Many scientists believe the biggest impact of CRISPR will come not in pharma but in farming. “The most profound thing we’ll see in terms of CRISPR’s effects on people’s everyday lives will be in the agricultural sector,” predicts Doudna.6 “The CRISPR craze has pretty much swept through plant biology,” agrees Dan Voytas, a professor at the University of Minnesota and cofounder of Calyxt.7 In 2017, state-owned ChemChina bought Syngenta, one of the top three agbiotech companies along with Germany’s Bayer and Corteva, for $43 billion. China is undertaking a massive effort to improve the quality of many key crops using CRISPR.8
Indeed, some commentators have been stressing this point since the birth of the CRISPR revolution in 2012-13. While most of the fanfare centered on CRISPR’s potential for treating human disease, some commentators, including British author and politician Matt Ridley, were struck by the implications for crops. Ten thousand years ago, farmers in what is now Turkey used cross-breeding to select a random mutation in wheat plants in the Q gene on chromosome 5A, which rendered the seed head less brittle and the seed husks easier to harvest efficiently.9
In 1798, English political economist Thomas Malthus published a famous treatise in which he showed that human population growth was outstripping the increase in agricultural productivity. The growing competition for resources leads inevitably to a Malthusian collapse caused by war, famine, or pestilence. In her book The Age of Living Machines, MIT president emerita Susan Hockfield argues that Malthus was wrong because of the repeated invention of new technologies that have increased agricultural productivity. One example was the introduction of four-field crop rotation, which succeeded (you guessed it) three-field crop rotation in the 18th century. Another is the extraordinary story of William Vogt and guano.
Vogt was an ecologist, ornithologist, and environmentalist, profiled in Charles Mann’s book The Wizard and the Prophet.10 Vogt (the prophet) discovered a natural resource—mountains of guano, or bird excrement, as birds roosted on the Chincha Islands off the coast of Peru. The nitrogen-rich guano was used for fertilizer, providing a large portion of Peru’s national income. In 1948, Vogt wrote about the earth’s “carrying capacity” caused by fundamental ecological processes that set limits on what we can do—or as Mann calls it, the first “we’re going to hell” book. After studying the cormorants and the weather patterns, Vogt concluded it was not possible to obtain more guano, “to augment the increment of excrement.” But as Hockfield points out, the export of guano to Great Britain caused another surge in agricultural productivity.
The wizard adversary to Vogt’s prophet was plant geneticist Norman Borlaug, the father of the Green Revolution. In the mid-1950s, Borlaug, an expert at interspecies hybridization, developed semi-dwarf wheat, which probably saved millions of lives after it was introduced to India in 1962, earning him a Nobel Prize. It now makes up 99 percent of all wheat planted around the world.
To speed up the generation of mutations, Lewis Stadler reported the first use of radiation mutagenesis to create novel mutations in plants in 1928. Half a century ago, scientists used a nuclear reactor to shoot gamma rays at barley seeds, inducing a plethora of random mutations in the DNA. One result was “Golden Promise,” a high-yielding, low-sodium barley variety popular with (ironically) organic farmers and brewers.
In the late 1970s, Mary-Dell Chilton, a researcher at Washington University in St. Louis, discovered that crown gall disease, a plant tumor, was caused by a bacterium called Agrobacterium inserting a sliver of its own DNA into the plant. That prompted the idea that the same bacterium could be used like a gene therapy vector to shuttle desired genes into plants. In January 1983, along with two other researchers, Chilton gave a talk at the annual Miami Winter Symposium, that she called “the symbolic coming of age of genetic engineering.”11 Indeed, Chilton is recognized as a pioneer of agricultural biotechnology and crop improvement. The method wasn’t called gene editing, but some did label it gene jockeying. Genes can also be introduced more directly, literally shooting them into plants as DNA-coated tungsten or gold particles with a gene gun.
Two decades ago, scientists at Syngenta inserted gene sequences from maize, encoding four enzymes into rice plants so that they could synthesize vitamin A, thereby creating transgenic “golden” rice. In Bangladesh, about one in five children are vitamin A–deficient. After interminable delays, the Bangladesh authorities are close to approving Golden Rice.
Anti-GMO activists may be aghast to learn that many of their favorite all-natural foods were in fact genetically modified by nature centuries or millennia ago. In 2015, scientists stumbled upon the fact that every domesticated breed of sweet potato contains DNA from the Agrobacterium. “All the sweet potatoes we eat are GMOs,” says Johns Hopkins’ professor Steven Salzberg.12 To that list, we can add bananas, cranberries, peanuts, walnuts, and two of my favorite beverages—tea and beer (hops).
To develop the new technologies that will feed almost 10 billion by 2050, not just accounting for our ballooning population but helping crops survive a changing climate, Hockfield says we’re going to have to invent our way out.13 CRISPR gave agricultural scientists a new razor-sharp tool in their gene-editing toolbox to complement if not supersede ZFNs and TALENs. The technology can prevent mushrooms browning, produce strawberries with a longer shelf life, and tomatoes that stay longer on the vine. Bing Yang’s group at Iowa State University has engineered promoter mutations to generate resistance to bacterial blight in rice.14 But for all the progress being made in Iowa cornfields, New York greenhouses, and Beijing rice paddies, scientists must also hope for some natural variation in the minds of regulators and politicians, especially in Europe.
For a serendipitous heirloom of our ability to engineer desirable traits in plants, exhibit A comes the Italian Renaissance artist Giovanni Stanchi. A Stanchi masterpiece from the mid-1600s depicts a selection of fruits—peaches, pears, and a watermelon cut open revealing contents that are almost unrecognizable. The flesh is mostly white, with pale red swirls and dark black seeds. It bears almost no resemblance to the succulent red flesh (the placenta) of the modern domesticated watermelon, as breeders selected for the lycopene-rich flesh.15
Go back even further to a few thousand years ago, the small fruit from southern Africa would have to be cracked open with a stone. A mere six varieties begat some 1,200 today. But humankind has been doing this since the dawn of agriculture almost 10,000 years ago. The domestication of maize from teosinte in Central America began when farmers in what is now Mexico practiced selective breeding. Corn today looks nothing like the “natural” crop. Nor do peaches or tomatoes or many other common fruits and vegetables.
But selective breeding only goes so far. “Nature hasn’t given us enough mutations,” says Zach Lippman, a leading plant geneticist at Cold Spring Harbor Laboratory (and an HHMI investigator). Lippman has had a peculiar fascination with tomatoes since he worked on a Connecticut farm as a teenager. Few consumers relish the anemic tomatoes typically available in the local supermarket. Lippman believes gene editing can lead to big improvements.
In 1923, researchers reported a natural mutation in a farmer’s field in Florida. Randomly, a rare mutant tomato plant had developed the property of self-pruning. Crossing these plants was predicted to give rise to “a valuable new race of early tomatoes.” These compact “determinate” varieties grow three to four months until they mature and ripen. A busy determinate tomato plant can give rise to twenty pounds of fruit and is the preferred plant for ketchup and paste production.