Cystic fibrosis breakthrough has given patients a chance to live longer(theatlantic.com)
theatlantic.com
Cystic fibrosis breakthrough has given patients a chance to live longer
https://www.theatlantic.com/magazine/archive/2024/04/cystic-fibrosis-trikafta-breakthrough-treatment/677471/
150 comments
One of the first friends I made in college was a friend with CF. I didn't know what CF was. He was very mature for our age and generally a very nice, happy, caring person. Got internships, studied with us. Went to bars with us but never drank because he couldn't. He had stories about how Make-a-Wish foundation has been dragging their feet not to give him his wish since his childhood.
He would take his enzymes, do the vibrating jacket treatment. He graduated and got a full time offer from a nice company. As he was relocating, he picked up some infection and passed away in a few weeks. None of us expected it. This was months before I heard of the approval of Trikafta.
He would take his enzymes, do the vibrating jacket treatment. He graduated and got a full time offer from a nice company. As he was relocating, he picked up some infection and passed away in a few weeks. None of us expected it. This was months before I heard of the approval of Trikafta.
My younger brother has CF and takes Trikafta and it's absolutely made all the difference in the world, it's wonderful to see. Watching all the years of research and CFF funding finally pay off is really something.
My personal situation is probably pretty unique, in that I have CF as well, but had a double lung tx many years ago. A couple years ago my transplant team (actually it may have been the CF people.. fuzzy memory) asked me if I was interested in getting on Trikafta and after thinking it over for about 30 seconds I told them I'd probably pass. It seemed like it wouldn't have any beneficial effect on my lungs, as they no longer "have CF", and that I assumed it would just make extra weight for my decently healthy but still under par lungs to have to drag around. They didn't disagree.
My personal situation is probably pretty unique, in that I have CF as well, but had a double lung tx many years ago. A couple years ago my transplant team (actually it may have been the CF people.. fuzzy memory) asked me if I was interested in getting on Trikafta and after thinking it over for about 30 seconds I told them I'd probably pass. It seemed like it wouldn't have any beneficial effect on my lungs, as they no longer "have CF", and that I assumed it would just make extra weight for my decently healthy but still under par lungs to have to drag around. They didn't disagree.
Yes but CF affects all liquids in your whole body. You can get diffuse long term damage anywhere and everywhere in your body. Having to eat calorie amounts like someone without CF sounds like a good tradeoff in order to not risk this damage.
Yeah and it'd help my sinuses too but at my age I'm used to taking the enzymes when I eat and they work well enough. Long term damage is basically my personality at this point, lol.
I'm in a similar situation so it's funny to see someone else here with the same. I had my transplant in 1988. There's also Steve Rasmussen (you can google him) who AFAIK also does not take Trikafta.
Sorry for the potentially insensitive question, but I really am wondering about this:
>One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.
I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?
>One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.
I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?
Just an anecdote.
My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us).
He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke.
He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.
My best friend died of CF just a few years ago. He talked candidly about his eventual death, to the extent it was uncomfortable at first (but we ended up being to the level of making jokes about it, which I think was a positive thing for both of us).
He changed his WhatsApp status to a coffin and skull-and-bones emoji right before he went, just as a joke.
He didn't live with a shred of anxiety - least anxious person I've ever met. Dude was down for anything and everything, and could have probably fought off a bear despite being comically short and concerningly skinny. Easily one of the most kind and relaxed souls I've ever met.
Most of us, especially adults, are pretty much settled in with the state of our condition - we've had it our entire lives. Anecdotal, but many CF patients (including in online communities I'm a part of) have reported a lot of increased anxiety.
> I would have imagined that most people with CF already had extreme anxiety - wondering when the infection that is going to end one's life will arrive. Is it really possible that Trikafta is causing noticeably worse anxiety?
There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal.
So it seems to be a bit of an open question and I'm sure an emotional one on both sides.
There's a discussion of this in the article. Essentially, a bunch of people have said that they started experiencing extreme anxiety when they started Trikafta, and that stopping or lowering the dose helped immensely. However, clinicians have said that there's no actual evidence that the Trikafta is causal.
So it seems to be a bit of an open question and I'm sure an emotional one on both sides.
Clinicians are always a day late and a dollar short. The evidence comes from these people reporting. These clinicians need a 50 million dollar grant to get that proof.
If you've ever had to organise a scientific study you'll understand why. Privacy and ethics are important but they make recruitment of a large and representative sample for any medical study a nightmare. First you'll need to run your protocol past an ethics board and do back and forth until it's agreed. Once you have that done you'll send out an invite (often blind) in hopes of getting people who fit your study aims and you will get who you get. There are often costs associated with this.
So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses.
Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion.
tldr; medical and scientific studies are hard if you want them to actually have any validity.
So now you have some willing participants you have to screen your initial group to filter it down to people who actually meet your recruiting criteria and consent them for your study. Finally you actually get to gather your data, if you need people to come in for sampling and have to cover their expenses.
Next you'll look at your data and realise there's some confounding effect which reduces your powers to infer anything (e.g. somehow you overrecruited a particular group and they turn out to do something which correlates with the thing you're studying). You'll cry a little and realise you need to recruit more people to have any statistical power to draw a conclusion.
tldr; medical and scientific studies are hard if you want them to actually have any validity.
It seems like we really need to move forward to 'indefinite/active studies'. I believe some researchers are trying to get onto this pattern but of course there are major privacy/quality of care concerns.
By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).
By 'indefinite/active studies' I mean that the studies never stop - data just keeps going back into the system as a flywheel of the drug distribution process. I take a second-generation drug for CML (leukemia) and none of my health data goes back into research unless my doctor decides to elevate my data into a paper or something (which I don't think has happened yet).
These kind of platform trials are getting more common luckily! Famous example is the COVID Recovery trial.
wouldn't this side-effect become visible in Phase4 data? (and there should be at least some hints of this in the previous ones)
so, what I'm trying to say is that for this particular drug we "just need to wait", no?
so, what I'm trying to say is that for this particular drug we "just need to wait", no?
(I left a previous comment as a similar sufferer of a lifelong genetic disease that was cured by a breakthrough medicine: https://news.ycombinator.com/item?id=37541222)
Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before.
A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.
Funnily enough, although in practical terms my life is infinitely better than it was before the drug in, I would rate my anxiety as higher than it was before.
A lot more options open in the world, a lot more to hope/pine for, a lot more to lose. Back in the days when my expected future was to just hang out in bed, there wasn't much else to do than to just chill and read a book.
Just an anecdotal experience so doesn't necessarily mean anything but the only person I knew that had CF had absolutely no anxiety from his condition.
If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.
If anything he was a very mature guy for his age, having realized he has limited time but of course I wouldn't know the internal struggles he might have kept from us.
People generally get acclimated to the situation they are in.
If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.
If you have anxiety over money, for instance, you'd probably still have it, regardless of whether you had $15,000 in your bank account, or $15,000,000.
I grew up with a lot of money insecurity, was homeless for a while and started my career with nothing - one change of clothes and a floor to sleep on. I’ve since done very well for myself and have a considerable amount of net worth at this point and a lucrative forward for as long as I want to keep working at it.
I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had.
That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.
I’ve lost most of my money anxiety, but it took a lot of purposeful work inside myself to achieve that including years of daily meditation and intentional study of Buddhism. Before that my money anxiety was unbearable. It didn’t matter how little or how much I had, because it wasn’t about money in truth. It was a fear of losing control and other things like self worth and identity issues as a result of my earlier life. As I learned to let go of the self and my identity and live life as it is rather than what I’m afraid it might be I’ve lost my fears, not just about money but all of them. In my experience lack of money instigated my anxieties but once they started it didn’t matter how little or much I had.
That said it drove me to get more and more, and I enjoy having more than when I had none. But even if I lost it all I would be ok now.
