12 May

The life of Ignaz Philipp Semmelweis (1818–1865) encompasses elements of heroism and tragedy more appropriate to treatment by a novelist than a historian. But some historians have argued that Semmelweis’s con- tributions to medical history have been grossly exaggerated, because mortality from childbed fever actually increased after his work was published. Moreover, Semmelweis was all but forgotten by the time the doctrine of antisepsis was accepted. It is true that both Semmelweis and Holmes had little or no impact on obstetrical practice among their contemporaries, but this unfortunate reality has generally been con- sidered part of the tragedy of puerperal fever. A native of Budapest, Hungary, Semmelweis was sent to Vienna in 1837 to study law, but he soon transferred to the school of medicine. At

Ignaz Philipp Semmelweis

Ignaz Philipp Semmelweis.

the time, the University of Vienna, especially the medical school, was aptly described as a hotbed of revolutionary activity, where senior, well-entrenched professors with close ties to the conservative govern- ment were being confronted by younger faculty members with opposing views of politics, society, and scientific research. Indeed, it was often said that the great physician-scientists of Vienna were more interested in scientific research than surgery and patient care. Semmelweis came under the influence of three of the leaders of the new approach to patho- logical and clinical investigation: Karl von Rokitansky (1804–1878), Josef Skoda (1805–1881), and Ferdinand von Hebra (1816–1880). While serving as professor of pathological anatomy, Rokitansky had person- ally conducted some 30,000 autopsies. Rudolf Virchow (1821–1902), the founder of cellular pathology, called Rokitansky the ‘‘Linnaeus of pathological anatomy.’’ After earning his medical degree, Semmelweis remained in Vienna for further training in midwifery and surgery. He also studied diagnostic and statistical methods with Skoda. In 1846, Semmelweis became titular house officer of the First Obstetrical Clinic at the Vienna General Hospital, under the direction of Professor Johann Klein (1788–1856). The Vienna General Hospital had been quite large even in the eigh- teenth century when Johann Peter Frank described it as having many advantages over other hospitals in terms of space and suitable divisions for the isolation of contagious diseases. Although the Vienna Hospital did not have all the special departments that Frank recommended, it did have a lunatic tower, wards for contagious diseases, small rooms for paying customers and pregnant women, and large sickrooms, with 20 or more beds. The purposes of the ideal hospital, according to Frank, were: curing poor, sick people, perfecting medical science, and educating good practitioners. Eighteenth- and nineteenth-century hospi- tals were generally far from ideal. Contagious diseases became a major threat to patients and staff in a general hospital because of overcrowd- ing and the lack of resources, which made it impossible to keep the wards clean and well ventilated. Such conditions were especially danger- ous to women during labor and the postpartum period. To protect new mothers from acquiring contagious diseases, Frank stipulated that the lying-in ward should be quite separate from the gen- eral hospital. Ideally, the lying-in ward should have three departments: one where pregnant women could rest and prepare for the ordeal of childbirth; the second should be dedicated to women giving birth; and the third should have small rooms with only two or three beds reserved for postpartum women. Women who needed surgical intervention dur- ing childbirth should not be kept in the common labor room, Frank warned, because the sights and sounds of such ‘‘artificial births’’ would have a bad effect on women in labor. The lying-in ward did not need rooms for the sick, because postpartum women who became ill should be transferred to the general hospital. Hospital managers and physi- cians, however, considered such elaborate precautions unnecessary, irrational, and, most of all, too costly for a largely charitable enterprise. In the 1840s, the Vienna Hospital provided medical researchers and teachers with a plethora of ‘‘clinical material’’—patients forced by poverty, if not expectation of a cure, to use the hospital. Doctors and stu- dents could anticipate thousands of childbirth cases and hundreds of autopsies annually. Vienna was, therefore, a magnet for foreign medical students. The founder of the Vienna Obstetrical Department, Lucas Boe¨r (1788–1822), established the enviable record of a 1.25 percent maternal mortality rate among some 70,000 patients. Boe¨r restricted medical students to practicing their skills on the ‘‘phantom’’ (a mannequin with a uterus and birth