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Chapter IV

Contents

CHAPTER IV

Administrative Considerations in the Zone of Interior

The blood and plasma program of the U.S. Army Medical Department in World War II involved the cooperation of a number of agencies, both in and out of the Department, including the Army Medical School; NRC (National Research Council); the Office of The Surgeon General; the National Institute of Health; the U.S. Navy; the American Red Cross; and the millions of donors who gave their blood to supply blood, plasma, and byproducts of blood for the Army, including the Army Air Forces, and the Navy. It was a magnificent national endeavor, and it saved countless lives.

The activities of these various agencies occurred, for the most part, at the same time, but they are most conveniently described under special headings (1).

ARMY MEDICAL SCHOOL

Organization of the Blood Research Branch

The first steps in the plasma and blood program in World War II were taken early in 1940 by Col. (later Brig. Gen.) Charles C. Hillman, MC, Chief, Professional Services Division, Office of The Surgeon General (fig. 6). His first action was to request Col. (later Brig. Gen.) George R. Callender, MC, Commandant, Army Medical School (fig. 7), to organize a blood research branch in the Division of Surgical Physiology at the school.

At the same time that Colonel Hillman made this request, he, acting for The Surgeon General, also requested the Division of Medical Sciences, NRC, to assemble a civilian committee to act informally, in an advisory capacity to the Surgeons General of the Army and the Navy. The Committee on Transfusions (p. 73) was appointed in response to this request.

The Division of Surgical Physiology at the Army Medical School had been set up in 1936, by Capt. (later Col.) Sam Seeley, MC, but it had ceased to function in 1938, after 2 years of very active operation, when he was transferred elsewhere. When it was reactivated in the spring of 1940, Capt. (later


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FIGURE 6.-Brig. Gen. Charles C. Hillman, Chief, Professional Services Division, Office of  The Surgeon General.

Col.) Douglas B. Kendrick, MC, was selected to head it, because of his earlier training and experience.1

Personnel

The original personnel of the division consisted of Captain Kendrick (fig. 8) and an enlisted man who served as technical assistant. The number of its personnel varied from time to time, but the list for July 1944 may be taken as typical of the roster for the greater part of the war:

Officers:

One lieutenant colonel, MC, whose chief duties were administrative.
Two captains, MC, whose chief duties concerned production and research.
One captain, SnC, whose chief duty was research.

1During a civilian surgical residency at Grady Hospital, in Atlanta, under Dr. Daniel C. Elkin, Captain Kendrick had a considerable experience in traumatic surgery, with its attendant problems, including shock. He also served under Dr. Fred Rudder, who was greatly interested in the use of whole blood in shock and who devised an ingenious apparatus for direct transfusion.
After his service at Grady Hospital, Captain Kendrick entered the Army Medical Corps and, because of his previous experience, he was sent for a year to the Institute of Experimental Medicine at the Mayo Clinic, Rochester, Minn., where he worked on gas gangrene; the special uses of the sulfonamides; anesthesia (under Dr. John S. Lundy); shock; and replacement fluids. The plan had been that on his return to the Army Medical School, Captain Kendrick should continue Captain Seeley's work. Funds for research, however, proved so inadequate that this plan could not be carried out. Captain Kendrick was therefore assigned to the orthopedic service, Walter Reed General Hospital, Washington, D.C., and he was transferred from it when, at Colonel Hillman's request, the Department of Surgical Physiology, Army Medical School, was reactivated, with research in blood and blood substitutes as its chief objective.-J. B. C., Jr.


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FIGURE 7.-Col. (later Brig. Gen.) George R. Callender, MC, Commandant, Army Medical School.

 

Enlisted male personnel:

One technical sergeant; one technician, fourth grade; one technician, fifth grade; one private, first class. Three-quarters of the time of these enlisted personnel was spent on production and the remainder on research.

Enlisted female personnel:

One technician, fifth grade, and four privates, first class, whose time was similarly divided.

Civilian personnel:

One laboratory technician, P-2, used for research.
Two clerk-typists, CAF-4, used for office work.
One laboratory helper, SP-1, used for utility purposes.

Liaison

As long as he was connected with the blood program (from 1940 until 18 November 1944), Colonel Kendrick served as chief of the research program at the Army Medical School. Even when he was given additional duty in the Office of The Surgeon General, in 1943, as Special Representative on Blood and Plasma Transfusions, it seemed wiser for him to continue to operate under the table of allowances at the School, so that he might continue to have free access to the research facilities needed in the program. Policies for the blood and plasma program were established in the Office of The Surgeon General, but all operations were conducted at the Army Medical School. The arrangement proved highly efficient.


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FIGURE 8.-Early experimental studies on blood, Division of Surgical Physiology, Army Medical School, Army Medical Center, Washington, D.C., July 1941, by Capt. (later Col.) Douglas B. Kendrick, MC. The plasma collecting bottle is the Baxter Plasmovac. The large bottle containing dried plasma is the original Sharp & Dohme ampule.

During Colonel Kendrick's connection with the blood program, there was always the closest possible cooperation between the Army Medical School and the Office of The Surgeon General. Colonel Callender at the School, General Hillman in the Office of The Surgeon General, and Col. (later Brig. Gen.) Fred W. Rankin, MC, Chief Surgical Consultant, Office of The Surgeon General, and his staff gave unlimited support to him in all his activities, and all matters concerned with blood, shock, and resuscitation were referred to him as a matter of routine. From the beginning of the blood program, although he was not officially appointed in that capacity until late in 1943, Colonel Kendrick, for all practical purposes, served as consultant to The Surgeon General in these matters.


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Development of the Program

The first activity of the blood research program was a survey and analysis of the relevant literature and the building up of a large reprint file. At this time, the literature on shock was voluminous (and confusing), but the literature on plasma and other blood substitutes was rather scanty, and contributions on liquid plasma were just beginning to appear.

Information on these subjects was also collected, by personal visits, from the following sources:

Mr. (later Captain SnC) John Elliott, Chief of Laboratory at the Rowan Memorial Hospital, Salisbury, N.C., who had developed a technique of processing sterile, pyrogen-free plasma in liquid form. When Mr. Elliott later entered the U.S. Army, he was assigned to the Army Medical School, where he instructed personnel in the processing of the liquid plasma used in Zone of Interior hospitals. He also contributed to the development of the vacuum bottle manufactured by the Baxter Co. and used, with certain modifications, for both plasma and whole blood during the war.

Dr. Max M. Strumia, pathologist at the Bryn Mawr Hospital, who had done special work on dried plasma.

Dr. John Reichel, of the Reichel Laboratories, Kimberton, Pa., who had worked with Dr. Strumia on the development of equipment for drying plasma.

Dr. Stuart Mudd, Professor of Bacteriology, University of Pennsylvania School of Medicine, Philadelphia, Pa., and Dr. Earl W. Flosdorf, an experienced refrigeration engineer, who had worked with Dr. Mudd as his research assistant in freezing and drying plasma and in the preparation of serum.

Information was also secured from Sharp & Dohme, a firm which had long been interested in the preparation of antisera and other immunizing agents. This company had done considerable work with typhoid and other vaccines, and, with the help of Dr. Reichel, had pioneered in the development of vacuum- drying equipment.

The activities of the Division of Surgical Physiology (fig. 9) included, in addition to the blood research program, studies on, or supervision of studies on, dried and liquid plasma and its production for use in the Zone of Interior (fig. 10); studies on human serum albumin and on bovine albumin; studies on various proposed blood substitutes, such as gelatin, pectin, synthetic plasma, and globin; studies on group O blood; studies on the Rh factor; studies on typing sera; and studies on blood preservatives. The design and testing of plasma and transfusion equipment were also part of the work of the division. These various activities are described under appropriate headings.

One of the functions of the Division of Surgical Physiology was the review of manuscripts and the evaluation of suggestions submitted by interested lay persons as well as by medical personnel. For various reasons, many papers were not considered suitable for publication in their current form. The suggestions covered a wide range: one physician suggested the treatment of shock by ultraviolet therapy. Another declared that if the technique he


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FIGURE 9.-Exhibit by Blood Research Division, Division of Surgical Physiology, Army Medical School, at annual meeting of District of Columbia Medical Society, Washington, D.C., 1941. A. Plasma drying equipment actually in use. Shell-freezing unit far left. Vacuum pump next to it, and next to it refrigeration trap to remove moisture from drying plasma. Metal cylinder in left foreground serves as drying chamber. Left, Capt. Douglas B. Kendrick, MC. Right, Cdr. Lloyd R. Newhouser, MC, USN. B. Closeup showing various types of plasma and plasma packaging.


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proposed for the surgical treatment of anuria resulting from transfusion incompatibility were not adopted, there would be thousands of deaths from uremia in crushing injuries and from the transfusion kidney during the invasion of the Continent. One manuscript was chiefly concerned with condemnation of the apparatus that had been used with great satisfaction for indirect transfusions for almost 3 years. Another was based on the false premise that the treatment of shock would be carried out by untrained enlisted personnel; the adoption of the apparatus described by the author for entering the veins would, in his opinion, solve this problem.

