Crazy about CRISPR

This guest blog post is by Sam Sternberg, a TEDMED 2015 speaker. You can watch Sam’s TEDMED talk, “What if we could rewrite the human genome?”, here. 

This thing called CRISPR seems to be all over the news these days, whether as a miracle treatment to cure genetic disease, an eradication strategy to rid the Earth of mosquitoes (together with Zika virus and the malaria parasite), a weapon of mass destruction alongside North Korean nukes and Syrian chemical weapons, or the reproductive technology that will usher in an era of so-called designer babies. CRISPR was even featured in the recent comeback season of the X-files, in conjunction with aliens and a global pandemic. What could possibly unite all these divergent topics?

The common thread is DNA, and more specifically, an amazing new tool that makes editing DNA virtually as easy as the “find and replace” function in word processing software (check out this neat video for an animated explanation). Of course, scientists have had the ability to modify DNA in the laboratory for decades – even to synthesize entire microbial chromosomes from scratch. But using the CRISPR technology, it’s now possible to rewrite DNA inside living cells with the same kind of control and accuracy, and to tweak billion-letter genomes in almost every way imaginable: deleting genes, adding genes, inverting genes, repairing genes, even turning genes on or off. After three short years of research and development, scientists have been hard-pressed to find things that CRISPR can’t do.

shutterstock_353873630So what is CRISPR, anyway? Although the acronym alone won’t tell you much – CRISPR stands for clustered regularly interspaced short palindromic repeats – the story behind these repeats, and how they came to revolutionize biology, is pretty cool. The short version: after first being detected in E. coli in 1987, CRISPR remained a complete mystery for nearly two decades, until scientists studying yogurt-producing bacteria realized it was a type of antiviral immune system. Subsequent research in flesh-eating bacteria not only revealed how CRISPR naturally worked, but also how it could be redesigned and repurposed for DNA editing in other organisms. (You can read more about some of the breakthrough discoveries here and here.)

After the first reports surfaced in 2013 demonstrating successful editing of the human genome, the CRISPR technology was rapidly applied to a huge number of plants and animals, everything from common model organisms like rice and mice to more exotic species like broccoli and butterflies. Meanwhile, labs all around the world began using CRISPR because of its low cost and easy implementation. Today, even ordinary online shoppers can order do-it-yourself CRISPR kits to edit DNA in the comforts of their own home.

Having spent my PhD years studying CRISPR in Jennifer Doudna’s laboratory, starting well before the technology exploded, I’ve been mesmerized by the myriad ways in which DNA editing is transforming biological research. After all, DNA contains the blueprints for all living things, and we now have total mastery over these blueprints, to alter them in virtually any way that suits our needs or fancies. Yet with this newfound power also comes a responsibility to use it safely, and ethically.

Should CRISPR be used to alter the human genome for generations to come, by editing DNA in fertilized embryos? To create genetically engineered designer pets, such as miniaturized pigs or extra-muscular dogs? Or to spread new traits like malaria resistance or female infertility into wild insect populations? By removing many of the technical barriers that previously limited attempts at DNA manipulation, CRISPR has changed the question facing society from “If we could do it, would we want to?” to, “Now that we can do it, should we?”

Scientists and a wide range of stakeholders have already begun tackling some of the issues raised by CRISPR, and governmental officials are quickly following suit. In the U.S., within the next year or so, we can expect the announcement of an updated system for the regulation of genetically modified products, and a comprehensive study outlining recommendations for the responsible use of gene editing in humans.

There are reasons to proceed cautiously and prudently. But I hope that – even with all the concern surrounding CRISPR – we don’t lose sight of the incredible possibilities. In a medical first, DNA editing saved the life of a one-year-old girl suffering from leukemia last fall, and that may be just the beginning. Whether as a tool to expose the vulnerabilities of cancer, a therapy for patients afflicted with HIV/AIDS, or a cure for muscular dystrophy and sickle cell anemia, CRISPR offers real promise to solve some of the world’s most challenging diseases. Let’s see what a few more years of research can achieve.