> "I’ve made hundreds of phone calls and e-mails, pleaded with physicians, pharmaceutical companies and clinical investigators. I’ve begged for appointments to establish care, open trial slots, opportunities to be screened for eligibility—really—for Jake’s life."
This just shouldn't be necessary. In 2023, we as a race should be able to figure out a better way to efficiently channel patients with needs towards clinical trials that might serve those needs.
(And I say this as someone who works in this industry.)
When someone says "it's [current year] so [bad thing] should have stopped by now", I get confused.
It feels like it's implying that humans today are fundamentally different from humans in the past. In fact it feels dangerous to me that we often speak of ourselves as almost a different species from humans in history. From an evolutionary perspective humans from any moment in recorded history are basically indistinguishable. Our brain capacity hasn't changed. We're not kinder. We're not less selfish.
We do know more about many things (and less about some things). We have better tools. We've refined more matter into new forms. We have access to more useful energy. But those changes don't change who people are.
No human at any point in history should be content with the state of things, but I don't think that struggle is easier today than it ever has been. We're pushing the boulder up the hill and we'll never reach the top, but should never stop pushing.
Being in the industry, I'm glad you're not content with the state of things. It takes people like you, so thank you for your effort to make our world a better place. Even if we may disagree with nuances of the motivation.
> It feels like it's implying that humans today are fundamentally different from humans in the past. In fact it feels dangerous to me that we often speak of ourselves as almost a different species from humans in history. From an evolutionary perspective humans from any moment in recorded history are basically indistinguishable. Our brain capacity hasn't changed. We're not kinder. We're not less selfish.
When people say this (myself included), I think it's a normative statement, not a positive one. Of course we're the same humans we have been for thousands of years. But the act of calling out our failings as a society can itself, sometimes, spur people to try to change it for the better.
In 2023, we are (positively) essentially the same as our ancestors. But also in 2023, we should (normatively) strive to be better than them, and to be conscious of our failings when we don't.
I’ll be honest, I don’t know a ton about medical trials and how they pick participants.
But is there any reason why people are excluded despite seeking out the trial runners, and have a terminal illness that their drug/procedure MIGHT help with?
I assume the chance it won’t work is legally dealt with for all trial patients, so I’m assuming that’s not the issue.
If they don’t fit the test profile, is there any risk to just simply acknowledging them as an outlier and letting them in anyway? You have one consistent cohort you’re studying, and a “who knows, maybe?” cohort of preliminary results from these Hail Mary folks. That seems useful, even if it lacks the sort of rigour of a group you selected.
That's a tragic story regardless of the medical hope. I don't think I would want to trade that level of discomfort for a little more time with my partner, but I couldn't say for sure.
My Dad had IPF a lung disease and struggled near the end mainly due to isolation at home. My Mom and myself were there but he missed his social outings like fishing and bargain hunting. Even struggling with his oxygen generator he fished struggling through mud and getting waders off and on.
He was great until blood clots caused more issues like taking morphine to calm smooth muscle to help him breathe. Morphine just that tiny pill caused terrible constipation (opioids are terrible).
My point being Dad would take anything just to feel even slightly better it meant he was still here. Death is terrifying and as long as you can limp along whatever makes it better is something people want. Really at that point you try to get to a point where you may just die in your sleep not knowing you did.
The "death is terrifying" social malady does have some FDA-unsanctioned treatments you might consider. Check in with your network's Elusinian priests for the traditional cautions.
Why would you say something like this, especially given your dad's situation? yes they can cause constipation, but without opioids the pain would be much, much worse. To me it's a no-brainer, and nobody is forcing you to take opioids if you would rather the pain. I think opioids are a wonderful gift of nature to us and I'm immensely glad we have them. It terrifies me to think that we are so demonizing them now that they are withholding them from people who need them, and telling them to "take extra stength tylenol" instead. It's barbaric and cruel.
I understand the existential fear of the eternal dirt nap - but I dont care how much my loved one will miss me - because the quality of those last memories will be poor - and eternally painful to them, and will color the memories of me from the good times.
Because of that, I would rather trade those moments of watching me die in the most agonizing, painful way imaginable, for the better memories - the times before I got sick.
I watched my grandmother die, of cancer - there is nothing, literally nothing - that would allow me to put someone else thru that - at least not without their full consent, and making sure they knew of what was to come.
