcare
| would be levied based on age.
|
| Then think about older, rich people taking advantage of
| this and retiring early (between age 50 to 65), and
| because they can afford to have very low income (but a
| lot of assets), they qualify for even more subsidies
| during their most expensive years to insure, without
| negatively affecting their lifestyle.
|
| https://www.healthcare.gov/glossary/premium-tax-credit
| eszed wrote:
| Yes, if you strictly view it from a short time horizon.
| If you think of it as an individual's risk over their
| whole lifetime, then it looks a lot better. A young
| person is "paying it forward" now, in exchange for having
| their own expensive treatments covered once they are old.
| This is the bargain that any social security or old-age
| pension system strikes.
|
| The trouble is, as social cohesion breaks down, and
| demographic cliffs approach, people lose faith that long-
| term programs will still be there for them as they age.
| Perceptual time horizons shrink, and the arguments that
| you have made begin to resonate.
|
| I don't have a good answer for either of those problems.
| Immigration solves the demographic cliff, but appears to
| threaten social cohesion. We can get into tedious and
| repetitious arguments about why that is, but let's please
| not?
| Scene_Cast2 wrote:
| Is it risk amortization because we just can't predict
| certain health issues? Let's suppose that we had a
| "health oracle" (or something not too far off) to predict
| medical issues in individuals. How would you structure
| health insurance in that case?
| soulbadguy wrote:
| If we had a health oracle, what would be the point of
| health insurance ? I think with a 100% health oracle,
| health inssurance will become more like group buys for
| negotiating better prices with health providers.
| lotsofpulp wrote:
| That is why the industry term for health insurers in the
| US is "managed care organizations" (MCOs).
|
| When you (or your employer) buys a policy from UNH,
| Elevance, Cigna, CVS, Humana, etc, part of what they pay
| for is access to the MCOs pricing services. And vetting
| services to minimize errors/fraud (a process which itself
| is ridden with errors/fraud).
| ajross wrote:
| > the collective probability of rare, but expensive health
| issues is basically 100%
|
| Not really, no. Most people will die of something
| expensive, but not $2M expensive. A quick google says that
| per-capita lifetime health care expediture is ~$300k.
| lotsofpulp wrote:
| If you are referencing this
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1361028/
|
| That data is from the late 1990s, before the Affordable
| Care Act greatly expanded access to healthcare, and many
| new treatment options have become available since then.
|
| What I meant, though, is that across a big population's
| entire lifetime, there will be a ton of high healthcare
| cost events. And with technological progress, new
| treatments will always be coming out. Which is a great
| thing, just not what is typically thought of as an
| "insurable risk".
| ajross wrote:
| > What I meant, though, is that across a big population's
| entire lifetime, there will be a ton of high healthcare
| cost events. And with technological progress, new
| treatments will always be coming out. Which is a great
| thing, just not what is typically thought of as an
| "insurable risk".
|
| Sorry, how does that follow? Insurance works any time you
| have a function with predictable average but high
| variance. Is the total health care expenditure across a
| relevant subscriber base in 2023 very close to 2022? Then
| you can make insurance work. It's just math.
| lotsofpulp wrote:
| Insurable risk as in charging someone an appropriate
| premium that is based on their specific expected loss.
| Property and casualty, term life, etc.
|
| Non insurable risk as in charging someone a premium
| unrelated to their specific expected loss (which is what
| health "insurance" is).
| ajross wrote:
| How exactly are health insurance premiums "unrelated" to
| care outflows (what you're calling "expected loss")? Are
| you saying that health insurers books don't balance and
| that they're losing money (they aren't) or making too
| much profit (not unless they're criminally hiding it)?
|
| What you're saying doesn't make sense. There's no
| difference between health insurance and any other
| insurance in the way it works. You collect reliable and
| regular premiums from everyone, pay out unreliable/bursty
| (but statistically very predictable in aggregate!) losses
| as contracted, and pocket the remainder as profit. And it
| works.
|
| Really, I don't know what you're talking about here.
| Health insurance is "expensive" in the US, sure. But it's
| not failing.
| lotsofpulp wrote:
| I meant the premium for a specific person is not related
| to their expected loss.
|
| For example, if you carelessly drive and get into car
| collisions where you are at fault, your premiums go up,
| because your expected loss goes up.
|
| In health "insurance", it does not matter what you do,
| because your premiums are not based on your expected
| health costs. Hence it is more akin to a tax (or
| subsidy).
