@JacobTref
OpenAI Foundation science!
stacy palmer @stacypalmerA.I. Fortunes Could Bring Critical Funds to Global Health. The Scramble Is On.
Jacob Trefethen @JacobTrefI believe that 1) siRNA will change medicine, with new treatments for tens of diseases, 2) tens of millions of people will take an siRNA drug in the 2030s, with some chance of >100M people, and 3) I will have taken at least one siRNA drug within a decade. I have never worked on siRNA, and I also don't think of myself as a hypester. So, why the confidence? There's the technical answer, then the structural answer. The technical answer is that siRNA has several attractive properties as a drug modality, and enough of the chemistry problems have been solved that I'm confident more drug approvals are on the way (though there are many important unsolved problems left, e.g. in delivering siRNA to organs other than the liver). The four most attractive properties are that with siRNA you can reduce production of previously undruggable proteins by going after the RNA that codes for them; they’re “programmable” to a gene/protein you’re going after; siRNA can last long, with slow release inside cells; and siRNA drugs have the potential to be relatively cheaply made and self-administered. The structural answer, I believe, is biotechnology’s combination of long timelines with particularly un-juicy, hard-to-remember concepts. If something takes 20 years, you can often spot it 10 years in -- but when it’s an acronym and involves chemical conjugation steps, it’s hard to remember to care. Many important ideas in biology are messy and technical and, unless you've caught the bug (intellectual or literal), boring. That means there are many important secrets lying in plain sight, as per @nayafia's last book. While disagreements and unknowns remain, it is not particularly controversial among scientists that siRNA holds a lot of promise (alongside some realised promise already!) -- and, yet, most people who will benefit from siRNA drugs in the 2030s have never heard of it. (PS: given my job involves stewarding charitable dollars related to science, I don’t invest in individual pharma/biotech stocks personally; this post isn’t about the financial prospects of particular companies.)
Saloni @saloniumCan we switch off diseases? siRNA drugs are, in my view and @JacobTref’s too, one of the most exciting developments in medicine. So we decided to do an episode! It’s a technology that can ‘silence’ harmful genes in the body. And there are lots of cases where you might want to silence genes: - Infectious diseases, where you can silence pathogen proteins or human proteins that pathogens depend on - Rare genetic diseases, where you can silence the production of mutated proteins - Cardiovascular diseases, by silencing proteins that raise cholesterol - Cancers, by silencing proteins that help tumour cells grow, survive, metabolize, metastasize, or resist treatment - and more! What’s even better is that siRNA drugs are: • Potentially tunable, meaning you could reduce the production of a protein, rather than silencing it entirely • Programmable, meaning you can quickly switch out which gene it targets by changing its sequence • Long-lasting: some drugs last for months, even half a year, with a single injection • Off-the-shelf: they typically don’t involve complicated surgeries or procedures, because of the way they’re delivered in the body Today, siRNA drugs are largely used to treat liver diseases, partly because that’s the easiest starting point. And they are extremely effective at it. One example is as a cholesterol drug: siRNAs can reduce PCSK9 levels by around 70%, reducing cholesterol levels by 50-60%, beyond the effect of statins. But we think it’s just a matter of time before they can be used to target other organs too. Will siRNA treat diseases of other organs? And what’s the catch? Listen to our latest episode of HARD DRUGS to find out! Chapters: 00:00 Introduction 09:58 siRNA trivia 28:14 The 20 year journey to make siRNA drugs 36:07 Which diseases could siRNA treat? 50:45 Programmable, long-lasting, scaleable drugs 54:32 The limits of siRNA 1:08:23 Conclusion
Jacob Trefethen @JacobTrefI believe that 1) siRNA will change medicine, with new treatments for tens of diseases, 2) tens of millions of people will take an siRNA drug in the 2030s, with some chance of >100M people, and 3) I will have taken at least one siRNA drug within a decade. I have never worked on siRNA, and I also don't think of myself as a hypester. So, why the confidence? There's the technical answer, then the structural answer. The technical answer is that siRNA has several attractive properties as a drug modality, and enough of the chemistry problems have been solved that I'm confident more drug approvals are on the way (though there are many important unsolved problems left, e.g. in delivering siRNA to organs other than the liver). The four most attractive properties are that with siRNA you can reduce production of previously undruggable proteins by going after the RNA that codes for them; they’re “programmable” to a gene/protein you’re going after; siRNA can last long, with slow release inside cells; and siRNA drugs have the potential to be relatively cheaply made and self-administered. The structural answer, I believe, is biotechnology’s combination of long timelines with particularly un-juicy, hard-to-remember concepts. If something takes 20 years, you can often spot it 10 years in -- but when it’s an acronym and involves chemical conjugation steps, it’s hard to remember to care. Many important ideas in biology are messy and technical and, unless you've caught the bug (intellectual or literal), boring. That means there are many important secrets lying in plain sight, as per @nayafia's last book. While disagreements and unknowns remain, it is not particularly controversial among scientists that siRNA holds a lot of promise (alongside some realised promise already!) -- and, yet, most people who will benefit from siRNA drugs in the 2030s have never heard of it. (PS: given my job involves stewarding charitable dollars related to science, I don’t invest in individual pharma/biotech stocks personally; this post isn’t about the financial prospects of particular companies.)
