Photo: Collecting tarantula venom

Tarantulas are raised for their venom, used in the study of neural and chemical paths in humans.

Photograph by Cary Wolinsky

Written by Cathy Newman

Republished from the pages of National Geographic magazine

Bad things come in small packages. On August 14, 1996, Karen Wetterhahn, a toxicologist and professor of chemistry at Dartmouth College, spilled a drop, a tiny speck, of dimethylmercury on her left hand. Wetterhahn, tall, thin, intense, was an expert on how toxic metals cause cancer once they penetrate cell membranes. When she spilled the poisonous droplet in her lab, she thought nothing of it; she was wearing latex gloves. What she didn't know killed her.

The dimethylmercury was volatile enough to penetrate the glove. Five months later Wetterhahn began stumbling into doors and slurring words. After three weeks in a hospital, she slipped into a coma.

"I went to see her, but it wasn't the kind of coma I'd expected," recalled Diane Stearns, one of her postdoctoral students, now a professor of chemistry herself. "She was thrashing about. Her husband saw tears rolling down her face. I asked if she was in pain. The doctors said it didn't appear that her brain could even register pain."

Karen Wetterhahn died five months later. She was 48 years old, a wife and mother of two. The mercury had devoured her brain cells "like termites eating away for months," one of her doctors said. How could such a brilliant, meticulous, worldclass toxicologist come to such an end?

"Only lion tamers are killed by lions," said Kent Sugdan, one of her postdoctoral fellows.

Poison is a stealth killer, effective in minuscule amounts, often undetectable. It's the treachery in the arsenictainted glass of wine. The fatal attraction: Snow White's poison apple, the deathdefying art of the snake handler, the Japanese roulette practiced by those who eat fugu. Without poison, comic book superheroes and villains in plays and movies would be considerably duller. Spiderman exists by the grace of a radioactive spider bite. The rise of the Teenage Mutant Ninja Turtles can be traced to their fall (as pet turtles) into a sewer along with a container of toxic materials. Laertes used a poison-dipped sword to kill Hamlet, and Claude Rains's nasty mother kept sneaking poison drops into Ingrid Bergman's drinks in the Hitchcock thriller Notorious.

You might say that a toxicologist studies substances that lead to death. But toxicology is also about life. What can kill, can cure. Said Paracelsus, a 16th-century German-Swiss physician and alchemist: "All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy." Poison is in the dose. Toxicology and pharmacology are intertwined, inseparable, a Jekyll-Hyde duality. A serpent coiled around a staff symbolizes Asclepius, the Greek god of medicine.

Consider arsenic, the poison of kings and king of poisons. Arsenic exploits certain pathways in our cells, binds to proteins, and creates molecular havoc. Small amounts taken over a long stretch produce weakness, confusion, paralysis. Take less than a tenth of an ounce (2.83 grams) at once, and the classic signs of acute arsenic poisoning ensue: nausea, vomiting, diarrhea, low blood pressure, then death.

Because it is colorless, tasteless, and odorless, arsenic was the poison of choice for the Borgias, the Italian Renaissance family skilled at artful murder, as well as for Hieronyma Spara, a 17th-century Roman entrepreneur who ran a school that taught wealthy young wives how to dispatch their husbands and become wealthy young widows. Arsenic, the poudre de succession, powder of succession, helped ambitious princes secure thrones. Fed in small amounts to a wet nurse, the poison could be expressed in breast milk and kill infant rivals.

From death to life: In the fifth century B.C., Hippocrates used arsenic to treat ulcers. It became an ingredient in Fowler's solution, created in 1786 and used for more than 150 years to treat everything from asthma to cancer. In 1910 an arsenic compound became the first effective remedy for syphilis (later to be replaced by penicillin). Arsenic derivatives are still used to treat African sleeping sickness. In 1890 William Osier, founder of modern medical education, pronounced arsenic the best drug for leukemia, and today it remains an effective chemotherapy agent for acute forms of the disease.

So is arsenic a poison or a drug?

"It's both," says Joshua Hamilton, professor of toxicology and pharmacology at Dartmouth. "It depends: Are you talking to a Borgia, or are you talking to a physician?"

Poisons surround us. It's not just too much of a bad thing like arsenic that can cause trouble, it's too much of nearly anything. Too much vitamin A, hypervitaminosis A, can cause liver damage. Too much vitamin D can damage the kidneys. Too much water can result in hyponatremia, a dilution of the blood's salt content, which disrupts brain, heart, and muscle function.

Even oxygen has a sinister side. "Oxygen is the ultimate toxin," says Michael Trush, a toxicologist at Johns Hopkins Bloomberg School of Public Health. Oxygen combines with food to produce energy, but our bodies also produce oxygen radicals—atoms with an extra electron that damage biomolecules, DNA, proteins, and lipids. "We are oxidizing all the time," says Trush. "The biochemical price of breathing is aging." Which is to say, we rust.

