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A History of Unethical Research: Syphilology
Rakesh Patalay, Kieron S Leslie, Nick J Levell
Dermanities September 27, 2005; 3(3)
A history of unethical research: Syphilology.
Introduction
Syphilis has been huge challenge for medical science throughout history. Medical research and treatments for syphilis of the past challenge the ethical standards of today.
The origins of syphilis are not known. Speculation of a New World origin has been supported by identification of classic lesions in Aztec, Mississippian and Inca bones from 1000 to 3000 years ago. The first recognized outbreak was in Naples in 1494, where the disease ravaged the army of Charles VIII of France. The name "syphilis" was first used by Fracastorii in 1530 from the name of a shepherd in a poem by Leonardo da Vinci. It was not until 1905 that the Treponema pallidum spirochete itself was isolated by Hoffmann & Schaudinn1 (Figure 1).
Early Research
In 1837, the Lancet published a series of lectures by William Wallace, an Irish physician at the Jervis Street Hospital, Dublin. In these lectures on skin and venereal diseases2 he described experiments aimed to prove secondary syphilis was contagious. He would create ‘a raw surface…which oozed blood’ on non-syphilitic patients that were admitted. This wound would be covered by ‘lint moistened with the discharge of diseased patches’ from inpatients with secondary syphilis. He would monitor these patients as they developed syphilitic lesions themselves. His only regret was that patients were treated with mercury too early and that he was not able to observe their constitutional symptoms more extensively. This type of research was by no means unique to Ireland. Similar work was conducted in 1859 by Dr Camille Gibert and Dr Joseph Alexandre Auziea-Turenne in Paris3.
Tuskegee
Arguably the most famous unethical research was the Tuskegee Syphilis Study between 1932-72 in Alabama, USA. It was conducted by the United States Public Health Service to study ‘untreated syphilis in the male Negro’ and enrolled over 400 African-American men with late stage syphilis. Over a 40 year period, patients were offered a number of tonics but were never treated with effective chemotherapy, even when penicillin became widely available in the late 1940’s. The medical uncertainly over how to treat late stage syphilis and the desire to retain the subjects perpetuated the deceit for many decades.
Mercury
Mercury is the earliest known chemotherapy for syphilis. As early as the late-fifteenth century, mercury was administered both topically and orally, and remained the treatment of choice for more than three centuries (Figure 2). Mercury is easily absorbed through the skin, respiratory and gastrointestinal tract. It caused such profuse salivation that patients were in danger of losing their teeth. It ulcerated the throat, palate and tongue, swelled the gums and loosened teeth. It is currently believed that the high therapeutic doses used probably neared lethal levels. High levels of exposure over long periods of time resulted in brain damage and ultimately death. It also posed major health risks to the unborn fetus.
Arsenic
In the early part of the 20th century Paul Ehrlich began to search for ‘the silver bullet’ against the syphilis spirochete (Figure 3). He was inspired by Breinl and Thomas’s success treating sleeping sickness with an organic arsenical. In 1907 he synthesized arsphenamine (later marketed as Salvarsan) with contained 32% arsenic4.
The treatment was lengthy and unpleasant. It was given by intravenous infusion and would be alternated with intramuscular mercury. Two month courses of intravenous arsphenamine would then be alternated with intramuscular Bismuth. The minimum duration of treatment would exceed 18 months and comprise about 60 injections5.
Silver arsphenamine was also used intravenously in children to treat congenital syphilis. Its dark brown color made it difficult to ensure the syringe was in a vein. When injected extravenously, it caused an acute tissue necrosis often followed by a generalised exfoliative dermatitis6. An effective treatment was not possible until dimercaprol was available (originally developed to treat arsenical blister gas in world war II). This too could be very toxic.
Neurosyphilis was treated by injecting a small amount of Silver arsphenamine into the cerebrospinal fluid. This was very painful and could cause severe spinal cord damage.
Fever Therapy
Julius Wagner, knight von Jauregg (1857-1940) an Austrian psychiatrist and neurologist invented fever therapy in 1917 (Figure 4). He induced malaria to treat patients who had central nervous involvement, having observed that patients with some nervous disorders improved after infections with fever. This method earned him the Nobel Prize in 1927.
By 1938, this method of inducing a fever was superseded by placing patients in a primitive microwave oven. This was only discontinued because it interfered with radar at the onset of the war9.
Conclusions
The Hippocratic Oath was conceived to give ethical guidance to the physicians of the future. Outlined above are examples when this principle was not followed, in the name of research. Although the treatments used in the past may seem barbaric by today’s standards, it should be remembered that many of these patients would have faced certain death without them. In 1949, in the wake of World War II and after further lapses in ethical research, the Nuremberg Code7 was written. Will this, together with the declaration of Human Rights, stop us from repeating the errors of our past?
References
1. Hoffman E, Schaudinn F. Vorlaufiger Bericht uber das vorkommen von sprochten in syphilitchen krank heits produkten und bei papillomen. Arbeit kalslichen gesundheitsamte 1905;22:520-34.
2. Wallace W. Clinical lectures and remarks. The Lancet 1836-7; ii:534-540.
3. Dracobly A. Ethics and experimentation on human subjects in mid-nineteenth-century France:the story of the 1859 syphilis experiments. Bull Hist Med. 2003 Summer;77(2):332-66.
4. Thorburn AL. Paul Ehrlich:pioneer of chemotherapy and cure by arsenic (1854-1915). Br J Vener Dis. 1983;59(6):404-5.
5. Marlow FW Jr. Syphilis then and now. JAMA 1974;230(9):1320-1.
6. Snedden IB. Then and now. Clin and Exp Dermatol 1984;9:3-17.
7. Tribunals of War Criminals before the Nuremberg Military Tribunals under Control Council Law No.10 Vol 2. Washington, DC. US Government Printing Office. 1949:181.
Images Courtesy of the National Library of Medicine, Welcome Library, The Nobel Foundation.
Figure 1. Illustration of T. pallidum from Schaudinn & Hoffmann’s paper on secondary syphilis in 1905.
Figure 2. Treatment for syphilis in a seventeenth century hospital. Amsterdam.
Figure 3. Paul Ehrlich (1854 – 1915) used Arsenic to cure syphilis.
Figure 4. Julius Wagner, knight von Jauregg (1857-1940) won the Nobel prize in 1927 for his work using malaria to treat syphilis.