The Medical Detectives Volume I

by Berton Roueche

  "I looked in on Mason the following morning. He was still sick, still flat on his back, but he seemed to be perfectly rational. Except, I should say, on the subject of his tomatoes. He knew what had happened. Somebody on the staff had already told him the cause of the family outbreak. But he didn't quite believe it. He had never heard of Jimson-weed poisoning. Jimson weed was a weed like any other weed to him. I didn't argue with him. We just talked, and I finally got him around to telling me about his grafting technique. The Jimson-weed plant he had used was growing in a fence row not far from his house. He made the graft at the first fork of a secondary branch, snipping off the branch and inserting the sharpened stem of a tomato plant into the pithy center of the stump. Then he fastened the parts together with a clothespin until the union healed. And that was all there was to it. It was simplicity itself. I was really quite impressed, and I told him so. I asked him how he happened to get the idea. He looked a little surprised. What idea? The idea of grafting tomatoes? Why, that wasn't his idea. He got it from a friend—a fellow over in the next valley. I'll give him the name of Clayton. Clayton had been growing tomatoes on Jimson-weed grafts for years. He was always fooling around with plants.

  "Well, that was an interesting piece of news. It was flabbergasting. And it raised some flabbergasting questions. Why hadn't we heard of this before? Or had Clayton never been poisoned? And if he hadn't been poisoned, why not? And so on. It was some little time before we got any answers. By 'we' I mean the State Health Department, the Hawkins County Health Department, and the interested doctors here at the hospital. The first step was one that would have been taken in any case. Somebody from the county went out to Mason's farm and got a sample Jimson-weed tomato and sent it in to Nashville for analysis. Then Clayton was interviewed. He confirmed what Mason had said. He and his family had been growing and eating Jimson-weed tomatoes for years— since 1958, to be exact. No, he never sold any. There were only enough for home use. They ate them raw, they ate them stewed, and they ate them canned. And without any ill effects. The very idea that they might be poisonous astonished him. He, too, had never heard of Jimson-weed poisoning. As it happened, he hadn't yet sampled this year's crop of Jimson-weed tomatoes, but he was glad to give the investigator a couple for analysis.

  "We got the report from the laboratory sometime the following week. It made rather curious reading. It raised as many questions as it answered. It fully confirmed the cause of the Mason family's outbreak. They were victims of Jimson-weed poisoning. There are no exact data on the toxicity of hyoscyamine, the principal stramonium alkaloid. It is known, however, that hyoscyamine is somewhat more toxic than atropine, and that as little as two milligrams of atropine will produce such symptoms as rapid pulse, dryness of the mouth, pupil dilation, and blurred vision. Well, the Mason tomato yielded 4.2 milligrams of stramonium alkaloid per hundred grams of tomato. That worked out to 6.36 milligrams of alkaloid for the whole tomato. In other words, it was very definitely toxic. But the Clayton tomatoes were different. They averaged just 1.9 milligrams per hundred grams of tomato. Or a scant three milligrams for the whole. I couldn't understand it. None of us could. Why should Mason's Jimson-weed tomatoes be twice as toxic as Clayton's? Why should there be any difference at all? That was one question. And how was it that the Claytons could eat their tomatoes with impunity? That was another question. The toxic content of the Clayton tomatoes wasn't very high, but it was far from negligible. There must surely have been times when Clayton and his wife each ate a whole tomato, and three milligrams of hyoscyamine is quite enough to cause trouble.

  "I think I can say that we found the answer to one of those questions. I can also say, I think, that I helped to find it although I certainly didn't realize it at the time. I picked up a piece of information, but I didn't know what it meant. It had to do with grafting. A few days after the laboratory report came in, I had another talk with Mason. I drove down to his farm. Both he and Mrs. Smart were home by then and fully recovered, and he took me out and showed me his Jimson-weed tomato plant. It was quite a sight—a tomato plant growing out of a big, bushy Jimson weed. 1 even took some pictures of it. On the way home, I dropped in on Clayton. I introduced myself and told him of my interest in the case, and we discussed it for a while. Then he showed me his Jimson-weed tomato patch. It didn't look much like Mason's. It seemed to be all tomato plants. They were growing out of Jimson- weed stock, but the Jimson-weed branches were practically bare. Only the tomato plants were lush and leafy. I spoke to Clayton about that, and told him how Mason's plants looked. Clayton shrugged. This was the way he did it, he said. He liked to keep the Jimson weed pretty well pruned of leaves in order to concentrate the growth in the tomato plant. He didn't know why Mason didn't do the same.

