Theodor Kocher was born on August 25, 1841 in Bern, Switzerland. He was the second of 6 children. His father was a first engineer in the office responsible with maintaining roads and waterways in the Canton of Bern and he was also a state expert for railway projects. Kocher's mother was a strictly religious person, whose faith deeply impinged on the way he himself thought and lived throughout his whole existence. (A monograph on Kocher’s life was written by the well known Swiss historian and son-in-law Edgar Bonjour [1]. Moreover, we owe a detailed essay on Kocher's medical performances within their historical context to Ulrich Tröhler-de Quervain [13]). Kocher was a brilliant student at the gymnasium of Burgdorf. He was a medical student at the University of Bern between 1860 and 1865, interrupted only by a short stay in Zürich. There he came into contact with Theodor Billroth, who was the full Professor of Surgery at the University of Zurich from 1860 to 1867. Kocher, an ambitious young man, was deeply impressed by the personality of Billroth, one of the fathers of modern surgery. The two men met also at a particular medical circle, where students were the referees and the professors the discussants and where the meetings were followed by a social event – adorned by a piano performance of Billroth. Kocher ended his studies with an excellent record in 1865 and was promoted "Doctor of Medicine" a year later.

Shortly after obtaining his degree, Kocher set out to visit the leading surgical clinics in Berlin, London and Paris (1865-66). In this way, he got acquainted not only with Billroth, but also with other most important representatives of a new surgical area, who strove to replace the traditional "conservative" surgery by more radical methods, i.e. by rational therapeutic approaches based on Rudolf Virchow's (1812-1902) concepts of cell- and organ pathology. In Berlin, Kocher paid visits to Bernhard von Langenbeck (1810-1887) and to the pathologist Virchow. In London, he was welcomed by Sir Thomas Spencer Wells (1818-1887), whom he knew form a visit in Zurich, where Spencer Wells – as a guest of Billroth – had performed an ovarectomy. Wells pioneered the radical approach to the treatment of large ovarial cysts, i.e. total exstirpation instead of mere puncture. Kocher was soon to adopt this radical approach in goitre surgery where he substituted the traditional therapeutic strategy using iodine injection for the operative removal of the diseased organ. In 1883 he reported on the first 100 thyroidectomies, in 1906 this number had increased to 3000, and in 1909, at the time of the "Nobel-Festschrift" he described his experience with 4250 goitre operations. Mortality was as low as 0.5% (8,13). In Paris, Kocher met Auguste Nélaton (1807-1873) and Louis Pasteur (1822-1895). In England, Kocher became aware of new "clean" surgical techniques. Wells intuitively performed aseptic surgery. Visits to the autopsy rooms were forbidden. In 1867, Sir Joseph Lister (1827-1912) reported on the antiseptic treatment of wound tissue. Much research was devoted to develop techniques aimed at reducing blood loss: in 1882 Kocher described his arterial clamp. Statistics ("arithmetical observations") were introduced to prove the beneficial effect of "radical surgical techniques" and to control their quality. Death rates, incidence of infections, follow-ups etc were assessed and reported. Wells and Kocher used to write so-called “notebooks” about diagnoses and surgical procedures, thus creating a basis for clinical investigations and further studies. Some examples are Kocher's reports on 119 operations of inguinal hernias (1892), 1513 appendectomies (1913) and on the effect of iodine injections into the goitres of 2712 schoolchildren (1873) [13].

After his return to Bern, Kocher resumed teaching duties and obtained his first academic degree ("Privatdozent"). From 1866 to 1869 he was the sole assistant of Georg Albert Lücke (1829-1894), a former fellow of Langenbeck. Lücke was full professor of surgery and holder of the chair. Still an assistant, Kocher introduced the antiseptic wound treatment – this against the will of the administrator! [13] With time, Bern became the centre of aseptic surgery. In 1869 Kocher got married and became obliged – for financial reasons – to enter private praxis, without, however, giving up research and teaching. During this time, he published papers on coagulation and haemostasis, as well as on a method to reduce a dislocated shoulder (1870). With this paper he became already internationally known. In 1872, Lücke left Bern to take a chair in Strasbourg (the town had been turned over to Germany). Kocher was appointed full professor of surgery and director of the University Clinic of Surgery. At that time, such an appointment was extraordinary for a Swiss citizen. Kocher's popularity and, in addition, the support of Langenbeck and Billroth helped in changing this situation.

