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COMMENT PAGE FOR:
HTML CRISPR tech selectively shreds cancer cells, including "undruggable" cancers
silexia wrote 3 hours 9 min ago:
Go CRISPR! I just lost a good friend Bobby to cancer who was a sweet
kind man. Die cancer.
hummuscience wrote 4 hours 58 min ago:
Apparently this group was a bit late. Here is the first group with the
same approach
HTML [1]: https://www.nature.com/articles/s41586-026-10466-y
est31 wrote 6 hours 2 min ago:
In order to kill all cancer cells in the body, it probably needs to be
delivered to every single cell in the organism, and scan the nucleus of
that cell. Viruses usually don't infect every single cell, just a small
percentage.
So one needs to figure out a delivery method that is efficient enough,
and that doesn't elicit an immune response. But I guess one can analyze
the cancer in the lab and figure out which receptors it expresses, and
then bind to those? We could have a toolkit of different delivery
methods, tailored for each patient's cancer.
andrewlin247 wrote 10 hours 3 min ago:
been hearing about CRISPR since I was in middle school. is there
actually any new development here?
Asfand3099 wrote 10 hours 57 min ago:
What stands out to me is how cancer therapy keeps moving from broad
destruction (chemo/radiation) toward increasingly precise
identification of malignant cells. The challenge no longer seems to be
"can we kill cancer cells?" but "can we reliably identify only cancer
cells and reach all of them?" This paper looks like another step in
that direction.
TaupeRanger wrote 10 hours 22 min ago:
I'm not sure what this comment means - we could always kill cancer
cells, and the challenge has always been "how can we ONLY kill the
cancer?" We've been burning cancer, cutting cancer out, and drugging
cancer cells for decades or centuries depending on the method. What
is changing is not the type of challenge, but the precision of our
tools - and even then, it remains to be seen if we actually can get
the precision while improving the lives of the patients.
himata4113 wrote 11 hours 41 min ago:
Does anyone know a website where I can see/read of how many cancers
(and their variants) we've effectively solved, have drugs to negate
their effects, have experimental drugs for and uncurable cancers? I
think that graph would be awe inspiring looking at the past decade of
advancements.
What's more crazy is that we're slowly going from millenia, to decades,
to likely years in the near future from being presented a biological
problem and achieving the next milestone in solving it. We might have
"AI", but we also have brilliant minds right now that are speeding up
development to a pace that would be unimaginable just few years ago.
da_chicken wrote 3 hours 3 min ago:
It's difficult to do that because we don't even really know how many
cancers there are.
Cancer is best understood as a family of tens of thousands of
diseases. They're a whole range of different genetic changes that can
happen which result in similar categories of symptoms and
consequences. They can also be incredibly complex, such as being the
result of hundreds of stacking genetic defects acquired over a
lifetime. There can be a thousand varieties of one specific type of
lung cancer, and they might all react differently. Some of our
solutions might work on a lot of them, but others might only work on
a handful. And we're at the beginning of figuring all this out.
CRISPR may eventually allow us to genetically profile a cancer and
design highly targeted medications to cure them, but we don't know
yet how well it will work. It may only work on a portion of them. It
may have worse outcomes than chemotherapy or radiation. It's nice to
think that we're going to find a magic solution to the entire
problem, but things almost never work that way. I think we're going
to be able to resolve a wide range of issues, but I don't think it
will really cure cancer as a whole.
flexagoon wrote 5 hours 55 min ago:
Not exactly what you're looking for, but OWID has a bunch of great
visualizations about cancer, including ones that really show the
progress we've made (and how much we've yet to make!)
HTML [1]: https://ourworldindata.org/cancer
TacticalCoder wrote 7 hours 29 min ago:
> We might have "AI" ...
Basically everything that was invented up to 3 years ago was invented
without the help of "AI". And that includes "AI" itself, for we,
humans, invented that too.
So yup, humans can be quite resourceful.
4k0hz wrote 9 hours 9 min ago:
Let the record reflect that I had this exact idea 2 years ago but
never finished it, and remembered it this morning.
photochemsyn wrote 9 hours 11 min ago:
The foundational problem with cancer is that multicellular organisms
rely on tight control of the cell division cycle and there are
hundreds of ways that can go off kilter. The record of understanding
and treatment is impressive, certainly, but the correct mental model
is more âthink of all the problems that can go wrong with a rocket
launch - from contaminated fuel to software glitchesâ than
âhereâs a list of cancers of different cell and organ typesâ.
Just as attacking such problems with rocket launches involves
hundreds of different approaches, thatâs the situation for cancer.
Iâd also point out that this is why it was really not trivial to
identify microbial and viral causes of disease in the 19th century -
especially since we now know that certain kinds of infectious disease
can themselves result in cancer initiation. Itâs definitely a hard
set of problems.
I would also add, there was a concerted effort by industry to promote
âinherent genetic malfunctionâ as the cause of cancer in the late
1990s and early 2000s, but the reality is that exposure to industrial
carcinogens tracks closely with a wide variety of cancers (skin,
digestive tract, etc.). This was a very deceptive and dishonest
approach to avoiding regulation.
rolph wrote 9 hours 12 min ago:
you should probably look at oncogenes in general. [1] at the simplest
level, the particular gene, and particular perturberance, sets the
"type" of cancer.
there will most often be additional genetic abnormalities giving
nuance to the character of the oncotype.
the tumour is originated from a cell type of specific
differentiation, and developmental potency, further widening the pool
of possible cancer type.
immunotype of cancer also sets the relationship between cancer and
the body.
the cells of the body are setup for a functional death and
replacement so when you try to rescue a particular cell [or cohort]
you are fighting against how the grand scheme of tissue maintenance
operates.
unless you have concern for a particular long lived cell, it is best
to destroy the tumour cell, and let the next cells in line replace
them.
it is still a multifacet strategy being developed, inhibit the
genetic properties of the tumour, and target the immunotype for
destruction.
HTML [1]: https://en.wikipedia.org/wiki/Oncogene
HTML [2]: https://en.wikipedia.org/wiki/Cancer_immunology
r58lf wrote 10 hours 39 min ago:
It's not as great as you might think, despite all the stories you see
like this one. That's because most of the stories are in cells (this
one) or mice.
The big success story, about 20 years old now, is testicular cancer.
You can have metastatic testicular cancer with tumors all over your
body (like Lance Armstrong had) and they can cure it. They use
platinum based chemotherapy and it's not really well understood why
it works for testicular cancer, but not others.
The story with childhood leukemias is similar. They figured out how
to combine a bunch of chemotherapy to get the cure rate up pretty
high. Leukemia in a child used to be (1990s) 90% fatal, it's like 10%
now.
Besides those, most of the advances in the past few decades come from
early detection/ surgery or just prevention (stop smoking).
There is some hope though. When people first started studying cancers
at the molecular level, one of the first things they noticed was how
often a gene called Ras was mutated in different cancers. It turns
out that designing a drug for Ras was really hard, but it finally got
done, it's called daraxonrasib. They just released phase III human
trials with this drug in pancreatic cancer a week or two ago and it
destroyed the standard of care (Chemotherapy), but that is saying
people who were dying in 1-2 months were still alive after 5-6
months.
The former senator Ben Sasse was diagnosed with metastatic pancreatic
cancer last December. Historically, that's like 5% survival rate for
5 years. He is on daraxonrasib. We will see how it works out.
FunHearing3443 wrote 1 hour 16 min ago:
They are starting to ship this out across the country. My uncle has
pancreatic cancer and is hoping to get a shipment in the next two
months. Apparently you discontinue chemo while on it because itâs
so unnecessary at that point.
unknownfuture wrote 9 hours 40 min ago:
I wouldn't understate advances in Melanoma treatment.
Immunotherapies have absolutely changed the game in that space.
It's not a curable cancer (few are) but it's far more treatable.
liamwire wrote 1 hour 42 min ago:
Dr. Richard Scolyer was at the forefront of this, and died only
recently after a long battle against brain cancer at 59. His open
letter is well worth the read.
HTML [1]: https://www.abc.net.au/news/2026-06-08/professor-richard...
jacinda wrote 10 hours 12 min ago:
Amen to childhood leukemia rates improving being awe-inspiring. I
had a friend I rode the bus with around 2001 who was diagnosed with
leukemia and didn't make it. They let us know over the PA system at
school. I suspect these days she would have survived.
himata4113 wrote 10 hours 29 min ago:
I guess then a graph of deaths from disagnosed cancer at various
stages would be just as awe inspiring. I'd settle for that as well.
zevets wrote 10 hours 22 min ago:
[1] Page 2 has the figure. Getting people to not smoke has been
the most effective treatment in our lifetime.
