THE PRINCES OF SERENDIP


THE PRINCES OF SERENDIP.
Read before The Hahnemann Club, Philadelphia, Pa., April 9, 1947.

VICTOR C. LAU…


Largely stimulated by a study of the professional career of Hahnemann, the circumstances surrounding his discovery and promulgation of the “Simili Principle in Medicine,” I became interested in the effect on science generally, and on medicine in particular, of discoveries accidentally or incidentally made.

Although chance or luck seems to play an important part in such discoveries, the fact that the observer has the mentality to comprehend their significance is the important thing. Similar observations by an untrained individual would likely pass unnoticed. Even though such occurrences are not anticipated, the comprehension of their importance removes the discovery from the category of sheer luck, coincidence or chance.

Soon I learned that my interest in such things was shared by others. The late Walter B. Cannon, former Professor of Physiology at Harvard University, produced a monograph, “The Way of an Investigator.” From this work I learned that there exists a word designating such accidental observations. The word is SERENDIPITY.

Serendipity was coined by Horace Walpole in 1754, and suggested after he had read a fairy tale entitled, “The Three Princess of Serendip.” Serendip, according to Cannon, is the ancient name of Ceylon. The story goes on to state that, “as their highnesses (the three princes) travelled, they were always making discoveries, by accident or sagacity, of things they were not in quest of.” Walpole suggested that SERENDIPITY be added to our vocabulary and Webster gives as its definition, “The gift of finding valuable or agreeable things not sought for.”.

Alton Ochsner+ The William Henderson, Professor of Surgery and Head of Department of Surgery, School of Medicine, Tulane University of Louisiana. of the Ochsner Clinic in New Orleans has been equally interested in these matters. I wish to give full credit to this author from whose works I have borrowed and quoted quite freely. In Ochsners words: The Influence of Serendipity on Medicine Jerome Cochran Lecture. “No reading is more stimulating than stories of accidental discoveries and their influence upon medical science. Often more amazing than tales of fiction and more exciting than fairy legends are these happenings in real life.”.

Let me remind you of a few examples:.

The Archimedian Principle- Tradition has bequeathed to us the intriguing account of Archimedes, Greek inventor and mathematician, who noted water overflowing as he stepped into his bath. The thought that struck him, as he ran home naked, crying, “Eureka I have found it” was the hydrostatic principle which bears his name a body immersed in a liquid sustains an upward pressure equal to the weight of the liquid displaced.

The Musical Scale and the Mathematics of Acoustics In the writings of Hippocrates, the father of medicine, we find many evidences of the strange and the unusual. Pythagoras. Greek philosopher, is said to have thought of the musical scale upon passing a blacksmiths shop and hearing the hammer strike the anvil, and later introduced the mathematics of acoustics.

The Law of Motion- There are the timeworn tales of Galileo, father of mathematics, watching the swaying lamps in the Cathedral of Pisa, envisioning the laws of motion.

There are many of these interesting stories to be told and as many Princes in the Realm of Serendip. There was the accidental discovery of America when Columbus was seeking a short route to the East; James Watt, as a youth, noting the possibility of the steam engine as he watched the tea kettle lid rise and fall; and of Sir Isaac Newton, observing the falling apple and introducing the theory of gravitation.

Galvanism In the 1780, in the city of Bologna, electrophysiology originated in the home of Aloiso Galvani. His fair wife Lucia, was not in good health and a diet of frogs legs was prescribed for her. The frogs legs were suspended by a copper wire from an iron balustrade and when, as a result of swinging in the breeze, they touched the iron, violent convulsions of the muscles were noted. Galvani set about to learn the cause of this reaction. His elaborate studies and experiments resulted in the description of galvanism. Volta, his contemporary, later analyzed this current and these were the chance beginnings of our knowledge of animal electricity.

The Father of Modern Surgery- Ambroisia Pare, who lived in the 16th century, quite by accident discovered that simple dressings were better for gunshot wounds than the timeworn cauterization with boiling oil which was the accepted method of the time.

“Following a heavy engagement in which there were many casualties, the supply of boiling oil ran out. At last my oil was used up and I was constrained to apply in its place a digestive made of yolks of eggs, oil of roses and turpentine. That night I could not sleep, fearing the effect on the poor patient.” The results were astonishing no inflammation and no swelling, obviously a superior method of wound treatment had been discovered.

Digitalis in Therapeutics There is a delightful story of a country doctors, William Withering, who knew a family of farmers in his native Shropshire who were very successful in treating dropsy with a secret concoction of herbs.