canal), but his successor, Johann Klein, let students take an active role in examinations and deliveries. In support of the doctrine that even dead patients could serve educational purposes, Klein allowed the bodies of women and infants who died in the hospital to be used for demonstrations of the birth process. Klein’s methods gave medical students better clinical experience, but maternal mortality soared to about 10 percent and above. During a period of expansion and reorganization, Klein divided the obstetrical service into two separate divisions: one was supervised by midwives training midwifery students. In the other division, medical students practiced under the supervision of physicians. Women in the First Clinic, the teaching division for medical students, were sometimes examined by five or more different students, who moved freely between the wards and the adjoining dissection room. From 1841 to 1846, the maternal mortality rate was about 10 to 13 percent; but during parti- cularly virulent epidemics, 20 to 50 percent of the maternity patients died of the fever. In contrast, the mortality rate in the Second Obstetrical Clinic, the section dedicated to the instruction of midwives, was usually about two to three percent. Some studies of maternal mortality suggest that, in contrast to hospital childbirths, about five women per thousand died in deliveries that took place at home. Unable to explain the high death rate of his patients, Semmelweis became obsessed by the problem of childbed fever. Each day he exam- ined every patient in his ward, demonstrated the proper methods for examining patients in labor, and performed operations. Before begin- ning work in the wards, Semmelweis conscientiously dissected the bodies of puerperal fever victims. During the first few months of his assistantship, the mortality from puerperal fever actually increased to about 18 percent. Ironically, it was not the systematic study of mortality rates, obser- vations of patients, or diligent work in the dissection room that gave Semmelweis his flash of insight into the cause of puerperal fever; it was the death of his friend Jakob Kolletschka (1804–1847), professor of forensic medicine at Vienna. While Semmelweis was away on vacation Kolletschka died of pathologist’s pyemia from a minor wound incurred during a postmortem examination. Pyemia (blood poisoning) was a well-known risk to anatomists. A small injury on the hands incurred during dissection might go unnoticed until redness, throbbing pain, and red streaks up along the arm announced the presence of a potentially fatal infection. When Semmelweis studied the results of the autopsy conducted on Kolletschka’s body, he realized that the findings were nearly identical to those characteristic of death from puerperal fever. Obviously, Kolletschka’s massive infection had been triggered by the introduction of ‘‘cadaveric matter’’ into a small wound caused by a dissection knife. Therefore, Semmelweis concluded, cadaveric matter must also be the cause of puerperal fever. Few maternity patients underwent any surgical interventions, but after childbirth, women were especially vulnerable to infection because, in addition to the trauma of the passage of the infant through the birth canal, a large internal wound was created by the detachment of the placenta from the wall of the uterus. Just as the dissecting knife introduced cadaveric matter into the anatomist’s blood stream, the contaminated hand of the examining physician carried cadaveric matter from the autopsy room to the labor- ing woman. As demonstrated by the persistence of cadaveric odor on the hands of the anatomist, ordinary washing with soap and water did not entirely remove the contamination carried from the autopsy room. The insight gained from Kolletschka’s tragic death was the foun- dation on which Semmelweis constructed what he called his doctrine: puerperal fever was identical to pathologist’s pyemia and was caused by the introduction of cadaveric matter or morbid poison into the body. In opposition to almost all medical authorities, Semmelweis asserted that only his doctrine was consistent with the statistics and facts observed at the Vienna Lying-In Hospital. His major argument was that none of the prevailing theories could explain away the threefold differ- ence in mortality rates between the First Division, staffed by medical students, and the Second Division, staffed by midwives. Actually, the difference was greater than threefold, because, whenever possible, women with puerperal fever were transferred to wards in the General Hospital and their deaths were not included in the reports of the First Division. Very few patients in the Second Division were transferred to other wards unless they had a contagious disease like smallpox. According to