Happy Accidents: Serendipity in Major Medical Breakthroughs in the Twentieth Century (2 page)

Introduction

Serendipity, Science's Well-Guarded Secret

I exist But only in you if you want me… All things are meaningless accidents, works of chance unless your marveling gaze, as it probes, connects and orders, makes them divine…

—W
ILHELM
W
ILLMS
, “G
OD
S
PEAKS
”
¹

Contemplating the genesis of the great medical breakthroughs of the last century, most people picture brilliant, well-trained scientists diligently pursuing a predetermined goal—laboriously experimenting with first this substance and then that substance, progressing step by step to a “Eureka!” moment when the sought-after cure is at last found. There in the mind's eye is Marie Curie stirring a vat of pitch-blende over many years to recover minute amounts of radium, or Paul Ehrlich testing one arsenical compound after another until he finds Salvarsan, the “magic bullet” against syphilis, on his 606th attempt. In the contemporary setting, one looks to what might be called Big Science. Surely, we imagine, in the halls of ivy-draped universities and the gleaming labs of giant pharmaceutical companies, teams of researchers in smart white coats are working in harmony to cure cancer,
banish the common cold, or otherwise produce the Next Big Thing in medicine.

For its own reasons, the medical establishment is happy to perpetuate these largely false images. By tradition and protocol, it presents science as a set of facts and strong beliefs that, like the Ten Commandments, have been set in stone by a distant all-knowing authority and, if followed, will lead inevitably through a linear process to the desired results. Furthermore, it portrays the history of scientific advances as a sequence of events that have led to more-or-less direct progress.

The reality is different. Progress has resulted only after many false starts and despite widespread misconceptions held over long periods of time. A large number of significant discoveries in medicine arose, and entirely new domains of knowledge and practice were opened up, not as a result of painstaking experimentation but rather from chance and even outright error. This is true for many of the common drugs and procedures that we rely on today, notably many antibiotics, anesthetics, chemotherapy drugs, anticoagulant drugs, and antidepressants.

Consider the following examples, all typical of how things happen in medical research:

• At the Johns Hopkins Hospital in 1947, two allergists gave a new antihistamine, Dramamine, to a patient suffering from hives. Some weeks later, she was pleased to report to her doctors that the car sickness she had suffered from all her life had disappeared. Drs. Leslie Gay and Paul Carliner tested the drug on other patients who suffered from travel sickness, and all were completely freed of discomfort, provided the drug was taken just before beginning the potentially nauseating journey. A large-scale clinical trial involving a troopship with more than 1,300 soldiers crossing the rough North Atlantic for twelve days (Operation Seasickness) decidedly proved the drug's value in preventing and relieving motion sickness. Dramamine is still used today, available over the counter.
²

• A professor of biological chemistry and medicine at the Johns Hopkins University School of Medicine was studying a particular blood protein when he found another protein contaminating his sample. Rather than simply discarding it, Dr. Peter Agre realized that he had stumbled upon the structure of the channel—folded-up proteins piercing cell walls—that can control the flow of water molecules into and out of living cells. For making this basic discovery, which, he said, “really fell into our laps,” he won the Nobel Prize in Chemistry in 2003.
³

• A similar circumstance proved very beneficial to the neurobiologist David Anderson of the California Institute of Technology, who publicly announced his serendipitous breakthrough in the
New York Times
in July 2001. Researching neural stem cells, the cells that build the nervous system in the developing embryo, Anderson discovered the “magic fertilizer” that allowed some of them to bloom into neurons, sprouting axons and dendrites: “It was a very boring compound that we used to coat the plastic bottom of the Petri dish in order to afford the cells a stickier platform to which to attach. Never would we have predicted that such a prosaic change could exert such a powerful effect. Yet it turned out to be the key that unlocked the hidden neuronal potential of these stem cells.”
⁴

• An unanticipated variable seriously hampered the efforts of biochemist Edward Kendall to isolate the thyroid hormone thyroxine, which partly controls the rate of the body's metabolism. After four years of meticulous work on the gland, he finally extracted crystals of the thyroid hormone on Christmas morning 1914 at the Mayo Foundation in Rochester,
Minnesota. But when he moved to expand production, Kendall could no longer recover active material. Only after fourteen months of futile efforts was he able to trace the cause of this setback to the decomposition of the hormone by the use of large galvanized metal tanks in which the extraction from the gland was being done. The iron and copper in the metal tanks rendered the crystals ineffective. From then on, he used enamel vessels. By 1917, Kendall had collected about seven grams of crystals and was able to start clinical studies.
⁵

T
HE
N
ORMAL VERSUS THE
R
EVOLUTIONARY

In his highly influential 1962 book
The Structure of Scientific Revolutions,
Thomas Kuhn contributed an idea that changed how we see the history of science.
⁶
Kuhn makes a distinction between “normal” and “revolutionary” science. In “normal” science, investigators work within current paradigms and apply accumulated knowledge to clearly defined problems. Guided by conventional wisdom, they tackle problems within the boundaries of the established framework of beliefs and approaches. They attempt to fit things into a pattern. This approach occupies virtually all working researchers. Such efforts, according to Nobel laureate Howard Florey, “add small points to what will eventually become a splendid picture much in the same way that the Pointillistes built up their extremely beautiful canvasses.”
⁷

Kuhn portrays such scientists as intolerant of dissenters and preoccupied with what he dismissively refers to as puzzle-solving. Nonetheless, a period of normal science is an essential phase of scientific progress. However, it is “revolutionary” science that brings creative leaps. Minds break with the conventional to see the world anew. How is this accomplished? The surprising answer may be “blindly”! Systematic research and happenstance are not mutually exclusive; rather they complement each other. Each leads nowhere without the other.