| ajross wrote:
| You're really not understanding this. That's got nothing
| to do with the insurance model. That's just a regulatory
| thing. All those choices do is change the _specific
| population_ that gets insured in a single pool, such that
| their specific computed premiums are different. But for
| _ANY_ such population, the total premiums paid == the
| total loss outflow + a reasonable profit. And you can
| tell that 's true because the accounting for those
| companies appears in their SEC filings.
|
| In practice, car insurers are allowed to partition their
| customers this way because it's felt to be "fair" and
| because it encourages safe driving. Trying to partition
| health insurance customers like that feels "unfair", and
| has minimal net benefit as health expenses aren't as
| controllable-by-the-subscriber as car accidents are. So
| we pass laws about how the partitioning gets done.
|
| But again, "insurance" as a business model (and
| mathematical model) works _EXACTLY THE SAME WAY_. The
| only difference is how you draw the lines around who gets
| insured at what rate.
| lotsofpulp wrote:
| > All those choices do is change the specific population
| that gets insured in a single pool, such that their
| specific computed premiums are different. But for ANY
| such population, the total premiums paid == the total
| loss outflow + a reasonable profit. And you can tell
| that's true because the accounting for those companies
| appears in their SEC filings.
|
| I do not dispute this. As I wrote in a sibling comment:
|
| >Insurance and tax/wealth redistribution is a spectrum.
| hanniabu wrote:
| I'm assuming they're setting the price so high since insurance
| will only approve payment of a fraction of that
| seydor wrote:
| i always find those prices unbelievable. What is the actual
| cost of all the expense and workhours for making the treatment
| quickthrower2 wrote:
| Throw that stone in the SaaS glass house. $100/m for 10c of
| compute and $1 of a devs time.
| refurb wrote:
| Sure. It's pretty typical for sickle cell patients to have to
| go to the hospital severe times per year for "sickle cell
| crisis".
|
| If this is a cure (I haven't looked at the data), imagine the
| NPV of a lifetime of multiple hospitalizations per year. It's
| likely in the millions.
| ufmace wrote:
| That's how technological progress works. The first version is
| expensive and not very good, so it isn't used much. But some
| use proves that it works, lets the kinks get worked out, and
| gives the makers funding and incentive to optimize the cost and
| quality. Give them time for a few iterations and it'll be cheap
| and plentiful. Just like the iPhone - the first one was super
| expensive, harder to get, and pretty limited. Now there's lots
| of cheap options and they're everywhere.
| mritchie712 wrote:
| Ohalo (the company Dave Friedberg is now CEO of) recently got
| approval for a potato edited by CRISPR:
|
| > Ohalo had two RSRs under consideration this year for its
| potato, one which focuses on higher concentrations of beta
| carotene - enhancing the overall health and nutrition value of
| the potato - and another which results in reduced glucose and
| fructose content in the potato, which, according to Ohalo, will
| reduce the adverse side effects that lead to significant spoilage
| during cold storage of potatoes.
|
| https://thespoon.tech/gene-edited-food-startup-ohalo-emerges...
| jabbany wrote:
| Hmmm. That second one reminds me of the Flavr Savr
| (https://en.m.wikipedia.org/wiki/Flavr_Savr).
|
| More shelf life in exchange for likely worse taste...
| huytersd wrote:
| Worse taste but probably healthier in this case.
| SoftTalker wrote:
| Yeah potatoes will fill your stomach and better than
| starving but they aren't really healthy food. Eat them in
| moderation, and prefer sweet potatoes/yams.
| pastor_bob wrote:
| >prefer sweet potatoes/yams.
|
| Sweet potatoes, as you might expect, have more sugar in
| them. As do garnet yams.
|
| The issue with potatoes isn't really their (low) sugar
| content.
| spondylosaurus wrote:
| On the contrary, potatoes are full of good stuff:
| https://www.mayoclinichealthsystem.org/hometown-
| health/speak...
|
| Just make sure to go easy on the toppings!
| 2devnull wrote:
| That says,
|
| " true that potatoes are high in starch or carbohydrates,
| the nutrients that cause spikes in blood sugar. But
| pairing them with foods high in protein, fiber and
| unsaturated fats can slow digestion and lead to a
| steadier release of glucose into the bloodstream."