prevailing medical dogma, childbed fever was caused by ‘‘atmospheric-cosmic-tellurgic influences’’ or an ‘‘epidemic consti- tution’’ that peculiarly affected puerperal women because of internal predisposing conditions, such as milk fever, or a peculiarity of the blood associated with childbirth and lactation. Many complicating factors were suggested to explain away the differences between Division I and Division II. Some physicians blamed overcrowding, but Division II was actually more crowded. Semmelweis drew attention to another interesting difference between the two sections: in the midwives’ ward long labors were not more life-threatening than short labors, but in Division I, women with long labors were especially prone to puerperal fever. Moreover, women brought into the hospital after so-called street births seemed to be immune to the fever. This anomaly could be explained by remembering that hospital charity was formally extended to women and their infants in return for their use as ‘‘teaching material.’’ Generally, the hospital accepted women after childbirth only if the patient could convince the authorities that she had intended to be delivered in the hospital but the birth occurred before she could get there. To avoid being used for ‘‘public instruction,’’ some women employed a midwife and then appeared at the hospital claiming to be victims of street births. Hospital administrators blamed high mortality rates on the miserable condition of the poor, desperate, unmarried women who needed the services of the maternity ward. While such a theory might explain the difference between charity patients in hospitals and private patients giving birth at home, it could not explain the difference between Divisions I and II. Another explanation attributed differential mortality to the shame women experienced when attended by male physicians and students. Ironically, delicate upper-class ladies were able to employ phy- sicians, rather than midwives, without dying of shame. The fear inspired by the bad reputation of Division I was also cited as a possible factor in the genesis of disease. Semmelweis proved that statistical differences in mortality rates between the two divisions preceded the recognition that such differences existed. He also dismissed the idea that fear could pro- duce the anatomical findings characteristic of both puerperal fever and pathologist’s pyemia as patently absurd. Foreign medical students had been singled out for being parti- cularly rough and coarse in their treatment of patients and, therefore, responsible for a high incidence of injuries during physical examina- tions. Semmelweis protested that compared to the birth of a baby, man- ual examination, even by the most uncouth medical student, hardly constituted a major trauma. Nevertheless, reducing the number of foreign medical students in the ward and the number of manual examinations per patient did produce a temporary decline in maternal mortality rates. Here again, Semmelweis explained, his doctrine was consistent with the observations. The attempt to improve medical education by giving students clinical experience and anatomical in- struction had produced ideal conditions for the transmission of puerperal fever. The foreign medical students, who had come to Vienna at great trouble and expense, were especially eager to take advantage of access to the cadavers and the ‘‘clinical material’’ available only in the great teaching hospitals of European cities. To eliminate the transmission of cadaveric particles, Semmelweis insisted that all medical students and hospital staff wash their hands with a solution of chlorinated lime each time they left the autopsy room to examine patients. Within a month the mortality from puerperal fever decreased from about thirteen to three percent. Contrary to popular belief, hand washing was not an unknown custom among nineteenth- century doctors. However, the soap and water wash that might bring hands to a state of socially acceptable cleanliness did not remove all the dangerous cadaveric matter. In 1848, the first full year of rigorous hand washing, the mortality rate in Division I fell below two percent. Transient increases in puerperal fever cases were traced to patients with other forms of infections, which indicated that the autopsy room was not the only source of the deadly contamination. Gradually, Semmelweis realized that disinfection procedures should be extended to include all the instruments that came in contact with patients in labor. Although the decrease in mortality in Division I was undeniably dramatic, the disinfection procedures that Semmelweis demanded were not thought appropriate for a charity hospital. Even in the absence of rigorous hand washing, fluctuations in the rate of puerperal fever were not