The Woman Behind the GMO
Two heads hovered over the lab bench. “It worked,” Myeong-Je Cho said, pointing to a single, fuzzy black band on the freshly printed paper. The size of a paper clip, it was what every geneticist hoped to see. The results indicated that his gene had made it, “transformed,” into the cell. Cho, a postdoc at the University of California, Berkeley in 1996, came there to work with one of the leaders in genetic transformation. He stepped aside so the expert, his supervisor, could see the results for herself.
Peggy Lemaux’s green eyes flicked from the paper to Cho with the glimmer of scientific discovery.
Prior to her arrival at UC Berkeley in 1991, Lemaux earned her degree in Microbiology from the University of Michigan. She now works as a crop biotechnology Cooperative Extension Specialist for UC Berkeley. Before joining the university, she did a stint in corporate agriculture, working at DeKalb Genetics Corporation, a seed company in Illinois. In the year leading to her transfer to UC Berkeley, she was among the first scientists to successfully insert DNA into corn that could be grown and fed to people. Other teams were racing to achieve what she had accomplished, but she chose to leave it behind.
Lemaux was never drawn to Big Ag. Her relationship to agriculture was much more intimate than that. On her grandfather’s Ohio truck farm, she recalls individually inspecting each strawberry for picking. Those fields were fertile soil for cultivating both discipline and curiosity. She was fascinated with growing plants and making food and she attributes that wonder to inspiring her career. “Neither of my parents had any formal training at all,” she says. “So somehow it just came up out of the farming, and connecting with the land, and being able to see how things grow.”
From mounds of soil, she constructed her own ant farms and searched for worms the way other kids looked for prizes in the cereal box. Unlike other kids, Lemaux didn’t have store-bought cereal at home. She butchered the family chickens, and her mother canned and froze the food that they grew and raised. “When you live on a farm… it does sensitize you to what it means to have stuff in a grocery store,” Lemaux said.
From her humble beginnings, Lemaux entered biotechnology with wide-eyed optimism. “We were very naive,” recalled DuPont researcher Dr. Bill Gordon-Kamm about his earlier work with Lemaux at Dekalb. “We came from a generation of Peace Corps hippies and we wanted to help feed the world. That was our motivation for getting into plant biotechnology.”
As Lemaux noticed the trajectory of industry at that time, she saw that it didn’t align with her aspirations. That decade, Monsanto Company of St. Louis, Missouri purchased 13 seed companies across the nation, consolidating genetic technologies in corn and soy. When she heard the corporation was approaching, Lemaux quit Dekalb, leaving her research and findings behind. She had no say in whose hands it would end up.
In 1991, Lemaux transferred from industry to UC Berkeley, hoping that academia would allow her to gain more autonomy over her research. Monsanto went on to buy Dekalb in 1998, and Lemaux’s technology along with it, for $2.3 billion following anti-trust scrutiny by the U.S. Justice Department. Today, over 90% of U.S. corn is genetically modified, or GM.
At the university, she struck a balance between academia and industry in a collaboration between the university, the U.S. Department of Agriculture (USDA), and two industry partners, Coors Brewing Company of Golden, Colorado and Applied Phytologics, a Sacramento-based startup that synthesized pharmaceutical and industrial proteins from genetically-engineered plants. Her team from the university included her postdoc, Dr. Cho, and her colleague, Dr. Bob B. Buchanan, a biochemist and leading expert on photosynthesis at UC Berkeley. They shared their work with the researchers at Coors and Applied Phytologics founder, Frank Hagie, a lawyer with prior experience in biological research.
These different parties were brought together by the UC BioSTAR Program, which partners UC scientists with California businesses funding collaborative research projects. If Lemaux was going to use her technology for real-world applications, she’d need industry funds to do so.
“It is hard to get funding for real applied research… because it costs so much to go through the regulatory [process],” Lemaux recently explained. “If it’s applied, you really have to have a corporate partner, because you can’t afford to do it otherwise.”
With the necessary funds, she was able to genetically modify barley into sprouting two days earlier than the conventional grain. This sped up the brewing process and would potentially save millions of dollars and energy. But Coors turned it down.
