> The company says that the drug was generally well tolerated, but that’s on the oncology scale.
> ...
> He’s been on daraxonrasib since early this year, and describes it this way: “. . .it’s a nasty drug. It causes crazy stuff like my body can’t grow skin and so I bleed all out of a whole bunch of parts of me that shouldn’t be bleeding” If you go to that link above, be prepared, because he also looks like he’s had aqua regia thrown all over him (and apparently feels a bit like that, too). But his tumor volume has gone down by about 75%, and there’s a very strong chance that he wouldn’t still be alive at all without having gone on the drug.
I am in the enviable position to not be actively dying from an untreatable disease, so obviously haven’t seen things from the other side of this sort of situation.
But to me, that doesn’t sound like a life worth living. Obviously different people will have different thresholds for when to throw in the towel, and I’m glad that we are finding medicines to allow people to make the choices that align with their own drives.
Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering.
I am truly terrified of death. I wish I wasn’t, but an infinity of nonexistence somehow seems unbearable (though, obviously, it will be trivial to bear in practice). I still hope that when my time comes, I will find the strength to exit gracefully if my life ever gets to the point where each day is filled with pain and discomfort, and where I can’t actually take part in any of the things I enjoy about life.
I hope that this is only a temporary treatment for this guy to get the tumor to a point where it can be operated on or treated with other therapies. Because his life sounds like a living hell and that breaks my heart.
I mean, he looks uncomfortable, but you would be surprised at how much people can tolerate when there is no alternative. Here is an interview I found [0].
I think he looks better than every 90 year old. But he also mentions that it still is terminal.
This may sound condescending but: you sound young, not disabled, and extremely sheltered from being exposed to disabled people.
I am in a position to be intimately familiar with illness. I will say that health is a spectrum and the mind is incredibly resilient. You will surprise yourself as you inevitably age how much your mind will adapt to always hurting. There is more to life than body discomfort. This patient sounds like he has his faculties and is making an informed decision to continue living, because his life is worth the discomfort he is going through. I am reminded of a line along the lines of every day you experience, no matter how terrible, is very likely a day that someone else yesterday would have desperately wanted.
I find both the honesty and tact of your comment a generous gift. After watching the Sasse interview, reading the parent comment and reading your comment, I’m reminded abstractly how much of the emotional and psychological work of reconciling biological mortality is built on personal cognitive context that a mind-body builds over its cycles living in the world. So much about mortality is shared. But so much of the context for interpreting mortality is radically personal.
There has been recent attention on what treatments oncologists choose for themselves when diagnosed with terminal illnesses—having seen firsthand what happens to quality of life for their patients—and what members of the general population choose.
Doctors tend to choose the treatments that bias quality of life over quantity of life. That’s all I’m getting at here. I personally hope that if it ever comes to it, I will have the strength to choose something like three months of high QoL over one year of grinding daily misery as I have personally seen others do.
Having your skin fail to regenerate, bleeding everywhere, and having skin that looks like you’ve had aqua regia poured over it seems to me like a poor quality of life. It sounded like a life of pain and one in which it would be difficult to do a lot of the things that bring me joy. Perhaps it’s not as bad as it sounds, and this is a poor example of it. I’m not judging this guy for his choices; they’re his to make. And maybe I’ve overestimated the amount of pain he’s in. But from the description above, it sounded awful.
Why do you feel the need to attack the person character by stating he is probably young and/or has not dealt with disability in his social circle? This is needlessly aggravating and actually pissed me of when reading it.
> Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering.
I often think about this, wondering how many of those animals would have chosen death if given the choice, and how often it is simply a way to spare the owner from seeing something that upsets them.
Always. Everything that pet owners do to their pets is driven by the owner's human feelings and not the pet's animal needs. Obviously, because we can't communicate with the pets and they can't tell us what we want. And we have total control over their lives so we do what we want.
I'm personally particularly upset by the easy conviction with which most people neuter their pets. I can rant for hours on the ethics of that, or the complete lack thereof, in my opinion. I'm shocked there is so little debate on that, even by philosophers and particularly of animal rights activists who really, really should know better than support such a cruel, egregious and obvious violation of an animal's individual existence.
At least in some countries neutering an animal for anything but medical reasons is illegal. Maybe I should move to Norway.
The harm of neutering and spaying needs to be balanced with the harm of having dramatically greater numbers of feral cats and dogs, whose lives are often what I will charitably describe as not enviable, and with the problems having large numbers of feral animals can cause to an area.
The alternative we in America have settled on right now is shelters which perform euthanasia on unwanted animals. I would love to know how communities that have banned these procedures deal with the issue.
There are plenty of places in the world were stray cats and dogs are normal and there's nothing wrong with that. You may find their lives not enviable; but you are a human. Er, presumably. Plenty of strays in Greece where I'm from are taken care of by volunteers so they're well fed and they have shelter and medical care when they need it. The greatest danger is traffic accidents but that's also true for domestic animals and neutering certainly doesn't protect from that.
You use the word "feral" but I find that's a bit of a loaded term because it makes it sound like those animals are wild and violent. They're usually not, or at least not more than domestic animals. In the UK, where I live, there are no strays and still there are thousands of dog attacks, some causing injury or even death every year. Cats of course don't attack humans unless you really piss them off and even then it's not like they can seriously injure you.
You could also think about all the "feral" animals we do not try to neuter in large numbers like pigeons or seagulls. Much of what's wrong with their lives is that people treat them like dirt. That's not a problem you solve by castrating an animal, or at least a non-human animal. Why only neuter cats and dogs? Because we care more about them? That sounds like some kind of perverse inversion to me.