Public health is a really big deal, and RFK et al are a disaster
for the nation.
HTML [1]: https://www.cancer.org/content/dam/cancer-org/research/c...
golem14 wrote 7 hours 5 min ago:
Well, depending on how cynical you are. I'm sure there are
those that are happy to let the 'senecent' people die of cancer
and have a younger population and healthier population pyramid.
Getting older, I'm not subscribing to that, but it sometimes
feels like the RFKjr -style interventions are calculated. Then
again, this theory makes zero sense when dismantling herd
status for measles (I don't think 'natural measles survivors'
are genetically 'better' than the rest of us)
bbor wrote 5 hours 3 min ago:
Wow, Iâve joked about the prospect so frequently that
realizing it has a real Twitter subculture hit me hard.
Describing people like that⦠itâs akin to derisively
referring to âthe dysfunctionalâ part of society, to pick
on my own disability. The parallels to the Naziâs ableism
are pretty hard to ignore :(
But on a lighter note: is there any belief more certain to
spoil?? My god. Donât underestimate the moral worth of
futureYou, folks. I guess delighting in their assured regret
is a bit of a guilty pleasure, but it helps!
RE:RFK, I think youâre indeed overestimating their
intentionality. They intuitively feel that measles wouldnât
affect them because theyâre stronger, and would do their
best to dance around that belief if pressed beyond their
comfort zone of cherry-picked facts.
But really, theyâd much prefer to just not think about that
part altogether IMO; âMAHAâ is much more about
hypernaturalism & tradwives than it is about public health.
This is all just annoying scaffolding to them.
consp wrote 1 hour 48 min ago:
It is always interesting to point out to people claiming it
would be better to not cure people that over half of the
people in the room would be dead by the age of 5. That
likely includes them.
lobocinza wrote 4 hours 32 min ago:
Utilitarianism can justify that kind of policy/behavior. It
makes economical sense, with your free the burden of
society it free resources so people be more productive,
afford things, live happier lifes (at least on the material
sense), have children.
Though I don't subscribe to utilitarianism or the notion
that the value of an human being can be reduced to its
economical aspects. It's not my moral compass.
arbitrarywords wrote 9 hours 25 min ago:
Looking through that, they seem to leave out what would be the
most interesting comparison - expectancy adjusted for stage at
detection against time?
Edit Claude suggests the problem is bordering on intractable,
but table 7 in this link is probably as good as it gets
HTML [1]: https://acsjournals.onlinelibrary.wiley.com/doi/10.332...
himata4113 wrote 10 hours 12 min ago:
Oh wow, not as impressive as I thought, but I guess we are
looking at broad categories rather than specific types and
variants. But overall the trend is down on ever cancer since
around a decade ago. Was expecting a sharper drop around 1-2
decades ago, but things just take time when it comes to
experimenting with human lives. Will be interesting to revisit
this in another decade when a lot of the treatments finally
leave the experimental stage.
parodysbird wrote 5 hours 22 min ago:
Unfortunately, we actually don't make the kind of general
widely applicable gains in treatment that people believe we
have. We're not in a much different place for major cancers
than we were 30 years ago, and I don't see much value in
assuming we will just suddenly improve.
tyre wrote 11 hours 27 min ago:
Have you asked Claude to pull this and graph it over time? It could
build a static site as well.
phyzome wrote 9 hours 8 min ago:
Have you tried just mashing on the keyboard and seeing if a great
comment comes out?
bitmasher9 wrote 11 hours 17 min ago:
Isnât this likely to lead to inaccurate data? I wouldnât know
enough about the domain to fact-check Claude.
supertroop wrote 11 hours 49 min ago:
Yes! I have a genetic disease that will take me out in my 70s and Iâm
really hoping CRISPR gets to it before I do!
dreambuffer wrote 5 hours 52 min ago:
I don't mean to sound insensitive, but don't most people die around
age 70-80?
aroman wrote 5 hours 44 min ago:
Life expectancy in many countries is mid 80s.
dreambuffer wrote 5 hours 35 min ago:
That doesn't seem to be true, the global expectancy is 73 and
only a dozen of the wealthiest countries are mid 80s. I wouldn't
be worried about dying at 70, but maybe I'm built of tougher
stuff.
aroman wrote 5 hours 1 min ago:
You say my claim is not true then proceed to acknowledge it is
true. To be clear about the fact: about 1/4 of all countries
have a life expectancy >80, and as you said, more than a dozen
in mid-80s.
bloppe wrote 9 hours 59 min ago:
A lot of people's genes will take them out in their 70s but cheers to
crispy
supertroop wrote 8 hours 24 min ago:
Very true!
cedel2k1 wrote 10 hours 25 min ago:
I hope for you and others that they will!
SilverElfin wrote 12 hours 44 min ago:
So how do drugs like this get fast tracked so that people who are in
danger of dying can exercise their freedom and opt into experimental
treatments very easily
jyounker wrote 12 hours 22 min ago:
First thing to remember: cancer drugs attack human cells. Because of
this they can very unexpected and traumatic side-effects.
Because of this initial trials consume lots of medical staff to deal
with the potential side effects. Normal side effects for cancer
treatments include:
* Your gut lining dissolves, your shit leaks into your body cavity,
and you get sepsis.
* Your heart stops during the infusion.
* Cumulative poisoning that nobody understands. (E.g. some agents
have lifetime limits, and if you go beyond that, then you die. Guess
how we found out.)
* Your immune system, and you get things like disseminated fungal
infections.
The danger of side-effects like this requires a medical team largely
dedicated to the experimental patients.
This puts a limit on how many patients you can put into a trial. I'm
under the impression that cancer trials are pretty much always full.
red_admiral wrote 13 hours 14 min ago:
For the state of new cancer-killing drugs and bottlenecks getting them
approved, see also the top few posts on [1] The post on AI and and
cures for cancer is [2] .
HTML [1]: https://www.writingruxandrabio.com/archive
HTML [2]: https://www.writingruxandrabio.com/p/a-response-to-dario-amode...
jyounker wrote 12 hours 52 min ago:
Cancer treatments are really scary things. There are all sorts of
impacts that we have no idea about when using drugs that
fundamentally attack pieces of our own body.
My partner of many years had one of the nastiest cancers around, one
with no targeted treatments. She went through an experimental
combination of existing
drugs. Some of the side effects included:
* Her heart stopping during a drug infusion. This happened multiple
times over the 18 months of treatment.
* Disseminated fungal infections.
* Sepis because holes were developing in her GI tract.
This is just a sampler of the horrible effects.
This was a good response. Other patients just died from the drug
combination.
This is what going slowly looks like in the world of cancer
treatment.
robotresearcher wrote 12 hours 24 min ago:
Sorry you both experienced that. We did too.
We relax âdo no harmâ quite a bit when the alternative is
certain death. People like to try stuff in order to hang on to
hope. Towards the end I became convinced that she made the wrong
choice to do aggressive interventions. Quality of life was very
bad.
On the other hand, she gave it her all trying to survive. Hopefully
that was satisfying for her.
toponijo wrote 12 hours 30 min ago:
The point of going slowly is that we make sure something works,
even if it has these bad side affects. Do we try experimental drugs
with worse effects so that we can find effective ones faster? There
are brave souls out there who will participate in clinical trials
or experimental exceptions
dekhn wrote 12 hours 20 min ago:
Typically what happens is that the new treatments with bad side
effects are given to the sickest patients (who have exhausted all
other mechanisms), rather than to the bravest souls with less
dire current circumstances.
This makes some sense in terms of compassion and matching new
experimental techniques with patients with no hope, but it skews
the results highly negative because the patients are already very
close to death's door. It does not provide an accurate signal
for what the results would be if we gave them to less sick
people.
I don't think any of this can be changed without large-scale
social acceptance of greater risk in clinical trials and
significant support from the government.
bonsai_spool wrote 8 hours 33 min ago:
> It does not provide an accurate signal for what the results
would be if we gave them to less sick people.
It provides an excellent signal because we want to prove that
these drugs are doing something that the standard of care is
unable to.
