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Science

Call it a poison, but it just may save your life

Some of the most toxic substances double as powerful medicines

TOKYO The assassination of Kim Jong Nam at a Malaysian airport in February was an alarming display of the power of poison. All it took to murder the half-brother of North Korean leader Kim Jong Un was to wipe a substance on his face.

That substance turned out to be the highly potent nerve agent VX, which can be used as poison gas.

Killing with toxins is nothing new, of course. We humans hunted with poison-dipped arrows before recorded history. They say one reason silverware came into use in Europe was that silver bonds with the compounds in arsenic and changes color -- giving a sign that one's food has been poisoned.

Yet, there is a thin line between poisons that take life and medicines that save it. Sometimes, the same basic stuff can fall into either category.

PICK YOUR POISON Nitrogen mustards are one example: These toxic compounds gave rise to the world's first cancer drug.

The treatment can be traced to mustard gas stockpiled in World War II. A U.S. cargo ship carrying the gas came under attack, causing leaks. Symptoms exhibited by survivors offered a hint at the medicinal possibilities -- specifically a drop in white blood cells.

Researchers were able to hone the gas into a chemotherapy agent that inhibits DNA synthesis, helping to prevent cancer cells from proliferating.

Other examples abound. The root of aconite, or wolfsbane -- a poisonous plant -- is used as a cardiotonic drug in Chinese herbal medicine. Paracelsus, a physician and chemist who lived in 16th-century Europe, was one of the first to put toxic compounds such as mercury to medicinal use; until then, they had been used only as poisons.

Many consider Paracelsus the father of modern medical chemistry.

"Toxins and medicines act on the human body in the same way," explained Shinji Funayama, a professor at Nihon Pharmaceutical University, describing medicine as simply the skillful use of that action to help people.

The use of toxins in health care does not always go according to plan. Consider heroin: The narcotic was released as a cough suppressant in the late 19th century, and was also seen as a promising painkiller. Patients, however, became dependent on it and experienced severe withdrawal symptoms. Excessive use was found to cause respiratory difficult and ultimately even death.

TOXIC QUIRKS Potency varies widely between poisons. Perhaps the best-known poisonous substances are potassium cyanide and arsenic compounds, but these are far from the most toxic. VX and the poison found in blowfish are 600 times stronger than potassium cyanide, and 1,000 times more potent than arsenic.

While VX is one of the most toxic substances ever chemically synthesized by people, even more powerful poisons can be found in nature. Clostridium botulinum, which produces the botulinum toxin -- a cause of food poisoning -- is considered the strongest. It is some 50,000 times more potent than VX.

Ricin, found in the castor oil plant, is 150 times as potent as VX.

Toxicity is only part of the equation, though. Arsenic compounds are colorless, odorless and tasteless, which makes them appealing to those with nefarious intentions.

In many cases, the efficacy of a poison (or drug) depends heavily on how it is administered -- say, orally, inhaled as a vapor or injected. This is because different poisons affect different parts of the body. Carbon monoxide and certain snake venoms affect the blood. VX and blowfish poison target the nerves. Even if a nerve agent enters the body, it will have little impact if it does not reach the nerves.

Curare, which has been used for poison arrows since ancient times, is potent when injected into muscle yet can be eaten safely. Hunters figured out that it can help bring down prey without ruining the meat.

Antibiotics make use of the way toxins zero in on specific things. Some of these drugs destroy the cell walls of pathogens, killing them. Since humans' own cells do not have walls, the antibiotics take out only the pathogens.

Then there are toxins that have become guilty pleasures: alcohol, the nicotine in tobacco and the caffeine in coffee and tea. A lethal dose of nicotine can be even smaller than a killer helping of potassium cyanide, when directly ingested.

"I think people like poison," Funayama said.

Research on tapping the medical potential of poisons is ongoing. Nagoya University professor Masaki Kita is focusing on toxic substances found in rare animals.

"The study of poisons from plants and microbes is being exhausted," he noted, explaining why he turned his gaze elsewhere. One hope is a poison produced by the platypus. The substance, which paralyzes nerves, could prove useful as a painkiller.

Throughout history, people have used poisons for both good and ill. We may have only scratched the surface of their capabilities.

Keyword: Lethal dose

A deadly dose of poison depends on various factors, including the size of the subject, the manner in which it is ingested and the condition of the toxin itself. The term "lethal dose" typically refers to the median lethal dose -- the amount that causes death in half of the animal test subjects in an experiment. Sometimes, it can refer to the minimum lethal dose, or the smallest amount capable of killing.

In some cases, death does not occur even when the lethal dose is exceeded. In others, even a smaller dose can prove deadly.

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