As if everyday poisons aren't enough to angst over, there are nature's more exotic hazards. It's a jungle out there. There are 1,200 kinds of poisonous marine organisms, 700 poisonous fish, 400 venomous snakes, 60 ticks, 75 scorpions, 200 spiders, 750 poisons in more than 1,000 plant species, and several birds whose feathers are toxic when touched or ingested.

Given the treachery of the world, why don't more of us die of poisoning? Because our bodies are designed to protect us from both natural and man-made toxins. The first line of defense, skin, is made of keratin—so waterproof, tough, and tightly woven that only the smallest and most fat-soluble molecules can get through. Our senses warn us of noxious substances; if they fail there is vomiting as backup. Finally, there is the liver, which turns fat-soluble poisons into watersoluble wastes that can be flushed out through our kidneys. The balance tilts over to toxicity only when we step over the threshold of dosage.

Mike Gallo, a toxicologist, knows the principle of threshold from the inside out. Literally. Gallo, a hyper-caffeinated personality wrapped in a wiry frame, is an associate director at the Cancer Institute of New Jersey in New Brunswick. In February 2004, at 64, he was diagnosed with non-Hodgkin's lymphoma. Two weeks later he became both toxicologist and patient at the cancer institute. His oncologist put him on a four-month intravenous diet of toxins, also known as chemotherapy, and he began treatment in a clinic four floors down from his office.

The ingredients of his cocktail included cytoxan, adriamycin, vincristine, prednisone, and Retuxan—toxic enough to cause side effects ranging from vomiting, diarrhea, and weight loss, to liver, heart, and bladder damage, to death from overwhelming infection due to a depressed immune system. In addition, as Gallo will cheerfully tell you, "Almost all cancer drugs are carcinogenic in their own right."

On the other hand, he says, "The moment they stuck the needle in my vein, I felt relief. I thought, They got the son of a bitch."

Gallo was lucky. His luxuriant mop of red hair fell out, and he took on the alien look of chemotherapy. But fatigue and the typical drop in blood-cell count aside, he continued working through the treatment.

"I did just fine," he says, "but in the room right next to me is the same person, the same age, the same physique, and he's getting the stuffing kicked out of him. Why? My drug-metabolizing enzymes must be slightly different from his."

It's these pieces of toxicology—the matter of difference, the question of how much or how little, the wavering line between killing and curing—that Gallo loves so much as a scientist. They are the heart of toxicology and thus of poison. "Toxicology gives you the chance to understand biology," he says.

Toxicology also saved his life. Six months and thousands of milligrams of toxic drugs later, Gallo's doctor gave him the all-clear. The lymphoma is in remission.

The tale of two toxicologists ends tragically for one, happily for the other. Karen Wetterhahn lost her life to poison. Michael Gallo owes his life to it. "I dodged a lethal bullet, thanks to a series of well-placed bullets," Gallo says. "I could have been a dead man. Thank God for toxicity."

The Curious Case of Napoleon B.

It's a game of Clue and historical whodunit all in one. The victim, Napoleon Bonaparte, died on May 5, 1821, on St. Helena, in exile after his defeat at Waterloo. An autopsy performed the next morning revealed perforation of the stomach due to an ulcer, possibly cancerous. The real cause of death? In dispute ever since. Some theories:

Political Murder

Murdered by arsenic poisoning, according to Ben Weider, founder of the International Napoleonic Society and head of a huge Canada-based body-building empire. Weider has relentlessly sought the cause of Napoleon's death for more than four decades and has poured considerable resources into the quest. In his view, Napoleon was poisoned by the British and by French royalists, who wanted him out of the way once and for all. Weider offers as the centerpiece of his hypothesis the hair analysis done by Pascal Kintz, a French lexicologist at the Legal Medicine Institute of Strasbourg. Kintz subjected samples of Napoleon's hair to a sophisticated technique known as nanosecondary ion mass spectrometry, which confirmed the longterm presence of arsenic. Kintz steps back from saying how or why the arsenic was there, but Weider is convinced that "the poisoning of Napoleon was planned and deliberate. Anything else is hogwash."

Environmental Poisoning

Poisoned by his wallpaper, theorizes David Jones, an immunologist at the University of Newcastle in England. The wallpaper at Longwood House, where Napoleon lived his last years, was painted with Scheele's green, an arsenic compound called copper arsenide. When attacked by certain molds, possibly present in the damp environment of St. Helena, arsenic would have been released into the air. In the late 1950s Clare Boothe Luce, the American ambassador to Italy, was diagnosed with arsenic poisoning caused by paint chips falling from the stucco roses on her bedroom ceiling.

Malpractice

Killed by his doctors, says Steven Karch, a cardiac pathologist in Berkeley, California. Napoleon's doctors gave him large doses of purgatives including tarter emetic and, the day before his death, a massive dose of mercurous chloride, called calomel. The medications threw Napoleon's electrolytes into total disarray, Karch says, disrupting his heartbeat and resulting in cardiac arrest. In pathologist terms, the immediate cause of Napoleon's death was cardiac arrhythmia precipitated by medical negligence and compounded by chronic exposure to arsenic.