There's this sense that medicine is easy and some evil cabal
are limiting health to their cronies. Most medications never
get to trial for their intended indications, and most fail
trials. There's no reason to believe oncology medications are
somehow uniquely unlikely to go through this well-described
process of failure.
dmbrThnYou wrote 13 hours 7 min ago:
That's a good article with a good point. As a caregiver impatiently
waiting for Daraxonrasib, I can at least acknowledge that the
institutional machinery is going as fast as it can. I've litterally
witnessed a trial patient in the first cohort of a drug (that went no
further) be rushed from infusion to the hospital; the trial process
cannot be sped up from its current state without endangering lives.
yelling_cat wrote 6 hours 29 min ago:
> As a caregiver impatiently waiting for Daraxonrasib
Same here. Are you and your care recipient familiar with the Optune
Pax device that the FDA approved in February? [1] My father's been
using it since April. It's a little cumbersome and only improves
overall survival rates by about two months over chemo alone, but
we're hoping that it helps him remain relatively healthy until
Daraxonrasib becomes available.
HTML [1]: https://www.fda.gov/news-events/press-announcements/fda-ap...
MontyCarloHall wrote 13 hours 33 min ago:
The idea of using CRISPR/Cas to detect tumor-specific mutations that
aren't necessarily oncogenic and then kill the cell is not a new one
[0, 1, 2]. However, previous studies used Cas9, which just damages the
DNA at the target site; this uses Cas12a2, which is far more
destructive because it shreds the chromatin in the cell once activated
by detecting the target sequence.
As with any cancer treatment, it's likely the tumor will evolve
resistance. My guess is that cells will find ways to reject the lipid
nanoparticles used to deliver the CRISPR/Cas mRNA and associated guide
sequence(s), either via modifications to the cell surface (preventing
LNP uptake) or via changes to endosomal/lysosomal pathways (causing the
mRNA payload to get degraded before it has a chance to be translated
into protein).
[0] [1] [2]
HTML [1]: https://pubmed.ncbi.nlm.nih.gov/28575452/
HTML [2]: https://www.nature.com/articles/s41598-018-30205-2
HTML [3]: https://www.nature.com/articles/s41467-020-18875-x
amluto wrote 3 hours 44 min ago:
Surely a far simpler way to evolve resistance would be a trivial
mutation in the p53 transcript that the guide RNA is looking for.
rolph wrote 10 hours 36 min ago:
turn the stick around and grasp the other end.
evolution isnt about generating a response to a challenge, its about
differential success.
those cells [oncocytes] that have properties conferring resistance
carry it as un-utilized baggage, those without said properties make a
living without that fetter.
the selective factor comes into play when payloaded LNP [in this
case] facillitates destruction of "nonresistant" oncocytes and spare
the "resistant"
the resistance is not generated in response to the challenge, it is
already present, and confers survivorship in the face of the
administration of the drug.
strbean wrote 13 hours 14 min ago:
Depending on how the LNPs are designed, would resistance also
potentially cripple the cancer cells? Like, it stops surfacing some
cholesterol receptor because the drug is being delivered by LNPs that
target that receptor, and now the cell is starved for cholesterol?
I've heard about drug resistance in bacteria leading to slower growth
/ reduced virulence. Maybe the same would occur with cancers. A drug
that could effectively switch an aggressive cancer into a
slow-growing one wouldn't be the worst thing.
chasil wrote 9 hours 37 min ago:
I'm no expert, but p53 is known as "the guardian of the genome."
If p53 is reactivated, the cancer cell dies. [1] Perhaps a
different mutation that disables p53 could evade the pattern match.
This article is all about p53.
Edit: This section of the wiki best explains this critical cellular
component...
p53 regulates cell cycle progression, apoptosis, and genomic
stability through multiple mechanisms:
-Activates DNA repair proteins in response to DNA damage,
suggesting a potential role in aging.
-Arrests the cell cycle at the G1/S checkpoint upon DNA damage,
allowing time for repair before progression.
-Initiates apoptosis if the damage is beyond repair.
-Essential for the senescence response triggered by short
telomeres.
HTML [1]: https://en.wikipedia.org/wiki/P53
rolph wrote 10 hours 21 min ago:
>would resistance also potentially cripple the cancer cells?<
this is the concept of genetic baggage, and metabolic budget.
there is only so much energy to a cell, and scant amounts to
"waste" on preservation of something that is not used. in the long
term, carrying unused properties are disadvantageous, and reduce
reproductive output [replication]
the result is "unfettered" oncocytes outgrow those with baggage,
and occlude access to resource. if there is no challange that
reduces population of nonresistant cells, the resistance will be
minimized and extinct in the face of large disparity of success.
MontyCarloHall wrote 13 hours 9 min ago:
>Depending on how the LNPs are designed, would resistance also
potentially cripple the cancer cells?
Yes, if the LNP could be engineered to target an essential surface
receptor, which is still a very tough problem. It would also not
solve the issue of the payload successfully entering the cell but
being subsequently degraded.
>I've heard about drug resistance in bacteria leading to slower
growth / reduced virulence. Maybe the same would occur with
cancers. A drug that could effectively switch an aggressive cancer
into a slow-growing one wouldn't be the worst thing.
This is essentially how treatment for chronic lymphocytic leukemia
happens (hence why it's called "chronic"). People with CLL can stay
on BTK inhibitors for decades, often until they die of other
natural causes.
strbean wrote 11 hours 12 min ago:
Interesting, thanks for the info!
Another question: how does this approach compare to trying to
repair the pathogenic variants in the cancer? I asked here about
that approach recently and the response was mainly about delivery
difficulties:
HTML [1]: https://news.ycombinator.com/item?id=48285386
MontyCarloHall wrote 10 hours 16 min ago:
Even with 100% delivery efficacy, editing efficacy is nowhere
near 100%. CRISPR/Cas editors will reliably detect the target
sequence but will not reliably edit it in order to repair the
mutant allele, whereas CRISPR/Cas12a2 will activate and destroy
chromatin ~100% of the time when it detects the target.
As is often the case, it's a lot easier to indiscriminately
destroy than precisely (re)build.
AnimalMuppet wrote 13 hours 23 min ago:
But cancer isn't an organism. Cancer cells in any specific
individual may evolve that way, but "human cancers" as a group will
not. (The only way they could is by evolving human DNA, but
"survival of the fittest" pushes the opposite direction for that.)
mikepurvis wrote 13 hours 15 min ago:
Indeed, there's no "be a better/stronger cancer and spread more
effectively to more hosts" the way there is with bacteria or a
virus. It's not like the flu where we need a new shot every winter
because every winter is a new flu.
Once we solve the cancers we know about, they're solved forever,
with the one caveat that more people will live longer, so that will
increase the window for eventually still ending up dying to one of
the cancers that happens to have a non-evolved built in resistance
to this or that treatment. Which is a great deal of course,
especially if it's a treatment that sounds way less destructive of
QoL than chemo, radiation, etc.
strbean wrote 13 hours 13 min ago:
> Indeed, there's no "be a better/stronger cancer and spread more
effectively to more hosts" the way there is with bacteria or a
virus.
The rare exception:
HTML [1]: https://en.wikipedia.org/wiki/Clonally_transmissible_can...
mikepurvis wrote 7 hours 34 min ago:
Well that's terrifying, TIL.
MontyCarloHall wrote 13 hours 13 min ago:
>there's no "be a better/stronger cancer and spread more
effectively to more hosts"
No, but there is "be a better/stronger cancer cell and don't
succumb to whatever therapy is killing its neighboring cells."
It's exactly akin to how dosing isolated populations of bacteria
with antibiotics selects for individual cells that are resistant,
which then multiply and dominate [0], just like a tumor.
[0]
HTML [1]: https://www.youtube.com/watch?v=plVk4NVIUh8
mikepurvis wrote 7 hours 35 min ago:
Right, but that's within a single host isn't it? Like patient A
gets that mutation and succumbs, that sucks, but the stronger
cancer cells don't them jump to patient B the way
antibiotic-resistant bacteria do.
(barring the transmissible cancers article that your sibling
comment linked to, but that's not the common case)
MontyCarloHall wrote 13 hours 19 min ago:
Nonetheless, we see the exact same resistance mechanisms to the
same therapies recur across individuals, e.g. [0]. Convergent
evolution is a harsh mistress.
[0]
HTML [1]: https://pmc.ncbi.nlm.nih.gov/articles/PMC2538882/
cyberax wrote 13 hours 25 min ago:
There are some ideas about making it triggerable. So first you load
the cells with a protein that is ready to start shredding but is
inactive. Then you trigger it with a second compound.
inglor_cz wrote 11 hours 55 min ago:
This will also cause problems because too many cells die at once.