|
| Which suggests you should add toppings or else potatoes
| are not very healthy if eaten on their own. (I think
| they're fairly high up on the glycemic index).
| freedomben wrote:
| thanks that's neat, although I wish it wasn't with a Solanaceae
| member. Do you know if they are working on other types of
| produce or are they just working on potatoes?
| biomcgary wrote:
| Are you concerned about off-target edits activating toxin
| producing pathways?
| Modified3019 wrote:
| Maybe they are referring to the small percentage of people
| are sensitive to the whole family (potatoes, tomatoes,
| peppers, tobacco, etc) and find any exposure produces
| inflammation/digestion issues.
| freedomben wrote:
| yes it's both actually! Potatoes are wildly toxic to
| humans when they have any green on them, and that can
| actually happen _in the refrigerator_ if left to long and
| then consumed. They have the capacity to really F us up.
| Editing those strikes me as like threading a needle
| between hair triggers. You don 't want to miss your
| target.
|
| But also yes exactly, the whole family can cause
| inflammation and difficulties in people sensitive to them
| (which tragically because I love spicy food, includes me
| D-:). So that means that any cool stuff they do I won't
| be able to try.
| imtringued wrote:
| Don't worry, once they figured it out they are going to
| put this stuff in every food and you won't be able to eat
| anything at the supermarket anymore.
| pastor_bob wrote:
| >and another which results in reduced glucose and fructose
| content in the potato,
|
| That's pretty amazing. Imagine if we can change apples to
| produce Aspartame instead of sugars!
| iwontberude wrote:
| I don't see how a plant is supposed to metabolize the
| aspartame for energy?
| maxerickson wrote:
| It would only be a successful reproductive strategy if some
| external actor decided to propagate the plants that were
| putting something not useful to the seeds into the fruit.
| hedora wrote:
| Unless you are diabetic, aspartame is much worse for you than
| sugar. It causes metabolic issues, such as reduced metabolism
| (leading to more weight gain than a subjectively equivalent
| amount of sugar), migraines in some people, interacts with
| drugs, is bad for your digestive tract, and probably has
| other side effects.
|
| Even if you are diabetic, you can already eat apples. They
| have a low glycemic index.
| liamwire wrote:
| Extraordinary claims require extraordinary evidence. Can
| you back any of this up, or provide a reason I should
| believe what you're saying? Because it directly contradicts
| decades of research on what is perhaps the most scrutinised
| and studied dietary supplement in the world.
|
| Aspartame is safe, and very well tolerated.
|
| You're spreading misinformation.
| BurningFrog wrote:
| > * reduced metabolism (leading to more weight gain than a
| subjectively equivalent amount of sugar),*
|
| Doesn't that mean aspartame somehow contains more energy
| than sugar?
|
| I mean, assuming the increased weight is fat, that is
| stored extra energy.
| mpol wrote:
| The idea works longterm. You take aspartame, which has a
| sweet taste but no energy. Your body starts all kinds of
| digestive functions and gets confused. After a lot of
| aspartame it doesn't know how to respond to sweet food
| anymore.
| oaktrout wrote:
| There is some evidence that artificial sweeteners
| increase insulin resistance:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014832/
|
| I have also heard that because artificial sweeteners
| increase insulin levels without increasing blood glucose
| to the same extent that sugars would, this leads to a
| blood sugar drop which induces increased eating.
| Lord-Jobo wrote:
| Decades of research have found rare, but still very mildly
| negative health results from aspartame, and an overwhelming
| flood of direct evidence for strong negative health effects
| from sugar.
|
| Back up what you are saying with some studies. Because what
| you are claiming is going against a LOT of modern medical
| knowledge.
| bborud wrote:
| Regardless of whether aspartame is better or worse than
| sugars (I neither know nor care) that sounds awful. I find
| the taste of aspartame revolting.
| seydor wrote:
| monster-potato?
| graphe wrote:
| I would have bred them for more potato protein. It's a very
| close meat protein substitute by essential amino acids. Might
| be why it tastes so good.
