A World Where Blood Was Made Possible

A World Where Blood Was Made Possible Joe Wahler Imagine a world with no blood transfusions. Millions would be lost to war, sickness, and surgery just because they were unable to receive fresh blood. Without the research carried out by two biochemists, Staurt Mudd and Earl Flosdorf in the early 1930’s at the University of Pennsylvania, this might have been the case. Their research was devoted to the drying and packaging of human blood serum, which is a medical technique that was developed and us
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  A World Where Blood Was Made PossibleJoe Wahler Imagine a world with no blood transfusions. Millions would be lost to war, sickness, and surgery just because they were unable to receive fresh blood. Without the research carried out by twobiochemists, Staurt Mudd and Earl Flosdorf in the early 1930’s at the University of Pennsylvania,this might have been the case. Their research was devoted to the drying and packaging of human blood serum, which is a medical technique that was developed and used in World War IIas a way to collect blood, specifically in the United States for export to Britain. Although thistechnique was developed in Philadelphia, its impact was felt worldwide and was crucial tosaving millions of lives during the war and even today is put to use in a variety of applications.In one of its first applications, dried blood was used in agriculture as a fertilizer in the early1900s. The blood was allowed to coagulate, then the clotted blood was separated out and dried,it was pulverized and directly applied to the ground. It was not until December of 1933 thatStaurt Mudd, native to Bryn Mawr, Pennsylvania and Dr. Earl W. Flosdorf at the University of Pennsylvania prepared the first dried human blood. These methods remained unperfected untilthe 1940s, when they became necessary for World War II Military programs. The findings of Flosdorf and Mudd in Pennsylvania, along with the contributions of Ronald Greaves in Englandwere largely responsible for the development of large scale applications of freeze drying.The problem of transporting blood over long distances to help in the fight overseas lied in thefact that blood is a composition of many proteins, which can and will eventually break downunder normal environmental conditions. Proteins are the basis of all living material and life itself is maintained through the building and breaking of these molecules. Biological proteins outsideof the living organism aggregate and become insoluble, a sequence of events known asdenaturation. Denaturation is influenced by time and temperature, and is a variable processdependent on the type of protein(s) involved. The problem with the commercial dryingtechniques available at the time was that application of heat destroyed crucial proteins in blood,due to denaturation. Therefore, different methods needed to be developed, specifically for bloodand biological materials.In short, the process developed by Mudd and Flosdorf was a method of drying by sublimationafter “high speed vertical spin freezing,” followed by a secondary desiccation. Now you may besaying to yourself, “Wait a minute, sublimation, desiccation… what?!” Simply put, blood isseparated into its components, frozen, and dried twice so that there is less than 0.5% water leftin the blood sample. This manner of drying blood is preferred over other methods since it leadsto little or no protein denaturation, or degradation. The reason for this is because the proteinsare dried by sublimation, which is the transition from a solid directly to a gas withouttransitioning through the intermediate liquid phase. This removes the water from the frozen stateblood without multiple transitions in temperature and time which is the cause of minimaldegradation to the proteins in blood.  When war broke out in 1939, it seemed that blood transfusion would play an important role inthe treatment of casualties. The problem with this was that whole blood, unless given fresh,needed to be refrigerated, and even then could only be used for a limited time after collection. Inaddition to this, the use of whole blood for transfusion in the field was limited due to thenecessity for cold storage. Therefore, the conditions of war demanded for a blood derivative,which was stable, transportable, and suitable for administration to any patients.The methods by Flosdorf and Mudd developed out of a laboratory curiosity in 1935 and finally10 years later in 1945, grew into a workable procedure. The techniques to carry out the highvacuum drying by sublimation involve two stages. In the first, ice is evaporated from a frozenstate. In this stage heat is introduced to the frozen material very rapidly so that it does not softenor melt, which would occur in a slower process. At the same time the heat introduced will creategas which will need to be removed with a maximal flow of air away from the solid. Two commonmethods to carry out the first step involve condensation at a low temperature with condenserschilled with dry ice or refrigerants such as Freon. The second method uses high capacity steamejectors for direct pumping and evacuation of vapor. Both methods need to occur at -9 ° to -12°Cwith regards to drying blood. In the second and final stage, the moisture is removed from thefinal dry solid to further reduce the residual content. This step is carried out at -40°C andinvolves another heating step which is not as strict in its execution as the first step since theremainder of water being evaporated is so small. Although Mudd and Flosdorf made major contributions to the process, other work was occurring overseas at the same time.Ronald Greaves worked in the Blood Drying Unit in Cambridge, England and worked to perfectthe process of blood drying in a pilot plant, which was a drying plant for large scale work andwar-time difficulties. To carry out this process, first, serologic studies were performed on eachblood donation. Then the blood was separated from the cellular elements in centrifuges. It wasfrozen in individual bottles via rotation in a cooling medium. Using this process, the blood couldbe desiccated from the frozen state under a high vacuum for long periods of storage. The basicmethods preferred by Greaves were nearly identical to those of Mudd and Flosdorf. A minor difference in the methods was with regards to chilling the condenser with an alcohol bath rather than dry ice, mainly for cost purposes. Another difference lay in the emphasis of centrifugalvacuum spin-freezing developed by Greaves and colleagues, which would become the industrystandard. This technique involves freezing the plasma by spinning the bottles at a high speed ina sub-freezing chamber. This centrifugal action evenly spreads the plasma on the inner walls of the container until it is frozen. This gives the benefit of a more even layer and the frozen crystalsare more finely divided, which allows for quicker reconstitution of the dried product. This methodwas more widely used in Canada and England.The work by these three men developed standards for freeze drying methods by 1945 thatbecame crucial parts of World War II blood and transfusion programs. The process blood goesthrough during its drying and storage is illustrated in Figure 1, in a service laboratory in Houston,Texas.    Image Source: U.S. Army Medical Department, Office of Medical History Figure 1. In the first picture blood is centrifuged, or spun at a high rate of speed to separateplasma from red blood cells. In the second illustration the plasma is pooled along with a glucosesolution, for help in preservation. The third photograph shows different containers used tocollect and store blood, as well as cultures to check the sterility of blood. The fourth imageshows pooled liquid plasma held in storage until cultures are reported negative; then it will befrozen. The final print shows a freezer loaded with frozen plasma, which will be kept in this stateuntil it is removed and thawed for shipment.When these techniques were put into action problems arose with regards to blood typing andthe rejection of certain blood transfusions in soldiers. This paved the way to new studies into thecomponents of blood and exactly how the body reacts when transfusions are performed.Therefore, the men who developed the process for drying blood for transfusions inspired othersto further study this field and to work to completely understand the transfusion process anddiscover all of the components involved.  The development of drying blood has led to the use of this process for the preservation of manyother biological products, including live viruses for use in vaccines, living bacteria, hormones,tissue extracts, antibiotics, such as penicillin, and even chemotherapeutics, or cancer therapydrugs. These techniques even became common in the food industry, specifically for milk, eggs,meat, vegetables, and fruit.According to the National Institutes of Health, every year nearly 5 million people in the UnitedStates receive life-saving blood transfusions. These methods helped to save millions of lives,not only within Pennsylvania, or even the United States, but throughout the world. The practiceof blood transfusion became crucial not only in the field of battle but also in civilian surgeriesand transfusions for the sick. The variety of applications that this process has been used for isinnumerable. These men have inspired other scientists to push the boundaries and open doorsin the study of blood. Mudd and Flosdorf have made contributions to the scientific world far beyond the scope they ever could have thought of when one day their tinkering in the lab lead tothe drying of human blood.
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