Withering was a skilled botanist. He found that the active ingredient used was the flower of the purple fox-glove, digitalis. Witherings monograph “An Account of the Fox-glove” is considered a medical masterpiece. Dropsy had been considered a primary disease until this physician showed it could be due to cardiac irregularities. Here again was an incidence of finding “valuable or agreeable things not sought for.”.

The Stethoscope (Auscultation and Percussion) Various legends are attached to the origin of the stethoscope. The shy and brilliant young French physician, Theophile Laennec, was quite disturbed that he could not properly examine the chest in the case of a robust young woman, in fact of many of his patients.

One day while walking through the Gardens of the Louvre, he noticed a youth tapping the end of a long beam while his companions at the opposite end had their ears pressed close to the beam to receive the sound travelling along this make-shift telephone.

Immediately he grasped the principle and hurried to the Necker Hospital, rolled a piece of paper into a cylinder and applied it to the chest of his patient.

Thus, in 1816, the stethoscope was born. Auscultation became practical to the crowning glory of physical diagnosis.

Fifteen years before, Leopold Auenbrugger, a young Austrian physician, had applied the “tapping system” or percussion, to the body because he had observed that innkeepers were able to determine how full beer kegs were by tapping the surface of the keg.

Puerperal Fever Ignaz Semmelweiss, a young Hungarian, died in 1865 at the age of 47, a victim of the disease he had clarified for the profession. In that day, from 10-30 per cent of mothers attended by medical students and doctors died, whereas, strangely enough, the mortality was only 3 per cent in the division of the hospital where midwives attended the patients. Semmelweiss was puzzled by this discrepancy. He studied the problem unceasingly, attended post-mortems of the dead women, but found no explanation.

A friend and co-worker died of blood poisoning which had been contracted while performing an autopsy upon a mother dead of childbed fever. Semmelweiss noted the similarity of the pathologic changes in his friends body and those dying from puerperal fever. He became convinced that puerperal sepsis was contagious and that it was carried from the autopsy room to the delivery room by the hands of the students and instructors. When he ordered scrubbing of the hands with soap, water and nail brush followed by disinfection with chloride of lime, the mortality rate showed a spectacular fall.

Semmelweiss was persecuted for preaching this doctrine. It would seem that persecution of its own is a thing which the medical profession has always been able to perform quite thoroughly, if not always judiciously.

The Etiological Factor in Scabies- In this instance it was a student, F. Rennuci, a pupil in the class of the famous dermatologist, Baron Aliberti, of Paris, who made the contribution. Rennuci persisted to argue in spite of an obstinant teacher that “all the old women in Corsica, my country, know the cause, and they know how to cure the itch.”.

He recalled to his superiors how the old women would prick the skin of their fingers and remove a little red spider or insect and following this the itch would disappear. Finally Rennuci was permitted t o demonstrate the validity of this theory and thus the etiologic factor in scabies was proved.

Vaccination against Smallpox- It was a milkmaid who, in 1768, said to the famous Edward Jenner, “I cannot take smallpox, because I have had the cowpox.” Jenner never forget this remark and later mentioned it to his teacher, John Hunter, the great English surgeon, explaining that this was an idea prevalent among the farmers and dairy maids in his native Gloucestershire. Considerable experimentation followed and in 1786, opportunity came. According to Jenners own words:.

“The first experiment was made upon a lad by the name of Phipps, in whose arm a little vaccine virus; was inserted which taken from the hand of the young woman who had been accidentally infected by a cow. Not withstanding the resemblance which this pustule, thus excited on the boys arm, bore to a variolous inoculation, I could scarcely persuade myself the patient was secure from the smallpox. However, on his being inoculated some months afterwards, it proved that he was secure.” This was the origin of smallpox control the scientific prophylaxis through vaccination.

Aspirin and the Coal-Tar Dyes- In 1856, an 18-year-old bus boy, William Perkins worked in the laboratory of Faraday. The chemistry teacher had set for him a task no less difficult than the making of synthetic quinine (finally accomplished in 1944 as a wartime expediency). Perkins obtained only a thick, black, tar- like substance by oxidizing aniline with chromic acid. In disgust he washed the dirty test tube and a purple solution resulted the first aniline dye. From this accidental discovery over 30,000 different dyes have resulted. Bayer then started with the same raw material and produced aspirin.

Preventive Vaccination- This therapeutic measure was enhanced through through the accidental observations of Louis Pasteur in 1880 who, together with his co-workers, Roux and Chamberland, was experimenting with cultures of chicken cholera. During his experiments some culture were allowed to get old. Pasteur knew that these were old cultures but was determined to find the effects of their injection into the chickens. The chickens became drowsy but did not die and were well the following morning.

