The human body is an extraordinary record keeper. Tattooed into its skin are the scars of old wounds; archived in the molecules of the immune system are the traces of past infections.
But when that history gets translated into written medical records, things can quickly get dicey. Every lost sheet of paper or inaccurately tallied statistic can raise a person’s risk of receiving inadequate care—an especially pressing issue in low- and middle-income countries, where health care resources are often scarce or inaccessible.
Now, a team led by MIT scientists has come forward with a bold proposition that could write a legible vaccination history back into the body’s repertoire. Solving medicine’s record-keeping riddle, they argue, might just involve injecting patterns of invisible nanoparticles under the skin. Like QR codes, these designs could be scanned and interpreted by smartphones, and someday allow health providers to archive and access patients’ past vaccinations without the muss and fuss of external records.
The tattoo-esque technology, described today in the journal Science Translational Medicine, is still in the early stages of development, and hasn’t yet been tested in humans. But the team’s experiments in rats suggest that these medical marks are both safe and long-lasting, and can be administered alongside vaccines without compromising efficacy.
If the team’s research progresses, future efforts will focus on delivering the technology to children in low- and middle-income countries, where many still rely on paper cards or certificates to track their vaccination history. But other experts caution that both technical and ethical hurdles might stymie its implementation—including in places where new tools to combat the spread of disease are needed most.
“Figuring out how to keep better track of vaccination is incredibly important from a health systems and public health perspective,” says Johns Hopkins University bioethicist Nancy Kass, who wasn’t involved in the project. But injectable nanoparticles that reveal private information about a patient “could be ripe for misinterpretations and rumors,” she says. That’s especially true given the fraught history of vaccination in countries at all socioeconomic strata, including the United States.
With similar concerns in mind, the researchers, led by bioengineers Robert Langer and Ana Jaklenec, are preparing to conduct surveys to assess whether the invisible tattoos would be accepted by locals in high-priority regions. Backed by the Bill & Melinda Gates Foundation, interviews in Malawi, Bangladesh, Benin and Kenya will begin early next year.
“We want people to be comfortable,” says study author Kevin McHugh, a bioengineer at Rice University. “The goal is widespread adoption.”
Though somewhat comparable to tattoos, the marks themselves are nothing like traditional ink. Delivered by a microneedle patch—a four-by-four grid of tiny, 1.5-millimeter-long spikes that hurt less than typical injections—they’re made up of nanoparticles that are undetectable in visible light, glowing only when viewed in infrared.
Over the course of two minutes, the nanoparticles diffuse from within the microneedles to a shallow layer of skin, where they’re deposited in simple patterns of dots, each smaller than your garden-variety freckle. The patch is then removed, leaving behind a subtle mark that can still be imaged after being exposed to the equivalent of five years’ worth of sunlight, the team’s experiments show.
“This ties the vaccine to the record itself, and ties the record to the person,” McHugh says. “It can never be lost, it can never be counterfeited.”
From there, reading the dots becomes a lot like scanning a QR code. Though invisible to the naked eye, dots stamped onto pieces of pig and human skin lit up in clear patterns—a circle, rectangle or cross—when viewed through a smartphone fitted with an infrared filter, the team found. In theory, each symbol could denote a different type of injection, McHugh says, and be read through a simple machine learning algorithm that the team’s already written and tested. Even with multiple shots, he adds, the marks are small enough that “your whole array of vaccines could fit within a couple inches.”
Although the nanoparticles themselves don’t contain medically relevant drugs, the researchers safely delivered them to rats alongside a polio vaccine, which seemed to still confer its protective benefits. That’s the ultimate goal, McHugh says: to always administer the medicine and the marker in tandem, so there’s no risk of getting one without the other. And when the team scanned the rats nine months later, they could still identify the symbols the microneedle patch had left.
Nine months is a long time for rats, which live only a couple years, but the blink of an immunologic eye for a human. The next step, McHugh says, is to test a similar protocol in longer-lived animals like pigs, which share a lot of anatomical commonalities with humans, including the structure of their skin. Ideally, the formulations will remain detectable for at least several years, and perhaps longer, as most vaccinations are delivered during early childhood, McHugh says. These longer-term experiments will also give the researchers the opportunity to do more testing for toxicity and other side effects. Though the dots’ glow eventually fades, the nanoparticles stick around for good.
For now, the patches can only encode a handful of simple shapes. But adding more microneedles could make the designs more intricate, potentially conveying information about a vaccination’s date, dosage, lot number and more. “To eradicate [diseases] like polio and measles,” Jaklenec says, “you really need this kind of data.”
More complexity, however, also introduces the possibility for more error. If the nanoparticles are misapplied, fast-fading, poorly imaged or even misinterpreted, public health officials could end up back at square one on the record-keeping front, points out Grace Lee, an infectious disease pediatrician at Stanford University’s Lucile Packard Children’s Hospital who wasn’t involved in the study.
What’s more, the team’s study represents the first pass at a product that could take years—even decades—to develop and clear stringent safety regulations, says Darrick Carter, a vaccine development expert at the Infectious Disease Research Institute in Seattle who wasn’t involved in the study. “It’s already difficult enough to get vaccines cleared to go into these countries,” he says. An accessory procedure like this, he says, could meet further resistance.
And that’s just on the practical side. Making a technology usable doesn’t guarantee it’ll be used, and there are plenty of reasons why patients might hesitate to sign on to such an unusual procedure. One of the biggest issues, Lee says, involves privacy, something that’s already a hot-button topic in the realm of health records. Carrying medical information on the body—even in a form that’s “invisible” without a special filter—could invite stigma, discrimination or worse.
The idea of administering tattoos en masse may not be well received, adds Kendall Hoyt, a biosecurity expert at Dartmouth College’s Geisel School of Medicine who wasn’t involved in the study. Potential patients could reject the procedure out of fear or mistrust, worrying, for instance, that authorities are using the patches to “encrypt” information onto individuals. Add that onto the backlash that already comes part and parcel with vaccines on the whole, and the situation could compound hesitancy and misinformation, she says.
Given the nature of these issues, the team’s tattoos could end up widening the chasm between patients and health providers, both foreign and local, Kass says. If communication about the product isn’t initiated early, “I worry about the unintended consequences,” she says. “It could make things worse than they already are.”
McHugh stresses that if the microneedle patches someday make it out to the field, they won’t be mandatory accompaniments to vaccination, and nanoparticle-free formulations would be available at the same sites. The team’s upcoming surveys, he adds, could also help the researchers adapt their product to patients’ needs, desires and concerns.
That’s critical, Kass says. Bringing in the voices and opinions of the people who stand to benefit the most from the product is something that should start early, and continue. After all, there’s no point in advancing a technology that no one’s going to use.
At the root of it all, the tattoos still address a very important problem, Hoyt says. It just has to be approached in the right way.
It remains to be seen if these microneedle patches fit the bill. Figuring that out will require “a robust discussion to optimize the use of this technology in an ethically appropriate fashion,” Lee says. “You want to advance science. But you also want to mindful of the potential impact that science might have."