The interest behind these suggestions was greatly appreciated, but most of them were entirely impractical and quite unsuited for field use. They were always acknowledged, and in these letters it was pointed out to the physicians and others who had made the suggestions that the circumstances of warfare permitted the use of only simple, proved, and accepted methods of treatment.

Personnel of the Division of Surgical Physiology during the course of the war prepared and published a large number of papers on the various phases of the blood and plasma program. They are cited in appropriate places in this volume.

The training courses conducted at the Army Medical School are described elsewhere (p. 86).

OFFICE OF THE SURGEON GENERAL

In 1939, before the outbreak of World War II, a blood transfusion service was organized in the British Army, headed by Brigadier (later Sir) Lionel E. H. Whitby, RAMC (p. 15). In sharp contrast, the Office of The Surgeon General did not organize a section devoted to this specialty until November 1943, and never, during the entire war, was there a single medical officer in the office whose entire time was devoted to matters concerned with blood and plasma transfusion (2). It is true that, for a brief period in 1943, Col. Charles F. Shook, MC, served as Special Representative of The Surgeon General for the Blood Plasma Program. His service in this capacity, however, did not parallel that of Brigadier Whitby; it was chiefly concerned with production and supply and not with the professional aspects of the problem.

The initial responsibility for the blood and plasma program, as just described, was given to the Division of Surgical Physiology, Army Medical School. In late 1942, it was transferred to the Surgery (later the Surgical Consultants) Division, Office of The Surgeon General, and Lt. Col. (later Col.) B. Noland Carter, MC (fig. 11), was made responsible, in addition to his other duties, for all matters connected with fluid replacement therapy in shocked casualties.


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FIGURE 10.-Preparation of liquid plasma, Blood Research Division, Division of Surgical Physiology, Army Medical School. A. Liquid plasma being dispensed into bottles, to be shell-frozen and dried for storage. Drums in foreground are drying cabinets, which are hooked up by metal tubes to refrigeration traps and vacuum pumps. Device on right was used to measure cabinet pressure. This plasma was used only in the continental United States. B. Liquid plasma collected under closed system and stored at room temperature at the Army Medical School. It was dispensed on requisition to hospitals in the Zone of Interior. At one time, five centers were preparing and dispensing liquid plasma.


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FIGURE l0.-Continued. C. Bottles of pooled liquid plasma ready for clinical administration. Note caution against refrigeration, which was not necessary.

Establishment of the Transfusion Branch

On 24 November 1943, a Transfusion Branch was created in the Surgery Division, Office of The Surgeon General, with Colonel Carter serving as Chief, again in addition to his other duties in the division, and Maj. Frederic N. Schwartz, MAC, as Operations Officer. The establishment of this branch was the outgrowth of a memorandum from General Rankin to The Surgeon General on 5 July 1943, in which General Rankin pointed out the necessity for such a branch because of the tremendous growth of the plasma and albumin programs and their increasing complexity(3).

Shortly after this branch was established, Colonel Kendrick was appointed Special Representative to The Surgeon General on Blood and Plasma Transfusion. On 18 November 1944, when Colonel Kendrick left the Zone of Interior on permanent change of station (p. 603), he was succeeded by Maj. John J. McGraw, Jr., MC, who had had a wide experience in this field in the Mediterranean theater (p. 402).


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FIGURE 11.-Lt. Col. (later Col.) B. Noland Carter, MC, Assistant Chief, Surgical Consultants Division, Office of The Surgeon General.

Functions

The Transfusion Branch eventually carried the entire responsibility for the blood procurement program from the collection of the blood to the point at which it was placed on planes for oversea shipment (chart 1). Major Schwartz had performed many of the same functions in his previous assignment in the Supply Division, Office of The Surgeon General.

The functions of the chief of the Transfusion Branch were as follows (4):

1. To act as liaison officer with the American Red Cross and as adviser to the director of its blood donor program, including the publicity and recruiting phases of the program and changes in donor quotas to fulfill existing contracts.

2. To provide and maintain a force of 60 medical officers for duty in the blood donor centers.

3. To assist in procurement of equipment and supplies for the blood donor centers and the processing laboratories.

4. To maintain contact with Selective Service, so as to secure deferment and retention of essential technical personnel.

5. To maintain data on bleedings, finished units, issues, and stocks.

6. To act as liaison officer between the Office of The Surgeon General and the Blood Substitutes Subcommittee, NRC; the National Institute of Health; the representative of


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CHART 1.-Final evolution of organization chart, Transfusion Branch, Surgical Consultants Division, Office of The Surgeon General, July 1944

 

the Navy on blood, plasma, albumin, and byproducts; and the albumin pilot laboratory at the Harvard Medical School under Dr. Edwin J. Cohn.

7. To coordinate with the commercial biological laboratories all technical matters pertaining to the production of plasma, albumin, byproducts, and intravenous solutions, and, by repeated inspection of these laboratories and testing of their products, to insure adequate production of acceptable material for the Armed Forces.

8. To secure from the Legal Division, Office of The Surgeon General, advice on any legal questions that might arise in connection with the control and use of plasma, albumin, and byproducts processed from blood collected by the American Red Cross and turned over to the Army for its use.

9. To coordinate action in the various divisions of the Office of The Surgeon General on all matters pertaining to plasma, albumin, blood substitutes, and intravenous solutions.

10. To represent The Surgeon General in transactions with military missions and purchasing agencies concerned with plasma and other products.


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FIGURE 12.-Army and Navy representatives, Blood and Plasma Program. A. Col. Douglas
B. Kendrick, MC. B. Capt. Lloyd R. Newhouser, MC, USN.

The Transfusion Branch was also responsible for the preparation of circular letters and other publications concerned with blood, plasma, albumin, and byproducts. Among these publications were:

1. Circular Letter No. 108, Office of The Surgeon General, 27 May 1943, subject: Transfusion of Whole Blood in the Theaters of Operations (5) (p. 463).

2. War Department Technical Bulletin (TB MED) 204, 24 Oct. 1945, subject: Complications of Blood Transfusion (6).

3. A laboratory manual of technical procedures, standard at all blood centers, and issued in March 1945 by the Army Whole Blood Procurement Service (7).

Liaison With the Navy

In April 1940, shortly after Captain Kendrick had been assigned to the Division of Surgical Physiology, Army Medical School, Lt. Cdr. (later Capt.) Lloyd R. Newhouser, MC, USN, was assigned, with comparable duties, to the National Naval Medical Center, Washington, D.C. (fig. 12). They encountered each other in the course of their work, and, since both were trying to accomplish the same purposes, it seemed only sensible to pool their efforts. This they did from 1940 until late in 1944, when both were assigned to oversea duty. Their collaboration, while entirely unofficial, was approved and encouraged by their superior officers in both services.


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This association proved extremely fruitful. From the beginning, Captain Kendrick and Commander Newhouser kept each other closely informed of their plans and their projects, and this exchange of information eliminated many duplicating and overlapping activities. Many items were standardized jointly by the Army and the Navy, and most orders could be placed with a consideration of joint needs. The intimate liaison was an important factor in the maintenance of a smoothly running program for the procurement of plasma, albumin, and, finally, whole blood. It was out of this informal arrangement that formal plans were eventually consummated for the Navy to assume the responsibility of flying blood to the Pacific (p. 599), since the Army was already occupied with the task of flying blood to Europe (p. 494).

NATIONAL RESEARCH COUNCIL

Historical Note

In 1916, when U.S. involvement in World War I began to seem imminent, the National Academy of Sciences offered its services to the Government (8). The offer was immediately accepted by President Wilson, who requested the academy to organize the scientific agencies of the country, not only in the interests of national defense but with the ultimate object of advancing scientific and industrial progress. The National Research Council was accordingly constituted by the academy and rendered noteworthy service in various fields during World War I.

In 1918, President Wilson, by Executive order, requested the academy to take the necessary steps to perpetuate the council, so that its services could be utilized in time of peace. This was done. As a result, when World War II broke out, the council was already organized for immediate action, and it did much useful work before the United States entered the war in December 1941. In fact, the activities of the council before this date furnished one more piece of evidence that the President and his advisers were aware that, for all practical purposes, the country was already at war.

Organization of Committees

Committee on Transfusions.-The Committee on Transfusions, Division of Medical Sciences, NRC, which held its first meeting on 31 May 1940 (9)2 consisted of:

Dr. Walter B. Cannon, Chairman, Professor of Physiology, Harvard Medical School.

2It is impossible to overemphasize the importance of the establishment of this committee at this time, 18 months before the United States was precipitated into World War II. It meant that significant advances could be made in the blood and plasma programs before the actual need for them arose. This committee and its subcommittees, as already noted, were established at the request of The Surgeon General (Maj. Gen. James C. Magee), and representatives of the Army and the Navy were present at all meetings to present the needs and interests of the services.


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Dr. Alfred Blalock, Professor of Surgery, Vanderbilt University School of Medicine.

Dr. Everett D. Plass, Professor of Obstetrics and Gynecology, State University of Iowa College of Medicine.

Dr. Strumia, Assistant Professor of Pathology, University of Pennsylvania Graduate School of Medicine.

Dr. Cyrus C. Sturgis, Professor of Internal Medicine, University of Michigan Medical School.

