Drug of Choice - The natural world contains many billions of potential medications. The question is how to find the ones that work.

AI. is transforming the way medicines are made. Bacteria produce numerous molecules that could become medicines, but most of them aren’t easily identified or synthesized with the technology that exists today. A small percentage of them, however, can be constructed by following instructions in the bacteria’s DNA. Burian helped me search the sequence for genes that looked familiar enough to be understandable but unfamiliar enough to produce novel compounds. We settled on a string of DNA that coded for seven linked amino acids, the same number found in vancomycin. Then Burian introduced me to Robert Boer, a synthetic chemist who would help me conjure our drug candidate.

- By Dhruv Khullar - Illustration by Daniel Liévano

When I first became a doctor, I cared for an older man whom I’ll call Ted. He was so sick with pneumonia that he was struggling to breathe. His primary-care physician had prescribed one antibiotic after another, but his symptoms had only worsened; by the time I saw him in the hospital, he had a high fever and was coughing up blood. His lungs seemed to be infected with methicillin-resistant Staphylococcus aureus (MRSA), a bacterium so hardy that few drugs can kill it. I placed an oxygen tube in his nostrils, and one of my colleagues inserted an I.V. into his arm. We decided to give him vancomycin, a last line of defense against otherwise untreatable infections.

Ted recovered with astonishing speed. When I stopped by the next morning, he smiled and removed the oxygen tube, letting it dangle near his neck like a pendant. Then he pointed to the I.V. pole near his bed, where a clear liquid was dripping from a bag and into his veins.

“Where did that stuff come from?” Ted asked.

“The pharmacy,” I said.

“No, I mean, where did it come from?”

At the time, I could barely pronounce the names of medications, let alone hold forth on their provenance. “I’ll have to get back to you,” I told Ted. He was discharged before I could. But, in the years that followed, I often thought about his question. Every day, I administer medicines whose origins are a mystery to me. I occasionally meet a patient for whom I have no effective treatment to offer, and Ted’s inquiry starts to seem existential. Where do drugs come from, and how can we get more of them?