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6245118/
|
| >Of the ten plant-based proteins included in the current
| analysis, potato protein is the only protein source containing
| the WHO/FAO/UNU requirements for all essential amino acids.
| Thus, when consuming potato protein as the only dietary protein
| source at the recommended adult protein intake level of 0.66
| g/kg/day, sufficient amounts of all essential amino acids
| should be consumed. It remains to be investigated whether the
| ingestion of a single meal-like amount of potato protein has
| the capacity to stimulate muscle protein synthesis.
|
| Anyone know about vegan protein profiles and best ones now?
| gen220 wrote:
| I supplement protein, filtered for vegan because my body
| doesn't like whey, and Pea protein is pretty solid. It's a
| "complete" protein and doesn't require any complicated
| processing steps, just drying, pulverizing, and a centrifuge
| step to spin out the fiber.
| smt88 wrote:
| Are you sure that's all they do? Peas aren't even close to
| 100% protein, so you'd be eating a very high-carb powder if
| that were the case.
| gen220 wrote:
| Yep, here's an article [1] describing the process. Here's
| some youtube video I found showing the various steps [2].
|
| They don't have to use any chemical solutions more exotic
| than water and air. I bungled the explanation with
| "centrifuge", it's more complicated than that, but the
| fiber content is removed in that step.
|
| [1]: https://gogood.co.nz/blogs/news/how-is-pea-protein-
| manufactu...
|
| [2]: https://www.youtube.com/watch?v=wbX_w0ZIunM
| byproxy wrote:
| Hence the "spinning out the fiber" bit. Likewise, whey
| protein is a byproduct of cheesemaking where fat gets
| separated from milk, otherwise it'd be a very high-fat
| powder.
| feoren wrote:
| I'm assuming that's the point of the centrifuge?
| mritchie712 wrote:
| Not quite vegan, but I like cricket protein.
| smt88 wrote:
| Cricket protein is still insanely expensive though.
| dsmmcken wrote:
| Cricket protein can trigger shellfish allergies, fyi.
| colordrops wrote:
| I skimmed the article but it seems to contradict itself:
|
| > Soy, brown rice, pea, corn, and potato protein have
| essential amino acid contents that meet the requirements as
| recommended by the WHO/FAO/UNU (WHO/FAO/UNU Expert
| Consultation 2007) (Fig. 2).
| hombre_fatal wrote:
| 1. Soy, brown rice, pea, corn, and potato all hit their
| EAA/total protein cut-off.
|
| 2. I don't see how amino acid % of total protein is a useful
| way to gauge a food's protein especially in this context.
| Wouldn't you want to look at protein per calorie or EAA per
| calorie?
|
| For example the paper's chart might make you think that you
| should eat potatoes and corn if you want to maximize plant-
| based protein, but that's not the case at all.
|
| - 500 calories of potatoes boiled: 10g protein (650g of food)
|
| - 500 calories of rib-eye steak: 54g protein (200g of food)
|
| - 500 calories of soy chunks (TVP): 75g protein (btw hits all
| EAA objectives for the day) (150g of food)
|
| - 500 calories of wheat gluten (seitan): 101g protein (135g
| of food)
|
| Potatoes are dense in other nutrients and a great part of a
| healthy diet, but you definitely wouldn't use potatoes as a
| "meat protein substitute". Even broccoli is 3x as protein
| dense as potatoes.
|
| On the other hand, seitan, tofu, and TVP are the trifecta of
| plant-based protein that can actually substitute for meat.
| runnerup wrote:
| > Wouldn't you want to look at protein per calorie or EAA
| per calorie?
|
| PDCAAS is a reasonable standard to use, pro-rated against
| total calories.
|
| https://en.m.wikipedia.org/wiki/Protein_Digestibility_Corre
| c...
| graphe wrote:
| Don't compare whole potato, it should be to potato protein
| extract.
| rcarr wrote:
| Pretty cool, I wonder if it changes the chemical composition of
| the soil in any way compared to a regular potato.
| downWidOutaFite wrote:
| How do the edited genes replace the body's genes?
| Nasrudith wrote:
| They technically never do the gene replacement within the body.
| They take the marrow alter it, grow and produce an external
| modified new marrow. Chemotherapy wipes out the old bone marrow
| out and the modified marrow is introduced instead.
|
| As breathtakingly advanced and unprecedented as CRISPR
| treatment is, the execution is still radical and crude by
| necessity. Not to diminish the accomplishments but to note that
| we still have a great deal of room to grow.
|
| Hopefully knowledge will eventually advance so that less
| extreme and unpleasant methods will take its place. But that
| would be a tough nut to crack.
| robwwilliams wrote:
| No replacement involved. The treatment edits and reactivates
| the fetal version of HBB gene that is inactivated after birth.