Subcommittee on Shock.-At its initial meeting on 31 May 1940, the Committee on Transfusions appointed a Subcommittee on Anesthesia and Shock (usually called the Subcommittee on Shock), consisting of:

Dr. Blalock, Chairman.

Dr. Henry K. Beecher, Professor of Anesthesia, Harvard Medical School. 

Dr. Norman E. Freeman, Assistant Professor of Research Surgery, University of Pennsylvania School of Medicine.

Dr. Paul D. Lamson, Professor of Pharmacology, Vanderbilt University School of Medicine.

Dr. John S. Lundy, Professor of Anesthesia, University of Minnesota Graduate School of Medicine.

Dr. Leo Eloesser, Clinical Professor of Surgery, Leland Stanford University School of Medicine.

Dr. Ralph M. Waters, Professor of Anesthesia, University of Wisconsin School of Medicine.

Dr. John Scudder, Instructor in Surgery, Columbia University College of Physicians and Surgeons.

Subcommittee on Blood Substitutes-The Subcommittee on Blood Substitutes appointed by the Committee on Transfusions at its initial meeting consisted of Dr. Sturgis, chairman, Dr. Plass, Dr. Strumia, and Dr. Oswald H. Robertson, Professor of Medicine, University of Chicago School of Medicine.

Dr. Sturgis and Dr. Plass resigned from this subcommittee on 19 April 1941 but continued to serve on the Committee on Transfusions. The Subcommittee on Blood Substitutes finally consisted, in addition to Dr. Robertson, Dr. Scudder (secretary), and Dr. Strumia, of the following:

Dr. Robert F. Loeb, Chairman, Professor of Medicine, Columbia University College of Physicians and Surgeons, who served until 2 June 1944, when he was succeeded by Dr. Joseph T. Wearn (10).

Dr. Edwin J. Cohn, Professor of Biological Chemistry, Harvard University Medical School.

Dr. Elmer L. DeGowin, Associate Professor of Internal Medicine, State University of Iowa College of Medicine.

Dr. Cornelius P. Rhoads, Director, Memorial Hospital, New York, N.Y.

Dr. Owen H. Wangensteen, Professor of Surgery, University of Minnesota Medical School.


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Subcommittee on Blood Procurement.-The Subcommittee on Blood Procurement appointed by the Committee on Transfusions consisted, in addition to Drs. Rhoads and Strumia, of:

Dr. Warfield M. Firor, Associate Professor of Surgery, Johns Hopkins University School of Medicine.

Dr. Carl W. Walter, Associate Professor of Surgery, Harvard Medical School.

Ad hoc committees-The Subcommittee on Blood Substitutes, like other NRC committees, promptly realized the impracticability of committee action on matters of detail and delegated the responsibility for special projects to individual members or ad hoc committees.

All of the members of these NRC committees, it should be noted, were experienced clinicians or had played an active part in the investigation of blood and plasma or had figured in both roles.

Functions and Activities

Although the Subcommittee on Blood Substitutes had come into existence at the request of The Surgeon General, almost a year earlier, it was not until 19 April 1941 that its functions were formally outlined, as follows (11):

1. To continue research work on the various blood substitutes and to establish their relative merits by clinical trials.

2. To determine the best techniques of preparing the various blood substitutes.

3. To standardize the best techniques of collecting and dispensing plasma and serum.

4. To select the type of container (containers) for preserving and dispensing plasma and serum.

All the emphasis at this time, it should be noted, was on blood plasma and so-called blood substitutes. Nothing was said about the possible functions of the committee in connection with blood. At the meeting of the subcommittee on 18 July 1941 (12), however, it was recommended that an adequate study of blood substitutes, especially human albumin, be made by a member of the Army Medical Corps at an institution at which an adequate number of cases would be treated to permit definite conclusions as to the efficacy of these substitutes in the prevention and treatment of shock. No action was taken officially on this recommendation of the subcommittee.

Summary of activities to 24 February 1943-As a matter of convenience, the actions of the Subcommittee on Blood Substitutes on such matters as whole blood, plasma, albumin, bovine albumin, and byproducts are discussed in detail under appropriate headings. The summarized report of the subcommittee, however, of 24 February 1943, on its activities during the first 2


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years of its existence is worth citing as an indication of the far-reaching scope of its activities and accomplishments (13). They included:

1. A study of the relative merits of the various preparations of human plasma and serum, with a recommendation to the Armed Forces that dried plasma be used.

2. Development of packaging and dispensing equipment for dried plasma.

3. Improvements in the methods of drying plasma, a study of the effects of these methods upon the products obtained, the development of equipment for drying plasma for use by hospitals as well as by large processors, and the recommendation to the Armed Forces that 0.1-percent citric acid be used as the diluent for dried plasma.

4. Recommendations to the American Red Cross covering: (a) the control of blood procurement centers by professional personnel, (b) techniques for blood procurement, (c) standardization of equipment at these centers, and (d) blood grouping.

5. Recommendations to the Surgeons General, Army and Navy, for the establishment of sections on shock and transfusion in their medical departments.

6. Preparation of a concentrated solution of human serum albumin which was stable over a wide range of conditions; which occupied little space in packaged form; which could be given with facility and without diluent; and which had been prepared to meet certain specific requirements of the Armed Forces, particularly the Navy. This product had been recommended to the Armed Forces and was then in preparation in large amounts for their use.

7. A study, then in progress, of the possible use of globulin byproducts of human albumin production for the control of measles, mumps, and other diseases, which gave hope of widespread practical application in the Armed Forces.

8. A study of the possible use of human fibrinogen and thrombin, also byproducts of albumin production, in the local treatment of burns.

9. Studies, still in progress, on the possible use of blood substitutes of other than human origin, including bovine albumin, gelatin, pectin, aldobionic acid, and glutamyl polypeptide.

10. Conferences to consider progress in these various studies and to examine their extension to various groups of workers.

11. Preparation of manuals on blood transfusion and blood plasma for the Office of Civilian Defense (p. 93).

As time passed, work on various aspects of these projects was extended, but the really important investigations to which the Subcommittee on Blood Substitutes devoted its major efforts are included in this 1943 summary.

Proposal for Intravenous Therapy Service for Armed Forces

At the Conference on Transfusion Equipment and Procedure on 25 August 1942 (14), it was the sense of the meeting that the question of using preserved blood for the Armed Forces was primarily one of feasibility. Dr. DeGowin was requested to draw up a statement and propose a plan for an intravenous therapy service which could be submitted to the Surgeons General of the Army and the Navy for their consideration. These proposals, which were drawn up in collaboration with Colonel Kendrick and Commander Newhouser, were handed to the membership of the Subcommittee on Blood Substitutes at the meeting on 10 November 1942 (15), and it was requested that comments and suggestions concerning them be sent to Dr. DeGowin by mail.

At the meeting of the subcommittee on 15 December 1942 (16), Dr. DeGowin reported that favorable comment on the proposals had been received


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from all the members. It was voted that the memorandum containing the proposal and the justifications for it be included in the minutes of the meeting and submitted to the Surgeons General of the Army and the Navy through channels. This was done on 20 January 1943.

Although the recommendation for a separate intravenous therapy service in the Armed Forces was never acted upon during World War II, the arguments for it were entirely valid and are worth recording. In substance, they were as follows:

1. Intravenous therapy is a medical specialty, training in which is not provided in a routine medical education. The complexity of the problems involved in the manufacture, processing, and preservation of blood, blood substitutes, and other parenteral fluids is little known to the average physician, nor has he acquired the knowledge to design equipment and to test it for efficiency in the collection and administration of these fluids. He also does not understand the techniques of typing and crossmatching of blood.

2. The average physician is not a specialist in intravenous therapy. When he orders infusions and transfusions in a civilian hospital, he trusts to the special knowledge of experts in the field to manufacture pyrogen-free solutions. He accepts apparatus designed and tested by persons with special knowledge. He relies on a special department for proper cleansing and sterilization of the apparatus used. He depends on the laboratory for the typing and cross-matching of blood. The discussion of transfusion reactions in medical textbooks is inadequate, and the civilian physician, if all goes smoothly, is completely unaware of the organization and painstaking control that make the use of parenteral fluids safe. When, however, he enters the Medical Corps, he is called upon to practice more intravenous therapy than he employed in civilian life. He will be unable to perform this work satisfactorily without personal instruction in the procedures involved and the apparatus required for them.

3. Military medicine presents special problems in intravenous therapy as compared with civilian practice: the incidence of shock, hemorrhage, and burns is many times greater, as is their severity. In their treatment, the methods of civilian medicine must be modified by considerations of transport, equipment, and environment. Determination of the blood group of an occasional civilian patient is far removed from the mass typing of thousands of men entering the Armed Forces. Special techniques must be devised that are both rapid and accurate. Only specialists are logically qualified to evaluate and select them. The testing and procurement of proper typing sera is a major procedure in itself.

4. If a medical officer were to attempt to accumulate a store of whole blood, he would find that none of the methods in use in civilian practice could be applied directly to his military problem without modifications in equipment and technique.

5. Commercially available transfusion and infusion equipment is designed for civilian use. Military equipment must be designed with emphasis on portability, compactness, expendability, and conservation of critical material,


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already in increasingly short supply. There are no textbooks to serve as guides, and few medical men in the country are qualified in this field. The development and testing of suitable plastics and synthetics to replace rubber tubing and stoppers require the combined knowledge of the chemist, the production engineer, and the medical expert in intravenous therapy.