  "I thought that was an interesting point. As I say, I didn't know what it meant. I didn't know if it had any significance at all. But I passed the information on to Dan Jones at the State Health Department in Nashville. He was handling the case at that end, and he was as fascinated, and as puzzled, by it as I was. And that was as far as my contribution went. Dr. Jones took it from there I understand he read everything he could find on Jimson weed in the hope of making some sense out of the case. Finally, he wrote to an expert on Datura stramonium—a professor of botany at Columbia University named Ray F. Dawson. Dr. Jones and I had both been under the impression that the alkaloid in Jimson weed was produced only in the roots of the plant and then distributed to the stem, the leaves, and the fruit. Dr. Dawson straightened us out on that. That was his contribution. The way he explained it to Dr. Jones, Clayton's pruning trick made a considerable difference. Hyoscyamine is synthesized also in the leaves of a Jimson- weed plant. So Mason could hardly have grown a more toxic tomato if that had been his aim.

  "The other question is still unanswered. We don't know how Clayton could have eaten his tomatoes with impunity, and I doubt if we ever will. There are certain facts that may have some bearing on the matter. Different Jimson-weed plants produce somewhat different amounts of stramonium alkaloid. It depends on where and how they grow. And people differ somewhat in their sensitivity to the alkaloid. But that doesn't take us very far. I'm afraid it doesn't take us anywhere at all."

  [1965]

  CHAPTER 12

  Man Named Hoffman

  Around ten o'clock on the morning of Wednesday, March 4, 1964, a man named Donald Hoffman presented himself for treatment at the Student Health Clinic of Miami University in Oxford, Ohio, some thirty miles northwest of Cincinnati. Hoffman was thirty-six years old, married, and a resident of Cincinnati, but, as he explained to the receptionist, he was currently employed, as an insulation installer, in Oxford—on a remodeling job at McCullough-Hyde Memorial Hospital—and his company had an arrangement with the clinic. He was here, he added, because his foreman had sent him. That was the only reason. His trouble was nothing—an itchy sore on the side of his neck. He had probably picked up a sliver of glass-wool fiber. It had happened several times before. It was a common complaint in his trade.

  The doctor who saw him was inclined to agree. There was no good reason not to. Hoffman worked with Fiberglas and his lesion had the look of a Fiberglas lesion. The history of the lesion, the doctor found, was equally suggestive. It had first appeared on Monday evening as a tiny red swelling that might have been caused by a chafing shirt collar. It was larger on Tuesday and somewhat sensitive. This morning it was larger still, and it alternately itched and burned. The doctor slipped a thermometer under Hoffman's tongue, and picked up a scalpel and nicked the edge of the lesion. There was no discharge. He removed and read the thermometer. Hoffman had a temperature of 99.2 degrees. He noted the reading on his record of the case, and added: "Has erythematous swollen area at base of neck anteriorly on left, extending over chest. A firm furuncle is present in the center of this area. Impression: Fiberglass dermatitis with secondary infection." The doctor then turned his attention to treatment. He covered the lesion with a bacitracin dressing, and got out a hypodermi
c needle. In view of the threat of infection, he said, a course of penicillin was indicated. He proposed to begin with an intramuscular injection of 300,000 units. Hoffman stood up. That wouldn't be necessary, he said. He had had all the treatment he wanted. He didn't believe in taking penicillin every time he had a little scratch. He put on his jacket and left.

  Hoffman drove back to the job and resumed his work. He worked until noon and then knocked off and sat down to lunch with one of his friends. He thought he was hungry, but after a couple of bites he changed his mind. His appetite had vanished. He only wanted to sit and rest. Nevertheless, when the lunch hour was over, he went back to work and finished out the day. When he got home, a little before six, he was exhausted. He stretched out on the living room sofa for a rest before dinner and instantly fell asleep. His wife let him sleep, and he slept two hours. He awoke feeling worse than ever. His head ached, his bones ached, and it hurt him to move his neck. He looked so sick that his wife was frightened. She insisted that he see a doctor at once. The Hoffmans had no regular doctor, but Mrs. Hoffman knew the name of a general practitioner in the neighborhood who kept evening office hours, and she looked up his address. Hoffman reluctantly agreed to go. He felt too sick to argue. He dragged himself out of the house and into his car and down to the doctor's office.

