Several years ago, Dean Ho bit into a sandwich and chipped a tooth. His dentist patched it up, but several months later the tooth started throbbing. “It was the worst pain I’d ever felt in my life,” Ho recalls.
The inside of the tooth’s root had become infected. Now it needed a root canal treatment. Many patients dread this procedure. It’s where a dentist drills into the tooth and then scrapes out the infected tissue. Afterward, this new hole is filled with a rubber-like material. More than he feared this process, Ho was intrigued by it.
He didn’t understand exactly what a root canal was. That might come as a surprise, since he works at the School of Dentistry at the University of California, Los Angeles. But Ho doesn’t treat patients. He is a bioengineer. Indeed, he heads a lab that uses science and engineering principles to solve problems in biology and medicine.
Reclining in the dental chair, tools and tubes sticking out of his mouth, Ho typed on his smartphone. This curious researcher wanted to “chat” as his dentist set to work. What are you doing? Is it going to hurt? How much longer? When the root-canal treatment was done, Ho had more questions — the kind a bioengineer might ask. Curious about the tooth-filling material, he asked: “Look, is there anything cool about it? Could anything be made better?”
Those timely musings were key. They spurred the creation of a new material that could improve root-canal treatments for generations to come. Ho isn’t the only scientist who has sunk his teeth into … well, teeth! A similar “what if” moment inspired a Boston biologist to try growing new teeth in the lab. And for one archaeologist, bad teeth have turned out to be a boon. They are chock full of DNA — genetic material that offers clues to the diets and diseases of ancient cultures.
A better tooth filling
As Ho learned, infections can be a big and painful problem for root-canal patients. Even after the dentist fills an infected tooth, the seal won’t be perfect. Often it will have little holes. These can allow bacteria to creep in.
Pondering this problem, Ho had an idea. “The wheels were turning while [my dentist] was working on me,” he notes. For years, Ho’s lab had worked with diamonds — not the kind in jewelry, but super-small ones known as nanodiamonds. They’re made from groups of carbon atoms. Each group can be less than a thousandth the width of a human hair. In 2007, his team showed that these teeny pieces of carbon have an unusual blend of flexibility and strength. That suits them for big jobs, such as carrying cell-killing drugs to cancer cells. Since then, Ho’s team has found more uses for nanodiamonds. The material can create sharper medical images and help bone regrow.
At his dentist’s office, Ho had another idea. How about using nanodiamonds to make a better root-canal filler?
Like ordinary diamonds, nanodiamonds are very hard. They can strengthen materials to which they are added. They also are great at latching onto chemicals, including bacteria-killing drugs. These medicines, called antibiotics, can shut down infections. Adding drug-carrying nanodiamonds to the existing filler material could make root-canal treatments more reliable. At the same time, Ho thought, they might keep teeth from getting re-infected.
Back in the lab, he and his coworkers got to work designing this new filler. They compared it to the usual material. For this work, they used teeth that dentists had already extracted from people’s mouths. To fill an infected tooth, dentists need something that’s squishy while it’s being applied, but tough once it hardens. The nanodiamond material looked promising. And lab tests proved it stronger than conventional fillers.
Best yet, this new material indeed can fight infections.
When the researchers spread bacteria onto the two different surfaces, far more bacteria died on the new filler than on the conventional one.
“If the bugs make contact [with the filler], the drug will get them,” Ho says. His team first described this filling material a little more than two years ago in the journal ACS Nano. So far they’ve tried the new filler in three people who needed root canals. When checked six months later, the new material was holding up well and the patients had no further tooth decay. The researchers reported these data in the Nov. 7, 2017 Proceedings of the National Academy of Sciences. Now they’re gearing up for a larger study with 30 people.
Ho also wants his research to motivate “future explorers of the world” — like his preschooler children. “Wouldn’t it be cool if the kids could actually know what I’m doing? There’s impact that can be made beyond the technical side,” he says. Toward that end, Ho has been working with an artist to create a comic book. It not only explains what nanodiamonds are but also how they’re used. (Take a peek at the comics, which you can find at the bottom of this webpage: http://www.projectndx.com/new-page/.)
