In 2003, Austin Burt, an evolutionary geneticist at Imperial College London, proposed a more finely tuned approach called a homing endonuclease gene drive, which would zero in on a specific section of DNA and alter it.

Burt mentioned the potential problem of resistance—and suggested some solutions—both in his seminal paper and in subsequent work. But for years, it was difficult to engineer a drive in the lab, because the available technology was cumbersome.

With the advent of genetic engineering, Burt’s idea became reality. In 2012, scientists unveiled CRISPR, a gene-editing tool that has been described as a molecular word processor. It has given scientists the power to alter genetic information in every organism they have tried it on. CRISPR locates a specific bit of genetic code and then breaks both strands of the DNA at that site, allowing genes to be deleted, added or replaced.

CRISPR provides a relatively easy way to release a gene drive. First, researchers insert a CRISPR-powered gene drive into an organism. When the organism mates, its CRISPR-equipped chromosome cleaves the matching chromosome coming from the other parent. The offspring’s genetic machinery then attempts to sew up this cut. When it does, it copies over the relevant section of DNA from the first parent—the section that contains the CRISPR gene drive. In this way, the gene drive duplicates itself so that it ends up on both chromosomes, and this will occur with nearly every one of the original organism’s offspring.

Just three years after CRISPR’s unveiling, scientists at the University of California, San Diego, used CRISPR to insert inheritable gene drives into the DNA of fruit flies, thus building the system Burt had proposed. Now scientists can order the essential biological tools on the internet and build a working gene drive in mere weeks. “Anyone with some genetics knowledge and a few hundred dollars can do it,” Messer said. “That makes it even more important that we really study this technology.”

Although there are many different ways gene drives could work in practice, two approaches have garnered the most attention: replacement and suppression. A replacement gene drive alters a specific trait. For example, an anti-malaria gene drive might change a mosquito’s genome so that the insect no longer had the ability to pick up the malaria parasite. In this situation, the new genes would quickly spread through a wild population so that none of the mosquitoes could carry the parasite, effectively stopping the spread of the disease.

A suppression gene drive would wipe out an entire population. For example, a gene drive that forced all offspring to be male would make reproduction impossible.

But wild populations may resist gene drives in unpredictable ways. “We know from past experiences that mosquitoes, especially the malaria mosquitoes, have such peculiar biology and behavior,” said Flaminia Catteruccia, a molecular entomologist at the Harvard T.H. Chan School of Public Health. “Those mosquitoes are much more resilient than we make them. And engineering them will prove more difficult than we think.” In fact, such unpredictability could likely be found in any species.

The Cornell group used a basic mathematical model to map how evolutionary resistance will emerge in a replacement gene drive. It focuses on how DNA heals itself after CRISPR breaks it (the gene drive pushes a CRISPR construct into each new organism, so it can cut, copy and paste itself again). The DNA repairs itself automatically after a break. Exactly how it does so is determined by chance. One option is called nonhomologous end joining, in which the two ends that were broken get stitched back together in a random way. The result is similar to what you would get if you took a sentence, deleted a phrase, and then replaced it with an arbitrary set of words from the dictionary—you might still have a sentence, but it probably wouldn’t make sense. The second option is homology-directed repair, which uses a genetic template to heal the broken DNA. This is like deleting a phrase from a sentence, but then copying a known phrase as a replacement—one that you know will fit the context.