Disease

Cancer and ulcers as reported in the autopsy, says Jean Tulard, the preeminent Napoleon historian in France. Tulard remains unconvinced by Kintz's hair analysis. In his estimation the provenance of the hair; whether it really belonged to Napoleon or not—is one of many problems standing in the way of definitive proof. "There are more samples of Napoleon's hair than relics of the Cross," he scoffs. Above all, Tulard discounts the poisoning theory on the grounds that no one has yet found anything linking Hudson Lowe, the British governor-general of St. Helena—or anyone else for that matter—to any plot against Napoleon's life. "A bogus discussion," he says, "even if it is important to know how he died."

Revenge

"One of my ancestors did it," says Francois de CandéMontholon with a whiff of pride. ("I'm an aristocrat. Aristocrats don't like revolution, and Napoleon made revolution.")

Candé-Montholon's great-great-great-greatgrandfather, the Count of Montholon, was stationed with Napoleon on St. Helena. Napoleon had an affair—and fathered a child—with the count's wife. The count, it is observed, had charge of Napoleon's wine cellar and food. Could he, motivated by revenge, have poisoned the wine?

No Conclusion...

"Everyone is right, and no one is right," says Paul Fornes, a forensic pathologist at the Hospital Georges Pompidou in Paris. Fornes has reviewed the 1821 autopsy report and other historical records and concludes: "Napoleon may have died with cancer, but he didn't die of cancer." Likewise he says that although the hair analysis indicates the presence of arsenic, no one can say if he was intentionally given the arsenic (or if it killed him). In Fornes's opinion the accusation of murder by poisoning would never fly in a court of law.

Believe what you will. "We have left the world of history and science behind," says Jean-François Lemaire, a doctor and French historian, disdaining the circus (press conferences! newspaper stories!) surrounding the debate. "We are now in the world of entertainment." Or perhaps, as the French would say, it's a case of couper les cheveux en quatre—splitting hairs.

One bad move and you're snakebit!

During a one-man wildlife survey on a deserted Florida barrier island, herpetologist Bruce Means finds his favorite venomous reptile.*

He knows better, but tries to capture the rattler with a stick…

Defending itself, the snake strikes!

It's only a pinprick on his finger, but Bruce knows the venom will start working within seconds.

Tissues break down as enzymes in the venom attack.

As toxins wreak havoc, Bruce crawls to find help before it's too late.

Blood and other fluids begin to leak into his tissues. His blood is losing its ability to clot. Will he die?

He made it.

Bruse managed to reach a hospital—and survived, but the eastern diamond-back still claims an occasional life. Venom strength varies depending on the snake's age, when it last ate, the time of day the strike occurs, how deeply the fangs penetrate, and how much venom is injected.

Worst-Case Scenario

Circulatory failure, shock, massive tissue necrosis, and internal and external blading lead to death. Medical help is the key, but some wait too long before seeking treatment. Others, often children, are just not robust enough to withstand the poison's lethal effect.

Concerto in b for Botox & Piano

"I was lost," Leon Fleisher says, and 40 years later you can still feel the suffocating despair. One of the world's premier concert pianists, Fleisher was talking about the aftermath of a day in 1965 when the career so carefully nurtured (his first public recital at 8; a performance with the New York Philharmonic in Carnegie Hall at 16) unexpectedly ended.

Fleisher, a man with a spirit as expansive as a Beethoven symphony, sits in the music room of his Baltimore home. Twin Steinway grands nest together; on one there are photographs of a young, gangly Leonard Bernstein and of George Szell, the legendary maestro of the Cleveland Orchestra ("looking cold as ever," Fleisher notes). The conversation drifts to the day in Cleveland's Severance Hall when Szell rehearsed Fleisher and the orchestra in final preparation for a tour of the Soviet Union. "It was the height of the Cold War. We were going to show the Russians what music was all about," Fleisher recalls. "I had noticed the fourth and fifth fingers on my right hand curling under involuntarily. I figured, Wow, I better work harder. I did. It got worse. George noticed too."

When rehearsal ended, Szell called Fleisher to his study. "I don't think you should come on tour," he said. That was it. Fleisher was 37. His life had evaporated.

There were doctors: orthopedists, neurologists, a hand surgeon, psychiatrists. There were injections, x-rays, medications, acupuncture, aromatherapy. All failed. All useless. "It was as if my hand had been taken over by aliens," he says. "It was not under my control."

A career ruined. A marriage wrecked. Thoughts, even, of suicide.

"Finally I realized my connection to music was stronger than just as a two-handed piano player. I started conducting, playing the left-handed repertory, and teaching at the Peabody Conservatory." Yet the pain of the missing piece of his life persisted. "I taught and conducted and every bloody day I tested this hand." He lifts the offending hand and demonstrates how the fingers curled under like claws.

There was, it should be noted, a brief respite in 1981 when the condition seemed to improve. Fleisher played at the opening of the Meyerhoff Hall in Baltimore. "I managed to get through," he recalls, "but just barely. Afterward I broke down backstage. A grown man weeping...."