uncommon and, skeptics argued, it is a very old adage in clinical medicine that correlation need not indicate causation. Professor Klein, who remained a bitter enemy of Semmelweis and his doctrine, accused his assistant of insubordination and other crimes. For Semmelweis, the discovery of the cause and prevention of puerperal fever was complete by the autumn of 1847. All further obser- vations, including some experiments on laboratory animals, simply con- firmed and extended the doctrine. Ironically, the discovery of the cause and prevention of puerperal fever brought him a terrible burden of guilt. Driven by concern for his patients and the desire to understand the dis- ease, Semmelweis had pursued pathological studies more diligently than any of his colleagues. Therefore, every day when he entered the clinic after his work in the autopsy room, he had carried with him the deadly cadaveric particles that caused the fever. Unfortunately, Semmelweis was unwilling to assume the burden of bringing his doctrine to the attention of the medical community, either through lectures or publications. His friend and mentor, Ferdinand von Hebra, published two articles about the etiology of puerperal fever and the use of chlorinated lime, but his accounts failed to generate signifi- cant attention. Skoda, who was impressed by Semmelweis’s statistical data, presented a lecture on puerperal fever to the Royal Academy of Sciences and urged the creation of a commission to investigate Semmelweis’s results. Although Hebra, Skoda, and Rokitansky sup- ported Semmelweis, they did not fully understand his procedures and their presentations were not totally accurate. Primarily, Semmelweis’s doctrine was a victim of the defeat of the liberal movement of 1848 and his own failure to present a compelling case to the medical community. Because of his political activities in support of the liberal movement and Klein’s resentment of a doctrine that was fundamentally an indictment of his management of the clinic, Semmelweis found himself unemployed. Although Semmelweis had provided a practical system of antisep- sis that could have mitigated the burden of postsurgical infection as well as puerperal fever, his discovery had little or no immediate impact on medical practice. Just as the term ‘‘classic’’ is generally applied to a book that nobody reads, the term ‘‘landmark’’ is often applied to an insight that was generally ignored. To say that Semmelweis’s discovery was a ‘‘breakthrough’’ would imply that after it was made, maternity wards were significantly safer places for women. In reality, Semmelweis lost his sanity and his life in the battle against puerperal fever and pre- vailing medical opinion. Unwilling to compromise with those he saw as corrupt and ignorant, and lacking any talent for diplomacy, public speaking, or literary exposition, Semmelweis ruined his own career and made few converts to his doctrine. He also displayed a perverse sense of timing by establishing his doctrine in 1848 as a wave of liberal revolutions swept through Europe. The time was quite appropriate for making a revolutionary discovery, but not a convenient time for a for- eigner in Vienna to achieve the official recognition that might win the support of the medical establishment. When Semmelweis finally received an appointment as a Privatdozent in midwifery, the official decree stipulated that he could only teach obstetrics using a mannequin. Angry, discouraged, and without hope of professional advancement in Vienna, Semmelweis abruptly left the city and returned to Hungary. Not surprisingly, misfortune followed him—poverty, professional rejection, and two broken limbs within a year. The only ray of hope to fall into Semmelweis’s life was his mar- riage to Marie Weidenhofer, a woman 20 years his junior. Their first child died within 48 hours of hydrocephalus; the second died when 4 months old of peritonitis, but two daughters and a son survived. For- tunately, Semmelweis obtained an appointment as chair of theoretical and practical midwifery at the University of Pest and an honorary posi- tion at Pest’s St.