Seeing the Light

Photosynthesis. It’s one of the first lessons taught in any high school biology class, and yet we take this almost alchemical process for granted. The sun shines, oxygen and carbohydrates are produced, life on Earth is sustained. We’re surrounded by the evidence of photosynthesis’ success, from mighty redwood forests to the air we breathe or even the humble leaf of iceberg lettuce that adorns our sandwich.

It’s a surprise, then, to learn that photosynthesis isn’t really very efficient, often utilizing only 1 percent of available sunlight. Part of the reason is that plants live in the real world, not in the tidy equations of long-forgotten Bio 101 textbooks. Clouds pass overhead, wind blows branches in and out of sunlight, and many leaves are literally overshadowed by higher-tier foliage. Moreover, leaves are surprisingly vulnerable to damage from bright light, and plants have evolved a photoprotective mechanism, called nonphotochemical quenching (NPQ), that allows them to blow off energy from excess light in the form of heat.

“The problem,” says Professor Krishna Niyogi, chair of the Department of Plant and Microbial Biology, “is that plants are really good at turning on this photoprotection in bright-light conditions, but they turn it off much more slowly when they’re back in the shade.” As a result of this lag time, leaves don’t perform photosynthesis as effectively as they could; they dump valuable solar energy while constantly shifting between sun and shade throughout the day.

But what if there were a way to encourage plants to turn down the dimmer setting more quickly? Imagine the cumulative effect on an entire field of crop plants if you could coax just a little more production out of each individual leaf. Working with a far-flung team of co-researchers, Niyogi theorized that a fairly small genetic modification might increase the “relaxation rate” of NPQ in plants, allowing them to get back to photosynthesis more quickly. Theoretical modeling done by other labs suggested that this could increase crop yields in the neighborhood of 10 to 30 percent—some absolutely staggering numbers.

In 2007, Niyogi happened to run into fellow biologist Dr. Stephen Long of the University of Illinois at a conference, and they batted around ideas that eventually led to Niyogi’s applying for a National Science Foundation (NSF) grant. “They said it would never work,” Niyogi recalls, without any apparent hard feelings. “And we didn’t get funded.” To be fair, the idea of a 20 percent increase in productivity must have sounded a little far-fetched, given that increases in crop yield per acre by all other methods combined have plateaued at about 1 percent per year.

Fortunately for Niyogi and his team, the NSF wasn’t the only game in town. “We’re always looking for breakthrough discoveries,” says Katherine Kahn, senior program officer at the Bill and Melinda Gates Foundation (and an accomplished plant biologist herself). “We’d talked to scientists in the field and looked at the literature, and we were specifically interested in increasing photosynthetic efficiency.”

But at that point it wasn’t clear if the idea truly had real-world promise. Then Niyogi and Long suggested their approach, and, according to Kahn, “it was just an ‘aha’ moment for me and my boss. Their thinking was very clear about how to improve crops; they had a lot of modeling, some initial data, and a testable hypothesis.” The foundation made a five-year, $25 million investment, funding Niyogi and Long’s project—and a half dozen others—under the umbrella of its Realizing Increased Photosynthetic Efficiency (RIPE) project.

Moving from a promising model to large-scale success is complicated, but when the Gates Foundation gets involved, you can be sure that it won’t be satisfied with exciting theoretical musings. “We invest in projects that will result in agricultural transformation for smallholder farmers who need to get their families out of poverty,” says Kahn. For rural communities eking out a living in the developing world, increasing yields without increasing acreage could be a game changer.

Niyogi and his postdocs, Lauriebeth Leonelli and Stéphane Gabilly, began attempting to prove their concept with tobacco plants, not because they valued that crop, but because it is well studied and easily manipulated: the white mouse of botany. In the lab, they altered three genes that they hoped would speed up the time it took plants to recover from photoprotection. Using a technique called transient expression, the researchers changed discrete spots on individual leaves, which Niyogi described as “a high-throughput way of testing genes in combination so we can see the resulting phenotype on even just a small section of a leaf.”