And let's not forget: the only difference between a "feral" or stray cat or dog and a pet is that someone's taken the pet in. I suppose in civilised countries you only get your pets from a certified breeder and you know their pedigree but where I come from if you want a cat or a dog you can just take one from the street. Or, often, they come to you on their own; cats mostly, but dogs, too some times. That was the case for most of the animals I've ever cared for: basically all the cats and a couple of the dogs too.
>> I would love to know how communities that have banned these procedures deal with the issue.
There's a famous documentary about the stray cats of Istanbul, called Kedi (meaning "cat" in Turkish). I haven't watched it yet but it sounds like the thing you'd want to watch if you haven't grown up with strays all over the place:
Well, I am in the situation you are so afraid of. Chemo, radiation and other treatments suck big time, let alone the effects of the cancer itself.
BUT ... this is not a binary situation, where suddenly life becomes unbearable. There's so much worth living for. And not just the obvious big things in life (kids, family, friends), but also many many small things. Man, that first cup of cappuchino once the effects of chemo wear off alone is almost worth all the puking beforehand :) Or having a nice piece of cheese. Seeing my small herb garden grow. Etc. etc.
The trick is to live a peaceful, content life. Be grateful for what you have. Enjoy your short time on earth.
Of course it’s never binary. And different people value different things.
I don’t think I was clear that I’m not afraid of being simply uncomfortable in my final days, but that there are absolutely medical treatments that can extend one’s life at extreme cost to quality of life. And there’s a threshold where I hope I’ll choose quality over quantity.
Sometimes you don’t know what that cost will be before starting treatment. Sometimes you’re holding out hope that the treatment will help you actually make it out the other side alive and healthy again. Sometimes you want to make it through long enough to see a child graduate, or meet a grandchild on the way, or some other meaningful event. There’s a million reasons one might choose between treatment options. And I don’t begrudge anyone for making the choice that’s right for them.
I’m sorry to hear what you’re going through, but I’m glad that it sounds like you’ve chosen a path that brings you the most fulfillment possible.
Sasse is a bad example of the drug. Entire institutions, at least the two I'm working with as a caregiver, have gone through the trials of 6236 without a single case of the rash as bad as his.
Insensitive comment in general. "Throw in the towel" really pissed me off.
I’m glad to hear that that’s not common. From the description GP gave it did not sound like a simple rash.
Obviously I am not saying that people should choose to forego treatment to avoid minor discomfort. I am saying that there are thresholds of quality of life where I think—given both foreknowledge of a treatment’s consequences and emotional distance from the situation—many would choose a shorter, higher quality of life than a longer, drawn out daily battle with little of the things we enjoy.
I’m sorry to hear what you are facing and send any good vibes I can. I lost my wife to a particularly nasty metastatic cancer (melanoma). There were a few complications that delayed her immunotherapy, which ultimately led to her death.
There is a targeted therapy that applies to many melanomas, but hers did not have the mutation that made it an option. Perhaps this treatment will be tweaked and developed to be less awful and offer that gift of time that my wife didn’t have.
Cancer and other diseases are insidious. While she didn’t make it, she had hope. And the reality is her hope was built on the shoulders of countless others who faced certain death and whose experiences led us to the 60/40 odds that melanoma patients have today.
I think the two key things to consider is that: (1) humans are quite good at getting accustomed to their current situation, and (2) these degraded living situations generally happen gradually. There's no hard cutoff where one might suddenly think "welp, I've passed my threshold of wanting to live just now". Boiling the frog, if you will.
There are so many different situations I could not imagine happily living in even when I try to, but then I try to think about how I would feel if I was born into the situation from day one. I wouldn't really know any other life, and so it would just be my life. With that in mind, the most troubling thing mostly seems to be what I have perceived to have lost, rather than what I currently have. That helps me understand how you can keep on living. Even when you lose something, you still have what you still have.
I'd first run across this decades ago in the context of FDA drugs trials, in which adverse incidents were noted. My understanding at the time was that certain chemotherapies tended to interfere with skin regeneration, particularly in areas subject to high wearing (hands, feet, elbows), or rapid replacement (particularly mucous membranes, lips and mouth especially).
Not all chemotherapies are brutal, but some can be quite fiendish, and quality of life is a legitimate consideration when considering whether to proceed with treatment. Informed decisionmaking and consent in a context where expertise is rare and clinicians don't directly experience the adverse effects is difficult at best.
You are excluding most government and charity funding into medical research.
VC funding includes firms inside of the medical industry, but also companies operating across most of the economy. It’s not just IT, but food, solar, EV’s, rockets, etc.
I'm happy to see corrections with citations. I'd posted what information I could find.
I found your original dismissal without any documentation unsatisfactory, and wanted to quantify overall rather than specific-firm-instance funding. And you're still not providing any citations for your claims.
I suspect that the overall spend going into AI / adtech / digital media is disproportionately large relative to pharma spending. Particularly given the relative social benefits of each. I'd like to be able to make an evidence-based assessment rather than just a gut feel, however.
Clear breakouts of total investment spend by sector are hard to find, presumably much of the accurate information is paywalled. However from a Bain report I'd turned up earlier:
AI pulled in about half of all US venture funding in the fourth quarter, with investment spanning infrastructure, model training platforms, and AI-native developer tools.
Other significant sectors include, presumably in order, "robotics, AI, semiconductors, and Web3 sectors", and "Early-stage activity was strengthened by AI, robotics, defense tech, and biotech". All of which suggests that biotech is a small fraction of the overall total, and new drug discovery a smaller fraction of that.
Total US pharmaceutical industry R&D spend per a 2021 Congressional Budget Office report was $83 billion.
