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Founding Years 1944-1953

This Committee unanimously, on both sides, without regard to party or politics or anything else, is supremely interested in this matter of providing proper clinical research facilities that will bring the sufferer, the human patient, into direct contact with the researchers. The time has come to recognize that we must provide trained people — clinicians and technicians and researchers — and at the same time giving to suffering humanity that has these diseases the opportunity to be studied....

Rep. Frank B. Keefe, chair, House Appropriations Subcommittee, on the initial Clinical Center construction appropriation, January 16, 1948

The story of the Clinical Center has many beginnings. Although its origins trace back to a 1911 Public Health Service proposal for a research hospital, 1 the Clinical Center is actually a product of the dynamic growth in American biomedicine following the end of World War II. The postwar years saw unprecedented growth and change at the National Institutes of Health. Between 1945 and 1953, the reservation grew by 214 acres. From the fields and woodlots surrounding the original Georgian-style campus rose 14 new buildings, the last of which was the mammoth Clinical Center. This construction cycle tripled NIH laboratory and office space and swelled the work force from 2,245 to 7,145 by 1958, when the initial Clinical Center staffing was complete. 2 What was once a small in-house federal laboratory was thereby transformed into a world-class biomedical research establishment and the focal point of the nation’s war on disease and disability.

Towering above the tree line "like the hull of a giant unfinished ship,” 3 the 514-bed hospital became emblematic of the era’s extravagant hopes for the conquest of chronic diseases and its persistent insecurities about the threat of atomic destruction. "A 90-year life expectancy is possible within half a century," predicted Collier’s magazine as the Clinical Center prepared to open in August 1952. A new era in scientific medicine was dawning in which basic science would reveal the causes of disease and clinicians would develop curative therapies. NIH was embarking on an epochal task, the magazine reported, to “put medicine back together again.” 4 By bringing together physicians, biochemists, nutritionists, and pathologists, and by fostering emergent technologies such as chemical pharmacology and radiation diagnostics and therapy, the Clinical Center would be the stage for a new synthesis of medical knowledge, which would radically improve the prospects of human health.

Clinical Center Construction Workers
Construction work gang rolling caisson toward Clinical Center excavation site. Courtesy of the National Library of Medicine. President Truman and Representatives
President Truman at the cornerstone ceremony, June 22, 1951. Behind him are (l. to r.) NIH Director William H. Sebrell, FSA Administrator Oscar R. Ewing, primary contractor John McShain, and Surgeon General Leonard A. Scheele. Courtesy of Sam Silverman.

New Frontiers in Scientific Medicine

The war years had convinced Public Health Service (PHS) leaders that a clinical research facility larger than any then operating was vital to sustain the revolutionary advances in medicine and science that followed the development of penicillin in 1941. 5 Successful antibiotic and chemical therapies for malaria, pneumonia, and tuberculosis encouraged popular expectations of cures for infectious diseases in general. By war’s end there was enormous public pressure through disease foundations, press and radio, and members of Congress to increase federal spending on hospitals and health care. 6

Surgeon General Thomas Parran, committed to the New Deal vision of a universally accessible national health care system, used popular anxieties about disease cures to widen PHS mandates in disease control, hospital care, and scientific research.
7 His deeper appreciation that clinical research would govern the development of scientific medicine came from his own clinical experience with arsenical therapies for syphilis in the early 1930s. Clinicians discovered then that patients reliably recovered only when an optimal dosage was determined through clinical trials conducted by different investigators with different patient groups, all following the same protocol. Since dozens or scores of research subjects were needed for each therapeutic evaluation, separately funded research wards in teaching hospitals had to be used to establish each drug’s viability. 8

The arrival of sulfa drugs and penicillin in 1941 launched a revolution in clinical medicine, which tied laboratory science inextricably to the world of the clinician. Formerly bound only to diagnose and observe, practitioners of internal medicine were now free to treat patients with chronic diseases and to devise experimental therapies. 9 Diagnostic technologies proliferated, disease processes were illuminated, and human biology became the essential proving ground for developmental biochemistry and physiology. As Parran saw it, the implications for NIH intramural research were foretold by the pattern of extramural grants the National Cancer Institute made in 1946. Cures would come, he told the House Appropriations Subcommittee, only after intensive basic research "directed toward fundamental problems of cellular life, the interaction of groups of cells and organ systems in this most complicated of all chemical structures, which is man himself". 10
With the successful elucidation of the structure of DNA in 1953, it became clear that molecular biology would be the new frontier of scientific medicine.

