Zach Lippman has big plans for agriculture

Cold Spring Harbor researcher Zach Lippman's work on producing bigger tomatoes will one day help feed a hungry world.

By GREGORY ZELLER // You say “tomato.” Zachary Lippman says “scientific breakthrough of global importance.”

He doesn’t literally say it, of course. The associate professor at Cold Spring Harbor Laboratory is too professional a scientist to jump to such grandiose conclusions.

But Lippman’s research on stem cell production in tomato plants has already produced supersized fruits. It’s already attracted the attention of commercial-scale breeders. And it appears to extend to other seed-bearing fruits and even some vegetables – potentially changing the way humanity cultivates its crops.

“It could have a dramatic effect on fruit production around the world,” Lippman told Innovate LI.

The scientist’s attempts to breed a better tomato stem from gene-manipulation work he started as an undergrad at Cornell University, where he majored in genetics – specifically, the science of breeding plants. After Cornell, Lippman earned a PhD in epigenetics at CSHL’s Watson School of Biological Sciences, focusing specifically on how DNA and genes are regulated by nearby proteins.

His work at the Watson School followed in the footsteps of one-time CSHL scientist Barbara McClintock, a mid-20th century geneticist who was awarded the 1983 Nobel Prize for Medicine for her discovery of genetic transposition. In layman’s terms, McClintock discovered “jumping genes,” which can create or reverse mutations in a DNA sequence.

“I was studying how they control and regulate the activity of nearby genes once they jump into the region near those genes,” Lippman said.

This focus led to three years of postdoctoral work in Israel, where Lippman turned his attention to manipulating stem cells in flowering plants, learning to manipulate the genes that control the production of branches where flowers are produced.

Ultimately, he chose to focus on tomatoes, a ripe subject for gene manipulation since it’s “a plant that happens to be a crop where flower production happens to be the driving factor for yield,” the scientist noted.

Zachary Lippman: Really big tomatoes first, then a host of oversized fruits and vegetables for a hungry world.

Lippman and genetically improved tomatoes.

“What I found were several genes that can control the architecture of those branches,” Lippman said. “Basically, we can increase the number of flowers by increasing the number of branches. Once we learned about those genes, the question became, how can we translate that into actual crop production?”

The manipulation of stem cells in plants involves two sets of genes, known as WUSCHEL genes, which promote stem cell formation, and CLAVATA genes, which inhibit stem cell production. When CLAVATA genes are working properly, they send signals to the WUSCHEL genes to slow down stem cell production – but when the CLAVATA are mutated, the WUSCHEL keep producing stem cells, leading to side effects like abnormal fruit growth.

The science, naturally, is much more involved. But the basic bottom line for Lippman and his CSHL team – including postdoc researchers from Mexico, China, South Korea and the United States – is that stem cell control repeatedly produced tomatoes of abnormally large size.

Don’t expect any pumpkin-sized tomatoes, however. “We’re not going after records,” Lippman warned. “If you make too large a fruit, you’re going to compromise the balance of growth in the plant and wind up with a plant that’s not useful as a breeder.

“You don’t want to swing the pendulum too far to the left or the right,” he added. “You have to find the sweet spot.”

His gene-manipulation work is “more about understanding the process of stem cell production so we can fine-tune it and control it,” Lippman said. By fine-tuning the number of stem cells produced, breeders can control the fruit size, and this is all about “having a set of tools that will allow a breeder to accurately predict fruit size.”

Even if he’s not growing tomatoes the size of beach balls, Lippman’s research is extremely promising to a world hungry for agricultural advances. The World Food Programme, the world’s largest hunger-focused humanitarian organization, estimates that 795 million people – one out of every nine on the planet – don’t have enough food to lead healthy lives.

Roughly 13.5 percent of the combined populations of all developing countries is undernourished, while 45 percent of deaths of children under the age of 5 are caused by malnutrition – some 3.1 million global deaths per year, according to the WFP.

The Borgen Project, an international nonprofit tackling global hunger issues, lists agricultural transformations – specifically, the creation of sustainable food sources – as its No. 1 solution. Other organizations, including the Farming First Coalition, champion agricultural solutions to global hunger issues.

Breeding “beefsteak” tomatoes – once considered freak occurrences of nature – and accurately predicting their numbers irrefutably serves these efforts. And perhaps most promising of all, Lippman’s gene manipulations aren’t limited to tomatoes; he specifically noted potential supersizing of not-too-distant tomato relatives including peppers, eggplants and soybeans.

“The principles for fine-tuning stem cell production are going to be applicable to other crops,” Lippman said. “The way you fine-tine them may not be identical, but the principle will be conserved.”

For now, his team will continue breeding small batches of genetically manipulated tomatoes at a tiny field about a half-mile from CSHL and on five acres the lab leases at Cornell’s Long Island Horticultural Research & Extension Center in Riverhead. While the team is “collaborating with a major breeding company,” Lippman is not yet close to announcing any commercial deals – the science still has some growing to do, he noted, because “there’s more than one way to skin the cat.”

“In one variety, a specific subset of tools will get the job done,” Lippman said. “In another variety, it’s going to be a different set of tools. We need to expand the toolkit. That’s going to be the big push for the next several years.”

Even when the science becomes commercially viable, its target market – producers who are used to “breeding blindly,” Lippmann noted – will likely take some convincing.

“The divide is going to be convincing a breeder to listen to a geneticist who works in a laboratory,” he said. “I believe that this is going to be adopted as a set of tools in the future, but for now we’re still trying to prove these principles and get the science into applied pipelines.

“The proof is in the pudding,” Lippmann added. “We’re going to produce our own high-yield varieties and go knock on their doors and say ‘this is what we’ve done.’”