the humanities in medicine: the medical and scientific significance of the seemingly small, trivial...

The American Journal of Cardiology VOLUME IX JANUARY 1962 NUMBER 1

Groedel Lecture

The Humanities in Medicine

The Medical and Scientific Significance of the Seemingly Small, Trivial and Insignificant *

WILLIAM BEAN, M.D.

Iowa City, Iowa

I T WAS NOT my fortune to know Dr. Groedel. Your memorial tribute to him and the list

of distinguished men who have addressed this annual convocation tell much of the man who was a major force in the formation of your society. This is known to you all so I need not dwell on it. .4 memorial address, one of the few in this country devoted to the humanities, naturally brings concern to the speaker. I am past the ordeal of preparation. Speaking tensely, the gerundive has merged into the present and now moves backward into the past; I hope not the past imperfect. It is impossible for anyone to decline an invitation to give a memorial address of this kind. I welcomed the challenge and accept the honor. Speakers experience a rapid and devastating shift of feelings as the pride and pleasure at being asked to talk fade into the sense of uneasiness as one casts about for an appropriate topic. I sought diligently for a theme which would dignify the occasion, but still be within my competence. To say that I was without re- sources would be to impugn the capacity of Dwight Harken and his committee which in- vited me to talk. I hope you of the audience who are victims will judge me without the harsh acerbities of objective criticism.

I keep on file a variety of topics to which inter- mittently I add passages from books, ideas which come into my mind, reprints and so on. I have, for instance, the makings of a two hour speech consisting of nothing but introductions culled from many sources. I might have talked about the annus mirabilis of science, the year 1543. Leonard Fuchs in Basle had just published his celebrated herbal De Historia Stirpium

Commentarii Insignes; Vesalius published the Fabrica and Copernicus, even as he lay dying, released the already aging manuscript of “The Revolution of the Celestial Spheres” with the orbits of the planets resolved mathematically by shifting the center of rotation of our universe from the earth to the sun. The authority of Aristotle’s dialecticwas assailed by PetrusRamus. De Montboissier, abbot of Cluny, edited and wrote an introduction to the Koran, now for the first time translated into Latin, by Robert Retensis and Herman Dalmata. It is claimed that Martin Luther wrote the praemonitio. These publications were disseminated with hitherto unknown speed. A rising tide of books was spawned by the busy printing presses. These works effectively laid low the great encyclo- pedists of late classical antiquity. The simian anatomy of Galen and the geocentric astron-

* From the Department of Internal Medicine, College of Medicine, State University of Iowa, Iowa City, Iowa. The Groedel I\lemorial Lecture in the Humanities in Medicine, delivered at the Tenth Annual Convocation of the American College of Cardiology, May 19, 1961, New York, New York.

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omy of Ptolemy went tumbling down together. But this forthright and complete declaration of scientific independence did not contravene all old ideas or practices. At this very moment the Vatican gave final recognition to the Jesuit Order and the Council of Trent gathered to reaffirm some of the most nonscientific concepts of the Middle Ages. Bigotry was still the order of the day as witnessed by the appearance in Basle of De veritate Fidie Christianae contra Ethicos Judaeous, Agarenos sive Mohametanos, ac Perverse Christianos, libri quinque. Cardano, a complex genius, physician, supreme mathematician and inveterate gambler, two years later had his printer, Petreius, publish in Nurnberg Ars Magnae Sue Regulis Algebraicis, usually called Ars Magna, The Great Art. The book is as fundamental to mathematics as Copernicus’ book on the planetary system is to astronomy and Vesalius’ book is to anatomy. But I must pass up the annus mirabilis, 1543, and the adjacent years.

Another thought was to extend my observations on the natural history of error, now filling many folders which encompass vast and growing accretions of data. But this would take too long. I considered displaying some of the many medical passages from Shakespeare’s plays and poems which delight and refresh the spirit. No doubt you are familiar with books and papers on this topic. This lode has been worked over. I thought about the large company of medical and scientific discoverers of the first magnitude who never married. Their genius and talents died with them. Whether it be that the dis- cipline is very demanding or that a career in science requires such high dedication that it can only be carried on in the cloistered seclusion of a celibate existence, I do not know, but Leonardo, Copernicus, Gilbert, Descartes, Pas- cal, Boyle, Newton, Hooke, Cavendish, Dalton, Mendel, Gibbs and so many others were not married. But this was too melancholy a subject. Another lesson might be drawn from many great men whose sons never reached the same high order of accomplishment. But if any morals are to be drawn they are so dour and sad that I should have reduced you to tears.

Occasionally when I stand up to deliver an address the thought has taken me to depart from the announced topic and talk about something entirely different. I do not wish to do this as a famous speaker from a famous medical center almost did when he found that he had picked up the wrong box of slides. Unable to

go on at all without props, unhorsed, he fled from the field of combat.

I certainly hope to avoid the predicament of another famous speaker who, going jauntily up to the podium with his hands in his pocket, tripped and fell flat on his stomach. The startled master of ceremonies was not too un- nerved to say he had never seen a Harvard man in this predicament and furthermore he would have to get out of it without any help. Lusty and mirthful applause came from the en- chanted audience. They had already witnessed the best part of the performance.