After decades a diagnosis emerged. Fleisher was afflicted with focal dystonia, a misfiring of the brain that causes muscles to contract into abnormal, and sometimes painful, positions. The disorder often strikes those who depend on small motor skills: musicians, writers, surgeons. At last relief seemed possible. He was referred to a clinical trial at the National Institutes of Health, where botulinum toxin was being tested as a remedy for the disabling contractions.

Botulinum toxin is produced from the bacterium Clostridium botulinum, one of the most poisonous substances known. A gram of botulinum toxin, if dispersed and ingested, could kill 20 million people. The toxin produces a protein that blocks the release of acetylcholine, a transmitter that tells a muscle to contract. In extremely dilute form the poison, delivered in the drug Botox, has proved effective and safe in medical applications ranging from the softening of wrinkles, to the relief of migraines, to a cure for crossed eyes, to a treatment for the spastic contractions of multiple sclerosis and cerebral palsy.

Botulinum toxin relieves symptoms without curing the condition, so Fleisher receives an injection every six months or so. But the six-month miracle is a miracle no less.

"I have had eight, maybe nine lives," Fleisher says. For each there is cause to celebrate, but maybe most of all for the ninth. He is performing and touring again, and recently released his first two-handed recording in 40 years.

Artur Schnabel, Fleisher's mentor, whose teacher's teacher was Beethoven himself, once said that life is about ascendancy. The only thing that grows down is potatoes, he told his protégé. A conductor beats up. A ballet dancer lifts up. We grow up and outward. "Play upward," Fleisher urges his students.

After 40 years, Fleisher's own life has turned upward as well.

Name Your Poison

Rye infected with ergot, a toxic fungus, has caused devastating epidemics through history. Symptoms include tremors and hallucinations; the hysteria of those accused of witchcraft in the 17th century may have been ergot poisoning.

Spies were sometimes issued lethal pills hidden in objects like eyeglasses to use if captured. "The KGB grabbed spies by the throat so they couldn't swallow," says Peter Earnest of the International Spy Museum in Washington, D.C.

A popcorn cat poisoned several New England children in 1955, when levels of orange food coloring reached toxic levels due to poor manufacturing controls. Victims recovered, and the manufacturer recalled the other cats.

The National Cancer Institute evaluates marine-animal toxins for potential cancer drugs. Animals with no armor and limited mobility rely on poison for defense. NCI scientist David Newman calls it "animal chemical warfare."

Georgi Markov, a Bulgarian dissident, was assassinated in London in 1978 when a man approached and jabbed him with an umbrella modified to fire a pellet with ricin, a deadly toxin. This replica is cut away to show the firing mechanism.

In 1971 a man in Bedford, New York, died of botulinum poisoning after eating vichyssoise made by the Bon Vivant Company. Over a million cans of possibly under–:processed soup were recalled. The company filed for bankruptcy.

A Delicacy to Die For

Meet the fugu, aka Takifugu rubripes, a fish with the thick-lipped, thuggish face of a Chicago gangster. Fugu, or puffer fish, as it is commonly known, is a delicacy in Japan. It can also be deadly. Those who eat the liver, ovaries, gonads, intestines, or skin swallow tetrodotoxin, a powerful neurotoxin that jams the flow of sodium ions into nerve cells and stops nerve impulses dead in their tracks. They run the risk of suffering the fate of the famous Kabuki actor Mitsugoro Bando, who in 1975 spent a night feasting on fugu liver because he enjoyed the pleasant tingling it created on his tongue and lips. The tingling was followed by paralysis of his arms and legs, difficulty breathing, then, eight hours later—death. There is no known antidote.

Fortunately, these days the making of a fugu chef is a carefully controlled and licensed enterprise. Aspiring chefs who would spend their days in the kitchen skinning and shaving the fugu into tissue-thin slices for sashimi (at $500 a plate) must take an exam: 20 minutes to dissect the fish into edible and inedible pieces, label the parts with plastic tags (red for toxic, black for edible), and prepare an artful arrangement. Of the 900 hopefuls who took last year's exam, 63 percent passed.

The source of the fugu's poison is a subject of debate. Tamao Noguchi, a researcher at Nagasaki University, believes the secret lies in the fugu's diet. Puffer fish, he explains, ingest toxins from small organisms—mollusks, worms, or shellfish—that have in turn ingested a toxic bacterium known as vibrio. In experiments, Noguchi has raised fugu in cages, controlled their diet, and produced toxin-free fish.

He hopes his research will result in the state-sanctioned sale of fugu liver. "A great delicacy; once you eat, you cannot stop," he says. Japan has forbidden the sale of fugu liver since 1983; before the ban, deaths of those who overindulged in the liver, or ate it by mistake, numbered in the hundreds.

If Noguchi succeeds in his efforts, gourmands may have cause to cheer, though the fish itself, he speculates, may have cause to mourn. "After all," he says, "a fugu without its poison is like a samurai without his sword."

Kendo Matsumura, a research biologist at the Yamaguchi Prefectural Research Institute of Public Health, discounts Noguchi's deadly diet theory. He says the fugu's toxicity comes from poison glands beneath its skin. Some fugu are poisonous, he says, some aren't, but even experts can't tell which is which.

