A married couple who met over a dissected brain and went on to create the first approved gene therapy for blindness have been awarded one of the most lucrative prizes in science.
Molecular biologist Jean Bennett and ophthalmologist Albert Maguire share the $3m (£2.2m) Breakthrough prize for life sciences with physician Katherine High for the 25-year-long project, during which the couple adopted a pair of dogs they had treated for blindness.
The therapy, named Luxturna, was approved in the US in 2017 and has transformed the lives of people born with Leber congenital amaurosis (LCA), a genetic disorder that typically causes total blindness by early adulthood.
Proof that the therapy worked came in a clinical trial in which one patient described seeing their child’s face for the first time, the fine grain in wooden furniture and branches waving in the wind. Other patients reported similar profound improvements.
“I was overwhelmed,” said Bennett, who is now retired from the University of Pennsylvania. “It was one of the most miraculous eureka moments you can imagine.”
Bennett said it was a “tremendously exciting time” for scientific and medical research, but warned that the US administration’s attacks on science could “cause damage for generations to come”, leading her to fear a brain drain that the country would struggle to recover from.
“Agendas have become politicised, government agencies that support basic and applied research have been undermined, knowledgable advisers and experts have been dismissed or have fled and revised guidelines contradict decades of rigorous research,” she said.
The Breakthrough prizes, described by their Silicon Valley founders as the Oscars of science, were handed out on Saturday night at a glitzy ceremony in Los Angeles. Further life science prizes celebrated a gene therapy for sickle cell anaemia and beta thalassaemia, and the discovery of genetic drivers of frontotemporal dementia and ALS, the form of motor neurone disease that affected the cosmologist Stephen Hawking.
Bennett and Maguire met at Harvard Medical School when they were paired up to dissect a brain. Later, at the University of Pennsylvania, they set about tackling LCA. The disease was linked to faults in a gene called RPE65, but scientists lacked the tools to fix them. Bennett pressed on regardless. “The nice thing about being young and naive is I didn’t know what I didn’t know,” she said.
After years of work, Bennett and Maguire developed a gene therapy that smuggled a working version of the gene into retinal cells. Tests in animals and human trials, developed with Katherine High, showed that it restored lost vision. Two dogs that they treated on the way, Venus and Mercury, became the couple’s pets.
A second life sciences prize went to Swee Lay Thein, a senior investigator at the US National Institutes of Health, and Stuart Orkin, a physician-scientist at Harvard Medical School, for work on a gene therapy for sickle cell disease and beta thalassaemia. Both are driven by faults in the adult versions of haemoglobin, the protein that allows red blood cells to ferry oxygen around the body.
The pair discovered that disabling a gene called BCL11A forced cells to produce the healthy foetal form of haemoglobin, effectively treating the diseases. The work led to Casgevy, a groundbreaking therapy that works by “editing” patients’ blood stem cells and reinfusing them back into the body.
Thein, who discovered BCL11A at King’s College London in the 2000s, said the therapy was “incredibly intense” but that the field was moving fast. Instead of extracting patients’ cells for editing, new approaches aim to correct them inside the body or to treat the diseases with pills.
“It’s not the kind of therapy, at least in this generation, that’s going to eliminate the disease for patients,” Orkin said. “In my mind right now, it’s the first big step. But in order to reduce the burden of disease, which is the goal, you’ve got to have a more user-friendly kind of therapy.”
Like Bennett, Orkin lamented the administration’s attacks on US science. “We were in a golden age of biomedical science. Universities and medical centres were operating at high efficiency and speed. Now there are attacks on academic institutions, they’re disassembling scientific infrastructure that was created over many years,” he said. “I’m at a total loss to explain why people in leadership would want to do this.”
The Breakthrough prize for mathematics went to work on nonlinear evolution equations, which describe how complex systems change over time, while the physics prizes honoured work on the force that holds atomic nuclei together and a multi-decade effort to measure muons, the heavy cousins of the electron.
