Now that it's easier than ever to modify DNA, the risks and rewards of experimentation are forcing researchers and the general public to deal with some of the hardest questions in genetic engineering.
A new genetic tool called CRISPR could help eradicate malaria, develop personalized gene therapy for HIV patients, cure genetic diseases, control agricultural pests and invasive species, revolutionize biological experiments, and achieve other amazing feats to benefit humanity. But behind its great power lurks potential—and potentially calamitous—danger.
CRISPR is a piece of bacterial DNA that targets and destroys viral predators, naturally acting like an immune system that protects bacteria from infection, illness, and death. Recently, scientists started repurposing CRISPR to target and edit DNA in other organisms the way we might repurpose a shoe heel to hammer nails. But CRISPR is no clumsy substitute—as a tool, it’s more precise than any other genome-editing method yet invented. It’s also fast, inexpensive, and easy enough for even non-experts to use.
But humans aren’t the first organisms to figure out how to repurpose CRISPR (pronounced “crisper”—a smaller mouthful than saying “clustered regularly interspaced short palindromic repeats”). Viruses have been known to steal CRISPR from bacteria, turning the bacterial immune system on its own host to kill the bacteria themselves. Kimberley Seed, an assistant professor in LSA’s Department of Molecular, Cellular, and Developmental Biology (MCDB), was the first to discover that viruses can hijack CRISPR.
“When you find something that’s traditionally referred to as not just bacterial, but used by bacteria against viruses, and then you find it in a virus, it’s easy to think that you made a mistake, rather than that nature has something crazy up its sleeve,” Seed says.
The virus’s talent as a CRISPR thief could end up benefiting people. In Seed’s study, the virus uses CRISPR against the bacterium Vibrio cholerae, the cause of cholera, which kills thousands of people each year. Seed continues to work with CRISPR, V. cholerae, and the wily viruses, “trying to understand natural systems, with the hope of one day improving our ability to predict and end cholera outbreaks.”
Other scientists want to use the new tool for public health, too, and they’re taking CRISPR to a new level.
Risks and Rewards
Most often, lab studies use CRISPR to edit one gene at a time in one organism at a time. With an eye toward speeding up results, a few scientists have used CRISPR to engineer aggressive genes that self-replicate and incorporate themselves wherever they land.
In mosquitoes, one such aggressive gene can block the spread of malaria and work its way into the DNA of all local mosquitoes at top speed, potentially even spreading through the entire species. As a method of eradicating malaria, it might be ingenious. But the ramifications of such methods are enormous and as yet totally unknown.
Any mistakes in the genetic code, for instance, also would spread unchecked through the population, potentially changing entire ecosystems. So researchers working with aggressive genes have been required to store CRISPR-enhanced organisms within three layers of containment and locked behind five doors with fingerprint-scanning security. Many scientists have called for a moratorium on some CRISPR methods—including aggressive genes and edits to human embryos—amid worries that the technology is advancing more quickly than our ability to reflect on the consequences.
Abby Lamb, an MCDB Ph.D. student, thinks a lot about how to harness the powers of CRISPR while avoiding the pitfalls. Lamb studies the noncoding portions of DNA—regions that were once called “junk” DNA and were long assumed to have no function.
“If you think about it, your entire genome is in every single one of your cells, for the most part. That means that in the tips of your fingers, you have the genes necessary to make your brain,” she says. “But your fingertips are not making brains! It’s because there are lots of complicated things in noncoding regions that tell this gene, which makes neurons, to turn on only in neural tissues.”
Lamb says that CRISPR can help us get to the bottom of those complicated processes. She spends much of her time testing and honing CRISPR methods, and carefully engineering the genes that she’ll introduce into lab organisms.
According to Seed, the historically indiscriminate application of innovations like CRISPR has produced such major contemporary challenges as antibiotic and pesticide resistance. “But how many peoples’ lives have been saved by the use of antibiotics?” she prompts. “Countless, right?”
Seed and Lamb are optimistic about maximizing CRISPR’s benefits, but they agree that researchers should proceed with caution. “So many of these concerns are the ramifications of anything that we do when we interrupt nature,” Seed says, “no matter how we do it.”
Infographic courtesy of David Speranza
This article appeared in the Fall 2015 LSA Magazine and on LSA website