6. A global war requires the adaptation of medical equipment and techniques in many situations and environments. The only practical methods of treating shock may be, variously, plasma or serum albumin, fresh blood, or banked blood. The procedures for their administration, however, are sufficiently simple to permit the average medical officer, with proper instruction, to become proficient in them. The issuance of directives is only supplementary to specific personal instruction, not a substitute for it.

Great progress, the subcommittee memorandum continued, had been made in the development of blood substitutes by the cooperation of appropriate committees of the National Research Council and by liaison with Army and Navy officers, but many delays could have been eliminated, and much more could have been accomplished before the United States entered the war, if the armed services had had well-organized sections on shock and transfusion, composed of experts in the field, with authority to act on problems of equipment, products, and procedures. With the rapid expansion of personnel in the military organization, the needs in the future would be even greater than they had been in the past.

In view of these considerations, it was the recommendation of the Subcommittee on Blood Substitutes that the Army and the Navy Medical Corps should recognize, as the Royal Army Medical Corps had recognized, that intravenous therapy is a medical specialty and that they should organize, as the British had organized, sections composed of experts in the field who were to be charged with the responsibility, and endowed with the authority, to act on:

1. Devising, testing, and authorizing techniques in this field.

2. Training medical personnel in intravenous therapy in the most practical possible manner.

3. Designing, and authorizing the production of, equipment and apparatus.

4. Supervising the procurement and processing of blood substitutes.

5. Participating in research in the field of intravenous therapy and cooperating with NRC in appropriate studies.

It is unfortunate that the recommendations of the Subcommittee on Blood Substitutes, NRC, for a separate transfusion service were not adopted. Both medical officers and technicians trained in the handling and care of whole blood continued in short supply throughout the war. As late as January 1945, officers and men necessary to handle the blood supply for the Pacific had to be trained on an emergency basis and used as cadres for the transfusion teams to be sent to that theater (p. 605).

To the end of the war, those in charge of the program continued to hold the view that blood banks should be operated only by specially trained personnel, who had a profound respect for the potential risks of blood transfusion and who


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believed that the careless submission of a wounded man to the inherent dangers of this form of therapy was totally unwarranted (1).

Dissemination of Information

At a meeting of the Subcommittee on Blood Substitutes on 19 April 1941 (11), arrangements were made for the subcommittee to issue a monthly bulletin for its own information as well as that of others with a concern in the blood program. This proved a very useful plan.

Limitations on the use of paper during the war sometimes made the publicizing of the results of various investigations sponsored by the National Research Council a good deal of a problem. In March 1944, for instance, such a shortage delayed the publicizing of important recent developments on the preparation and use of byproducts of human blood plasma. It was essential that medical officers be familiar with this work, and in the course of several weeks the dispute was resolved favorably, but it was not the first time such difficulties had developed, nor was it to be the last.

At a meeting of the Subcommittee on Blood Substitutes on 20 October 1942 (17), there was a considerable discussion on an editorial on the toxicity of plasma that had appeared in the Journal of the American Medical Association for 19 September 1942 (18) and that was based on an article by Levine and State (19), which appeared in the same journal the following week. Dr. Strumia's extensive experience, reported at this meeting, was in sharp contrast to these authors' observations; he had had only five reactions in 2,200 transfusions with human plasma. It was agreed that the editorial contained numerous errors of fact, and a communication was sent to the editor of the Journal, asking for a retraction and pointing out that the publication of such data might cause serious difficulties in the blood procurement program. Dr. William Thalhimer had already prepared an article in which the misstatements concerning the supposed toxicity of plasma were refuted.

As had been feared, the editorial in the Journal made serious trouble for the Blood Plasma Section, Office of Civilian Defense, and also interfered with blood procurement by the American Red Cross. At the meeting of the subcommittee on 23 March 1943 (20), galley proof of the retraction requested was available and it was agreed to take no further action in the matter, though the statement was not considered entirely satisfactory.

This experience, like others related elsewhere, is indicative of the highly sensitive character of the blood and plasma program and of the matters with which the Subcommittee on Blood Substitutes had to concern itself.

Proposed Field Investigations

It has already been mentioned that nothing ever came of the proposal made at the first meeting of the Subcommittee on Blood Substitutes on 31 May 1940, that a group of physicians be allowed to work in the Army, freed


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from any of the obligations of Army officers, to investigate shock on a large scale (p. 41). The matter was brought up again at the meeting of the Subcommittee on Blood Substitutes on 30 November 1940 (21), by Dr. Sturgis, who proposed that a team, financed by the Red Cross, be sent to study transfusion in England. Dr. Lewis H. Weed did not think that the proposal was feasible at this time, because of the situation abroad, but stated that it would be discussed with British authorities.

There was no further discussion of a field investigation until the meeting of 9 April 1943 (22), at which it was decided that the subcommittee had reached a point at which it could no longer function effectively without more precise information concerning field problems and the conditions imposed on therapy by the military requirements of the war.

A considerable portion of the present knowledge of the mechanism of shock and its treatment had come about through the physiologic studies of specially qualified and completely integrated groups of investigators in the field (Cannon, for instance, Bayliss, Keith, and Robertson, among others). The Medical Research Council of Great Britain had continued to support this policy. The National Research Council had not.

It was therefore the unanimous recommendation of the Subcommittee on Blood Substitutes, to be transmitted to Dr. Weed for submission to The Surgeon General, that a qualified fact-finding group be appointed, without special function of command, which should report its findings through official channels, these findings to be transmitted subsequently to the subcommittee, to serve as a basis for continued investigation. It was further recommended that the research group in the field should receive, through official channels, reports of recent significant developments in Zone of Interior research and should transmit this information, through official channels, to medical officers in the field.

The study which the subcommittee proposed was to cover plasma, albumin, crystalloid solutions, and whole blood, with respect to their requirements, use, effectiveness, and limitations.

The subcommittee specified that professional personnel for the proposed investigative group should be chosen from the best informed and best qualified personnel, irrespective of their present military or civilian status.

This recommendation was duly transmitted to the Surgeons General of the Army and the Navy, through channels, and was repeated at the meeting of the Subcommittee on Blood Substitutes on 24 September 1943 (23), when it was found that no action had been taken on it. At the same time, the subcommittee reiterated its recommendation that intravenous therapy be considered as a special branch of military medicine (p. 76).

These recommendations, as such, were never acted upon. The recommendation that replacement therapy be studied in the field was, however, implemented to some extent in June 1944, when General Rankin, Chief Surgical Consultant, Office of The Surgeon General, arranged for Colonel Kendrick to


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visit the Pacific areas and study shock, transfusion, supply, and all other phases of replacement therapy (p. 590).

Both during and after the war, comments were frequently heard to the effect that the studies of NRC committees and subcommittees were conducted from an ivory tower and in a sort of nonmilitary vacuum. The criticism is not justified in view of the repeated endeavors of the Subcommittee on Blood Substitutes to secure its information at first hand and to base its recommendations on the information thus secured. The subcommittee was frustrated in its endeavors, and DeBakey (24), in 1946, wrote quite correctly of "the barrier between military surgeons and civilian investigators that was never completely crossed on either side."

NATIONAL INSTITUTE OF HEALTH

The NIH (National Institute of Health) played little part in the blood and plasma program until 1941, when Dr. Cohn, at the Harvard Medical School, succeeded in fractionating plasma protein and, at about the same time, dried plasma was prepared successfully. No question of interstate commerce had previously been involved. With these achievements, the products, under strict interpretation of the law, became biologicals, with whose manufacture, storage, and utilization NIH was intimately concerned. It was unlawful to produce and sell biologicals, which included serum, albumin, dried plasma, and byproducts of plasma, without a license from this agency.

Throughout the war, close liaison was maintained by the Army, the Navy, and the Subcommittee on Blood Substitutes, NRC, with Dr. Milton V. Veldee, Chief, Laboratory of Biologics Control, National Institute of Health. The excellent cooperation between NIH and the Army, the Navy, and NRC offers one more explanation of the success of the blood-plasma program.

Minimum specifications were prepared by Dr. Veldee and his associates for the processing and packaging of plasma and the products of plasma fractionation (25). Later modifications in both apparatus and techniques for the program were made only after consultation with, and approval by, Dr. Veldee, Captain Newhouser, and Colonel Kendrick. Representatives of NIH frequently visited the commercial laboratories producing plasma and other blood derivatives, aiding them in the establishment of techniques and assisting them in the solution of special problems.

LEGAL ASPECTS OF THE BLOOD AND PLASMA PROGRAM

Ownership of Blood and Its Components

The matter of ownership of the blood donated for use of the Armed Forces at the Red Cross blood donor centers seems to have been handled by default until the meeting of the Subcommittee on Blood Substitutes on 23 June 1942 (26), when the proposal to release a certain amount of plasma to OCD (Office


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of Civilian Defense) came up for discussion (p. 92). It was the sense of the meeting that the responsibility of the Red Cross for the blood collected ceased as soon as the blood was delivered to the processing laboratories. It was also brought out that, at this time, none of the interested parties (American Red Cross, Army, Navy) exercised any supervision over losses in the plant. While it was not clear who owned the material from the time the blood was delivered to the processing laboratories by the Red Cross until the laboratories delivered it to the Armed Forces as dried plasma, the assumption was, since the laboratories could not hold title to it, that it must indeed be the property of the Armed Forces.

