[HN Gopher] CRISPR cancer trial success paves the way for person...
___________________________________________________________________
CRISPR cancer trial success paves the way for personalized
treatments
Author : dsign
Score : 731 points
Date : 2022-11-10 22:04 UTC (1 days ago)
(HTM) web link (www.nature.com)
(TXT) w3m dump (www.nature.com)
| sniperjoe360 wrote:
| "Five patients had stable disease, and the other 11 had disease
| progression as best response on therapy"
|
| great science, but disappointing clinical results
| awillen wrote:
| > Although the efficacy of the treatment was low, the
| researchers used relatively small doses of T cells to establish
| the safety of the approach, says Ribas. "We just need to hit it
| stronger the next time," he says.
| _joel wrote:
| They did a low dose as this is new technology, the next round
| will have a higher count, so hopefully we'll see greater
| efficacy.
| joshxyz wrote:
| shit man i pray to fucking god for better resutls
| TaupeRanger wrote:
| They weren't trying to get results, only giving a low dose to
| verify acceptable side effects. Wait for the larger doses to
| render judgement on clinical results of the treatment modality
| itself.
| sniperjoe360 wrote:
| I completely agree with you. If there was even one response I
| would be much more optimistic. Since there is no clinical
| signal this is at best a proof of concept and safety.
| borissk wrote:
| This is very good news for the wealthy, not so much for the
| average Joe - it will take a lot of time for this treatment to
| become cheap enough to be used at scale.
| culopatin wrote:
| It's still good news for average joe because at least there is
| something to look forward to.
| danuker wrote:
| Reminds me of this story:
|
| https://spellbinders.org/the-smell-of-baking-bread/
|
| The smell of bread in this story is the knowledge that
| treatment exists.
| xattt wrote:
| What is the sound of jingling money in this story?
| danuker wrote:
| I guess, ad impressions on the site you've seen the news
| about the treatment.
| [deleted]
| vtail wrote:
| On the contrary, it's a very, very good news for an average
| Joe. _Every_ sufficiently advanced technology starts very
| expensive. Then capitalism and progress do their job, and it
| becomes available for masses.
|
| The path to "make it cheaper" is generally easier than the path
| to "make it possible".
| cmeacham98 wrote:
| > Every sufficiently advanced technology starts very
| expensive. Then capitalism and progress do their job, and it
| becomes available for masses.
|
| http://media2.s-nbcnews.com/j/newscms/2016_33/1676741/epipen.
| ..
| tjohns wrote:
| There are generic epi-pens available now.
|
| With GoodRx (no insurance), retail price is now about $100
| - and with insurance, it's sometimes closer to $0.
| cmeacham98 wrote:
| While not as bad as $400, $100 would still be a
| significant price _increase_ compared to 2008 (even when
| accounting for inflation).
| tjohns wrote:
| Keep in mind $100 is the retail price, not the wholesale
| price (which is what's plotted on the above graph). I do
| not know what the current wholesale price is for a
| generic epi-pen.
|
| My point is merely that the price is trending back down
| now that there's competition. And again, with insurance
| it's effectively free for most people - either through
| private insurance or medicaid.
| marricks wrote:
| Couple points:
|
| - MRNA COVID vaccine patents weren't open sourced or
| available for the third world but Cuba's vaccine solutions
| are
|
| - simple things like dental care aren't offered in the US
|
| I think you should replace "available for the masses" with
| available "to the middle classes" which may seem the same to
| the average HN reader but not the average inhabitant of our
| planet
| nine_k wrote:
| MRNA vaccines are not banned to sell in poorer countries.
| They are currently just too expensive for them, I suppose.
|
| Once Moderna recoups the cost of R&D and pockets some
| profits, it will face the need to keep selling. With the
| pandemic basically over, they'll need to sell to wider
| markets, because they have the production capacity. They'll
| lower the price and try to use the economies of scale by
| selling large amounts.
|
| The fact that any technological advances first become
| available to those who can pay a high initial price (not
| only in money) is pretty inevitable. If something is a
| runaway success, the price goes down with volume, and
| ideally with pressure from competition.
|
| If you want to make something vitally important available
| at a low price, you have to find enough money to let the
| producers make some profit, or at least to recover the cost
| of development. If you don't, nobody will consider working
| on it, even if they wanted, because getting an investment
| would become impossible, and you can't do biotech on pocket
| money.
|
| (You could of course force them work at gunpoint, but not
| being forced to work at gunpoint is usually even more
| vitally important for the health of a society.)
| worik wrote:
| > Once Moderna recoups the cost of R&D...
|
| No.
|
| Once the patent runs out....
| chasil wrote:
| Moderna was in the news this morning because heart
| problems are much higher with their vaccine.
|
| I think the R&D isn't quite done yet.
|
| https://www.cnbc.com/2022/02/04/though-rare-moderna-
| covid-va...
| pmoriarty wrote:
| This should stop absolutely nobody from vaccinating.
|
| From the article: _" People face a much higher risk of
| developing myocarditis from Covid infection than the
| vaccines, according to the Department of Health and Human
| Services. The risk of myocarditis from Covid is 100 times
| higher than developing the condition after Covid
| vaccination, according to a recent paper in Nature
| Reviews Cardiology."_
| chasil wrote:
| ...and for any other use, the safety profile is
| unacceptable.
|
| The R&D is far from done.
| Firmwarrior wrote:
| Good news: We cured cancer
|
| Bad news: Some people are still poor
| Tozen wrote:
| Good news: We found new alternative methods to treat
| cancer
|
| Bad news: You need to be very rich and very lucky
| smallnix wrote:
| Good news: We will cure some people with cancer
|
| Bad news: We will not cure some people with cancer
| praveen9920 wrote:
| Good news: We will cure some rich people with cancer Bad
| news: We will kill some rich people with cancer
| marricks wrote:
| I was directly calling out the bold and wrong claim that
| "it will be available for the masses" because that is
| entirely wrong.
|
| If I get cancer 10 years from now I could be in luck! But
| it doesn't mean I should immediately assume everyone else
| is.
| brigandish wrote:
| > I think you should replace "available for the masses"
| with available "to the middle classes" which may seem the
| same to the average HN reader but not the average
| inhabitant of our planet
|
| The statistics simply don't back you up, as not only do the
| middle classes make up the vast majority of people on the
| planet now, but those coming from poverty into the middle
| class is increasing. The much missed Hans Rosling goes
| through it here:
|
| https://www.youtube.com/watch?v=5JiYcV_mg6A
| pishpash wrote:
| That's the easy part.
| jojobas wrote:
| When penicillin was just introduced a week's course was about
| $100,000 in today's money. Today its better derivatives are
| sometimes given away for free.
| chasil wrote:
| That particular problem was solved by a mold-covered
| cantaloupe from Peoria, Illinois.
|
| "After a worldwide search in 1943, a mouldy cantaloupe in a
| Peoria, Illinois market was found to contain the best strain
| of mould for production using the corn steep liquor process."
|
| https://en.wikipedia.org/wiki/Penecillin
| jojobas wrote:
| The cantaloupe strain alone was not enough to make mass-
| production feasible. The process took years of refinement
| to take it where we are now.
| chasil wrote:
| Reviewing a larger section of the wiki, the Peoria
| cantelope certainly seems to have helped.
|
| "On March 14, 1942, the first patient was treated for
| streptococcal sepsis with US-made penicillin produced by
| Merck & Co. Half of the total supply produced at the time
| was used on that one patient, Anne Miller. By June 1942,
| just enough US penicillin was available to treat ten
| patients. In July 1943, the War Production Board drew up
| a plan for the mass distribution of penicillin stocks to
| Allied troops fighting in Europe. The results of
| fermentation research on corn steep liquor at the NRRL
| allowed the United States to produce 2.3 million doses in
| time for the invasion of Normandy in the spring of 1944.
| After a worldwide search in 1943, a mouldy cantaloupe in
| a Peoria, Illinois market was found to contain the best
| strain of mould for production using the corn steep
| liquor process. Pfizer scientist Jasper H. Kane suggested
| using a deep-tank fermentation method for producing large
| quantities of pharmaceutical-grade penicillin. Large-
| scale production resulted from the development of a deep-
| tank fermentation plant by chemical engineer Margaret
| Hutchinson Rousseau. As a direct result of the war and
| the War Production Board, by June 1945, over 646 billion
| units per year were being produced."
| jojobas wrote:
| It sure did, just pointing out that there was way more
| involved in engineering a cheap mass-manufacturing
| process than scavenging at markets. Somewhere near that
| section is a sentence on X-ray irradiation to induce
| mutations, just imagine the trial and error in that, and
| then these labour-intensive scaling experiments.