See the comments in other threads; killing the entire cancer at
once is very hard on the body.
cyberax wrote 11 hours 41 min ago:
Tumor lysis syndrome is a thing, but it can be managed. It's far
better than the alternative.
The new therapies will also likely be applied after surgical
resection and/or classic therapies to reduce the bulk of the
cancer.
MontyCarloHall wrote 13 hours 15 min ago:
This would shorten the timeframe for cells to mutate and acquire
resistance mechanisms, but would not address the issue of cells
with preexisting (epi)genetic resistance mechanisms that would then
be promptly selected for.
cyberax wrote 11 hours 59 min ago:
Yes, and if you shorten the timeframe enough, there's a chance
that it can clear all the cancerous cells. You also ideally would
use multiple variations of the therapy to further reduce the
chance of a pre-existing escape mutation.
That's how we deal with HIV. No single HIV therapy (so far) is
effective enough to suppress the virus all by itself, but a
combination of them provides a barrier that is too high for
mutations to jump.
MontyCarloHall wrote 10 hours 38 min ago:
Agreed. Assuming it's ultimately proven to work in vivo, I
think the endgame of this therapy is multiple guides targeting
multiple mutations along with multiple delivery mechanisms (a
formulation-diverse cocktail of LNPs + eVLPs [0]?). Sure, tech
like [0] is futuristic and fanciful, but so is the tech of the
OP, and both will probably reach in vivo maturity around the
same time.
[0]
HTML [1]: https://pmc.ncbi.nlm.nih.gov/articles/PMC8809250/
yieldcrv wrote 13 hours 54 min ago:
Cool. How can I help
needSomeCoffee wrote 14 hours 37 min ago:
Jennifer Doudna again. What an amazing scientist. Wow.
sidsud wrote 11 hours 55 min ago:
just finished reading The Code Breaker, interesting stuff on Doudna &
CRISPR
ordinaryradical wrote 14 hours 50 min ago:
CRISPR is an extremely overhyped approach which found a marketing
engine via popular science. There is 1 FDA approved CRISPR therapy as
compared to 7 for AAV and 7 for Lentivirus.
Counting all viral vector therapies that have been approved, weâre
sitting at 19 approved therapies versus 1 for CRISPR.
I think CRISPR ideas in a lab are just an easy way into the mainstream
press, but viral vector delivery is the real future. It just didnât
get the same news cycle, for whatever reason.
tstactplsignore wrote 10 hours 17 min ago:
This comment doesn't understand why CRISPR is such a big deal in
science. While Cas-as-a-therapeutic is easy for the public to
understand, and therefore often emphasized in popular science, the
primary use of CRISPR Cas systems is in modifying genes in the lab.
Tens of thousands of papers have made important scientific advances
using it successfully and CRISPR-Cas methods are used routinely
throughout almost all of biology.
This is like calling PCR "overhyped" because PCR-based infectious
disease diagnostics are limited.
WhitneyLand wrote 10 hours 52 min ago:
I would guess you did not first write âCRISPR is an overhyped
approachâ, then after careful reflection decide, I donât think
that quite captures the intensity, better go with âextremely
overhypedâ.
The comparison is kind of a category error. One is a DNA editing
technique and the others are deliver platforms. I recall the hype
mostly being how revolutionary it could be, not comparing it on a
timeline to specific technologies that are at different levels of the
stack.
tty456 wrote 11 hours 9 min ago:
You're confusing the beurocratic FDA stamp of approval with safety
and effectiveness. Those are not the same thing.
JumpCrisscross wrote 12 hours 36 min ago:
Do mammals have a CRISPR analog?
spligak wrote 8 hours 35 min ago:
Background on this question: CRISPR-Cas is a naturally occurring
process in bacteria that is used to adapt to viral attacks. We've
coopted the system for use in mammals.
As far as I know a few labs in this space are operating under the
basic question, "why haven't viruses killed everything by now?"
So this category of research is more or less the answer.
> Do mammals have a CRISPR analog?
Not exactly. There are things like [1] that nuke cells and are
stimulated by interferons. This might be why interferon injections
are common chronic therapeutics for diseases in this space.
The closest thing we have is probably whatever adaptability B or T
cells can muster on their own? I'm sure someone lurking in the
comments has a better answer.
HTML [1]: https://en.wikipedia.org/wiki/Ribonuclease_L
perlgeek wrote 14 hours 12 min ago:
CRISPR is foremost a research tool. Calling it "extremely overhyped"
without restricting it medical treatment seems disingenuous.
The CRISPR-Cas9 gene-editing tool was developed in 2012, so I don't
find it surprising that merely 14 years later, there's only one
approved treatment. From discovery to approval, drug development
often takes 10-15 years, and often much longer for novel techniques.
So I'd say it too early to call it overhyped for treatments.
Finally, I think we'll see a lot of treatments that don't use
CRISPR-Cas9, but related gene editing techniques, but it'll take
another 10 to 20 years.
Take a look at [1] for how long another novel technique has been in
development before it became really widespread with the mrna-based
covid-19 vaccines.
HTML [1]: https://en.wikipedia.org/wiki/MRNA_vaccine#History
shevy-java wrote 13 hours 29 min ago:
Why does it take 20 years? Except, of course, that it does not work
nowhere near as well as it is being promoted - aka hyped.
mRNA vaccines are also quite different. Do they modify the DNA? Of
course not. So that's already very different.
ufmace wrote 11 hours 39 min ago:
One of the reasons is, you don't get really good data on how
something works until you start running clinical trials for it.
It's all very time-consuming - having to plan how the trial is
going to work, getting approval for it, finding subjects who meet
the criteria (here, a specific type of cancer at a specific stage
probably) and sites near them willing to work with you,
manufacturing and shipping the treatments, and only then can you
start gathering data. If it didn't work, you gotta start over,
And it all costs a boatload of money too.
perlgeek wrote 12 hours 22 min ago:
Let's see... first of all, 14 years ago was the discovery of the
base mechanism, not of specific treatments. So specific
treatments need to be developed, delivery systems need to be
developed, side effects reduced. Then you need safety tests and
efficacy tests.
> mRNA vaccines are also quite different. Do they modify the DNA?
Of course not. So that's already very different.
And yet it took more than 30 years after the first mRNA
experiments to develop a successful vaccine. Why it should be so
much faster for CRISPR & Co?
jagged-chisel wrote 14 hours 15 min ago:
âVirusâ - thatâs why.
ramraj07 wrote 14 hours 17 min ago:
Devils advocate, I also vehemently shat on RNAi therapeutics a decade
back. We do have RNAi therapies in market now though. I do think
Crispr will find its place similarly.
roncesvalles wrote 14 hours 19 min ago:
CRIPSR was a game-changer for genetics research. A lot of gene
knockout studies use CRISPR. However, it was always weirdly overhyped
for clinical use from the beginning and this was obvious to anyone
with a genetics background.
The public in general doesn't have a good understanding of basic
genetics and I blame high school science curriculums for not covering
it well enough. Too much time is wasted on Mendelian genetics without
covering the Central Dogma.
You basically cannot "edit" your somatic DNA in a meaningful
wholesale way since every single cell in your body has a copy of the
DNA, and it's a foolish endeavor. What you can conceivably edit to
good effect is your germline DNA, stem cell DNA, or modify mRNA
expression (e.g. retinoids; yes putting retinol/adapalene cream on
your face is "gene therapy"), or introduce foreign mRNA for your
translation machinery to co-opt (e.g. mRNA vaccines).
asdff wrote 12 hours 37 min ago:
It was a game changer in terms of making things cheaper and a
little easier. However the actual functionality was still possible
with other methods. Zinc finger nucleases for example. Knockdown
via RNAi is often still done because a knockout target may be
inviable, and it is pretty cheap and easy to knockdown in most
model systems.
projektfu wrote 13 hours 27 min ago:
I disagree that it's "gene therapy" to affect the natural
regulation of mRNA production. If that were true then the term
"gene therapy" loses its meaning, as just about everything changes
the expression of mRNA. You can probably do so somewhere just by
thinking really hard about it.
Expressing mRNA that doesn't exist in the genome, that would be
gene therapy. Or just a virus.
Bjartr wrote 14 hours 13 min ago:
Edit every cell? No.
Edit enough cells to impact health outcomes for a meaningful period
of time?
