Book Review

Happy Accidents: Serendipity in Modern Medical Breakthroughs

N Engl J Med 2007; 356:2658-2659June 21, 2007

Article

Happy Accidents: Serendipity in Modern Medical Breakthroughs
By Morton A. Meyers. 390 pp., illustrated. New York, Arcade Publishing, 2007. $29.95. ISBN: 978-1-55970-819-7

According to the Oxford English Dictionary, the word “serendipity” was coined by Horace Walpole in a letter to his friend Sir Horace Mann in January 1754. He explained that he had based it on a fairy tale, The Three Princes of Serendip (a former name for Sri Lanka), whose protaganists “were always making discoveries, by accidents and sagacity,” of things they were not looking for. In this well-researched and well-documented book, Morton Meyers details many examples of serendipity in medical advances. He divides the subject into four parts: antibiotics, anticancer drugs, cardiovascular medicine, and psychotherapeutic drugs. The various essays include not only well-known examples of chance observations that led to important developments, but also many examples that are not as well known.

Alexander Fleming's chance observation of the lysis of a culture of staphylococci by contaminating penicillin, which led to the development of antibiotics, is familiar. But perhaps less well known is the interesting example of John Cade's studies of the effects of injecting uric acid and other components of urine, which were considered to be possibly toxic, into guinea pigs. In one experiment, he used lithium urate, and astonishingly, the injected guinea pigs became relaxed and placid. Cade conjectured that lithium salts might therefore be beneficial in the treatment of mania in humans, a theory that proved to be correct. More recently, sildenafil, which was being considered for the treatment of angina, failed to boost cardiac blood flow but unexpectedly increased blood flow to the penis. This discovery led to the development of Viagra and its use as a treatment for erectile dysfunction. Particularly valuable and interesting was the chance finding of Helicobacter pylori as a cause of peptic ulcers and stomach cancer.

Meyers discusses many other fascinating examples in detail, but the introduction and conclusion hold the key to the work. In the introduction, he discusses the nature of serendipity in discovery and emphasizes that more than chance is involved. As Louis Pasteur once stated, “chance favors only the prepared mind.” The investigator must recognize the singular importance of a chance observation. Intuition also plays a large part, and as Peter Medawar emphasized, a true discovery is unpredictable and essentially a creative act.

In the conclusion, Meyers explains how our knowledge of past serendipitous discoveries can inform current medical research. He argues that with peer review committees so often enmeshed in conventional and accepted wisdom, truly original or maverick ideas may not attract support. Furthermore, Meyers cites many examples of reports of groundbreaking studies that have been rejected by prestigious journals. He reserves his most trenchant criticism for certain drug companies that now seem less concerned with creating new drugs than with marketing. Meyers emphasizes the need for medical education to foster serendipity, arguing that “mainstream medical research stubbornly continues to assume that new drugs and other advances will follow exclusively from a predetermined research path.” Some will, of course. For example, the first use of positional cloning to identify the gene causing a single-gene disorder (Duchenne's muscular dystrophy) was the result of much painstaking and directed research. Serendipity should therefore not be overemphasized, but neither should it be ignored. It is possible that current research, through advances in molecular genetics and related studies, may lead to effective treatments for diseases such as Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis. But it is also quite possible that answers may come through chance observations made by investigators working outside the mainstream. As Alexander Fleming himself said in a lecture at Harvard, “The clue provided by fate [may] lead you to some important advance.” And Terence, the 2nd-century B.C. Roman dramatist, said, “You must by skill make good what has fallen by chance.” This very readable and well-researched book provides much food for thought.

Alan Emery, M.D., Ph.D., D.Sc.
Green College, University of Oxford, Oxford OX2 6HG, United Kingdom
alan.emery@green.ox.ac.uk