Chase, Chance, and Creativity

by James H Austin

  We have now seen Sir Alexander Fleming's modest comment about his Irish Sweepstakes luck under Chance I, and can infer that Chance II entered his life not only because he had ventured a long way from the hills of Ayrshire, and was sufficiently energetic to be a polo-playing swimmer, but also because he continued to be an experimentalist who followed diverse interests in his laboratory. These years, of course, involved generalized motions, common to most of us whose activities have been far less fruitful. We later observed how receptive he was (Chance III), having noted why a sensitizing event nine years earlier had already left his mind so well prepared, and saw finally how his hobby of swimming drew him to one particular London hospital. Here, one wayward mold spore might just happen to intersect a life style leaning toward frugal, if not invariably tidy, habits (Chance IV). Anyone who has ever recovered from a severe infection with the aid of penicillin (or from pneumonia with a sulfa drug) will realize how major was the impact of Fleming's discovery. This was not only the "magic bullet" against syphilis that Ehrlich moved toward all his life, but also a treatment for the streptococcal infection that Semmelweiss had shown was so contagious. Fleming's discovery earned him the Nobel Prize in physiology and medicine in 1945. (He shared it with Florey and Chain, who achieved the large-scale production of penicillin.) In Fleming's life, then, we see a fusion of all four forms of chance, and from this there follows a simple conclusion: the most novel, if not the greatest discoveries occur when several varieties of chance coincide. Let us call this unifying observation the Fleming tffect. His own life exemplifies it so well, and it deserves special emphasis.

  A personal element of Chance IV also entered into Paul Ehrlich's discovery. When he was only eight, he already had enough motivation toward medical chemistry to persuade the town pharmacist to make cough drops for him after his own prescription. Even as a child, Ehrlich had this passionate hobby to find a treatment for something. But when he started out as a child, he really didn't know what he was looking for. What he would find would be decided to some degree by the luck of the draw-by what drugs a chemist could synthesize for him. For what influenced his discoveries beyond that point, we ourselves must explore the personality of Ehrlich, the man, and the modest expectations of the age in which he lived. Ehrlich stands out among his contemporaries because he was a very special man in the grip of a special private obsession: the idea that dyes which stained microorganisms would selectively kill them. Other researchers in those early days would try out dozens of compounds in many different experiments, and even in our own day, some still do for other goals on an even more sweeping scale. But the rest of us would stop at a hundred trials, and a few investigators might go on to test two or three hundred, and then give up. How many would be compulsive enough to try out hundreds more-and then insist that his associate, Hata, go back all over again to retest an apparent failure? The astonishing thing is that a laboratory error, which obliterated the beneficial effects of the drug, had occurred without Ehrlich's knowledge when "606" was first tested two years earlier. How many would later have retested compound 606, working beyond all rational hope that something useful might turn up? It is in this sense that some elements of Ehrlich's discovery seem to move beyond the ordinary limits of the curiosity and exploration in Chance II and enter the personal domain of Chance IV as well.

  Why do we still remember these men? We cherish them, not as prize-winning scientists alone. There is more to it than that. The fact is that, as men, their total contribution transcends their scientific discoveries. Perhaps we remember them, too, because their lives show us how malleable our own futures are. In their work we perceive how many loopholes fate has left us-how much of destiny is still in our own hands. In them, we see that nothing is predetermined. Chance can be on our side, if we but stir it up with our energies, stay receptive to its every random opportunity, and continually provoke it by individuality in our hobbies, attitudes, and our approach to life.

  20

  Never on Monday; The Unhappy Accidents

  A fisherman must be of contemplative mind, for it is often a long time between bites. He is by nature an optimist or he would not go fishing; for we are always going to have better luck in a few minutes or tomorrow.

  Herbert Hoover

  Up to now, I have emphasized the beneficial aspects of chance. But research is defeated as well as helped by circumstances. Chance is not always a welcome guest, either in the laboratory or anywhere else. "Fisherman's luck" rarely happens. And whimsy is also part of the picture. The purpose of this chapter is to redress the balance.

  The snags and backlashes of bad luck are everywhere. It is a hard fact that in laboratory research unpredictable circumstances are more often arrayed against you than in your favor. For example, I have learned from long experience never to do major experiments on Mondays. It is just too difficult to pull everything "together" on Monday, and get it to work smoothly. Gremlins also thwart experiments on Tuesdays through Sundays. Test tubes crack, equipment breaks down, fuses blow, communication problems arise, etc. Each researcher has had a full quota of these misadventures-of the had luck, or no luck, which serves to more than balance out his good luck. Years of these experiences breed a philosophical attitude. As one adage has it: "If you think God has no sense of humor, just tell Him your plans for the future, and then see what actually happens."

  The investigator comes to know, as a fisherman does, that if he isn't occasionally soaked by water spilling over his boot tops then he isn't fishing aggressively enough in the deeper streams where the big trout lie. Moreover, a certain perverse optimism also creeps in. Indeed, some with a wryly humorous bent have handed down timeless maxims that deal with these unpredictable situations. These sayings, "Murphy's Laws," have since found their way into many laboratories and offices. Murphy's Laws are instructive and merit our attention. They give notice that many unhappy events can, and do, thwart our best intentions. Moreover, they tell us-as humor does-where the anxieties lie.