Sometimes, teeth rot so much that they cannot be fixed by a root-canal treatment. Instead, dentists have to replace them with dentures or tooth implants. In general, however, such “fake” teeth are far from ideal. “People don’t like them,” notes Pamela Yelick. She’s a biologist at Tufts University School of Dental Medicine in Boston. The reason: Dentures don’t “feel” the same as real teeth do. They also don’t adapt as well to the effects of chewing. Finally, many people find them inconvenient to clean and uncomfortable to wear.
Dental implants have the opposite problem, Yelick adds. Normally teeth attach to soft tissue, called ligaments, which help absorb the forces of chewing. But dentures and implants have no such cushion. That can make fake teeth painful or cause them to break.
Yelick wondered if her team could do a better job. She wanted to find a way to help people grow new teeth.
The idea popped into her head during a lecture by a scientist from the Massachusetts Institute of Technology, in Cambridge. The MIT scientist spoke about his team’s work to engineer artificial livers for kids awaiting a liver transplant.
To grow new livers, the MIT group was using stem cells. Those are rare cells within the human body. Instead of dividing into just one type of cell — such as a skin cell, neuron or bone cell — they can produce any of many different types of cells. Hearing about that research, “I was blown away,” Yelick recalls. “I was like: ‘This is so cool! Could you do this with teeth?’”
To pursue this idea, her team first needed the right stem cells — ones that can give rise to all of the different cell types that make up a tooth. For that, they needed a cheap source of teeth for study. Yelick got creative. She found a pig slaughterhouse that was willing to provide jaws from butchered animals.
Back at the lab, Yelick’s team chiseled out the buds of would-be molars.
Using existing methods for sorting rare stem cells out of immune-cell mixtures, the researchers isolated stem cells from the pig’s teeth. (Stem cells are identified by a signature collection of proteins on their surface.) The researchers placed the stem cells into dishes filled with a liquid made from cell nutrients. The dishes also contained a three-dimensional mesh known as a scaffold. In several months, those cells grew and organized into “beautiful little tooth crowns,” Yelick says. That was quite a feat. It made the front page of the Boston Globe in 2002.
Since then, Yelick’s team has made tooth crowns starting with dental stem cells from people. They often use wisdom teeth or other teeth extracted by an orthodontist. One day the researchers hope to use this method as an alternative to root canals.
They aren’t there yet. But here’s how they think it could work. Instead of filling damaged teeth with some rubber-like material, they’d apply a gel that contains dental stem cells. Those cells would develop into the various cell types that make up the tooth’s connective tissue. Essentially, Yelick says, this would let stem cells grow on site to replace rotten tissue that had been cleared out during a root canal.
Before anything is done in people, the team needs to do more work in pigs. The pig experiments cost hundreds of thousands of dollars. And these studies would need to be repeated many times to get reliable data. However, Yelick predicts, it should be possible to regenerate human teeth from stem cells within the next 10 years.
While Ho and Yelick work to save or replace bad teeth, Christina Warinner relishes the rotting chompers. And, she adds, the dirtier, the better!
Warinner works at the University of Oklahoma in Norman. But until 2020, she’ll be a visiting scientist at the Max Planck Institute for the Science of Human History in Jena, Germany. As a molecular anthropologist, she analyzes DNA in ancient bones. Her goal: to learn more about the lives of ancient peoples. Surprisingly, “teeth are one of the best-preserved parts of the skeleton,” she says.
And the most valuable part of ancient teeth? Plaque. “All that stuff getting stuck in your teeth?” It turns rock hard, Warinner says. And that allows it to survive the ravages of time. Materials from saliva cover the tooth with a tough buildup of minerals. As a result, a tooth “doesn’t decompose in the same way as the rest of your body.”
For Warinner, that hardened stuff that dentists scrape off of our teeth holds a remarkable wealth of information. That’s because dental plaque contains loads of DNA from trapped food particles, bacteria in the mouth — even a person’s own cells. By analyzing those bits of genetic information, she and others can learn about what ancient people ate and which diseases they suffered.
The true ‘Paleo’ diet
For example, Warinner’s team discovered that the same microbes that cause gum disease today also troubled ancient peoples. And on the food side, her research has shown that the term “Paleo diet” is misleading. People who follow this modern diet avoid dairy and grains. They eat only fruits, vegetables and other foods that they believe humans consumed during the Paleolithic Era, some 10,000 to 2.6 million years ago.
