The Cholera Hero's Therapeutic Vaccine for Tuberculosis Killed Patients and Almost Destroyed His Reputation

Robert Koch was the most prominent German medical scientist of the 1880s. His 1882 identification of Mycobacterium tuberculosis and his 1883 identification of Vibrio cholerae had effectively established the bacteriological framework of late-19th-century European medicine. He had been awarded a chair at the University of Berlin in 1885 and a personal institute (the Institute of Hygiene, modelled on Pasteur’s Paris institute) in 1891. By the time he stood up at the International Medical Congress in Berlin on 4 August 1890 to announce that he had developed a treatment for tuberculosis, he was substantively the dominant figure in continental European bacteriology.

The treatment did not work. Several hundred patients died of it. The fiasco came close to substantively destroying Koch’s institutional position.

What he announced

Koch’s August 1890 Berlin announcement described a substance — initially called only ‘Koch’s lymph’, later renamed tuberculin — that he claimed produced a substantively curative response in tuberculosis patients. He provided no details on what the substance actually was: he stated only that it was the substantively concentrated product of an extraction process from cultured tuberculosis bacteria, that it produced a substantively diagnostic reaction in infected patients (a substantial localised inflammation at the injection site combined with a substantial systemic fever), and that the substantively repeated administration of the substance over a course of weeks produced a substantively curative effect on the underlying tuberculosis infection.

The substantively secrecy was unusual by German academic standards. Koch’s substantive justification was that he wanted to maintain the commercial-licensing position for the substantive clinical introduction of the treatment — a substantive deviation from the Pastorian model of substantively transparent scientific announcement and public-domain therapeutic distribution. The deviation was widely commented on at the substantive Congress and afterwards.

The clinical disaster

The substantive clinical trials began at Berlin’s Charité Hospital and at provincial clinics in October 1890. The initial reports were substantively positive: patients receiving the tuberculin appeared to show localised inflammation at lesion sites (which was substantively interpreted as the immune system substantively attacking the bacteria) followed by fever (which was substantively interpreted as a substantive systemic clearance reaction). The European medical press substantively celebrated the announcement through November and December 1890.

The substantively negative results substantively accumulated through January and February 1891. The localised inflammation was substantively not associated with subsequent clinical improvement. The systemic fever was substantively associated with accelerated patient deterioration in advanced tuberculosis cases. The autopsies of treated patients who had died showed that the tuberculin reaction had substantively disrupted the protective fibrous-capsule walls that normal tuberculosis patients form around bacterial lesions — substantively the body’s natural containment of the infection — and that the systemic spread of tuberculosis from these disrupted lesions was substantively the proximate cause of patient deaths.

The mortality estimates for the 1890–1891 tuberculin trials varied. The most substantively conservative figures ran at substantively about 50 direct tuberculin-attributable deaths; the substantively most estimates ran at several hundred. The Berlin clinical register recorded 21 tuberculin-attributable deaths at the Charité Hospital alone between October 1890 and March 1891.

What tuberculin actually was

Koch released the formula in January 1891 under professional pressure. The substance was a concentrated glycerol extract of heat-killed tuberculosis bacterial cultures — no active therapeutic principle, nothing that could have produced bacterial killing in vivo. The systemic reaction patients experienced was an immune-system response to the injected bacterial proteins, not a therapeutic effect on the underlying infection.

The fiasco produced an immediate and intense round of professional criticism. Rudolf Virchow — the dean of German pathology, who had long been sceptical of Koch’s bacteriological framework — published a detailed pathological report in January 1891 demonstrating that the post-mortem findings in tuberculin-treated patients showed accelerated bacterial spread rather than therapeutic clearance. The criticism was professionally devastating because Virchow was personally and institutionally the heavyweight German medical authority of the period.

The afterlife

Koch survived the fiasco institutionally. The Berlin Institute of Hygiene opened in 1891 on schedule; Koch held its directorship until 1904; his Egyptian and Indian cholera-research expeditions of 1883–1884 had given him an institutional position that could absorb a major therapeutic failure without permanent damage. He retreated from clinical-therapeutic work and returned to pure bacteriology and to tropical-disease field research in the late 1890s and 1900s. He received the Nobel Prize for Physiology or Medicine in 1905 for the tuberculosis bacterium identification of 1882, not for tuberculin.

Tuberculin itself was not entirely useless. The diagnostic skin reaction Koch had identified — a localised inflammation at the injection site in patients with active or latent tuberculosis — turned out to be a reliable diagnostic test for tuberculosis infection. The Pirquet skin test (1907) and the Mantoux test (1908) are direct refinements of Koch’s tuberculin reaction and remain in routine clinical use for tuberculosis screening worldwide today.

But as a cure for tuberculosis, the 1890 Koch tuberculin was a failure. Effective tuberculosis chemotherapy would not arrive for another half-century — streptomycin in 1944, isoniazid in 1952, rifampin in 1957 — by which point Koch had been dead for forty-six years.