For help with the fundamental science of how NPQ works, Niyogi collaborated with Berkeley’s Graham Fleming, a chemistry professor who specializes in ultrafast spectroscopic techniques of working with light on a nanoscale. “This is all so very complicated to study, because if you start pulling pieces out, nothing happens,” says Fleming. “It’s a whole system, and so doing these simplifying experiments is crucial.” Eventually the team developed stable plants that could pass the desired characteristics on to subsequent generations.

For the critical next stage of greenhouse and field work, the project shifted to the University of Illinois and Long’s lab. “The modeling predicted that we could get a 20 percent increase in yield,” says Long. “I’m not sure I was convinced that it would actually happen, though. Many considered that if there were a free lunch out there, evolution would have found it. Others had tried this with single genes or mutants, but ours was the first study to try this three-gene combination and take it from in silico prediction all the way through to testing with replicated field-plot trials.”

“This study is so remarkable,” says Niyogi. “The idea for speeding up the relaxation rate of NPQ came from a theoretical paper from 12 years ago out of Dr. Long’s lab. We came up with a way to accomplish this and did the proof-of-concept lab work at Berkeley, but we don’t have the growth facilities and fields that Illinois does. Neither of our labs could have done this on our own.”

Once the modified tobacco plants were allowed to grow in the field, the results were every bit as stunning as the modeling had predicted: a 14 to 20 percent increase in total dry weight per plant. “I should have had more faith in our modeling,” says Long. “But when we saw success in the greenhouse and then were able to replicate it in field trials, well…I’ve had a few lucky breaks in my career, but this is the biggest.”

The leap from a Berkeley laboratory to an Illinois test plot will be dwarfed by the next step: helping this technology to enter the agricultural mainstream. Luckily, that sort of scaling is exactly what the Gates Foundation does best. It requires that the projects it funds develop a global-access strategy that details exactly how the technology will be made available to those most in need in the developing world. “Sometimes that means partnering with the private sector,” says Kahn, in order to access the mass production and distribution channels enjoyed by for-profit companies.

First, of course, the project will have to expand beyond tobacco. “We should have an idea of how this works in rice within a year or so,” says Niyogi. And under the umbrella of the RIPE project, the Gates Foundation has been connecting American scientists with counterparts in Nigeria and Ghana in hopes of expanding the technology to cowpea, a highly nutritious legume common in West Africa.

The idea is not without its detractors, however. Plants altered in this way fit the definition of genetically modified organisms, which have become a hotly debated flash point. Niyogi and the others are sensitive to this concern, but remain confident that the process is safe. “We put in extra copies of a gene that is already present in the plant,” says Long, “so, while it is genetic engineering, we don’t have to introduce foreign material.” In the future, it may even be possible to get the same effect by editing promoter or repressor elements—basically, getting a plant to express more of a gene that it already possesses.

The Gates Foundation takes the 30,000-foot view, says Kahn. “Things look different in rural Tanzania versus Berkeley, where issues of economic survival are less prominent. We want to do whatever we can to help small farmers get what they need in a way that’s safe and that respects their choices.”

Beyond crop yield, the promise of the research extends to sustainability and food security. Climate change is already altering everything from cloud patterns to pest infestations; increasing yield per plant is an excellent way to stabilize overall production without putting more acres into cultivation. Even better, this increased caloric production doesn’t require more water—a huge benefit when dealing with drought and newly unstable atmospheric conditions. If these techniques prove effective for growing biofuels, the process might even reduce reliance on coal and oil.

The UN’s Food and Agriculture Organization has issued a warning that global food production needs to increase by 70 percent by 2050 to keep pace with the expanding population. Current technologies simply aren’t prolific enough to meet that large a goal in so short a time. And while increasing photosynthetic efficiency alone can’t solve all the world’s food problems, it’s clearly one of the most promising technologies on the horizon.

Such potential impact is a dream come true for many basic scientists, who rarely see the real-world application of their research. Fleming remembers some words of wisdom from his thesis adviser, who told him that “there’s no such thing as useless science—you just don’t know when it’s going to be applied.”

Niyogi agrees. “At the beginning of grant proposals, everyone always says, ‘If this all works, it will have massive applications,’” he says. “But I honestly never thought I’d see something this big come out of basic research. It’s what every scientist hopes for. It feels awesome.”