A Crack In Creation: A Nobel Prize Winner's Insight into the Future of Genetic Engineering

by Jennifer A. Doudna

disease-resistant rice, tomatoes that ripen more slowly, soybeans with healthier polyunsaturated fat content, and potatoes with lower levels of a potent neurotoxin.

Food scientists are achieving these improvements not with transgenic techniques—the splicing of one species’ DNA into a different species’ genome—but by fine-tuned genetic upgrades involving changes to just a few letters of the organism’s own DNA.

In laboratory-grown human cells, this new gene-editing technology was used to correct the mutations responsible for cystic fibrosis, sickle cell disease, some forms of blindness, and severe combined immunodeficiency, among many other disorders.

(Gene names are written in italics; the proteins they code for are in regular typeface. For example, the HTT gene codes for a protein called huntingtin; Huntington’s disease is caused by a mutation in the HTT gene.)

They concluded that a single cell in her body must have experienced an uncommon and usually catastrophic event called chromothripsis—a recently discovered phenomenon in which a chromosome suddenly shatters and is then repaired, leading to a massive rearrangement of the genes within it.

The human genome comprises about 3.2 billion letters of DNA,

The sick rabbits had much more arginase in their systems, and much less arginine, than healthy rabbits. What’s more, Rogers found that researchers who had worked with the virus also had lower-than-normal levels of arginine in their blood. Apparently these scientists had contracted the infections from the rabbits, and these infections had led to lasting changes in the researchers’ bodies as well.

A full 8 percent of the human genome—over 250 million letters of DNA—is a remnant of ancient retroviruses that infected ancestors of our species millennia ago.

or allow cells to soak it up spontaneously by bathing them in a specially prepared mixture of DNA and calcium phosphate.

this thing—CRISPR—referred to a region of bacterial DNA and that the acronym stood for “clustered regularly interspaced short palindromic repeats.”

more than 50 percent of the human genome—well over one billion letters of DNA—comprises different types of repetitive arrays, some of which are copied millions of times.

CRISPR-associated genes, or cas genes,

Matching RNA strands can pair with each other, forming an RNA-RNA double helix, but a single strand of RNA can also pair with a matching single strand of DNA, forming an RNA-DNA double helix.

gene drive, so called because it gives bioengineers a way to “drive” new genes—along with their associated traits—into wild populations at unprecedented speeds, a kind of unstoppable, cascading chain reaction.

That’s not to say it’ll be easy to get CRISPR to these locations, much less get it inside the cells themselves. This delivery problem is one of the greatest challenges that somatic gene-editing technologies will have to face.

(Remember that gene editing repairs mutated genes directly in the genome, whereas gene therapy splices new, healthy genes into the genome.)

The wonders of penicillin would never have been discovered had Alexander Fleming not been conducting simple experiments with Staphylococci bacteria. Recombinant DNA research—the foundation for modern molecular biology—became possible only with the isolation of DNA-cutting and DNA-copying enzymes from gut- and heat-loving bacteria. Rapid DNA sequencing required experiments on the remarkable properties of bacteria from hot springs. And my colleagues and I would never have created a powerful gene-editing tool if we hadn’t tackled the much more fundamental question of how bacteria fight off viral infections.