US federally-funded medical research largely occurs through the National Institutes of Health, which has an annual budget of $48 billion. I'd be quite surprised if state-level and other countries' spend doubled that. It increases my earlier figure by about 20%, which isn't nothing, but pales next to the venture tech investment. Again, that's all medical spending, not limited to new drug discovery.
As the previously-cited CBO report notes: "Much of that [NIH] funding has supported basic research (in genomics, molecular biology, and other life sciences) that has identified new disease mechanisms." So, not strictly new drug discovery, though not entirely unrelated either.
Most new drug discovery is likely not venture-backed, so considering my top-line $400 billion vs. $200 billion still seems to point to a roughly-appropriate comparison ratio. If anything, further research suggests the $200 billion value for pharma is probably high-side when it comes to drugs.
The 425B VC numbers are global, and again include some medical funding 25B in 2024, so ~25B in 2025 seems reasonable thus non medical VC at 400B flat is a reasonable number. https://dealroom.co/guides/healthtech-guide
“In the US, the federal government, private companies, universities, states, associations, and philanthropic foundations collectively invest more than $245 billion (PDF)Note 2 in medical research each year. https://unbreaking.org/issues/medical-research-funding/
That suggest the numbers work out to global non medical VC funding at 400B vs 500B for medical research globally.
I’m not saying these numbers are particularly accurate, and they aren’t limited to drug research, but it does provide a different perspective.
PS: As to US federal funding of medical research quite a lot is sitting in the tax code rather than being handed out as grants, it’s not directly relevant. Except it rather inflates what companies label as medical R&D. This makes my position worse, but I bring it up because the actual numbers are dependent on how you interpret what’s going on. Do we include VC funding that’s essentially a private sale of equity from the founders to investors which doesn’t provide the company money? ¯\_(ツ)_/¯
I'd argue that the numbers suggest that venture spend on info tech / AI / social media is at least of the same order of magnitude as new drug discovery, if not more.
It would be interesting to compare blockbuster drugs of the past 5--10 years or so to see what types of investment have been made there. mRNA / Covid19 vaccines, and GLP1s.
A Deloitte report gives oncology, infectious disease, and chronic conditions (particularly obesity and diabetes) as key areas.
It also gives some relevant numbers re investment and revenue:
The increase in IRR is driven by promising late-stage pipeline candidates and impressive trial outcomes (the average forecast peak sale has increased to US$510 million). However, high R&D costs, which reached an average of US$2.23 billion per asset in 2024, present a continuing challenge.
(And if you're confused by exactly what that 'graph is actually communicating, I am too: "$2.23 billion per asset" is an odd and unclear phrasing.
From StartUs Insights, "Drug Discovery Market Report 2025":
The global drug discovery industry was valued at approximately USD 106.70 billion in 2025.
(Emphasis added.)
And...
The drug discovery sector includes 5370 companies with 990+ startups. The leading country hubs are the USA, the UK, India, China, and Japan, and major city hubs include San Diego, Cambridge, London, New York City, and San Francisco. ...
Over 9550 funding rounds closed with an average of USD 34 million per round. More than 7600 investors invested in over 2220 companies.
Doing the maths on that last: about $325 billion in funding.
AI, which leads infotech venture spend presently, is valued at $515 billion in 2026, and is projected to grow at 30.6% CAGR, reaching $1 trillion in 20209 and $3.5 trillion by 2033.
(Whether or not you, or I, believe these projections is less material than what the markets and investors believe, and they seem to be acting on the assumption that the market and asset values will grow.)
Pharma by contrast, is estimated at $1.7 billion 2025, growing at 6.08%, and reaching $2.8 trillion by 2033.
Which is to say that whilst projected AI and pharma markets in five years are comparable, growth in AI is seen as 5x the rate of pharma. And investment follows growth, not total value.
Pharma spend is largely capped by public and private insurance spend, which tends to be mature, already high relative to total economic activity, is constrained on multiple fronts, and divides results and rewards amongst multiple entities (both drugs/therapies and companies). Biggest growth is projected in Asia-Pacific.
Projections for AI spend are ... somewhat unhindered by empirical data or practical realities, and at least as told at investor storytime, promise both the heavens and stars and winner-take-all dynamics, such that money is chasing the possibility of landing on the top of the heap.
Again: quite probable that there's a lot more money available for AI moonshots than new drug discovery, though perhaps grounded more in anticipation and psychology than reality or net social benefit.
The recently-read-out trial is in the 'second line' - meaning patients will have received one 'line' of treatment before this - typically chemotherapy +/- surgery. The chemotherapy regimes used for pancreatic cancer can be pretty brutal, and patients can usually tolerate one, max two lines overall. As such, this trial administering only daraxonrasib monotherapy made sense.
The first line trial of daraxonrasib is already underway, and includes both darax monotherapy and darax + chemo arms. (They are combining with a slightly less brutal chemotherapy called GnP, with an eye to the overall side effect burden considering the non-trial side effects that darax also brings.)
It'll be very interesting to see the outcome of this trial; there are some examples elsewhere in oncology where a treatment is recommended by guidelines without chemotherapy over a combination with chemotherapy, as the small survival benefit the addition of chemotherapy brings is seen as outweighed by the additional toxicity.
I hope they can get this to people quickly. Someone I love has been diagnosed with stage 3 end of Feb this year and it's utter hell. For everyone, not just the patient.
While not fully approved, the company has early access available to people who meet the treatment criteria and would potentially benefit. Their HCP should evaluate this (it's not all types of pancreatic cancer, and it's not a silver bullet - but it looks like its double the survival time than current chemo). Hopefully this evolves into a new class of treatment.
Honestly. for the ~2 months my mum had between a totally out-of-the-blue stage 4 melanoma diagnosis and the day she died in the hospice, I don’t think there’s anything she would have wanted less than to endure more of that existence, if someone had offered her that pill.