Place your bets. Matsumura has never eaten fugu. "I am not a gambling man," he says. However, Noguchi considers it the ne plus ultra of fine dining.

When it comes to fugu, one man's poisson is another man's poison.

In the Morgue With Al and Marcella

Marcelle Fierro is chief medical examiner of the Commonwealth of Virginia and a professor in the Department of Legal Medicine at Virginia Commonwealth University School of Medicine in Richmond. She oversees the medical investigation of all violent, suspicious, and unnatural deaths in Virginia, and she inspired the character Kay Scarpetta in Patricia Cornwell's crime novels. Alphonse Poklis is director of toxicology and professor of pathology, chemistry, forensics, pharmacology, and toxicology at VCU. He works with Fierro to analyze medical evidence in homicide cases and testifies as an expert in court.

When does the red flag go up? How do you know you're dealing with a murder by poison?

MF: There are a couple of presentations. If someone takes a huge overdose of something toxic, you expect a classic range of symptoms even a first-year resident can pick up on. Chronic poisonings—when toxins are fed slowly, continuously—are easier to misdiagnose. Antifreeze in the Gatorade was a recent case. A common warning sign is when the clinical history is florid. For example, lots of trips to the internist for weird symptoms or stomach pains. The victim doesn't feel well; it's diffuse, nonspecific. Of course over time classic elements of poisoning may present: He doesn't eat, he's losing weight, he's sounding more teched each day. It looks like natural disease, but isn't.

At what point do you get called in?

MF: We see any death that is sudden, unexpected, violent, or where there is allegation of foul play. If we have the body before it's in the ground, we deal with it. But often it takes time for an allegation to be made or for someone to believe it. Perhaps a family member has a motive: there's dissension about property, inheritance, a new wife, a child not getting a fair shake. Those things set a chain of events into motion. The body has to be exhumed.

Then what? How do you proceed?

MF: I take umpteen tissue samples at autopsy: heart, liver, lungs, brain, spleen, hair, nails. Blood tells you what was going on in the body at the time of death. Vitreous humor from the eye is great. It's clean. No fermentation or contamination from bacteria. Al and I work together. What poisons are candidates? What best to collect? You have to have a strategy. We'd want to know what poison the defendant would have access to. If it's a farmer, we look for agricultural things like pesticides or herbicides. We need to have an idea of where we are going. We can easily run out of tissue and blood samples before we run out of tests to do.

So the technology you use to detect poisons in a corpse must be pretty sophisticated?

AP: Very. I call it the vanishing zero. In the 1960s it took 25 milliliters of blood to detect morphine. Today we can use one milliliter to do the same work. In terms of sensitivity, we've gone from micrograms to nanograms, which is parts per billion, to parts per trillion with mass spectrometry. You can find anything if you do the research. Of course some substances are more apparent. You can smell cyanide the minute you open a body at autopsy. Cyanide works fast—like in movies where the captured spy bites on the capsule and dies. It's a chemical suffocation; cyanide hits the mitochondria in the cells, and every cell is deprived of oxygen. You die quickly, dramatically, violently.

Is there a personality profile specific to poisoners?

AP: The poisoner tries to cover up what he does, as opposed to somebody who shoots, strangles, or rapes you. A forensic psychologist I know calls poisoners custodial killers. Often you are dealing with a family situation. It happens over a period of months or a year. The perpetrator is taking care of the victim, watching him die. Poison is the weapon of controlling, sneaky people with no conscience, no sorrow, no remorse. They are scary, manipulative; if you weren't convinced by the evidence, you wouldn't believe they could do such a thing.

MF: Al sees the poisoner as a controller. I see the poisoner as a smooth psychopath who could lie to Christ on the Cross, and you would believe him. I only know of two who pled guilty.

A case that sticks in your mind?

MF: There was this fellow at the University of Virginia hospital. Kept getting admitted for weird gastrointestinal complaints. The doctors were twisting themselves inside out to figure it out. He'd get better; his wife would come in to see him in the hospital and bring him banana pudding. Someone finally ordered a heavy metals [toxicity tests] on him, but he was discharged before the results came back—off the charts for arsenic. By the time someone saw the labs it was too late. We called the wife Banana Pudding Lily.

How many cases of suspected homicidal poisonings do you evaluate in the course of a year?

AP: Frankly, relatively few. It's not in the American character. If you are going to kill someone and you are a true American, you shoot them. A real man doesn't sneak around. In our culture everything is solved in 30 minutes, so you aren't going to plan, go someplace to get poison, and figure out How am I going to give it? In our culture, we act directly.

You're the expert. If you had to design the perfect poison for murder, what would it be made of?

AP: I could think of a few things, but I'm not going to share them.

Death in Venice

When you think about it, not much has changed in 500 years. Spies, assassinations, covert contracts, secret payoffs—it's all part of the everyday business of running a country.

In Renaissance Italy "poison was the solution to delicate political problems," says Paolo Preto, a professor of modern history at the University of Padua. So it should be no surprise that poisoning was as much an art as painting, architecture, or sculpture. A touch of arsenic, hemlock, or hellebore added to the wine was discreet, nearly undetectable (autopsies were rare at the time), and considerably less messy than using a knife or gun.

