Dr. Mauceri had already paid Steve two house calls. Mauceri was not only Gelson’s doctor but also a friend; in fact, he had been a guest at the first dinner party on Saturday night. He saw Steve at home on Wednesday and was somewhat concerned, but when he saw him again on Thursday, at about 2 PM, he sent Gelson straight to the hospital. “I remember he took my portable phone,” said Steve, “and called a neurologist, Dr. Pickard, on the telephone. He said, ‘I’ve got a patient I’d like you to see today. I’m concerned he could have Guillain-Barré syndrome.’”
By four o’clock that afternoon, the consulting neurologist, Dr. Leonard Pickard, was evaluating Steve Gelson in the emergency department. Pickard at this point was still unaware that Art and Pam were also ill. When he finished examining Steve, he was both puzzled and worried. Two major possibilities occurred to him—myasthenia gravis and Guillain-Barré syndrome, both potentially fatal neurological disorders. “But Steve’s symptoms didn’t quite fit with either diagnosis,” Pickard recalls, “and there was one other possibility that Dr. Mauceri and I discussed.”
Pam Stogess remembers, “Shortly after 4 PM, Art and I joined Steve at the emergency room, and we must have been quite a sight. Steve’s head hung limp to one side. His eyelids drooped shut so that when he spoke, he had to pry them open with his fingers. Art, a community leader, looked like a drunken bum. He hadn’t shaved for a couple of days, and he wore a baseball cap cocked to one side.”
“After I examined Mr. Gelson,” recalls Dr. Pickard, “his father told me about Pam Stogess and Art Landry. The clustering of cases was what clinched it. Even though I’d never seen a case, I knew they had botulism.”
Botulism, which derives from botulus, the Latin word for sausage, is a rare but often fatal form of food poisoning caused by the bacterium Clostridium botulinum. According to Dr. A. Barnett Christie’s eminently readable textbook on epidemiology and infectious diseases, the history of the word “botulism” and the discovery of the causative organism dates back more than two hundred years. Christie wrote, “The term was first used in the last years of the eighteenth century following an outbreak of the disease in Wildbad, in Southern Germany, in 1793: a large sausage had been shared by thirteen people, all of whom became ill and six of whom died.”
Much of what is currently known about the clinical effects of botulism was catalogued by a young district medical officer in the duchy of Württemberg named Dr. Justinus Kerner. At the beginning of the nineteenth century in the area surrounding Stuttgart, the medical administration of the dukedom noticed an increase in cases of fatal food poisoning, which they ascribed to the general decline in hygienic measures for food production that resulted from the poverty caused by the devastating Napoleonic wars. In July 1802, the government in Stuttgart issued a public notice and warning about the “harmful consumption of smoked blood sausages.”
Kerner, who also developed a lasting reputation as a Romantic poet, began publishing his findings in 1817. By 1820, he had written a monograph that included data from seventy-six patients he had seen with “sausage poisoning,” as it was referred to at the time. Kerner performed animal experiments and did many autopsies on patients who had died from botulism. By the mid-1820s, he had established most of what we currently know to be true. He wrote, “The tear fluid disappears, the gullet becomes a dead and motionless tube. . . . No saliva is secreted. No drop of wetness is felt in the mouth, no tear is secreted anymore.”
Using various extracts that he made from the sausages, Kerner experimented on cats, rabbits, birds, snails, insects, and frogs. He was able to produce all the typical symptoms—dilated pupil, droopy eyelids, vomiting, problems with swallowing, and respiratory failure—in these animals. But Kerner went even further. Like many physicians of his time, he experimented on himself. After taking very diluted extracts from the sausage, he wrote, “some drops of the acid brought onto the tongue [produced] great drying out of the palate and the pharynx.” When the university professor who had been his instructor discovered that Kerner was poisoning himself in the name of research, he wisely forbade future self-experimentation.
Although Kerner tried in vain to produce the toxin, he did uncover the three major principles about sausage poisoning: he learned that the toxin is created in the bad sausage when it is stored in an oxygen-free state; that the toxin acted on both the motor and autonomic portions of the nervous system; and that the toxin was extremely potent and could lead to symptoms in very small doses. Most remarkably, Kerner speculated in his 1820 report that certain diseases that are caused by a “hyperstimulated” or “hyperexcited” nervous system might in fact be treated by the toxin.