Kocher held the chair of surgery at the University of Berne for 45 years, up to his death in 1917. Under his tenure, Bern became a world centre of modern surgery. Kocher was so closely connected to Bern that he declined a number of most honourable offers from universities such as Prague, Vienna, Berlin. His way of scientific reasoning, his clinical and manual mastery and his extraordinary work enthusiasm became hallmarks of his "radical surgery", which gradually turned into a "physiological surgery" and into a "system of safe surgery". This development was documented in a large number of publications, monographs and dissertations, above all by the famous handbook "Chirurgische Operationslehre". This textbook was much acclaimed, translated into many languages and distributed worldwide. Between 1892 and 1907 it was printed in 5 editions. It contained a large variety of chapters such as antisepsis and asepsis, abdominal surgery (mobilisation of the duodenum including the head of the pancreas, a procedure worldwide known as "Kocher's manoeuvre"), surgical aspects of infectious diseases, fractures and spinal lesions, gun wounds ("Improvement of bullets from a humanitarian standpoint",1874), osteomyelitis, tuberculosis of bones and joints, inguinal hernias, neurosurgery and surgery of the brain, research on the pathology of shock [13]. However, Kocher’s most important area of research concerned the pathology, pathophysiology and surgery of the thyroid. It is in thyroid surgery that his innovative scientific reasoning and his extraordinary surgical skills were particularly impressive and successful.

Kocher was a highly independent self-made man. He introduced a new operative manner or style, profoundly different from the traditional one: This was a meticulously precise technique to dissect tissues with minimal blood loss. It was an out-of-time procedure, and it was rather slow ("not fast, but safe") [1], so that occasional spectators could become quite irritated. However, many high-ranking surgeons all over the world paid tribute to his work, among them such illustrious men as William Halsted (1852-1922) from Baltimore, his fellow Harvey Cushing (1869-1932), the American-Swiss Nicholas Senn (1844-1908) from Chicago, René Leriche (1879-1955) from France [3,13]. Kocher’s anatomically precise dissecting technique greatly contributed to avoid “infection of haematomas and of necrotic tissues”. As for the thyroid, Kocher's technique amounted to a precise dissection directly on the capsula propria of the thyroid gland, a technique called nowadays capsular dissection ("Kapseldissektion") [3, 4]. This technique allows for the total and selective removal of all diseased thyroid tissue, if necessary of the entire gland. In Kocher's hands, even large goitres were removed without damage to the laryngeal nerves and the parathyroid glands, even though the anatomy (1880) and function (1891) of the latter were described only later.

Total thyroidectomies had also been performed by two surgeons from Geneva, Jacques-Louis Reverdin (1842-1929) and his cousin Auguste (1848-1908). They had drawn Kocher's attention to a postoperative condition they called "Myxoedème opératoire " [13]. Subsequently, Kocher himself found this sequela in 30 out of the first 100 patients he had operated in this way. He coined the name of "Cachexia strumipriva" for this clinical consequence of total thyroidectomy. In 1883 he reported on the clinical picture and the possible causes at the German Congress of Surgery [7]. It is difficult to understand that Kocher refused to acknowledge the merits of Reverdin, although contests about priorities were as common at that time as they are today [13]. “Myxoedème opératoire " was the more adequate term. Reverdin was aware of the disease "myxoedema", which had been described as a corollary to atrophic thyroiditis by William Orr (1814-1902) and others and became now the subject of a new evaluation by a "Myxoedema-Committee" of the Clinical Society in London [5]. Orr exchanged letters with Kocher. The committee concluded that "myxoedema" as well as "Cachexia" and cretinisme were all the consequence of the deficiency of an unknown function of the thyroid gland. It was only years later that Kocher renamed "his" clinical picture "Cachexia thyreopriva".

