Delivering Drugs With Plants, Penn’s Henry Daniell Aims to Save Lives

An admonishment to eat your greens may take on a whole new meaning if Henry Daniell, who recently joined the faculty of the University of Pennsylvania School of Dental Medicine, has anything to do with it.

Daniell, a molecular biologist with a focus on plants, pursued basic science research after earning a biochemistry Ph.D. from Madurai Kamaraj University in his native India. Yet he began to think differently about his work upon recognizing what he perceived as a human-rights injustice: the sky-high costs of medications taken for chronic or lengthy illnesses.

“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.”

His outside-the-box thinking has turned lettuce leaves into drug-delivery systems, with results that have the potential to make disease treatment and prevention affordable to a global population. Now at Penn, Daniell is working to take his plant-based medicine platform from the lab to the clinic, and to begin saving lives.

His platform addresses a shortcoming in vaccine production. Because vaccines contain pathogens — even if they are killed or inactivated — they must be refrigerated to ensure the organisms don’t reproduce and pose threats to people receiving the inoculations.

“Many vaccines are based on ‘killed’ or inactivated viruses, but there’s no such thing as one hundred percent killed,” says Daniell.

The required “cold chain” of refrigeration increases the cost of vaccines and makes them difficult to transport to remote areas in developing nations where electrical connections are scarce. Diabetics who take daily injections of insulin face the same challenge, as insulin must be kept cool. Envisioning a shelf-stable delivery system for vaccines and other drugs, Daniell turned to plants.

Plants have several properties that lend themselves well to producing and carrying biomedical molecules in the body. First, their cells are totipotent; in other words, all the different tissues of a plant can be grown starting from a single cell in a culture dish. This characteristic enables scientists to make modifications to one plant cell and, from that, grow a plant in which every cell has those modifications.

Plant cells also have fibrous walls made of cellulose, which cannot be broken down by human enzymes, though they can be degraded by the microbes that reside in the gut. This feature enables therapeutic proteins produced inside plant cells to travel partway through our digestive systems before being released in the intestines, where they can disseminate into the bloodstream.

In addition, because plants are commonly consumed foods, most people wouldn’t be allergic to them as they might be to some synthetically produced drugs, or those based on egg proteins, to which a substantial number of people are sensitive.

And finally, plants can be easily grown; Daniell has reported that just an acre of genetically modified tobacco plants, for example, could produce enough anthrax vaccine to immunize every person in the United States.

Since developing the concept of a plant-based vaccine in the 1990s, Daniell has methodically tested each step — from introducing proteins into a plant, to designing molecular tags to direct the proteins from the gut into the bloodstream or immune system, to harvesting and freeze-drying the specially engineered plants in capsules.

Animal studies have shown this platform’s power. In 2012, Daniell and colleagues published a paper in the Journal of Plant Biotechnology describing the creation of lettuce plants engineered to express a protein that stimulates the pancreas to produce insulin. Mice fed capsules of the freeze-dried plant material produced insulin and had normal sugar levels in their blood and urine, the appearance of a functional cure for diabetes. What’s more, the capsules could be stored at room temperature for as long as 15 months and retain their potency. Similarly, a 2010 publication in the journal PNAS demonstrated the ability to block severe immune reaction and death in hemophilic mice. His lab has also developed oral vaccines against cholera, malaria, tuberculosis, anthrax and plague.

Daniell arrived at Penn Dental Medicine this spring from a position at the University of Central Florida. There, he established a reputation as a path-breaker and attained the title of Pegasus Professor, the institution’s most prestigious honor given to faculty members, for “outstanding accomplishments in teaching, research and service.” He was also the only Board of Trustees Chair in UCF’s medical school and is a foreign member of Italy’s National Academy of Sciences, only the 14th American to be inducted. (The first was Penn founder Benjamin Franklin, inducted in 1786.)

Daniell’s work earned him more than 150 patents and has attracted attention from multiple funding bodies, including the National Institutes of Health, the Juvenile Diabetes Research Foundation and the Bill and Melinda Gates Foundation. The Gates Foundation grant, awarded in 2011, has the specific aim of eradicating polio, once and for all. Though the disease was mostly wiped out thanks to an effective vaccination campaign in the latter half of the 20th century, localized outbreaks and new mutated strains have prevented it from disappearing completely. The vaccine that Daniell is working on aims to offer protection against multiple strains of polio and would be free of the cold chain, aiding delivery to those areas of the world where the disease is still present.

“Gates wants me to develop a booster vaccine that will offer protection against multiple serotypes of the polio virus,” Daniell says. “We have all the key players in place to move this to the clinic.”

By the end of September, he will have a greenhouse on Penn’s South Bank campus in the Gray’s Ferry neighborhood where plants harboring vaccine or drug proteins can grow and be harvested. The facility will be used first for a collaborative project with Novo Nordisk. Daniell also has current support from Bayer for translational research.

Penn’s dental school is well positioned for Daniell to take advantage of interdisciplinary collaborations. Within Penn Dental Medicine, he is collaborating with Anh Le, chair and Norman Vine Endowed Professor of Oral Rehabilitation, to work on vaccines against oral tumors. Cross-school partnerships within Penn are also developing. A project involving the Perelman School of Medicine, for example, will focus on developing a vaccine to protect hemophilia patients from developing immune reactions against injected blood clotting factors. Daniell has been already invited to join Penn’s graduate programs in immunology and in gene therapy and vaccines.

“I’m quite excited because the rationale for me to move here is that hospitals and clinics are in place for the technology to be validated,” he says. “President Amy Gutmann’s mantra about integrating knowledge was also very attractive to me. Many universities have these brick walls around their disciplines. But, if I were to work in isolation, I’d never get to the finish line.”

At its core, Daniell’s work aims to improve the human condition with the same energized sense of innovation that led to the tech boom.

“Unlike the fantastic inventions that we see in things like cell phones and IT and so on, medicine hasn’t had the same types of leaps and bounds of progress,” says Daniell. “I see a lot of room for improvement.”

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