That's interesting - does your career require any formal education? Or were you able to develop some crucial skill on your own? Can you share what is your career about and where you started and where are you now? For example - do you hire employees or are you a landlord now, or are you an employee?
No, I’m a software engineer. I barely graduated high school because I was too busy smoking pot and programming at a time when you needed a degree to get a good job so didn’t have much opportunities despite being pretty skilled at programming. I got a job at Netscape tho as one of the first tech companies that didn’t look at credentials before skill. I did well there and did my own companies. But before I had nothing and move to California with $5 and a change of clothes, slept on the floor of someone I randomly met on irc (I was lucky it didn’t turn out worse than it did don’t try this at home!) until I found a job. Anyway, after Netscape and my startups I became a quant on Wall Street, finished my cs degree, and have had a successful career since. Now I’m the top IC at a late stage startup.
I don't really see how you become a quant on Wall Street before you finish the CS degree, they I think look at credentials a lot, can you at least give the name of the prop shop that hired you without a formal education? Did you have any good results in algorithmic competitions or math competitions in high school? And how did you learn programming without an actual computer? Did your parents buy you a computer when you were young?
A lot of quants didn’t go to college. On my team at a top trading desk at a top bank we had about 15 people, 4 of which never went to college. I actually got an internship due to a person on the desk having worked for me prior and went full time then finished my degree, so was already in school. But many folks took an alternate route. They were usually well experienced when they were hired. But in an arms race where what you can do is more important than nominal credentials a degree simply makes it easier.
No, I was a total loser in high school. I barely graduated and had awful test scores and did no extracurricular activities other than smoke pot.
My grandparents bought me a computer when I was young, I think because my mom saw how much I was interested in them. It was a c64, but had no storage devices so I had to type in programs from scratch each time which was a tall order for a 6yo, but I did it anyway. At some point someone gave me a 486dx2 board that was an extra and I built my first Linux box running 0.96. My schools also had an internet connection and I could get dialup access to some sunos boxes and some NeXT boxes in the library when I was in high school. One of my greatest wishes growing up was to have enough money to have the best monitor since my monitors were always garbage. My house now has nice TVs and monitors everywhere LOL, but they’ll never hold a candle to my first VGA monochrome monitor I delivered papers for a year to buy.
No, I was a total loser in high school. I barely graduated and had awful test scores and did no extracurricular activities other than smoke pot.
My grandparents bought me a computer when I was young, I think because my mom saw how much I was interested in them. It was a c64, but had no storage devices so I had to type in programs from scratch each time which was a tall order for a 6yo, but I did it anyway. At some point someone gave me a 486dx2 board that was an extra and I built my first Linux box running 0.96. My schools also had an internet connection and I could get dialup access to some sunos boxes and some NeXT boxes in the library when I was in high school. One of my greatest wishes growing up was to have enough money to have the best monitor since my monitors were always garbage. My house now has nice TVs and monitors everywhere LOL, but they’ll never hold a candle to my first VGA monochrome monitor I delivered papers for a year to buy.
early 2000s was a different time also. nerd career paths hadn’t yet become prestigious and formalized.
there were no middle schoolers optimizing their resumes for how to get a Jane Street internship in 8 years bc Jane Street was only a few years old. same for a lot of other firms.
there were no middle schoolers optimizing their resumes for how to get a Jane Street internship in 8 years bc Jane Street was only a few years old. same for a lot of other firms.
It really started around 1994 with Netscape and then the dotcom cultural mindset that valued ability over credentials.
Also at that time, as you say, there wasn’t a broad cultural awareness of the money to be made in quantitative fields. In fact this was the era of Revenge Of the Nerds movies and glorification of the idiot jock getting a business degree and the passionate nerd being the butt of the joke. You really only went my route if you were a total fuck up loser. Now the social view of things has completely pivoted.
I would say interestingly the middle school kids optimizing their resume only make it so far in industry. They’re never really passionate about what they’re doing they’re just laddering. At some point they shift to management or product or something. At the top firms though the people who really make the money and whose opinion has ultimate power are the fuck up losers who live and breathe their passion and would do it for free if that’s all there was.
Also at that time, as you say, there wasn’t a broad cultural awareness of the money to be made in quantitative fields. In fact this was the era of Revenge Of the Nerds movies and glorification of the idiot jock getting a business degree and the passionate nerd being the butt of the joke. You really only went my route if you were a total fuck up loser. Now the social view of things has completely pivoted.
I would say interestingly the middle school kids optimizing their resume only make it so far in industry. They’re never really passionate about what they’re doing they’re just laddering. At some point they shift to management or product or something. At the top firms though the people who really make the money and whose opinion has ultimate power are the fuck up losers who live and breathe their passion and would do it for free if that’s all there was.
Some shops care more than others. Going to a target school also matters a lot more for interns/new grads than for more experienced hires.
How do you practice for becoming a quant outside of the academic system?
You do things because you love it and couldn’t do anything other than that. You build and study not because you want a job but because when you wake up in the morning everything else you have to do is a chore and the reason you live is to learn and see things work. If that’s who you are, you will struggle with the chores of life like shelter and food for a while but you’ll learn and do so much of value people can’t ignore it.
Ok, so how do you practice in practice? What specific actions do you do to make yourself more attractive to prop shops?
You might even have more with 15M! It’s much harder to replace if you lose it.
On the subject of correlation/causation, I once took a drug called Accutane to cure my teenage acne. Listed side effects included: "Mental health issues depression, psychosis, aggressive behaviour and suicide ideation and attempts"
Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects.
However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem.
For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge.
So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.
Accutane was the best medicine I ever took. It resolved my acne (permanently) in a matter of weeks. I felt elated afterwards and never experienced mental side effects.
However, prior to the drug, I'd experienced several of the listed side effects, due to the acne itself and its devasting effect on my self-esteem.
For many teenagers suffering from serious acne, they'd also have mental side effects due to the skin disorder, meaning there would be a strong correlation between Accutane use and people suffering mental episodes. And if the wonder drug didn't cure the acne, as promised, I can imagine that failure might push some acne sufferers over the edge.
So, Accutane itself could be harmless, but the circumstances of its use might suggest causal link to mental side effects which are not causal at all.
Yeah a lot of the side effects you listed sound a bit like they could be within normal expectations for teenagers, or just slightly heightened. Reminds me of an SSRI that happened to also massively reduce caffeine metabolisation without anyone noticing, and loads of the known side effects were really just effects of caffeine overdose – insomnia, jitters, headaches, etc.
It takes a lot including many suicides to get that side effect listed. You are lucky it didn't reach that point for you. With a little more time or repeated usage it probably would have got you as well.
weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame
This seems like a no-brainer way to treat obesity, by restricting or blocking such enzymes. Obviously the downside is diarrhea and other malabsorption symptoms, but obese people have too much nutrition. Blocking absorption seems easier than dieting, as no willpower required. You shit out the undigested food.
This seems like a no-brainer way to treat obesity, by restricting or blocking such enzymes. Obviously the downside is diarrhea and other malabsorption symptoms, but obese people have too much nutrition. Blocking absorption seems easier than dieting, as no willpower required. You shit out the undigested food.
They sort of tried this in the '90s — not in the form of suppressing the required enzymes for nutrient absorption, but rather in the form of diet foods that contained inherently non-absorbable nutrients. The downsides were basically the same — the non-absorbed nutrients had to come out. People didn't generally respond well to these products. See e.g. https://web.archive.org/web/20060113084223/http://www.zug.co...
Olestra! I ate a whole bag of the Lay’s with Olean as a kid. They had the audacity to say that they assumed that people would only eat a handful at a time. Of near zero calorie potato chips that taste like potato chips…
Orlistat. Look at Alli — very available to buy. A very common side effect is steatorrhea. Oily leakage/poops. But not like, “oops I gotta run to the bathroom” but like, a tiny bear down and oil shoots out your bum. There is a clear warning on it about malabsorption as well of fat soluble vitamins.
