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Journal Vol (46)4

Introduction

Serendipity in Research Involving Laboratory Animals

William C. Campbell

William C. Campbell, Ph.D., was Senior Director of Parasitology at Merck & Co., Inc., Rahway, New Jersey. He is a member of the Research Institute for Scientists Emeriti at Drew University, Madison, New Jersey, and holds adjunct faculty appointments at Drew University (Biology Department and Caspersen School of Graduate Studies) and New York Medical College. Dr. Campbell is also a member of the National Academy of Sciences.

Key Words: chance; laboratory animals; research strategy; science; serendipity

The word “serendipity” has become immensely popular and has acquired a certain appeal in the naming of boats and boutiques. More to the point, it is often bandied about as a fashionable alternative to “chance”—but it is not mere chance. Chance is fundamentally inimical to rationality, whereas serendipity presupposes a smart mind. There are few important discoveries that do not involve an element of chance; and it might even be said of science in general that the more rigid the research process, the more pedestrian the outcome. Chance (as Pasteurians forever remind us) favors the prepared mind. Productive scientists allow themselves to be guided by surprises, big and small, at every step. So what is so special about serendipity? The answer seems to lie in two factors: (1) a discovery that is not merely aided by chance, but arises from chance; and (2) an intellectual effort or intuitive leap that derives the discovery from the chance event.

For this issue of ILAR Journal, we have adopted a broad view, consistent with that of modern lexicographers. We define serendipity as the rational exploitation of chance observation, especially in the discovery of something useful or beneficial. To qualify as serendipity sensu stricto, the thing discovered should not have been something that the discoverer has sought; but in practice, the distinction between finding something sought and something unsought is difficult to maintain. Research is often goal directed, and the objective may be defined only in general terms. Thus a chance event may lead to success that has been sought in general, but not specific, terms. Important discoveries have been made in this way, and can be accepted as serendipity sensu latu.

Although much has been written about serendipity, its significance in laboratory animal research has not received a great deal of attention. This journal issue is not so much an attempt to redress the balance as an examination of whether the experience of serendipity in animal research can shed light on the research process and point to possible improvement. It will at once be pointed out that the idea of enhancing the quality or quantity of serendipitous discovery is intrinsically oxymoronic. Chance events cannot be planned; we take that as given. Yet no less an authority than Thomas Merton argued that special sociocultural microenvironments can foster scientific discovery, including discovery that is “fully serendipitous” (Merton and Barber 2004). He argued that it is not merely a matter of psychological predisposition but rather a matter of sociological arrangement, subject to human intervention. We are not concerned here with the details of this debate, but we have concluded that it would be timely, interesting, and potentially advantageous to ask a variety of scientists to reflect on the role of serendipity in research involving the use of animals. Their reflections are presented in the pages that follow.

The origin of the word serendipity is known quite precisely: it was coined in 1754 by the English literateur Horace Walpole, who introduced it in a letter to his friend Horace Mann. Walpole derived the new word from a set of fables about princes of Serendip (now Sri Lanka). The fables, of ancient and uncertain origin, had been published in English 32 years before, having been translated from a French version that had, in turn, been taken from an Italian work of 1557 titled Peregrinaggio di tre giovani figliuoli del re di serendippo. The connection between the tales and Walpole's definition was tenuous at best. (What the princes really excelled at was not discovery but the making of clever deductions on the basis of flimsy and fragmentary evidence. It was the sort of skill flaunted by the actual John Bell and the fictional Sherlock Holmes.) Nevertheless, Walpole was quite explicit as to what his new word should mean.

As originally coined, serendipity meant an ability to apply sagacity to chance observation and thereby find something other than what one was looking for. This meaning was soon extended to refer to the process as well as the aptitude; thus discoveries made in this fashion are considered examples of serendipity. Nowadays, discoveries, rather than persons, are likely to be described as “serendipitous.”

In early usage, the hallmark of serendipity was “sagacity,” but that word is now old-fashioned and tainted with pedantry. It was often coupled with “prudence,” which was then, I believe, akin to wisdom, and did not have the current overtones of caution and timidity. In the modern world, perhaps “wisdom” would convey the correct sense of acute mental discernment and sound judgment, but the adjectival “wise” hardly seems appropriate. Other terms used in modern times include “intelligence” (which smacks of mere brains) and “enlightened intelligence” (which seems pretentious in this context).

Inconvenient questions were soon raised by the second element of the original meaning viz. the requirement that the thing found had not been sought. It is hardly surprising that this aspect has generally been overlooked, but it has a bearing on the designation of specific discoveries as serendipity. An event that has frequently been cited as serendipitous is Goodyear's discovery of the vulcanization of rubber; but it has rightly been pointed out that it does not fully meet the requirements. Goodyear was looking for a way to make rubber both resilient and stable. Anything that even remotely suggested an avenue to success was seized upon and tested, so he did not ignore what happened when he accidentally dropped a sulfur-rubber combination onto the kitchen stove. Because of such incidents, Walpole's insistence on the unsought nature of the finding has been widely flouted, and the modern definition has been modified accordingly.

In this journal issue, no attempt is made to review the now copious literature on serendipity. Much information on the history and significance of serendipity can be found in works by Remer (1965), who provides an English version of the tales themselves, and Merton and Barber (2004). Halacy (1967) gives a “popular” account of serendipity, while more scholarly analyses of the role of chance are found in Beveridge (1957) and Taton (1957) and other works on the philosophy of science.