The Borgias—Alexander VI and his son Cesare—specialized in faith-based poisonings. As pope, Alexander appointed wealthy men as bishops and cardinals, allowed them to increase their holdings, then invited them to dinner. The house wine, dry, with overtones of arsenic, neatly dispatched the guests, whose wealth, by church law, then reverted to their host. English essayist Max Beerbohm wrote: "The Borgias selected and laid down rare poisons in their cellars with as much thought as they gave to their vintage wines. Though you would often in the 15th century have heard the snobbish Roman say ...'I am dining with the Borgias tonight,' no Roman ever was able to say 'I dined last night with the Borgias.' "

But the capital of conspiracy in Italy was Venice, where the architects of evil were the Council of Ten, a special tribunal created to avert plots and crimes against the state. To accomplish poisoning, the council would contract with an assassin, usually from another city. The deed, when done, was paid for through an intermediary. Funds were readily available for such matters, and the council kept two accountings: one for public dealings and one for those of a private nature.

The council's cloak-and-poison-dagger proceedings were recorded officially (opposite, bottom) in a thin volume marked Secreto Secretissima ("top top secret"). Those present swore twice on the Bible to keep the meetings secret, forbidden even to admit they took place. Today the ledger sits in a soaring arched space in the state archives in Venice.

Consider the scheme proposed in its pages by a doctor to a Venetian general fighting against the Turks in Dalmatia. He offered to cut the infected glands off bubonic plague victims and create a toxic potion to be spread on woolen caps, which could then be sold cheaply behind enemy lines to the Turks. Presumably, plague and buyer's remorse would result. The plot was enthusiastically endorsed by the general until someone gently reminded him that because so many Venetian troops were stationed behind the lines in Dalmatia, his soldiers could be infected too and perish along with the enemy.

Last year poison, dioxin to be exact, was the lead player in the drama of Ukrainian President Viktor Yushchenko, victim of an attempt to remove him from the political scene. In the United States such covert plots became the subject of congressional investigations after the early 1960s, when the elimination of Cuban dictator Fidel Castro was a top CIA priority. Mobsters enlisted in the planning advised against a hail of machine-gun fire in favor of a more subtle approach: a bottle of botulinum-laced pills. Other plans, considered then rejected, included the delivery of a box of botulinum-soaked cigars, contaminating Castro's scuba breathing apparatus with tubercle bacilli, or sprinkling his shoes with thallium salts in hopes that hair loss, one of the common side effects of thallium absorption, would make his beard fall off.

Though the recurring narrative of poisoning plots might lead one to despair for the human race, Paolo Preto, who spent eight years researching dark dealings in the Venetian state, takes a pragmatic approach. "History is made up of bad acts," he says.

Zyklon B and the Camp of Death

In the summer of 1941 Himmler informed me of the following: "The Fuhrer has ordered the final solution of the Jewish question. We, the SS, are to carry out the order. The existing extermination sites in the east cannot cope with the large scale of the planned operation. I have therefore designated Auschwitz for this purpose. "

—Rudolf Hoss, Commandant, Auschwitz

On September 3, 1941, at Auschwitz, a concentration camp in Poland, Nazi security guards forced 600 Soviet prisoners of war and 250 ill inmates into a locked room. They poured pellets of Zyklon B, a crystallized form of hydrogen cyanide normally used as an insecticide, through a vent and watched.

Previous mass killings had been carried out by shooting squads or by pumping exhaust fumes into sealed vans. The former method, however, was too slow and created too much of a public spectacle; the latter was unreliable and required special equipment.

The Zyklon B pellets proved effective, efficient, and infallible. Exposed to air, they turned to gas, which killed all occupants of the room in 20 minutes. After the experiment the Nazis built four larger, permanent gas chambers and crematories in Birkenau, a sub-camp of Auschwitz. The key to the final solution, Adolf Hitler's plan to exterminate the Jews of Europe, was Zyklon B.

Stefan Polchlopek, who grew up and still lives in Krynica, Poland, was arrested by the Gestapo on December 28, 1942. He was 26 years old, a law-school graduate, and an active member of the resistance. When he was arrested, someone told his mother, who ran to the railway tracks and managed to wave goodbye to her son as he was hauled away.

Polchlopek was taken to a collection point, then put on another train for Birkenau. The car was a solid, stifling mass of prisoners. When the train stopped, he recalls, "the doors opened; we heard shots, howling of dogs, and screams. Searchlights glared in our faces. They told us to jump off, and we fell to an indescribable hell."

In the summer of 1943, Polchlopek worked in a labor crew assigned to extend the railway line from a depot outside the camp right up to the gas chambers. Transports from throughout Europe were arriving two or three a day. Jews, Gypsies, political dissidents like Polchlopek, homosexuals—anyone considered undesirable by the Nazis—were unloaded from railcars and either taken to the gas chambers or consigned to slave labor.

One day, an SS officer approached Polchlopek and three other prisoners working on the line and ordered them into the undressing room, the chamber in front of the room where the gassings took place. He made them collect the clothes and belongings of those who had been killed.

