SimpleBio 6

A Chinese researcher sparked controversy in November when he claimed he’d produced the world’s first genetically edited babies. He Jiankui said he used Crispr to alter the genes of a pair of twins while they were embryos to make the babies resistant to HIV, the virus that causes AIDS. The announcement prompted mostly criticism from other experts in the field. Using Crispr to make changes to embryos and germline cells — sperm, eggs and zygotes —  is especially contentious because the modifications are passed to progeny. After a year of studying the debate, a U.S. science and medicine advisory group in 2017 decided to support research using technologies like Crispr to modify human embryos for prevention of serious diseases and disabilities. A growing number of labs are using Crispr to experiment with germline modifications, though other applications are more common. These include killing off malaria-carrying mosquitoes, making wheat invulnerable to the blight of powdery mildew, producing eggs suitable for people allergic to them and bringing a woolly mammoth back from extinction. In experiments with human cells, researchers have used Crispr to repair a mutation that causes blindness and correct the defect responsible for cystic fibrosis. Researchers in late 2015 published results on the successful use of the technique to treat mature animals. They repaired a defective gene in mice with Duchenne muscular dystrophy and watched as muscles throughout the animals’ bodies strengthened. The first human trial began in China in 2016 using Crispr-modified T-cells to treat lung-cancer patients. In late 2018, a trial in Europe began recruiting volunteers with the blood disorders sickle-cell anemia and beta thalassemia. Two studies published in mid-2018 found that cells edited by Crispr have the potential to seed tumors, raising the risk that they’d trigger cancer, but the link is still under investigation.

The Background

Crispr-Cas9 is a rudimentary immune system that Japanese scientists first noticed in bacteria nearly 30 years ago. Clustered Regularly Interspaced Short Palindromic Repeats are sequences of genetic code broken up by remnants of genes from past invaders that help bacteria identify them when they appear again so the Cas9 enzyme can slice through them. Understanding of how the system can chop through and then replace segments of DNA grew slowly until 2012, when researchers at the University of California, Berkeley published a paper on making molecular “guides” that allow Crispr to skim along DNA, targeting exactly the right spot to make a slice. Soon afterward, scientists at the Harvard-affiliated Broad Institute said they’d adapted Crispr for use in human cells. That led to a patent dispute, with possible implications for scientific prizes. In 2017, the U.S. Patent Office ruled that the Broad and UC Berkeley patents were sufficiently different; Berkeley lost an appeal. A researcher with basic skills and a few thousand dollars’ worth of equipment can employ Crispr, creating enormous space for innovation, and abuse. The gene-editing system isn’t perfect, at least not yet. It makes unintended cuts in DNA as often as 60 percent of the time in some applications, with effects unknown.