Laying the Groundwork

The Clinical Center first appeared in PHS building plans in October 1944. Heading the 10-year PHS prospectus for postwar construction were proposals for a 500-bed Medical Center hospital and a 200-bed Neuropsychiatric Institute and hospital on the Bethesda reservation. 11 The 79th Congress was averse to President Franklin D. Roosevelt’s domestic spending programs and preferred to locate postwar research authority in a private body, which would contract clinical research to leading medical schools and university centers.  12 Temporarily blocked, Parran and NIH Director Rolla G. Dyer enlisted the services of Mary E. Switzer, Parran’s superior in the Federal Security Agency, to write legislation authorizing the mental health clinical unit as well as a nationwide hospital building program, which Congress readily funded in August 1946. 13 The administration froze public works spending before considering the $18 million PHS proposal to start the Bethesda expansion, but Parran managed to get the Bureau of the Budget to approve $2.6 million for land purchasing and architectural services in December 1946. A building committee was hastily set up within the PHS, and in January Parran’s staff submitted the first comprehensive plan for expanding the Bethesda reservation. 14

Preparations for a dozen new buildings began in earnest in April 1947, after Parran established a symbiotic relationship with the new Republican chair of the House Appropriations Subcommittee, Frank B. Keefe of Wisconsin. With only a promise of $22 million for construction expenses in 1948, an NIH research facilities committee chaired by Norman Topping plunged ahead with a 30-line site agenda projected to cost $116,246,765. 15

The catalyst of this new, full-speed-ahead political environment was extramural research. Requests for research funding from medical schools, academic departments, and hospital centers surged at the end of the war, but philanthropies and drug companies proved unwilling to invest enough capital to sustain the research boom. Moreover, the proposed National Science Foundation became mired in congressional debates complicated by the insistence of leading academic scientists that basic research be kept separate from agencies controlling research applications. Keefe and other key members of Congress decided that spring that the study sections and advisory councils Parran and Dyer had organized in 1945 and 1946 were the only effective instruments available to fund the wave of emergent medical technology. 16 In October, President Harry S Truman joined this consensus by accepting the Steelman Committee’s recommendation that medical research spending be tripled quickly. The upshot was a resolution by the Federal Bureau of Hospitalization on November 4, 1947, authorizing construction of a “research hospital, together with ancillary structures,” which would combine mental health and chronic/infectious disease research. 17

After a whirlwind of planning activity between the NIH Director’s Office and the Public Building Service, Representative Keefe on March 5 accepted a special appropriation request for $31,830,000 to construct the main building.  18  The substructure contract was let in July, and in the fall steam shovels excavated the hillock behind Top Cottage, creating a mountain of spoil dirt, which dwarfed existing buildings. Behind the scenes the planning focus slipped, reflecting the abrupt dismissal of Surgeon General Parran in February and the need to accommodate within the organization two more categorical institutes, Heart and Dental Research, which Congress chartered at mid-year.  19

Dr. Jack Masur, assistant director at Montefiore Hospital and a specialist in chronic care administration, was appointed director of the embryonic hospital staff on April 1, 1948. One of 55 consulting specialists to the planning committee, Dr. Masur used New York’s Goldwater and Memorial Hospitals as institutional models in designing the Clinical Center. His leadership of the later planning phases diminished the importance of PHS traditions in both clinic and laboratory. Impatient with the lack of training and professional development in the Marine Hospital clinical service, which after 1944 was barred from using patients for research,
20 Masur set out to create new professional standards and to optimize patient care in the emerging world of scientific medicine.