The company was undergoing management changes and layoffs that cut into the research department. Meanwhile, a controversial study from 1999 suggested that GM corn endangered the monarch butterfly. The Coors Research and Development team “felt the sentiment of the country at the time,” said Berry Treat, who was head of Coors’ barley malting research. “That’s about the time that marketing said, ‘You’re not putting this in our barley, are you?’” Amidst the mounting stigma against GM foods, Lemaux observed a second transformation in the Big Ag landscape. A wave of negative press swept across the nation, pitting the public against the manufacturers, including Monsanto. Coors did not respond for comment.
But Lemaux didn’t let negative press, GMO stigma, or regulatory costs deter her. She was determined to help farmers like her family and she knew not to let labels define her. As a woman pursuing science, she says she encountered obstacles from high school through her PhD. “Being a woman in science is tough,” remarked Hagie. Speaking from his experience as a biotech executive and a scientist, he noticed, “Historically, women have been held to a standard… different from the standard of men.” Stereotypes aside, he observed that “men are hired and retained and promoted based on what we think they can do, whereas women have to go an extra step and say what they’ve already done.” Undeterred, Lemaux wouldn’t let gender labels interfere with her goals.
Nor would she let politicized views of genetic modification deter her work.
She proceeded to push into a new domain of research. Rather than raise yields or speed up growth, she shifted to a medicinal focus, an idea sparked by Buchanan.
‘Gluten-free’ wheat. It sounded like an oxymoron, but he theorized that he could solve the problem of gluten allergies and celiac disease.
He knew that wheat seeds naturally produced a protein called thioredoxin. And from his chemistry knowledge, he recognized that thioredoxin could break the bonds that hold together wheat and normally make it difficult for those who are allergic to digest it.
To generate this chemical reaction, Buchanan needed the wheat seed to produce more thioredoxin. This meant he had to genetically modify the wheat by “transforming” genes with those specific instructions into the wheat. He needed a transformation expert in cereals, so he turned to Lemaux.
Together, they set out to make a hypoallergenic wheat.
They turned to Cho for his expertise in gene expression: getting the thioredoxin production in the right places, at the right time, and in the right amount within the wheat seed. “Bob and I were involved in conceiving that, and then Myeong-Je was the one that made it happen,” Lemaux explained. The trio was thrilled with Cho’s success and eager to share it with others. They submitted the research for publication and a lab member was scheduled to present it to the public for the first time on September 30, 1997.
One day prior to the presentation, Lemaux rounded the corner of the hallway near her UC Berkeley lab, manuscript in hand, and ran into Hagie.
Lemaux showed him the manuscript and recalls excitedly telling Hagie about her recent work. Hagie became excited. Up until that moment, his company hadn’t figured out how to reliably mass produce its proteins. Hagie realized that Lemaux was, literally, holding the answer to his problem in her hand. He interjected, “Everybody’s racing to get the results, and you’ve got it,” he told her.
Having stepped away from industry for so long, Lemaux was winning yet another race, but this time, she hadn’t realized it. He told her that her invention needed to be patented, but she ran out of funding. Hagie offered to pay for it, and in the middle of the hallway they came up with a plan to exclusively license the technology to Applied Phytologics in exchange for the patent filing funds.
At that moment, the clock started ticking.
Frank fumbled for the small keypad on his heavy, 90s-era cell phone. Once the lab member delivered the presentation, the research would be public knowledge and unpatentable. He dialed the university’s Office of Technology Licensing to get the final go-ahead on filing the patent.
Lemaux rushed down the hall to update Buchanan, and Hagie raced to his office. He dialed a second number to his patent attorney and the two worked till 4 a.m. to finish paperwork that often took more than three weeks. He dropped it off in the outgoing mail basket and the provisional U.S. patent application was filed on the 30th, just in time.
One year later, an international patent application titled “Production of proteins in plant seeds” was filed, naming the inventors Peggy G. Lemaux, Myeong-Je Cho, and Bob B. Buchanan; and the applicant The Regents of the University of California. It took five years for the application for the U.S. patent to be granted. And it took almost ten years for other American and European attorneys to secure the European patent.
Hagie spent those five years pitching the technology to potential investors in an attempt to bring it up to industrial scale at his company.
With Applied Phytologics as their corporate partner, the research trio continued making and testing their seeds.