I thought of my collection of medical people who have achieved eponymic immortality through a few lines, a few paragraphs, or a page or two of writing. To show you how fickle is the selective finger which beckons casually to immortality, Babinski’s thirty-eight lines, Janeway’s three sentences, the two brief pages describing the Fick principle, a casual allusion to Stoke’s collar, the Austin Flint murmur, the Eck fistula, Koplick’s spots-all were told to the world in masterpieces of brevity. But though I deal in small matters I shall not be brief.

You see what worlds of temptations I have resisted. Though I had ample warning I had inadequate time or wisdom to do justice to such spacious topics. I decided to talk about the importance to medicine and science of the small, the trivial, the rare and the obscure, selecting examples which might illuminate the theme and dignify this memorial occasion. I was very much like the lad who had failed his first examination at prep school. He did not quite know how he was going to break the word on the home front. He wired his brother to prepare his father so that the homecoming would be tol- erable. His brother wired back, “Father is prepared-prepare yourself.”

At this moment my reaction is to call for help in the words used by a Negro preacher to invoke divine assistance at the beginning of his sermon: “Oh Lawd, give Thy servant de eye of de eagle and de wisdom of de owl; connect his soul wid de gospel telephone in de central skies; ‘luminate his brow wid de sun of heaben; pizen his mind wid love for de people but doan prod his cussedness ; turpentine his ‘magination; grease his lips wid possum oil; loosen his tongue wid de sledge hammer of Thy power and de honey of Thy words ; ‘lectrify his brain wid de lightnin’ of de gospel; put ‘petual motion in his ahms ; fill him plum full of the dynamite of

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Humanities in Medicine 3

Thy glory; ‘noint him all over wid de kerosene oil of Thy salvation, 0 Lord, and set him on fire. Amen.”

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My sermon ranges beyond just medicine. It encompasses biology and science generally. The text comes from the legal maxim De Min-

imis :b-on Curat Lex, which can be translated freely as “the law doesn’t fret about trifles.” It highlights a difference between the medical and legal mind, for the lesson I bring is how important small matters have been in advancing learning in medicine and science.

up an article dealing with sewage disposal. A chemist happened to look at crystals under a microscope and detect their mirror-image relationship. A stray mold landed on a petri dish and produced an effect which is still ex- tending its impact. Some historic illustra- tions will display other details of my theme.

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Happily it is characteristic of science that the importance of its subject matter is not related to size. A little search reveals that much, perhaps most, progress has come from attention to the minute, study of the trivial and an exalta- tion into proper prominence of what seems to be insignificant. The continually sharpening focus has shifted from macrocosm to microcosm. Historically the development of anatomy by dissection and exploration of gross aspects of the human body was the first major step forward. After that it was possible to develop the notion of organs, systems and functions. Then the com- prehensions of pathology ranged from body to organ, to tissue, to ~11, to humor. Further advances are coming with knowledge of the ultrastructure of the cell, the enzyme systems needed to mediate energy and material trans- formations and the fantastically elegant mecha- nisms by \vhich chromosome and nuclear material conduct, in infinite intricacy, the compli- cated metabolic processes of life itself. All these daily give emphasis to the importance of the small without illustrating it self-consciously. Yet another aspect of smallness may be seen in our gleaning of neglected residues, little nuggets missed by the original prospectors.

Think of the great effect small things have on everyday lives. A few molecules of artificial musk fill a whole room with a characteristic smell. A thousandth part of a milligram of vitamin Bl? daily keeps most of us from getting pernicious anemia. Only the faintest trace of iron is needed for many biological oxidations; and toxic substances may kill in even smaller amounts.

I. As my first example of the importance of the small let me discuss one of the remarkable discoveries of Henry Cavendish, a most fascinating and eccentric genius. His worship of precision and scrupulous compulsion in experimental technics led to the discovery out of which evolved the periodic table and recognition of the principle of radioactivity. He came from a family of lords and dukes, inherited un- told wealth from an uncle to become the weal- thiest man in England of his time. Patho- logically shy, voice squeaky, and speech scarred with an impediment, his crankiness made him an extreme vexation to his portly bankers who had a dreadful time getting him to accept all the money or responsibility for it. Henry Cavendish, cold, aloof, avoiding people, a cantankerous and morose bachelor, was so mortally afraid of women that he communicated with his servants by leaving written messages, with a stern edict that they should always keep out of his sight. He was tragically without friends. This moody man was able to concentrate all his talents and energies in a cold devotion to science. In the 1770’s Priestley and Lavoisier had shown that when a substance was burned in an enclosed space the residual gas decreased in volume and would no longer support combustion. Cavendish performed this experiment in an inverted glass set in water. He found that the water rose through a fifth of the space originally occupied by air. This was the proportion of oxygen. But what was left? He determined to find out. Priestley had thought that the amount of oxygen in the air varied from time to time and from place to place. In 1781, Cavendish patiently col- lected samples from some sixty places, day and night, city and country, slum and castle, rainy or dry, cold or warm. In every case ten forty- eighths of the atmosphere was oxygen.