"I saw the undressing room and the gas chamber," Polchlopek, now 89, says. "I remember the showerheads. I remember the clothes, shoes, the personal possessions left in pockets. We had to gather up the clothes and load them into trucks. The belongings would go to warehouses where they would be sorted. The smell of burned corpses was in the air; dark smoke poured out of the chimneys. We realized we should flee. Witnesses were killed. We could be next." And so they fled. They ran back to the barracks.

"Everyone knew about the chambers. Once I saw two trucks crowded with women. They knew where they were going. One woman was praying. One was cursing. All were screaming. They were followed by two trucks filled with firewood. The women were killed with Zyklon B. The naked corpses were taken out, thrown into pits, and burned."

At the height of operations, nearly 8,000 people were gassed each day at Auschwitz Birkenau. By November 1944, more than one million men, women, and children had died. "Those of us who survived Birkenau are assured a place in heaven," Polchlopeksays. "We have already experienced hell."

Stings & Arrows

History is one long arms race—from sticks and stones to nuclear weapons. According to Adrienne Mayor, a classical folklorist, the Greek superhero Hercules invented the first biological weapon described in Western literature, and it's been downhill ever since.

Hercules slew Hydra, a mythical manyheaded serpent, then dipped his arrows in the venom to ensure their lethality. The legacy endures in the word "toxic," from toxikon, Greek for poison arrow.

In A.D. 199 the Romans attacked Hatra, a city in today's Iraq. Citizens retaliated by lobbing clay pots filled with deadly scorpions over the walls. Hannibal had devised a similar strategy 400 years earlier. His sailors catapulted pots full of venomous snakes onto the decks of the opposing fleet. In Neolithic times, some scholars suggest, a plugged beehive tossed into a cave may have flushed an enemy out.

Other biological weapons in history's armory of terror include the smallpox-infected blankets the British sent to American Indians during the French and Indian Wars; the animal carcasses thrown by Confederate forces into wells during the U.S. Civil War; the sharp bamboo stakes smeared with feces by the Vietcong.

Today's toxic weaponry includes anthrax letters, which killed five people in the U.S. in 2001, and sarin, which killed 12 when members of a cult released the poison gas in a Tokyo subway in 1995. Such grim reality prompts defensive maneuvers like the exercise held by the U.S. Capitol Police last November in Washington, D.C.—a rehearsal for a scenario in which a poisonous substance is released in the Capitol Building.

What goes around comes around. Along with enemies, Hercules' poison arrows killed old friends and innocent bystanders. Ultimately, the law of unintended consequences claimed Hercules too. Tricked by one of his victims, Hercules made the fatal mistake of putting on a robe dipped in Hydra venom. The mythmakers specialized in irony.

Before Hercules died, he passed his poison arrows on to Philoctetes, a gifted archer, who killed many soldiers in the Trojan War. Death begets death, but—at least this time—reason prevailed. Philoctetes decided not to pass his deadly arrows on to a younger generation. He founded a temple and left the poison arrows behind. In a gesture of hope, he dedicated them to Apollo, god of healing.

The Monk Who Embalmed Himself

To live according to the precepts of a stringent religion can be difficult. To die by the precepts of a religion is another thing altogether.

In the shadow of Mount Yudono in Japan's Yamagata prefecture, the landscape lifts into a corrugated carpet of evergreen. This is the land of mummified priests, those who have, in a purification rite known as the "thousand day training," deliberately poisoned—and at the same time preserved—themselves in compliance with the teachings of a ninth-century monk named Kukai, follower of an esoteric sect of Buddhism called Shingon.

"It is the principle of 'I suffer so that you might live,'" explains Yugaku Endo, the chief priest (95th in a line) of the Dainichibo temple, home to one of 27 such mummified priests in Japan.

For 76 years, Yugaku Endo recounts, the priest known as Daijuku Bosatsu Shinnyokai Shonin lived in austerity. He ate nothing except berries, bark, and nuts. He spent his days and nights climbing in the mountains, through the heat of summer and snows of winter.

Finally he sensed his days were coming to an end and ate nothing. He feasted on the idea of starvation and self-sacrifice. He grew thin, then thinner. He sipped tea made from the toxic sap of the urushi tree, used to make lacquer. Near the end he drank only from hotspring waters that, unbeknownst to him, contained high levels of arsenic.

The urushi sap, a purgative, induced vomiting and urination, desiccating the priest's body. Arsenic, a preservative, killed bacteria that would cause decay. Shriveled, emaciated, he withered away. When he died in 1783 at 96, he was buried in a mound of earth and stones. Three years later, when exhumed, his skin looked as if lacquered onto a skeleton. He had become a sokushinbutsu, instant Buddha.

Often we die as we have lived. The brave die bravely. Cowards die cowardly.