Having taken orlistat in low/intermittent doses, I can say it really matters what you eat fatty stuff with, on top of quantity. A regular "balanced" low-mid fat diet, and you're (well, I've been) okay.
If you eat a tub of ice cream as dinner, you're going to have a bad time.
If you eat a tub of ice cream as dinner, you're going to have a bad time.
Appetite suppression/regulation seems like a much better route to pursue than intentionally inducing malabsorption.
I've played with my enzyme dosage, and there are a lot of unpleasant side effects as you've mentioned. Overall, the best approach has been what everyone else has to do: watch carbs and sugar, reasonable exercise, etc.
I had a close family friend (many decades older than me) lose his young daughter to CF back in the 60s or 70s. He and his family helped run the CF walk each year in their area and I'm sure made some major donations to research regarding it.
Hearing about any kind of advancement is huge. I can't even begin to understand what you've gone through, but am so happy to hear there is a new medicine to help with such a cruel disease and that it's made a world of difference to you. Sometimes it feels like medical science is still in the dark ages and I get saddened that we haven't got flying cars or Dr. Beverly Crusher can't wave some device over me and fix all the ailments I now have. Other days I hear about these kinds of advancements and it makes me smile!
Hearing about any kind of advancement is huge. I can't even begin to understand what you've gone through, but am so happy to hear there is a new medicine to help with such a cruel disease and that it's made a world of difference to you. Sometimes it feels like medical science is still in the dark ages and I get saddened that we haven't got flying cars or Dr. Beverly Crusher can't wave some device over me and fix all the ailments I now have. Other days I hear about these kinds of advancements and it makes me smile!
Reading your comment, I was certain I remembered it - and I see that you've now added a link to its previous home.
So I just wanted to say: it was an impactful piece of writing, enough so that I remembered it quite clearly after a single read these few months ago.
So I just wanted to say: it was an impactful piece of writing, enough so that I remembered it quite clearly after a single read these few months ago.
Thank you. My aim isn't to wax poetic or elicit sympathy, but to provide insight for others.
> The only real downside: weight gain.
Interesting. I'm an uncle to a family member with CF (and I'm a carrier) and one of their long battles has actually been weight. To the point of doing things like downing olive oil to try and keep up the weight. They've eventually had to take the fairly drastic measure of getting a feeding tube installed. Getting enough calories in just hasn't been possible until the feeding tube.
Interesting. I'm an uncle to a family member with CF (and I'm a carrier) and one of their long battles has actually been weight. To the point of doing things like downing olive oil to try and keep up the weight. They've eventually had to take the fairly drastic measure of getting a feeding tube installed. Getting enough calories in just hasn't been possible until the feeding tube.
Yeah, it's been quite a shock trying to reverse the first 40+ years of my life where I was told to eat eat eat. Not just for the weight, which is really a vanity thing, but also to counteract the diabetes that most with CF develop, since that can directly impact overall health and the ability to fight off infection.
Can you elaborate on the weight gain? I'm curious why that is a downside of the Trikafta? You say with CF the pancreas is blocked, so why did the weight come as a side-effect of the drug, and not with the disease initially?
Med student here. My guess is the following:
So with CF your pancreas can’t secrete many of the enzymes that are necessary to actually digest food. You can take medications to help with that digestion, but regardless, you aren’t actually getting all the calories in your food with CF because it isn’t making its way into your body (notably patients with CF have steatorrhea which is fat in their stool because they can’t absorb a lot of fat from their foods like a non-CF patient). The med helps the pancreas recover some of its ability to secrete digestive enzymes and so patients can now eat and get more from their food. The issue is that there needs to be a recalibration in terms of how much patients are eating. Previously a 2000 calorie diet may not have gotten them so far because they didn’t absorb much of it, but now they’re absorbing a lot more of it. Plus increased work of breathing with CF expends more calories compared to a non-CF patient (and patients on this drug).
This is exactly right.
Source: have CF.
Source: have CF.
Some of the blockage of the pancreas is due to scarring, some of it to thick mucus. The scarring can't be undone, but with a reduction of mucus blockage, food may be digested better. That said, I think that there's other causes, given how fast most who start Trikafta gain weight.
Assuming your anxiety medication is an SSRI or similar, your weight gain could be attributed to this as it’s been observed in people who take these medications.
Oh wow. I remember a kid in elementary school with CF. I didn't understand at the time what he and his family was going through. I remember his personality and intelligence, his skill on the soccer team. He was unusually driven for an 8-9 year old.
As I got older and into my 20s, I thought about him a lot -- it was understood that most CF patients don't make it out of their early 20s and I knew even if he were particularly lucky, as time went on and I aged, he was probably gone.
My father also recently died from lung cancer, and had a few months where he was effectively drowning in his own lung fluids, requiring doctors to drain his lungs with long needles through his back. That experience also brought me back to that schoolmate, considering what he had had to endure.
Recently, I was reorganizing my personal library and came across my elementary school yearbook and flipping through, saw his picture. It's been decades since he's likely passed on. It gave me pause to contemplate certain priorities in my life and try to cultivate greater compassion.
It's a particularly cruel disease, and this news is wonderful.
As I got older and into my 20s, I thought about him a lot -- it was understood that most CF patients don't make it out of their early 20s and I knew even if he were particularly lucky, as time went on and I aged, he was probably gone.
My father also recently died from lung cancer, and had a few months where he was effectively drowning in his own lung fluids, requiring doctors to drain his lungs with long needles through his back. That experience also brought me back to that schoolmate, considering what he had had to endure.
Recently, I was reorganizing my personal library and came across my elementary school yearbook and flipping through, saw his picture. It's been decades since he's likely passed on. It gave me pause to contemplate certain priorities in my life and try to cultivate greater compassion.
It's a particularly cruel disease, and this news is wonderful.
My brother passed about a decade ago from complications from a double lung transplant, which he needed because of CF.
It seems like something every day reminds me of him. I’m really glad there’s hope for people with it. It’s a particularly shitty disease and he was the nicest most thoughtful person I’ve ever known. I miss him dearly.
Bittersweet. Glad there’s progress, wish it were earlier.
It seems like something every day reminds me of him. I’m really glad there’s hope for people with it. It’s a particularly shitty disease and he was the nicest most thoughtful person I’ve ever known. I miss him dearly.
Bittersweet. Glad there’s progress, wish it were earlier.
Those were wonderful words and moved me a lot.
Have you tried looking him up? He could still be alive.
This article gives short shrift to the role the pharmaceutical industry played in making this life-changing treatment a reality. It barely mentions Vertex. Vertex is the biotech company that made the big bet on cystic fibrosis, a rare disease that most companies wouldn’t touch because of the small market and unknown biology made it too risky. They were the ones that believed in the science and developed multiple CF drugs and got them into the hands of patients. Here’s a 2019 STAT article that gives a fuller account of Vertex’s role:
https://www.statnews.com/2019/10/23/we-conquered-a-disease-h...
https://www.statnews.com/2019/10/23/we-conquered-a-disease-h...
Yes, the CFF has partnered with companies like Vertex to take an almost VC-like approach towards developing new drugs (Trikafta being one of many similar drugs they've developed with Vertex)
Thanks for this. Very cool to read these types of stories.
Trikafta is a real breakthrough for CF patients. What's not mentioned is the cost - about $300 000 per person per year. [1]
In 2037 the patent will run out, and the generic price will likely be 90% less.
Fortunately, for Americans with good-enough health insurance, it's covered, so ... yay? For those without insurance, or in other countries where $300k is basically unaffordable, well bummer for you, you'll be the last generation to die of it.
