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Poison. From ancient times through the Cold War and even up to today, it’s always been a popular method of offing one’s enemies.

Depending on the toxin you go with, you can kill someone slowly and quietly, or abruptly and dramatically -- although, to be clear, we do not recommend any of this... Murder is bad. But is there really such a thing as a “perfect,” undetectable poison?

Well, probably not -- but some are definitely more challenging than others to identify and treat because of how they interact with the body. Here are six poisons that, at various times throughout history, have confounded doctors and medical examiners. We’ll start with one you’ve probably heard of: arsenic.

This poison has been around for a long time, and mixtures of it were known and used going all the way back to the Roman Empire. Arsenic is a type of element called a metalloid -- one whose traits put it in a fuzzy gray area between metals and nonmetals -- and it’s actually pretty common in the Earth’s crust. When it’s mixed into food or drink, it’s odorless, colorless, and tasteless, and the symptoms of a single large dose resemble those of bad, fatal food poisoning.

Which can seem pretty sneaky if you don’t know you’ve been poisoned. Arsenic can also be given in smaller doses over a longer period of time. That produces subtler, slowly progressing symptoms, including weakness, confusion, paralysis, and, yes, eventually death.

Which is even sneakier. Arsenic is absorbed through the small intestine, and once it gets into the bloodstream, the body mistakenly substitutes them for phosphate. This wreaks havoc on around 200 enzyme-based systems necessary for a functioning metabolism.

Arsenic was a popular murder weapon for much of modern human history, but it’s a lot less common these days, because it’s easier to detect. A chemical test for confirming the presence of arsenic in bodily fluids was perfected back in the early 19th century. Around that time, it had been discovered that when zinc is added to arsenic dissolved in sulfuric acid, a colorless, smelly gas -- called arsine -- will form, along with hydrogen.

Marsh used this to develop his test. He suspended a piece of zinc in one arm of a closed, U-shaped glass tube, which was filled with sulfuric acid. Then, when a sample -- a bit of the victim’s blood, for example -- was added to the opposite arm of the U, hydrogen and arsine would form if there was any arsenic in the sample.

After that, the tube was opened, and the escaping gas was lit on fire. If you held a piece of glass over the flame, it would show a characteristic brownish spot if arsine was there, proving that a victim had indeed been murdered. Once it could be reliably detected, arsenic’s popularity began to wane, and today, murder by arsenic is mostly found in old detective stories.

Another classic, cyanide was supposedly used in an attempt to murder the famously hard-to-kill. Russian mystic Rasputin back in 1916. And it’s still used for the occasional murder today.

Cyanide is made of a carbon atom stuck to a nitrogen atom, and it has several forms. Hydrogen cyanide is a pale blue or colorless liquid at room temperature, while sodium cyanide and potassium cyanide are white powders. All of them may smell like bitter almonds.

Once someone ingests some cyanide, it quickly enters their bloodstream. But it might not always be deadly. In small doses, the body can get rid of cyanide by tacking on a sulfur ion onto it.

That converts the poison into a different chemical called thiocyanate, which can leave the body through urine. But with larger doses, the body gets overwhelmed, and it can’t turn all the poison into thiocyanate. At that point, the cyanide starts preventing cells from using oxygen, and eventually, cells start dying off.

And a lack of oxygen is not good news for the heart, respiratory system, or central nervous system. Because all of these essential systems are affected, there’s a pretty long list of symptoms for cyanide poisoning, including weakness, nausea, difficulty breathing, seizures, or cardiac arrest. But what makes cyanide especially tricky for doctors, even today, is that it’s so fast-acting.

Depending on the form of cyanide and the dose, it can kill in hours or even minutes. It can be detected in blood, but a patient would probably be dead before the lab results came back -- the commonly used test takes about a day. Still, there are some secondary indicators doctors can check for.

One is extra oxygen in the blood, which happens because cells can’t use all the oxygen someone’s breathing. Unfortunately, some of those indicators can actually show up with other poisons as well. Ultimately, a patient’s best chance for survival is for doctors to make a careful, educated guess based on the symptoms and circumstances, and to start treatment right away.

So cyanide poisoning may be detectable -- but by the time doctors know for sure, it’ll probably be too late. Thallium is a heavy metal with multiple radioactive isotopes. It was discovered in 1861, and it’s been implicated in murders worldwide ever since.

Although today, it’s also used in some types of medical imaging. As a poison, thallium is tasteless, odorless, and very deadly -- ingesting as little as a single gram of the stuff can kill you, and it can also be inhaled or absorbed through the skin. Once it gets into the body, it corrodes the lining of the digestive tract, which leads to abdominal pain, diarrhea, and vomiting.

It also replaces potassium in certain enzyme systems throughout the body -- like how arsenic replaces phosphate. That impairs the production of proteins. Still, thallium is at least pretty slow-acting compared to some other poisons.

The gastrointestinal symptoms last from 12 to 96 hours. Then, 1 to 5 days after the poisoning, neurological, cardiac, liver, and kidney symptoms can kick in. Patients also eventually lose all their hair -- if they live long enough.

Now, even though thallium is slow-acting, that doesn’t necessarily mean it’s easy to detect -- at least, not at first. Which is partly why it’s such a popular choice. Thallium can be detected in blood and urine, but the slow progression of symptoms may not be caught right away.

