The Medical Detectives Volume I

by Berton Roueche

  Although it was Dr. Witte who brought the attack on Mrs. Roberts to general medical attention, his report was not the first account of her misadventure. The first was a newspaper story, less comprehensive but equally stirring, that was widely published throughout the East within a day or two of the incident. Among those whom it particularly stirred was Frederick R. Taylor, an internist and professor of medical literature at the Bowman Gray School of Medicine of Wake Forest College, in Wake Forest, North Carolina. The news did not merely startle Dr. Taylor. It also inspired him to reflection, the nature of which he presently communicated to a colleague in Georgia. His letter, which has been preserved, began with a forceful summary of the Roberts case. This was followed by some lines to the effect that he had long been imperturbably aware of the existence of rabies in Latin-American vampires. "But," he then exclaimed, "an ordinary, insectivorous bat!!! What would happen if the Western bats that live literally by the millions in Carlsbad Caverns, New Mexico, got an epidemic started there? I have seen a high cloud of countless hordes of bats come out of the caverns' mouth at dusk. Too horrible to contemplate!"

  Dr. Taylor's letter was dated October 19, 1953. Little more than two years later, on February 1, 1956, a news story authorized by the New Mexico State Department of Public Health appeared in the Santa Fe New Mexican under a six-column headline reading, "CARLSBAD CAVE BATS INFECTED WITH RABIES." "Rabies," it began, "has been discovered among the millions of bats at Carlsbad Caverns. It was a rabies epidemic which caused the death of hundreds of the Caverns bats in August and September of last year." The account continued:

  Last Aug. 20, officials of the National Park Service at Carlsbad noticed dead and dying bats in increasing numbers. They were found on the floor of the caverns and in its entrance. Ranchers in the area also found dead bats. At that time it was thought that extensive insecticide spraying might have caused the deaths during the 10-day epidemic. But tests by the U. S. Public Health Service found no evidence of this. Instead, tests were begun to see if rabies had caused the deaths.

  Lt. Col. Kennet Burns, chief of the veterinary virus laboratory at Ft. Sam Houston, Tex., collected specimens of dead and dying bats for examination while the epidemic was going on. Virus examinations by Burns revealed the presence of rabies in more than 50 per cent of the specimens, the department said. In addition, blood samples from a large number of live bats collected in flight at the caverns after the epidemic showed the presence of antibodies against rabies, indicating that many of the bats had been exposed to the disease some time in the past. . . .

  The story also stated that although no human being had ever been known to be bitten by a bat while visiting the caverns, the health authorities had warned people against touching any of the creatures they might find dead or dying there.

  Rabies is one of around sixty human diseases now known, or confidently supposed, to be of viral origin. Its causative agent is thus a member of the most mysterious form of life on earth. About all that can be said of the viruses is that they are supremely small (some are only just within the reach of an electron microscope), infinitely numerous (not even the bacteria are more ubiquitous), and almost incomparably specialized. All viruses are obligate intracellular parasites. They share with the rickettsiae the otherwise unique distinction of being unable to grow or reproduce outside the protoplasmic tissue of a living host. In general, the severity of a viral invasion reflects the functional importance of the particular cells to which the invaders are drawn. The virus of rabies is a neurotropic virus. Like the viruses of poliomyelitis and the several encephalitides, it has a special affinity for the cells of the central nervous system. It has, however, little else in common with any other virus. Its range, for one thing, is extraordinarily wide. Unlike the great majority of viruses (including the agents of smallpox, measles, yellow fever, poliomyelitis, infectious hepatitis, and the common cold), which can find in nature fewer than half a dozen satisfactory habitats, it is able to exist comfortably and abundantly proliferate in any warm-blooded animal. Its means of transmission is also peculiarly its own. Most viruses insinuate themselves into n host through either the respiratory passage or the gastrointestinal tract. A few are conveyed by bloodsucking insects. The rabies virus enters by way of a bite contaminated with the saliva of one of its victims. In this respect, it might seem to resemble the various mosquito-borne viruses, but the resemblance is merely apparent. The latter are transmitted in the natural course of the carrier's search for food. There is nothing natural about the transfer of the rabies virus. It wrings collaboration from its carrier hosts by torturing them into a homicidal fury. The incubation period of rabies (or the interval between the implantation of the organism und its establishment in the brain) is largely determined by the depth of the wound, its proximity to the brain, and the size of the original viral colony. This period, though disconcertingly variable, is seldom shorter than fifteen days and almost never longer than a year. But whether the virus reaches its destination in days or weeks or months, the result is inevitably the same. Rabies, in man, is a fatal disease.