I get the insane costs, and risks, of developing these things. I get that the profit motive is what drives there to be any research at all in pharma. I get that the price has to be high for everyone, or insurance companies will balk.
And yet, even knowing all that, there's a sour taste when we -could- (literally) save lives, but, well, money first ya-know...
I don't have an answer to this issue- there are downsides to all proposals I've heard. But this approach seems, well, pretty harsh.
[1] https://www.statnews.com/2023/11/03/trikafta-cystic-fibrosis....
In 2037 the patent will run out, and the generic price will likely be 90% less.
Fortunately, for Americans with good-enough health insurance, it's covered, so ... yay? For those without insurance, or in other countries where $300k is basically unaffordable, well bummer for you, you'll be the last generation to die of it.
I get the insane costs, and risks, of developing these things. I get that the profit motive is what drives there to be any research at all in pharma. I get that the price has to be high for everyone, or insurance companies will balk.
And yet, even knowing all that, there's a sour taste when we -could- (literally) save lives, but, well, money first ya-know...
I don't have an answer to this issue- there are downsides to all proposals I've heard. But this approach seems, well, pretty harsh.
[1] https://www.statnews.com/2023/11/03/trikafta-cystic-fibrosis....
"In 2037 the patent will run out, and the generic price will likely be 90% less."
Unfortunately, that's not guaranteed to bring a price drop. Humira is a good example of that; it recently went generic but much of the savings went to higher rebates to pharmacy benefits managers.
Some reading for anyone curious:
https://www.reuters.com/business/healthcare-pharmaceuticals/...
Unfortunately, that's not guaranteed to bring a price drop. Humira is a good example of that; it recently went generic but much of the savings went to higher rebates to pharmacy benefits managers.
Some reading for anyone curious:
https://www.reuters.com/business/healthcare-pharmaceuticals/...
You're talking apples and oranges...
Humira is a monoclonal antibody (a biologic drug), not a small molecule. Biologics require cell culture systems and a completely different manufacturing process than small molecules, and are very complex drugs. The "generics" (called biosimilars) aren't significantly cheaper because they're simply very expensive to manufacture at scale. Humira or its "generics/biosimilars" will never be cheap. It's physically impossible with today's bio processing technology.
Trikafta is a mix of three small molecules, which are manufactured in large chemical batches and are the more traditional class of drugs. Many even have total synthesis pathways known which means you can basically make them by the train car scale for cheap.
When the patent on Trikafta runs out, it'll be very cheap.
I'll note that vanishingly few patients ever pay the full list price in the US--if you have insurance, the copay is small.
Your insurance pays (as they should, that's why you pay them premiums!). The company even pays the co-pay in most cases so the actual cost to patients in many cases is $0.
If you truly need it and don't have insurance, the company provides it for basically free with a patient assistance program, it's there on their website.
Kudos to the scientists who invented this, I don't feel bad for the insurance companies really, they charge their premiums and it's their responsibility to the policyholders to pay the applicable fees for care.
*edit: typo
Humira is a monoclonal antibody (a biologic drug), not a small molecule. Biologics require cell culture systems and a completely different manufacturing process than small molecules, and are very complex drugs. The "generics" (called biosimilars) aren't significantly cheaper because they're simply very expensive to manufacture at scale. Humira or its "generics/biosimilars" will never be cheap. It's physically impossible with today's bio processing technology.
Trikafta is a mix of three small molecules, which are manufactured in large chemical batches and are the more traditional class of drugs. Many even have total synthesis pathways known which means you can basically make them by the train car scale for cheap.
When the patent on Trikafta runs out, it'll be very cheap.
I'll note that vanishingly few patients ever pay the full list price in the US--if you have insurance, the copay is small.
Your insurance pays (as they should, that's why you pay them premiums!). The company even pays the co-pay in most cases so the actual cost to patients in many cases is $0.
If you truly need it and don't have insurance, the company provides it for basically free with a patient assistance program, it's there on their website.
Kudos to the scientists who invented this, I don't feel bad for the insurance companies really, they charge their premiums and it's their responsibility to the policyholders to pay the applicable fees for care.
*edit: typo
What I like to say about pharma, especially small-molecule, is that the first dose costs $billions, and the rest a few cents.
Humira's biosimilars are roughly 20% of the cost of name-brand Humira ($600/mo). It can even be down to 10% of the original cost, or lower, in some shops. You can buy a month's supply for ~75 from an Indian pharam supplier online, for example. The slight kicker is that the biosimilars are not 100% the same (fat) molecule as the original adalimumab.
Insurance companies are starting to say they wont cover name-brand Humira without a strong doctor's note.
Still, the price of the drug went down from being completely unaffordable without insurance to the price of an car payment. It's still expensive, but much better than before. You're not as tied to your company providing good insurance, for example.
Insurance companies are starting to say they wont cover name-brand Humira without a strong doctor's note.
Still, the price of the drug went down from being completely unaffordable without insurance to the price of an car payment. It's still expensive, but much better than before. You're not as tied to your company providing good insurance, for example.
Oops: Humira ($600/mo) -> Humira ($6000/mo)
I don't feel bad for the insurance companies either, but it is the case that they get their money from the people they cover, expensive treatments will drive up overall premiums.
Vertex is very good about providing programs to put it in the hands of those who need it. I have great insurance and a great income, and they even apply deductible assistance to me.
In the online CF communities I'm a part of, I've never heard of anyone who couldn't get access to the medication (aside from the country they're in not approving it) (I'm in the US so my perspective is probably skewed)
In the online CF communities I'm a part of, I've never heard of anyone who couldn't get access to the medication (aside from the country they're in not approving it) (I'm in the US so my perspective is probably skewed)
drugs are priced differently country to country and the price has nothing to do with the unit cost to manufacture. The US is the least regulated pharmaceuticals market in the world and drugs here usually cost significantly more than drugs in other locals. For example semaglutide/ozempic costs like 1300/month in the US, but only 100-200/month in European countries. Also, the "1300/month" cost in the US is only paid by people who are paying cash and not covered by insurance, if the drug is covered by the patients insurance than the Pharmacy benefits manager usually pays a fraction of the 1300/month price as it is a "bulk negotiated discount, so they often pay 200-300 USD, the actuall price in these deals is a closely guarded trade secret.
So note that although Semaglutide/Ozempic cost that amount retail, most are absolutely not paying that price.
https://glp1.guide/content/glp1-pricing-2024-02
Of course, insurers are struggling to not cover the bill, and although it's in the medicaid list it's up to states to choose whether to cover it or not
https://glp1.guide/content/glp1-pricing-2024-02
Of course, insurers are struggling to not cover the bill, and although it's in the medicaid list it's up to states to choose whether to cover it or not
I've seen conversations like this before, regarding the heavy cost that Big Pharma levies on treatments for major diseases. And US companies frequently come up in these discussions.
But the alternative, without the massive cashflows, is a world where the research never happens, and the diseases haunt us forever.
The Big Pharma treatments will eventually become public domain, and may inspire other cheaper treatments prior to that.
The fact that these conversations come up frequently is a symptom of the fact that Big Pharma is frequently doing fantastic things. Curing diseases that have plagued humanity for millenia and killed millions.
We have a very bright future. But the future is not free of charge, as we'll continue to require a lot of medical research, and medical researchers have families to feed, like the rest of us. Medicine costs money - there's no escaping it.
In the UK, we sometimes mistakenly imagine that our socialised healthcare system is "free." It's not. It's one of the most expensive in the world, and employs over 2 million people. The component of tax that I paid to fund the National Health Service was £8919 last year - the largest single expenditure of my taxes, and vastly more than I'd need to spend to get private healthcare.
So while American medical pricing is scary and sometimes ruthless, I think we need to put things in perspective and recognise their leadership in medical research - without which, we'd all be in a worse situation.