A doctor met some children at play trans- Priestley and War-hire had used a spark from mitting sounds over some long planks. A an electrical friction machine to explode hy- physicist left a photographic plate covered in the drogen in a glass globe containing some ordinary usual manner near an electric tube from which air. After each explosion a small amount of a discharge was taking place. A surgeon picked moisture appeared inside the glass. They dis-

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regarded it. This first small residue Cavendish thought was derived from the combustion of oxygen. He then exploded hydrogen in a sealed tube, varying the proportions until the air was reduced precisely by the amount of one-fifth which was the proportion of oxygen it contained. This occurred when the volume of hydrogen was just twice the volume of oxygen. Since the glass tube had been sealed and it weighed the same before and after the explosion, Cavendish naturally concluded that the “dew” formed was equal the weight of the hydrogen and oxygen which had exploded together. He did not know what it was. He obtained enough to test and found that “it seemed pure water.” In his own words he concluded that “almost all the inflammable air and about one- fifth of the common air had turned into pure water.” Here was excitement indeed. For the first time in history the compound nature of water was revealed. But Cavendish did not stop. He must find whether pure oxygen and pure hydrogen, exploded in a similar way-, would give the same result. Most of the time he did in fact get pure water. Occasionally the water contained an acid. Here was a new problem, something altogether unanticipated. Pro- ceeding with his scrupulous care, he discovered nitrous acid derived from contamination of the hydrogen or oxygen. When he eliminated nitrogen, the combustion of pure hydrogen and pure oxygen gave only pure water. Even Cavendish was still bemused by the notion that hydrogen was phlogiston and, therefore, he thought that oxygen was nothing but de- phlogisticated or dehydrogenated water. If phlogiston plus oxygen equals water, then water minus phlogiston equals oxygen. In these experiments Cavendish continued to study the separation of nitrogen from air by passing electric sparks through glass containing air with an excess of oxygen, and the nitrous oxide gen- erated was absorbed by caustic potash. The oxygen was then removed by another absorbent. According to his understanding at the time, when this process was complete no gas should remain in the tube. Time after time he repeated his meticulously designed and performed experiments. Each time a small bubble re- mained. It was one-one hundred and twentieth of the gas introduced into the tube. Cavendish felt strongly that it was significant. But he never learned what the bubble was and this bubble, this small residue, did not soon excite anyone’s fancy. No one bothered to investigate

this annoying discrepancy, assuming it to he an experimental error or something of no conse- quence. Chemistry in those y-ears was in the doldrums, suffering from the rejection of specula- tive thought which sometimes masquerades for scientific austerity when new ideas or inspiration run low.

We pick up the thread 1CO years later. An- other Englishman, the third Lord Kayleigh, was a very different man, an ultraconservative

. squire who used his leisure and his seclusion, uninterrupted by committee meetings or travel or giving speeches, to become one of the chief investigators of his day. To him this unexplained residue was a nagging annoyance and he had the dogged determination, the patience and the stability to solve the problem of the mysterious and unexplained bubble. He was trying to determine whether Prout’s hypothesis of a simple numerical relationship between the atomic weights of hydrogen and other elements was true, despite its rejection b!- those en- trenched in authority. He had to weigh gases with exquisite precision and used a long, cum- bersome and painstaking method. Despite prodigious work, he never could get the atomic weight of hydrogen any closer to 16 than 15.882. He decided then to tackle nitrogen which was less exacting. After much preliminary work he obtained a gas which met his stringent requirements. He was not satisfied merely to determine the vveight of nitrogen taken from air. He repeated all of the studies with the nitrogen obtained chemically. Here, a little thing, his decision not to take the easy way, was one of those unnoticed and too often forgotten crises in the history of science, more dramatic than most better known historic events. The nitrogen he had prepared chemically- was onc- half of 1 per cent lighter than atmospheric nitrogen. This he determined exactly, such was the precision of his methods. Further brilliant studies led to the discovery that air had another and unknown constituent. The bubble in Henry Cavendish’s apparatus which had failed to inspire any chemist for more than 100 lazy years turned out to be argon perhaps the most inert substance in all the physical world. This single, apparently trifling observation, this little bubble which was a nuisance, produced a chain reaction in the ph>-sical sciences. It led to the discovery and understanding of helium, the development and comprehension of the periodic table, insight into the mode of disintegration of radioactive elements, isotopes,

‘I‘HE AhlERICAN Jo”R”“L OF CARDIOLOGY


and an understanding of radioactivity. This small bubble, this forgotten residue, one-half of 1 per cent, was possibly the most momentous little thing in the whole history of chemistry and physics.