Designing a Biomedical Community 

The hospital concept that unfolded as substructure construction proceeded during 1949 envisioned a self-contained medical community of clinicians, laboratory scientists, patients, and support staff, all focused on conquering chronic disease. Under the guidance of Dr. Masur, the Research Facilities Planning Committee designed provisions for patient care and research operations far more elaborate than at a typical teaching hospital. To offset the longer stays required of research patients, special amenity services such as communal dining and recreation, as well as facilities for physical and occupational therapy, were included. The building was to be fully air-conditioned and wired for bedside television, then seen as available within five years. 21

The double-corridor design of the main building, or “headworks,” allowed patients billeted in south-facing rooms to be brought into a central nursing area for treatment, and it also enabled clinicians to conduct diagnostic and other research services in north-facing laboratory modules across the corridor. The six protruding wings of the building were reserved for nonclinical laboratories, allowing clinicians to mingle with bench scientists and share emergent technologies, such as the radiation therapeutics housed in Wing C north. Support functions were to be located in satellite buildings, connected to the hospital by tunnels. Animal handling facilities, a power station and incinerator, shops and storehouses, as well as on-site housing for 300 nurses and 300 interns and trainees, were also projected. 22

Initially, the hospital relied upon Washington-area physicians and the six area medical schools for patient referrals. To maintain harmonious relations with local doctors, Masur and Dyer established a “closed staff” system whereby Clinical Center physicians would not practice for pay in the Washington area, and interns would generally not be accepted from area medical schools.
23 In other aspects, interaction with outside practitioners was encouraged. Area specialists were invited to serve as consultants, and intramural investigators were largely recruited outside the Northeast, to ensure a national distribution. The resulting influx of leading clinicians and scientists in 1949 began a cycle of dynamic growth in clinical science. 24

Framing Organizational Roles 

A series of legislative enactments beginning with the National Heart Act in June 1948 had pluralized the NIH administrative structure, creating five autonomous research institutes modelled on NCI. The Heart Institute, backed by a $5 million special appropriation and inheriting ongoing cardiovascular projects, began to reorganize the entire intramural program after Dr. James Shannon was appointed scientific director in April 1949. Shannon, who formerly led a highly regarded pharmacology clinic at the Goldwater Hospital, aggressively recruited key staff for newly vacated laboratories in Building 3.  25  He also presented Heart’s expansion program to a gathering of institute directors in late October, 26 touching off two months of extended discussions, which produced an organizational model for clinical research still in use today.

An early version of the Easton retreats for key NIH staff in the present era, the Institute Directors’ Conferences in December 1949 drew lines of authority strongly favoring the new research institutes over centralized hospital services. Apart from conducting laboratory investigations, institutes were made responsible for providing medical care to patients from admission to discharge, for professional supervision of nursing staff, and for staffing and fiscal support of centralized services such as surgery, clinical pathology, and outpatient services. 27 The directors stopped short of recognizing “six autonomous hospitals” within the Clinical Center, but they decentralized authority to the point where even laboratory services such as housekeeping and fire protection were kept out of the director’s hands. 28

The result was an extremely flexible administrative structure designed to maximize “the effective conduct of experiments,” subject to patient welfare as a “controlling factor.” 29  The institute directors were careful to separate special clinical services such as surgery, pathology, and radiology from research functions usually available to specialists in these areas, but they were also very supportive of dietary, social work, and employee health service departments as centralized services. Shannon also gained acceptance for a single model of institute administration giving precedence to laboratory heads over administrators. 30  The upshot was a pragmatic compromise reflecting the working requirements of clinical research, particularly the scientific investigator’s need for freedom from administrative restraint.

Korean War Uncertainties 

The following two years proved difficult, however, for political reasons. The legislative environment for health issues turned adverse in 1949. Southern Democrats, who traditionally spearheaded health care extension, were disaffected by Truman’s advocacy of civil rights in 1948. The anticommunist activities led by Senator Joseph McCarthy targeted the PHS as a subversive agent of “socialized medicine,” and administration zeal for budget reductions produced a freeze in public building starts. 31  The Appropriations Subcommittee began looking askance at follow-on buildings in the Bethesda expansion project. The Budget Bureau cut half of Masur’s $2.5 million request for Clinical Center housing in November 1949. Fearing that nonresident nurses would be unwilling to travel to the reservation for night duty, Dr. Dyer protested that the lack of on-site housing for nurses “may well impose an insuperable deterrent to adequate staffing of the Clinical Center operations.” 32

On January 4, 1950, work began on the $16,814,200 contract for the superstructure of the hospital, but a combination of strikes and bad weather seriously delayed progress during the spring. 33  Dr. Masur’s strong personal leadership style kept the project on track during the rest of 1950. When the mechanical contractor threatened to quit the job in June, Masur reminded the construction chiefs that the project would be “the major hospital center in the country or in the world,” and that “there are 17 million square feet in this job and 17 million details,” none of which would prevent completion. 34