It must depend on the person, how memories weigh. I watched a man who was basically my adoptive grandfather go through chemo and die of cancer in a hospital bed set up in our living room, but the memories of all our beach and forest excursions are much more prominent to me now, and its a bittersweet memory to me to think of the old westerns we watched (his favorite genre) when he was stuck in bed.
I guess I would try to figure out, based on the people around me, how I could make them happiest long term (which I think is the same thing you're saying)
I watched my grandpa die of cancer, not being able to eat for few weeks among other worse things and think it's a bit weird to think of it as something you'd put others through.
Yes it's difficult to support someone in their last days, and it's never pretty, but it's not their fault. It also didn't make forget all the other years I had with my grandpa.
You never know how people will going to respond - on the other hand, if there was some chance for five year or whatever survival, the people you're closest to might never forgive you for not trying if you refuse treatment... You'd hope not, but you never know.
Then there's the problem that some have a few of the people closest to them in one camp, fully accepting, and some in the other camp, which can be terrible (I've seen it especially with people I know where it's their parent who was dying, with different siblings going either way).
I watched two incredible grandparents' life ebb away painfully in hospital beds and hospice care. It was agonizing to sit helplessly while they suffered for days on end. But it helped me come to peace with my actual powerlessness in the most important aspects of life. Personally, I'm glad they didn't take that from me by choosing their own moment of death away from family.
Just my experience and I don't discount that that same experience could have been traumatizing for someone else.
I have to say, the impression I get is that she loves her partner far more than the mother of my son and I love each other, but perhaps even this is a double-edged sword
Those articles by both Jake and his wive are so well written and I would love to read them fully but I can't.
It's gut wrenching that I am just a CT scan away to being in the same (somewhat comparable) situation.
I shouldn't compare fates and still my mind wanders around the topic every time.
The facts they both present in a scientific manner (like remission rates) scare me to my bone. I cannot fathom what he and his loved ones are going through and that makes it even clearer what I have burdened on my wife, children and family.
I know this comment is ultimately me shouting "please let us both live" with many words and maybe this is me being a self serving asshole, maybe it is that. I don't know anymore.
I would love to offer the promise that everything is going to be alright but I cannot. I am just scared as hell and somehow I needed to get this out.
I have never understood how can we, in the same breath, admit the horrifying death that await us all, and also parrot that Gilgamesh story or the like about how futile is to resist. Sure, the blood of the virgins doesn't work, but now we have incredibly good science and technology. For God's sake, we even have enough compute to run monstrous language models; I have an inkling that kind of compute would go a long way on simulating cellular processes. Shouldn't we all[1] just go a bit crazy and start trying to prevent our little, chaotic sacks of bio-molecules from going amok?
[^1]:"All", as opposed to just scientists and clinicians.
I don't think it's as easy as "simulating cellular processes". I feel like sometimes HN tends to severely underestimate the difficulty of problems in other fields. Just off the top of my head I can see several hard problems in this situation
- How precise do you want the simulation? Do you want physical processes fully simulated? You'd need that to get an accurate simulation of molecular interactions, but full physical simulation is computationally expensive even for single, simple molecules.
- Even simplificated simulations are hard. Simulating just the shape of DNA strands is computationally very expensive (usually done with Monte Carlo simulations).
- How many cells do you simulate? The body has ~37 trillion cells. Even if it only took one processor cycle to simulate a cell, you'd need 9250 4GHz processors. That should give an idea of how hard it would be to simulate just an organ.
- How do you take into account interactions? There's a lot of difficulty in understanding how drugs affect the whole human system. Lots of trials show promising results against in-vitro cells and then fail spectacularly in animal models. There's a lot influencing how drugs work and single cellular processes are just a small part of it. The body is incredibly complex.
- How do you validate the models? It's not like we can go into a cell and see where the molecules are. We don't have enough visibility into actual cellular processes to build such complex models to a sufficient degree of accuracy.
Compared to even a single human cell, a monstruous language model is a trivial thing.
All of those things you say are correct, but scientists are doing it anyway[^1]. In that paper, you will see there are ways to "compress" the amount of computation needed.