Through history poison has served such ends. Socrates, sentenced to death by an Athenian jury in 399 B.C., on charges of corrupting the city's youth and interfering with its religion, accepted the judgment with grace, drank hemlock, and died in the company of his friends. Defiant Cleopatra, preferring death to being paraded as a spoil of war by the conquering Roman Octavian, opted, it is said, for the fatal bite of an asp. Adolf Hitler, confronted with defeat, chose cyanide (after first dosing his Alsatian to test the toxin's efficiency).

Today Daijuku Bosatsu Shinnyokai Shonin resides in a glass case in the Dainichibo temple, wrapped in red and gold robes. He sits in a pose of meditation—a man of holy belief shriveled by time, the tradition of his religion, and the deliberate ingestion of poison, intent on serving others through the suffering and obliteration of the self.

Along Came a Spider…

Chuck Chuck Kristensen has 70,000 mouths to feed and didn't get to bed until 6 a.m., so he is entitled to doze off in the middle of an interview. Kristensen's dependents are spiders: 20,000 black widow babies, thousands of brown recluses and tarantulas, and a few scorpion species besides. The horde constitutes the holdings of Kristensen's company, SpiderPharm. It takes 16 hours to get the spider cafeteria in order each day. No sooner is one meal finished then it's time for the next. The round-the-clock menu includes four sizes of houseflies and fruit flies, wax worms, and, for the tarantulas, an occasional mouse.

Kristensen raises spiders for their venom, which he extracts into tiny vials. It is powerful stuff. A black widow bite can cause severe pain and muscle spasms in a recipient. Brown recluse venom degrades tissue and produces a gangrene-like wound. Funnel spider venom leads to trembling, increased blood pressure, and vomiting. Other spider venoms punch holes in cell membranes, leading to cell death.

Kristensen sends his vials of spider venom to scientists around the world because poison, the death dealer, teaches about life as well. Roderick MacKinnon, winner of the 2003 Nobel Prize in chemistry, used tarantula and scorpion venom to help decipher the structure and function of potassium ion channels in cells.

Ion channels are conduits, like gates, that control the transmission of electrical impulses within cells. Because their opening and shutting in the cell's membrane controls the entry of potassium, calcium, sodium, or chloride ions, the channels and their receptors act as on-off switches that allow a thought, a heartbeat, a breath, the lift of an eyebrow to proceed—or not.

Tarantula toxins can stimulate receptors to hold a gate open in the neurological equivalent of an electrical surge, or slam it shut in the equivalent of a power failure. A busted gate provokes conditions ranging from numbing to outright paralysis on one end to muscle contractions or convulsions on the other. The same malfunction can provoke high blood pressure, cardiac arrhythmia, or epilepsy.

Spider venoms provoke such potent physiological responses that they turn a spider into a virtual Svengali. But why doesn't a spider just knock out its prey and sit down to lunch? In life things are always complicated, Kristensen says. A tree spider may not want a fast knockout: Its meal would curl up and fall out of the tree. Paralysis is the better option. It's the insect equivalent of the surgical strike.

So scientists seek the chemical mastery of the spider. Says Kristensen, "Who controls potassium channels controls the world."

When Your First Bite Might Be Your Last

Among the occupational hazards of being king, tsar, or maharaja, few are so permanently incapacitating as a pinch of arsenic slipped into the soup. For that the royals have long had a remedy: the food taster.

For three generations the family of Mathura Prasad held the post of food taster to the thakur, or lord, of Castle Mandawa in India's Thar desert. "Food was kept under lock and key," he recalls. Before entering the kitchen, "the cook would bathe and change into different clothes. Guards would check his pockets and turban to make sure he wasn't hiding anything. Only then would he be allowed in. When the food was ready, some from each dish would be fed to a dog. Next I would taste, then the guards. The food would go to table under armed escort. Several trusted generals would test it. Finally, the lord and his guest would exchange bits of each dish. Just in case."

Such things are no longer done at Castle Mandawa, now a hotel. But recently, when the vice president of India came to lunch, a food taster sampled the spread. Just in case....

Mithridates, King of Pontus and enemy of Rome, tested poison antidotes on prisoners and nibbled a mix of 54 ingredients to protect himself against poisoning. The Roman emperor Nero commandeered slaves to differentiate between edible and poisonous mushrooms. An armed guard escorted dinner to the table at the court of Louis XIV, and Columbus carried dogs on his second voyage to taste foods his crew had to eat in exchanges of goodwill with natives of newfound cultures.

Medieval rulers experimented with crystal goblets and stones reputed to detect poison on contact. But the tried-and-true means of aftersupper survival was the you-go-first food taster. By tradition, food to be tested before it was served to the ruler was set on a sideboard, or credenza. The Italian word comes from the Latin credential, meaning "confidence."

These days, employment opportunities for tasters are in decline. In England, Buckingham Palace reports there is no formal procedure for food tasting. "The in-house help are fully vetted," a palace spokesman says. The Japanese emperor hasn't used a food taster in years, though President George W. Bush has used Navy mess specialists to handle the job. In the state kitchens of Thailand, humans are factored out altogether. There, in an inspired example of equal opportunity employment, the taste-test heroes of the banquet table, directed by the Ministry of Health, are a legion of white mice.

Extras: See photos, field notes, and more from this National Geographic article.

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