After a two weeks vacation, Pasteur returned to his experiments. The only chickens that had survived previous injections were the two that had been given the old cultures. It was decided to reinject them, together with other chicks, this time with new and virulent culture. The only chicks to survive again were the two which were previously injected with old cultures.

Making this chance observation, Pasteur said, “This is my most remarkable discovery, a vaccine more scientific than the one for smallpox where no one has seen the germ; we will apply this to anthrax and we will save lives” and he did.

The development of collateral circulation John Hunter, who was forever experimenting, tied the external carotid artery on one side of a deer, observed the antler on that side become cold to touch, and a week later, much to his surprise, found it warm again and the antler actually growing. After sacrificing the buck he found the ligature in place and also noted that small branches of the ligated vessel above and below the ligature were enlarged and that the ligated segment was being circumvented through the newly opened channels, restoring the normal blood supply to the antler.

Several months later he was called upon to treat a patient with a popliteal aneurysm a condition which was usually treated by amputation above the site of the aneurysm. He recalled the experience he had had with the buck ligated the artery above the aneurysm in the lower part of the canal which now bears his name, and in six weeks the patient was discharged as well.

Claude Bernard, who lived from 1813 to 1878, was one of the worlds greatest physiologists, and was an experiment who coupled imagination with ability. Three discoveries which are examples of his recognizing the importance of accidental phenomena were the discovery of the glycogenic function of the liver, the finding of the true nature of the action of the pancreatic juice, and the discovery of the function of the vasomotor nerves;.

Pancreatic Function-(Bernard, Claude 1813-1878) I quote from Goldstein in the Annals of Medical History- “Practically all present knowledge of absorption of food materials was determined by the light of Bernards discoveries relating to intestinal digestion. It was the picture of fat emulsion that first brought his attention to pancreatic secretion.

He was investigating comparative digestion in herbivorous and carnivorous animals and noted that fat introduced into the stomach of a rabbit did not become milky and chyle-like until it reached a point much lower in the intestine than was observed when a similar procedure was instituted in a dog, where the entrance of the pancreatic duct is common with the bile duct. He further noticed that fat emulsification always occurs below the entrance of the pancreatic duct and never above it, excluding the action of the bile. He immediately investigated the nature of this phenomenon, which culminated in the discovery of the digestive nature of the pancreatic juice.”.

Vasomotor Nerves- (Bernard, Claude- 1813-1878) This discovery established the reflex control of circulation and was of immense value in clearing up heretofore obscure physiologic and pathologic phenomena which had been thought vital processes, and not explainable on a physio-chemical basis. This discovery was an unlooked-for observation. He was studying the effect of sectioning certain nerves on the nutrition and heat production, in the tissues they supply.

He thought that the nerves were the factors controlling heat production and was greatly surprised to find that section of the cervical nerves in the neck of a rabbit caused a marked increase in heat production, instead of the expected fall. He also noted the accompanying vascular congestion, but did not correlate the two, since he believed firmly that nervous influences were sufficient to account for the thermal change. It remained for Brown-Sequard to identify the increased heat as due to paralysis of the blood vessel wall, resulting in vascular dilation and congestion.

Glycogenic Function- (Bernard, Claude 1813-1878) Bernard was concerned with diabetes, and, in feeding animals on a rich diet of sugar, discovered an abundant presence of sugar in the hepatic vein, but none in the portal vein. The liver then evidently manufactured sugar out of certain substances brought to it by the blood in the portal vein. He later showed that sugar had a precursor in the liver which he called glycogen (sugar former), which produced sugar after the action of certain enzymes. The present-day studies of nutrition and dietetics are indebted to the fundamental works of Bernard in establishing the fate and mechanism of utilization of carbo-hydrates.

The Operation for Hypertrophic Pyloric Stenosis -Although the original operative treatment of congenital hypertrophic pyloric stenosis consisted of gastro-jejunostomy, the Fredet-Weber operation which consisted of a longitudinal incision of the hypertrophic musculature and its transverse closure was the great advance in the treatment of this condition. On August 23, 1911, Conrad Ramstead, when operating upon an infant with hypertrophic pyloric stenosis in which he attempted a classical Fredet-Weber operation, had difficulty in closing the longitudinal incision by transverse suture. The exposed mucosa was covered with the tag of omentum.

His account of this was as follows: “When I was first confronted with an operation for pyloric stenosis, I decided to perform the partial pyloro-plasty according to Weber. During the operation I noticed, after section of the firmly contracted, almost bloodless and hypertrophied muscular ring, that the would edges gaped markedly. I had the impression that the stenosis was already overcome.