Kocher’s work contributed a great deal to the growing understanding of the physiology of the thyroid gland, although not all of his ideas and conclusions turned out to be correct. So, he insisted initially on the mechanistic view that the thyroid gland was an important regulator of blood flow to the organs of the neck and the brain. Equally unsuccessful was a search for ischemic tracheitis in thyroidectomized patients, a task confided to his first assistant César Roux (1857-1934), who later became full Professor for Surgery at the University of Lausanne. In 1893 Kocher reported that patients suffering from "Cachexia strumipriva" could be cured by the ingestion of raw thyroid from an animal source, as "sandwich for breakfast" as he proposed. This was shortly after George Murray (1865-1939) had successfully introduced organotherapy to treat spontaneous myxoedema. In 1894 Paul von Bruns (1846-1916), a surgeon in Tübingen, reported on the shrinking of goitres with organotherapy, an observation first mentioned by a German psychiatrist, G.Reinhold, who administered thyroid organotherapy not only to myxedematous, but to all mentally diseased patients, some of them with an incidental goitre! The finding of Bruns was confirmed by Kocher in 1895. Already in 1820, Coindet in Geneva had described the beneficial effect of iodine on goitre volume. Therefore, Kocher concluded that the iodine content of ingested thyroid tissue was the active agent. However, his laboratory in Bern failed to prove the presence of iodine in the minced thyroid tissue. Careful clinical observations soon revealed that iodine and organotherapy were not efficient in all goitre patients. On the contrary, these therapeutic measures were prone to trigger a new complication, severe hyperthyroidism, particularly so in patients bearing huge goitres or those already suffering from Basedow's disease. For this reason, Kocher vigorously rejected indiscriminate use of iodide for goitre treatment. It is conceivable that Kocher's attitude delayed the use of iodide as a thyrostatic agent in Basedow's disease – until this treatment was reintroduced by Plummer in 1923 [14]. On a purely empiric basis, Kocher and Bruns chose either a conservative therapeutic approach (in modern terms: a TSH suppressive therapy) or surgery to treat their goitre patients. We can only speculate today that the radical surgical approach was often necessary because of the presence, in many large goitres, of autonomously growing and autonomously hormone secreting nodules or clusters of follicles [12]. This indeed precludes any form of TSH suppressive therapy and even aggravates preexisting subclinical hyperthyroidism [3].

The thyroid gland was the centre of Kocher's interest up to the end of his life. In 1909, the Nobel Prize was bestowed on him as a reward for this work on the thyroid and its diseases. In Kocher's clinic and in his private practice, the impressive number of 7052 goitre excisions were performed, 5314 of which were done by Kocher himself. [13]. Still in 1913, the famous thyroidologist David Marine (1880-1976) spent several weeks in Bern discussing thyroid problems with Kocher. In 1917, a few weeks before his death, he gave a talk at the Annual Conference of Swiss Surgeons, addressing the difficult problem of the recurring endemic goitre after its presumable cure by surgical means. In this presentation, he mentioned the efficacy of prophylactic iodine application to school children, but he failed to mention the impending begin of goitre prophylaxis through iodination of table salt in Switzerland.

Kocher in Bern, William Halsted in Baltimore and Billroth's pupil Johann von Mikulicz (1850-1905) in Krakau, Königsberg and Breslau were, at the time, the leading representatives of a physiological surgery based on a biological background (Mikulicz coined the term "Innere Chirurgie” (internal surgery) [3,13].

