Whenever I learn more about something, I find myself overwhelmed by the inadequacy of the world.
I learn about clinical trials, and it is horribly inadequate. We suffer and die much more than we have to.
I learn about housing, and it is horribly inadequate. We are impoverished and our futures are curtailed for stupid reasons.
I learn about education, and it is horribly inadequate. We condemned half a century of kids to functional illiteracy because of a combination of an understandable mistake and a refusal to check our work.
Everywhere you look, it's like this. I suppose I could get depressed about it, but it does mean there's a lot of leverage by which to do good.
Whenever I learn more about things like the progress of modern medicine, energy, infrastructure, manufacturing, technology, etc., I find myself inspired by the ingenuity, passion, and effort that countless unknown have put into making the world the way it is. So many things that pass for granted about everyday life have incredible histories behind them, explaining why they are the way they are. I'm grateful to this newsletter shedding light on these stories of the builders behind the scenes making advances in their fields.
The downside is that everything is ran by humans who are self-preserving and can’t stick their head out without fear of it getting cut off, resulting in frustrating institutional inertia that make for inadequate decisions and waste.
The upside is that everything is ran by humans who are intelligent and collectively can make massive differences if only we are brave enough to stick our heads out.
As someone who has lived through much of the progress described here, I was already familiar with many aspects of it. But it was wonderful to see that progress presented so clearly and quantified so compellingly. A brilliant and fascinating piece. Let’s hope this progress can continue, even as parts of the world seem to be growing increasingly skeptical of science.
I have Narcolepsy and the FDA has just approved a novel treatment. Coincidentally it affects almost exactly 1 in 2000 people therefore is a "rare" condition. This post made me reflect that I'm fortunate it's one that 1/ has a direct impact on productivity in the US therefore has an easy-to-understand business case, and 2/ may also help with other wakefulness or attention disorders - which is probably why it's receiving this level of funding (a potential cash cow if it proves to be like GLP-1 and can help with ADHD also).
This was another example of a condition that people didn't understand until very recently, and we're seeing progress happening before our eyes, in real-time. I agree, the average person really doesn't reflect enough on how miraculous this relentless medical progress has been.
Thanks for the excellent piece. My 10 year old daughter has been battling brain cancer over the last 2 years. It's been a very hard journey, but there are many parents that have been on this journey before us. Death Be Not Proud, written by John Gunther in 1949 documents his harrowing journey of watching his son battle and ultimately succumb to brain cancer. Like us, he wanted to find any treatment that may save his child. What was experimental back then - use of radiation, chemotherapy drugs, change in diet, surgery... now there is a standard treatment protocol with lots of scientific data to back it up that has led to significant improvements in prognosis. Like the tone of your writing, I'm hopeful that the future will bring more improvements to tackle diseases (both common and rare) that will reduce side effects and improve quality of life together with the gift of more time. Maybe in 20-30 years time (sooner I hope), people will look back on 2020s and be amazed that the standard operating protocol was to inject harmful toxins into our bodies and resort to cutting and exposing our bodies to radiation to cure ourselves. I wanted to subscribe to your print edition, but I reside in Hong Kong and it doesn't seem to be offered here yet. Please let me know how else I could become a paying subscriber to your excellent writing. Thank you. - From a hopeful dad -
We sadly don't sell in Hong Kong just yet but that may change quite soon. If you're interested in being notified once we've expanded, you can leave your details below. Thanks for reading and the nice comment!
What IYO underpins the impression (I think it’s quite common) that medical advances are rare and basically staggerstep rather than linear? I think that’s a quite common perception - was certainly my own, until I became more familiar!
Brilliant article. Absolutely fascinating statistics. What’s frustrating is that so much more could be done, and so many people with the means choose not to.
Every so often there will be an announcement that the clever scientists have come up with something amazing, and all of the Reddit commenters will say that it will be sent on by greedy pharma companies, and they're right to be cynical because they're not going to see this affecting them lives, but they're wrong about the cause.
The obvious effects are bad enough, but the downstream effects make everybody mean and cynical. We should care a lot more about solving this.
This was excellent, and the choice to argue against the low-hanging fruit story rather than repeat it is what makes it worth reading.
Your Beatles problem and the repurposing cliff look like the same force seen twice: patent expiry both removes the reward for testing an old drug in new uses and makes it a cheaper competitor to the next one. So generic entry raises the bar and freezes what we know about the incumbent at the same moment.