  A glance was enough to tell the doctor's nurse that Hoffman was seriously ill. She spoke to the doctor, and the doctor saw him at once. He heard from Hoffman an account of his trouble, and removed the bandage and examined the lesion. The lesion was about the size of an aspirin tablet. It was brightly inflamed and firm to the touch. Surrounding it were several blistery swellings. The doctor could see that an attempt had been made to lance it. He also noted a swelling below the lesion that extended along the neck and halfway down the left side of the chest. He then took Hoffman's temperature. The reading was 102.2 degrees. That decided him. His diagnosis, he told Hoffman, was an abscess with cellulitis. Cellulitis was a potentially dangerous inflammation of the cellular tissue and could best be treated in a hospital. He suggested that Hoffman go home and pack a bag. He, meanwhile, would call Christ Hospital and arrange for his admission. It was now a little past nine. He would meet him there at ten.

  Mrs. Hoffman drove her husband to the hospital. On the way, he told her that he felt even worse than he had an hour before. His voice, she thought, had a strained and scratchy sound. He was admitted to the hospital under a tentative diagnosis of abscess of neck with cellulitus and (as the apparent victim of a communicable disease) placed in isolation. The admission examination showed "marked swelling of the left side of the neck with induration; redness and swelling of the neck, with redness and swelling over the left anterior chest down to the sixth intercostal space." The routine diagnostic tests—chest X-ray, electrocardiography, urinalysis—were made, and the results of all were normal. So, with one exception, were the results of the usual blood studies. Hoffman's white cell count, a generally reliable barometer of infection, was very slightly elevated—10,800, or about a thousand beyond the normal range. His pulse rate was 92, or a little faster than normal for a man, and his temperature had risen to 103 degrees. The doctor prescribed an immediate intramuscular injection of 500 mg. of chloramphenicol, to be followed at six-hour intervals by oral doses of 250 mg. each. Hoffman received the injection at ten-thirty. Five minutes later, he was sound asleep.

  Hoffman spent a comfortable night. He awoke on Thursday morning feeling much improved. When the doctor came by on his morning round, Hoffman asked to be discharged. He was ready, he said, to go home. The doctor smiled and said he would think it over, and introduced a consultant. The consultant examined the lesion and generally confirmed his colleague's diagnosis. He added, however, that the situation of the lesion, and to some extent its appearance, suggested the possibility of erysipelas. In any event, he concluded, the patient was clearly mistaken. Hoffman was still a sick man. The attending physician agreed. He also decided to revise and increase his antibiotic attack. At one o'clock that afternoon, Hoffman was given an intravenous injection consisting of 1,000,000 units of penicillin and one gram of chloramphenicol. To this was added, as a routine supportive measure, 1000 cc. of a five per cent glucose solution. At four o'clock, his blood pressure suddenly dropped. Its fall was checked by the prompt administration of blood, plasma, and vasopressor drugs, and he remained entirely conscious. By six o'clock, when the doctor looked in with another consultant, Hoffman seemed encouragingly convalescent. His lesion was conspicuously larger— it was now about an inch in length and almost half that wide— but his only complaint was a headache. The consultant confirmed the diagnosis of abscess with cellulitis. There was nothing about the look of the lesion to make him question it.

  Hoffman continued comfortably convalescent until about eight o'clock. He then began to find it difficult to breathe. The swelling around the lesion had increased and was now constricting his throat. Supplementary oxygen was administered nasally, and he soon relaxed and fell asleep. He slept for two or three hours. Just before midnight, his blood pressure dropped and he went into shock again. He was rallied as before, but this time his response was only briefly satisfactory. In spite of every attention, his blood pressure swung mercurially up and down throughout the rest of the night. Around six o'clock on Friday morning, he had a sudden attack of nausea, and vomited. A moment later, he was seized by a racking convulsion. The convulsions continued for several minutes. A little before seven, he died.