| pknerd wrote:
| I wonder whether in the future doctors have a visual
| designer(WYSIWYG) similar what programmers have in the form of
| Visual Basic/QT to alter DNA. It'd be pretty interesting if it
| happens
| huytersd wrote:
| Also terrifying in a sense. Instead of some wacko shooting up a
| school, he's going to make an apocalyptic virus instead.
| quickthrower2 wrote:
| I wonder if they will have a natural language chat interface
| w0mbat wrote:
| The gene that causes sickle cell anaemia actually provides
| partial immunity to malaria, which is why this gene has not been
| bred out of the population over time.
| lostlogin wrote:
| > which is why this gene has not been bred out of the
| population over time.
|
| Is that why? Or is it just the people with it aren't sick
| enough to die before procreating?
| freeone3000 wrote:
| In regions where malaria was endemic, this mutation was
| selected _for_ , as malaria kills children.
| SoftTalker wrote:
| Malaria often kills people before they reach the age of being
| able to procreate.
| vidarh wrote:
| Without access to modern hospital treatments it is fairly
| normal to die very young from sickle cell disease - it causes
| 100k+ deaths a year.
|
| An in-law of an ex has it, and regularly spends days in
| hospital during crises. Without access to a high quality
| hospital he'd have been dead a long time ago.
|
| The average life expectancy for someone with sickle-cell
| disease _in developed countries_ is 40-60 years, and serious
| crises tend to start from childhood.
|
| That said, it's recessive, and so it's likely the reverse of
| what you think: It's not primarily the people with full-blown
| disease who contributes most to the long term survival of the
| trait, but that the trait alone confers fairly significant
| advantage in regions where Malaria is huge killer mostly
| without causing health problems. So across the combined set
| of carriers and those with the full disease, the life
| expectancy in Malaria stricken areas tends to be higher.
|
| Pattern of change of the prevalence of the trait correlating
| with changes in prevalence of Malaria has been observed many
| places. E.g. the prevalence among US black people is
| significantly lower and dropping than in the areas their
| ancestors came from.
| interroboink wrote:
| I think this is right, but just to spell out the recessive
| gene implications for readers, here's the Punnnett
| square[1] : R | r +----+----+
| R | RR | Rr | --+---------+ r | Rr | rr |
| +---------+
|
| The people with sickle cell disease are "rr" -- that's 1/4
| the population.
|
| The people who have some malaria resistance are all of the
| ones with "r". In particular, the "Rr" folks have the
| resistance, but not the anemia.
|
| So basically, this gene screws over 1/4 of the population
| and benefits 1/2. In areas with lots of malaria, this
| tradeoff is worthwhile, evolutionarily speaking.
|
| One of those harsh cases where evolution (if we personify
| it) does not care about individuals -- only the species.
|
| [1] https://en.wikipedia.org/wiki/Punnett_square
| __loam wrote:
| Worth noting punnet squares are kind of bunk:
| https://youtu.be/zpIqQ0pGs1E?si=SDRQP-PW2u_6Jq3d
|
| Although sickle cell does seem to be one of the rare
| cases where they work out.
| wizzwizz4 wrote:
| Punnet squares are as "bunk" as Ohm's Law.
| ls612 wrote:
| No the important part is that the mutation is recessive, but
| being heterozygous for it is enough to confer malaria
| resistance.
| graphe wrote:
| Africa wasn't colonized by Europe until vaccines and
| treatments were invented because of malaria and other
| tropical diseases. Quinine was one of the last ingredients
| needed to conquer Africa.
| CobrastanJorji wrote:
| It's a recessive/heterozygous thing. If you get the gene from
| neither parent, you're vulnerable to malaria. If you get the
| gene from either parent, you're immune to malaria and don't
| get sickle cell. If you get the gene from both parents, you
| get sickle cell. A hypothetical future person who's going to
| be born in an area with a lot of malaria would really want
| exactly one parent with sickle cell and one parent lacking
| the gene completely to guarantee the best personal outcome,
| or they'd want exactly one heterozygous parent (for a 50%
| chance of being immune to malaria with no downside), or they
| might settle for the gamble of two heterozygous parents (50%
| chance of immunity, 25% chance of sickle cell).
| eszed wrote:
| Can they do sperm (or egg) selection to change those odds
| for IVF?
| CobrastanJorji wrote:
| In fact yes! https://punchng.com/value-of-ivf-in-
| elimination-of-sickle-ce...