A formal resolution was passed at this meeting to the effect that the blood collected by the Red Cross should "become as heretofore the property of the armed forces from the time it enters the processing plant." It was further resolved that the Armed Forces assume responsibility and authority for the processing, preparation, and disposition of the blood and plasma as "safe and effective therapeutic material."

Before the legal aspects of the disposition and ownership of red blood cells and other byproducts of the plasma program became an issue, the policy had been to permit commercial processing houses to furnish red blood cells to adjacent hospitals, with the specification that the Office of The Surgeon General be furnished reports of the studies made with them. It was further understood that the laboratories should not charge the hospitals; that the hospitals should not charge the patients treated, who, preferably would be those unable to pay; and that the hospitals should agree to indemnify the Government for any claims which might arise out of the use of the red blood cells.

At the Conference on Blood Grouping on 23 March 1943 (27), it was agreed that the arrangements made up to this time were no more than temporary expedients, that the question of charges and other problems would recur as other byproducts were developed, and that a group of experts must formulate a policy that would be legal and that would meet the obligations to the donors of the blood. It was the sense of the meeting that Dr. Weed call a conference on the subject, to be attended by representatives of the Army, the Navy, and American Red Cross, as well as by Dr. Cohn, Dr. Rhoads, and Dr. Veldee.

Statement of the Problem

On 6 April 1943, Dr. Cohn, in whose laboratory at the Harvard Medical School most of the work on byproducts had been done, prepared a statement of the problem for Dr. Weed, as follows (28):

1. Clearly, these byproducts could not become a source of profit to commercial houses. At the present time, these substances, which were considered the property of the Government, were being retained "in the cold," under the most favorable conditions to permit the preservation, for protracted periods


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of time, of some-though not all-of their properties. All of these byproducts (red cells, fibrinogen, thrombin, isohemagglutinins, measles protective antibodies) could be brought into more stable states, including the dry state, although additional processing would be required.

2. The present problem was more clearly exemplified in connection with fraction II, which contained the highly promising measles antibodies. Under optimum circumstances, the amounts which could be processed would presumably be greatly in excess of any needs the Armed Forces might have for this byproduct. The results of tests with small amounts released on the authorization of The Surgeon General, Navy, for experimental purposes to commercial laboratories, under controlled conditions, had been hopeful. The material must not be allowed to deteriorate, and the excess, beyond what was needed for the Armed Forces, should be used for "social value." The Red Cross, Dr. Cohn thought, might well be put in the position of making "a public restitution" of the byproducts not needed by the Armed Forces.

Recommendations

Dr. Cohn's letter was read at the Conference on Albumin and By-Products called by Dr. Weed on 10 May 1943 (28). In the discussion, it was brought out that the largest byproduct of plasma processing, in point of bulk, was the red blood cells, but that the globulin fractions would probably prove to be of greater importance. The problem was financial as well as legal: the Red Cross considered it better that it should take title to the byproducts than have another agency do it; but the estimated cost, on the assumption that the entire quantity of globulin now available would be worked up into forms suitable for military and civilian use, would be about $1 million.

At the meeting of the Subcommittee on Blood Substitutes on 13 May 1943 (29), it was reported that the Red Cross Medical and Health Advisory Committee had met since the conference on 10 May and had requested that the subcommittee make specific recommendations concerning the ownership of the byproducts of the blood and plasma program. The organization was willing to exercise ownership, supervise the processing of the byproducts under conditions which "would give prior lien" on all material to the Armed Forces, and arrange for the financing and distribution "for the public good" of the material not required by the Armed Forces.

Although some doubt was expressed as to the legality of the proposed arrangements, the following recommendations were made:

1. Title to the byproducts of the blood procurement program shall be transferred from the Army and the Navy to the American Red Cross if there are no legal impediments to this arrangement

2. The Red Cross shall assume responsibility for financing the program and for the processing, control, and redistribution of these byproducts

3. To carry out the program, the Red Cross, acting on the advice of its National Medical and Health Advisory Committee, shall appoint a small group of representative technical


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experts (Army, Navy, Public Health Service, National Research Council, Committee on Medical Research) to supervise and control the processing of these byproducts by contract with university or pharmaceutical laboratories.

4. The Army and the Navy shall have priority in requisitioning such quantities of these byproducts as they may need. The excess shall be used for civilian purposes, foreign relief, or such experimental procedures as may be considered essential by the supervisory group. The Red Cross (or some other designated agency) shall arrange the best method of distribution of the excess.

5. As the value of each new byproduct is established, subordinate groups shall be appointed, of not more than three members each, representing, respectively, the National Institute of Health, the National Research Council, and the Armed Forces.

Dr. Cohn stated that he had already asked for an appraisal group for each byproduct of the albumin program.

Further Actions

The ownership of these byproducts was discussed by letters and at meetings during the remainder of 1943 from all points of view. One of the principal objections to the proposed plan was that the Red Cross might not be able to obtain the necessary equipment for processing the byproducts.

The Navy believed that all contracts for byproducts from the albumin program should be let by the Navy, which was already handling all albumin contracts. Dr. Cohn agreed, on the ground that plasma fractionating is an integrated process. At the meeting of the Albumin and By-Products Group on 28 July 1943 (30), he pointed out that the settlement of the issue was pressing, since measles antibodies (fraction II), thrombin, and fibrin film had been thoroughly tested and were ready for appraisal. At the meeting of the Subcommittee on Blood Substitutes on 24 September 1943 (23), Captain Newhouser reported requests from civilian physicians for allocation of serum albumin for the treatment of their patients.

At the meeting of the subcommittee on 6 October 1943 (31), it was announced that a red blood cell suspension service had been set up at Halloran General Hospital, Staten Island, N.Y., and the recommendation was made that, for administrative purposes, it would be a good idea to give the Red Cross ownership of red blood cells, since similar services would shortly be set up in other cities. On 7 January 1944, Maj. Gen. George F. Lull, Deputy Surgeon General, approved this arrangement (32). This information was duly conveyed to the processing laboratories, which were directed to release the cells at the times and in the amounts specified by the Red Cross. These laboratories had previously been reminded (27 August 1943) that all blood received from the Red Cross and all plasma processed from it remained the property of the Government and none of its byproducts should be released without written authorization by responsible authorities.

On 27 May 1944, Maj. Gen. Norman T. Kirk notified the Director, Medical and Health Service, American Red Cross, that the Navy had agreed to turn


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over to it all immune serum globulin in excess of requirements of the Armed Forces, to be distributed to the civilian population through the state health agencies designated by the Red Cross. General Kirk gladly concurred in this arrangement (33).

Note-As a matter of convenience, certain other legal aspects of the blood program are discussed elsewhere in this volume. The accounting problems of the processing laboratories are discussed in connection with the plasma program.

TRAINING

In any consideration of the training of medical officers and enlisted men in the handling and use of plasma and blood, it must be borne in mind that when time United States entered World War II, plasma was an almost unknown agent and the use of blood transfusion was far from general. Both theory and demonstration were therefore equally important phases of all training programs.

National Research Council

The Subcommittee on Blood Substitutes recognized the importance of training in intravenous therapy by suggesting at its first meeting on 31 May 1940 (9) that (1) there should be some center in every Army organization at which men would receive training in caring for shocked casualties, and (2) there should also be centers in which men could be trained in all aspects of intravenous therapy. At a later meeting, on 9 April 1943 (22), a visitor from the Canadian Army who was present pointed out that the British had found it necessary to have medical officers with specialized training in charge of transfusions. Colonel Kendrick made the same point at the meeting of the subcommittee on 17 November 1943 (34), when he stated, in reply to an inquiry concerning oversea training, that the Office of The Surgeon General would issue a memorandum on the technique of transfusion and on methods of preserving blood but had no authority to recommend techniques to surgeons in theaters of operations.

Questions concerning training were also raised at the meeting of the subcommittee on 19 April 1941 (11) and at the Conference on Transfusion Equipment on 25 August 1942 (14). Some medical officers, it was stated, had not yet even seen dried plasma, let alone having had any instruction in its use. Dr. Cannon, basing his remarks on his own observations, stated that it was more important to teach men to needle veins than to provide them with blood substitutes, since the substitutes could not be used without training in venipuncture. It was reported that, in the summer of 1940, Dr. (later Major, MC) Robert C. Hardin had taken several enlisted men of a National Guard unit to the State University of Iowa Hospital and instructed them in this procedure. Although they had had no previous medical training, they all learned readily.


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FIGURE 13.-Laboratory technicians in training, Army Medical School, Walter Reed Army Medical Center.

Army Medical School

Two formal training courses (fig. 13) were conducted at the Army Medical School, listed in Army Service Forces Manual M3 for November 1944 (35) as:

1. Course MO-20, Red Cross Blood Donor Center, Operation of. This course lasted for 2 weeks and was intended for medical officers who were to be sent to liquid plasma processing centers in Zone of Interior hospitals (p. 274). Instructions included (a) general plans of organization and operation and (b) techniques of bleeding donors. The course was concluded with several days of supervised practice at the Washington, D.C., Red Cross Blood Donor Center.