Cavendish and Rayleigh were able to avoid a curious foible of our time-the increase in credulity which the great modern instruments of precision engenders in their users. An instrument good enough to record accurately to the nth figure can give results no more accurate than allowed by the material fed into it. As Allen Gregg has said, “An instrument delicate to the fourth significant figure seems to quad- ruple the credulity of the observer, not only in the reading obtained but in the value of the particular choice of instrument.” This is a lesson to be remembered by those who, “pro- graming” thinking machines, hope that they will derive codified, condensed and illuminating information of a kind which is not in the original nutrient data fed into the hungry maw of the calculator. Its electrical digestive ferments, feeding back and forth, cannot construct the silk purses of mathematical syntheses out of the sows’ cars of inadequate data.

II. I have a layman’s unbounded admiration for the uncanny accuracy of predictions of eclipses and the way astronomers can tell us when to look for the awe-inspiring orbiting of Echo. I suppose I share with them the appre- hension growing out of their description of the retreating galaxies which seem to be pushing away on out into limbo. From astronomy we can get another example of the importance of small things. Toward the end of the eighteenth century when Cavendish was busy at work on his small gas bubble, William Herschel was making an effort to detect stellar parallax, following a suggestion by Galileo. About 100 years before this Isaac Newton had formulated the ground rules, if I may use the term, for the proper behavior of planets in public places. On March 13, 1781, while observing two close stars, Herschel saw a star or comet in Taurus which had an appreciable disk. When he observed the star moving in relation to other stars he plotted its orbit with the Astronomer Royal, Maskeleyne, and thus discovered Uranus, the first new planet ever to be observed. There were, however, some discrepancies. Despite repeated calculations the observed and calcu- lated orbits did not quite agree. This was

JANUARY 1962

appropriately blamed on instrumental error and the whole business conveniently forgotten. However, the discrepancy did not go entirely unnoticed. Joseph Leverrier, a French astronomer, brooded. Might not, he wondered, a still more distant planet cause the aberration. From this novel speculation it was fairly easy to calculate where the other and unobserved planet would have to be. He communicated this information to a German colleague, Johann Galle, who had a powerful telescope. Sure enough, there was the planet. You would suppose at this time that everyone would be content that the long oversights were rectified and Newton triumphantly justified. But the story repeats itself again. Astronomers, meas- uring more accurately, found another discrepancy between calculations and observations. And so, many years later, in 1906, Percival Lowell predicted that yet another planet would be found. The telescopes of that day were not quite good enough, but in 1930 the planet Pluto was observed just as predicted. The neglect of small residues again had retarded the ad- vancement of understanding. Perhaps still more precise observations will reveal still other planets. Or maybe man-made satellites will grow sufficiently large and plentiful to throw the calculations out of kilter and we will have to start all over again.

,4 tale is told of Michelangelo, beset as great people are, by visitors. He was explaining small changes he had made in a statue. It was ob- jected that they were but trifles. “It may be so,” he said, “but recollect that trifles make perfection and perfection is no trifle.” Here is another example-Rodin, never given to small talk, once was highly annoyed by a lady who said, “Master, you make it all look so easy, just how do you do it?” Rodin replied, “It is easy. All you have to do is take a large piece of marble and with your chisel knock away, a little at a time, all that you don’t need.”

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III. One of the most exciting observations of the last decade has to do with sex. Without removing it from its natural habitat in the Police Gazette, sex has spread, entering and indeed dominating many laboratories. I refer to that little biological laundry tag, the sex chromatin, which gives a clue to genetic sex in various representative tissues and cells. How many thousands of histologists, looking at how many millions of cells, had seen these nucleolar

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satellites. Murray Barr, in his brilliant ob- with all the external markings of a cock servations on neurons and neuroglial cells in was sentenced to be burned at the stake cats, found a distinctive nuclear morphology “for the heinous and unnatural crime of laying related to the animal’s sex. Females had a an egg.” There was great dread that this vio- larger special mass of chromatin than did males. lation of nature had diabolical significance. This hint has been extended by geneticists, It was feared widely that the issue of its eggs morphologists and endocrinologists all over the might be made into a witch’s brew to facilitate world. We hear exciting case reports of super- carnal knowledge of innocent women by evil females, with chromosomal number 47 and a spirits. The cock must be martyred lest he chromosomal sex of XXX. There may be a become an evil procurer to his Satanic majesty, profound lesson, although at the moment the the devil. The actual putting to death of the only one I find depresses me, in the fact that the creature occurred on a height near the city triple X females, genetically super-sexed women, called the Kohlenberg. The creature was con- are all feebleminded. All sorts of sex-linked signed to death with as great solemnity as would and sex-jinked maldevelopments are coming to have been reserved in other places for a heretic. light, with new information about Klinefelter’s It was witnessed by an immense crowd of syndrome, Turner’s syndrome and Mongolian townsmen and peasants. Gross, in his Basle idiots. We are getting ironic answers to the Chronicle, recorded that the executioner, on question raised in parody, “Breathes there a man cutting open the cock, found three more eggs with soul so tough who thinks two sexes aren’t inside. It might be said in support of the good enough?” From Barr’s small observation have burghers of Basle that this was the only witch arisen new concepts of intersexes, infertility, they ever burned. They abstained from the anomalous hermaphroditic creatures, and the witch-killing mania which harried to death forever fascinating problem of sex reversal. tens of thousands of innocent but perhaps hor- The power of this little sex-speck is wonderful, rible looking old hags or hysterical young girls presaging such new laboratory units as milli- in Europe during this period. They were iden- Marilyn Monroes or multi-Tarzans. Nowhere tified by tinv blemishes or signs, the legendary else in biology do so many owe so much to so but ill-described witch’s marks, vague clinical little. sigmata of a dreaded era.