Masur’s interest in renewed funding brought him into a PHS consensus in May, which attempted to secure new appropriations by offering to convert the Clinical Center to defense research. This gambit, inspired by atomic war planning within the National Security Council before the outbreak of fighting in Korea, was made more serious by Truman’s July 27 order to cease funding public building projects not vital to national defense. 35  Anticipating emergency Defense Department requests for military research, NIH began investigations on biological warfare, shock, radiation defense, and thermal burns in the summer of 1950. Preparations were made to turn the Clinical Center into a “potential defense facility” in the event of an atomic attack on Washington. 36  In August, NIH supported separate attempts by Senators Warren G. Magnuson and Claude Pepper to add $64 million and $30 million to PHS’s budget, to eliminate funding arrears and sponsor direct military research, but Congress voted down both measures. 37  The intramural project grew only modestly during the Korean War years, classified work was minimized, and administrators assured themselves that, “extensive conversion of the existing program would not, as a matter of fact, have contributed to national defense.” 38

Research as the Means to Health Security 

If the failure to undertake defense research in the summer of 1950 demonstrated the organic limits of intramural research, Truman’s visit to lay the cornerstone the following June was a reminder of its political limits. Truman had never forgiven the American Medical Association for thwarting his national health insurance program, and in the spring of 1951 he embarked on several whistle-stop tours promoting a compromise version, which would entitle Social Security recipients to hospital care financed by payroll deductions. 39 In dedicating the half-finished Clinical Center building on June 22, Truman had higher praises for public health work than for clinical research. “Medical care,” he insisted, “is for the people and not just for the doctors—and the rich.” Warning that the 75 million Americans then without health insurance would soon become a "medically indigent class,”he challenged the scientific community to “translate the new knowledge gained by research into better care for more people.” Truman’s real target was the first Hoover Commission report, the new conventional wisdom among NIH’s administrators and congressional bill writers, which held that “research to prevent disease" was a better investment for federal dollars than “providing unlimited hospitalization to treat it.” 40 In Truman' s view, it was only a matter of time before the people or their representatives would claim a return on their research investment.

The Primacy of Scientific Freedom 

None of this dampened the spirits of the young scientists and clinicians hired by the six institutes in 1951 and 1952 before the hospital’s opening. “We are living through an exciting and, in some respects, awe-inspiring burst of creative energy,” Surgeon General Leonard A. Scheele noted in mid-1950.  41  The prospect of assigned patient beds for clinical research galvanized a plethora of investigations, and the lack of growth in intramural spending during the Korean War years seemed not to matter at all. 42  Dr. Masur, who left the director’s post in January 1951 to oversee the PHS hospital system, had successfully applied the Goldwater Hospital maxim, “Unity with diversity.” The pattern of flexible administration and scientific control of laboratories was the essential precondition of dynamic growth. Even before its doors were opened, scientific freedom had become the Clinical Center’s hallmark. What remained to be seen, as growth ensued, was whether clinician specialists and scientific investigators could find new elements of synthesis for their divergent interests at the frontiers of molecular biology. 43