Five years ago, I would have said that we were further away from having a computer correctly interpret a joke (i.e., I would have agreed with [2]) than from simulating E.Coli. The thing is, people went and did (both) anyway. But they did one more than the other. Research effort and capital flowed, and now we have LLMs. IMO, a big reason for this paradox is that there is no stigma in wanting to make a computer smarter, and everybody started playing with computer code and data and due to the huge amount of effort, there have been results. But when it comes to the very things that keep us alive, we are not so eager to play with computer code. That, I think, has less to do with the complexity of the subject and more with a certain moral disposition...which is the thing I find perplexing.
“Let us grant that this woman is correct about the science and that the project is technologically possible, although I don’t think that has actually been proven. Now she desires that we get rid of the dragon. Presumably, she thinks she’s got the right not to be chewed up by the dragon. How willful and presumptuous. The finitude of human life is a blessing for every individual, whether he knows it or not. Getting rid of the dragon, which might seem like such a convenient thing to do, would undermine our human dignity. The preoccupation with killing the dragon will deflect us from realizing more fully the aspirations to which our lives naturally point, from living well rather than merely staying alive. It is debasing, yes debasing, for a person to want to continue his or her mediocre life for as long as possible without worrying about some of the higher questions about what life is to be used for. But I tell you, the nature of the dragon is to eat humans, and our own species-specified nature is truly and nobly fulfilled only by getting eaten by it...”
You could live just well without a dragon alive. It's just that it's easy to assume things will always be the way you have known them and that the absence of this or that constraint would render things meaningless. Bollocks, I say to that!
It is my opinion and my direct lived experience that yes, we should all start trying to prevent our little chaotic sacks of bio-molecues from going amok.
I would emphatically suggest starting here: Read scientific papers. Read the academic literature.
Read. Know you can read.
And, please bear with me: Know that your doctors most probably do not read.
It sounds so paranoid or bitter. I haven’t found another way to put it into words.
If only for the fact that doctors are usually very busy people. Many of them are probably overworked.
And even among those doctors that do read, a doctor will not be able to view the literature from the urgent perspective of the individual. We are all specialists in ourselves, know the details of our lives, our family history.
It is possible for a layman to read academic literature. To the point that you can help the doctor help you. Don’t tell anyone you can’t read.
There is a severe disease in my close family. The doctors missed the diagnosis for years. Diagnosis happened through sheer luck, insistent advice from a nurse speaking “out of their place”, and our persistence. At diagnosis, biomarkers were so far out of range that it can be known that death would most probably have occurred within days.
After this, we read academic literature.
After this, we trust the doctor like we trust our parachute.
As proof that a layman can read academic literature to save their life and preserve their health:
After the diagnosis, papers we have read have clearly shown that a course of action ordered by a doctor is wrong, harmful, potentially life-threatening. Multiple times. Harmful prescriptions, or abject denial of severe side-effects known to occur in some people. We have had to step in and intercede. The crucial part: This has then been confirmed by another doctor’s opinion. Multiple times.
Relatedly, I am in a Facebook group for $condition, and I can’t tell you how many times I’ve seen people post that a doctor prescribed them $treatment. Although $treatment is a very common thing to give to healthy people, $treatment is KNOWN to potentially cause death in patients with $condition. The other patients in the group always jump in and alert the original poster to the danger, but I can’t believe it still happens week after week and year after year.
My point is that fully outsourcing your healthcare—even to specialists—is a very bad idea, especially if you might have a rare condition of any sort. No doctor will ever care about you/your family member the way that you do. And they are always so pressed for time that mistakes are to be expected.
i’ve been following Jake’s story since one of his posts was here on HN a few months ago. Both him and his wife are excellent writers. I cannot emphasize enough how horrified I am reading every word. What an utterly ghastly experience. I watched my uncle die from cancer as well. I am all too familiar with how this (usually) goes in the end stages.
good luck, jake. may your days be filled with appreciation and love and tranquility.
Suffering from a serious (physical or mental) illness and caring for a sufferer are obviously different experiences, but I don’t think the perspective of the direct sufferer automatically ought to take priority. Caring is it’s own thing, it’s hard and lonely, and often the carers suffer longer. In the case of mental illness, the patient may forget the worst of what happened, and only the carer remembers literally pulling them back from the brink. In the case of physical illness, the patient’s death is not even the half way mark for the carer’s experience.