While we are on the subject of sex let me allude briefly to transvestism in the plumage of the fickle fowl, a spontaneous variation in sex. My colleagues in Iowa tell me that old hens have a tendency to develop male characteristics. Their propensity to crow connotes the trouble predicted for “whistling girls and crowing hens.” Per contra, the unhappy consequences for the male fowl’s not adhering to the lines of duty in the activities laid down by the laws of Nature for his sex have been condemned as evil derelic- tions in the past. The ancient tradition of cock’s eggs in medieval literature is full of all sorts of whimsical magic and fearful mythology. If such an egg hatched it was supposed to give rise to a fearsome conglomerate known as a cockatrice, sometimes considered to be identical with a basilisk. The anterior aspects resembled those of its unnatural mother, the cock, trailing off in clouds of glory with the tail of a lizard or serpent. It had power to kill by a glance or a whiff of its breath. There are many allusions to the trial and condemnation of cocks for laying eggs. The most famous occurred in Basle, Switzerland, in 1474. This probably produced history’s smallest martyr. An unfortunate fowl

It is related that William Harvey, the dis- coverer of the circulation of the blood, once engaged in a hunt for witch’s marks. He was called in to give expert testimony about the famous Lancashire witches. The official report reads as follows:

“Surgeons Hall in Monkwell Street, London.

2 July A.D. 1634.

“We in humble obedience to your Lordship’s command have this day called unto us the Chirur- geons and midwives whose names are hereunder written who have by the direction of Mr. Dr. Harvey (in our presence and his) made diligent search and inspection on those women which were lately brought up from Lancaster and find as followeth, viz.:-

“On the bodies of Jennett Hargreaves, Frances Dicconson and Mary Spencer nothing unnatural nor anything like a teat or mark or any other signs that such a thing hath ever been.

“On the body of Margaret Johnson we find two things which may be called teats. The first in shape like to the teat of a witch but in our judgment nothing but the skin as it will be drawn out after the ap- plication of leeches. The second is like the nipple or teat of a woman’s breast, but of the same colour with the rest of the skin without any hollowness or issue for any blood or juice to come from thence.”



The report was signed by ten midwives, by Alexander Reid, M.D., lecturer in anatomy at the Barber-Surgeons’ Hall, whom Harvey must have gotten to take his place, and by six of the most noted surgeons in London. The four women were pardoned, an act of justice which may have been due to the enlightened views and prompt and energetic action of Dr. Harvey. I have no idea what the witch’s mark really was, but this was one small thing it was best to be without.

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IV. It is fascinating to think that the entire process of evolution depends on smallness. An infinitesimally small genetic mistake leads to mutation, which even if it does not derail the victim, introduces an alteration, usually minute but occasionally extensive. The specific adaptations brought about by natural selection arise out of repeated small variations by aiding in the survival of those provided with some con- sistant structural, physical or psychological advantage. Here is an example which Julian Huxley suggests is the only one of an animal -mimicking a miniature portrait of a special kind of person-protected by taboo from human consumption. I refer to the crab Dorippe japonica which is widespread in Japanese waters. There is a legend about it and some facts. In the dark and musty recesses of antiquity the legend goes that two Japanese feudal families, the Heike and the Genji, having fought for generations, clashed in a showdown naval battle off the southwest tip of the country. The Heike met overwhelming defeat. In accordance with the requirements for etiquette under the Samurai tradition and in the spirit of hara-kari, the con- quered war lords, their families and the entire military entourage committed a lemming-like mass suicide by throwing themselves into the sea. The astonishing effect of such behavior was said to have been that the crabs in this part of the ocean suddenly had stamped on the back of their carapace, the mournful and resentful faces of the defunct Japanese warriors. Crabs thence- forth were looked upon as reincarnations of the suicidal Heike nobility. Japanese will not eat it despite the fact that it is eaten with impunity by anybody else and is said to be delicious. A surviving accolade for profound ugliness in Japan is “You look like a Heike crab” but this is reserved only for carrying homeliness far beyond the call of duty. So much then for the legend.

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What facts are there? Interestingly enough the Heike were indeed defeated at Dan-no-m-a in 1155. The crab Dorippe japonica is known familiarly to the Japanese as He&e-gani or Heike crabs and one may see from photographs how neatly it resembles the Samurai warrior of ancient times. Another folk tale is that in centuries gone by the crab was sometimes called Oni-gani, indicating that this was a ghost or demon crab. The identity of this particular crab as the recipient of the transmigrant spirit of an ancient warrior are too specific to be merely accidental. Here is an example of adaptation by a kind of sophisticated natural selection operating over the centuries. The closer the resemblance of the crab to the departed Samurai warrior the less was its chance of getting eaten, the better its chance to survive against its major natural enemy, man. The statements that this is ridiculous or impossible, or how can an animal know the way it ought to look? or that it is a miracle and must have been induced by divine intervention, or is purely accidental, are beside the mark.

