The Perils and Promises of Gene-Drive Technology

What if, with a wave of the wand, we could eliminate some of the world’s most devastating causes of illness and death? First, we might fight over which of our many maladies causes the most harm. Cardiovascular disease kills more people every year than any other, but it almost always develops over a lifetime: heart attacks may be sudden, but their causes are not. H.I.V./AIDS is another worthy candidate; it claims more than a million lives each year, and nearly forty million people are currently infected.

But my vote would go to malaria. Despite progress in reducing infections and deaths over the past decade, malaria still kills as many as half a million people a year, most of whom are under the age of five. They are invariably the poorest people in the world. Nearly two hundred million people become infected every year, and almost half of the planet’s population lives in areas in which the anopheles mosquito, malaria’s carrier, thrives. The global economic burden of the disease—including the impact on impoverished families from time lost at work, at school, and on the farm—is, as it has always been, nearly incalculable.

The magic wand is now within reach. It is called a gene drive, and it works by overriding the traditional rules of genetic inheritance. Normally, the progeny of any sexually reproductive organism receives half its genome from each parent. For decades, however, biologists have been aware that some genetic elements are “selfish”: evolution has bestowed on them a better-than-fifty-per-cent chance of being inherited. But, until scientists began to work with CRISPR, which permits DNA to be edited with uncanny ease and accuracy, they lacked the tools to make those changes.

Then the evolutionary biologist Kevin Esvelt, who runs the Sculpting Evolution Group at M.I.T.’s Media Lab, realized that, by attaching a gene drive to a desired DNA sequence with CRISPR, you could permanently alter the genetic destiny of a species. That’s because, with CRISPR, a change made on one chromosome would copy itself in every successive generation, so that nearly all descendants would inherit the change. A mutation that blocked the parasite responsible for malaria, for instance, could be engineered into a mosquito and passed down every time it reproduced. Within a year or two, none of the original mosquito’s offspring would be able to transmit the infection. And if gene drives work for malaria they ought to work for other mosquito-borne diseases, such as dengue, yellow fever, and Zika.

This is tremendously promising news, but nothing so powerful comes without risk—and there has never been a more powerful biological tool. Esvelt hopes to use the very power of gene-drive technology as a lever to force scientists to make their work more accessible than it has ever been. It should be possible to eliminate a variety of illnesses: editing white-footed mice, for example, so that they are resistant to tick bites or the pathogen that causes Lyme disease would make them incapable of passing the infection along to us (or other species). And, by vanquishing invasive species and saving those that are endangered, gene drives could alter entire ecosystems.

As a worthy, if somewhat tepid, report released this week by the National Academies of Sciences, Engineering, and Medicine stresses, research needs to move forward, but deliberately and openly. Communities that could be affected—and, eventually, that would include us all—need to be engaged before experiments are designed, or even seriously contemplated.

Pretty soon, we are going to have to make some of the most pressing decisions we have ever made about how, whether, and when to deploy a new technology. The science and some of the researchers may be ready, but society clearly is not, and these decisions are far too consequential to be left to scientists alone. Once released from the laboratory, an engineered organism might be difficult to contain in the wild. Its new genes might have unintended consequences. People who express fears over G.M.O. crops often worry about what might happen if the modified genes spread throughout the environment, to other organisms. This has proved to be a baseless concern, but altering the environment would be the entire purpose of introducing a gene drive. Why else use one?

The pioneering geneticist George Church, who has joint appointments at Harvard Medical School and M.I.T., and was Esvelt’s mentor, has told me that he considers it essential to design reversal mechanisms for any gene drive. If you can edit genes, you ought to be able to restore them to their original condition.

This is not a trivial matter, and I have not encountered a single scientist who fails to understand the stakes. Fear of new or altered technologies is common. People were reluctant to get into elevators when operators began to be superfluous. Driverless cars will present similar anxieties. Gene drives, too, have many people worried, and not without reason. Until we do it, we simply cannot know the full impact of releasing a mosquito that is unable to carry the parasite that causes malaria. By the time we realize the consequences, it could be too late to turn back. Organisms do not always behave in the wild the way they do in the perfectly controlled environment of a laboratory.

In the case of gene drives, the fear is warranted—but we also need to contemplate the horrific cost of doing nothing. Malaria, dengue, yellow fever, and now Zika, among other vector-borne diseases, are responsible for untold suffering. Tens of millions of lives have been destroyed by a mosquito bite. What are we willing to risk to make that stop?


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