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2. Course ME-12, Blood Plasma Bank Technique. This course lasted 4 weeks and was planned for medical technicians who had already had some portion, or all, of the Army basic course for technicians and who were to be sent to the liquid plasma processing centers. The material included the technical procedures used in the operation of a blood donor center and methods of preparing and storing liquid plasma.

In all, 23 officers completed Course MO-20 and 15 spent at least a month of temporary duty learning to operate liquid plasma centers, each of which eventually had 3 officers assigned to it. Forty-three technicians completed Course ME-12.

In addition to the supervision of these formal courses, Captain Kendrick taught the principles and practices of resuscitation, along with the management of war wounds, to the classes of officers who attended the Army Medical and Dental Schools. He also lectured on the same subjects at the Medical Field Service School at Carlisle Barracks, Pa.

Field Training

Training in the use of plasma was also conducted during maneuvers before the United States entered the war and in the Zone of Interior during the war (figs. 14, 15, and 16).

Training Aids

A training film (FS 8-51), with appropriate comments, was prepared at Carlisle Barracks by Major Kendrick in January 1942. In February 1943, a manual was prepared to be used in conjunction with it. It contained a statement of general principles and a detailed, fully illustrated, description of each step of the use of the plasma package and the administration of the plasma (p. 698). The material was essentially the same as that contained on the instruction sheet enclosed in all plasma packages except for those issued at the very beginning of the program. When demonstration packages of plasma became available, they were distributed with each copy of the film.

Demonstration Packages of Plasma

Practically all of the packages of dried plasma distributed in the United States were for training purposes only (36). The question of providing them came to a head in October 1942, when the Director, Biological Division, Lilly Research Laboratories, wrote General Hillman that he had received a number of requests from medical officers, particularly those in charge of replacement training centers, for demonstration packages of the standard Army-Navy dried plasma. Up to this time, he had simply sent dummy packages, filled with contaminated plasma and marked Not for human use. A recent request for 12 packages for a single installation, however, indicated that such an informal method of supply could no longer be used; if all camps were to make such requests, the number of packages necessary would run into the hundreds.


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FIGURE 14.-Dried blood plasma arriving for emergency use at emergency landing field, Hoffman, N.C., during maneuvers in the Carolinas, November 1941.

This letter was the beginning of a correspondence, chiefly with Colonel Carter in the Surgery Division, Office of The Surgeon General, which continued until July 1943.

There was complete agreement on the part of all concerned that in the program of instruction being planned for medical officers in station and general hospitals in the Zone of Interior and for those attached to Ground Forces, it was imperative that there be actual demonstrations of the reconstitution of plasma, which was, as already pointed out, a new technique. There were, however, a number of problems to be solved.

Form of package-The first problem was what to use in the plasma bottle. The use of contaminated plasma was not desirable, partly because it might, through some mischance, be used clinically and partly because research had shown that it could be safely converted into albumin (p. 303). The use of any colored material would destroy the realism of the demonstration. Horse serum had obvious risks. Shell-frozen dextrose became so powdered when it was dried that it collapsed in the bottle and did not look like plasma. Also, it tended to clump when water was introduced and did not go into solution readily.


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FIGURE 15.-Boxes of dried plasma ready for immediate use in operating tent during maneuvers, Rockingham, N.C., November 1941.

The addition of dextran made it possible to shell-freeze glucose and the final demonstration package, prepared in this manner, contained 25 gm. of glucose and 3 gm. of dextran. In solution, this combined material had the approximate color and haziness characteristic of normal human plasma. If it were inadvertently used clinically, it would cause no reactions, especially as it was decided that, for added safety (though at an increased cost), all packages must be sterilized.

All labels used were marked in red Not for human use. For demonstration use only.

The Red Cross was supplied with a number of these demonstration packages for display at blood procurement centers and for mobile units.

Procurement-When the form of the demonstration package had been settled, problems of procurement arose. Army rules did not permit the acceptance of the offer of Eli Lilly and Co. to make up a number of packages at once, without waiting for bids. Instead, it was necessary to set up separate contracts for them. When bids were requested, in July 1943, for 10,000 demonstration packages, seven of the nine laboratories then processing plasma were not interested because they were changing over to the 500-cc. plasma


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FIGURE l6.-Demonstration of administration of blood plasma as part of field training program set up by medical group at Camp Ellis, Ill., 1943, and designed to acquaint other branches of the service with methods and equipment used in field hospital units. A. Demonstration without gas mask. B. Demonstration with posed casualty and corpsmen wearing gas masks.


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package within the next 3-4 weeks and they had no excess equipment to make up the smaller demonstration package. In addition, cans could be ordered only in 25,000 lots. The necessary number of demonstration sets was finally produced by Eli Lilly and Co., which continued to make the smaller package of plasma.

Instructions for use-Circular Letter No. 55, Office of The Surgeon General, Services of Supply, War Department, 22 February 1943 (37), was entitled "Instruction of medical officers in the reconstitution and use of the Standard Army-Navy Package of Normal Human Plasma, Dried." It explained that the demonstration packages (which were not then available for distribution) were designed to accompany Film Strip 8-51, dealing with the same subject. After it had been shown, the instructor should demonstrate the reconstitution and use of one package and then distribute others to small groups of students, so that they might become familiar, individually, with the technique of reconstituting plasma.

OFFICE OF CIVILIAN DEFENSE

Planning

Provision of blood and plasma for the Office of Civilian Defense was not the responsibility of the Armed Forces program, but, as was inevitable, there was some cooperation between the two programs, and it is remarkable that there was so little conflict.

The question was first brought up at the Blood Procurement Conference on 14 February 1942 (38), at which it was pointed out that throughout the country there were feelings of restlessness and anxiety lest blood or a blood substitute be needed for a civilian catastrophe arising from enemy action or accidents in industrial plants and there be no provision for the care of casualties.

At this conference, Dr. (later Major, MC) Earl S. Taylor, Technical Director, American Red Cross, reported that on a recent trip to the Pacific coast, he had found a disturbing situation, apparently related to this sense of apprehension: Blood and plasma banks were being set up without the affiliation of either the Red Cross or the Office of Civilian Defense. The directors of some of these banks clearly lacked the qualifications necessary for the preparation of safe products, and he feared that their continued growth would lead to great waste of blood or serious accidents.

On 11 April 1942, the sum of $292,500 was allotted to the U.S. Public Health Service, from an emergency fund controlled by the President, to be expended in emergencies affecting the national security and defense and for setting up reserves of liquid, frozen, or dried blood plasma or serum albumin for the treatment of casualties from enemy action. These grants were to be made to public or private hospitals located not more than 300 miles from the oceans or the gulf coast. On 17 April 1942, the Federal Security Agency set up regulations governing these grants (39).


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Provision of Plasma

The question of plasma for the Office of Civilian Defense came up again at the meeting of the Subcommittee on Blood Substitutes on 23 June 1942 (26). Dr. G. Canby Robinson, National Director, American Red Cross Blood Donor Service, speaking for the Red Cross, proposed that letters be written to The Surgeon General, U.S. Army, from his agency, the U.S. Public Health Service, and the Office of Civilian Defense asking that the limits of the programs of the Red Cross and the Office of Civilian Defense be clarified in respect to blood donors. He made the suggestion because, since the Japanese attack on Dutch Harbor in the Aleutians earlier this year, a number of communities had attempted to collect blood for local use, and their efforts had interfered with the Red Cross National Blood Procurement Program to obtain blood for the Armed Forces.

It was proposed that 55,000 of the 96,762 units of plasma then held in the frozen state in various processing plants be released and distributed as follows:

25,000 units to be transferred to the Red Cross, for delivery to the Office of Civilian Defense for distribution to suitable civilian hospitals in exposed areas, with the understanding that cities in which the Red Cross had blood donor centers would all be protected in this manner.

30,000 units to be placed at the disposal of the chief medical officer, OCD, or one of the regional medical officers, to be used in grave emergencies, with the understanding that the Office of Civilian Defense would thereafter refrain from collecting blood within a radius of 75 miles from the (seven) Red Cross blood donor centers presently in operation.

The considerable discussion that followed the introduction of these proposals covered the mechanics of such a transfer and the legal aspects of ownership of the plasma (p. 81). A motion was finally passed, as already noted, to the effect that the blood collected by the American Red Cross remained "as heretofore the property of the armed forces from the time it entered the processing plant." A second motion was then passed requesting The Surgeon General, U.S. Army, to release 55,000 units of frozen plasma to the Office of Civilian Defense for the allocation and use just specified. It was hoped that the announcement of the release of such a large amount of frozen plasma to OCD would relieve public apprehension caused by fears of inadequate supplies in case of an enemy attack and would enable the Red Cross to continue to concentrate on the needs of the Armed Forces, which might be tripled within the coming year.