But the alternative, without the massive cashflows, is a world where the research never happens, and the diseases haunt us forever.
The Big Pharma treatments will eventually become public domain, and may inspire other cheaper treatments prior to that.
The fact that these conversations come up frequently is a symptom of the fact that Big Pharma is frequently doing fantastic things. Curing diseases that have plagued humanity for millenia and killed millions.
We have a very bright future. But the future is not free of charge, as we'll continue to require a lot of medical research, and medical researchers have families to feed, like the rest of us. Medicine costs money - there's no escaping it.
In the UK, we sometimes mistakenly imagine that our socialised healthcare system is "free." It's not. It's one of the most expensive in the world, and employs over 2 million people. The component of tax that I paid to fund the National Health Service was £8919 last year - the largest single expenditure of my taxes, and vastly more than I'd need to spend to get private healthcare.
So while American medical pricing is scary and sometimes ruthless, I think we need to put things in perspective and recognise their leadership in medical research - without which, we'd all be in a worse situation.
What about direct government funding? Isn't that a reasonable alternative? Maybe not a politically-popular one, but I wouldn't be surprised if health care overall would be cheaper under a system where pharma research is done with public money, and then isn't allowed to be patented. Might even in save enough money to avoid much in the way of extra taxes to fund it.
Hell, a lot of medical research is funded (in part) by public dollars, and then the results get locked up behind patents for years, which is gross.
Hell, a lot of medical research is funded (in part) by public dollars, and then the results get locked up behind patents for years, which is gross.
Having the government direct funds and choose winners and losers seems a lot more dangerous than leaving it to free market forces.
It's easier to corrupt one or two government officials than it is the entire international capital marketplace.
It's easier to corrupt one or two government officials than it is the entire international capital marketplace.
Most taxpayers don't have cystic fibrosis and hence don't want to pay to have it cured. Not feasible. This hypothetical is kind of lame.
The U.S. government already funds a lot of research including some on conditions (or non-medical problems) that don’t affect the majority so that doesn’t seem to be an actual barrier. Polls tend to show Americans support existing funding [0].
Obviously there is a limit to how much spending the public will support, but I don’t think it’s a complete nonstarter.
[0]: https://www.pewresearch.org/short-reads/2018/07/03/americans...
Obviously there is a limit to how much spending the public will support, but I don’t think it’s a complete nonstarter.
[0]: https://www.pewresearch.org/short-reads/2018/07/03/americans...
I love this reply.
It's a particularly touchy subject because it involves people's health and the ability/inability to pay for it.
But as a sufferer of a debilitating disease with a miracle drug that costs an arm and a leg, I've become a convert to the US pharma-industrial complex. These drugs take billions of dollars and decades to research--that funding/development isn't going to happen without venture capitalists who shoulder that risk for the profit reward. An equal number of pharma venture capitalists lose all their money, researching dead-end drugs.
I'm incredibly blessed to have both a cure invented during my lifetime and the means to pay for it. But even if I lacked the means, I would still infinitely prefer a world where a cure exists that I need to somehow access, as opposed to a hopeless world with no cure.
It's a particularly touchy subject because it involves people's health and the ability/inability to pay for it.
But as a sufferer of a debilitating disease with a miracle drug that costs an arm and a leg, I've become a convert to the US pharma-industrial complex. These drugs take billions of dollars and decades to research--that funding/development isn't going to happen without venture capitalists who shoulder that risk for the profit reward. An equal number of pharma venture capitalists lose all their money, researching dead-end drugs.
I'm incredibly blessed to have both a cure invented during my lifetime and the means to pay for it. But even if I lacked the means, I would still infinitely prefer a world where a cure exists that I need to somehow access, as opposed to a hopeless world with no cure.
It feels like there's a lack of imagination here. Could you conceive of a world that was successful in its research of drugs, but was propped up by an economic model other than pharma venture capitalism?
Freedom of choice means you have the right to try to create such a system. As other people can try what they want, VC funding, astrology, etc. It's all legal and competes.
But, if someone is selling a system which doesn't exist yet, but is supposed to be better, but that will only work if we also shut off the one working system first, before knowing... well, I'm skeptical.
But, if someone is selling a system which doesn't exist yet, but is supposed to be better, but that will only work if we also shut off the one working system first, before knowing... well, I'm skeptical.
In many other countries, patents do not apply to personal use, where there is no sale.
Since Trikafta is a blend of 3 small-molecule drugs, is it possibly feasible to publish a do-it-yourself synthesis process?
Or perhaps the community could even come together to set up a lab, where individuals could travel and go through the motions to produce their own?
I recognize this isn't ideal, but it might be legal...
Since Trikafta is a blend of 3 small-molecule drugs, is it possibly feasible to publish a do-it-yourself synthesis process?
Or perhaps the community could even come together to set up a lab, where individuals could travel and go through the motions to produce their own?
I recognize this isn't ideal, but it might be legal...
If you’re going to do all that why bother with legality, just push pills on a black market.
Yeah.
In all seriousness, you can buy the APIs directly from China/India and compound them yourself. It's easy and dirt cheap, in most cases. This is typically how underground steroid labs and other illicit pharmacies work. It's in some cases how legitimate compounding pharmacies work.
So how do you know what you're getting is pure, or even real? Simple, before shipping it to the US, you send it over to an analytical lab in China and have them run GC/MS or LC/MS on the chemical raw material. Since it's supposedly a pure compound, that should be easy, and there's very rarely any ambiguity as to the results. This also ensures that you're not inadvertently importing anything on the DEA's scheduled list.
In all seriousness, you can buy the APIs directly from China/India and compound them yourself. It's easy and dirt cheap, in most cases. This is typically how underground steroid labs and other illicit pharmacies work. It's in some cases how legitimate compounding pharmacies work.
So how do you know what you're getting is pure, or even real? Simple, before shipping it to the US, you send it over to an analytical lab in China and have them run GC/MS or LC/MS on the chemical raw material. Since it's supposedly a pure compound, that should be easy, and there's very rarely any ambiguity as to the results. This also ensures that you're not inadvertently importing anything on the DEA's scheduled list.
This feels very Dallas Buyer's Club.
I assume communities exist on the Internet for this kind of "drug piracy"?
I assume communities exist on the Internet for this kind of "drug piracy"?
Yeah, IRL too. 5-10 years ago there were some biohacking collectives around the Bay Area that did everything from pharmaceuticals to experiments with CRISPR. I don't know if they're still around -- I left that scene when I left the USA a few years ago -- but if you're in the area you might want to give it a look. (As an aside, I heard that a few scene-adjacent people have recently gotten gene-mod therapy; Patri Friedman, for instance, received follistatin therapy.)
Nootropics were a pretty popular trend around the same time, and I knew a lot of guys who would import weird drugs and peptides from Russia and China. It's the same sort of procedure I outlined in my last post, in that you're ordering drugs or drug-active-ingredient-powder from abroad... And then hopefully testing it.
Roughly 10 years ago, when [redacted breakthrough drug] was released, I helped some friends set up a pirate pharmacy. Those were good times.
Nootropics were a pretty popular trend around the same time, and I knew a lot of guys who would import weird drugs and peptides from Russia and China. It's the same sort of procedure I outlined in my last post, in that you're ordering drugs or drug-active-ingredient-powder from abroad... And then hopefully testing it.
Roughly 10 years ago, when [redacted breakthrough drug] was released, I helped some friends set up a pirate pharmacy. Those were good times.
That's really cool. I don't have a bio/pharma technical background but I'm very sympathetic to the scene and the ethos so I'll have to check it out.
[deleted]
It is mentioned. Quoting directly from this piece...