[Yes]( [1] )
HTML [1]: https://www.youtube.com/watch?v=J3FcbFqSoQY
shevy-java wrote 13 hours 30 min ago:
This approach can work for some genetic diseases such as
blindness based on some cells in the retina or partial blindness.
For others this is not really a cure. If you want to cure people
with progeria, does curing 20% of the cells really help? Perhaps
100% is not necessary, but it would seem strange to cure only
some cells but not others. You'd have a mosaic of cells where
some would work and others don't. Cells interact; timing also
plays a role in development. I don't really see that aiming for
anything but a very high number of cells cured, can work.
spligak wrote 14 hours 27 min ago:
You're correct about CRISPR Cas9. The off-target affects are
difficult to manage.
The paper describes Cas12a2. This is a different mechanism with
discovery origins in - of all things - agriculture. It does not
attempt in any way to reprogram cells. It uses a guide protein to
locate a specific mutation with exacting precision and, when it
activates, unleashes total destruction of the cell.
The implications of Cas12a2 on undruggable conditions that exhibit
known driver mutation profiles is profound.
Source: I have personally funded novel research based on Cas12a2 for
an undruggable condition I have. I have personally seen my condition
"cured" in vitro using this technology and it left all of my WT cells
unharmed. Some of the researchers I've funded are co-authors in the
paper linked. I am a layperson in this field (I'm a SWE, not in
biotech), but I am happy to answer questions.
acomjean wrote 13 hours 3 min ago:
We did whole genome crispr designs at my last university job. Can
confirm that off target effects are an issue with cas9. Pattern
matching across the genome to see if a design is unique takes some
time. These were interesting pipelines to work on.
Itâs only a matter of time before the next better thing shows up.
rozap wrote 13 hours 12 min ago:
This is wild, have you written about it publicly, or can you expand
on it here?
spligak wrote 11 hours 46 min ago:
I have now :) I replied to a sibling comment. Thank you for the
nudge to share.
shevy-java wrote 13 hours 36 min ago:
So how does Cas12a2 mitigate off-target effects?
If it were to work, gene therapy as-is would be possible. Which it
is not,
not even for those overpriced therapies. I have no doubt that
sooner or later
it will happen, as the problem space is finite, not infinite, but I
simply
don't see the correlation here.
> The implications of Cas12a2 on undruggable conditions that
exhibit known driver mutation profiles is profound.
So what does this change exactly? Humans defined it as "undruggable
conditions". You can reason this is an improvement, but I still see
it in failure-territory. If it were to work, gene therapy would be
an accurate - and affordable - technique. Which it is not right
now.
> I am a layperson in this field (I'm a SWE, not in biotech), but I
am happy to answer questions.
How does "answering questions" offset the technology being inferior
right now?
spligak wrote 12 hours 0 min ago:
> So how does Cas12a2 mitigate off-target effects?
Others in this thread may be able to give a better analogy, but
I'll try:
Cas9 is like open heart surgery on millions of cells all at once.
We know the specific outcome we want - a surgical replacement of
a sliver of a sequence - but just like open heart surgery, it's
an inexact operation. Cas9 tolerates mismatches which
categorically allows off-target matching. It also operates on
DNA, so any off-target effects reprogram the cell's primary
source code.
We want the Cas9 "patient" cell to survive.
In contrast, Cas12a2 is key-locked self-destruction switch. It
targets single-stranded RNA transcripts with a specific guide
protein. So the specificity is two-fold: the guide protein
doesn't tolerate mismatches, and its operating on a _downstream
byproduct_ of the DNA. When the key (guide protein) matches, it
unleashes total destruction within the cell.
We want the Cas12a2 "patient" cell to die.
> If it were to work, gene therapy would be an accurate - and
affordable - technique. Which it is not right now.
Correct on the first point. If it were to work, gene therapy
could be more common. I do not know how to make it affordable,
yet. In the models I've built to commercialize this I estimate a
Cas12a2 treatment would cost approximately as much as a bone
marrow transplant.
> How does "answering questions" offset the technology being
inferior right now?
In fairness, asking and seeking answers to questions is all I
have right now. There is no cure to my disease so the upside - no
matter how futile you may perceive it to be - to me, is infinite.
If I can solve it I may get a few more years with my daughter. If
I can't, I can show her how to live fighting for an answer that
may never come.
You're not wrong, you and I just have different perspectives on
the upside.
Gethsemane wrote 13 hours 55 min ago:
Have you written about your experience anywhere? It would be
interesting to see how you approached the research sector as a
layperson. Are there any plans to move to in vivo? Best of luck
with your research!
spligak wrote 11 hours 23 min ago:
> Are there any plans to move to in vivo?
Yes! That's the next step. There wasn't a mouse model for my
variant so they're building that, too. But in vivo testing should
be underway this calendar year.
spligak wrote 12 hours 27 min ago:
I haven't written about it publicly, but I can elaborate here. I
don't mind answering further questions about it even if you
believe they'd make me uncomfortable - they won't.
I've come to terms with what's happening to my body and that I
may not benefit from my efforts.
Background: ~3 years ago I was diagnosed with a very rare
MPLW515L-driven blood cancer known as a myeloproliferative
neoplasm. My hematopoietic stem cells (HSCs) acquired this
mutation and they produce busted downstream products.
Most notably, one of those downstream products are
hyper-lobulated megakaryocytes that spew inflammatory cytokines
into my bone marrow and destroy the bone marrow niche over time.
The destruction happens specifically because the inflammation
mobilizes stromal cells and they erroneously produce scar tissue
(fibrosis) all along the walls of the good, spongy marrow. There
are other sources of damage but this is the one path most aligned
to abbreviated survival and transformation into AML.
In effect, my bone marrow is rusting and very slowly failing. The
failure could speed up with the acquisition of additional
mutations or any other systemic inflammatory condition.
Anyway, 3 years ago my first retail hematologist told me "it's
rare, you're fine, take aspirin and go home."
I couldn't accept that - this seemed bad. I decided that if I
wanted to know the truth I needed to physically stand in front of
the foremost expert in the world on the topic and ask them "what
is the state-of-the-art?"
I came to this conclusion after about a year of reading all the
most well-cited academic papers about AML, Myelofibrosis, and
Essential Thrombocythemia. In particular, anything that mentioned
MPL. There are virtually no papers mentioning MPL.
To put that in perspective: 500,000 patients in the US deal with
the broad disease category. 5% of those are MPL, and 40% of those
are the -K variant. So 10,000 people - which means anything
targeting it would be well into orphan drug designation
territory. I'd need to find a pretty niche researcher.
So, I laddered up the academic food chain using a little cash
(donations), emails, airline tickets, and conference admission.
~2 years after my diagnosis I found myself in a closed-door
session called the MPN Roundtable in Chicago with 100 of the
foremost experts in the world. No cameras, no transcripts, just
some of the greatest minds in the field earnestly debating the
path forward to a cure.
I listen carefully to them, ask dumb questions, connect dots
across research. I rehomed my care to an academic research
hospital specializing in MPN research, and started funding
research on the condition it includes my specific MPL mutation.
Researchers happily oblige.
Cas12a2 was the keynote topic at this year's meeting and there
was _very little_ dissent.
junon wrote 9 hours 24 min ago:
This is amazing. Thank you for sharing.
btam wrote 9 hours 39 min ago:
This is so impressive - kudos to you. Thanks for sharing and
being open to questions.
How much overall has this costed you? Do you think that a
middle-class person could afford to do what you did?
> So, I laddered up the academic food chain using a little cash
(donations), emails, airline tickets, and conference admission.
~2 years after my diagnosis I found myself in a closed-door
session called the MPN Roundtable in Chicago with 100 of the
foremost experts in the world. No cameras, no transcripts, just
some of the greatest minds in the field earnestly debating the
path forward to a cure.
Why don't they allow recordings at the MPN Roundtable? It could
be useful for others to learn from.
spligak wrote 9 hours 1 min ago:
> How much overall has this costed you?
For this project, seed capital low six figures. I am
collaborating with family and friends, non-profits, and using
doubling mechanisms available to me to at work to fund the
very early speculative bench research. This is where we are
and its sustainable today.
Once we have the basic tech worth scaling up - to raise the
first round of capital, I estimate $1-2m with a wider friends
& family and angel investor round. This will be early
de-risking research and delivery mechanism testing.
Beyond that I can see a path to a ~$20m round to further
de-risk any assets that come out of these speculative
efforts, but I haven't gotten this far.
