Dr. Priscilla Chan and mark Zuckerberg. Image Credit: Chan Zuckerberg SOURCE IN BRIEF The Chan Zuckerberg initiative has taken a huge first step toward their…
Cancer has become an innovation priority, and researchers in a wide variety of fields are proposing novel approaches to finding, containing, and destroying it. In the near term, the R&D poised to have the biggest impact involves more powerful data analysis and new drug therapies. But in the decades to come, it’s robots that will be called upon to pilot themselves through the bodies of patients, to relay diagnostic data back to doctors, and to deliver precision-guided drug payloads inside tumors.
The recent history of cancer treatment is surprisingly full of robots. In 2000, the FDA cleared the Da Vinci Surgical System, a hulking, multi-armed robot remotely operated by humans for use in general laparoscopic surgery, during which instruments and cameras enter the body through small incisions. Laparoscopic surgery existed long before the Da Vinci, but the machine promised to increase the precision of those using it, and to reduce the chances of fatigue during hours-long operations. Instead of hunching over a patient while holding long, body-penetrating instruments, the surgeon sits at a console, peers at a 3-D video feed, and manipulates robotic tools with joysticks.
The promise of fewer complications and shorter hospital stays (since the procedures involve such small incisions) made Da Vinci systems wildly popular among the medical elite. They’re now found in every state in the U.S., including at the country’s leading cancer centers at the Mayo Clinic in Minnesota and Memorial Sloan Kettering Cancer Center in New York City. Of the more than 200,000 minimally-invasive procedures carried out annually using Da Vincis, the majority are cancer-related.
With more than 3,000 sold worldwide, these machines have been at the forefront of cancer surgery. But as robots go, their age is showing. Da Vincis have no autonomy, and are only as skilled as the people controlling them. They require multiple human helpers, as well, from those who swap out the instruments on the robot’s arms to people tasked with moving tissue and whole organs out of the way while the surgeon works. They are also huge, expensive devices, taking up precious real estate in operating rooms, and they’re priced at up to $2 million, a figure that’s only risen in the 16 years since their introduction despite strong global demand.
The future of cancer-fighting bots is, in many ways, the polar opposite of the Da Vinci, with systems that are smaller, more autonomous, and self-contained — less like advanced surgical tools and more like a robotic version of the body-exploring miniature vessel from the 1966 sci-fi film, Fantastic Voyage.
Researchers at Vanderbilt University’s STORM Lab in Tennessee are developing capsule robots that can navigate patients’ gastrointestinal tracts, gathering diagnostic data and extracting tissue. Present-day medical capsules are sensors that you swallow, with no onboard motors to change the orientation of cameras. The researchers at STORM Lab want to roboticize these devices, adding digital intelligence and actuators to control those tiny cameras, as well as components that can alter the capsule’s passage through the body, and even take biopsies from specific areas. Functioning like miniature unmanned submarines, these capsules could also vent gases from exhaust ports, distending the intestine in order to get a better look at a given stretch of organ wall.
The team’s initial focus — to improve the detection of colorectal cancers — happens to be one of the explicit goals of Biden’s moonshot initiative. But the larger trend in anti-cancer robots is moving beyond the merely small, and into the microscopic.
During the past year, three separate teams of researchers around the world have presented work related to the use of bacteria to deliver drug therapies to tumors. Though none of this year’s experiments employs actual robots, researchers see a direct link between the use of naturally-occurring microorganisms and the micro and nanobots to come. According to Sylvaine Martel, director of the Polytechnic Montréal Nanorobotics Laboratory, his three-university research team picked bacteria that would act as biological stand-ins for robots. They chose bacteria that were not only attracted to low-oxygen areas — such as tumor sites, since cancer cells consume oxygen as they multiply — but that possess a kind of internal compass, and would be drawn to magnetic fields.
“We looked at it like engineers,” Martel says. “This thing has all the components that we’d want to put in a future nanorobot.” That includes what he describes as “rotary motors,” functioning as tiny propellers. “They’re very fast, moving at 200 times their body length per second,” Martel says. “Very efficient machines.”