> Or stopped being covered by insurance? Trikafta’s sticker price is more than $300,000 a year. Insurance typically covers most of that cost—minus what can be significant co-pays and deductibles—and Vertex offers co-pay assistance. But patients’ lives ultimately depend on decisions made by nameless bureaucrats in rooms far away: Insurance plans can suddenly change what they cover, and in 2022, Vertex announced that it would substantially reduce its financial assistance.
> Or stopped being covered by insurance? Trikafta’s sticker price is more than $300,000 a year. Insurance typically covers most of that cost—minus what can be significant co-pays and deductibles—and Vertex offers co-pay assistance. But patients’ lives ultimately depend on decisions made by nameless bureaucrats in rooms far away: Insurance plans can suddenly change what they cover, and in 2022, Vertex announced that it would substantially reduce its financial assistance.
I suspect very strongly at 300k a year, its still cheaper than treating CF via existing means.
Yes, I (CF patient) just had a one-week hospital stay, and right now the (retail) price of that vacation is around $100k the last time I looked at all of the bills. (fortunately I have amazing insurance)
When I saw you mention multiple hospital stays a year, I went "well a single admission runs about 20k" and extrapolated from there.
Of course. All medicine producers know to price their product just below the alternative.
Take away the money and watch the development go away ;)
In other countries this will be covered by the social safety net (that doesn’t exist in the US, hence the need for “good-enough health insurance”).
It’s not. That’s what a lot of people don’t understand.
These drugs from Vertex started being approved in 2014. US insurers pretty much covered them from approval. Even Medicaid (health insurance for low income) started paying for it.
Other countries? The UK just started in 2020.
In Canada? Last I checked only 5 of the 10 provinces paid for it and only if you’re under 18.
The US healthcare is expensive for a lot of reasons, and one of them is new technology gets paid for really quickly.
These drugs from Vertex started being approved in 2014. US insurers pretty much covered them from approval. Even Medicaid (health insurance for low income) started paying for it.
Other countries? The UK just started in 2020.
In Canada? Last I checked only 5 of the 10 provinces paid for it and only if you’re under 18.
The US healthcare is expensive for a lot of reasons, and one of them is new technology gets paid for really quickly.
Looks like every province pays for Trikafta now: https://www.cysticfibrosis.ca/our-programs/advocacy/access-t...
Of course, it's Canada, so you may have private drug coverage and then it depends on province whether you fall back to the public coverage if the private payor doesn't cover it.
> The third-generation of modulators, Trikafta, is a new transformational drug that can treat up to 90% of Canadians with cystic fibrosis. Trikafta was approved for sale in Canada on Friday, June 18th, 2021, by Health Canada for people aged 12 and up with cystic fibrosis and at least one F508del mutation and on April 20, 2022 for those aged six and up. As of September 13, 2022, every province, territory and federal drug program is funding this drug for those six and up. Unfortunately, it is not accessible to all who can benefit from it, and therefore our advocacy work continues
https://www.cysticfibrosis.ca/our-programs/advocacy/access-t...
Of course, it's Canada, so you may have private drug coverage and then it depends on province whether you fall back to the public coverage if the private payor doesn't cover it.
> The third-generation of modulators, Trikafta, is a new transformational drug that can treat up to 90% of Canadians with cystic fibrosis. Trikafta was approved for sale in Canada on Friday, June 18th, 2021, by Health Canada for people aged 12 and up with cystic fibrosis and at least one F508del mutation and on April 20, 2022 for those aged six and up. As of September 13, 2022, every province, territory and federal drug program is funding this drug for those six and up. Unfortunately, it is not accessible to all who can benefit from it, and therefore our advocacy work continues
https://www.cysticfibrosis.ca/our-programs/advocacy/access-t...
Not necessarily. I don't know about other countries, but I remember there being a campaign here in Ireland (with one of the highest rates of cystic fibrosis in the world) to get Orkambi covered under the Drug Payment Scheme when it was new.
The socialized medicine systems don't have infinite money just like private health systems don't; if they can't negotiate a cheaper price for the medicine they won't purchase it.
(It's not "health insurance". Insurance covers unpredictable outcomes; needing a medicine every month for the rest of your life is not unpredictable.)
(It's not "health insurance". Insurance covers unpredictable outcomes; needing a medicine every month for the rest of your life is not unpredictable.)
'other countries' would not even developed the drug...Vertex, a US pharma company, developed Trikafta. No one is paying the 300k out of pocket. The high price incentivizes research. Expensive drugs seems like a tradeoff for more innovation.
I literally just received a box of Trikafta on Wednesday. My copay was $150 on a $31,855 retail price. (I actually don't pay the $150, due to Vertex's copay assistance)
No country pays unlimited amounts of public money for brand new drugs.
I just checked, $30 a refill in Australia (or $7 if you're low income). No limits, just whatever the doctor prescribes.
Or the country decides to not import the medicine due to the cost.
Interesting note about Trikafta and other advancements in cystic fibrosis: the Make a Wish Foundation announced that children with CF now no longer automatically qualify for their program due to the advancements in care.
https://wish.org/cf-update
https://wish.org/cf-update
My friend that had CF was eligible. He was asked by the foundation what he wanted when he was 5-6 years old. He said he wanted to go Zorbing in Australia.
They dragged it until he was 18. He always jokingly said "make a wish foundation is waiting, hoping I'll die".
He finally got to go Zorbing when he was 19. Passed away a few years later.
Not surprised the foundation jumped on Trikafta to remove eligibility.
They dragged it until he was 18. He always jokingly said "make a wish foundation is waiting, hoping I'll die".
He finally got to go Zorbing when he was 19. Passed away a few years later.
Not surprised the foundation jumped on Trikafta to remove eligibility.
This is also mentioned in the article:
> Recently, Make-A-Wish announced that children with CF would no longer automatically be eligible for the program, because “life-changing advances” had radically improved the outlook for them.
I know this is a long piece, but half the comments in this thread seem like people didn't even bother to read it before commenting...
> Recently, Make-A-Wish announced that children with CF would no longer automatically be eligible for the program, because “life-changing advances” had radically improved the outlook for them.
I know this is a long piece, but half the comments in this thread seem like people didn't even bother to read it before commenting...
Fair enough. As someone who takes Trikafta, I skimmed the article since it wasn't news to me :-)
There’s a sign-up process required.
Ah! Fair enough. I assumed HN links bypassed the paywall.
This is great news and hopefully with time there will be a definitive cure. I found out about CF when we did genetic testing for family planning. It turned out me and my spouse were carriers of the gene. They said about 25% chance that the embryo would have CF, and since I soon learnt it is a terrible disease I did not want to risk bringing a child in this world with CF.
We did IVF instead and to my surprise, 60% of viable embryos had CF, which I thought was unusually high compared to what I had been told prior to the procedure.
We were very fortunate that we did the testing and had successful IVF pregnancies, but so many other families aren't so lucky. I hope advancements in CF treatment will make it a non-issue for parents in the near future.
We did IVF instead and to my surprise, 60% of viable embryos had CF, which I thought was unusually high compared to what I had been told prior to the procedure.
We were very fortunate that we did the testing and had successful IVF pregnancies, but so many other families aren't so lucky. I hope advancements in CF treatment will make it a non-issue for parents in the near future.
I loved the book The Billion Dollar Molecule (Reviewed by Nature here: https://www.nature.com/articles/nbt0594-521.pdf) about the founding of Vertex Pharma. Really drives home the amount of money, time and luck it takes to make a breakthrough - the author needed to write an entire second book to get to the part where they started making real revenue. The second book isn't as good, but if you like the first enough you might try it anyway.
I had a coworker with CF that started this treatment. Over the course of their first year of treatment, as it became plain to them just how effective it was and what the implications for their long-term survival might be, their behavior changed drastically. Within 18 months of starting treatment they were showing worrying indications of both budding mental health issues and heavy substance abuse. Their marriage, which had been stable for years, was in shambles as well. I can only speculate that their exuberance at being given a stay of execution lead them to "oversteer" into some questionable lifestyle choices.