In rare disease therapeutics the challenge isn't raw capital,
it's finding the _right_ capital that understands how assets
like these get de-risked and can tolerate the shape of the
upside. Anything CRISPR-based is usually not a chronic
therapeutic, so that disqualifies most of big pharma. Acute,
curative technology like this requires informed capital.
> Do you think that a middle-class person could afford to do
what you did?
Yes.
In the rare disease field even a small amount of capital
attracts enough attention to have meaningful conversation
with bench researchers. If you're willing to travel to the
niche conferences, ask dumb questions, grind out the
studying, and approach the speakers after their sessions.
Researchers respect people who do their homework and mobilize
to meet them. They want (need) to hear from patients and
caregivers - so they tend to listen very carefully.
Fun fact: I've had multiple researchers ask me for samples of
my bone marrow. Has only happened in-person :)
> Why don't they allow recordings at the MPN Roundtable? It
could be useful for others to learn from.
I don't know, it's been going on for a while. I can
speculate: they're discussing pre-publication data, some of
which had come out of their labs only hours prior to their
presentation. It's completely unfiltered. I think there's
real risk of some of the things that are shown being
sensationalized or taken out of context.
The audience is trained and practiced in keeping a sober,
skeptical lens on everything they see - so it's more about
the debate and tear-down of the early data for the betterment
of the niche.
There's zero attempt to hide anything, it's just a forum for
collegial debate.
ticulatedspline wrote 11 hours 50 min ago:
wow, very interesting I can't say I've really ever heard of
anyone financing research themselves, hope things work out and
maybe a treatment arrives in time for you.
As an aside if you end up cryogenically freezing yourself for a
future treatment don't forget to actually cure your boneitis
when they thaw you out.
darkwizard42 wrote 11 hours 55 min ago:
Incredible story, just pure resourcefulness and grit in
following this through. I know it sucks to have this disease,
but kudos for how you approached this.
reenorap wrote 11 hours 59 min ago:
My aunt had the same disease you mention and was on medications
since the 90s. She lead a healthy life with no real side
effects from her medication and she passed away last year in
her 80s. To be perfectly honest, she did die of the disease,
because her medication stopped working and her bone marrow was
all scarred. But up until a year before she passed away she was
very active and healthy. Once the medication stopped working,
she went steadily downhill until she passed away.
Hopefully you get great progress on your research but I just
wanted to reassure you that the name sounds scary but the
current treatment appears to work well and hopefully gives you
enough runway to find your cure.
andy_ppp wrote 12 hours 20 min ago:
"When have you most successfully hacked a non-computer system
to your advantage?" Amazing resourcefulness, you should
consider applying to YC if you haven't! And I hope you manage
to find a solution to your problem it sounds very promising.
CamperBob2 wrote 12 hours 12 min ago:
And by the way, when Anthropic (sic) tells you that it's too
dangerous to allow
GPT-2/GPT-3/GPT-4/GPT-5/Sonnet/Opus/Mythos/Fable to discuss
human biology, and some of us object vociferously to their
premise, this is what we're talking about.
gleenn wrote 11 hours 47 min ago:
I haven't heard anyone specifically state their
justification for blocking bio research along I can only
assume it's to prevent manufacturing bio weapons or virii?
p1esk wrote 12 hours 39 min ago:
Iâd also like to read about your experience.
spligak wrote 11 hours 45 min ago:
Done! Wrote a bit more in a comment above. Thank you for the
interest.
ordinaryradical wrote 13 hours 16 min ago:
Seconding this comment. I would love to read a write-up about
your experience and how youâve been trying to work on solutions
for yourself. Stories like these are valuable to the field and
inspiring to other folks dealing with a tough diagnosis.
spligak wrote 11 hours 47 min ago:
Thank you. I want to make sure you see the comment above - I
think it was your comment that nudged me into writing it :)
Happy to answer any other questions, here or over email (in my
user profile).
> other folks dealing with a tough diagnosis
The toughest part has been the spiritual journey. Loneliness
unlike anything I've experienced. I felt forgotten without the
opportunity to be known in the first place. I was happy - and
emotional - to learn I wasn't alone. It took me 2 years, but
I've found my people.
GaggiX wrote 14 hours 18 min ago:
I know nothing about this field, but I imagine the actual problem
is how do you deliver the Cas12a2 protein to each individual cancer
cell compare to a viral gene therapy?
spligak wrote 14 hours 9 min ago:
There are two major problems, delivery is one of them. Collateral
damage of mass cell destruction leading to systemic inflammation
is the other.
The approach I'm reviewing now uses lipid nanoparticles (LNPs)
for delivery. It isn't great for targeting my bone marrow
condition but its workable. The team hasn't optimized it at all,
either. There are also viral delivery mechanisms that I haven't
studied yet.
The collateral damage problem is the backpressure on the delivery
problem. If you get really good at delivery, you can destroy A
LOT of cells very quickly. The human body (usually) responds to
these events by releasing a lot of pro-inflammatory cytokines.
This can lead to cytokine storms or worse.
As you "get good" at killing the target cells, the net effect can
turn bad. It will probably be a balancing act.
shevy-java wrote 13 hours 33 min ago:
Lipid nanoparticles are quite old as-is. How do you target
cells specifically?
> If you get really good at delivery, you can destroy A LOT of
cells very quickly.
You can destroy cells quickly. Ok. So the question is: how do
you detect specifically only cancer cells via lipid
nanoparticles? That was already a problem years ago with
Herceptin. The rationale that is always used is that "we need
to do something" for certain aggressive cancers. It has never
been a super-effective technique, despite all the promo of how
monoclonal antibodies are so accurate.
> As you "get good" at killing the target cells, the net effect
can turn bad. It will probably be a balancing act.
That's already the status quo in the whole cancer field. I
don't think that more than sloppy accuracy is acceptable for
any gene therapy - and the off-target cleaving of CRISPR has
always been the number #1 problem here.
spligak wrote 11 hours 15 min ago:
> I don't think that more than sloppy accuracy is acceptable
for any gene therapy
Valid critiques of Cas12a2 must acknowledge the mechanistic
differences between Cas9 and Cas12a2. There is no research to
suggest Cas12a2 is "sloppy" and significant research that
demonstrates it is not "sloppy."
I appreciate the skepticism but I would encourage you to
study the actual mechanism discussed in the paper.
cyberax wrote 13 hours 22 min ago:
> So the question is: how do you detect specifically only
cancer cells via lipid nanoparticles?
You don't. Healthy cells will also get these nanoparticles,
but without the triggering DNA sequence, the mRNA payload
will remain inert and eventually will be degraded.
spligak wrote 11 hours 57 min ago:
> Healthy cells will also get these nanoparticles, but
without the triggering DNA sequence, the mRNA payload will
remain inert and eventually will be degraded.
This is my understanding as well.
im3w1l wrote 13 hours 40 min ago:
Naively, I would deal with this by deciding how many cells I
want to kill each day and then figure out a dosing schedule
that achieves that. Or maybe it's better to do one dose every
few days. But yeah either way.
spligak wrote 8 hours 57 min ago:
> I would deal with this by deciding how many cells I want to
kill each day
Yes, this is an approach. This starts to exceed my
understanding of the problems the teams are facing - but
there are concerns about the efficacy of Cas12a2-based
approaches fading. Not because the cells adapt, but because
your immune system starts acting funny in the presence of the
payload.
I don't recall the specifics but there seems to be a window
of opportunity for these things.
fastball wrote 14 hours 36 min ago:
Viral vector delivery is indeed harder to sell with PopSci, what with
movies like "I am Legend".
jvanderbot wrote 14 hours 29 min ago:
Great first half of a movie, by the way. Up there with Sunshine for
"Sit down for a great hour-long ambiance".
I usually end Legend after the mannequin trap, and end Sunshine
after the transit of mercury.
anovikov wrote 14 hours 48 min ago:
Bingo! CRISPR has an advantage of being relatively easy to describe
to a layman, giving it a PR advantage.
fragmede wrote 14 hours 40 min ago:
So is the "idea" of microchips in vaccines. Should we just give up
and let everything else have the PR advantage
Almondsetat wrote 14 hours 51 min ago:
Can anyone point to some resources about how cancers might adapt to
CRISPR treatments?
wombatpm wrote 14 hours 29 min ago:
Same problem with chemo and radiation. A tumor may start off with a
single cancerous mutation, but by the time it spreads there may be
several. Once the cell repair machinery has been broken, the cancer
cells are prone for more mutations.