Books and posters often depict the Paleo diet as one full of bright, healthy foods. “I don’t disagree that eating a breakfast of eggs, avocados and blueberries sounds wonderful,” says Warinner. Alas, her data show, these foods are “brighter, fleshier, sweeter and more calorie-dense than anything a person back then would have had access to.”
Wild avocados of old, for example, had almost no edible fruit — at least not compared to the plump Haas avocados that grocery stores sell today. As for carrots and broccoli, Warinner says, those weren’t even “invented” until the 16th and 17th centuries, after years of plant breeding. Veggies eaten by ancient people were woody, fibrous and tough. Today we would consider these weeds or ornamental plants, says Warinner. Indeed, she adds, “Many people today would not recognize common Paleolithic foods as foods at all.”
As a child, Warinner recalls, someone gave her a book of stamps with Egyptian hieroglyphs (HY-roh-glifs). The ancient world it described enthralled her. A little while later, she got interested in science. The young student had no idea that it was possible to blend elements of history and biology. But that’s what she’s now able to do.
“I loved learning about the natural world, understanding how things work and why they work,” she says. In college, Warinner discovered archaeology. She loved the way that this field could merge with other sciences. “I could look at questions that relate to the human past.” And she could do it, she says, “using tools and techniques coming out of biology and chemistry, which I loved so much.”
Warinner’s studies have taken her all over the globe. She has excavated in the hot, wet Central American jungles of Belize (Beh-LEEZ) and in a beautiful, cold, mountainous region of Mexico.
More recently, Warinner went to Nepal, high in the Himalayas. She traveled with a team of high-altitude archaeologists. They studied ancient people who colonized some of the world’s harshest, high-altitude environments. These sites have few sources of food or other resources.
When a debate arose over which population arrived first, the team settled the issue by reconstructing human genes and more from DNA fragments in excavated bones. Now they’re trying to identify genetic features that helped those ancient people adapt to such cold areas, such intense sun and so little oxygen.
Warinner’s advice to students: “Stay curious and keep your minds open. I never dreamed I could be doing something so much fun!”
antibiotic A germ-killing substance, usually prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.
archaeology (also archeology) The study of human history and prehistory through the excavation of sites and the analysis of artifacts and other physical remains. Those remains can range from housing materials and cooking vessels to clothing and footprints. People who work in this field are known as archaeologists.
atom The basic unit of a chemical element. Atoms are made up of a dense nucleus that contains positively charged protons and uncharged neutrons. The nucleus is orbited by a cloud of negatively charged electrons.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals).
bioengineer Someone who applies engineering to solve problems in biology or in systems that will use living organisms.
biology The study of living things. The scientists who study them are known as biologists.
biomedical Having to do with medicine and how it interacts with cells or tissues.
calorie The amount of energy needed to raise the temperature of 1 gram of water by 1 degree Celsius. It is typically used as a measurement of the energy contained in some defined amount of food.
cancer Any of more than 100 different diseases, each characterized by the rapid, uncontrolled growth of abnormal cells. The development and growth of cancers, also known as malignancies, can lead to tumors, pain and death.
carbon The chemical element having the atomic number 6. It is the physical basis of all life on Earth. Carbon exists freely as graphite and diamond. It is an important part of coal, limestone and petroleum, and is capable of self-bonding, chemically, to form an enormous number of chemically, biologically and commercially important molecules.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells.
chemical A substance formed from two or more atoms that unite (bond) in a fixed proportion and structure. For example, water is a chemical made when two hydrogen atoms bond to one oxygen atom. Its chemical formula is H2O. Chemical also can be an adjective to describe properties of materials that are the result of various reactions between different compounds.
chemistry The field of science that deals with the composition, structure and properties of substances and how they interact. Scientists use this knowledge to study unfamiliar substances, to reproduce large quantities of useful substances or to design and create new and useful substances.
compound (often used as a synonym for chemical) A compound is a substance formed when two or more chemical elements unite (bond) in fixed proportions. For example, water is a compound made of two hydrogen atoms bonded to one oxygen atom. Its chemical symbol is H2O.
crown The upper region of something.
culture (n. in social science) The sum total of typical behaviors and social practices of a related group of people (such as a tribe or nation). Their culture includes their beliefs, values and the symbols that they accept and/or use. Culture is passed on from generation to generation through learning. Scientists once thought culture to be exclusive to humans. Now they recognize some other animals show signs of culture as well, including dolphins and primates.
