Ignaz Philipp Semmelweis (1818 - 1865)
When in 1855 Oliver Wendell Holmes published the reprint of his 1843 article on puerperal fever, he provided not only an Introduction but also a supplement entitled Additional References and Cases. In this supplement he briefly reviewed journal articles and other works printed since 1843 which further documented the contagiousness of puerperal fever. Among these publications were two reports on the research in Vienna of a Dr. Semmelweis whose "doctrine" of the cause and control of epidemic puerperal fever was highly commended by the authors of the reports. Reference to these reports in his supplement was a recognition by Holmes that Semmelweis's observations, of which he was learning for the first time, were possibly of great significance - as indeed they proved to be.  
Semmelweis, of German ancestry and Hungarian birth, studied medicine at the University of Vienna where in 1844, at the age of 25 he received the degree of Doctor of Medicine. Later in the same year he qualified for the degree of Master of Midwifery, and from that time forward devoted the remainder of his life to the science and practice of Obstetrics. Upon receiving his Master's degree he at once applied for the position of Assistant in the Lying-in Division of the huge Vienna General Hospital (Das allgemeine Krankenhaus), and was eventually appointed to that post.
The General Hospital's Lying-in Division was the largest of its kind in the world. It was also one of the most deadly due to prevalence among its postpartum patients of what was known as "the endemic puerperal fever of Vienna."  James Simpson, eminent British obstetrician and father of chloroform anesthesia, pronounced this censure of the situation in Vienna. He said "he knew in what a lamentable condition midwifery in Germany, and especially Vienna, still remained; he knew for certain that the cause for the high mortality lay only in the unbounded carelessness with which patients were treated." Incidentally, the great Simpson completely rejected Semmelweis's discoveries. 
The sensitive and deeply humanitarian Semmelweis was appalled by the death rate from puerperal fever in the Lying-in Division, and search for the cause and control of this pitiless disease became his life's work. For a laboratory he had the First and Second Obstetrical Clinics, each averaging about 3000 deliveries per year. When he tabulated the deliveries and deaths by month and year in each of the Clinics for the six-year period from 1841 to 1846, he found that First Clinic, where medical students were trained, had a death rate from puerperal fever of 9.9%; whereas, the death rate in Second Clinic where midwives did the deliveries was 3.3% - only one-third that of First Clinic. It would be too chilling to list the grotesque explanations offered by the medical "authorities" and a government commission in Vienna to account for the evil reputation of First Clinic where patients were in mortal fear to go because they believed that a doctor's interference was always the precursor of death.  Johann Klein, the reactionary Professor of Obstetrics who presided over the upsurge of puerperal fever which Semmelweis found so disturbing, ridiculed the theory that the disease was contagious. 
These circumstances were especially troubling to Semmelweis for he himself had been in charge of the First Clinic since February of 1846, and the high death rate persisted in spite of all his efforts. He had studied the problem from every angle in the wards. He also frequented the pathology department where he participated in the post mortem examinations of the many victims, becoming increasingly mindful of the nauseous fetor that clung to his hands and clothes long after an autopsy. There is no indication that Semmelweis, at this stage of his career, accepted the concept of contagion as defined by Holmes of whom he was not aware until years later. Yet by 1847 there was no one in Vienna with greater knowledge of endemic childbed fever than Semmelweis, and his mind was prepared to grasp the solution to the mystery of its cause when chance provided the clue - as it soon did in the sad loss of a dear friend, Dr. Kolletschka, who died of infection.
By a singular coincidence, a physician's death from overwhelming sepsis following a simple puncture wound received while performing an autopsy created circumstances that led both Holmes and Semmelweis to their independent conceptions of the cause of epidemic puerperal fever. From time immemorial, pyemia had stalked the deadhouses as a dreaded foe of all anatomists, pathologists, surgeons and others who dissected. It was well known that a swiftly fatal infection might follow even the slightest prick of a knife or needle during anatomical dissection, autopsy, or an operation such as amputation of a gangrenous limb. Holmes in 1843 and Semmelweis four years later in 1847 both recognized the similarities between this accidentally acquired infection and puerperal fever. It was the genius of Semmelweis to derive from this observation a new principle of prophylaxis and, by experiment, to demonstrate its validity.
