One of the World’s Most Hated Plants Is Becoming a Public Health Rock Star
The recent Ebola virus outbreak in the Democratic Republic of Congo has refocused attention on the vaccine and treatment prospects for the highly contagious and deadly disease. As of late May, more than 7,500 doses of an experimental vaccine made by Merck Pharmaceuticals had been shipped to the beleaguered African nation, according to a World Health Organization press release.
Research was focused on the production of antibodies and vaccines in a novel manufacturing system: the tobacco plant.
Meanwhile, Ebola treatments were also sent. One of these, ZMapp, was successfully used to treat two American missionaries in Liberia in 2014. Charles Arntzen, who helped develop the treatment, calls that moment the highlight of his career: "It started in a lab as a fanciful idea that needed to be validated. In ten years, it was being used and people went from almost dead to almost recovered."
His initial research was focused on the production of antibodies and vaccines in a novel manufacturing system. That system was the tobacco plant—not the smoking variety, or nicotiana tabacum. But rather, a distant cousin called nicotiana benthamiana, which is native to Australia, where it grows abundantly.
ZMapp is made from the plant, as are other therapeutics and vaccines. Indeed, the once-maligned plant family has turned its image upside down in the public health world, now holding promise to prevent and treat many conditions.
Cheap, easy and plentiful
Research on the tobacco plant's medicinal potential goes back a few decades. In the early 1990s, research on plants as vaccine production platforms was just beginning. "We wanted to make a lower-cost vaccine manufacturing system to be used in developing countries to broaden our manufacturing base in the developing world," said Arntzen, who is the founding director of the Biodesign Center for Immunotherapy, Vaccines and Virotherapy at Arizona State University. "There was and still is a shortage of vaccines in the poorest countries."
"I've got a list of about fifty vaccines that should be made in tobacco."
Initially, research focused on food plants: bananas, tomatoes, and potatoes. While these efforts were successful, they were stymied by the "anti-GMO food establishment," Arntzen said. "I didn't want to spend my time fighting." So, they switched to the tobacco plant.
"I've got a list of about fifty vaccines that should be made in tobacco," said Denis Murphy, professor of biotechnology at the University of South Wales. "We know a lot about how to express genes in tobacco and get it made."
Unlike egg-based vaccines, which require a clean, sterile laboratory to make, and can therefore be an expensive process, Murphy said, tobacco-based vaccines are relatively cheap to make. The process is simple: Three weeks after being planted, the plants are dipped into a liquid containing proteins from the given virus. The plants grow the proteins for another week and then are harvested and chopped up. The green liquid that results is the vaccine, which is purified and then bottled up in precise doses.
"The tobacco plant doesn't seem to mind making all this foreign protein," Murphy added. "The plants will stay alive and look okay, and they will be full of vaccine protein. If you did this with an animal, you'd probably kill it."
Still, there are certain challenges to producing tobacco-based vaccines, particularly in the developing world, said Murphy, who is also a biotech consultant for the Food and Agricultural Organization of the United Nations.
"The purification process of the vaccine protein from leaves is still something for which you need a specialized lab. You couldn't have that in the Congo," he said. Security is another concern. "Someone could steal the plant and grow it themselves as a pirate version."
Even birds could be the culprit for tobacco plant theft. "What if a bird came and started eating the leaves? You might want netting or greenhouse growing. That can be much more problematic in a developing country."
While the ZMapp treatment for Ebola is produced from tobacco, efforts to develop a vaccine this way have not proved fruitful so far. (Merck's Ebola vaccine is made from livestock.) "Our tobacco-based vaccine would require three doses for a full effect, while the vaccine made by Merck may only require a single dose," Arntzen said. "Having to give three doses, over about a month, makes the tobacco-made vaccine much more cumbersome and expensive to deliver." Yet a tobacco-derived vaccine for another newsworthy illness is in the works.
On the frontier of a flu vaccine
Quebec City-based biopharmaceutical company Medicago is using a novel technique to make a flu vaccine with tobacco. This offers several advantages over the current method of developing the vaccine from eggs.
First of all, the production is quicker: five to six weeks, versus four to six months, which means that researchers can wait to identify the circulating flu strain for the upcoming season, rather than guess and risk being wrong.
Also, with tobacco, developers can use something called virus-like particles, instead of the actual flu virus.
"We hope to be on the market by the 2020/21 flu season."
"They have the structure of the flu virus, but not its full genetic code, so the virus doesn't replicate," said Anne Shiraishi, Medicago's communications manager. That's a big deal because the flu is a rapidly mutating virus, and traditional egg-based vaccines encourage those mutations – which wind up making the vaccines less effective.