Who has not marveled at the elegance and accuracy of mimicry among insects and the pro- tective camouflage which ranges from a change from winter to summer plumage or fur in birds and mammels, to insects which resemble leaves or sticks or flowers or other insects which birds have learned to let alone because they have a bad taste. It is now established that minute changes, occurring from time to time, which confer ever so little advantage on an animal, increase its chance of survival and thus of re- producing itself. In this fashion natural selection leads to the survival of those with some small advantage.

An animal does not wish or will or invent or have such advantages conferred by some divine manipulation. There is no evidence that experience leaves any imprint which can be transferred genetically, no shred of evidence for a Lamarckian inheritance of acquired char- acters. Heritable variations, mutations occurring from time to time, mostly prove harmful, a handicap favoring elimination. But the rare favorable ones, conferring a benefit because they increase the efficiency, extend the life or facilitate reproduction, foster the species. Evidence is accumulating that variations which occur in the process of natural selection tend to be extremely small. They have only a slight effect upon an individual’s capacities or his visible characteristics.

How did the crab’s mimicry begin? We can only assume that it was accidental or if one wishes to use more precise terms that genetic alterations in the highly organized nuclear material occurred under the cumulative effect of chance encounters with radioactivity. Be- cause of the personal arrangements of crabs the design on the back is related to the underlying contents of the carapace. The back is not smooth but is broken into a series of bumps, ridges and irregularities which may bear a quite accidental resemblance to something or other. In several cases it resembles a human face, as it does in the little crab seen off the coast of England which happens to be named after the ancient chieftain who led the Britons in war against Julius Caesar. This crab is too little to bother to eat so the resemblance to the human face has never had survival value. It is still quite rough. But probably- in ancient times, perhaps many thousand of years ago, primitive and superstitious precursors of the Japanese must have felt that a supernatural force or a spirit himself had imprinted his face on the back of the crab. Thus it had mystical and ominous significance. It became taboo and was left scrupulously alone. Thus a resemblance that must have been well established long before the battle of the feudal feuding families in the twelfth Century probably had been providing survival value to this crab from ancient and immemorial time. Folk fear based on the unlikely- resemblance of a crab to a special class of person determined its later survival. So the mighty changes of evolution depend on small matters.

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v. Another way of emphasizing the small and the trivial is to show how the large, the great and the conceptually magnificent may backfire. At various stages in the history of medicine heroic therapy has deviated as far as it possibly could from approaching things by attention to the small and the trivial. As an example of this let me tell you about the treatment which was prescribed by his Royal physicians for King Charles II of England when he lay sick in 1685. A pint of blood was extracted from his right arm, then eight ounces from the left shoulder. Next he was given an emetic, two physics and an enema containing fifteen substances. Then his head was shaved and a blister was raised on his scalp. To purge the brain a sneezing powder was given. Then

cowslip powder to strengthen it. Meanwhile, more emetics, soothing drinks and more bleed- ing. A plaister of pitch and pigeon dung was applied to the Royal feet. Not to leave anything undone the following substances were taken internally: melon seeds, manna, slippery elm? black cherry water, extract of lily of the valley, peony, lavender, pearls dissolved in vinegar, gentian root, nutmeg, and finally forty drops of extract of the human skull. As a last resort a bezoar stone was employed. The Royal patient died.

A corrective to this orgiastic therapy at length arose out of a strange cult of the little. Home- opathy, which was founded by Hahnemann early in the nineteenth century, had surprisingly helpful repercussions on medical theory and practice. The three tenets of Hahnemann’s homeopathic philosophy were that like cure like, medicine increases in potency- with dilution and that psora, the itch, “is the sole true and fundamental cause that produces all the count- less forms of disease which go under the names of nervous debility.” Hahnemann named thirty, including rickets, gout, cancer, jaundice, drops), asthma, cataract and such. In some of Hahnemann’s prescriptions the dilutions as high as one-sextillionth, one fol’owed by twenty-one zeros, get past single molecules into the subatomic pi mesons and beyond, and we have the true reductio ad absurdum of littleness. But these ridiculous attenuations had one wonderfully salutary effect. Sick people taking them did get well. A careful observer saw that more patients got better more quickly than those given the heroic treatments then in vogue. The demonstration of the effectiveness of a null form of treatment gradually caused the medical profession to temper its therapeutic passion. Here littleness made a great contribution. Hahnemann had the ill luck to arrive on the scene when what used to flourish under the older systematists unchallenged, was promptly checked. The ideas upon which his program was based were found to be thoroughly at fault. However, good came of this error. LYherever a monistic pathology and a derived thera- peutics exist side by side and are tested, modern medical philosophy evolves by exposing error. During times of depressed medical, social and sociological sophistication under which a one to one relationship of cause and effect is held- chiropractic, Christian Science and their ilk, where one cause and one cure explain everything-people either are bewildered and be-



guiled or the doctrinaires have skimmed off the broth of scientifically proved ideas and in- corporated them into the system playing both ends against the middle in the eternal game of legerdemain whereby the ignorant gull the gullible.

