Andrew G.

Only about a quarter of human diseases have an approved therapy. By some estimates it's a few percent. Most of those treatments slow a disease rather than stop it. Closing that gap is what the AI-cures-everything story promises. Build a system smart enough and the cures hidden in what we already know will fall out. I have worked at the intersection of machine learning and biology for three decades, and I believe #AI will eventually transform human health. The capabilities arriving now are extraordinary. But the promise rests on an assumption that is simply false: that we already understand human biology well enough for a clever enough reasoner to find the answers in it. We don't. More than 90% of drugs entering clinical trials fail, a number that has barely moved in decades. In the large majority of those failures the molecule was engineered just fine. The mechanism it targeted was wrong. We are doing a pretty good job at manufacturing keys, but they are generally for the wrong locks. And because nobody wants to fail in the clinic, the industry has retreated to the locks it already trusts: 38 targets now have more than 50 programs against each of them, while the number of novel targets advanced per year fell from roughly 100 in 2015 to about 30 in 2024. AI will not reason its way past this. Biology wasn't engineered. It is the product of billions of years of messy, stochastic evolution, and the variation that produced is too vast and too idiosyncratic to work out in the abstract. You have to measure it. Aimed at a biology this thinly sampled, AI will mostly help us generate failures faster. I founded @insitro because getting to the right locks requires a different kind of system. We generate multimodal human and cellular data at scale, use machine learning to find causal drivers of disease, and test those hypotheses experimentally. Virtual Human™ is built for causal discovery; TherML™ turns what it finds into the right therapeutic intervention. It is working: first-in-class programs internally and with partners, three #ALS targets that Virtual Human™ identified and @bmsnews nominated, and additional collaborations with @EliLillyandCo and @GileadSciences . Today we are launching Deep Phenotype: Scaled Biology, Deep Causality. Issue one is "Drug Discovery Has No Magic Wands," the first half of a two-part essay on the magical thinking currently running through our field and what I think it will actually take. After that you will hear from insitro's own scientists and engineers, people who work across computation and experiment because the problem requires both. Getting this right is hard, and we do not have all of it worked out. I hope you will follow along and think it through with us. DeepPhenotype.Substack.com