Chemo, radiation, and CRISPR will kill everything it can reach that
is susceptible. That leaves everything that was unreachable or
resistant behind to start growing again.
Kill cancer cells is easy. Killing ONLY cancer cells is very hard.
zouhair wrote 15 hours 5 min ago:
This is why I hate patents. If CRISPR were put behind a paywall, none
of this would have happened. Everything having to be about profit is
getting tiring.
bonsai_spool wrote 15 hours 1 min ago:
> This is why I hate patents. If CRISPR were put behind a paywall,
none of this would have happened. Everything having to be about
profit is getting tiring.
CRISPR was the cause of a huge patent case and likely led to a change
in US patent law because of the impracticability of deciding who did
something first in the laboratory.
It continues to influence research as some nations took a while to
decide how they would resolve their own researchers' CRISPR claims
with respect to MIT/UC Berkeley.
And yet... all the research has continued apace.
Edit: the CRISPR patent cases are continuing even today [1]
HTML [1]: https://news.berkeley.edu/2025/05/12/federal-appeals-court-s...
HTML [2]: https://www.broadinstitute.org/crispr/journalists-statement-...
sourcegrift wrote 15 hours 11 min ago:
Over on reddit people were debating whether cancer should be cured
since it disproportionately affects rich people and it made me realise
how far reddit has fallen. It's just a botnet now to manipulate
elections.
projektfu wrote 13 hours 23 min ago:
The flip side is that "fuck cancer" is a shibboleth there, to the
point where a headline, "[Bad person] has contracted cancer" has
every comment thread starting with "First, fuck cancer."
egeozcan wrote 14 hours 22 min ago:
Just spend 15 minutes in /b/ and everything else will feel better.
toraway wrote 14 hours 42 min ago:
I would imagine the charitable characterization of that discussion is
much closer to âawesome, this will mean the Peter Thiels and Elon
Musks of the world will live to 150 while both me and my children
will be dead long before this trickles down to regular peopleâ vs.
âwe shouldnât cure cancerâ.
OsrsNeedsf2P wrote 15 hours 8 min ago:
After we launched our startup, we had all sorts of folks reach out to
sell their GTM services. I went with one group from Vietnam that
would make engagement bait Reddit questions with some accounts, and
advertise our product in the comments section with others. It was
expensive but it worked
yummybrainz wrote 14 hours 41 min ago:
Do you think (or care) about the ethics of this sort of behavior?
Do you consider it unethical and if you do, under what conditions
would you decide to do it anyway?
sourcegrift wrote 15 hours 5 min ago:
Reddit is a huge danger to society. There's no doubt that subs
about specific non political (and non popular) topics are hugely
beneficial, the overall damage the echo chambers do still outweigh
these benefits.
mannyv wrote 14 hours 15 min ago:
Well, now that it's becoming "the community source" for LLMs it's
becoming even more of a target for large-scale manipulation.
whyenot wrote 14 hours 40 min ago:
The way the voting system works at Reddit encourages group think
and bubbles. All it takes is five more down votes than up votes
and a comment or post essentially disappears from view. It's a
design that actively avoids debate.
polshaw wrote 13 hours 31 min ago:
That's a huge misreading. Hiding comments in the UI empirically
does not suppress discussion, if anything it actually attracts
engagement. Lots of people are seeking the "wrong" to "correct"
it.
Suppressed debate is almost universally due to biased/captured
moderation teams aggressively using bans.
Vaslo wrote 13 hours 4 min ago:
You're wrong, because if your karma fall below a certain
number, your comments wont show up anymore. I can show you
if you like.
People shouldn't be blocked from commenting because their
karma goes negative. Spamming, hateful talk, etc should be a
completely different system. Just because what you say is
unpopular (in one place mind you) doesn't mean your words
should be hidden.
sebzim4500 wrote 15 hours 8 min ago:
I'm certain that is not a mainsteam opinion on reddit, but by its
nature you will be able to find arbitrarily stupid opinions in
individual echo chambers
airstrike wrote 14 hours 48 min ago:
I am not so certain
perlgeek wrote 15 hours 16 min ago:
The article is pretty light on details, but
> Much like other CRISPR therapies, delivery is a critical challenge,
i.e., getting the large genome-cutting enzyme to all the targeted cells
efficiently.
makes me think this is in vitro so far. So, years to decades away from
being available for actual treatment in humans. Still good news.
Metacelsus wrote 7 hours 36 min ago:
Yeah. With cancer, delivering to 99% of the cells won't cut it, the
surviving 1% will quickly grow back.
daedrdev wrote 14 hours 55 min ago:
Basically the issue is often that gene therapies end up in the liver
since its the livers job to detoxify, but that may cause a dangerous
immune response if the immune system notices it in the liver and
attacks the organ, since the person could die from the damage.
JumpCrisscross wrote 14 hours 52 min ago:
Iâm assuming this has been tried, but why doesnât
nano-encapsulated mRNA (that then makes the CRISPR sequences in
cells) or whatever the peptide injectors do solve the problem?
amelius wrote 15 hours 11 min ago:
(removed)
perlgeek wrote 14 hours 52 min ago:
You can target an individual by injecting that very individual with
something lethal.
If that's not what you want, you'd need something like a virus to
spread it. But then you have to ask yourself: what if that virus
mutates? The specialization to certain gene markers is an
evolutionary disadvantage, so evolution will tend to make it lose
that restriction. Ooops.
im3w1l wrote 12 hours 59 min ago:
I can think of ways to deal with that. I think the threat is
serious enough that I won't post about those ways publicly.
ACCount37 wrote 15 hours 5 min ago:
Old concern, but it really doesn't work that way. Genetics don't
respect human ideas like "nationalities" or "borders" - the
targeting you can get by selecting on singular DNA variants is
coarse enough to make ICBMs look like precision weapons.
Like many things of this nature, people keep bringing it up because
it sounds Very Scary and Very Dystopian - not because it's worth
giving an actual fuck about.
ikrenji wrote 14 hours 25 min ago:
I mean maybe not right now, but in 100-1000 years a complicated
enough "nanobot/virus" could possibly be made to target a single
person
ACCount37 wrote 14 hours 20 min ago:
If it's year 2126, and you have this kind of tech floating
around, and you aren't equipping the entire population with
artificial immune systems capable of dealing with known and
unknown biological threats? You've done something wrong.
matheusmoreira wrote 15 hours 6 min ago:
I suppose it could also be used to assassinate specific persons
with the precision of DNA matching. Like FOXDIE.
bonsai_spool wrote 15 hours 27 min ago:
Here's their preprint from a month ago, in case you can't access the
Nature paper: [1] Nature -
HTML [1]: https://www.biorxiv.org/content/10.64898/2026.05.08.723607v1
HTML [2]: https://www.nature.com/articles/s41586-026-10738-7
sssilver wrote 15 hours 32 min ago:
What economic / political model would cause the society to prioritize
this over adtech? It seems so unsettling that brilliant human minds are
trying hard, every day, to figure out how to make it impossible to
bypass watching ads on YouTube, instead of helping cure cancer.
mattlondon wrote 12 hours 22 min ago:
I said it elsewhere but I'll say it here - we need one of the top 10
richest people in the world - the Bezos, the Musks etc - to suddenly
get very interested at a personal level about cancer treatment.
Then the money will flow.
inglor_cz wrote 11 hours 53 min ago:
Bezos and several other billionaires stuck a load of money into
Altos Labs, an organization that studies aging and longevity.
Cancer prevention is downstream from that, as cancer frequency
grows exponentially with age. If you can truly rejuvenate a person,
you will also reduce their risk of cancer.
csallen wrote 12 hours 38 min ago:
Not sure why you're getting downvoted, it's quite an interesting (and
important!) question.
Also wonder, outside of politics and economics, whether there's a
social and cultural component that can contribute. TV shows, movies,
books, and other forms of media that put science and scientists in
the spotlight in a positive light can be tremendously inspirational.
tjpnz wrote 13 hours 48 min ago:
>brilliant human minds are trying hard, every day, to figure out how
to make it impossible to bypass watching ads on YouTube, instead of
helping cure cancer.
And even more brilliant minds are defeating it, every day. I have
doubts about how useful they would be in a research lab.
ksd482 wrote 14 hours 56 min ago:
I don't think an economic model would work. Only a political one
would work where the government would redirect a lot of funds towards
this, making it a lucrative profession.
Adtech works because there is a lot of money in it. There is a lot of
money in it because people seek quick entertainment, and we have a
LOT of people driving the demand.