|
| But practically, it'd be a huge challenge. Nigeria's one
| of the main victims of malaria and, not by coincidence,
| one of the main victims of sickle cell. There are IVF
| clinics in Nigeria, but they're very expensive even
| before you consider sickle cell testing. It likely
| wouldn't scale to all of the births per day, and
| something like a quarter of the country would need it.
|
| But it's not IMPOSSIBLE. You'd need to do maybe 75 or so
| per day to cover the 25% or so of the country that have
| the gene and would need it. Hard and expensive and
| impractical, but perhaps possible?
| quickthrower2 wrote:
| Or add the DNA tests to dating apps.
| graphe wrote:
| This sounds like Tay Sachs for Africans. Read that carriers
| of Tay Sachs might have defended them against tuberculosis,
| and they're also looking at gene therapy for it.
|
| Prevention is the preferred method of passing this trait on
| however.
| Infinitesimus wrote:
| (You already know this but for the general audience)
|
| The train doesn't make you immune to malaria but it does
| increase resistance after infection.
| robwwilliams wrote:
| Good point and thanks for being on-topic. Humans have three
| variants of the HBB gene and having sickling mutations in the
| variant expressed in adult is causal to SC disease.
|
| The FDA-approved treatments reactivate the fetal HBB gene in
| adults and this change in gene expression control effectively
| prevents SCD.
|
| Very cool and transformative work. Now we have to get the price
| tag down from seven figures to four or five figures so that it
| will be used widely. That may be a few decades. Let's hope that
| more efficient alternatives are developed soon.
| firejake308 wrote:
| From an efficiency standpoint, I think having to harvest and
| modify the patient's stem cells is probably the biggest choke
| point, right? I would imagine that if you could inject
| something once and be done with it (I'm thinking like
| Zolgensma), you could mass produce it more effectively
| firejake308 wrote:
| Correct, but if we have good treatments for malaria (e.g.
| hydroxychloroquine, atorvaquinone) then I would argue that we
| no longer need that partial immunity
| imtringued wrote:
| That is true but even the unreliable malaria vaccines that are
| out there are more effective and reliable against malaria than
| sickle blood cells.
| joshuamcginnis wrote:
| Here's basically how the process works:
|
| * Harvest stem cells from the patient.
|
| * Prepare a DNA plasmid with the Cas9 gene, guide RNA for the
| desired genetic modification, and an antibiotic resistance gene.
|
| * Electroporate the plasmid into the harvested stem cells. Grow
| the electroporated stem cells in antibiotic-containing nutrient
| media. Only cells with the plasmid (and thus antibiotic
| resistance) survive.
|
| * Expand and freeze the genetically modified cells.
|
| * Administer chemotherapy to the patient to eliminate defective
| bone marrow stem cells.
|
| * Inject the modified stem cells back into the patient, where
| they repopulate the bone marrow with the CRISPR edits, aiming to
| correct the genetic mutation.
|
| This process isn't new but one of the biggest challenges is
| propagating genetic modifications to all effected cells in the
| body. This is why it's much easier to GMO an egg / sperm because
| once the change is made there, it's replicated in every new cell
| thereafter.
|
| Other techniques utilize harmless viruses to transfect genetic
| modifications to the body, but this has other trade-offs. mRNA
| vaccines don't propagate to every cell, but the cells which do
| successfully transcribe the mRNA are able to generate enough of
| the target protein that the body can recognize it and develop an
| immunity to it. Eventually, the modified cells will die and no
| cells will be left to produce the mRNA vaccine protein.
| sjkoelle wrote:
| is crispr a big improvement here over AAVs or zinc fingies?
| stanford_labrat wrote:
| AAV or adeno-associated virus is a delivery method for
| getting cas9 mRNA (the code that says, make cas9 protein and
| do gene editing). Zinc finger nucleases are a similar class
| of dna editing proteins.
|
| In this specific experiment they chose to transfect cells
| with plasmid directly rather than transduce with virus.
| jryb wrote:
| ZFNs are difficult and slow to engineer. There are certainly
| tradeoffs but the fact that almost the entire industry is
| using CRISPR-based approaches tells you where things lie on
| balance
| JumpCrisscross wrote:
| Do you know why they're having the marrow synthesise fetal
| hemoglobin versus hemoglobin A(2)? (Is it simply because HbF is
| one molecule while HbA and HbA2 are two?)