| [deleted]
| [deleted]
| yieldcrv wrote:
| I love that this form of reproducible science converges with the
| goals and beliefs of holistic practitioners which relies on non-
| reproducible methods
|
| Maybe the latter will go away once we have holistic/personalized
| solutions via CRISPR
| ck2 wrote:
| Random but CRISPR babies are going to sweep the Olympics in 2040
|
| China and Russia have to be fiddling with it at this point and it
| will either be completely undetectable or un-bannable in
| competition by then.
| timbit42 wrote:
| It won't be undetectable. If the changes are something no one
| else on earth has, it will show up. If the changes are
| something other people have, it will still show up when
| comparing with their parent's DNA.
| thret wrote:
| I read an article (or watched an interview) a few years ago,
| where they were saying that because cancer is unique to the
| individual, to truly cure cancer you would have to target each
| cancer individually. Hence CRISPR. But they also warned that this
| kind of control could also be used to target individuals or
| groups of individuals. The example they gave of what could
| theoretically be possible was 'making women of a certain racial
| group hyper sensitive to sunlight'.
|
| Was this hyperbole? I can't find any references to it today.
| UltraViolence wrote:
| This entire treatment is motivated by the urge to make money from
| it. The "correct" thing would be to repair the faulty genes in
| the cancerous cells and letting the body get rid of the tumors
| itself.
|
| We should stop treating cancer as foreign tissue that needs to be
| killed, destroyed or eliminated.
| WalterBright wrote:
| > This entire treatment is motivated by the urge to make money
| from it.
|
| Nearly all our high standard of living came from people
| motivated to make a buck.
|
| See James Burke's "Connections" (both the TV series and the
| book)
| nine_k wrote:
| When you find a way to do so, by all means let everyone know!
|
| Ideally please make all your technological knowledge public
| domain. (I hope you're a billionaire and will pay to your lab
| staff and for other research expenses from your pocket for a
| decade, or for whatever it takes.)
| dotnet00 wrote:
| That is both a more difficult technical/scientific challenge
| and a more difficult ethical issue. This could be trialed
| precisely because it doesn't require gene editing an entire
| human body.
| yitr wrote:
| lmao
| OJFord wrote:
| Why is one approach more linked to '[making] money from it'
| than the other?
| timy2shoes wrote:
| > We should stop treating cancer as foreign tissue that needs
| to be killed, destroyed or eliminated.
|
| ....but that's how t-cells work.
| RichEO wrote:
| I don't think I follow how your first sentence ties into the
| rest of your comment.
|
| Could you elaborate?
| 127 wrote:
| Money is just a form of accounting for value creation. Should
| people stop creating value to each other? I do not think so.
| People who only want to extract value of course do not want any
| credible accounting because then they would lose.
| chasil wrote:
| There are a few interesting aspects to cancer that you might
| find enlightening.
|
| First is "p53, the guardian of the genome." It has the ability
| to trigger apoptosis in a cancer cell, when stimulated
| correctly. It is usually active, and (likely) terminates most
| of your precancerous cells via apoptosis, the controlled cell
| suicide pathway.
|
| https://en.wikipedia.org/wiki/P53
|
| The second thing that cancer must do is shut down the
| mitochondria, because they are involved in apoptosis.
|
| An interesting thing about cancer is that it needs glucose, and
| lots of it because it cannot use efficient mitochondria, and
| instead relies on anaerobic respiration.
|
| The last interesting thing is autophagy, starvation (of sugar)
| which will slow down any cancer and potentially reactivate p53,
| depending upon your willingness to avoid prolific glucose
| sources.
|
| https://en.wikipedia.org/wiki/Autophagy
| chasil wrote:
| Zinc might help.
|
| "central DNA-binding core domain (DBD). Contains one zinc
| atom and several arginine amino acids: residues 102-292. This
| region is responsible for binding the p53 co-repressor LMO3."
| TulliusCicero wrote:
| Username doesn't check out.
|
| But seriously, not only is that probably enormously harder, you
| realize companies would still make money off of that treatment,
| right?
| msla wrote:
| > This entire treatment is motivated by the urge to make money
| from it. The "correct" thing would be to repair the faulty
| genes in the cancerous cells and letting the body get rid of
| the tumors itself.
|
| Do you have any hint of an idea about how to do this?
| ethbr0 wrote:
| This pulls together so many advancements that it would make a 90s
| oncologist cry.
|
| 1) Being able to rapidly sequence the genomes of cancer cells to
| detect common mutations
|
| 2) Computationally simulating those mutations to look for viable
| T-cell targets
|
| 3) Custom building T-cell receptor proteins [0] capable of
| recognizing those targets
|
| 4) Inserting those custom receptor proteins into the patients'
| own T-cells with CRISPR
|
| Truly, we're living in the days of future medicine...
|
| [0] https://en.m.wikipedia.org/wiki/T-cell_receptor
| someweirdperson wrote:
| > 1) Being able to rapidly sequence the genomes of cancer cells
| to detect common mutations
|
| Only of the cancer cells? How are mutations detected in the
| 0.4% of the DNA that differs in different human beings? Can't
| there be non-cancerous changes in the other 99.6% that are
| present in all cells? Is it just a matter of cost, sequencing
| both too expensive?
| joshuahedlund wrote:
| My initial guess would be that they would compare cancerous
| vs non-cancerous cells _within the same human being_
| doctoring wrote:
| The article mentions: "...sequencing DNA from blood samples
| and tumour biopsies, to look for mutations that are found in
| the tumour but not in the blood."
|
| This is pretty common for most cancer genotyping tests.
| (Sometimes they compare tumor with saliva or some other
| "benign" source, but the principle is the same.)
| shellfishgene wrote:
| > Custom building T-cell receptor proteins [0] capable of
| recognizing those targets
|
| How does this part work? Is this some sort of selection of
| cells in the lab, or done in silico?
| projektfu wrote:
| There are processes such as this one. Sequencing specific
| T-cell DNA gives you the fragments you need to insert into
| the target genome.
| ramraj07 wrote:
| It's good progress but I want to say it's still not a magical
| cure - the fundamental idea is flawed - the tumor can and
| likely will in many patients just mutate the immunogenic
| epitope.
| dm319 wrote:
| I haven't seen evidence of cancers re-mutating mutations.
| They tend to develop new mutations (as in the clonal
| evolution hypothesis), and they can completely change their
| cell surface expression. But I suspect that they are unlikely
| to mutate an already mutated gene.
|
| I guess for the treatment to be most effective you need to
| target some of the earlier mutations, rather than a small
| clone.
|
| From my perspective, and not having read the paper, I thought
| the technology to predict what TCR would bind a particular
| peptide on a particular MHC-1 was not there yet.
| suslik wrote:
| > But I suspect that they are unlikely to mutate an already
| mutated gene
|
| Could you elaborate? I'd like to understand what you mean,
| as I don't work on onc. Aren't recurring mutations in
| response to treatment in f.e EGFR is the reason we keep
| developing multiple generations of small molecule therapies
| for it?
| dm319 wrote:
| Yes, I didn't mean impossible, I just mean compared to
| accumulating new mutations elsewhere, and compared to
| downregulating surface proteins (which can be the issue
| in CAR-T).
| evandijk70 wrote:
| Different treatment, but tumors receptive to EGFR-treatment
| almost always develop secondary resistance to treatment by
| additional mutations.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367712/
| dm319 wrote:
| Yes good point.
| ramraj07 wrote:
| Cancers have higher mutation rates and also constantly
| rearrange their genome including deletions. Given that
| they're looking for Novel epitopes it goes to reason these
| are not high copy number hence deletions can also remove
| them fully. It'll be hard for me to believe that a
| mutagenic cancer (which is a given here since you're
| looking to treat cancers with actual mutations) will not
| eventually gain resistance to this therapy.
| dm319 wrote:
| Yes you are right, I should have said that re-mutation of
| mutations happen far less often than accumulation of
| additional mutations.
|
| Novel epitopes should be high copy number - and driver
| mutations will be present in 80-100% of the cancer cells.
| It depends how many cancer cells you get in your biopsy
| that you sequence I guess.
|
| It is easier for a cancer cell to mutate or remove a cell
| surface protein than to mutate the same mutation
| targeted, but you are right - that can happen and I'm
| sure will be a form of treatment resistance for these
| types of treatment in the future.
| theptip wrote:
| How fast can a tumor mutate to resistance? If we're iterating
| our therapy faster than this cadence do we win the battle?
| ramraj07 wrote:
| An iterative approach could work, yes. My guess would be
| that it takes months to grow resistance to a new therapy.
| chasil wrote:
| I might not understand it correctly, but the t4 helper cells
| don't directly work on antigens/pathogens.
|
| They do stimulate macrophages, and activate b-cells.
|
| This from some cartoons, and the associated book by Detmer,
| _Immune_.
| ethbr0 wrote:
| Only tangentially my field, but both cytotoxic and helper
| T-cells bind on antigens, and indeed this work CRISPR edited
| anything with a TCR to their (3) preferred, cancer-targeting
| receptors (for each patient).
