When it comes to emotions, the face is a window to the soul – each bearing its own cracks and imperfections that have captivated AAAS Fellow Ichiro Nishimura for decades. A trained dentist and bioengineer, Nishimura specializes in the human visage and its role in our world, from features viewed as “desirable” throughout history to deformities that might impact someone’s ability to function in everyday society.
The latter – rare cases of facial distortion – often make their way to UCLA's Weintraub Center for Reconstructive Biotechnology, established by Nishimura in 2002 to research oral, head and neck tissue defects.
“To some patients, losing their face is scarier than losing their life,” says Nishimura, who is most passionate about helping those with rare facial abnormalities. “When you lose your face, you lose the ability to communicate with others.”
Nishimura’s latest project focuses on osteonecrosis of the jaw (ONJ), a painful condition where the jawbone begins to die and collapse, sometimes exposing itself in the mouth. ONJ is an extremely uncommon side effect of a class of drugs called “bisphosphonates,” used in treating osteoporosis and bone cancers. Bisphosphonates target areas of high bone turnover by inhibiting the activity of osteoclasts, which break down and remove bone as part of an immune response.
Nishimura’s team has developed a drug that neutralizes bisphosphonates in the mouth, mitigating the risk for ONJ. His next step is approval from the U.S. Food and Drug Administration, though identifying a pharmaceutical partner to eventually manufacture the drug, he adds, could be an uphill battle.
“We found the treatment and we tried to find a company to proceed with clinical trials, and no one took it,” Nishimura says. “You don’t have enough patients for the investment. That’s the challenge for rare disease investigation.”
Currently a professor at UCLA, Nishimura’s decades of research were never part of his original plan growing up in a family of successful practicing dentists in Japan.
“I’m a first son. Ichiro literally means ‘first son.’ I was going to take over my parents' family clinic.”
After attending dental school in Tokyo, Nishimura headed to Harvard School of Dental Medicine for additional clinical training, intending to return home after a few years. Postdoctoral projects in cellular and molecular biology led Nishimura to start researching tissue regeneration and biotechnology. Some of his projects focused on gene expression of collagen, which plays a role in the structure of bone, skin and other tissues. Upon receiving a grant from the National Institutes of Health, Nishimura opted to stay in the United States.
“It’s destiny, I thought.”
Over the years, Nishimura has become an expert – and a historian of sorts – on what makes the face so special. Facial expressions, he says, are a defining characteristic of what makes humans human. Other species – frogs, for example – don’t have the ability to smile. Within our species, genetic conditions are one attribute that can cause different facial structures, Nishimura adds. Down syndrome, for example, is often characterized by a flattened face with almond shaped eyes. People with Char syndrome also have flattened facial features, including droopy eyes with the corners pointing downward.
“But, when they smile, can you see any differences?” Nishimura asks. “The facial expressions supersede the structural abnormalities.”
A “normal” face is very subjective, he says. Still, this doesn’t stop people from stereotyping a person’s intelligence based on their facial features. In fact, Nishimura points out, it’s been happening to humans since the dawn of time – starting with the Neanderthals.
Preserved skulls show these early human ancestors had elongated heads, similar to footballs, with prominent ridges above their eyes and big, wide noses. In the early 1900s, the first depictions of Neanderthals were hardly discernible from those of monkeys. Early researchers, based on Neanderthals’ facial structure, assumed their intelligence was low – hence the early moniker “Homo stupidus,” Nishimura says. More recent genomic sequencing shows Neanderthals had white skin, blue to green eyes and blonde or red hair. Contrary to assumptions, they were also highly intelligent, Nishimura notes.
Facial structure has also been used in a more disturbing sense as a means of identifying society’s undesirables, Nishimura says. In the late 19th century, Sir Francis Galton created composite photos to visualize different “types” of people. One famous example – Galton combined several photos of convicts to depict the facial features of criminality.
“It’s stereotyping,” Nishimura adds. “Even today, some people still have the idea that a face that’s different from your own can’t really be trusted.”
More recently, a large percentage of the world has adopted mask-wearing as a means of stopping transmission of COVID-19. This phenomenon – and its lasting effects on human development – was discussed at the 2022 AAAS Annual Meeting in a scientific session organized and moderated by Nishimura, titled “Masked Face Unmasked: Human Face Rediscovered through the Pandemic Experience.”
“There are some questions about prolonged masking – hiding the lower part of the face,” Nishimura says. “Is that affecting children’s development? Is that affecting our social construct? The answer seems to be yes. How do we learn to communicate amongst each other with facial coverings? I don’t really know.” And this gap in knowledge is what drives Nishimura to keep pursuing his research on the human face and its role in society.