It is now possible to “edit” the human germline — the genetic cargo carried in sperm and eggs and which is passed to the next generation — in a way that snips out the mutations which cause inherited disease.
“That’s not a future fantasy. It’s here,” Nobel laureate Jennifer Doudna, PhD, winner of the 2020 Vanderbilt Prize in Biomedical Science, said last week during a web-based Discovery Lecture. “We’re not going to put that genie back in the bottle … It’s really, really important to be on top of what’s happening.
“On the other hand, I think that it also does provide potentially valuable opportunities to correct disease-causing mutations in a way that would remove that from a family’s line,” she said.
“Might we one day conclude that that would actually be the best, most ethical way to treat a disease?” Doudna asked. “It’s possible. We have to just continue to evaluate the technology, but more importantly to have transparent public discussion about it.”
Doudna, a professor at the University of California, Berkeley, was awarded the 2020 Nobel Prize in Chemistry with Emmanuelle Charpentier, PhD, for their development of the revolutionary genome editing technology known as CRISPR-Cas9.
She is the 15th recipient of the Vanderbilt Prize, which recognizes women scientists with a stellar record of research accomplishments who also have made significant contributions to mentoring other women in science.
While the ethics of conducting germline editing in humans are being debated, genome editing already is being used to correct mutations in non-reproductive somatic cells that cause inherited disorders like sickle cell disease.
People with sickle cell disease are born with two copies of a mutated gene for the oxygen-carrying protein, hemoglobin. The resulting abnormal protein, in turn, deforms red blood cells into a “sickle” shape that can clog blood vessels, triggering severe pain and increasing the risk of organ damage and strokes.
A problem is cost. Replacement of the abnormal gene with a normal one currently requires a bone-marrow transplant that can cost $1 million to $2 million.
“One of the reasons I started the Innovative Genomics Institute (in 2014) was to focus on how we ensure that CRISPR technology becomes widely available and affordable to everyone who can benefit from it.”
Another potential application of genome editing is the diagnosis, treatment and prevention of viral diseases, including COVID-19.
“The challenge is that if you really wanted to use it clinically, you would have to figure out how to deliver it effectively,” Doudna said. “It’s not so much intrinsic ability of the CRISPR system, it’s more the how do we get it into all the cells that need protection?”
Following the lecture, the 2020 Vanderbilt Prize Student Scholar, Katherine Paulin, who is being mentored by Doudna, discussed her research. Paulin is a PhD student in the Department of Biological Sciences at Vanderbilt University.
Doudna’s lecture was delayed by the pandemic and was sponsored by the Offices of the Executive Vice President for Research and the Dean of Basic Sciences.
For a complete list of Vanderbilt Prize winners, go to the VUMC Office of Research website at www.vumc.org/oor and click on the pull-down menu on the “Research” tab.
