Brian Staskawicz (left) and Myeong-Je Cho stand among potted cacao trees growing in an Oxford Tract greenhouse.
Brian Staskawicz (left) and Myeong-Je Cho stand among potted cacao trees growing in an Oxford Tract greenhouse. 

(Not) The End of Chocolate

Berkeley researchers are working to safeguard the planet’s supply of cacao from disease.

A world without chocolate seems like a dreary place. But according to Brian Staskawicz, it’s not hyperbole to fear the confection’s extinction.

Chocolate, made from the cacao plant (cocoa is the powder, cacao the organism), is a combination of fermented and ground cacao beans, sugar, and milk powder that undergoes a labor-intensive process of drying, heating, and cooling before it melts in your mouth. Seventy percent of it comes from West Africa, mostly from Côte d’Ivoire and Ghana. But the crop is under siege—disease wipes out 20-30% every year, and now climate change is piling on. Excessive rains damaged last year’s harvest as did the ravages of Cacao Swollen Shoot Virus (CSSV), an infection spread by tiny insects called mealybugs. Once the plant is infected, cacao stems swell, leaf veins turn red, leaves turn yellow, and within three to four years the trees die. There is no cure. Reductions in supply last year made cacao a more lucrative commodity than bitcoin—good for investors but bad for your wallet—as prices soared. 

When the Innovative Genomics Institute (IGI)—a collaboration between UC Berkeley, UC San Francisco, and UC Davis—launched in 2015, saving chocolate was not top of mind. But when Staskawicz, a longtime professor in the Department of Plant and Microbial Biology, was recruited to apply genetic engineering solutions as head of the IGI’s Climate and Sustainable Agriculture program, he thought big and broad, well beyond the scope of staple crops. 

From left: Researcher Abigail Stevens, Brian Staskawicz, Myeong-Je Cho, and researcher Maxwell Vetterli examine a cacao plant in growth medium at the Plant Genomics and Transformation Facility.

From left: Researcher Abigail Stevens, Brian Staskawicz, Myeong-Je Cho, and researcher Maxwell Vetterli examine a cacao plant in growth medium at the Plant Genomics and Transformation Facility.

“If you can use this technology to save a consumer crop like chocolate that everybody loves, you’ll likely start to gain more acceptance of these methods,” Staskawicz tells me, leaning back in an office chair in a brightly lit conference room at the IGI building. He’s flanked by Myeong-Je Cho, director of the IGI’s Plant Genomics and Transformation Facility (PGTF)

“This is also one of the major crops for developing countries,” Cho says, reminding us that cacao provides the livelihood for about two million small-scale farmers in Côte d’Ivoire and Ghana, where they make only a few dollars a day.

The technology the pair speaks of is headlined by CRISPR, a form of genetic engineering pioneered by UC Berkeley professor and IGI founder Jennifer Doudna

The mouthful of a name (Clustered Regularly Interspaced Short Palindromic Repeats) refers to actual sequences of DNA found in bacteria that reflect past viral infections, but as Staskawicz explains, it’s more useful to think of it as “a natural immune system in bacteria” that we can adapt for our purposes. The gist: scientists hijack the DNA blueprint used to make antiviral molecules in bacteria and insert them into a host organism’s DNA so that it can either defend itself from viruses or alter the host’s DNA to produce other desirable traits.

CRISPR is a game changer. Staskawicz and Cho see it as their powerhouse weapon in the fight to improve global food security. While Earth’s population will eventually decline given current models, it will peak around ten billion sometime after 2050—a lot of mouths to feed in a volatile climate that threatens food supply. IGI researchers apply CRISPR to wheat and rice to address this challenge, along with specialty crops like tomatoes and cacao. 

“I don’t think people understand that we have a serious problem,” Staskawicz warns. “Once you don’t have food, you don’t have food security, and that will cause wars. People will start invading to get food.” 

The cacao challenge

Over the course of an hour, Staskawicz and Cho give me a crash course in genetic engineering, patiently walking me through the basics and turning the knob to eleven only when necessary. Staskawicz’s pedagogical instincts have been honed throughout a half century during which entire disciplines have been invented. He got his PhD studying disease in bean plants at Berkeley in 1980 and returned three years later as an assistant professor. 

Cho also bleeds blue and gold, having worked under legendary Plant and Microbial Biology professors like Bob Buchanan and Peggy Lemaux for more than a decade during the 1990s and mid-2000s. He also spent several years in industry, co-founding Byotix, Inc. and later working for DuPont Pioneer (currently Corteva Agriscience). Shortly after Doudna tapped Staskawicz to run point on IGI’s agricultural genomics program, Cho arrived to head up the PGTF’s research efforts. And then, chocolate came knocking. 