Now compare that to cancer research. There's no short term
gratification about it.
JumpCrisscross wrote 15 hours 0 min ago:
> would cause the society to prioritize this over adtech?
Private pharmaceutical R&D spending in the U.S. is around $100bn per
year [1]. NIH spends another $50bn a year on biomedical research [2].
That eclipses total investments into adtech per se, which generously
counted shouldnât exceed $50 to 60bn. (And that only by counting
like a third to a half of Google, Amazon, et cetera R&D and capital
spending as adtech.) More precisely counted, it probably doesnât
exceed $10bn. [1]
HTML [1]: https://phrma.org/blog/phrma-member-companies-rd-investments...
HTML [2]: https://www.science.org/content/article/final-nih-budget-202...
s1artibartfast wrote 11 hours 37 min ago:
One of the primary challenges of drug and device economics is the
long lead time between capital deployment and returns. One of the
selling points of tech is speed to Market.
Factors that would make it more attractive our lower interest
rates, higher returns, or faster development.
All of these are theoretically possible to adjust, but the last is
most feasible to do in a tailor-made way through FDA review and
approval reform. An ambitious example would be allowing conditional
Market approval after Phase 2 and treating phase 3 deliverables as
post-market commitments.
Advancing the revenue curve two to three years while maintaining
the same patent expiration dates can dramatically change the ROI of
a pharmaceutical development program.
Beyond this, even conditional Market allowance allows firms to
better gauge Market interest and validate Financial investment
models sooner.
Similarly, there's also some really low hanging fruit in this area
to help manufacturers get to Market faster. For example, the FDA
approval of trade names and label content is one of the last steps
in Market authorization. Moving this earlier in the process would
help products itself sooner and start producing Revenue sooner.
Imagine having your billion dollar annual revenue shift out a
quarter because the FDA wanted some last minute change to how a
cartoon belly button looks in the instructions for use.
JumpCrisscross wrote 10 hours 50 min ago:
Totally agree. Iâm just pointing out that OPâs precondition
is baseless: we do âprioritize this over adtech.â
9dev wrote 15 hours 16 min ago:
There's a fair bit of frequency illusion involved here. A lot of
brilliant human minds aren't, in fact, working on ad tech, and a lot
of the people working on ad tech aren't, in fact, that brilliant (as
evidenced by them working adversarially against their own fellow
humans, for one).
There's a wide world outside big tech, Silicon Valley, and software
in general. It only tends to be a bit less visible online.
odyssey7 wrote 15 hours 16 min ago:
The bargaining dynamics are stacked against biology researchers at
every stage of their career, from needing years and years of
unrelated performance to be admitted to terribly expensive programs
before they can begin to do experiments, to requiring costly
equipment and resources to work, to needing to work with a small
number of very powerful companies.
As a result, life science researchers are more price-taking than
proce-setting when it comes to their wages / salary. If money is the
motivator, then the market as-is isnât addressing this one.
tencentshill wrote 15 hours 12 min ago:
The US government funds a lot of these programs, as they are
obviously in the public interest. Until one man decided to stop it.
strangattractor wrote 15 hours 18 min ago:
Humans are a bunch of hairless monkeys that have evolved to scam each
other rather than hunt and gather food from Nature.
paytonjjones wrote 15 hours 24 min ago:
When you reframe ads as "control of human attention" it suddenly
makes a lot more sense why so many resources are poured into them.
abirch wrote 15 hours 10 min ago:
And when you can measure how effective those ads are in changing
human behavior; it's easier for businesses to spend there. As an
American, I would love it if pharmaceutical companies couldn't
market to consumers. It would free up money for research or lower
prices.
eecc wrote 15 hours 25 min ago:
I remember seeing a comic strip about this exact argument but I
canât find it any more
Ifkaluva wrote 15 hours 50 min ago:
I hope this finally works out. I remember almost exactly ten years ago
I got excited about one of these proposed cancer cures, tried to talk
about it at lunch with my coworkers, and they laughed at me for
believing.
colechristensen wrote 15 hours 37 min ago:
Real in vivo genetic engineering isn't going away and will indeed be
a powerful tool to face cancer. Any particular effort is doubtful
because this is a journey measured in decades. It is not the same
story as any one particular wonder drug fizzling out to nothing, it
is a class of tools that is maturing into the realm of early
therapeutic deployment.
arcticfox wrote 15 hours 39 min ago:
I'm pretty optimistic. I think it's a threshold question where we
need a number of basic technologies to all get over certain bars
before the floodgates start to open.
Over the past 1-2 decades there has been unbelievable progress at the
basic technology level but most people are unimpressed because they
haven't translated yet due to not individually being sufficient to
cause an explosion of progress. IMO, we're starting to see it finally
as so many different technologies have gotten so cheap, fast, and
good.
anovikov wrote 14 hours 47 min ago:
The floodgates open = the market will see that at least some of
that can actually work and make money => they will pour funding =>
new approaches built on that funding will start working, too?
visha1v wrote 15 hours 11 min ago:
the public experiences biotechnology as decades of nothing,
followed by years of everything once bottlenecks align
toponijo wrote 12 hours 27 min ago:
I think it's just a tech thing! Same as when the internet really
got going or what's happening with AI
dylan604 wrote 15 hours 12 min ago:
So we're waiting for the Apple of the medical world to take a bunch
of preexisting things to be applied together in a way that makes
the whole much more valuable than the pieces. Or we need all of the
individual lions to come together to make the Voltron?
mattlondon wrote 12 hours 26 min ago:
I think realistically we're waiting for someone in the top 10-20
richest people in the world to get cancer (or a close relative
etc) who will then throw billions at research to try and fix the
problem.
robotresearcher wrote 10 hours 42 min ago:
We spend upwards of $15B a year globally on cancer research.
About half of that is funded by government and charities, half
by pharmaceutical companies.
If spending billions was the main trick, weâd know it
already.
dylan604 wrote 10 hours 28 min ago:
Do we actually spend it, or do we raise that much money while
only a fraction of it goes to research?
ben_w wrote 13 hours 54 min ago:
Usually it takes about a decade for most medical inventions to
work their way through medical bureaucracy[0], so I'd say that 10
years ago we were at the stage of watching Matthew Broderick
war-dialling with an acoustic coupler and reading Usborne Books
telling us that criminals of the future would work from home, and
today we're in the exciting early days of dialup, AltaVista, and
GeoCities[1].
[0] The covid vaccines collectively were faster only due to the
fact that when money is no object you can parallelise a lot of
options and can pipeline the testing stages rather than waiting
for full review and another funding round before progressing to
the next stage [1] Where they-don't-tile-but-we-did-it-anyway
animated gif backgrounds are the metaphor for home kits to make
random things bioluminescent:
HTML [1]: https://www.the-odin.com/gfp-bacteria/
dylan604 wrote 10 hours 47 min ago:
So according to your timeline, we're ~10 years from medical
research becoming enshitified?
ben_w wrote 10 hours 26 min ago:
Depends where in the history of the web you count it as such.
For me it was more like the late 2010s when that happened, so
20 years. And of course vanity surgery is already a thing, so
it may have already happened to an extent with medicine?
10-20 years for an Alastair Reynolds' style Indoctrinal
Virus? I hope not, but I can totally see it happening
eventually.
smm11 wrote 14 hours 46 min ago:
We already had this. It was called Theranos.
fragmede wrote 14 hours 37 min ago:
I don't know if we "had" something called Theranos. In fact, I
believe that was the subject of a couple of lawsuit because we
didn't.
rowanG077 wrote 14 hours 39 min ago:
I'm not sure what this comment is trying to say. Theranos was a
company build from the ground up on fraud. Apple, for all its
faults, is provably at the forefront of technology used in
personal computing devices.
im3w1l wrote 13 hours 16 min ago:
Apple is first and foremost an affordable luxury brand that
makes sleek hardware.
rowanG077 wrote 12 hours 37 min ago:
And theranos did that too? Theranos, a medical company, was
an affordable luxury (??) brand that makes sleek hardware?
In fact the hardware was not sleek at all, since it didn't
function.
huxley wrote 14 hours 24 min ago:
I think you've captured exactly what they are trying to say
rowanG077 wrote 12 hours 39 min ago:
This doesn't exactly make it clearer. I can think of two
things it can imply. Neither make a lick of sense:
- Theranos was at the forefront of medical technology
- Apple is a fraudulent company to the core
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