dairy Containing milk or having to do with milk. Or a building or company in which milk is prepared for distribution and sale.
decay The process (also called “rotting”) by which a dead plant or animal gradually breaks down as it is consumed by bacteria and other microbes.
dental (adj.) Meaning related to teeth.
dentin The hard and dense material that makes up most of a tooth. It sits beneath a protective mineral layer known as enamel.
dentures False teeth, usually made from white ceramic materials, to replace teeth lost to injury or disease.
develop (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.
diamond One of the hardest known substances and rarest gems on Earth. Diamonds form deep within the planet when carbon is compressed under incredibly strong pressure.
diet The foods and liquids ingested by an animal to provide the nutrition it needs to grow and maintain health. (verb) To adopt a specific food-intake plan for the purpose of controlling body weight.
DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.
edible Something that can be eaten safely.
element (in chemistry) Each of more than one hundred substances for which the smallest unit of each is a single atom. Examples include hydrogen, oxygen, carbon, lithium and uranium.
enamel (in biology) The glossy, hard substance that covers a tooth.
engineer A person who uses science to solve problems. As a verb, to engineer means to design a device, material or process that will solve some problem or unmet need.
environment The sum of all of the things that exist around some organism or the process and the condition those things create. Environment may refer to the weather and ecosystem in which some animal lives, or, perhaps, the temperature and humidity (or even the placement of components in some electronics system or product).
field An area of study, as in: Her field of research was biology. Also a term to describe a real-world environment in which some research is conducted, such as at sea, in a forest, on a mountaintop or on a city street. It is the opposite of an artificial setting, such as a research laboratory.
force Some outside influence that can change the motion of a body, hold bodies close to one another, or produce motion or stress in a stationary body.
fruit A seed-containing reproductive organ in a plant.
gel A gooey or viscous material that can flow like a thick liquid.
generation A group of individuals (in any species) born at about the same time or that are regarded as a single group. Your parents belong to one generation of your family, for example, and your grandparents to another. Similarly, you and everyone within a few years of your age across the planet are referred to as belonging to a particular generation of humans.
genetic Having to do with chromosomes, DNA and the genes contained within DNA. The field of science dealing with these biological instructions is known as genetics. People who work in this field are geneticists.
hieroglyph Words or phrases in some written language (usually ancient) that are depicted by common, simplistic and recognizable pictures.
Himalayas A mountain system in Asia that divides the Tibetan Plateau to its north from the plains of India to the south. Containing some of the highest mountains in the world, the Himalayas include more than 100 that rise at least 7,300 meters (24,000 feet) above sea level. The tallest is known as Mount Everest.
immune (adj.) Having to do with the immunity. (v.) Able to ward off a particular infection. Alternatively, this term can be used to mean an organism shows no impacts from exposure to a particular poison or process. More generally, the term may signal that something cannot be hurt by a particular drug, disease or chemical.
implant A device manufactured to replace a missing biological structure, to support a damaged biological structure, or to enhance an existing biological structure. Examples include artificial hips, knees and teeth; pacemakers; and the insulin pumps used to treat diabetes. Or some device installed surgically into an animal’s body to collect information on the individual (such as its temperature, blood pressure or activity cycle).
infection A disease that can spread from one organism to another. It’s usually caused by some type of germ.
ligament A fibrous and elastic material that connects one bone to another.
liver An organ of the body of animals with backbones that performs a number of important functions. It can store fat and sugar as energy, break down harmful substances for excretion by the body, and secrete bile, a greenish fluid released into the gut, where it helps digest fats and neutralize acids.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
mineral Crystal-forming substances that make up rock, such as quartz, apatite or various carbonates. Most rocks contain several different minerals mish-mashed together. A mineral usually is solid and stable at room temperatures and has a specific formula, or recipe (with atoms occurring in certain proportions) and a specific crystalline structure (meaning that its atoms are organized in regular three-dimensional patterns). (in physiology) The same chemicals that are needed by the body to make and feed tissues to maintain health.
nano A prefix indicating a billionth. In the metric system of measurements, it’s often used as an abbreviation to refer to objects that are a billionth of a meter long or in diameter.
neuron An impulse-conducting cell. Such cells are found in the brain, spinal column and nervous system.
nutrient A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.