|
| The press release has a few more details (in addition to the
| Nature paper): https://pactpharma.com/news/pact-pharma-
| reports-data-from-fi...
| dm319 wrote:
| Your CD4 T cells are basically the directors of your immune
| system. They license CD8 T cells (T killer cells), B cells
| and recruit NK and immune cells to sites. The type thought to
| be most anti-cancer are the Th1, which recruit CD8 T cells
| and NKs, and are optimised for intracellular pathogens.
| Cancer can be thought of as an intracellular pathogen because
| it harbors mutations.
| piyushpr134 wrote:
| As per the article, calling this a "success" is a little over the
| top. Out of 16 patients, it stopped progression of tumour in 5
| had stopped but it doesn't say it decreased. Moreover for 2, it
| had adverse reactions when admittedly the dosage was low. I won't
| call that a success. IT is a good start and promising result.
| "Success" would mean at least 50% patients REDUCED the tumour. So
| let us not hold our breath yet
| timbit42 wrote:
| While removing the cancer cells would be preferable, killing
| them all so they no longer replicate means the patient will not
| die from that cancer.
| candiddevmike wrote:
| How does this compare to mRNA treatments for cancer?
| [deleted]
| _joel wrote:
| They're both in vary nascent stages in terms of having a
| comparable dataset in my layman's understanding. Both look
| extremely promising, some may be better suited to different
| classes so that's what larger studies will hopefully help
| detail.
| dumbmrblah wrote:
| MD and I work in the field. The technology is called CAR-T, as
| the article mentioned. It's been used pretty widely for "liquid"
| tumors for a while (eg leukemia, lymphoma, and multiple
| myeloma),but solid tumors are particularly difficult to target
| using current CAR-T therapy. If this CRISPR tech can be applied
| widespread to solid tumors that opens up a huge swath of patients
| that can be treated.
|
| However cost and logistics are a huge factor. CAR-T therapy
| currently cost about $300,000-$500,000 to treat a patient. Beyond
| the cost of the immunotherapy you require a huge institutional
| investment because there are characteristic side effects that
| occur within the first 30 days of treatment which necessitates
| patients to be either admitted to the hospital for 30 days or
| stay in close proximity with daily check-ins (yes the cancer is
| getting treated BUT now your immune system is hyperactive which
| can be very dangerous in the short term).
|
| Very few academic hospitals, let alone community hospitals, have
| this bandwidth which will lead to cancer care being concentrated
| in a handful of a few very large cancer specific institutions.
| [deleted]
| dm319 wrote:
| This isn't CAR-T, which is a chimeric antigen receptor
| (antibody) grafted onto a T cell. This is a T cell with an
| edited TCR receptor. This is quite different and comes under
| the 'adoptive TIL' category of treatments. It allows targeting
| of antigens not displayed on the cell surface. Every cell has
| to process their protein through a proteasome and present those
| peptides on the cell surface, which is where the advantage of
| this type of treatment comes in. In CAR-T we target a surface
| protein, and there's nothing to stop the cancer removing that
| protein from the cell surface.
| marstall wrote:
| For comparison on the cost question:
|
| I received conventional, pre-CAR-T treatment for ALL Leukemia
| about 9 years ago. That consisted of chemo, total body
| irradiation and a successful bone marrow transplant. Cost was
| $300,000.
| jojobas wrote:
| Does that $300,000-$500,000 go mainly to super-highly qualified
| labour, expensive materials or rare machine time? Still more or
| less on par with a few rounds of chemo.
| dumbmrblah wrote:
| Good question and I should have been more clear. The _drug_
| itself is $300,000-$500,000. It's crazy expensive, but it's
| not like a hedge fund patenting 100 year old insulin or
| something, it's a bespoke medication. I still think they are
| price gouging however.
|
| The medical care would likely add another $500,000.
|
| https://ashpublications.org/ashclinicalnews/news/3469/CAR-T-.
| ..
|
| All in about $1,000,000 per patient.
|
| There were some drama in England about NICE not willing to
| put the medication on NHS formulary because of the sheer
| expense. Is it better to treat 1000 diabetics or one cancer
| patient?
|
| https://www.biopharma-
| reporter.com/Article/2018/09/21/Novart...
|
| They ultimately approved it.
| wanderingmoose wrote:
| To put this in perspective, a family member was treated for
| leukemia and our billed* medical expenses hit $300,000 in
| the first 2 weeks of treatment. This included the initial
| hospitalization, attempted install of PIC line, install of
| broviac catheer. And secondary hospitalization in hepa
| controlled room due to other illness during an immuno
| compromised period.
|
| The standard treatment continues for ~2.5 years so this was
| only a small portion of the bills we received.
|
| *obviously what is paid by insurance + out of pocket is
| very different, but that level of billing is insane. Also
| you really don't want to be fighting insurance and the
| medical center over billing while your family is undergoing
| cancer treatment.
|
| This was at UCLA
| jojobas wrote:
| Well what makes the drug so expensive? Is it mostly mark-up
| for a high risk venture, is it actually taking 2+ man-years
| to formulate the drug for a particular patient, does it
| require already expensive components/reactants/whatever,
| bespoke machinery that would only produce a few doses in
| its lifetime, or some combination thereof?
| [deleted]
| surfaceofthesun wrote:
| Not responding with regard to any specific treatment,
| rather more generally. It's a mixture of several things:
| * New/Niche Equipment * Few few commoditized inputs (e.g.
| lentiviral vector) * Labor Intensive * These setups look
| more like labs than large continuous or batch
| manufacturing sites * Everything requires GMP * This can
| mean weeks of training new personnel (even for well known
| manufactures) * Additional time & resources for FDA
| approval (safety testing, documentation, validation,
|
| This is a good reference:
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363291/
| ETH_start wrote:
| We need to massively scale back regulatory regimentation in
| medicine
|
| "FDA Deregulation Increases Safety and Innovation and
| Reduces Prices"
|
| https://marginalrevolution.com/marginalrevolution/2022/11/f
| d...
|
| We will never get the pace of innovation and price
| reduction in medicine that we see in more market based
| product classes if we don't.
| electriclove wrote:
| Seriously, innovation needs to be encouraged and all the
| gates hamper that. But being critical of the medical
| cartel gets flagged/downvoted quickly here. See comment
| higher up.
| yosame wrote:
| It might reduce prices, but I wouldn't trust pharma
| companies to put safety over profit. We've seen time and
| time again that pharma companies will do the bare minimum
| to prove safety, which has lead to a large amount of harm
| (see Vioxx, Thalidomide, etc). I don't think reducing
| what safety measures they have to prove will make
| therapies safer.
| jojobas wrote:
| Safety can legitimately be in the backseat when you're
| trying to cure a disease that has a 50% chance to kill
| you in a year.
| worik wrote:
| > Safety can legitimately be in the backseat when you're
| trying to cure a disease that has a 50% chance to kill
| you in a year.
|
| Yes.
|
| Standards are lower in that case. Back in the 1990s when
| I was up to date, clinical trials for HIV ad cancer
| treatments were truncated.
|
| We saw the rapid development of COVID vaccines recently,
| much quicker than normal drug development
| bawolff wrote:
| Its not just safety, but to prevent shady people from
| taking advantage of desperate people.
| zo1 wrote:
| I'd be curious to see what would happen if reasonable
| regulations stayed in place but we capped/removed the
| risk associated with litigation (assuming regulations
| were followed). I.e. what portion of "adhering to
| regulation" is reducing the speed of advancement because
| of fear of litigation, as opposed to just the cost of
| sticking to the regulation.
| ETH_start wrote:
| The study on medical devices indicates that safety
| actually improves with deregulation, due to the
| combination of a larger market and litigation.
|
| In any case it's obvious to me at least that in the long
| run, if medicine sees the same pace of innovation that,
| say, smartphones have seen, or even that the cosmetic
| surgery field has seen, we would have much safer medical
| products and services just by virtue of them being
| significantly more sophisticated, less invasive etc.
|
| Finally - even if all this weren't true - without price
| reductions, it will be increasingly the case that the
| safest and most effective treatments will be out of reach
| of the masses, due to simple economics/scarcity. I would
| rather have some lower quality products/services
| available to the public, and the best quality ones be
| more accessible, than remove the lower quality offerings
| but also deprive the public of the best quality ones.
| candiodari wrote:
| Why this choice? In the case that a treatment is life-
| saving the ethics board can approve experimental
| treatments on a case-by-case basis. Medical laws just
| don't allow patients to make this choice for themselves.
| ETH_start wrote:
| The problem with the centralization (regulation) approach
| is that it assumes one body can be chosen that will be
| optimal at risk assessment. In practice, the process of
| developing good risk analysis frameworks - that strike
| the right balance between cost, risk and efficacy - is
| often best discovered through trial and error, and that
| requires the freedom to try new products in the market.
