Think Tank
Smoke Screening
For a pair of molecular pathobiology professors at NYU, the e-cigarette issue felt personal from day one. Back in 2014, Deepak Saxena and Xin Li were College of Dentistry colleagues whose kids also happened to be elementary school classmates and close friends. Just a block away from their school was an eye-catching ad proclaiming that e-cigarettes were so “cool” you could smoke them in bed. Saxena remembers his 8-year-old son sounding out the words of the sign aloud and asking his father if smoking indeed was “cool.”
At the time, vaping was largely unregulated and its proponents were touting it as a healthy alternative to conventional smoking for adults—even as a means to quit tobacco. But Saxena and Li were appalled at the schoolyard-adjacent recruitment of their children. The more they learned about e-cigarettes’ marketing—cotton candy flavors, Hello Kitty vaping pens—the more they felt, says Li, that “it’s pretty evil who they were targeting.”
Because Li and Saxena were dentistry professors, their professional curiosity quickly kicked in. It had long been established that cigarette smoke caused problems in the mouth, even before it reached the lungs. Although there were differences between the two habits, how harmless, they wondered, could e-cigarettes really be?
Vaping was still so new that no one in any field of medicine or drug use prevention was studying it. “There was no funding,” says Saxena, “because nobody was even aware of it.” But the two researchers procured some seed money from NYU and, in 2016, theirs was among the first projects on the topic to receive a grant—of $1.6 million—from the National Institutes of Health.
Their team divided 119 test subjects into three groups—cigarette smokers, e-cigarette smokers, and nonsmokers—and compared their oral health at six-month intervals. They also used a “smoking machine” developed by Terry Gordon of the NYU Grossman School of Medicine to pump e-cigarette vapor into laboratory mucosa cells to replicate the effects of those substances onto oral tissue. Li and Saxena’s research confirmed their suspicions that the nicotine vapor ingested from e-cigarettes is problematic for oral health, although not necessarily in the exact same way as cigarettes.
In a 2020 paper in iScience, they reported that test subjects’ exams and saliva samples revealed that gum disease and oral infection were highest among cigarette smokers (72.5 percent) and lowest among nonsmokers (28.2 percent). E-cigarette users were in the middle at 42.5 percent. The researchers found that the microbiome of e-cigarette smokers was different from that of the other groups. Users had more Porphyromonas bacteria (a marker for gum disease) than smokers and nonsmokers, plus elevated amounts of certain cytokines associated with inflammation. While periodontal disease overall remained higher among the combustible tobacco smokers, Li and Saxena reported in a 2021 Frontiers in Oral Health paper that only the e-cigarette smokers had a markedly high incidence of clinical attachment loss—the syndrome in which the gums separate from the tooth, forming pockets that then become breeding grounds for bacteria.
Nonetheless, as the study has progressed, the dental environments of the two kinds of smokers have become more alike. Our mouths contain hundreds of varieties of bacteria, and rather than labeling them as “good” or “bad,” Li explains, it’s helpful to think of them as a community—“and as with our human society, we need diversity.” As some types of bacteria expand their numbers, others get crowded out—the dental equivalent of coyotes or raccoons going from playing a useful role in nature to taking over an urban park. These types of imbalances were seen in both groups.
One explanation is that the cigarette smokers are older and have been smoking longer, so the effects appeared early in the study. With time, however, the e-cigarette smokers seem to have caught up. “For patients at the same periodontal disease stage,” the researchers note in a 2022 Molecular Oral Microbiology paper, “cigarette smokers and e-cigarette smokers shared more similarities in their oral bacterial composition.”
Their bacteria profiles still have some differences, so the jury is out on whether the e-cigarette users will end up with all the same oral issues that come from cigarettes. “You need to have follow-up studies for many years [to know if] this change in the microbiome or the changes in the bacterial profile in your mouth is causing any major diseases” like ulcers or oral cancer, says Saxena. “We have no idea about that, because this is a very new product.” As part of this ongoing research, he and Li have applied for funding to examine the dental effects of vaping marijuana.
For all the scientific unknowns, the lure of e-cigarettes among the young is crystal clear. In the seven years since Li and Saxena began their research, e-cigarettes have become more popular with young people than they are with adults, and more popular than tobacco with youth who smoke. According to the Centers for Disease Control and Prevention, 14.1 percent of high school students and 3.3 percent of middle school students were users in 2022. “For everybody who’s quitting,” says Saxena, “there are 10 junior high school kids who are taking it up.”
—Lindsy Van Gelder
Search and Destroy
The last decade has seen profound advancements in cancer therapies, especially in the treatment of blood cancers. Some patients who might have received a one-size-fits-all drug with a slim chance of slowing down or eradicating the disease are now getting a new treatment, in which the “drug” is actually made up of their own immune system’s T cells. The extracted T cells are engineered to make proteins called chimeric antigen receptors (CARs). When returned to the body, they find and bind to specific proteins or antigens on the cancer cells, which they then destroy. “The great news,” says associate professor of biology Neville Sanjana, “is that in many kinds of blood cancers it’s been quite durable. There are people who have not only gone into remission, but have remained in remission. Even many years later, they can sample their blood and see these engineered T cells are still there. It’s almost like they installed a security surveillance system that’s running around, making sure that cancer doesn’t come back.”