  Four days later, at nine o'clock on Tuesday morning, March 10, T. Aidan Cockburn, assistant commissioner of the Cincinnati Hoard of Health and the executive in charge of its communicable disease section, received a telephone call from Christ Hospital. His caller identified himself as Evans A. Schmidt, the hospital bacteriologist. He was calling, he said, in response to a recent request by Dr. Cockburn that he be promptly informed of any unusual occurrence in the field of communicable disease. Well, something unusual had just turned up at Christ Hospital. Or so, at any rate, it seemed. A patient named Hoffman had died at the hospital on Friday of what the attending physician had tentatively described on the death certificate as "septic shock due to abscess with cellulitis of neck and anterior chest." An autopsy was performed within three or four hours, but its findings were equally ambiguous. However, Dr. Schmidt went on to say, blood samples taken from the patient at admission had been cultured, and this morning, when he returned to the laboratory after a short holiday, an assistant had shown him the plates. At this point, of course, he couldn't be more than suspicious, but the cultures had produced an organism that looked unpleasantly like the organism of anthrax. He thought Dr. Cockburn would want to know.

  Dr. Cockburn took a deep breath. He didn't disbelieve Dr. Schmidt's report, but he couldn't help but wonder. A couple of months before, around the end of December, five laboratory goats at the University of Cincinnati College of Medicine had sickened and died of what a preliminary investigation indicated was anthrax. For several days, until a more thorough investigation unmasked an animal pathogen called PPLO (pleuro-pneumonia-like organism) as the responsible agent, the threat of an epidemic had loomed in the local press. So anthrax was a touchy subject at the Board of Health. But it was also one that couldn't be ignored, and he thanked Dr. Schmidt for his ready cooperation. He supposed, he then went on to say, that Dr. Schmidt would be sending a subculture sample to the State Department of Health, at Columbus, for further examination. Would he be good enough to send him a sample, too? And by messenger. As luck would have it, he was flying down to Atlanta that afternoon for a meeting at the Communicable Disease Center of the United States Public Health Service there, and he would like to take it along. Dr. Schmidt said he would, and did. By the time the sample—a pale lump of nutrient jelly at the bottom of a stoppered test tube—was on his desk, Dr. Cockburn had made the arrangements regarding it that protocol required. He had telephoned Columbus, and then made a call to Atlanta. Columbus had given him permission to take the culture to Atlanta. And Atl
anta had agreed to receive it.

  Dr. Cockburn carried the culture down to Atlanta in the pocket of his shirt. That was to keep the organism warm enough to grow and proliferate. It was received at the Communicable Disease Center by Philip S. Brachman, chief of the Investigations Section of the Center's Epidemiology Branch. Dr. Brachman examined the culture with professional interest, and passed it along to the Laboratory Branch for continued cultivation and the standard identification tests. Dr. Cockburn would be informed as soon as its identity was determined. The first progress report was telephoned to Dr. Brachman on Wednesday afternoon. It was squarely inconclusive. In spite of Dr. Cockburn's incubatory efforts, the organism had suffered an inhibiting chill and was only now resuming its growth. The second report, which came on Thursday morning, was tentatively negative. The reaction of the organism to a staining test for type had not been typically that of the anthrax bacillus. At eleven o'clock on Friday morning, the laboratory called again. The staining test of yesterday had been a little premature. That and other tests now told a more straightforward story. The culture was unequivocally positive for Bacillus anthracis. Dr. Brachman politely acknowledged the news. He hung up the phone and rang for his secretary. He asked her to put in a call to Columbus, Ohio—to the Ohio State Department of Health. He wanted to speak to Harold Decker, chief of its Division of Communicable Disease.

  Anthrax is a disease of animals to which man occasionally succumbs. It is also one that occupies a unique position in the history of medical science. It was anthrax whose elucidation by the then obscure German country doctor Robert Koch at the University of Breslau in 1876 (in a paper entitled "Die Atiologie der Milz-brandkrankheit begrundet auf die Entwicklungsgeschichte des Bacillus Anthracis") provided the first proof that a specific microorganism could cause a specific disease, a demonstration that largely completed the establishment of the germ theory of disease causation. And it was from the procedure he so successfully followed in his anthrax study that Koch conceived the celebrated postulates of experimental evidence that bear his name. This formulation, which establishes four conditions that must be met before a given microorganism can be accepted as the cause of a given disease, is the keystone of modern bacteriology.