This problem happens because the flu virus mutates a key protein to better attach to receptors in bird cells, but in humans, this mutation won't trigger an effective immune response, according to a Medicago fact sheet. That's why some people who have been vaccinated still get the flu. Indeed, the 2017 flu season had the lowest vaccine effectiveness record ever for H3N2 at 10 percent in the Southern Hemisphere, and 0 percent effective in the EU and UK in people over age 65. At least theoretically, their tobacco-derived flu vaccine could be far more successful, since no such mutations occur with the virus-like particles.
Last year, Medicago, which is 40 percent owned by cigarette company Philip Morris, began a phase 3 trial of the flu vaccine with 10,000 subjects in five countries: half are getting the vaccine, and half are getting a placebo. "We hope to announce really good results this fall," Shiraishi said. "We hope to be on the market by the 2020/21 flu season."
They're also preparing phase I trials for vaccines for the rotavirus and norovirus, two intractable gastro-intestinal viruses. They hope to roll those trials out in the next year or two.
Meanwhile, other research on antibodies is in their pipeline—all of it using tobacco, Shiraishi said. "We've taken something bad for public health and made it our mini factories."
This man spent over 70 years in an iron lung. What he was able to accomplish is amazing.
It’s a sight we don’t normally see these days: A man lying prone in a big, metal tube with his head sticking out of one end. But it wasn’t so long ago that this sight was unfortunately much more common.
In the first half of the 20th century, tens of thousands of people each year were infected by polio—a highly contagious virus that attacks nerves in the spinal cord and brainstem. Many people survived polio, but a small percentage of people who did were left permanently paralyzed from the virus, requiring support to help them breathe. This support, known as an “iron lung,” manually pulled oxygen in and out of a person’s lungs by changing the pressure inside the machine.
Paul Alexander was one of several thousand who were infected and paralyzed by polio in 1952. That year, a polio epidemic swept the United States, forcing businesses to close and polio wards in hospitals all over the country to fill up with sick children. When Paul caught polio in the summer of 1952, doctors urged his parents to let him rest and recover at home, since the hospital in his home suburb of Dallas, Texas was already overrun with polio patients.
Paul rested in bed for a few days with aching limbs and a fever. But his condition quickly got worse. Within a week, Paul could no longer speak or swallow, and his parents rushed him to the local hospital where the doctors performed an emergency procedure to help him breathe. Paul woke from the surgery three days later, and found himself unable to move and lying inside an iron lung in the polio ward, surrounded by rows of other paralyzed children.
Hospitals were commonly filled with polio patients who had been paralyzed by the virus before a vaccine became widely available in 1955. Associated Press
Paul struggled inside the polio ward for the next 18 months, bored and restless and needing to hold his breath when the nurses opened the iron lung to help him bathe. The doctors on the ward frequently told his parents that Paul was going to die.But against all odds, Paul lived. And with help from a physical therapist, Paul was able to thrive—sometimes for small periods outside the iron lung.
The way Paul did this was to practice glossopharyngeal breathing (or as Paul called it, “frog breathing”), where he would trap air in his mouth and force it down his throat and into his lungs by flattening his tongue. This breathing technique, taught to him by his physical therapist, would allow Paul to leave the iron lung for increasing periods of time.
With help from his iron lung (and for small periods of time without it), Paul managed to live a full, happy, and sometimes record-breaking life. At 21, Paul became the first person in Dallas, Texas to graduate high school without attending class in person, owing his success to memorization rather than taking notes. After high school, Paul received a scholarship to Southern Methodist University and pursued his dream of becoming a trial lawyer and successfully represented clients in court.
Paul Alexander, pictured here in his early 20s, mastered a type of breathing technique that allowed him to spend short amounts of time outside his iron lung. Paul Alexander
Paul practiced law in North Texas for more than 30 years, using a modified wheelchair that held his body upright. During his career, Paul even represented members of the biker gang Hells Angels—and became so close with them he was named an honorary member.Throughout his long life, Paul was also able to fly on a plane, visit the beach, adopt a dog, fall in love, and write a memoir using a plastic stick to tap out a draft on a keyboard. In recent years, Paul joined TikTok and became a viral sensation with more than 330,000 followers. In one of his first videos, Paul advocated for vaccination and warned against another polio epidemic.
Paul was reportedly hospitalized with COVID-19 at the end of February and died on March 11th, 2024. He currently holds the Guiness World Record for longest survival inside an iron lung—71 years.