My point is not to say that patients have it easy, but that both parties have their burdens to bear, and it is not necessary for every essay to cover both sides.
Edit: I see you have deleted your comment, which is a shame, I don’t think you should be afraid to express this sentiment.
Readit News
This just shouldn't be necessary. In 2023, we as a race should be able to figure out a better way to efficiently channel patients with needs towards clinical trials that might serve those needs.
(And I say this as someone who works in this industry.)
It feels like it's implying that humans today are fundamentally different from humans in the past. In fact it feels dangerous to me that we often speak of ourselves as almost a different species from humans in history. From an evolutionary perspective humans from any moment in recorded history are basically indistinguishable. Our brain capacity hasn't changed. We're not kinder. We're not less selfish.
We do know more about many things (and less about some things). We have better tools. We've refined more matter into new forms. We have access to more useful energy. But those changes don't change who people are.
No human at any point in history should be content with the state of things, but I don't think that struggle is easier today than it ever has been. We're pushing the boulder up the hill and we'll never reach the top, but should never stop pushing.
Being in the industry, I'm glad you're not content with the state of things. It takes people like you, so thank you for your effort to make our world a better place. Even if we may disagree with nuances of the motivation.
When people say this (myself included), I think it's a normative statement, not a positive one. Of course we're the same humans we have been for thousands of years. But the act of calling out our failings as a society can itself, sometimes, spur people to try to change it for the better.
In 2023, we are (positively) essentially the same as our ancestors. But also in 2023, we should (normatively) strive to be better than them, and to be conscious of our failings when we don't.
But is there any reason why people are excluded despite seeking out the trial runners, and have a terminal illness that their drug/procedure MIGHT help with?
I assume the chance it won’t work is legally dealt with for all trial patients, so I’m assuming that’s not the issue.
If they don’t fit the test profile, is there any risk to just simply acknowledging them as an outlier and letting them in anyway? You have one consistent cohort you’re studying, and a “who knows, maybe?” cohort of preliminary results from these Hail Mary folks. That seems useful, even if it lacks the sort of rigour of a group you selected.
He was great until blood clots caused more issues like taking morphine to calm smooth muscle to help him breathe. Morphine just that tiny pill caused terrible constipation (opioids are terrible).
My point being Dad would take anything just to feel even slightly better it meant he was still here. Death is terrifying and as long as you can limp along whatever makes it better is something people want. Really at that point you try to get to a point where you may just die in your sleep not knowing you did.
Why would you say something like this, especially given your dad's situation? yes they can cause constipation, but without opioids the pain would be much, much worse. To me it's a no-brainer, and nobody is forcing you to take opioids if you would rather the pain. I think opioids are a wonderful gift of nature to us and I'm immensely glad we have them. It terrifies me to think that we are so demonizing them now that they are withholding them from people who need them, and telling them to "take extra stength tylenol" instead. It's barbaric and cruel.
Because of that, I would rather trade those moments of watching me die in the most agonizing, painful way imaginable, for the better memories - the times before I got sick.
I watched my grandmother die, of cancer - there is nothing, literally nothing - that would allow me to put someone else thru that - at least not without their full consent, and making sure they knew of what was to come.
I guess I would try to figure out, based on the people around me, how I could make them happiest long term (which I think is the same thing you're saying)
Yes it's difficult to support someone in their last days, and it's never pretty, but it's not their fault. It also didn't make forget all the other years I had with my grandpa.
The end doesn't have to make you forget the rest.
Then there's the problem that some have a few of the people closest to them in one camp, fully accepting, and some in the other camp, which can be terrible (I've seen it especially with people I know where it's their parent who was dying, with different siblings going either way).
Just my experience and I don't discount that that same experience could have been traumatizing for someone else.
It's gut wrenching that I am just a CT scan away to being in the same (somewhat comparable) situation.
I shouldn't compare fates and still my mind wanders around the topic every time.
The facts they both present in a scientific manner (like remission rates) scare me to my bone. I cannot fathom what he and his loved ones are going through and that makes it even clearer what I have burdened on my wife, children and family.
I know this comment is ultimately me shouting "please let us both live" with many words and maybe this is me being a self serving asshole, maybe it is that. I don't know anymore.
I would love to offer the promise that everything is going to be alright but I cannot. I am just scared as hell and somehow I needed to get this out.
