History of Medicine

ALBERT NEISSER AND HUMAN EXPERIMENTATION

     Medical experimentation on humans has a long and sometimes depressing history, brought into high relief by experiences in Germany and Japan during WWII. After the war numerous papers, declarations, and laws emerged, coalescing into a more definitive approach to human experimentation. Long before the war, though, the case of Albert Neisser aroused great interest in Germany and gave birth to what is thought to be the first governmental guidelines for human experimentation.

     Albert Neisser was born in 1855 in a small Silesian town to a physician father. He studied medicine at the pretigious Breslau University Medical School (where Robert Koch had given his demonstration of the cause of anthrax in 1876, probably while Neisser was there). After obtaining his MD degree he joined the Breslau University Dermatology Clinic. 

Albert Neisser (National Library of Medicine)

     Dermatology, in those days, dealt with venereal diseases, including gonorrhea. Bacteriology, the new, popular science, induced Neisser to seek a bacterial cause for gonorrhea. He had learned microbiology at Breslau and was familiar with Abbe’s condenser and oil immersion techniques, new in the 1870s, that improved the resolution of microscopic images. At the age of 24, using the latest microscopic equipment, he discovered, in urethral discharges, the paired cocci that bear his name (Neisseria gonorrhea), and cultured them shortly afterward – an important discovery.

     After a trip to Norway to work with Armauer Hansen on leprosy, that ended in a priority dispute, Neisser returned to Germany and rose to head the Breslau dermatology clinic after his chief died. Neisser was impressed with the recent demonstrations by Behring and Kitasato of the healing effects of antiserum in cases of diphtheria. He wondered if serum from people with syphilis, made cell-free for purity, could provide similar “passive immunization” against the disease. First he injected subcutaneously serum from a patient with early syphilis into four female patients, aged 10 to 24. None developed syphilis. Next, using cell-free serum from patients with syphilis in various stages, he injected up to 30cc intravenously into four prostitutes, aged 17 to 20. They all developed syphilis. None had given informed consent.

     News of the experiments reached the press, creating an uproar. Neisser wrote a statement defending his work, suggesting also that that the latter four women contracted syphilis because they were prostitutes and not because of his serum injections. Similar experiments were done by other physicians, and he was supported by the majority of his colleagues though one, the psychiatrist Albert Moll, who was writing a book on physicians’ ethics, spoke out against him. Neisser was fined by the Royal Disciplinary Court - because he had not obtained the patients’ consent, not because of questionable science.

     The Prussian Parliament took up the case and sought an opinion from the Scientific Medical Office of Health. Rudolf Virchow, Emil von Behring, and other prominent physicians were on the panel. Lawyers were also consulted. In 1900 the Minister for Religious, Educational, and Medical affairs issued a directive. All medical interventions other than for diagnosis or treatment were prohibited if the subject was a minor or not competent, or if consent was not obtained after proper explanation of possible negative consequences. All research interventions had to be authorized by the medical director of the institution and all details had to be documented in the medical record. The directive was not legally binding.

     Evidently similar cases subsequently came to light and in 1931, in the context of an overall reform of criminal law in Germany, the national government issued “guidelines for new therapy and human experimentation”. These guidelines distinguished between experimental new treatments and experiments intended to extend knowledge but without therapeutic benefit. In both cases minors and incompetents were excluded, and consent from a properly informed and autonomous subject was required for any experiment. The only exception was if a new treatment were desired in urgent cases and immediate consent was impossible. Experimentation on dying patients was prohibited and animal experimentation should precede that on humans. Exploitation of financial or social needs was prohibited. The physician’s special responsibilities in clinical trials should be emphasized in medical teaching. A form of institutional review board was discussed but the review and oversight function was left with the medical director. The complete guidelines (translated) are found at: file://localhost/Users/john/Documents/ history of medicine & science/ethics,GERMAN GUIDELINES ON HUMAN EXPERIMENTATION 1931.webarchive. They are believed to be the first such guidelines issued by a government. They were not annulled during the Nazi era but were certainly ignored. 

Fritz Schaudinn, co-discoverer with E. Hoffmann
of Treponema Pallidum
(National Library of Medicine)

     Neisser turned to monkeys for further syphilis research and moved to Java where monkeys were abundant. He clarified several aspects of syphilis, including showing 

Erich Hoffmann, co-discoverer of Treponema
Pallidum (Wellcome Library)

inability to arrest the disease by removal of the primary chancre (a common belief at the time), or to immunize monkeys. He published a book summarizing the work. While he was in Java the causative Treponema pallidum was discovered and on his return he and his assistants worked with August Wasserman to develop the Wasserman test (1906). 

August Wassermann (Wikipedia)

     Neisser took an increasing interest in public health aspects of venereal disease, advocating public health clinics and regulation of prostitution, all at a time when these subjects were seldom discussed in public. He died in 1931 from complications after surgery for bladder stone.

      Neisser’s career encompassed much of modern knowledge of syphilis. His one irresponsible experiment brought the issue of human experimentation into the German public arena, where the first governmental guidelines for human experimentation were formulated, well before similar rules existed in the United States.

 SOURCES:

Vollmann, J and Winau, R. “Informed Consent in Human Experimentation before the Nuremberg Code” 1996: BMJ 313: 1445-7

Oriel, J. “Eminent Venereologists, 1. Albert Neisser” 1989; Genitourin Med 65: 229-234.

Ligon, B L. “Albert Ludwig Sigesmund Neisser: Discoverer of the Cause

of Gonorrhea” 2005; Semin Pediatr Infect Dis 16: 336-41.

 Benedek, T G. “Case Neisser: Experimental Design, the Beginnings of Immunology, and Informed Consent” 2014; Perspect Biol Med 57(2): 249-67.