One more thing is that companies are also not rewarded for being the first to discover a successful target - fast-followers can often improve on the first mover without having eaten as much R&D cost. A similar dynamic is playing out for indications which have no treatments - they carry efficacy risk but also a ton of regulatory uncertainty (which endpoints will be accepted by the regulators? Which other trial design issues will regulators take issue with?)
I don't know the right policy to fix this, maybe being the first to prove a target or the first to treat an indication gets a % of the revenue of the followers?
I would add- “prevent” and cure all diseases. We should also work on prevention. As a person with chronic illness I would like to see more research on why our modern world is making us sicker and what we can do to counter that. We can do prevention and cures together.
Very thorough piece, thank you. Just one concern: I would not cite AZT as a win given how toxic it was for patients amidst of the HIV epidemic in the 80s. I think it caused more harm than good. But I also get patients needed a lifeline during such difficult times.
Also, regarding cervical cancer. I don’t think the vaccine covers all types. My wife has received it but there’s a few types of HPV most commonly linked to cancer that the jab doesn’t cover. Thankfully she does a pap every year and we plan to take action after we finish having kids, but I think it’s inaccurate to say there is a cure. At least that’s what our OB/GYN tells us.
Thank you - I think you're right that it doesn't contain all the strains, including some that are more common in Africa, though I didn't describe it as a cure. I think AZT was a clear win versus the standard treatment at the time, even though it only lengthened survival by some months and was toxic, but more importantly, like the pancreatic cancer breakthrough, it gave scientists something to build upon. You might enjoy a long episode I did about the history of HIV treatment: https://harddrugs.worksinprogress.co/episodes/lenacapavir-the-miracle-drug-that-could-end-aids
Got it, apologies on my misunderstanding. Overall, really good piece! As someone who worked in corporate innovation, I believe medical innovation will drive a lot of positive change.
Whenever I learn more about something, I find myself overwhelmed by the inadequacy of the world.
I learn about clinical trials, and it is horribly inadequate. We suffer and die much more than we have to.
I learn about housing, and it is horribly inadequate. We are impoverished and our futures are curtailed for stupid reasons.
I learn about education, and it is horribly inadequate. We condemned half a century of kids to functional illiteracy because of a combination of an understandable mistake and a refusal to check our work.
Everywhere you look, it's like this. I suppose I could get depressed about it, but it does mean there's a lot of leverage by which to do good.
Whenever I learn more about things like the progress of modern medicine, energy, infrastructure, manufacturing, technology, etc., I find myself inspired by the ingenuity, passion, and effort that countless unknown have put into making the world the way it is. So many things that pass for granted about everyday life have incredible histories behind them, explaining why they are the way they are. I'm grateful to this newsletter shedding light on these stories of the builders behind the scenes making advances in their fields.
The downside is that everything is ran by humans who are self-preserving and can’t stick their head out without fear of it getting cut off, resulting in frustrating institutional inertia that make for inadequate decisions and waste.
The upside is that everything is ran by humans who are intelligent and collectively can make massive differences if only we are brave enough to stick our heads out.
Incredibly useful summary and reflections on it. I'll keep it around to re-read now and again.
Look into the development and acceleration of biotech and pharmaceutical research in China. That will inform one on how fast things are progressing.
Excellent piece, thanks much.
As someone who has lived through much of the progress described here, I was already familiar with many aspects of it. But it was wonderful to see that progress presented so clearly and quantified so compellingly. A brilliant and fascinating piece. Let’s hope this progress can continue, even as parts of the world seem to be growing increasingly skeptical of science.
Amazing article.
I have Narcolepsy and the FDA has just approved a novel treatment. Coincidentally it affects almost exactly 1 in 2000 people therefore is a "rare" condition. This post made me reflect that I'm fortunate it's one that 1/ has a direct impact on productivity in the US therefore has an easy-to-understand business case, and 2/ may also help with other wakefulness or attention disorders - which is probably why it's receiving this level of funding (a potential cash cow if it proves to be like GLP-1 and can help with ADHD also).
This was another example of a condition that people didn't understand until very recently, and we're seeing progress happening before our eyes, in real-time. I agree, the average person really doesn't reflect enough on how miraculous this relentless medical progress has been.
I’ve been a doctor for 5 years and this is the first time I’ve heard of mycetoma. Lots of great insights and concrete examples here, thanks!