It was not until 1870 that the word “botulism” was formally coined by another German physician. It took nearly thirty more years for the causative organism to be defined, in part because the necessary tools of bacteriology were still in their infancy during the late nineteenth century.
Finding the organism that was actually causing botulism is a story in itself. It starts in the tiny village of Ellezelles, Belgium. Thirty-four individuals attended a funeral on a cold day in December 1895. The food served for the occasion included both smoked and pickled ham. The latter had been pickled within twenty-four hours of slaughter and kept in brine for eleven days before it was consumed. It didn’t look right and it didn’t smell right, but that did not seem to have dampened the enthusiasm with which it was eaten by the guests and members of the village band, who apparently were playing both for the funeral as well as a local festival. The first victims fell ill in less than twenty-four hours, and in all, twenty-three people became sick. Three died, and ten nearly died. Some who had eaten smaller amounts had a mild illness, and a few, who had eaten only fat or very small pieces of the meat, had no symptoms at all.
Dr. Emile Pierre van Ermengem, who had studied under the great German pathologist Robert Koch, investigated. He found a large anaerobic (grows in the absence of oxygen) bacillus (long bacterium) in the ham that had been served at the funeral and in the tissues of some of the victims as well. From these samples, he grew the bacteria in the laboratory. Finally, when he fed cats food laced with the organism, they developed paralysis. Dr. Ermengem had finally found the cause. He published his findings in a German microbiology journal. This was the first recorded isolation of Clostridium botulinum. Nine years later, in 1904, an outbreak of botulism from canned white beans surprised researchers, for it had been thought that only meat or fish could lead to the disease.
Over succeeding decades, researchers worked out additional details that built on the early pioneers’ theories. The active bacterium, C. botulinum, has a biological peculiarity in that it grows only in the absence of oxygen. The organism has an inactive stage called a spore. The spores can live indefinitely, even in extreme cold or heat; they remain active even after being boiled for hours. Under anaerobic conditions, the spores germinate into the active bacterium, and then the bacteria produce the toxin, one of the most deadly known. Somewhat unbelievably, in 1964 it was estimated that fourteen ounces of botulism toxin could kill the entire population of the world. Kerner was quite fortunate with his forays in self-experimentation, because even so much as a nibble of tainted food can be fatal.
In one small outbreak, in Loch Maree, Scotland, in 1923, eight members of a fishing party lunched on duck paté sandwiches; within a week, all eight were dead. Botulism toxin, a relatively small molecule, affects the nervous system by rapidly and tightly binding to the area where the nerve transmits its impulse to the muscle. Normally, the transmission of this impulse from the nerve to a muscle is mediated by the release of a chemical neurotransmitter, acetylcholine. The acetylcholine then binds to the muscle, causing it to contract. If insufficient acetylcholine binds to the muscle side of the connection, the muscle will not fire. If the diaphragm, the muscle that controls breathing, is affected, one can no longer breathe and will die unless emergency treatment is begun.
There are at least seven types of C. botulinum—somewhat unimaginatively
labeled A through G—but types A, B, and E cause most disease in humans. The bacteria, and its spores, are everywhere, yet botulism is quite rare. In part this is because, although the spores are quite hardy, the toxin is quite frail. Even though heating does not destroy the spores, it routinely destroys the toxin, an Achilles heel that the prudent cook must exploit to avoid the dreaded disease. Contaminated food does not always show signs (such as blown cans or putrid smells) of being contaminated.
Consider the case of a twenty-two-year-old man from Orange County, California. He awoke one morning at 2 AM, vomiting, with blurred vision and a “thick tongue.” Within hours, he was completely paralyzed and he had stopped breathing. He was placed on a ventilator for respiratory support. About forty hours before the onset of his symptoms, he had eaten some stew that his roommate had prepared from fresh ingredients (meat, carrots, and potatoes). The roommate had eaten the same stew while it was still hot, but the other man had tasted it at room temperature, sixteen hours later. The heat-resistant spores had survived the first cooking. Any toxin that was in the stew would have been deactivated by the heating, which is why the roommate remained well. While the food was cooling on the stovetop, however, the spores, deep in the stew (and therefore in an anaerobic environment) germinated into C. botulinum bacteria. When the temperature became cool enough, the live bacteria began making toxin, which caused the young man to fall dangerously ill.