Jakob Kolletschka, a 43 year-old Professor of Forensic Medicine, was a former teacher and friend whom Semmelweis held in the highest esteem. Kolletschka's death early in 1847 from a scalpel wound, incurred during an autopsy, had a profound effect upon Semmelweis who assuaged his anguish by studying in detail the reports of his friend's fatal illness and autopsy. These records disclosed that after a puncture wound in his finger from the knife of one of his pupils, Kolletschka developed lymphangitis and phlebitis in the same upper extremity. From there the infection spread. He developed pleurisy, pericarditis, peritonitis, and meningitis; and a few days before his death an abscess occurred in one of his eyes. This generalized dissemination of infection was exactly the same that Semmelweis had seen at autopsy in women who died of puerperal fever. A new thought was forced upon his mind with irresistible clarity - the disease from which Kolletschka died was identical with that from which he had seen so many hundred puerperae die. 
Semmelweis designated the causative agent as "cadaveric particles" that enter the circulation after being introduced by the knife in the case of pathologist's pyemia. In puerperal fever, the particles are introduced into women in labor by students and others who do vaginal examination with hands contaminated by such particles during autopsy or anatomical dissections, or during examination of patients with puerperal fever or other infections. Contaminated instruments and bedclothes might also transfer the causative agent. He also observed: 
Owing to a filthy discharge from an ulcer of the leg in one of the patients, several women who were confined at the same time were infected. Thus, therefore, the conveyance of a foul exudation from a living organism may be one cause which produces the puerperal process.
By this conjecture Semmelweis is thought by some to have foreshadowed the germ theory by proposing that, while puerperal fever is in most cases a cadaveric infection, it is sometimes traceable to other sources, i. e., to a "living organism." 
Now the explanation for the higher mortality from puerperal fever in First Clinic became obvious to Semmelweis - medical students and doctors carried cadaveric particles to the patients on hands contaminated at post mortem dissections. In Second Clinic the midwives, who did no dissections, were not thus contaminated. 
Since students and others could not be banned from work in the pathology and anatomy laboratories, it was necessary to establish a procedure for the decontamination of their hands. (It was not until 1890 that rubber gloves were introduced by Halsted of Johns Hopkins to protect the hands of his surgical team from irritating antiseptics.) Semmelweis associated cadaveric particles with the foul clinging odor of the autopsy and dissecting rooms, and knew that soap and water would not dispel it. However, he found a solution of chlorinated lime to be effective and therefore chose it as the decontaminant. The system of prophylaxis introduced into the regular obstetric practice of First Clinic in May 1847 was simple. Placards with the following directions were posted conspicuously in the wards: 
All students or doctors who enter the wards for the purpose of making an examination must wash their hands thoroughly in a solution of chlorinated lime which will be placed in convenient basins near the entrance of the wards. This disinfection is considered sufficient for this visit. Between examinations the hands must be washed in soap and water.
The experiment was successful. Within a few months, the mortality rate in First Clinic was no greater than in Second Clinic, and remained so as long as Semmelweis's directions were strictly followed. In 1848, the first full year in which the chlorine-washing was carried out assiduously, 45 out of 3556 puerperae died of puerperal fever in the First Clinic for a mortality of 1.27 %. In the Second Clinic, during the same period, 43 died out of 3219 delivered, or 1.34%.  These results were a clear validation of the concept and method of prophylaxis which became known as the Semmelweis "doctrine."
Far from bringing him preferment in the University, Semmelweis's discovery divided the faculty. Professor Klein, head of obstetrics, was adamantly opposed to the Semmelweis doctrine and squelched a proposal by Skoda, Professor of Chest Diseases, for a commission to evaluate its effectiveness. Believing it better to prevent contamination than to remove it, Semmelweis petitioned the authorities for a regulation preventing students occupied in the Lying-in Hospital from engaging in any dissection whatsoever. Here again, Professor Klein barred the way. 
When Semmelweis's Assistantship expired in March 1849, Klein refused to renew it. Semmelweis appealed, precipitating a faculty feud between Klein and Skoda from which Klein emerged the victor, and Semmelweis the loser. Frustrated and demeaned by the rejection, he departed abruptly for Budapest in 1850 without expressing his gratitude to Skoda and others who had supported his doctrine and his quest for a position in Vienna. Semmelweis's erratic and inconsiderate behavior was never forgotten.
Soon after his arrival in Budapest, Semmelweis was made head of the obstetrical service at the St. Rochus Hospital in Pest. There he conducted a six-year clinical trial (1850-1856) of his doctrine and achieved a mortality rate of 0.85% on a maternity service where puerperal fever had previously raged. In 1855 his academic aspirations were at last gratified by his appointment as Professor of Midwifery at the University of Pest. He took over an obstetrical service in shambles and, during the first full year of his tenure, reduced the death rate from puerperal fever to 0.39 %, an unheard of record on the continent.  Now full of confidence in his doctrine, he spent the remainder of his career zealously promoting it. 