Kocher himself and his work had a considerable impact on surgery all over the world. On the one hand, he was acquainted with a large number of distinguished surgeons within and outside Europe, he presided over many committees and scientific bodies and he travelled a great deal. On the other hand, his reputation was spread by his pupils, among them César Roux, Fritz de Quervain 1868-1940), Carl Garré (1857-1928). A considerable number of male and female students from Russia visited the "Kocher University" (once the Bernese government voiced concern about the "Slavic Girl School") [1]. Harvey Cushing (1869-1939) spent several months with Kocher and subsequently developed his neurosurgical techniques on grounds of Kocher's particular surgical techniques [9a, 11,13]. A large number of visitors, such as William Halsted, George Crile, Charles Mayo, René Leriche a.o., in addition to American surgeons with Swiss roots (Nicholas Senn, Henry Banga, Albert J. Ochsner, Martin Stamm a.o.) acknowledged Kocher’s influence on their work [9, 9a, 10]. One particular piece of acknowledgment came from northern Manchuria where a volcano was named after Theodor Kocher [1]. Not only did the Russian nobility send their sick relatives to Kocher, but even Lenin brought his wife Nadesha Konstantinowa Krupskaja (1669-1939) to Bern to be operated by Kocher [1]

Modern surgeons would attribute to the genius of Kocher two substantial and lasting progresses [3]: First, Kocher had a kind of "molecular vision" when he empirically felt that the growth of goitre nodules is an early determined event in development and that normal thyroid tissue rarely, if ever, is the source of a goitre recurrence. In this way, he conceived the concept of autonomously growing, focally distributed clusters of follicular cells and, following this idea, he advocated the total and selective removal of all thyroid nodules, if necessary by total thyroidectomy. All this was about 100 years before modern thyroidology, including molecular biology, basically confirmed these views [12]. Thus Kocher (and others [3]) had already realized that the so-called "subtotal" thyroidectomy, leaving behind naturally growth-prone tissue, would lead to goitre recurrence. He was also aware that most of these nodules could neither be prevented nor treated by any hormonal therapy, a fact that was definitely proven only in modern times. However, the high incidence of hypothyroidism following radical extirpation of a goitre, a sequela realized in 1883, caused considerable alarm and even a kind of shock that persisted for decades, long after Kocher, and until the second half of the 20th century. There is no doubt that the fear of hypothyroidism was out of proportion to the clinical significance of this condition, given the easy availability of thyroxine substitution. Nevertheless, this fear combined with the persistence of outdated surgical methods, prevented a correct, i.e. a selective surgery for a considerable time period. Second, Kocher’s new operative style, based on the precise identification of anatomical structures, permitted the radical surgical removal of all diseased tissue with minimal morbidity. It is only around 1980, after the so-called method of "subtotal" thyroidectomy had been overcome, that Kocher's technique of capsular dissection was rediscovered [3]. However, even today, not all thyroid surgeons are familiar with this technique. Kocher’s approach to goitre surgery is an example of how the surgical technique largely determines the quality and the outcome of an operative procedure [6]. Not unlike in other surgical domains, e.g. such as in surgery of the rectum, it is the surgeon’s technique of dissection which decides the appropriateness, the surgical morbidity and the oncological outcome of operations [3]. The surgeon himself may represent a largely undefined confounding prognostic variable.

Kocher was a very popular man, an excellent medical doctor and a teacher highly praised by his students and by his peers [1]. Some critics found fault with a certain sternness and aloofness, even a sense of mission, but all this went along with modesty and kindness. His way of thinking and his whole character were akin to that of Halsted [9a,10,13], while he was lacking the warm immediacy of Billroth [13]. Paul Clairmont (1875-1942), Swiss surgeon trained in Vienna and successor to Sauerbruch in Zurich, mentioned in his obituary to Kocher a "disparity of different characters" [2], a fact that may well have influenced differences in surgical technique.

Ernst Gemsenjäger<sup>1

1</sup>Ernst Gemsenjäger, Prof. emerit., Gellertstrasse 18, 4052 Basel, Switzerland. (gemsen@bluewin.ch)

Acknowledgment: The author greatly acknowledges the contribution of Prof. emerit. H. Studer to the English translation of the original manuscript.