In October, two pivotal discoveries were announced on the same day: one published in Science, the other in Nature. Together, they were 2017’s biggest contribution to a revolutionary trend of the past decade: Scientists are getting better and better at editing genes.
Among other applications, these findings could help transform efforts to treat genetic disorders.
David Liu, a Harvard University researcher and core member at the Broad Institute of MIT and Harvard, who led the team that produced the research published by Nature, built an “adenine base editor” — basically a gene-editing pencil that allows scientists to single out and rearrange individual atoms within the structure of DNA, the double helix-shaped molecule that contains genetic code for living things.
The research published in Science, meanwhile, by a separate team led by Feng Zhang of the Broad Institute, described, through a different line of research, a way to use a variant of the same technique to edit RNA, which acts as a temporary genetic messenger within cells.
Over the past few years, scientists have figured out how to use a genome-editing tool called CRISPR/Cas9 easily and inexpensively to cut and replace segments of DNA. CRISPR/Cas9, which Liu calls “molecular scissors,” empowered scientists to pursue expanding areas of research based on genetic manipulation — making possible everything from modifying crops to, perhaps, bringing back the Woolly Mammoth, as 2015 Global Thinker George Church wants to do. More controversially, it has been used to edit the genomes of viable human embryos, a step the ethical implications of which most people have barely begun to consider.
Liu’s and Zhang’s innovations represent even further progress.
Having a tool precise enough to change DNA without slicing through it, as CRISPR/Cas9 does, could vastly reduce the number of unintended problems produced by gene editing. When the goal is simply to fix some kinds of single-point mutations, “base editing offers a more efficient and substantially cleaner solution,” Liu says. “It’s important to point out that for some applications, scissors are the best tool for the job, while for other applications, such as fixing a single letter in DNA, a pencil is best.”
The potential uses of DNA base editing are hard to wrap one’s head around. Some 32,000 of the more than 50,000 genetic mutations known to cause disease, including sickle cell anemia and cystic fibrosis, are of the sort that base editing might theoretically repair. Liu has already tried it successfully in cell cultures, introducing a mutation that would suppress sickle cell anemia (although any clinical applications are still far off).
Many researchers and ethicists, however, balk at problems posed by changing the human genome. The work of Zhang and his team on RNA editing could allow for more temporary changes — easing concerns about long-term impact.
Editing DNA is “permanent and very difficult to reverse, which poses a safety concern,” while editing RNA isn’t, Zhang said in October.
The two approaches, each with its own separate range of applications, are poised to change the future of genetic science.
“Dozens of papers have been published from laboratories around the world using base editing to install or correct point mutations in a wide variety of organisms including bacteria, fungi, rice, wheat, corn, tomatoes, fish, mice, and even human embryos,” Liu says. “These reports have established that base editing is a robust and widely applicable technology.”
Benjamin Soloway is an associate editor at Foreign Policy.
Liu doesn’t think gene-editing technology will be used to create genetically modified superhumans. “Perhaps the biggest misconception is that complex traits such as intelligence, beauty, or athletic ability have a simple genetic basis,” he says. “The fact that hundreds if not thousands of genes likely contribute to such traits means that it’s extremely unlikely that genome editing, or any technology for that matter, will ever be used to create humans with tailor-made complex traits."