orthodontics A field of dentistry that focuses on straightening misaligned teeth or closing big gaps between teeth. The term comes from orthos, Greek for straight, and dontos, meaning teeth. A specialist who works in this field is known as an orthodontist.
oxygen A gas that makes up about 21 percent of Earth's atmosphere. All animals and many microorganisms need oxygen to fuel their growth (and metabolism).
paleo A prefix that means associated with ancient — especially geologically early — times.
paleolithic An adjective meaning old stone, it refers to the early Stone Age. This period began about 750,000 years ago and ended about 200,000 years ago. A hunter-gather period, it predates when people began farming.
plaque An accumulation of materials in the body from the fluids that move through an area or bathe it. They can be minerals, proteins or other substances that collect as deposits. (in dental medicine) A biofilm, or community of bacterial species, that grows on teeth and other surfaces in the mouth.
population (in biology) A group of individuals from the same species that lives in the same area.
Proceedings of the National Academy of Sciences A prestigious journal publishing original scientific research, begun in 1914. The journal's content spans the biological, physical, and social sciences. Each of the more than 3,000 papers it publishes each year, now, are not only peer reviewed but also approved by a member of the U.S. National Academy of Sciences.
protein A compound made from one or more long chains of amino acids. Proteins are an essential part of all living organisms. They form the basis of living cells, muscle and tissues; they also do the work inside of cells. Among the better-known, stand-alone proteins are the hemoglobin (in blood) and the antibodies (also in blood) that attempt to fight infections. Medicines frequently work by latching onto proteins.
pulp The fibrous inner part of a vegetable or fruit (such as an orange).
root canal A dental procedure to remove the living tissue inside a tooth that has become infected (and intensely painful).
slaughterhouse A facility where animals are killed in order to produce meat.
smartphone A cell (or mobile) phone that can perform a host of functions, including search for information on the internet.
stem cell A “blank slate” cell that can give rise to other types of cells in the body. Stem cells play an important role in tissue regeneration and repair.
tissue Made of cells, any of the distinct types of materials that make up animals, plants or fungi. Cells within a tissue work as a unit to perform a particular function in living organisms. Different organs of the human body, for instance, often are made from many different types of tissues.
transplant (in medicine) The replacement of a tissue or an organ with that from another organism. It is also a term for the material that will be transplanted.
weed (in botany) A plant growing wild in, around — and sometimes smothering over — valued plants, such as crops or landscape species (including lawn grasses, flowers and shrubs). Often a plant becomes such a botanical bully when it enters a new environment with no natural predators or controlling conditions, such as hard frosts. (in biology, generally) Any organism may be referred to as a “weed” if it enters an environment and begins to overwhelm the local ecosystem.
Journal: D.K. Lee et al. Clinical validation of a nanodiamond-embedded thermoplastic biomaterial. Proceedings of the National Academy of Sciences. Vol 114, November 7, 2017, p. E9445. doi: 10.1073/pnas.1711924114.
Journal: W. Zhang et al. Decellularized tooth bud scaffolds for tooth regeneration. Journal of Dental Research. Vol. 96, May 1, 2017, p. 516. doi: 10.1177/0022034516689082.
Journal: E.E. Smith and P.C. Yelick. Progress in bioengineered whole tooth research: from bench to dental patient chair. Current Oral Health Reports. Vol. 3, December 2016, p. 302. doi: 10.1007/s40496-016-0110-2.
Journal: C. Jeong et al. Long-term genetic stability and a high-altitude East Asian origin for the peoples of the high valleys of the Himalayan arc. Proceedings of the National Academy of Sciences. Vol. 113, July 5, 2016, p. 7485. doi: 10.1073/pnas.1520844113.
Journal: D.K. Lee et al. Nanodiamond—gutta percha composite biomaterials for root canal therapy. ACS Nano. Vol. 9, November 24, 2015, p. 11490. doi: 10.1021/acsnano.5b05718.
Journal: H. Huang et al. Active nanodiamond hydrogels for chemotherapeutic delivery. Nano Letters. Vol. 7, November 2007, p. 3305. doi: 10.1021/nl071521o.
Journal: C.S. Young et al. Tissue engineering of complex tooth structures on biodegradable polymer scaffolds. Journal of Dental Research. Vol. 81, October 1, 2002, p. 695. doi: 10.1177/154405910208101008.