Cooking food to a high enough temperature just before it is eaten will reliably prevent the disease. According to Christie’s textbook: “It is clear that any food may cause botulism if it is contaminated with the organism and is first given inadequate heat treatment, then stored for some time, and finally eaten without further cooking. This last point is important, for it will be remembered that botulinum toxin is easily destroyed by heat, and if only home-canned food were re-cooked before being eaten, most of the deaths caused by home-canned food could be avoided.”
Botulism usually develops when a person eats improperly processed food. Outbreaks have been attributed to bottled mushrooms, roasted eggplant in oil, baked potatoes, stews, soups, sautéed onions, carrot juice, home-canned fruits and vegetables, chili, meat, and fish. In one sad cluster in 1975, an elderly woman canned some mushrooms, ate some of them, and promptly died. After the funeral, her daughter and daughter-in-law ate some more of the canned mushrooms and they both developed botulism. Type B C. botulinum was isolated from the mushrooms as well as the gastrointestinal tracts of all three women.
In 2002, fourteen Alaskans dined on the meat from a beached whale. Eight developed botulism, and two would have died without ICU-level care. Native Alaskans are particularly at risk because they eat seal and whale meat, and their most common food preparation practice is to ferment the flesh. In this process, the fresh meat is allowed to putrefy for one to two weeks in either a pit in the ground or a closed or airtight container. This anaerobic environment is ideal for the formation of botulism toxin.
One large outbreak was traced to commercially canned soup. On a hot day in mid-June 1971, a sixty-one-year-old banker and his wife from Bedford Village, New York, cooled off with some chilled vichyssoise. They didn’t eat the whole bowl because it had an odd taste, but they ate enough. By the next morning, the man had double vision, followed by weakness of his entire body. Twenty-four hours later, he was dead. Only after his wife developed similar symptoms did the doctors suspect botulism. On July 2, the Food and Drug Administration (FDA) released a public warning after learning about the death, and the soup company, Bon Vivant of Newark, New Jersey, launched a recall of the 6,444 cans of vichyssoise that came from the same batch.
Bon Vivant manufactured 4 million cans of soup per year, so finding and retrieving these particular cans was no small feat. Five cans of the vichyssoise were found to be contaminated with the botulinum toxin, and cans from the company’s other products also showed signs of improper handling. Therefore the FDA extended the recall to include all Bon Vivant products, and shut down the company’s plant in Newark just five days after the original warning. By the end of the summer, the company had filed for bankruptcy.
Alaskan salmon is another source of at least two instances of botulism linked to commercially canned food. One of the most recent occurrences from a commercially prepared product was the Castleberry canned chili outbreak that erupted during the summer of 2007. Two patients from Texas and two others from Indiana became severely ill. The first two cases were a brother and sister from Lubbock, Texas. Both ate some canned chili made by the Castleberry Company, based in Atlanta, Georgia. Both required long hospitalizations; the sister was on a ventilator for more than a month. What is noteworthy in these cases is how widely scattered geographically the victims can be.
In another unusual outbreak, in 1979 in Nairobi, Kenya, botulism resulted from people eating white ants, which are nutritious even if unappetizing to some. The ants were caught in Kakamega, three hundred miles from Nairobi. People who ate fresh ants there remained well. But others placed the ants in sealed plastic bags and brought them to Nairobi three days later. By then enough time had elapsed in this oxygenfree environment so that the Clostridia spores that were present germinated and began producing toxin. Five of the six people who ate the transported white ants died from botulism. Foods that are entirely unprocessed and uncooked do not lead to botulism, as long as they are eaten fresh (because the spores themselves do not cause the disease); some kind of storage or processing is required for the toxin to form.