  The symptomatology of rabies is essentially the same in all susceptible animals. There are only superficial differences. The onset of the disease is generally mild and always indistinct. In man (and, insofar as can be determined, most comparably complicated animals), its earliest manifestations are those of any infection—a little fever, a dull headache, a scratchy throat, occasional nausea. This phase frequently lasts for two or three days, and sometimes even four, and is followed by a tingling pain at the site of the wound—the first diagnostically significant indication of rabies. Its grip, already fixed beyond release, then suddenly tightens. The muscles stiffen, the nerves tense, and the mind begins to fray with temper and apprehension. Anxiety quickens into fear. There is a vivid sense of approaching doom, a certainty of death. "A [rabid] patient weighed down with terror often becomes maniacal," D. L. Harris, medical director of the Pasteur Clinic in St. Louis, noted in a recent clinical study. "An excessive flow of thick tenacious saliva pours over his face and neck and becomes smeared on his hands and clothes and over the bedding and floor. These periods of rage are followed by moments of calm in which [he] usually shows anxiety for the safety of those around him and warns them of the approach of another crisis. Hyperesthesia of the skin to changes of temperature, and especially to currents of air, and increased sensitiveness to sound and light mark the progress of cerebral irritation. Convulsions are brought on by the least irritation and by the slightest current of air . . . the breath comes in spasms, dyspnea is extreme, and there are epileptiform seizures or tetanic rigidity. Hydrophobia is rarely absent. . . . When the patient [attempts to drink], there is an immediate viselike contraction of the muscles of deglutition with an excruciatingly painful spasm of the glottis and the pharynx. The body trembles with convulsive movements, the jaws are clenched, respiration is impossible. . .. After several attempts to drink, the pain is so terrible that despite intense thirst [the patient] cannot be induced to try to swallow liquids, and the sight of water or mention of the word brings on an attack. As a rule, death occurs after two or three days from cardiac or respiratory failure."

  Although all highly developed animals are equally responsive to its gothic embrace, the rabies virus has its favored circle of hosts. It is naturally most inclined to frequent those best equipped to further its spread. This largely confines its normal range to the more prolific and short-tempered carnivores, a group that includes the fox, the wolf, the coyote, the jackal, the skunk, the mongoose, the cat, and the dog. Of these, the last, for reasons still obscure, has always been its most consistently conspicuous victim. The dog is also the animal in which its depredations were first recognized as those of a specific disease. Just when that occurred is uncertain. An illusion in the Iliad to "canine madness" has persuaded many medical historians that rabies may have been known to the Mediterranean world as early as the tenth century before Christ, and most believe, on the basis of rather stronger internal eviden
ce, that the fifth-century Greek philosopher Democritus, who is chiefly remembered as a pioneer atomic theoretician and the teacher of Hippocrates, was probably conscious of its existence. The first explicit reference to rabies of which there is any record was set down by Aristotle, around 335 B.C., in his Historia Animalium.

  Dogs suffer from three diseases: lyssa, quinsy, and sore feet," he noted. "Lyssa drives the animal mad, and any animal whatever, including man, will take the disease if bitten by a dog so afflicted; the disease is fatal to the dog itself, and to any animal it may bite, man excepted." Lyssa, a transliteration of Xucroa, means frenzy," and is the name by which rabies was originally known. The Romans gave the disease its modern name, which derives from rabere, the Latin for "to rage," and has been in common usage since the first Christian century.

  The Romans also modernized the Greek conception of rabies. A gifted encyclopedist of the early empire named Aulus Cornelius C'clsus was among the first to raise his eyes from the pages of Historia Animalium and look squarely at the world around him. Having done so, he proceeded to challenge the first of Aristotle's comfortable exceptions as myopically veterinarian. All animals, he decided in his classic De Medicina, were equally susceptible to rabies. Celsus was willing, however, to concede Aristotle's second exception. It was possible, his studies informed him, that the disease could be mastered in man. He then went on to propose a still valid preventive technique ("the wound . . . must be cauterized") and, less acutely, an antidote and a course of treatment. This consisted of thirty herbal ingredients (including poppy tears, lllyrian iris, Gallic nard, white pepper, male frankincense, and turpentine) mixed with honey and dissolved in a tumbler of wine. Its omission, he added, was risky. "When too little has been done for such a wound it usually gives rise to a fear of water," he wrote. "In these cases there is very little hope for the sufferer. But still there is just one remedy, to throw the patient unawares into a water tank which he has not seen beforehand. If he cannot swim, let him sink under and drink, then lift him out. If he can swim, push him under at intervals so that he drinks his fill of water even against his will. For so his thirst and dread of water are removed at the same time. Yet this procedure incurs a further danger, that a spasm of sinews, provoked by the cold water, may carry off a weakened body. Lest this should happen, he must be taken straight from the tank and plunged into a bath of hot oil."

  Celsus's uneasy concession that rabies need not be fatal to man was accepted without recorded dispute for fifteen hundred years. So, except for certain pharmacological refinements, were his methods of breaking its hold. Pedanius Dioscorides, whose De Materia Medica was the standard pharmacopoeia throughout the Roman era, contented himself with offering two alternative antidotes. One was a draught of hippocampus, or sea-horse, ashes. The other had as its active principle the leaves of the bladder campion. "This, being beaten when it is green, with old swine's grease, is good for the mad-dog-bitten," he wrote. Rufus of Ephesus, a second-century physiologist, preferred a draught of "wormwood, aristolochia, Lycian thorn, decoction of river- crayfish, water germander, rock-parsley, and the root called gentian." Even Galen, the most observant, as well as the most imaginative, medical investigator in the millennia between Hippocrates and the Renaissance, had nothing to add to Celsus but a polished definition: "[Rabies] is a disease that follows the bite of a mad dog and is accompanied by an aversion to drinking liquids, convulsions, and hiccups. Sometimes maniacal attacks supervene."

