Genome Editing Opens Brave New World

From Brave New World to Gattaca, the repercussions of gaining genetic control over people’s traits has constantly preoccupied science fiction. The recent development of the CRISPR/Cas9 genome-editing technique is now making those concerns a preoccupation of science, no fiction necessary.

Jennifer Doudna, one of the authors on the first report describing using a CRISPR system to genetically engineer an organism, spoke about the ethical ramifications of the technology during the annual Gordon Tomkins memorial lecture at UCSF on February 26.

Before delving into the ethics of human genome editing, Dr. Doudna shared stories about the key discoveries that lead to the development of the gene editing technique and an explanation of how the CRISPR/Cas9 system works.

CRISPR, which stands for “clustered regularly interspaced short palindromic repeats,” are part of the genetic material of a bacterium that flank short regions of viral DNA inserted into the bacterial genome. When a virus attacks a bacterium, a bacterial CRISPR-associated protein (Cas) takes up an RNA copy of the stored viral DNA, matches this to the invader’s DNA, and cuts the virus’s DNA.

Doudna and her colleagues realized they could repurpose this bacterial immune mechanism to target any piece of DNA with a known sequence.

The potential for the CRISPR/Cas9 technique to revolutionize biological research and medicine has thrust both the technology and the biologists behind into the spotlight. In addition to Doudna and colleagues’ many speaking engagements and extensive coverage of the technology by popular science journalism outlets, CRISPR has also been referenced in pop culture, including arecent episode of the new season of the science-fiction TV show The X-Files.

“It’s a privilege to be part of this opportunity to harness something as a technology that you can see will be able to help people and really solve real world problems,” Dr. Doudna said. “It’s an exciting time scientifically, and it’s an exciting time for me personally.”

The CRISPR/Cas9 system can be used to alter DNA in humans, a technique that could be used as a therapy for heritable diseases. By altering the pathological DNA, a disorder could potentially be stopped in its tracks.There is also the possibility of editing germline DNA which would allow changes to be passed down from one generation to the next.

Changes to the genome of an embryo could be incorporated into its egg or sperm cells and as a result passed to its children, grand-children, and so on. This process could eliminate the genetic components associated with certain diseases from the human genome.

However, it is controversial whether anyone has the right to make such far-reaching genetic changes. There is also controversy about the idea of using the technique for cosmetic, rather than health-related, reasons.

The ethical concerns surrounding CRISPR/Cas9 arise from its potential for altering DNA in humans, including the possibility of editing germline DNA which would allow changes to be passed down from one generation to the next. Changes to the genome of an embryo could be incorporated into its egg or sperm cells and as a result passed to its children, grand-children, and so on. It is controversial whether anyone has the right to make such far-reaching genetic changes, especially for cosmetic (as opposed to health-related) reasons.

Another concern is that the technology is still so new that the long-term health effects of using CRISPR systems for genome editing are unknown, thus many questions about its safety remain unanswered.

So far, few labs have used CRISPR/Cas9 to edit the DNA of human embryos or primates, but Dr. Doudna argued in her talk that “scientists should self restrict” this kind of work until a consensus about ethical ways to use it has been reached. Additionally, she is advocating for work to proceed cautiously in non-primate model organisms.

The lecture at UCSF is one of many ways Dr. Doudna is engaging with scientists and the general public to achieve these goals.

“I feel like I’m on a rapid learning curve here figuring out how to… explain the science to non-scientists and talk about issues that I think are really important in this area having to do with ethics and having to do with safety and public perception,” Doudna said.

In addition to writing for the scientific community and speaking to scientists, policymakers, and the general public, she is the executive director of the Innovative Genomics Institute, a collective of Bay Area scientists that aims to promote the responsible use of CRISPR technology among the broader scientific and medical communities.