Carbon nanotubes rule.
In this year’s STAT Madness, a bracket-style competition to honor the best in recent biomedical research, each finalist exploited carbon nanotubes to tackle one of the two leading causes of death in the U.S.: heart disease and cancer.
One finalist, a team from MIT’s Koch Institute for Integrative Cancer Research, engineered a fluorescing carbon nanotubule — an “amazing” material — to better see the multitude of tiny ovarian cancer tumors deep in the body and unseen by a surgeon’s eyes. The other finalist, from the Texas Heart Institute and Rice University, created fibers from “magical” carbon nanotubes to bridge over scarred heart tissue following a heart attack to prevent deadly rhythm disturbances.
After five weeks and a record-setting 699,315 votes, we have a champion: the Koch Institute, which drew 70% of the votes in the final round.
Angela Belcher, chair of MIT’s Department of Biological Engineering, and her team tackled the daunting challenge of ovarian cancer, which owes its disappointing survival rates to late detection, usually after the initial cancer cells have spread like wildfire from the ovary to other organs and tissues throughout the abdomen.
The initial treatment is an operation known as surgical debulking, where as many tumors as a surgeon can see are removed before giving chemotherapy. The more tumors removed, the longer the patient survives. Belcher and her colleagues asked how they could help surgeons see better.
Working with oncologists from Harvard-affiliated hospitals and engineers at MIT’s Lincoln Laboratory, they developed a system that manipulates carbon nanotubes so they fluoresce in the wavelengths needed to penetrate tissue deep inside the body. The nanotubes are 1 nanometer in diameter — far thinner than a human hair — and are injected 24 hours before surgery.
These probes find ovarian cancer cells by piggybacking on bacteriophages genetically engineered to latch onto a specific protein found in abundance on these invasive cancer cells. Their fluorescence in low wavelengths is boosted by infrared light to show the anatomy — organs and tissues where the tumors are lurking. And a third light source illuminates it all for the surgeon, who is guided by a software-enabled display on a monitor.
“We built about five generations of new imaging instruments over the last couple of years all around the idea of non-invasively trying to see deep inside the body to find tiny tumors or early events in the disease process, which could help surgeons or physicians diagnose or intervene with treatment,” Belcher said.
Their experiments are just in mice now, but Belcher is encouraged by the 40% improvement in survival found in the animals. Tumors smaller than a poppy seed glowed enough for surgeons to remove them. Prototypes for humans are being scaled up, with an eye toward one day using the system not just in debulking operations but also in diagnosing ovarian cancer early — like a mammogram for breast cancer — and in monitoring progress after surgery, all without the radiation other imaging tools use.
In March the imaging system won acceptance into a testing program run by the National Cancer Institute’s Nanotechnology Characterization Laboratory, where it will be evaluated and then promoted for clinical translation into therapies. Belcher’s team is also talking to the Food and Drug Administration about launching a small Phase 1 trial in people.
“We’re working on a problem that we feel very, very passionately about,” Belcher said. “And getting a footing for that, I think, has been exciting and humbling.”
The STAT Madness runner-up also confronted a disease with dire outcomes. People who have suffered a heart attack are vulnerable to a type of heart rhythm disturbance that causes sudden death unless a defibrillator is available to reset the heart’s electrical signaling. This susceptibility is caused by scar tissue that forms when the heart is starved of oxygen during a heart attack — and that can disrupt the normal flow of electrical signals. The disruption causes the ventricles, the heart’s lower chambers, to quiver in a chaotic rhythm that quickly leads to the most common cause of sudden cardiac death.
Surgical ablation is sometimes used to burn away the scar tissue, but that can compound the problem of a weakened heart. Mehdi Razavi, director of electrophysiology clinical research and innovations at the Texas Heart Institute, performs these procedures as a cardiologist focused on electrophysiology, and he wanted to find a better way to treat these patients.
Picture the heart’s electrical signals as a wave approaching the shore. If you are standing in the water, the wave breaks around you and eddy currents form. Ventricular fibrillation is like eddy currents of electricity in the heart, which form where a wave of electrical impulses can’t pass through scar tissue.
Razavi’s Texas Heart team and colleagues at Rice University devised sutures made from carbon nanotubes, fibers that conduct electricity twice as well as the copper found in almost all wiring. The carbon nanotube threads can be seamlessly sewn across damaged heart tissue to bypass lethal disruptions in electrical signals.
The approach has been tested in mice and in sheep during surgery, but one day Razavi hopes the threads could also be delivered to the heart through a catheter and stitched into place in that less-invasive way. More intensive biocompatibility studies of the material over time will be needed.
Currently, patients whose previous heart attack puts them at risk of a fatal rhythm abnormality take anti-anxiety medications that Razavi said have a success rate of 30% to 50%. Surgical ablation can help, but cauterizing healthy heart cells should be done with caution. And defibrillators work only as a reaction to the problem. Razavi hopes to prevent it from happening at all.
There are other lines of research: One is regenerative medicine, which grows new heart tissue on scaffolds seeded with stem cells and implanted in the heart, and another is genetic engineering, to manipulate the production of healthy new heart cells.
“We believe that this is somewhat more straightforward,” Razavi said about bridging over scar tissue with carbon nanotube threads. “You have an endpoint where you do the procedure, the [electrical] conduction improves, and you see it right away.”
The two finalists emerged from 128 total entries from U.S. research institutions, out of which the field was narrowed to the bracket of 64 discoveries and inventions published in peer-reviewed journals in 2019, based on the scientific rigor of the research, the originality and novelty of the work, and its potential beneficial impact in its respective field or for patients and society. They came from 18 states and Washington, D.C., spread across every time zone and region.
In a world transfixed by the public health, medical, and scientific challenge of a lifetime, the scientists welcomed a chance to look away from the coronavirus pandemic and celebrate the best in biomedical research through STAT Madness — which is modeled on the NCAA college basketball tournament.
“Our team had a great time with this,” said Razavi, who’s a big college basketball fan. “It was a little bit of a bright spot during a pretty scary time.”
MIT’s Belcher said her family loyally follows different teams in the March Madness basketball tournament every year, but this year, when the basketball version was canceled due to Covid-19, they were united behind her team.
“What an extraordinary time we’re living through right now,” she said. “In the end, having something that you look forward to, that people are rallying around, it’s a way of lifting up. I think that it’s been even more important in this time than it would be in a normal year.”