66 Scientific American September 2000 Edible VaccinesVaccines have accomplished near miracles inthe fight against infectious disease. They haveconsigned smallpox to history and should soondo the same for polio. By the late 1990s an internationalcampaign to immunize all the world’s children againstsix devastating diseases was reportedly reaching 80 per-cent of infants (up from about 5 percent in the mid-1970s) and was reducing the annual death toll fromthose infections by roughly three million. Yet these victories mask tragic gaps in delivery. The 20percent of infants still missed by the six vaccines—againstdiphtheria, pertussis (whooping cough), polio, measles,tetanus and tuberculosis—account for about two millionunnecessary deaths each year, especially in the most re-mote and impoverished parts of the globe. Upheavals inmany developing nations now threaten to erode the ad-vances of the recent past, and millions still die from infec-tious diseases for which immunizations are nonexistent,unreliable or too costly. This situation is worrisome not only for the places thatlack health care but for the entire world. Regions harbor-ing infections that have faded from other areas are likebombs ready to explode. When environmental or socialdisasters undermine sanitation systems or displace com-munities—bringing people with little immunity into con-tact with carriers—infections that have been long gonefrom a population can come roaring back. Further, as in-ternational travel and trade make the earth a smallerplace, diseases that arise in one locale are increasinglypopping up continents away. Until everyone has routineaccess to vaccines, no one will be entirely safe.In the early 1990s Charles J. Arntzen, then at TexasA&M University, conceived of a way to solve many ofthe problems that bar vaccines from reaching all toomany children in developing nations. Soon after learningof a World Health Organization call for inexpensive,oral vaccines that needed no refrigeration, Arntzen visit-ed Bangkok, where he saw a mother soothe a cryingby William H.R. Langridge Edible VaccinesFOODS UNDER STUDY as alternatives to injectable vac-cines include bananas, potatoes and tomatoes, as well aslettuce, rice, wheat, soybeans and corn.One day children may get immunized by munchingon foods instead of enduring shots. More important, food vaccines might save millions whonow die for lack of access to traditional inoculantsJOHNSON & FANCHERCopyright 2000 Scientific American, Inc.baby by offering a piece of banana. Plant biologists had al-ready devised ways of introducing selected genes (the blue-prints for proteins) into plants and inducing the altered, or“transgenic,” plants to manufacture the encoded proteins.Perhaps, he mused, food could be genetically engineered toproduce vaccines in their edible parts, which could then beeaten when inoculations were needed.The advantages would be enormous. The plants could begrown locally, and cheaply, using the standard growingmethods of a given region. Because many food plants can beregenerated readily, the crops could potentially be producedindefinitely without the growers having to purchase moreseeds or plants year after year. Homegrown vaccines wouldalso avoid the logistical and economic problems posed byhaving to transport traditional preparations over long dis-tances, keeping them cold en route and at their destination.And, being edible, the vaccines would require no syringes—which, aside from costing something, can lead to infectionsif they become contaminated. Efforts to make Arntzen’s inspired vision a reality are stillquite preliminary. Yet studies carried out in animals over thepast 10 years, and small tests in people, encourage hope thatedible vaccines can work. The research has also fueled spec-ulation that certain food vaccines might help suppress au-toimmunity—in which the body’s defenses mistakenly attacknormal, uninfected tissues. Among the autoimmune disor-ders that might be prevented or eased are type I diabetes (thekind that commonly arises during childhood), multiple scle-rosis and rheumatoid arthritis.By Any Other Name …Regardless of how vaccines for infectious diseases are de- livered, they all have the same aim: priming the immunesystem to swiftly destroy specific disease-causing agents, orpathogens, before the agents can multiply enough to causesymptoms. Classically, this priming has been achieved by pre-senting the immune system with whole viruses or bacteriathat have been killed or made too weak to proliferate much.On detecting the presence of a foreign organism in a vac-cine, the immune system behaves as if the body were underattack by a fully potent antagonist. It mobilizes its variousforces to root out and destroy the apparent invader—target-ing the campaign to specific antigens (proteins recognized asforeign). The acute response soon abates, but it leaves be-hind sentries, known as “memory” cells, that remain onalert, ready to unleash whole armies of defenders if the realpathogen ever finds its way into the body. Some vaccinesprovide lifelong protection; others (such as those for choleraand tetanus) must be readministered periodically.Classic vaccines pose a small but troubling risk that thevaccine microorganisms will somehow spring back to life,causing the diseases they were meant to forestall. For thatreason, vaccine makers today favor so-called subunit prepa-rations, composed primarily of antigenic proteins divorcedfrom a pathogen’s genes. On their own, the proteins have noway of establishing an infection. Subunit vaccines, however,are expensive, in part because they are produced in culturesof bacteria or animal cells and have to be purified out; theyalso need to be refrigerated.Food vaccines are like subunit preparations in that they areengineered to contain antigens but bear no genes that wouldenable whole pathogens to form. Ten years ago Arntzen un-derstood that edible vaccines would therefore be as safe assubunit preparations while sidestepping their costs and de-mands for purification and refrigeration. But before he andothers could study the effects of food vaccines in people, theyhad to obtain positive answers to a number of questions.Would plants engineered to carry antigen genes producefunctional copies of the specified proteins? When the foodplants were fed to test animals, would the antigens be de-graded in the stomach before having a chance to act? (Typi-cal subunit vaccines have to be delivered by