According to this view, chance is to scientific discovery as blind genetic mutation and natural selection are to biological evolution. The
appearance of a variation is due not to some insight or foresight but rather to happenstance. In groping blindly for the “truth,” scientists sometimes accidentally stumble upon an understanding that is ultimately selected to survive in preference to an older, poorer one.

As explained by Israeli philosophers of science Aharon Kantorovich and Yuval Ne'eman, “Blind discovery is a necessary condition for the scientific revolution; since the scientist is in general ‘imprisoned’ within the prevailing paradigm or world picture, he would not intentionally try to go beyond the boundaries of what is considered true or plausible. And even if he is aware of the limitations of the scientific world picture and desires to transcend it, he does not have a clue how to do it.”
⁸

© The New Yorker Collection 2005 Leo Cullum from
cartoonbank.com
. All Rights Reserved.

An anecdote about Max Planck, the Nobel Prize–winning physicist, hammers home this reality. When a graduate student approached him for a topic of research for his Ph.D. thesis, asking him for a problem
he could solve, Planck reportedly scoffed: “If there was a problem I knew could be solved, I would solve it myself!”

Induction and deduction only extend
existing
knowledge. A radically new conceptual system cannot be constructed by deduction. Rational thought can be applied only to what is known. All new ideas are generated with an irrational element in that there is no way to predict them. As Robert Root-Bernstein, physiology professor and author of
Discovering,
observed, “We invent by intention; we discover by surprise.”
⁹
In other words, accidents will happen, and it's a blessing for us that they do.

T
HE
R
ECEPTIVE
S
CIENTIFIC
M
IND

“Accident” is not really the best word to describe such fortuitous discoveries. Accident implies mindlessness. Christopher Columbus's discovery of the American continent was pure accident—he was looking for something else (the Orient) and stumbled upon this, and never knew, not even on his dying day, that he had discovered a new continent. A better name for the phenomenon we will be looking at in the pages to follow is “serendipity,” a word that came into the English language in 1754 by way of the writer Horace Walpole. The key point of the phenomenon of serendipity is illustrated in Walpole's telling of an ancient Persian fairy tale,
The Three Princes of Serendip
(set in the land of Serendip, now known as Sri Lanka): “As their highnesses traveled, they were always making discoveries,
by accidents and sagacity,
of things they were not in quest of.”
¹⁰

Accidents
and
sagacity. Sagacity—defined as penetrating intelligence, keen perception, and sound judgment—is essential to serendipity. The men and women who seized on lucky accidents that happened to them were anything but mindless. In fact, their minds typically had special qualities that enabled them to break out of established paradigms, imagine new possibilities, and see that they had found a solution, often to some problem other than the one they were working on. Accidental discoveries would be nothing without keen, creative minds knowing what to do with them.

The term “serendipity” reached modern science by way of physiologist
Walter B. Cannon, who introduced it to Americans in his 1945 book
The Way of an Investigator.
¹¹
Cannon thought the ability to seize on serendipity was the mark of a major scientist. The word is now loosely applied in the popular media to cover such circumstances as luck, coincidence, or a fortunate turn of events. This sadly distorts it. Serendipity means the attainment or discovery of something valuable that was not sought, the unexpected observation seized upon and turned to advantage by the prepared mind. The key factor of sagacity has been lost. Chance alone does not bring about discoveries. Chance with judgment can.

Serendipity implies chance only insofar as Louis Pasteur's famous dictum indicates: “In the field of observation, chance favors only the prepared mind.” Salvador Luria, a Nobel laureate in medicine, deemed it “the chance observation falling on the receptive eye.”
I have the answer. What is the question?
Turning an observation inside out, seeking the problem that fits the answer, is the essence of creative discovery. Such circumstances lead the astute investigator to solutions in search of problems and beyond established points of view.

The heroes of the stories told in this book are not scientists who merely plodded rationally from point A to point B, but rather those who came upon X in the course of looking for Y, and saw its potential usefulness, in some cases to a field other than their own. Chance is but one element, perhaps the catalyst for creativity in scientific research. And, yes, the process of discovery is indeed creative. It involves unconscious factors, intuition, the ability to recognize an important anomaly or to draw analogies that are not obvious. A creative mind is open and can go beyond linear reasoning to think outside the box, look beyond conventional wisdom, and seize on the unexpected. Most important, a creative scientific mind recognizes when it is time to start viewing something from a whole new perspective.

T
URNING
R
EALITY ON
I
TS
S
IDE

One day in 1910, the Russian painter Wassily Kandinsky returned to his studio at dusk and was confronted with an object of dazzling beauty on his easel. In the half-light, he could make out no subject but
was profoundly moved by the shapes and colors in the picture. It was only then that he realized the painting was resting on its side. Like an epiphany, this experience confirmed his growing belief in the emotional powers of colors and in the ultimate redundancy of the traditional subject of a picture. Kandinsky, who broke through to what he called “nonobjective” painting, is widely acknowledged as the father of abstract art.