May 30, 2024

Proof of concept is a video series profiling the science and scientists behind some of the environment’s most unexpected research.

Almost all life on Earth – plants, animals, humans – largely owes their entire existence to one microscopic protein. It’s called ribulose bisphosphate carboxylase/oxygenase, better known as RuBisCO, and it’s an enzyme: a biological machine that helps turn CO2 into energy.

Of the millions of enzymes on earth, RuBisCO is perhaps the most important. It is essential for photosynthesis, and without it plants will not be able to grow. Without RuBisCO, almost all life on Earth would starve.

But even though it’s everywhere, and has been around for billions of years, RuBisCO is kind of his job. And it’s getting worse as the world warms.

Today, a global team of scientists is trying to achieve something that evolution could not do before: building a better RuBisCO.

RuBisCO was kind of discovered by accident. It was the 1940s, and called an aimless grad student Sam Wildman came across a newly released book on botany in his university library. The book described a simple way to get protein from leaves, using common laboratory ingredients. Curious, and maybe a little bored, Wildman started messing around in the lab.

When he adds a certain chemical to the spinach juice, a giant cloud of protein will appear. He didn’t know it at the time, but that cloud was RuBisCO. He has just discovered the enzyme that is directly responsible for taking CO2 from the air and starting photosynthesis. He also had no idea that that cloudy test tube contained a clue that would haunt scientists for the next eight decades.

Two test tubes, one full of green liquid and the other full of liquid with green particles floating on top and clear liquid below
A cloud of RuBisCO extracted from spinach leaves forms inside a test tube.
April Wu

You can think of photosynthesis like a huge assembly line that takes in CO2 and turns it step by step into food. Each stop on the assembly line is an enzyme: tiny biological machines that each perform a step. And if they all work together, the plants can soak up a lot of carbon, make a lot of food, and the whole operation runs like clockwork.

Unfortunately, this is not what happens, because of one incompetent enzyme: RuBisCO. The first problem is that it is very slow, hundreds of times slower than many other enzymes. And it ends up slowing down the entire factory, resulting in much less food.

Second, it makes a lot of mistakes. Instead of grabbing CO2, RuBisCO will often grab an oxygen molecule. This wreaks havoc on the assembly line, and the entire operation must go into cleanup mode. This happens so often that plants waste nearly a third of their energy correcting this sloppy mistake.

Finally, this enzyme performs even worse during hot weather. This means that as climate change warms our planet, our farms may produce less food, and our plants may become worse at sequestering carbon.

In the face of all these problems, plants have developed an incredible temporary solution:

They just make tons and tons of RuBisCO. That’s why there was so much of that cloudy protein in Sam Wildman’s test tube. RuBisCO alone makes up almost half of the protein in leaves of spinach and many other plants.

Soon after its discovery, scientists began to wonder if a better RuBisCO was possible. They envisioned futuristic plants that could produce higher yields and absorb more carbon. They saw it as a way to feed the world’s growing population, and the billions more to come—not through bigger farms or more fertilizer, but by improving the fundamental nature of plants.

On the other hand, neither billions of years of evolution nor decades of scientific research have solved RuBisCO’s problems. For some, this is a sign that a better RuBisCO is not possible. The lack of progress seems so hopeless that one source told me that scientists are sometimes reluctant to even admit that they are working on this challenge.

But not everyone sees it that way. Robbie Wilson is a research scientist and self-described “rubicologist” at the Massachusetts Institute of Technology. He is one of the scientists who see this evolutionary paradox as more of a challenge. Wilson is part of an international collaboration that aims to develop a better RuBisCO – not in a field, or even a greenhouse, but in a petri dish of bacteria.

A man with a beard and long hair wearing a white lab coat looking at samples in a lab
Robbie Wilson is a research scientist studying RuBisCO at MIT.
Jesse Nichols / Grist

Evolution usually takes place over millions of years. But with bacteria, scientists can speed up this process. Bacteria are fairly easy to genetically modify, meaning scientists can actually design their own sequences instead of waiting for random mutations. And their generations are only about 25 minutes long. “I would say it makes it a million times better — maybe a billion times easier — to work with bacteria,” Wilson said.

That’s what’s so special about Wilson’s technique: He found a way to engineer bacteria to create and test thousands of different versions of RuBisCO in the lab. Just as in nature, where threats such as predators and disease drive species to develop certain strengths, Wilson’s designed a special laboratory environment to push the bacteria to develop better forms of RuBisCO.

Once each bacterial colony produced a slightly different version of RuBisCO, Wilson and his team essentially poisoned the bacteria. The poison comes from a second enzyme, called phosphoribulokinase, or PRK.

A petri dish with writing and some very small red dots on it
Genetically engineered bacteria grow in a petri dish at MIT.
Jesse Nichols / Grist

Like RuBisCO, this enzyme is an important part of photosynthesis in plants. In nature, PRK produces a chemical that RuBisCO needs to do its job – to capture carbon and turn it into food. But in the petri dish, that same chemical can be deadly. The bacteria are not designed for photosynthesis, so unless RuBisCO acts quickly, that chemical will just build up until it eventually kills the entire colony of bacteria.

RuBisCO is essentially an antidote to this poison. The better the RuBisCO, the healthier the bacteria.

On a recent visit to Wilson’s lab at MIT, I watched as he removed two petri dishes from the experiment. This first petri dish contained RuBisCO that you would find in nature – which was not very good, so the petri dish was empty. The second petri dish was full of bacteria with new versions of RuBisCO. That dish was covered with small dots. Those bacteria colonies survived because their new RuBisCO enzymes worked very well.

Wilson saw evolution—but it happens in hours instead of millions of years.

Once the team has identified the best candidates in the petri dish, they need to see if the new versions of RuBisCO actually work in real plants. With a syringe, they inject the new DNA into the plants. You can actually see the liquid spreading through the leaf. Those plants will continue to produce the brand new versions of RuBisCO, and Wilson’s team will see if they actually grow better in the real world.

hands wearing purple gloves inject a liquid into a leaf
A scientist injects new DNA into a leaf at the Whitehead Institute greenhouse at MIT.
Jesse Nichols / Grist

Although it’s still a long process from the lab to the field, Wilson hopes that this project can finally demonstrate that a better RuBisCO is actually possible. “I’m secretly pretty confident that we’re going to change the way people think about RuBisCO’s engineering potential, which is going to have huge implications for ongoing research,” he said.

But as important as improving RuBisCO is, it is only one part of the enormous effort to develop more productive and climate-resistant crops. Right now, other scientists are devising ways to make plants that can capture more colors of sunlight, or dreaming up projects that build on the natural solutions that certain plants have developed to circumvent RuBisCO’s weaknesses.

“There have been very encouraging results from many other projects that have made me very excited,” Wilson said. “I think if all of these can be combined together, we’re going to have something very special.”

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