And it’s uncommon enough that doctors don’t necessarily think to test for it. So by the time doctors figure out what’s going on or the victim dies... the poisoner might have already fled the country. Polonium-210 is a metal found in uranium ore, which often shows up as a byproduct of nuclear reactors.

It can be processed into a tasteless, odorless compound that dissolves in water, which makes it a good candidate as far as undetectable poisons go. This stuff is also many times more deadly than even cyanide: The lethal dose is as little as a few milligrams. And if you don’t know exactly what you’re looking for, it’s really hard to pin down.

Thankfully, as far as anyone knows, this has only ever happened once. In 2006, a former Russian spy named Alexander. Litvinenko was assassinated in London, likely with tea laced with polonium-210.

Litvinenko was taken to the hospital that afternoon, feeling ill. Then, he died three weeks later after experiencing multiple organ failures. Doctors first thought our friend thallium might be to blame.

Then, they eventually figured out that Litvinenko had some sort of radiation poisoning, thanks to his hair loss and immune system failure. But they didn’t ID the culprit as polonium until just a few hours before his death. What makes polonium-210 so dangerous is that, as the molecules break down, they emit alpha radiation, positively charged particles made of two protons and two neutrons.

Outside the body, alpha particles can be blocked with a sheet of paper. But inside the body, the radiation breaks apart oxygen molecules to create dangerous, highly reactive free radicals, which damage DNA and kill cells. In this case, those alpha particles also helped doctors figured out what poisoned Litvinenko.

See, the ones emitted by polonium-210 have a characteristic energy of around 5.3 mega-electronvolts -- which is a unit of momentum used in high-energy physics. And when doctors found particles with that exact, unique trait in Litvinenko’s urine, they finally identified the element that killed the spy. As far as we know, this is the only case where polonium-210 was used as a poison.

But it was definitely a tricky one and, if it turns up again, we’ll hopefully have a better idea how to identify it. Ethylene glycol is the base for a lot of common antifreeze you use in your car. It tastes sweet, and it’s readily available, making it a popular choice for murder by poison in the U.

S. But to be clear, no matter how it good it tastes, you should not drink it. After someone ingests it, they’ll seem fine for a few hours -- but their body is actually busy breaking down the poison into other, toxic substances.

Eventually someone will start to feel groggy, experience abdominal distress, and then go into a coma. [acid-osis -- like it looks] One of the byproducts ethylene glycol breaks down into is glycolic acid, which causes a dangerous condition called metabolic acidosis. This is when someone’s blood becomes too acidic, keeping all the chemical reactions that make up their metabolism from functioning properly. The poison also creates calcium oxalate crystals in the kidneys, which physically tear up kidney tissue.

Sounds...not fun. Ethylene glycol can be definitively detected in the blood, but for most hospitals, it’ll require sending a sample to an outside lab and waiting days for results. So, kind of like with cyanide, doctors generally have to diagnose ethylene glycol poisoning indirectly, using tests for things like the presence of osmotically active substances in the body.

These are substances that can’t move across cell membranes, like ethylene glycol. But also like with cyanide, the results of these tests aren’t really conclusive, making it hard to ID this type of poisoning fast enough to treat it effectively. The moral of this story?

Don’t drink antifreeze, and also, prevent other people from drinking antifreeze. No matter how delicious it tastes. California mortician Timothy Waters died in 1985 of what was originally believed to be a heart attack.

At first, no one suspected that the culprit might be a poisonous plant called oleander. Until his alleged murderer started bragging about the crime. The name “oleander” refers to several small, shrubby trees in the genus Nerium, which have attractive pink or purple flowers and are commonly used in gardens.

What makes oleander toxic are two potent cardiac glycosides, oleandrin and neriine, which are found in every part of the plant. These molecules are similar to digitalis, which you may have heard of because it’s sometimes used as a heart medication. Cardiac glycosides work by manipulating the ion pump that powers heart muscle cells, which increases the force of heart muscle contraction.

This makes them useful for treating some heart conditions in small, controlled doses -- but they’re not so good if you ingest a whole lot at once, as they can totally mess up your heart rhythm. In addition to cardiac symptoms, oleander poisoning also causes nausea, vomiting, cramps, and diarrhea, usually about four hours after ingestion. Waters spent two days vomiting before he died.

But oleander isn’t a common poison, and medical examiners had no reason to test for it at first. Only when a rival funeral home owner supposedly bragged to an informant about poisoning Waters did investigators expand their search. During an autopsy where the cause of death isn’t certain, medical examiners typically check for about 100 compounds, including alcohol, common illicit drugs, and common poisons.

If those tests all come back negative, then the examiner might order detailed tests to check for less-common toxins. In Waters’s case, it took analysis by two outside labs to finally isolate oleander compounds in samples of his blood. But even then, the murder charges were ultimately dismissed when a toxicologist hired by the defense couldn’t confirm the results.

So either this wasn’t a case of death-by-oleander after all… or oleander really is the perfect poison. It should go without saying that we here at SciShow do not condone poisoning your enemies. Or your friends.

But the chemistry and medicine behind a lot of these compounds and how they’re used is undeniably cool. And if this wasn’t enough poison for you and you’d like to learn even more, you can also watch our episode about 10 plants that could kill you. [♩OUTRO].