Unfortunately, Semmelweis did not personally author a single publication about his work until 1861. His findings were first announced to the profession at large in December 1847, not by himself, but by his good friend Ferdinand von Hebra, editor of the Journal of the Royal Imperial Society of Physicians in Vienna, who wanted to encourage him and gain recognition for him in spite of Professor Klein. The article, written by v. Hebra, was entitled "Experience of the highest importance concerning the etiology of epidemic puerperal fever at the Lying-in Hospital."   
Other of Semmelweis's friends and supporters also wrote articles and tried to win adherents to his doctrine, but with indifferent success. It was two of these articles that came to Holmes's attention and were referred to by him in the 1855 reprint of his 1843 article. Finally, in 1861, Semmelweis published his magnum opus of 543 pages entitled The Etiology, Concept, and Prophylaxis of Puerperal Fever. This monograph was an exhaustive account of his studies, experience and evolving conception of puerperal fever. The Etiology documented his life's work and contained a vigorous defense of his doctrine that for the previous 14 years had been mired in controversy and counterclaims that deterred its general acceptance. In fact, to his great distress, his doctrine had been ignored or dismissed as unsound by many of the leaders in the field of obstetrics.   
Rebuffs to his struggle for wider application of his doctrine were disturbing to Semmelweis. He particularly resented attacks by the self-serving forces of the authoritarian medical establishment, and he lashed out against them. His doctrine was opposed by powerful members of the academic hierarchy such as Professors Busch of Berlin; Hamernik of Prague; Hecker of Munich; Kiwisch of Würzburg, Lumpe of Vienna; Rosshirt of Erlangen; Scanzoni of Würzburg (formerly of Vienna); and others. Mortality from puerperal fever on the services of some of these Professors of Midwifery ranged as high as a barbarous 26% (under Kiwisch at Würzburg).  The damning evidence that they were themselves the remorseless messengers of death was a scarcely veiled threat to their pride and eminence. Semmelweis was unsparing in his condemnation of those who denied his doctrine in spite of the high mortality rates in their own institutions. This from his open letter to Professor Scanzoni of Würzburg who, while professor at Vienna, had disparaged Semmelweis's earliest work: 
Your teaching (that the Würzburg epidemic of childbed fever is caused by unknown atmospheric influences or puerperal miasma is false), and is based on the dead bodies of lying-in women slaughtered through ignorance. . . I have formed the unshakable resolution to put an end to this murderous work as far as lies in my power so to do. . . (If you continue teaching your students this false doctrine), I denounce you before God and the world as a murderer, and the History of Puerperal Fever will not do you an injustice when, for the service of having been the first to oppose my life-saving Lehre, it perpetuates your name as a medical Nero.
At last, although acceptance of his principles was gaining ground, the long years of controversy and intense preoccupation with defense of his doctrine affected Semmelweis's mind. Because of increasingly eccentric behavior, he was admitted to a sanatorium for mental disorders. There an infected wound on his finger, received during a gynecological operation, was discovered. Defying all efforts at control, the infection progressed to gangrene followed by extensive sepsis, leading to his death in 1865 at the age of 47. By a tragic irony Semmelweis died from the same manifestations of pyemia as his friend, Kolletschka, whose death provided the clue to the prevention of puerperal fever.
The importance of Semmelweis as a forerunner of Pasteur and Lister is in his doctrine of puerperal fever as a bloodstream infection (septicemia) caused by a specific transferable agent, and preventable by destroying the agent with an antiseptic (20 years before Lister published a description of his antiseptic principle). No one before Semmelweis had articulated a concept of the etiology and prophylaxis of this disease so consistent with all the facts as later determined. His demonstration by controlled experiment that the incidence of puerperal fever could be significantly reduced by an antiseptic method ranks Semmelweis among the foremost medical scientists of his day. The ultimate price of a broken spirit that he paid for his devotion to the spread of his life-saving doctrine ordains him as a martyr to Medicine. 
