The Medical Detectives Volume I

by Berton Roueche

  The time, as it turned out, was only a few weeks off. Pasteur Ireated his first human patient on July 6, 1885. This now famous pioneer was a nine-year-old Alsatian boy named Joseph Meister. Two days before, while walking on a country road near his home, he had been attacked by a plainly rabid dog, knocked down, and bitten fourteen times. When Pasteur saw him, at the request of a family doctor, the boy was more dead than alive. In fact, Pasteur later recalled, it was only the apparent hopelessness of the case that induced him to attempt its treatment. The procedure he used was a freehand adaptation of the one he had developed in his most recent experiments with dogs, and it took ten days. During that time, the boy received thirteen inoculations, of increasingly potent vaccine. His immediate reaction was encouraging, and it continued satisfactory throughout the treatment. At the end of a month, his wounds having healed, he seemed to be fully recovered. He was. Joseph Meister lived to be sixty-four. He died in 1940, a suicide.

  The rehabilitation of Joseph Meister, which Pasteur described in a paper, entitled "Methode pour Prevenir la Rage apres Morsure" and presented at a meeting of the Academie des Sciences on October 26, 1885, created an instant and appreciative stir throughout the medical world. "[Rabies], that dread disease against which all therapeutic measures had hitherto failed, has at last found a remedy," the formidable neuropathologist Edme-Felix-Alfred Vulpian proclaimed. Assisted by this and other resounding testimonials, the Pasteur treatment, as the procedure came to be called, was in international use within a decade, and it has since been administered many thousands of times, with sufficient success to establish its worth as a reliable defensive tool. Or so it is generally assumed. To what extent the Pasteur treatment protects human beings against the development of rabies, however, is not known, and probably (in view of the natural scarcity of volunteers available for a series of controlled experiments) never will be. Its powers, in any event, are somewhat less than total. In a recent monograph, Harald N. Johnson, a staff member of the Rockefeller Foundation, observes, "On the basis of clinical evidence, there seems to be no doubt that rabies vaccine is effective in preventing the disease in the majority of the instances in which there is an expected incubation period of more than one month." But such an incubation period can only be expected in cases involving bites on the arms, legs, or torso. The chances that the Pasteur treatment will prevent the development of the disease when the victim is bitten severely on the head or neck are slight.

  Only one more or less controlled test of rabies immunization in human beings has ever been made. That was conducted by a World Health Organization team in 1954, in Iran. Its purpose was to evaluate an antirabies serum developed that year by Hilary Koprowski, assistant director of viral and rickettsial research at the Lederle Laboratories of the American Cyanamid Company. Serum differs from vaccine in that it contains—rather than merely stimulates the body to produce—the immunizing agents known as antibodies. A rabid wolf had burst into a mountain village, not far from the W. H. O. team's station, and bitten twenty-nine men, women, and children. As a matter of course, the Pasteur treatment was prescribed at once for all the victims. In addition, seventeen of the group, whose wounds included bites on the head or neck, were given immediate injections of serum. Eleven of them received one injection, the others two or more. The results were unmistakably clear. Twenty-five of the victims, including all who had received at least two injections of serum, survived. Of the four who died, three had been given only the Pasteur treatment, and the other a single serum inoculation. The limited efficacy of the Pasteur treatment is not, unfortunately, its only flaw. It has others. 1t is unpleasantly long (the present regimen, even when supplemented by serum, requires from fourteen to twenty-one days), it is, usually expensive (the average injection costs about five dollars), and, above all, it is disturbingly dangerous. Reactions to antirabies treatment range from those common in allergic conditions—erythematous or urticarial rashes, edema, syncope—to one known as neuroparalytic accident. Neuroparalytic accident varies in degree from a polyneuritis to ascending encephalomyelitis. The latter, in an uncomfortable number of cases, is permanently incapacitating, and sometimes fatal.

