The earliest recorded reference to oral disease is from an ancient (5000 BC) Sumerian text that describes “tooth worms” as a cause of dental decay, and there is historical evidence that the Chinese used acupuncture around 2700 BC to treat pain associated with tooth decay. And in ancient Egypt, written between 1700 and 1500 BC, there were references to substances to ease pain and treat decay in teeth. Aesculapius, a Greek physician, who lived between 1300 and 1200 BC is credited by many with the concept of extracting diseased teeth. Throughout the Middle Age in Europe, dentistry was made available to the wealthy by physicians who would go to their homes. Dentistry for the poorer people took place in the market places, where self-taught vagabonds would extract teeth for a small fee. From the Middle Ages to the early 1700s, much dental work was provided by so called “barber surgeons.” Pierre Fauchard (1678-1761), a French surgeon, is credited with being the “father of modern dentistry.” Dental practitioners migrated to the American colonies in the 1700s and devoted themselves primarily to the removal of diseased teeth and insertion of artificial dentures. Until the mid-1800s, dentures continued to be individually constructed by skilled artisans. Gold, silver, and ivory were common components, causing them to be very expensive and available only to the very wealthy. In1851 a process to mould material against a model of the patient’s mouth and attach artificial porcelain teeth allowed the manufacture of less expensive dentures. Later, acrylic plastics replaced the use of rubber and porcelain in denture construction. 

       A major contribution came from Horace Wells in 1844 when he initiated the use of nitrous oxide (laughing gas), founding the concept of inhalation analgesia and anesthesia. The medical community later adopted inhalation anesthesia as a standard surgical practice. Greene Vardiman Black (1831-1915) was the leading reformer of American dentistry. He devised a foot engine that allowed the dentist to keep both hands free while powering the dental drill. He also developed modern techniques for filling teeth based upon biological principles and microscopic evaluation, and proposed that dental caries and periodical disease were infections initiated by bacteria—not confirmed scientifically, however, until the early 1960s.

        Xenobots, named after the African clawed frog (Xenopus laevis), are synthetic lifeforms that are designed by computers to perform some desired functions and built by combining together different biological tissues. Whether xenobots are robots, organisms, or something else entirely remains a subject of debate among scientists. 

        The first xenobots were built by Douglas Blackiston according to blueprints generated by an AI program. Xenobots built to date have been less than one millimeter wide and composed of just two things: skin cells and heart muscle cells, both of which are derived from stem cells harvested from early frog embryos. The skin cells provide rigid support and the heart cells act as small motors, contracting and expanding in volume to propel the xenobot forward. The shape of a xenobot’s body and its distribution of skin and heart cells are automatically designed in simulation to perform a specific task, using a process of trial and error (an evolutionary algorithm). 

       Xenobots have been designed to walk, swim, push pellets, carry payloads, and work together in a swarm to aggregate debris scattered along the surface of their dish into neat piles. They can survive for weeks without food and heal themselves after lacerations. Xenobots can also self-replicate via “kinetic replication”—a process that is known to occur at the molecular level but has never been observed before at the scale of whole cells or organisms. They can gather loose stem cells in their environment and form them into new xenobots with the same capability.

       Currently, xenobots are primarily used as a scientific tool to understand how cells cooperate to build complex bodies during morphogenesis. However, the behavior and biocompatibility of current xenobots suggest several potential applications to which they may be put in the future. 

       Given that xenobots are composed solely of frog cells, they are biodegradable. And as swarms of xenobots tend to work together to push microscopic pellets in their dish into central piles, it has been speculated that future xenobots might be able do the same thing with microplastics in the ocean: find and aggregate tiny bits of plastic into a large ball of plastic that a traditional boat or drone can gather and bring to a recycling center. Unlike traditional technologies, xenobots do not add additional pollution as they work and degrade: they behave using energy from fat and protein naturally stored in their tissue, which lasts about a week, at which point they simply turn into dead skin cells. In future clinical applications, such as targeted drug delivery, xenobots could be made from a human patient’s own cells, which would bypass the immune response challenges of other kinds of micro-robotic delivery systems. Such xenobots could potentially be used to scrape plaque from arteries, and with additional cell types and bioengineering, locate and treat diseases.