Nevertheless, I sutured the incision transversely in order to complete the Weber pyloroplasty. The tension of the wound edges was, however, very great and the sutures cut through so that the union of the wound edges in the opposite direction was incomplete. I therefore covered the sutured area with a tag of omentum for protection.” In this way he proved that transverse closure of the incision was unnecessary and probably harmful since it contributed to further obstruction through infolding of the mucosa.

Ethylene as an Anesthetic Agent- The use of ethylene as an anesthetic agent was largely the result of an accidental observation. It was not until 1918 when Arno B. Luckhardt and R.C. Thompson began working with ethylene as an anesthetic agent. Their original observations were made upon animals. Their work was stimulated by the observations of William Crocker and Lee Irving Knight, who, in 1908, had studied the effects of ethylene on carnations. They showed that carnations brought into the city frequently wilted very early.

They found that the illuminating gas which contained about 4 percent of ethylene was the guilty offender. In order to determine what effect this poison had on animal life, they undertook their investigation. Ethylene gas was administered to an animal; the animal presumably died. On removing the gas however, it was found that the animal was simply asleep and that ethylene was an efficient anesthetic agent.

Diabetes and its relation to Pancreatic disease- The discovery of diabetes and its relationship to pancreatic disease was accidental. Von Mering and Minkowski, in the latter part of the last century, were studying the role of the pancreas in digestion. Pancreatectomy was done in a number of dogs. Following this procedure a chance observation was made by a laboratory assistant that swarms of flies were attracted to the urine of these animals. Upon examination of the urine it was found to contain a great quantity of sugar. Thus, relationship between the pancreas and the production of glycosuria was established.

A chance observation led to the discovery of insulin by Frederick Banting, who, in perusing an article by Moses Baron in Surgery, Gynecology and Obstetrics, learned that this article described a case in which a stone had blocked the pancreatic duct and had caused atrophy of the pancreatic cells except those of the islands of Langerhans. Baron reproduced this syndrome experimentally in the dog by ligating the pancreatic duct.

According to Banting, he was greatly impressed by this observation and at two oclock in the morning he rose and jotted in his notebook the following: “Ligate pancreatic ducts of dogs. Wait 6 to 8 weeks for degeneration. Remove the residue and extract.” He reasoned that an extract of the island of Langerhans might relieve the excess secretion of sugar in diabetes, which theory was subsequently proved by his experimental results.

The discovery of Xray- Wilhelm Conrad Roentgen truly electrified the meeting of the Physical and Medical Society, December 18, 1895, when he presented his four-thousand-word paper, “On a New Kind of Ray”. That his finding is purely accidental is true, but Roentgen was prepared to investigate intelligently this new phenomenon and was diligently perseverant in continuing his investigation which established the science of radiology.

He was working alone in a darkened laboratory when he discovered by chance that those astonishing new rays had the property of passing through solid matter. He was working with a cathode ray tube with a jacket of black cardboard and was testing the opacity of the cover by agitating the tube when he suddenly noticed a light which appeared some distance from the tube of his barium platinocyanide screen. Accidentally his hand passed between the tube and the screen and there appeared a faint image of the hand on the screen.

The outline of the fingers was visible and even the bones, which appeared as dark shadows. He was so impressed by this that he begged his wife to place her hand on the holder loaded with a photographic plate. For thirteen minutes the rays were directed from one of his tubes on to the hand, and when the plate was developed it was possible to visualize the outline of the hand, the bones appearing lighter within the darker image of the finger, and the two rings on her fingers appeared lightest of all. By this accidental observation, x rays and their value in diagnosis in medicine were discovered.

Uranium and Radium- In 1896, Henri Becquerel, a distinguished French physicist, wrote upon radiation from uranium. He tells how he experimented with various substances exposed in the sunlight, and placed them in a dark room on photographic plates for varying periods of time in order to determine the intensity of irradiation of the various substances with which he experimented. Among these were Uranium and pitch-blend. One day the experiments were not done because there was no sun.

He states, “I kept my arrangements all prepared and put back the holders in the drawer of the case and left in place the crusts of uranium salt. Since the sun did not show itself for several days, I developed the photographic plate, expecting to find images very feeble. On the contrary, the silhouettes appeared with great intensity.” Thus radiation from uranium was discovered.

Becquerel extended his experiments to include radium and subsequently observed that radiation from this element would destroy skin because, while carrying a glass tube of radium in the pocket of his waistcoat, he became burned. He complained to the Curies, from whom he had received the radium, and declared,: “I love this radium, but Ive got a grudge against it.” It is because of the original observations by Becquerel that the Curies became interested in radioactive substances and demonstrated radium.

Victor C. Laughlin