  The imperfections of the Pasteur treatment are not, of course, sufficient to deny it a place in the modern medical kit. There is, after all, nothing with which to replace it. In the opinion of most investigators, however, the imperfections are pronounced enough to discourage its use in any but cases of certain—or suspicious but unverifiable—exposure. It is also their urgent conviction that postexposure prophylaxis is, at best, an indirect defense against the menace of rabies. "There can be no question that the ultimate solution to the rabies problem is predicated on the control and eventual elimination of the disease from animal populations," the American Journal of Public Health commented editorially in May, 1955. "This may be accomplished by the setting up of transmission barriers, such as animal immunization, elimination of stray dogs, and the reduction of excessive numbers of wildlife vectors." It has been accomplished in a considerable number of countries. Britain, where a system of controls, rigidly enforced by the Ministry of Agriculture and Fisheries, was established around 1900, is perhaps the most notable of these. The last human exposure to rabies in England occurred nearly fifty years ago, and except for a handful of cases among imported dogs held in quarantine, there have been no outbreaks among animals there since shortly after the First World War. The Scandinavian countries— Denmark, Sweden, and Norway—have, by similar exertions, achieved almost as admirable a record, and so, among others, have Australia, New Zealand, and Malaya.

  The record of the United States, despite the existence of an elaborate apparatus of legislative controls, is less imposing. Except for Hawaii, where rabies has somehow never gained a foothold, few parts of this country are wholly free of the disease. Last year (1953), around half a million Americans were treated for bites inflicted by animals. Of these, sixty thousand were judged to have been exposed to rabies and received the Pasteur treatment. Three of them died. There were nine additional fatalities among persons who received incomplete or no treatment. The lowest incidence of human rabies in recent years was ten cases, in 1949. The highest was fifty-six cases, in 1944. Among domestic animals the average annual mortality is between seven and eight thousand. The persistence of rabies in man and beast throughout the United States has been variously explained, but two factors are considered decisive. One of these is indifference. Although many states have laws that specify a certificate of vaccination as a prerequisite for obtaining a dog license, and although all make some provision for the disposal of strays, such measures are seldom enforced, and then only in moments of epidemic panic. The other is the still enormous number of wild animals among which the rabies organism is endlessly perpetuated. This indigenous reservoir includes not only such conspicuous vectors as the fox and the skunk but badgers, raccoons, beavers, squirrels, and, since the early nineteen-fifties, the insectivorous bat.

  The full significance of the bat attacks on Frances Roberts, Carl Dayton, David Bonner, and Mabel Tate has yet to be determined. One thing, however, seems certain. These four people were not the victims of a fleeting freak of nature. Their experiences have since been duplicated elsewhere in the country. Three more attacks by rabid bats were reported in 1954. All occurred in Texas—the first, early in April, in San Antonio, and the second and third, in May and July, near Austin. The victims were a youth of twenty and two small children. Another was reported in October, 1955, in Madera, California, and involved a middle-aged man. Two more attacks—one certain and the other probable—were added to the record in 1956, and in May, 1957, an eleven-year-old boy was attacked near his home in Jamesville, Wisconsin, and bitten on the arm and chin. The 1956 victims were a soldier on maneuvers in Louisiana and a Texas State Health Department field epidemiologist named George C. Menzies. Dr. Menzies, at the time of his exposure, had been collecting specimens of cave-dwelling bats in central Texas to be examined for evidence of rabies infection. How and when he wa
s exposed is not known. It is only known that he returned to his home, in Austin, on January 1, and the following morning developed symptoms of rabies. Two days later he was dead. The six other victims received the Pasteur treatment, and survived.

  Dr. Menzies's last assignment was one of a number of similar studies that have been undertaken in collaboration with the United States Public Health Service since the Bonner episode in 1953. The investigation, which was understandably intensified by the harrowing discovery at Carlsbad Caverns two years later, is expected to continue for at least another year. Some months will then be required to accurately assess its results. The preliminary findings, however, have been tentatively correlated by Ernest S. Tierkel, chief of Rabies Control Activities at the service's Communicable Disease Center (now the Center for Disease Control) in Atlanta, and they are hardly reassuring. "During the last eighteen months or so, various field units have bagged in the neighborhood of ten thousand bats, in sixteen different states," Dr. Tierkel says. "About a hundred and fifty of them were positive for rabies. The group included four species of tree-living, or solitary, bats and eight species of cave-dwellers, or colonials. All, of course, insectivorous. Every state in which we've made a thorough study has yielded its quota of positives. The list, at the moment, is Alabama, California, Florida, Georgia, Louisiana, Michigan, Minnesota, Montana, New Mexico, New York, Ohio, Oklahoma, Pennsylvania, Texas, Utah, and Wisconsin. Those are the facts that we have to work with. What they mean—their epidemiological significance—is what we hope to find out.