Imagine if tomorrow, it was announced there had been a discovery that doubled average human life expectancy to 150. There would be happiness, but there would also be chaos. How many people would quit all the things they'd told themselves they were too old to change? The job they were grinding out until retirement. The marriage they'd resigned themselves to? Imagine billions of people getting pulled backwards back across the midlife crisis line, realizing that yes, maybe there IS more to life than "this". The days and weeks after that announcement would be some of the most chaotic the world has ever seen.
>There would be happiness, but there would also be chaos
Which is good in the short term, correct? Long term people hopefully would be wise to settle for stable relationships, jobs etc...
Which is good in the short term, correct? Long term people hopefully would be wise to settle for stable relationships, jobs etc...
This section seems to speak to your observation (edited for brevity):
Doctors told me they could think of only one other comparable breakthrough in recent memory: the arrival of powerful HIV drugs in the 1990s. Like Trikafta, those drugs were not a cure, but they transformed AIDS from a terminal illness into a manageable chronic one. Young men got up from their deathbed, newly strong and hale. ... This was a remarkable turn of events. But it elicited a complicated mix of emotions, not all of them joyful. Some patients who were no longer dying grew depressed, anxious, and even suicidal at the thought of living. This phenomenon became known as “Lazarus syndrome.”
Death is an end, after all. Life comes with problems...the writer Andrew Sullivan, who is HIV-positive, described life after the advent of the HIV drugs in his essay “When Plagues End”:
Doctors told me they could think of only one other comparable breakthrough in recent memory: the arrival of powerful HIV drugs in the 1990s. Like Trikafta, those drugs were not a cure, but they transformed AIDS from a terminal illness into a manageable chronic one. Young men got up from their deathbed, newly strong and hale. ... This was a remarkable turn of events. But it elicited a complicated mix of emotions, not all of them joyful. Some patients who were no longer dying grew depressed, anxious, and even suicidal at the thought of living. This phenomenon became known as “Lazarus syndrome.”
Death is an end, after all. Life comes with problems...the writer Andrew Sullivan, who is HIV-positive, described life after the advent of the HIV drugs in his essay “When Plagues End”:
When you have spent several years girding yourself for the possibility of death, it is not so easy to gird yourself instead for the possibility of life. What you expect to greet with the euphoria of victory comes instead like the slow withdrawal of an excuse. And you resist it.
The intensity with which you had learned to approach each day turns into a banality, a banality that refuses to understand or even appreciate the experience you have just gone through.
I have CF, and my whole life I avoided things like CF communities explicitly because I felt these ties to the disease would lead to a crisis in my life if it was ever something I could stop centering my life around.
Chronic illness forums are almost universally terrible. I try to navigate the online communities for a family member’s disease to keep up with new developments. A decade ago I found some value in the way they presented news and research and anecdotes.
Now, the forums are overrun by small numbers of constantly online members who feel the need to dominate every conversation. The content has become almost entirely venting and memes, with an unreasonable amount of alternative medicine being pushed as fact. It’s understandable that they’re frustrated, to say the least, but the way their frustration gives way to a communal rage against doctors has weirdly opened doors to alternative medicine peddlers. It’s disgusting to me to see how the alternative medicine pushers have arrived with open arms and comforting smiles for vulnerable communities, which slowly becomes a sales pitch for their products.
I’ve seen everting from people peddling custom diet consulting based on your 23andMe results to invitations to private, paid Telegram channels where they supposedly share their secret cures, to doctors from Eastern Europe who claim to have cured the condition (which has eluded many researchers and pharmaceutical companies) with a custom treatment made from the patients’ own urine. The way these communities set themselves up to rage together at modern medicine opens the door for friendly alternative medicine scams.
It’s depressing.
Now, the forums are overrun by small numbers of constantly online members who feel the need to dominate every conversation. The content has become almost entirely venting and memes, with an unreasonable amount of alternative medicine being pushed as fact. It’s understandable that they’re frustrated, to say the least, but the way their frustration gives way to a communal rage against doctors has weirdly opened doors to alternative medicine peddlers. It’s disgusting to me to see how the alternative medicine pushers have arrived with open arms and comforting smiles for vulnerable communities, which slowly becomes a sales pitch for their products.
I’ve seen everting from people peddling custom diet consulting based on your 23andMe results to invitations to private, paid Telegram channels where they supposedly share their secret cures, to doctors from Eastern Europe who claim to have cured the condition (which has eluded many researchers and pharmaceutical companies) with a custom treatment made from the patients’ own urine. The way these communities set themselves up to rage together at modern medicine opens the door for friendly alternative medicine scams.
It’s depressing.
IME one reason (out of many) why chronic illness forums tend to be terrible is that people who are managing their conditions reasonably well don't participate much. Which makes sense—the better you're doing, the less time you spend thinking about it and the less time you're inclined to spend discussing it—but that creates an environment where the most miserable voices become the loudest.
And so (1) there's often a disproportionate focus on doom and gloom rather than success stories, which paints a pessimistic picture for anyone joining after a recent diagnosis, and (2) the most prominent voices have a wounded-cornered-animal mentality that makes them defensive and/or prone to lashing out. And I can't totally blame them, given how hard it is to live with a treatment-resistant chronic condition, but it's not the most constructive environment for everyone else.
And so (1) there's often a disproportionate focus on doom and gloom rather than success stories, which paints a pessimistic picture for anyone joining after a recent diagnosis, and (2) the most prominent voices have a wounded-cornered-animal mentality that makes them defensive and/or prone to lashing out. And I can't totally blame them, given how hard it is to live with a treatment-resistant chronic condition, but it's not the most constructive environment for everyone else.
I'll echo this - I have had two left leg DVTs, spaced about 7 years apart, and after the second event, really started diving into medical publications - surgical journals, medical textbooks, clinical trials - as a means to better understand the condition, it's pathology, etc. I ultimately submitted to testing and discovered a congenital stenosis of the left iliac vein with heavy retroperitoneal collateralization that necessitated a stent to keep that iliac vein open.
I also had a quick look into the social media (primarily reddit) aspect of these vascular conditions, and it's a pile of dogshit. Most of these patient communities bill themselves as "support groups", but there's never any real discussion on meaningful research, drug, or device advancements. They places serve primarily as "pity pits" for chronic moaners and scammers selling alternative medicine.
I also had a quick look into the social media (primarily reddit) aspect of these vascular conditions, and it's a pile of dogshit. Most of these patient communities bill themselves as "support groups", but there's never any real discussion on meaningful research, drug, or device advancements. They places serve primarily as "pity pits" for chronic moaners and scammers selling alternative medicine.
This is interesting -- I have Factor V Leiden (heterozygous) and have had one DVT. It never would have occurred to me to seek out a support group.
I also have the same mutation, as does my wife. From what I've been told by various hematologists, vascular surgeons, and interventional radiologists, it's a very weak clotting disorder, but you do have to keep an eye on certain environmental factors: smoking, hydration, movement, and trauma/surgery. To put it another way, FVL is fairly benign until you're already way into Virchow's danger done, and at that point it's gonna work against you. When it comes to VTE in the presence of ONLY FVL, I would shoot serious side-eye at a doc that chalked it up to the mutation - there's usually something else going on.
Possibly true, but don't sleep on it -- I happened to be transitioning insurance when it happened, so I dragged it out for several days before ending up at the ER. They sent me home later that day, but with strict warnings about calling 911 immediately for any sign of stroke, heart attack or pulmonary embolism. Fortunately all I have to show for it is weakened vein flow in the affected leg.