Footnotes

  1. U.S. Treasury Department, Public Health Service, Annual Report of the Surgeon General of the Public Health Service of the United States, Washington, DC: Government Printing Office, 1911, p. 78.
  2. NIH Almanac, 1992, NIH Publication 92-5, pp. 121-25, 116.
  3. Donald S. Fredrickson, ms, “Values and the Advance of Medical Science,”Proceedings of Conference on Integrity in Institutions, University of Texas Health Center, May 25, 1989, p. 7.
  4. Collier’s, August 30, 1952, p. 33.
  5. PHS proposed 10-year budget for NIH, October 23, 1944, exhibits H, I, in MS C 204, History of Medicine Division, National Library of Medicine (hereafter NLM); The Reminiscences of Charles V. Kidd, Columbia University Oral History Collection (hereafter CUOHP), 13-14; Reminiscences of Norman H. Topping, 17-18; Reminiscences of Leonard A. Scheele, 22-24; Reminiscences of Vane M. Hoge, 21, National Library of Medicine Oral History Collection (hereafter, NLMOHC).
  6. David P. Adams, “Wartime Bureaucracies and Penicillin Allocation: The Committee on Chemotherapeutic and Other Agents,” Journal of the History of Medicine and Allied Sciences, 44: 196-201, 209, 1989; Milton Wainwright, Miracle Cure: The Story of Penicillin, Oxford: Blackwell, 1990, pp. 63, 122-27.
  7. Parran testimony, House Committee on Appropriations, 79th Congress, 1st Session, Hearings, Dept. of Labor/FSA, part 2, FY 1946 (April 18, 1945), pp. 269-77; NIH postwar program outline, National Advisory Health Council (hereafter, NAHC), agenda notes for June 19-20, 1945, meeting, in folder 0240, box 1, Accession 90-62A-490 [Records of the Public Health Service, Office of the Surgeon General], Washington National Records Center (hereafter WNRC), Suitland, MD.
  8. Minutes, NAHC meeting, September 28, 1945, box 1, Acc. 90-62A-490, WNRC; Harry M. Marks, “Notes from Underground: The Social Organization of Therapeutic Research,” in Russell C. Maulitz and Diana E. Long, eds., Grand Rounds: One Hundred Years of Internal Medicine, Philadelphia: University of Pennsylvania Press, 1988, pp. 299-312, 319-20.
  9. Lewis Thomas, The Youngest Science: Notes of a Medicine Watcher, New York: Viking Press, 1983, pp. 27-35.
  10. Parran testimony, House Appropriations Subcommittee, 80th Congress, 1st Session, Hearings, Dept. of Labor/FSA part 2, FY 1948 (February 7, 1947), p. 477.
  11. MSC 204, History of Medicine Division, NLM.
  12. Allan Drury, A Senate Journal, 1943-1945, New York: McGraw-Hill, 1963, pp. 4-5, 395-410.
  13. Martha Lenz Walker, Beyond Bureaucracy: Mary Elizabeth Switzer and Rehabilitation, New York: University Press, 1988, pp. 112-17.
  14. Memoranda, Dyer to J.K. Hoskins, Asst. Surgeon General (SG), December 17, 1946, Buildings and Grounds File, Office of the Director, NIH; PHS building proposals, transmitted with Crabtree to W.E. Reynolds, Commissioner of Public Buildings, January 19, 1947, in Acc. 90-62A-490, box 1, PBA Correspondence. Of 45 projects proposed nationwide, 31 were to be located on the Bethesda site.
  15. House, Report #178, 80th Congress, 1st Session, March 21, 1947, pp. 24-26; Agenda for July 30, 1947, SG Conference, attached to memoranda, Parran to Dyer, “Clinical Research Facility... ," July 25, 1947, Buildings and Grounds File, Office of the Director, NIH.
  16. Daniel Fox, “The Politics of the NIH Extramural Program, 1937-1950,” Journal of the History of Medicine and Allied Sciences, 42: 458-65, 1987.
  17. Truman statement, October 8, 1947, in Public Papers of the Presidents, Harry S Truman, 1947, Washington, DC: GPO, 1965, pp. 473-74; Federal Board of Hospitalization, Resolution 320, November 4, 1947, Official File, Harry S Truman Library (hereafter, HSTL); Summary of minutes, Federal Board of Hospitalization meeting, November 4, 1947, Acc. 90-62A-490, box 17.
  18. A. Siepert, planning review, 1952, Historian’s Office Papers, History of Medicine Division, NLM; House, Report #1519, 80th Congress, 2nd Session, March 5, 1948, pp. 29-30.