Some anxiety was expressed over the actions taken: Dr. Loeb, chairman of the subcommittee, pointed out that OCD was undertaking a grave responsibility in assuming control of a large amount of frozen plasma, with its problems of supervision, storage, and administration. If, through lack of proper controls, unfortunate accidents should occur, they might, entirely unjustifiably,


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reflect on the Red Cross procurement program. Fortunately, no such accidents occurred.

It should be noted that the distribution of plasma proposed at this time was possible only because the Red Cross was collecting blood equal to, or in excess of, the current combined drying facilities of the processing laboratories (p. 120).

Of the 88,000 donations procured by the Red Cross and used for plasma made available to the Office of Civilian Defense, 29,000 units were secured from the backlog of frozen plasma held in processing laboratories (40). Another 50,000 units were processed for this special purpose, most of it in a processing laboratory equipped for this type of work but not yet in production for the Army. The balance was provided by the Army from reserve stocks late in 1942. Some of this lot was returned to the Army later, to meet potential emergency needs in the Pacific.

As a result of these arrangements, the initial confusion, that could have had rather serious consequences, was completely eliminated early in the war. Fortunately, it was never necessary to use OCD supplies of plasma for casualties from enemy action. At the end of the war, by act of Congress, the U.S. Public Health Service was authorized to make OCD stocks available for civilian use. And so, to quote Dr. Robinson, "It was eventually returned to the American public who had donated it"(40).

Preparation of Manuals

The only other activity of the Office of Civilian Defense that concerned the blood-plasma program dealt with the preparation of manuals for OCD use by members of the Subcommittee on Blood Substitutes. The manual on plasma (38, 41) was the responsibility of Dr. Strumia and the manual on blood banks (41) of Dr. DeGowin (42). The subcommittee informed responsible OCD authorities that these manuals represented the best practice at the time they were prepared (1942) but warned that the procedures described in them should be undertaken only by technically qualified and adequately trained personnel.

PLASMA FOR ALLIED NATIONS

There was never any question about the emergency use of plasma provided by the Red Cross for soldiers of other nations. When it came to providing a stockpile for troops of Allied nations, however, generous instincts came into conflict with the realities of the situation (4, 43, 44). For one thing, supplies of plasma, particularly early in the war, were not inexhaustible, and they had to be kept for the needs of the U.S. Armed Forces. More important, the blood from which the plasma was made had been donated for that special purpose. The legal as well as the moral right of the Red Cross and the Armed Forces to utilize it for other purposes, however worthy they might be, was


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limited by the representations made to the public when the donations were secured and the releases signed by the donors, which included the statement that the blood was to be used for the Armed Forces.

There could be no legitimate criticism of the transfer of certain amounts of plasma to the British for use in their hospitals, since many U.S. soldiers were cared for in them. Later in the war, arrangements were made for the British to purchase plasma from one of the commercial laboratories which had excess capacity after fulfilling its Army contracts. The blood was procured from professional donors, without newspaper advertising or any other solicitation that would interfere with the Red Cross program.

The British needs were always small, for their own fine blood transfusion service furnished almost all of the blood and plasma needed for their own casualties. The supply of plasma for the Free French was another and more difficult problem.

The Free French, up to the liberation of Paris, at least, had no home population from which to procure blood. The idea of the French Military Medical Mission to the United States that they should process their own plasma in North Africa was discouraged by those in charge of the blood program in the Office of The Surgeon General, because of the cost, the lack of trained personnel, and the delay that would be inevitable in training personnel and procuring equipment.

The first plasma supplied to the Free French was delivered under Lend-Lease arrangements and made from blood purchased from professional donors, as just described. When the U.S. Army supply program began to include medical equipment and supplies for the French Army, the plasma included in U.S. supplies was removed from the maintenance units. It was realized, however, that the U.S. Army and the Red Cross would be open to serious criticism if an agent publicly proclaimed as lifesaving were withheld from Allied troops, even though the blood from which the plasma was made had been donated specifically for U.S. Armed Forces.

The whole subject was discussed at a conference in the Office of The Surgeon General on 8 June 1943 (45), and two plans were considered:

1. That the Red Cross ask for blood donations designated for the Free French, with the donors asked to sign a special release to that effect. If the blood were treated as fungible, it would not be necessary to segregate these particular donations but merely to make sure that the amount of plasma given to the Free French did not exceed the amount of blood donated for it.

2. That the plasma, as previously, be made from blood purchased in commercial channels. Procurement of blood in this way would not interfere with the Red Cross Blood Donor Program, and two commercial laboratories were then in a position to undertake the processing of the necessary amounts of plasma without interference with their contracts for plasma for the U.S. Armed Forces.

The latter plan was eventually put into effect, with the assistance of the Armed Services Medical Procurement Agency, Brooklyn, N.Y.


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A number of the countries in South America were desirous of making dried plasma for their own use and consulted the personnel of the U.S. blood program about their plans. They were always advised to use liquid plasma: The U.S. experience had shown that the production of dried plasma was an onerous and complex problem, quite aside from the difficulty of procuring equipment and the length of time it took to procure it.

The Russian experience illustrates the procurement difficulties just mentioned (46). In September 1943, at the request of the Russian Red Cross, an outline of current methods of drying plasma was drawn up, and, a little later, Soviet Red Cross representatives were shown the various drying equipment in use in Zone of Interior commercial laboratories.

When the Soviet authorities decided to proceed with the drying of plasma, all possible cooperation was given to them by the Office of The Surgeon General, through Colonel Kendrick, the Special Representative on Blood and Plasma Transfusions; the American Red Cross; and the National Research Corp. of Boston, through which the equipment was ordered. The equipment was not completed, however, and the necessary testing was not carried out, until the spring of 1945. The war in Europe was over before the departure date of Capt. (later Maj.) John Reichel, Jr., MC, who had been designated to supervise the equipment in the Soviet Union and instruct medical officers and technicians in its use. Later, he spent several weeks in the Soviet Union on this mission.

OFFERS FROM OTHER COUNTRIES

During the war, a number of friendly nations conceived the idea of setting up projects for the collection of blood and the processing of plasma, some or all of which they would make available to the United States (47). The stumbling block to the acceptance of these offers was always the same: Scarcities of essential materials and high priorities of other branches of the Armed Forces were making it difficult for the U.S. blood and plasma program to procure equipment for its own needs. Moreover, the processing of plasma was such a delicate operation and required such careful supervision that, until a laboratory was well equipped with apparatus and operated by trained personnel, satisfactory qualitative and quantitative results were impossible.

SUPPLIES OF PLASMA FOR ZONE OF INTERIOR HOSPITALS

Liquid Plasma

The details of the program by which liquid plasma was supplied to Zone of Interior hospitals during the war is part of the story of plasma and is related under that heading (p. 274). The Blood Research Division, Army Medical School, acted as the Blood Plasma Coordinating Center; it exercised general control of the program, and after March 1944, on requisition from the surgeons


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of the various service commands, it supplied all the plasma used in Zone of Interior hospitals.

This was a highly successful program from every standpoint (40). Of the 310,135 blood donations delivered to military hospitals in the Zone of Interior from the blood donor centers, 295,200 were used for liquid plasma. The Washington center, which continuously used some of its donations for this purpose, devoted 88,387 bloods to this program. The Denver center, which opened 14 September 1942, delivered its entire output to Fitzsimons General Hospital, Denver, Colo. When this center was closed on 15 September 1945, it had delivered to the hospital 150,880 donations, 140,578 of which were processed into liquid plasma.

There were no confirmed reports of the distribution of contaminated plasma, and the incidence of posttransfusion reactions was very small, probably because of continuous policing of every phase of the program.

No special training was required for the administration of liquid plasma. When bulk was undesirable, it could be given undiluted. In these circumstances, the ordinary rate of 8 to 10 cc. per minute was reduced to 5 cc. or less per minute until it was found that so-called speed shock did not really exist and that the rate of administration made no difference unless there were clinical contraindications to fluid administration.

Liquid plasma contained Merthiolate 1:10,000 or phenylmercuric borate 1:25,000 as a preservative. For this reason, it was the practice to limit the quantity given over a 24-hour period to 2,000 cc. When dried plasma was employed, quantities up to 4,000 cc. per 24-hour period could be used, since the concentrations of Merthiolate or phenylmercuric nitrate in it were, respectively, 1:35,000 and 1:50,000.

The safety and efficiency of liquid plasma were evident almost as soon as the program was started. Also, it soon became evident that original dating periods had been set much too low and that, if liquid plasma were prepared under proper conditions of sterility and kept in the frozen state, it would last almost indefinitely. The inconvenience, expense, and personnel required for the production of dried plasma for Zone of Interior hospitals therefore did not seem justified.

Dried Plasma

Dried plasma prepared at the Army Medical School was, however, given to smaller hospitals, whose needs were limited, and in which the turnover of liquid plasma would be very slow. In April 1945, the amounts of liquid plasma being requisitioned by Zone of Interior hospitals exceeded the amounts being produced with current facilities. At the same time, the quantity of dried plasma on hand exceeded oversea requirements. When stocks of liquid plasma were exhausted, therefore, dried plasma was supplied to the hospitals in the United States, which were informed at the same time that one form of plasma was no more useful than the other (48).