| candiodari wrote:
| There's an ethics board per hospital. And there's
| different countries. You can in fact shop around if
| that's what you want to do. You can do this, both as a
| patient and as a pharmaceutical company. It's just really
| expensive.
| worik wrote:
| > The study on medical devices indicates that safety
| actually improves with deregulation, due to the
| combination of a larger market and litigation.
|
| I doubt it, very much.
|
| Appropriate regulation, not deregulation, is the name of
| the game.
| ETH_start wrote:
| >>Appropriate regulation, not deregulation, is the name
| of the game.
|
| Based on what case studies of industries? Look at the
| prices in the most regulated sectors. In medicine, it
| makes the most effective treatments inaccessible to the
| wider public, with innovation that reduces costs
| progressing at a glacial pace.
| worik wrote:
| Pharmac and Medsafe in New Zealand.
|
| Medsafe regulates medicines, what is effective, and
| Pharmac buys them, for the whole country.
|
| Pharmac drives hard bargains with pharmaceutical
| companies. There is a lot of money to be made (even in a
| small market like New Zealand) if a medicine is -bought
| (read subsidised) by Pharmac.
|
| The effective treatments are available. The highly
| experimental, might work, might not, might kill you,
| might make you sicker, might cure you medicines are held
| at bay by medsafe, and when approved are made affordable
| by Pharmac.
|
| Of course Pharmac is under constant attack by the
| completely unethical pharmaceutical industry and equally
| unethical senior doctors - all hopelessly corrupted by
| the enormous sums at stake. Huge astroturfing campaigns
| exploiting ill people and their families. But the
| benefits are so huge that it has survived.
|
| There is talk about extending the model to medical
| devices and consumables.
|
| Appropriate regulation is absolutely needed because the
| incentives that drug companies and medical equipment
| manufacturers face are opposed to the incentives of the
| community.
|
| Free markets, in this case, make people sick and
| impoverished.
| concordDance wrote:
| Sometimes availability is more important than safety. Let
| the patient decide if they want to take the risk, just
| mandate they be informed.
| MichaelZuo wrote:
| What do you estimate is a fair price?
| newyankee wrote:
| My question would be more like, what would be needed for
| it to fall to 10% of its price ? Still only limited to
| developed world, but at least would make it more
| accessible
| 120photo wrote:
| Do you know if CAR-T or CRISPR technology goes into the brain?
| dumbmrblah wrote:
| There are clinical trials on Glioblastoma CAR-T treatment but
| it faces the same problems as any other solid tumor - namely
| the solid tumor microenvironment is not amenable to the
| current generation of CAR-T treatments
|
| In addition one of the dreaded side effects of CAR-T is
| neurotoxicity. CAR-T can cross the blood-brain barrier and
| leads to inflammation in the brain. You can treat it pretty
| quick with steroids but this side effect along with several
| other pro-inflammatory ones is the reason for the 30 day
| hospitalization sp treatment.
| 120photo wrote:
| I seen what inflammation in the brain causes, not pretty.
| erisian wrote:
| Not CAR-T or CRISPR AFAIK, but there's been some recent
| breakthroughs with getting treatments past the blood brain
| barrier, and promising glioblastoma treatments are in the
| pipeline as well. This is just what I've seen on the internet
| news, you'd find more than I know about it with some internet
| searches.
|
| I hope you aren't affected by GBM. If you are, or someone you
| know is, my only advice is to live life to the fullest while
| you can and don't let yourself fall into denial of the
| prognosis.
| 120photo wrote:
| Not me but my wife. Will just put this out there for anyone
| else, the advancements made in Cancer treatment in the past
| few years are impressive. Don't lose hope.
|
| Also, listen to your doctors as all of the sudden everyone
| is oncologist. Listen to your doctors, seek second
| opinions, do research but question everything as there is a
| lot of snake oil for sale.
| erisian wrote:
| I'm so sorry. My mom was diagnosed a few years ago and
| she got preyed on by snake oil salesmen to the tune of 6
| digits. The money doesn't matter to me, but people are
| really fucked up.
|
| I can recommend Duke's neuro-oncology center though. They
| did a great job with her when Sloan Kettering wouldn't
| touch her.
|
| Best of luck to the both of you and hang in there.
| tauwauwau wrote:
| How do hospitals spend $10000 to $16000 a day?
| a99c43f2d565504 wrote:
| To pay the people who make these things happen I suppose.
| daguava wrote:
| Is that the real COST or the markup "cost"
| newZWhoDis wrote:
| xeromal wrote:
| Don't forget R&D costs
| someweirdperson wrote:
| Also, don't forget government money for funding of
| research.
| test6554 wrote:
| But please pay no attention to marketing costs.
| inglor_cz wrote:
| The madness of the US healthcare aside, CAR-T is really a
| somewhat complicated therapy. There are no economies of scale
| there, unlike in pills. Each patient requires a lot of
| painstaking work that can only be done on specialized
| machines by highly qualified people, plus the safety
| requirements are really high.
|
| Activating the immune system is risky. It is strong and it
| can crush cancer in mere weeks, but it is also very dangerous
| to friend and foe alike. Basically, you gather a lot of
| absolutely ruthless and stupid troops and tell them "here is
| ze Flammenwerfer, burn the enemy to crisp, but don't destroy
| anything else".
|
| Easier said than done.
| yosame wrote:
| Probably both, they've got to make back the cost of
| developing and testing the therapy, but there's probably a
| profit markup on top of that.
| skissane wrote:
| US-based pharmaceutical companies maximise their margins in
| the US to make up for smaller margins in other markets. In
| many other countries, most prescription drugs are purchased
| by the government, which gives the government a lot of
| bargaining power which it uses to drive margins down.
| Prescription drug purchasing is much more disjointed in the
| US (negotiating with many private insurers instead of just
| the government), giving more bargaining power to the
| vendors and supporting higher margins.
| texasbigdata wrote:
| This doesn't make sense. Consider two scenarios: company
| ABC sells only in the USA and Company XYZ is otherwise
| identical but also sells to Asia.
|
| You are implying that because XYZ has lower profit as a
| percentage yet higher profit as a nominal dollar amount,
| that XYZ will charge its American patients more. My
| intuition says both ABC and XYZ will charge Americans the
| same, namely the highest amount it possibly can under
| market/regulatory/PR/competitive considerations.
| ThinkBeat wrote:
| I sadly know little about all this technology. It is
| fantastically expensive at the moment from what you say. That
| keeps it away from the vast majority of cancer patients in the
| world.
|
| Technology does tend to get cheaper over time, though not
| always.
|
| Do you think this treatment could reach $30.000 in 2,5,10,15
| years? And $300 in another 10,20,50 more years?
| chefkoch wrote:
| Another therapy mentioned often in the comments here CAR-T is
| at the moment around 300k from the pharmaceutical companies.
|
| A study in germany predicts a cost of around 30k if
| universities or other bigger health care providers create the
| CAR-T cells in their own labs.
| heavyset_go wrote:
| I've watched the prices of patented drugs quadruple in less
| than 5 years, to the point where a 30 day prescription can
| cost thousands of dollars despite the same medication costing
| $40 in countries like the UK. Drug companies have absolutely
| no reason to drive down prices of the patented treatments
| they have a literal monopoly on.
| worik wrote:
| Corporate capture
| solveit wrote:
| > Technology does tend to get cheaper over time, though not
| always.
|
| What technology didn't get cheaper?
| John23832 wrote:
| Not in the medical field, but space flight?
|
| I think the point is that technology that has to constantly
| progress to stay relevant doesn't stay cheap.
| BurningFrog wrote:
| Space-X has lowered costs by almost an order of
| magnitude, if I remember the numbers.
| John23832 wrote:
| SpaceX is a small fraction of total lifts though.
| XenophileJKO wrote:
| Something like 20-25% of all launchs globally doesn't
| seem like a small fraction.
| [deleted]
| etothepii wrote:
| I don't think this is true. It's something Musk likes to
| say, but a source would be useful.
| midoridensha wrote:
| I'm sure the launch costs (which can be worked into $/kg
| for payload) can be easily looked up, and show that
| SpaceX's reused rockets are much cheaper than what came
| before.
| etothepii wrote:
| Do you have a source?
|
| We haven't seen a reduction in space insurance premiums
| of any particularly large magnitude which I would expect
| if the costs of launching satellites into space had been
| substantially reduced.
| someweirdperson wrote:
| Falcon 9 is as cheap as Proton M according to something
| google found somewhere.
| lost_tourist wrote:
| Insulin, also a lot of pharmaceuticals have gone up over
| the past 10 years, at least in the USA from price gouging.
| bluetwo wrote:
| > What technology didn't get cheaper?
|
| Insulin.
| anthk wrote:
| In the US.
| rootusrootus wrote:
| Yeah, Europe bends us over on pricing.
