SXSWORLD

Dr. Jennifer Doudna. Photo by Sam Willard FROM BACTERIA TO HUMANS ... A Gene Editing Revolution Has Transformational Potential By CisCo Gilliland 1 0 SXS W O R L D | N O V E M B E R 2 0 1 6 | SXSW.COM products. DuPont, an early investor, has a multi-year agreement across several fields, from agricultural and industrial segments to human and animal therapeutics. Caribou is also collaborating with a U.K. company, Genus, to target a debilitating virus in pigs, cattle and other livestock, and with Novartis to address a range of medical needs, from vaccines to eye care.  On the surface, this technology sounds a lot like an extension of the GMO (genetically modified organisms) work being done by cor- porations such as Monsanto, but the processes are quite different. GMOs are created when a gene from a radically different species is introduced, such as an antifreeze gene from a cold-weather flounder inserted into a tomato to protect it from frost. CRISPR, on the other hand, edits the existing genome rather than inserting foreign ones. This technique can be just as successful as GMOs in achieving the desired outcome, potentially with a much lower price tag, which might eventually make current GMO techniques (and the controversies surrounding them) moot.  One scientist whose work has been fueled by Doudna's discovery is Sarah Richardson, a keynote speaker at SXSW Eco 2016. As a child, Richardson looked to the stars and science fiction for inspira- tion. Now as chief scientist at a startup called Ignition Genomics, she still has the same sense of awe about the invisible world teeming all around us and calls herself the "bacteria whisperer." In 2013 and 2014, Richardson was working at the U.S. Department of Energy's Joint Genome Institute, close to Doudna's labs at UC Berkeley. The two met regularly to discuss their projects, and Richardson now leverages CRISPR-Cas9 to help accelerate her efforts to coax bacteria to create products such as fuel, pesticides and industrial cleaning agents with broad environmental implica- tions. "There are bacteria out there now that can pull heavy metals from water," she says. "We just need to make it happen faster." t was only a few years ago that Dr.Jennifer Doudna, along with Emmanuelle Charpentier, her lab partner at the time, devised a revolutionary process for gene editing. The process, called CRISPR-Cas9, has since taken scientists and investors by storm, creating a media frenzy in the process with cures for cancer, cystic fibrosis or Alzheimer's; disease-free crops; designer babies for the rich and entitled (and maybe even uni- corns) among its possible applications.  Like so many major breakthroughs, this seemingly radical shift is actually the next step in a continuum that has been unfolding for years. "Genome engineering is actually not new; it's been in development since the 1970s," Doudna noted in a 2015 TED Talk. "We've had technologies for sequencing DNA, for copying DNA and even for manipulating DNA. And these technologies were very promising, but the problem was that they were either inefficient, or they were difficult enough to use that most scientists had not adopted them." CRISPR, short for clustered regularly interspaced short palin- dromic repeats, is a segment of DNA derived from bacteria such as the one that causes strep throat, and Cas9 refers to a par- ticular protein. Paired up, the protein and the DNA segment act like a surgical tool that can recognize and cut strands of DNA, allowing scientists to effectively remove or change existing genes within an organism.  The CRISPR discovery has radically accelerated the pace of genomic research. One reason is its simplicity. Doudna compares CRISPR to running a software application, versus previous genome engineering techniques, which were more like rewiring a whole computer. Also, genetic changes, once introduced, can be carried down through generations—so-called "germline" transformations. Now, experiments requiring mice with specific gene modifications can be conducted over a matter of weeks or months, rather than years.  That speed has led to an outpouring of CRISPR-derived research in both the private and public sectors, ranging from environmental uses to agricultural and medicinal applica- tions. A pathologist at Penn State University successfully used CRISPR-Cas9 to edit out the genetic base pairs that make white button mushrooms turn brown. Researchers have used CRISPR to make both tomato and cotton plants resistant to common dis- eases. Chinese scientists even claim (the results have not been made public) to have used the CRISPR tool to treat lung cancer.  Doudna herself has co-founded a startup, Caribou Biosciences, which has partnered with several corporations to develop new

• Cover