The additional support allowed them to start a collaboration with Dr. Oscar Lee Frick, an expert allergist at the University of California, San Francisco. From his research, he found dogs were better models for testing human allergies than the standard mice and rats. He had devoted more than 15 years working with the Animal Resources Service, School of Veterinary Medicine at the University of California, Davis to breed a colony of dogs with food allergies. He measured the dogs’ allergic reactions with a painless immunoblotting technique. Frick couldn’t be reached for comment.
Frick’s technique required injecting extracts from the wheat seeds followed by a blue dye, to illuminate the activated antibodies mounting an immune response — the signal of an allergic reaction. A blue circle, proportional in size to the severity of the allergic reaction, would appear on the dog’s soft underbelly.
For the control, the scientists micro dosed the sensitive dogs with regular wheat and observed a blue dot the size of a penny. For the experiment, they swapped the regular wheat with the GM wheat. The scientists went in for a belly scratch and, to their excitement, measured a smaller blue dot, this time the size of a dime. In repeated experiments, they found that the blemish consistently shrank by 30% to 40%. The seeds worked.
Hagie had less positive news to report. Investors were blown away by the technology, but his challenges with scaling it dampened their interest. Moreover, they were skeptical about Frick’s novel use of canines, since the industry standard was to use cheaper rodent models. Come 2001, Hagie couldn’t afford to sustain the project any longer and sold his company, now known as Ventria Biosciences.
Lemaux and Buchanan continued, without success, to seek grants. Without the necessary funds to continue, the trio moved on to explore other grains, including rice and barley and grass. In the meantime, the wheat seeds sat dormant in a dark cabinet of their laboratory, until 2007, when they were stirred awake from their slumber.
BASF SE of Ludwigshafen, Germany, the world’s second largest producer of chemicals, came across the European patent for the trio’s gene expression technology. However, BASF wasn’t looking to invest in hypoallergenic wheat; they had other plans for the invention.
On August 29, 2007, the very last day of the opposition period, BASF filed an appeal of the European Patent. The company responded with the following statement. “Our patent attorneys only do this [initiate the procedure to revoke a patent] at the request of a business unit and with the support of the technical experts. BASF of course respects valid patents and supports the patent system.”
In their opposition notice, BASF alleged that the patent’s claims were neither novel, nor inventive, nor sufficiently clear and complete, and that the patent’s claims extended beyond the content of the filed application.
“Lawsuits, in part, reflect how valuable [the technology] is. Everybody wants to try to invalidate your patent, because they want to use it,” Hagie recently said.
Lemaux knew this and was accustomed to defending her technology. In her first years at the university, she recalled “a whole army of lawyers” had approached her for depositions on other patent challenges. Her former employers in industry needed to defend the patents on her technologies they still owned. The questioning usually proceeded along the lines of: “‘Was it truly an invention?’ In other words, ‘Wasn’t it obvious, what you guys did?’” she said. “I can’t tell you how many times I’ve defended that topic.”
On January 29, 2009, Lemaux appeared in a courtroom in central Munich to defend the patent. The university also sent a representative on behalf of Ventria Biosciences and a Swedish patent attorney, Martin Holmberg, to represent the UC Regents. Lemaux defended the science as the inventor and technical expert. She was anxious, but prepared. That is, until BASF’s outside counsel took the floor.
The pace of the proceedings nearly knocked Lemaux out of her chair. The rapid German hit her ears faster than the translator could keep up. “We wouldn’t get the translation until they were already on the next page,” she said of the attorney, who quickly flipped through the pages of the patent. “Three minutes later… you get the translation and then you have to answer them while they’re conversing about other [things],” Lemaux said.
“I remember the day as very tough,” Holmberg recalled. “I found it quite difficult to follow the simultaneous translation. The translator was very skilled, but he spoke more slowly and in a neutral tone, and there was a stark contrast between his translation and [the attorney’s] onslaught.” The attorney representing BASF did not respond to requests for comment.
“I felt naked… I felt like there was no way that I could possibly win,” she said. Before the decision was reached, Lemaux already felt she had lost.
About 3 p.m., after a whirlwind of testimony, the judge revoked the patent. “It was probably one of the most depressing days of my scientific career, leaving that courtroom and realizing that, you know, the university really couldn’t fight these big companies,” Lemaux said.