In experiments with mice, these bacteria were guided to the general area of a tumor with magnets, and then left to autonomously zero in on their targets based on low oxygen levels — since cancer cells consume oxygen as they multiply, a drop in oxygen is a tell-tale sign of their presence. At a size of 1.5 microns, the bacteria were small enough slip into holes in the sides of a tumor’s blood vessels, and travel to the heart of the tumor before releasing their chemical payloads.
That size is key to the mission of any bacteria or bacteria-mimicking delivery system. For all the discussion of nanorobots in science fiction, constructing motors and other robotic components that are a fraction of the size of a human hair (which are roughly 80 microns across) remains out of reach. And if a body-navigating bot can’t release drugs inside cancerous tissue, then it’s little better than traditional chemotherapy, which floods the body with powerful chemicals in the hopes of hitting vital targets, and often wreaks havoc on the patient in the process. If chemotherapy is carpet-bombing, nanobot therapy is a laser-guided munition.
The idea of hunter-seeker nanobots is strange enough, but Martel believes doctors could eventually craft cancer fighters that merge bacteria with artificial components, or what amounts to microorganic cyborgs. Bacteria might need special sensors that aren’t found in nature, or additional propulsion and protection, what Martel describes as a submarine-like shell to help them navigate the powerful blood flow in arteries. Another option is to program bacteria at the genetic level, altering the organism’s makeup and behaviors by introducing or tweaking genes.
Researchers at MIT demonstrated this approach earlier this year, transforming a harmless strain of E.coli into an autonomous triple-threat against tumors. The team added three artificial genetic circuits to the bacteria before injecting it into mice. These circuits are biological components — made up of genes or proteins — that don’t naturally occur in a given organism, and can change how they operate. The circuits introduced to E.coli helped them create chemicals that would cause the tumor’s cells to break down and self-destruct, as well as signaling the body’s immune system to join the attack.
Though MIT’s experiments were limited to genetically-programmed bacteria, researchers are exploring the overlap between today’s hacked bacteria and tomorrow’s potential nanobots, as well as the potential to apply robotic approaches to drug delivery. Swarm engineering, for example, has traditionally focused on the development of robots that cooperate towards a given purpose. Sabine Hauert, a roboticist and swarm engineer at Bristol University in the U.K., has devoted half of her lab to actual swarming bots — 1,000 coin-sized machines — and the other half to nanomedicine. The latter includes nanoparticles that serve as nano-scale vehicles, of sorts, for targeted drug therapies.
“I try to use techniques from swarm robotics, in terms of thinking of how you design these systems,” Hauert says. “We’d like to understand how to engineer the particle so that when they are in that complex tumor environment, they behave in the way you want them to, in a collective.”
Nanoparticles, which are exponentially smaller than bacteria, have no motors or moving parts. But they could be coated with specific particles to guide their otherwise passive travel, and be built to mimic the swarm communication found in some bacteria. For its modified E.coli, researchers at MIT took advantage of quorum sensing, or the ability of some bacteria to detect the presence of other nearby bacteria based on specific molecules they produce. Once that detection reached a critical mass, the E.coli released their chemicals all at once.
This coordinated release is one of the swarming behaviors that Hauert is hoping to apply to nanoparticles, letting them determine precisely when and how to attack a tumor as a group. Hauert hasn’t developed true swarming nanoparticles yet — “These are early days,” she says — but her lab is studying the distribution of particles in tumor tissue, and running computer simulations of potential swarming behaviors in more advanced particles.
Whether these cancer-attacking microorganisms are genetically modified, bionically enhanced, or inspirations for bots and particles of the future, the lines between these research efforts will continue to blur. As of right now, there’s no timetable for when robotic capsules or bio-mimicking nanobots might be deployed in cancer patients. The immediate future of cancer-related technology, including much of the work being done in Biden’s cancer moonshot initiative, is concerned mainly with the better use and sharing of medical data, and improved access to existing treatments. But new tactics and strategies are coming, and the use of drug-delivering bacteria appears to be on the horizon, with multiple clinical trials underway right now. Once those are cleared for use, the bots, cyborgs and other tiny fighters can’t be far behind.