|
| Though plain old insulin is actually pretty cheap. It's
| the fancy stuff that's really expensive.
| est31 wrote:
| Webcams. They have barely improved in the last 10 years
| technology wise, and in fact even got more expensive due to
| covid.
| musicale wrote:
| Phone cameras have improved phenomenally and are great
| webcams. You can even clip them to your laptop if needed.
|
| For webcams we now also have eye/head/movement tracking,
| automatic background insertion, and other improvements
| (as well as added features like turning you into an
| animated cartoon character) although arguably those are
| from webcam software rather than hardware (though there
| are examples like the Apple Studio Display webcam which
| uses their neural engine hardware.)
| [deleted]
| concordDance wrote:
| Small planes. The exact same plane from the 1970s costs 4x
| as much.
| someweirdperson wrote:
| Those fancy digital glass cockpit avionics in the modern
| versions are not cheap. On the other hand, those ancient
| mechanical avionics were crazily expensive, too.
| concordDance wrote:
| When I say the exact same plane I mean the same plane,
| not one with fancier avionics.
| someweirdperson wrote:
| Same model from the 70s with the same avionics in 2022?
| I'm not sure that's even available. C172 entry model is
| full glass today. Interior looks a lot more shiny, too.
|
| Maybe not same model but actually same plane? If it was
| new in the 70s it is used and much cheaper now. If it was
| new in the 50s, the used price in the 70s might have been
| lower than it is today though. That's caused by the
| minimum price the market defines for anything that's
| airworthy.
|
| Maybe that's an investment stragtegy, buying used planes
| when they reach their minimum price, then keeping them,
| flying minimal hours to keep the engine alive, to sell 50
| years later. But any potential gain will be neglected by
| hangar and maintenance cost.
| club_tropical wrote:
| This is criminally underinvested.
| queuebert wrote:
| General aviation is quite a ways behind where cars are
| right now. There are new planes like the Cirrus SR22 that
| have made advances, but they are far from ubiquitous.
| Most GA planes are like driving a 57 Chevy except if the
| engine dies, you die.
| macintux wrote:
| Although I'm hesitant to make strong statements because
| inflation plays a significant role here, cars are much more
| sophisticated than they used to be but also very expensive
| as a result.
| andy_ppp wrote:
| Depends on the car... there are still some extremely
| cheap options out there that do a surprising amount of
| stuff.
| somenameforme wrote:
| In 1916 a barebones model-T cost $360 [1]. That's $8400
| in 2019 dollars, and $9800 in 2022 dollars. This is
| actually what led to the normalization of planned
| obsolescence. [2] The widespread availability of reliable
| and cheap vehicles posed a problem for manufacturers
| which had, to that date, primarily just competed on
| quality and price.
|
| What do do when you can't create something more cheaply,
| or of a higher quality? Curve some edges, strap a layer
| of chrome on it, and market it endlessly to get people to
| buy the fundamentally identical product over and over and
| over again. Progress!
|
| "Oh god, I can't believe you're still driving a 1916 -
| that's soooo last year."
|
| [1] - https://modeltfordfix.com/the-1916-model-t-ford/
|
| [2] - https://en.wikipedia.org//wiki/Planned_obsolescence
| #History
| mlyle wrote:
| > In 1916 a barebones model-T cost $360 [1]. That's $8400
| in 2019 dollars, and $9800 in 2022 dollars.
|
| Not too much like a modern car to compare, though. Still
| no electric starting, and not a lot of capacity, creature
| comforts, or speed. Time between major overhauls was
| ~15,000 miles. Overall lifespan of the car was estimated
| as 100,000.
|
| > What do do when you can't create something more
| cheaply, or of a higher quality? Curve some edges, strap
| a layer of chrome on it, and market it endlessly to get
| people to buy the fundamentally identical product over
| and over and over again. Progress!
|
| When we're comparing to vehicles with anything like
| modern speeds and capacities,... average vehicle age /
| longevity is higher than its ever been. (It's a bit more
| difficult to compare before the mid-1960s because
| vehicles were rebuilt and overhauled so much before
| then...)
| somenameforme wrote:
| I don't think technology improving over long time scales
| runs contrary to the nature of the question, or answers
| it. The first computer, the ENIAC, required a small
| building of space, cost about $6 million, and ran at
| around 500 FLOPs. Today a modern GPU is several inches
| long, costs a couple of hundred dollars for a pretty
| decent one, uses minimal electricity, and will run
| literally tens of billions times faster than the ENIAC.
| mlyle wrote:
| Well, overall hedonistic adjustments to price are
| complicated and controversial.
|
| I'm just saying: there's not really any cars like a model
| T anymore. Not just because of increased technology, but
| because of improved underlying technology: customers
| expect more (volume, mass capacity, interior comforts,
| ancillary features, speed, etc) and that increases cost.
|
| We could probably make something a lot like a model T
| pretty cheaply still, if there were a big market for it.
| baggy_trough wrote:
| Also, the government makes it illegal to make cars like a
| model T now.
| macintux wrote:
| I think that depends on what you classify as "extremely
| cheap". The cheapest car in the U.S. market is the Spark
| at under $14k, but it's been discontinued. The Versa and
| Mirage both start around $16k.
|
| I'm unaware of anything else under $20k, although the
| Ford Maverick is impressively reasonable at $21k.
| mlyle wrote:
| > because inflation plays a significant role here
|
| A new, average midsize new car in 1985 was approximately
| $11,000. (~$30,500 after inflation).
|
| A new, average midsize sedan is now approximately
| $31,886.
|
| In 1927 Model A Ford in the Town Car configuration was
| $1400-- this is like $24,000 now, but of course, it's a
| lot less car than a modern midsize.
|
| IMO, car pricing hasn't changed much.
| pbourke wrote:
| Today's car is safer, more fuel efficient and more
| capable as well.
| LegitShady wrote:
| ti calculators
| TedDoesntTalk wrote:
| Hearing aids
| midoridensha wrote:
| Like a lot of things, you need to add "in the US" to
| stuff like this, because outside the US these things are
| dirt cheap.
| yitchelle wrote:
| Sadly, physical calculators will soon be extinct as it
| will be replaced with calc app on the mobile phones.
| imiric wrote:
| The fact that hasn't happened after 15 years of
| smartphones suggests it won't happen at all.
|
| There's still a market for dedicated calculators. Schools
| don't allow students access to smartphones during tests,
| but calculators are fine.
| quickthrower2 wrote:
| Because of calculator lobbyists?
| LegitShady wrote:
| because of schools and cheating
| worik wrote:
| > What technology didn't get cheaper?
|
| Military hardware?
| colinmhayes wrote:
| Obviously not op, but it sounds like the issue is that the
| cure makes you sick in the short term which requires
| expensive care. If the sickness is inherent to the solution
| it's hard to see how this gets cheaper.
| dumbmrblah wrote:
| The next generation CAR-T treatments are supposed to be
| "easier" on the immune system and hopefully don't require
| the prolonged hospitalizations. But that is 5-10 years
| away.
| nicwilson wrote:
| As with many medical drugs, the marginal cost of production
| of the medication is small, but it is dwarfed by the cost of
| research, trial conduction and FDA approval and is patented.
| Additionally for CAR-T there is rather intense post-
| adminitsation care required.
|
| For the pharma research companies to be profitable, they need
| to recoup the above costs on the limited number of cancer
| patients there are.
|
| For a widely applicable technology like CAR-T, if you can
| figure out how to distribute the costs over multiple types of
| cancers, you could have a much larger pool of patients to
| distribute the cost over, such that the marginal cost of
| production is a more meaningful component of the cost to
| patient/insurer.
| fredophile wrote:
| There are companies doing research in applying CAR-T for
| treating animals. This has a much easier approval process
| since it is run through USDA and not FDA. I'd expect to see
| faster advancements in treatment and lowering costs and
| then having this tech brought over to humans later.
| erisian wrote:
| Pharma typically spends a lot more on marketing than
| research. In fact, there is little to no correlation
| between research costs and the cost of a drug.
|
| https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559086/
|
| https://www.wired.com/story/drug-research-pricing/
|
| https://www.washingtonpost.com/news/wonk/wp/2015/02/11/big-
| p...
|
| https://www.cbsnews.com/news/higher-drug-prices-support-
| prof...
| rmak wrote:
| Cancer won't be a problem by 2027, at least for the people
| who don't already have cancer. By 2030 there will be drugs
| that can even cure stage 4 cancer with next to nothing side
| effects. (AI and some form of quantum computing will help
| find these drugs)
| teux wrote:
| That seems like a very confident statement. How are you
| reaching that? (Other than a magic AI.)
|
| Quantum is not at that point, and won't be in 3 years.
| evandijk70 wrote:
| Researcher working in a related field. The above is just
| patently false. There are currently no drugs that can do
| this in lab-animals, let alone make it through clinical
| trials in time by 2027.