[^1]:"All", as opposed to just scientists and clinicians.
- How precise do you want the simulation? Do you want physical processes fully simulated? You'd need that to get an accurate simulation of molecular interactions, but full physical simulation is computationally expensive even for single, simple molecules.
- Even simplificated simulations are hard. Simulating just the shape of DNA strands is computationally very expensive (usually done with Monte Carlo simulations).
- How many cells do you simulate? The body has ~37 trillion cells. Even if it only took one processor cycle to simulate a cell, you'd need 9250 4GHz processors. That should give an idea of how hard it would be to simulate just an organ.
- How do you take into account interactions? There's a lot of difficulty in understanding how drugs affect the whole human system. Lots of trials show promising results against in-vitro cells and then fail spectacularly in animal models. There's a lot influencing how drugs work and single cellular processes are just a small part of it. The body is incredibly complex.
- How do you validate the models? It's not like we can go into a cell and see where the molecules are. We don't have enough visibility into actual cellular processes to build such complex models to a sufficient degree of accuracy.
Compared to even a single human cell, a monstruous language model is a trivial thing.
Five years ago, I would have said that we were further away from having a computer correctly interpret a joke (i.e., I would have agreed with [2]) than from simulating E.Coli. The thing is, people went and did (both) anyway. But they did one more than the other. Research effort and capital flowed, and now we have LLMs. IMO, a big reason for this paradox is that there is no stigma in wanting to make a computer smarter, and everybody started playing with computer code and data and due to the huge amount of effort, there have been results. But when it comes to the very things that keep us alive, we are not so eager to play with computer code. That, I think, has less to do with the complexity of the subject and more with a certain moral disposition...which is the thing I find perplexing.
[^1]: https://www.frontiersin.org/articles/10.3389/fchem.2023.1106...
[^2]: https://karpathy.github.io/2012/10/22/state-of-computer-visi...
https://nickbostrom.com/fable/dragon
I would emphatically suggest starting here: Read scientific papers. Read the academic literature.
Read. Know you can read.
And, please bear with me: Know that your doctors most probably do not read.
It sounds so paranoid or bitter. I haven’t found another way to put it into words.
If only for the fact that doctors are usually very busy people. Many of them are probably overworked.
And even among those doctors that do read, a doctor will not be able to view the literature from the urgent perspective of the individual. We are all specialists in ourselves, know the details of our lives, our family history.
It is possible for a layman to read academic literature. To the point that you can help the doctor help you. Don’t tell anyone you can’t read.
There is a severe disease in my close family. The doctors missed the diagnosis for years. Diagnosis happened through sheer luck, insistent advice from a nurse speaking “out of their place”, and our persistence. At diagnosis, biomarkers were so far out of range that it can be known that death would most probably have occurred within days.
After this, we read academic literature.
After this, we trust the doctor like we trust our parachute.
As proof that a layman can read academic literature to save their life and preserve their health:
After the diagnosis, papers we have read have clearly shown that a course of action ordered by a doctor is wrong, harmful, potentially life-threatening. Multiple times. Harmful prescriptions, or abject denial of severe side-effects known to occur in some people. We have had to step in and intercede. The crucial part: This has then been confirmed by another doctor’s opinion. Multiple times.
Relatedly, I am in a Facebook group for $condition, and I can’t tell you how many times I’ve seen people post that a doctor prescribed them $treatment. Although $treatment is a very common thing to give to healthy people, $treatment is KNOWN to potentially cause death in patients with $condition. The other patients in the group always jump in and alert the original poster to the danger, but I can’t believe it still happens week after week and year after year.
My point is that fully outsourcing your healthcare—even to specialists—is a very bad idea, especially if you might have a rare condition of any sort. No doctor will ever care about you/your family member the way that you do. And they are always so pressed for time that mistakes are to be expected.
Don’t tell anyone you can’t read.
→ should have been →
Don’t let anyone tell you you can’t read.
good luck, jake. may your days be filled with appreciation and love and tranquility.
My point is not to say that patients have it easy, but that both parties have their burdens to bear, and it is not necessary for every essay to cover both sides.
Edit: I see you have deleted your comment, which is a shame, I don’t think you should be afraid to express this sentiment.
https://jakeseliger.com