After Jennifer Doudna and other scientists improved the technology known as CRISPR to edit human genomes, a long-awaited, and sometimes feared, milestone arrived.
For the first time in human existence, it became practical to change genes throughout the entire human genome with high precision and accuracy. And today, a decade after the introduction of CRISPR, it’s newly apparent that such manipulations have been made to human embryos — a feat achieved by scientists at the Salk Institute in La Jolla and elsewhere.
Tinkering with genetics, a system that has been produced through billions of years of evolution, takes humanity into unknown territory. This powerful technology can be used for many purposes, not just stopping disease. Alterations in an embryo’s edited genome would be passed along to generations of descendants — for good or ill.
Doudna, a UC Berkeley molecular biologist, said during a visit to San Diego this week that society needs to catch up to this potentially world-transforming field of science. She has co-authored a book, “A Crack in Creation,” on the benefits, perils and ethics of what scientists call germline editing.
“The question will be as the technology comes to fruition ... should we use it in that fashion?” Doudna said about germline editing in a Monday interview at the American Association for Clinical Chemistry’s scientific meeting in San Diego.
“It’s a question that has many facets to it,” she said. “Who decides who gets access, who pays for it and under what circumstances should that type of editing be done? These are important questions because the technology is already at the point where it’s possible to do this.”
Her points were underscored by reports last week of a germline-editing study performed by a team in the United States (including the Salk researchers), China and Korea. The report showed that CRISPR could be used to repair a genetic defect in single-celled human embryos. The embryos were not allowed to develop beyond a few days.
This project received private funding, allowing it to sidestep government restrictions on such genetic editing.
The study was leaked to a British reporter and hasn’t been published yet.
Doudna said she wasn’t cognizant of the ethical issues when she and collaborator Emmanuelle Charpentier began exploring CRISPR.
Beyond the call for society to grapple with the ramifications of germline editing, Doudna said, it’s difficult to get more specific, except to exercise general caution.
In many cases, genetic defects don’t even need to be repaired if multiple embryos are being generated, she said. These embryos could simply be screened for genetic defects, and a healthy embryo would be chosen.
“In my opinion, we still need to respect the recommendations in the (National Academy of Sciences) report published in February that recommended refraining from clinical use of human germline editing until and unless there’s broad societal consensus about the value,” Doudna said.
The report — available at j.mp/nasgene — doesn’t actually spell out how the technology should be used; it merely suggests a method for making decisions, Doudna said.
“The challenge is how to actually implement discussions that might lead to a broad societal consensus. The debate is still out on how we might proceed.”
International scientific organizations, leading research and medical groups in the United States, the Trump administration and others have neither taken the lead nor been able to unify the wide spectrum of parties to arrive at a joint set of standards.
Amid the political, ethical and cultural questions, Doudna emphasized that CRISPR also might transform human suffering by treating or even eradicating various diseases. The method can do so by altering the genome of non-reproductive cells, and these changes wouldn’t get transferred to the next generation.
“It's important to for people to appreciate that this is a powerful technology that has the potential to do a lot of good, to solve real-world problems not only in clinical medicine but also in agriculture and synthetic biology,” Doudna said.
Invented by bacteria
Untold millions of years ago, Mother Nature invented genetic editing.
Bacteria use CRISPR — short for Clustered Regularly Interspaced Short Palindromic Repeats — to fight viral infections.
The system contains an RNA sequence that can locate a complementary DNA sequence, along with an enzyme called Cas that acts as molecular scissors to cut up the DNA. The RNA matches sequences from previous infections, which the bacteria capture and incorporate into the CRISPR system.
Humans entered the picture when they realized that the RNA sequence could be swapped out with other sequences specifying various DNA segments of interest. This approach could be used to chop up a defective sequence.
Doudna said her lab is exploring genetic editing to treat diseases of the brain. This endeavor is strictly in the research stage, and much more testing will be needed before it can be considered for testing in people.
“I think we’re still years away from having a clinical application, especially for things like Huntington’s disease,” Doudna said.
In the end, she said, it’s important for the public to understand that all the good CRISPR might produce has emerged from basic research.
“It really came about from fundamental science that was going on in international collaboration, that led to an understanding of a system that could be harnessed as a tool for gene editing,”
Doudna said. “The value of fundamental research is really underscored when you look at what can happen when scientists are allowed to do creative work that is not applied in a particular direction.”