Turning over an old leaf

US plant biologist pioneers the use of tobacco as a base for genetic engineering of improved vaccines.

tobacco plant 224.88 (photo credit: William Rafti of the William Rafti Institute)
tobacco plant 224.88
(photo credit: William Rafti of the William Rafti Institute)
Sitting on the King David Hotel's patio, visiting plant biologist Prof. Charles Arntzen points out the ring of white petunias that line the balcony's edge as if he were waving at a good friend in a crowd. Petunias, he says in an interview before getting an honorary doctorate from the Hebrew University, are members of the same botanical family as the tobacco plant. He is certainly no smoker, but feels affection for the fast-growing leafy plant, as Arntzen is a leading researcher in molecular biology, biochemistry and biotechnology who has pioneered the development of edible vaccines for animals and humans using tobacco plants as a base. He had toyed with raw potatoes, bananas and tomatoes but found that tobacco has the best potential to save lives through genetic engineering. Bananas, he says, are very slow, taking three years to get data; more than a little raw potato can't be ingested; while tomatoes result in low levels of vaccine. Tobacco farmers have been breeding their plants for hundreds of years to produce lots of biomass and disease-free plants (although smoking kills people), and tobacco companies are helping out in the hope that the research will put a dent in their bad image. CO-DIRECTOR of the center for infectious diseases and vaccinology at Arizona State University (ASU), Arntzen was a pioneer in identifying the potential application of molecular biology to plant science. The plant-based vaccines he created produce the antigens needed for vaccinations. "Indeed, his development of low-cost, sustainable and easily administered human and animal immunization," according to the HU citation, "has brought hope for the prevention of diseases such as hepatitis and cholera, most significantly in developing countries." He has conducted research with several leading Israeli scientists, including the HU's brilliant science dean Prof. Hermona Soreq. "I see some wonderful programs at HU that are starting to happen. If Israel is going to move ahead, it will have to do this translational research in many fields." Arntzen grew up on a farm in Minnesota. "My father raised mixed crops such as corn and soybeans as well as farm animals, but my brother, sister and I never wanted to work in agriculture. I also never seriously thought of being doctor, because I didn't like killing animals in a lab," he recalls in a Jerusalem Post interview during his "maybe fifth visit" to Israel. "There were only two Jewish families in the town where I grew up," he says. "Agriculture was a way of life for many US families, but today it is an industry. It's almost impossible to be a small farmer today. Jobs have shifted to large farms and the businesses that support them." HE MARRIED his wife Kathy when he was 21, and their one son is a Houston attorney; Kathy is an interior decorator, putting a lot of her style into the Arntzen home at Superstition Mountain near Phoenix. "The Indians told the white men who came to Arizona that there were ghosts among the rocks. I suppose it was an attempt to keep the white intruders away," Arntzen says with a grin. But he hasn't long been in Arizona - instead, his career has propelled him like tumbleweed from one research center or university to another. He earned his bachelor's degree in horticulture and master's degree in biochemistry and other interdisciplinary studies at the University of Minnesota, topped by his Ph.D. in cell biology. He did his post-doctoral work at the Yellow Springs Institute in Ohio, where he met Tel Aviv University Prof. Joseph Neuman, who was on sabbatical at its Kettering research lab. Neuman, now retired, was Arntzen's first contact with an Israeli. "Prof. Neuman was my best mentor; he taught me how to do science. My official adviser was busy travelling, so I sat with Joe, who explained to me about the design of experiments. He was very patient and thoughtful, and I met him last in Israel eight years ago." Arntzen spent 15 years doing research on photosynthesis - a process on which nearly all life on Earth depends. Carbon dioxide and water are the raw materials; sunlight is the power source, and the end products are oxygen and carbohydrates such as sugars and starches. Israeli researchers, he notes, are among the world's leaders in photosynthesis. Arntzen moved to the University of Illinois to conduct agricultural research, especially the use of herbicides and plants resistant to them. He subsequently smoothed the transition of Michigan State University' plant research lab into the era of molecular biology, served in strategic roles at Texas A&M University, was president and CEO of the Boyce Thompson Institute at Cornell University, and director of biotechnology at the DuPont Company. An acknowledged leader of American science, Arntzen is a member of President George Bush's Council of Advisors on Science and Technology, and a member of the US National Academy of Sciences. AFTER FIVE years at Cornell, his wife decided she didn't like the cold weather of upper New York and bought a condo in Arizona near her mother. "I decided that if I wanted to visit Kathy," he joked, "I should move to Arizona. She likes Israel's climate, as it's the same as in Arizona." There, he was hired by ASU, which he found to be very exciting. Its new president is Prof. Michael Crow from Columbia University. "He revolutionized the place to build on interdisciplinary themes, bridging units. Our institute designs for the