The authors in this issue of ILAR Journal have approached the subject of serendipity in different ways. Some authors are ruminative, and others are more cut-and-dried; but all of them provide food for thought as well as unusual glimpses of history. Michael Stoskopf (2005) found his colleagues mostly resistant to the notion that their discoveries might have been serendipitous—an unfortunate consequence of today's habit of equating serendipity with luck. To some extent, their reaction is understandable because scientists often accept the role of chance in their own discoveries but fear that others will exaggerate or misunderstand that role. One can sympathize with Sir Howard Florey's discomfort at a remark made while he was in Stockholm to accept the Nobel Prize for the role he had played (together with Chain and Fleming) in the discovery of penicillin as a therapeutic agent. The King of Sweden, upon meeting Florey, started off with “So! It was all an accident.” Suppressing his anger, Florey diplomatically remarked that His Majesty was not the only one to hold that view (Lax 2004). Such misunderstandings about the element of luck in scientific research must reinforce the sort of defensiveness encountered by Stoskopf. Fortunately, many scientists cheerfully acknowledge the helping hand of Lady Luck.

Although we are familiar with the concept of the “prepared mind,” Stoskopf (2005) reminds us that fruitful visual observation is facilitated by the prepared eye—which is, of course, connected to the prepared brain. When it comes to the discovery of spontaneous mutation in animals, as Muriel Davisson (2005) points out, investigator and technician alike—with eye and brain prepared—regularly make observations of great scientific and practical value. New phenotypes point to novel physiological as well as anatomical genotypes and thus often lead to new animal models of disease. Spontaneous as the mutations may be, there is nothing capricious about their detection under the circumstance she describes. If anyone doubts the truth of Merton and Barber's contention that certain cultural environments promote serendipity, Davisson's article may dispel that doubt. A wealth of practical guidance accompanies her general thesis that serendipity can flourish in suitably managed breeding colonies.

Morton and Swindler (2005) take a broad view of serendipity as seen from the perspective of research involving nonhuman primates. They stress the importance of serendipitous findings in research on nonhuman primates because of the likelihood that such findings will be applicable to humans. They also point to the role of animal husbandry staff in making observations that lead to important insights into such phenomena as periodicity in births occurring under laboratory conditions. Morton and Swindler further note that it is easy to find examples of serendipity but difficult to pin down its precise meaning. Having examined the question from a variety of angles, they are led to suspect that for a given discovery, serendipity lies in the eye of the beholder. This view meshes with that of Campbell (2005), who arrives at a variety of options for identifying serendipitous moments in the discovery of the antiparasitic drug ivermectin. Throughout history, he suggests, serendipity has been pervasive in drug discovery, and its role has not been limited to any particular class of drug or any one approach to the discovery process.

In contrast to Morton and Swindler's wide-ranging survey, the article of Jon Kass (2005) focuses on a single discovery. The discovery arose from a single observation on a single cat, yet opened up a new field of research, with ramifications in the areas of genetics, anatomy, and neurobiology. The unfolding of new knowledge, especially relating to vision in mammals, is described within the context of serendipity in animal research.

Quimby, Casey, and Arquette (2005) look at field studies as well as laboratory experiments, and cover a wide variety of animal species. From their studies in a Mohawk community near the St. Lawrence River, they report a different kind of serendipity. Instead of finding something there that they had not sought, they found that something they sought was not there! On several occasions they had collected frogs at a particular cove, but at a later date frogs were no longer seen at that site. This observation prompted an inquiry into the reason for such froglessness and led to important new information on contamination of the environment by toxic industrial wastes.

These very different essays have in common not only serendipity but serendipity in research involving animals. Examples of serendipity abound in these pages, but so do speculations, reflections, and suggestions. Taken together, they may prompt a deeper awareness of opportunities to enhance the probability of improbable events.

References

Beveridge WIB. 1957. The art of scientific investigation. New York: Norton.

Campbell WC. 2005. Serendipity and new drugs for infectious disease. ILAR J 46:352-356.

Davisson MT. 2005. Discovery genetics: Serendipity in basic research. ILAR J 46:338-345.

Halacy DS. 1967. Science and Serendipity. Philadelphia: Macrae Smith Co.

Kaas JH. 2005. Serendipity and the siamese cat: The discovery that genes for coat and eye pigment affect the brain. ILAR J 46:357-363.

Lax E. 2004. The Mold in Dr. Florey's Coat. Henry Holt & Co., New York.

Morton WR, Swindler K. 2005. Serendipitous insights involving nonhuman primates. ILAR J 46:346-351.

Merton RK, Barber E. 2004. The Travels and Adventures of Serendipity. Princeton: Princeton University Press.

Quimby FW, Casey AC, Arquette M. 2005. From dogs to frogs: How pets, laboratory animals, and wildlife aided in elucidating harmful effects arising from a hazardous dumpsite. ILAR J 46:364-369.

Remer TG, ed. 1965. Serendipity and the Three Princes. Norman: University of Oklahoma Press.

Stoskopf MK. 2005. Observation and cogitation: How serendipity provides the building blocks of scientific discovery. ILAR J 46:332-337.

Taton R. 1957. Reason and Chance in Scientific Discovery. New York: Philosophical Library.