Yet despite CAR T-cell therapy’s game-changing status, little progress has been made in its use against solid tumors such as those in the lungs, bones, breasts, liver, and pancreas, which make up 95 percent of all cancers. This led Sanjana and his team, including researchers at the Grossman School of Medicine, to try something radically different. Rather than search for new CARs, the focus of past efforts, they looked at about 12,000 individual genes—driving high levels of expression in each—“to see what genes, when overexpressed, increased T cell proliferation,” says Sanjana. Some dramatically increased CAR T-cell therapy’s ability to destroy cancer cells, he says: “They enhance T cells in several ways. They are more resilient and better able to divide and proliferate. They make the T cells better at their job.”
The team also discovered that combined with CAR T-cell therapy, the enhanced T cells not only did a better job of eradicating leukemia, but they also destroyed pancreatic cancer cells, a finding that could lead to even more effective blood cancer therapies and long-sought success against solid tumors. While identifying which genes best maximize T cell potential is key, understanding the mechanism behind the process is critical to the development of future therapies. So the scientists developed a screening method called OverCITE-seq, which allows them to look inside a cell for a detailed picture of how each modifier gene boosts T cell activity. When will these supercharged T cells become standard care? “My hope,” says Sanjana, “is that we can have a first in human trial within the next few years.”
Memory Serves
NYU Gallatin’s Mitchell Joachim remembers the 7:00 pm clanging of pots across New York City in the early days of the pandemic—a way of thanking frontline workers. As codirector of the COVID Memory Research Group, Joachim wants to ensure that the world will remember what we’ve endured over the last three years. Working with coprincipal investigator and fellow Gallatin professor Peder Anker, plus DJ Spooky, MIT’s Sarah Williams, and computational designer Sky Achitoff, the idea is to create a memorial, “a device for spatial storytelling and social solidarity in the aftermath of COVID-19.” The memorial could take various forms—like a structure or a wearable pin—and is meant to be not just about loss but also about hope. “Part of the reason for a memorial is not only to remember those who died,” says Joachim, “but also to suggest a path forward.”
The memorial will be about creating closure and community
“I was at Harvard when 9/11 happened. As an architect, it seemed ridiculous to work on anything else except for what 9/11 would and could mean. My thesis was on the idea of matter and memory and how architects work to create memorials for historical reasons and to bring closure to communities. With COVID, we need some way of building a community of people to deal with what we’re all experiencing. We’re calling it a research project on memorialization. We’re doing a large-scale survey of memorialization, everything from Indigenous burial grounds to temples in parts of Asia. [Now] the thesis question is ‘What is a global memorial?’ The idea is to eventually hold a global competition, and I imagine for each locale there will be their own citywide or region-wide memorial project.”
The memorial could be more than a physical space—something like the AIDS Memorial Quilt or the breast cancer pink ribbon
“COVID is so ubiquitous, such an everyday, quotidian event that you experience in many different spaces, in many different kinds of shapes and volumes and geometries. But some of the things we’re thinking would not be spatial at all. They would be a universal ring or brooch or trinket or ribbon.”
We might want to move on, but there is work to be done to fully understand the pandemic and learn from it
“Some major phase of this pandemic is over, and the idea that we would still be working on this in some ways is a bit problematic because we all want to move on with our lives. There is this feeling of helplessness, and we want to retreat and move on to other positive things. But I think somewhere in this is a bright burning star of a kind of an answer, or a way forward. And so that’s what research is: you just don’t know until you get down there, roll up your sleeves, and do the dirty work of trying to answer these questions.”
We need to be prepared for the next big event that will affect us all
“This is for the first time recognizing the problem at its scale. This affects every single one of us, meaning plants, animals, humans. So this is the first time we’re realizing we’re one biology. And therefore, we’ve got to get our act together to work as a unified team. A planetary structure needs to be in place to handle planetary-scale problems, and we don’t have that on any level. Globalization is there for materials and resources and trade, but not necessarily for a whole host of other problems that have massive externality costs. So this might be a way to create a bridge to some kind of physical network of how humans need to act together in a time of crisis.”
The Science Behind...
The Shape of Ice
Trekking to the polar regions swaddled in Gore-Tex isn’t the only way to make significant discoveries about the vanishing ice caps. A team of NYU mathematicians and physicists from Arts and Science’s Center for Soft Matter Research and the Courant Institute’s Applied Mathematics Lab has done just that in the university’s own backyard. Braving the cold of a refrigerated room, the researchers conducted a series of experiments with a focus on temperatures between zero and 10 degrees Celsius and found that the shape and pattern of melting ice submerged in water depends on the water’s temperature. In the most frigid H2O (below about five degrees Celsius) the ice took the shape of a downward-pointing pinnacle, like an icicle, but was completely smooth on its surface. Ice melting in warmer water (above around seven degrees Celsius) had a spiky form too, but pointed upward. And water at in-between temperatures (between five and seven degrees Celsius) caused the ice to melt with a scalloped pattern, similar to what’s seen on icebergs. Observing how variations in environmental conditions alter the shapes and patterns of melting ice in the lab and getting a handle on the physics and math behind it offers useful insights into the effects of ambient water temperature in the real world and how it relates to climate change. As associate professor of physics and study coauthor Alexandra Zidovska explains, “Our work helps to understand how melting induces unusual flow patterns that in turn affect melting, which is one of the many complexities affecting the ice on our planet.”
—Dulcy Israel
Photos from top: Toshiro Shimada/Getty Images; illustration by Richard Mia; Jill Greenberg; BlackJack3D/iStock