Thanks for the excellent piece. My 10 year old daughter has been battling brain cancer over the last 2 years. It's been a very hard journey, but there are many parents that have been on this journey before us. Death Be Not Proud, written by John Gunther in 1949 documents his harrowing journey of watching his son battle and ultimately succumb to brain cancer. Like us, he wanted to find any treatment that may save his child. What was experimental back then - use of radiation, chemotherapy drugs, change in diet, surgery... now there is a standard treatment protocol with lots of scientific data to back it up that has led to significant improvements in prognosis. Like the tone of your writing, I'm hopeful that the future will bring more improvements to tackle diseases (both common and rare) that will reduce side effects and improve quality of life together with the gift of more time. Maybe in 20-30 years time (sooner I hope), people will look back on 2020s and be amazed that the standard operating protocol was to inject harmful toxins into our bodies and resort to cutting and exposing our bodies to radiation to cure ourselves. I wanted to subscribe to your print edition, but I reside in Hong Kong and it doesn't seem to be offered here yet. Please let me know how else I could become a paying subscriber to your excellent writing. Thank you. - From a hopeful dad -
We sadly don't sell in Hong Kong just yet but that may change quite soon. If you're interested in being notified once we've expanded, you can leave your details below. Thanks for reading and the nice comment!
https://airtable.com/appYLHseqbAs4aOV9/paglNkIcTXDSx6Bz5/form
What IYO underpins the impression (I think it’s quite common) that medical advances are rare and basically staggerstep rather than linear? I think that’s a quite common perception - was certainly my own, until I became more familiar!
Brilliant article. Absolutely fascinating statistics. What’s frustrating is that so much more could be done, and so many people with the means choose not to.
Has anyone tried prompting the AIs yet? "You should do a breakthrough and cure all diseases."
https://chatgpt.com/share/6a60b2eb-0b64-83ee-9c76-7931ca1de063
I know you're being silly here, but have you read this?
https://www.writingruxandrabio.com/p/intelligence-is-not-the-main-bottleneck
Every so often there will be an announcement that the clever scientists have come up with something amazing, and all of the Reddit commenters will say that it will be sent on by greedy pharma companies, and they're right to be cynical because they're not going to see this affecting them lives, but they're wrong about the cause.
The obvious effects are bad enough, but the downstream effects make everybody mean and cynical. We should care a lot more about solving this.
This was excellent, and the choice to argue against the low-hanging fruit story rather than repeat it is what makes it worth reading.
Your Beatles problem and the repurposing cliff look like the same force seen twice: patent expiry both removes the reward for testing an old drug in new uses and makes it a cheaper competitor to the next one. So generic entry raises the bar and freezes what we know about the incumbent at the same moment.
"The deeper problem is that technology isn’t always the barrier: sometimes it’s about the funding, the incentives, and the institutions."
The response to Ebola proves that will power and coordination can handle the other barriers as well.
One more thing is that companies are also not rewarded for being the first to discover a successful target - fast-followers can often improve on the first mover without having eaten as much R&D cost. A similar dynamic is playing out for indications which have no treatments - they carry efficacy risk but also a ton of regulatory uncertainty (which endpoints will be accepted by the regulators? Which other trial design issues will regulators take issue with?)
I don't know the right policy to fix this, maybe being the first to prove a target or the first to treat an indication gets a % of the revenue of the followers?
I would add- “prevent” and cure all diseases. We should also work on prevention. As a person with chronic illness I would like to see more research on why our modern world is making us sicker and what we can do to counter that. We can do prevention and cures together.
Excellent article, thanks. One comment, I think ring vaccination goes pretty far back - Foege used it in the 60s on smallpox in Africa, right?
Yes that’s right! But ring vaccination clinical trials were first developed for the Ebola vaccines
Very thorough piece, thank you. Just one concern: I would not cite AZT as a win given how toxic it was for patients amidst of the HIV epidemic in the 80s. I think it caused more harm than good. But I also get patients needed a lifeline during such difficult times.
Also, regarding cervical cancer. I don’t think the vaccine covers all types. My wife has received it but there’s a few types of HPV most commonly linked to cancer that the jab doesn’t cover. Thankfully she does a pap every year and we plan to take action after we finish having kids, but I think it’s inaccurate to say there is a cure. At least that’s what our OB/GYN tells us.
Thank you - I think you're right that it doesn't contain all the strains, including some that are more common in Africa, though I didn't describe it as a cure. I think AZT was a clear win versus the standard treatment at the time, even though it only lengthened survival by some months and was toxic, but more importantly, like the pancreatic cancer breakthrough, it gave scientists something to build upon. You might enjoy a long episode I did about the history of HIV treatment: https://harddrugs.worksinprogress.co/episodes/lenacapavir-the-miracle-drug-that-could-end-aids
Got it, apologies on my misunderstanding. Overall, really good piece! As someone who worked in corporate innovation, I believe medical innovation will drive a lot of positive change.