|
| Computation is also not the bottleneck of research, it's
| the amount of training data, see ICGC https://dcc.icgc.org
| for the current state of the art.
|
| Remember that each tumor has 3 billion base pairs
| (A,C,G,T), each of which can be duplicated, deleted,
| mutated. It can also be affected by methylation. Expression
| of the genes comprised by these base pairs is also affected
| by the micro-environment of the cell. Any machine learning
| model will have far to many parameters for far to few
| observations, to pick the rare drug that can cure stage 4
| cancer (assuming it even exists) out of millions of
| possible chemical compounds.
| derefr wrote:
| > yes the cancer is getting treated BUT now your immune system
| is hyperactive which can be very dangerous in the short term
|
| Can immune-suppressive drugs be used during treatment?
| fnordpiglet wrote:
| This sounds like something that works out with time and scale.
| Thanks for the insight.
| bobmaxup wrote:
| > which will lead to cancer care being concentrated in a
| handful of a few very large cancer specific institutions
|
| Wouldn't that be a good thing? Aren't specialized hospitals
| better at treating things that they specialize in?
| ugh123 wrote:
| From what OP said, I doubt they'd be able to keep up with the
| additional load of patient care (admittance especially) so
| there could be long wait times.
|
| At some point, capabilities like this mature on the science
| end but are slowed down on technology (scaled manufacturing).
| That would take significant investment by a big pharma or a
| new venture-backed investment to go after things like this.
| Fingers cross this happens within my lifetime.
|
| From the article: >"This is a tremendously complicated
| manufacturing process," says Joseph Fraietta, who designs
| T-cell cancer therapies at the University of Pennsylvania in
| Philadelphia. In some cases, the entire procedure took more
| than a year.
| dumbmrblah wrote:
| Good for people with money, resources to know where to get
| the best treatment and live close by; bad for everyone else.
|
| Disclaimer: I work at a giant cancer institution.
| aantix wrote:
| If money weren't an issue, which institution/doctor would you
| send a loved one to if they needed such treatments?
| throwaway12245 wrote:
| You'll want to sign them up for a clinical trial. Only CAR-T
| cell therapies that are FDA approved are for leukemias. [ and
| as a commentator points out, for lymphomas, I had always
| thought lymphomas were a subset of leukemia. mea culpa ]
| msla wrote:
| I personally got CAR T-cell therapy (Yescarta) for Primary
| Mediastinal Large B-Cell Lymphoma:
|
| https://www.yescarta.com/
|
| https://en.wikipedia.org/wiki/Axicabtagene_ciloleucel
|
| > On 1 April 2022, the FDA approved axicabtagene ciloleucel
| for adults with large B-cell lymphoma (LBCL) that is
| refractory to first-line chemoimmunotherapy or relapses
| within twelve months of first-line chemoimmunotherapy.
|
| I was in a clinical trial, though, but that was to
| determine the effectiveness of Anakinra in preventing
| serious side-effects; in my case, I only got a few mild
| fevers, which is the biochemical equivalent of winning the
| lottery, in a lottery where losers end up comatose and
| intubated.
|
| https://en.wikipedia.org/wiki/Anakinra
| sergiotapia wrote:
| I am very happy for your outcome, can't imagine the
| stress and fear you felt. So glad you had success, let's
| hope this becomes commonplace and people are saved from
| such a wretched fate.
| msla wrote:
| I'm also very happy, especially since I was in complete
| remission as per a PET/CT scan a month after infusion
| after my cancer had survived two previous lines of
| chemotherapy (DA-EPOCH-R and R-GemOx) and had even shrunk
| but became more metabolically active after the second
| line. I'm still in complete remission, with further
| destruction of the tumor, six months after infusion, and
| there's some evidence the CAR T-cells can persist a
| decade after infusion:
|
| https://www.nature.com/articles/s41586-021-04390-6
| worthless-trash wrote:
| This story made my day.
| aledalgrande wrote:
| We need more stories like this.
| dumbmrblah wrote:
| Incorrect. Yescarta, Tecartus among others are approved for
| certain types of lymphoma.
|
| Multiple myeloma has Carvykti and Abecma
|
| https://www.cancer.gov/sites/g/files/xnrzdm211/files/styles
| /...
|
| With respect to institutions:
|
| East coast: Sloan Kettering in NYC and Dana Farber in
| Boston
|
| Middle America: MD Anderson in Houston
|
| West coast: City of Hope and UCLA in Los Angeles.
| jcims wrote:
| Took my wife to MSK for a second opinion on the treatment
| plan for her ovarian cancer. They were beyond useless.
| They wouldn't say or recommend anything until the current
| treatment plan (eg round of chemo or surgery) was
| complete, yet it was incredibly difficult to arrange time
| with them to review results when that time came.
|
| Basically we got nothing from them.
|
| Not sure what my point is other than if you're getting a
| second opinion, discuss how the provider will integrate
| their assessment with the existing treatment plan. And at
| the end of the day it's the doctors and nurses you get
| that make the difference in your care, not the building.
| voisin wrote:
| I hope that this didn't negatively impact your wife's
| outcome and that she got better care elsewhere.
| jcims wrote:
| Thank you. We visited Cleveland Clinic as well and
| received very similar results. I briefly thought about
| starting a class for cancer patients to help them
| navigate the medical system in the US. I had to try to
| learn to fly from the front seat of the plane and it was
| a bad experience.
|
| She passed in 2020, just two years after diagnosis.
| cauthon wrote:
| Hutch/SCCA?
| Enginerrrd wrote:
| How do they handle controls in cancer trials? Is it
| compared against what is otherwise the standard of care?
| mcbain wrote:
| There's not one answer but often: yes, split into "arms"
| receiving SoC or trial.
|
| Details on this is part of the trial listing which is
| usually on https://clinicaltrials.gov/
| polar wrote:
| What is MD?
| [deleted]
| texasbigdata wrote:
| Medical Doctor in the United States. Undergraduate (4 years)
| + Med School (3 years) + Residence (1 to 3 years), roughly.
| ramraj07 wrote:
| Are you sure THIS treatment above is only 500k? It's too
| bespoke and no way I can imagine it costing less than a few
| million per patient.
| dumbmrblah wrote:
| I responded to another post similar down but you are correct.
| The _drug_ is $500k, the surrounding medical care /
| hospitalizations etc pushes the total cost to over $1,000,000
| midoridensha wrote:
| >The drug is $500k, the surrounding medical care /
| hospitalizations etc pushes the total cost to over
| $1,000,000
|
| In the US. Outside the US, hospitalization isn't that
| expensive.
| zo1 wrote:
| For reference, here in South Africa, it's about 250$ per
| day of hospitalization. Or 1500$ for ICU hospitalization
| per day.
|
| And we have private Healthcare here.
| [deleted]
| vagrantJin wrote:
| Pardon me.
|
| Is the 250$ per day in a public or private health
| facility?
| zo1 wrote:
| Private, though you don't pay it out of pocket for 95% of
| stuff as the medical aid covers it using your premium.
| Public is probably much much cheaper (free) but not a
| place any sane middle class person here would ever want
| to experience.
| refurb wrote:
| It's not as expensive as the US, but it's still bloody
| expensive to get intensive care in a hospital.
|
| It's not unusual for a premie baby who stays in an nICU
| in Canada for a month to have a treatment cost well over
| $500,000.
| cjrp wrote:
| Actual cost, or billed cost? Because they're not the
| same.
| refurb wrote:
| There is no difference in Canada for public hospitals.
| All billing rates are set by the government.
| throwaway69123 wrote:
| Are you saying hospitalization isnt that expensive to the
| patient or where its socialized medicine the overall
| cost?
| dodslaser wrote:
| US healthcare really does put a new spin on the term
| "life savings".
|
| Here in the Democratic People's Republic of Sweden
| healthcare is government funded and universal.
| nisegami wrote:
| Would the Democratic People's Republic of Sweden be
| willing to drop that kind of dole on a single patient? It
| seems wasteful to me.
| koevet wrote:
| yes, in the Democratic People's Republic of Germany
| (specifically in the anarchist Berlin enclave), a friend
| of mine received successful cancer treatment that ended
| up costing well over 500k (and she is not even German)
| nisegami wrote:
| Reading stuff like this just short circuits my brain
| because I can't even fathom such a society existing. Yet,
| it clearly does.
| thrawn0r wrote:
| this member of the anarchist enclave berlin is paying
| 750EUR per month (plus the 750EUR my employer does) for
| these treatments. solidarity ftw!
| dodslaser wrote:
| Depends on your definition of waste. Is it wasteful if it
| ends up saving a life?
| nisegami wrote:
| But it could save more lives if spent differently.
| sedeki wrote:
| Independently of where one stands politically, we Swedes
| are lucky that our government can import expensive
| medical treatments from large evil US corporations that
| do the work for us.