. . . . . . . . . .

VI. Neglect of the small and trivial leads the medical mind to disregard diseases which produce few or mild symptoms. Rubella is one of the gentlest of viral infections. Thousands, perhaps millions, of women have had German measles. Many have had it in the first tri- mester of pregnancy without anyone connecting this event with anything that followed. Gregg in 1941 announced an increase in cataracts in the eyes of infants whose mothers had rubella early in pregnancy. We then began to pay attention to it. Although prospective studies indicate that the risk is not as dangerous as we first thought, this is a brilliant example of medical trivia, rarely recognized, which can be put to use for the benefit of mankind only by the observation and insight of an imaginative person who puts together an unlikely two and two to make what everyone then recognizes as the obviously and now ridiculously apparent four. If he had not at this exact time made this observation it might have had to wait another 100 years.

. . . . . . . . .

Time will not permit me to expatiate upon many other examples of notice of the small and little things which change the course of history. The most striking example that comes to mind is Fleming’s alertness which enabled him to identify in the effect of a mold growing on his bacterial culture, a force which opened the whole field of contemporary antibiotic therapy. We are beginning to get insight into the infinite variety of disorders which very small variations in protein molecules may produce, as exemplified by the very slight alterations in the arrangement or kind of amino acids in the hemoglobin mole- cule which cause the sickle cell trait, disease and other aberrations. Tiny differences in the molecules governing genetic and chromosomal processes account for the unique biochemical individuality which makes each person in the world different from every other person.

Among other belatedly recognized residues perhaps the most spectacular is the time lag which separated the discovery of the cause and

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cure of scurvy by James Lind, published in 1754, from the identification of the chemically fairly simple vitamin C. Only forty ponderous years elapsed before the Lords of the British Admiralty, applying this knowledge to the health of sailors, slowly recognized that this small disease, scurvy, was more destructive of seamen and ships than were the murderous vehicles of naval warfare and the armamentaria of de- struction at sea. A by-product was the extension of the British Empire and its dominions overseas. One of the clearest and most dramatic hints in the whole field of medical practice rested before the averted eyes of physiologists and biochemists for 150 years before vitamin C was isolated, identified and synthesized.

Another neglected residue is the belated discovery of serotonin, that enchanting compound now most unexpectedly linking together psychiatrists, pharmacologists, biochemists, cardiologists, coagulationists, geneticists and others. The pharmacologic effect of this substance was recognized by Ludwig ninety years ago. In perfusion experiments he noted that defibrinated blood had an intense vasoconstric- tive capacity it did not have before coagulation. This force could be removed by profusing the blood through the lungs so that in subsequent perfusion of the heart, kidney or other organs it was possible to avoid this powerful effect. No one paid much attention. This clue languished until Page and Raport, looking for any vasoconstrictor of possible significance in hypertension, went back to this ancient observation. The substance, that nuisance which vexed the early experimenters, was serotonin, isolated, identified and synthesized only after a ninety year wait. It was recognized by Erspamer to be the enteramine he had been studying so extensively.

I will throw in for ballast a few examples of discoveries which arose from small beginnings: Lady luck has a large hand in them but only for the person who can attend, concentrate and have his mind prepared. Such was the chance discovery by the old time prospector stumbling on uranium, or in times gone by when someone discovered a lake, a mountain or a glacier. Helmholtz found the principle of the ophthalmoscope when he was kissing his children good night. With a candle behind his eye he saw the retinal reflection. From this observation he devised the ophthalmoscope. Garcia’s idea of the laryngoscope came to him when he happened to notice a little dental mirror in a shop

10 Bean

window in Paris. Laennec’s invention of the stethoscope came from similar small beginnings.

These are but a few of the innumerable examples in the long history of medical science which fumbles along, slowly purifying its ideas, weeding out one misconception after another, throwing out anthropomorphisms here, expunging errors there, combing out one by one these foreign bodies which may stifle the intellect, sometimes only to replace one error by others which must await future debridement.

When discoveries are made or brilliant suc- cesses in science are recognized or even those minor accomplishments in diagnosis and therapy which may mean the recovery or cure of a very ill patient, when all these are seen, the greatness of the results and implications of the accomplishments frequently cloud our eyes to the fact that they arose out of littleness. When we see splendid discoveries we are apt to grant mental powers far beyond our own. But it is not prodigious mental feats that we lack, it is humbleness, the humility to take note of little things. We lack the simple approach, daring to bother with what looks like a ridiculously unsophisticated experiment, especially one which we think will lead to no important results. Often we seem to be afraid of littleness itself, wanting the grand, the magnificent and the big.

