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In Their Own Words: NIH Researchers Recall the Early Years of AIDS
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There was one other consequence of the meeting in Vienna (1983). In the talk I gave there, I spoke about the importance of the natural history of infectious diseases. This is a subject that is oftentimes overlooked today. The natural history of a disease is concerned with all aspects of its manifestations, from beginning to end, and the circumstances surrounding its occurrence. Natural history requires the skills of the clinician, the scientist, the epidemiologist.

I recognize that we would need to study many patients for a long time, from beginning to end, if we were to learn about the full complexity of AIDS, the variation in the course of the disease from one patient to the next, etc. In the 1920s and the 1930s, Drs. T. Duckett Jones and Edward F. Bland did the landmark study on the natural history of rheumatic fever and rheumatic heart disease. This disease can have many different permutations and combinations during its course. In some instances, the disease can progress very rapidly, in others, it progresses very slowly. Many patients live a normal life with heart disease, and in others there is a rapid decline. I knew that we would have to do something similar to the work of Jones and Bland for the study of the natural history of AIDS.

So we organized the Multicenter AIDS Cohort Study (MACS). This was a program in which grants were awarded to four or five clinical centers in the United States. It was their job to follow the natural history for as long as it would take to learn about the manifestations of the disease from beginning to end. One important aspect that has emerged from this study is that there are those individuals who seem to do quite well during the course of their infection. In fact, some do remarkably well, and therefore an important area of investigation concerns the reasons some people, although infected with the virus, do not come down with AIDS for a long period of time. What are the immune mechanisms in such people that result in a long delay in the occurrence of AIDS? Much has been learned from the Multicenter AIDS Cohort Study, and you should get more information about it from those in NIAID that are responsible for it. I think the MACS was probably one of the most important contributions that I made to the AIDS epidemic in addition to the initiative that led to Projet SIDA in Zaire. After all, had I not done that, perhaps Jonathan Mann would not now be famous.

Harden: Before we stop, is there anything else you would like to say?

Krause: Yes, one thing that I think is important is to draw a parallel with syphilis. [William] McNeill gave a very important commentary on this, in his book Plagues and People. He emphasized that syphilis had little demographic effect because those who died of it would have died anyway from something else. This is not true in the case of AIDS. McNeill traced the influence of syphilis in the context of the emergence of Puritan tradition in the seventeenth century, 100 years after syphilis got going. When syphilis finally settled in, it became a disease of those at the top, the nobility, and those at the bottom. Neither group was “contaminated” by Puritanism. As a result, syphilis was a devastating disease for the lower orders and it also decimated the ruling houses of Europe. The Puritan middle classes prospered. McNeill concludes that the rise of Puritanism grew out of the efforts by the bourgeoisie and the middle class to protect themselves.

I have written recently, and I will send you a copy, about the history of syphilis in this century. From 1900 to 1910, there was a decade of discovery that transformed our understanding of syphilis from ignorance to “magic bullets.” The decade started in 1900, after almost thirty years of research. Although many people had tried, no one had been able to discover the cause of syphilis. It was assumed that the cause was an infectious agent, but there was no treatment. In 1903 the organism was found. Before the organism was found, an animal model became available. The infection could be maintained in the cornea of the eye of the rabbit and in the testicles of the rabbit. You can transfer the organism from the testicle of one rabbit to that of another rabbit. [Dr. Paul] Ehrlich began his research looking for an arsenical “magic bullet," and the Wassermann test was developed. The Georg Speyer Haus was formed in Frankfurt, and a Japanese chemist joined Ehrlich. If you read Ehrlich's notebooks, he started with compound 306 and ended up with compound 606. He did 300 experiments–most of them failures–and then, of course, with the success of 606, he developed Salvarsan (arsphenamine) as a treatment. The drug cured the experimental infection in the rabbit. In humans with syphilis this drug for the first time caused a reversal of the Wassermann reaction. With treatment, the patient's blood test would go from positive to negative, and this had never been seen before. Prior to the treatment, once you were positive you remained positive.

At first, it was hard to get a pharmaceutical firm to manufacture arsphenamine, but then they could not make enough. There was criticism, terrible criticism, that they were making too much money, that the drug cost too much, and that Ehrlich was profiting from it. He never did profit from it. Some money went to the research at the Speyer Haus in Frankfurt, but he himself did not profit. There was a social reaction, a prediction that with an effective treatment people would become more licentious. In a sense, the story of syphilis provides a parallel for the story of AIDS.

Harden: Thank you, Dr. Krause.

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