Tucked behind old factory buildings on Penn’s South Bank campus stands a gleaming greenhouse. The $2 million structure, completed late last year, is state-of-the-art. Drip irrigation ensures each pot receives just the right amount of water. Humidity and temperature are precisely monitored and can be accessed and modified remotely. And if short winter days, snow cover, or cloudy skies prevent enough sunlight from entering the greenhouse, panels and lights on the ceiling adjust automatically to provide light that matches solar radiation.
Such cutting-edge technology might seem over-the-top for a mere greenhouse. But the plants grown inside are not destined for a garden, farm, or windowsill; their intended fate is to save lives.
The greenhouse is the domain of the School of Dental Medicine’s Henry Daniell, a professor in the departments of Biochemistry and Pathology and director of translational research. Daniell joined Penn’s faculty last year and has been working diligently to see his research move from the lab to the clinic.
His life’s work centers on a unique means of delivering drugs and vaccinations to the human body. Instead of relying upon sterile injections to ferry the therapeutic protein of interest to the intended tissue, Daniell has used a humbler vehicle: lettuce leaves.
His research has demonstrated the effectiveness of plant-based vaccines and therapeutics in treating nearly 30 conditions, from infectious diseases such as cholera, malaria, and anthrax, to autoimmune diseases such as diabetes and hemophilia.
The way Daniell sees it, plant-based vaccines have a number of advantages over their traditional counterparts. They’re shelf-stable and don’t require refrigeration, they’re less likely than egg-based injections to provoke an allergy, they’re relatively easy to grow, and they’re safer because they only contain proteins from a pathogen, rather than the pathogen itself.
Perhaps the greatest advantage of these vaccines and therapeutic agents, however, is their cost.
“Interferon, a common cancer drug, for example, costs $30,000 to $40,000 for a four-month treatment, and a third of the global population earns $2 or less a day,” Daniell says. “To me, there is something morally not right about that. If you have something that saves lives, you have an obligation to make it available to everyone.”
Manufacturing these so-called “green vaccines” does not require expensive purification equipment, and transporting and storing them doesn’t require a costly “cold chain” of refrigeration. Freed from these constraints, Daniell says the therapies could be produced and distributed relatively inexpensively, even to remote areas where refrigeration and electricity are rare commodities.
How, then, does one transform an ordinary lettuce plant into a drug? Daniell and his research team have spent years meticulously refining each step of the process. First they have to identify the protein of interest. In diabetes, for instance, it’s insulin. In polio, it’s a protein produced by the virus that the human immune system can be taught to recognize and attack.
These proteins are introduced into plant cells with a “gene gun” that uses helium under intense pressure to push the protein through the lettuce’s tough cell wall, where it is incorporated into the plant’s genome. The proteins have molecular tags that direct them to the appropriate tissue in the body. After the lettuce plants expressing the therapeutic protein are selected, grown, and harvested, their leaves are freeze-dried, powdered, and put into capsules that a patient can easily swallow.
Perfecting, testing, and proving the value of this platform has resulted in more than 200 publications and more than 150 patents for Daniell—and counting.
In 2012, for example, Daniell and colleagues published a paper in the Journal of Plant Biotechnology that showed that diabetic mice fed capsules of specially engineered lettuce plants could be induced to produce insulin, effectively curing the animals of the disease. And last month, reporting in the journal Molecular Therapy, Daniell’s team demonstrated that the plant-based platform could send molecules across the blood-brain barrier, delivering a drug that dissolved plaques in the brains of mice with Alzheimer’s disease.
In addition, the Gates Foundation is funding Daniell to work on a booster for polio, a disease that was once close to being eradicated but has persisted in small outbreaks in recent years.
“Soon we’ll be publishing work on a booster vaccine that produces immunity against multiple serotypes of polio,” he says.
Daniell is not content with these successes, however. In a soon-to-be published article that has attracted attention from pharmaceutical companies eager to scale up his techniques and make them available to patients, Daniell and colleagues have shown that his platform effectively counteracts one of the most dangerous complications of hemophilia treatment. And in the new greenhouse, he’s growing genetically modified tobacco and lettuce plants that could be used to vastly improve treatment for diabetes, HPV, polio, and hemophilia. Trials in humans could begin as early as next year.
“This will be a paradigm shift in delivery of drugs,” Daniell says. “This will change the landscape and save lives.”