A recurring amazing feature in man-made scientific discoveries is the element of natural surprise. The one lesson which a careful study of history tells us over and over again is the small beginnings of large events. Even in the natural world, earthquakes, avalanches, erup- tion of volcanoes, everything seems to be done by leaps and bounds. But such cataclysms, such catastrophes mark me august finale build up of aggregates of a multitude of tiny geological phenomena. We look today at the magnificent volcano Paracutin, but few remember the first small hump of volcanic dust, ashes and pumice which notified the world that a volcano was in the making. Minute changes, little by little, continuing obscurely for ages culminate in dramatic events. The downfall of the walls of Jericho and fall of the Campanile in Venice were not so much the result of a sudden massive push as the collaborative effort of a thousand minute separate forces yielding a magnificent and instantaneous effect.

Before I conclude I must tell you a little story: Last year I gave a very brief talk before a small medical society dealing with the topic I have

been presenting to you tonight. In the subsequent discussion I pointed out that, had I followed the sagacious instructions of my good wife, expunging item after item from my talk (They know all that!) ultimately I would have wound up with a paper no longer than the fabulous chapter on owls in the reverent Bishop Pontoppidan’s history of Iceland. The good bishop wrote simply that there are no owls in Iceland. That was his whole chapter. One of the discussants of the paper, Dr. Gordon Meade, who doubles as an ornithologist, got directly in communication with Mr. Finnar Gudmundson, the Curator of Ornithology at the Natturugripasafnid at Reykjavik, Iceland, and found that in fact there had been no owls in Iceland at the time Bishop Pontoppidan was in business. But now as a sign of progress of sorts two sets of owls, the short-eared owl and the snowy owl, have moved in. I was not one to let such matters rest, passing them over lightly, and I set my literary beaters, blood hounds and birdwatching medical and literary colleagues to see what game they could flush from ancient lore of Iceland. I am proud to relate that in a footnote in Volume XI of Islandica is a statement that there is a volume of Icelandic manuscripts in the Maurer Collection, Harvard University Library (No. 26, 20) with an essay by Jon Gudmundsson, possibly an ancestor of Finnar, toward the end of which mention is made that an owl, Kattugla, was seen in Skalholt during the episcopate of Jon Vidalin (1697-1720). So it is possible that after all the good Bishop Pon- toppidan just might not have had the last little word to say on owls in Iceland. You see that small matters may lead to all kinds of complica- tions.

. . . . . . . . . .

In medicine there are enough absolute im- pediments and large difficulties which we cannot overcome. But our worst errors come from failure to pay attention to the multitudinous little details of the patient’s history or those slight omissions in the physical examination which hide the diagnostic secret, or casual words dropped as an aside, a parenthesis or a footnote, which give the stage directions for interpreting the patient’s problems with clarity and skill rather than fumbling to unhappy failure. AS Wier Mitchell said, “There is a potent combina- tion of alertness in observation, with a never satisfied desire to know even the trifles of the case, which with sagacity, give a medical mental



character as rare as it is valuable.” In the larger picture each tiny key to medical or scientific progress is like the seed of a gigantic tree, for out of the small arises the great.

I have extolled the small, puffed up the little and emphasized the use of the microscopy of the intellect. These points we must cherish, not being ashamed of cultivating small facts or minute suggestions, hoping to get large ideas. I cannot tell you the more important things such as how to free mankind from greed and fear, how to enjoy beauty, find silence or solitude or escape our besetting paranoias in some distant utopia. For the present we must be content with the small and trivial, that we may savor and learn from their essence.

My theme has a simple lesson. Attending to the small may bring forth great fruits. Few of us are aroused by the slow fallout of useful little residual facts from the explosion of an idea or a careful but seemingly trivial observation. Facts lying all about us we reject as trifling, or disregard with casual apathy. Familiarity breeds contempt. We can never have enough seeing-eye dogs for our blind spots. A bird would be the last creature in the world to discover air, or a fish to discover water. May I conclude this certainly not short nor I hope small talk in tribute to your patron saint, Franz Groedel, with this admonition in the words of William Harvey :

“If you will but consent to examine the inferior animals-as did Heraclitus who, as Aristotle remarks, entered for that reason into a bake-house-I would say this to you, enter therein also for the immortal gods are not absent. It is in the little things that the Creator seems most great and in inferior beings that, sometimes, he reveals himself most clearly.”

ACKNOWLEDGMENTS

You who heard or have read this address will realize that my indebtedness to others is no little thing. I have in mind many obvious and some hidden lodes I have mined, stones I have at least lifted to pick up a nugget by the way-side. I first encountered the tale of Henry Cavendish long ago but renewed my inspiration from Wilfred Trotter who also emphasized the long lag between Lind’s discovery and the identification of vitamin C. Dr. Emil Witschi and Dr. John Opitz gave me the facts about the martyred cock of Basle. The tale of the Japanese crabs comes directly from Julian Huxley. Some of the things about the year 1543 I got from Heckshire’s fascinating study of Rembrandt’s “The Anatomist.” I have borrowed here and there from John Ryle, Alan Gregg, teachers, colleagues and students, many other friends whom I thank for my vast but amorphous indebtedness.

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the humanities in medicine: the medical and scientific significance of the seemingly small, trivial...

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