Two other forms of this disease should be mentioned—wound botulism and infant botulism. In wound botulism, spores in a closed contaminated wound can germinate into the bacteria that then form toxin, which is released into the circulation. This same mechanism has been reported in intravenous drug users. Infant botulism, a newcomer to the botulism family, was recognized only in 1976. In this form of the disease, infants between one and thirty-eight weeks old ingest foods that contain the spores, which germinate in the intestine, where they then form toxin, which is absorbed into the baby’s bloodstream. The baby develops constipation, then altered sucking, swallowing, and crying and finally becomes “floppy.” Some cases of sudden infant death syndrome may be due to botulism. Because honey contains C. botulinum spores and has been associated with clinical cases of infant botulism, pediatricians advise that children less than a year old not be fed honey.
There is even one other form of botulism. Precisely as Justinus Kerner predicted, botulinum toxin is now used therapeutically in an odd assortment of syndromes of hyperactive muscle tone—various dystonias, and spasm of the eyelids. More recently, and very commonly, the toxin is used for cosmetic reasons. Marketed as Botox, it temporarily paralyzes the facial muscles, which reduces wrinkles. In 2006, a thirtyfour-year-old woman received a Botox injection from a friend who was an unlicensed physician. The product was research grade, but not pharmaceutical grade. Two days after the injection, she developed double vision, problems swallowing, and weakness. By the time she called an ambulance, her breathing was failing. She was placed on a ventilator and treated with antitoxin. However, her case progressed so rapidly to complete paralysis that it was three weeks before she could shrug her shoulders or move her eyes, and five weeks before she could speak. After a nearly four-month hospital stay, she was discharged to a rehabilitation facility.
In the standard food-borne botulism, symptoms typically begin within thirty-six hours after ingestion of the toxin, and include dry mouth and difficulty talking and swallowing. Patients frequently have double vision from problems with the muscles that move the eyes up and down and from side to side. Blurred vision also occurs in the majority of cases, perhaps from the droopy eyelids, or ptosis, as physicians call it. Fatigue is profound. In half of the instances, nausea and vomiting never occur, so many patients do not suspect a food-related illness. Fever is absent, and the victims remain mentally intact.
As recently as thirty years ago, as many as half of all botulism cases proved fatal. Improvements in intensive c
are, use of ventilators for respiratory failure, and the development of an antitoxin have dramatically lowered that dismal statistic. Of course the benefit of those improvements is all predicated on making an accurate diagnosis. Today severely afflicted patients can be placed on sophisticated ventilators for weeks if necessary, until the poison’s deadly grip on the diaphragm has relaxed. The antitoxin is horse serum, prepared by immunizing horses with injections of botulism toxin, then extracting the horse’s antibody-rich blood serum and giving it to patients. Because the antitoxin is a horseserum product, patients may develop allergic side effects from the foreign protein, sometimes severe ones.
Because of these side effects, doctors like to be sure of the diagnosis before administering a therapy so potentially toxic. On the other hand, because the antitoxin must be delivered as rapidly as possible, they often must give the treatment based on a presumptive diagnosis.
Pam Stogess and Art Landry’s doctors wanted to try to exclude Guillain-Barré syndrome, another cause of paralysis that can also affect a patient’s ability to breathe, so they performed spinal taps on these dinner-party guests. If they had Guillain-Barré, the protein levels in the spinal fluid should be high.
They weren’t.
Dr. Pickard phoned the federal Centers for Disease Control and Prevention (CDC) as soon as he thought that the diagnosis of botulism was likely. His next call was to the state health officials. At 5 PM on Thursday, Perry Smith of the New York State Department of Health in Albany took Pickard’s call. Alarmed, he immediately informed his director, Dale Morse.
Morse recalls, “Dr. Smith received the call and we each got on the phone. Stan Kondracki [an epidemiologist] was about to step on the elevator to leave for the day, and I motioned for him to come back. I had him begin working on mobilizing the antitoxin from New York City, while Perry was still on the line with Dr. Pickard. Meanwhile, I began talking with the Ulster County officials. We did a lot of work in a very short period of time. We also had to notify the state lab to be prepared to receive specimens used to confirm the diagnosis.”
The Deadly Dinner Party: and Other Medical Detective Stories Page 2