The relative merits of the contributions of Holmes and Semmelweis have often been debated. Holmes, man of letters and one of the most perceptive medical thinkers in early American medicine, analyzed the experience and views of British contagionists. From these abundant data, refined by his own judgement and colored by his indignation and sense of urgency, Holmes fashioned a powerful and convincing brief in defense of women in childbirth. That puerperal fever was contagious was not the question. The extensive and horrifying evidence was undeniable. At issue was the incredible, monstrous failure of the medical profession to recognize a "momentous fact, which is no longer to be considered for trivial discussions, but to be acted upon with silent promptitude."  Holmes concluded his thoroughly documented treatise with a warning that those who fail to heed its conclusions must answer at the bar of judgement for their crime; and he promulgated the most comprehensive and effective set of principles yet published to prevent the spread of the contagion of puerperal fever. Holmes made an eloquent appeal to the common sense and conscience of the profession. As such, his message was the most trenchant, timely and persuasive of its kind in the medical literature, and remains so to the present day. It unquestionably saved thousands of lives. Herein lies its merit. The life's work of Semmelweis - humanitarian, experienced clinician, dedicated scientist - is of another category and order of magnitude, and should not be compared to the treatise of Holmes. As the exponent of the most advanced concept of infection up to his time, and harbinger of the antiseptic method, Semmelweis simply has no peer.
It was not until after 1867 that Lister's antiseptic method, having proven its value in the prevention of infection in surgery, was applied with success in maternity hospitals, obstetricians in general having finally acknowledged the contagiousness of puerperal fever. According to Dr. Emile Roux, one of Pasteur's assistants, the actual cause of the disease was not revealed until 11 March 1879. On that day Pasteur was attending the Academy of Medicine in Paris and the subject of puerperal fever came under discussion:  
One of (Pasteur's) most weighty colleagues was eloquently enlarging upon the causes of epidemics in lying-in hospitals; Pasteur interrupted him from his place. "None of these things cause the epidemic; it is the nursing and medical staff who carry the microbe from an infected woman to a healthy one." And as the orator replied that he feared that the microbe would never be found, Pasteur went to the blackboard and drew a diagram of the chain-like organism (the streptococcus), saying: "There, that is what it is like!". His conviction was so deep that he could not help expressing it forcibly. It would be impossible now to picture the state of surprise and stupefaction into which he would send the students and doctors in hospitals, when, with an assurance and simplicity almost disconcerting in a man who was entering a lying-in ward for the first time, he criticized the appliances, and declared that all the linen should be put into a sterilizing stove.
Thus ended the agonizing search for the cause and prevention of puerperal fever. Vive Pasteur!
In keeping with our purpose, this account of the contributions of Holmes and Semmelweis to the control of puerperal fever will serve as a reminder of the state of the art in their time. It will also call attention to the striking contrast between the slowness with which medical advances were accepted in the mid 1800's and the readiness with which new concepts and technologies are adopted in the present day.
Cooper's Antiseptic Use of Alcohol.
Much has been made of the fact that Dr. Elias Cooper was using alcohol in the management of surgical wounds as early as 1850 when Semmelweis was completing his clinical trials of chlorinated lime as an antiseptic.
In a journal article in 1929 Professor Emmet Rixford of Stanford expressed the opinion that: 
Much of Cooper's operative success was due to his free use of alcohol on instruments and hands and parts to be operated on and for the irrigation of his wounds, although he was inclined to account for the fact that his wounds did better in California than in Illinois by the difference in climate, or rather that the combination of climate and alcohol had a most remarkably favorable influence in the healing of wounds.
In an article published the previous year, Professor Rixford stated that Cooper "washed his wounds with 25 percent alcohol." 
No source is cited for these statements and it is assumed that Rixford received the information about Cooper's surgical use of alcohol from Levi Cooper Lane. The inference of Rixford's comments is that Cooper independently conceived and practiced a primitive form of antisepsis.
Perhaps he did, but we can find only such statements from Cooper himself as the following: 
(The wound) was dressed in accordance with my universal plan in these cases, viz: by filling it with lint wet with evaporating solution, composed of one part alcohol and ten of water.
In another article Cooper indicates that the use of an "evaporating lotion" for wound care is not original with him He says that a lotion composed of one part of alcohol to ten of water is "much better for our climate than that used in London, composed of one of alcohol to five of water." 
As far as we can determine, we have from Cooper's own hand reference to the use of alcohol only as an ingredient of an "evaporating lotion." As for its rationale we have the implication that he thought use of the lotion would help to control inflammation.
Actually, Cooper had a most sensible approach to wound healing in the pre-antiseptic era. He insisted on adequate incisions for the drainage of infection, including septic joints, with wounds packed open for free drainage until suppuration subsided and clean granulation was established. He had sound surgical instincts. We can surmise that he would have been prompt to accept and apply Listerian principles could he have lived to the day of their dawning.