  It has been difficult to track down the origins of these proverbial truths. One account attributes them to Captain Ed Murphy, both a pilot and aircraft engineer.' The Murphy story begins in 1949, after an inept (unnamed) technician had miswired a strain gauge. The technician's mistake prompted Murphy to say: "If there is any way to do it wrong, he will!" This remark was then rephrased as "Murphy's Law" by a Mr. George Nichols, and things took off from there.

  1. MURPHY'S LAWS AND EXTRAPOLATIONS THEREFROM:

  a. If anything can go wrong, it will.

  b. Left to themselves, things always go from bad to worse.

  c. If there is a possibility of several things going wrong, the one that will go wrong is the one that will do you the most damage.

  d. Nature always sides with the hidden flaw.

  e. If anything seems to be going well, you have obviously overlooked something.

  II. PATRICK'S THEOREM:

  If the experiment works, you must be using the wrong equipment.

  III. HOMER'S FIVE THUMB POSTULATE:

  Experience varies directly with the equipment ruined.

  IV. FLAGEL'S LAW OF THE PERVERSITY OF INANIMATE OBJECTS:

  Any inanimate object, regardless of composition or configuration may be expected to perform at any time in a totally unexpected manner for reasons that are entirely obscure or completely impossible.

  V. ALLEN'S AXIOM:

  When all else fails, read the instructions.

  VI. SPARE PARTS PRINCIPLE:

  The accessibility of small parts that fall from the work bench varies directly with the size of the part and inversely with its importance to the completion of your work.

  VII. THE COMPENSATION COROLLARY:

  The experiment may be considered a success if no more than 50 percent of your observed results must be discarded to obtain a correlation with your hypothesis.

  VIII. GUMPERSON'S LAW:

  The probability of a given event happening is inversely proportional to its desirability.

  IX. THE O
RDERING PRINCIPLE:

  The supplies necessary for yesterday's experiment must be ordered no later than tomorrow noon.

  X. THE ULTIMATE PRINCIPLE:

  By definition, when you are working in the unknown, you know not what you will find.

  XI. FUTILITY FACTOR:

  No experiment is ever a complete failure; it can always serve as a bad example.

  XII. GORDON'S LAW:

  If a research project is not worth doing at all, it is not worth doing well.

  XIII. PARDEE'S LAW:

  There is an inverse relationship between the novelty of an observation and the number of investigators who report it simultaneously.

  XIV. GUMMIDGE'S LAW:

  The amount of expertise varies inversely with the number of statements understood by the general public.

  XV. LOEB'S LAW:

  If it works, keep on doing it.

  XVI. THE HARVARD LAW:

  The experimental animal, brought up under strict genetic and environmental conditions, still reacts as it damn well pleases.

  XVII. THE CLIFF-HANGER THEOREM:

  Each problem solved introduces a new unsolved problem.

  XVIII. COMPUTER MAXIM:

  To err is human, but to really foul things up requires a computer.

  XIX. LENIN'S LAW:

  Whenever the cause of the people is entrusted to professors it is lost.

  XX. O'TOOLE'S COMMENTARY ON MURPHY'S LAW:

  Murphy was an optimist.

  Despite all the setbacks, researchers still press on in the laboratory. If, in their muddled ignorance, they see through a glass darkly, it will still appear as a glass half full rather than half empty. Vulnerable everywhere, experimenters persist in their contrary, buoyant optimism about the future. Part of this attitude reflects their sense, as Bruce Barton once phrased it, that: "Nothing splendid has ever been achieved except by those who dared believe that something inside them was superior to circumstance."' But most of their approach acknowledges a simple fact pointed out by Pogo when he said with greater whimsy and far greater accuracy: "We are confronted with insurmountable opportunities."'

  The express purpose of this closing chapter of part II was to acknowledge ill-fortune, a very real hazard. O'Toole's final commentary on Murphy's Law serves as a reality check for anyone who carries a Pollyanna approach constantly to the workbench. Serious mistakes are inevitable. A technician could drop that irreplaceable test tube which contains the extracts from the nerve biopsy of your patient with hypertrophic neuritis; someone else might discard another test tube containing years of harvested Lewy bodies-two examples of the kinds of serious mistakes that can occur, and did.

  It was a secondary purpose of this chapter to recommend a lighter approach, both to one's own everyday foibles and to those of other persons. Many investigators discover that, as they mature and become more secure in their profession, they have less "face" to lose. Now they can openly admit their mistakes, or at least the ones they make at the tactical level. Less easily confessed to are one's big blunders at the level of policy.

  Looking back at the earlier chapters of part II, we began by describing the historical background of serendipity, noting this word's playfully creative origins, and honoring the contribution Walpole's term made to our everyday appreciation of luck. Two and a half centuries ago, Walpole would limit serendipity to the discovery "by accidents and sagacity" of things not being looked for.* Accidents and sagacity are two important factors in the processes of discovery and invention. "Accidents" is clear enough in any era. But just before we leave part II, we'll proceed to clarify several nuances of meaning within this word "sagacity."