I'm sorry your mom had to suffer like that :( My loved one really wants to live, and I suppose some people are at different stages of mind with this horrible disease. I wouldn't want to extend suffering too, but if the patient wants to fight the disease, it is up to them.
It's an extra 6 months or so, and it's almost certain a better solution won't be come available in that 6 months, and even if it did you are very close to death and unlikely to recover even if a miracle cure is developed. In the meantime you are in intense pain and suffering wild side effects.
> More than 90% of patients with the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (mPDAC), have a mutation in the Kras gene.
So pancreatic cancer is basically a genetic disease for most patients instead of environmental?
While it's a useful scientific achievement, and I am not second guessing any individuals decision, and any time is likely tempting to take if even to have time to make arrangements, this still only gives about 1 year survival on average to the scenario being quoted in the title, and that year is gruesomely painful.
"survival" is the wrong word; its terminal. honestly the drugs and chemo and treatments they put pancreatic patients through for possibly a few more (not very nice) weeks is almost criminal. a good doctor will tell you to go make the most of those 3 months post diagnosis. that said its nice to see progress against one of the worst cancers out there and i hope it leads to genuine breakthroughs. but this drug is nothing anybody wants, even if they think they do
> Thus the treatment had provided them a median life extension of about 3/4 years. The lucky ones probably have got more than an extra year.
The 'median' patient in this trial lived ~6.6m longer if they received daraxonrasib. It's worth noting that the performance of the chemotherapy arms was stronger in this trial than previous trials of second-line chemotherapy; whether this reflects better care or a prognostically-superior trial population remains to be seen.
I have quoted exactly the numbers that were written in the abstract of the article yesterday, at the same link that you have used.
What is very weird is that the abstract of the article has been changed, and now it is as you say.
So the numbers from today are worse than those from yesterday.
Perhaps the abstract of yesterday corresponded with a preliminary version of the study report, but meanwhile more patients have died, which has been taken into account in the final version, lowering both the median values for overall survival and for progression-free survival.
No offense intended. I guess someone in the RevMed Scientific Comms team had a more stressful day than they'd envisaged.
> Perhaps the abstract of yesterday corresponded with a preliminary version of the study report, but meanwhile more patients have died, which has been taken into account in the final version, lowering both the median values for overall survival and for progression-free survival.
No. The 'data cut' that these numbers are based on will have been taken (at least) weeks ago. You don't get (anything close to) real-time updates in the manner that you're implying. It was probably just a simple snafu somewhere along the line.
The operative term isn't simply "survival" but "survival time", that is, the time, post-diagnosis, a patient cohort may be expected to survive on average. It is a term of art.
It's also meaningful insofar as extended survival time suggests progress against the disease mechanism. This may not mean long-term survival for present sufferers of this particular disease, but may suggest future research which is more promising, or if this route hits a wall on any additional outcomes improvements, limitations to this approach. The advance of knowledge is a benefit, regardless of ultimate patient outcomes.
(Where the trade-off in knowledge gains vs. patient outcomes lies is yet another realm of medical ethics.)
Language-lawyering the term is however specious. If you want to comment on quality of life or other matters, those are separate and meritorious discussions. You're embarking on them in a manner that's not likely to be especially conducive however.
Derek Lowe’s writeup is good: https://www.science.org/content/blog-post/progress-against-p...
> The company says that the drug was generally well tolerated, but that’s on the oncology scale.
> ...
> He’s been on daraxonrasib since early this year, and describes it this way: “. . .it’s a nasty drug. It causes crazy stuff like my body can’t grow skin and so I bleed all out of a whole bunch of parts of me that shouldn’t be bleeding” If you go to that link above, be prepared, because he also looks like he’s had aqua regia thrown all over him (and apparently feels a bit like that, too). But his tumor volume has gone down by about 75%, and there’s a very strong chance that he wouldn’t still be alive at all without having gone on the drug.
I am in the enviable position to not be actively dying from an untreatable disease, so obviously haven’t seen things from the other side of this sort of situation.
But to me, that doesn’t sound like a life worth living. Obviously different people will have different thresholds for when to throw in the towel, and I’m glad that we are finding medicines to allow people to make the choices that align with their own drives.
Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering.
I am truly terrified of death. I wish I wasn’t, but an infinity of nonexistence somehow seems unbearable (though, obviously, it will be trivial to bear in practice). I still hope that when my time comes, I will find the strength to exit gracefully if my life ever gets to the point where each day is filled with pain and discomfort, and where I can’t actually take part in any of the things I enjoy about life.
I hope that this is only a temporary treatment for this guy to get the tumor to a point where it can be operated on or treated with other therapies. Because his life sounds like a living hell and that breaks my heart.
I mean, he looks uncomfortable, but you would be surprised at how much people can tolerate when there is no alternative. Here is an interview I found [0].
I think he looks better than every 90 year old. But he also mentions that it still is terminal.
[0] https://www.nytimes.com/video/opinion/100000010826256/what-d...
This may sound condescending but: you sound young, not disabled, and extremely sheltered from being exposed to disabled people.
I am in a position to be intimately familiar with illness. I will say that health is a spectrum and the mind is incredibly resilient. You will surprise yourself as you inevitably age how much your mind will adapt to always hurting. There is more to life than body discomfort. This patient sounds like he has his faculties and is making an informed decision to continue living, because his life is worth the discomfort he is going through. I am reminded of a line along the lines of every day you experience, no matter how terrible, is very likely a day that someone else yesterday would have desperately wanted.
