Jorge Diego Martin-Rufino (he/him) wants the human genome to one day be as legible as a book, with each letter — and the words they form — readily understood. “Of course,” he acknowledges, “that’s science fiction right now.” Our DNA, after all, contains 3 billion letters and 20,000 genes. A few are well understood. Most are not.
Still, Martin-Rufino is doing his best to make that future a reality. He hadn’t intended to become a geneticist. Growing up in Spain, he wanted to be a doctor. But in medical school, he saw medicine’s limits. Children with leukemia could be cured with stem cell transplants, a decades-old procedure, but only at great cost to their bodies. For some, the procedure was too risky.
His work since at The Broad Institute and Boston Children’s Hospital has focused on picking apart the genome in blood stem cells, with the goal of finding ways to engineer safer and more effective cell therapies. In a Cell paper last year, he used a technology called base editing to examine how changing individual DNA letters in blood stem cells affected their development. It’s the best way scientists have of understanding what stretches of DNA do: See what happens when you change them.
Martin-Rufino’s approach requires devising new techniques to edit cells that don’t like to be edited, and to track how a single change affected their long-term development. But they unveiled potential paths to developing new treatments for leukemia and sickle cell disease.
Already, he’s watched other labs begin applying the technique while he tries to devise new techniques for probing the entire genome. Eventually, he thinks he can find just the right letters that, when changed, could make transplants far safer. “This is just the tip of the iceberg,” he said.
—Jason Mast