  In the interim, however, the actual tale of Serendip illustrates yet another factor: an additional active agency at work in creative discoveries. These princes had ventured far from home; they were engaged in generalized exploratory behavior, never knowing what next might happen to them on their travels. Did Walpole himself make it easier for us to identify, as implicit in their tale, this third ingredient of chance? He did.

  In his original letter to Mann, we find him pointing to the fact that serendipity will be better understood by examining how the term was derived. We, too, can derive the generic principle underlying Chance II. Our firsthand experience tells us that travel, by its very nature, involves an adventure, that it carries the potential for unplanned consequences. Both these issues are exemplified in the odyssey of the princes of Serendip (Appendix A). They were travelers, willing to explore.

  It then turned out that four generic principles, not three, were applicable to the roles played by chance processes in discovery. The first was clearly acknowledged by Fleming; the final three of these principles were enunciated with prescience by Kettering, Pasteur, and Disraeli in ways that rounded out and went beyond some of serendipity's inherent semantic limitations. Their statements paved the way for a broad operational definition of chance in four varieties (table 1).

  Conceptual mistakes of commission or omission creep into the culture of science as a whole, and do so on a very large scale. They evolve over years, and are not limited to Mondays. Thomas Kuhn and many others have commented on the ways that such errors infiltrate our attitudes on the higher levels of policy. There, they take several forms including: false systems of belief, (asserted as truths and acted upon as such); or depths of ignorance, incomprehension, and active disbelief.

  It becomes easier to recognize the outlines of the denial syndromes if you have once belonged to a major institution that overvalues and overbelieves in its own proud reputation for priorities in research. Often, its first reflexive response will be to deny merit to any claim reported from some lesser center elsewhere. We used to refer jokingly to this phenomenon as "the N.I.H. syndrome."' Of course, when one voiced the abbreviation in this restricted manner, it simply implied that any finding "not invented here" (i.e., outside the walls of our great institution) could not possibly be valid.

  In the next section, part III, we will go on to examine the roots of creativity. Here again, it will become important to keep focusing on the personality of the individual scientist at the workbench. So, by way of a preamble to this subject of creativity, we will still need to take a final look at the traits favored by chance. For a question lingers: What enabled researchers like Fleming, and Pasteur,' and Rontgen to pierce their own and their society's existing misinformation, ignorance, and attempts at denial?

  The early chapters of part III will reveal sagacity to be an important attribute, and we haven't yet fully described its decisive ingredients. Keen powers of observation are among the first of these components, powers so keen that they can quickly "arrest an exception." Each scientist began by sensing some novel incongruity in the fact in front of him, discerned at once that this anomaly didn't fit the pattern of other concepts available during that era. Charles Darwin's son, we will find, employed this "arresting" phrase to describe his father's characteristic attribute.

  Beyond this, we will also find that each scientist was astute, a word meaning that keen intuitive powers were an integral aspect of his sagacity. Each man realized that his new observation was part of a pattern that could satisfy a huge information gap, and comprehended how significant this fact was in its new larger relationship. So, he did more than simply "arrest" the exception. He realized that he would need to handcuff it, subject it to rigorous cross-examination, and report details of his investigation in print.

  We of succeeding generations are still making practical use of concepts these pioneers initiated in earlier centuries, forgetting how remarkably "new" these ideas once were on the days when they were first recognized, and how contingent their whole outcomes were on chance events.

  Part III

  The Roots of Creativity

  The creative individual is a person who regularly solves problems, fashions products, or defines new questions in a domain in a way that is initially considered novel but that ultimately becomes accepted in a particular cultural setting.
r />   Howard Gardner

  21

  Some Dimensions of Creativity

  Many of the ideas which have been developed and rooted in the earlier literature on creativity are poorly conceived, frequently unsupported, and largely untenable. More rigorous treatment of the subject suggests that there is no one creative process and that indeed, the creative process is any thinking process which solves a problem in an original and useful way. Since the creative process and creativity itself are recognizable only through the creative product, the creative product must be original and useful and, if the creative product is an idea, it must be communicated or implemented.

  H. Herbert Fox

  In the foregoing chapters we have seen examples of how chance events collide at odd angles and at key intersections during creative meanderings in ways that helped resolve problems in molecular medicine. With these illustrations in mind, let us now examine creativity itself. My purpose in this third part of the book is briefly to summarize something of what is known, and not known, about creativity in the biomedical sciences. In a very real sense we will consider both the ecological and the neurophysiological determinants of the creative process, exploring the ways creativity springs from interactions between the person and his environment and speculating about a few of the many ways the brain might function in this process.

  Most chapters that follow are largely in the essay form. They are still a personal commentary, though they necessarily differ in style from earlier portions of the book and differ from each other. In fact, I have selected only those observations from a sizable literature justified in terms of my own experience. It follows that this statement is what I think creativity is all about. My perspective is that of a biomedical investigator, but you will find most points apply broadly to creative activity in general. There are really many creativiti's, far more than illustrated here, and if I seem arbitrarily to define creativity in ways that fit myself, I ask the reader's forbearance and apologize in advance.