future, from nanotechnology to bioinformatics and biotechnology. Some of the older faculty members have needed time to adjust. As in Israel, younger members love the change." At ASU today, Arntzen's job is to pull together teams of researchers to do interdisciplinary research in plant engineering, especially for vaccines. He has no fears that genetically engineered plants will swallow the world's conventional agriculture or cause any harm to health. "We've been doing genetically engineered crops since 1986 and have never seen crops outcompeting weeds. In the US, the amount of herbicides we use has dropped dramatically because of the introduction of insect-resistant crops. But genetic engineering of plants is being slowed in the developing world, precisely where it is needed to make up for food shortages." The current high prices of agricultural products, he continues, "can partially be explained as an artificial bump. The price of rice has gone up, even though rice yields this year are supposed to be the highest ever. But the people of China, India and Indonesia are getting richer; they can afford to buy more food, and due to the US banking crisis, investors looking for alternatives are buying grain futures. There isn't a global shortage of corn or soybeans. I think it's a necessary first step to build the infrastructure for biofuels, but since such crops are often subsidized by governments, in the longer term we should go to alternative sources. In the US, we must find large-scale and sustainable alternatives for national security, and solar or wind energy is still too expensive," insists Arntzen. He was in plant biotechnology, but when physician friends asked why no one was working on plant-based vaccines, Arntzen decided to go into it. "It was a totally new, collaborative idea. I moved from Baylor University in Houston to Cornell to be president of its research institute, and took my team with me. We published our first paper on the concept of putting vaccines into plants in the early 1990s. Then, the World Health Organization launched its Global Children's Vaccine Initiative to find new ways to manufacture vaccines and make them more cost effective. Until then, vaccines were produced using cultured animal cells or fermentation of bacteria to grow and inactivate or kill them." "Vaccines can't be heated, so when vegetables are used as a basis, they had to be raw. We initially thought of raw potato and bananas, but found that tobacco cells are better for moving the DNA into," he explains. "The cells have no nicotine or any of the toxins in tobacco smoke. We sprinkle the resulting vaccine on chicken feed; the poultry don't detect it - they feed as usual - and it protects them from diseases that otherwise would have to be treated with antibiotics. It will take time, but we'll be able to take antibiotics completely out of poultry and aquaculture. For cows, it will be harder, especially for prophylactic use." Because of government regulations, it is much easier to get approval for an animal vaccine than for one designed for humans, but he says it can be done. Arntzen and his team have been working on a tobacco-cell-based vaccine against norovirus (also known as Norwalk's virus), which is spread by contaminated food and causes potentially fatal diarrhea in children throughout the Third World. "A small Arizona company named VAXX is working toward marketing. We're now developing protocols, as our research is in Phase I trials. It takes five to six years before such a product can be introduced for general use," says Arntzen. "We used to make our vaccine with transgenic plants, but now do it in normal tobacco plants using the virus as a vector. We take the green juice from squeezing the antigen-treated tobacco cells, filter them out for purity and can get a very good immunological response - even better in a nasal spray than oral because via the nose it encourages a mucosal immune response in the gut. The vaccine's protection is not lifelong, but for about a year, as the antibodies don't last forever. This is attractive to industry, as they can always sell more." "We hope eventually to partner with big pharmaceutical firms. All the major ones prefer to invest at the Phase II stage, as the risk is lower. They like to take ideas from universities and their technology-transfer companies, since big pharmaceutical companies have bureaucracies and understand that it's more cost-effective for somebody else to do the early work." OTHER TOBACCO-CELL-BASED human vaccines in the pipeline are improved, cheaper ones against hepatitis B and human papilloma virus (HPV), whose existing vaccine, Gardisil, is very expensive. A plant-based vaccine could offer added components. "We have not worked on flu vaccine," says Arntzen, "because the virus keeps changing." A rotavirus vaccine - against the pathogen that is the leading cause of severe diarrhoea among infants and young children - is also being worked on. As such diseases are widespread in the Far East and South America, local companies are interested in vaccines against them, and already understand how to make the active ingredients. In India and South Korea, for example, there is an existing customer base. But funding is needed from the World Bank and other agencies. Tobacco-cell-based vaccines have also been shown to help patients' immune systems fight non-Hodgkin's lymphoma. "It would be easy," says Arntzen, "to quickly develop a customized vaccine from the patient's own cells and give it as treatment. Further down the road are treatments for chronic diseases such as Alzheimer's and Parkinson's - thus tobacco, which kills millions around the world each year - also has the potential to save lives."