In the seemingly never-ending battle to catch up with nature's killers, Ingber's work is a promising and potentially game-changing development: a device that filters deadly pathogens out of the blood and allows the body's immune system to catch up. And it is effective against at least 90 ailments, including Ebola, E. coli and HIV.
In a paper published in the journal Nature Medicine on Sunday, Ingber's team found that of a group of rats that were infected with deadly levels of E. coli or staphylococcus, 89 percent of the ones whose blood had been filtered by the device survived, compared to 14 percent who survived with no blood filter.
The device itself functions like a dialysis machine. It removes blood from the body, filters it, then returns it to the body. The key innovation, however, lies in a single protein that naturally occurs in the human body that was genetically modified to maximize its pathogen-fighting abilities with the fewest side effects.
In a healthy immune system, the protein, mannose-binding lectin (MBL), naturally attaches to carbohydrate molecules found on bacteria, viruses and fungi, and it helps trigger the immune system response that allows the body to destroy those invaders.
This process works fine for most people. But when infections turn deadly, it typically is because the virus has overwhelmed the body's natural ability to fight it.
Sepsis, the result of a toxic buildup in the blood of dead pathogens that result from the body's immune system response to invasion, is the dark side of this process. It can can lead to fever and low blood pressure and eventually lead to multiple organ failure.
In Ebola patients, for example, with no cure or therapy, while the virus attacks the immune system, doctors can only try to support patients' bodily functions with rehydration and fluid replacement so they can live long enough for their immune systems to fight the virus. Researchers believe there may be similarities between septic shock and how the Ebola virus eventually kills its human host.
"Infection is a battle," said Ingber, who is also the founding director of Harvard's Wyss Institute for Biologically Inspired Engineering. "And you basically hit a tipping point where the invader is overcoming your ability to fight them."
At that point, a few things happen. When the immune system kills pathogens, it leaves behind fragments of the bugs that are toxic. A build up of these dead pathogens "triggers a cascade to inflammation that can lead to multiple organ failure," Ingber said.
The naturally-occurring form of MBL also causes another adverse effect: excessive blood coagulation.
To create this device, Ingber's team genetically modified MBL to keep the best parts -- its ability to identify and bind with a wide variety of pathogens -- while getting rid of the worst features -- its role in activating inflammation in the body and causing blood coagulation that both lead to septic shock.
Magnetic nano-sized microbeads are then coated with the genetically modified proteins. When the blood goes through the device, the MBL proteins bind to it, then are pulled out of the blood -- toxins attached -- through magnetic forces.
"Clean" blood then reenters the body, which allows the immune system to regroup and catch up with its invader.
The next phase of his team's work will involve more animal trials on a more simplified device. And team members are also working on using a magnetic particle that they can be more certain completely leaves human blood before it goes back into the body. (There are several particles FDA approved to cleanse blood already in use in other devices, for example.)
The potential implications are as big as they are widespread. While it isn't a cure for the viruses and infections that ail us, the device could provide life-saving support to an immune system under siege by deadly invader, without the use of antibiotic drugs that increase the population of drug-resistant bacteria.
"There’s a huge need for treatment of patients with sepsis, especially because it increases antibiotic resistance," Ingber said.