-Rochus Hospital. Despite initial resistance by the hos- pital staff, Semmelweis enforced his system of disinfection and eventually reduced the mortality rate in the maternity ward to less than one percent. A textbook on childbirth and gynecology published by Johann Baptist Chiari (1817–1854), Ritter von Fernwald Braun (1822–1891), and Joseph Spa¨ th (1823–1896) in 1855, was the first to include information about Semmelweis’s doctrine of rigorous hand washing as a means of preventing puerperal fever. Chiari, who had worked at the first obstetrical clinic in Vienna under Professor Klein from 1842 to 1848, died of cholera before the text was published. Even among his friends, Semmelweis’s doctrine was generally mis- understood as a simplistic attempt to link childbed fever to cadaveric matter. Thus, some rather half-hearted attempts to test the Semmelweis doctrine were failures because of the lack of attention to related factors, such as the disinfection of instruments, linens, dressings, and the isolation of patients with purulent infections. Indeed, after Semmelweis had explained the doctrine to a visiting obstetrician, his skeptical colleague replied that this was certainly not new. All English doctors washed their hands when they left the hospital. The resistance and apathy that greeted Semmelweis’s doctrine were due in part to medicine’s conservative traditions, but his reluctance to publish his observations also played a role. Declaring himself pathologically averse to writing, Semmelweis left the task of publicizing the doctrine to colleagues who overemphasized the problem of cadaveric matter. Since some hospitals were plagued by high maternal mortality rates despite the absence of routine autopsies, the doctrine appeared to be irrelevant to their problem. Moreover, hand washing seemed too sim- ple an answer to epidemics supposedly spawned by the ineluctable cos- mic forces that ostensibly absolved the doctor of responsibility for the fate of his patients. In 1861 Semmelweis finally overcame his aversion to writing, and published The Etiology, Concept, and Prophylaxis of Childbed Fever. Semmelweis explained that he had developed his doctrine and written the book ‘‘in order to banish the terror from lying-in hospitals, to pre- serve the wife to the husband, and the mother to the child.’’ Unfortu- nately, by the 1860s, many physicians who knew of the doctrine from vague, secondhand accounts assumed that it had been discredited since the 1840s. Critics dismissed the book as the obsolete ravings of the ‘‘Pester Narr’’ (the fool from Budapest). Having finally accepted the burden of authorship, Semmelweis launched a flood of vitriolic pamph- lets and open letters accusing his critics of having massacred mothers and infants. Citing the names of his enemies, he denounced them ‘‘before God and the world’’ as medical Neros, guilty of willful homi- cides. His depression deepened as he brooded upon the deaths that could have been prevented had his doctrine been accepted in 1848. His condition continued to deteriorate until his wife agreed to send him to a mental asylum where he died two weeks later. His death was originally attributed to septicemia caused by an infected dissection wound, but there is some evidence that suggests the unfortunate Semmelweis was suffering from dementia, syphilitic psychosis, or Alzhei- mer’s disease when he was beaten to death by keepers at the asylum. Despite demonstrations of the value of the doctrine in the hospitals of Vienna and Budapest, few physicians were aware of or interested in the work of Semmelweis. Rudolf Virchow, the German ‘‘Pope of Pathology,’’ initially rejected the doctrine in favor of the theory that pregnant women were predisposed to inflammations. Not until 1864 did Virchow accept the concept of the contagiousness of puerperal fever. Shortly after Semmelweis died, Joseph Lister (1827–1912) began to publish a series of papers describing his antiseptic system. By 1880, as part of the Listerian antiseptic system, rather than the work of Semmelweis, the doctrine was more or less incorporated into obstetrical practice throughout Europe. Although Lister later graciously acknowl- edged Semmelweis as his ‘‘clinical precursor,’’ Lister’s immediate inspiration was the work of the great French chemist Louis Pasteur (1822–1895) on the diseases of wine and beer. Nevertheless, the concept of a special epidemic constitution of parturient women was still blamed for puerperal fever when Pasteur announced his discovery of the probable causative agent of puerperal fever at a meeting of the Paris Academy of Medicine in 1879. Actually, the role of germ theory in the transformation of obstet- rics and surgical practice is problematic. Oliver Wendell Holmes, for example, did not think that the germ theory of disease was prerequisite to the acceptance of his theory of the contagiousness of puerperal fever. Indeed, in the 1880s, he reminded his colleagues that he had given his warning and advice long before the advocates of germ theory had mar- shaled their ‘‘little army of microbes’’ in support of the doctrine he shared with Semmelweis. Moreover, despite the general adoption of antisepsis and asepsis in surgery, the mortality rate from puerperal fever remained quite high until the introduction of sulfonamide and penicil- lin. Maternal mortality rates remained higher in the United States and Great Britain than in continental Europe.

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