  "In the early phases of our investigation, one possible conjecture was that what we were turning up wasn't really rabies. We thought it might be a new virus disease of bats so closely related antigenically to the rabies virus that the two couldn't be differentiated by the usual laboratory tests. But a little more laboratory work disposed of that possibility. The disease is definitely rabies. Another basic question is whether the disease has always been present in the insectivorous bats of the United States and we have only just discovered it, or whether it represents a recent northward invasion into this country from the vampire-bat-rabies areas in Latin America. I'm inclined to suspect that the latter is the answer. We know, at any rate, that the Mexican free-tails of our Southwest migrate deep into the vampire country of Mexico. According to some authorities, the vampires and the free-tails even share the same winter caves. We hope that's all they share. If it turns out, as some preliminary findings have suggested, that our bats also share the vampires' resistance to rabies, we're up against an extremely difficult problem. Vampires—some of them, at least —are known to be capable of transmitting the disease for long periods of time without showing any signs of illness themselves. In other words, they're like Typhoid Mary. They're true carriers. If our bats have that capacity, if we find that they sometimes attack simply because they're frightened and not because they've been driven into a frenzy by the disease, and if we also find that the bat represents an important reservoir of rabies in the United States . . . Well, those are only possibilities, of course. We don't have the data yet to even hazard an answer. But what if they're shown to be facts? I think it would be a very good idea to tighten up our system of rabies controls."

  [1956]

  CHAPTER 5

  ch3co2c6h4co2h

  (Aspirin)

  Around five o'clock on the afternoon of Wednesday, May 4, 1955, an office boy walked into the office of Dr. Harold Jacobziner, Assistant Commissioner for Maternal and Child Health of the New York City Health Department and chief of the department's newly established Poison Control Center, with a memorandum initialed by a clerk in the report room of the center. Dr. Jacobziner had his hat on his head and his briefcase in his hand, but the message turned him back to his desk. He sat down, glanced again at the paper, and paused for a moment of geographical calculation. Then he picked up the telephone and dialed the department's Bureau of Public Health Nursing. An official of his acquaintance answered the call, and after a brisk exchange of civilities Dr. Jacobziner got briskly down to business. He had a job for one of the nurses on the staff of the municipal health center that served the Corona section of Queens. The assignment was an investigatory visit to the home of a couple named (I'll say) Mr. and Mrs. Francis R. Poole. They lived on Alburtis Avenue, in Corona. According to a formal notification just received by the Poison Control Center, their son, a boy of three named Richard, had been admitted to Whitestone Memorial Hospital a few hours earlier. It was another case of acute acetylsalicylic-acid intoxication.

  Acetylsalicylic acid is the universal comforter known in the Esperanto of the laboratory as CH,C02C6H4C02H and almost everywhere else as aspirin. The latter is a term of proprietary origin that has achieved an all but total nomenclatural ascendancy over science. This triumph, though unique in medical history, was in no way uniquely accomplished. In common with all such fabrications that have outgrown the stigma of trade, the widespread acceptance of the name is generally attributable to its distinctive sound, to its attractive brevity, and to many years of pertinacious advertising. Nevertheless, unlike much commercial coinage, "aspirin" is not altogether an etymological freak. Its lineage is acceptably legitimate. It derives, roughly but rationally, from Spiraea, a botanical genus whose more prominent members (bridal wreath, meadowsweet, hardhack) are natural sources of salicylic acid, the active principle in aspirin. As it happens, however, the vegetable secretion of the acid is far from confined to plants of the Spiraea group. It also occurs in many other shrubs (jasmine, madder, partridgeberry), and in many legumes (peas, beans, clover), grasses (wheat, rye, sugar cane), and trees (beech, birch, olive, poplar, willow). The Spiraea were merely among the first such plants to be identified by modern pharmacology.

