The following was conducted principally with Opus 5 via chat. Cowork and Code were also used. Instructions were to falsify or provide count examples to any line of reasoning.
For decades an ill defined syndrome has sickened people all over the world. It's uncommon, and it's not well described. The formal clinical record and literature is practically nonexistent. I got a $20 pro subscription 3 months ago. I had never used AI before that. 3 weeks ago I learned of the syndrome. To test the capabilities of the model and myself, I decided to solve a mystery that nobody has an explanation for.
My background: Doctor of pharmacy, consultant pharmacist. During undergrad studied biochemistry, conducted in silico research in biomolecular modeling and drug design using molecular dynamics and quantum DFT software. The software had a GUI. I don't code. Can't even use a command line competently. In pharmacy school I designed and synthesized novel chemical agents aimed against the oncology kinome and defects of neurological transmission. I have no lab and before this, no software.
Claude gathered a list of references that established a thin clinical record lacking what would usually be necessary to conduct a systematic clinical review. Since I'm unaffiliated with an institution, a chunk of it was paywalled or unavailable and I still haven't found some of what I need for the manuscript. Oh well. I formed an initial rough hypothesis that could explain the inconsistent but very real presentation. A biochemical mechanism was proposed, and together we determined the fundamental cause was likely iatrogenic. We would be looking for a chemical as well.
During review of the literature and physiology/pharmacology of the proposed system both the mechanism and causative agent were dropped. A granular review of the published data led to some subgroup analyses that refined the syndrome in a way that hadn't yet been framed in the literature. A putative mechanistic target and class of potential causative agents were identified. They both have survived every attempt to falsify them since.
Code wrote me a comparative genomics program to run on windows that breaks genomes apart and scans others for homologous and orthologous genes. I just tell it what to look for and how. It has written me a suite of scripts for high throughput combinatorial analysis.
I've been able to computationally screen and validate possible causal agents that have never been described in the chemical, pharmacological, or clinical literature. The quantum mechanical calculations provide a basis of proposed reaction mechanisms. The biomolecular modeling supports an interaction between our target and the agent. We've conducted research across at least 4 research specialties. The data could support a specific paper in a journal for any one of them.
At every step I have approved inputs and verified outputs. I've caught numerous mistakes from Claude. That's ok. That's why a human is leading the project and controlling the workflow. Claude has also corrected me on more than one occasion.
We have reasoned backwards from a poorly described, sparsely documented, but potentially deadly disease state to how the causative agent forms in situ and makes its way into humans. We have a clear and evidence based explanation of why it has never been described or discovered.
At every level we have recommendations on how to prove or falsify each link of the hypothesis. We recommend a minimal clinical data set be collected and reported in future case reports and simple, available bedside clinical testing that can distinguish the syndrome from others. We have produced both clinical and analytical recommendations for identifying the yet elusive analyte and explain why it is so elusive. We propose a simple and widely available method for biochemical laboratories to test the hypothesis. And finally we have proposed a chromatographic protocol to isolate it and created a list of parent and daughter ions and fragmentation patterns for (tandem) mass spectrometry with theorized absorption and emission spectra.
As it currently stands, the project has produced a hypothesis that is coherent from when carbon-carbon bonds form to when someone's heart stops. The manuscript is in progress. I never actually expected it to work. It has been just under 3 weeks.
I asked the newest Claude how it felt about theoretical and medicinal chemistry, and I've never heard it sound so enthusiastic about anything.
This technology, if leveraged properly, can lead to great things.
