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 used in World War II
as a way to collect blood, specifically in the United States for export to Britain. Although this
technique was developed in Philadelphia, its impact was felt worldwide and was crucial to
saving 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 early
1900s. 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 that
Staurt 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 until
the 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 England
were 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 the
fact that blood is a composition of many proteins, which can and will eventually break down
under 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 outside
of the living organism aggregate and become insoluble, a sequence of events known as
denaturation. Denaturation is influenced by time and temperature, and is a variable process
dependent on the type of protein(s) involved. The problem with the commercial drying
techniques 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 blood
and biological materials.

In short, the process developed by Mudd and Flosdorf was a method of drying by sublimation
after “high speed vertical spin freezing,” followed by a secondary desiccation. Now you may be
saying to yourself, “Wait a minute, sublimation, desiccation… what?!” Simply put, blood is
separated into its components, frozen, and dried twice so that there is less than 0.5% water left
in the blood sample. This manner of drying blood is preferred over other methods since it leads
to little or no protein denaturation, or degradation. The reason for this is because the proteins
are dried by sublimation, which is the transition from a solid directly to a gas without
transitioning through the intermediate liquid phase. This removes the water from the frozen state
blood without multiple transitions in temperature and time which is the cause of minimal
degradation to the proteins in blood.
When war broke out in 1939, it seemed that blood transfusion would play an important role in
the 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. In
addition to this, the use of whole blood for transfusion in the field was limited due to the
necessity 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 finally
10 years later in 1945, grew into a workable procedure. The techniques to carry out the high
vacuum drying by sublimation involve two stages. In the first, ice is evaporated from a frozen
state. In this stage heat is introduced to the frozen material very rapidly so that it does not soften
or melt, which would occur in a slower process. At the same time the heat introduced will create
gas which will need to be removed with a maximal flow of air away from the solid. Two common
methods to carry out the first step involve condensation at a low temperature with condensers
chilled with dry ice or refrigerants such as Freon. The second method uses high capacity steam
ejectors for direct pumping and evacuation of vapor. Both methods need to occur at -9° to -12°C
with regards to drying blood. In the second and final stage, the moisture is removed from the
final dry solid to further reduce the residual content. This step is carried out at -40°C and
involves another heating step which is not as strict in its execution as the first step since the
remainder 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 perfect
the process of blood drying in a pilot plant, which was a drying plant for large scale work and
war-time difficulties. To carry out this process, first, serologic studies were performed on each
blood donation. Then the blood was separated from the cellular elements in centrifuges. It was
frozen in individual bottles via rotation in a cooling medium. Using this process, the blood could
be desiccated from the frozen state under a high vacuum for long periods of storage. The basic
methods 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 centrifugal
vacuum spin-freezing developed by Greaves and colleagues, which would become the industry
standard. This technique involves freezing the plasma by spinning the bottles at a high speed in
a 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 crystals
are more finely divided, which allows for quicker reconstitution of the dried product. This method
was more widely used in Canada and England.

The work by these three men developed standards for freeze drying methods by 1945 that
became crucial parts of World War II blood and transfusion programs. The process blood goes
through 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 separate
plasma from red blood cells. In the second illustration the plasma is pooled along with a glucose
solution, for help in preservation. The third photograph shows different containers used to
collect and store blood, as well as cultures to check the sterility of blood. The fourth image
shows pooled liquid plasma held in storage until cultures are reported negative; then it will be
frozen. The final print shows a freezer loaded with frozen plasma, which will be kept in this state
until it is removed and thawed for shipment.

When these techniques were put into action problems arose with regards to blood typing and
the rejection of certain blood transfusions in soldiers. This paved the way to new studies into the
components 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 others
to further study this field and to work to completely understand the transfusion process and
discover all of the components involved.
The development of drying blood has led to the use of this process for the preservation of many
other biological products, including live viruses for use in vaccines, living bacteria, hormones,
tissue extracts, antibiotics, such as penicillin, and even chemotherapeutics, or cancer therapy
drugs. 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 United
States 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 practice
of blood transfusion became crucial not only in the field of battle but also in civilian surgeries
and transfusions for the sick. The variety of applications that this process has been used for is
innumerable. These men have inspired other scientists to push the boundaries and open doors
in 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 to
the drying of human blood.
Bibliography
Blood Transfusion and Donation. National Institutes of Health, 16 Mar. 2010. Web. 6 Apr.
2010. <http://www.nlm.nih.gov/medlineplus/bloodtransfusionanddonation.html>.

Churchill, Edward D. "The Physiologic Effects of Wounds." Office of Medical History. Ed.
Joseph H. McNinch. U.S. Army Medical Department, 1952. Web. 15 Feb. 2010.
<http://history.amedd.army.mil/booksdocs/wwii/PhysiologicEffetsofWounds/defa
ult.htm#Contents>.

Flosdorf, Earl W., Staurt Mudd, and Lewis W. Hull. "Drying by Sublimation." The Journal of
Immunology 50.1 (1945): 21-54. Web. 15 Feb. 2010.
<http://www.jimmunol.org/cgi/content/abstract/50/1/21>.

Flosdorf, Earl W. “Advances in Drying by Sublimation.” The Journal of Chemical Education.

(1945): 470 – 480.

Greaves, Ronald Ivan Norreys. “The Preservation of Proteins by Drying, With Special
Reference to the Production of Dried Human Serum and Plasma for Transfusion.”
London: H.M. Stationery Off, 1946.

Kendrick, Douglas B. Blood Program in WWII. Washington D.C.: The Surgeon General, 1964.
Web. 15 Feb. 2010. <http://history.amedd.army.mil/booksdocs/wwii/blood/default.htm>.

Meryman, H T. "Historical recollections of freeze-drying." Dev Biol Stand 36.10. (1976): 29-
32. Web.15 Feb. 2010. <http://www.ncbi.nlm.nih.gov/pubmed/801137>.

"Mudd, Stuart Harvey." American Men & Women of Science. Ed. Katherine H. Nemeh,
Pamela M. Kalte, and Noah Schusterbauer. 22nd ed. Vol. 5. Detroit: Gale, 2005. 543.
Gale Virtual Reference Library. Web. 15 Feb. 2010.

"The 1930s: Medicine And Health: People in the News." American Decades Primary
Sources. 2001. Web. 15 Feb. 2010. <http://www.encyclopedia.com/doc/1G2-
3468301303.html>.

Vendelmans, Henry. The Manual of Manures. New York: C. Scribner's sons, 1916.