With CSSV decimating cacao trees in West Africa, it’s getting more difficult for farmers to grow the amount of cacao that chocolate producers need. Mars Inc.—producer of Snickers, Twix, and many other popular sweets—approached IGI about potential opportunities. 

But cacao presented some major problems. It’s a finicky, slow-growing plant in vitro, and unlike wheat and rice, it’s highly genetically diverse, meaning it can’t be bred easily from seed in the lab. However, to produce plants that are genetically identical to the parent, it can be propagated through somatic embryogenesis, a process that involves reproducing plants from just a tiny piece of flower petal or staminode tissue. After this process, the researchers infected the tissue with Agrobacterium, using it as a sort of Trojan horse to smuggle DNA into the genome of their test plants. Whole plants were later regenerated from these infected tissues. Tissue from these whole plants glowed when placed under a fluorescence microscope, verifying that the gene had been successfully delivered.

“It was extremely difficult,” Staskawicz says. “It took more than a year to actually regenerate a cacao plant.” The IGI is now one of only a few institutions in the world capable of successfully transforming and editing the cacao genome and growing the plants in culture.

Once this genetic transformation was established, the researchers put Agrobacterium to work once again, this time packaging it with the CRISPR machinery that would arm cacao with defense against CSSV.

Gene edited cacao plants start as a tiny propagation from a flower petal or staminode tissue, then mature in growth medium before they are planted in soil and eventually become full-size cacao trees over 15 feet tall.

Gene edited cacao plants start as a tiny propagation from a flower petal or staminode tissue, then mature in growth medium before they are planted in soil and eventually become full-size cacao trees over 15 feet tall.

Saving Chocolate

After an hour of discussion, Staskawicz and Cho are eager for me to see the actual work—the plants and the science in action. A few minutes later we’re on the move in the IGI halls. Cho ushers me into the main lab, a bright chamber packed with flow hoods, lab benches, microscopes, and researchers. Here and in multiple walk-in growth chambers are cacao plants in various stages of growth, from the early stages of a tiny green leaflet with squiggly brown roots sitting in a Petri dish to the bright green cluster of a potted plant.

The team’s first major CRISPR experiment with cacao is nearing completion. Based on the known genome of CSSV, they designed a guide RNA sequence that is complementary to the virus’ DNA, which they packed with the DNA code for a type of molecular scissors, a protein called Cas9, in a single cell of Agrobacterium, which acts as genetic engineering’s FedEx. The team inoculated young cacao plant tissue with the Agrobacterium and its CRISPR package; the cacao cells took up the package, and the Agrobacterium inserted its deliveries into the cacao genome. When the plants are infected with CSSV, if all works as planned, the guide RNA will allow the cacao to detect and bind to the invader, and the Cas9 protein will chop it up, destroying the virus.

Image of Myeong-Je Cho at the Plant Genomics and Transformation Facility

Myeong-Je Cho sits at a fluorescence microscope in the Innovative Genomics Institute's Plant Genomics and Transformation Facility.

Plants in the Oxford Tract greenhouse—some now nearly 13 feet tall—are almost large enough to be transferred to a Mars facility where they’ll be tested by collaborators there for virus resistance. 

In addition to these experiments, the team has plans to use CRISPR to knock out a gene in the cacao genome, enabling broad disease resistance.

The toughest challenge may not be viruses like CSSV, but public perception itself. “We don’t want to make the same mistakes as GMOs,” Staskawicz says. “There was a lot of public backlash and fear of Frankenfood.” Debate continues over whether or not CRISPR-edited crops should be labeled as GMO; generally speaking, GMO is reserved for the introduction of DNA from an unrelated species into a host’s genome, and technically the CRISPR machinery, derived from bacteria, fits this definition. But there’s the potential to remove the CRISPR molecules after the gene editing phase post-edit—a set of experiments Staskawicz is eager to start. 

The team at the IGI knows that winning the war on climate change and food insecurity means gaining the confidence of the general public, and they have dedicated an entire arm of the operation to public impact. The IGI’s Public Impact team is focused on fostering meaningful dialogue with diverse stakeholder communities, providing free educational resources, promoting responsible governance, and ensuring equitable access. 

Overcoming CSSV in a way that is palatable to consumers will go a long way toward securing chocolate’s future, but other challenges remain—like another insidious disease threat called black pod rot and local government policies in West Africa fixing prices for farmers. The tools and willpower appear to be there from groups like the IGI. If they succeed, Halloween will remain flush with chocolate for generations to come.