I find both the honesty and tact of your comment a generous gift. After watching the Sasse interview, reading the parent comment and reading your comment, I’m reminded abstractly how much of the emotional and psychological work of reconciling biological mortality is built on personal cognitive context that a mind-body builds over its cycles living in the world. So much about mortality is shared. But so much of the context for interpreting mortality is radically personal.
There has been recent attention on what treatments oncologists choose for themselves when diagnosed with terminal illnesses—having seen firsthand what happens to quality of life for their patients—and what members of the general population choose.
Doctors tend to choose the treatments that bias quality of life over quantity of life. That’s all I’m getting at here. I personally hope that if it ever comes to it, I will have the strength to choose something like three months of high QoL over one year of grinding daily misery as I have personally seen others do.
Having your skin fail to regenerate, bleeding everywhere, and having skin that looks like you’ve had aqua regia poured over it seems to me like a poor quality of life. It sounded like a life of pain and one in which it would be difficult to do a lot of the things that bring me joy. Perhaps it’s not as bad as it sounds, and this is a poor example of it. I’m not judging this guy for his choices; they’re his to make. And maybe I’ve overestimated the amount of pain he’s in. But from the description above, it sounded awful.
probably articles like this
https://hms.harvard.edu/news/how-doctors-die
> Physicians are less likely than the general population to undergo intense end-of-life treatments
Why do you feel the need to attack the person character by stating he is probably young and/or has not dealt with disability in his social circle? This is needlessly aggravating and actually pissed me of when reading it.
> Still, I can’t help but think that this is the sort of life virtually none of us would choose to inflict on our pets, even if cost was no option. We give them a far more graceful exit from this world than we give ourselves, and I think that’s worth considering.
I often think about this, wondering how many of those animals would have chosen death if given the choice, and how often it is simply a way to spare the owner from seeing something that upsets them.
Always. Everything that pet owners do to their pets is driven by the owner's human feelings and not the pet's animal needs. Obviously, because we can't communicate with the pets and they can't tell us what we want. And we have total control over their lives so we do what we want.
I'm personally particularly upset by the easy conviction with which most people neuter their pets. I can rant for hours on the ethics of that, or the complete lack thereof, in my opinion. I'm shocked there is so little debate on that, even by philosophers and particularly of animal rights activists who really, really should know better than support such a cruel, egregious and obvious violation of an animal's individual existence.
At least in some countries neutering an animal for anything but medical reasons is illegal. Maybe I should move to Norway.
Bonus: great Black Metal scene.
The harm of neutering and spaying needs to be balanced with the harm of having dramatically greater numbers of feral cats and dogs, whose lives are often what I will charitably describe as not enviable, and with the problems having large numbers of feral animals can cause to an area.
The alternative we in America have settled on right now is shelters which perform euthanasia on unwanted animals. I would love to know how communities that have banned these procedures deal with the issue.
There are plenty of places in the world were stray cats and dogs are normal and there's nothing wrong with that. You may find their lives not enviable; but you are a human. Er, presumably. Plenty of strays in Greece where I'm from are taken care of by volunteers so they're well fed and they have shelter and medical care when they need it. The greatest danger is traffic accidents but that's also true for domestic animals and neutering certainly doesn't protect from that.
You use the word "feral" but I find that's a bit of a loaded term because it makes it sound like those animals are wild and violent. They're usually not, or at least not more than domestic animals. In the UK, where I live, there are no strays and still there are thousands of dog attacks, some causing injury or even death every year. Cats of course don't attack humans unless you really piss them off and even then it's not like they can seriously injure you.
You could also think about all the "feral" animals we do not try to neuter in large numbers like pigeons or seagulls. Much of what's wrong with their lives is that people treat them like dirt. That's not a problem you solve by castrating an animal, or at least a non-human animal. Why only neuter cats and dogs? Because we care more about them? That sounds like some kind of perverse inversion to me.
And let's not forget: the only difference between a "feral" or stray cat or dog and a pet is that someone's taken the pet in. I suppose in civilised countries you only get your pets from a certified breeder and you know their pedigree but where I come from if you want a cat or a dog you can just take one from the street. Or, often, they come to you on their own; cats mostly, but dogs, too some times. That was the case for most of the animals I've ever cared for: basically all the cats and a couple of the dogs too.
>> I would love to know how communities that have banned these procedures deal with the issue.
There's a famous documentary about the stray cats of Istanbul, called Kedi (meaning "cat" in Turkish). I haven't watched it yet but it sounds like the thing you'd want to watch if you haven't grown up with strays all over the place:
https://en.wikipedia.org/wiki/Kedi_(2016_film)
Well, I am in the situation you are so afraid of. Chemo, radiation and other treatments suck big time, let alone the effects of the cancer itself.
BUT ... this is not a binary situation, where suddenly life becomes unbearable. There's so much worth living for. And not just the obvious big things in life (kids, family, friends), but also many many small things. Man, that first cup of cappuchino once the effects of chemo wear off alone is almost worth all the puking beforehand :) Or having a nice piece of cheese. Seeing my small herb garden grow. Etc. etc.
The trick is to live a peaceful, content life. Be grateful for what you have. Enjoy your short time on earth.
Of course it’s never binary. And different people value different things.
I don’t think I was clear that I’m not afraid of being simply uncomfortable in my final days, but that there are absolutely medical treatments that can extend one’s life at extreme cost to quality of life. And there’s a threshold where I hope I’ll choose quality over quantity.
Sometimes you don’t know what that cost will be before starting treatment. Sometimes you’re holding out hope that the treatment will help you actually make it out the other side alive and healthy again. Sometimes you want to make it through long enough to see a child graduate, or meet a grandchild on the way, or some other meaningful event. There’s a million reasons one might choose between treatment options. And I don’t begrudge anyone for making the choice that’s right for them.
