The US military’s race to make fake blood

The US military and civilian healthcare systems face a severe shortage of blood, which is critical for treating hemorrhage, the leading cause of preventable deaths on battlefields and maternal deaths worldwide. In the US, about 10,000 preventable deaths occur annually due to blood shortages, with 1% of 1.2 million trauma patients receiving blood before reaching a hospital. Globally, the figure is likely in the millions. Whole blood lasts only 35 days when refrigerated, and separated components like platelets (lasting a week or less) and frozen red blood cells or plasma (spoiling within days after thawing) have limited shelf lives. The military’s reliance on ‘blood runs’—emergency missions to transport blood—exposes crews to high risks, as seen in the 2007 crash of helicopter Morphine 1-2, which was transporting blood when shot down.

To address the blood shortage, the US military’s research arm, DARPA (Defense Advanced Research Projects Agency), launched a $73 million program called RAPIID in 2026. Led by Lieutenant Commander Robert Murray, RAPIID aims to create shelf-stable synthetic versions of plasma, platelets, and red blood cells by 2029. This follows earlier efforts like FSHARP ($47.5 million), which showed promising animal results. The urgency stems from a JAMA study indicating that trauma patients need transfusions within 36 minutes to survive. Synthetic blood could eliminate logistical risks, such as relying on a single blood bank in Okinawa, which could be disabled by a missile strike.

Plasma, the liquid part of blood (55% of its volume), is the most advanced synthetic blood component. Freeze-dried plasma has been used since World War II to restore blood volume and aid clotting, though it was abandoned in the 1960s due to hepatitis transmission risks. Improved techniques revived its use in 2010, and the FDA now allows two types of freeze-dried plasma for emergencies, including civilian use. Plasma is easier to synthesize because it consists of water, salts, and proteins, without the complex structures of cells. However, it does not carry oxygen, making it only a partial solution.

Platelets are tiny cells that help blood clot, but they are difficult to preserve or replicate. Traditional methods to extend their shelf life date back to the 1950s, with limited success. Bioengineers have tried attaching platelet membranes to synthetic particles or freeze-drying actual human platelets, as done by the company Cellphire. While Cellphire’s product has shown safety in human trials, its reliance on donor blood makes scaling uncertain. Synthetic alternatives, like those being developed by Anirban Sen Gupta at Case Western Reserve University, aim to mimic platelets’ clotting functions without biological limitations.

Red blood cells carry oxygen using hemoglobin, but delivering hemoglobin without its natural cell membrane is challenging. Naked hemoglobin breaks down quickly, causes organ damage, and constricts blood vessels by scavenging nitric oxide. In the 1980s and 1990s, hemoglobin-based oxygen carriers (HBOCs) like HemAssist were tested but failed due to safety issues, including a 24% higher death rate in clinical trials. Recent advances, such as KaloCyte’s ErythroMer, use lipid nanoparticles to protect hemoglobin, allowing it to release oxygen safely. ErythroMer can be freeze-dried for two-year storage at room temperature and has shown promise in animal studies.

Another approach, ‘blood pharming,’ involves growing red blood cells from stem cells, but this method faces high costs (tens of thousands of dollars per unit) and low yields. A DARPA initiative in 2008 failed to reduce costs below this threshold, leading to its termination. Even if affordable, lab-grown blood still requires refrigeration and special handling, making it impractical for battlefield use. Murray notes that these cells are not shelf-stable like synthetic alternatives, highlighting the need for non-cellular solutions. The focus has shifted to developing components that can be stored in backpacks and rehydrated on demand.

KaloCyte, led by CEO Elaine Haynes, is developing ErythroMer, a synthetic red blood cell substitute. It uses hemoglobin from expiring donor blood, encased in a lipid nanoparticle to mimic a cell membrane. The product includes a lipid called KC-1003, which regulates oxygen release based on pH levels in the lungs and tissues. ErythroMer can be freeze-dried for two-year storage and rehydrated in the field. Currently, KaloCyte sources 1,000–2,000 units of hemoglobin monthly but plans to use lab-grown hemoglobin from yeast to scale production. The goal is to combine ErythroMer with synthetic platelets and plasma for a complete battlefield transfusion solution.

Synthetic platelets, like those being developed by Anirban Sen Gupta at Case Western Reserve University, aim to replicate the clotting functions of natural platelets. These particles carry peptides—short chains of amino acids—that act like tools on a Swiss Army knife, helping the synthetic platelets stick to broken blood vessels and to each other. Unlike natural platelets, which degrade quickly, synthetic versions could last longer and be stored at room temperature. Their integration with ErythroMer and plasma could create a three-part synthetic blood system, though challenges remain in ensuring compatibility and effectiveness in real-world conditions.