  That the bark, fruit, and leaves of these plants contain some revitalizing agent has long been common, if largely rustic, knowledge. Potions rich in salicylic acid are as old as herbal therapy, and almost as ubiquitous. Practically all races seem to have early grasped their usefulness. A draught whose ingredients included the juice of willow bark was esteemed by many North American Indian tribes as an antipyretic, or fever reducer. Another aboriginal people—the Hottentots of South Africa—made good use of an essentially similar decoction to ease the agony of rheumatism. The willow, among other salicylate plants, was also held in high regard throughout the early Mediterranean world. Hippocrates, in the fourth century before Christ, recognized its capacity for relieving both pain and fever. He also perspicaciously recommended topical applications of willow leaves, presumably as an antiseptic, in the post-partum care of maternity cases, and, less perspicaciously, the juice of poplar bark for various eye diseases. A generation later, Theophrastus, a pioneer botanist who succeeded Aristotle as head of the Lyceum at Athens, proclaimed the analgesic excellence of madder bark. He was, in addition, commendably inspired to urge the inclusion of madder in the manual of mild but effective diuretics. Theophrastus's success in thus broadening the therapeutic range of the salicylates was presently matched by other investigators. Around a.d. 75, Dioscorides, a Greek surgeon in Roman military service, rose from a series of experiments with the discovery that a paste composed of willow ash would safely remove such callosites as corns. In the course of this study, he had stumbled upon the further fact that his corn cure was almost as useful in combating the torments of gout. Pliny the Elder, the celebrated Roman encyclopedist, placed willow juice on the diuretic list. He then went on to propose an infusion of poplar bark as a specific for sciatica, and, amending, if not improving upon, Hippocrates, suggested poplar gum to druggists in search of a satisfactory eyewash. To these innovations, more imaginative minds rapidly added an unguent of willow bark as a cure for earache, one of willow leaves as a dressing for bloody wounds, and a willow poultice to dissipate fistulas and erysipelatous lesions. By the end of the second century, when Galen completed his valiant thirty- volume pharmacopoeia, all the remedial powers—great, small, illusory—of the salicylates had been noted and defined. Galen was the mighties
t of the Greco-Roman empirical pharmacists. He was also the last pharmacist of any stature anywhere until almost modern times. With the foundering of Rome, the whole of rational herbal therapy was lost to most of the Western world in the mists of Christian mysticism for well over a thousand years. ("All diseases of Christians are to be ascribed to demons," St. Augustine announced in the fifth century.) But for a scattering of practical folk-physicians, too simple to comprehend the complexities of fashionable piety, it might well have been lost forever.

  The classic grasp of botanical medicine managed to survive both Imperial Rome and the Holy Roman Empire only in the country kitchen. Among salicylate plants, the willow was the first to be recalled to the attention of science. An eighteenth-century English clergyman and naturalist named Edward Stone is usually considered its rediscoverer. His find, though unexpected, was not entirely adventitious. He knew, in a way, just what he was looking for. Stone, like many others of his time and inquisitive bent, had long diverted himself with the hope of finding in some common plant an inexpensive antipyretic substitute for Peruvian bark (or cinchona), as quinine was then called. One afternoon in 1763, while enjoying a rural ramble, he got wind of the fact (possibly during a pause in a country kitchen) that willow bark was locally much admired as a household remedy for the feverish chills of ague. A hint was all he needed. He sampled a piece of bark, found that it shared with cinchona an "extraordinary bitterness," and buckled down to work. Some months later, in a letter to the president of the Royal Society of London for Improving Natural Knowledge, he summarized his findings. His paper began with a word on the willow. "As this tree," he noted, "delights in a moist or wet soil, where agues chiefly abound, the general maxim, that many natural maladies carry their cures along with them, or that their remedies lie not far from their causes, was so very apposite to this particular case, that I could not help applying it; and that this might be the intention of Providence here, I must own, had some little weight with me." Then, having delivered himself of this rather shaky ratiocination, Stone got firmly down to cases. Providence had provided him with fifty of them. All were victims of "agues, and intermitting disorders," and although their seizures varied in severity, all were placed on the same regimen—twenty grains of powdered willow bark dissolved in a gram of water, administered every four hours. The results, he was happy to record, had been uniformly excellent.