Tobacco leaf infected with Tobacco Mosaic Virus. Courtesy of Clemson University - USDA Cooperative Extension Slide Series
Timeline, 2008: If you’ve ever been asked about allergy to egg products before receiving a flu vaccine, you have had a little encounter with the facts of vaccine making. Flu viruses to produce the vaccine are painstakingly grown in chicken eggs because eggs make perfect little incubators for the bugs.
There are problems—in addition to the allergy issue—that arise with this approach. First of all, growing viruses for a million vaccine doses usually means using a million fertilized, 11-day-old eggs. For the entire population of the United States, 300 million eggs would be required. Second, the process requires months of preparation, meaning a slow turnaround time for vaccines against a fast-moving, fast-changing disease. Last, if there is anything wrong with the eggs themselves, such as contamination, the whole process is a waste and crucial vaccines are lost.
The day may come when we can forget about eggs and turn to leaves. Plants can contract viral disease just like animals do. In fact, an oft-used virus in some research fields is the tobacco mosaic virus, which, as its name implies, infects tobacco plants. It gives a patchy look to the leaves of infected plants, and researchers use this feature to determine whether the virus has taken hold.
Bitter little avatars of evil used for good?
Tobacco plants themselves, bitter little avatars of evil for their role in the health-related effects of smoking, serve a useful purpose in genetic research and have now enhanced their approval ratings for their potential in vaccine production. Plants have caught the eye of vaccine researchers for quite a while because they’re cheaper and easier to work with than animal incubators. Using plants for quick-turnaround vaccine production has been a goal, but a few problems have hindered progress.
To use a plant to make a protein to make a vaccine, researchers must first get the gene for the protein into the plant. Previous techniques involved tedious and time-consuming processes for inserting the gene into the plant genome. Then, clock ticking, there was the wait for the plant to grow and make the protein. Add in the Byzantine process of obtaining federal approval to use a genetically modified plant, and you’ve got the opposite of “rapid” on your hands.
One solution to this problem would simply be to get the gene into the plant cell cytoplasm for immediate use. It’s possible but involves meticulously injecting a solution with the gene sequence into each leaf. Once the gene solution is in, the plant will transcribe it—copy it into mRNA—in the cell cytoplasm and then build the desired protein based on the mRNA code. But there has been no way to take hand injection to the large-scale production of proteins, including for vaccines.
Age-old vacuum suction = high-tech high-throughput
To solve this problem, researchers turned to one of our oldest technologies: vacuum suction. They grew tobacco plants to maturity and then clipped off the leaves, which they submerged in a solution. The solution was spiked with a nasty bug, Agrobacterium tumefaciens, a pathogen responsible for the growth of galls, or tumors, on plants. Anyone working in agriculture fears this bacterium, a known destroyer of grapes, pitted fruit trees, and nut trees. But it does have one useful feature for this kind of work: It can insert bits of its DNA into plant cells. The researchers tricked A. tumefaciens into inserting another bit of DNA instead, the code for the protein they wanted to make.
To get the solution close to the cells, the investigators had to get past air bubbles, and that’s where the vacuum came in. They placed the submerged leaves into a vacuum chamber and flipped a switch, and the activated chamber sucked all the air out of the leaves. When the vacuum was turned off, the solution flowed into the now-empty chambers of the leaf, allowing the A. tumefaciens-spiked solution to bathe the plant cells. After 4 days and a few basic protein-extraction steps, the research team had its protein batch. According to the team lead, “any protein” could be made using this process, opening up almost unlimited possibilities and applications for this approach.
Vaccines…or combating bioterrorism?
The technology has come far enough that a US company has taken steps toward manufacturing vaccines using tobacco leaves. And it appears that the applications go beyond vaccines, as one news story has noted…the tobacco plants might also be used to produce antidotes to common agents of bioterrorism.