I’m sorry to hear what you’re going through, but I’m glad that it sounds like you’ve chosen a path that brings you the most fulfillment possible.
Sasse is a bad example of the drug. Entire institutions, at least the two I'm working with as a caregiver, have gone through the trials of 6236 without a single case of the rash as bad as his.
Insensitive comment in general. "Throw in the towel" really pissed me off.
I’m glad to hear that that’s not common. From the description GP gave it did not sound like a simple rash.
Obviously I am not saying that people should choose to forego treatment to avoid minor discomfort. I am saying that there are thresholds of quality of life where I think—given both foreknowledge of a treatment’s consequences and emotional distance from the situation—many would choose a shorter, higher quality of life than a longer, drawn out daily battle with little of the things we enjoy.
I’m sorry to hear what you are facing and send any good vibes I can. I lost my wife to a particularly nasty metastatic cancer (melanoma). There were a few complications that delayed her immunotherapy, which ultimately led to her death.
There is a targeted therapy that applies to many melanomas, but hers did not have the mutation that made it an option. Perhaps this treatment will be tweaked and developed to be less awful and offer that gift of time that my wife didn’t have.
Cancer and other diseases are insidious. While she didn’t make it, she had hope. And the reality is her hope was built on the shoulders of countless others who faced certain death and whose experiences led us to the 60/40 odds that melanoma patients have today.
I think the two key things to consider is that: (1) humans are quite good at getting accustomed to their current situation, and (2) these degraded living situations generally happen gradually. There's no hard cutoff where one might suddenly think "welp, I've passed my threshold of wanting to live just now". Boiling the frog, if you will.
There are so many different situations I could not imagine happily living in even when I try to, but then I try to think about how I would feel if I was born into the situation from day one. I wouldn't really know any other life, and so it would just be my life. With that in mind, the most troubling thing mostly seems to be what I have perceived to have lost, rather than what I currently have. That helps me understand how you can keep on living. Even when you lose something, you still have what you still have.
Hand-foot syndrome, a/k/a chemotherapy-induced acral erythema, is a similar condition, though there may be another I'm confusing with.
<https://en.wikipedia.org/wiki/Chemotherapy-induced_acral_ery...>
I'd first run across this decades ago in the context of FDA drugs trials, in which adverse incidents were noted. My understanding at the time was that certain chemotherapies tended to interfere with skin regeneration, particularly in areas subject to high wearing (hands, feet, elbows), or rapid replacement (particularly mucous membranes, lips and mouth especially).
Not all chemotherapies are brutal, but some can be quite fiendish, and quality of life is a legitimate consideration when considering whether to proceed with treatment. Informed decisionmaking and consent in a context where expertise is rare and clinicians don't directly experience the adverse effects is difficult at best.
The founders of Lovable and Builder.ai individually received more funds than the whole group of the researchers behind this medicine...
That’s like talking about the ROI of a winning lottery ticket.
We can’t know ahead of time which medicine works so you need to fund many teams at the beginning.
The pharmaceutical new drug development R&D market saw about $200 billion invested in 2025.
<https://hardmanandco.com/research/corporate-research/2025-ph...>
Total VC tech investment in 2025 was $425 billion.
<https://news.crunchbase.com/venture/funding-data-third-large...>
You are excluding most government and charity funding into medical research.
VC funding includes firms inside of the medical industry, but also companies operating across most of the economy. It’s not just IT, but food, solar, EV’s, rockets, etc.
So, IMO these numbers are pretty reasonable.
I'm happy to see corrections with citations. I'd posted what information I could find.
I found your original dismissal without any documentation unsatisfactory, and wanted to quantify overall rather than specific-firm-instance funding. And you're still not providing any citations for your claims.
I suspect that the overall spend going into AI / adtech / digital media is disproportionately large relative to pharma spending. Particularly given the relative social benefits of each. I'd like to be able to make an evidence-based assessment rather than just a gut feel, however.
Clear breakouts of total investment spend by sector are hard to find, presumably much of the accurate information is paywalled. However from a Bain report I'd turned up earlier:
AI pulled in about half of all US venture funding in the fourth quarter, with investment spanning infrastructure, model training platforms, and AI-native developer tools.
<https://www.bain.com/insights/global-venture-capital-outlook...>
Other significant sectors include, presumably in order, "robotics, AI, semiconductors, and Web3 sectors", and "Early-stage activity was strengthened by AI, robotics, defense tech, and biotech". All of which suggests that biotech is a small fraction of the overall total, and new drug discovery a smaller fraction of that.
Total US pharmaceutical industry R&D spend per a 2021 Congressional Budget Office report was $83 billion.
<https://www.cbo.gov/publication/57126>
US federally-funded medical research largely occurs through the National Institutes of Health, which has an annual budget of $48 billion. I'd be quite surprised if state-level and other countries' spend doubled that. It increases my earlier figure by about 20%, which isn't nothing, but pales next to the venture tech investment. Again, that's all medical spending, not limited to new drug discovery.
<https://www.nih.gov/about-nih/organization/budget>
As the previously-cited CBO report notes: "Much of that [NIH] funding has supported basic research (in genomics, molecular biology, and other life sciences) that has identified new disease mechanisms." So, not strictly new drug discovery, though not entirely unrelated either.
Most new drug discovery is likely not venture-backed, so considering my top-line $400 billion vs. $200 billion still seems to point to a roughly-appropriate comparison ratio. If anything, further research suggests the $200 billion value for pharma is probably high-side when it comes to drugs.