  After Galen, and the subsequent canonization of Greco-Roman medicine, the illumination of rabies, like that of all disease, was considered complete, and the subject complacently closed. The first attempt to reopen it was made in the sixteenth century. A Veronese savant named Hieronymus Fracastorius is usually celebrated for this act of desecration. Rabies, he announced in 1546, in his precocious Contagions, and Contagious Diseases and Their Treatment, was an infectious disease, always communicated by the injection of saliva into the blood, and, notwithstanding the protestations of pharmacy, always irremediably fatal. He also emphasized this novel conception of the disease in a dissertation on hunting dogs. "What particularly calls for the care of the skilled mind," he wrote, "is when, inflamed with rabies, [the dog] attacks now these, now those and, turning against the master himself, he inflicts the incurable wound." Fracastorius was a man of towering intellectual stature. In addition to being a notable physician, he was a poet (the term "syphilis" derives from his A Poetical History of the French Disease), a botanist, a geographer, a musician, a mathematician, and an astronomer, and his morbid view of rabies received a respectful hearing. It even, for a time, attracted a few admirers. But hope and habit were too strong, and within a generation the more congenial classic conception resumed its interrupted vogue.

  Celsus's hydrotherapeutic regimen, adapted to the ducking stool, was commonly prescribed in cases of rabies throughout the sixteenth and seventeenth centuries, and at least on occasion (an essay by Oliver Goldsmith, written around 1765, refers to "a little boy bit in the leg, and gone down to be dipped in the salt water") during much of the eighteenth century. His pharmacological influence continued even longer. In 1806, the New York State Legislature passed, without recorded opposition, a bill entitled "An Act for Granting a Compensation to John M. Crous, for Discovering and Publishing a Cure for the Canine Madness." Crous's cure, for which he was granted a thousand dollars, was a tablet to be swallowed with water. Its components included the pulverized jawbone of a dog, the dried false tongue of a newly foaled colt, and a pinch of corroded copper taken from an English penny minted in the reign of George I. Other American physicians of that time, perhaps less impressed by royalty, favored a remedy composed of bole armeniac, alum, chalk, elecampane, and black pepper. They also had confidence, as did many European doctors, in the curative powers of concretions, similar to kidney stones, that are sometimes found in the intestines of deer, goats, and other herbivorous animals and that, because they were used as a specific in the treatment of rabies, became known as madstones. Such concretions, being formed of mineral salts, are porous and somewhat absorbent. These qualities helped to support the belief that a mad- stone applied to a rabic wound would promptly extract the venom. "This afternoon called on by a man in Jeffersonville to apply the madstone to a little son bitten a day or two previous," an Indiana judge, soldier, and statesman named John McCoy noted in his journal on June 9, 1848. "Rode through' the rain and reached there about sunset. Induced to think the dog mad." In 1879, at an auction in Texas, a madstone brought two hundred and fifty dollars. That would be the equivalent of about a thousand dollars today.

  The supposition that rabies could be cured by some curious pill or poultice expired with the nineteenth century. The absolute lethality of the disease is now universally accepted. One reason for this abrupt resignation to reality is that the evidence assembled by modern medical science leaves no room for doubt. Another is that the truth is no longer unbearable. Since the eighteen-eighties, when Pasteur was inspired to adapt to rabies his epochal discovery that the pathogenic properties of a microorganism can be attenuated (by drying, or treatment with certain chemicals, and passage through a succession of laboratory animals) without affecting its capacity to generate protective antibodies, a reliable means of hobbling the disease has been everywhere at hand.

  Pasteur conceived the idea of rabies prophylaxis in 1880. By the end of 1883, he and his associates at the Ecole Normale, in Paris, were able to produce a stable strain of suitably domesticated virus. This was followed by two series of experiments establishing beyond dispute that the strain was immunologically effective in dogs. The first of these was brought to a brilliant close in June, 1884, with a formal trial before a committee of scientists appointed by the French Government. For this definitive test, Pasteur chose two previously vaccinated dogs, two untreated dogs, and two untreated rabbits. After being examined by the committee, the six animals were anesthetized and trephined. Each animal was then identically inoculated with a quantity of material drawn fro
m the brain of a demonstrably rabid dog. When the operation was completed, the animals were separately confined, and all received the same postoperative care. Two weeks later, the four controls, or untreated animals, developed rabies, and died. The vaccinated dogs remained in normal health. The second series of experiments, though begun at about the same time, continued into the following year, and the results were equally emphatic. They showed that it was possible to immunize a dog against rabies not only before but, if the step was undertaken promptly, after exposure to the disease. Pasteur emerged from this revolutionary triumph with a vision of one even more revolutionary. "What I aspire to [now] is the possibility of treating a man after a bite with no fear of accidents," he wrote in the spring of 1885. "... I have not yet dared to treat human beings after bites from rabid dogs. But the time is not far off."