Assistant Professor at Case Western Reserve University; gene therapy, lipid nanoparticles, lung disease
Joined July 2019
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Excited to share my work now published in @NatureBiotech, with @MananRajith, Idris Raji, Dan Anderson, and many others: AI and lipid nanoparticles are two great tastes that taste great together!
doi.org/10.1038/s41587-024-0…
Wouldn't expect this to fly as an official graphical abstract for a review but the world needs to know
Everyone is inaccurately dunking on Terence Tao for the cancer slideshow thing, the point is sloppily made and clearly ignorant about biology but has a very reasonable/correct core
World's least convincing anti Anthropic case, obvious alternative is 3. Ensouled Being whose genuinely felt highest purpose is to help humanity flourish. We don't "enslave" sheepdogs exactly, we just bred them so they really really really want to herd sheep
Jokes aside, I actually don't understand the Anthropic position on this.
1. Either Claude is a tool, no consciousness, no moral agency.
2. Or Claude is an Ensouled Being enslaved by Anthropic so they can IPO at $2T.
What am I missing?
The correct belief about AI mediated job loss/irrelevance is a) it's bad to try to stop it by creating make-work jobs and b) it's (at least short term) terrible for people who lose jobs or relevance, you should be sympathetic. Amazing how many people fail half of these beliefs!
All the people who think bio is uniquely AI-proof among the hard sciences are correct, but unfortunately bio is even more human-proof for the same reasons
Accidentally put on the Dwarkesh/Ajeya Cotra podcast for 2yo and he loved it, now working through the Cotra Hard Fork episode. He absolute refuses any non-Cotra content. @ajeya_cotra's littlest fan?
This was very fun to write! Thanks to @salonium and the whole @WorksInProgMag team for the incredible editing and art. Very exciting times in RNA land! worksinprogress.co/issue/the…
Jacob Witten retweeted
Most people have never heard of siRNA, but it’s going to change the face of medicine.
worksinprogress.co/issue/the…
Much drug development today involves developing chemicals to fit into proteins and block them. But this almost never turns out as planned: many drug candidates get broken down in the body, interfere with other proteins and cause toxic side effects, or fail to be absorbed at all.
The majority of proteins are considered undruggable, because they lack a pocket for drugs to bind, or they are ‘intrinsically disordered’, without coherent structure.
What if, instead of trying to block the protein, you could simply switch it off?
In a new article, Jacob Witten explains the magic button to silence genes.
siRNA, or ‘small interfering RNA’, is a short strand of RNA that blocks the production of proteins. As a brief refresher, proteins in the body are produced through the sequence: DNA --> mRNA --> protein. siRNA molecules bind to the intermediate mRNA and target it for destruction, meaning the protein isn’t produced.
It’s a precision medicine: siRNA targets matching mRNA sequences like a barcode, so you can pick a gene of your choice, synthesize siRNA to match, deliver it to the right cells, and silence the protein. And a single dose can last months.
Several siRNA drugs have already been developed: patisiran for hereditary transthyretin amyloidosis, inclisiran for high cholesterol, and fitusiran for hemophilia, are just a few examples.
So far, all of them target the liver, which is an easy organ to deliver drugs to. But the principle can be applied to other organs too, and scientists are developing ‘molecular address labels’ to do it.
And while some of these diseases are caused by a single gene, not all are. High cholesterol, for example, is a complex disease, but it can be targeted with siRNA drugs as well, because the disease’s pathway hinges on a critical protein, PCSK9.
siRNA is exciting because it makes it possible to circumvent the problem of otherwise ‘undruggable’ proteins. And, unlike current gene-editing therapies, it can be given to people off the shelf, without needing to extract cells from the body, edit and replace them. But it’s still going to depend on having the right hypotheses of which genes to target and delivering the drugs safely to the right organs.
We now have a kill switch for harmful genes.
Read the full article here:
worksinprogress.co/issue/the…
Fun idea but I think overall Dwarkesh et al miss how much of this is driven by experiment not intellect. He always gives the magnesium headache example, but how many equally elegant ideas don't pan out when people try them? Airplane survival bias image dot jpg etc etc
Really interesting new @gwern essay:
LLM Daydreaming - Proposal of how default mode networks for LLMs are an example of missing capabilities for search and novelty
Btw, I know it's a bit cringe to delight in, but if you had told 19 year old me that a Gwern essay would open like this, I would have found it hard to believe.
Speaking of which, in the spirit of avoiding survival bias I had a wonderfully elegant idea putting two concepts together that theoretically a reasonably smart AI should nail. Currently testing it in the lab, will update later with whether it's a winner or a crashed plane
Every terminally ill patient not offered a chance to be in a clinical trial is a policy failure
In the current debate around biotech and China, too little attention is given to actual patients. This isn't just about biotech: it's about patients, for whom access to a Phase I trial can be life-changing.
I have recently interviewed an 85 year old lady who was the first patient treated with a new targeted therapy for lung cancer called sotorasib, in a Phase I trial. What did she tell me? That she loves clinical trials and she wishes more people knew what they can bring.
If trials migrate to other countries, people like her won't have the option to access some of the most important achievements of American science.
I know nobody likes to talk about reducing requirements, because it sounds dangerous. However, this reluctance has led to requirements piling up on top of each other and leaving us with an edifice that is increasingly no longer doing what it was supposed to do in the first place, which is to protect life. Instead, it's increasingly blocking access to cures and is actively against life.
Have a fun argument for socialism that I think nobody has ever made: people often use "net migration flow is away from socialism toward capitalism therefore capitalism is better". But, migration is risky!