The 425B VC numbers are global, and again include some medical funding 25B in 2024, so ~25B in 2025 seems reasonable thus non medical VC at 400B flat is a reasonable number. https://dealroom.co/guides/healthtech-guide
“In the US, the federal government, private companies, universities, states, associations, and philanthropic foundations collectively invest more than $245 billion (PDF)Note 2 in medical research each year. https://unbreaking.org/issues/medical-research-funding/
“The US carries out 46% of global research and development (R&D) in the life sciences, making it the world leader in medical research.[1] https://en.wikipedia.org/wiki/Biomedical_research_in_the_Uni...
That suggest the numbers work out to global non medical VC funding at 400B vs 500B for medical research globally.
I’m not saying these numbers are particularly accurate, and they aren’t limited to drug research, but it does provide a different perspective.
PS: As to US federal funding of medical research quite a lot is sitting in the tax code rather than being handed out as grants, it’s not directly relevant. Except it rather inflates what companies label as medical R&D. This makes my position worse, but I bring it up because the actual numbers are dependent on how you interpret what’s going on. Do we include VC funding that’s essentially a private sale of equity from the founders to investors which doesn’t provide the company money? ¯\_(ツ)_/¯
Thanks for that.
I'd argue that the numbers suggest that venture spend on info tech / AI / social media is at least of the same order of magnitude as new drug discovery, if not more.
It would be interesting to compare blockbuster drugs of the past 5--10 years or so to see what types of investment have been made there. mRNA / Covid19 vaccines, and GLP1s.
A Deloitte report gives oncology, infectious disease, and chronic conditions (particularly obesity and diabetes) as key areas.
It also gives some relevant numbers re investment and revenue:
The increase in IRR is driven by promising late-stage pipeline candidates and impressive trial outcomes (the average forecast peak sale has increased to US$510 million). However, high R&D costs, which reached an average of US$2.23 billion per asset in 2024, present a continuing challenge.
<https://www.deloitte.com/ch/en/Industries/life-sciences-heal...>
(And if you're confused by exactly what that 'graph is actually communicating, I am too: "$2.23 billion per asset" is an odd and unclear phrasing.
From StartUs Insights, "Drug Discovery Market Report 2025":
The global drug discovery industry was valued at approximately USD 106.70 billion in 2025.
(Emphasis added.)
And...
The drug discovery sector includes 5370 companies with 990+ startups. The leading country hubs are the USA, the UK, India, China, and Japan, and major city hubs include San Diego, Cambridge, London, New York City, and San Francisco. ...
Over 9550 funding rounds closed with an average of USD 34 million per round. More than 7600 investors invested in over 2220 companies.
Doing the maths on that last: about $325 billion in funding.
<https://www.startus-insights.com/innovators-guide/drug-disco...>
Also relevant is projected growth of industries.
AI, which leads infotech venture spend presently, is valued at $515 billion in 2026, and is projected to grow at 30.6% CAGR, reaching $1 trillion in 20209 and $3.5 trillion by 2033.
<https://resourcera.com/data/artificial-intelligence/ai-marke...>
(Whether or not you, or I, believe these projections is less material than what the markets and investors believe, and they seem to be acting on the assumption that the market and asset values will grow.)
Pharma by contrast, is estimated at $1.7 billion 2025, growing at 6.08%, and reaching $2.8 trillion by 2033.
<https://www.grandviewresearch.com/industry-analysis/pharmace...>
Which is to say that whilst projected AI and pharma markets in five years are comparable, growth in AI is seen as 5x the rate of pharma. And investment follows growth, not total value.
Pharma spend is largely capped by public and private insurance spend, which tends to be mature, already high relative to total economic activity, is constrained on multiple fronts, and divides results and rewards amongst multiple entities (both drugs/therapies and companies). Biggest growth is projected in Asia-Pacific.
Projections for AI spend are ... somewhat unhindered by empirical data or practical realities, and at least as told at investor storytime, promise both the heavens and stars and winner-take-all dynamics, such that money is chasing the possibility of landing on the top of the heap.
Again: quite probable that there's a lot more money available for AI moonshots than new drug discovery, though perhaps grounded more in anticipation and psychology than reality or net social benefit.
If you want to see what the side effects look like, look at ex Senator Ben Sasse: https://youtu.be/7CFo6-6BN9k?si=2B3dqB4rOhAnPiZl
Paper: https://www.nejm.org/doi/full/10.1056/NEJMoa2605555?query=fe...
Totally naive question: is this a situation where stacking the drug with chemo might be even better?
There are some trials underway testing that hypothesis.
Yes, with nuances.
The recently-read-out trial is in the 'second line' - meaning patients will have received one 'line' of treatment before this - typically chemotherapy +/- surgery. The chemotherapy regimes used for pancreatic cancer can be pretty brutal, and patients can usually tolerate one, max two lines overall. As such, this trial administering only daraxonrasib monotherapy made sense.
The first line trial of daraxonrasib is already underway, and includes both darax monotherapy and darax + chemo arms. (They are combining with a slightly less brutal chemotherapy called GnP, with an eye to the overall side effect burden considering the non-trial side effects that darax also brings.)
It'll be very interesting to see the outcome of this trial; there are some examples elsewhere in oncology where a treatment is recommended by guidelines without chemotherapy over a combination with chemotherapy, as the small survival benefit the addition of chemotherapy brings is seen as outweighed by the additional toxicity.
I hope they can get this to people quickly. Someone I love has been diagnosed with stage 3 end of Feb this year and it's utter hell. For everyone, not just the patient.
While not fully approved, the company has early access available to people who meet the treatment criteria and would potentially benefit. Their HCP should evaluate this (it's not all types of pancreatic cancer, and it's not a silver bullet - but it looks like its double the survival time than current chemo). Hopefully this evolves into a new class of treatment.