  19. Oscar E. Ewing, memoranda to Truman, February 12, 1948, file 7B, Official Files, HSTL. Ewing — and Truman — believed Parran wanted reappointment in order to select his own successor, and this would have made the PHS too powerful. Ewing notes on four possible candidates, same file; minutes, NAHC meeting October 22-23, 1948, p. 4, in box 2, Acc. 90-62A-490, WNRC.
  20. Memoranda, Masur to Dyer and Parran, January 6, 1948, Research Facilities Planning Committee File (hereafter, RFPC), Office of the Director, NIH; Masur and N.P. Thompson, “A National Clinical Center for Chronic Disease Research,” Hospitals, 1949 (November):1-2; Masur, Reminiscences, CUOHC, 19-22; Remarks of Dr. Otis L. Anderson, Chief, PHS Hospital Div., September 15, 1947, Conference of Medical Officers in Charge, U.S. Marine Hospitals, p.12, in box 18, Acc. 90-62A-490, WNRC.
  21. Masur and Thompson, Hospitals, 1949 (November): 3-10; FSA/PHS press release, June 29, 1948, NIH Historian’s Papers, NLM; Memoranda, RFPC, December 31, 1948, Office of the Director, NIH.
  22. NIH press release, September 9, 1949; RFPC memoranda #245 and #248, September 21, 1948 and October 7, 1949, RFPC file; Norman Topping, “The United States Public Health Service Clinical Center for Medical Research,” Journal of the American Medical Association, 150: 542-43 (October 11, 1952).
  23. NIH memorandum for reference, “Conference of Deans...,“ May 28, 1949, p. 6, attached to Masur to Rev. McNally, June 2, 1949, RFPC file.
  24. Robert Kanigel, Apprentice to Genius: The Making of a Scientific Dynasty, New York: Macmillan, 1986, 11-30, 65-71; Shannon, Reminiscences, NLMOHC, pp. 22-30.
  25. Robert Kanigel, Apprentice to Genius: The Making of a Scientific Dynasty, New York: Macmillan, 1986, 11-30, 65-71; Shannon, Reminiscences, NLMOHC, pp. 22-30.
  26. Shannon to Masur, 10/31/49, RFPC file.
  27. RFPC memoranda, “Present Status of Organizational Planning for the Clinical Center,” January 11, 1950, RFPC file.
  28. Minutes, Institute Directors Meetings, December 9, 1949, p. 6, and December 13, 1949, p. 5, RFPC file.
  29. RFPC memoranda, “Present Status...,“ January 11, 1950.
  30. RFPC memoranda, “Further Discussions at Conf. with Dr. Kaplan,” September, pp. 3-4; minutes, Institute Directors meeting, December 1, 1949, pp. 1-12.
  31. Monty M. Poen, Harry S Truman Versus the Medical Lobby: The Genesis of Medicare, Columbia, MO: University of Missouri Press, 1979, pp. 161-69.
  32. Memoranda #272 to PBA, December 13, 1949, RFPC file. Funding was also denied for an overpass on Rockville Pike and mechanical equipment for Building 10.
  33. Memoranda, W.E. Reynolds, Commissioner of Public Buildings, to SG Scheele, June 22, 1950, RFPC file; House, Committee on Appropriations, 81st Congress, 2nd Session, Hearings, FSA part 1, FY 1951 (January 11, 1950), p. 579.
  34. Minutes, PBS conference, June 27, 1950, Project 18-063, RFPC file.
  35. Memoranda, K. Nasi to SG, 5/18/50, PHS Building Committee files, folder 0245, Secretary Memoranda, box 1, Acc. 90-62A-490, WNRC; Masur to Nasi, May 24, 1950, “Assessment of Buildings...,“ RFPC file, Office of the Director, NIH.
  36. Memoranda, C.V. Kidd, “Assumptions Underlying NIH Defense Planning,” August 2, 1950, and note to Truman, August 3, 1950, both in Office of Research Plans, NIH Director’s Office, Subject Files, folder Defense, 1950-51, box 2, RG 443, National Archives.
  37. Congressional Record, 153: 96, August 3, 1950, pp. 11841-11860, 11876; Memorandum, “Justification of $30 million,” n.d., Office of Research Plans, Subject Files, box 2, folder Magnuson Amendment, RG 443.
  38. Defense Activities of the NIH, May 13, 1952, p.12, in OPR Subject Files, same folder.
  39. Poen, Harry S Truman Versus the Medical Lobby, pp. 188-92; Harry S Truman, Memoirs, Vol. II, Years of Trial and Hope, Garden City, NY: Doubleday, 1956, pp. 17-23.
  40. First Hoover Commission Report, quoted in memorandum, Larsen to Kidd, May 13, 1952, RFPC file.
  41. Speech draft, August 15, 1950, Office of Research Plans, Subject Files, 1948-1956, box 2, RG443.
  42. U.S. Dept. of Health, Education and Welfare, The Advancement of Medical Research and Education, Washington, DC: HEW, 1958, pp. 55-56.
  43. Masur to Haas, September 1, 1949, RFPC file; N. Topping, JAMA, October 11, 1952, pp. 541-43.