Published online by Cambridge University Press: 18 December 2021
A decade before his CRISPR study got offthe ground, Carl June led an experiment that was dubbed the “first-in-human” gene-editing trial. June was working with zinc fingers, the old-school molecular biology tool likened to record players by my NIH instructors. It was 2009, the year after news of a medical breakthrough: Timothy Ray Brown, the “Berlin Patient,” had just experienced the world's first HIV cure.
Brown was diagnosed with HIV in 1995. Initially he thought that the diagnosis was a death sentence. Soon, though, new antiviral medicines turned his infection into a manageable but chronic condition. Brown was a gregarious American expat who lived with his boyfriend in Germany. But his life was upended again in 2006 when a new, unrelated disease cropped up—leukemia. As he discussed options for treating the leukemia, the doctor offered him an experimental bone-marrow transplant. They had found a bone marrow donor with a rare genetic condition: a mutation to the CCR5 gene, which meant that the donor had enjoyed HIV resistance from birth. Scientists discovered CCR5 years earlier when they studied the genes of people who had been infected by HIV but never became sick. Brown's doctor decided to take a gamble: to see if he could treat the leukemia and transfer genetic resistance to the virus at the same time. Three months after the procedure, there were no traces of HIV in Timothy Ray Brown's blood.
Carl June's team hoped to synthetically replicate the Berlin Patient effect: they wanted to produce targeted damage to the CCR5 gene. The June laboratory already knew how to manufacture synthetic T cells, and they just needed a good tool for the job. They began collaborating with Sangamo Therapeutics, a company in California that had been promoting zinc fingers to edit the human genome. Together this interdisciplinary team started engineering resistance to HIV into living blood cells in hopes of producing a cure.
This HIV clinical trial was innovative and inclusive—at least compared with Carl June's later cancer experiments. A diverse group of patients signed up, representing the demographics of the local HIV-positive population: five white men, four black men, a Hispanic man, an Asian man, a black woman, and an Indian woman.