| joshuamcginnis wrote:
| Fetal hemoglobin has a lot of biochemical advantages for
| fighting sickle-cell disease on its own so this is leveraged
| in the CRISPR solution - e.g. create more of the cells that
| inhibit the disease in the first place.
|
| https://en.wikipedia.org/wiki/Fetal_hemoglobin#Treatment_of_.
| ..
| 1letterunixname wrote:
| And US patients won't be able to get it because they're going to
| be overcharged and drowned in debt to the point of bankruptcy.
| marcusverus wrote:
| Compared to similarly developed countries, Americans are
| actually in great shape when it comes to debt. See the OECD
| Data: https://data.oecd.org/hha/household-debt.htm
| matteoraso wrote:
| Don't be facetious. Parent was obviously referring to medical
| debt, which most first worlders never have to think about.
| marcusverus wrote:
| I wasn't being facetious, I (wrongly) assumed you could
| infer the argument:
|
| Americans have significantly less debt than Western
| Europeans. Their average appears to be 50% higher than
| ours. Including medical debt.
|
| The idea, as per GP, that this treatment will inexplicably
| drive Americans to bankruptcy, is stupid. It's offensively
| dumb. It's the kind of uninformed doomer nonsense that runs
| rampant online progressive echo chambers, but has no basis
| in reality.
|
| > ...which most first worlders never have to think about.
|
| Those lucky bastards. With 50% more debt.
| refurb wrote:
| A very lazy reply.
|
| Look at access to the cystic fibrosis therapies ($300,000 per
| year). The US (including Medicaid) were paying for them from
| launch in 2012.
|
| The UK just came to an agreement for NHS to pay for it in 2020.
| 8 years later.
|
| In Canada, only 5 of the 12 provinces/territories pay for it
| and only if your a child. Adults don't get it.
|
| You actually stand the highest chance of getting it in the US.
| dang wrote:
| Recent and related:
|
| _FDA considers first CRISPR gene editing treatment that may cure
| sickle cell_ - https://news.ycombinator.com/item?id=38354939 -
| Nov 2023 (124 comments)
| thenerdhead wrote:
| Historic. This opens the door for CRISPR. Very exciting to have
| followed this in Science/Nature magazine till today.
| EvanAnderson wrote:
| The mechanism by which this treatment works is really neat (some
| notes in [0]). The treatment increases the production of a fetal
| version of hemoglobin. That fetal hemoglobin is unaffected by the
| sickle cell mutation. Presumably everybody who is alive (and not
| a fetus) has a good copy of this fetal hemoglobin gene and it
| "just" needs re-activated.
|
| [0] https://sciencebasedmedicine.org/first-crispr-treatment-
| appr...
| user3939382 wrote:
| Does anyone who's more familiar with exactly how this works know
| if this could be applied or potentially applied to thalassemia?
| From what I understand those are also related to genetically-
| driven misshapen red blood cells.
| ryankuykendall wrote:
| CRISPR Therapeutics also has a therapy for Beta Thalassemia in
| human trials that is up for approval in February 2024.
|
| "Editing Humanity" by Kevin Davies covers the history and near
| future of CRISPR and includes a great chapter on describing
| both of these therapies.
| ezarowny wrote:
| This is such good news! I bet a lot of monogenic disorders are on
| the table now.
| thinkcontext wrote:
| My neighbor has 2 adult children with sickle cell. Its very tough
| watching what the have to go through. Frequent ambulance visits
| followed by multiple days in the hospital. Lots of pain in
| everyday life. The daughter is legally blind from complications.
|
| The son tried for a long time to hold a job but couldn't because
| of how much time he would miss.
|
| I hope they are able to get this.
| renewiltord wrote:
| Would be interesting if they could do this in embryos.
| carabiner wrote:
| Any status updates on the next gen CHEWR?
| totorovirus wrote:
| could we have a CRISPR based penis elongation medicine in future?
| I would like to invest to that startup
| ugh123 wrote:
| Go for curing baldness first
| fasteo wrote:
| Every time I read[1] about CRISPR there seem to be concerns about
| off-target editing, that might cause all kinds of trouble. Is
| this a solved issue ?
|
| Note: I am not a doctor, but I do have a genetic condition that
| might benefit from CRISPR therapies, hence my interest.
|
| [1]
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10034092/#:~:te....
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