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PROVISION OF WHOLE BLOOD IN ZONE OF INTERIOR HOSPITALS

Until well into 1944, all hospitals in the Zone of Interior were responsible for the collection of their own supplies of whole blood. By that time, however, it became apparent that certain hospitals were located in areas so sparsely populated, and had so few service troops attached to them, that it was impractical for them to maintain donor lists to meet even their limited requirements. In March 1944, therefore, by agreement with the American Red Cross and with the concurrence of the Transfusion Branch, Office of The Surgeon General, arrangements were made to supply blood to such hospitals when the location of bleeding centers made this plan practicable (49). It was possible for 23 hospitals to take advantage of this plan, their supply coming from 16 of the 35 blood donor centers then in operation.

Only type O blood was supplied, in 500 cc. amounts, and it was supplied only as oversea surpluses permitted (50). The transportation of the blood and equipment between the centers and the receiving hospitals, as well as the return of all equipment sent to the hospitals, was the responsibility of the receiving hospitals. The receiving hospitals were also responsible for retyping and crossmatching of the blood, for its serologic investigation, for reporting all unsatisfactory (that is, positive) tests, for the administration of time blood, and for the recording of clinical results. The blood was furnished according to a prearranged schedule, running parallel with the delivery of red blood cells (p. 313). Emergency needs were not supplied.

In June 1945, 556 pints of O blood were shipped to Halloran, England (Atlantic City, N.J.), Tilton (Fort Dix, N.J.), Lovell (Ayer, Mass.), and Torney (Palm Springs, Calif.) General Hospitals and to the Chelsea Naval Hospital, Chelsea, Mass. In August 1945, 804 pints were delivered to these and other hospitals and to the Philadelphia Naval Hospital. Once the availability of this service was realized, there were numerous requests for it from hospitals all over the country. The reply was always the same, that other hospitals would be included in the distribution as soon as possible if demands from overseas were not too heavy. The end of the war, with the termination of the Red Cross blood collection program, ended this particular service.

RECOMMENDATIONS

Basic Recommendations

In his formal report at the end of the war on the blood-plasma program (1), Colonel Kendrick made the following recommendations:

1. The Transfusion Branch, Surgical Consultants Division, Office of The Surgeon General, should be discontinued as not necessary in peacetime. In the light of postwar events, his opinion at the present time (1962) is that even


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in peacetime, there should be a knowledgeable consultant on transfusion and allied matters in this office.

2. The position of Special Representative to The Surgeon General on Blood and Plasma Transfusions should be retained, but with a less cumbersome title, perhaps Transfusion Consultant or Transfusion Service Consultant.

3. This consultant should be responsible for providing the Medical Department with the most recent information on advances in fluid replacement therapy.

4. In the event of future mobilization, a transfusion branch should at once be established in the Office of The Surgeon General, the chief of the branch to serve as Transfusion Consultant, with the rank of colonel, and to have an adequate staff for the functions assigned to him.

References

1. Kendrick, D. B.: History of Blood and Plasma Program, United States Army During World War II, 1 Aug. 1952.

2. Annual Report of the Activities of the Transfusion Branch, Surgical Consultants Division, Office of The Surgeon General, fiscal year 1945.

3. Memorandum, Brig. Gen. Fred W. Rankin for Maj. Gen. Norman T. Kirk, 5 July 1943, subject: Establishment of a Transfusion and Intravenous Solutions Branch of the Surgery Division of the Surgeon General's Office.

4. Memorandum, Col. Tracy S. Voorhees, JAGD, for Maj. Gen. Norman T. Kirk, 23 Oct. 1943, subject: Use for the Armed Forces of our Allies of Plasma from Donated Blood, and Use of By-Products of Plasma and Albumin Programs.

5. Circular Letter No. 108, Office of The Surgeon General, U.S. Army, 27 May 1943, subject: Transfusion of Whole Blood in the Theaters of Operations.

6. War Department Technical Bulletin (TB MED) 204, 24 Oct. 1945, subject: Complications of Blood Transfusion.

7. Army Whole Blood Procurement Service. Laboratory Manual, March 1945.

8. National Research Council. In The Surgeon General's Office, The Medical Department of the United States Army in the World War. Washington: Government Printing Office, 1923, vol. I, pp. 566-573.

9. Minutes, meeting of Committee on Transfusions, Division of Medical Sciences, NRC, 31 May 1940.

10. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 2 June 1944.

11. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 19 Apr. 1941.

12. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 18 July 1941.

13. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 24 Feb. 1943.

14. Minutes, Conference on Transfusion Equipment and Procedure, Division of Medical Sciences, NRC, 25 Aug. 1942.

15. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 10 Nov. 1942.

16. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 15 Dec. 1942.

17. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 20 Oct. 1942.

18. Editorial, Toxicity of Human Plasma. J.A.M.A. 120: 206-207, 19 Sept. 1942.


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19. Levine, M., and State, D.: A and B Substances as a Cause of Reactions Following Human Plasma Transfusions. J.A.M.A. 120: 275-277, 26 Sept. 1942.

20. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 23 Mar. 1943. 

21. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 30 Nov. 1940.

22. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 9 Apr. 1943.

23. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 24 Sept. 1943.

24. DeBakey, M. E.: Military Surgery in World War II. A Backward Glance and a Forward Look. New England J. Med. 236: 341-350, 6 Mar. 1947.

25. Minimum Requirements for Unfiltered Normal Human Plasma, NIH, 20 Feb. 1941.

26. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 23 June 1942.

27. Minutes, Conference on Blood Grouping, Division of Medical Sciences, NRC, 23 Mar. 1943.

28. Minutes, meeting of the Albumin and By-Products Group, Division of Medical Sciences, NRC, 10 May 1943.

29. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 13 May 1943.

30. Minutes, Conference of Albumin and By-Products Group, Division of Medical Sciences, NRC, 28 July 1943.

31. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 6 Oct. 1943.

32. Letter, Lt. Col. Douglas B. Kendrick, MC, to The Surgeon General, 7 Jan. 1944, subject: Release of Red Blood Cells to American Red Cross for Transfusions. Approved Maj. Gen. George F. Lull, Deputy Surgeon General.

33. Letter, Maj. Gen. Norman T. Kirk to Dr. G. Foard McGinnes, 27 May 1944, subject: Use of By-Products of Plasma by Civilian Population.

34. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 17 Nov. 1943.

35. Army Service Forces Manual M3, Courses of Instruction Given in Schools of Army Service Forces. Headquarters, Army Service Forces, November 1944.

36. Correspondence concerning demonstration packages of plasma, 22 Oct. 1942-16 July 1943. [On file, General Reference and Research Branch, Historical Unit, AMEDS, Walter Reed Army Medical Center, Washington, D.C.]

37. Circular Letter No. 55, Office of The Surgeon General, Services of Supply, War Department, 22 Feb. 1943, subject: Instruction of Medical Officers in the Reconstitution and Use of the Standard Army-Navy Package of Normal Human Plasma, Dried.

38. Minutes, Blood Procurement Conference, Division of Medical Sciences, NRC, 14 Feb. 1942.

39. Regulations Governing Grants to Hospitals for Establishing Reserves of Blood Plasma. Federal Security Agency, U.S. Public Health Service, 17 Apr. 1942.

40. Robinson, G. C.: American Red Cross Blood Donor Service During World War II. Its Organization and Operation. Washington: The American National Red Cross, 1 July 1946.

41. A Technical Manual on Citrated Human Blood Plasma Detailing Its Procurement, Processing, and Use. Washington: U.S. Office of Civilian Defense, November 1942.

42. The Operation of a Hospital Transfusion Service. A Technical Manual. Washington: Medical Division, Office of Civilian Defense, March 1944.

43. Minutes, meeting of Subcommittee on Blood Substitutes, Division of Medical Sciences, NRC, 10 Mar. 1942.


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44. Correspondence and memorandums concerning supply of plasma to Allied nations, 25 Nov. 1942-31 Jan. 1944. [On file, General Reference and Research Branch, Historical Unit, AMEDS, Walter Reed Army Medical Center, Washington, D.C.]

45. Memorandum re Conference at Surgeon General's Office, 8 June 1943, concerning Use of Plasma and Albumin for Other United Nations, and Disposition of By-Products from Plasma and Albumin Processing, 8 June 1943.

46. Correspondence and memorandums concerning supply of plasma-drying equipment to Russia, September 1943-June 1944. [On file, General Reference and Research Branch, Historical Unit, AMEDS, Walter Reed Army Medical Center, Washington, D.C.]

47. Correspondence and memorandums concerning Cuban proposal to supply dried plasma for Allied use, 18 Sept. 1942-31 Oct. 1945. [On file, General Reference and Research Branch, Historical Unit, AMEDS, Walter Reed Army Medical Center, Washington, D.C.]

48. Letters, Maj. Gen. Norman T. Kirk and Brig. Gen. Fred W. Rankin to Commanding Generals, all Service Commands, 27 Apr. 1945, subject: Dried Plasma for Hospitals in Zone of Interior.

49. Letter, Lt. Col. Douglas B. Kendrick, MC, to Dr. G. Canby Robinson, 11 Mar. 1944.

50. Memorandum, Maj. Earl S. Taylor, MC, subject: The Methods to be Employed in Furnishing Whole Blood to Military Hospitals.

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