Book Review

The Elusive Magic Bullet: The search for the perfect drug

N Engl J Med 1999; 341:1320-1321October 21, 1999

Article

The Elusive Magic Bullet: The search for the perfect drug
By John Mann. 209 pp. New York, Oxford University Press, 1999. $29.95. ISBN: 0-19-850093-9

On April 19, 1910, Paul Ehrlich announced the development of a specific cure for syphilis, a drug soon known worldwide as Salvarsan (arsphenamine). Salvarsan was not the “magic bullet” that Ehrlich predicted, since its assault on a pathogen was coupled with a deleterious effect on healthy tissues. But the development of Salvarsan established a precedent in the history of therapeutics: it was a drug scientifically designed to treat a disease caused by a specific organism. So it is little wonder that John Mann begins The Elusive Magic Bullet with the story of Salvarsan. Two decades passed, a period known as the doldrum years of chemotherapy, before Ehrlich's principles for the development of chemotherapeutic agents were put into successful systematic practice with the rise of the sulfa drugs. Therapeutic bullets (magic or otherwise) thereafter had a greater role in the medical armamentarium, as Mann relates in several interesting and well-told tales that cover selected advances against bacterial and viral diseases throughout the 20th century.

After a brief introductory chapter on Ehrlich's contributions, The Elusive Magic Bullet has a lengthy chapter on chemotherapy for bacterial diseases, another extensive chapter on the treatment of viral diseases, and finally a few pages on progress in chemotherapy generally over the past two decades. This book, which was written for a popular audience, has no footnotes; instead, some additional readings are offered for each chapter.

With some exceptions, the central two chapters are organized according to disease; Mann traces the background and impact of the disease, the emergence of a treatment, and its mode of action as we understand it today. Although his technical analysis of the mode of action at times might be lost on a general audience, and although some of these stories have been revisited as often as The Rocky Horror Picture Show, this organization works surprisingly well. His discussions of the “superbugs” and smallpox are especially good.

Mann has chosen good case studies, but some missing elements should be noted. For example, although the first chapter is properly devoted to Ehrlich, he certainly was not the first to attempt rational drug design. The attempts to establish connections between chemical structure and pharmacologic activity by James Blake, Benjamin Ward Richardson, Alexander Crum Brown, Thomas R. Fraser, and Thomas Lauder Brunton between the 1830s and the 1880s may not have been as successful as those of Ehrlich, but they certainly merit some consideration.

Little is said about the development of serum treatment and other biologicals created to combat bacterial diseases. To the extent that the topic is discussed, in the case of the announcement by Albert Calmette and Camille Guérin in 1924 of a vaccine for tuberculosis, we learn only that it was effective and has been distributed widely in developing countries. The disaster in Lübeck, Germany, that resulted in the deaths of 77 infants, which seriously damaged the reputation of bacille Calmette–Guérin, and the difficulty of using the tuberculin test once this vaccine has been administered are not mentioned. An important omission from the discussion of antibiotics is the fact that there have been no new classes of antibiotics introduced since the late 1950s.

Attention should also be paid to the author's confusion about the Elixir Sulfanilamide disaster, in which more than 100 people died from a poisonous ingredient in a medication; the source of the contamination of Alexander Fleming's culture plates, which Ronald Hare addressed convincingly several years ago; the relative impact of the Surgeon General's report of 1964 on the public awareness of the hazards of smoking; and the diagnostic value of prostate-specific antigen in screening. It was not Mann's intent to be comprehensive, so these little errors really do not detract from the value of the book overall. However, one sees surprisingly little discussion of what we — and perhaps researchers — can learn from these stories in terms of understanding and even advancing therapeutics. For example, was the cooperative penicillin program, involving hundreds of researchers from all estates of science on both sides of the Atlantic, crucial to what we learned about this important drug? If so, could this model be applied in any practical way today?

Most of the episodes covered in this book have been dealt with very capably before by Harry Dowling, M. Weatherall, and Walter Sneader, among others. However, The Elusive Magic Bullet provides some useful epidemiologic and pharmacologic context for these stories of drug discovery, in part because the way it is organized allows for a more in-depth treatment of each discovery. This, combined with Mann's readable literary style, should make the book a useful resource for its intended audience.

John P. Swann, Ph.D.
Food and Drug Administration, Rockville, MD 20857