The ultimate blood substitute? The U.S. military is betting $46 million on it

🌈 Abstract

The article discusses the history and current state of research on artificial blood substitutes, focusing on a product called ErythroMer developed by researchers at the University of Maryland. It covers the challenges of developing effective blood substitutes, the limitations of past attempts, and the potential advantages of ErythroMer's approach of encapsulating hemoglobin in an artificial membrane to mimic natural red blood cells.

🙋 Q&A

[01] History of Blood Substitutes

1. What was the motivation behind early attempts to use milk as a blood substitute in the 19th century? In the 19th century, severe bleeding was often a death sentence, and doctors were looking for less risky alternatives to blood transfusions. Theodore Gaillard Thomas, a prominent gynecologist, advocated for using milk as a blood substitute, believing it could help stabilize hemorrhaging patients.

2. What were the limitations of early blood substitute attempts using milk and unencapsulated hemoglobin? Milk transfusions were not successful, as they caused side effects like fever and high heart rate in patients. Unencapsulated hemoglobin-based oxygen carriers (HBOCs) also had issues, leading to complications like hypertension, heart attacks, and kidney failure due to the free hemoglobin's interaction with nitric oxide.

[02] ErythroMer: A New Approach to Blood Substitutes

1. How does ErythroMer differ from past HBOC attempts? ErythroMer encapsulates recycled human hemoglobin in an artificial membrane designed to mimic the natural function of red blood cells. This includes controlling the availability of 2,3-DPG, a molecule that regulates hemoglobin's oxygen affinity, to optimize oxygen transport.

2. What are the potential advantages of ErythroMer compared to donated blood? ErythroMer has a longer shelf life than donated blood, can be freeze-dried for easy storage and transport, and should be compatible with any blood type since it doesn't contain the surface proteins that cause mismatches. It could be useful in settings where fresh blood is scarce, such as battlefields and rural areas.

3. What is the current status of ErythroMer's development and testing? ErythroMer is still in the early stages of animal testing, but has shown promising results in delivering oxygen effectively in animal models. The researchers hope to begin initial safety testing in healthy humans within the next 4 years, as part of a $46 million grant from DARPA.

[03] Challenges and Outlook for Blood Substitutes

1. What are some of the key challenges in developing effective blood substitutes? Blood is a complex mixture of cells and molecules, and imitating its full functionality has proven very difficult. Past attempts with HBOCs faced issues like toxicity, vasoconstriction, and increased mortality rates compared to standard blood transfusions.

2. How do experts view the prospects for ErythroMer and other new HBOC products? Opinions are mixed, with some experts skeptical that encapsulated hemoglobin can overcome the limitations of past HBOCs. However, others believe the field has advanced enough that with proper financing, one or more safe and effective blood substitutes could reach the market to address the ongoing shortage of donated blood.