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I also have CF, and my diagnosis was different than most: I grew up dirt poor and wasn't diagnosed until I was almost 14. Even after diagnosis, it pretty much became incumbent on me to manage my care. I feel that not being put in a bubble and not being told I was going to die kept CF from shaping my perspective (today I'm 47 and have all the boring problems people my age have. My health is tolerable, sitting at about 50-60% lung capacity)
Many have reported severe anxiety due to Trikafta. As I mentioned in another comment, I believe I experienced the same, but I also started Lexapro around the same time for other non-CF reasons, so independent test variables and all that.
I lost a cousin and a family friend to CF. Both in their 20's. One after a lung transplant added some time.
It is such a horrible disease and the breakthroughs are amazing. So many families will be much more fortunate than mine and I am happy for them!
It is such a horrible disease and the breakthroughs are amazing. So many families will be much more fortunate than mine and I am happy for them!
When I was a kid, I was told my cousins would die before they turned 30 because of CF. One of them ended up dying when he was 10, but other is now above 30 and seems incredibly healthy.
The amount of development in the treatment of CF over the last 20 or so years is so incredible it’s insane.
The amount of development in the treatment of CF over the last 20 or so years is so incredible it’s insane.
Around the time Trikafta became widely available I used to work for a
clinical trials company. I remember one guy with CF telling us the full story of his life, how plenty of his friends with CF died in their 20s, and how, after taking the new meds, he felt effects within the first hour. It was like a miracle. If I remember correctly, there’s still some 10% of CF patients for whom it doesn’t work but I hope we will soon eradicate this horrendous disease altogether.
If I can be allowed a bit of sophistry:
It's a beautiful thing for treatments to be devised for rare conditions, to give people decades more life. It would be more wonderful still if we devised treatments for aging, the universal condition, to grant everyone decades more life.
Hardly anyone deserves to die. The vast majority of people are singularly incredible and worthy of life. They deserve to be equally safe from murder, fatal accidents, rare diseases like cystic fibrosis and the universal disease of aging.
It's a beautiful thing for treatments to be devised for rare conditions, to give people decades more life. It would be more wonderful still if we devised treatments for aging, the universal condition, to grant everyone decades more life.
Hardly anyone deserves to die. The vast majority of people are singularly incredible and worthy of life. They deserve to be equally safe from murder, fatal accidents, rare diseases like cystic fibrosis and the universal disease of aging.
>It would be more wonderful still if we devised treatments for aging, the universal condition, to grant everyone decades more life.
Well, people are people. Somehow the life of a 90 year old is less worthy that than that of 20 year old. As to how they arrived at the magic number of 90 remains a mystery to the fictitious society where individuals routinely live for 9000 years.
Well, people are people. Somehow the life of a 90 year old is less worthy that than that of 20 year old. As to how they arrived at the magic number of 90 remains a mystery to the fictitious society where individuals routinely live for 9000 years.
Many incurable diseases come with an awful quality of life, like CF. Even cancer, treated or not, is a terrible experience. Just aging, what you call “a disease”, is nothing like that.
Aging comes with a terrible quality of life. By the end, the person is severely debilitated.
Osteoporosis can make it so that a fall can lead to major fractures, which leads to a severe reduction in a person's independence. Macular degeneration can make an elderly person blind.
Neurological deterioration can take the form of conditions like Alzheimer's, where a person loses their memory of everyone they love.
The body, as it ages, becomes much more susceptible to other, terrible, diseases as well, like cancer, heart disease, and diabetes, each carrying its own set of debilitating effects that degrade quality of life.
Osteoporosis can make it so that a fall can lead to major fractures, which leads to a severe reduction in a person's independence. Macular degeneration can make an elderly person blind.
Neurological deterioration can take the form of conditions like Alzheimer's, where a person loses their memory of everyone they love.
The body, as it ages, becomes much more susceptible to other, terrible, diseases as well, like cancer, heart disease, and diabetes, each carrying its own set of debilitating effects that degrade quality of life.
Alzheimer is not aging, it is a specific disease. Same as cancer. Sure, advanced age can make you more susceptible to some diseases, but aging itself is not one.
Aging eventually makes you orders of magnitude more susceptible to most major diseases, while coming with its own set of debilitating effects.
Aging is the gradual accumulation of cellular and bodily damage. Nothing would do more for human health than having effective treatments for arresting and reversing that degradation.
Aging is the gradual accumulation of cellular and bodily damage. Nothing would do more for human health than having effective treatments for arresting and reversing that degradation.
It appeared too late to make a difference for my dear friend and the kindest human being I knew. The manifestation of life's injustice drives me mad ngl.
This is the future I want to live in: one where radical advances in gene therapy are curing (or nearly curing) horrible illnesses humanity has suffered with for thousands of years.
already a thing: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512634/
Summarize it in plain layman's language for me please...
They take out some of your cells, tinker with their genetic sequence, and put them back into you.
I remember studying about how CF was an agonizing death sentence just 10 years ago in highschool. It's both interesting to learn that even at that time the life expectancy info was outdated, and even cooler to hear this news.
If CF like breathing through a coffee straw, as some sources say? I tried it myself, and god I hope not. I lasted a few minutes and was gasping for air.
I have CF. My lung capacity is around 55% (many have lower, and around 20-30% is when they tend to start talking lung transplant)
I wouldn't use that analogy. It's more like breathing in a deep swimming pool or a very humid sauna. Slight physical exertion (like stairs or hills) can be like most people doing strenuous exercise. Laziness tends to be a way of life :-)
I wouldn't use that analogy. It's more like breathing in a deep swimming pool or a very humid sauna. Slight physical exertion (like stairs or hills) can be like most people doing strenuous exercise. Laziness tends to be a way of life :-)
Once it gets bad, yeah. I was very end stage before my lung transplant and it's an accurate description.
Breath From Salt is a great book on CF and it's history in medicine.
https://benbellabooks.com/shop/breath-from-salt/
https://benbellabooks.com/shop/breath-from-salt/
This is incredible. I wonder if there will be medicine that cures idiopathic pulmonary fibrosis. New class of drugs like Ofev stop worsening of the IPF but doesn't cure it.
I wonder if this applies to kidneys cystic fibrosis?
I friend of mine passed away a few years ago from it, and it was painful to watch slow degradation in his health over the years.
I friend of mine passed away a few years ago from it, and it was painful to watch slow degradation in his health over the years.
I wasn't able to read the article (behind paywall) but this was also in the news recently, related to CF & Zn.
https://newatlas.com/medical/zinc-lung-macrophages-anti-bact...
https://newatlas.com/medical/zinc-lung-macrophages-anti-bact...
The internet archive has your back. Here is TFA: https://archive.is/gD49J
This sounds bad and can give edge to republicans as generally rightist people have more incidence of CF
Trikafta changed my situation dramatically. I've had no hospitalizations, and most the classic CF symptoms are either gone or extremely diminished. It can't undo a life of damage to things like my pancreas, vas deferens, etc, and I still take medicine to digest my food, but overall, it's as close to "normal" as I could hope for at this point.
The only real downside: weight gain. With CF the pancreas is blocked, so you lack in digestive enzymes, and it's a struggle to maintain a healthy enough weight to battle respiratory infections. After Trikafta, I gained some 30 pounds, and have a big belly on my small frame, and went up some 6 inches in the waist. To add insult to injury, it happened during the spring and summer of 2020, when buying clothes was a challenge due to the pandemic.
Speaking of the pandemic, the timing of Trikafta was amazing: it kept the normally full "CF floors" of hospitals empty, opening up those beds for those with COVID and keeping CF patients less exposed.
One side effect I should mention: many report extreme anxiety. However, I was starting an anxiety medication for the first time (something I should have done 20 years ago, but alas ...) and so those effects were muted or hidden to me.
(copied from the last time Trikafta was mentioned here: https://news.ycombinator.com/item?id=37540731)