| saiya-jin wrote:
| Its not like US is the only manufacturer of medical tools
| which and treatments for the only way to pay is via that
| ridiculous medical system they have there. Thats a nice
| fable that US pharma would like you to believe since they
| profit from it generously.
|
| Those items are done all around the world, ie in
| Switzerland. And a lot of tools come from ie Germany
| (Siemens), Netherlands (Philips) etc.
| tomhallett wrote:
| I chuckled when I read this, because when I think about
| the "brand" for Philips/Siemens, my default assumption is
| "American company". When you mentioned it, I recalled "Oh
| yeah, I've heard that Siemens is german before", but
| being raised with the "American Exceptionalism" mental
| framework means this thought isn't the default. (Versus
| brands like Volkswagen/Ikea/Toyota).
|
| Embarrassing example: I was watching Federer play Nadal
| and thought "Wow, American athletes are great. I'm proud
| that we have the best. Wait... neither of these guys are
| american. Let me google where they're from. What am I so
| proud of exactly??"
|
| The number of times we hear "this is the greatest country
| in the world" on a daily basis is really quite sad.
| sedeki wrote:
| I am not trying to come across as patronizing, but the US
| is, in my opinion, the greatest country in the history of
| the world.
|
| I am sorry that you feel that way about your country as a
| fellow human (I am not being sarcastic), but my positive
| view on American exceptionalism has nothing to do with
| you personally, just your culture.
| atdrummond wrote:
| Americans are often embarrassed of America, which I think
| tends to stem from the fact that they think it can be
| even better than it is. Which isn't a bad way of looking
| at things, IMHO.
| mrtranscendence wrote:
| The US has for 70 years enjoyed the distinction of being
| the most powerful country in the world by various
| reasonable metrics, almost certainly the most powerful to
| have ever existed. But is it the _greatest country in the
| history of the world_? Depends on what you mean by
| "great". We've undertaken atrocities; started wars;
| destabilized entire regions. Despite being unbelievably
| rich we have people dying to treatable illnesses like
| diabetes for lack of medical care. We face more violent
| crime than other comparably rich nations, and whole
| swathes of non-white individuals have valid reasons to
| fear the very police force that should serve a protecting
| role. Despite being in certain respects undereducated, we
| saddle those who seek higher education with enormous debt
| burden. I could go on and on.
|
| I'm not saying that other nations haven't done things
| worth vehemently criticizing, but it seems a bit ...
| gauche to call the US the greatest country in history
| full stop.
| tomhallett wrote:
| If you re-read my comment and the comment I was replying
| to, you will see that I wasn't making any claims about
| America being or not being the greatest country in the
| world. I was pointing out how "American Exceptiolism"
| will sometimes cause me to think things which "are great"
| as being american when they aren't american at all.
|
| * you: Swedes can import expensive treatments from US
| corporations
|
| * Parent: Alot of those are from non-US (Switzerland,
| Germany, Philips)
|
| * my comment: When I think of "Philips", I think it's an
| american company
|
| * my comment: When I was watching 2 top athletes, my
| default assumption was that they were american, even
| though it's extremely obvious that they aren't. Which
| exposes how ridiculous the framing is.
|
| Unless a company actively promotes that it's a foreign
| company in their branding, "German engineering"/"Swedish
| design" or similar with their name/branding, I will
| assume it's an American company.
|
| I think _one_ of the reasons "American Exceptionalism"
| is dangerous, is that it holds us back from improving on
| things which aren't actually the best. If an American
| politican says "This is the greatest country in the
| world", that is an emotional argument to keep things
| exactly the same.
| sedeki wrote:
| Makes sense, thank you!
| [deleted]
| dm319 wrote:
| OP is talking about CAR-T therapy which is in routine
| clinical practice. In the UK costs have gone from PS600k to
| around PS250K That includes the surrounding medical, nursing
| and follow up care. In the US costs are likely to be more
| than that.
|
| The article is talking about a very bespoke process where
| they take a patient's cancer, sequence the whole thing,
| select mutations they think will be presented on MHC-1,
| predict the antigens visible, and 'somehow' (I need to read
| the article more carefully to figure out how they did this)
| select a TCR sequence which will bind to that. Then they use
| CRISPR to graft that onto the TCR gene of a T cell from the
| patient (3 types by the looks of it), and re-infuse the
| targeted cells.
|
| So yes, that would cost several million.
| kwhitefoot wrote:
| > that would cost several million.
|
| But it sounds like many of the steps should be amenable to
| an engineering solution so the cost should fall
| dramatically if only it can get started.
| queuebert wrote:
| All of you AI people reading this should work on predicting
| side effects and outcomes from these therapies. That would help
| decrease the cost tremendously.
| lll-o-lll wrote:
| Ahhh, personalised treatment for the mega rich. Soon our
| billionaire gods will be able to live far beyond a normal
| lifespan. I wonder how this will impact society?
| noduerme wrote:
| If it wrecks the rest of social media the way it's on its way
| to destroying Twitter, could be a long term good for
| everyone.
| quickthrower2 wrote:
| Rich get a few years head start while effectively financing
| the making it cheaper part. Not "fair" but at the same time
| there is trickle down.
| chasb wrote:
| My 27 year old sister got CAR-T for leukemia earlier this year
| after a failed stem cell transplant. She's in remission. It's
| incredible, literally curing cancer.
| gleenn wrote:
| If you don't mind me asking, how was her pain for the 30-days
| after period? Another poster said they were extremely lucky to
| only have suffered a few fevers but some people were in a coma.
| teaearlgraycold wrote:
| Had no idea we were at this point. But I'm so glad! Hope your
| sister lives to be 100.
| znpy wrote:
| I'm happy for you, best of luck to your sister.
| jmacd wrote:
| My friend's 68 year old mother also had it (after being quite
| sure she was facing a fairly rapid death after other treatments
| failed).
|
| She's pretty much back to normal. I might say better than
| before as she now takes her overall health much more seriously.
|
| Amazing.
| dis-sys wrote:
| Incredible, hope your sister's remission to be a complete &
| permanent one.
|
| Literally curing cancer, just incredible.
| 29_29 wrote:
| My mom has a very serious type of Breast Cancer, Triple Negative,
| so this news is very encouraging. She's undergoing immunotherapy
| - but this looks even more promising. Thanks for posting.
| roschdal wrote:
| Cure for cancer, nice.
| [deleted]
| daniloalmeida wrote:
| yay. I read the headline in order to be elated. Now I'll read the
| article to get carefully optimistic and then I'll visit the HN
| comment section to come crashing down.
| lost_tourist wrote:
| Nah just a reality check. This will only work for very rich
| people. However as they learn more and costs come down it can
| trickle down to us plebes :)
| bragr wrote:
| Is the end state of this to eventually modify people's bone
| marrow to produce modified T cells, or do they envision treating
| people with infusions of modified T cells? On one hand,
| permanently modifying people's immune systems seams fraught with
| challenges. On the other, a steady supply of cancer killing T
| cells sounds like a strong protection against recurrence.
| ethbr0 wrote:
| It sounds like the "treating people with infusions of modified
| T cells" approach.
| nine_k wrote:
| People's immune system gets irreversibly changed with every new
| infection it fends off.
| candiodari wrote:
| CAR T-cells are cytotoxic T-cells modified so they do not
| cooperate with the rest of your immune system (they do
| reproduce inside your body, they just don't care what your
| "normal" immune system thinks on the matter). They do not
| listen to instructions from your immune system. They are
| modified from your own immune system so _they_ don 't get
| attacked, your immune system can't tell the difference between
| its own cells and CAR T-cells.
|
| They are then further modified to go looking for specific
| targets (they go through your body, randomly, and check for
| specific molecules on cell membranes), and become "cytotoxic"
| towards them (they fire exploding acidic "bubbles" that digest
| a target cell).
|
| Needless to say, this is a _very_ dangerous treatment
| (uncontrolled killer T-cells roaming around inside your body
| multiplying ... not hard to imagine what happens if they target
| normal cells) and small mistakes will kill patients. In
| addition to directly killing off important cells, they may can
| also make the immune system overactive (which in fact happened
| in this study to three of the patients). They have a bad
| reputation in research for killing off entire batches of test
| animals when making a small mistake in less time than you 'll
| need to diagnose the problem and, uh, "fix" it (you're supposed
| to kill test animals when a treatment doesn't work so they
| don't suffer). This is not allowed, and has to be explained to
| the authorities when it does happen and has ended research
| careers.
|
| Normally, or should I say ideally, after multiplying a more-or-
| less set number of times, they die off and are removed by the
| body.
|
| So no, this does not modify the bone marrow of the patient. Not
| at all. It just attacks and digests specific cells inside your
| body and dies off.
| rubatuga wrote:
| TLDR: It attacks and digests specific cells inside your body
| and dies off.