Upon returning back to the lab, however, her teammates didn’t see it that way. “She took it in stride,” Buchanan recalled. “It was like an experiment that didn’t work, and so she thought, ‘We’ll just have to try a different way.’” The trio found another use for thioredoxin, preventing pre-harvest sprouting and reducing food waste.
Meanwhile, Holmberg identified what he called “a serious procedural violation” by the court and filed an appeal of its decision. The court had not analyzed any of the supporting documents that UC submitted in advance in order to strengthen their case. Holmberg pointed out that the court was wrong to claim that the documents went beyond the content of the application.
On December 4, 2012, another patent attorney presented Holmberg’s case to a board of experts. The patent went through the wringer one last time, as did Lemaux. Although she had moved on to other projects, three years later, she hadn’t forgotten the traumatic experience in that German courtroom. “It was just really unnerving, because — as a scientist — this is not what you’re trained to do.” She couldn’t fit the legal outcomes to a quantitative model like in her research. She didn’t know what to expect. And so Lemaux anxiously awaited the outcome of the appeal from California.
She received the final ruling and printed it out. Evidence. The European patent was validated. The wide-eyed optimist in her reawakened. She framed the results and hung it in her office, where it remains today. “It was nice to see that academic institutions can win sometimes, and it’s not always the large companies [with] so much money and so many lawyers… I was very happy,” she said.
For the inventors, like Lemaux, such legal disputes can feel like battles. But to patent attorneys, like Martin Holmberg, the initial opposition was an encouraging sign. “The fact that a patent is opposed is an indication that there’s commercial interest in the invention,” he explained. The patent application survived thorough investigation and claims before three levels of the European Patent Office (EPO) — the Examining Division, the Opposition Division, and finally the Boards of Appeal. After all that, Holmberg asserts, the fact that the EPO maintained the patent in amended form proved that “there was indeed substance in this invention!”
Still, the success was bittersweet. The scientists owned their technology, but they never implemented it to do what they sought out, to improve lives.
Most recently, Lemaux has taken her goal to improve life for others to a global scale. She and Buchanan, her longtime friend, were selected by the Bill and Melinda Gates Foundation’s Grand Challenges program to tackle world hunger. The program devoted $16.94 million to fortify sorghum, a staple food in Africa, with essential nutrients. Lemaux and Buchanan were awarded $627,932 to make the fortified sorghum more digestible. They adapted what they learned from thioredoxin and their wheat and produced a GM sorghum to combat malnutrition abroad. This product never made it to market either. Lemaux chalks it up to the high costs and continued consumer reluctance to accept GM foods.
Lemaux also applied sorghum’s drought-resistant properties to help farmers in California. Today, she leads the $12.3 million Department of Energy Biological and Environmental Research-funded research project. In addition to coordinating the different research teams on the project and conducting her own experiments, Lemaux interacts directly with the growers who use these crops. As UC Berkeley’s Cooperative Extension Specialist, Lemaux meets with these farmers in their fields, applying her science to help with their harvest — and in the process, revisiting the scenery of her childhood.
“I don’t see how you would have a feel for agriculture the way she does without growing up on a farm,” said Buchanan, who similarly grew up on a farm in Virginia.
For her next project, she is rejoining with Cho, who is currently the director of the Plant Genomics and Transformation Facility at the Innovative Genomics Institute at UC Berkeley. Together, they are tackling food waste. They are revisiting wheat and adapting what they learned in their research with Coors. Rather than speed up sprouting, however, they want to delay the process to prevent the crop from soiling before harvests.
Although the trio’s hard-won patent had expired in 2018, the pursuit of hypoallergenic wheat has caught on elsewhere, for example, at Washington State University in Pullman, where rows of modified grain thrive.
As for her own wheat, Lemaux’s seeds haven’t yet seen the sun. Rather, they sit in the dark basement of her research building on the Berkeley campus. Dormant. Ready to sprout, if given the chance.
Note: From 2019–2020, I worked closely with Dr. Lemaux, volunteering on her outreach and science literacy efforts in Berkeley. This afforded me a rare perspective to shadow her and observe her work up-close. I did not receive class grades or any other compensation from Dr. Lemaux.
Special thanks to Marilyn Chase for her guidance and a wonderful semester in Intro. to Narrative at UC Berkeley.