Blood and Blood Derivatives EDWIN J. COHN BLOOD has been related t o Lie in the minds of men since the earliest times. Swage tribes have d e b r a t e d symbolic blood brotherhoods and blwd sacrifices. I n Biblical times and in the middle ages hlood was regarded with superstition and awe, and often associated with the spirit of man. I n this war also blood has symbolized the spirit relating a civilian population to its sans in distant parts. The blood collected by the American Red Cross has not only brought relief but also evidence of social coherence to the most distant corners of the world to which it has been sent. What is the scientific knowledge regarding blood, as a result of which superstition and awe are receding and are slowly being replaced by an understanding of the chemical nature of the substances of which blood is composed and of their value in medicine and surgery? Blwd is a tissue, composed of many of the same kinds of suhstances as the other tissues of the body, of water and salts, sugars and fats, and proteins, but fluid, since i t must circulate and maintain equilibrium within the body. I t s circulation was discovered by Harvey in the early 17th century, and the k t step in unraveling its complexity followed the development later in that century of powerful lenses which revealed the presence of cells suspended in this circulatingfluid. The cells are readily separated from the fluid in which they are suspended by centrifugation, the same process used t o separate cream from milk. The lighter layer is called the plasma. The heavy layer contains all of the cells of the blood stream. These cells are of more than one kind, but one type of cell, red in color, occupies nearly half the volume of the blood. The primary function of the red cells is to provide for the respiration of the body. Every time you breathe you bring a fresh supply of oxygen from the air to your lungs where i t is combined with a special agent, the hemoglobin of the red cell, which carries it to the tissues. This special agent, hemog1obin;is a protein which contains iron in the state responsible both for the color and the great affinity of blood far oxygen. Red hlood cells are needed when there has been severe loss of blood, when major operations are t o be performed, and to combat the anemia which frequently occurs in convalescence from wounds. Whole blood is, therefore, made available whenever these conditions obtain. However, many of the functions of the whole blood are performed not by the red cells but by the plasma proteins. In these'conditions plasma, or the special plasma proteins that are needed, may be used. The plasma can he dried by methods that had been developed just before this war. Dry plasma has been prepared from the blood of many millions of Red Cross Donors and proved effective in the prevention and treatment of shock. Shock, as observed in military medicine, generally results from a rapid decrease in the volume of the blood due t o the loss of blood and plasma proteins. Reduced in volume and often thickened by the loss of more fluid than red cells the circulation of the blood becomes inadequate. Restoration of the volume of the blwd so that its circulation by the heart again approaches normal may be brought about by administration of plasma proteins. Proteins are very large molecules, and are the highly specialized substances which are most responsible for the structure and the complex functions of the body. The proteins of the plasma, as of other tissues, differ in size and shape. The smallest dimension of all plasma protein molecules-their diameter-is roughly the same. This diameter i5 five times that of sugar molecules. Small molecules, indeed all the :nolecules that have been studied which are appreciably smaller than the plasma proteins, are readily lost from the blood stream into the tissues or through the kidney. They are, therefore, of less value in the prevention and treatment of shock than the plasma proteins which are normally retained in the blood stream. Two out of every three of the protein molecules of plasma are of one kind, called albumin. Albumin is tbe protein in plasma 'largely responsible for the maintenance of blood volume. Albumin molecules are the smallest in size, the most nearly spherical
in shape, the most soluble, and the most stable of the plasma proteins. Albumin can therefore be prepared as a concentrated solution which is as fluid as whole blood, and is effective in the treatment of shock. Large amounts of this very compact derivative of plasma have been prepared and are in use b y our Navy. The separation of albumin from plasma b y the large-scale methods which have been developed releases the other plasma proteins for uses in medicine and surgery closely related t o their Functions in the body. How do we separate the plasma proteins from each other? Even closely related proteins can he separated because of their different solubilities in water or in alcohol-water mixtures, a t different acidities and a t different temperatures. As conditions are attained in which a fraction of the plasma proteins becomes insoluble, i t is separated as a precipitate in the centrifure and dried as a stable white oowder. These ourified r l r i t 4 product, rru he rtorrC ir~definittlyand redi\solved when nerdcd aispriifir conccntratrd thcrapeutir agrnrs. Let u i r u n 4 r r the physical propcrtic> of anorher dcrivativc of plasma, fibrinogen, which is concentrated in another plasma fraction. Only one in every hundred of the protein molecules in plasma is fibrinogen. Fibronogen is farlesssoluble than albumin. Its molecules are of roughly the same diameter but six times as long as albumin. Indeed fibrinogen molecules are like needles. 20 times as long as they are thick. This shape is closely related to the fibrous structure of the clot formed of fibrinogen which stops the flow of blood from a c u t or wound. The chemical nature of the fibrinogen molecule endows products made from this protein with remarkable elastic and mechanical properties not unlike those of certain synthetic fibers such as nylon. Films of fibrinogen have been used as substitutes for the d u n , the lining membrane of the brain. Fibrinogen can also he formed intoplastics. The transformation of the fibrinogen dissolved in the plasma into the insoluble blood clot involves a series of reactions in which a protein we call thrombin is liberated. To stop the 5ow of blood in many surgical procedures thrombin is the only component which must besupplied. Thrombin is bestapplied, however. with a matrix which can hold the thrombin in the bleeding area until clotting is completed. Such a matrix formed of human fibrin and called fibrin foam is now in use in military neurosurgery. If the properties of hemoglobin, of albumin, and of the fibrinogen of the blood stream are so different, how are we to understand the functions of the variety of other plasma proteins which have been called globulins? Globulins are of many kinds. One group holds fats in solution and transports them in the plasma. Another small group agglutinates the red cells of different blwd types. These may be used as reagents for the typing of whole hlwd. The mast important globulins from the point of view of the public health are, however, the gamma globulins which are the antibodies to infectious diseases. Not all of the antibodies concentrated from human plasma will he of value in the contrvl of disease. However, in the case of measles, the concentrated antibodies have been employed with great success, either to a m m protection or to modify the severity of the disease. Gamma globulins are now being supplied to the Armed Forces and through the American Red Cross t o public health agencies for protection against mearles. Their value in the control of infectious jaundice has also recently been demonstrated. All of these products may be separated, purified. and concentrated from the same blood. The chemist is fulfilliur his function
blood performs an important natural function, we must make available in the postwar world, as we have in this war., as many as possible of its diverse cellular, protein, and fatty components. separated and concentrated as specific therapeutic agents, of value in different conditions, in the interests of the most effective and economical use by a society of the blood which it contributes. -A radio talk, refirinled by permission of the United Stelel Rubber Comfiany.
