Today, when we think of the dangers of the battlefield, we think of wounds caused by bullets, bombs, and other weapons. But as late as the Spanish American war of 1898, the number of soldiers who died from infectious diseases as opposed to directly from combat injuries was seven to one. Thanks to the discovery of penicillin and other antibiotics, that ratio has swung dramatically the other way, but it’s still a major problem, not only for military personnel, but civilians too. DARPA is developing an artificial spleen, or "biospleen," as a way to help fight deadly infections without antibiotics.
The reason why infection is so dangerous in both the military and civilian spheres is because it can lead to sepsis. That is, the body overreacts to the infection with often fatal results. According to DARPA, 18 million people worldwide contract sepsis every year with a mortality rate of 30 to 50 percent.
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The usual way to combat this is through antibiotics, but that brings its own problems. For one thing, in combat situations, surgeons use massive doses of antibiotics that in civilian life would be more suitable for treating an elephant. Another is that killing the bacteria causing the infection doesn't help if the toxins left behind aren't cleaned out. And even if successful, the routine use of antibiotics adds to the increasing danger of breeding antibiotic-resistant strains of microbes.
Sepsis microbes and toxins (blue and orange) stick to the protein-covered beads (white) (Image: DARPA)
An alternative way of handling infection is through dialysis. Similar to artificial kidney machines that clean the blood of waste products when the patient’s kidneys have failed, such a dialysis machine can also be configured to act like an artificial spleen.
For most people, what the spleen does is as mysterious as that switch they found under the sink when they moved in, but the liver-like organ plays a vital role in fighting infection by removing microbes and toxins from the bloodstream. Using a machine that can do the same thing could be a great help in dealing with combat-related sepsis, but such devices are large, expensive, and the exact opposite of portable.
DARPA’s Dialysis-Like Therapeutics (DLT) program aims at removing that bottleneck by coming up with a range of devices that can identify infections, move blood and other fluids about without the need for anticoagulants to keep the workings from gumming up, remove pathogens, and generally provide a sort of "closed loop" therapy for dealing with infections.
The biospleen is one example of the DLT technology. The goal isn't just to make a dialysis machine to do what a spleen does, but to make it integrated, portable, and rugged enough for field use, because the closer aid is to the soldier, the better their chances of survival.
The result is a prototype that’s about the size of a shoebox. Inside is circulating equipment and a series of small tubes like the interwoven blood vessels in the spleen. Like those blood vessels, the tube network is designed to act as a blood filter. The tricky bit is to get it to filter out the germs without taking blood cells with them and without triggering an immune response by the body.
It does this by having one of the tubes containing blood and the other a saline solution. These tubes are connected to one another by microscopic slits. So far, so conventional, but the key is that as the blood is pumped into the biospleen, it’s mixed with magnetic beads 128 nanometers in diameter. These are coated with an engineered human immune system protein called opsonin or mannose-binding lectin (MBL).
DARPA says that the engineered MBL is the breakthrough for the artificial spleen. The structure of the molecule allows its "head" to stick to the microbes or toxins while the "tail" sticks to the magnetic beads. The hard part was structuring the MBL molecule so it wouldn't attach itself to autoimmune system molecules, which would trigger a dangerous immune reaction or coagulation.
Once the microbes are stuck to the beads, a magnet pulls the beads through the slit into the saline channel where they’re flushed away for collection and removal, while the clean blood is returned to the patient. According to DARPA, this method removes Gram-positive bacteria, fungi, and endotoxins from whole human blood flowing through the biospleen unit at up to 1.25 l/hr (42.2 oz/hr) without the need to identify the bacteria or toxins first, which could save days in actual treatment.
When the system was tested on rats infected with a mix of Staphylococcus aureus and Escherichia coli, the biospleen removed 90 percent of the infectious agents inside of five hours.
DARPA says that development of the biospleen and other DLT technologies is ongoing and that if later tests can demonstrate the biospleen’s safety and efficacy, an application would be sought from the US Food and Drug Administration for human clinical trials.
"Sepsis is a massive problem for both civilian and military healthcare, which is why DARPA set out to develop more effective and portable technologies for sepsis treatment," says U.S.Army Col. Matt Hepburn, DARPA program manager. "Our ‘artificial spleen’ prototype shows a promising new way to fight sepsis more quickly and thoroughly. The technology is also small and light, and usable either on its own or with commercial dialysis equipment. We’re hopeful that this new technology could give doctors new tools to save lives in the future."
The artificial spleen is described in Nature Medicine.
Source: DARPAView gallery - 4 images