Polio thankfully no longer circulates in the United States, or in most of the world, thanks to vaccines. But Paul continues to serve as a reminder of the importance of vaccination—and the power of the human spirit.
““I’ve got some big dreams. I’m not going to accept from anybody their limitations,” he said in a 2022 interview with CNN. “My life is incredible.”
When doctors couldn’t stop her daughter’s seizures, this mom earned a PhD and found a treatment herself.
Twenty-eight years ago, Tracy Dixon-Salazaar woke to the sound of her daughter, two-year-old Savannah, in the midst of a medical emergency.
“I entered [Savannah’s room] to see her tiny little body jerking about violently in her bed,” Tracy said in an interview. “I thought she was choking.” When she and her husband frantically called 911, the paramedic told them it was likely that Savannah had had a seizure—a term neither Tracy nor her husband had ever heard before.
Over the next several years, Savannah’s seizures continued and worsened. By age five Savannah was having seizures dozens of times each day, and her parents noticed significant developmental delays. Savannah was unable to use the restroom and functioned more like a toddler than a five-year-old.
Doctors were mystified: Tracy and her husband had no family history of seizures, and there was no event—such as an injury or infection—that could have caused them. Doctors were also confused as to why Savannah’s seizures were happening so frequently despite trying different seizure medications.
Doctors eventually diagnosed Savannah with Lennox-Gaustaut Syndrome, or LGS, an epilepsy disorder with no cure and a poor prognosis. People with LGS are often resistant to several kinds of anti-seizure medications, and often suffer from developmental delays and behavioral problems. People with LGS also have a higher chance of injury as well as a higher chance of sudden unexpected death (SUDEP) due to the frequent seizures. In about 70 percent of cases, LGS has an identifiable cause such as a brain injury or genetic syndrome. In about 30 percent of cases, however, the cause is unknown.
Watching her daughter struggle through repeated seizures was devastating to Tracy and the rest of the family.
“This disease, it comes into your life. It’s uninvited. It’s unannounced and it takes over every aspect of your daily life,” said Tracy in an interview with Today.com. “Plus it’s attacking the thing that is most precious to you—your kid.”
Desperate to find some answers, Tracy began combing the medical literature for information about epilepsy and LGS. She enrolled in college courses to better understand the papers she was reading.
“Ironically, I thought I needed to go to college to take English classes to understand these papers—but soon learned it wasn’t English classes I needed, It was science,” Tracy said. When she took her first college science course, Tracy says, she “fell in love with the subject.”
Tracy was now a caregiver to Savannah, who continued to have hundreds of seizures a month, as well as a full-time student, studying late into the night and while her kids were at school, using classwork as “an outlet for the pain.”
“I couldn’t help my daughter,” Tracy said. “Studying was something I could do.”
Twelve years later, Tracy had earned a PhD in neurobiology.
After her post-doctoral training, Tracy started working at a lab that explored the genetics of epilepsy. Savannah’s doctors hadn’t found a genetic cause for her seizures, so Tracy decided to sequence her genome again to check for other abnormalities—and what she found was life-changing.
Tracy discovered that Savannah had a calcium channel mutation, meaning that too much calcium was passing through Savannah’s neural pathways, leading to seizures. The information made sense to Tracy: Anti-seizure medications often leech calcium from a person’s bones. When doctors had prescribed Savannah calcium supplements in the past to counteract these effects, her seizures had gotten worse every time she took the medication. Tracy took her discovery to Savannah’s doctor, who agreed to prescribe her a calcium blocker.
The change in Savannah was almost immediate.
Within two weeks, Savannah’s seizures had decreased by 95 percent. Once on a daily seven-drug regimen, she was soon weaned to just four, and then three. Amazingly, Tracy started to notice changes in Savannah’s personality and development, too.
“She just exploded in her personality and her talking and her walking and her potty training and oh my gosh she is just so sassy,” Tracy said in an interview.
Since starting the calcium blocker eleven years ago, Savannah has continued to make enormous strides. Though still unable to read or write, Savannah enjoys puzzles and social media. She’s “obsessed” with boys, says Tracy. And while Tracy suspects she’ll never be able to live independently, she and her daughter can now share more “normal” moments—something she never anticipated at the start of Savannah’s journey with LGS. While preparing for an event, Savannah helped Tracy get ready.
“We picked out a dress and it was the first time in our lives that we did something normal as a mother and a daughter,” she said. “It was pretty cool.”