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Meet Ebola’s Soft-Spoken, Plant-Loving Arch Nemesis

Charles Arntzen created ZMapp, the world’s most promising anti-Ebola drug, from tobacco plants.

Meet Ebola’s Soft-Spoken, Plant-Loving Arch Nemesis
The secret life of plants: Charles Arntzen is artfully developing drugs via a technique known as pharming.

As the Ebola virus swept through West Africa in 2014, health experts could do little but try to quarantine the sick and watch helplessly as thousands died. There was no known cure, no vaccine. Then two American health workers, who had been infected in Liberia, became the first human recipients of an experimental drug called ZMapp, and they both recovered. One of the Americans credited God. Perhaps he also should have thanked Charles Arntzen.

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A professor at Arizona State University, Arntzen is considered the godfather of a growing field of research sometimes called “pharming”: engineering plants to produce specialized vaccines and other drugs. ZMapp, an injectable synthetic serum made of genetically engineered antibodies grown in tobacco plants, is currently the most promising drug treatment for people infected with Ebola. Just as significant is the technology used to produce it, which could be employed to combat other infectious disease threats and lower the cost of expensive drugs used to fight cancer, HIV, and other chronic health conditions.

Arntzen was a director of biotechnology at DuPont in the 1980s, but he found his life’s mission in the early 1990s with the announcement of the Children’s Vaccine Initiative, a collaboration between the Rockefeller Foundation, WHO, World Bank, and UNICEF that aimed to expand vaccine availability worldwide. “I knew the vaccine field was changing fast,” he says. Improvements in biotechnology meant that vaccines could be produced in new, more economical ways—from engineered proteins, say, rather than from live viruses. Arntzen wondered if it could be done using bioengineered plants.

In 1992, Arntzen succeeded in engineering tobacco plants to create a human hepatitis B antibody, and for the next decade he tried numerous ways to coax plants into producing other drugs for humans. For some time, he worked on what he now calls “an academic’s naive dream” of engineering banana plants whose fruit would contain an edible vaccine against norovirus, a potentially deadly diarrheal disease.

After the U.S. Army granted his group $3.7 million in 2002 to develop plant-based methods for producing defenses against pathogens that could potentially be used in terrorist attacks, Arntzen started focusing on Ebola. Partnering with San Diego–based drug company Mapp Biopharmaceutical, Arntzen gathered a diverse team of experts in plant molecular biology, antibody engineering, and protein analysis. First, they successfully “humanized” Ebola antibodies taken from mice, removing all of the mouse-specific DNA so that the human body wouldn’t reject them. Next, they planned to genetically modify tobacco plants to produce the antibodies—but soon recognized they would have trouble producing the quantities necessary to create a drug.

Then, about a year into the project, Arntzen changed his approach. Rather than using plants to produce antibodies—the conventional strategy at the time—he started engineering viruses that attacked plants, effectively using them as Trojan horses for the humanized Ebola antibodies. Infect a tobacco plant with the virus, he discovered, and as it spreads, the plant spins out millions of copies of the antibody, which can be purified and formulated for injection. “It has been a revolution for the field,” says Nobuyuki Matoba, a professor at the University of Louisville School of Medicine, who works on plant-based manufacturing of HIV and cancer drugs.

The Ebola project got a fortuitous boost in 2009, when the Defense Advanced Research Projects Agency, in response to that year’s H1N1 influenza pandemic, created the Blue Angel initiative, which invested nearly $100 million in new technologies for developing, testing, and quickly mass-producing vaccines. Some of that money went to Kentucky BioProcessing—a high-tech tobacco grower, now owned by tobacco giant Reynolds American—allowing it to expand its operation and work with Arntzen and his colleagues to produce a far greater supply of antibodies, which were then tested on monkeys.

“The amount spent directly on ZMapp, by the time it went into humans, was approximately $5 or $6 million,” says Arntzen. (It can cost as much as $1 billion to develop fully approved drugs.) “It was a very modest, part-time project.”

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The drug still wasn’t approved for human use when it was given to the health care workers in Liberia last year, and Arntzen didn’t even find out about the real-life trial until after the fact. But by the time he got the news, the patients were showing rapid improvement, “which was very exciting,” he says. Because the drug has so far only been used in emergencies, not in controlled clinical trials, it’s premature to conclude that ZMapp saved the lives of the health workers (and at least three others who recovered after receiving it), who also benefited from state-of-the-art medical care in top Western facilities. But it is widely considered the most encouraging Ebola therapy, and last fall, the U.S. Department of Health and Human Services pledged up to $42 million in funding to speed the development of more serum. By February, there was enough supply to begin clinical trials in Liberia and the U.S. Although the Ebola outbreak in West Africa has slowed, the threat of recurrence is real—and the risk of similar epidemics may be increasing. Pharming could be the key to responding to these future threats, providing a large supply of drugs or vaccines at epidemic speed.

As the focus with ZMapp has moved from research to testing and manufacturing, Arntzen has taken on a “cheerleader” role, he says. In his lab, he’s currently concentrating on devising low-cost methods for producing plant-based vaccines for the developing world. Meanwhile, Big Pharma, which previously viewed plant-based drug manufacturing as too risky to invest in, has come calling. The behemoths now see it as a scalable, affordable alternative method of creating valuable therapies, including “biosimilar” formulations of blockbuster cancer drugs like Herceptin and Rituxan. “There is a huge global market for cheaper—equivalent or better—versions of these drugs,” says Arntzen. Tobacco as a major lifesaver—that’s an idea that may take some getting used to.

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