Big Idea of 2015: The Rise of Gene Editing

In April, Chinese scientists quietly published a game-changing paper in an obscure journal.

For the first time ever, it revealed, we’d edited the genome of a human embryo. One of our own.

The results were not definitive: only 28 of 54 embryos tested by lead researcher Junjui Huang of Sun Yat-sen University were successfully modified. In addition, two of the six embryos Huang’s team sequenced for analysis contained mistaken edits. On the other hand, the scientists’ use of non-viable embryos allowed them to bypass any glaring ethical issues and observe how edits affect development. That could be considered admissible progress.

Here are Tim De Chant and Rachel Becker, reporting for NOVA Next in April:

Despite the fact that the embryos weren’t viable, many scientists are concerned that Huang and his group plowed ahead before the rest of the community had arrived at a consensus on how to proceed. Back in the 1970s, when researchers first discovered how to splice new bits of DNA into a genome, a technology known as recombinant DNA, they held a conference at Asilomar in California in 1975 to hash out a number of guidelines. In January of this year, scientists met in Napa, California, to do the same for genome editing. They identified a number of guidelines, including calling for a moratorium on any modifications to the earliest phases of development, known as the germline.

“When you cross the germline bright line, you’re also opening the door to eugenic reasons—improvement, enhancement—not just disease,” Caplan says. The scientific community, he adds, hasn’t “even talked about that very much.”

Huang’s paper may serve as a cautionary tale—or better yet, a manual for future researchers endeavoring to edit the germline. Regardless, it will certainly provide a launchpad for the kind of conversation Caplan has alluded to.

Earlier this year, scientists modified human embryos for the first time.

That’ll Do, Pig

Typically, experts employing the new CRISPR-Cas9 technique modify a single gene; the lead researcher for the Protein & Cell paper, Junjui Huang of Sun Yat-sen University, used it to alter genes in a single zygote. Humans have not yet been able to edit multiple genes at once using this new technology—but in October, yet another development in the CRISPR saga foreshadowed the possibility. George Church of Harvard Medical School and his colleagues announced in the journal Science that they’d successfully altered 62 pig genes (in more than one cell) at once. The hope was that these genes could be wiped clean of harmful pathogens or viral genes like PERVs—porcine retroviruses that seemed impossible to erase before the dawn of gene editing. Editing PERVs so that they don’t produce runaway viruses would allow researchers to pursue xenotransplantation, or the use of pig organs in humans.

Here’s Carl Zimmer, reporting for the New York Times:

To eradicate these viruses, Dr. Church and his team engineered a new set of genes and inserted them into pig cells. The genes produced enzymes that hunted for PERVs and snipped out bits of the viral DNA. After two weeks, the modified pig cells had altered all of their own viral DNA.

After the experiment, the viruses in the pig genome exhibited little activity. And despite the drastic genomic surgery, the chromosomes showed no abnormalities and the cells grew normally.

For every step forward, though, scientists run the risk of producing potentially disastrous results. Gene editing strategies could, of course, be abused by anyone with access to them. NPR has the latest on that.

In July, Amy Maxmen reported for Wired on the state of gene editing post-Huang’s study. She noted that most of what scientists intend to do with CRISPR is not actually that controversial. Research designed to deepen our understanding of evolution, for instance, has proved relatively innocuous. Here’s Maxmen:

The real money is in human therapeutics. For example, labs are working on the genetics of so-called elite controllers, people who can be HIV-positive but never develop AIDS. Using Crispr, researchers can knock out a gene called CCR5, which makes a protein that helps usher HIV into cells. You’d essentially make someone an elite controller. Or you could use Crispr to target HIV directly; that begins to look a lot like a cure.

Read Maxmen’s thorough account of DNA editing’s uncertain future. And for more background on CRISPR, don’t miss our original, comprehensive report published last July.