Honestly. for the ~2 months my mum had between a totally out-of-the-blue stage 4 melanoma diagnosis and the day she died in the hospice, I don’t think there’s anything she would have wanted less than to endure more of that existence, if someone had offered her that pill.
I'm sorry your mom had to suffer like that :( My loved one really wants to live, and I suppose some people are at different stages of mind with this horrible disease. I wouldn't want to extend suffering too, but if the patient wants to fight the disease, it is up to them.
Unfortunately, it seems that this just provides an extra year of life or so.
Of course this is better than nothing, but it is not a cure.
Moreover, the link provided by another poster to an article that discusses the side effects, shows that they are unpleasant.
Still, an extra year of life may provide a chance to survive until the appearance of a better solution.
It's an extra 6 months or so, and it's almost certain a better solution won't be come available in that 6 months, and even if it did you are very close to death and unlikely to recover even if a miracle cure is developed. In the meantime you are in intense pain and suffering wild side effects.
The abstract of the article claims that the median value of extra life time was between 8 months and 9 months.
Therefore those well above the median might have reached an extra year of life.
I agree however that because almost all of them (96%) had severe side effects, many people would prefer to not choose this kind of life extension.
My own parents were such people.
> More than 90% of patients with the most common form of pancreatic cancer, pancreatic ductal adenocarcinoma (mPDAC), have a mutation in the Kras gene.
So pancreatic cancer is basically a genetic disease for most patients instead of environmental?
No, the KRAS mutations are somatic (spontaneous), not inherited
So presumably something causes the spontaneous mutations?
Nature.
DNA is unstable. Lots of stuff cause mutations: background radiation, chemicals, viruses, even our own normal metabolism [1].
[1] https://en.wikipedia.org/wiki/Reactive_oxygen_species#Oxidat...
Source article for those interested:
https://www.nejm.org/doi/full/10.1056/NEJMoa2505783
Paywalled but has a free access option if you make an account.
While it's a useful scientific achievement, and I am not second guessing any individuals decision, and any time is likely tempting to take if even to have time to make arrangements, this still only gives about 1 year survival on average to the scenario being quoted in the title, and that year is gruesomely painful.
"survival" is the wrong word; its terminal. honestly the drugs and chemo and treatments they put pancreatic patients through for possibly a few more (not very nice) weeks is almost criminal. a good doctor will tell you to go make the most of those 3 months post diagnosis. that said its nice to see progress against one of the worst cancers out there and i hope it leads to genuine breakthroughs. but this drug is nothing anybody wants, even if they think they do
> "survival" is the wrong word; its terminal.
No one actually knows that one way or the other since some patients were still taking it after the study ended according to the article.
According to the abstract of the article, there were 2 groups of patients.
One group had median values of 8.5 months for progression-free survival and 13.1 months for overall survival.
The other group had median values of 8.1 months for progression-free survival and 15.6 months for overall survival.
Overall Survival (OS) measures the time until death from any cause.
Progression-Free Survival (PFS) evaluates how long a treatment can delay disease progression or death.
So at least most of the patients from the study have died, because otherwise median values could not have been computed.
Thus the treatment had provided them a median life extension of about 3/4 years. The lucky ones probably have got more than an extra year.
Your numbers are a little off. The NEJM article was published a few hours ago: https://www.nejm.org/doi/full/10.1056/NEJMoa2605555
RAS G12 population mOS: daraxonrasib 13.2 months / chemotherapy 6.6 months Overall population mOS: daraxonrasib 13.2 months / chemotherapy 6.7 months
RAS G12 population mPFS: daraxonrasib 7.3 months / chemotherapy 3.5 months Overall population PFS: daraxonrasib 7.2 months / chemotherapy 3.6 months
> Thus the treatment had provided them a median life extension of about 3/4 years. The lucky ones probably have got more than an extra year.
The 'median' patient in this trial lived ~6.6m longer if they received daraxonrasib. It's worth noting that the performance of the chemotherapy arms was stronger in this trial than previous trials of second-line chemotherapy; whether this reflects better care or a prognostically-superior trial population remains to be seen.
My numbers were not at all off.
I have quoted exactly the numbers that were written in the abstract of the article yesterday, at the same link that you have used.
What is very weird is that the abstract of the article has been changed, and now it is as you say.
So the numbers from today are worse than those from yesterday.
Perhaps the abstract of yesterday corresponded with a preliminary version of the study report, but meanwhile more patients have died, which has been taken into account in the final version, lowering both the median values for overall survival and for progression-free survival.
No offense intended. I guess someone in the RevMed Scientific Comms team had a more stressful day than they'd envisaged.
> Perhaps the abstract of yesterday corresponded with a preliminary version of the study report, but meanwhile more patients have died, which has been taken into account in the final version, lowering both the median values for overall survival and for progression-free survival.
No. The 'data cut' that these numbers are based on will have been taken (at least) weeks ago. You don't get (anything close to) real-time updates in the manner that you're implying. It was probably just a simple snafu somewhere along the line.
The operative term isn't simply "survival" but "survival time", that is, the time, post-diagnosis, a patient cohort may be expected to survive on average. It is a term of art.
It's also meaningful insofar as extended survival time suggests progress against the disease mechanism. This may not mean long-term survival for present sufferers of this particular disease, but may suggest future research which is more promising, or if this route hits a wall on any additional outcomes improvements, limitations to this approach. The advance of knowledge is a benefit, regardless of ultimate patient outcomes.
(Where the trade-off in knowledge gains vs. patient outcomes lies is yet another realm of medical ethics.)
Language-lawyering the term is however specious. If you want to comment on quality of life or other matters, those are separate and meritorious discussions. You're embarking on them in a manner that's not likely to be especially conducive however.
Why would you want to double the survival time for cancer cells?