| dm319 wrote:
| This is an ongoing discussion in CAR-T. At the moment we only
| have 'autologous' CAR-T, which means they are manufactured from
| our own cells. The big advantage to 'allogeneic' CAR-T is that
| we don't have to take the time (several weeks) to modify T
| cells for adminstration, during which patients can die of the
| disease. 'Off the shelf' would be preferable, but there are
| lots of problems with trying to use someone else's T cells for
| the job.
|
| The main issue is that our immune system is very good at
| removing non-self, so a lot of work would need to go into
| stopping the immune system doing this.
|
| The article isn't talking about CAR-T though, rather TCR-
| modified T cells. These are very patient-specific because we
| have a unique MHC signature (this is why we have to find a
| 'match' for a transplant recipient). Previously people have
| taken the T cells from the tumour site, boosted them in the
| lab, and re-infused with some remarkable and curative results.
| The outcomes in this trial weren't so great but it is novel to
| splice in a new TCR.
| pishpash wrote:
| The end state might be a little machine inside that does all of
| it without specific treatment, i.e. an enhanced immune system
| that knows what "cancer" is.
| airstrike wrote:
| The end end state is a bigger machine that replaces
| everything except the brain, i.e. an enhanced body that knows
| that "metabolism" is
| HPMOR wrote:
| The real end state is having an instance of our
| consciousness across a distributed system of servers that
| is provably impossible to error.
| lossolo wrote:
| Then you (origin you in meat body) will die anyway but
| your digital copy will survive.
| sagebird wrote:
| Only if a man named Noah scans your brain and stores it
| in a secure underground bunker to be found after a
| nuclear holocaust.
| test6554 wrote:
| Someone makes a copy of your consciousness, runs millions
| of ads by this copy until it perfectly predicts your
| responses to various advertising strategies. Fast forward
| 2 months and you are broke.
|
| An oppressive government makes a copy of your
| consciousness, tortures it. Learns everything. You never
| know it happened.
| dm319 wrote:
| I'm a haematologist who is involved with patients who have CAR-T
| (I don't do it myself, but do other types of transplant and I
| look after the patients before and after) and my research area is
| in the way T cells target cancer.
|
| This study isn't CAR-T. It is more similar to adoptive TIL
| therapy because it is using the T cell receptor (TCR) to target
| the cancer's mutations. This has a huge advantage over CAR-T.
|
| At the moment we use CAR-T to target, mostly, B cell cancers.
| These cancers have CD19 and CD20 on their cell surface, as do
| most B cells. We can safely target these cells because it turns
| out your B cells aren't critical for life. Think of it like an
| amputation. Your B cells went rogue, you wipe them out.
|
| The problem is this doesn't translate to other cancers, which
| don't have an obvious cell protein you can target specific to a
| group of cells you can do without.
|
| All cancer cells have mutations, and all cells in the human body
| have to display a sample of its proteins on its cell surface.
| This way our immune system regularly identifies cancer and
| removes it. Cancers that get established have somehow leveraged
| local immunosuppression to hold off the immune system, and so the
| immune system and cancer become a stalemate, or worse the cancer
| takes off and kills the person.
|
| If we can target the mutations of the cancer, then we can get at
| the heart of the cancer itself.
|
| You might ask why the cancer just doesn't display it's antigens
| on the surface. If a cell does this it gets removed by NK cells
| (natural killers) - our body's fail safe.
|
| What I find interesting is that I didn't think we were close to
| predicting what TCRs can bind to to a peptide on MHC on the cell
| surface. I'm going to need to look at the article to findout how
| they did this. I suspect they used a library of known TCR-antigen
| interactions.
| readittwice wrote:
| Since there are people here that seem to know a bit about this
| stuff, I will take the chance to ask some naive questions ;)
|
| Do I have this right that CAR T-cells have this engineered
| B-cell/antibody like receptor that recognizes antigens only on
| the cell membrane. While the regular T-cell receptor can look
| into cells as well? And that's why the T-cell receptor is
| potentially better at recognizing solid cancers?
|
| So cancers usually create this immunosuppresive environment,
| wouldn't this stop this engineered T-cells as well?
| dm319 wrote:
| Yes, CAR-Ts are really a B cell receptor (otherwise known as
| an antibody) grafted onto a T cell. Antibody directly binds
| things like proteins, and usually targeted to things found on
| cell membranes.
|
| Also on the cell membrane is MHC-1, which shows a short (9-11
| amino acid) fragment of protein produced from inside the
| cell. Our T cells are trained in our T cell kindergarten (the
| thymus) to not identify our usual self proteins, but detects
| anything different. They have already been demonstrated to
| identify single amino acid changes from normal.
|
| Yes, the micro-environment means the immune cells reach a
| dynamic equibrium. This is because when a cancer presents to
| healthcare, it is already a chronic process. The T cells are
| termed 'exhausted', but it's debatable whether this is a good
| term for it, because they are still active.
|
| A lot of cancer treatment 'shakes up' the microenvironment.
| This can be enough to tip into a cure. When you make CAR-Ts
| and adoptive TILS you either pick healthy T cells not
| involved in the cancer or buff them up in the lab, both in
| numbers and health.
|
| The hope is that a refreshed army of T cells will push that
| dynamic equilibrium towards a cure.
| dsign wrote:
| Despite what the article says, this can't be more complicated
| than producing 5 nm process chips. It's just less funded.
| bpodgursky wrote:
| The regulation and risk-aversion is far more impactful than the
| funding.
|
| It's not entirely unwarranted regulation, but fundamentally
| Intel can mess up 20 batches of 5nm chips before getting it
| right, and nobody cares. If a CRISPR trial kills someone, it's
| a BIG DEAL, and could potentially set the field back by years.
| breck wrote:
| Biology is OOM more complicated than electronics, IMHO.
| (Background in software then joined UH Cancer Center in 2018)
| [deleted]
| loeg wrote:
| You think the cancer / biotech industry is less funded than 5
| nm nodes?
| brutus1213 wrote:
| Yes. I think any of the major sport franchise is more well
| funded than most forms of cancer research.
| [deleted]
| Retric wrote:
| Cancer finding doesn't all go to any one approach, so you can
| draw the lines fairly arbitrarily around each problem.
| rjdagost wrote:
| I have worked in both semiconductor manufacturing and drug
| discovery industries. Reliably and profitably producing 5 nm
| chips is an extreme engineering challenge, but- it is an
| engineering challenge. Drug discovery is a question of science
| and requires a fundamentally different mindset that
| semiconductor manufacturing. Human biology is much more
| complicated than manufacturing chips (and that is extremely
| complicated); drug discovery is about "unknown unknowns".
| Discovering a drug that has the intended effects without
| causing terrible adverse effects is something that some of the
| best-funded companies on the planet struggle with.
| thomastjeffery wrote:
| But this _isn 't_ about drugs. This is about editing genes to
| manufacture T cells. That's a lot more like engineering than
| drug trials.
| kelnos wrote:
| Not in medicine, but I don't think that's true. It's very
| hard to understand what all the consequences are going to
| be when you manufacture those T cells, and you also have to
| figure out what to manufacture in the first place, based on
| experimental trial and error.
| chris_va wrote:
| I've done some engineering and drug development...
|
| Image trying to write code where you can't actually see
| what you wrote, where each time you compile it costs $1000
| and the binary randomly is corrupted 50% of the time. And
| the only way to find out is to push it to prod and wait a
| few months for someone to call you. And every prod setup is
| subtly different without any documentation. That's about
| 100x easier than drug development.
|
| :)
| nitwit005 wrote:
| The nature of cutting edge stuff, regardless of the
| field, is that the process barely works, and costs a lot.
| lost_tourist wrote:
| Drugs ultimately have to be converted from the lab to mass
| production. How is it any different, they all require
| research, iteration, and ultimately (hopefully) engineered
| mass production?
| guelo wrote:
| Some of the best-funded companies on the planet also struggle
| to produce 5nm chips.
| davidf18 wrote:
| dekhn wrote:
| Making safe and effective medicines is a lot harder than modern
| chip production because the subject is humans and we have to do
| medicine ethically.
|
| The pharmaceutical industry predates chiptech by quite some
| time, represents a fairly large market, the companies are quite
| technological, but the underlying problems are very different
| from making chips. And if trials like this succeed, that area
| of biotech will see billions in funding.
|
| It's not funded as much as chips but it's also a smaller
| overall market.
| [deleted]
| ethbr0 wrote:
| > _this can 't be more complicated than producing 5 nm process
| chips_
|
| Chips don't randomly decide to unmake themselves: there's no
| active, living system you're interacting with.
|
| The other thing that makes biology so confounding is its
| diversity. E.g. something that works without side effect for
| 100,000 people will kill 1 of them, because they were in some
| way different than the others.
| borissk wrote:
| High performance computers bring far higher economic benefits
| than curing some types of cancer, so naturally they are better
| funded.
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