Jacob Trefethen @JacobTrefI believe that 1) siRNA will change medicine, with new treatments for tens of diseases, 2) tens of millions of people will take an siRNA drug in the 2030s, with some chance of >100M people, and 3) I will have taken at least one siRNA drug within a decade. I have never worked on siRNA, and I also don't think of myself as a hypester. So, why the confidence? There's the technical answer, then the structural answer. The technical answer is that siRNA has several attractive properties as a drug modality, and enough of the chemistry problems have been solved that I'm confident more drug approvals are on the way (though there are many important unsolved problems left, e.g. in delivering siRNA to organs other than the liver). The four most attractive properties are that with siRNA you can reduce production of previously undruggable proteins by going after the RNA that codes for them; they’re “programmable” to a gene/protein you’re going after; siRNA can last long, with slow release inside cells; and siRNA drugs have the potential to be relatively cheaply made and self-administered. The structural answer, I believe, is biotechnology’s combination of long timelines with particularly un-juicy, hard-to-remember concepts. If something takes 20 years, you can often spot it 10 years in -- but when it’s an acronym and involves chemical conjugation steps, it’s hard to remember to care. Many important ideas in biology are messy and technical and, unless you've caught the bug (intellectual or literal), boring. That means there are many important secrets lying in plain sight, as per @nayafia's last book. While disagreements and unknowns remain, it is not particularly controversial among scientists that siRNA holds a lot of promise (alongside some realised promise already!) -- and, yet, most people who will benefit from siRNA drugs in the 2030s have never heard of it. (PS: given my job involves stewarding charitable dollars related to science, I don’t invest in individual pharma/biotech stocks personally; this post isn’t about the financial prospects of particular companies.)
Jacob Trefethen @JacobTrefI believe that 1) siRNA will change medicine, with new treatments for tens of diseases, 2) tens of millions of people will take an siRNA drug in the 2030s, with some chance of >100M people, and 3) I will have taken at least one siRNA drug within a decade. I have never worked on siRNA, and I also don't think of myself as a hypester. So, why the confidence? There's the technical answer, then the structural answer. The technical answer is that siRNA has several attractive properties as a drug modality, and enough of the chemistry problems have been solved that I'm confident more drug approvals are on the way (though there are many important unsolved problems left, e.g. in delivering siRNA to organs other than the liver). The four most attractive properties are that with siRNA you can reduce production of previously undruggable proteins by going after the RNA that codes for them; they’re “programmable” to a gene/protein you’re going after; siRNA can last long, with slow release inside cells; and siRNA drugs have the potential to be relatively cheaply made and self-administered. The structural answer, I believe, is biotechnology’s combination of long timelines with particularly un-juicy, hard-to-remember concepts. If something takes 20 years, you can often spot it 10 years in -- but when it’s an acronym and involves chemical conjugation steps, it’s hard to remember to care. Many important ideas in biology are messy and technical and, unless you've caught the bug (intellectual or literal), boring. That means there are many important secrets lying in plain sight, as per @nayafia's last book. While disagreements and unknowns remain, it is not particularly controversial among scientists that siRNA holds a lot of promise (alongside some realised promise already!) -- and, yet, most people who will benefit from siRNA drugs in the 2030s have never heard of it. (PS: given my job involves stewarding charitable dollars related to science, I don’t invest in individual pharma/biotech stocks personally; this post isn’t about the financial prospects of particular companies.)
Naomi Handly @lnhandly@JacobTref nails the challenge of drug disco on the head "...we collectively don’t know enough to deliver treatments that are excellent for patients" Looking forward to seeing what else comes out of @FoundationOAI
Asterisk @asteriskmgznZambia approved a new HIV drug in just 12 days, far outpacing the average of 4-7 years in sub-Saharan Africa. How did they do it? Most countries spend years reviewing drug applications that have already been approved by the FDA or EMA. Zambia decided to do things differently, building a system that treated prior approvals from trusted agencies as a starting point. @EnlliMcA dives into Zambia’s process, and what we can learn from their experience:
Jacob Trefethen @JacobTrefHere's more on our initial strategy behind these grants, and other grants we're investigating in Public Data for Health, that may be of interest to researchers: Our starting hypotheses for areas OpenAI Foundation support can be most useful are: connected data, scarce data, and direct data. Datasets we fund will usually have one or two of these properties, described in more detail in the next tweets, and in rare cases will share all three properties. Across all datasets, we believe making data broadly accessible, while ensuring privacy whenever that relates to patient data, will become increasingly important. This will allow researchers to build on each other’s work, and scientific progress to emerge from unexpected places.
Jacob Trefethen @JacobTrefAt the OpenAI Foundation, we believe breakthroughs against disease will come from pairing intelligence with more observations of the world – in other words, more data. Today, we're announcing over $125M in grants, launching our second science program:
